bluuebunny/crossref_metadata_2025 huggingface dataset:
A survey on multi-omics-based cancer diagnosis using machine learning with the potential application in gastrointestinal cancer
Authors: Wang Suixue , Wang Shuling , Wang Zhengxia
Published: January 2023

Gastrointestinal cancer is becoming increasingly common, which leads to over 3 million deaths every year. No typical symptoms appear in the early stage of gastrointestinal cancer, posing a significant challenge in the diagnosis and treatment of patients with gastrointestinal cancer. Many patients are in the middle and late stages of gastrointestinal cancer when they feel uncomfortable, unfortunately, most of them will die of gastrointestinal cancer. Recently, various artificial intelligence techniques like machine learning based on multi-omics have been presented for cancer diagnosis and treatment in the era of precision medicine. This paper provides a survey on multi-omics-based cancer diagnosis using machine learning with potential application in gastrointestinal cancer. Particularly, we make a comprehensive summary and analysis from the perspective of multi-omics datasets, task types, and multi-omics-based integration methods. Furthermore, this paper points out the remaining challenges of multi-omics-based cancer diagnosis using machine learning and discusses future topics.
Baduanjin improves neck pain and functional movement in middle-aged and elderly people: A systematic review and meta-analysis of randomized controlled trials
Authors: Liu Zicai , Hu Hao , Wen Xin , Liu Xuejin , Xu Xiaqing , Wang Zhenjiang , Li Li , Liu Huiyu
Published: January 2023

Background

Neck pain (NP), one of the most common musculoskeletal diseases, exercises a great influence on the daily life of individuals, especially the elderly. Baduanjin is a traditional Qigong therapy from China, but there is no evidence for its use in the treatment of neck pain in middle-aged and elderly people.

Objective

We hope to summarize the efficacy evidence of Baduanjin in the treatment of middle-aged and elderly patients with neck pain (NP) for the first time, conduct a systematic review and meta-analysis, and provide basic evidence-based evidence for clinical practice.

Methods

Two researchers collectively searched PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine disk (Sino-Med), China National Knowledge Infrastructure (CNKI), Wanfang database, and China Science and Technology Journal Database (VIP). The search time is set from initial to 27 September 2022, to find out RCT articles that may meet the criteria. The risk bias assessment tool Cochrane was applied to assess the methodological quality of involved studies. RevMan 5.3 was used for the meta-analysis with a mean difference (MD) and 95% confidence interval (CI), and the model type was a random effects model. The VAS scores of the intervention and control groups were extracted and the results of the meta-analysis were presented using a forest plot.

Results

In total, 13 randomized controlled trials were meta-analyzed, including 840 patients. The results turned out that the VAS score in the intervention group was below the control group, which was statistically significant [MD = −1.15, 95% CI (−1.39, −0.92) and P < 0. 001]. The result of general efficiency suggests that the Baduanjin group was better than the control group [RR = 1.19, 95% CI (1.10, 1.29), P < 0.001].

Conclusion

The existing results seem to show that Baduanjin is safe and has a trend of positive benefits in the treatment of neck pain in middle-aged and elderly people. However, considering the limitations of this study, we need to be cautious in our conclusions, and more studies are needed to verify it in future.
Recent technologies in cardiac imaging
Authors: Counseller Quinn , Aboelkassem Yasser
Published: January 2023

Cardiac imaging allows physicians to view the structure and function of the heart to detect various heart abnormalities, ranging from inefficiencies in contraction, regulation of volumetric input and output of blood, deficits in valve function and structure, accumulation of plaque in arteries, and more. Commonly used cardiovascular imaging techniques include x-ray, computed tomography (CT), magnetic resonance imaging (MRI), echocardiogram, and positron emission tomography (PET)/single-photon emission computed tomography (SPECT). More recently, even more tools are at our disposal for investigating the heart’s physiology, performance, structure, and function due to technological advancements. This review study summarizes cardiac imaging techniques with a particular interest in MRI and CT, noting each tool’s origin, benefits, downfalls, clinical application, and advancement of cardiac imaging in the near future.
Genome Mining Shows Ubiquitous Presence and Extensive Diversity of Toxin-Antitoxin Systems in Pseudomonas syringae
Authors: Kandel Prem P. , Naumova Marina , Fautt Chad , Patel Ravikumar R. , Triplett Lindsay R. , Hockett Kevin L.
Published: January 2023

Bacterial toxin-antitoxin (TA) systems consist of two or more adjacent genes, encoding a toxin and an antitoxin. TA systems are implicated in evolutionary and physiological functions including genome maintenance, antibiotics persistence, phage defense, and virulence. Eight classes of TA systems have been described, based on the mechanism of toxin neutralization by the antitoxin. Although studied well in model species of clinical significance, little is known about the TA system abundance and diversity, and their potential roles in stress tolerance and virulence of plant pathogens. In this study, we screened the genomes of 339 strains representing the genetic and lifestyle diversity of the Pseudomonas syringae species complex for TA systems. Using bioinformatic search and prediction tools, including SLING, BLAST, HMMER, TADB2.0, and T1TAdb, we show that P. syringae strains encode 26 different families of TA systems targeting diverse cellular functions. TA systems in this species are almost exclusively type II. We predicted a median of 15 TA systems per genome, and we identified six type II TA families that are found in more than 80% of strains, while others are more sporadic. The majority of predicted TA genes are chromosomally encoded. Further functional characterization of the predicted TA systems could reveal how these widely prevalent gene modules potentially impact P. syringae ecology, virulence, and disease management practices.
Advanced mycotoxin control and decontamination techniques in view of an increased aflatoxin risk in Europe due to climate change
Authors: Loi Martina , Logrieco Antonio F. , Pusztahelyi Tünde , Leiter Éva , Hornok László , Pócsi István
Published: January 2023

Aflatoxins are toxic secondary metabolites produced by Aspergillus spp. found in staple food and feed commodities worldwide. Aflatoxins are carcinogenic, teratogenic, and mutagenic, and pose a serious threat to the health of both humans and animals. The global economy and trade are significantly affected as well. Various models and datasets related to aflatoxins in maize have been developed and used but have not yet been linked. The prevention of crop loss due to aflatoxin contamination is complex and challenging. Hence, the set-up of advanced decontamination is crucial to cope with the challenge of climate change, growing population, unstable political scenarios, and food security problems also in European countries. After harvest, decontamination methods can be applied during transport, storage, or processing, but their application for aflatoxin reduction is still limited. Therefore, this review aims to investigate the effects of environmental factors on aflatoxin production because of climate change and to critically discuss the present-day and novel decontamination techniques to unravel gaps and limitations to propose them as a tool to tackle an increased aflatoxin risk in Europe.
A bivalent subunit vaccine efficiently produced in Pichia pastoris against SARS-CoV-2 and emerging variants
Authors: Xu Huifang , Wang Tiantian , Sun Peng , Hou Xuchen , Gong Xin , Zhang Bin , Wu Jun , Liu Bo
Published: January 2023

The emergence of severe acute respiratory syndrome coronavirus type II (SARS-CoV-2) variants have led to a decline in the protection of existing vaccines and antibodies, and there is an urgent need for a broad-spectrum vaccination strategy to reduce the pressure on the prevention and control of the pandemic. In this study, the receptor binding domain (RBD) of the SARS-CoV-2 Beta variant was successfully expressed through a glycoengineered yeast platform. To pursue a more broad-spectrum vaccination strategy, RBD-Beta and RBD-wild type were mixed at the ratio of 1:1 with Al(OH)3 and CpG double adjuvants for the immunization of BALB/c mice. This bivalent vaccine stimulated robust conjugated antibody titers and a broader spectrum of neutralizing antibody titers. These results suggested that a bivalent vaccine of RBD-Beta and RBD-wild type could be a possible broad-spectrum vaccination strategy.
Determination of the ability of matrix-assisted laser desorption ionization time-of-flight mass spectrometry to identify high-biofilm-producing strains
Authors: Rodríguez-Temporal David , Díez Rafael , Díaz-Navarro Marta , Escribano Pilar , Guinea Jesús , Muñoz Patricia , Rodríguez-Sánchez Belén , Guembe María
Published: January 2023

Background

The traditional method for assessing the capacity of a microorganism to produce biofilm is generally a static in vitro model in a multi-well plate using the crystal violet (CV) binding assay, which takes 96 h. Furthermore, while the method is simple to perform, its reproducibility is poor.

Objective

We evaluated whether matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) could make it possible to differentiate between high-and low-biofilm-producing microorganisms on 24-h cultures of Staphylococcus aureus and Candida albicans.

Methods

We included 157 strains of S. aureus and 91 strains of C. albicans obtained from the blood cultures of patients with bacteremia/candidemia. We tested biofilm production using the CV binding assay as the gold standard to classify strains as low or high biofilm producers. We then applied MALDI-TOF MS to create a machine learning–based predictive model using 40 strains of S. aureus and C. albicans, each with extreme absorbance values, and validated this approach with the remaining 117 and 51 strains using the random forest algorithm and the support vector machine algorithm, respectively.

Results

Overall, 81.2% of the S. aureus strains (95/117) and 74.5% of the C. albicans strains (38/51) used for validation were correctly categorized, respectively, as low and high-biofilm-producing.

Conclusion

Classification based on MALDI-TOF MS protein spectra enables us to predict acceptable information about the capacity of 24-h cultures of S. aureus and C. albicans to form biofilm.
Salivary protein kinase C alpha and novel microRNAs as diagnostic and therapeutic resistance markers for oral squamous cell carcinoma in Indian cohorts
Authors: Saproo Sheetanshu , Sarkar Shashanka S. , Gautam Vishakha , Konyak Chingmei W. , Dass Gouri , Karmakar Arpita , Sharma Mansi , Ahuja Gaurav , Gupta Anand , Tayal Juhi , Mehta Anurag , Naidu Srivatsava
Published: January 2023

Oral squamous cell carcinoma (OSCC) is the second leading cause of cancer-related morbidity and mortality in India. Tobacco, alcohol, poor oral hygiene, and socio-economic factors remain causative for this high prevalence. Identification of non-invasive diagnostic markers tailored for Indian population can facilitate mass screening to reduce overall disease burden. Saliva offers non-invasive sampling and hosts a plethora of markers for OSCC diagnosis. Here, to capture the OSCC-specific salivary RNA markers suitable for Indian population, we performed RNA-sequencing of saliva from OSCC patients (n = 9) and normal controls (n = 5). Differential gene expression analysis detected an array of salivary RNAs including mRNAs, long non-coding RNAs, transfer-RNAs, and microRNAs specific to OSCC. Computational analysis and functional predictions identified protein kinase c alpha (PRKCA), miR-6087, miR-449b-5p, miR-3656, miR-326, miR-146b-5p, and miR-497-5p as potential salivary indicators of OSCC. Notably, higher expression of PRKCA, miR-6087 and miR-449b-5p were found to be associated with therapeutic resistance and poor survival, indicating their prognostic potential. In addition, sequencing reads that did not map to the human genome, showed alignments with microbial reference genomes. Metagenomic and statistical analysis of these microbial reads revealed a remarkable microbial dysbiosis between OSCC patients and normal controls. Moreover, the differentially abundant microbial taxa showed a significant association with tumor promoting pathways including inflammation and oxidative stress. Summarily, we provide an integrated landscape of OSCC-specific salivary RNAs relevant to Indian population which can be instrumental in devising non-invasive diagnostics for OSCC.
Temporal prediction error triggers amygdala-dependent memory updating in appetitive operant conditioning in rats
Authors: Tavares Tatiane Ferreira , Bueno José Lino Oliveira , Doyère Valérie
Published: January 2023

Reinforcement learning theories postulate that prediction error, i.e., a discrepancy between the actual and expected outcomes, drives reconsolidation and new learning, inducing an updating of the initial memory. Pavlovian studies have shown that prediction error detection is a fundamental mechanism in triggering amygdala-dependent memory updating, where the temporal relationship between stimuli plays a critical role. However, in contrast to the well-established findings in aversive situations (e.g., fear conditioning), only few studies exist on prediction error in appetitive operant conditioning, and even less with regard to the role of temporal parameters. To explore if temporal prediction error in an appetitive operant paradigm could generate an updating and consequent reconsolidation and/or new learning of temporal association, we ran four experiments in adult male rats. Experiment 1 verified whether an unexpected delay in the time of reward’s availability (i.e., a negative temporal prediction error) in a single session produces an updating in long-term memory of temporal expectancy in an appetitive operant conditioning. Experiment 2 showed that negative prediction errors, either due to the temporal change or through reward omission, increased in the basolateral amygdala nucleus (BLA) the activation of a protein that is critical for memory formation. Experiment 3 revealed that the presence of a protein synthesis inhibitor (anisomycin) in the BLA during the session when the reward was delayed (Error session) affected the temporal updating. Finally, Experiment 4 showed that anisomycin, when infused immediately after the Error session, interfered with the long-term memory of the temporal updating. Together, our study demonstrated an involvement of BLA after a change in temporal and reward contingencies, and in the resulting updating in long-term memory in appetitive operant conditioning.
Research on a hybrid neural network task assignment algorithm for solving multi-constraint heterogeneous autonomous underwater robot swarms
Authors: Ru Jingyu , Hao Dongqiang , Zhang Xiangyue , Xu Hongli , Jia Zixi
Published: January 2023

Studying the task assignment problem of multiple underwater robots has a broad effect on the field of underwater exploration and can be helpful in military, fishery, and energy. However, to the best of our knowledge, few studies have focused on multi-constrained underwater detection task assignment for heterogeneous autonomous underwater vehicle (AUV) clusters with autonomous decision-making capabilities, and the current popular heuristic methods have difficulty obtaining optimal cluster unit task assignment results. In this paper, a fast graph pointer network (FGPN) method, which is a hybrid of graph pointer network (GPN) and genetic algorithm, is proposed to solve the task assignment problem of detection/communication AUV clusters, and to improve the assignment efficiency on the basis of ensuring the accuracy of task assignment. A two-stage detection algorithm is used. First, the task nodes are clustered and pre-grouped according to the communication distance. Then, according to the clustering results, a neural network model based on graph pointer network is used to solve the local task assignment results. A large-scale cluster cooperative task assignment problem and a detection/communication cooperative work mode are proposed, which transform the cooperative cooperation problem of heterogeneous AUV clusters into a Multiple Traveling salesman problem (MTSP) for solving. We also conducted a large number of experiments to verify the effectiveness of the algorithm. The experimental results show that the solution efficiency of the method proposed in this paper is better than the traditional heuristic method on the scale of 300/500/750/1,000/1,500/2,000 task nodes, and the solution quality is similar to the result of the heuristic method. We hope that our ideas and methods for solving the large-scale cooperative task assignment problem can be used as a reference for large-scale task assignment problems and other related problems in other fields.
Research on the spatial layout optimization strategy of Huaihe Road Commercial Block in Hefei city based on space syntax theory
Authors: Zhou Qinghua , Zheng Yiran
Published: January 2023

Commercial block not only serves as a public space for the consumption, entertainment, and recreation of residents but also witnesses the history of urban commercial development. With the urban development and the improvement of people’s living standards, most commercial blocks are faced with such problems as traffic congestion, simple commercial form, and unreasonable spatial layout. By taking the commercial block of Huaihe Commercial Pedestrian Street as an example and combining the axis and viewshed analysis method of space syntax theory, this article has analyzed the space and quantified the relevant data to analyze the spatial layout relationships of commercial blocks. As the outcomes, this article summarizes the strategies for optimizing the traffic space, scenic space, and commercial space of commercial blocks, hoping to facilitate the commercial block space layout optimization in the era of stock.
Evident lower blood levels of multiple nutritional compounds and highly prevalent malnutrition in sub-acute stroke patients with or without dysphagia
Authors: van Wijk Nick , Studer Bettina , van den Berg Claudia A. , Ripken Dina , Lansink Mirian , Siebler Mario , Schmidt-Wilcke Tobias
Published: January 2023

Introduction

Malnutrition is prevalent after stroke, particularly if post-stroke oropharyngeal dysphagia (OD) reduces nutritional intake. To further understand stroke-related malnutrition, a thorough nutritional assessment was performed in ischemic stroke patients with or without OD during sub-acute inpatient rehabilitation.

Methods

In this exploratory, observational, cross-sectional, multi-center study in Germany (NTR6802), ischemic stroke patients with (N = 36) or without (N = 49) OD were age- and sex-matched to healthy reference subjects. Presence of (risk of) malnutrition (MNA-SF), blood concentration of stroke-relevant nutritional compounds and metabolites, nutritional intake, quality of life (EQ-5D-5L), and activities of daily living (Barthel index) were assessed.

Results

More than half of the stroke patients displayed (risk of) malnutrition, with higher prevalence in patient with OD vs. without OD. Fasted blood concentrations of vitamins B1, B2, B6, A, D, and E, selenium, choline, coenzyme Q10, albumin, pre-albumin, transferrin, docosahexaenoic acid, and eicosapentaenoic acid were all lower in stroke patients compared to their matched healthy reference subjects, irrespective of OD status. Reported energy, macronutrient, and water intake were lower in stroke patients vs. healthy reference subjects. As expected, quality of life and activities of daily living scores were lower in stroke vs. healthy reference subjects, with OD scoring worse than non-OD patients.

Discussion

This study shows that malnutrition is highly prevalent in sub-acute stroke patients during rehabilitation. Even though patients with OD were more likely to be malnourished, blood levels of specific nutritional compounds were similarly lower in stroke patients with or without OD compared to healthy reference subjects. Furthermore, subgroup analysis showed similarly lower blood levels of specific nutritional compounds in patients that are normal nourished vs. patients with (risk of) malnutrition. This might imply disease-specific changes in blood levels on top of overall protein-energy malnutrition. The results of the current study underline that it is important to screen for nutritional impairments in every stroke patient, either with or without OD.
CSF biomarkers for early-onset Alzheimer's disease in Chinese population from PUMCH dementia cohort
Authors: Lei Dan , Mao Chenhui , Li Jie , Huang Xinying , Sha Longze , Liu Caiyan , Dong Liling , Xu Qi , Gao Jing
Published: January 2023

Introduction

Alzheimer's disease (AD) is one of the highly concerned degenerative disorders in recent decades. Though vast amount of researches has been done in various aspects, early-onset subtype, however, needs more investigation in diagnosis for its atypical manifestations and progression process. Fundamental CSF biomarkers of early-onset AD are explored in PUMCH dementia cohort to depict its laboratory characteristics.

Materials and methods

A total of 125 individuals (age of onset <65 years old) from PUMCH dementia cohort were recruited consecutively and classified into AD, non-AD dementia, and control groups. Levels of amyloid-β 42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau) were measured using ELISA INNOTEST (Fujirebio, Ghent, Belgium). Students' t-test or non-parametric test are used to evaluate the differences between groups. Area under curve (AUC) of receiver operating characteristic (ROC) curve was introduced to prove the diagnostic powers of corresponding markers. Logistic regression is used to establish diagnostic model to combine several markers together to promote the diagnostic power.

Results

The average of all three biomarkers and two calculated ratios (t-tau/Aβ42, p-tau/Aβ42) were statistically different in the AD group compared with the other two groups (Ps < 0.01). From our data, we were able to provide cutoff values (Aβ42 < 570.9 pg/mL; p-tau > 56.49 pg/mL; t-tau > 241.6 pg/mL; t-tau/Aβ42 > 0.529; p-tau/Aβ42 > 0.0846) with acceptable diagnostic accuracy compared to other studies. Using a combination of biomarkers and logistic regression (area under curve 0.951), we were able to further improve diagnostic efficacy.

Discussion

Our study supports the diagnostic usefulness of biomarkers and defined cutoff values to diagnose early-onset AD. We showed that the ratios of t-tau/Aβ42 and p-tau/Aβ42 are more sensitive than relying on Aβ42 levels alone, and that we can further improve diagnostic accuracy by combining biomarkers.
Detection of astrocytic slow oscillatory activity and response to seizurogenic compounds using planar microelectrode array
Authors: Kuroda Taeko , Matsuda Naoki , Ishibashi Yuto , Suzuki Ikuro
Published: January 2023

Since the development of the planar microelectrode array (MEA), it has become popular to evaluate compounds based on the electrical activity of rodent and human induced pluripotent stem cell (iPSC)-derived neurons. However, there are no reports recording spontaneous human astrocyte activity from astrocyte-only culture sample by MEA. It is becoming clear that astrocytes play an important role in various neurological diseases, and astrocytes are expected to be excellent candidates for targeted therapeutics for the treatment of neurological diseases. Therefore, measuring astrocyte activity is very important for drug development for astrocytes. Recently, astrocyte activity has been found to be reflected in the low-frequency band < 1 Hz, which is much lower than the frequency band for recording neural activity. Here, we separated the signals obtained from human primary astrocytes cultured on MEA into seven frequency bands and successfully recorded the extracellular electrical activity of human astrocytes. The slow waveforms of spontaneous astrocyte activity were observed most clearly in direct current potentials < 1 Hz. We established nine parameters to assess astrocyte activity and evaluated five seizurogenic drug responses in human primary astrocytes and human iPSC-derived astrocytes. Astrocytes demonstrated the most significant dose-dependent changes in pilocarpine. Furthermore, in a principal component analysis using those parameter sets, the drug responses to each seizurogenic compound were separated. In this paper, we report the spontaneous electrical activity measurement of astrocytes alone using MEA for the first time and propose that the MEA measurement focusing on the low-frequency band could be useful as one of the methods to assess drug response in vitro.
Clinical characteristics and prognosis of acute low-frequency hearing loss and ascending sensorineural sudden sensorineural hearing loss
Authors: Diao Tongxiang , Chen Yurun , Jing Yuanyuan , Ma Xin
Published: January 2023

Objective

The present study aimed to explore the pathogenesis of the ascending sudden sensorineural hearing (SSNHL) loss by comparing the clinical characteristics and prognosis of acute low-frequency hearing loss (ALFHL) and ascending SSNHL.

Methods

A total of 43 patients with ALFHL and 122 patients with ascending SSNHL were enrolled in this study. First, the prognosis of patients with ALFHL and ascending SSNHL were compared, and the prognostic factors of AFHL and ascending SSNHL were analyzed.

Results

Acute low-frequency hearing loss and ascending SSNHL have no remarkable difference in complete recovery rate. Compared to ascending SSNHL, ALFHL has younger onset age, female prevalence, lower hearing threshold, shorter time from onset to recovery, and a lower proportion of combined tinnitus. The PTA at admission and delay from onset to therapy were significantly related to the prognosis of patients with ascending SSNHL, while only delay from onset to therapy was significantly related to the prognosis of patients with ALFHL. The majority of patients with ascending SSNHL and ALFHL recovered completely within 10 days from onset.

Conclusion

Audiogram shape plays a critical role in the prognosis of SSNHL. Ascending SSNHL and ALFHL may share a common pathological mechanism.
What is the role of lipids in prion conversion and disease?
Authors: Alves Conceição Cyntia , Assis de Lemos Gabriela , Barros Caroline Augusto , Vieira Tuane C. R. G.
Published: January 2023

The molecular cause of transmissible spongiform encephalopathies (TSEs) involves the conversion of the cellular prion protein (PrPC) into its pathogenic form, called prion scrapie (PrPSc), which is prone to the formation of amorphous and amyloid aggregates found in TSE patients. Although the mechanisms of conversion of PrPC into PrPSc are not entirely understood, two key points are currently accepted: (i) PrPSc acts as a seed for the recruitment of native PrPC, inducing the latter’s conversion to PrPSc; and (ii) other biomolecules, such as DNA, RNA, or lipids, can act as cofactors, mediating the conversion from PrPC to PrPSc. Interestingly, PrPC is anchored by a glycosylphosphatidylinositol molecule in the outer cell membrane. Therefore, interactions with lipid membranes or alterations in the membranes themselves have been widely investigated as possible factors for conversion. Alone or in combination with RNA molecules, lipids can induce the formation of PrP in vitro-produced aggregates capable of infecting animal models. Here, we discuss the role of lipids in prion conversion and infectivity, highlighting the structural and cytotoxic aspects of lipid-prion interactions. Strikingly, disorders like Alzheimer’s and Parkinson’s disease also seem to be caused by changes in protein structure and share pathogenic mechanisms with TSEs. Thus, we posit that comprehending the process of PrP conversion is relevant to understanding critical events involved in a variety of neurodegenerative disorders and will contribute to developing future therapeutic strategies for these devastating conditions.
Transcriptional and epigenetic regulation of microglia in maintenance of brain homeostasis and neurodegeneration
Authors: Maurya Shashank Kumar , Gupta Suchi , Mishra Rajnikant
Published: January 2023

The emerging role of microglia in brain homeostasis, neurodegeneration, and neurodevelopmental disorders has attracted considerable interest. In addition, recent developments in microglial functions and associated pathways have shed new light on their fundamental role in the immunological surveillance of the brain. Understanding the interconnections between microglia, neurons, and non-neuronal cells have opened up additional avenues for research in this evolving field. Furthermore, the study of microglia at the transcriptional and epigenetic levels has enhanced our knowledge of these native brain immune cells. Moreover, exploring various facets of microglia biology will facilitate the early detection, treatment, and management of neurological disorders. Consequently, the present review aimed to provide comprehensive insight on microglia biology and its influence on brain development, homeostasis, management of disease, and highlights microglia as potential therapeutic targets in neurodegenerative and neurodevelopmental diseases.
Radiometal chelators for infection diagnostics
Authors: Akter Asma , Lyons Oliver , Mehra Varun , Isenman Heather , Abbate Vincenzo
Published: January 2023

Infection of native tissues or implanted devices is common, but clinical diagnosis is frequently difficult and currently available noninvasive tests perform poorly. Immunocompromised individuals (for example transplant recipients, or those with cancer) are at increased risk. No imaging test in clinical use can specifically identify infection, or accurately differentiate bacterial from fungal infections. Commonly used [18F]fluorodeoxyglucose (18FDG) positron emission computed tomography (PET/CT) is sensitive for infection, but limited by poor specificity because increased glucose uptake may also indicate inflammation or malignancy. Furthermore, this tracer provides no indication of the type of infective agent (bacterial, fungal, or parasitic). Imaging tools that directly and specifically target microbial pathogens are highly desirable to improve noninvasive infection diagnosis and localization. A growing field of research is exploring the utility of radiometals and their chelators (siderophores), which are small molecules that bind radiometals and form a stable complex allowing sequestration by microbes. This radiometal-chelator complex can be directed to a specific microbial target in vivo, facilitating anatomical localization by PET or single photon emission computed tomography. Additionally, bifunctional chelators can further conjugate therapeutic molecules (e.g., peptides, antibiotics, antibodies) while still bound to desired radiometals, combining specific imaging with highly targeted antimicrobial therapy. These novel therapeutics may prove a useful complement to the armamentarium in the global fight against antimicrobial resistance. This review will highlight current state of infection imaging diagnostics and their limitations, strategies to develop infection-specific diagnostics, recent advances in radiometal-based chelators for microbial infection imaging, challenges, and future directions to improve targeted diagnostics and/or therapeutics.
Innovation in sweet rice wine with high antioxidant activity: Eucommia ulmoides leaf sweet rice wine
Authors: Ren Na , Gong Weiwei , Zhao Yichen , Zhao De-gang , Xu Yiwen
Published: January 2023

The dried leaves of Eucommia ulmoides Oliv., which have a high nutritional value, are mainly used in both medicine and food. In this study, we used Eucommia ulmoides leaf superfine powder as an additive in the fermentation of glutinous rice (Semen Oryzae Glutinosae) to develop a new healthcare product, Eucommia leaf sweet rice wine. The fermentation conditions were optimized, and the nutrient value was evaluated through analyses of metabolites, functional compositions, antioxidant capacity, and antihyperglycemic, antihyperlipidemic, and antihypertensive abilities. The metabolic analysis demonstrated that Eucommia leaf sweet rice wine contained a large number of flavonoids and other metabolites. Eucommia leaf sweet rice wine had higher contents of flavonoid (729.0 ± 0.11 μg/g), free amino acids (55.0 ± 0.37 μg/g), polyphenol (150.0 ± 0.43 μg/g), and polysaccharide (0.25 ± 0.03 μg/g) than traditional sweet rice wine, with increases of 14.7, 2.6, 6.8, and 6.3 times, respectively. In addition, an analysis of antioxidant capacity in vitro revealed that Eucommia leaf sweet rice wine had a high level of activity in scavenging 2, 2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion, and hydroxyl radicals, as well as in reducing iron, indicating that it was a strong antioxidant. Furthermore, Eucommia leaf sweet rice wine had a high cholate binding capacity and could significantly inhibit α-amylase, α-glucosidase, and angiotensin-converting enzyme (ACE) activity. In conclusion, this study developed a new application of Eucommia leaf in sweet rice wine fermentation and brewed Eucommia leaf sweet rice wine with strong antioxidant activity and positive antihypertensive, antihyperglycemic, and antihyperlipidemic effects in vitro. This study suggests new opportunities for the wider use of Eucommia ulmoides leaves and adds variety to sweet rice wine.
Prediction of bone metastasis in non-small cell lung cancer based on machine learning
Authors: Li Meng-Pan , Liu Wen-Cai , Sun Bo-Lin , Zhong Nan-Shan , Liu Zhi-Li , Huang Shan-Hu , Zhang Zhi-Hong , Liu Jia-Ming
Published: January 2023

Objective

The purpose of this paper was to develop a machine learning algorithm with good performance in predicting bone metastasis (BM) in non-small cell lung cancer (NSCLC) and establish a simple web predictor based on the algorithm.

Methods

Patients who diagnosed with NSCLC between 2010 and 2018 in the Surveillance, Epidemiology and End Results (SEER) database were involved. To increase the extensibility of the research, data of patients who first diagnosed with NSCLC at the First Affiliated Hospital of Nanchang University between January 2007 and December 2016 were also included in this study. Independent risk factors for BM in NSCLC were screened by univariate and multivariate logistic regression. At this basis, we chose six commonly machine learning algorithms to build predictive models, including Logistic Regression (LR), Decision tree (DT), Random Forest (RF), Gradient Boosting Machine (GBM), Naive Bayes classifiers (NBC) and eXtreme gradient boosting (XGB). Then, the best model was identified to build the web-predictor for predicting BM of NSCLC patients. Finally, area under receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity were used to evaluate the performance of these models.

Results

A total of 50581 NSCLC patients were included in this study, and 5087(10.06%) of them developed BM. The sex, grade, laterality, histology, T stage, N stage, and chemotherapy were independent risk factors for NSCLC. Of these six models, the machine learning model built by the XGB algorithm performed best in both internal and external data setting validation, with AUC scores of 0.808 and 0.841, respectively. Then, the XGB algorithm was used to build a web predictor of BM from NSCLC.

Conclusion

This study developed a web predictor based XGB algorithm for predicting the risk of BM in NSCLC patients, which may assist doctors for clinical decision making
Mild oxidative stress protects against chemotherapy-induced hair loss
Authors: Zhang Yusheng , Jimenez Joaquin J.
Published: January 2023

Chemotherapy induces hair loss in most cancer patients who undergo treatment, which causes them significant psychosocial trauma. Scalp cooling has demonstrated some efficacy in attenuating chemotherapy-induced alopecia, but response rate varies between patients and chemotherapy class. Here, we showcase in rats a proof-of-concept treatment of using subcutaneous hydrogen peroxide and cumene hydroperoxide injections to provide total protection from hair loss against multiple classes of chemotherapy. We found that subcutaneous peroxides induce cell cycle arrest via P53 activation, thereby protecting hair follicles from the cytotoxic effects of chemotherapy on actively dividing cells. This treatment represents a highly effective and accessible way for cancer patients to maintain quality of life while undergoing treatment for cancer.
Efficient feature extraction from highly sparse binary genotype data for cancer prognosis prediction using an auto-encoder
Authors: Shen Junjie , Li Huijun , Yu Xinghao , Bai Lu , Dong Yongfei , Cao Jianping , Lu Ke , Tang Zaixiang
Published: January 2023

Genomics involving tens of thousands of genes is a complex system determining phenotype. An interesting and vital issue is how to integrate highly sparse genetic genomics data with a mass of minor effects into a prediction model for improving prediction power. We find that the deep learning method can work well to extract features by transforming highly sparse dichotomous data to lower-dimensional continuous data in a non-linear way. This may provide benefits in risk prediction-associated genotype data. We developed a multi-stage strategy to extract information from highly sparse binary genotype data and applied it for cancer prognosis. Specifically, we first reduced the size of binary biomarkers via a univariable regression model to a moderate size. Then, a trainable auto-encoder was used to learn compact features from the reduced data. Next, we performed a LASSO problem process to select the optimal combination of extracted features. Lastly, we applied such feature combination to real cancer prognostic models and evaluated the raw predictive effect of the models. The results indicated that these compressed transformation features could better improve the model’s original predictive performance and might avoid an overfitting problem. This idea may be enlightening for everyone involved in cancer research, risk reduction, treatment, and patient care via integrating genomics data.
Intraoperative use of the machine learning-derived nociception level monitor results in less pain in the first 90 min after surgery
Authors: van der Wal Imeen , Meijer Fleur , Fuica Rivka , Silman Zmira , Boon Martijn , Martini Chris , van Velzen Monique , Dahan Albert , Niesters Marieke , Gozal Yaacov
Published: January 2023

In this pooled analysis of two randomized clinical trials, intraoperative opioid dosing based on the nociception level-index produced less pain compared to standard care with a difference in pain scores in the post-anesthesia care unit of 1.5 (95% CI 0.8–2.2) points on an 11-point scale. The proportion of patients with severe pain was lower by 70%. Severe postoperative pain remains a significant problem and associates with several adverse outcomes. Here, we determined whether the application of a monitor that detects intraoperative nociceptive events, based on machine learning technology, and treatment of such events reduces pain scores in the post-anesthesia care unit (PACU). To that end, we performed a pooled analysis of two trials in adult patients, undergoing elective major abdominal surgery, on the effect of intraoperative nociception level monitor (NOL)-guided fentanyl dosing on PACU pain was performed. Patients received NOL-guided fentanyl dosing or standard care (fentanyl dosing based on hemodynamic parameters). Goal of the intervention was to keep NOL at values that indicated absence of nociception. The primary endpoint of the study was the median pain score obtained in the first 90 min in the PACU. Pain scores were collected at 15 min intervals on an 11-point Likert scale. Data from 125 patients (55 men, 70 women, age range 21–86 years) were analyzed. Sixty-one patients received NOL-guided fentanyl dosing and 64 standard care. Median PACU pain score was 1.5 points (0.8–2.2) lower in the NOL group compared to the standard care; the proportion of patients with severe pain was 70% lower in the NOL group (p = 0.045). The only significant factor associated with increased odds for severe pain was the standard of care compared to NOL treatment (OR 6.0, 95% CI 1.4 −25.9, p = 0.017). The use of a machine learning-based technology to guide opioid dosing during major abdominal surgery resulted in reduced PACU pain scores with less patients in severe pain.
Multiple congenital anomalies and adverse developmental outcomes are associated with neonatal intensive care admission and unilateral hearing loss
Authors: Horrocks Lucy M. , Kitterick Pádraig T. , Jayasinghe Dulip S. , Willis Karen R. , Martin Katherine R. M. , Dixit Abhijit , Thornton Sally K.
Published: January 2023

Aim

To determine congenital and developmental outcomes of children with Unilateral Hearing Loss (UHL) who were admitted to the Neonatal Intensive Care Unit (NICU).

Method

Retrospective, single-site study that followed 25 children with permanent congenital UHL and a NICU admission to a NICU of Nottingham University Hospital. Birth and two-year developmental follow-up data were collected. They were compared to matched control group who had a NICU admission but no hearing loss (matched on gestational age, weight and sex).

Results

The median birthweights, gestational ages and number of days spent on the NICU for the UHL population were 2510 g, 36 weeks, and 12 days respectively. Most children (20/25; 80%) with UHL and a NICU admission were diagnosed with a congenital anomaly within the first two years of life. Only half (13/25) of these children were diagnosed with a congenital anomaly at discharge. Children with UHL and a NICU admission were more likely than the matched group (NICU admission only; p < .001) to have multiple congenital anomalies. We found a positive association between multiple congenital anomalies and developmental impairment for the NICU graduates with UHL (p = .019). This UHL-NICU group were also more likely than the matched NICU children to have developmental impairment (7/25 vs. 0/25; p = .01), speech and language therapy (13/25 vs. 1/25; p < .001), inner ear malformations (14/25 vs. 0/25, p < .001) or craniofacial anomalies (12/25 vs. 2/25; p = .004).

Interpretation

Children with UHL and a NICU admission were at high risk of congenital anomalies and certain adverse developmental outcomes. Improved congenital anomaly screening is needed at birth for this population. Having multiple congenital anomalies suggests closer developmental monitoring is needed. This study contributes towards producing clinical screening and management guidelines to ensure consistent high-quality care for this unique population.
Advocacy training tool for pediatric residents to strengthen firearm safety laws
Authors: Risney Scott , Hollon Hannah , Dodington James
Published: January 2023

Firearm injury is the leading cause of death in children and adolescents in the US, surpassing motor vehicle crashes. There is a need for greater legislative advocacy around firearm injury prevention, specifically around safer storage of firearms. A national medical trainee-based program convened in 2021 with the goal of increasing advocacy efforts around common causes of pediatric injury. A focus was to create a set of advocacy training tools that could be utilized by a wide variety of stakeholders. The subgroup sought to design policy-based training tools; one focused on general firearm injury prevention principles and another specifically focused on Child Access Prevention (CAP) laws. We explicate the utility of these documents and the need for greater advocacy around pediatric firearm injuries
Polysomnographic characteristics and treatment modalities in a referred population of children with trisomy 21
Authors: Gaza Kaelyn , Gustave Jodi , Rani Seema , Strang Abigail , Chidekel Aaron
Published: January 2023

Background

Children with Trisomy 21 (T21) are at an increased risk of sleep-disordered breathing (SDB), which can impact daily functioning and cause other health complications. Accordingly, it is imperative to diagnose and treat SDB in this population. Current guidelines recommend screening polysomnogram by age 4 or sooner if clinically indicated. There are limited published studies describing characteristics of SDB in children with T21, particularly in infants and young children.

Objective

The objective of this study is to characterize SDB and treatment modalities in infants and young children with T21.

Methods

This is a retrospective review of a cohort of children (≤60 months of age) with T21 who completed a polysomnogram (PSG) between 2015 and 2020 at a pediatric referral center. Demographic information, relevant medical history, polysomnography parameters, and treatment details of these children were collected from EMR. Descriptive and comparative statistics were calculated for the cohort; additional subgroup analysis was completed by age 0–35 months and 36–60 months.

Results

Most of the cohort met criteria for sleep apnea (84.1%), and airway surgery was the most common treatment modality (71.4%). The mean AHI was high (21.4 events/hour) with a trend towards hypoventilation (mean EtCO2 = 55.9 mmHg; mean percentage of TST with EtCO2 > 50 mmHg 20.8%). Mean arousal index was elevated (32 events/hour). There were no significant differences in SDB by age when we compared children 0–35 months and 36–60 months.

Conclusions

This cohort of referred children with T21 showed high prevalence of SDB with a trend towards hypoventilation and disrupted sleep quality with no significant differences by age. These data highlight the importance of maintaining a high index of suspicion for SDB in young patients with T21 and obtaining PSG testing to characterize sleep and breathing.
Downregulation of ICCs and PDGFRα+ cells on colonic dysmotility in hirschsprung disease
Authors: Gu Aiming , Wu Zhihao , Wang Peng , Liu Jun , Wang Jianfeng , Wang Qianqian , Chen Jie
Published: January 2023

Background

To investigate the effect of the distribution and expression of interstitial cells of Cajal (ICCs) and platelet-derived growth factor receptor-α positive (PDGFRα+) cells in different colon segments on colonic motility in children with Hirschsprung disease (HSCR).

Methods

Smooth muscles of the narrow and dilated segments of the colon were obtained from 16 pediatric patients with HSCR. The proximal margin was set as the control section. The mRNA and protein expressions of c-Kit, PDGFRα, ANO1, and SK3 channels were examined. Circular smooth muscle strips of the colon were prepared for performing electrophysiology experiments using electric field stimulation (EFS) and intervention from different drugs (TTX, NPPB, Apamin, L-NAME, and CyPPA).

Results

The mRNA and protein expressions of c-Kit, ANO1, PDGFRα, and SK3 were much lower in the narrow segment than those in the dilated and proximal segments of the colon. The narrow segment showed a considerably spontaneous contraction of the muscle strip. After the EFS, the relaxation response decreased from the proximal to the narrow segment, whereas the contraction response increased. TTX blocking did not cause any significant changes in the narrow segment. In contrast, when NPPB, Apamin, L-NAME, and CyPPA were used to intervene in the muscle strips, the proximal segment showed a more sensitive inhibitory or excitatory response than the narrow segment.

Conclusions

Downregulation of the ICCs and PDGFRα+ cells from the proximal to narrow segment may be responsible for the dysmotility of the colon in pediatric HSCR.