bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell-type specific transcriptomic signatures of neocortical circuit organization and their relevance to autism
Authors: Moussa Anthony J. , Wester Jason C.
Published: September 2022

A prevailing challenge in neuroscience is understanding how diverse neuronal cell types select their synaptic partners to form circuits. In the neocortex, major classes of excitatory projection neurons and inhibitory interneurons are conserved across functionally distinct regions. There is evidence these classes form canonical circuit motifs that depend primarily on their identity; however, regional cues likely also influence their choice of synaptic partners. We mined the Allen Institute’s single-cell RNA-sequencing database of mouse cortical neurons to study the expression of genes necessary for synaptic connectivity and physiology in two regions: the anterior lateral motor cortex (ALM) and the primary visual cortex (VISp). We used the Allen’s metadata to parse cells by clusters representing major excitatory and inhibitory classes that are common to both ALM and VISp. We then performed two types of pairwise differential gene expression analysis: (1) between different neuronal classes within the same brain region (ALM or VISp), and (2) between the same neuronal class in ALM and VISp. We filtered our results for differentially expressed genes related to circuit connectivity and developed a novel bioinformatic approach to determine the sets uniquely enriched in each neuronal class in ALM, VISp, or both. This analysis provides an organized set of genes that may regulate synaptic connectivity and physiology in a cell-type-specific manner. Furthermore, it identifies candidate mechanisms for circuit organization that are conserved across functionally distinct cortical regions or that are region dependent. Finally, we used the SFARI Human Gene Module to identify genes from this analysis that are related to risk for autism spectrum disorder (ASD). Our analysis provides clear molecular targets for future studies to understand neocortical circuit organization and abnormalities that underlie autistic phenotypes.
Intervals of endovascular treatment for coincidental non-adjacent unruptured aneurysms in patients with symptomatic intracranial atherosclerotic stenosis
Authors: Jin Hengwei , Wang Jing , Meng Xiangyu , Li Youxiang , He Hongwei
Published: September 2022

Background and purpose

To explore the safety of endovascular therapy for concomitant non-adjacent unruptured intracranial aneurysms (UIAs) which is incidentally found in severe patients with symptomatic intracranial atherosclerotic stenosis at the same session and different sessions.

Methods

Patients between January 2019 to December 2020 were retrospectively reviewed at our institution. Patients with concomitant non-adjacent incidental UIA in severe symptomatic intracranial atherosclerotic stenosis, who underwent endovascular treatment for both lesions were included. They were divided into two groups according to the intervals (The aneurysm was treated at the same session as stenosis or at separated sessions). The demographics, procedure details, complications, and clinical outcomes were compared between groups.

Results

A total of 22 patients were involved. In total, ten patients underwent endovascular treatment for UIA and stenosis at one session and 12 patients at separate sessions. In total, three (13.6%) patients experienced procedural related complications, including 2 (20%) in the one session group and 1(8.3%) in the separate sessions group. Follow-up (Range 6–12, mean = 8.5 months) results showed good clinical outcome in all the patients. There is no statistical significance in terms of complication rate and unfavorable clinical outcome between groups.

Conclusions

Non-adjacent concomitant UIA and severe symptomatic intracranial atherosclerotic stenosis will not pose additional endovascular treatment risks. Both simultaneous endovascular management and short intervals between separated procedures are technically feasible and safe.
Recurrence of chronic subdural hematoma due to low-grade infection
Authors: Dubinski Daniel , Won Sae-Yeon , Trnovec Svorad , Gounko Kseniya , Baumgarten Peter , Warnke Philipp , Cantré Daniel , Behmanesh Bedjan , Bernstock Joshua D. , Freiman Thomas M. , Gessler Florian , Sola Steffen
Published: September 2022

Despite the high incidence and multitudes of operative techniques, the risk factors for chronic subdural hematoma (CSDH) recurrence are still under debate and a universal consensus on the pathophysiology is lacking. We hypothesized that clinically inapparent, a low-grade infection could be responsible for CSDH recurrence. This investigation is a single-center prospective observational study including patients with recurrent CSDH. In total, 44 patients with CSDH recurrence received an intraoperative swab-based microbiological test. The intraoperative swab revealed an inapparent low-grade hematoma infection in 29% of the recurrent CSDH cases. The majority (69%) of the identified germs belonged to the staphylococcus genus. We therefore, propose a novel potential pathophysiology for CSDH recurrence.
Topologically Disrupted Gray Matter Networks in Drug-Naïve Essential Tremor Patients With Poor Sleep Quality
Authors: Peng Jiaxin , Yang Jing , Li Nannan , Lei Du , Li Junying , Duan Liren , Chen Chaolan , Zeng Yan , Xi Jing , Jiang Yi , Gong Qiyong , Peng Rong
Published: September 2022

Background

Sleep disturbances are widespread among patients with essential tremor (ET) and may have adverse effects on patients' quality of life. However, the pathophysiology underlying poor quality of sleep (QoS) in patients with ET remains unclear. Our study aimed to identify gray matter (GM) network alterations in the topological properties of structural MRI related to QoS in patients with ET.

Method

We enrolled 45 ET patients with poor QoS (SleET), 59 ET patients with normal QoS (NorET), and 66 healthy controls (HC), and they all underwent a three-dimensional T1-weighted MRI scan. We used a graph-theoretical approach to investigate the topological organization of GM morphological networks, and individual morphological brain networks were constructed according to the interregional similarity of GM volume distributions. Furthermore, we performed network-based statistics, and partial correlation analyses between topographic features and clinical characteristics were conducted.

Results

Global network organization was disrupted in patients with ET. Compared with the NorET group, the SleET group exhibited disrupted topological GM network organization with a shift toward randomization. Moreover, they showed altered nodal centralities in mainly the frontal, temporal, parietal, and cerebellar lobes. Morphological connection alterations within the default mode network (DMN), salience, and basal ganglia networks were observed in the SleET group and were generally more extensive than those in the NorET and HC groups. Alterations within the cerebello-thalamo-(cortical) network were only detected in the SleET group. The nodal degree of the left thalamus was negatively correlated with the Fahn-Tolosa-Marin Tremor Rating Scale score (r = −0.354, p =0.027).

Conclusion

Our findings suggest that potential complex interactions underlie tremor and sleep disruptions in patients with ET. Disruptions within the DMN and the cerebello-thalamo-(cortical) network may have a broader impact on sleep quality in patients with ET. Our results offer valuable insight into the neural mechanisms underlying poor QoS in patients with ET.
Contribution of intracranial artery stenosis to white matter hyperintensities progression in elderly Chinese patients: A 3-year retrospective longitudinal study
Authors: Zhong Tingting , Qi Yunwen , Li Rui , Zhou Huadong , Ran Boli , Wang Jiao , Cai ZhiYou
Published: September 2022

Background and purpose

There have been controversial results in previous studies for the association between intracranial artery stenosis (ICAS) and white matter hyperintensities (WMHs), and the correlation of ICAS with the progression of WMHs is uncertain. The aim of this study was to investigate the association between ICAS and the progression of WMHs.

Methods

In this retrospective longitudinal study, we enrolled 302 patients aged 60 years and older who had received two brain MRI scans with a 3-year interval and was examined by CTA in the first MRI scan. We measured the stenosis of major intracranial arteries by CTA and assessed the progression of WMHs using the modified Rotterdam Progression scale (mRPS). We performed binary logistic regression analyses and established linear regression model to determine the relationship between the degree of ICAS and the progression of WMHs.

Results

A total of 302 patients were enrolled, of which 48.3% experienced WMHs progression. After adjustment for confounding factors, the patients with Grade 2 ICAS had an OR of 2.8 (95% CI 1.4–5.5), and those with Grade 3 ICAS had an OR of 3.0 (95% CI 1.2–7.3) for the progression of WMHs. The ICAS degree remained associated with PVWMHs but had an attenuated relation to SCWMHs. ICAS severity was significantly associated with WMHs progression scores, higher for Grade 3 ICAS [β (SE) = 0.18 (0.18)] followed by Grade 2 ICAS [β (SE) = 0.10 (0.15)] compared with Grade 1 ICAS.

Conclusions

Patients with more severe ICAS are more likely to have WMHs progression and have distinct relevancy to PVWMHs and SCWMHs, which may provide clues for understanding mechanisms of WMHs progression.
Intracranial tumors mimicking benign paroxysmal positional vertigo: A case series
Authors: Chen Yuan Xing , Sun Han Jun , Mu Xue Tao , Jiang Chao , Wang Hui Bing , Zhang Qing Hua , Qu Yuan Yi , Li Jian , Zhou Ling Ling , Zhao Long Zhu , Yu Ning , Sun Qing
Published: September 2022

Background

A few intracranial lesions may present only with positional vertigo which are very easy to misdiagnose as benign paroxysmal positional vertigo (BPPV); the clinicians should pay more attention to this disease.

Objectives

To analyze the clinical characteristics of 6 patients with intracranial tumors who only presented with positional vertigo to avoid misdiagnosing the disease.

Material and methods

Six patients with intracranial tumors who only presented with positional vertigo treated in our clinic between May 2015 to May 2019 were reviewed, and the clinical symptoms, features of nystagmus, imaging presentation, and final diagnosis of the patients were evaluated.

Results

All patients presented with positional vertigo and positional nystagmus induced by the changes in head position or posture, including one case with downbeating nystagmus in a positional test, two cases with left-beating nystagmus, one case with apogeotropic nystagmus in a roll test, one case with right-beating nystagmus, and one case with left-beating and upbeating nystagmus. Brain MRI showed the regions of the tumors were in the vermis of the cerebellum, the fourth ventricle, the lateral ventricle, and the cerebellar hemisphere.
Case report: Thirty-year progression of an EMPF1 encephalopathy due to defective mitochondrial and peroxisomal fission caused by a novel de novo heterozygous DNM1L variant
Authors: Lhuissier Charlène , Wagner Bart E. , Vincent Amy , Garraux Gaëtan , Hougrand Olivier , Van Coster Rudy , Benoit Valerie , Karadurmus Deniz , Lenaers Guy , Gueguen Naïg , Chevrollier Arnaud , Maystadt Isabelle
Published: September 2022

Mutations in DNM1L (DRP1), which encode a key player of mitochondrial and peroxisomal fission, have been reported in patients with the variable phenotypic spectrum, ranging from non-syndromic optic atrophy to lethal infantile encephalopathy. Here, we report a case of an adult female patient presenting with a complex neurological phenotype that associates axonal sensory neuropathy, spasticity, optic atrophy, dysarthria, dysphasia, dystonia, and ataxia, worsening with aging. Whole-exome sequencing revealed a heterozygous de novo variant in the GTPase domain of DNM1L [NM_001278464.1: c.176C>A p.(Thr59Asn)] making her the oldest patient suffering from encephalopathy due to defective mitochondrial and peroxisomal fission-1. In silico analysis suggested a protein destabilization effect of the variant Thr59Asn. Unexpectedly, Western blotting disclosed profound decrease of DNM1L expression, probably related to the degradation of DNM1L complexes. A detailed description of mitochondrial and peroxisomal anomalies in transmission electron and 3D fluorescence microscopy studies confirmed the exceptional phenotype of this patient.
Revisiting the relation between syntax, action, and left BA44
Authors: Kemmerer David
Published: September 2022

Among the many lines of research that have been exploring how embodiment contributes to cognition, one focuses on how the neural substrates of language may be shared, or at least closely coupled, with those of action. This paper revisits a particular proposal that has received considerable attention—namely, that the forms of hierarchical sequencing that characterize both linguistic syntax and goal-directed action are underpinned partly by common mechanisms in left Brodmann area (BA) 44, a cortical region that is not only classically regarded as part of Broca’s area, but is also a core component of the human Mirror Neuron System. First, a recent multi-participant, multi-round debate about this proposal is summarized together with some other relevant findings. This review reveals that while the proposal is supported by a variety of theoretical arguments and empirical results, it still faces several challenges. Next, a narrower application of the proposal is discussed, specifically involving the basic word order of subject (S), object (O), and verb (V) in simple transitive clauses. Most languages are either SOV or SVO, and, building on prior work, it is argued that these strong syntactic tendencies derive from how left BA44 represents the sequential-hierarchical structure of goal-directed actions. Finally, with the aim of clarifying what it might mean for syntax and action to have “common” neural mechanisms in left BA44, two different versions of the main proposal are distinguished. Hypothesis 1 states that the very same neural mechanisms in left BA44 subserve some aspects of hierarchical sequencing for syntax and action, whereas Hypothesis 2 states that anatomically distinct but functionally parallel neural mechanisms in left BA44 subserve some aspects of hierarchical sequencing for syntax and action. Although these two hypotheses make different predictions, at this point neither one has significantly more explanatory power than the other, and further research is needed to elaborate and test them.
External walking environment differentially affects muscle synergies in children with cerebral palsy and typical development
Authors: Kim Yushin , Bulea Thomas C. , Damiano Diane L.
Published: September 2022

Despite external environmental changes in walking, such as manipulating gait speed, previous studies have shown that the underlying muscle synergy structures (synergy weights or vectors) rarely vary. The purpose of this study is to examine if external environmental changes to the walking task influence muscle synergies in children with cerebral palsy (CP) and/or typical development (TD). To identify muscle synergies, we extracted muscle synergies from eight children with CP and eight age-matched TD in three treadmill walking conditions, e.g., baseline (adjusted to individual comfortable walking speed), variable speed (VS), or restricted foot width (RW). Then, we grouped similar muscle synergies using k-mean clustering and discriminant analyses from all datasets of individual synergy structures. Proportion tests exhibited six clusters of muscle synergies predominantly arising from children with CP and four clusters from children with TD. Also, the proportion of muscle synergies was significantly different in four of the CP-preferred clusters across conditions. Specifically, the proportion of the baseline condition was significantly different from VS and RW conditions in one and two clusters, respectively. The proportion was significantly different between VS and RW conditions in four clusters. Cadence and step lengths differed across conditions but not groups which makes the group differences in proportion even more notable. In contrast, step width, while significantly lower in CP, did not differ across conditions. Our findings demonstrate that muscle synergies in children with CP are more sensitive to changes in the external walking environment than in typically developing children.
A domain adaptation benchmark for T1-weighted brain magnetic resonance image segmentation
Authors: Saat Parisa , Nogovitsyn Nikita , Hassan Muhammad Yusuf , Ganaie Muhammad Athar , Souza Roberto , Hemmati Hadi
Published: September 2022

Accurate brain segmentation is critical for magnetic resonance imaging (MRI) analysis pipelines. Machine-learning-based brain MR image segmentation methods are among the state-of-the-art techniques for this task. Nevertheless, the segmentations produced by machine learning models often degrade in the presence of expected domain shifts between the test and train sets data distributions. These domain shifts are expected due to several factors, such as scanner hardware and software differences, technology updates, and differences in MRI acquisition parameters. Domain adaptation (DA) methods can make machine learning models more resilient to these domain shifts. This paper proposes a benchmark for investigating DA techniques for brain MR image segmentation using data collected across sites with scanners from different vendors (Philips, Siemens, and General Electric). Our work provides labeled data, publicly available source code for a set of baseline and DA models, and a benchmark for assessing different brain MR image segmentation techniques. We applied the proposed benchmark to evaluate two segmentation tasks: skull-stripping; and white-matter, gray-matter, and cerebrospinal fluid segmentation, but the benchmark can be extended to other brain structures. Our main findings during the development of this benchmark are that there is not a single DA technique that consistently outperforms others, and hyperparameter tuning and computational times for these methods still pose a challenge before broader adoption of these methods in the clinical practice.
Correlation Analysis Between Magnetic Resonance Imaging-Based Anatomical Assessment and Behavioral Outcome in a Rat Contusion Model of Chronic Thoracic Spinal Cord Injury
Authors: Xing Cong , Jia Zeyu , Qu Haodong , Liu Song , Jiang Wang , Zhong Hao , Zhou Mi , Zhu Shibo , Ning Guangzhi , Feng Shiqing
Published: September 2022

Although plenty of evidences from preclinical studies have led to potential treatments for patients with spinal cord injury (SCI), the failure to translate promising preclinical findings into clinical advances has long puzzled researchers. Thus, a more reliable combination of anatomical assessment and behavioral testing is urgently needed to improve the translational worth of preclinical studies. To address this issue, the present study was designed to relate magnetic resonance imaging (MRI)-based anatomical assessment to behavioral outcome in a rat contusion model. Rats underwent contusion with three different heights to simulate various severities of SCI, and their locomotive functions were evaluated by the grid-walking test, Louisville swim scale (LSS), especially catwalk gait analysis system and basic testing, and Basso, Beattie, Bresnahan (BBB) score. The results showed that the lesion area (LA) is a better indicator for damage assessment compared with other parameters in sagittal T2-weighted MRI (T2WI). Although two samples are marked as outliers by the box plot analysis, LA correlated closely with all of the behavioral testing without ceiling effect and floor effect. Moreover, with a moderate severity of SCI in a contusion height of 25 mm, the smaller the LA of the spinal cord measured on sagittal T2WI the better the functional performance, the smaller the cavity region and glial scar, the more spared the myelin, the higher the volatility, and the thicker the bladder wall. We found that LA significantly related with behavior outcomes, which indicated that LA could be a proxy of damage assessment. The combination of sagittal T2WI and four types of behavioral testing can be used as a reliable scheme to evaluate the prognosis for preclinical studies of SCI.
Software for near-real-time voltammetric tracking of tonic neurotransmitter levels in vivo
Authors: Goyal Abhinav , Hwang Sangmun , Rusheen Aaron E. , Blaha Charles D. , Bennet Kevin E. , Lee Kendall H. , Jang Dong Pyo , Oh Yoonbae , Shin Hojin
Published: September 2022

Tonic extracellular neurotransmitter concentrations are important modulators of central network homeostasis. Disruptions in these tonic levels are thought to play a role in neurologic and psychiatric disease. Therefore, ways to improve their quantification are actively being investigated. Previously published voltammetric software packages have implemented FSCV, which is not capable of measuring tonic concentrations of neurotransmitters in vivo. In this paper, custom software was developed for near-real-time tracking (scans every 10 s) of neurotransmitters’ tonic concentrations with high sensitivity and spatiotemporal resolution both in vitro and in vivo using cyclic voltammetry combined with dynamic background subtraction (M-CSWV and FSCAV). This software was designed with flexibility, speed, and user-friendliness in mind. This software enables near-real-time measurement by reducing data analysis time through an optimized modeling algorithm, and efficient memory handling makes long-term measurement possible. The software permits customization of the cyclic voltammetric waveform shape, enabling experiments to detect a specific analyte of interest. Finally, flexibility considerations allow the user to alter the fitting parameters, filtering characteristics, and size and shape of the analyte kernel, based on data obtained live during the experiment to obtain accurate measurements as experimental conditions change. Herein, the design and advantages of this near-real-time voltammetric software are described, and its use is demonstrated in in vivo experiments.
Crosstalk between regulated necrosis and micronutrition, bridged by reactive oxygen species
Authors: Zhang Lei , Liu Jinting , Dai Ziyan , Wang Jia , Wu Mengyang , Su Ruicong , Zhang Di
Published: September 2022

The discovery of regulated necrosis revitalizes the understanding of necrosis from a passive and accidental cell death to a highly coordinated and genetically regulated cell death routine. Since the emergence of RIPK1 (receptor-interacting protein kinase 1)-RIPK3-MLKL (mixed lineage kinase domain-like) axis-mediated necroptosis, various other forms of regulated necrosis, including ferroptosis and pyroptosis, have been described, which enrich the understanding of pathophysiological nature of diseases and provide novel therapeutics. Micronutrients, vitamins, and minerals, position centrally in metabolism, which are required to maintain cellular homeostasis and functions. A steady supply of micronutrients benefits health, whereas either deficiency or excessive amounts of micronutrients are considered harmful and clinically associated with certain diseases, such as cardiovascular disease and neurodegenerative disease. Recent advance reveals that micronutrients are actively involved in the signaling pathways of regulated necrosis. For example, iron-mediated oxidative stress leads to lipid peroxidation, which triggers ferroptotic cell death in cancer cells. In this review, we illustrate the crosstalk between micronutrients and regulated necrosis, and unravel the important roles of micronutrients in the process of regulated necrosis. Meanwhile, we analyze the perspective mechanism of each micronutrient in regulated necrosis, with a particular focus on reactive oxygen species (ROS).
Dehydration and rehydration affect brain regional density and homogeneity among young male adults, determined via magnetic resonance imaging: A pilot self-control trial
Authors: Zhang Na , Zhang Jianfen , Du Songming , Ma Guansheng
Published: September 2022

The effects of dehydration and rehydration on brain regional density and homogeneity are unknown and have been infrequently studied. In this pilot self-control study, twelve participants aged 18-25 years were recruited and the brain was scanned using magnetic resonance imaging for three tests under different hydration statuses. In three tests, urine osmolality was determined to assess hydration status. Test 1 was conducted after 12 h of overnight fasting. Test 2 was conducted in a dehydration state induced by 36 h of water deprivation. Test 3 was conducted in a rehydration state, which was induced by 1.5 L of purified water supplementation. Compared with test 1, participants under the dehydration state in test 2 had higher cerebrospinal fluid density (p < 0.001). Compared with test 2, participants under the rehydration state in test 3 showed an extensive increase in gray matter density in widespread brain regions, mainly involving the left middle temporal gyrus, cuneus, right thalamus, left rolandic opercula, Brodmann area 39, right precentral, left postcentral gyrus, and cingulate gyrus (p < 0.001); a higher white matter density in the temporal lobe, sub-lobar, and sub-gyral areas; and a lower cerebrospinal fluid density (p < 0.001). The multimodal, multiscale neuroimaging marker of the human brain connection—the regional homogeneity (ReHo) index—was used for evaluating the connectivity of nodes in the brain. Compared with test 1, participants in test 2 had a lower ReHo value in the right amygdala, left occiput median, right lingual, opercula part of right inferior frontal gyrus, and right precuneus (p < 0.01). Compared with test 2, participants in test 3 had a higher ReHo value in the right amygdala, right lingual, opercula part of the right inferior frontal gyrus, and right precuneus (p < 0.01). Dehydration state increased cerebrospinal fluid density, decreased brain regional homogeneity. Rehydration state increased brain gray matter and white matter density widespreadly, and increased brain regional homogeneity.
Influence of nutrition claims on different models of front-of-package nutritional labeling in supposedly healthy foods: Impact on the understanding of nutritional information, healthfulness perception, and purchase intention of Brazilian consumers
Authors: Prates Sarah Morais Senna , Reis Ilka Afonso , Rojas Carlos Felipe Urquizar , Spinillo Carla Galvão , Anastácio Lucilene Rezende
Published: September 2022

Nutrition claims are positive information about foods, which are widely used as a marketing strategy on labels. On the contrary, front-of-package nutritional labeling (FoPNL) aims to make it easier for consumers to understand the nutritional composition of foods and favor healthy food choices. However, the concomitant presence of nutrition claims and FoPNL may hinder the understanding, judgment, and choices of consumers at the moment of purchase. Therefore, the objective of this study was to evaluate the influence of nutrition claims on the efficacy of FoPNL models in the understanding of nutritional information, healthfulness perception, and purchase intention of Brazilian consumers. It was an experimental cross-sectional study carried out using an online questionnaire, with a total of 720 participants randomly divided into four FoPNL conditions: control, octagon, triangle, and magnifying glass. Each participant looked at 12 food packages, which were produced following the factorial design: (i) food category (cereal bar, whole grain cookies, and snacks); (ii) product type (containing one critical nutrient × containing two critical nutrients); and (iii) nutrition claims (present × absent). The comprehension of nutritional information was evaluated through the identification of excessive nutrients, and the healthfulness perception and purchase intention were evaluated using a seven-point scale. The results indicated that the presence of FoPNL increased the understanding of the information and reduced healthfulness perception and purchase intention. The presence of nutrition claims influenced the three outcomes, decreasing the probability of understanding information about food composition by 32% (OR 0.68, 95% confidence interval 0.58–0.78, p < 0.01) and significantly increasing (p < 0.05) average health scores (1.95–2.02) and purchase intention (2.00–2.05). Nonetheless, the interaction “FoPNL × claims” was not significant, which indicated that claims act independently. All FoPNL models were more effective than the control. For the least healthful type of product (two nutrients in excess), the octagon and triangle models were superior to the magnifying glass, regarding the outcome of healthfulness perception. The results prove the efficacy of FoPNL in consumer understanding and judgment. Despite the positive effects of FoPNL, it did not cancel the positivity bias generated by the claims.
Fear of COVID-19, healthy eating behaviors, and health-related behavior changes as associated with anxiety and depression among medical students: An online survey
Authors: Nguyen Minh H. , Do Tinh X. , Nguyen Tham T. , Pham Minh D. , Pham Thu T. M. , Pham Khue M. , Kim Giang B. , Do Binh N. , Nguyen Hiep T. , Nguyen Ngoc-Minh , Dam Hoa T. B. , Nguyen Yen H. , Nguyen Kien T. , Nguyen Thao T. P. , Nguyen Trung T. , Duong Tuyen Van
Published: September 2022

Background

Medical students' health and wellbeing are highly concerned during the COVID-19 pandemic. This study examined the impacts of fear of COVID-19 (FCoV-19S), healthy eating behavior, and health-related behavior changes on anxiety and depression.

Methods

We conducted an online survey at 8 medical universities in Vietnam from 7th April to 31st May 2020. Data of 5,765 medical students were collected regarding demographic characteristics, FCoV-19S, health-related behaviors, healthy eating score (HES), anxiety, and depression. Logistic regression analyses were used to explore associations.

Results

A lower likelihood of anxiety and depression were found in students with a higher HES score (OR = 0.98; 95%CI = 0.96, 0.99; p = 0.042; OR = 0.98; 95%CI = 0.96, 0.99; p = 0.021), and in those unchanged or more physical activities during the pandemic (OR = 0.54; 95%CI = 0.44, 0.66; p < 0.001; OR = 0.44; 95%CI = 0.37, 0.52; p < 0.001) as compared to those with none/less physical activity, respectively. A higher likelihood of anxiety and depression were reported in students with a higher FCoV-19S score (OR = 1.09; 95%CI = 1.07, 1.12; p < 0.001; OR = 1.06; 95%CI = 1.04, 1.08; p < 0.001), and those smoked unchanged/more during the pandemic (OR = 6.67; 95%CI = 4.71, 9.43; p < 0.001; OR = 6.77; 95%CI = 4.89, 9.38; p < 0.001) as compared to those stopped/less smoke, respectively. In addition, male students had a lower likelihood of anxiety (OR = 0.79; 95%CI = 0.65, 0.98; p = 0.029) compared to female ones.

Conclusions

During the pandemic, FCoV-19S and cigarette smoking had adverse impacts on medical students' psychological health. Conversely, staying physically active and having healthy eating behaviors could potentially prevent medical students from anxiety and depressive symptoms.
The most effective exercise to prevent obesity: A longitudinal study of 33,731 Taiwan biobank participants
Authors: Lin Wan-Yu
Published: September 2022

Regular physical exercise is recommended to reduce the risk of obesity. However, it remains unclear which activities are more effective in preventing obesity. In this study, five obesity indices and lifestyle factors of 33,731 Taiwan Biobank adults were measured/collected twice with a mean time interval of 4.06 years. A linear mixed effects model was fitted to assess the associations of exercises with obesity indices, in which a random intercept term was used to account for individual differences. The five obesity indices included body mass index (BMI), body fat percentage (BFP), waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR). Among 23 exercises, jogging and yoga were consistently the most effective choices across all five obesity indices. One more weekly hour to jog was associated with a 0.093 kg/m2 decrease in BMI (p = 4.2E-20), a 0.297% decrease in BFP (p = 3.8E-36), a 0.398 cm decrease in WC (p = 1.6E-21), and a 2.9E-3 decrease in WHR (p = 1.3E-17). One more weekly hour to perform yoga was associated with a 0.225 cm decrease in HC (p = 6.4E-14). Jogging is an exercise for the entire body. Arms swing, waist turn, legs and feet run, and shoulders and abdomen are also involved in this act. By contrast, many yoga poses use muscles around the hips and pelvis, and therefore yoga is the most effective exercise to reduce HC.
Sleep dimensions are associated with obesity, poor diet quality and eating behaviors in school-aged children
Authors: Ramírez-Contreras Catalina , Santamaría-Orleans Alicia , Izquierdo-Pulido Maria , Zerón-Rugerio María Fernanda
Published: September 2022

Objectives

The aim of this cross-sectional study was to investigate the association between sleep dimensions (duration, patterns, and disturbances) with body mass index (BMI), diet quality, and eating behaviors in school-aged children. Additionally, we aimed to investigate whether obesogenic eating behaviors (higher food responsiveness, lower satiety responsiveness, and less slowness in eating) and poor diet quality could mediate the potential association between sleep and obesity in school-aged children.

Materials and methods

For all participants (n = 588 children, age 5–12 years; 51% girls) we evaluated: sleep dimensions, BMI, diet quality, eating behaviors (food responsiveness, satiety responsiveness and slowness in eating). Linear regression models were used to test associations between exposure and outcome variables. Additionally, path analysis was conducted to test whether eating behaviors mediated the relationship between sleep and obesity.

Results

Shorter sleep duration (β = −0.722, p = 0.009) and greater sleep disturbances (β = 0.031, p = 0.012) were significantly associated with BMI. Additionally, we observed that diet quality was significantly associated with sleep duration (β = 0.430, p = 0.004), the midpoint of sleep (β = −0.927, p < 0.001), and sleep disturbances (β = −0.029, p < 0.001). Among other findings, greater sleep disturbances were associated with food responsiveness (β = 0.017, p < 0.001), satiety responsiveness (β = 0.015, p < 0.001), and slowness in eating (β = 0.012, p < 0.001). Importantly, food responsiveness was found as significant mediator of the relationship between sleep and BMI (R = 0.427, R2 = 0.182, p < 0.001).

Conclusions

Late sleep patterns, short sleep duration, and greater sleep disturbances are significantly related with what and how school-aged children eat. Importantly, poor diet quality was significantly related to all three sleep dimensions, while eating behaviors had a significant relationship with greater sleep disturbances. These findings may be relevant to the development of behavioral targets to prevent childhood obesity, including sleep hygiene guidelines as a strategy to improve children's eating habits, as well as their BMI.
Biomarkers to assess the risk of bladder cancer in patients presenting with haematuria are gender-specific
Authors: Duggan Brian , O’Rourke Declan , Anderson Neil , Reid Cherith N. , Watt Joanne , O’Kane Hugh , Boyd Ruth , Curry David , Evans Mark , Stevenson Michael , Kurth Mary Jo , Lamont John V. , Fitzgerald Peter , Ruddock Mark W.
Published: September 2022

Introduction

Haematuria is a common red flag symptom of urinary tract cancer. Bladder cancer (BC) is the most common cancer to present with haematuria. Women presenting with haematuria are often underdiagnosed. Currently, no gender-specific tests are utilized in clinical practice. Considerable healthcare resources are needed to investigate causes of haematuria and this study was set up to help identify markers of BC. The aim of the study was to define biomarker algorithms in haematuria patients using an expanded panel of biomarkers to diagnose BC and investigate if the algorithms are gender-specific.

Materials and Methods

A total of n=675 patients with a history of haematuria were recruited from Northern Ireland hospitals. Patients were collected on a 2:1 ratio, non-BC (control) n=474: BC n=201. A detailed clinical history, urine and blood samples were collected. Biomarkers, known to be involved in the pathobiology underlying bladder carcinogenesis were investigated. Biomarkers differentially expressed between groups were investigated using Wilcoxon rank sum and linear regression.

Results

Biomarkers were gender specific. Two biomarker-algorithms were identified to triage haematuria patients; male – u_NSE, s_PAI-1/tPA, u_midkine, u_NGAL, u_MMP-9/TIMP-1 and s_prolactin (u=urine; s=serum); sensitivity 71.8%, specificity 72.8%; AUROC 0.795; and female urine biomarkers - IL-12p70, IL-13, midkine and clusterin; sensitivity 83.7%, specificity 79.7%; AUROC 0.865. Addition of the clinical variable infection to both algorithms increased both AUROC to 0.822 (DeLong p=0.014) and to 0.923 (DeLong p=0.004) for males and females, respectively. Combining clinical risk factors with biomarker algorithms would enable application of the algorithms to triage haematuria patients.

Conclusion

Using gender-specific biomarker algorithms in combination with clinical risks that are associated with BC would allow clinicians to better manage haematuria patients and potentially reduce underdiagnosis in females. In this study, we demonstrate, for the first time, that blood and urine biomarkers are gender-specific when assessing risk of BC in patients who present with blood in their urine. Combining biomarker data with clinical factors could improve triage when referring patients for further investigations.
Focus on pattern recognition receptors to identify prognosis and immune microenvironment in colon cancer
Authors: Ren Pengtao , Zhang Yuan
Published: September 2022

In 2011, J. Hoffman, and B. Beutler won the Nobel Prize of medicine for the fact that they discovered the pattern recognition receptors (PRRs) and meanwhile described their effect on cell activation from the innate and adaptive immune systems. There are more and more evidences that have proved the obvious effect of PRRs on tumorigenesis progression. Nevertheless, the overall impact of PRR genes on prognosis, tumor microenvironmental characteristics and treatment response in patients with colon adenocarcinoma (COAD) remains unclear. In this research, we systematically assessed 20 PRR genes and comprehensively identified the prognostic value and enrichment degree of PRRs. The unsupervised clustering approach was employed for dividing COAD into 4 PRR subtypes, namely cluster A, cluster B, cluster C and cluster D, which were significantly different in terms of the clinical features, the immune infiltrations, and the functions. Among them, cluster B has better immune activities and functions. Cox and LASSO regression analysis was further applied to identify a prognostic five-PRR-based risk signature. Such signature can well predict patients’ overall survival (OS), together with a good robustness. Confounding parameters were controlled, with results indicating the ability of risk score to independently predict COAD patients’ OS. Besides, a nomogram with a strong reliability was created for enhancing the viability exhibited by the risk score in clinical practice. Also, patients who were classified based on the risk score owned distinguishable immune status and tumor mutation status, response to immunotherapy, as well as sensitivity to chemotherapy. A low risk score, featuring increased tumor stemness index (TSI), human leukocyte antigen (HLA), immune checkpoints, and immune activation, demonstrated a superior immunotherapeutic response. According to the study results, the prognostic PRR-based risk signature could serve as a robust biomarker for predicting the clinical outcomes as well as evaluating therapeutic response for COAD patients.
Intracellular radar: Understanding γδ T cell immune surveillance and implications for clinical strategies in oncology
Authors: Cherry Anne B. C. , Gherardin Nicholas A. , Sikder Hafiz I.
Published: September 2022

T cells play a key role in anticancer immunity, with responses mediated through a diversity of αβ or γδ T cell receptors. Although αβ and γδ T cells stem from common thymic precursors, the development and subsequent biological roles of these two subsets differ considerably. γδ T cells are an unconventional T cell subset, uniquely poised between the adaptive and innate immune systems, that possess the ability to recognize intracellular disturbances and non-peptide-based antigens to eliminate tumors. These distinctive features of γδ T cells have led to recent interest in developing γδ-inspired therapies for treating cancer patients. In this minireview, we explore the biology of γδ T cells, including how the γδ T cell immune surveillance system can detect intracellular disturbances, and propose a framework to understand the γδ T cell-inspired therapeutic strategies entering the clinic today.
Orocutaneous Fistula Formation in Free Flap Reconstruction for Oral Squamous Cell Carcinoma
Authors: Fang Qigen , Yuan Junhui , Du Wei , Dai Liyuan , Zhang Xu , Luo Ruihua
Published: September 2022

Objective

The aim of this study is to identify the risk factors associated with orocutaneous fistula (OCF) formation after free flap reconstruction for oral squamous cell carcinoma (SCC).

Methods

Patients undergoing free flap reconstruction for oral SCC were retrospectively enrolled. The relationship between clinicopathologic variables and OCF formation was analyzed by univariate and multivariate analyses.

Results

A total of 87 OCFs occurred in 856 patients. Univariate analysis revealed cachexia, tumor at the tongue/floor of the mouth (TFOM), T4 stage, preoperative hemoglobin level, pull-through procedure, preoperative albumin level, and surgical site infection were associated with the formation of OCF. Multivariate analysis confirmed the independence of cachexia, TFOM, T4 stage, and surgical site infection in predicting OCF development. Conventional wound care could achieve successful fistula closure in 82.4% of the patients with a median time of 28 days.

Conclusions

OCF formation was common after free flap reconstruction. The presence of cachexia, TFOM tumor site, T4 stage, and surgical site infection significantly increased the risk of OCF formation. Although it required a long period, conventional wound care can obtain satisfactory outcomes in OCF management.
ICSBP-induced PD-L1 enhances osteosarcoma cell growth
Authors: Sung Jee Young , Kim June Hyuk , Kang Hyun Guy , Park Jong Woong , Park Seog-Yun , Park Byung-Kiu , Kim Yong-Nyun
Published: September 2022

Background

Interferon (IFN) consensus sequence binding protein (ICSBP) is a transcription factor induced by IFN-γ. We previously reported that ICSBP expression promotes osteosarcoma progression by enhancing transforming growth factor-β signaling. In cancer cells, programmed death-ligand 1 (PD-L1) contributes to immune escape and may also be involved in tumor progression. Because IFN-γ induces the expression of both ICSBP and PD-L1, we explored the association between ICSBP and PD-L1 expression in terms of osteosarcoma progression.

Methods

Three osteosarcoma cell lines (Saos2, U2OS, and 143B) were employed. Gene expression was measured by qRT-PCR, and protein levels were assessed by immunoblotting. PD-L1 expression was evaluated in cells overexpressing ICSBP and in ICSBP knockdown cells. The effects of PD-L1 expression on cell growth were examined by MTS assays, Incucyte analysis, soft agar assays, and three-dimensional (3D) culture. Cell cycle and apoptosis were evaluated by FACS analysis of cells stained with propidium iodide (PI) and annexin V/PI, respectively. The antitumor effects of PD-L1 knockdown without or with doxorubicin treatment were evaluated in vivo in nude mice bearing ICSBP-overexpressing 143B cell xenograft. The clinical relevance of PD-L1 and ICSBP expression was evaluated immunohistochemically using a human osteosarcoma microarray and through analysis of publicly available data using Gene Expression Profiling Interactive Analysis2.

Results

ICSBP overexpression upregulated PD-L1 expression in all three cell lines, whereas ICSBP knockdown decreased the PD-L1 expression. PD-L1 knockdown attenuated the cell growth and reduced colony-forming capacity in both soft agar assays and 3D culture. PD-L1 knockdown increased apoptosis and induced G2/M arrest, which was associated with decreased expression of survivin, cyclin-dependent kinase 4 (CDK4), cyclin E, and cyclin D1 expression and increased the expression of p27, phosphorylated Cdc2, and phosphorylated Wee1. PD-L1 knockdown decreased the growth of tumor xenografts and increased the doxorubicin sensitivity of ICSBP-overexpressing 143B cells both in vitro and in vivo. PD-L1 was expressed in human osteosarcoma tissues, and its expression was moderately correlated with that of ICSBP in osteosarcoma patients.

Conclusion

ICSBP regulates PD-L1 expression in osteosarcoma cells, and PD-L1 knockdown combined with doxorubicin treatment could represent a strategy for controlling osteosarcoma expressing ICSBP.
MRI-based radiomics analysis for preoperative evaluation of lymph node metastasis in hypopharyngeal squamous cell carcinoma
Authors: Lu Shanhong , Ling Hang , Chen Juan , Tan Lei , Gao Yan , Li Huayu , Tan Pingqing , Huang Donghai , Zhang Xin , Liu Yong , Mao Yitao , Qiu Yuanzheng
Published: September 2022

Objective

To investigate the role of pre-treatment magnetic resonance imaging (MRI) radiomics for the preoperative prediction of lymph node (LN) metastasis in patients with hypopharyngeal squamous cell carcinoma (HPSCC).

Methods

A total of 155 patients with HPSCC were eligibly enrolled from single institution. Radiomics features were extracted from contrast-enhanced axial T-1 weighted (CE-T1WI) sequence. The most relevant features of LN metastasis were selected by the least absolute shrinkage and selection operator (LASSO) method. Univariate and multivariate logistic regression analysis was adopted to determine the independent clinical risk factors. Three models were constructed to predict the LN metastasis status: one using radiomics only, one using clinical factors only, and the other one combined radiomics and clinical factors. Receiver operating characteristic (ROC) curves and calibration curve were used to evaluate the discrimination and the accuracy of the models, respectively. The performances were tested by an internal validation cohort (n=47). The clinical utility of the models was assessed by decision curve analysis.

Results

The nomogram consisted of radiomics scores and the MRI-reported LN status showed satisfactory discrimination in the training and validation cohorts with AUCs of 0.906 (95% CI, 0.840 to 0.972) and 0.853 (95% CI, 0.739 to 0.966), respectively. The nomogram, i.e., the combined model, outperformed the radiomics and MRI-reported LN status in both discrimination and clinical usefulness.

Conclusions

The MRI-based radiomics nomogram holds promise for individual and non-invasive prediction of LN metastasis in patients with HPSCC.