bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypertension Subtypes, Mortality Risk, and Differential Effects Between Two Hypertension Guidelines
Authors: Mai Hui , Li Chao , Chen Kangyu , Wu Zhenqiang , Liang Xuanyi , Wang Yongjuan , Chen Tao , Chen Fengjian
Published: July 2022

Aim:

To examine which hypertension subtypes are primarily responsible for the difference in the hypertension prevalence and treatment recommendations, and to assess their mortality risk if 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guideline were adopted among Chinese adults.

Methods

We used the nationally representative data of China Health and Retirement Longitudinal Study (CHARLS) to estimate the differences in the prevalence of isolated systolic hypertension (ISH), systolic diastolic hypertension (SDH) and isolated diastolic hypertension (IDH) between the 2017 ACC/AHA and the 2018 China Hypertension League (CHL) guidelines. We further assessed their mortality risk using follow-up data from the China Health and Nutrition Survey (CHNS) by the Cox model.

Results

The increase from the 2017 ACC/AHA guideline on hypertension prevalence was mostly from SDH (8.64% by CHL to 25.59% by ACC/AHA), followed by IDH (2.42 to 6.93%). However, the difference was minuscule in the proportion of people recommended for antihypertensive treatment among people with IDH (2.42 to 3.34%) or ISH (12.00 to 12.73%). Among 22,184 participants with a median follow-up of 6.14 years from CHNS, attenuated but significant associations were observed between all-cause mortality and SDH (hazard ratio 1.56; 95% CI: 1.36,1.79) and ISH (1.29; 1.03,1.61) by ACC/AHA but null association for IDH (1.15; 0.98,1.35).

Conclusion

Adoption of the 2017 ACC/AHA may be applicable to improve the unacceptable hypertension control rate among Chinese adults but with cautions for the drug therapy among millions of subjects with IDH.
Investigation of Functional Synergism of CENPF and FOXM1 Identifies POLD1 as Downstream Target in Hepatocellular Carcinoma
Authors: Ho Daniel Wai-Hung , Lam Wai-Ling Macrina , Chan Lo-Kong , Ng Irene Oi-Lin
Published: July 2022

Background

Lines of evidence implicate CENPF and FOXM1 may have novel co-operative roles in driving hepatocellular carcinoma (HCC).

Objective

We investigated the clinicopathological correlation, functional characterization, molecular mechanism and translational significance of CENPF and FOXM1.

Methods

We carried out integrative studies investigating functional synergism of CENPF and FOXM1 in HCC and its metastasis. Human HCC samples, HCC cell lines and mouse model were used in the studies. Stable knockdown, q-PCR, Western blotting, whole-transcriptomic sequencing (RNA-seq), as well as cell and mouse assays were performed.

Results

Upon clinicopathological correlation, we found that co-overexpression of CENPF and FOXM1 in human HCCs was associated with more aggressive tumor behavior including presence of venous invasion, tumor microsatellite formation, and absence of tumor encapsulation. Moreover, co-silencing FOXM1 and CENPF using shRNA approach in HCC cell lines resulted in significantly reduced cell proliferation. Furthermore, our RNA-seq and differential gene expression analysis delineated that CENPF and FOXM1 co-regulated a specific set of target genes in various metabolic processes and oncogenic signaling pathways. Among them, POLD1, which encodes the catalytic subunit of DNA polymerase δ, was ranked as the top downstream target co-regulated by CENPF and FOXM1. POLD1 expression was positively correlated with that of FOXM1 and CENPF in HCCs. In addition, POLD1 expression was significantly upregulated in HCC tumors. Functionally, in vivo orthotopic injection model showed that stable knockdown of POLD1 in HCC cells suppressed tumor incidence and tumorigenicity and had a trend of diminished lung metastasis.

Conclusion

Taken together, our data suggest that CENPF and FOXM1 could synergistically support hepatocarcinogenesis via the regulation of POLD1. CENPF and FOXM1 may represent new vulnerabilities to novel drug-based therapy in HCC.
The Value of Cognitive and Physical Function Tests in Predicting Falls in Older Adults: A Prospective Study
Authors: Zhou Rong , Li Jiayu , Chen Meiling
Published: July 2022

Introduction

Previous studies suggested that physical and cognitive function can be indicators to assess the risk of falls in the elderly. Various tests are widely used in geriatric clinical studies as assessment tools of physical and cognitive function. However, large sample studies comparing the fall predictive value of these tests are still sparse. This study was conducted to investigate the value of cognitive and physical function tests in predicting the risk of subsequent falls in the elderly, with the overarching goal of providing more evidence on fall-risk assessment.

Methods

The current study was based on the data of respondents aged 60 and above from the China Health and Retirement Longitudinal Study (CHARLS). Data from the 2015 CHARLS national survey were used as the baseline data, and the fall data in 2018 were used as the follow-up data. Physical function tests included balance, walking speed, the five times sit-to-stand test (FTSST), and grip strength. The value of cognitive and physical function tests in predicting falls was evaluated by logistic regression analysis and receiver operating characteristic (ROC) curves.

Results

The incidence of falls among the 4,857 subjects included in this study was 20.86%. Results showed that cognition (OR = 0.83, 95% CI: 0.70–0.98), the FTSST (OR = 3.51, 95% CI: 1.66–7.46), and grip strength (OR = 1.02, 95% CI: 1.01–1.03) were independent predictors of falls in the full sample after adjusting for various confounders. Notably, the above tests showed better predictive value for falls for the oldest-old (≥ 80 years) subjects.

Conclusion

Overall, results showed that grip strength, the FTSST, and cognition tests are simple and practicable tools for identifying individuals at higher risk of falls in the community. Moreover, the fall predictive performance of physical and cognitive function tests was age-dependent, with a higher predictive value in older adults aged 80 and above.
Validation of Messenger Ribonucleic Acid Markers Differentiating Among Human Acute Respiratory Distress Syndrome Subgroups in an Ovine Model of Acute Respiratory Distress Syndrome Phenotypes
Authors: Wildi Karin , Hyslop Kieran , Millar Jonathan , Livingstone Samantha , Passmore Margaret R. , Bouquet Mahé , Wilson Emily , LiBassi Gianluigi , Fraser John F. , Suen Jacky Y.
Published: July 2022

Background

The discovery of biological subphenotypes in acute respiratory distress syndrome (ARDS) might offer a new approach to ARDS in general and possibly targeted treatment, but little is known about the underlying biology yet. To validate our recently described ovine ARDS phenotypes model, we compared a subset of messenger ribonucleic acid (mRNA) markers in leukocytes as reported before to display differential expression between human ARDS subphenotypes to the expression in lung tissue in our ovine ARDS phenotypes model (phenotype 1 (Ph1): hypoinflammatory; phenotype 2 (Ph2): hyperinflammatory).

Methods

We studied 23 anesthetized sheep on mechanical ventilation with observation times between 6 and 24 h. They were randomly allocated to the two phenotypes (n = 14 to Ph1 and n = 9 to Ph2). At study end, lung tissue was harvested and preserved in RNAlater. After tissue homogenization in TRIzol, total RNA was extracted and custom capture and reporter probes designed by NanoString Technologies were used to measure the expression of 14 genes of interest and the 6 housekeeping genes on a nCounter SPRINT profiler.

Results

Among the 14 mRNA markers, in all animals over all time points, 13 markers showed the same trend in ovine Ph2/Ph1 as previously reported in the MARS cohort: matrix metalloproteinase 8, olfactomedin 4, resistin, G protein-coupled receptor 84, lipocalin 2, ankyrin repeat domain 22, CD177 molecule, and transcobalamin 1 expression was higher in Ph2 and membrane metalloendopeptidase, adhesion G protein-coupled receptor E3, transforming growth factor beta induced, histidine ammonia-lyase, and sulfatase 2 expression was higher in Ph1. These expression patterns could be found when different sources of mRNA – such as blood leukocytes and lung tissue – were compared.

Conclusion

In human and ovine ARDS subgroups, similar activated pathways might be involved (e.g., oxidative phosphorylation, NF-κB pathway) that result in specific phenotypes.
Insights Into the Dynamics and Composition of Biofilm Formed by Environmental Isolate of Enterobacter cloacae
Authors: Misra Tripti , Tare Meghana , Jha Prabhat Nath
Published: July 2022

Bacterial biofilms are clinically admissible and illustrate an influential role in infections, particularly those related to the implant of medical devices. The characterization of biofilms is important to understand the etiology of the diseases. Enterobacter cloacae are known for causing infections by forming biofilms on various abiotic surfaces, such as medical devices. However, a detailed characterization in terms of morphology and the molecular composition of the formed biofilms by this bacterium is sparse. The present study provides insights into the biofilm formation of E. cloacae SBP-8, an environmental isolate, on various surfaces. We performed assays to understand the biofilm-forming capability of the SBP-8 strain and characterized the adhering potential of the bacteria on the surface of different medical devices (foley latex catheter, enteral feeding tube, and glass) at different temperatures. We found that medical devices exhibited strong colonization by E. cloacae SBP-8. Using field emission-scanning electron microscopy (FE-SEM) studies, we characterized the biofilms as a function of time. It indicated stronger biofilm formation in terms of cellular density and EPS production on the surfaces. Further, we characterized the biofilm employing surface-enhanced Raman spectroscopy (SERS) and identified the vast heterogenic nature of the biofilm-forming molecules. Interestingly, we also found that this heterogeneity varies from the initial stages of biofilm formation until the maturation and dispersion. Our studies provide insights into biofilm composition over a period of time, which might aid in understanding the biofilm dispersion phases, to enhance the presently available treatment strategies.
Analysis of Bacterial Diversity in Different Types of Daqu and Fermented Grains From Danquan Distillery
Authors: Shang Changhua , Li Yujia , Zhang Jin , Gan Shanling
Published: July 2022

Bacterial communities in high-temperature Daqu and fermented grains are important for brewing Jiang-flavor Baijiu such as Danquan Baijiu. Daqu is a saccharifying and fermenting agent, which has a significant impact on the flavor of Baijiu. However, bacterial communities in three different types of samples from the Danquan distillery (dqjq_ck, dqjqcp, and dqjp3) were still unclear, which limited further development of Danquan Baijiu. “dqjq_ck” and “dqjqcp” indicate high-temperature Daqu at days 45 and 135, respectively. “dqjp3” indicates fermented grains. In this study, the bacterial communities of three samples were analyzed by Illumina Miseq high-throughput sequencing. The bacterial communities of three samples primarily composed of thermophilic bacteria and bacteria with stress resistance. The most abundant species in dqjq_ck, dqjqcp, and dqjp3 were Comamonas, Bacillus, and unclassified Lactobacillales, respectively. The main bacteria included Bacillus, Comamonas, Myroides, Paenibacillus, Acetobacter, Kroppenstedtia, Staphylococcus, Saccharopolyspora, Planifilum, Lactobacillus, Acinetobacter, Oceanobacillus, Enterococcus, Thermoactinomyces, Lactococcus, Streptomyces, Saccharomonospora, Tepidimicrobium, Anaerosalibacter, unclassified_Lactobacillales, unclassified_Thermoactinomycetaceae_1, unclassified_Bacillaceae_2, unclassified_Bacillales, unclassified_Microbacteriaceae, unclassified_Rhodobacteraceae, unclassified_Actinopolysporineae, and unclassified_Flavobacteriaceae in three samples (percentage was more than 1% in one of three samples). In our study, the succession of microbiota in three samples representing three important stages of Danquan Baijiu brewing was revealed. This article lays a good foundation for understanding the fermentation mechanism and screening some excellent indigenous bacteria to improve the quality of Danquan Baijiu in future.
Gregatins, a Group of Related Fungal Secondary Metabolites, Inhibit Aspects of Quorum Sensing in Gram-Negative Bacteria
Authors: Beenker Wouter A. G. , Hoeksma Jelmer , den Hertog Jeroen
Published: July 2022

Quorum sensing (QS) is a process that regulates gene expression based on cell density. In bacteria, QS facilitates collaboration and controls a large number of pathways, including biofilm formation and virulence factor production, which lead to lower sensitivity to antibiotics and higher toxicity in the host, respectively. Inhibition of QS is a promising strategy to combat bacterial infections. In this study, we tested the potential of secondary metabolites from fungi to inhibit bacterial QS using a library derived from more than ten thousand different fungal strains. We used the reporter bacterium, Chromobacterium violaceum, and identified 39 fungal strains that produced QS inhibitor activity. These strains expressed two QS inhibitors that had been described before and eight QS inhibitors that had not been described before. Further testing for QS inhibitor activity against the opportunistic pathogen Pseudomonas aeruginosa led to the identification of gregatins as an interesting family of compounds with QS inhibitor activity. Although various gregatins inhibited QS in P. aeruginosa, these gregatins did not inhibit virulence factor production and biofilm formation. We conclude that gregatins inhibit some, but not all aspects of QS.
Clinical Metagenomic Next-Generation Sequencing for Diagnosis of Secondary Glaucoma in Patients With Cytomegalovirus-Induced Corneal Endotheliitis
Authors: Wu Wei , Jiang Hua , Zhang Ying , Zhou Yang , Bai Guannan , Shen Lingwei , Zhou Hongwei , Chen Xiangjun , Hu Lidan
Published: July 2022

Glaucoma is the second leading cause of blindness globally. Growing scientific evidence indicated that inflammation of the trabecular meshwork induced by corneal endotheliitis could lead to secondary glaucoma. Cytomegalovirus (CMV) has been identified as the most common herpes virus in corneal endotheliitis patients. Early detection is critical in preventing endothelial cell loss, and patient management should vary based on different pathological factors. However, routine culture and real-time polymerase chain reaction (qPCR) have difficult in distinguishing whether CMV, Varicella Zoster Virus (VZV) or Herpes Simplex Virus (HSV) causes endothiliitis. This may result in inappropriate treatment, which may prolong or aggravate the status of disease. We compared the sensitivity and specificity of qPCR and Metagenomic Next-Generation Sequencing (mNGS) in the aqueous humor of patients with suspected CMV endotheliitis in this study. Our results showed that four out of 11 (36.4%) of our patients were positive for CMV by qPCR, whereas mNGS had a 100% detection rate of CMV. Our findings implied that mNGS could be a useful diagnostic tool for CMV-induced endotheliitis.
Molecular Epidemiology and Antifungal Resistance of Cryptococcus neoformans From Human Immunodeficiency Virus-Negative and Human Immunodeficiency Virus-Positive Patients in Eastern China
Authors: Zhou Ziyi , Zhu Chendi , Ip Margaret , Liu Manjiao , Zhu Zhaoqin , Liu Ryon , Li Xiaomin , Zeng Lingbing , Wu Wenjuan
Published: July 2022

Cryptococcosis is an opportunistic and potentially lethal infection caused by Cryptococcus neoformans and Cryptococcus gattii complex, which affects both immunocompromised and immunocompetent people, and it has become a major public health concern worldwide. In this study, we characterized the molecular epidemiology and antifungal susceptibility of 133 C. neoformans isolates from East China Invasive Fungal Infection Group (ECIFIG), 2017–2020. Isolates were identified to species level by matrix-assisted laser desorption ionization-time of flight mass spectrometry and confirmed by IGS1 sequencing. Whole-genome sequencing (WGS) was conducted on three multidrug-resistant isolates. Among the 133 strains, 61 (45.86%) were isolated from HIV-positive patients and 72 (54.16%) were isolated from HIV-negative patients. In total, C. neoformans var. grubii accounted for 97.74% (130/133), while C. neoformans var. neoformans was rare (2.06%, 3/133). The strains were further classified into nine sequence types (STs) dominated by ST5 (90.23%, 120/133) with low genetic diversity. No association was observed between STs and HIV status. All strains were wild type to voriconazole, while high antifungal minimal inhibitory concentrations (MICs) above the epidemiological cutoff values (ECVs) were observed in C. neoformans strains, and more than half of isolates were non-wild-type to amphotericin B (89.15%, 109/133). Eight isolates were resistant to fluconazole, and eight isolates were non-wild type to 5-fluorocytosine. Furthermore, WGS has verified the novel mutations of FUR1 in 5-fluorocytosine-resistant strains. In one isolate, aneuploidy of chromosome 1 with G484S mutation of ERG11 was observed, inducing high-level resistance (MIC: 32 μg/ml) to fluconazole. In general, our data showed that there was no significant difference between HIV-positive and HIV-negative patients on STs, and we elucidate the resistant mechanisms of C. neoformans from different perspectives. It is important for clinical therapy and drug usage in the future.
Integrative Genomic and Transcriptomic Analysis of Primary Malignant Gliomas Revealed Different Patterns Between Grades and Somatic Mutations Related to Glioblastoma Prognosis
Authors: Jin Huawei , Yu Zhenhua , Tian Tian , Shen Guoping , Chen Weian , Fan Miao , He Qun , Dai Dandan , Zhang Xuan , Liu Dawei
Published: July 2022

Background: As reflected in the WHO classification of glioma since 2020, genomic information has been an important criterion in addition to histology for glioma classification. There is a significant intergrade difference as well as intragrade difference of survival probability among glioma patients. Except the molecular criteria used in the WHO classification, few studies have explored other genomic factors that may be underlying these survival differences, especially in Chinese populations. Here, we used integrative genomic approaches to characterize a Chinese glioma cohort to search for potential prognostic biomarkers.

Methods: We recruited 46 Chinese patients with primary malignant glioma. All the patients were analyzed with whole-exome sequencing (WES) and 27 of them were analyzed with RNA-seq. We compared the molecular features between patients in different WHO grades. We classified the glioblastoma (GBM) patients into two groups (good vs poor survival) using six-month progression-free survival (PFS6) status and compared the genomic profiles between the two groups.

Results: We found grade II and grade III patients cluster together (LGG) and they are different from GBM in unsupervised clustering analysis with RNA-seq data. Gene set enrichment analysis (GSEA) comparing GBM and the LGG group suggested that GBM had upregulation of multiple pathways related to genome integrity and immune cell infiltration. Further comparison of somatic mutations between the two groups revealed TOPAZ1 as a novel mutation associated with GBM and prevalence of CNV in multiple genes in GBM. Comparison between PFS6 good and poor GBM patients revealed six genes (TRIML2, ROCK1, PKD1, OBSCN, HECTD4, and ADCY7) were significantly mutated and two genes (NTRK1 and B2M) had more CNV alterations in the poor prognosis group.

Conclusion: Taken together, our molecular data revealed that GBM patient showed distinct characteristics related to individual gene, chromosome integrity, and infiltrating immune cells compared to LGG (grade II/III) patients. We also identified few novel genes with SNV or CNV, which might be the potential markers for clinical outcome of GBM.
Abnormalities in the Fractional Amplitude of Low-Frequency Fluctuation and Functional Connectivity in Parkinson's Disease With Excessive Daytime Sleepiness
Authors: Zi Yuheng , Cai Sainan , Tan Changlian , Wang Tianyu , Shen Qin , Liu Qinru , Wang Min , Li Junli , Zhang Lin , Zhou Fan , Song Chendie , Yuan Jiaying , Liu Yujing , Liu Jun , Liao Haiyan
Published: July 2022

Background

Excessive daytime sleepiness (EDS) is one of the most important non-motor symptoms of Parkinson's disease (PD), and its neuropathologic basis is still unclear.

Objective

This study investigated the changes of neuronal activity in PD patients with EDS (PD-EDS) in the resting state.

Methods

Forty-three PD patients were recruited and divided into the PD-EDS group (n = 21) and PD-NEDS group (PD patients without excessive daytime sleepiness, n = 22) according to the Epworth sleepiness scale (ESS) scores. Patients in both groups received resting-state functional magnetic resonance imaging (rs-fMRI). The differences in fractional amplitude of low-frequency fluctuation (fALFF) between the two groups, correlations between fALFF and ESS, and functional connection (FC) between the brain regions with different fALFF values and the whole brain were analyzed.

Results

PD-EDS patients exhibited a decreased fALFF in the Cingulum-Ant-R, but an increased fALFF in the Putamen-R and Thalamus-L when compared with PD-NEDS patients; an increased functional connectivity between these three seed regions with different fALFF values and the right medial frontal gyrus, bilateral superior temporal gyrus, left insular, and right precuneus was observed (p < 0.05), but a deceased functional connectivity between these three seed regions and the right cerebellum anterior lobe/right brainstem, right middle temporal gyrus and inferior temporal gyrus, right hippocampus/parahippocampal gyrus, right medial cingulate gyrus and bilateral middle occipital gyrus was observed (p < 0.05). The value of fALFF was negatively correlated with the ESS score in the Cingulum-Ant-R, but positively correlated with the ESS score in the Putamen-R and Thalamus-L.

Conclusions

EDS in PD patients may be associated with changes in brain neuron activity and functional connectivity.
Inhibition of Hippocampal Neurogenesis Starting in Adolescence Increases Anxiodepressive Behaviors Amid Stress
Authors: Larivee Rachelle , Johnson Natalie , Freedgood Natalie R. , Cameron Heather A. , Schoenfeld Timothy J.
Published: July 2022

Stressors during the adolescent period can affect development of the brain and have long-lasting impacts on behavior. Specifically, adolescent stress impairs hippocampal neurogenesis and can increase risk for anxiety, depression, and a dysregulated stress response in adulthood. In order to model the functional effects of reduced hippocampal neurogenesis during adolescence, a transgenic neurogenesis ablation rat model was used to suppress neurogenesis during the adolescent period and test anxiodepressive behaviors and stress physiology during adulthood. Wildtype and transgenic (TK) rats were given valganciclovir during the first two weeks of adolescence (4-6 weeks old) to knock down neurogenesis in TK rats. Starting in young adulthood (13 weeks old), blood was sampled for corticosterone at several time points following acute restraint stress to measure negative feedback of the stress response, and rats were tested on a battery of anxiodepressive tests at baseline and following acute restraint stress. Although TK rats had large reductions in both cell proliferation during adolescence, as measured by bromodeoxyuridine (BrdU), and ongoing neurogenesis in adulthood (by doublecortin), resulting in decreased volume of the dentate gyrus, negative feedback of the stress response following acute restraint was similar across all rats. Despite similar stress responses, TK rats showed higher anxiety-like behavior at baseline. In addition, only TK rats had increased depressive-like behavior when tested after acute stress. Together, these results suggest that long-term neurogenesis ablation starting in adolescence produces hippocampal atrophy and increases behavioral caution and despair amid stressful environments.
Delayed Diagnosis of Wilson's Disease Report From 179 Newly Diagnosed Cases in China
Authors: Yu Minling , Ren Linxiang , Zheng Muxin , Hong Mingfan , Wei Zhisheng
Published: July 2022

Objective

To analyze the initial symptom and the cause of the misdiagnosis of Wilson's Disease (WD) so as to enhance awareness of this condition and reduce diagnostic errors.

Methods

The clinical data of 179 patients with the confirmed diagnosis of WD who were hospitalized in the First Affiliated Hospital of Guangdong Pharmaceutical University from October 2014 to September 2021 were analyzed. Those patients who had attended two or more hospitals, had been misdiagnosed as other diseases, or failed to get a clear diagnosis for 3 months and over before hospitalization were included in the group of clinical misdiagnosis or the group without a definite diagnosis.

Results

One hundred twenty-nine cases (72.1%) were misdiagnosed, 39 cases (21.8%) failed to be diagnosed as a specific disease, and only 11 cases (6.2%) had been diagnosed as WD within 3 months at the early stage of the disease. WD was easily masqueraded as a variety of diseases, including all types of hepatitis, cirrhosis, splenomegaly, hepatomegaly, encephalitis, encephalopathy, peripheral neuropathy, psychosis, osteoarthrosis, nephrosis, anemia, and other illnesses.

Conclusion

Wilson's Disease is prone to long-term misdiagnosis or unclear diagnosis. Early diagnosis and treatment are the most important determinations of the prognosis. Therefore, when facing patients with doubtful WD, it is valued to perform Kayser–Fleischer ring, copper metabolism, imaging examination, genetic tests, and radioactive copper test if necessary.
Selenium Nanoparticles Improved Intestinal Health Through Modulation of the NLRP3 Signaling Pathway
Authors: Chen Yanhong , Wu Wei , Zhou Huajin , Liu Xingbo , Li Shu , Guo Yanbing , Li Yuxin , Wang Yongqiang , Yuan Jianmin
Published: July 2022

Selenium nanoparticles (SeNPs) play important roles in promoting animal health, however, their impact on intestinal health remains elusive. This study was intended to evaluate the effects of different doses of SeNPs on the intestinal health, especially the development of goblet cells in the broiler jejunum. A total of 480 1-day-old Arbor Acres broilers were randomly allotted to 5 treatments with 6 replications of 16 chicks each. Birds were fed with low selenium corn-soybean meal-based diets supplemented with 0.1, 0.2, 0.3, or 0.4 mg/kg of SeNPs. On d 21, dietary supplementation of SeNPs effectively reduced the mortality of broilers. The villus height and the villus height/crypt depth ratio of the jejunum showed significant quadratic effects with the increasing concentration of SeNPs (P < 0.05). The mRNA expression of zonula occluden-1 (ZO-1), ZO-2, claudin-3, and claudin-5 in the jejunum decreased linearly with the increasing dose of SeNPs (P < 0.05). The mRNA expression levels of interleukin 1 beta (IL-1β), IL-18, and the concentration of reactive oxygen species (ROS) in the jejunum decreased linearly with the increase of SeNPs concentration (P < 0.05). Compared with the control group, the number of goblet cells in the jejunum was significantly increased by adding 0.1 and 0.4 mg/kg SeNPs(P < 0.05). In addition, the mRNA expression of Mucin2 (Muc2) showed a significant quadratic relationship that increased after adding 0.1 mg/kg SeNPs (P < 0.05). Dietary SeNPs also linearly reduced the expression of v-myc avian myelocytomatosis viral oncogene homolog (c-myc) (P < 0.05). The mean density of TUNEL positive cells in the 0.2 and 0.4 mg/kg SeNPs groups were lower than the control group (P < 0.05). Similarly, the mRNA expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), NLR family pyrin domain containing 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (Caspase-1), toll-like receptor-2 (TLR-2), and myeloid differentiation factor 88 (MyD88) in the jejunum decreased linearly with the increase of SeNPs concentration (P < 0.05). Results show that supplementation with 0.2 mg/kg SeNPs may decrease intestinal oxidative stress and inflammation by modifying the activation of NLRP3 signaling pathway, which can effectively promote intestinal goblet cells of 21-day-old broilers.
Dietary-Nutraceutical Properties of Oat Protein and Peptides
Authors: Rafique Hamad , Dong Rui , Wang Xiaolong , Alim Aamina , Aadil Rana Muhammad , Li Lu , Zou Liang , Hu Xinzhong
Published: July 2022

Oats are considered the healthiest grain due to their high content of phytochemicals, dietary fibers, and protein. In recent years, oat protein and peptides have gained popularity as possible therapeutic or nutraceutical candidates. Generally, oat peptides with bioactive properties can be obtained by the enzymatic hydrolysis of proteins and are known to have a variety of regulatory functions. This review article focused on the nutraceutical worth of oat proteins and peptides and also describes the application of oat protein as a functional ingredient. Outcomes of this study indicated that oat protein and peptides present various therapeutical properties, including antidiabetic, antioxidant, antihypoxic, antihypertensive, antithrombotic, antifatigue, immunomodulatory, and hypocholestrolaemic. However, most of the conducted studies are limited to in vitro conditions and less data is available on assessing the effectiveness of the oat peptides in vivo. Future efforts should be directed at performing systematic animal studies; in addition, clinical trials also need to be conducted to fully support the development of functional food products, nutraceutical, and therapeutical applications.
Implementing Pharmacogenetic Testing in Gastrointestinal Cancers (IMPACT-GI): Study Protocol for a Pragmatic Implementation Trial for Establishing DPYD and UGT1A1 Screening to Guide Chemotherapy Dosing
Authors: Varughese Lisa A. , Bhupathiraju Madhuri , Hoffecker Glenda , Terek Shannon , Harr Margaret , Hakonarson Hakon , Cambareri Christine , Marini Jessica , Landgraf Jeffrey , Chen Jinbo , Kanter Genevieve , Lau-Min Kelsey S. , Massa Ryan C. , Damjanov Nevena , Reddy Nandi J. , Oyer Randall A. , Teitelbaum Ursina R. , Tuteja Sony
Published: July 2022

Background

Fluoropyrimidines (fluorouracil [5-FU], capecitabine) and irinotecan are commonly prescribed chemotherapy agents for gastrointestinal (GI) malignancies. Pharmacogenetic (PGx) testing for germline DPYD and UGT1A1 variants associated with reduced enzyme activity holds the potential to identify patients at high risk for severe chemotherapy-induced toxicity. Slow adoption of PGx testing in routine clinical care is due to implementation barriers, including long test turnaround times, lack of integration in the electronic health record (EHR), and ambiguity in test cost coverage. We sought to establish PGx testing in our health system following the Exploration, Preparation, Implementation, Sustainment (EPIS) framework as a guide. Our implementation study aims to address barriers to PGx testing.

Methods

The Implementing Pharmacogenetic Testing in Gastrointestinal Cancers (IMPACT-GI) study is a non-randomized, pragmatic, open-label implementation study at three sites within a major academic health system. Eligible patients with a GI malignancy indicated for treatment with 5-FU, capecitabine, or irinotecan will undergo PGx testing prior to chemotherapy initiation. Specimens will be sent to an academic clinical laboratory followed by return of results in the EHR with appropriate clinical decision support for the care team. We hypothesize that the availability of a rapid turnaround PGx test with specific dosing recommendations will increase PGx test utilization to guide pharmacotherapy decisions and improve patient safety outcomes. Primary implementation endpoints are feasibility, fidelity, and penetrance. Exploratory analyses for clinical effectiveness of genotyping will include assessing grade ≥3 treatment-related toxicity using available clinical data, patient-reported outcomes, and quality of life measures.

Conclusion

We describe the formative work conducted to prepare our health system for DPYD and UGT1A1 testing. Our prospective implementation study will evaluate the clinical implementation of this testing program and create the infrastructure necessary to ensure sustainability of PGx testing in our health system. The results of this study may help other institutions interested in implementing PGx testing in oncology care.

Clinical Trial Registration

https://clinicaltrials.gov/ct2/show/NCT04736472, identifier [NCT04736472].
Circulating Tumor DNA Characteristics Based on Next Generation Sequencing and Its Correlation With Clinical Parameters in Patients With Lymphoma
Authors: Wu Xiao-Bo , Hou Shu-Ling , Zhang Qiao-Hua , Jia Ning , Hou Min , Shui Wen
Published: July 2022

Background

Lymphoma is a heterogeneous group of tumors in terms of morphological subtypes, molecular alterations, and management. However, data on circulating tumor DNA (ctDNA) mutated genes are limited. The purpose of this study was to investigate the features of the ctDNA mutated genes, the prognosis, and the association between the ctDNA mutated genes and the clinical parameters in lymphoma.

Methods

Differences in the ctDNA between the mutated genes and the prognosis of 59 patients with Hodgkin’s lymphoma (HL) (10.2%), germinal center B-cell–like lymphoma (GCB) (28.8%), nongerminal center B-cell–like lymphoma (non-GCB) (50.8%), and marginal zone lymphoma (MZL) (10.2%) were analyzed by next generation sequencing (NGS) targeting 121 lymphoma-relevant genes.

Results

Genetic alterations were identified in the ctDNA samples with a median of 6 variants per sample. The genetic variation of the ctDNA in the plasma was found to be significantly correlated with the clinical indices in lymphoma. The genetic heterogeneity of different lymphoma subtypes was clearly observed in the ctDNAs from HL, GCB, non-GCB, and MZL, confirming that distinct molecular mechanisms are involved in the pathogenesis of different lymphomas.

Conclusion

Our findings suggest that NGS-based ctDNA mutation analysis reveals genetic heterogeneity across lymphoma subtypes, with potential implications for discovering therapeutic targets, exploring genomic evolution, and developing risk-adaptive therapies.
Evaluating the Microsatellite Instability of Colorectal Cancer Based on Multimodal Deep Learning Integrating Histopathological and Molecular Data
Authors: Qiu Wenjing , Yang Jiasheng , Wang Bing , Yang Min , Tian Geng , Wang Peizhen , Yang Jialiang
Published: July 2022

Microsatellite instability (MSI), an important biomarker for immunotherapy and the diagnosis of Lynch syndrome, refers to the change of microsatellite (MS) sequence length caused by insertion or deletion during DNA replication. However, traditional wet-lab experiment-based MSI detection is time-consuming and relies on experimental conditions. In addition, a comprehensive study on the associations between MSI status and various molecules like mRNA and miRNA has not been performed. In this study, we first studied the association between MSI status and several molecules including mRNA, miRNA, lncRNA, DNA methylation, and copy number variation (CNV) using colorectal cancer data from The Cancer Genome Atlas (TCGA). Then, we developed a novel deep learning framework to predict MSI status based solely on hematoxylin and eosin (H&E) staining images, and combined the H&E image with the above-mentioned molecules by multimodal compact bilinear pooling. Our results showed that there were significant differences in mRNA, miRNA, and lncRNA between the high microsatellite instability (MSI-H) patient group and the low microsatellite instability or microsatellite stability (MSI-L/MSS) patient group. By using the H&E image alone, one can predict MSI status with an acceptable prediction area under the curve (AUC) of 0.809 in 5-fold cross-validation. The fusion models integrating H&E image with a single type of molecule have higher prediction accuracies than that using H&E image alone, with the highest AUC of 0.952 achieved when combining H&E image with DNA methylation data. However, prediction accuracy will decrease when combining H&E image with all types of molecular data. In conclusion, combining H&E image with deep learning can predict the MSI status of colorectal cancer, the accuracy of which can further be improved by integrating appropriate molecular data. This study may have clinical significance in practice.
Evaluation of the Efficiency of MRI-Based Radiomics Classifiers in the Diagnosis of Prostate Lesions
Authors: Li Linghao , Gu Lili , Kang Bin , Yang Jiaojiao , Wu Ying , Liu Hao , Lai Shasha , Wu Xueting , Jiang Jian
Published: July 2022

Objective

To compare the performance of different imaging classifiers in the prospective diagnosis of prostate diseases based on multiparameter MRI.

Methods

A total of 238 patients with pathological outcomes were enrolled from September 2019 to July 2021, including 142 in the training set and 96 in the test set. After the regions of interest were manually segmented, decision tree (DT), Gaussian naive Bayes (GNB), XGBoost, logistic regression, random forest (RF) and support vector machine classifier (SVC) models were established on the training set and tested on the independent test set. The prospective diagnostic performance of each classifier was compared by using the AUC, F1-score and Brier score.

Results

In the patient-based data set, the top three classifiers of combined sequences in terms of the AUC were logistic regression (0.865), RF (0.862), and DT (0.852); RF “was significantly different from the other two classifiers (P =0.022, P =0.005), while logistic regression and DT had no statistical significance (P =0.802). In the lesions-based data set, the top three classifiers of combined sequences in terms of the AUC were RF (0.931), logistic regression (0.922) and GNB (0.922). These three classifiers were significantly different from.

Conclusion

The results of this experiment show that radiomics has a high diagnostic efficiency for prostate lesions. The RF classifier generally performed better overall than the other classifiers in the experiment. The XGBoost and logistic regression models also had high classification value in the lesions-based data set.
The Cellular and Molecular Effects of Fetoscopic Endoluminal Tracheal Occlusion in Congenital Diaphragmatic Hernia
Authors: Olutoye II Oluyinka O. , Short Walker D. , Gilley Jamie , Hammond II J. D. , Belfort Michael A. , Lee Timothy C. , King Alice , Espinoza Jimmy , Joyeux Luc , Lingappan Krithika , Gleghorn Jason P. , Keswani Sundeep G.
Published: July 2022

Congenital diaphragmatic hernia (CDH) is a complex disease associated with pulmonary hypoplasia and pulmonary hypertension. Great strides have been made in our ability to care for CDH patients, specifically in the prenatal improvement of lung volume and morphology with fetoscopic endoluminal tracheal occlusion (FETO). While the anatomic effects of FETO have been described in-depth, the changes it induces at the cellular and molecular level remain a budding area of CDH research. This review will delve into the cellular and molecular effects of FETO in the developing lung, emphasize areas in which further research may improve our understanding of CDH, and highlight opportunities to optimize the FETO procedure for improved postnatal outcomes.
The Effect of Statins on Clinical Outcome Among Hospitalized Patients With COVID-19: A Multi-Centric Cohort Study
Authors: Umakanthan Srikanth , Senthil Sanjum , John Stanley , Madhavan Mahesh K. , Das Jessica , Patil Sonal , Rameshwaram Raghunath , Cintham Ananya , Subramaniam Venkatesh , Yogi Madhusudan , Bansal Abhishek , Achutham Sumesh , Shekar Chandini , Murthy Vijay , Selvaraj Robbin
Published: July 2022

The coronavirus disease-2019 (COVID-19) is caused by SARS-CoV-2, leading to acute respiratory distress syndrome (ARDS), thrombotic complications, and myocardial injury. Statins, prescribed for lipid reduction, have anti-inflammatory, anti-thrombotic, and immunomodulatory properties and are associated with reduced mortality rates in COVID-19 patients. Our goal was to investigate the beneficial effects of statins in hospitalized COVID-19 patients admitted to three multi-specialty hospitals in India from 1 June 2020, to 30 April 2021. This retrospective study included 1,626 patients, of which 524 (32.2%) were antecedent statin users among 768 patients (384 statin users, 384 non-statin users) identified with 1:1 propensity-score matching. We established a multivariable logistic regression model to identify the patients’ demographics and adjust the baseline clinical and laboratory characteristics and co-morbidities. Statin users showed a lower mean of white blood cell count (7.6 × 103/µL vs. 8.1 × 103/µL, p < 0.01), and C-reactive protein (100 mg/L vs. 120.7 mg/L, p < 0.001) compared to non-statin COVID-19 patients. The same positive results followed in lipid profiles for patients on statins. Cox proportional-hazards regression models evaluated the association between statin use and mortality rate. The primary endpoint involved mortality during the hospital stay. Statin use was associated with lower odds of mortality in the propensity-matched cohort (OR 0.52, 95% CI 0.33-0.64, p < 0.001). These results support the previous evidence of the beneficial effects of statins in reducing mortality in hospitalized COVID-19 patients.
AKT/PACS2 Participates in Renal Vascular Hyperpermeability by Regulating Endothelial Fatty Acid Oxidation in Diabetic Mice
Authors: Shu Zhihao , Chen Shuhua , Xiang Hong , Wu Ruoru , Wang Xuewen , Ouyang Jie , Zhang Jing , Liu Huiqin , Chen Alex F. , Lu Hongwei
Published: July 2022

Diabetes is a chronic metabolic disorder that can cause many microvascular and macrovascular complications, including diabetic nephropathy. Endothelial cells exhibit phenotypic and metabolic diversity and are affected by metabolic disorders. Whether changes in endothelial cell metabolism affect vascular endothelial function in diabetic nephropathy remains unclear. In diabetic mice, increased renal microvascular permeability and fibrosis, as well as increased MAMs and PACS2 in renal endothelial cells, were observed. Mice lacking PACS2 improved vascular leakage and glomerulosclerosis under high fat diet. In vitro, PACS2 expression, VE-cadherin internalization, fibronectin production, and Smad-2 phosphorylation increased in HUVECs treated with high glucose and palmitic acid (HGHF). Pharmacological inhibition of AKT significantly reduced HGHF-induced upregulation of PACS2 and p-Smad2 expression. Blocking fatty acid β-oxidation (FAO) ameliorated the impaired barrier function mediated by HGHF. Further studies observed that HGHF induced decreased FAO, CPT1α expression, ATP production, and NADPH/NADP+ ratio in endothelial cells. However, these changes in fatty acid metabolism were rescued by silencing PACS2. In conclusion, PACS2 participates in renal vascular hyperpermeability and glomerulosclerosis by regulating the FAO of diabetic mice. Targeting PACS2 is potential new strategy for the treatment of diabetic nephropathy.
Erectile Dysfunction: Key Role of Cavernous Smooth Muscle Cells
Authors: Souza Iara Leão Luna de , Ferreira Elba dos Santos , Vasconcelos Luiz Henrique César , Cavalcante Fabiana de Andrade , Silva Bagnólia Araújo da
Published: July 2022

Erectile dysfunction is increasingly affecting men, from the elderly to young adults, being a sexual disorder related to the inability to generate or maintain a penile erection. This disorder is related to psychosocial factors such as anxiety, depression, and low self-esteem, to organic factors such as the presence of preexisting conditions like hypertension, diabetes and dyslipidemia. The pathophysiology of the disease is related to changes in the neurotransmission of the autonomic or the non-cholinergic non-adrenergic nervous system, as well as the release of local mediators, such as thromboxane A2 and endothelin, and hormonal action. These changes lead to impaired relaxation of cavernous smooth muscle, which reduces local blood flow and impairs penile erection. Currently, therapy is based on oral vasodilation, such as sildenafil, tadalafil, vardenafil and iodenafil, or by direct administration of these agents into the corpus cavernosum or by intraurethral route, such as alprostadil and papaverine. Despite this, studies that consolidate the understanding of its pathophysiological process contribute to the discovery of new more efficient drugs for the treatment of erectile dysfunction. In this sense, in the present work an extensive survey was carried out of the mechanisms already consolidated and the most recent ones related to the development of erectile dysfunction.
Use of the Capture-Recapture Method to Estimate the Frequency of Community- and Hospital-Acquired Drug-Induced Acute Kidney Injuries in French Databases
Authors: Rey Amayelle , Gras Valérie , Moragny Julien , Choukroun Gabriel , Masmoudi Kamel , Liabeuf Sophie
Published: July 2022

Drug-induced acute kidney injury (AKI) can occur both in primary care (i.e., community-acquired AKI (CA-AKI)) and in hospital settings (i.e., hospital-acquired AKI (HA-AKI)). The reported prevalence of these events varies markedly from one study to another, mainly due to differences in the study design. To estimate the frequency of drug-induced AKIs (both CA-AKIs and HA-AKIs) observed in a French university hospital, we applied the capture-recapture method to 1) the French national pharmacovigilance database (FPVD) and 2) a cohort of hospitalized patients with drug-induced AKIs (documented by analyzing the French national hospital discharge database and the patients’ electronic medical records). Drug-induced AKIs were determined according to the Naranjo algorithm and then categorized as CA-AKIs or HA-AKIs. A total number of 1,557 episodes of AKI were record during the study period, of them, the estimated total number of drug-induced AKIs was 593 [95% confidence interval (CI): 485–702], and the estimated prevalence was 38.1% [95%CI: 35.67–40.50]. The prevalences of HA-AKIs and CA-AKIs were similar (39.4% [36.24–42.54] and 37.4% [33.67–41.21], respectively). Only 6.1% of the drug-induced AKIs were recorded in the FPVD, and the proportions of recorded HA-AKIs and CA-AKI differed markedly (3.0% vs. 10.5%, respectively). One of the most frequently involved drug classes were antibiotics in the HA-AKI subgroup (13.0%) and antineoplastics in the CA-AKI subgroup (8.3%). Application of the capture-recapture method to two incomplete data sources can improve the ability to identify and quantify adverse drug reactions like AKIs. The frequency of drug-induced AKI is relatively high and is probably underestimated. The clinical management of an AKI might depend on where it originated.