bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogenetic Structure and Comparative Genomics of Multi-National Invasive Haemophilus influenzae Serotype a Isolates
Authors: Topaz Nadav , Tsang Raymond , Deghmane Ala-Eddine , Claus Heike , Lâm Thiên-Trí , Litt David , Bajanca-Lavado Maria Paula , Pérez-Vázquez María , Vestrheim Didrik , Giufrè Maria , Van Der Ende Arie , Gaillot Olivier , Kuch Alicja , McElligott Martha , Taha Muhamed-Kheir , Wang Xin
Published: March 2022

Recent reports have indicated a rise of invasive disease caused by Haemophilus influenzae serotype a (Hia) in North America and some European countries. The whole-genome sequences for a total of 410 invasive Hia isolates were obtained from 12 countries spanning the years of 1998 to 2019 and underwent phylogenetic and comparative genomic analysis in order to characterize the major strains causing disease and the genetic variation present among factors contributing to virulence and antimicrobial resistance. Among 410 isolate sequences received, 408 passed our quality control and underwent genomic analysis. Phylogenetic analysis revealed that the Hia isolates formed four genetically distinct clades: clade 1 (n = 336), clade 2 (n = 13), clade 3 (n = 3) and clade 4 (n = 56). A low diversity subclade 1.1 was found in clade 1 and contained almost exclusively North American isolates. The predominant sequence types in the Hia collection were ST-56 (n = 125), ST-23 (n = 98) and ST-576 (n = 51), which belonged to clade 1, and ST-62 (n = 54), which belonged to clade 4. Clades 1 and 4 contained predominantly North American isolates, and clades 2 and 3 predominantly contained European isolates. Evidence of the presence of capsule duplication was detected in clade 1 and 2 isolates. Seven of the virulence genes involved in endotoxin biosynthesis were absent from all Hia isolates. In general, the presence of known factors contributing to β-lactam antibiotic resistance was low among Hia isolates. Further tests for virulence and antibiotic susceptibility would be required to determine the impact of these variations among the isolates.
Recruitment of Mobile Genetic Elements for Diverse Cellular Functions in Prokaryotes
Authors: Benler Sean , Koonin Eugene V.
Published: March 2022

Prokaryotic genomes are replete with mobile genetic elements (MGE) that span a continuum of replication autonomy. On numerous occasions during microbial evolution, diverse MGE lose their autonomy altogether but, rather than being quickly purged from the host genome, assume a new function that benefits the host, rendering the immobilized MGE subject to purifying selection, and resulting in its vertical inheritance. This mini-review highlights the diversity of the repurposed (exapted) MGE as well as the plethora of cellular functions that they perform. The principal contribution of the exaptation of MGE and their components is to the prokaryotic functional systems involved in biological conflicts, and in particular, defense against viruses and other MGE. This evolutionary entanglement between MGE and defense systems appears to stem both from mechanistic similarities and from similar evolutionary predicaments whereby both MGEs and defense systems tend to incur fitness costs to the hosts and thereby evolve mechanisms for survival including horizontal mobility, causing host addiction, and exaptation for functions beneficial to the host. The examples discussed demonstrate that the identity of an MGE, overall mobility and relationship with the host cell (mutualistic, symbiotic, commensal, or parasitic) are all factors that affect exaptation.
Structure, Function and Protein Engineering of Cereal-Type Inhibitors Acting on Amylolytic Enzymes
Authors: Møller Marie Sofie , Svensson Birte
Published: March 2022

Numerous plants, including cereals, contain seed proteins able to inhibit amylolytic enzymes. Some of these inhibitors, the CM-proteins (soluble in chloroform:methanol mixtures)—also referred to as cereal-type inhibitors (CTIs)—are the topic of this review. CM-proteins were first reported 75 years ago. They are small sulfur-rich proteins of the prolamine superfamily embracing bifunctional α-amylase/trypsin inhibitors (ATIs), α-amylase inhibitors (AIs), limit dextrinase inhibitors (LDIs), and serine protease inhibitors. Phylogenetically CM-proteins are predicted across poaceae genomes and many isoforms are identified in seed proteomes. Their allergenicity and hence adverse effect on humans were recognized early on, as were their roles in plant defense. Generally, CTIs target exogenous digestive enzymes from insects and mammals. Notably, by contrast LDI regulates activity of the endogenous starch debranching enzyme, limit dextrinase, during cereal seed germination. CM-proteins are four-helix bundle proteins and form enzyme complexes adopting extraordinarily versatile binding modes involving the N-terminal and different loop regions. A number of these inhibitors have been characterized in detail and here focus will be on target enzyme specificity, molecular recognition, forces and mechanisms of binding as well as on three-dimensional structures of CM-protein–enzyme complexes. Lastly, prospects for CM-protein exploitation, rational engineering and biotechnological applications will be discussed.
An Update on the Molecular Mechanism of the Vertebrate Isthmic Organizer Development in the Context of the Neuromeric Model
Authors: Hidalgo-Sánchez Matías , Andreu-Cervera Abraham , Villa-Carballar Sergio , Echevarria Diego
Published: March 2022

A crucial event during the development of the central nervous system (CNS) is the early subdivision of the neural tube along its anterior-to-posterior axis to form neuromeres, morphogenetic units separated by transversal constrictions and programed for particular genetic cascades. The narrower portions observed in the developing neural tube are responsible for relevant cellular and molecular processes, such as clonal restrictions, expression of specific regulatory genes, and differential fate specification, as well as inductive activities. In this developmental context, the gradual formation of the midbrain-hindbrain (MH) constriction has been an excellent model to study the specification of two major subdivisions of the CNS containing the mesencephalic and isthmo-cerebellar primordia. This MH boundary is coincident with the common Otx2-(midbrain)/Gbx2-(hindbrain) expressing border. The early interactions between these two pre-specified areas confer positional identities and induce the generation of specific diffusible morphogenes at this interface, in particular FGF8 and WNT1. These signaling pathways are responsible for the gradual histogenetic specifications and cellular identity acquisitions with in the MH domain. This review is focused on the cellular and molecular mechanisms involved in the specification of the midbrain/hindbrain territory and the formation of the isthmic organizer. Emphasis will be placed on the chick/quail chimeric experiments leading to the acquisition of the first fate mapping and experimental data to, in this way, better understand pioneering morphological studies and innovative gain/loss-of-function analysis.
Protocol for the Exercise, Cancer and Cognition – The ECCO-Study: A Randomized Controlled Trial of Simultaneous Exercise During Neo-/Adjuvant Chemotherapy in Breast Cancer Patients and Its Effects on Neurocognition
Authors: Kiesl David , Kuzdas-Sallaberger Marina , Fuchs David , Brunner Silvana , Kommenda Romana , Tischler Clemens , Hornich Herwig , Akbari Kaveh , Kellermair Jörg , Blessberger Hermann , Ocenasek Helmuth , Hofmann Peter , Zimmer Philipp , Vosko Milan R.
Published: March 2022

Introduction

Epidemiological studies show that increased physical activity is linked to a lower risk of breast cancer and mortality. As a result, physical activity can significantly improve patients' quality of life (QOL) both during and after therapy.

Many breast cancer patients demonstrate a decrease in cognitive capacity, referred to as the symptom-complex cancer related cognitive impairment (CRCI). Most frequently reported impairments are mild to moderate deficits in processing speed, attention, memory, and executive functions. Cognitive symptoms persist for months or even years, following medical treatment in roughly 35% of afflicted people, impairing everyday functioning, limiting the ability to return to work, and lowering the overall QOL. Recent studies point toward a key role of inflammatory pathways in the CRCI genesis. Attention to physical activity as a potential supportive care option is therefore increasing. However, evidence for the positive effects of exercise on preventing CRCI is still lacking.

Patients and Methods

Against this background, the prospective, two-arm, 1:1 randomized, controlled trial investigates the influence of first line chemotherapy accompanied by exercise training on preventing CRCI in 126 patients with breast cancer at the local University Hospital. The study will evaluate biomarkers and secondary assessments suspected to be involved in the pathogenesis of CRCI in addition to objective (primary outcome) and subjective cognitive function. CRCI is believed to be connected to either functional and/or morphological hippocampal damage due to chemotherapy. Thus, cerebral magnetic resonance imaging (MRI) and hippocampal volume measurements are performed. Furthermore, a specific neuropsychological test battery for breast cancer patients has been developed to detect early signs of cognitive impairments in patients and to be integrated into practice.

Discussion

This study will explore how a long-term supervised exercise intervention program might prevent CRCI, enables optimization of supportive care and objectifies limits of psychological and physical resilience in breast cancer patients during and after chemotherapy treatment.

Trial Registration

ClinicalTrials.gov: Identifier: NCT04789187. Registered on 09 March 2021.
The Effects of Combined Cognitive-Physical Interventions on Cognitive Functioning in Healthy Older Adults: A Systematic Review and Multilevel Meta-Analysis
Authors: Rieker Jennifer A. , Reales José M. , Muiños Mónica , Ballesteros Soledad
Published: March 2022

Research has shown that both physical exercise and cognitive training help to maintain cognition in older adults. The question is whether combined training might produce additive effects when the group comparisons are equated in terms of exercise intensity and modality. We conducted a systematic electronic search in MEDLINE, PsycInfo, and Cochrane Central Register of Controlled Trials (CENTRAL) databases to identify relevant studies published up to February 2021. Seven hundred and eighty-three effect sizes were obtained from 50 published intervention studies, involving 6,164 healthy older adults, and submitted to a three-level meta-analysis. Results showed that combined training produced a small advantage in comparison to single cognitive training on executive functions, whereas both types of training achieved similar effects on attention, memory, language, processing speed, and global cognition. Combined training achieved higher training gains in balance than single physical training, indicating a transfer from cognitive training to balance. Performing cognitive and physical exercise simultaneously, and interactive training (e.g., exergames, square stepping) produced the largest gains in executive functions, speed, and global cognition, as well as the largest improvements in physical functions. Aerobic training was associated with higher effects in attention and fitness, whereas non-aerobic training produced larger effects in global cognition and balance. For all cognitive and physical outcomes, training resulted more advantageous when performed in a social context, even though individual training obtained similar results in balance as group training.

Systematic Review Registration:www.crd.york.ac.uk/prospero/, identifier: CRD42020175632.
The Changes of Amygdala Transcriptome in Autism Rat Model After Arginine Vasopressin Treatment
Authors: Zhou Bo , Zheng Xiaoli , Chen Yunhua , Yan Xuehui , Peng Jinggang , Liu Yibu , Zhang Yi , Tang Lei , Wen Min
Published: March 2022

Background

Some studies have shown that arginine vasopressin (AVP) can significantly improve the social interaction disorder of autism, but the mechanism remains unclear.

Methods

Female Wistar rats were intraperitoneally injected with VPA or normal saline at embryonic day 12.5 to establish an autism model or normal control in their offspring. Male offspring prenatally exposed to VPA were randomly assigned to two groups: the VPA-induced autism model group and the AVP group. The rats in the AVP group were treated with intranasal AVP at postnatal day (PND) 21 and for 3 weeks. The VPA-induced autism model group was given the same dose of normal saline in the same way. Behavioral responses were evaluated in the open field and three-chambered social test apparatus; the expression levels of AVP in serum were detected by enzyme-linked immunosorbent assay kit, and the gene expression levels on the amygdala were measured by RNA-seq at PND42.

Results

Intranasal administration of AVP can significantly improve the social interaction disorder and elevate the levels of AVP in serum. Transcriptome sequencing results showed that 518 differently expressed genes (DEGs) were identified in the VPA-induced autism model group compared with the control in this study. Gene Ontology biological process enrichment analysis of DEGs showed that the VPA-induced autism model group had significant nervous system developmental impairments compared with the normal group, particularly in gliogenesis, glial cell differentiation, and oligodendrocyte differentiation. Gene Set Enrichment Analysis (GSEA) enrichment analysis also showed that biological process of oligodendrocyte differentiation, axoneme assembly, and axon ensheathment were inhibited in the VPA-induced autism model group. Pathway enrichment analysis of DEGs between the control and VPA-induced autism model group showed that the PI3K/AKT and Wnt pathways were significantly dysregulated in the VPA-induced autism model group. Few DEGs were found when compared with the transcriptome between the VPA-induced autism model group and the AVP treatment group. GSEA enrichment analysis showed deficits in oligodendrocyte development and function were significantly improved after AVP treatment; the pathways were mainly enriched in the NOTCH, mitogen-activated protein kinase, and focal adhesion signaling pathways, but not in the PI3K/AKT and Wnt pathways. The expression patterns analysis also showed the same results.

Conclusion

AVP can significantly improve the social interaction disorder of VPA-induced autism model, and AVP may target behavioral symptoms in autism by modulating the vasopressin pathways, rather than primary disease mechanisms.
Altered Cingulum Functioning in Major Depressive Disorder Patient With Suicide Attempts: A Resting-State Functional Magnetic Resonance Imaging Study
Authors: Yang Chunxia , Duan Yajuan , Lei Lei , Liu Penghong , Zhang Aixia , Li Gaizhi , Sun Ning , Wang Yikun , Liu Zhifen , Zhang Kerang
Published: March 2022

Background

Major depressive disorder (MDD) with suicide attempts (SA) poses a significant public health issue. This study aims to identify neurobiological markers for MDD with SA on resting-state brain functional magnetic resonance imaging (rs-fMRI).

Methods

Fifty-one unmedicated adult MDD participants, 27 with SA on the Beck Scale for Suicidal Ideation and 24 without SA, underwent rs-fMRI scanning. A group of 30 healthy controls (HC) matched for age, gender, and education-level with MDD were chosen. A whole brain analysis of regional homogeneity (ReHo) was performed on subjects to identify regions where brain activity was associated with SA. Multiple comparison analysis was performed for ReHo. Pearson’s correlation analysis was performed between HAMD-SA scores and ReHo. The statistical significance level was set at p < 0.05.

Results

We examined whether there were significant differences among the three groups in whole brain ReHo during resting state. Subjects with SA showed significant increase of ReHo in the right Cingulum Post in comparison with those without SA. Subjects with SA showed significant decrease of ReHo in the right Cingulate Gyrus/Precuneus in comparison with HC. The mean ReHo from the significant brain region was associated with HAMD-SA (item 3 of the HAMD) scores (r = 0.349, P = 0.012) but was not associated with HAMD-24 scores.

Conclusion

These results indicate that SA is associated with altered resting-state brain activity. The pattern of elevated activity in the cingulum functioning may be related to SA. Identifying cingulum activity associated with SA may help to elucidate its pathogenesis and etiology.
Lipid Homeostasis and Its Links With Protein Misfolding Diseases
Authors: Vendruscolo Michele
Published: March 2022

The maintenance of lipid homeostasis is essential for the normal functioning of living organisms. Alterations of the lipid homeostasis system remodel the composition of the lipidome, potentially leading to the formation of toxic lipid species. In turn, lipidome changes can affect the protein homeostasis system by causing perturbations that elicit protein condensation phenomena such as protein liquid-liquid phase separation and protein aggregation. Lipids can also be more directly involved the formation of aberrant condensed states of proteins by facilitating the early events that initiate these processes and by stabilizing the condensed states themselves. These observations suggest that lipid-induced toxicity can contribute to protein misfolding diseases, including Alzheimer’s and Parkinson’s diseases. According to this view, an impairment of the lipid homeostasis system generates toxic states of lipids that disturb the protein homeostasis system and promote the formation of toxic states of proteins.
A Natural Low Phytic Acid Finger Millet Accession Significantly Improves Iron Bioavailability in Indian Women
Authors: Reddy Bellam H. Rajashekar , Thankachan Prashanth , Hatakayama Masoami , Hiremath Netravati , Moretti Diego , Nanjareddy Yellodu A. , Thumilan Mathi B. , Ravikumar Ramapura L. , Phadnis Shamprasad , Bose Beena , Poveda Lucy , Kalaiah Geetha , Zimmermann Michael B. , Shimizu Kentaro K. , Schlapbach Ralph , Kurpad Anura V. , Sreeman Sheshshayee M.
Published: March 2022

Iron deficiency and anemia are common in low- and middle-income countries. This is due to a poor dietary iron density and low iron absorption resulting from the high inhibitory phytic acid content in cereal and millet-based diets. Here, we report that a naturally occurring low phytic acid finger millet accession (571 mg 100 g−1), stable across three growing seasons with normal iron content (3.6 mg 100 g−1), increases iron absorption by 3-folds in normal Indian women. The accessions differing in grain phytic acid content, GE 2358 (low), and GE1004 (high) were selected from a core collection of 623 accessions. Whole genome re-sequencing of the accessions revealed significant single nucleotide variations segregating them into distinct clades. A non-synonymous mutation in the EcABCC phytic acid transporter gene between high and low accessions could affect gene function and result in phytic acid differences. The highly sensitive dual stable-isotope erythrocyte incorporation method was adopted to assess the fractional iron absorption. The low phytic acid accession resulted in a significantly higher iron absorption compared with the high phytic acid accession (3.7 vs. 1.3%, p < 0.05). The low phytic acid accession could be effective in preventing iron deficiency in regions where finger millet is habitually eaten. With its low water requirement, finger millet leaves low environmental footprints and hence would be an excellent sustainable strategy to mitigate iron deficiency.
Distribution and Influencing Factors of the Sialic Acid Content in the Breast Milk of Preterm Mothers at Different Stages
Authors: Chen Zekun , Chang Yanmei , Liu Hui , You Yanxia , Liu Yanpin , Yu Xue , Dou Yuqi , Ma Defu , Chen Lijun , Tong Xiaomei , Xing Yan
Published: March 2022

Background and Aims

This study aimed to detect breast milk sialic acid (SA) content and the changing pattern, to understand the various stages of breastfeeding SA secretion, and the influence factors of the human milk SA content.

Methods

We recruited mothers and their infants as our subjects. At days 7, 14, 30, 120, and 365 after delivery, the contents of SA in breast milk were collected and detected through Fluorescence Detector-High Performance Liquid Chromatography. The participants completed the baseline questionnaire at ≤day 7 and were followed up at days 30, 120, and 365.

Results

A total of 95 mothers with 122 infants were included in the analysis, including 22 mothers with 22 term infants, 25 mothers with 35 late preterm infants, 31 mothers with 39 very preterm infants, and 17 mothers with 26 extremely preterm infants. Similar to previous findings, the results of the study showed that, compared with breast milk of term mothers at the same period, breast milk of preterm mothers contained more SA at each time node, and the content of SA in breast milk increased with decreasing gestational weeks. Moreover, maternal age, pre-pregnancy BMI, and delivery mode had significant effects on total SA in breast milk, especially for the preterm infant breast milk. Significant negative associations occurred between SA contents and infant growth status, especially in preterm infants.

Conclusions

We have confirmed the previous observations showing that with the prolongation of lactation time, the content of SA in breast milk gradually decreased, and the content of SA in the breast milk of preterm mothers was higher than that of term mothers. In addition, SA content was associated with maternal age, pre-pregnancy BMI, and delivery mode.
Mango Pectic Oligosaccharides: A Novel Prebiotic for Functional Food
Authors: Wongkaew Malaiporn , Tangjaidee Pipat , Leksawasdi Noppol , Jantanasakulwong Kittisak , Rachtanapun Pornchai , Seesuriyachan Phisit , Phimolsiripol Yuthana , Chaiyaso Thanongsak , Ruksiriwanich Warintorn , Jantrawut Pensak , Sommano Sarana Rose
Published: March 2022

Prebiotics are functional food ingredients that assist probiotic growth and render many other health benefits. Mango peel is the biomass of the processing industry and has recently been value-added as a dietary fiber pectin. Besides its general use as a food additive, mango peel pectin (MPP) is partially hydrolyzed by pectinase to obtain pectic oligosaccharides (POSs) that have recently gained attention as novel prebiotic products and in medical research. This review describes probiotic candidates responsible for the digestion of pectin derivatives and the advantages of POSs as functional additives and their current best retrieval options. Mango pectic oligosaccharide (MPOS) recovery from low methoxyl MPP from mango with prebiotic performance both in vivo and in vitro environments is discussed. Current research gaps and potential developments in the field are also explored. The overall worthiness of this article is the potential use of the cheap-green food processing bioresource for high-value components.
Hyperprogressive Disease in Malignant Carcinoma With Immune Checkpoint Inhibitor Use: A Review
Authors: Liu Xiaojun , Qiao Liang
Published: March 2022

Immune checkpoint inhibitors (ICIs) have shown durable remissions and improved long-term survival across a variety of cancer types. However, there is growing evidence that a significant subset of nonresponsive patients may exhibit hyperprogressive disease (HPD) during the initiation of immune checkpoint inhibitors (ICIs). Moreover, patients with HPD triggered by ICIs are always correlated with a deteriorating quality of life and poor prognosis. The ability to predict such rapid disease progression phenotypes is of great importance. More precision parameters to evaluate the response pattern to ICIs are urgently needed. To date, the mechanisms of HPD are still unclear. Aberrant alterations of driven genes, tumor microenvironment, or T cell immunophenotype may involve in HPD. In this article, we aim to provide an updated overview of available studies on HPD and summarize the potential predictors associated with HPD and the underlying mechanisms of HPD.
Classification of the Occurrence of Dyslipidemia Based on Gut Bacteria Related to Barley Intake
Authors: Maruyama Satoko , Matsuoka Tsubasa , Hosomi Koji , Park Jonguk , Nishimura Mao , Murakami Haruka , Konishi Kana , Miyachi Motohiko , Kawashima Hitoshi , Mizuguchi Kenji , Kobayashi Toshiki , Ooka Tadao , Yamagata Zentaro , Kunisawa Jun
Published: March 2022

Barley is a grain rich in β-glucan, a soluble dietary fiber, and its consumption can help maintain good health and reduce the risk of metabolic disorders, such as dyslipidemia. However, the effect of barley intake on the risk of dyslipidemia has been found to vary among individuals. Differences in gut bacteria among individuals may be a determining factor since dietary fiber is metabolized by gut bacteria and then converted into short-chain fatty acids with physiological functions that reduce the risk of dyslipidemia. This study examined whether gut bacteria explained individual differences in the effects of barley intake on dyslipidemia using data from a cross-sectional study. In this study, participants with high barley intake and no dyslipidemia were labeled as “responders” to the reduced risk of dyslipidemia based on their barley intake and their gut bacteria. The results of the 16S rRNA gene sequencing showed that the fecal samples of responders (n = 22) were richer in Bifidobacterium, Faecalibacterium, Ruminococcus 1, Subdoligranulum, Ruminococcaceae UCG-013, and Lachnospira than those of non-responders (n = 43), who had high barley intake but symptoms of dyslipidemia. These results indicate the presence of certain gut bacteria that define barley responders. Therefore, we attempted to generate a gut bacteria-based responder classification model through machine learning using random forest. The area under the curve value of the classification model in estimating the effect of barley on the occurrence of dyslipidemia in the host was 0.792 and the Matthews correlation coefficient was 0.56. Our findings connect gut bacteria to individual differences in the effects of barley on lipid metabolism, which could assist in developing personalized dietary strategies.
Prognostic Value of Geriatric Nutritional Risk Index in Esophageal Carcinoma: A Systematic Review and Meta-Analysis
Authors: Zhou Jianfeng , Fang Pinhao , Li Xiaokun , Luan Siyuan , Xiao Xin , Gu Yinmin , Shang Qixin , Zhang Hanlu , Yang Yushang , Zeng Xiaoxi , Yuan Yong
Published: March 2022

Esophageal cancer (EC) is one of the most common cancers worldwide. Malnutrition often leads to poor prognosis of patients with EC. Geriatric nutritional risk index (GNRI) was reported as an objective nutrition-related risk index. We intend to comprehensively review evidence of GNRI in predicting EC prognosis. To explore the influence of GNRI on the long-term survival outcome of patients with EC, a meta-analysis was needed. We searched the Web of Science, Medline, Embase, and the Cochrane Library databases. The association between prognosis of patients with EC and GNRI was evaluated by pooling hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). The fixed model or random model method was chosen according to the heterogeneity among the studies. Totally, 11 studies with 1785 patients who met the inclusion criteria were eventually included in our meta-analysis. Comparing the lower level GNRI group and the higher level GNRI group, the pooled results showed that lower GNRI had a negative impact on overall survival (OS) (HR: 1.75, 95% CI: 1.45–2.10, P < 0.01) and cancer-specific survival (CSS) (HR: 1.77, 95% CI: 1.19–2.62, P < 0.01), indicating that lower GNRI significantly predicted poor OS. In conclusion, lower GNRI could predict the poor prognosis of patients with EC. Meanwhile, more well-designed randomized controlled trials (RCTs) are needed to confirm the findings.
Diversity Analysis of Bacterial and Function Prediction in Hurunge From Mongolia
Authors: Bao Wuyundalai , He Yuxing , Liu Wei
Published: March 2022

With the continuous infiltration of industrialization and modern lifestyle into pastoral areas, the types and processing capacity of Hurunge are decreasing, and the beneficial microbial resources contained in it are gradually disappearing. The preservation and processing of Hurunge are very important for herdsmen to successfully produce high-quality koumiss in the second year. Therefore, in this study, 12 precious Hurunge samples collected from Bulgan Province, Ovorkhangay Province, Arkhangay Province, and Tov Province of Mongolia were sequenced based on the V3–V4 region of the 16S rRNA gene, and the bacterial diversity and function were predicted and analyzed. There were significant differences in the species and abundance of bacteria in Hurunge from different regions and different production methods (p < 0.05). Compared with the traditional fermentation methods, the OTU level of Hurunge fermented in the capsule was low, the Acetobacter content was high and the bacterial diversity was low. Firmicutes and Lactobacillus were the dominant phylum and genus of 12 samples, respectively. The sample QHA contained Komagataeibacter with the potential ability to produce bacterial nanocellulose, and the abundance of Lactococcus in the Tov Province (Z) was significantly higher than that in the other three regions. Functional prediction analysis showed that genes related to the metabolism of bacterial growth and reproduction, especially carbohydrate and amino acid metabolism, played a dominant role in microorganisms. In summary, it is of great significance to further explore the bacterial diversity of Hurunge for the future development and research of beneficial microbial resources, promotion, and protection of the traditional ethnic dairy products.
The Association Between Visceral Adiposity Index and Worsening Renal Function in the Elderly
Authors: Lei Li , Dai Lei , Zhang Qiuxia , Lu Junyan , Tang Yongzhen , Xiao Min , Li Guodong , Yan Shaohua , Li Xiaobo , Chen Yejia , Chen Yaode , Li Yun , An Shengli , Xiu Jiancheng
Published: March 2022

Background

Visceral adiposity index (VAI) is an indicator of visceral fat accumulation and dysfunction. However, little is known about whether VAI is associated with worsening renal function (WRF) in the elderly. Therefore, our study aimed to explore the association between VAI and WRF among the elderly population.

Methods

In total, 5,583 elderly participants (aged ≥ 65 years) who participated in the annual health checkups at least twice between January 2017 and July 2021 were enrolled and divided into four groups according to the VAI quartiles. The primary endpoint was incident chronic kidney disease (CKD), defined as incident estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. The secondary endpoint was rapid kidney function decline (RKFD), defined as decline in eGFR of 40%. To evaluate the association between VAI and WRF, three Cox regression models were conducted, where VAI was treated as a continuous variable and a categorical variable (Q1 as reference), respectively. Subgroup analysis in participants with different baseline characteristics was also performed.

Results

During a median of 2.46 year follow-up, 931 (16.68%) participants developed CKD. After fully adjusting for confounding factors, VAI was significantly associated with incident CKD (HR, 1.052; 95% CI: 1.029–1.076, p < 0.001), and RKFD (HR, 1.077; 95% CI: 1.041–1.114, p < 0.001). Moreover, compared to those with the lowest VAI quartiles, subjects with the highest quartiles had a higher risk of incident CKD (HR, 1.286; 95% CI: 1.033–1.601, p = 0.024), and RKFD (HR, 1.895; 95% CI: 1.086–3.307, p = 0.025). The risk of incident CKD also tended to increase with elevated VAI quartiles (all p-values for trend <0.05). This positive association remained consistent among participants with different genders, baseline weights, or kidney functions.

Conclusion

In our study, elevated VAI was associated with increased risk of incident CKD and RKFD in the elderly population.
Spectrum of Interventional Procedures During Hybrid Central Line Placement in Pediatric Intestinal Rehabilitation Patients With End-Stage Vascular Access
Authors: Sieverding Ludger , Michel Jörg , Urla Christian , Sturm Ekkehard , Winkler Franziska , Hofbeck Michael , Fuchs Jörg , Hilberath Johannes , Warmann Steven Walter
Published: March 2022

Background

Loss of available central vein access sites for parenteral nutrition delivery represents one of the main indications for intestinal transplantation in children with intestinal failure. Placement of central venous catheters can be challenging in advanced loss of patent venous pathways. We recently described the hybrid technique (interventional plus surgical approach) of central line placement in children. The aim of this study was to describe and analyze the interventions used during the hybrid procedures regarding feasibility, safety and outcome.

Methods

We retrospectively analyzed the course of all children in our intestinal rehabilitation program undergoing hybrid central line placement. We evaluated patients' conditions, interventional techniques and surgical peculiarities as well as outcome.

Results

203 children were treated in our intestinal rehabilitation program between 2010 and 2021. Due to loss of venous access, hybrid technique was performed in 53 children during 76 interventions. In 40 cases the same vessel was reused via Seldinger technique. Among the 30 ultrasound-guided new vessel punctures, 12 were performed by puncture of collateral vessels. Extended interventions due to thoracic central venous obstruction and/or thrombosis requiring additional access via a femoral vein for rehabilitation of the vascular system was performed during 29 procedures including catheter extraction (1), angioplasties (18), stent placement (1), revascularization (5) and thrombectomy (4). Placement of a central line was not possible in 6 children which eventually underwent extended thoracic/vascular surgery: in three children the previously placed catheter could not be removed, in one child, placement of a thrombectomy-catheter was not possible because of inferior vena cava occlusion, and in two children, revascularization failed. Intestinal transplantation was considered in one patient because of impending loss of vascular access. Two self-limiting minor extravasations and one intervention-associated pericardial effusion occurred.

Conclusions

Hybrid interventions for central venous catheter placement and vascular rehabilitation enable a high success rate in children with intestinal failure and end-stage vascular access, circumventing the need for intestinal transplantation or advanced surgery. The relevant procedures are complex and require a foresighted and individualized approach with a wide range of interventional techniques. If performed with expertise, this combined interventional/surgical approach is feasible and safe.
Protective Effects of Intestinal Gallic Acid in Neonatal Dairy Calves Against Extended-Spectrum β-lactamase Producing Enteroaggregative Escherichia coli Infection: Modulating Intestinal Homeostasis and Colitis
Authors: He Zhiyuan , Ma Yulin , Chen Xu , Liu Shuai , Xiao Jianxin , Wang Yajing , Wang Wei , Yang Hongjian , Li Shengli , Cao Zhijun
Published: March 2022

Calf diarrhea induced by enteroaggregative E. coli (EAEC) spreads fast among young ruminants, causing continuous hazard to dairy industry. Antimicrobial drug abuse aggravates the incidence rate of multi-drug resistant (MDR) extended-spectrum β-lactamase-producing E. coli (ESBL-EC). However, knowledge of detection and significance of disease-related biomarkers in neonatal female calves are still limited. Gallic acid (GA), a natural secondary metabolite mostly derived from plants, has attracted increasing attention for its excellent anti-inflammatory and anti-oxidative properties. However, it is vague how GA engenders amelioration effects on clinical symptoms and colitis induced by ESBL-EAEC infection in neonatal animals. Here, differentiated gut microbiome and fecal metabolome discerned from neonatal calves were analyzed to ascertain biomarkers in their early lives. Commensal Collinsella and Coriobacterium acted as key microbial markers mediating colonization resistance. In addition, there exists a strongly positive relation between GA, short-chain fatty acid (SCFA) or other prebiotics, and those commensals using random forest machine learning algorithm and Spearman correlation analyses. The protective effect of GA pretreatment on bacterial growth, cell adherence, and ESBL-EAEC-lipopolysaccharide (LPS)-treated Caco-2 cells were first assessed, and results revealed direct antibacterial effects and diminished colonic cell inflammation. Then, oral GA mediated colitis attenuation and recovery of colonic short-chain fatty acid (SCFA) productions on neonatal mice peritonitis sepsis or oral infection model. To corroborate this phenomenon, fecal microbiota transplantation (FMT) method was adopted to remedy the bacterial infection. Of note, FMT from GA-treated neonatal mice achieved profound remission of clinical symptoms and colitis over the other groups as demonstrated by antibacterial capability and prominent anti-inflammatory abilities, revealing improved hindgut microbiota structure with enriched Clostridia_UCG-014, Lachnospiraceae, Oscillospiraceae, and Enterococcaceae, and upregulation of SCFA productions. Collectively, our findings provided the direct evidence of hindgut microbiota and intestinal metabolites, discriminating the health status of neonatal calves post ESBL-EAEC infection. The data provided novel insights into GA-mediated remission of colitis via amelioration of hindgut commensal structure and upregulation of SCFA productions. In addition, its eminent role as potential antibiotic alternative or synergist for future clinic ESBL-EAEC control in livestock.
Sodium Ions Affect Pyrraline Formation in the Maillard Reaction With Lys-Containing Dipeptides and Tripeptides
Authors: Liang Zhili , Chen Xu , Yang Zhao , Liu Yan , Qiu Xueying , Zeng Zhenzhen , Lu Shuidi , Liu Yuehan
Published: March 2022

Advanced glycation end products (AGEs) are potentially-hazardous chemical compounds, produced by the Maillard reaction between reducing sugars and Lysine side-chain amino groups in proteins. AGEs are strongly associated with diabetes, Alzheimer's disease and atherosclerosis. Pyrraline, a sugar derivative of Lysine, is a major AGE and an established marker for the presence of dietary AGEs. In this study, the effects of NaCl and different dipeptide and tripeptide structures were compared on the formation of pyrraline-containing peptides and the glucose derivative 3-deoxyglucosone in the presence of glucose and at different NaCl concentrations. The physicochemical properties (polarizability, dipole moment, molecular volume and dissociation constant) and the thermodynamic properties of the peptides were determined. The amount of the pyrraline decreased significantly in the following order of peptides (at the same concentrations): Lys-Phe > Lys-Ala > Lys-Gly; Lys-Gly-Phe > Lys-Gly-Ala > Lys-Gly-Gly. The highest levels of both pyrraline and 3-deoxyglucosone occurred at 0.2 mol/L Na+. Sodium ions appear to alter the intramolecular electron density and charge distribution of the peptides and facilitate the reaction by stabilizing some of the intermediates in the reaction sequence.
Altered Signaling Pathways Revealed by Comprehensive Genomic Profiling in Patients With Unknown Primary Tumors
Authors: Yang Zhen , Cui Wei , Yu Ruoying , Dong Xinhua , Zhao Jian , Dai Lu , Ou Qiuxiang , Bao Hua , Wu Xue , Wu Chuanxin , Lai Jinhuo
Published: March 2022

Purpose

Carcinoma of unknown primary (CUP) is a clinically aggressive disorder with early tumor dissemination. Identifying molecular traits of CUP can be not only beneficial for a better therapeutic approach but also potentially valuable for patients with general metastatic dissemination.

Patients and Methods

We retrospectively investigated a total of 35 unique CUP cases. Tumor tissue samples were available in 26 patients, and plasma samples were available in 22 patients. Targeted sequencing was performed with a panel of 416 pan cancer-related genes.

Results

A genomic landscape of the CUP cohort showed that TP53 mutation was the most frequently observed mutation while MYC amplification was the most common CNV. Aberrant TP53, RTK-RAS, and PI3K signaling pathways were also prevalent, identified in more than half of the cases with tumor tissue. Around 58% of the CUP cases harbored homologous recombinant repair (HRR) pathway gene alterations. The tumor mutational load of CUP patients with altered HRR pathway displayed a significant increase than that of patients with intact HRR. Clinically actionable mutations were identified in eight patients, which may benefit from targeted therapies. Eight patients were treated with platinum-based chemotherapy, showing different responses, HRR, and LOH status.

Conclusion

Collectively, our data have provided much-need insights into the treatment options for patients diagnosed with CUP in the era of precision medicine.
OCT4 and SOX2 Specific Cytotoxic T Cells Exhibit Not Only Good Efficiency but Also Synergize PD-1 Inhibitor (Nivolumab) in Treating Breast Cancer Stem-Like Cells and Drug-Resistant Breast Cancer Mice
Authors: Peng Wei , Chang Liang , Li Wenqiang , Liu Yanan , Zhang Min
Published: March 2022

Purpose

This study aimed to investigate the effect of OCT4&SOX2 specific cytotoxic T lymphocytes (CTLs) plus programmed cell death protein-1 (PD-1) inhibitor (nivolumab) on treating breast cancer stem-like cells (BCSCs) in vitro and drug-resistance breast cancer (DRBC) mice in vivo.

Methods

In total, 160 breast cancer patients were enrolled following the immunofluorescence assay to detect tumor OCT4 and SOX2 expressions. CD154-activated B cells were co-cultured with CD8+ T cells (from breast cancer patients) in the presence of OCT4&SOX2 peptides, CMV pp65 peptides (negative control), and no peptides (normal control). MCF7-BCSCs were constructed by drug-resistance experiment and sphere-formation assay, then DRBC mice were constructed by planting MCF7-BCSCs. Subsequently, different doses of OCT4&SOX2 CTLs and PD-1 inhibitor (nivolumab) were used to treat MCF7-BCSCs and DRBC mice.

Results

OCT4 and SOX2 correlated with poor differentiation, more advanced stage, and worse prognosis in breast cancer patients. In vitro, OCT4&SOX2 CTLs with effector-target ratio (ETR) 5:1, 10:1 and 20:1 presented with increased cytotoxic activity compared to CMV pp65 CTLs with ETR 20:1 (negative control) and Control CTLs with ETR 20:1 (normal control) on killing MCF7-BCSCs. Besides, PD-1 inhibitor (nivolumab) improved the cytotoxic activity of OCT4&SOX2 CTLs against MCF7-BCSCs in a dose-dependent manner. In vivo, OCT4&SOX2 CTLs plus PD-1 inhibitor (nivolumab) decreased tumor volume and tumor weight while increased tumor apoptosis rate compared to OCT4&SOX2 CTLs alone, PD-1 inhibitor (nivolumab) alone, and control.

Conclusion

OCT4&SOX2 CTLs exhibit good efficiency and synergize PD-1 inhibitor (nivolumab) in treating BCSCs and DRBC.
Long Non-Coding RNA Cancer Susceptibility Candidate 9 Regulates the Malignant Biological Behavior of Nasopharyngeal Carcinoma Cells by Targeting miR-497-5p/Wnt3a/β-catenin Signaling Pathway
Authors: Lei Yue , Luo Wenlong , Gong Qiuyue , Luo Lan , Jing Wuyang
Published: March 2022

Nasopharyngeal carcinoma (NPC) is a major kind of head and neck epithelial carcinoma. Increasing evidences reveal that long noncoding RNAs are considered as vital regulators in tumorigenesis and progression. Although previous studies have found that cancer susceptibility candidate 9 (CASC9) highly expresses in NPC, the underlying mechanisms need to be further studied. In this study, we found that CASC9 was overexpressed and associated with worse prognosis in NPC. CASC9 knockdown significantly inhibited the cell proliferation, migration and invasion in vitro and enhanced the sensitivity of tumor cells to cisplatin and paclitaxel. Mechanism research confirmed CASC9 regulated the malignant biological behavior of nasopharyngeal carcinoma cells by targeting miR-497-5p/Wnt3a/β-catenin signaling pathway. The present study might provide a novel mechanism for tumorigenesis and progression of NPC and contribute to the development of an effective molecular target therapy.
Quality of Life Predictors in Patients With Melanoma: A Machine Learning Approach
Authors: Pinto Monica , Marotta Nicola , Caracò Corrado , Simeone Ester , Ammendolia Antonio , de Sire Alessandro
Published: March 2022

Health related quality of life (HRQoL) is an important recognized health outcome for cancer treatments, but also disease course with slower recovery and increased morbidity. These issues are of implication in melanoma, which maintains a risk of disease progression for many years after diagnosis. This study aimed to explore and weigh factors in the perception of the quality of life and possible relationships with demographic–clinical characteristics in people with melanoma via a machine learning approach. In this observational study, patients with melanoma, without metastatic disease, were recruited from January 2020 to December 2021 with a follow-up of at least one year. Demographic variables and clinics were collected, and the 12-Item Short-Form Health Survey (SF-12) was adopted as the physical and mental aspects of the Health-Related Quality of Life (HRQoL) measure. All the variables were processed in a random forest model to weigh at each node of each tree of this machine learning regression model, their actual weight in SF-12 score. We included 203 melanoma patients, mean aged 59.25 ± 15.1 years: 56 (27%) affecting the upper limbs and 147 (73%) affecting the trunk. The model of 142 patients with no missing value, generating 92 trees (MSE = 0.45, R2 of 0.78), reported that the lesion site was the most influencing variable on HRQoL based on the decrease in Gini impurity in variable weighing at each node intersection in forest generation. In this scenario, we built two distinct models for lesion sites and demonstrated that the variable that most influenced the quality of life in upper limb melanoma was lymphedema, while BMI was in the trunk. Given these results, random forest regressions could play a crucial role in the clinical and rehabilitation approach. The machine-learning model for detecting the HRQoL predictor in melanoma patients indicates that the experienced lymphedema and BMI may influence the HRQoL perception. This study suggests that the prevention and treatment of lymphedema and bodyweight reduction might improve the quality of life in melanoma.