bluuebunny/crossref_metadata_2025 huggingface dataset:
Deoxynivalenol in food and feed: Recent advances in decontamination strategies
Authors: Li Yingfeng , Gao Huihui , Wang Ru , Xu Qing
Published: March 2023

Deoxynivalenol (DON) is a mycotoxin that contaminates animal feed and crops around the world. DON not only causes significant economic losses, but can also lead diarrhea, vomiting, and gastroenteritis in humans and farm animals. Thus, there is an urgent need to find efficient approaches for DON decontamination in feed and food. However, physical and chemical treatment of DON may affect the nutrients, safety, and palatability of food. By contrast, biological detoxification methods based on microbial strains or enzymes have the advantages of high specificity, efficiency, and no secondary pollution. In this review, we comprehensively summarize the recently developed strategies for DON detoxification and classify their mechanisms. In addition, we identify remaining challenges in DON biodegradation and suggest research directions to address them. In the future, an in-depth understanding of the specific mechanisms through which DON is detoxified will provide an efficient, safe, and economical means for the removal of toxins from food and feed.
Multi-gene phylogeny and taxonomy of the genus Bannoa with the addition of three new species from central China
Authors: Chai Chun-Yue , Lei Ting , Chu Xue-Ying , Hui Feng-Li
Published: March 2023

The genusBannoais a small group of ballistoconidium-forming yeasts in the family Erythrobasidiaceae (Cystobasidiomycetes). Prior to this study, seven species belonging to this genus have been described and published. In this study, phylogenetic analyzes ofBannoabased on the combined sequences of the small ribosomal subunit (SSU) rRNA gene, the internal transcribed spacer (ITS) regions, the D1/D2 domains of the large subunit rRNA gene (LSU) and the translation elongation factor 1-α gene (TEF1-α) were conducted. Three new species, namelyB. ellipsoidea,B. foliicola, andB. pseudofoliicola, were delimited and proposed based on morphological and molecular evidence.B. ellipsoideawas found to be closely related to the type strains ofB. guamensis,B. hahajimensis, andB. tropicalis, but with 0.7–0.9% divergence (4–5 substitutions) in the LSU D1/D2 domains and 3.7–4.1% divergence (19–23 substitutions and one−two gaps) in the ITS regions.B. foliicolawas found to belong to the same clade asB. pseudofoliicolafrom which it differed by 0.4% divergence (two substitutions) in the LSU D1/D2 domains and 2.3% divergence (13 substitutions) in the ITS regions. The distinguishing morphological characteristics of the three new species, with respect to closely related taxa, are discussed. The identification of these new taxa significantly increases the number ofBannoathat have been described on the surface of plant leaves. Additionally, a key for the identification ofBannoaspecies is provided.
Brain effective connectivity and functional connectivity as markers of lifespan vascular exposures in middle-aged adults: The Bogalusa Heart Study
Authors: Chuang Kai-Cheng , Ramakrishnapillai Sreekrishna , Madden Kaitlyn , St Amant Julia , McKlveen Kevin , Gwizdala Kathryn , Dhullipudi Ramasudhakar , Bazzano Lydia , Carmichael Owen
Published: March 2023

Introduction

Effective connectivity (EC), the causal influence that functional activity in a source brain location exerts over functional activity in a target brain location, has the potential to provide different information about brain network dynamics than functional connectivity (FC), which quantifies activity synchrony between locations. However, head-to-head comparisons between EC and FC from either task-based or resting-state functional MRI (fMRI) data are rare, especially in terms of how they associate with salient aspects of brain health.

Methods

In this study, 100 cognitively-healthy participants in the Bogalusa Heart Study aged 54.2 ± 4.3years completed Stroop task-based fMRI, resting-state fMRI. EC and FC among 24 regions of interest (ROIs) previously identified as involved in Stroop task execution (EC-task and FC-task) and among 33 default mode network ROIs (EC-rest and FC-rest) were calculated from task-based and resting-state fMRI using deep stacking networks and Pearson correlation. The EC and FC measures were thresholded to generate directed and undirected graphs, from which standard graph metrics were calculated. Linear regression models related graph metrics to demographic, cardiometabolic risk factors, and cognitive function measures.

Results

Women and whites (compared to men and African Americans) had better EC-task metrics, and better EC-task metrics associated with lower blood pressure, white matter hyperintensity volume, and higher vocabulary score (maximum value of p = 0.043). Women had better FC-task metrics, and better FC-task metrics associated with APOE-ε4 3–3 genotype and better hemoglobin-A1c, white matter hyperintensity volume and digit span backwards score (maximum value of p = 0.047). Better EC rest metrics associated with lower age, non-drinker status, and better BMI, white matter hyperintensity volume, logical memory II total score, and word reading score (maximum value of p = 0.044). Women and non-drinkers had better FC-rest metrics (value of p = 0.004).

Discussion

In a diverse, cognitively healthy, middle-aged community sample, EC and FC based graph metrics from task-based fMRI data, and EC based graph metrics from resting-state fMRI data, were associated with recognized indicators of brain health in differing ways. Future studies of brain health should consider taking both task-based and resting-state fMRI scans and measuring both EC and FC analyses to get a more complete picture of functional networks relevant to brain health.
Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain
Authors: Hernández-Parra Héctor , Reyes-Hernández Octavio Daniel , Figueroa-González Gabriela , González-Del Carmen Manuel , González-Torres Maykel , Peña-Corona Sheila I. , Florán Benjamín , Cortés Hernán , Leyva-Gómez Gerardo
Published: March 2023

Diverse neurological symptoms have been reported in patients with SARS-CoV-2 disease (COVID-19), including stroke, ataxia, meningitis, encephalitis, and cognitive impairment. These alterations can cause serious sequelae or death and are associated with the entry of SARS-CoV-2 into the Central Nervous System (CNS). This mini-review discusses the main proposed mechanisms by which SARS-CoV-2 interacts with the blood-brain barrier (BBB) and its involvement in the passage of drugs into the CNS. We performed a search in PubMed with the terms “COVID-19” or “SARS-CoV-2” and “blood-brain barrier injury” or “brain injury” from the year 2019 to 2022. We found proposed evidence that SARS-CoV-2 infects neurovascular cells and increases BBB permeability by increasing the expression of matrix metalloproteinase-9 that degrades type IV collagen in the basement membrane and through activating RhoA, which induces restructuring of the cytoskeleton and alters the integrity of the barrier. The breakdown of the BBB triggers a severe inflammatory response, causing the cytokine storm (release of IL-1β, IL-6, TNF-α, etc.) characteristic of the severe phase of COVID-19, which includes the recruitment of macrophages and lymphocytes and the activation of astrocytes and microglia. We conclude that the increased permeability of the BBB would allow the passage of drugs that would not reach the brain in a normal physiological state, thus enhancing certain drugs’ beneficial or adverse effects. We hope this article will encourage research on the impact of drugs on patients with COVID-19 and recovered patients with sequelae, focusing mainly on possible dose adjustments and changes in pharmacokinetic parameters.
Case report: Delayed outflow obstruction of a DVA: A rare complication of brainstem cavernoma surgery
Authors: Agyemang Kevin , Gómez Rodríguez Rony , Rocha Marussi Victor Hugo , Marte Arias Sally Allinson , Feliciano Vilcahuaman Paitań Alexander , Campos Filho José Maria , Chaddad-Neto Feres
Published: March 2023

Introduction

Developmental venous anomalies (DVAs) are considered variants of normal transmedullary veins. Their association with cavernous malformations is reported to increase the risk of hemorrhage. Expert consensus recommends meticulous planning with MR imaging, use of anatomical “safe zones”, intraoperative monitoring of long tracts and cranial nerve nuclei, and preservation of the DVA as key to avoiding complications in brainstem cavernoma microsurgery. Symptomatic outflow restriction of DVA is rare, with the few reported cases in the literature restricted to DVAs in the supratentorial compartment.

Case

We present a case report of the resection of a pontine cavernoma complicated by delayed outflow obstruction of the associated DVA. A female patient in her 20's presented with progressive left-sided hemisensory disturbance and mild hemiparesis. MRI revealed two pontine cavernomas associated with interconnected DVA and hematoma. The symptomatic cavernoma was resected via the infrafacial corridor. Despite the preservation of the DVA, the patient developed delayed deterioration secondary to venous hemorrhagic infarction. We discuss the imaging and surgical anatomy pertinent to brainstem cavernoma surgery, as well as the literature exploring the management of symptomatic infratentorial DVA occlusion.

Conclusion

Delayed symptomatic pontine venous congestive edema is extremely rare following cavernoma surgery. DVA outflow restriction from a post-operative cavity, intraoperative manipulation, and intrinsic hypercoagulability from COVID-10 infection are potential pathophysiological factors. Improved knowledge of DVAs, brainstem venous anatomy, and “safe entry zones” will further elucidate the etiology of and the efficacious treatment for this complication.
Results of treatment with alemtuzumab in a Spanish cohort of patients with multiple sclerosis in the real world: The RealMS study
Authors: Eichau Sara , López Ruiz Rocío , Ruíz de Arcos María , Ruiz-Peña Juan Luis , Navarro Guillermo , Calleja Miguel Ángel , Moreno-Amador José Luis , Dotor García-Soto Julio
Published: March 2023

Background

Alemtuzumab (ALZ) is a humanized monoclonal antibody approved for the treatment of patients with highly active relapsing-remitting multiple sclerosis (RRMS) administered in two annual courses. The objective of this study was to describe the effectiveness and safety data of ALZ and to report the health resource utilization in patients receiving this treatment.

Methods

In this retrospective, non-interventional study, information was retrieved from patients' medical charts at one center in Spain. Included patients were ≥18 years old, and ALZ treatment was initiated between 1 March 2015 and 31 March 2019, according to routine clinical practice and local labeling.

Results

Of 123 patients, 78% were women. The mean (standard deviation, SD) age of patients at diagnosis was 40.3 (9.1) years, and the mean time since diagnosis was 13.8 (7.3) years. Patients were previously treated with a median (interquartile range; IQR) number of two (2.0–3.0) disease-modifying treatments (DMTs). Patients were treated with ALZ for a mean (SD) of 29.7 (13.8) months. ALZ reduced the annualized relapse rate (ARR) (1.5 before vs. 0.05 after;p< 0.001) and improved the median EDSS (4.63 before vs. 4.00 after;p< 0.001). Most (90.2%) patients were relapse-free while receiving ALZ. The mean number of gadolinium-enhancing [Gd+] T1 lesions was reduced (1.7 before vs. 0.1 after;p< 0.001), and the mean number of T2 hyperintense lesions was maintained (35.7 before vs. 35.4 after;p= 0.392). A total of 27 (21.9%) patients reported 29 autoimmune diseases: hyperthyroidism (12), hypothyroidism (11), idiopathic thrombocytopenic purpura (ITP) (3), alopecia areata (1), chronic urticaria (1), and vitiligo (1). The mean number of health resources (outpatient visits, emergency room visits, hospital admissions, and tests performed in the hospital) used while patients were treated with ALZ progressively decreased from year 1 to year 4, except for a slight increase at year 2 of outpatient visits.

Conclusion

The ReaLMS study provides real-world evidence that ALZ can promote clinical and magnetic resonance imaging disease remission, as well as disability improvement in patients with MS, despite several prior DMT failures. The ALZ safety profile was consistent with data available from clinical trials and other real-world studies. Healthcare resource use was reduced throughout the treatment period.
Research on brain functions related to visual information processing and body coordination function of pilots based on the low-frequency amplitude method
Authors: Xu Kaijun , Liu Rui , Chen Xipeng , Chen Xi , Yang Yong , Wang Quanchuan , Yang Jiazhong
Published: March 2023

Objective

Research on the differences in physiological and psychological mechanisms of practitioners in different occupations is a current hot spot, such as pilots. This study explores the frequency-dependent changes of pilots’ low-frequency amplitudes in the classical frequency band and sub-frequency band between pilots and general occupations. The goal of the current work is to provide objective brain images for the selection and evaluation of outstanding pilots.

Methods

Twenty-six pilots and 23 age-, sex-, and education-matched healthy controls were included in this study. Then the mean low-frequency amplitude (mALFF) of the classical frequency band and sub-frequency band was calculated. The two-sample t-test was performed on SPM12 to analyze the differences between the flight group and control group in the classic frequency band. To explore the main effects and the inter-band effects of the mean low-frequency amplitude (mALFF), the mixed design analysis of variance was applied in the sub-frequency bands.

Results

Compared with the control group, left cuneiform lobe and the right cerebellum six area of pilots show significant difference in the classic frequency band. And the main effect results in the sub-frequency bands show that the area with higher mALFF in the flight group is located on the left middle occipital gyrus, the left cuneiform lobe, the right superior occipital gyrus, the right superior gyrus, and the left lateral central lobule. However, the area where the value of mALFF decreased is mainly located on the left rectangular cleft with surrounding cortex and the right dorsolateral superior frontal gyrus. Besides, compared with the slow-4 frequency band, the mALFF of the left middle orbital middle frontal gyrus of the slow-5 frequency band was increased, while the mALFF value of the left putamen, left fusiform gyrus, and right thalamus was decreased. The sensitivity of the slow-5 frequency band and the slow-4 frequency band to the pilots’ different brain areas was also different. Also, the different brain areas in the classic frequency band and the sub-frequency band were significantly correlated with pilots’ flight hours.

Conclusion

Our findings showed that the left cuneiform brain area and the right cerebellum of pilots changed significantly during resting state. And there was a positive correlation between the mALFF value of those brain area and flight hours. The comparative analysis of sub-frequency bands found that the slow-5 band could elucidate a wider range of different brain regions, providing new ideas for exploring the brain mechanisms of pilots.
Cellular complexity of the peripheral nervous system: Insights from single-cell resolution
Authors: Zhao Lili , Huang Weixiao , Yi Sheng
Published: March 2023

Single-cell RNA sequencing allows the division of cell populations, offers precise transcriptional profiling of individual cells, and fundamentally advances the comprehension of cellular diversity. In the peripheral nervous system (PNS), the application of single-cell RNA sequencing identifies multiple types of cells, including neurons, glial cells, ependymal cells, immune cells, and vascular cells. Sub-types of neurons and glial cells have further been recognized in nerve tissues, especially tissues in different physiological and pathological states. In the current article, we compile the heterogeneities of cells that have been reported in the PNS and describe cellular variability during development and regeneration. The discovery of the architecture of peripheral nerves benefits the understanding of the cellular complexity of the PNS and provides a considerable cellular basis for future genetic manipulation.
Stochastic surprisal: An inferential measurement of free energy in neural networks
Authors: Prabhushankar Mohit , AlRegib Ghassan
Published: March 2023

This paper conjectures and validates a framework that allows for action during inference in supervised neural networks. Supervised neural networks are constructed with the objective to maximize their performance metric in any given task. This is done by reducing free energy and its associated surprisal during training. However, the bottom-up inference nature of supervised networks is a passive process that renders them fallible to noise. In this paper, we provide a thorough background of supervised neural networks, both generative and discriminative, and discuss their functionality from the perspective of free energy principle. We then provide a framework for introducing action during inference. We introduce a new measurement called stochastic surprisal that is a function of the network, the input, and any possible action. This action can be any one of the outputs that the neural network has learnt, thereby lending stochasticity to the measurement. Stochastic surprisal is validated on two applications: Image Quality Assessment and Recognition under noisy conditions. We show that, while noise characteristics are ignored to make robust recognition, they are analyzed to estimate image quality scores. We apply stochastic surprisal on two applications, three datasets, and as a plug-in on 12 networks. In all, it provides a statistically significant increase among all measures. We conclude by discussing the implications of the proposed stochastic surprisal in other areas of cognitive psychology including expectancy-mismatch and abductive reasoning.
Toward long-term storage of nuclear materials in MOX fuels fabrication facility
Authors: Hirooka Shun , Nakamichi Shinya , Matsumoto Taku , Tsuchimochi Ryota , Murakami Tatsutoshi
Published: March 2023

Storage of plutonium (Pu)-containing materials requires extremely strict attention to physical safety and material accounting. For the emphasized importance of storage management, many reports are available in the public, e.g., experience in PuO2 storage in the UK and safety standards in the storage of Pu-containing materials in the US. Japan also stores plutonium, mainly in the form of uranium-Pu mixed oxide (MOX) mostly in powder form. Robust conditioning and storage arrangements must be adopted that are appropriate to the characteristics of the MOX, such as raw powder obtained by reprocessing of spent Light Water Reactor fuels, MOX samples from research and development on the remains of fuel fabrication, which can contain organic materials, and dry-recycled powder during fuel fabrication. A reduction in MOX fuel fabrications operations and experience in degradation of MOX containers during extended period of storage have led to JAEA to review the MOX storage arrangements in the Plutonium Fuel Development Center in Japan Atomic Energy Agency. The present work discusses the various nuclear materials, storage methods, experience in degradation of containers that occur during storage, and strategies for future long-term storage.
Changes in the gut microbiota composition of healthy young volunteers after administration of Lacticaseibacillus rhamnosus LRa05: A placebo-controlled study
Authors: Gai Zhonghui , Dong Yao , Xu Fei , Zhang Junli , Yang Yujiao , Wang Yuwen
Published: March 2023

The gut microbiota promotes gastrointestinal health in humans; however, the effect of probiotics on the gut microbiota of healthy adults has not been documented clearly. This placebo-controlled study was conducted to assess the effect of Lacticaseibacillus rhamnosus LRa05 supplementation on the gut microbiota of healthy adults. The subjects (N = 100) were randomized 1:1 to receive (1) maltodextrin (placebo, CTL group) and (2) maltodextrin + strain LRa05 (1 × 1010 colony-forming units/day, LRa05 group). The duration of the intervention was 4 weeks, and changes in the gut microbiota from before to after the intervention were investigated using 16S rRNA high-throughput sequencing. In terms of alpha diversity, no significant difference in the composition of the gut microbiota was found between the LRa05 and CTL groups. 16S rRNA sequencing analysis showed that the relative abundance of Lacticaseibacillus significantly increased after supplementation with LRa05. Furthermore, a decreasing trend in the abundance of Sellimonas and a significant decrease in the salmonella infection pathway were observed in the LRa05 group compared with the CTL group. These findings indicate the potential of LRa05 to colonize the human gut and reduce the abundance of harmful bacteria in the microbiota.
Fortification of puffed biscuits with chitin and crayfish shell: Effect on physicochemical property and starch digestion
Authors: Bai Chan , Zhu Jiguo , Xiong Guangquan , Wang Wenqing , Wang Juguang , Qiu Liang , Zhang Qingfang , Liao Tao
Published: March 2023

Chitin is a polysaccharide and possesses numerous beneficial properties such as nontoxicity, biodegradability and biocompatibility, which draws much attention to its applications in food. Crayfish shell is a source of chitin alongside an antioxidants and a potential source of beneficial dietary fiber. In this study, chitin (CH) and crayfish shell (CS) with different concentrations were used to study their impact on pasting characteristics of flour mixture (wheat flour and glutinous rice flour) and influence on physicochemical and starch digestion property of puffed biscuit. The Rapid Visco-Analyzer results showed that the viscosity of powder mixture was decreased with the ratio of CH and CS increased. CH resulted in lowest peak viscosity and breakdown values of mixed powder. It was indicated that increasing amounts of CH and CS led to significantly reduced moisture content, expansion ratio but raised density of biscuits. CH and CS inhibited starch digestion and promoted a remarkable increase (P < 0.05) of resistant starch (RS) content. The hydrolysis kinetic analysis suggested a decelerating influence of CH on the hydrolysis content with lower values of equilibrium hydrolysis percentage (C∞) while CS on hydrolysis rate with lower kinetic constant (K). The estimated glycemic index (eGI) of the CH (15-20%) samples were below 55. These results are of great significance in delaying starch digestion and provided a better choice in design of fried puffed snacks for special crowd with chronic diseases such as diabetes, cardiovascular disease, and obesity.
Exposure to essential and non-essential trace elements and risks of congenital heart defects: A narrative review
Authors: Liang Yipu , Pan Zijian , Zhu Mingzheng , Gao Ruonan , Wang Yijue , Cheng Yijuan , Zhang Nannan
Published: March 2023

Congenital heart defects (CHDs) are congenital abnormalities involving the gross structures of the heart and large blood vessels. Environmental factors, genetic factors and their interactions may contribute to the pathogenesis of CHDs. Generally, trace elements can be classified into essential trace elements and non-essential trace elements. Essential trace elements such as copper (Cu), zinc (Zn), iron (Fe), selenium (Se), and manganese (Mn) play important roles in human biological functions such as metabolic function, oxidative stress regulation, and embryonic development. Non-essential trace elements such as cadmium (Cd), arsenic (As), lead (Pb), nickle (Ni), barium (Ba), chromium (Cr) and mercury (Hg) are harmful to health even at low concentrations. Recent studies have revealed the potential involvement of these trace elements in the pathogenesis of CHDs. In this review, we summarized current studies exploring exposure to essential and non-essential trace elements and risks of CHDs, in order to provide further insights for the pathogenesis and prevention of CHDs.
Integrating conservation agriculture with intensive crop diversification in the maize-based organic system: Impact on sustaining food and nutritional security
Authors: Ansari Meraj Alam , Ravisankar N. , Ansari Majhrool Hak , Babu Subhash , Layek Jayanta , Panwar A. S.
Published: March 2023

Introduction

Developing an intensive sustainable model and feeding a rising population are worldwide challenges. The task is much more daunting in the North Eastern Himalayas, where, low productive maize (Zea mays)- fallow is the main production system in the upland. To increase farm productivity, nutritional security, and energy dietary returns while maintaining environmental sustainability and economic viability, short-duration crops must be included in the maize–fallow system.

Methods

A field study was conducted in sandy clay loam soil with a randomized complete block design with three replications for three continuous years (2018–2021) under organic management with two crop management practices, viz., (i) conservation agriculture and (ii) conventional agriculture, and six crop diversification options, viz., (i) maize–sweet corn (Zea mays saccharata)–vegetable pea (Pisum sativa) (M-SC-VP), (ii) maize–sweet corn-mustard (Brassica juncea) (M-SC-M), (iii) maize–sweet corn–lentil (Lens culinaris) (M-SC-L), (iv) maize–sweet corn–vegetable broad bean (Vicia faba) (M-SC-VB), (v) maize (local)–vegetable pea (M-VP), and (vi) maize (local)–fallow (M-F).

Results

The results showed that, the average system productivity was 5.3% lower for conventional agriculture than conservation agriculture. System carbohydrate, protein, fat, dietary fiber, and dietary energy were ~6.9, 6.8, 7.8, 6.7, and 7%, higher in conservation agriculture than in conventional agriculture, respectively. Similarly, system macronutrients (Ca, Mg, P, and K) and system micronutrients yield (Fe, Mn, Zn, and Cu) were, 5.2–8% and 6.9–7.4% higher in conservation agriculture than in conventional agriculture, respectively. On average, over the years, crop diversification with M-SC-VP/M-SC-VB intensive crop rotation had higher system productivity (158%), production efficiency (157%), net returns (benefit–cost ratio) (44%), and dietary net energy returns (16.6%) than the local maize–vegetable pea system. Similarly, the M-SC-VP/M-SC-VB system improved the nutritional security by improving Ca, Mg, P, K, Fe, Mn, Zn, and Cu yield by 35.5–135.7% than the local M-VP system.

Discussion

Conservation agriculture with M-SC-VP/M-SC-VB rotation showed significantly (p < 0.05) higher productivity, carbohydrate yield, protein yield, fat yield, and dietary fiber production. It is concluded that conservation agriculture improved soil health and performed better than conventional agriculture in maize-based intensive cropping systems. Overall results indicate that crop diversification with M-SC-VP/M-SC-VB can potentially increase calorie and protein consumption and farm profitability.
Genetic polymorphisms in CYP4F2 may be associated with lung cancer risk among females and no-smoking Chinese population
Authors: Shi Hongyang , Zhang Yonghong , Wang Yu , Fang Ping , Liu Yun
Published: March 2023

Background

Our study aimed to explore the potential association of CYP4F2 gene polymorphisms with lung cancer (LC) risk.

Methods

The five variants in CYP4F2 were genotyped using Agena MassARRAY in 507 cases and 505 controls. Genetic models and haplotypes based on logistic regression analysis were used to evaluate the potential association between CYP4F2 polymorphisms and LC susceptibility.

Results

This study observed that rs12459936 was linked to an increased risk of LC in no-smoking participants (allele: OR = 1.38, p = 0.035; homozygote: OR = 2.00, p = 0.035; additive: OR = 1.40, p = 0.034) and females (allele: OR = 1.64, p = 0.002; homozygote: OR = 2.57, p = 0.006; heterozygous: OR = 2.56, p = 0.001; dominant: OR = 2.56, p < 0.002; additive: OR = 1.67, p = 0.002). Adversely, there was a significantly decreased LC risk for rs3093110 in no-smoking participants (heterozygous: OR = 0.56, p = 0.027; dominant: OR = 0.58, p = 0.035), rs3093193 (allele: OR = 0.66, p = 0.016; homozygote: OR = 0.33, p = 0.011; recessive: OR = 0.38, p = 0.021; additive: OR = 0.64, p = 0.014), rs3093144 (recessive: OR = 0.20, p = 0.045), and rs3093110 (allele: OR = 0.54, p = 0.010; heterozygous: OR = 0.50, p = 0.014; dominant: OR = 0.49, p = 0.010; additive: OR = 0.54, p = 0.011) in females.

Conclusions

The study demonstrated that CYP4F2 variants were associated with LC susceptibility, with evidence suggesting that this connection may be affected by gender and smoking status.
Clinical updates on gliomas and implications of the 5th edition of the WHO classification of central nervous system tumors
Authors: Guo Xiaopeng , Shi Yixin , Liu Delin , Li Yilin , Chen Wenlin , Wang Yaning , Wang Yuekun , Xing Hao , Xia Yu , Li Junlin , Wu Jiaming , Liang Tingyu , Wang Hai , Liu Qianshu , Jin Shanmu , Qu Tian , Guo Siying , Li Huanzhang , Yang Tianrui , Zhang Kun , Wang Yu , Ma Wenbin
Published: March 2023

Background

The 5th edition of the World Health Organization (WHO) classification of central nervous system tumors incorporated specific molecular alterations into the categorization of gliomas. The major revision of the classification scheme effectuates significant changes in the diagnosis and management of glioma. This study aimed to depict the clinical, molecular, and prognostic characteristics of glioma and its subtypes according to the current WHO classification.

Methods

Patients who underwent surgery for glioma at Peking Union Medical College Hospital during 11 years were re-examined for tumor genetic alterations using next-generation sequencing, polymerase chain reaction-based assay, and fluorescence in situ hybridization methods and enrolled in the analysis.

Results

The enrolled 452 gliomas were reclassified into adult-type diffuse glioma (ntotal=373; astrocytoma, n=78; oligodendroglioma, n=104; glioblastoma, n=191), pediatric-type diffuse glioma (ntotal=23; low-grade, n=8; high-grade, n=15), circumscribed astrocytic glioma (n=20), and glioneuronal and neuronal tumor (n=36). The composition, definition, and incidence of adult- and pediatric-type gliomas changed significantly between the 4th and the 5th editions of the classification. The clinical, radiological, molecular, and survival characteristics of each subtype of glioma were identified. Alterations in CDK4/6, CIC, FGFR2/3/4, FUBP1, KIT, MET, NF1, PEG3, RB1, and NTRK2 were additional factors correlated with the survival of different subtypes of gliomas.

Conclusions

The updated WHO classification based on histology and molecular alterations has updated our understanding of the clinical, radiological, molecular, survival, and prognostic characteristics of varied subtypes of gliomas and provided accurate guidance for diagnosis and potential prognosis for patients.
Discovery of BAR502, as potent steroidal antagonist of leukemia inhibitory factor receptor for the treatment of pancreatic adenocarcinoma
Authors: Di Giorgio Cristina , Bellini Rachele , Lupia Antonio , Massa Carmen , Bordoni Martina , Marchianò Silvia , Rosselli Rosalinda , Sepe Valentina , Rapacciuolo Pasquale , Moraca Federica , Morretta Elva , Ricci Patrizia , Urbani Ginevra , Monti Maria Chiara , Biagioli Michele , Distrutti Eleonora , Catalanotti Bruno , Zampella Angela , Fiorucci Stefano
Published: March 2023

Introduction

The leukemia inhibitory factor (LIF), is a cytokine belonging to IL-6 family, whose overexpression correlate with poor prognosis in cancer patients, including pancreatic ductal adenocarcinoma (PDAC). LIF signaling is mediate by its binding to the heterodimeric LIF receptor (LIFR) complex formed by the LIFR receptor and Gp130, leading to JAK1/STAT3 activation. Bile acids are steroid that modulates the expression/activity of membrane and nuclear receptors, including the Farnesoid-X-Receptor (FXR) and G Protein Bile Acid Activated Receptor (GPBAR1).

Methods

Herein we have investigated whether ligands to FXR and GPBAR1 modulate LIF/LIFR pathway in PDAC cells and whether these receptors are expressed in human neoplastic tissues.

Results

The transcriptome analysis of a cohort of PDCA patients revealed that expression of LIF and LIFR is increased in the neoplastic tissue in comparison to paired non-neoplastic tissues. By in vitro assay we found that both primary and secondary bile acids exert a weak antagonistic effect on LIF/LIFR signaling. In contrast, BAR502 a non-bile acid steroidal dual FXR and GPBAR1 ligand, potently inhibits binding of LIF to LIFR with an IC50 of 3.8 µM.

Discussion

BAR502 reverses the pattern LIF-induced in a FXR and GPBAR1 independent manner, suggesting a potential role for BAR502 in the treatment of LIFR overexpressing-PDAC.
Uncoupled nitric oxide synthase activity promotes colorectal cancer progression
Authors: Alam Asim , Smith Steven C. , Gobalakrishnan Sundaresan , McGinn Mina , Yakovlev Vasily A. , Rabender Christopher S.
Published: March 2023

Increased levels of reactive oxygen/nitrogen species are one hallmark of chronic inflammation contributing to the activation of pro-inflammatory/proliferative pathways. In the cancers analyzed, the tetrahydrobiopterin:dihydrobiopterin ratio is lower than that of the corresponding normal tissue, leading to an uncoupled nitric oxide synthase activity and increased generation of reactive oxygen/nitrogen species. Previously, we demonstrated that prophylactic treatment with sepiapterin, a salvage pathway precursor of tetrahydrobiopterin, prevents dextran sodium sulfate–induced colitis in mice and associated azoxymethane-induced colorectal cancer. Herein, we report that increasing the tetrahydrobiopterin:dihydrobiopterin ratio and recoupling nitric oxide synthase with sepiapterin in the colon cancer cell lines, HCT116 and HT29, inhibit their proliferation and enhance cell death, in part, by Akt/GSK-3β–mediated downregulation of β-catenin. Therapeutic oral gavage with sepiapterin of mice bearing azoxymethane/dextran sodium sulfate–induced colorectal cancer decreased metabolic uptake of [18F]-fluorodeoxyglucose and enhanced apoptosis nine-fold in these tumors. Immunohistochemical analysis of both mouse and human tissues indicated downregulated expression of key enzymes in tetrahydrobiopterin biosynthesis in the colorectal cancer tumors. Human stage 1 colon tumors exhibited a significant decrease in the expression of quinoid dihydropteridine reductase, a key enzyme involved in recycling tetrahydrobiopterin suggesting a potential mechanism for the reduced tetrahydrobiopterin:dihydrobiopterin ratio in these tumors. In summary, sepiapterin treatment of colorectal cancer cells increases the tetrahydrobiopterin:dihydrobiopterin ratio, recouples nitric oxide synthase, and reduces tumor growth. We conclude that nitric oxide synthase coupling may provide a useful therapeutic target for treating patients with colorectal cancer.
Risk factors and outcomes of intraoperative hypothermia in neonatal and infant patients undergoing general anesthesia and surgery
Authors: Zhao Jialian , Le Zhenkai , Chu Lihua , Gao Yi , Zhang Manqing , Fan Jiabin , Ma Daqing , Hu Yaoqin , Lai Dengming
Published: March 2023

Objective

The incidence of intraoperative hypothermia remains high in pediatric patients during anesthesia and surgery even though core body temperature monitoring and warming systems have been greatly improved in recent years. We analyzed the risk factors and outcomes of intraoperative hypothermia in neonates and infants undergoing general anesthesia and surgery.

Methods

The data on the incidence of intraoperative hypothermia, other clinical characteristics, and outcomes from electronic records of 1,091 patients (501 neonates and 590 infants between 28 days and 1 year old), who received general anesthesia and surgery, were harvested and analyzed. Intraoperative hypothermia was defined as a core temperature below 36°C during surgery.

Results

The incidence of intraoperative hypothermia in neonates was 82.83%, which was extremely higher than in infants (38.31%, p < 0.001)—the same as the lowest body temperature (35.05 ± 0.69°C vs. 35.40 ± 0.68°C, p < 0.001) and the hypothermia duration (86.6 ± 44.5 min vs. 75.0 ± 52.4 min, p < 0.001). Intraoperative hypothermia was associated with prolonged PACU, ICU, hospital stay, postoperative bleeding, and transfusion in either age group. Intraoperative hypothermia in infants was also related to prolonged postoperative extubation time and surgical site infection. After univariate and multivariate analyses, the age (OR = 0.902, p < 0.001), weight (OR = 0.480, p = 0.013), prematurity (OR = 2.793, p = 0.036), surgery time of more than 60 min (OR = 3.743, p < 0.001), prewarming (OR = 0.081, p < 0.001), received >20 mL/kg fluid (OR = 2.938, p = 0.004), and emergency surgery (OR = 2.142, p = 0.019) were associated with hypothermia in neonates. Similar to neonates, age (OR = 0.991, p < 0.001), weight (OR = 0.783, p = 0.019), surgery time >60 min (OR = 2.140, p = 0.017), pre-warming (OR = 0.017, p < 0.001), and receive >20 mL/kg fluid (OR = 3.074, p = 0.001) were relevant factors to intraoperative hypothermia in infants along with the ASA grade (OR = 4.135, p < 0.001).

Conclusion

The incidence of intraoperative hypothermia was still high, especially in neonates, with a few detrimental complications. Neonates and infants each have their different risk factors associated with intraoperative hypothermia, but younger age, lower weight, longer surgery time, received more fluid, and no prewarming management were the common risk factors.
Efficacy and safety of sequential immunosuppressive treatment for severe IgA nephropathy: A retrospective study
Authors: Luo Mian-Na , Pan Qingjun , Ye Ting , Li Shangmei , Yang Lawei , Liu Hua-Feng , Xu Yongzhi
Published: March 2023

Background:This study compared the efficacy and safety of sequential immunosuppressive therapy in patients with non-end-stage IgA nephropathy (IgAN) with Lee’s classification of IV ∼ V and provided evidence for the use of immunotherapy in patients with severe IgAN.

Methods:We retrospectively analyzed the clinical data of patients with Lee’s IV ∼ V non-end-stage IgA nephropathy.

Results:436 patients were diagnosed with IgAN, and 98 patients who met the inclusion criteria were included in this retrospective study. Of these, 17 were in the supportive care group, 20 in the P group (prednisone-only), 35 in P + CTX group (the prednisone combined with cyclophosphamide followed by mycophenolate mofetil), and 26 in the P + MMF group (prednisone combined with mycophenolate mofetil). The four groups showed differences in the segmental glomerulosclerosis score and the proportion of patients with Lee’s grade IV (p< 0.05), but no differences in other indicators. Compared with the baseline values, urine protein-to-creatinine ratio (PCR) significantly decreased and serum albumin increased (p< 0.05), but there was no significant difference between the groups. The estimated Glomerular Filtration Rate (eGFR) of the P, P + MMF, and P + CTX groups were higher than that of the supportive care group at the 6th and 24th month after treatment (allp< 0.05). At the 24th month, the eGFR in the P + CTX group was higher than that in the P + MMF group (p< 0.05). The effective remission rate of the P + CTX group was higher than that of the supportive care group (p< 0.05). At 12 months, the effective remission rate of the P group was higher than that of the supportive care group (p< 0.05). At the 24th month, there was no significant difference in the effective remission rates among the three groups (P, P + MMF, and P + CTX). Nine patients with severe IgA nephropathy reached the endpoint.

Conclusion:This study showed that immunosuppressive therapy insevere IgAN patient scan effectively reduce urinary protein, increase albumin, and protect renal function in the early stages of IgAN. P + CTX is the most commonly used, which has a high effective remission rate of urine protein and a low incidence of end-point events.
Dynamic changes in marker components during the stir-frying of Pharbitidis Semen, and network analysis of its potential effects on nephritis
Authors: Li Yuman , Lu Yuhe , Zhu Yujie , Yao Jingchun , Hua Haibing , Shen Jinyang , Gao Xun , Qin Kunming
Published: March 2023

Introduction: Pharbitidis Semen (PS) has been widely used in traditional Chinese medicine to treat several diseases such as nephritis. PS is usually stir-fried to enhance its therapeutic efficacy before use in clinical practice. However, the changes in phenolic acids during stir-frying and the mechanisms of their therapeutic effects on nephritis are still unclear.

Methods: Here, we studied the processing-induced chemical changes and elucidated the mechanism of PS in the treatment of nephritis. We determined the levels of the 7 phenolic acids in raw PS (RPS) and stir-fried PS (SPS) using high-performance liquid chromatography, analyzed the dynamic compositional changes during stir-frying, and used network analysis and molecular docking to predict and verify compound targets and pathways corresponding to nephritis.

Results: The dynamic changes in the 7 phenolic acids in PS during stir-frying are suggestive of a transesterification reaction. Pathway analysis revealed that the targets of nephritis were mainly enriched in the AGE-RAGE, hypoxia-inducible factor-1, interleukin-17, and tumor necrosis factor signaling pathways among others. Molecular docking results showed that the 7 phenolic acids had good binding ability with the key nephritic targets.

Discussion: The potential pharmaceutical basis, targets, and mechanisms of PS in treating nephritis were explored. Our findings provide a scientific basis for the clinical use of PS in treating nephritis.
Arctiin-encapsulated DSPE-PEG bubble-like nanoparticles inhibit alveolar epithelial type 2 cell senescence to alleviate pulmonary fibrosis via the p38/p53/p21 pathway
Authors: Xiong Dian , Gao Fei , Shao Jingbo , Pan Yueyun , Wang Song , Wei Dong , Ye Shugao , Chen Yuan , Chen Rui , Yue Bingqing , Li Juan , Chen Jingyu
Published: March 2023

Background: Idiopathic pulmonary fibrosis is a severe and deadly form of diffuse parenchymal lung disease and treatment options are few. Alveolar epithelial type 2 (AEC2) cell senescence is implicated in the pathogenies of IPF. A major bioactive compound from the traditional Chinese medicine Fructus arctii, arctiin (ARC) has robust anti-inflammatory, anti-senescence, and anti-fibrosis functions. However, the potential therapeutic effects of ARC on IPF and the underlying mechanisms involved are still unknown.

Methods: First of all, ARC was identified as an active ingredient by network pharmacology analysis and enrichment analysis of F. arctii in treating IPF. We developed ARC-encapsulated DSPE-PEG bubble-like nanoparticles (ARC@DPBNPs) to increase ARC hydrophilicity and achieve high pulmonary delivery efficiency. C57BL/6 mice were used to establish a bleomycin (BLM)-induced pulmonary fibrosis model for assessing the treatment effect of ARC@DPBNPs on lung fibrosis and the anti-senescence properties of AEC2. Meanwhile, p38/p53 signaling in AEC2 was detected in IPF lungs, BLM-induced mice, and an A549 senescence model. The effects of ARC@DPBNPs on p38/p53/p21 were assessed in vivo and in vitro.

Results: Pulmonary route of administration of ARC@DPBNPs protected mice against BLM-induced pulmonary fibrosis without causing significant damage to the heart, liver, spleen, or kidney. ARC@DPBNPs blocked BLM-induced AEC2 senescence in vivo and in vitro. The p38/p53/p21 signaling axis was significantly activated in the lung tissues of patients with IPF, senescent AEC2, and BLM-induced lung fibrosis. ARC@DPBNPs attenuated AEC2 senescence and pulmonary fibrosis by inhibiting the p38/p53/p21 pathway.

Conclusion: Our data suggest that the p38/p53/p21 signaling axis plays a pivotal role in AEC2 senescence in pulmonary fibrosis. The p38/p53/p21 signaling axis inhibition by ARC@DPBNPs provides an innovative approach to treating pulmonary fibrosis in clinical settings.
Exploring interpretability in deep learning prediction of successful ablation therapy for atrial fibrillation
Authors: Ogbomo-Harmitt Shaheim , Muffoletto Marica , Zeidan Aya , Qureshi Ahmed , King Andrew P. , Aslanidi Oleg
Published: March 2023

Background: Radiofrequency catheter ablation (RFCA) therapy is the first-line treatment for atrial fibrillation (AF), the most common type of cardiac arrhythmia globally. However, the procedure currently has low success rates in dealing with persistent AF, with a reoccurrence rate of ∼50% post-ablation. Therefore, deep learning (DL) has increasingly been applied to improve RFCA treatment for AF. However, for a clinician to trust the prediction of a DL model, its decision process needs to be interpretable and have biomedical relevance.

Aim: This study explores interpretability in DL prediction of successful RFCA therapy for AF and evaluates if pro-arrhythmogenic regions in the left atrium (LA) were used in its decision process.

Methods: AF and its termination by RFCA have been simulated in MRI-derived 2D LA tissue models with segmented fibrotic regions (n = 187). Three ablation strategies were applied for each LA model: pulmonary vein isolation (PVI), fibrosis-based ablation (FIBRO) and a rotor-based ablation (ROTOR). The DL model was trained to predict the success of each RFCA strategy for each LA model. Three feature attribution (FA) map methods were then used to investigate interpretability of the DL model: GradCAM, Occlusions and LIME.

Results: The developed DL model had an AUC (area under the receiver operating characteristic curve) of 0.78 ± 0.04 for predicting the success of the PVI strategy, 0.92 ± 0.02 for FIBRO and 0.77 ± 0.02 for ROTOR. GradCAM had the highest percentage of informative regions in the FA maps (62% for FIBRO and 71% for ROTOR) that coincided with the successful RFCA lesions known from the 2D LA simulations, but unseen by the DL model. Moreover, GradCAM had the smallest coincidence of informative regions of the FA maps with non-arrhythmogenic regions (25% for FIBRO and 27% for ROTOR).

Conclusion: The most informative regions of the FA maps coincided with pro-arrhythmogenic regions, suggesting that the DL model leveraged structural features of MRI images to identify such regions and make its prediction. In the future, this technique could provide a clinician with a trustworthy decision support tool.
Deep learning for the screening of primary ciliary dyskinesia based on cranial computed tomography
Authors: Duan Bo , Lv Hui-Ying , Huang Yue , Xu Zheng-Min , Chen Wen-Xia
Published: March 2023

Objective: To analyze the cranial computed tomography (CT) imaging features of patients with primary ciliary dyskinesia (PCD) who have exudative otitis media (OME) and sinusitis using a deep learning model for early intervention in PCD.

Methods: Thirty-two children with PCD diagnosed at the Children’s Hospital of Fudan University, Shanghai, China, between January 2010 and January 2021 who had undergone cranial CT were retrospectively analyzed. Thirty-two children with OME and sinusitis diagnosed using cranial CT formed the control group. Multiple deep learning neural network training models based on PyTorch were built, and the optimal model was trained and selected to observe the differences between the cranial CT images of patients with PCD and those of general patients and to screen patients with PCD.

Results: The Swin-Transformer, ConvNeXt, and GoogLeNet training models had optimal results, with an accuracy of approximately 0.94; VGG11, VGG16, VGG19, ResNet 34, and ResNet 50, which are neural network models with fewer layers, achieved relatively strong results; and Transformer and other neural networks with more layers or neural network models with larger receptive fields exhibited a relatively weak performance. A heat map revealed the differences in the sinus, middle ear mastoid, and fourth ventricle between the patients with PCD and the control group. Transfer learning can improve the modeling effect of neural networks.

Conclusion: Deep learning-based CT imaging models can accurately screen for PCD and identify differences between the cranial CT images.