bluuebunny/crossref_metadata_2025 huggingface dataset:
MStoCIRC: A powerful tool for downstream analysis of MS/MS data to predict translatable circRNAs
Authors: Cao Zhou , Li Guanglin
Published: August 2022

CircRNAs are formed by a non-canonical splicing method and appear circular in nature. CircRNAs are widely distributed in organisms and have the features of time- and tissue-specific expressions. CircRNAs have attracted increasing interest from scientists because of their non-negligible effects on the growth and development of organisms. The translation capability of circRNAs is a novel and valuable direction in the functional research of circRNAs. To explore the translation potential of circRNAs, some progress has been made in both experimental identification and computational prediction. For computational prediction, both CircCode and CircPro are ribosome profiling-based software applications for predicting translatable circRNAs, and the online databases riboCIRC and TransCirc analyze as many pieces of evidence as possible and list the predicted translatable circRNAs of high confidence. Simultaneously, mass spectrometry in proteomics is often recognized as an efficient method to support the identification of protein and peptide sequences from diverse complex templates. However, few applications fully utilize mass spectrometry to predict translatable circRNAs. Therefore, this research aims to build up a scientific analysis pipeline with two salient features: 1) it starts with the data analysis of raw tandem mass spectrometry data; and 2) it also incorporates other translation evidence such as IRES. The pipeline has been packaged into an analysis tool called mass spectrometry to translatable circRNAs (MStoCIRC). MStoCIRC is mainly implemented by Python3 language programming and could be downloaded from GitHub (https://github.com/QUMU00/mstocirc-master). The tool contains a main program and several small, independent function modules, making it more multifunctional. MStoCIRC can process data efficiently and has obtained hundreds of translatable circRNAs in humans and Arabidopsis thaliana.
Correlation of matrix metalloproteinase 3 and matrix metalloproteinase 9 levels with non-motor symptoms in patients with Parkinson’s disease
Authors: Liu Chuan Ze , Guo Da Shuai , Ma Jian Jun , Dong Lin Rui , Chang Qing Qing , Yang Hong Qi , Liang Ke Ke , Li Xiao Huan , Yang Da Wei , Fan Yong Yan , Gu Qi , Chen Si Yuan , Li Dong Sheng
Published: August 2022

Objective

Matrix metalloproteinases (MMPs) are essential for tissue formation, neuronal network remodeling, and blood–brain barrier integrity. MMPs have been widely studied in acute brain diseases. However, the relationship with Parkinson’s disease (PD) remains unclear. The purpose of this study was to evaluate the serum MMP3 and MMP9 levels of PD patients and analyze their correlation with non-motor symptoms.

Methods

In this cross-sectional study, we recruited 73 patients with idiopathic PD and 64 healthy volunteers. Serum MMP3 and MMP9 levels were measured by enzyme-linked immunosorbent assay (ELISA). Patients with PD were assessed for non-motor symptoms using the Non-motor Symptoms Scale (NMSS) and Parkinson’s disease sleep scale (PDSS) and Mini Mental State Examination (MMSE).

Results

Serum MMP3 levels were significantly decreased in PD patients, predominantly those with early-stage PD, compared with controls [12.56 (9.30, 17.44) vs. 15.37 (11.33, 24.41) ng/ml;P= 0.004], and the serum MMP9 levels of PD patients were significantly higher than those of healthy controls [522 (419, 729) vs. 329 (229, 473) ng/ml;P< 0.001]. MMP3 levels were positively correlated with the NMSS total score (r= 0.271,P= 0.020) and the single-item scores for item six, assessing the gastrointestinal tract (r= 0.333,P= 0.004), and there was an inverse correlation between serum MMP3 levels and PDSS score (r= –0.246,P= 0.036); meanwhile, MMP9 levels were positively correlated with the NMSS total score (r= 0.234,P= 0.047), and higher serum MMP9 levels were detected in the cognitive dysfunction subgroup than in the cognitively intact subgroup [658 (504, 877) vs. 502 (397, 608) ng/ml,P= 0.008].

Conclusion

The serum MMP3 level of PD patients (especially early-stage patients) was significantly lower than that of the healthy control group, and the MMP9 level was significantly higher than that of the healthy control group. MMP3 and MMP9 levels correlate with sleep disturbance and cognitive function in PD patients, respectively.
Microglial infiltration mediates cognitive dysfunction in rat models of hypothalamic obesity via a hypothalamic-hippocampal circuit involving the lateral hypothalamic area
Authors: Song Chong , Wei Wei , Wang Tong , Zhou Min , Li Yunshi , Xiao Bing , Huang Dongyi , Gu Junwei , Shi Linyong , Peng Junjie , Jin Dianshi
Published: August 2022

This study aimed to explore the mechanism underlying cognitive dysfunction mediated by the lateral hypothalamic area (LHA) in a hypothalamic-hippocampal circuit in rats with lesion-induced hypothalamic obesity (HO). The HO model was established by electrically lesioning the hypothalamic nuclei. The open field (OP) test, Morris water maze (MWM), novel object recognition (NOR), and novel object location memory (NLM) tests were used to evaluate changes in cognition due to alterations in the hypothalamic-hippocampal circuit. Western blotting, immunohistochemical staining, and cholera toxin subunit B conjugated with Alexa Fluor 488 (CTB488) reverse tracer technology were used to determine synaptophysin (SYN), postsynaptic density protein 95 (PSD95), ionized calcium binding adaptor molecule 1 (Iba1), neuronal nuclear protein (NeuN), and Caspase3 expression levels and the hypothalamic-hippocampal circuit. In HO rats, severe obesity was associated with cognitive dysfunction after the lesion of the hypothalamus. Furthermore, neuronal apoptosis and activated microglia in the downstream of the lesion area (the LHA) induced microglial infiltration into the intact hippocampusviathe LHA-hippocampal circuit, and the synapses engulfment in the hippocampus may be the underlying mechanism by which the remodeled microglial mediates memory impairments in HO rats. The HO rats exhibited microglial infiltration and synapse loss into the hippocampus from the lesioned LHAviathe hypothalamic-hippocampal circuit. The underlying mechanisms of memory function may be related to the circuit.
Association between risk polymorphisms for neurodegenerative diseases and cognition in colombian patients with frontotemporal dementia
Authors: López-Cáceres Andrea , Cruz-Sanabria Francy , Mayorga Pilar , Sanchez Ana Isabel , Gonzalez-Nieves Silvia , Ayala-Ramírez Paola , Zarante Ignacio , Matallana Diana
Published: August 2022

Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disease of presenile onset. A better characterization of neurodegenerative disorders has been sought by using tools such as genome-wide association studies (GWAS), where associations between single nucleotide polymorphisms (SNPs) and cognitive profiles could constitute predictive biomarkers for these diseases. However, in FTD, associations between genotypes and cognitive phenotypes are yet to be explored. Here, we evaluate a possible relationship between genetic variants and some cognitive functions in an FTD population.

Methodology

A total of 47 SNPs in genes associated with neurodegenerative diseases were evaluated using the Sequenom MassARRAY platform along with their possible relationship with performance in neuropsychological tests in 105 Colombian patients diagnosed with FTD.

Results and discussion

The SNPs rs429358 (APOE), rs1768208 (MOBP), and rs1411478 (STX6), were identified as risk factors for having a low cognitive performance in inhibitory control and phonological verbal fluency. Although the significance level was not enough to reach the corrected alpha for multiple comparison correction, our exploratory data may constitute a starting point for future studies of these SNPs and their relationship with cognitive performance in patients with a probable diagnosis of FTD. Further studies with an expansion of the sample size and a long-term design could help to explore the predictive nature of the potential associations we identified.
Effects of 3-month CPAP therapy on brain structure in obstructive sleep apnea: A diffusion tensor imaging study
Authors: Liu Xiang , Wei Zhipeng , Chen Liting , Duan Wenfeng , Li Haijun , Kong Linghong , Shu Yongqiang , Li Panmei , Li Kunyao , Xie Wei , Zeng Yaping , Huang Ling , Long Ting , Peng Dechang
Published: August 2022

White matter (WM) fiber alterations in patients with obstructive sleep apnea (OSA) is associated with cognitive impairment, which can be alleviated by continuous positive airway pressure (CPAP). In this study, we aimed to investigate the changes in WM in patients with OSA at baseline (pre-CPAP) and 3 months after CPAP adherence treatment (post-CPAP), and to provide a basis for understanding the reversible changes after WM alteration in this disease. Magnetic resonance imaging (MRI) was performed on 20 severely untreated patients with OSA and 20 good sleepers. Tract-based spatial statistics was used to evaluate the fractional anisotropy (FA), mean diffusion coefficient, axial diffusion coefficient, and radial diffusion coefficient (RD) of WM. To assess the efficacy of treatment, 20 patients with pre-CPAP OSA underwent MRI again 3 months later. A correlation analysis was conducted to evaluate the relationship between WM injury and clinical evaluation. Compared with good sleepers, patients with OSA had decreased FA and increased RD in the anterior thalamic radiation, forceps major, inferior fronto-occipital tract, inferior longitudinal tract, and superior longitudinal tract, and decreased FA in the uncinate fasciculus, corticospinal tract, and cingulate gyrus (P < 0.05). No significant change in WM in patients with post-CPAP OSA compared with those with pre-CPAP OSA. Abnormal changes in WM in untreated patients with OSA were associated with oxygen saturation, Montreal cognitive score, and the apnea hypoventilation index. WM fiber was extensively alteration in patients with severe OSA, which is associated with cognitive impairment. Meanwhile, cognitive recovery was not accompanied by reversible changes in WM microstructure after short-term CPAP therapy.
What is the optimal duration of home-video-EEG monitoring for patients with <1 seizure per day? A simulation study
Authors: Vander Tatiana , Stroganova Tatiana , Doufish Diya , Eliashiv Dawn , Gilboa Tal , Medvedovsky Mordekhay , Ekstein Dana
Published: August 2022

Ambulatory “at home” video-EEG monitoring (HVEM) may offer a more cost-effective and accessible option as compared to traditional inpatient admissions to epilepsy monitoring units. However, home monitoring may not allow for safe tapering of anti-seizure medications (ASM). As a result, longer periods of monitoring may be necessary to capture a sufficient number of the patients' stereotypic seizures. We aimed to quantitatively estimate the necessary length of HVEM corresponding to various diagnostic scenarios in clinical practice. Using available seizure frequency statistics, we estimated the HVEM duration required to capture one, three, or five seizures on different days, by simulating 100,000 annual time-courses of seizure occurrence in adults and children with more than one and <30 seizures per month (89% of adults and 85% of children). We found that the durations of HVEM needed to record 1, 3, or 5 seizures in 80% of children were 2, 5, and 8 weeks (median 2, 12, and 21 days), respectively, and significantly longer in adults −2, 6, and 10 weeks (median 3, 14, and 26 days; p < 10−10 for all comparisons). Thus, longer HVEM than currently used is needed for expanding its clinical value from diagnosis of nonepileptic or very frequent epileptic events to a presurgical tool for patients with drug-resistant epilepsy. Technical developments and further studies are warranted.
Identification of genetic molecular markers and immune infiltration characteristics of Alzheimer's disease through weighted gene co-expression network analysis
Authors: Duan KeFei , Ma Yuan , Tan Jin , Miao Yuyang , Zhang Qiang
Published: August 2022

Background

Alzheimer's disease (AD) is a progressive neurodegenerative disease that leads to cognitive impairment and memory loss. Currently, the pathogenesis and underlying causative genes of AD remain unclear, and there exists no effective treatment for this disease. This study explored AD-related diagnostic and therapeutic biomarkers from the perspective of immune infiltration by analyzing public data from the NCBI Gene Expression Omnibus database.

Method

In this study, weighted gene co-expression network analysis (WGCNA) was conducted to identify modules and hub genes contributing to AD development. A protein–protein interaction network was constructed when the genes in the modules were enriched and examined by Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Furthermore, a gene network was established using topological WGCNA, from which five hub genes were selected. Logistic regression analysis and receiver operating characteristic curve analysis were performed to explore the clinical value of genes in AD diagnosis. The genes in the core module intersected with the hub genes, and four intersection genes (ATP2A2, ATP6V1D, CAP2, and SYNJ1) were selected. These four genes were enriched by gene set enrichment analysis (GSEA). Finally, an immune infiltration analysis was performed.

Results

The GO/KEGG analysis suggested that genes in the core module played a role in the differentiation and growth of neural cells and in the transmission of neurotransmitters. The GSEA of core genes showed that these four genes were mainly enriched in immune/infection pathways (e.g., cholera infection and Helicobacter pylori infection pathways) and other metabolic pathways. An investigation of immune infiltration characteristics revealed that activated mast cells, regulatory T cells, plasma cells, neutrophils, T follicular helper cells, CD8 T cells, resting memory CD4 T cells, and M1 macrophages were the core immune cells contributing to AD progression. qRT-PCR analysis showed that the ATP6V1D is upregulated in AD.

Conclusion

The results of enrichment and immuno-osmotic analyses indicated that immune pathways and immune cells played an important role in the occurrence and development of AD. The selected key genes were used as biomarkers related to the pathogenesis of AD to further explore the pathways and cells, which provided new perspectives on therapeutic targets in AD.
Normative data for rotational chair considering motion susceptibility
Authors: Yu Jiaodan , Wan Yi , Zhao Jieli , Huang Ruonan , Wu Peixia , Li Wenyan
Published: August 2022

Objective

Rotational Chair Test (RCT) is considered one of the most critical measures for vestibular functionality, which generally includes the sinusoidal harmonic acceleration test (SHAT), velocity step test (VST), and visual suppression (VS). The purpose of this study was to establish normal values for different age groups on the RCT and investigate whether motion susceptibility, such as with a history of motion sickness or migraine, has any effects on test metrics.

Methods

One hundred and nine subjects aged from 20 to 59 years who were free from neurotological and vestibular disorders were enrolled. According to the history of motion sickness or migraine, participants were divided into four groups: the motion sickness (MS) group (n = 13), the migraine group (n = 8), comorbidity group (n = 11), and the control group (n = 77). The 77 subjects without any history of MS and migraine were then further separated into four age groups: youth group (20–29 years), young and middle-aged group (30–39 years), middle-age group (40–49 years), and middle-age and elderly group (50–59 years). All participants underwent SHAT, VST, and VS, and a comprehensive set of metrics including gain, phase, asymmetry, time constant (TC), and Fixation Index were recorded.

Results

Regarding the VST and VS, no significant differences were observed either across the four groups (MS, migraine, comorbidity, and control group) or four age categories within the control group. For SHAT, VOR gain at the frequency of 0.01 Hz, VOR phase from 0.08 to 0.64 Hz, and asymmetry at 0.01, 0.16, and 0.64 Hz indicated significant differences among various age groups (P < 0.05 for all comparisons). The VOR phase lead was lower in the migraine and comorbidity group than that in the control group at 0.64 Hz (P = 0.027, P = 0.003, respectively).

Conclusions

Age slightly affects the result of SHAT, but not for VST and VS. VOR gain is more susceptible to aging at low frequency, while the phase is opposite. Subjects with both migraine and motion sickness show abnormal velocity storage mechanisms. Phase bias should be considered when assessing motion susceptibility with the RCT. SHAT is more sensitive than VST in terms of reflecting motion susceptibility.
Genetic spectrum and characteristics of autosomal optic neuropathy in Korean: Use of next-generation sequencing in suspected hereditary optic atrophy
Authors: Seo Yuri , Kim Tae Young , Won Dongju , Shin Saeam , Choi Jong Rak , Lee Seung-Tae , Lee Byung Joo , Lim Hyun Taek , Han Sueng-Han , Han Jinu
Published: August 2022

Aims

To evaluate the clinical characteristics and causative genetic variants in autosomal optic atrophy diagnosed using next-generation sequencing (NGS).

Methods

A cohort of 57 unrelated families affected with bilateral optic atrophy were recruited from two university-based tertiary referral hospitals from May 2016 to April 2022. Genetic variants were detected using a target enrichment panel consisting of 429 or 595 genes and known deep intronic variants associated with inherited eye diseases, exome sequencing, or genome sequencing. The results of detailed clinical examinations, disease-causing variants, and clinical diagnoses were analyzed.

Results

Among the 57 probands, 33 (57.9%) were men, and the median age at genetic testing was 19.1 years (interquartile range, 7.6–42.5 years). We identified 22 likely causative variants in 18 families and corresponding diagnostic yields of 31.6% (95% confidence interval, 21.0–44.5%). The diagnostic rate of NGS was higher in patients with infantile or early childhood onset optic atrophy than in those with late-onset or unknown optic atrophy (18/39, 46.2% vs. 0/18, 0%, P < 0.001). Among the 22 variants, 15 were novel in our cohort. The OPA1 variants (n = 7) were found to be the major genetic causes, followed by the NR2F1 variant (n = 4). The causative variants in PTPN23, TMEM126A, NBAS, and WFS1 genes were identified in 4 probands with a recessive form of optic atrophy.

Conclusions

Based on the results of diagnostic NGS for optic atrophy, the causative variant could be detected in 31.6% of patients. Our study also demonstrated that NGS is unlikely to help identify molecular causes in late-onset unexplained optic atrophy.
Multimodal brain features at 3 years of age and their relationship with pre-reading measures 1 year later
Authors: Manning Kathryn Y. , Reynolds Jess E. , Long Xiangyu , Llera Alberto , Dewey Deborah , Lebel Catherine
Published: August 2022

Pre-reading language skills develop rapidly in early childhood and are related to brain structure and functional architecture in young children prior to formal education. However, the early neurobiological development that supports these skills is not well understood. Here we acquired anatomical, diffusion tensor imaging (DTI) and resting state functional MRI (rs-fMRI) from 35 children at 3.5 years of age. Children were assessed for pre-reading abilities using the NEPSY-II subtests 1 year later (4.5 years). We applied a data-driven linked independent component analysis (ICA) to explore the shared co-variation of gray and white matter measures. Two sources of structural variation at 3.5 years of age demonstrated relationships with Speeded Naming scores at 4.5 years of age. The first imaging component involved volumetric variability in reading-related cortical regions alongside microstructural features of the superior longitudinal fasciculus (SLF). The second component was dominated by cortical volumetric variations within the cerebellum and visual association area. In a subset of children with rs-fMRI data, we evaluated the inter-network functional connectivity of the left-lateralized fronto-parietal language network (FPL) and its relationship with pre-reading measures. Higher functional connectivity between the FPL and the default mode and visual networks at 3.5 years significantly predicted better Phonological Processing scores at 4.5 years. Together, these results suggest that the integration of functional networks, as well as the co-development of white and gray matter brain structures in early childhood, support the emergence of pre-reading measures in preschool children.
There is no F in APC: Using physiological fluoride-free solutions for high throughput automated patch clamp experiments
Authors: Rapedius Markus , Obergrussberger Alison , Humphries Edward S. A. , Scholz Stephanie , Rinke-Weiss Ilka , Goetze Tom A. , Brinkwirth Nina , Rotordam Maria Giustina , Strassmaier Tim , Randolph Aaron , Friis Søren , Liutkute Aiste , Seibertz Fitzwilliam , Voigt Niels , Fertig Niels
Published: August 2022

Fluoride has been used in the internal recording solution for manual and automated patch clamp experiments for decades because it helps to improve the seal resistance and promotes longer lasting recordings. In manual patch clamp, fluoride has been used to record voltage-gated Na (NaV) channels where seal resistance and access resistance are critical for good voltage control. In automated patch clamp, suction is applied from underneath the patch clamp chip to attract a cell to the hole and obtain a good seal. Since the patch clamp aperture cannot be moved to improve the seal like the patch clamp pipette in manual patch clamp, automated patch clamp manufacturers use internal fluoride to improve the success rate for obtaining GΩ seals. However, internal fluoride can affect voltage-dependence of activation and inactivation, as well as affecting internal second messenger systems and therefore, it is desirable to have the option to perform experiments using physiological, fluoride-free internal solution. We have developed an approach for high throughput fluoride-free recordings on a 384-well based automated patch clamp system with success rates >40% for GΩ seals. We demonstrate this method using hERG expressed in HEK cells, as well as NaV1.5, NaV1.7, and KCa3.1 expressed in CHO cells. We describe the advantages and disadvantages of using fluoride and provide examples of where fluoride can be used, where caution should be exerted and where fluoride-free solutions provide an advantage over fluoride-containing solutions.
Cholinergic REST-G9a gene repression through HMGB1-TLR4 neuroimmune signaling regulates basal forebrain cholinergic neuron phenotype
Authors: Crews Fulton T. , Vetreno Ryan P.
Published: August 2022

Lipopolysaccharide (LPS) and high-mobility group box 1 (HMGB1) are Toll-like receptor (TLR4) agonists that activate proinflammatory neuroimmune signaling linked to loss of basal forebrain cholinergic neurons (BFCNs) and cognitive deficits. Loss of choline acetyltransferase immunoreactive (ChAT + IR) BFCNs is generally interpreted as cell death, but recent in vivo studies find anti-inflammatory interventions restore adolescent ethanol exposure-induced persistent loss of adult ChAT + IR neurons and cognitive deficits, suggesting proinflammatory signaling-induced reversible gene repression of ChAT in BFCNs. Using an ex vivo Wistar rat basal forebrain slice culture (FSC) model to investigate TLR4 involvement in repression of the BFCN phenotype, we report that direct TLR4 activation with LPS decreases expression of multiple BFCN markers in the absence of observable neuronal loss or cell death. Inhibition of HMGB1 blunts while inhibition of TLR4 blocks the LPS-induced loss of ChAT + IR neurons. TLR4 activation induces the transcriptional repressor RE1-silencing transcription factor (REST) and the methyltransferase G9a while increasing repressive histone 3 lysine 9 dimethylation and REST occupancy at cholinergic gene promoters. G9a inhibitors both prevent and reverse the LPS-induced loss of ChAT + IR whereas siRNA inhibition of REST blocks the LPS-induced loss of ChAT + IR BFCNs. These data suggest in vivo HMGB1-TLR4 signaling in BFCNs leads to a reversible loss of the cholinergic neuron phenotype through epigenetic gene repressive mechanisms.
Coffee and caffeine consumption and risk of renal cell carcinoma: A Mendelian randomization study
Authors: Li Bing-Hui , Yan Si-Yu , Li Xu-Hui , Huang Qiao , Luo Li-Sha , Wang Yun-Yun , Huang Jiao , Jin Ying-Hui , Wang Yong-Bo
Published: August 2022

Background

The association between coffee and caffeine consumption and the risk of renal cell carcinoma was inconsistent among observational studies, and whether these observed associations were causal remained unclear. Therefore, we performed two-sample Mendelian randomization (MR) study to assess the causal nature of the association.

Materials and methods

In this study, 12 and two independent single nucleotide polymorphisms (SNPs) related to coffee and caffeine consumption at a genome-wide significance level of p < 5 × 10–8 were used as instrumental variables (IVs), respectively. Summary-level data for renal cell carcinoma were taken from the FinnGen consortium with up to 174,977 individuals, and the International Agency for Research on Cancer (IARC) with 13,230 individuals. We used inverse-variance weighted (IVW) as the main method, followed by the weighted median method, the MR-Egger regression method, and the MR robust adjusted profile score method. Outlier and pleiotropic variants were assessed by the MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression. We used meta-analysis methods in fixed-effects to combine the estimates from the two sources.

Results

The genetically predicted coffee consumption was not associated with the risk of renal cell carcinoma in the FinnGen consortium, and the relationship was consistent in the IARC consortium. The pooled odds ratio (OR) per 50% increase of coffee consumption was 0.752 [95% confidence interval (CI), 0.512–1.105; p = 0.147]. In addition, complementary analyses that separated the coffee-related SNPs according to their relationship with blood levels of caffeine metabolites (higher, lower, or unrelated) found no relationship with renal cell carcinoma. The results were consistent after excluding eight SNPs due to potential risk factors at genome-wide significance (p < 5 × 10–8). Moreover, genetically predicted per 80-mg increase in caffeine consumption was not associated with the risk of renal cell carcinoma (pooled OR = 0.872, 95% CI: 0.676–1.125, p = 0.292).

Conclusion

Our MR study provided no convincing evidence for a causal effect between coffee and caffeine consumption and the risk of renal cell carcinoma. The associations for renal cell carcinoma need to be verified in well-powered studies.
Digestive stability and transport ability changes of β-lactoglobulin–catechin complexes by M cell model in vitro
Authors: Dai Yan , Yang Ruoting , Yan Yuting , Wu Yong , Meng Xuanyi , Yang Anshu , Wu Zhihua , Shi Linbo , Li Xin , Chen Hongbing
Published: August 2022

The current research on interaction between catechin and protein has focused on non-covalent crosslinking, however, the mechanism of free radical-induced crosslinking between catechin and β-lactoglobulin (BLG) is not known. In this study, BLG bound to four catechins [epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG)]. The structure change of complex was investigated by circular dichroism spectroscopy, ultraviolet-visible (UV-vis) spectroscopy and Acid and 8-Anilino-1-naphthalenesulfonic acid (ANS) fluorescence spectroscopy. M cell model was constructed to evaluate the transintestinal epithelial transport capacity of complex digestive products. The results showed that catechins were covalently bound to BLG by C-S and C-N bonds and their binding content was EGCG>EGC>ECG>EC. Moreover, catechins could change the secondary structure of BLG, with the decrease of α-helix and reduction of the irregular coilings, which leads to the loose spatial structure of the protein. Moreover, the catechin could enhance further the digestibility of BLG. Transport capacity of digestive products of M cell model was about twice of that of the Caco-2 cell model, indicating that M cell model had better antigen transport capacity. The difference between groups indicated that the transport efficiency of digestive products was decreased with the presence of catechin, in which BLG-EGCG and BLG-EGC groups were transported more strong than those of BLG-EC and BLG-ECG groups. The transport efficiency of BLG-catechin complexes were lower than that of BLG, indicating that catechin had the protective and repair roles on intestinal barrier permeability.
Sustained effect of habitual feeding time on daily rhythm of core body temperature in mice
Authors: Ando Hitoshi , Nagata Naoto , Hosono Takashi , Hasan Nazmul , Morishige Jun-ichi , Daikoku Takiko , Maida Yoshiko , Ono Masanori , Fujiwara Tomoko , Fujiwara Hiroshi
Published: August 2022

Background and aim

Circadian clocks in most peripheral tissues are entrained mainly by feeding. Therefore, this study aimed to investigate whether the daily rhythm of core body temperature (CBT), including the effect of diet-induced thermogenesis, varies according to habitual feeding time.

Methods

Wild-type and uncoupling protein 1 (UCP1) knockout mice were fed only during the first 4 h (Breakfast group) or the last 4 h of the dark period (Dinner group) for 17 days. On day 18, both groups were fed twice for 2 h, at the same starting times. Locomotor activity and CBT were measured continuously during the experiment.

Results

On day 18, CBT increased at the beginning of each feeding period, regardless of the group and strain. However, the CBT increase induced by the first meal decreased sharply in the Breakfast group and mildly in the Dinner group; the opposite was observed after the second meal. In UCP1 knockout, but not wild-type, mice, the total amount of CBT was significantly lower in the Dinner group than in the Breakfast group. These effects were mostly independent of the locomotor activity and food intake.

Conclusion

These results reveal that the effect of habitual feeding time on the daily rhythm of CBT is sustained at least until the following day. These effects may be mediated by both UCP1-dependent and -independent mechanisms.
Clinical independent prognostic factors and overall survival prognostic nomogram for intracranial subependymoma: A SEER population-based analysis 2004–2016
Authors: Zhang Zibin , Pang Xiaojun , Wei Yuyu , Lv Qingping , Jin Xuhong , Chen Huai
Published: August 2022

Purpose

This study was launched to ascertain the independent prognostic factors influencing the overall survival (OS) prognosis of intracranial subependymoma and construct a prognostic model to predict OS time.

Materials and methods

We collected data from patients with intracranial subependymoma, including treatment data, follow-up data, and clinical and pathological characteristics from the SEER database within 2004 to 2016, and patients were randomly classified into training and validation cohorts. Univariate and multivariate analyses were applied to the training group through building a Cox proportional hazards model. According to the results of multivariate analysis, we established a nomogram to forecast the OS rate of the per-case patient graphically, then calculated the accuracy of verification in both training and validation cohorts by concordance index (C-index). Univariate and multivariate analyses were used for different subgroups of unoperated versus operated, gross total resection (GTR), subtotal resection (STR), and biopsy after using the propensity score matching (PSM) analyses.

Results

A total of 667 patients were enrolled, and we randomly assigned 535 patients (80.21%) into the training cohort and 132 patients (19.79%) into the validation cohort. Age [hazard ratio (HR) = 6.355; 95% confidence interval (CI), 2.240–18.029; p = 0.001] and sex (HR = 0.475; 95% CI, 0.232–0.974; p = 0.042) were the independent prognostic factors in the training cohort. On the basis of age and sex, the nomogram was established to predict the OS for every patient (C-index = 0.733 ± 0.065 in the training cohort and 0.850 ± 0.065 in the validation cohort), and calibration plots reflected the reliability of the nomogram. Age, gender, or laterality was the independent prognostic factor for OS in the different matched subgroups of unoperated versus operated, GTR, STR, and biopsy. Surgical treatment, race, year of diagnosis, insurance, tumor location, tumor size, pathology, tumor grade, and radiation were not statistically significantly different in OS for subependymoma in our research.

Conclusion

Age and sex were the independent prognostic variables for OS in intracranial subependymoma. According to our research, we should not be more inclined to choose conservative or surgical treatment. Nonetheless, the information that we present might be useful to suggest potential hypotheses to be tested in the clinical research setting.
Expression, correlation, and prognostic significance of different nicotinic acetylcholine receptors, programed death ligand 1, and dopamine receptor D2 in lung adenocarcinoma
Authors: Pal Krishnendu , Hussain Tabish , Xie Hao , Li Shenduo , Yang Ping , Mansfield Aaron , Lou Yanyan , Chowdhury Shantanu , Mukhopadhyay Debabrata
Published: August 2022

Objective

The objective of this study is to evaluate the expression of different nicotinic acetylcholine receptors (nAChRs), programmed death ligand-1 (PD-L1), and dopamine receptor D2 (DRD2) as prognostic factors in lung cancer and any correlation among them. Since all of the above genes are typically upregulated in response to smoking, we hypothesized that a correlation might exist between DRD2, PD-L1, and nAChR expression in NSCLC patients with a smoking history and a prediction model may be developed to assess the clinical outcome.

Methods

We retrospectively analyzed samples from 46 patients with primary lung adenocarcinoma who underwent surgical resection at Mayo Clinic Rochester from June 2000 to October 2008. The expression of PD-L1, DRD2, CHRNA5, CHRNA7, and CHRNA9 were analyzed by quantitative PCR and correlated amongst themselves and with age, stage and grade, smoking status, overall survival (OS), and relapse-free survival (RFS).

Results

Only PD-L1 showed a statistically significant increase in expression in patients older than 65. All the above genes showed higher expression in stage IIIB than IIIA, but none reached statistical significance. Interestingly, we did not observe significant differences among never, former, and current smokers, but patients with pack years greater than 30 showed significantly higher expression of CHRNA9. We observed a strong positive correlation between PD-L1/DRD2, PD-L1/CHRNA5, and CHRNA5/CHRNA7 and a weak positive correlation between DRD2/CHRNA5 and DRD2/CHRNA7. Older age was independently associated with poor OS, whereas lower CHRNA7 expression was independently associated with better OS.

Conclusions

We observed strong positive correlations among PD-L1, DRD2, and some of the nAChRs. We investigated their prognostic significance in lung cancer patients and found CHRNA7 to be an independent prognostic factor. Overall, the results obtained from this preliminary study warrant a large cohort-based analysis that may ultimately lead to potential patient-specific stratification biomarkers predicting cancer-treatment outcomes.
Racial disparities in liver cancer: Evidence for a role of environmental contaminants and the epigenome
Authors: Vidal Adriana C. , Moylan Cynthia A. , Wilder Julius , Grant Delores J. , Murphy Susan K. , Hoyo Cathrine
Published: August 2022

Liver cancer incidence has tripled since the early 1980s, making this disease one of the fastest rising types of cancer and the third leading cause of cancer-related deaths worldwide. In the US, incidence varies by geographic location and race, with the highest incidence in the southwestern and southeastern states and among racial minorities such as Hispanic and Black individuals. Prognosis is also poorer among these populations. The observed ethnic disparities do not fully reflect differences in the prevalence of risk factors, e.g., for cirrhosis that may progress to liver cancer or from genetic predisposition. Likely substantial contributors to risk are environmental factors, including chemical and non-chemical stressors; yet, the paucity of mechanistic insights impedes prevention efforts. Here, we review the current literature and evaluate challenges to reducing liver cancer disparities. We also discuss the hypothesis that epigenetic mediators may provide biomarkers for early detection to support interventions that reduce disparities.
Importance of the endometrial immune environment in endometrial cancer and associated therapies
Authors: van der Woude Hannah , Hally Kathryn Elizabeth , Currie Margaret Jane , Gasser Olivier , Henry Claire Elizabeth
Published: August 2022

Endometrial cancer is rising in prevalence. The standard treatment modality of hysterectomy is becoming increasingly inadequate due primarily to the direct link between endometrial cancer and high BMI which increases surgical risks. This is an immunogenic cancer, with unique molecular subtypes associated with differential immune infiltration. Despite the immunogenicity of endometrial cancer, there is limited pre-clinical and clinical evidence of the function of immune cells in both the normal and cancerous endometrium. Immune checkpoint inhibitors for endometrial cancer are the most well studied type of immune therapy but these are not currently used as standard-of-care and importantly, they represent only one method of immune manipulation. There is limited evidence regarding the use of other immunotherapies as surgical adjuvants or alternatives. Levonorgestrel-loaded intra-uterine systems can also be effective for early-stage disease, but with varying success. There is currently no known reason as to what predisposes some patients to respond while others do not. As hormones can directly influence immune cell function, it is worth investigating the immune compartment in this context. This review assesses the immunological components of the endometrium and describes how the immune microenvironment changes with hormones, obesity, and in progression to malignancy. It also describes the importance of investigating novel pathways for immunotherapy.
Local ablation of pulmonary malignancies abutting pleura: Evaluation of midterm local efficacy and safety
Authors: Hu Hong-Tao , Zhao Xiao-Hui , Guo Chen-Yang , Yao Quan-Jun , Geng Xiang , Zhu Wen-Bo , Li Hong-Le , Fan Wei-Jun , Li Hai-Liang
Published: August 2022

Objective

To retrospectively evaluate the efficacy and safety of local ablation treatment for adjacent pleural lung tumors.

Materials and methods

Sixty-two patients who underwent pulmonary nodule ablation at the Affiliated Cancer Hospital of Zhengzhou University were enrolled between January 2016 and December 2020. All patients were followed up with enhanced computed tomography or magnetic resonance imaging within 48 h after treatment and 2, 4, 6, 9, and 12 months after treatment. All patients were followed for at least 12 months.

Results

A total of 84 targeted tumors (62 patients) underwent 94 ablations. In the 12-month follow-up images, 69 of the 84 targeted tumors were completely ablated, 15 had incomplete ablation, and the 12-month incomplete ablation rate was 17.8% (15/84). Of the 15 incompletely ablated tumors, six had partial responses, five had stable disease, and four had progressive disease. The most common adverse event was pneumothorax, with an incidence of 54.8% (34/62). The second most common complication was pleural effusion, with an incidence rate of 41.9% (26/62). The incidence of needle-tract bleeding was 21% (13/62) and all patients were cured using hemostatic drugs. Serious complications were bronchopleural fistula in four patients (6.5%, 4/62) and needle tract metastasis in one patient. Four cases of bronchopleural fistula were found in the early stages and were cured after symptomatic treatment.

Conclusion

Local ablation is effective for the treatment of adjacent pleural lung tumors, and its operation is safe and controllable.
Effect of infection with hepatitis B virus on the survival outcome of diffuse large B-cell lymphoma in the prophylactic antiviral era
Authors: Nuersulitan Reyizha , Li Miaomiao , Mi Lan , Wu Meng , Ji Xinqiang , Liu Yiqi , Zhao Hong , Wang Guiqiang , Song Yuqin , Zhu Jun , Liu Weiping
Published: August 2022

Patients with lymphoma who are also infected with Hepatitis B virus (HBV) have a poor prognosis. This could be partly explained by the delay or premature termination of anti-tumor treatment because of HBV reactivation. However, there is limited data on the survival outcome of patients HBV-related lymphoma in the era of prophylactic antivirals. Data for 128 patients with HBV surface antigen-positive diffuse large B-cell lymphoma was collected. The median age was 54 years and the ratio of men to women was 1.2:1. All patients received immune-chemotherapy and prophylactic antiviral therapy. The median number of cycles of immune-chemotherapy was six. The overall response rate was 82%, with a complete remission rate of 75%. With a median follow-up of 58.4 months, the 5-year progression-free survival and overall survival rates were 75.7% and 74.7%, respectively. Nine patients experienced HBV reactivation but none experienced HBV-associated hepatitis. Patients with low and high HBV DNA loads had comparable survival outcomes. In conclusion, HBV infection had no negative effect on the prognosis of DLBCL in the era of prophylactic antiviral therapy.
Cancer cachexia: Pathophysiology and association with cancer-related pain
Authors: Law Michelle L.
Published: August 2022

Cachexia is a syndrome of unintentional body weight loss and muscle wasting occurring in 30% of all cancer patients. Patients with cancers most commonly leading to brain metastases have a risk for cachexia development between 20 and 80%. Cachexia causes severe weakness and fatigue and negatively impacts quality and length of life. The negative energy balance in cachectic patients is most often caused by a combination of increased energy expenditure and decreased energy intake. Basal metabolic rate may be elevated due to tumor secreted factors and a systemic inflammatory response leading to inefficiency in energy production pathways and increased energy demand by the tumor and host tissues. A growing body of research explores physiological and molecular mechanisms of metabolic dysregulation in cachexia. However, decreased energy intake and physical functioning also remain important contributors to cachexia pathogenesis. Pain associated with metastatic malignancy is significantly associated with inflammation, thus making inflammation a common link between cancer pain and cachexia. Pain may also influence appetite and food intake and exacerbate fatigue and functional decline, potentially contributing to cachexia severity. Cancer pain and cachexia often occur simultaneously; however, causal relationships remain to be established. Appropriate assessment and treatment of pain in advanced cancer patients may positively impact nutrition status and physical functioning, slowing the progression of cachexia and improving quality and length of life for patients.
Designing and validating the Dubai Tool for Developmental Screening (DTDS)
Authors: Alolama Fatma Mohammad , Mohammad Haitham Mahmoud , Alhmid Idris Helal , Alhammadi Hanan Mohammed
Published: August 2022

Background

Early detection of developmental problems is vital for facilitating early access to targeted intervention and augmenting its beneficial outcomes. Standardized developmental screening tools are known to enhance detection rates of developmental problems compared to clinical judgment alone and are widely recommended to be used in infants and young children. Most of the available developmental screening tools have been developed in Western countries. Many of their items may not be suitable for other cultures while others are expensive. Currently, none of the developmental screening tools have been validated in the United Arab Emirates (UAE), with only a few available in the Arabic language.

Objective

To create and validate a developmental screening tool, in both English and Arabic, that is simple, quick to use, and culturally relevant to the United Arab Emirates (UAE) child population aged 9–48 months.

Methods

The available literature was used to create a list of developmental milestones in five domains for children aged 9–48 months, divided into seven age groups. The selected milestones were used to create questionnaires in both English and Arabic, which were pilot tested twice. Each time, the results were analyzed and used to select, modify, and rephrase questions. Validation of the Dubai Tool for Developmental Screening (DTDS) was done against Parents' Evaluation of Developmental Status (PEDS) as a gold standard instrument. The DTDS and PEDS were administered cross-sectionally to parents of 1,400 children in seven age groups. Sensitivity, specificity, and kappa agreement of the DTDS compared with PEDS were calculated.

Results

The DTDS had a sensitivity of 100% in four age groups and 75–78% in the other three age groups. Specificity ranged from 96 to 99% across all age groups. The kappa measure showed substantial agreement in five age groups, a moderate agreement in one age group, and a fair agreement in one age group.

Conclusions

The DTDS is a valid screening tool for early identification of developmental delays and disabilities in early childhood.
Case report: A Chinese boy with facial dysmorphism, immunodeficiency, livedo, and short stature syndrome
Authors: Jiang Lihong , Chen Xin , Zheng Jiaqi , Wang Meilin , Bo Hui , Liu Geli
Published: August 2022

Facial dysmorphism, immunodeficiency, livedo, and short stature (FILS) syndrome is a rare autosomal recessive disease. In this study we reported the first Chinese patient with FILS syndrome. The patient had short stature and suffered from recurrent respiratory infections up to the age of 4 years. Other symptoms of the disease included livedo on the inner side of upper limbs and thigh skin, prominent forehead, low anterior and posterior hairline, short and down-slanting palpebral fissure, low-set ears, long nasal tip and columella, and a small mouth with irregular teeth. A whole exome sequencing (WES) was performed and revealed two variants within the polymerase ε (POLE) gene. One of the variants was a splicing variant (c.5811 + 2T > C) derived from the mother, while the other was a nonsense variant (c.2006G > A) derived from the father. These two variants were not reported in previous FILS syndrome cases. Therefore this case provides further insight into the POLE gene variant spectrum that enriches the clinical phenotype.