bluuebunny/crossref_metadata_2025 huggingface dataset:
Questions and controversies surrounding the perception and neural coding of pitch
Authors: Oxenham Andrew J.
Published: January 2023

Pitch is a fundamental aspect of auditory perception that plays an important role in our ability to understand speech, appreciate music, and attend to one sound while ignoring others. The questions surrounding how pitch is represented in the auditory system, and how our percept relates to the underlying acoustic waveform, have been a topic of inquiry and debate for well over a century. New findings and technological innovations have led to challenges of some long-standing assumptions and have raised new questions. This article reviews some recent developments in the study of pitch coding and perception and focuses on the topic of how pitch information is extracted from peripheral representations based on frequency-to-place mapping (tonotopy), stimulus-driven auditory-nerve spike timing (phase locking), or a combination of both. Although a definitive resolution has proved elusive, the answers to these questions have potentially important implications for mitigating the effects of hearing loss via devices such as cochlear implants.
New insights into the regulation of Cystathionine beta synthase (CBS), an enzyme involved in intellectual deficiency in Down syndrome
Authors: Conan Pierre , Léon Alice , Caroff Noéline , Rollet Claire , Chaïr Loubna , Martin Jennifer , Bihel Frédéric , Mignen Olivier , Voisset Cécile , Friocourt Gaëlle
Published: January 2023

Down syndrome (DS), the most frequent chromosomic aberration, results from the presence of an extra copy of chromosome 21. The identification of genes which overexpression contributes to intellectual disability (ID) in DS is important to understand the pathophysiological mechanisms involved and develop new pharmacological therapies. In particular, gene dosage of Dual specificity tyrosine phosphorylation Regulated Kinase 1A (DYRK1A) and of Cystathionine beta synthase (CBS) are crucial for cognitive function. As these two enzymes have lately been the main targets for therapeutic research on ID, we sought to decipher the genetic relationship between them. We also used a combination of genetic and drug screenings using a cellular model overexpressing CYS4, the homolog of CBS in Saccharomyces cerevisiae, to get further insights into the molecular mechanisms involved in the regulation of CBS activity. We showed that overexpression of YAK1, the homolog of DYRK1A in yeast, increased CYS4 activity whereas GSK3β was identified as a genetic suppressor of CBS. In addition, analysis of the signaling pathways targeted by the drugs identified through the yeast-based pharmacological screening, and confirmed using human HepG2 cells, emphasized the importance of Akt/GSK3β and NF-κB pathways into the regulation of CBS activity and expression. Taken together, these data provide further understanding into the regulation of CBS and in particular into the genetic relationship between DYRK1A and CBS through the Akt/GSK3β and NF-κB pathways, which should help develop more effective therapies to reduce cognitive deficits in people with DS.
On separating long- and short-term memories in hyperdimensional computing
Authors: Teeters Jeffrey L. , Kleyko Denis , Kanerva Pentti , Olshausen Bruno A.
Published: January 2023

Operations on high-dimensional, fixed-width vectors can be used to distribute information from several vectors over a single vector of the same width. For example, a set of key-value pairs can be encoded into a single vector with multiplication and addition of the corresponding key and value vectors: the keys are bound to their values with component-wise multiplication, and the key-value pairs are combined into a single superposition vector with component-wise addition. The superposition vector is, thus, a memory which can then be queried for the value of any of the keys, but the result of the query is approximate. The exact vector is retrieved from a codebook (a.k.a. item memory), which contains vectors defined in the system. To perform these operations, the item memory vectors and the superposition vector must be the same width. Increasing the capacity of the memory requires increasing the width of the superposition and item memory vectors. In this article, we demonstrate that in a regime where many (e.g., 1,000 or more) key-value pairs are stored, an associative memory which maps key vectors to value vectors requires less memory and less computing to obtain the same reliability of storage as a superposition vector. These advantages are obtained because the number of storage locations in an associate memory can be increased without increasing the width of the vectors in the item memory. An associative memory would not replace a superposition vector as a medium of storage, but could augment it, because data recalled from an associative memory could be used in algorithms that use a superposition vector. This would be analogous to how human working memory (which stores about seven items) uses information recalled from long-term memory (which is much larger than the working memory). We demonstrate the advantages of an associative memory experimentally using the storage of large finite-state automata, which could model the storage and recall of state-dependent behavior by brains.
Early different cognitive processes evoked by carnival vs. general promotions when shopping online: An ERPs study
Authors: Han Wei , Zhang Xuefeng
Published: January 2023

Introduction

The booming development of online shopping has intensified market competition. In addition to general sales promotions, online shopping has introduced new changes including artificial carnival promotions.

Method

This study aims to investigate cognitive processes to an unknown e-commerce platform after exposure to carnival and general promotion activities using event-related potentials. Thirty-three participants were recruited in this study to probe how consumers perceive carnival and general promotion information using event-related potentials (ERPs). Carnival or general promotion posters were presented first, then an unknown e-commerce platform brand was presented in the second stage, at which time the subjects’ cognitive process to the brand were observed in an implicit paradigm.

Results

The results showed that after priming with carnival promotion posters, the unknown e-commerce platform stimuli elicited larger P2 and N2 components than were observed after the presentation of general promotion posters; however, the P3 component did not show a significant difference. These findings indicate that the target identification and cognitive control mechanism with regard to an unknown e-commerce platform are likely influenced by the implicit memory of different promotion activities when shopping online.

Discussion

The results suggest that ERP components may have the potential to be employed as indices to estimate the effectiveness of promotion methods for an unknown brand.
GAT inhibition preserves cerebral blood flow and reduces oxidant damage to mitochondria in rodents exposed to extreme hyperbaric oxygen
Authors: Demchenko Ivan T. , Suliman Hagir B. , Zhilyaey Sergey Y. , Alekseeva Olga S. , Platonova Tatyana F. , Makowski Matthew S. , Piantadosi Claude A. , Gasier Heath G.
Published: January 2023

Oxygen breathing at elevated partial pressures (PO2’s) at or more than 3 atmospheres absolute (ATA) causes a reduction in brain γ-aminobutyric acid (GABA) levels that impacts the development of central nervous system oxygen toxicity (CNS-OT). Drugs that increase brain GABA content delay the onset of CNS-OT, but it is unknown if oxidant damage is lessened because brain tissue PO2 remains elevated during hyperbaric oxygen (HBO2) exposures. Experiments were performed in rats and mice to measure brain GABA levels with or without GABA transporter inhibitors (GATs) and its influence on cerebral blood flow, oxidant damage, and aspects of mitochondrial quality control signaling (mitophagy and biogenesis). In rats pretreated with tiagabine (GAT1 inhibitor), the tachycardia, secondary rise in mean arterial blood pressure, and cerebral hyperemia were prevented during HBO2 at 5 and 6 ATA. Tiagabine and the nonselective GAT inhibitor nipecotic acid similarly extended HBO2 seizure latencies. In mice pretreated with tiagabine and exposed to HBO2 at 5 ATA, nuclear and mitochondrial DNA oxidation and astrocytosis was attenuated in the cerebellum and hippocampus. Less oxidant injury in these regions was accompanied by reduced conjugated microtubule-associated protein 1A/1B-light chain 3 (LC3-II), an index of mitophagy, and phosphorylated cAMP response element binding protein (pCREB), an initiator of mitochondrial biogenesis. We conclude that GABA prevents cerebral hyperemia and delays neuroexcitation under extreme HBO2, limiting oxidant damage in the cerebellum and hippocampus, and likely lowering mitophagy flux and initiation of pCREB-initiated mitochondrial biogenesis.
Lack of iron, zinc, and vitamins as a contributor to the etiology of atopic diseases
Authors: Peroni Diego G. , Hufnagl Karin , Comberiati Pasquale , Roth-Walter Franziska
Published: January 2023

Micronutritional deficiencies are common in atopic children suffering from atopic dermatitis, food allergy, rhinitis, and asthma. A lack of iron, in particular, may impact immune activation with prolonged deficiencies of iron, zinc, vitamin A, and vitamin D associated with a Th2 signature, maturation of macrophages and dendritic cells (DCs), and the generation of IgE antibodies. In contrast, the sufficiency of these micronutrients establishes immune resilience, promotion of regulatory cells, and tolerance induction. As micronutritional deficiencies mimic an infection, the body’s innate response is to limit access to these nutrients and also impede their dietary uptake. Here, we summarize our current understanding of the physiological function of iron, zinc, and vitamins A and D in relation to immune cells and the clinical consequences of deficiencies in these important nutrients, especially in the perinatal period. Improved dietary uptake of iron is achieved by vitamin C, vitamin A, and whey compounds, whereas zinc bioavailability improves through citrates and proteins. The addition of oil is essential for the dietary uptake of beta-carotene and vitamin D. As for vitamin D, the major source comesviasun exposure and only a small amount is consumedviadiet, which should be factored into clinical nutritional studies. We summarize the prevalence of micronutritional deficiencies of iron, zinc, and vitamins in the pediatric population as well as nutritional intervention studies on atopic diseases with whole food, food components, and micronutrients. Dietary uptakeviathe lymphatic route seems promising and is associated with a lower atopy risk and symptom amelioration. This review provides useful information for clinical studies and concludes/emphasizes that a healthy, varied diet containing dairy products, fish, nuts, fruits, and vegetables as well as supplementing foods or supplementation with micronutrients as needed is essential to combat the atopic march.
Effect of almond consumption on insulin sensitivity and serum lipids among Asian Indian adults with overweight and obesity– A randomized controlled trial
Authors: Gayathri Rajagopal , Abirami Kuzhandhaivelu , Kalpana Natarajan , Manasa Valangaiman Sriram , Sudha Vasudevan , Shobana Shanmugam , Jeevan Raman Ganesh , Kavitha Vasudevan , Parkavi Karthikeyan , Anjana Ranjit Mohan , Unnikrishnan Ranjit , Gokulakrishnan Kuppan , Beatrice D. Annette , Krishnaswamy Kamala , Pradeepa Rajendra , Mattes Richard D. , Salas-Salvadó Jordi , Willett Walter , Mohan Viswanathan
Published: January 2023

Background

Asian Indians have an increased susceptibility to type 2 diabetes and premature coronary artery disease. Nuts, like almonds, are rich in unsaturated fat and micronutrients with known health benefits.

Objectives

This study aimed to assess the efficacy of almonds for reduction of insulin resistance and improving lipid profile in overweight Asian Indian adults.

Methods

This parallel-arm, randomized, controlled trial was conducted in Chennai, India on 400 participants aged 25–65 years with a body mass index ≥ 23 kg/m2. The intervention group received 43 g of almonds/day for 12 weeks, while the control group was advised to consume a customary diet but to avoid nuts. Anthropometric, clinical, and dietary data were assessed at periodic intervals. Glucose tolerance, serum insulin, glycated hemoglobin, C-peptide and lipid profile were assessed at baseline and end of the study. Insulin resistance (homeostasis assessment model-HOMA IR) and oral insulin disposition index (DIo) were calculated.

Results

A total of 352 participants completed the study. Significant improvement was seen in DIo [mean (95% CI) = + 0.7 mmol/L (0.1, 1.3);p= 0.03], HOMA IR (−0.4 (−0.7, −0.04;p= 0.03) and total cholesterol (−5.4 mg/dl (−10.2, −0.6);p= 0.03) in the intervention group compared to the control group. Incremental area under the curve (IAUC) and mean amplitude of glycemic excursion (MAGE) assessed using continuous glucose monitoring systems were also significantly lower in the intervention group. Dietary 24-h recalls showed a higher significant reduction in carbohydrate and increase in mono unsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) intake in the intervention group compared to the control group.

Conclusion

Daily consumption of almonds increased the intake of MUFA with decrease in carbohydrate calories and decreases insulin resistance, improves insulin sensitivity and lowers serum cholesterol in Asian Indians with overweight/obesity. These effects in the long run could aid in reducing the risk of diabetes and other cardiometabolic disease.
Raw potato starch alters the microbiome, colon and cecal gene expression, and resistance to Citrobacter rodentium infection in mice fed a Western diet
Authors: Smith Allen D. , Chen Celine , Cheung Lumei , Dawson Harry D.
Published: January 2023

Resistant starches (RS) are fermented in the cecum and colon to produce short-chain fatty acids and other microbial metabolites that can alter host physiology and the composition of the microbiome. We previously showed that mice fed a Total Western Diet (TWD) based on NHANES data that mimics the composition of a typical American diet, containing resistant potato starch (RPS), produced concentration dependent changes to the cecal short-chain fatty acids, the microbiome composition as well as gene expression changes in the cecum and colon that were most prevalent in mice fed the 10% RPS diet. We were then interested in whether feeding TWD/RPS would alter the resistance to bacterial-induced colitis caused by Citrobacter rodentium (Cr), a mouse pathogen that shares 66.7% of encoded genes with Enteropathogenic Escherichia coli. Mice were fed the TWD for 6 weeks followed by a 3-weeks on the RPS diets before infecting with Cr. Fecal Cr excretion was monitored over time and fecal samples were collected for 16S sequencing. Mice were euthanized on day 12 post-infection and cecal contents collected for 16S sequencing. Cecum and colon tissues were obtained for gene expression analysis, histology and to determine the level of mucosa-associated Cr. Feeding RPS increased the percentage of mice productively infected by Cr and fecal Cr excretion on day 4 post-infection. Mice fed the TWD/10% RPS diet also had greater colonization of colonic tissue at day 12 post-infection and colonic pathology. Both diet and infection altered the fecal and cecal microbiome composition with increased levels of RPS resulting in decreased α-diversity that was partially reversed by Cr infection. RNASeq analysis identified several mechanistic pathways that could be associated with the increased colonization of Cr-infected mice fed 10% RPS. In the distal colon we found a decrease in enrichment for genes associated with T cells, B cells, genes associated with the synthesis of DHA-derived SPMs and VA metabolism/retinoic acid signaling. We also found an increase in the expression of the potentially immunosuppressive gene, Ido1. These results suggest that high-level consumption of RPS in the context of a typical American diet, may alter susceptibility to gastrointestinal bacterial infections.
Effects of pretreatment with a combination of ultrasound and γ-aminobutyric acid on polyphenol metabolites and metabolic pathways in mung bean sprouts
Authors: Wang Lidong , Li Xiaoqiang , Gao Fei , Liu Ying , Lang Shuangjing , Wang Changyuan
Published: January 2023

Background

Polyphenols play an important role in human nutrition, therefore, how to improve its content with innovative approach is important, and understanding the metabolic pathys is necessary. Mung beans are rich in polyphenols, which made them have physiological functions such as hypoglycemia, antioxidant, and hypotension. However, the content of polyphenols in natural mung bean is relatively low, and it needs to be increased. The methods of increasing polyphenol content in grains and beans by enrichment include physical stress, such as ultrasonic stress, hypoxia stress and ultraviolet radiation, and single exogenous substance stress, such as exogenous amino acids, exogenous sugars. But, the enrichment of polyphenols using exogenous substances in combination with physical stress is less applied. Therefore, this study innovated the use of exogenous γ-aminobutyric acid (GABA) combined with ultrasonic stress to enrich mung bean sprouts polyphenols and enhance their content. The metabolic pathways of the enrichment process were also analyzed to provide a reference for studies related to the enrichment of polyphenols.

Methods

Mung bean seeds were pretreated with a combination of ultrasound and GABA under different conditions. Single-factor test and response surface methodology were used for optimizing pretreatment conditions of mung bean. Effects of combined pretreatments on the polyphenols content and antioxidant activity of sprouted mung beans were investigated. Additionally, metabolites were identified, and metabolic pathways were analyzed using non-targeted metabolomics techniques.

Results

Optimal conditions of mung bean pretreatment were found to be 370 W for ultrasound power, 40 min for ultrasonication time, 10 mmol/L for GABA concentration, and 8 h for the soaking duration. Under these conditions, the predicted polyphenol content was found to be 4.52 mg GAE/g DW. The pretreatment of mung beans with a combination of ultrasound and exogenous GABA resulted in mung bean sprouts with enhanced polyphenol content and antioxidant activity compared to mung beans germinated without pretreatment. A significant increase in the content of six polyphenols [Genistein, (-)-Epigallocatechin, Epicatechin, Nobiletin, Naringenin, Biochanin A] in the pretreated and germinated mung beans was found, and six metabolic pathways (flavonoid biosynthesis, isoflavones biosynthesis, biosynthesis of phenylpropanoids, anthocyanin biosynthesis, biosynthesis of secondary metabolites, and metabolic pathways) were significantly activated.

Conclusion

The obtained results suggest that a combination of ultrasound and exogenous GABA treatment can be used to produce mung bean sprouts with enriched polyphenols content and enhanced antioxidant activity.
Correlation analysis on physicochemical and structural properties of sorghum starch
Authors: Yan Shouxin , Li Zhao , Wang Bin , Li Tingting , Li Zhiyang , Zhang Nan , Cui Bo
Published: January 2023

This manuscript analyzed physicochemical and structural properties of 30 different types of sorghum starches based on their apparent amylose content (AAC). Current results confirmed that sorghum starch exhibited irregular spherical or polygonal granule shape with 14.5 μm average particle size. The AAC of sorghum starch ranged from 7.42 to 36.44% corresponding to relative crystallinities of 20.5 to 32.4%. The properties of enthalpy of gelatinization (ΔH), peak viscosity (PV), relative crystallinity (RC), degree of double helix (DD), degree of order (DO), and swelling power (SP) were negatively correlated with AAC, while the cool paste viscosity (CPV) and setback (SB) were positively correlated with AAC. Correlations analyzed was conducted on various physicochemical parameters. Using principal component analysis (PCA) with 20 variables, the difference between 30 different types of sorghum starch was displayed. Results of current study can be used to guide the selection and breeding of sorghum varieties and its application in food and non-food industries.
A novel bacteriocin isolated from Lactobacillus plantarum W3-2 and its biological characteristics
Authors: Wang Zengguang , Zhang Yixuan , Chen Chengcheng , Fan Shichao , Deng Fangming , Zhao Lingyan
Published: January 2023

In this study, screening bacteriocin-producing strains from 2,000 plant-derived strains by agar well diffusion method was conducted. The corresponding produced bacteriocin was purified and identified by Sephadex gel chromatography, reversed-phase high-performance liquid chromatography (RP-HPLC), and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Meanwhile, the biological characteristics of bacteriocin were investigated. The targeted strain W3-2 was obtained and identified as Lactobacillus plantarum by morphological observation and 16S rRNA gene sequence analysis. Correspondingly, a novel bacteriocin (named plantaricin W3-2) produced by L. plantarum W3-2 with a molecular weight of 618.26 Da, and an amino acid sequence of AVEEE was separated, purified by Sephadex gel chromatography and RP-HPLC, and identified by LC-MS/MS. Further characteristics analysis displayed that plantaricin W3-2 had good thermal, pH stability, and broad-spectrum antimicrobial ability. In conclusion, plantaricin W3-2 can be used as a new food preservative.
The different trends in the burden of neurological and mental disorders following dietary transition in China, the USA, and the world: An extension analysis for the Global Burden of Disease Study 2019
Authors: Liang Shan , Wang Li , Wu Xiaoli , Hu Xu , Wang Tao , Jin Feng
Published: January 2023

Introduction

The highly processed western diet is substituting the low-processed traditional diet in the last decades globally. Increasing research found that a diet with poor quality such as western diet disrupts gut microbiota and increases the susceptibility to various neurological and mental disorders, while a balanced diet regulates gut microbiota and prevents and alleviates the neurological and mental disorders. Yet, there is limited research on the association between the disease burden expanding of neurological and mental disorders with a dietary transition.

Methods

We compared the disability-adjusted life-years (DALYs) trend by age for neurological and mental disorders in China, in the United States of America (USA), and across the world from 1990 to 2019, evaluated the dietary transition in the past 60 years, and analyzed the association between the burden trend of the two disorders with the changes in diet composition and food production.

Results

We identified an age-related upward pattern in disease burden in China. Compared with the USA and the world, the Chinese neurological and mental disorders DALY percent was least in the generation over 75 but rapidly increased in younger generations and surpassed the USA and/or the world in the last decades. The age-related upward pattern in Chinese disease burdens had not only shown in the presence of cardiovascular diseases, neoplasms, and diabetes mellitus but also appeared in the presence of depressive disorders, Parkinson’s disease, Alzheimer’s disease and other dementias, schizophrenia, headache disorders, anxiety disorders, conduct disorders, autism spectrum disorders, and eating disorders, successively. Additionally, the upward trend was associated with the dramatic dietary transition including a reduction in dietary quality and food production sustainability, during which the younger generation is more affected than the older. Following the increase in total calorie intake, alcohol intake, ratios of animal to vegetal foods, and poultry meat to pulses, the burdens of the above diseases continuously rose. Then, following the rise of the ratios of meat to pulses, eggs to pulses, and pork to pulses, the usage of fertilizers, the farming density of pigs, and the burdens of the above disease except diabetes mellitus were also ever-increasing. Even the usage of pesticides was positively correlated with the burdens of Parkinson’s disease, schizophrenia, cardiovascular diseases, and neoplasms. Contrary to China, the corresponding burdens of the USA trended to reduce with the improvements in diet quality and food production sustainability.

Discussion

Our results suggest that improving diet quality and food production sustainability might be a promising way to stop the expanding burdens of neurological and mental disorders.
Clinical effect of nighttime snacking on patients with hepatitis B cirrhosis
Authors: Han Zuoqing , Li Rongkuan , Zhong Zhiwei , Piao Yuetong , Guo Rong
Published: January 2023

Objective

Nighttime snacking is an effective intervention to avoid abnormal protein consumption caused by prolonged fasting. This article aims to evaluate the clinical efficacy of nighttime snacking on patients with hepatitis B cirrhosis and to provide new ideas for clinical nutritional intervention.

Methods

The study participants were randomly assigned to the control group (n = 30) and the observation group (n = 30); the former was administered medical system treatment and routine dietary intervention, and the latter was administered the same treatment with the addition of nighttime snacking. After 3 months of intervention with different dietary guidance, the dry body weight body mass index (BMI), upper arm muscle circumference (AMC), grip strength, triceps skinfold thickness (TSF), third lumbar skeletal muscle index (L3-SMI), albumin (ALB), total bilirubin (T-BIL), cholinesterase (CHE), Fried's frailty phenotype score, Child–Pugh score and various cirrhosis complication rates were compared between the two groups.

Results

There was no significant difference in the baseline data between the two groups before the dietary intervention. After 3 months of regular dietary guidance in the control group, the grip strength increased compared with the baseline data (p < 0.05), while the dry body weight BMI, AMC, TSF, L3-SMI, ALB, T-BIL, CHE, prothrombin time, international normalized ratio, prothrombin activity, and Child–Pugh scores were not significantly different (p > 0.05). After 3 months of dietary guidance with nighttime snacking in the observation group, the dry body weight BMI, grip strength, TSF, L3-SMI, and CHE scores all increased, compared with the baseline data, while the Child–Pugh score decreased compared with the baseline level (all p < 0.05). After 3 months of intervention, the Child–Pugh score of the observation group showed a more significant decrease than the control group, while the dry body weight BMI, grip strength, ALB and CHE scores were all significantly higher than those in the control group (all p < 0.05). Overall, the improvement rate was significantly higher in the observation group than in the control group (p < 0.05).

Conclusion

Nighttime snacking for hepatitis B cirrhosis patients with nutritional risk is beneficial in terms of the recovery of liver synthesis functions, improvements in clinical indicators, sarcopenia corrections and improvements in malnutrition-related complications.
MIF promotes cell invasion by the LRP1-uPAR interaction in pancreatic cancer cells
Authors: Sun Huizhi , Cheng Runfen , Zhang Danfang , Guo Yuhong , Li Fan , Li Yanlei , Li Yue , Bai Xiaoyu , Mo Jing , Huang Chongbiao
Published: January 2023

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is characterized by high aggressiveness and a hypoxic tumour microenvironment. Macrophage migration inhibitory factor (MIF) is a hypoxia-related pleiotropic cytokine that plays important roles in cancer. However, its role in PDAC progression has not been fully elucidated.

Methods

The clinical significance of MIF and hypoxia inducible factor 1 subunit alpha (HIF1A) in PDAC was analysed using immunohistochemical staining on PDAC tissues and data from KM-Plotter database. Spatial distribution of MIF and HIF1A gene expression was visualized by spatial transcriptomics in PDAC cell xenografts. To monitor the role of MIF in PDAC cell malignancy, immunostaining, lentivirus shRNA, migration assays, flow cytometry, transcriptomics and in vivo tumorigenicity were performed.

Results

The spatial distribution of MIF and HIF1A was highly correlated and that high MIF expression was associated with poor prognosis of PDAC patients. MIF knockdown impaired cell invasion, with a decrease in the expression of urokinase-type plasminogen activator receptor (uPAR). Although PLAUR transcript was not reduced, a uPAR endocytic receptor, low-density lipoprotein receptor–related protein 1 (LRP1), was upregulated at both the mRNA and protein levels after MIF knockdown. The LRP1 antagonist RAP restored uPAR expression and invasiveness. MIF attenuated the nuclear translocation of p53, a transcriptional regulator of LRP1. Furthermore, MIF downregulation blunted the growth of PDAC cell xenografts and inhibited cell proliferation under normoxia and hypoxia. Transcriptome analysis also provided evidence for the role of MIF in cancer-associated pathways.

Discussion

We demonstrate a novel link between the two pro-invasive agents MIF and uPAR and explain how MIF increases PDAC cell invasion capability. This finding provides a basis for therapeutic intervention of MIF in PDAC progression.
A semi-supervised learning approach with consistency regularization for tumor histopathological images analysis
Authors: Jiang Yanyun , Sui Xiaodan , Ding Yanhui , Xiao Wei , Zheng Yuanjie , Zhang Yongxin
Published: January 2023

Introduction

Manual inspection of histopathological images is important in clinical cancer diagnosis. Pathologists implement pathological diagnosis and prognostic evaluation through the microscopic examination of histopathological slices. This entire process is time-consuming, laborious, and challenging for pathologists. The modern use of whole-slide imaging, which scans histopathology slides to digital slices, and analysis using computer-aided diagnosis is an essential problem.

Methods

To solve the problem of difficult labeling of histopathological data, and improve the flexibility of histopathological analysis in clinical applications, we herein propose a semi-supervised learning algorithm coupled with consistency regularization strategy, called“Semi- supervised Histopathology Analysis Network”(Semi-His-Net), for automated normal-versus-tumor and subtype classifications. Specifically, when inputted disturbing versions of the same image, the model should predict similar outputs. Based on this, the model itself can assign artificial labels to unlabeled data for subsequent model training, thereby effectively reducing the labeled data required for training.

Results

Our Semi-His-Net is able to classify patches from breast cancer histopathological images into normal tissue and three other different tumor subtypes, achieving an accuracy was 90%. The average AUC of cross-classification between tumors reached 0.893.

Discussion

To overcome the limitations of visual inspection by pathologists for histopathology images, such as long time and low repeatability, we have developed a deep learning-based framework (Semi-His-Net) for automatic classification subdivision of the subtypes contained in the whole pathological images. This learning-based framework has great potential to improve the efficiency and repeatability of histopathological image diagnosis.
Development and validation of a nomogram to predict overall survival and cancer-specific survival in patients with primary intracranial malignant lymphoma: A Retrospective study based on the SEER database
Authors: Yang Ziyue , Li Zhenfen , Fu Chunmeng , Zhu Yuanyuan , Lin Ying , Deng Ying , Li Ning , Peng Fang
Published: January 2023

Introduction

Primary intracranial malignant lymphoma (PIML) is a rare form of lymphoma that most often occurs in the brain and has an extremely low 5-year survival rate. Although chemotherapy and radiotherapy are widely used in the clinical management of PIML, the choice of treatment regimen and the actual circumstances of patients remain challenges when assessing survival rates in different patients.

Methods

Considering this, we obtained clinical treatment and survival information from the Surveillance, Epidemiology, and End Results database (SEER) on patients with lymphoma, the primary site of which was the brain, and performed statistical analyses of the demographic characteristics. Survival analyses were performed using the Kaplan–Meier method, and univariate and multivariate Cox proportional hazards regression analyses were performed to identify independent prognostic factors.

Result

We identified age, pathology, the Ann Arbor stage, and treatment as the risk factors affecting patient prognosis. The areas under the curve (AUCs) for overall survival at 1, 3, and 5 years were 0.8, 0.818, and 0.81, respectively. The AUCs for cancer-specific survival at 1, 3, and 5 years were 0.8, 0.79, and 0.79. The prediction ability in the development and verification cohorts was in good agreement with the actual values, while we plotted the clinical decision curves for the model, suggesting that the nomogram can provide benefits for clinical decision-making.

Conclusion

Our model provides a prognostic guide for patients with PIML and a reliable basis for clinicians.
Can the sustainable development goals for cancer be met in Brazil? A population-based study
Authors: De Camargo Cancela Marianna , Bezerra de Souza Dyego Leandro , Leite Martins Luís Felipe , Borges Leonardo , Schilithz Arthur Orlando , Hanly Paul , Sharp Linda , Pearce Alison , Soejomataram Isabelle
Published: January 2023

Background

A one-third reduction in premature mortality (30-69 years) from chronic noncommunicable diseases is goal 3.4 of the United Nations Sustainable Development Goals (UN SDG). The burden of NCDs is expected to continue to increase in low- and middle-income countries, including Brazil.

Objectives

The aim of this study was to assess geographical and temporal patterns in premature cancer mortality in Brazil between 2001 and 2015 and to predict this to 2030 in order to benchmark against the 3.4 SDG target.

Methods

We used data on deaths from cancer in those aged 30-69, by age group, sex and cancer site, between 2001 and 2015 from the National Mortality Information System of Brazil (SIM). After correcting for ill-defined causes, crude and world age-standardised mortality rates per 100,000 inhabitants were calculated nationally and for the 5 regions. Predictions were calculated using NordPred, up to 2030.

Results

The difference in observed (2011-2015) and predicted (2026-2030) mortality was compared against the SDG 3.4 target. Between 2011-2015 and 2026-2030 a 12.0% reduction in premature cancer age-standardised mortality rate among males and 4.6% reduction among females is predicted nationally. Across regions this varied from 2.8% among females in North region to 14.7% among males in South region. Lung cancer mortality rates are predicted to decrease among males but not among females nationally (men 28%, females 1.1% increase) and in all regions. Cervical cancer mortality rates are projected to remain very high in the North. Colorectal cancer mortality rates will increase for both sexes in all regions except the Southeast.

Conclusions and recommendation

Cancer premature mortality is expected to decrease in Brazil, but the extent of the decrease will be far from the SDG 3.4 target. Nationally, only male lung cancer will be close to reaching the SDG 3.4 target, reflecting the government’s long-term efforts to reduce tobacco consumption. Projected colorectal cancer mortality increases likely reflect the epidemiological transition. This and, cervical cancer control will continue to be major challenges. These results will help inform strategic planning for cancer primary prevention, early detection and treatment programs; such initiatives should take cognizance of the regional differences highlighted here.
Anticancer properties of bromelain: State-of-the-art and recent trends
Authors: Pezzani Raffaele , Jiménez-Garcia Manuel , Capó Xavier , Sönmez Gürer Eda , Sharopov Farukh , Rachel Tchokouaha Yamthe Lauve , Ntieche Woutouoba David , Rescigno Antonio , Peddio Stefania , Zucca Paolo , Tsouh Fokou Patrick Valere , Martorell Miquel , Gulsunoglu-Konuskan Zehra , Ydyrys Alibek , Bekzat Tynybekov , Gulmira Tussupbekova , Hano Christophe , Sharifi-Rad Javad , Calina Daniela
Published: January 2023

Bromelain is a key enzyme found in pineapple (Ananas comosus (L.) Merr.); a proteolytic substance with multiple beneficial effects for human health such as anti-inflammatory, immunomodulatory, antioxidant and anticarcinogenic, traditionally used in many countries for its potential therapeutic value. The aim of this updated and comprehensive review focuses on the potential anticancer benefits of bromelain, analyzing the cytotoxic, apoptotic, necrotic, autophagic, immunomodulating, and anti-inflammatory effects in cancer cells and animal models. Detailed information about Bromelain and its anticancer effects at the cellular, molecular and signaling levels were collected from online databases such as PubMed/MedLine, TRIP database, GeenMedical, Scopus, Web of Science and Google Scholar. The results of the analyzed studies showed that Bromelain possesses corroborated pharmacological activities, such as anticancer, anti-edema, anti-inflammatory, anti-microbial, anti-coagulant, anti-osteoarthritis, anti-trauma pain, anti-diarrhea, wound repair. Nonetheless, bromelain clinical studies are scarce and still more research is needed to validate the scientific value of this enzyme in human cancer diseases.
Potassium channels: Novel targets for tumor diagnosis and chemoresistance
Authors: Li Meizeng , Tian Peijie , Zhao Qing , Ma Xialin , Zhang Yunxiang
Published: January 2023

In recent years, the role of potassium channels in tumors has been intensively studied. Potassium channel proteins are widely involved in various physiological and pathological processes of cells. The expression and dysfunction of potassium channels are closely related to tumor progression. Potassium channel blockers or activators present antitumor effects by directly inhibiting tumor growth or enhancing the potency of classical antitumor agents in combination therapy. This article reviews the mechanisms by which potassium channels contribute to tumor development in various tumors in recent years, introduces the potential of potassium channels as diagnostic targets and therapeutic means for tumors, and provides further ideas for the proper individualized treatment of tumors.
The upregulation of CLGN in hepatocellular carcinoma is potentially regulated by hsa-miR-194-3p and associated with patient progression
Authors: Cui Zhongyuan , Wang Jielong , Chen Gang , Li Dongliang , Cheng Bianqiao , Lai Yanhua , Wu Zhixian
Published: January 2023

Background

Patients with hepatocellular carcinoma (HCC) have poor prognosis, especially in advanced stages. Targeted therapy is the main treatment for advanced HCC patients, but the optimal targets for HCC remain poorly understood. The main purpose of this study was to identify potential novel prognostic markers and therapeutic targets.

Methods

Firstly, differentially expressed genes (DEGs) in HCC were identified from the Gene Expression Omnibus (GEO) database. The expression, significance in prognosis, and potential mechanisms of DEGs were analyzed using GEPIA, TIMER, HPA, Kaplan Meier Plotter, CBioPortal, miRWalk, TargetScan, and ENCORI databases. Immunohistochemical staining was used to determine the protein expression levels of potential candidate genes.

Results

The mRNA levels of MND1, STXBP6, and CLGN were significantly increased in HCC (p< 0.01). HCC patients with elevated CLGN mRNA levels had poorer overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and disease-specific survival (DSS) (p < 0.05). Higher MND1 mRNA levels significantly correlated with poorer DFS in HCC patients (p< 0.05). However, there was no significant correlation between STXBP6 expression and prognosis of HCC (p> 0.05). Further analysis revealed that patients with elevated CLGN mRNA expression in advanced pathology stages had poorer prognosis (p< 0.01). In addition, CLGN protein levels were elevated in HCC compared to their levels in normal tissues. The mRNA levels of CLGN had no significant correlation with the abundance of six common tumor infiltrating lymphocytes in HCC (COR < 0.5). Moreover, the mutation rate of CLGN was less than 1% in HCC patients (10/1089). Finally, the expression level of hsa-miR-194-3p in HCC was significantly lower than that in normal tissues (p < 0.05), and prognosis of HCC with low expression of hsa-miR-194 was poor (p < 0.05).

Conclusion

The upregulation of CLGN in HCC is significantly associated with poor patient prognosis, especially in the advanced stages, and may be regulated by hsa-miR-194-3p. These findings suggest that CLGN may be closely related to the progression of HCC, and is a potential therapeutic target and prognostic indicator for patients with advanced HCC.
Immune evasion in esophageal squamous cell cancer: From the perspective of tumor microenvironment
Authors: Li Rongyang , Huang Bing , Tian Hui , Sun Zhenguo
Published: January 2023

Esophageal cancer (EC) is one of the most life-threatening malignancies worldwide. Esophageal squamous cell carcinoma (ESCC) is the dominant subtype, accounting for approximately 90% of new incident EC each year. Although multidisciplinary treatment strategies have advanced rapidly, patients with ESCC are often diagnosed at advanced stage and the long-term prognosis remains unsatisfactory. In recent decades, immunotherapy, such as immune checkpoint inhibitors (ICIs), tumor vaccines, and chimeric antigen receptor T-cell (CAR-T) therapy, has been successfully used in clinical practice as a novel therapy for treating tumors, bringing new hope to ESCC patients. However, only a small fraction of patients achieved clinical benefits due to primary or acquired resistance. Immune evasion plays a pivotal role in the initiation and progression of ESCC. Therefore, a thorough understanding of the mechanisms by which ESCC cells escape from anti-tumor immunity is necessary for a more effective multidisciplinary treatment strategy. It has been widely recognized that immune evasion is closely associated with the crosstalk between tumor cells and the tumor microenvironment (TME). TME is a dynamic complex and comprehensive system including not only cellular components but also non-cellular components, which influence hallmarks and fates of tumor cells from the outside. Novel immunotherapy targeting tumor-favorable TME represents a promising strategy to achieve better therapeutic responses for patients with ESCC. In this review, we provide an overview of immune evasion in ESCC, mainly focusing on the molecular mechanisms that underlie the role of TME in immune evasion of ESCC. In addition, we also discuss the challenges and opportunities of precision therapy for ESCC by targeting TME.
Efficacy of non-enhanced computer tomography-based radiomics for predicting hematoma expansion: A meta-analysis
Authors: Jiang Yan-Wei , Xu Xiong-Jei , Wang Rui , Chen Chun-Mei
Published: January 2023

Background

This meta-analysis aimed to assess the efficacy of radiomics using non-enhanced computed tomography (NCCT) for predicting hematoma expansion in patients with spontaneous intracerebral hemorrhage.

Methods

Throughout the inception of the project to April 11, 2022, a comprehensive search was conducted on PubMed, Embase, and Cochrane Central Register of Controlled Trials. The methodological quality of studies in this analysis was assessed by the radiomics quality scoring system (RQS). A meta-analysis of radiomic studies based on NCCT for predicting hematoma expansion in patients with intracerebral hemorrhage was performed. The efficacy of the radiomics approach and non-contrast CT markers was compared using network meta-analysis (NMA).

Results

Ten articles comprising a total of 1525 patients were quantitatively analyzed for hematoma expansion after cerebral hemorrhage using radiomics. Based on the included studies, the mean RQS was 14.4. The AUC value (95% confidence interval) of the radiomics model was 0.80 (0.76-0.83). Five articles comprising 846 patients were included in the NMA. The results synthesized according to Bayesian NMA revealed that the predictive ability of the radiomics model outperformed most of the NCCT biomarkers.

Conclusions

The NCCT-based radiomics approach has the potential to predict hematoma expansion. Compared to NCCT biomarkers, we recommend a radiomics approach. Standardization of the radiomics approach is required for further clinical implementation.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=324034, identifier [CRD42022324034].
The value of brain MRI functional connectivity data in a machine learning classifier for distinguishing migraine from persistent post-traumatic headache
Authors: Dumkrieger Gina , Chong Catherine D , Ross Katherine , Berisha Visar , Schwedt Todd J
Published: January 2023

Background

Post-traumatic headache (PTH) and migraine often have similar phenotypes. The objective of this exploratory study was to develop classification models to differentiate persistent PTH (PPTH) from migraine using clinical data and magnetic resonance imaging (MRI) measures of brain structure and functional connectivity (fc).

Methods

Thirty-four individuals with migraine and 48 individuals with PPTH attributed to mild TBI were included. All individuals completed questionnaires assessing headache characteristics, mood, sensory hypersensitivities, and cognitive function and underwent brain structural and functional imaging during the same study visit. Clinical features, structural and functional resting-state measures were included as potential variables. Classifiers using ridge logistic regression of principal components were fit on the data. Average accuracy was calculated using leave-one-out cross-validation. Models were fit with and without fc data. The importance of specific variables to the classifier were examined.

Results

With internal variable selection and principal components creation the average accuracy was 72% with fc data and 63.4% without fc data. This classifier with fc data identified individuals with PPTH and individuals with migraine with equal accuracy.

Conclusion

Multivariate models based on clinical characteristics, fc, and brain structural data accurately classify and differentiate PPTH vs. migraine suggesting differences in the neuromechanism and clinical features underlying both headache disorders.