bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomining-Based Elucidation of Natural Product Biosynthetic Pathways in Streptomyces
Authors: Linardi Darwin , She Weiyi , Zhang Qian , Yu Yi , Qian Pei-Yuan , Lam Henry
Published: July 2022

The genusStreptomycesis known to harbor numerous biosynthetic gene clusters (BGCs) of potential utility in synthetic biology applications. However, it is often difficult to link uncharacterized BGCs with the secondary metabolites they produce. Proteomining refers to the strategy of identifying active BGCs by correlating changes in protein expression with the production of secondary metabolites of interest. In this study, we devised a shotgun proteomics-based workflow to identify active BGCs during fermentation when a variety of compounds are being produced. Mycelia harvested during the non-producing growth phase served as the background. Proteins that were differentially expressed were clustered based on the proximity of the genes in the genome to highlight active BGCs systematically from label-free quantitative proteomics data. Our software tool is easy-to-use and requires only 1 point of comparison where natural product biosynthesis was significantly different. We tested our proteomining clustering method on threeStreptomycesspecies producing different compounds. InStreptomyces coelicolorA3(2), we detected the BGCs of calcium-dependent antibiotic, actinorhodin, undecylprodigiosin, and coelimycin P1. InStreptomyces chrestomyceticusBCC24770, 7 BGCs were identified. Among them, we independently re-discovered the type II PKS for albofungin production previously identified by genome mining and tedious heterologous expression experiments. InStreptomyces tenebrarius, 5 BGCs were detected, including the known apramycin and tobramycin BGC as well as a newly discovered caerulomycin A BGC in this species. The production of caerulomycin A was confirmed by LC-MS and the inactivation of the caerulomycin A BGC surprisingly had a significant impact on the secondary metabolite regulation ofS. tenebrarius. In conclusion, we developed an unbiased, high throughput proteomics-based method to complement genome mining methods for the identification of biosynthetic pathways inStreptomycessp.
Strategy to Evaluate Changes in Bacterial Community Profiles and Bacterial Pathogen Load Reduction After Sewage Disinfection
Authors: Tang Mandy Lok Yi , Lau Stanley Chun Kwan
Published: July 2022

Sewage effluent discharge is a major source of pathogenic contamination to the environment. The disinfection process is critical for the elimination of pathogens in sewage. In this study, we examined the impact of chlorine disinfection on the total, viable, and culturable populations of indicator bacteria, pathogens, and bacterial communities in two contrasting types of effluents (primarily treated saline and secondarily treated freshwater). Effluents collected bimonthly over 1 year were examined using cultivation, quantitative PCR (qPCR), and 16S rRNA gene amplicon sequencing coupled with or without propidium monoazide (PMA) treatment. The results showed that each type of effluent was characterized by a specific set of representative genera before disinfection. Salinity appeared to be the major abiotic factor associated with the differences in bacterial community compositions. The pathogen analysis pipeline revealed over 20 viable clinically important pathogenic species in the effluents. Although the bacterial communities differed markedly between the two types of effluents before disinfection, the species of pathogens persisting after disinfection were similar, many of them were members of Enterobacter and Vibrio. The relative abundances of all pathogens identified in the amplicon sequences were multiplied by the 16S rRNA gene copy numbers of total bacteria detected by PMA-qPCR to estimate their concentrations. Pathogens remained viable after disinfection reached 8 log10 16S rRNA copies ml−1 effluent. Meanwhile, around 80 % of the populations of three indicator bacteria including Escherichia coli, Enterococcus, and Bacteroidales were viable after disinfection, but over 99 % of the viable E. coli and Enterococcus were in the non-culturable state. We estimated the total pathogen load by adding the concentrations of all viable pathogens and examined their correlations with indicator bacteria of different types, physiological states, and effluents. The results showed that the PMA-qPCR measurement of E. coli is a reliable proxy of bacterial pathogen loads in both types of effluents. The utility of viable indicator bacteria as a biological index to assess the overall bacteriological hazards in effluents is discussed.
Deficiency of GntR Family Regulator MSMEG_5174 Promotes Mycobacterium smegmatis Resistance to Aminoglycosides via Manipulating Purine Metabolism
Authors: Deng Wanyan , Zheng Zengzhang , Chen Yi , Yang Maoyi , Yan Jun , Li Wu , Zeng Jie , Xie Jianping , Gong Sitang , Zeng Huasong
Published: July 2022

The increasing incidence of drug-resistant tuberculosis is still an emergency for global public health and a major obstacle to tuberculosis treatment. Therefore, deciphering the novel mechanisms of mycobacterial antibiotic resistance is crucial for combatting the rapid emergence of drug-resistant strains. In this study, we identified an unexpected role of Mycobacterium smegmatis GntR family transcriptional regulator MSMEG_5174 and its homologous gene Mycobacterium tuberculosis Rv1152 in aminoglycoside antibiotic resistance. Deficiency of MSMEG_5174 rendered Mycobacterium smegmatis highly resistant to aminoglycoside antibiotic treatment, and ectopic expression of Rv1152 in MSMEG_5174 mutants restored antibiotic-induced bacterial killing. We further demonstrated that MSMEG_5174 negatively regulates the expression of purine metabolism-related genes and the accumulation of purine metabolites. Moreover, overexpression of xanthine dehydrogenase MSMEG_0871 or xanthine treatment elicited a significant decrease in aminoglycoside antibiotic lethality for Mycobacterium smegmatis. Together, our findings revealed MSMEG_5174 as a metabolic regulator and hint toward unexplored crosstalk between purine metabolism and antibiotic resistance.
Dairy Cows Experimentally Infected With Bovine Leukemia Virus Showed an Increased Milk Production in Lactation Numbers 3–4: A 4-Year Longitudinal Study
Authors: Yang Yi , Gong Zaicheng , Lu Yi , Lu Xubin , Zhang Jilei , Meng Ye , Peng Yalan , Chu Shuangfeng , Cao Wenqiang , Hao Xiaoli , Sun Jie , Wang Heng , Qin Aijian , Wang Chengming , Shang Shaobin , Yang Zhangping
Published: July 2022

Bovine leukemia virus (BLV) is widespread in global cattle populations, but the effects of its infection on milk quantity and quality have not been clearly elucidated in animal models. In this study, 30 healthy first-lactation cows were selected from ≈2,988 cows in a BLV-free farm with the same criteria of parity, age, lactation number, as well as milk yield, SCS, and composition (fat, protein, and lactose). Subsequently, these cows were randomly assigned to the intervention (n = 15) or control (n = 15) group, and reared in different cowsheds. Cows in the intervention group were inoculated with 1 × phosphate-buffered solution (PBS) resuspended in peripheral blood mononuclear cells (PBMC) from a BLV-positive cow, while the controls were inoculated with the inactivated PBMC from the same individual. From June 2016 to July 2021, milk weight (kg) was automatically recorded by milk sensors, and milk SCS and composition were originated from monthly performed dairy herd improvement (DHI) testing. Fluorescence resonance energy transfer (FRET)–qPCR and ELISA showed that cows in the intervention group were successfully infected with BLV, while cows in the control group were free of BLV for the entire period. At 45 days post-inoculation (DPI), the numbers of whole blood cells (WBCs) (P = 0.010), lymphocytes (LYMs) (P = 0.002), and monocytes (MNCs) (P = 0.001) and the expression levels of IFN-γ (P = 0.013), IL-10 (P = 0.031), and IL-12p70 (P = 0.008) increased significantly in the BLV infected cows compared to the non-infected. In lactation numbers 2–4, the intervention group had significantly higher overall milk yield (P < 0.001), fat (P = 0.031), and protein (P = 0.050) than the control group, while milk SCS (P = 0.038) and lactose (P = 0.036) decreased significantly. Further analysis indicated that BLV infection was associated with increased milk yield at each lactation stage in lactation numbers 3–4 (P = 0.021 or P < 0.001), but not with SCS and milk composition. Together, this 4-year longitudinal study revealed that artificial inoculation of BLV increased the milk yield in cows in this BLV challenge model.
High Expression of Plasma Extracellular HSP90α is Associated With the Poor Efficacy of Chemotherapy and Prognosis in Small Cell Lung Cancer
Authors: Huang Baoyue , Pan Jinmiao , Liu Haizhou , Tang Yamei , Li Shirong , Bian Yingzhen , Ning Shufang , Li Jilin , Zhang Litu
Published: July 2022

Purpose: eHSP90α is closely related to tumor progression and prognosis. This study aimed to investigate the significance of eHSP90α in the response evaluation and prediction of small cell lung cancer.

Methods: We analyzed the relationship between eHSP90α expression and clinicopathological features in 105 patients with small cell lung cancer. Univariate and multivariate analyses were used to determine the association of parameters and ratios with response assessment, progression-free survival (PFS), and overall survival (OS).

Results: In SCLC patients, eHSP90α and NSE were positively correlated. The cutoff values of eHSP90α in OS, PFS, and response evaluation were 61.2 ng/ml, 48.7 ng/ml, and 48.7 ng/ml, respectively. eHSP90α could better predict OS, PFS, and response evaluation (AUC OS 0.791, PFS 0.662, 0.685). Radiotherapy and eHSP90α were independent variables for effective chemotherapy through univariate and multivariate analysis. In contrast, radiotherapy, eHSP90α, NSE, and M stage were independent variables for OS. eHSP90α, and M stage were independent variables for PFS. Kaplan-Meier analysis showed that higher eHSP90α expression predicted poorer OS and earlier progression in patients.

Conclusions: This study aims to provide new evidence for the efficacy response and prognostic assessment of SCLC. eHSP90α may be a better biomarker for SCLC.
Cryo-EM Structure of an Atypical Proton-Coupled Peptide Transporter: Di- and Tripeptide Permease C
Authors: Killer Maxime , Finocchio Giada , Mertens Haydyn D. T. , Svergun Dmitri I. , Pardon Els , Steyaert Jan , Löw Christian
Published: July 2022

Proton-coupled Oligopeptide Transporters (POTs) of the Major Facilitator Superfamily (MFS) mediate the uptake of short di- and tripeptides in all phyla of life. POTs are thought to constitute the most promiscuous class of MFS transporters, with the potential to transport more than 8400 unique substrates. Over the past two decades, transport assays and biophysical studies have shown that various orthologues and paralogues display differences in substrate selectivity. The E. coli genome codes for four different POTs, known as Di- and tripeptide permeases A-D (DtpA-D). DtpC was shown previously to favor positively charged peptides as substrates. In this study, we describe, how we determined the structure of the 53 kDa DtpC by cryogenic electron microscopy (cryo-EM), and provide structural insights into the ligand specificity of this atypical POT. We collected and analyzed data on the transporter fused to split superfolder GFP (split sfGFP), in complex with a 52 kDa Pro-macrobody and with a 13 kDa nanobody. The latter sample was more stable, rigid and a significant fraction dimeric, allowing us to reconstruct a 3D volume of DtpC at a resolution of 2.7 Å. This work provides a molecular explanation for the selectivity of DtpC, and highlights the value of small and rigid fiducial markers such as nanobodies for structure determination of low molecular weight integral membrane proteins lacking soluble domains.
A Bibliometric Review on Gut Microbiome and Alzheimer’s Disease Between 2012 and 2021
Authors: Trejo-Castro Alejandro I. , Carrion-Alvarez Diego , Martinez-Torteya Antonio , Rangel-Escareño Claudia
Published: July 2022

Research on the microbiome has drawn an increasing amount of attention over the past decade. Even more so for its association with disease. Neurodegenerative diseases, such as Alzheimer’s disease (AD) have been a subject of study for a long time with slow success in improving diagnostic accuracy or identifying a possibility for treatment. In this work, we analyze past and current research on microbiome and its positive impact on AD treatment and diagnosis. We present a bibliometric analysis from 2012 to 2021 with data retrieved on September 2, 2021, from the Scopus database. The query includes “Gut AND (Microbiota OR Microbiome) AND Alzheimer*” within the article title, abstract, and keywords for all kinds of documents in the database. Compared with 2016, the number of publications (NPs) on the subject doubled by 2017. Moreover, we observe an exponential growth through 2020, and with the data presented, it is almost certain that it will continue this trend and grow even further in the upcoming years. We identify key journals interested in the subject and discuss the articles with most citations, analyzing trends and topics for future research, such as the ability to diagnose the disease and complement the cognitive test with other clinical biomarkers. According to the test, mild cognitive impairment (MCI) is normally considered an initial stage for AD. This test, combined with the role of the gut microbiome in early stages of the disease, may improve the diagnostic accuracy. Based on our findings, there is emerging evidence that microbiota, perhaps more specifically gut microbiota, plays a key role in the pathogenesis of diseases, such as AD.
Sleepiness in Cognitively Unimpaired Older Adults Is Associated With CSF Biomarkers of Inflammation and Axonal Integrity
Authors: Carvalho Diego Z. , St. Louis Erik K. , Przybelski Scott A. , Morgenthaler Timothy I. , Machulda Mary M. , Boeve Bradley F. , Petersen Ronald C. , Jack Clifford R. , Graff-Radford Jonathan , Vemuri Prashanthi , Mielke Michelle M.
Published: July 2022

Introduction

Sleepiness has been associated with cognitive decline and dementia in the elderly. Older adults with excessive daytime sleepiness appear to be more vulnerable to longitudinal amyloid PET accumulation before the onset of the dementia. However, it remains unclear whether sleepiness is similarly associated with other biomarkers of Alzheimer’s disease (AD), axonal integrity, and inflammation, which may also contribute to neurodegeneration and cognitive decline.

Methods

In this cross-sectional analysis, we identified 260 cognitively unimpaired adults (>60 years) from the Mayo Clinic Study of Aging, a population-based cohort from Olmsted County (MN), who underwent CSF quantification of AD biomarkers (Aβ42, p-tau, p-tau/Aβ42) in addition to at least one of the following biomarkers [neurofilament light chain (NfL) interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α)]. We fit linear regression models to assess associations between sleepiness, as measured by the Epworth Sleepiness Scale (ESS), and CSF biomarkers, controlling for age, sex, APOε4 status, body mass index, hypertension, dyslipidemia, and prior diagnosis of obstructive sleep apnea.

Results

Higher ESS scores were associated with higher CSF IL-6 and NfL, but not with the other CSF biomarkers. For every ESS score point increase, there was a 0.009 ([95% CI 0.001–0.016], p = 0.033) increase in the log of IL-6 and 0.01 ([95% CI 0.002–0.018], p = 0.016) increase in the log of NfL. A sensitivity analysis showed an association between ESS scores and log of p-tau/Aβ42 only in participants with an abnormal ratio (>0.023), highly predictive of amyloid positivity. For every ESS score point increase, there was a 0.006 ([95% CI 0.001–0.012], p = 0.021) increase in the log of CSF p-tau/Aβ42.

Conclusion

Sleepiness was associated with greater CSF IL-6 and NfL levels, which could contribute to neurodegeneration or alternatively cause sleepiness. Higher NfL levels may result from sleep disruption and/or contribute to sleepiness via disturbed connectivity or damage to wake-promoting centers. Associations between sleepiness and p-tau/Aβ42 in participants with abnormal ratio suggest that amyloid positivity contributes to vulnerability to sleep disturbance, which may further amyloid accumulation in a feed-forward loop process. Prospective studies of these markers are needed to determine cause-effect relationships between these associations.
An Attention-Based CoT-ResNet With Channel Shuffle Mechanism for Classification of Alzheimer’s Disease Levels
Authors: Li Chao , Wang Quan , Liu Xuebin , Hu Bingliang
Published: July 2022

Detection of early morphological changes in the brain and early diagnosis are important for Alzheimer’s disease (AD), and high-resolution magnetic resonance imaging (MRI) can be used to help diagnose and predict the disease. In this paper, we proposed two improved ResNet algorithms that introduced the Contextual Transformer (CoT) module, group convolution, and Channel Shuffle mechanism into the traditional ResNet residual blocks. The CoT module is used to replace the 3 × 3 convolution in the residual block to enhance the feature extraction capability of the residual block, while the Channel Shuffle mechanism is used to reorganize the feature maps of different groups in the input layer to improve the communication between the feature maps from different groups. Images of 503 subjects, including 116 healthy controls (HC), 187 subjects with mild cognitive impairment (MCI), and 200 subjects with AD, were selected and collated from the ADNI database, and then, the data were pre-processed and sliced. After that, 10,060 slices were obtained and the three groups of AD, MCI and HC were classified using the improved algorithms. The experiments showed that the refined ResNet-18-based algorithm improved the top-1 accuracy by 2.06%, 0.33%, 1.82%, and 1.52% over the traditional ResNet-18 algorithm for four medical image classification tasks, namely AD: MCI, AD: HC, MCI: HC, and AD: MCI: HC, respectively. The enhanced ResNet-50-based algorithm improved the top-1 accuracy by 1.02%, 2.92%, 3.30%, and 1.31%, respectively, over the traditional ResNet-50 algorithm in four medical image classification tasks, demonstrating the effectiveness of the CoT module replacement and the inclusion of the channel shuffling mechanism, as well as the competitiveness of the improved algorithms.
An EvoDevo Study of Salmonid Visual Opsin Dynamics and Photopigment Spectral Sensitivity
Authors: Eilertsen Mariann , Davies Wayne Iwan Lee , Patel Dharmeshkumar , Barnes Jonathan E. , Karlsen Rita , Mountford Jessica Kate , Stenkamp Deborah L. , Patel Jagdish Suresh , Helvik Jon Vidar
Published: July 2022

Salmonids are ideal models as many species follow a distinct developmental program from demersal eggs and a large yolk sac to hatching at an advanced developmental stage. Further, these economically important teleosts inhabit both marine- and freshwaters and experience diverse light environments during their life histories. At a genome level, salmonids have undergone a salmonid-specific fourth whole genome duplication event (Ss4R) compared to other teleosts that are already more genetically diverse compared to many non-teleost vertebrates. Thus, salmonids display phenotypically plastic visual systems that appear to be closely related to their anadromous migration patterns. This is most likely due to a complex interplay between their larger, more gene-rich genomes and broad spectrally enriched habitats; however, the molecular basis and functional consequences for such diversity is not fully understood. This study used advances in genome sequencing to identify the repertoire and genome organization of visual opsin genes (those primarily expressed in retinal photoreceptors) from six different salmonids [Atlantic salmon (Salmo salar), brown trout (Salmo trutta), Chinook salmon (Oncorhynchus tshawytcha), coho salmon (Oncorhynchus kisutch), rainbow trout (Oncorhynchus mykiss), and sockeye salmon (Oncorhynchus nerka)] compared to the northern pike (Esox lucius), a closely related non-salmonid species. Results identified multiple orthologues for all five visual opsin classes, except for presence of a single short-wavelength-sensitive-2 opsin gene. Several visual opsin genes were not retained after the Ss4R duplication event, which is consistent with the concept of salmonid rediploidization. Developmentally, transcriptomic analyzes of Atlantic salmon revealed differential expression within each opsin class, with two of the long-wavelength-sensitive opsins not being expressed before first feeding. Also, early opsin expression in the retina was located centrally, expanding dorsally and ventrally as eye development progressed, with rod opsin being the dominant visual opsin post-hatching. Modeling by spectral tuning analysis and atomistic molecular simulation, predicted the greatest variation in the spectral peak of absorbance to be within the Rh2 class, with a ∼40 nm difference in λmaxvalues between the four medium-wavelength-sensitive photopigments. Overall, it appears that opsin duplication and expression, and their respective spectral tuning profiles, evolved to maximize specialist color vision throughout an anadromous lifecycle, with some visual opsin genes being lost to tailor marine-based vision.
Upper Limb Sensory-Motor Control During Exposure to Different Mechanical Environments in Multiple Sclerosis Subjects With No Clinical Disability
Authors: Pierella Camilla , Pellegrino Laura , Muller Margit , Inglese Matilde , Solaro Claudio , Coscia Martina , Casadio Maura
Published: July 2022

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease resulting in motor impairments associated with muscle weakness and lack of movement coordination. The goal of this work was to quantify upper limb motor deficits in asymptomatic MS subjects with a robot-based assessment including performance and muscle synergies analysis. A total of 7 subjects (MS: 3 M−4 F; 42 ± 10 years) with clinically definite MS according to McDonald criteria, but with no clinical disability, and 7 age- and sex-matched subjects without a history of neurological disorders participated in the study. All subjects controlled a cursor on the computer screen by moving their hand or applying forces in 8 coplanar directions at their self-selected speed. They grasped the handle of a robotic planar manipulandum that generated four different environments: null, assistive or resistive forces, and rigid constraint. Simultaneously, the activity of 15 upper body muscles was recorded. Asymptomatic MS subjects generated less smooth and less accurate cursor trajectories than control subjects in controlling a force profile, while the end-point error was significantly different also in the other environments. The EMG analysis revealed different muscle activation patterns in MS subjects when exerting isometric forces or when moving in presence of external forces generated by a robot. While the two populations had the same number and similar structure of muscle synergies, they had different activation profiles. These results suggested that a task requiring to control forces against a rigid environment allows better than movement tasks to detect early sensory-motor signs related to the onset of symptoms of multiple sclerosis and to differentiate between stages of the disease.
Expanding the Phenotypic and Genetic Spectrum of Neuromuscular Diseases Caused by DYNC1H1 Mutations
Authors: Li Jia-Tong , Dong Si-Qi , Zhu Dong-Qing , Yang Wen-Bo , Qian Ting , Liu Xiao-Ni , Chen Xiang-Jun
Published: July 2022

Objectives

Spinal muscular atrophy with lower extremity predominance 1 (SMALED1) and Charcot–Marie-Tooth diseasetype 2O (CMT2O) are two kinds of hereditary neuromuscular diseases caused by DYNC1H1 mutations. In this study, we reported two patients with SMALED1 caused by DYNC1H1 mutations. The genotype–phenotype correlations were further analyzed by systematically reviewing previous relevant publications.

Materials and Methods

Two patients' with SMALED1 and their parents' clinical data were collected, and detailed clinical examinations were performed. WES was then applied, which was confirmed by Sanger sequencing. PubMed, Web of Science, CNKI, and Wanfang Data were searched, and all publications that met the inclusion criteria were carefully screened. Any individual patient without a detailed description of clinical phenotypes was excluded.

Results

The two patients manifested delayed motor milestones and muscle wasting of both lower extremities. The diagnosis was further confirmed as SMALED1. Genetic testing revealed heterozygous DYNC1H1 mutations c.1792C>T and c.790C>G; the latter is a novel dominant mutation. Genotype–phenotype analysis of DYNC1H1 variants and neuromuscular diseases revealed that mutations in the DYN1 region of DYNC1H1 protein were associated with a more severe phenotype, more complicated symptoms, and more CNS involvement than the DHC_N1 region.

Conclusion

Our study potentially expanded the knowledge of the phenotypic and genetic spectrum of neuromuscular diseases caused by DYNC1H1 mutations. The genotype–phenotype correlation may reflect the pathogenesis underlying the dyneinopathy caused by DYNC1H1 mutations.
An Automated Approach for the Detection of Alzheimer's Disease From Resting State Electroencephalography
Authors: Perez-Valero Eduardo , Morillas Christian , Lopez-Gordo Miguel A. , Carrera-Muñoz Ismael , López-Alcalde Samuel , Vílchez-Carrillo Rosa M.
Published: July 2022

Early detection is crucial to control the progression of Alzheimer's disease and to postpone intellectual decline. Most current detection techniques are costly, inaccessible, or invasive. Furthermore, they require laborious analysis, what delays the start of medical treatment. To overcome this, researchers have recently investigated AD detection based on electroencephalography, a non-invasive neurophysiology technique, and machine learning algorithms. However, these approaches typically rely on manual procedures such as visual inspection, that requires additional personnel for the analysis, or on cumbersome EEG acquisition systems. In this paper, we performed a preliminary evaluation of a fully-automated approach for AD detection based on a commercial EEG acquisition system and an automated classification pipeline. For this purpose, we recorded the resting state brain activity of 26 participants from three groups: mild AD, mild cognitive impairment (MCI-non-AD), and healthy controls. First, we applied automated data-driven algorithms to reject EEG artifacts. Then, we obtained spectral, complexity, and entropy features from the preprocessed EEG segments. Finally, we assessed two binary classification problems: mild AD vs. controls, and MCI-non-AD vs. controls, through leave-one-subject-out cross-validation. The preliminary results that we obtained are comparable to the best reported in literature, what suggests that AD detection could be automatically detected through automated processing and commercial EEG systems. This is promising, since it may potentially contribute to reducing costs related to AD screening, and to shortening detection times, what may help to advance medical treatment.
Dietary Valine/Isoleucine Ratio Impact Carcass Characteristics, Meat Edible Quality and Nutritional Values in Finishing Crossbred Duroc × Landrace × Yorkshire Pigs With Different Slaughter Weights
Authors: Xu Doudou , Wang Yubo , Zhang Xin , Yan Enfa , He Linjuan , Wang Lu , Ma Chenghong , Zhang Pengguang , Yin Jingdong
Published: July 2022

The aim of this study was to investigate effects of dietary ratio of valine to isoleucine [R(V/I)] on carcass characteristics and meat quality of finishing pigs and whether slaughter weight influence the effect. We carried out a 2 × 3 factorial trial with two slaughter weight (105 vs. 130 kg) and three R(V/I) (0.58, 1.23, and 2.60 at 75–100 kg body weight, and 0.70, 1.24, and 2.39 at 100–135 kg body weight for L-, N- and H-R (V/I), respectively). Data show that increasing slaughter weight significantly increased meat color (a*45 min and b*45 min), drip loss and shear force (P < 0.05). Meanwhile, increasing slaughter weight reduced sarcomere length, the proportion of protein-bound water, and most kinds of muscular total amino acid contents except for tryptophan and arginine, while increased contents of muscular free lysine, tryptophan, leucine, isoleucine, valine, alanine, and arginine in the M. longissimus thoracis (P < 0.05). Health lipid indices based on fatty acid composition of intramuscular lipid were improved as the slaughter weight increased (P < 0.05). Notably, pigs received N-R (V/I) diet improved carcass traits in terms of thinner backfat thickness and higher fat-free lean index, as well as increased meat flavor-contributing amino acids at the cost of reduced intramuscular fat content and increased shear force of cooked meat compared with the pigs fed L-R (V/I) and H-R(V/I) diets (P < 0.05). H-R (V/I) diet decreased ultimate pH value and sarcomere length of the skeletal muscle but increased the proportion of free water (T23), consequently, increased drip loss and cooking loss of fresh meat in pigs (P < 0.05). In conclusion, both slaughter weight and dietary ratio of valine to isoleucine exerted significant impacts on carcass characteristics, meat quality and nutrition values. In particular, carcass traits and meat color of lighter pigs were more susceptible to the influence of dietary R (V/I) relative to heavier pigs.
Maternal Mental Health in Late Pregnancy and Longitudinal Changes in Postpartum Serum Vitamin B-12, Homocysteine, and Milk B-12 Concentration Among Brazilian Women
Authors: Batalha Mônica Araujo , dos Reis Costa Paula Normando , Ferreira Ana Lorena Lima , Freitas-Costa Nathalia C. , Figueiredo Amanda C. Cunha , Shahab-Ferdows Setareh , Hampel Daniela , Allen Lindsay H. , Pérez-Escamilla Rafael , Kac Gilberto
Published: July 2022

Background

Little is known regarding the association between mental health distress during pregnancy and postpartum maternal serum biomarkers of vitamin B-12 status and milk B-12 concentration.

Objective

To evaluate the association between depressive and anxiety symptoms in the third trimester of pregnancy and changes in postpartum serum B-12, homocysteine, and B-12 milk concentration.

Methods

A total of 101 women (18–40 years) were studied in a prospective cohort with data at the third trimester of pregnancy (baseline) and three postpartum time-points (TPs): 2–8 days (TP1), 28–50 days (TP2), and 88-119 days (TP3) postpartum. B-12 concentrations in milk were measured by competitive chemiluminescent enzyme immunoassay at TP1, TP2, and TP3. Serum B-12 and homocysteine concentrations were evaluated at baseline, TP1, TP2, and TP3 by chemiluminescent immunoassays. Depressive and anxiety symptoms were measured with the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory at baseline. Spearman's correlation test and multiple linear mixed-effect models were performed.

Results

The prevalence of depressive and anxiety state symptoms was 35.6 and 39.6% at baseline. High prevalence of low milk B-12 concentration (<310 pmol/L) were observed at TP1 (53.2%), TP2 (71.4%), and TP3 (71.1%). Women with anxiety symptoms at baseline presented higher median concentrations of serum homocysteine at TP1 and lower concentrations of serum and milk B-12 at TP2 compared with women without anxiety symptoms [8 (7; 9) vs. 6 (5; 8) and 266 (188; 369) vs. 332 (272; 413)]. Milk B-12 concentrations were positively and significantly correlated with maternal serum B-12 concentrations at different TP. Women with anxiety symptoms at baseline exhibited a decrease in daily postpartum homocysteine concentrations compared to women without anxiety symptoms (β = −0.002, SE = 0.001, p = 0.024).

Conclusion

Anxiety symptoms at the end of pregnancy were associated with longitudinal changes in maternal serum homocysteine concentrations during the first 3 months postpartum.
Association Between Serum Iron Status and Muscle Mass in Adults: Results From NHANES 2015–2018
Authors: Chen Zhi , Chen Jing , Song Chenyang , Sun Jun , Liu Wenge
Published: July 2022

Background

Iron deficiency or overload may contribute to complications associated with diseases, but the link between iron status and skeletal muscle disorder is poorly understood. This study aimed to investigate the relationship between serum iron status, reflected by serum ferritin concentration, and muscle mass in U.S. adults.

Methods

We utilized data from National Health and Nutrition Examination Survey (NHANES) 2015-2018 for analysis. Data on serum ferritin, appendicular skeletal muscle mass (ASM), body mass index (BMI) and confounding factors were extracted and analyzed. Multivariate linear regression analyses and smooth curve fittings were employed to investigate the association between serum ferritin and muscle mass. Subgroup analysis based on iron status, age, gender and race were performed.

Results

A total of 2,078 participants were included, and divided into iron deficiency (n = 225), normal iron status (n = 1,366), and iron overload (n = 487) groups. Participants with iron overload had significantly lower ASM and appendicular skeletal muscle index (ASMI) (ASM: 19.329 ± 4.879, ASMI: 0.709 ± 0.138) compared to those with iron deficiency (ASM: 22.660 ± 6.789, ASMI: 0.803 ± 0.206) and normal iron status (ASM: 22.235 ± 6.167, ASMI: 0.807 ± 0.201). The serum ferritin was negatively linked with muscle mass after adjusting for potential confounders (β = −0.0001, 95% CI: −0.0001, −0.0000). When stratified by iron status, the trend test between them remained significant (P for trend: 0.008). Furthermore, subgroup analysis identified a stronger association in men (β = −0.0001, 95% CI: −0.0002, −0.0001), age ≥ 40 years (β = −0.0001, 95% CI: −0.0002, −0.0000), non-Hispanic black (β = −0.0002, 95% CI: −0.0003, −0.0001) and other races (β = −0.0002, 95% CI: −0.0003, −0.0000).

Conclusions

Our study revealed an inverse relationship between serum iron status and muscle mass in adults. This finding improves our understanding of the impact of serum iron status on muscle mass, and sheds new light on the prevention and treatment of muscle loss.
Evaluation of Epidermal Growth Factor Receptor 2 Status in Gastric Cancer by CT-Based Deep Learning Radiomics Nomogram
Authors: Guan Xiao , Lu Na , Zhang Jianping
Published: July 2022

Purpose

To explore the role of computed tomography (CT)-based deep learning and radiomics in preoperative evaluation of epidermal growth factor receptor 2 (HER2) status in gastric cancer.

Materials and methods

The clinical data on gastric cancer patients were evaluated retrospectively, and 357 patients were chosen for this study (training cohort: 249; test cohort: 108). The preprocessed enhanced CT arterial phase images were selected for lesion segmentation, radiomics and deep learning feature extraction. We integrated deep learning features and radiomic features (Inte). Four methods were used for feature selection. We constructed models with support vector machine (SVM) or random forest (RF), respectively. The area under the receiver operating characteristics curve (AUC) was used to assess the performance of these models. We also constructed a nomogram including Inte-feature scores and clinical factors.

Results

The radiomics-SVM model showed good classification performance (AUC, training cohort: 0.8069; test cohort: 0.7869). The AUC of the ResNet50-SVM model and the Inte-SVM model in the test cohort were 0.8955 and 0.9055. The nomogram also showed excellent discrimination achieving greater AUC (training cohort, 0.9207; test cohort, 0.9224).

Conclusion

CT-based deep learning radiomics nomogram can accurately and effectively assess the HER2 status in patients with gastric cancer before surgery and it is expected to assist physicians in clinical decision-making and facilitates individualized treatment planning.
Publication Trends of Research on Gallbladder Cancer During 2001–2021: A 20-Year Bibliometric Analysis
Authors: Sun Wentao , Wan Wenze , Gao Zhihui , Suo Tao , Shen Sheng , Liu Houbao
Published: July 2022

Gallbladder cancer (GBC) is one of the lethal cancers with an extremely poor prognosis. In the recent 20 years, research on GBC has developed rapidly. Here we aim to perform a systematical bibliometric analysis on the current foci and status of GBC research. This study analyzes trends in GBC research and compares contributions from different countries and regions, institutions, and authors. All publications in GBC research from 2001 to 2021 in the Web of Science Core Collection (WoSCC) database were collected. Microsoft Excel 2010 and GraphPad Prism 9 were used to analyze publication data and publication trends. VOSviewer 1.6.17 was adapted to generate a visual network of keywords in surgical training research. A total of 3,323 publications were included. China was the most productive country, with the highest number of publications (n = 900, 27.08%). Shanghai Jiaotong University and Roa JC were the most productive institution and authors, contributing 215 and 89 publications, respectively. Keywords were classified into five clusters, each representing a key topic. The main clusters of GBC are related to surgery therapy, mechanism research-related study, and non-surgery therapy, while migration is the current hotspot of GBC research. The scientific progression of GBC research over the past two decades was comprehensively analyzed by this bibliometric study. Finding deeper mechanisms in the migration of GBC cells, new biomarkers, and highly effective nomograms will be the major problems and directions in the future.
Differentiation of Benign From Malignant Parotid Gland Tumors Using Conventional MRI Based on Radiomics Nomogram
Authors: Qi Jinbo , Gao Ankang , Ma Xiaoyue , Song Yang , zhao Guohua , Bai Jie , Gao Eryuan , Zhao Kai , Wen Baohong , Zhang Yong , Cheng Jingliang
Published: July 2022

Objectives

We aimed to develop and validate radiomic nomograms to allow preoperative differentiation between benign- and malignant parotid gland tumors (BPGT and MPGT, respectively), as well as between pleomorphic adenomas (PAs) and Warthin tumors (WTs).

Materials and Methods

This retrospective study enrolled 183 parotid gland tumors (68 PAs, 62 WTs, and 53 MPGTs) and divided them into training (n = 128) and testing (n = 55) cohorts. In total, 2553 radiomics features were extracted from fat-saturated T2-weighted images, apparent diffusion coefficient maps, and contrast-enhanced T1-weighted images to construct single-, double-, and multi-sequence combined radiomics models, respectively. The radiomics score (Rad-score) was calculated using the best radiomics model and clinical features to develop the radiomics nomogram. The receiver operating characteristic curve and area under the curve (AUC) were used to assess these models, and their performances were compared using DeLong’s test. Calibration curves and decision curve analysis were used to assess the clinical usefulness of these models.

Results

The multi-sequence combined radiomics model exhibited better differentiation performance (BPGT vs. MPGT, AUC=0.863; PA vs. MPGT, AUC=0.929; WT vs. MPGT, AUC=0.825; PA vs. WT, AUC=0.927) than the single- and double sequence radiomics models. The nomogram based on the multi-sequence combined radiomics model and clinical features attained an improved classification performance (BPGT vs. MPGT, AUC=0.907; PA vs. MPGT, AUC=0.961; WT vs. MPGT, AUC=0.879; PA vs. WT, AUC=0.967).

Conclusions

Radiomics nomogram yielded excellent diagnostic performance in differentiating BPGT from MPGT, PA from MPGT, and PA from WT.
Pemetrexed Plus Lenalidomide for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Prospective Single-Arm Phase II Study
Authors: Ma Jingjing , Lin Zhiguang , Ding Tianling , Li Qing , Zhang Mengxue , Kang Hui , Johnston Patrick B. , Ma Yan , Chen Bobin
Published: July 2022

The prognosis of relapsed/refractory (R/R) primary central nervous system lymphoma (PCNSL) is dismal, and there are limited treatment options for these patients. This was a prospective single-arm phase II study of combined pemetrexed and lenalidomide for salvage treatment of R/R PCNSL. Patients with R/R PCNSL (n = 38) who had undergone two or more different therapeutic regimens and experienced disease progression or recurrence were enrolled. The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Patients were followed up for a median of 18 (range, 1–36) months. ORR was 68.4%, with median PFS and OS of 6 and 18 months, respectively. Adverse events (AEs) included myelosuppression, fatigue, nausea, fever, infection, cardiac disease, and thrombogenesis. Commonly observed grade ≥ 3 AEs included neutropenia (5.3%), leukopenia (2.6%), thrombocytopenia (7.9%), and infection (2.6%). Elevated lactate dehydrogenase (LDH) levels (χ2 = 13.25; P = 0.0003) and bulky disease (P = 0.032; χ2 = 4.580) were associated with short PFS. Elevated serum LDH level (P = 0.011; χ2 = 6.560), abnormal lymphoma cells in the cerebrospinal fluid (CSF) [P = 0.011; χ2 = 6.445], and multiple lesions (P = 0.036; χ2 = 4.404) were significantly associated with poorer OS. Abnormal lymphoma cells in the CSF were an independent predictor of poor prognosis on multivariate analysis (P = 0.034; hazard ratio (HR) = 2.836; 95% confidence interval, 1.082–7.434). Our results indicate that pemetrexed plus lenalidomide is effective for heavily treated R/R PCNSL, with moderate toxicity. Trial registration: #ChiCTR1900028070.
Association Between Metformin Use and the Risk, Prognosis of Gynecologic Cancer
Authors: Yao Kui , Zheng Heng , Li Tao
Published: July 2022

Background

For gynecological cancer patients, the beneficial effect of metformin use remains controversial due to inconsistent results of published articles. By conducting a meta-analysis, we aimed to evaluate the effect of metformin in reducing the risk and improving the survival of gynecological cancer among women with diabetes mellitus (DM).

Methods

Articles exploring association between metformin use and the risk, as well as prognosis of gynecologic cancer in DM, were searched in the databases: PubMed, Web of Science, SCOPUS, EMBASE, EBSCO, and PROQUEST. Articles were published before May 2022. All the studies were conducted using STATA 12.0 software.

Results

The meta-analysis showed no significant association between metformin use and risk of gynecologic cancer in DM with a random effects model [odds ratio (ORs)/relative risk (RR) = 0.91, 95% confidence intervals (CI) 0.77 to 1.08, I2 = 84.2%, p < 0.001]. Metformin use was associated with reduced overall survival (OS) and progression-free survival (PFS) of gynecologic cancer in DM with random effects models [OS: hazard ratio (HR) = 0.60, 95% CI 0.49–0.74, I2 = 55.2%, p = 0.002; PFS: HR = 0.55, 95% CI 0.33–0.91, I2 = 69.1%, p = 0.006], whereas no significant association was showed between metformin use and recurrence-free survival (RFS), as well as cancer-specific survival (CSS) of gynecologic cancer in DM with random effects models (RFS: HR = 0.60, 95% CI 0.30–1.18, I2 = 73.7%, p = 0.010; CSS: HR = 0.78, 95% CI 0.43–1.41, I2 = 72.4%, p = 0.013).

Conclusions

In conclusion, this meta-analysis indicated that metformin may be a useful adjuvant agent for gynecological cancer with DM, especially for patients with ovarian cancer and endometrial cancer.
S-Ketamine Oral Thin Film—Part 1: Population Pharmacokinetics of S-Ketamine, S-Norketamine and S-Hydroxynorketamine
Authors: Simons Pieter , Olofsen Erik , van Velzen Monique , van Lemmen Maarten , Mooren René , van Dasselaar Tom , Mohr Patrick , Hammes Florian , van der Schrier Rutger , Niesters Marieke , Dahan Albert
Published: July 2022

Ketamine is administered predominantly via the intravenous route for the various indications, including anesthesia, pain relief and treatment of depression. Here we report on the pharmacokinetics of sublingual and buccal fast-dissolving oral-thin-films that contain 50 mg of S-ketamine in a population of healthy male and female volunteers. Twenty volunteers received one or two oral thin films on separate occasions in a randomized crossover design. The oral thin films were placed sublingually (n = 15) or buccally (n = 5) and left to dissolve for 10 min in the mouth during which the subjects were not allowed to swallow. For 6 subsequent hours, pharmacokinetic blood samples were obtained after which 20 mg S-ketamine was infused intravenously and blood sampling continued for another 2-hours. A population pharmacokinetic analysis was performed in NONMEM pharmacokinetic model of S-ketamine and its metabolites S-norketamine and S-hydroxynorketamine; p < 0.01 were considered significant. S-ketamine bioavailability was 26 ± 1% (estimate ± standard error of the estimate) with a 20% lower bioavailability of the 100 mg oral thin film relative to the 50 mg film, although this difference did not reach the level of significance. Due to the large first pass-effect, 80% of S-ketamine was metabolized into S-norketamine leading to high plasma levels of S-norketamine following the oral thin film application with 56% of S-ketamine finally metabolized into S-hydroxynorketamine. No differences in pharmacokinetics were observed for the sublingual and buccal administration routes. The S-ketamine oral thin film is a safe and practical alternative to intravenous S-ketamine administration that results in relatively high plasma levels of S-ketamine and its two metabolites.
Performance of Imaging Techniques in Non-invasive Diagnosis of Non-alcoholic Fatty Liver Disease in Children: A Systematic Review and Meta-Analysis
Authors: Yu Qun , Liu Yiwei , Hu Peipei , Gao Feng , Huang Guoqing
Published: July 2022

Background and Aim

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children. With the continuous emergence of various non-invasive diagnostic methods, imaging techniques have always been considered as potential alternative methods to liver biopsy. This study aimed to evaluate the diagnostic performance of imaging techniques so as to search for the most promising technology.

Methods

We searched English and Chinese databases. English databases included Cochran library, Embase, PubMed, and Web of Science, while Chinese databases included the Wanfang database and China National Knowledge Internet.

Results

Finally, 11 articles were included (12 studies, one of which included studies on both fibrosis and steatosis). Further, 26.2% of the participants had mild steatosis, 34.1% had moderate steatosis, and 34.9% had severe steatosis. Also, 64.0% had any fibrosis, 29.1% had significant fibrosis, 13.8% had advanced fibrosis, and 2.8% had cirrhosis. Irrespective of the grade of fibrosis, transient elastography (TE) had higher sensitivity (97–100%), whereas magnetic resonance elastography (MRE) had the lowest sensitivity (58–63%). The pooled sensitivity and specificity of imaging techniques in diagnosing steatosis were 89% (95% CI, 71–96) and 89% (95% CI, 72–96), and AUROC 0.95 (95% CI, 93–97), multifrequency magnetic resonance elastography-hepatic fat fraction (mMRE-HFF) had the highest sensitivity (87%, 95% CI 77–97), ultrasonography (US) had the lowest specificity (96%, 95% CI 92–98%).

Conclusion

Imaging techniques have a good diagnostic performance for children with NAFLD, especially the diagnosis of liver fibrosis based on ultrasound or magnetic resonance elastography. Compared with different imaging techniques, TE has the best performance in diagnosing significant fibrosis. Liver stiffness measurement (LSM) is expected to become a biological indicator for routine screening, dynamic monitoring of disease changes, and prognostic evaluation.