bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-4521 perturbs FOXM1-mediated DNA damage response in breast cancer
Authors: Kuthethur Raviprasad , Adiga Divya , Kandettu Amoolya , Jerome Maria Sona , Mallya Sandeep , Mumbrekar Kamalesh Dattaram , Kabekkodu Shama Prasada , Chakrabarty Sanjiban 
Published: March 2023

Introduction: Forkhead (FOX) transcription factors are involved in cell cycle control, cellular differentiation, maintenance of tissues, and aging. Mutation or aberrant expression of FOX proteins is associated with developmental disorders and cancers. FOXM1, an oncogenic transcription factor, is a promoter of cell proliferation and accelerated development of breast adenocarcinomas, squamous carcinoma of the head, neck, and cervix, and nasopharyngeal carcinoma. High FOXM1 expression is correlated with chemoresistance in patients treated with doxorubicin and Epirubicin by enhancing the DNA repair in breast cancer cells.Method: miRNA-seq identified downregulation of miR-4521 in breast cancer cell lines. Stable miR-4521 overexpressing breast cancer cell lines (MCF-7, MDA-MB-468) were developed to identify miR-4521 target gene and function in breast cancer.Results: Here, we showed that FOXM1 is a direct target of miR-4521 in breast cancer. Overexpression of miR-4521 significantly downregulated FOXM1 expression in breast cancer cells. FOXM1 regulates cell cycle progression and DNA damage response in breast cancer. We showed that miR-4521 expression leads to increased ROS levels and DNA damage in breast cancer cells. FOXM1 plays a critical role in ROS scavenging and promotes stemness which contributes to drug resistance in breast cancer. We observed that breast cancer cells stably expressing miR-4521 lead to cell cycle arrest, impaired FOXM1 mediated DNA damage response leading to increased cell death in breast cancer cells. Additionally, miR-4521-mediated FOXM1 downregulation perturbs cell proliferation, invasion, cell cycle progression, and epithelial-to-mesenchymal progression (EMT) in breast cancer.Discussion: High FOXM1 expression has been associated with radio and chemoresistance contributing to poor patient survival in multiple cancers, including breast cancer. Our study showed that FOXM1 mediated DNA damage response could be targeted using miR-4521 mimics as a novel therapeutic for breast cancer.
Early detection of cognitive decline in Alzheimer’s disease using eye tracking
Authors: Tokushige Shin-ichi , Matsumoto Hideyuki , Matsuda Shun-ichi , Inomata-Terada Satomi , Kotsuki Naoki , Hamada Masashi , Tsuji Shoji , Ugawa Yoshikazu , Terao Yasuo 
Published: March 2023

BackgroundPatients with Alzheimer’s disease (AD) are known to exhibit visuospatial processing impairment, as reflected in eye movements from the early stages of the disease. We investigated whether the pattern of gaze exploration during visual tasks could be useful for detecting cognitive decline at the earliest stage.MethodsSixteen AD patients (age: 79.1 ± 7.9 years, Mini Mental State Examination [MMSE] score: 17.7 ± 5.3, mean ± standard deviation) and 16 control subjects (age: 79.4 ± 4.6, MMSE score: 26.9 ± 2.4) participated. In the visual memory task, subjects memorized presented line drawings for later recall. In the visual search tasks, they searched for a target Landolt ring of specific orientation (serial search task) or color (pop-out task) embedded among arrays of distractors. Using video-oculography, saccade parameters, patterns of gaze exploration, and pupil size change during task performance were recorded and compared between AD and control subjects.ResultsIn the visual memory task, the number of informative regions of interest (ROIs) fixated was significantly reduced in AD patients compared to control subjects. In the visual search task, AD patients took a significantly longer time and more saccades to detect the target in the serial but not in pop-out search. In both tasks, there was no significant difference in the saccade frequency and amplitude between groups. On-task pupil modulation during the serial search task was decreased in AD. The number of ROIs fixated in the visual memory task and search time and saccade numbers in the serial search task differentiated both groups of subjects with high sensitivity, whereas saccade parameters of pupil size modulation were effective in confirming normal cognition from cognitive decline with high specificity.DiscussionReduced fixation on informative ROIs reflected impaired attentional allocation. Increased search time and saccade numbers in the visual search task indicated inefficient visual processing. Decreased on-task pupil size during visual search suggested decreased pupil modulation with cognitive load in AD patients, reflecting impaired function of the locus coeruleus. When patients perform the combination of these tasks to visualize multiple aspects of visuospatial processing, cognitive decline can be detected at an early stage with high sensitivity and specificity and its progression be evaluated.
Epidemiological features of traumatic spinal cord injury in China: A systematic review and meta-analysis
Authors: Hu Youpeng , Li Lianxin , Hong Binxue , Xie Yizhou , Li Tong , Feng Chaoqun , Yang Fei , Wang Yehui , Zhang Jie , Yu Yang , Fan Xiaohong 
Published: March 2023

BackgroundTraumatic spinal cord injury (TSCI) is a highly fatal and disabling event, and its incidence rate is increasing in China. Therefore, we collated the epidemiological factors of TSCI in different regions of China to update the earlier systematic review published in 2018.MethodWe searched four English and three Chinese electronic databases from 1978 to October 1, 2022. From the included reports, information on sample characteristics, incidence, injury characteristics, prognostic factors, and economic burden was extracted. The selection of data was based on the PRISMA statement. The quality of the included studies was assessed by the Agency for Healthcare Research and Quality (AHRQ) tool. The results of the meta-analysis were presented in the form of pooled frequency and forest plots.ResultsA total of 59 reports (60 studies) from 23 provinces were included, of which 41 were in the Chinese language. The random pooled incidence of TSCI in China was estimated to be 65.15 per million (95% CI: 47.20–83.10 per million), with a range of 6.7 to 569.7 per million. The pooled male-to-female ratio was 1.95:1. The pooled mean age of the cases at the time of injury was 45.4 years. Motor vehicle accidents (MVAs) and high falls were found to be the leading causes of TSCI. Incomplete quadriplegia and AISA/Frankel grade D were the most common types of TSCI. Cervical level injury was the most prevalent. The pooled in-hospital mortality and complication rates for TSCI in China were 3% (95% CI: 2–4%) and 35% (95% CI: 23–47%). Respiratory problems were the most common complication and the leading cause of death.ConclusionCompared with previous studies, the epidemiological data on TSCI in China has changed significantly. A need to update the data over time is essential to implement appropriate preventive measures and formulate interventions according to the characteristics of the Chinese population.
Case report: Two clusters of Creutzfeldt–Jakob disease cases within 1 year in West Michigan
Authors: Rong Ling Ling , Lannen Nicholas J. , Tank Evan C. , Feistel Jessica L. , Therasse Christopher J. , Potluri Anvita , Khan Muhib , Min Jiangyong 
Published: March 2023

BackgroundCreutzfeldt–Jakob disease (CJD) is a rare, rapidly progressive, and uniformly fatal neurodegenerative disease. The reported incidence of CJD is 1 to 2 per million people worldwide annually, with fewer than 1,000 cases in the United States per year. In this study, we report a unique case series on temporo-spatial clusters of CJD cases in West Michigan.MethodsA total of five CJD cases consisting of two temporal clusters were seen from July 2021 to June 2022 at Corewell Health West hospitals. All patients had brain MRI, EEG, and CSF tests. Four patients underwent autopsies.ResultsAll patients' MRIs showed characteristic CJD patterns. Four patients had positive CJD panels in CSF. One patient had typical CJD EEG findings. Four patients were confirmed as sporadic CJD by autopsy. All patients died within 3 months after CJD was suspected.DiscussionAll patients lived within a 90-mile radius of Grand Rapids, MI, and two lived in the same county. West Michigan has a population of 1.6 million people, and the four counties where five patients lived have a combined population of 395,104, indicating CJD's new case rate of 3.1 and 12.5 per million people, respectively. Corewell Health is one of the three major healthcare systems in West Michigan. The actual incidence of CJD in West Michigan is likely even higher. This dense temporal and spatial cluster of CJD cases poses a serious public health challenge and warrants urgent investigation.
Relationships between respiratory and oromotor events differ between motor phenotypes in patients with obstructive sleep apnea
Authors: Okura Mutsumi , Kato Takafumi , Mashita Midori , Muraki Hisae , Sugita Hideko , Ohi Motoharu , Taniguchi Mitsutaka 
Published: March 2023

PurposeThe present study investigated the relationship between sleep bruxism (SB) and obstructive sleep apnea (OSA) in relation to the sleep architecture.MethodsWe conducted a cross-sectional study. Polysomnographic recordings were performed on 36 patients. Sleep, respiratory, and oromotor variables, such as rhythmic masticatory muscle activity (RMMA) and non-specific masticatory muscle activity (NSMA), were compared between OSA patients with or without SB. A correlation analysis of the frequency of respiratory and oromotor events in NREM and REM sleep was performed. The frequency of oromotor events following respiratory events was also assessed.ResultsThe proportion of REM sleep was higher in OSA patients with SB than in those without SB (p = 0.02). The apnea-hypopnea index (AHI) did not significantly differ between the two groups; however, AHI was approximately 8-fold lower during REM sleep in OSA patients with SB (p = 0.01) and the arousal threshold was also lower (p = 0.04). Although the RMMA index was higher in OSA patients with than in those without SB (p &lt; 0.01), the NSMA index did not significantly differ. The percentage of RMMA following respiratory events was significantly higher in OSA patients with than in those without SB, whereas that of NSMA did not significantly differ. The frequency of oromotor events throughout the whole night positively correlated with AHI. However, regardless of the sleep state, AHI did not correlate with the RMMA index, but positively correlated with the NSMA index.ConclusionIn consideration of the limitations of the present study, the results obtained indicate that OSA patients with SB have a unique phenotype of OSA and also emphasize the distinct relationship of respiratory events with RMMA and NSMA.
A new biomarker combining multimodal MRI radiomics and clinical indicators for differentiating inverted papilloma from nasal polyp invaded the olfactory nerve possibly
Authors: Du Lianze , Yuan Qinghai , Han Qinghe 
Published: March 2023

Background and purposeInverted papilloma (IP) and nasal polyp (NP), as two benign lesions, are difficult to distinguish on MRI imaging and clinically, especially in predicting whether the olfactory nerve is damaged, which is an important aspect of treatment and prognosis. We plan to establish a new biomarker to distinguish IP and NP that may invade the olfactory nerve, and to analyze its diagnostic efficacy.Materials and methodsA total of 74 cases of IP and 55 cases of NP were collected. A total of 80% of 129 patients were used as the training set (59 IP and 44 NP); the remaining were used as the testing set. As a multimodal study (two MRI sequences and clinical indicators), preoperative MR images including T2-weighted magnetic resonance imaging (T2-WI) and contrast-enhanced T1-weighted magnetic resonance imaging (CE-T1WI) were collected. Radiomic features were extracted from MR images. Then, the least absolute shrinkage and selection operator (LASSO) regression method was used to decrease the high degree of redundancy and irrelevance. Subsequently, the radiomics model is constructed by the rad scoring formula. The area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the model have been calculated. Finally, the decision curve analysis (DCA) is used to evaluate the clinical practicability of the model.ResultsThere were significant differences in age, nasal bleeding, and hyposmia between the two lesions (p &lt; 0.05). In total, 1,906 radiomic features were extracted from T2-WI and CE-T1WI images. After feature selection, using 12 key features to bulid model. AUC, sensitivity, specificity, and accuracy on the testing cohort of the optimal model were, respectively, 0.9121, 0.828, 0.9091, and 0.899. AUC on the testing cohort of the optimal model was 0.9121; in addition, sensitivity, specificity, and accuracy were, respectively, 0.828, 0.9091, and 0.899.ConclusionA new biomarker combining multimodal MRI radiomics and clinical indicators can effectively distinguish between IP and NP that may invade the olfactory nerve, which can provide a valuable decision basis for individualized treatment.
Morphological feature and mapping inflammation in classified carotid plaques in symptomatic and asymptomatic patients: A hybrid 18F-FDG PET/MR study
Authors: Zhang Yue , Cui Bixiao , Yang Hongwei , Ma Jie , Yang Yu , Yang Bin , Ma Yan , Jiao Liqun , Li Xiang , Lu Jie 
Published: March 2023

PurposeTo investigate morphological and inflamed-metabolism features of carotid atherosclerotic plaques between symptomatic and asymptomatic patients with hybrid 18F-FDG PET/MR imaging.MethodsA total of 20 symptomatic and 20 asymptomatic patients with carotid plaques underwent hybrid 18F-FDG PET/MR scans. American heart association (AHA) lesion types were classified, and plaque compositions were further determined on consecutive MRI axial sections in both carotid arteries. 18F-FDG uptake in carotid arteries was quantified using region of interest (ROI) methods based on maximum standardized uptake values (SUVmax) and target-to-background ratio (TBR) on corresponding positron emission tomography (PET) images.ResultsA total of seventy-one carotid plaques were quantified. AHA type VI was the most common (23, 32.4%), and the region of carotid bifurcation was the most common place presenting lesions (32, 45.1%). Compared with the asymptomatic group, the prevalence of high-risk features including plaque burden, lumen stenosis, maximum necrotic core area, and maximum intra-plaque hemorrhage area increased in the symptomatic group. Carotid TBR values of plaque in symptomatic group (TBR = 2.56 ± 0.34) was significantly higher than that in asymptomatic group (TBR = 1.57 ± 0.14) (P &lt; 0.05). hs-CRP is an independent risk factor for the stability of carotid plaque. The correlation between normalized wall index (NWI) and TBR values was significantly positive in both the symptomatic and the asymptomatic groups (P &lt; 0.01), and both NWI and TBR were significantly correlated with the level of hs-CRP (P &lt; 0.01).ConclusionIntegrated 18F-FDG PET/MR scans presented distinct risk features between symptomatic and asymptomatic patients. Hybrid 18F-FDG PET/MR systems combined with clinical serum hs-CRP may help distinguish vulnerable carotid plaques.
Cerebral blood flow characteristics of drug-naïve attention-deficit/hyperactivity disorder with social impairment: Evidence for region–symptom specificity
Authors: Zhang Kangfuxi , Yuan Jing , Pei Xuyao , Fu Zhao , Zhao Yilu , Hu Na , Wang Yufeng , Yang Li , Cao Qingjiu 
Published: March 2023

BackgroundSocial deficits are among the most important functional impairments in attention-deficit/hyperactivity disorder (ADHD). However, the relationship between social impairment and ADHD core symptoms as well as the underlying cerebral blood flow (CBF) characteristics remain unclear.MethodsA total of 62 ADHD subjects with social deficits (ADHD + SD), 100 ADHD subjects without social deficits (ADHD-SD) and 81 age-matched typically developing controls (TDC) were enrolled. We first examined the correlation between the Social Responsiveness Scale (SRS-1) and ADHD core symptoms (inattention, hyperactivity, and impulsion) and then explored categorical and dimensional ADHD-related regional CBF by arterial spin labeling (ASL). For the categorical analysis, a voxel-based comparison of CBF maps between the ADHD + SD, ADHD-SD, and TDC groups was performed. For the dimensional analysis, the whole-brain voxel-wise correlation between CBF and ADHD symptoms (inattention, hyperactivity/impulsivity, and total scores) was evaluated in three groups. Finally, correlations between the SRS-1 and ADHD-related regional CBF were investigated. We applied Gaussian random field (GRF) for the correction of multiple comparisons in imaging results (voxel-level P &lt; 0.01, and cluster-level P &lt; 0.05).ResultsThe clinical characteristics analysis showed that social deficits positively correlated with ADHD core symptoms, especially in social communication and autistic mannerisms domains. In the categorical analysis, we found that CBF in the left middle/inferior temporal gyrus in ADHD groups was higher than TDCs and was negatively correlated with the social motivation scores. Moreover, in dimensional analysis, we found that CBF in the left middle frontal gyrus was negatively correlated with the inattention scores, SRS total scores and autistic mannerisms scores in ADHD + SD subjects.ConclusionThe present study shows that inattention, hyperactivity, and impulsivity may be responsible for the occurrence of social deficits in ADHD, with autistic traits being another significant contributing factor. Additionally, CBF in the left middle/inferior temporal gyrus and the left middle frontal gyrus might represent the corresponding physiological mechanisms underlying social deficits in ADHD.
Development and validation of a short nutrition literacy scale for young adults
Authors: Vrinten Jules , Van Royen Kathleen , Pabian Sara , De Backer Charlotte , Matthys Christophe 
Published: March 2023

BackgroundDue to their high media use, young adults are frequently exposed to contradictory or even erroneous nutrition information. To properly handle and critically assess nutrition information, young adults (both general population and patient populations) need adequate levels of nutrition literacy. Currently there is a lack of suitable instruments to measure nutrition literacy in young adults (18–25 years). Therefore the aim of this study was to develop and validate a Short Nutrition Literacy (S-NutLit) scale for use in this age group.MethodsDevelopment and validation of the S-NutLit consisted of six phases: (1) item generation based on literature, (2) expert assessments to evaluate content validity, (3) cognitive interviews with the target population to assess face validity and readability, (4) pre-test to reduce the number of items, (5) validation survey to assess dimensionality with exploratory factor analyses, internal reliability with Cronbach alpha, construct and criterion validity by examining associations with age, gender, education level, health literacy, general literacy, dietary behaviors and physical activity with correlations, ANOVAs, and t-tests, (6) two-week follow-up survey to assess test–retest reliability with intra-class correlations.ResultsStarting from an initial pool of 53 items, expert assessments and cognitive interviews led to the reformulation, removal, and construction of items. Young adults aged 18–25 years participated in cognitive interviews (n = 12), pre-test (n = 101), validation survey (n = 300), and reliability survey (n = 92). The final S-NutLit consisted of 11 items rated on a 5-point scale distributed across two subscales (i.e., information skills and expert skills). Cronbach alpha values ranged from 0.79 to 0.83 and intraclass correlations from 0.61–0.79 (p &lt; 0.001). Significant associations were observed with health literacy (r = 0.27, p &lt; 0.001), general literacy and numeracy (rs = 0.12, p = 0.046), and education level (rs = 0.13, p = 0.025).ConclusionFindings indicate that the S-NutLit is a valid and reliable tool to assess nutrition literacy among young adults. The S-NutLit fills a gap in the field by offering a short measure of nutrition literacy and may be incorporated in digital technology to support the nutrition care process.
Docosahexaenoic acid supplementation in gestational diabetes mellitus and neonatal metabolic health biomarkers
Authors: Xu Ya-Jie , Wang Wen-Juan , Zhang Qiu-Yi , Yang Meng-Nan , Zhang Lin , He Hua , Dong Yu , Ouyang Fengxiu , Gao Ying , Zhang Jun , Zheng Tao , Luo Zhong-Cheng 
Published: March 2023

Background and objectiveGestational diabetes mellitus (GDM) “programs” an elevated risk of metabolic dysfunctional disorders in the offspring, and has been associated with elevated leptin and decreased adiponectin levels in cord blood. We sought to assess whether docosahexaenoic acid (DHA) supplementation in GDM affects neonatal metabolic health biomarkers especially leptin and adiponectin.MethodsIn a randomized controlled trial, singleton pregnant women with de novo diagnosis of GDM at 24–28  weeks of gestation were randomized to dietary supplementation of 500 mg DHA per day (intervention, n = 30) until delivery or standard care (control, n = 38). The primary outcomes were cord blood leptin and total adiponectin concentrations. Secondary outcomes included high-molecular-weight (HMW) adiponectin and insulin-like growth factor-1 (IGF-1) concentrations in cord blood, maternal glycemic control post-intervention and birth weight (z score). In parallel, 38 euglycemic pregnant women were recruited for comparisons of cord blood biomarkers.ResultsThere were no significant differences in cord serum leptin, total and HMW adiponectin and IGF-1 concentrations between DHA supplementation and control groups (all p &gt; 0.05). Maternal fasting and 2-h postprandial blood glucose levels at 12–16 weeks post-intervention were similar between the two groups. The newborns in the DHA group had higher birth weight z scores (p = 0.02). Cord blood total and HMW adiponectin concentrations were significantly lower in GDM vs. euglycemic pregnancies.ConclusionDocosahexaenoic acid supplementation at 500  mg/day in GDM women did not affect neonatal metabolic biomarkers including leptin, adiponectin and IGF-1. The results are reassuring in light of the absence of influence on neonatal adipokines (leptin and adiponectin), and potential benefits to fetal growth and development.Clinical Trial Registration: Clinicaltrials.gov, NCT03569501.