bluuebunny/crossref_metadata_2025 huggingface dataset:
The Application Value of Syndecan-2 Gene Methylation for Colorectal Cancer Diagnosis: A Clinical Study and Meta-Analyses
Authors: Yue Congbo , Zhang Yaping , Wang Yanlei , Zhang Zhenhong , Zhang Mengjiao , Wang Huayang , Chen Wendan , Shang Ziqi , Xin Yiwei , Zhang Xin , Zhang Yi
Published: March 2022

Objective

Syndecan-2 (SDC2) methylation has been previously reported as a sensitive biomarker for the early detection of colorectal cancer (CRC). Droplet digital PCR (ddPCR) is the latest development of PCR technology. It can accurately detect and quantify the target sequence of nucleic acid. ddPCR is widely used in research and clinical diagnosis. In the present study, we aimed to develop a ddPCR method to detect SDC2 gene methylation and evaluate the diagnostic value of SDC2 gene methylation.

Methods

First, a ddPCR method was developed to measure SDC2 methylation in stool samples collected from 51 cases of normal, 23 cases of adenoma, and 86 cases of CRC. Subsequently, a meta-analysis of existing studies was conducted to judge the diagnostic value of SDC2 gene methylation in CRC. PUBMED, EMBASE, Web of Science, and Scopus databases were searched for relative studies. Meta-analysis was performed using Meta Disc 1.4 and STATA 15.0 software.

Results

The ddPCR showed that the linearity, sensitivity, and specificity for the detection of SDC2 gene methylation could be down to 0.1% methylation level and 5 ng of methylated DNA input. In 109 cases of CRC, 107 cases could be detected, and the sensitivity was 98.17%. The median value of the percentage of methylated reference (PMR) in colorectal adenoma and CRC patients was significantly higher compared with the normal individuals (p < 0.001). In addition, we found that the PMR value was associated with the clinical staging of CRC. The difference of PMR in stage II and stage IIIA was statistically significant (p < 0.05). Moreover, the meta-analysis showed that 11 out of 87 studies were identified to report the feasibility of SDC2 gene methylation as a method to diagnose early CRC. The pooled sensitivity and specificity of SDC2 gene methylation test for CRC were 0.80 [95% CI (0.68–0.88)] and 0.93 [95% CI (0.91–0.94)], respectively. The pooled diagnostic odds ratio (DOR) and area under curve (AUC) were 52.46 [95% CI (30.43–90.45)] and 0.94 [95% CI (0.92, 0.96)], respectively.

Conclusions

The ddPCR method was more sensitive and convenient to detect SDC2 gene methylation, and the pooled analysis showed that methylated SDC2 was a valuable biomarker for the non-invasive detection of CRC.
Sexual Dimorphisms of Protein-Coding Gene Profiles in Placentas From Women With Systemic Lupus Erythematosus
Authors: Li Hui-hui , Sai Lin-tao , Tian Shan , Liu Yuan , Freel Colman I. , Wang Kai , Zhou Chi , Zheng Jing , Shu Qiang , Zhao Ying-jie
Published: March 2022

Background

Systemic lupus erythematosus (SLE) may cause pathogenic changes in the placentas during human pregnancy, such as decreased placental weight, intraplacental hematoma, ischemic hypoxic change, placental infarction, and decidual vasculopathy, which contribute to high maternal and fetal mortality and morbidity. Sex-specific adaptations of the fetus are associated with SLE pregnancies. The present study aimed to determine the transcriptomic profiles of female and male placentas from women with SLE.

Methods

RNA sequencing (RNA-seq) was performed to identify differentially expressed protein-coding genes (DEGs) in placentas from women with SLE vs. normal term (NT) pregnancies with female and male fetuses (n= 3-5/sex/group). Real-time-quantitative PCR was performed (n= 4 /sex/group) to validate the RNA-seq results. Bioinformatics functional analysis was performed to predict the biological functions and pathways of SLE-dysregulated protein-coding genes.

Results

Compared with NT-female (NT-F) placentas, 119 DEGs were identified in SLE-female (SLE-F) placentas. Among these 119 DEGs, five and zero are located on X- and Y-chromosomes, respectively, and four are located on the mitochondrial genome. Compared with NT-male (NT-M) placentas, 458 DEGs were identified in SLE-male (SLE-M) placentas, among which 16 are located on the X-chromosome and zero on the Y-chromosome and mitochondrial genome. Twenty-four DEGs were commonly dysregulated in SLE-F and -M placentas. Functional analysis showed that SLE-dysregulated protein-coding genes were associated with diverse biological functions and pathways, including angiogenesis, cellular response to growth factor stimulus, heparin-binding, HIF (hypoxia-inducible factor)-1 signaling pathway, and Interleukin-17 (IL-17) signaling pathway in both SLE-F and -M placentas. Biological regulations were differentially enriched between SLE-F and -M placentas. Regulation of blood circulation, response to glucocorticoid, and rhythmic process were all enriched in SLE-F, but not SLE-M placentas. In contrast, tumor necrosis factor production, Th17 cell differentiation, and MDA (melanoma differentiation-associated gene)-5 signaling pathway were enriched in SLE-M but not SLE-F placentas.

Conclusion

This report investigated the protein-coding gene profiles of placenta tissues from SLE patients using RNA-seq. The results suggest that the SLE-dysregulated protein-coding genes in placentas may contribute to the pathophysiological progress of SLE pregnancies in a fetal sex-specific manner, leading to adverse pregnancy outcomes.
Statin Use Is Associated With a Lower Risk of Blepharitis: A Population-Based Study
Authors: Feng Kathy Ming , Chung Chi-Hsiang , Chen Yi-Hao , Chien Wu-Chien , Chien Ke-Hung
Published: March 2022

Background

Blepharitis is a common eye disorder that may be overlooked by patients and clinical practitioners. The symptoms of blepharitis often manifest as irritation, a burning sensation, grittiness, and itchiness and may decrease visual acuity if not treated promptly. Meibomian gland dysfunction (MGD), a common cause of blepharitis, is believed to be associated with increased inflammatory marker levels that may disrupt the composition of lipids produced by the sebaceous glands in the eyelids and ultimately cause tear film instability.

Methods

This is a retrospective, population-based study using National Health Insurance Research Database (NHIRD) data from a 14-year period (2000–2015). Pearson chi-squared and Student's t-tests were used to assess the differences in categorical and continuous variables, respectively, between statin users and non-statin users. Univariate and multivariate Cox regression analyses were performed to calculate the hazard ratios (HRs) after adjusting for confounders. Kaplan-Meier analysis was used to assess the cumulative risk of blepharitis between the two cohorts.

Results

A total of 67,014 patients who used statins were enrolled as the study cohort, and 268,056 patients who did not use statins were enrolled as the comparison cohort. The incidence of blepharitis was 3.04% with statin treatment and 3.72% without statin treatment (p < 0.001). Patients who used statins had a lower risk of developing blepharitis [adjusted hazard ratio (aHR): 0.746, p < 0.001] than those who did not. In addition, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), stroke, chalazion, rosacea, Sjogren syndrome, psoriasis and atopy were found to be possible risk factors for blepharitis.

Conclusion

Statin use can decrease the risk of developing blepharitis. However, further prospective studies are needed to evaluate statin treatment for various subtypes of blepharitis and to identify the associated mechanism.
Clinical Overview of Progressive Fibrotic Interstitial Lung Disease
Authors: Case Amy Hajari
Published: March 2022

Interstitial lung diseases (ILD) on the whole have variable prognoses, but there are those which manifest with fibrosis and are characterized by disease progression. Chief among these is idiopathic pulmonary fibrosis, but other ILDs, including autoimmune ILD and chronic hypersensitivity pneumonitis, may have a progressive fibrotic phenotype also. A usual interstitial pneumonia pattern of lung involvement is a prominent risk factor for such a course, suggesting shared fibrotic pathways that may be targeted by antifibrotic therapies. This brief review describes ILDs that are most commonly fibrotic, shared risk factors for development of PF-ILD, and evidence for antifibrotic use in their management.
Proteomic Signatures of Microbial Adaptation to the Highest Ultraviolet-Irradiation on Earth: Lessons From a Soil Actinobacterium
Authors: Zannier Federico , Portero Luciano R. , Douki Thierry , Gärtner Wolfgang , Farías María E. , Albarracín Virginia H.
Published: March 2022

In the Central Andean region in South America, high-altitude ecosystems (3500–6000 masl) are distributed across Argentina, Chile, Bolivia, and Peru, in which poly-extremophilic microbes thrive under extreme environmental conditions. In particular, in the Puna region, total solar irradiation and UV incidence are the highest on Earth, thus, restraining the physiology of individual microorganisms and the composition of microbial communities. UV-resistance of microbial strains thriving in High-Altitude Andean Lakes was demonstrated and their mechanisms were partially characterized by genomic analysis, biochemical and physiological assays. Then, the existence of a network of physiological and molecular mechanisms triggered by ultraviolet light exposure was hypothesized and called “UV-resistome”. It includes some or all of the following subsystems: (i) UV sensing and effective response regulators, (ii) UV-avoidance and shielding strategies, (iii) damage tolerance and oxidative stress response, (iv) energy management and metabolic resetting, and (v) DNA damage repair. Genes involved in the described UV-resistome were recently described in the genome of Nesterenkonia sp. Act20, an actinobacterium which showed survival to high UV-B doses as well as efficient photorepairing capability. The aim of this work was to use a proteomic approach together with photoproduct measurements to help dissecting the molecular events involved in the adaptive response of a model High-Altitude Andean Lakes (HAAL) extremophilic actinobacterium, Nesterenkonia sp. Act20, under artificial UV-B radiation. Our results demonstrate that UV-B exposure induced over-abundance of a well-defined set of proteins while recovery treatments restored the proteomic profiles present before the UV-challenge. The proteins involved in this complex molecular network were categorized within the UV-resistome subsystems: damage tolerance and oxidative stress response, energy management and metabolic resetting, and DNA damage repair.
CXCL8 in Tumor Biology and Its Implications for Clinical Translation
Authors: Xiong Xingyu , Liao Xinyang , Qiu Shi , Xu Hang , Zhang Shiyu , Wang Sheng , Ai Jianzhong , Yang Lu
Published: March 2022

The chemokine CXCL8 has been found to play an important role in tumor progression in recent years. CXCL8 activates multiple intracellular signaling pathways by binding to its receptors (CXCR1/2), and plays dual pro-tumorigenic roles in the tumor microenvironment (TME) including directly promoting tumor survival and affecting components of TME to indirectly facilitate tumor progression, which include facilitating tumor cell proliferation and epithelial-to-mesenchymal transition (EMT), pro-angiogenesis, and inhibit anti-tumor immunity. More recently, clinical trials indicate that CXCL8 can act as an independently predictive biomarker in patients receiving immune checkpoint inhibitions (ICIs) therapy. Preclinical studies also suggest that combined CXCL8 blockade and ICIs therapy can enhance the anti-tumor efficacy, and several clinical trials are being conducted to evaluate this therapy modality.
HER2 Low, Ultra-low, and Novel Complementary Biomarkers: Expanding the Spectrum of HER2 Positivity in Breast Cancer
Authors: Venetis Konstantinos , Crimini Edoardo , Sajjadi Elham , Corti Chiara , Guerini-Rocco Elena , Viale Giuseppe , Curigliano Giuseppe , Criscitiello Carmen , Fusco Nicola
Published: March 2022

HER2 status in breast cancer is assessed to select patients eligible for targeted therapy with anti-HER2 therapies. According to the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP), the HER2 test positivity is defined by protein overexpression (score 3+) at immunohistochemistry (IHC) and/or gene amplification at in situ hybridization (ISH). The introduction of novel anti-HER2 compounds, however, is changing this paradigm because some breast cancers with lower levels of protein expression (i.e. score 1+/2+ with no gene amplification) benefited from HER2 antibody-drug conjugates (ADC). Recently, a potential for HER2 targeting in HER2 “ultra-low” (i.e. score 0 with incomplete and faint staining in ≤10% of tumor cells) and MutL-deficient estrogen receptor (estrogen receptor)-positive/HER2-negative breast cancers has been highlighted. All these novel findings are transforming the traditional dichotomy of HER2 status and have dramatically raised the expectations in this field. Still, a more aware HER2 status assessment coupled with the comprehensive characterization of the clinical and molecular features of these tumors is required. Here, we seek to provide an overview of the current state of HER2 targeting in breast cancers beyond the canonical HER2 positivity and to discuss the practical implications for pathologists and oncologists.
Potential Roles of Enterochromaffin Cells in Early Life Stress-Induced Irritable Bowel Syndrome
Authors: Tao Enfu , Zhu Zhenya , Hu Chenmin , Long Gao , Chen Bo , Guo Rui , Fang Marong , Jiang Mizu
Published: March 2022

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, also known as disorders of the gut–brain interaction; however, the pathophysiology of IBS remains unclear. Early life stress (ELS) is one of the most common risk factors for IBS development. However, the molecular mechanisms by which ELS induces IBS remain unclear. Enterochromaffin cells (ECs), as a prime source of peripheral serotonin (5-HT), play a pivotal role in intestinal motility, secretion, proinflammatory and anti-inflammatory effects, and visceral sensation. ECs can sense various stimuli and microbiota metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids. ECs can sense the luminal environment and transmit signals to the brain via exogenous vagal and spinal nerve afferents. Increasing evidence suggests that an ECs-5-HT signaling imbalance plays a crucial role in the pathogenesis of ELS-induced IBS. A recent study using a maternal separation (MS) animal model mimicking ELS showed that MS induced expansion of intestinal stem cells and their differentiation toward secretory lineages, including ECs, leading to ECs hyperplasia, increased 5-HT production, and visceral hyperalgesia. This suggests that ELS-induced IBS may be associated with increased ECs-5-HT signaling. Furthermore, ECs are closely related to corticotropin-releasing hormone, mast cells, neuron growth factor, bile acids, and SCFAs, all of which contribute to the pathogenesis of IBS. Collectively, ECs may play a role in the pathogenesis of ELS-induced IBS. Therefore, this review summarizes the physiological function of ECs and focuses on their potential role in the pathogenesis of IBS based on clinical and pre-clinical evidence.
Cognitive Impairment Early After Initiating Maintenance Hemodialysis: A Cross Sectional Study
Authors: Schorr Melissa , Zalitach Mariah , House Cindy , Gomes Janice , Wild Conor J. , Salerno Fabio R. , McIntyre Christopher
Published: March 2022

Background

Abnormalities in cognitive function are almost universal in patients receiving hemodialysis (HD) and are associated with worse quality of life, impaired decision making, increased healthcare utilization and mortality. While cognitive impairment in the HD population is increasingly recognized, it is unclear how quickly it develops after starting HD.

Methods

This was a cross-sectional study of a cohort of low dialysis vintage HD patients (<12 months). We used the validated Cambridge Brain Science (CBS) battery of web-based tests to evaluate cognition compared to age- and sex matched controls across three cognitive domains: verbal processing, reasoning and short-term memory.

Results

Forty-nine HD patients were included in this study; 43 completed the full battery of tests. The average scores for HD patients were consistently below the age and sex-matched controls. Fifty-five percent of HD patients had cognitive impairment in verbal skills, 43% in reasoning and 18% in short-term memory.

Conclusions

There is a high prevalence of CI evident early after starting HD, with the largest deficits seen in reasoning and verbal processing. These deficits may be attributable to the HD treatment itself. Further studies are needed to characterize the natural history of CI in this patient population and to test interventions aimed at preventing or slowing its progression.
Brain Functional Connectivity in de novo Parkinson's Disease Patients Based on Clinical EEG
Authors: Conti Matteo , Bovenzi Roberta , Garasto Elena , Schirinzi Tommaso , Placidi Fabio , Mercuri Nicola B. , Cerroni Rocco , Pierantozzi Mariangela , Stefani Alessandro
Published: March 2022

In Parkinson's disease (PD), cortical–subcortical interplay plays a relevant role in affecting clinical performance. Functional MRI sequences described changes in functional connectivity at different stages of disease. Scarce are, instead, the investigations examining brain connectivity in patients with PD at early stages of disease. For this aim, here we analyzed the differences in functional connectivity between de novo, never treated, PD patients and healthy controls. The analyses were based upon custom-written scripts on the Matlab platform, combined with high-level functions of Fieldtrip, Brainstorm, and Brain Connectivity toolboxes. First, we proceeded to the spectral analysis of the EEG data in the five frequency bands (δ-θ-α-β-γ). Second, we calculated functional connectivity matrices based on both coherency (COH) and imaginary part of coherency (iCOH), in the δ-θ-α-β-γ frequency bands. Then, four network measures (density, transitivity, global efficiency, and assortativity) were computed in identified connectivity matrices. Finally, we compared the spectral density, functional connectivity matrices, and network measured between healthy controls and de novo PD patients through two-samples T-test. A total of 21 de novo PD patients and 20 healthy subjects were studied. No differences were observed in spectral analysis between the two groups, with the exception of the γ band where a significant increase in power density was found in PD patients. A reduced connectivity in the main EEG frequency bands (α-β frequency bands) was observed in PD patients compared to controls, while a hyperconnectivity was found in PD patients in γ band. Among the network measures, a reduced assortativity coefficient was found in de novo PD patients in α frequency band. Our results show the occurrence of early EEG functional connectivity alterations from the initial stages of PD. From this point of view, connectivity analysis may ease a better understanding of the complexity of PD physiopathology.
Aberrant Cerebral Iron Trafficking Co-morbid With Chronic Inflammation: Molecular Mechanisms and Pharmacologic Intervention
Authors: Rosenblum Shaina L. , Kosman Daniel J.
Published: March 2022

The redox properties that make iron an essential nutrient also make iron an efficient pro-oxidant. Given this nascent cytotoxicity, iron homeostasis relies on a combination of iron transporters, chaperones, and redox buffers to manage the non-physiologic aqueous chemistry of this first-row transition metal. Although a mechanistic understanding of the link between brain iron accumulation (BIA) and neurodegenerative diseases is lacking, BIA is co-morbid with the majority of cognitive and motor function disorders. The most prevalent neurodegenerative disorders, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple System Atrophy (MSA), and Multiple Sclerosis (MS), often present with increased deposition of iron into the brain. In addition, ataxias that are linked to mutations in mitochondrial-localized proteins (Friedreich's Ataxia, Spinocerebellar Ataxias) result in mitochondrial iron accumulation and degradation of proton-coupled ATP production leading to neuronal degeneration. A comorbidity common in the elderly is a chronic systemic inflammation mediated by primary cytokines released by macrophages, and acute phase proteins (APPs) released subsequently from the liver. Abluminal inflammation in the brain is found downstream as a result of activation of astrocytes and microglia. Reasonably, the iron that accumulates in the brain comes from the cerebral vasculatureviathe microvascular capillary endothelial cells whose tight junctions represent the blood-brain barrier. A premise amenable to experimental interrogation is that inflammatory stress alters both the trans- and para-cellular flux of iron at this barrier resulting in a net accumulation of abluminal iron over time. This review will summarize the evidence that lends support to this premise; indicate the mechanisms that merit delineation; and highlight possible therapeutic interventions based on this model.
Functional Connectivity Analysis and Detection of Mental Fatigue Induced by Different Tasks Using Functional Near-Infrared Spectroscopy
Authors: Peng Yaoxing , Li Chunguang , Chen Qu , Zhu Yufei , Sun Lining
Published: March 2022

Objectives

The objective of this study was to investigate common functional near-infrared spectroscopy (fNIRS) features of mental fatigue induced by different tasks. In addition to distinguishing fatigue from non-fatigue state, the early signs of fatigue were also studied so as to give an early warning of fatigue.

Methods

fNIRS data from 36 participants were used to investigate the common character of functional connectivity network corresponding to mental fatigue, which was induced by psychomotor vigilance test (PVT), cognitive work, or simulated driving. To analyze the network reorganizations quantitatively, clustering coefficient, characteristic path length, and small worldness were calculated in five sub-bands (0.6–2.0, 0.145–0.600, 0.052–0.145, 0.021–0.052, and 0.005–0.021 Hz). Moreover, we applied a random forest method to classify three fatigue states.

Results

In a moderate fatigue state: the functional connectivity strength between brain regions increased overall in 0.021–0.052 Hz, and an asymmetrical pattern of connectivity (right hemisphere > left hemisphere) was presented. In 0.052–0.145 Hz, the connectivity strength decreased overall, the clustering coefficient decreased, and the characteristic path length increased significantly. In severe fatigue state: in 0.021–0.052 Hz, the brain network began to deviate from a small-world pattern. The classification accuracy of fatigue and non-fatigue was 85.4%. The classification accuracy of moderate fatigue and severe fatigue was 82.8%.

Conclusion

The preliminary research demonstrates the feasibility of detecting mental fatigue induced by different tasks, by applying the functional network features of cerebral hemoglobin signal. This universal and robust method has the potential to detect early signs of mental fatigue and prevent relative human error in various working environments.
Diagnosis of Sleep Apnoea Using a Mandibular Monitor and Machine Learning Analysis: One-Night Agreement Compared to in-Home Polysomnography
Authors: Kelly Julia L. , Ben Messaoud Raoua , Joyeux-Faure Marie , Terrail Robin , Tamisier Renaud , Martinot Jean-Benoît , Le-Dong Nhat-Nam , Morrell Mary J. , Pépin Jean-Louis
Published: March 2022

Background

The capacity to diagnose obstructive sleep apnoea (OSA) must be expanded to meet an estimated disease burden of nearly one billion people worldwide. Validated alternatives to the gold standard polysomnography (PSG) will improve access to testing and treatment. This study aimed to evaluate the diagnosis of OSA, using measurements of mandibular movement (MM) combined with automated machine learning analysis, compared to in-home PSG.

Methods

40 suspected OSA patients underwent single overnight in-home sleep testing with PSG (Nox A1, ResMed, Australia) and simultaneous MM monitoring (Sunrise, Sunrise SA, Belgium). PSG recordings were manually analysed by two expert sleep centres (Grenoble and London); MM analysis was automated. The Obstructive Respiratory Disturbance Index calculated from the MM monitoring (MM-ORDI) was compared to the PSG (PSG-ORDI) using intraclass correlation coefficient and Bland-Altman analysis. Receiver operating characteristic curves (ROC) were constructed to optimise the diagnostic performance of the MM monitor at different PSG-ORDI thresholds (5, 15, and 30 events/hour).

Results

31 patients were included in the analysis (58% men; mean (SD) age: 48 (15) years; BMI: 30.4 (7.6) kg/m2). Good agreement was observed between MM-ORDI and PSG-ORDI (median bias 0.00; 95% CI −23.25 to + 9.73 events/hour). However, for 15 patients with no or mild OSA, MM monitoring overestimated disease severity (PSG-ORDI < 5: MM-ORDI mean overestimation + 5.58 (95% CI + 2.03 to + 7.46) events/hour; PSG-ORDI > 5–15: MM-ORDI overestimation + 3.70 (95% CI −0.53 to + 18.32) events/hour). In 16 patients with moderate-severe OSA (n = 9 with PSG-ORDI 15–30 events/h and n = 7 with a PSG-ORD > 30 events/h), there was an underestimation (PSG-ORDI > 15: MM-ORDI underestimation −8.70 (95% CI −28.46 to + 4.01) events/hour). ROC optimal cut-off values for PSG-ORDI thresholds of 5, 15, 30 events/hour were: 9.53, 12.65 and 24.81 events/hour, respectively. These cut-off values yielded a sensitivity of 88, 100 and 79%, and a specificity of 100, 75, 96%. The positive predictive values were: 100, 80, 95% and the negative predictive values 89, 100, 82%, respectively.

Conclusion

The diagnosis of OSA, using MM with machine learning analysis, is comparable to manually scored in-home PSG. Therefore, this novel monitor could be a convenient diagnostic tool that can easily be used in the patients’ own home.

Clinical Trial Registration

https://clinicaltrials.gov, identifier NCT04262557
Psychedelic Cognition—The Unreached Frontier of Psychedelic Science
Authors: Bălăeţ Maria
Published: March 2022

Psychedelic compounds hold the promise of changing the face of neuroscience and psychiatry as we know it. There have been numerous proposals to use them to treat a range of neuropsychiatric conditions such as depression, anxiety, addiction and PTSD; and trials to date have delivered positive results in favor of the novel therapeutics. Further to the medical use, the wider healthy population is gaining interest in these compounds. We see a surge in personal use of psychedelic drugs for reasons not limited to spiritual enhancement, improved productivity, aiding the management of non-pathological anxiety and depression, and recreational interests. Notably, microdosing—the practice of taking subacute doses of psychedelic compounds—is on the rise. Our knowledge about the effects of psychedelic compounds, however, especially in naturalistic settings, is still fairly limited. In particular, one of the largest gaps concerns the acute effects on cognition caused by psychedelics. Studies carried out to date are riddled with limitations such as having disparate paradigms, small sample sizes, and insufficient breadth of testing on both unhealthy and healthy volunteers. Moreover, the studies are majoritarily limited to laboratory settings and do not assess the effects at multiple dosages within the same paradigm nor at various points throughout the psychedelic experience. This review aims to summarize the studies to date in relation to how psychedelics acutely affect different domains of cognition. In the pursuit of illuminating the current limitations and offering long-term, forward-thinking solutions, this review compares and contrasts findings related to how psychedelics impact memory, attention, reasoning, social cognition, and creativity.
Dysautonomia in Parkinson’s Disease: Impact of Glucocerebrosidase Gene Mutations on Cardiovascular Autonomic Control
Authors: Carandina Angelica , Lazzeri Giulia , Rodrigues Gabriel Dias , Franco Giulia , Monfrini Edoardo , Arienti Federica , Frattini Emanuele , Trezzi Ilaria , da Silva Soares Pedro Paulo , Bellocchi Chiara , Furlan Ludovico , Montano Nicola , Di Fonzo Alessio , Tobaldini Eleonora
Published: March 2022

Evidence from clinical practice suggests that PD patients with the Glucocerebrosidase gene mutations (GBA-PD) are characterized by more severe dysautonomic symptoms than patients with idiopathic PD (iPD). Therefore, an accurate assessment of cardiovascular autonomic control (CAC) is necessary to clarify the role of GBA mutations in the pathophysiology of PD. We evaluated the CAC at rest and during orthostatic challenge of 15 iPD, 15 GBA-PD and 15 healthy controls (CTR). ECG and respiration were recorded in supine position and during active standing. The analysis of Heart Rate Variability (HRV) was performed on ECG recordings using two different approaches, linear spectral analysis and non-linear symbolic analysis. GBA-PD patients presented more frequently an akinetic-rigid phenotype and cognitive dysfunction than iPD patients. Both iPD and GBA-PD group were characterized by a lower spectral HRV than CTR group. At rest, the GBA-PD group was characterized by a lower parasympathetic modulation and a shift of the sympathovagal balance toward a sympathetic predominance compared to the CTR group. Moreover, the GBA-PD patients presented a lower HR increment and a lower or absent reduction of the vagal modulation in response to the active standing than iPD patients. Lastly, the cardiovascular autonomic dysfunction in PD patients was associated with longer disease duration, and with the occurrence of REM sleep behavior disorder and constipation. Our findings suggest a more severe impairment of the CAC in PD patients with GBA mutations. These results and further studies on the role of GBA mutations could allow a stratification based on cardiovascular risk in PD patients and the implementation of specific prevention programs.
Microalgae Bioactive Carbohydrates as a Novel Sustainable and Eco-Friendly Source of Prebiotics: Emerging Health Functionality and Recent Technologies for Extraction and Detection
Authors: Gouda Mostafa , Tadda Musa A. , Zhao Yinglei , Farmanullah F. , Chu Bingquan , Li Xiaoli , He Yong
Published: March 2022

There is a global interest in the novel consumption, nutritional trends, and the market of new prebiotic sources and their potential functional impacts. Commercially available nutritional supplements based on microalgae that are approved to be edible by FDA, like Arthrospira platensis (Cyanobacteria) and Chlorella vulgaris (Chlorophyta) become widely attractive. Microalgae are rich in carbohydrates, proteins, and polyunsaturated fatty acids that have high bioactivity. Recently, scientists are studying the microalgae polysaccharides (PS) or their derivatives (as dietary fibers) for their potential action as a novel prebiotic source for functional foods. Besides, the microalgae prebiotic polysaccharides are used for medication due to their antioxidant, anticancer, and antihypertensive bioactivities. This review provides an overview of microalgae prebiotics and other macromolecules’ health benefits. The phytochemistry of various species as alternative future sources of novel polysaccharides were mentioned. The application as well as the production constraints and multidisciplinary approaches for evaluating microalgae phytochemistry were discussed. Additionally, the association between this potential of combining techniques like spectroscopic, chromatographic, and electrochemical analyses for microalgae sensation and analysis novelty compared to the chemical methods was emphasized.
Association of Serum Adipokines and Resting Energy Expenditure in Patients With Chronic Kidney Disease
Authors: Abi Nanzha , Xu Xiao , Yang Zhikai , Ma Tiantian , Dong Jie
Published: March 2022

Background and Aim

Metabolic disorders are prevalent in patients with chronic kidney disease (CKD) and may lead to protein energy wasting (PEW). Adipokines improve connections between PEW and energy metabolism. We aimed to determine the relationship between adipokine levels and resting energy expenditure (REE) in patients with CKD.

Methods

A total of 208 patients in non-dialyzed CKD stages 3–5 were enrolled in this cross-sectional study. Serum adipokines (leptin, adiponectin, and interleukin 6 (IL-6) were measured using enzyme-linked immunosorbent assay. Patient's REE was measured using indirect calorimetry. Fat mass (FM) and lean tissue mass (LTM) were measured using multiple-frequency bioimpedance analysis. Spearman correlation analyses and multivariate linear regression models were used to assess the association between serum adipokines and REE.

Results

The mean age was 52.7 ± 14.6 years, and 26.9, 26.4, and 46.7% of our participants had CKD stages 3, 4, and 5, respectively. The median values of serum adiponectin, leptin, and IL-6 were 470.4 (range, 291.1–802.2), 238.1 (range, 187.9–418.4), and 4.0 (range, 2.4–9.5) pg/mL, respectively. The male participants had significantly lower FM% (P = 0.001) and lower leptin levels (P < 0.001) than the female participants. After adjusting for age, diabetes, high-sensitivity C-reactive protein, intact parathyroid hormone, LTM, and FM, multiple linear regression analysis revealed that serum leptin levels were significantly positively associated with REE in men rather than in women (P < 0.05). Serum adiponectin levels were inversely associated with REE in men, but this association disappeared while FM was additionally adjusted. Adiponectin levels in women were not correlated with REE (P > 0.05). IL-6 was not significantly associated with REE in either men or women.

Conclusions

A sex-specific relationship between serum adipokines (leptin and adiponectin) and REE was observed in patients with CKD stages 3–5, which was partly confounded by FM.
Three Nutritional Indices Are Effective Predictors of Mortality in Patients With Type 2 Diabetes and Foot Ulcers
Authors: Hong Jing , Huang Qi-Qi , Liu Wen-Yue , Hu Xiang , Jiang Fei-Fei , Xu Ze-Ru , Shen Fei-Xia , Zhu Hong
Published: March 2022

Introduction

Malnutrition has been associated with mortality in various diseases. This retrospective cohort study aimed to investigate the relationship between three nutritional indices and all-cause mortality in patients with diabetic foot ulcers (DFUs).

Materials and Methods

A total of 771 patients diagnosed with DFUs in the First Affiliated Hospital of Wenzhou Medical University from 2015 to 2019 were included in this retrospective cohort study. Patients were classified as high nutritional risk groups or low nutritional risk groups according to the optimal cut-off values of the geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status (CONUT), respectively. The associations of three nutritional indices with all-cause mortality were evaluated by multivariable Cox regression analyses.

Results

Log-rank tests indicated that patients with high nutritional risk had lower overall survival rates (all p < 0.001). The multivariable Cox regression revealed that low GNRI (adjusted HR 2.01, 95% CI: 1.37–2.96, P < 0.001), low PNI (adjusted HR 2.04, 95% CI: 1.29–3.23, P = 0.002) and high CONUT (adjusted HRs 1.54, 95% CI: 1.07–2.23, P = 0.021) were independently associated with high all-cause mortality. In subgroup analyses, only GNRI predicted higher all-cause mortality in patients with severe DFUs, while all of the three indices persisted as independent prognostic factors in patients with no severe DFUs.

Discussion

The present study demonstrated that three nutritional indices were effective predictors of all-cause mortality in patients with DFUs. Routine screening for malnutrition using any of the three nutritional indices might be a simple and effective way to identify high-risk patients with DFUs. GNRI can be used as an independent prognostic indicator in patients with severe DFUs.
Associations of Dietary Copper, Selenium, and Manganese Intake With Depression: A Meta-Analysis of Observational Studies
Authors: Ding Jun , Zhang Yi
Published: March 2022

Objective

To comprehensively summarize the evidence on the associations of dietary copper, selenium, and manganese intake with depression based on a meta-analysis of observational studies.

Methods

The electronic database of PubMed, Web of Science, and Embase were searched up to January 7, 2022, for observational studies on the associations of dietary copper, selenium and manganese intake with depression (no restriction was set for the initiate time). The pooled relative risk (RR) of depression for the highest vs. lowest dietary copper, selenium, and manganese intake category were calculated.

Results

A total of 11 observational studies (61,430 participants) were identified as meeting the inclusion criteria. Specifically, five studies were related to the dietary copper intake. The overall multi-variable adjusted RR demonstrated that dietary copper intake was inversely associated with depression (RR = 0.63, 95% CI: 0.52–0.76; P < 0.001; I2 = 2.4%). With regard to the dietary selenium intake, six studies were identified for meta-analysis. The overall multi-variable adjusted RR showed that dietary selenium intake was also negatively associated with depression (RR = 0.63, 95% CI: 0.54–0.74; P < 0.001; I2 = 37.8%). In addition, four studies were specified for the dietary manganese intake, and the overall multi-variable adjusted RR indicated a negative relationship between dietary manganese intake and depression (RR = 0.71, 95% CI: 0.58–0.86; P < 0.001; I2 = 0.0%).

Conclusions

Our results suggest a negative relationship between dietary copper, selenium and manganese intake and depression, respectively. However, due to the limited prospective evidence, our results are restricted to cross-sectional design that precludes causal relationships. More well-designed prospective cohort studies are still needed.
Search for Key Genes and Functional Pathways of Ulcerative Colitis to Colon Cancer Based on Bioinformatics
Authors: Wang Shengbao , Zhen Lingling , Li Xiaoli , Fu Xu , Li Peiwu , Zhang Dekui
Published: March 2022

Ulcerative colitis (UC) is a persistent and diffuse inflammatory disease of the intestine. It is widely prevalent in developed countries. Approximately 30% of patients with UC suffer from widespread and aggressive colitis and are at increased risk of colon cancer. In this study, the genetic features and potential molecular mechanisms shared between UC and colorectal cancer were investigated. The datasets from GEO and TCGA were analyzed to obtain differentially expressed genes, of which there were 116 overlapping genes. A module containing 15 genes was obtained using String and Cytoscape to analyze the module and identify hub genes. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules associated with UC and colon cancer, with 52 overlapping genes. Functional clustering of the two gene cohorts was performed using the Metascape online tool, with three significant functions or pathways associated with both gene cohorts. A total of 19 key genes were included, and CCT2 was identified after expression and survival analyses. CCT2 is highly expressed in colon cancer and lowly expressed in UC, and its low expression is associated with a poor prognostic ratio. This study reveals, for the first time, that CCT2 may be a promoter of UC transformation into colon cancer and identifies new gene candidates that could be used as biomarkers or potential therapeutic targets.
Clinical Applications of Circulating Tumour Cells and Circulating Tumour DNA in Non-Small Cell Lung Cancer—An Update
Authors: Kapeleris Joanna , Ebrahimi Warkiani Majid , Kulasinghe Arutha , Vela Ian , Kenny Liz , Ladwa Rahul , O’Byrne Kenneth , Punyadeera Chamindie
Published: March 2022

Despite efforts to improve earlier diagnosis of non-small cell lung cancer (NSCLC), most patients present with advanced stage disease, which is often associated with poor survival outcomes with only 15% surviving for 5 years from their diagnosis. Tumour tissue biopsy is the current mainstream for cancer diagnosis and prognosis in many parts of the world. However, due to tumour heterogeneity and accessibility issues, liquid biopsy is emerging as a game changer for both cancer diagnosis and prognosis. Liquid biopsy is the analysis of tumour-derived biomarkers in body fluids, which has remarkable advantages over the use of traditional tumour biopsy. Circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) are two main derivatives of liquid biopsy. CTC enumeration and molecular analysis enable monitoring of cancer progression, recurrence, and treatment response earlier than traditional biopsy through a minimally invasive liquid biopsy approach. CTC-derived ex-vivo cultures are essential to understanding CTC biology and their role in metastasis, provide a means for personalized drug testing, and guide treatment selection. Just like CTCs, ctDNA provides opportunity for screening, monitoring, treatment evaluation, and disease surveillance. We present an updated review highlighting the prognostic and therapeutic significance of CTCs and ctDNA in NSCLC.
Explicating Child-Driven Patterns of Parent-Child Responsivity in Fragile Families: A Longitudinal Approach
Authors: Blume Jessica , Park SuJung , Cox Miranda , Mastergeorge Ann M.
Published: March 2022

It has been well-established that development occurs in the context of a transactional framework, with bidirectional parent-child interactions influencing both proximal and distal outcomes. In particular, child vocabulary development is sensitive to parenting qualities including warmth, sensitivity, and control as well as parental stimulation including language input and access to learning enrichment activities. Similarly, these parenting qualities are influenced by and influence children's development of pro-social behaviors. Given the foundational role of both language and pro-social skills for academic achievement and the establishment of healthy relationships across the lifespan, a comprehensive understanding of the magnitude, stability, and reciprocity of such interactions across childhood has the potential to better inform early intervention and prevention practices and highlight risk and resilience factors. This study investigated the concurrent and successive transactional relationships between child pro-social behavior, child emergent language, and parenting qualities within a large, longitudinal sample. This study utilized Waves 3, 4, and 5 of the Fragile Families and Child Well Being Study (FFCWBS), corresponding to focal child age 3, 5, and 9 years, respectively. A series of Structural Equation Modeling (SEM) with full-information likelihood (FIML) estimation (n = 3,422) including child prosocial behavior, receptive vocabulary, and supportive parenting behaviors was tested and compared. Our findings indicate significant, positive associations over time between child pro-social behavior and receptive vocabulary, and parenting quality across all three stages of early child development. The steady decline in magnitude of these associations over time highlights the importance of synergistic parent-child interactions in toddlerhood as an early opportunity to propel these developmental outcomes and supportive parenting behaviors. Patterns of change in child pro-social behavior skills and parenting qualities remained positive and relatively stable, while observed growth in child receptive vocabulary skills increased in magnitude over time. Additional investigation of indirect effects specified the role of receptive vocabulary, as well as the bolstering role of prosocial behavior, in eliciting responsive parenting qualities over time.
Gypenoside L and Gypenoside LI Inhibit Proliferation in Renal Cell Carcinoma via Regulation of the MAPK and Arachidonic Acid Metabolism Pathways
Authors: Liu Hui , Li Xiuming , Xie Jinbo , Lv Chengcheng , Lian Fangchao , Zhang Shouyi , Duan Yu , Zeng Yu , Piao Xianglan
Published: March 2022

Renal cell carcinoma (RCC) has the highest mortality rate of all urological malignancies. Clear cell renal cell carcinoma (ccRCC) accounts for approximately 80% of all RCC cases and is often accompanied by the accumulation of lipid droplets. Growing evidence indicates that ccRCC is a metabolism-related disease. Gypenosides are commonly used for the clinical treatment of hyperlipidemia, and their antitumor activity has also been recognized. However, the potential inhibitory effects and mechanisms of action of gypenoside L (Gyp L) and gypenoside LI (Gyp LI) in ccRCC remain unclear. In this study, we confirmed that Gyp L and Gyp LI significantly inhibited proliferation and induced apoptosis in ccRCC cells in vitro. We performed network pharmacology and RNA-seq, and verified the results by Western blotting, RT-qPCR, and immunofluorescence experiments. Our results demonstrated that Gyp L and Gyp LI upregulate the expression of COX2 and downregulate the expression levels of cPLA2 and CYP1A1, resulting in reduced arachidonic acid and apoptosis. Gyp L and Gyp LI upregulated the protein levels of DUSP1, p-JUN, and p-JNK, and downregulated p-MEK1/2, p-ERK, and p-P38 levels. Moreover, gypenosides significantly inhibited tumor growth in vivo, and gypenosides significantly reduced cPLA2 and CYP1A1 expression. Furthermore, we performed absolute quantification of arachidonic acid (AA) content in ccRCC cells and tumor tissues by HPLC-MS, and found that the arachidonic acid content was significantly reduced after Gyp L, Gyp LI, and gypenoside intervention. In conclusion, our data suggest that Gyp L, Gyp LI, and gypenosides decrease the content of arachidonic acid in ccRCC cells and tumor tissues, but do not have cytotoxic effects on nude mice. Thus, Gyp L, Gyp LI, and total gypenosides extracted from Gynostemma pentaphyllum exhibited antitumor activities against ccRCC.