bluuebunny/crossref_metadata_2025 huggingface dataset:
Downmodulation of Regulatory T Cells Producing TGF-β Participates in Pathogenesis of Leprosy Reactions
Authors: Gomes de Castro Katherine Kelda , Lopes da Silva Pedro Henrique , Nahar dos Santos Luciana , Leal Julia Monteiro Pereira , de Pinho Pereira Mylena Masseno , Alvim Iris Maria Peixoto , Esquenazi Danuza
Published: July 2022

Leprosy reactions are an acute and systemic manifestation, which occurs suddenly, can be severe and lead leprosy patients to disability. Reactional episodes are observed among half of the multibacillary patients, mainly in borderline lepromatous and lepromatous forms. They may begin at any time during multidrug therapy, and even before the treatment. Physical disabilities, which are the source of extreme suffering and pain for patients, occur in progression of the cellular immune response associated with a reaction and are still poorly understood. Thus, this work aimed to phenotypically and functionally characterize CD4+ and CD8+ Treg cells ex vivo and in response to Mycobacterium leprae (ML). We studied 52 individuals, including 18 newly diagnosed and untreated multibacillary leprosy patients, 19 reactional multibacillary patients (Type I or Type II episodes) and 15 healthy volunteers, included as controls, all residents of the city of Rio de Janeiro. The functional activity and frequencies of these cells were evaluated through multiparametric flow cytometry. In addition, the production of cytokines in supernatant from peripheral blood mononuclear cell cultures was also investigated against ML by enzyme-linked immunosorbent assay. Our results showed a decrease in CD4+TGF-β+ Treg and CD8+ TGF-β+ Treg in leprosy multibacillary patients during both types of reactional episodes. Alterations in the cytokine profile was also observed in Type II reactions, along with upregulation of IL-17 and IL-6 in supernatant. Thus, our study suggests that downregulation of Treg cells is related with both classes of reactional episodes, improving our understanding of immune hyporesponsiveness in multibacillary patients and hyperesponsiveness in both reactions.
Insights of Host Physiological Parameters and Gut Microbiome of Indian Type 2 Diabetic Patients Visualized via Metagenomics and Machine Learning Approaches
Authors: De Debjit , Nayak Tilak , Chowdhury Subhankar , Dhal Paltu Kumar
Published: July 2022

Type 2 diabetes (T2D) is a serious public health issue and may also contribute to modification in the structure of the intestinal microbiota, implying a link between T2D and microbial inhabitants in the digestive tract. This work aimed to develop efficient models for identifying essential physiological markers for improved T2D classification using machine learning algorithms. Using amplicon metagenomic approaches, an effort has also been made to understand the alterations in core gut microbial members in Indian T2D patients with respect to their control normal glucose tolerance (NGT). Our data indicate the level of fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) were the most useful physiological indicators while random forest and support vector machine with RBF Kernel were effective predictions models for identifications of T2D. The dominating gut microbial membersAllopreotella, Rikenellaceae RC9 gut group, Haemophilus, Ruminococcus torques group, etc. in Indian T2D patients showed a strong association with both FBG and HbA1c. These members have been reported to have a crucial role in gut barrier breakdown, blood glucose, and lipopolysaccharide level escalation, or as biomarkers. While the dominant NGT microbiota (Akkermansia, Ligilactobacillus, Enterobacter, etc.) in the colon has been shown to influence inflammatory immune responses by acting as an anti-inflammatory agent and maintaining the gut barrier. The topology study of co-occurrence network analysis indicates that changes in network complexity in T2D lead to variations in the different gut microbial members compared to NGT. These studies provide a better understanding of the gut microbial diversity in Indian T2D patients and show the way for the development of valuable diagnostics strategies to improve the prediction and modulation of the T2D along with already established methods.
Characterization of a Lytic Bacteriophage vB_SurP-PSU3 Infecting Staphylococcus ureilyticus and Its Efficacy Against Biofilm
Authors: Kwon Hyemin , Park Seon Young , Kim Min-Soo , Kim Sang Guen , Park Se Chang , Kim Ji Hyung
Published: July 2022

In response to the increasing nosocomial infections caused by antimicrobial-resistant coagulase-negative staphylococci (CoNS), bacteriophages (phages) have emerged as an alternative to antibiotics. Staphylococcus ureilyticus, one of the representative species of the CoNS, is now considered a notable pathogen that causes nosocomial bloodstream infections, and its biofilm-forming ability increases pathogenicity and resistance to antimicrobial agents. In this study, a lytic phage infecting S. ureilyticus was newly isolated from wastewater collected from a sewage treatment plant and its biological and antimicrobial characteristics are described. The isolated phage, named vB_SurP-PSU3, was morphologically similar to Podoviridae and could simultaneously lyse some S. warneri strains used in this study. The sequenced genome of the phage consisted of linear dsDNA with 18,146 bp and genome-based phylogeny revealed that vB_SurP-PSU3 belonged to the genus Andhravirus. Although its overall genomic arrangement and contents were similar to those of other members of the Andhravirus, the predicted endolysin of vB_SurP-PSU3 distinctly differed from the other members of the genus. The bacteriolytic activity of vB_SurP-PSU3 was evaluated using S. ureilyticus ATCC 49330, and the phage could efficiently inhibit the planktonic growth of the bacteria. Moreover, the anti-biofilm analysis showed that vB_SurP-PSU3 could prevent the formation of bacterial biofilm and degrade the mature biofilm in vitro. In an additional cytotoxicity assay of vB_SurP-PSU3, no significant adverse effects were observed on the tested cell. Based on these findings, the newly isolated phage vB_SurP-PSU3 could be classified as a new member of Andhravirus and could be considered an alternative potential biocontrol agent against S. ureilyticus infections and its biofilm.
Microbiome Composition and Dynamics of a Reductive/Oxidative Bioelectrochemical System for Perchloroethylene Removal: Effect of the Feeding Composition
Authors: Di Franca Maria L. , Matturro Bruna , Crognale Simona , Zeppilli Marco , Dell’Armi Edoardo , Majone Mauro , Petrangeli Papini Marco , Rossetti Simona
Published: July 2022

Chlorinated solvents still represent an environmental concern that requires sustainable and innovative bioremediation strategies. This study describes the microbiome composition of a novel bioelectrochemical system (BES) based on sequential reductive/oxidative dechlorination for complete perchloroethylene (PCE) removal occurring in two separate but sequential chambers. The BES has been tested under various feeding compositions [i.e., anaerobic mineral medium (MM), synthetic groundwater (SG), and real groundwater (RG)] differing in presence of sulfate, nitrate, and iron (III). In addition, the main biomarkers of the dechlorination process have been monitored in the system under various conditions. Among them, Dehalococcoides mccartyi 16S rRNA and reductive dehalogenase genes (tceA, bvcA, and vcrA) involved in anaerobic dechlorination have been quantified. The etnE and etnC genes involved in aerobic dechlorination have also been quantified. The feeding composition affected the microbiome, in particular when the BES was fed with RG. Sulfuricurvum, enriched in the reductive compartment, operated with MM and SG, suggesting complex interactions in the sulfur cycle mostly including sulfur oxidation occurring at the anodic counter electrode (MM) or coupled to nitrate reduction (SG). Moreover, the known Mycobacterium responsible for natural attenuation of VC by aerobic degradation was found abundant in the oxidative compartment fed with RG, which was in line with the high VC removal observed (92 ± 2%). D. mccartyi was observed in all the tested conditions ranging from 8.78E + 06 (with RG) to 2.35E + 07 (with MM) 16S rRNA gene copies/L. tceA was found as the most abundant reductive dehalogenase gene in all the conditions explored (up to 2.46 E + 07 gene copies/L in MM). The microbiome dynamics and the occurrence of biomarkers of dechlorination, along with the kinetic performance of the system under various feeding conditions, suggested promising implications for the scale-up of the BES, which couples reductive with oxidative dechlorination to ensure the complete removal of highly chlorinated ethylene and mobile low-chlorinated by-products.
Systematic Investigation of LC Miniaturization to Increase Sensitivity in Wide-Target LC-MS-Based Trace Bioanalysis of Small Molecules
Authors: Fitz Veronika , El Abiead Yasin , Berger Daniel , Koellensperger Gunda
Published: July 2022

Covering a wide spectrum of molecules is essential for global metabolome assessment. While metabolomics assays are most frequently carried out in microbore LC-MS analysis, reducing the size of the analytical platform has proven its ability to boost sensitivity for specific -omics applications. In this study, we elaborate the impact of LC miniaturization on exploratory small-molecule LC-MS analysis, focusing on chromatographic properties with critical impact on peak picking and statistical analysis. We have assessed a panel of small molecules comprising endogenous metabolites and environmental contaminants covering three flow regimes—analytical, micro-, and nano-flow. Miniaturization to the micro-flow regime yields moderately increased sensitivity as compared to the nano setup, where median sensitivity gains around 80-fold are observed in protein-precipitated blood plasma extract. This gain resulting in higher coverage at low µg/L concentrations is compound dependent. At the same time, the nano-LC-high-resolution mass spectrometry (HRMS) approach reduces the investigated chemical space as a consequence of the trap-and-elute nano-LC platform. Finally, while all three setups show excellent retention time stabilities, rapid gradients jeopardize the peak area repeatability of the nano-LC setup. Micro-LC offers the best compromise between improving signal intensity and metabolome coverage, despite the fact that only incremental gains can be achieved. Hence, we recommend using micro-LC for wide-target small-molecule trace bioanalysis and global metabolomics of abundant samples.
Integrative Conformational Ensembles of Sic1 Using Different Initial Pools and Optimization Methods
Authors: Gomes Gregory-Neal W. , Namini Ashley , Gradinaru Claudiu C.
Published: July 2022

Intrinsically disordered proteins play key roles in regulatory protein interactions, but their detailed structural characterization remains challenging. Here we calculate and compare conformational ensembles for the disordered protein Sic1 from yeast, starting from initial ensembles that were generated either by statistical sampling of the conformational landscape, or by molecular dynamics simulations. Two popular, yet contrasting optimization methods were used, ENSEMBLE and Bayesian Maximum Entropy, to achieve agreement with experimental data from nuclear magnetic resonance, small-angle X-ray scattering and single-molecule Förster resonance energy transfer. The comparative analysis of the optimized ensembles, including secondary structure propensity, inter-residue contact maps, and the distributions of hydrogen bond and pi interactions, revealed the importance of the physics-based generation of initial ensembles. The analysis also provides insights into designing new experiments that report on the least restrained features among the optimized ensembles. Overall, differences between ensembles optimized from different priors were greater than when using the same prior with different optimization methods. Generating increasingly accurate, reliable and experimentally validated ensembles for disordered proteins is an important step towards a mechanistic understanding of their biological function and involvement in various diseases.
Absence of Bacteria Permits Fungal Gut-To-Brain Translocation and Invasion in Germfree Mice but Ageing Alone Does Not Drive Pathobiont Expansion in Conventionally Raised Mice
Authors: Parker Aimée , James Steve A. , Purse Catherine , Brion Arlaine , Goldson Andrew , Telatin Andrea , Baker David , Carding Simon R.
Published: July 2022

Age-associated changes in the structure of the intestinal microbiome and in its interaction with the brain via the gut-brain axis are increasingly being implicated in neurological and neurodegenerative diseases. Intestinal microbial dysbiosis and translocation of microbes and microbial products including fungal species into the brain have been implicated in the development of dementias such as Alzheimer’s disease. Using germ-free mice, we investigated if the fungal gut commensal, Candida albicans, an opportunistic pathogen in humans, can traverse the gastrointestinal barrier and disseminate to brain tissue and whether ageing impacts on the gut mycobiome as a pre-disposing factor in fungal brain infection. C. albicans was detected in different regions of the brain of colonised germ-free mice in both yeast and hyphal cell forms, often in close association with activated (Iba-1+) microglial cells. Using high-throughput ITS1 amplicon sequencing to characterise the faecal gut fungal composition of aged and young SPF mice, we identified several putative gut commensal fungal species with pathobiont potential although their abundance was not significantly different between young and aged mice. Collectively, these results suggest that although some fungal species can travel from the gut to brain where they can induce an inflammatory response, ageing alone is not correlated with significant changes in gut mycobiota composition which could predispose to these events. These results are consistent with a scenario in which significant disruptions to the gut microbiota or intestinal barrier, beyond those which occur with natural ageing, are required to allow fungal escape and brain infection.
Impact of the Neck and/or Shoulder Pain on Self-reported Headache Treatment Responses – Results From a Pharmacy-Based Patient Survey
Authors: Gaul Charly , Gräter Heidemarie , Weiser Thomas , Michel Martin C. , Lampert Anette , Plomer Manuel , Förderreuther Stefanie
Published: July 2022

Neck and/or shoulder pain (NSP) frequently occurs together with headache. Therefore, we explored how patients with and without concomitant NSP differ in their baseline characteristics and in perceived treatment responses to an analgesic. An anonymous survey was performed among 895 patients with headache (735 self-reported tension-type headache [TTH]) who used an analgesic fixed-dose combination containing 400 mg ibuprofen and 100 mg caffeine as a non-prescription treatment. NSP was abundant among patients in our survey (60%) and was associated with >1 additional day of headache per month. Patients with NSP reported predominantly sedentary work more frequently than those without (40 vs. 29%); they also reported physical tension/poor posture as a perceived trigger factor more frequently (70 vs. 16%). The reported pain reduction was comparable in those with and without concomitant NSP regardless of whether assessed as mean pain rating (from about 6 to 1.5 on a 10-point rating scale), patients experiencing a ≥50% in pain reduction (89.6 vs. 88.8%) or becoming pain-free within 2 h (57 vs. 64%). However, recurrence of pain and use of another dose within the same day were more frequent with than without NSP. We conclude that concomitant NSP is frequent in patients with headache but does not substantially alter responses to a non-prescription medication.
Transcriptional Down-Regulation of Major Histocompatibility Complex as a Possible Pathogenesis for Meniere's Disease
Authors: Choi Kwang-Dong , Oh Eun Hye , Kim Hyun Sung , Kim Hyang-Sook , Park Ji-Yun , Choi Seo Young , Choi Jae-Hwan
Published: July 2022

Objectives

This study aimed to determine the underlying pathogenesis of Meniere's disease (MD) using transcriptome analysis.

Methods

Total RNA was extracted from the peripheral blood mononuclear cells of 39 patients with MD and 39 controls. Through microarray analysis for nine patients and controls, the differentially expressed genes (DEGs) of those two groups were screened based on cut-off criteria (|fold changes| > 2.0 and adjusted p-value < 0.05). The functional enrichment analysis of DEGs was performed using Gene Ontology (GO).

Results

There were 996 DEGs identified in the MD group: 415 were upregulated and 581 were downregulated. A functional enrichment analysis indicated that the downregulated DEGs were significantly enriched in terms related to immune system processes. Among them, 17 genes were enriched in terms for the major histocompatibility complex (MHC) protein complex, and the relative messenger RNA (mRNA) levels of three markedly downregulated DEGs [fold changes < −5: human leukocyte antigen (HLA)-DMA, HLA-DRB1, and HLA-DPB1] were significantly decreased in another 30 patients with MD compared with normal controls by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). However, there were no correlations between the expression levels of these three genes and clinical data, such as age, onset age, time course, or hearing threshold.

Conclusions

Our transcriptome analysis showed that the downregulated DEGs in MD were mainly associated with the immune system pathways including the MHC protein complex in MD. Remarkably, a breakdown in immunological tolerance mediated by MHC class II may contribute to the MD development, which has implications for targeted treatment.
Identifying Risk and Resilience Factors in the Intergenerational Cycle of Maltreatment: Results From the TRANS-GEN Study Investigating the Effects of Maternal Attachment and Social Support on Child Attachment and Cardiovascular Stress Physiology
Authors: Buchheim Anna , Ziegenhain Ute , Kindler Heinz , Waller Christiane , Gündel Harald , Karabatsiakis Alexander , Fegert Jörg
Published: July 2022

Introduction

Childhood maltreatment (CM) is a developmental risk factor and can negatively influence later psychological functioning, health, and development in the next generation. A comprehensive understanding of the biopsychosocial underpinnings of CM transmission would allow to identify protective factors that could disrupt the intergenerational CM risk cycle. This study examined the consequences of maternal CM and the effects of psychosocial and biological resilience factors on child attachment and stress-regulatory development using a prospective trans-disciplinary approach.

Methods

Mother-child dyads (N = 158) participated shortly after parturition (t0), after 3 months (t1), and 12 months later (t2). Mothers’ CM experiences were assessed at t0, attachment representation at t1 and psychosocial risk and social support were assessed at t1 and t2. At t2, dyads participated in the Strange Situation Procedure (SSP). Children’s attachmen status were classified as organized vs. disorganized, including their level of disorganized behavior, and heart rate (HR) and respiratory sinus arrhythmia (RSA) were recorded as stress response measures of the autonomic nervous system. Maternal caregiving during SSP was assessed using the AMBIANCE scale. Child’s single nucleotide polymorphisms rs2254298 within the oxytocin receptor (OXTR) and rs2740210 of the oxytocin gene (OXT) were genotyped using DNA isolated from cord blood.

Results

Maternal CM experiences (CM+) were significantly associated with an unresolved attachment status, higher perceived stress and more psychological symptoms. These negative effects of CM were attenuated by social support. As expected, maternal unresolved attachment and child disorganized attachment were significantly associated. Maternal caregiving did not mediate the relationship between maternal and child attachment but influenced children’s HR and RSA response and disorganized behavior. Moreover, the rs2254298 genotype of the OXTR gene moderated the stress response of children from mothers with CM. Children carrying the rs2740210 risk allele of the OXT gene showed more disorganized behavior independent from maternal CM experiences.

Conclusion

We replicated and extended existing CM and attachment models by co-examining maternal attachment, social support, and child genetic susceptibility on child attachment and cardiovascular stress regulation. The findings contribute to an extended understanding of risk and resilience factors and enable professionals to target adequate services to parents and children at risk.
A Disentangled Representation Based Brain Image Fusion via Group Lasso Penalty
Authors: Wang Anqi , Luo Xiaoqing , Zhang Zhancheng , Wu Xiao-Jun
Published: July 2022

Complementary and redundant relationships inherently exist between multi-modal medical images captured from the same brain. Fusion processes conducted on intermingled representations can cause information distortion and the loss of discriminative modality information. To fully exploit the interdependency between source images for better feature representation and improve the fusion accuracy, we present the multi-modal brain medical image fusion method in a disentangled pipeline under the deep learning framework. A three-branch auto-encoder with two complementary branches and a redundant branch is designed to extract the exclusive modality features and common structure features from input images. Especially, to promote the disentanglement of complement and redundancy, a complementary group lasso penalty is proposed to constrain the extracted feature maps. Then, based on the disentangled representations, different fusion strategies are adopted for complementary features and redundant features, respectively. The experiments demonstrate the superior performance of the proposed fusion method in terms of structure preservation, visual quality, and running efficiency.
EEG Evaluation of Stress Exposure on Healthcare Workers During COVID-19 Emergency: Not Just an Impression
Authors: LoMauro Antonella , Molisso Maria Takeko , Mameli Francesca , Ruggiero Fabiana , Ferrucci Roberta , Dellarosa Chiara , Aglieco Giada , Aliverti Andrea , Barbieri Sergio , Vergari Maurizio
Published: July 2022

Psychological distress among healthcare professionals, although already a common condition, was exacerbated by the COVID-19 pandemic. This effect has been generally self-reported or assessed through questionnaires. We aimed to identify potential abnormalities in the electrical activity of the brain of healthcare workers, operating in different roles during the pandemic. Cortical activity, cognitive performances, sleep, and burnout were evaluated two times in 20 COVID-19 frontline operators (FLCO, median age 29.5 years) and 20 operators who worked in COVID-19-free units (CFO, median 32 years): immediately after the outbreak of the pandemic (first session) and almost 6 months later (second session). FLCO showed higher theta relative power over the entire scalp (FLCO = 19.4%; CFO = 13.9%; p = 0.04) and lower peak alpha frequency of electrodes F7 (FLCO = 10.4 Hz; CFO = 10.87 Hz; p = 0.017) and F8 (FLCO = 10.47 Hz; CFO = 10.87 Hz; p = 0.017) in the first session. FLCO parietal interhemispheric coherence of theta (FLCO I = 0.607; FLCO II = 0.478; p = 0.025) and alpha (FLCO I = 0.578; FLCO II = 0.478; p = 0.007) rhythms decreased over time. FLCO also showed lower scores in the global cognitive assessment test (FLCO = 22.72 points; CFO = 25.56; p = 0.006) during the first session. The quantitative evaluation of the cortical activity might therefore reveal early signs of changes secondary to stress exposure in healthcare professionals, suggesting the implementation of measures to prevent serious social and professional consequences.
Head circumference as an epigenetic risk factor for maternal nutrition
Authors: Miele Maria J. , Souza Renato T. , Calderon Iracema M. , Feitosa Francisco E. , Leite Debora F. , Rocha Filho Edilberto A. , Vettorazzi Janete , Mayrink Jussara , Fernandes Karayna G. , Vieira Matias C. , Pacagnella Rodolfo C. , Cecatti Jose G. ,   Preterm SAMBA study group
Published: July 2022

Nutrition indicators for malnutrition can be screened by many signs such as stunting, underweight or obesity, muscle wasting, and low caloric and nutrients intake. Those deficiencies are also associated with low socioeconomic status. Anthropometry can assess nutritional status by maternal weight measurements during pregnancy. However, most studies have focused primarily on identifying changes in weight or Body Mass Index (BMI), and their effects on neonatal measures at present time. Whereas head circumference (HC) has been associated with nutrition in the past. When the mother was exposed to poor nutrition and unfavorable social conditions during fetal life, it was hypothesized that the intergenerational cycle was potentially mediated by epigenetic mechanisms. To investigate this theory, maternal head circumference (MHC) was associated with neonatal head circumference (NHC) in pregnant women without preexisting chronic conditions, differentiated by sociodemographic characteristics. A multiple linear regression model showed that each 1 cm-increase in MHC correlated with a 0.11 cm increase in NHC (β95% CI 0.07 to 0.15). Notwithstanding, associations between maternal and neonatal anthropometrics according to gestational age at birth have been extensively explained. Path analysis showed the influence of social status and the latent variable was socioeconomic status. A model of maternal height and head circumference was tested with effects on neonatal HC. The social variable lacked significance to predict neonatal HC in the total sample (p = 0.212) and in the South/Southeast (p = 0.095), in contrast to the Northeast (p = 0.047). This study highlights the potential intergenerational influence of maternal nutrition on HC, suggesting that maternal nutrition may be more relevant in families with major social vulnerability.
Interaction Analysis Based on Shapley Values and Extreme Gradient Boosting: A Realistic Simulation and Application to a Large Epidemiological Prospective Study
Authors: Orsini Nicola , Moore Alex , Wolk Alicja
Published: July 2022

Background

SHapley Additive exPlanations (SHAP) based on tree-based machine learning methods have been proposed to interpret interactions between exposures in observational studies, but their performance in realistic simulations is seldom evaluated.

Methods

Data from population-based cohorts in Sweden of 47,770 men and women with complete baseline information on diet and lifestyles were used to inform a realistic simulation in 3 scenarios of small (ORM = 0.75 vs. ORW = 0.70), moderate (ORM = 0.75 vs. ORW = 0.65), and large (ORM = 0.75 vs. ORW = 0.60) discrepancies in the adjusted mortality odds ratios conferred by a healthy diet among men and among women. Estimates were obtained with logistic regression (L-ORM; L-ORW) and derived from SHAP values (S-ORM; S-ORW).

Results

The sensitivities of detecting small, moderate, and large discrepancies were 28, 83, and 100%, respectively. The sensitivities of a positive sign (L-ORW > L-ORM) in the 3 scenarios were 93, 100, and 100%, respectively. Similarly, the sensitivities of a positive discrepancy based on SHAP values (S-ORW > S-ORM) were 86, 99, and 100%, respectively.

Conclusions

In a realistic simulation study, the ability of the SHAP values to detect an interaction effect was proportional to its magnitude. In contrast, the ability to identify the sign or direction of such interaction effect was very high in all the simulated scenarios.
Maternal exposure to genistein during pregnancy and oxidative DNA damage in testes of male mouse offspring
Authors: Godschalk Roger W. L. , Janssen Margit C. M. , Vanhees Kimberly , Doorn-Khosrovani Sahar Barjesteh van Waalwijk van , Schooten Frederik-Jan van
Published: July 2022

Background

Genistein is a dietary supplement with phyto-estrogenic properties. Therefore, high intake of genistein during pregnancy may have adverse effects on the genetic integrity of testes and germ cells of male offspring. In this study, we examined whether maternal exposure to genistein during pregnancy induced oxidative DNA damage in the male germline at adolescence.

Methods

Atm-ΔSRI mice have lower glucose-6-phosphate dehydrogenase (G6PDH) activity, which is important for maintaining levels of reduced glutathione and therefore these mice have an increased susceptibility to oxidative stress. Parental heterozygous Atm-ΔSRI mice received a genistein-rich or control diet, after which they were mated to obtain offspring. During pregnancy, mothers remained on the respective diets and after delivery all animals received control diets. Redox status and oxidative DNA damage were assessed in testes and sperm of 12 weeks old male offspring. Gene expression of Cyp1b1, Comt, and Nqo1 was assessed in testes, and DNA methylation as possible mechanism for transmission of effects to later life.

Results

Intake of genistein during pregnancy increased oxidative DNA damage in testes of offspring, especially in heterozygous Atm-ΔSRI mice. These increased DNA damage levels coincided with decreased expression of Comt and Nqo1. Heterozygous Atm-ΔSRI mice had higher levels of DNA strand breaks in sperm compared to wild type littermates, and DNA damage was further enhanced by a genistein-rich maternal diet. G6PDH activity was higher in mice with high maternal intake of genistein compared to control diets, suggesting compensation against oxidative stress. A positive correlation was observed between the levels of DNA methylation and oxidative DNA damage in testes.

Conclusion

These data indicate that prenatal exposure to genistein altered gene expression and increased DNA damage in testes and sperm of adolescent male offspring. These effects of genistein on DNA damage in later life coincided with alterations in DNA methylation.
Effects of Coix Seed Extract, Bifidobacterium BPL1, and Their Combination on the Glycolipid Metabolism in Obese Mice
Authors: Zhang Wei , Jia Xiuzhen , Xu Yuhan , Xie Qiaoling , Zhu Meizhen , Zhang Hesong , Zhao Zifu , Hao Jingyu , Li Haoqiu , Du Jinrui , Liu Yan , Liu Wei-Hsien , Ma Xia , Hung Weilian , Feng Haotian , Li Hongwei
Published: July 2022

Coix seed extract (CSE) and probiotics have been reported to regulate glycolipid metabolism via different modes of action. We tested the effects of CSE, Bifidobacterium BPL1, and their combination to determine their effects on glycolipid metabolism in obese mice. Male C57BL/6J mice were fed a high-fat diet for 8 weeks to establish an obesity model. Obese mice were selected and divided into four groups: the model control group and three intervention groups. After 10 weeks of continuous gavage intervention, the mice in the intervention groups exhibited lower body weight (lower about 2.31 g, vs. HFD mice 42.23 g) and epididymal (lower about 0.37 g, vs. HFD mice 2.5 g) and perirenal fat content (lower about 0.47 g, vs. HFD mice 0.884 g); decreased fasting blood glucose, total cholesterol, triglycerides, and VLDL; and increased HLDL, respiratory exchange ratio, energy expenditure, and amount of exercise performed. CSE, BPL1 and their combination can effectively control the weight gain in obese mice, reduce fat content, and regulate blood lipids and abnormal blood sugar. These results may be related to reduce the chronic inflammatory states, improve energy metabolism, exercise, relieve insulin sensitivity, and reduce lipid synthesis via the intervention of CSE, BPL1 and their combination. Compared with the single use of CSE alone, the combination of CSE + BPL1 can better exert the regulation function of intestinal flora, and change in the abundance of bacteria that could improve the level of inflammatory factors, such as increasing Bifidobacterium, reducing Lactococcus. Compared with the use of BPL1 alone, the combination of CSE and BPL1 can better regulate pancreatic islet and improve blood sugar. CSE may act directly on body tissues to exert anti-inflammatory effects. BPL1 and CSE + BPL1 may improve the structure and function of the intestinal flora, and reduce tissue inflammation.
Application of enzymes in the preparation of wheat germ polypeptides and their biological activities
Authors: Du Ke , Tian Shuangqi , Chen Hu , Gao Sensen , Dong Xianyou , Yan Feng
Published: July 2022

Wheat germ, a byproduct of wheat industrial processing, contains 30% protein and is a comprehensive source of plant-based protein. But a large amount of wheat germs are disposed of as waste every year. Wheat germ protein can be hydrolyzed into polypeptides with antioxidant, antihypertensive, anti-tumor, bacteriostatic and other activities. At present, researches on the hydrolysis of wheat germ protein and the preparation of bioactive peptides from wheat germ protein have attracted increasing attentions. However, the traditional protein hydrolysis method, protease hydrolysis, can no longer meet the market's needs for efficient production. Various auxiliary means, such as ultrasound, microwave and membrane separation, were applied to boost the yield and biological activity of wheat germ peptides by enzymatic hydrolysis. Under ultrasound and microwave, the protein structure may expand to increase the binding sites between enzyme and substrate and promote hydrolysis efficiency. Membrane separation is applied to separate products from enzymatic hydrolysate to reduce the inhibitory effect of the product on the hydrolysis reaction. The paper reviewed the hydrolysis methods of wheat germ protein and summarized the biological activity of wheat germ peptides to provide references for further study of wheat germ peptides.
The effect of urinary essential and non-essential elements on serum albumin: Evidence from a community-based study of the elderly in Beijing
Authors: Li Ang , Zhou Quan , Mei Yayuan , Zhao Jiaxin , Liu Liu , Zhao Meiduo , Xu Jing , Ge Xiaoyu , Xu Qun
Published: July 2022

Background & aims

Few epidemiological studies have investigated the relationships of urinary essential and non-essential elements with serum albumin, an indicator of nutritional status, especially for the elderly in China.

Methods

A community-based study among elderly participants (n = 275) was conducted in Beijing from November to December 2016. We measured 15 urinary elements concentrations and serum albumin levels. Three statistical methods including the generalized linear model (GLM), quantile g-computation model (qgcomp) and bayesian kernel machine regression (BKMR) were adapted.

Results

In GLM analysis, we observed decreased serum albumin levels associated with elevated urinary concentrations of aluminum, arsenic, barium, cobalt, chromium, copper, iron, manganese, selenium, strontium, and zinc. Compared with the lowest tertile, the highest tertile of cadmium and cesium was also negatively associated with serum albumin. Urinary selenium concentration had the most significant negative contribution (30.05%) in the qgcomp analysis. The negative correlations of element mixtures with serum albumin were also observed in BKMR analysis.

Conclusions

Our findings suggested the negative associations of essential and non-essential elements with serum albumin among the elderly. Large-scare cohort studies among the general population are required to validate our findings and elucidate the relevant underlying mechanisms.
The Predictive Value of Pretreatment Lactate Dehydrogenase and Derived Neutrophil-to-Lymphocyte Ratio in Advanced Non-Small Cell Lung Cancer Patients Treated With PD-1/PD-L1 Inhibitors: A Meta-Analysis
Authors: Zhang Qianning , Gong Xiaoling , Sun Lei , Miao Liyun , Zhou Yujie
Published: July 2022

Background

The Lung Immune Prognostic Index (LIPI) combines the lactate dehydrogenase (LDH) level and the derived neutrophil-to-lymphocyte ratio (dNLR). A lot of studies have shown that LDH and dNLR are associated with the prognosis of advanced non-small cell lung cancer (NSCLC) in patients treated with programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors. However, previous results were inconsistent, and the conclusions remain unclear. This meta-analysis aimed to investigate the predictive value of pretreatment LDH and dNLR for NSCLC progression in patients treated with PD-1/PD-L1 inhibitors.

Methods

PubMed, Embase, and the Cochrane Library were searched by two researchers independently for related literature before March 2020. Hazard ratios (HRs) with 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) were extracted to assess the predictive value of LDH and dNLR. STATA 15. 0 was used to perform the meta-analysis.

Results

A total of 3,429 patients from 26 studies were included in this meta-analysis. The results revealed that high pretreatment LDH was related to poor OS (HR = 1.19, 95%CI = 1.11–1.24, p < 0.001), but not closely related to poor PFS (HR = 1.02, 95%CI = 1.00–1.04, p = 0.023 < 0.05). The pooled results for dNLR suggested that high pretreatment dNLR was related to poor OS (HR = 1.55, 95%CI = 1.33–1.80, p < 0.001) and PFS (HR = 1.33, 95%CI = 1.16–1.54, p < 0.001).

Conclusion

Both pretreatment LDH and dNLR have the potential to serve as peripheral blood biomarkers for patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors. However, more studies on LDH are needed to evaluate its predictive value for PFS in patients with NSCLC.
Efficacy and Safety of Minimally Invasive Surgery Versus Open Laparotomy for Interval Debulking Surgery of Advanced Ovarian Cancer After Neoadjuvant Chemotherapy: A Systematic Review and A Meta-Analysis
Authors: Zeng Siyuan , Yu Yongai , Cui Yuemei , Liu Bing , Jin Xianyu , Li Zhengyan , Liu Lifeng
Published: July 2022

Objective

The selection of minimally invasive surgery (MIS) or open laparotomy for ovarian cancer (OC) after neoadjuvant chemotherapy still remains controversial. This study aimed to assess the efficacy and safety of MIS versus open laparotomy following neoadjuvant chemotherapy for advanced OC, so as to provide another option to select optimal surgical procedures for patients with OC.

Methods

Relevant literature studies about the risks of progression or mortality between women receiving MIS and open laparotomy for interval debulking surgery (IDS) were searched in the online databases, including PubMed, Embase, and the Cochrane Library with the following keywords: “ovarian neoplasms”, “minimally invasive surgical procedures”, “laparotomy”, and “neoadjuvant therapy”. Eligible studies were screened out for further meta-analysis.

Results

Six eligible literature studies, with 643 patients in the MIS group and 2,885 patients in the open laparotomy group, were included in this meta-analysis. No significant differences were detected in the overall survival (OS) of patients with OC who were treated with MIS or open laparotomy [hazard ratio (HR) = 0.85; 95% confidence interval (CI) = 0.59–1.23; heterogeneity: P = 0.051, I2 = 57.6%]. However, the progression-free survival (PFS) was significantly higher in patients with OC treated with MIS than those treated with laparotomy (HR = 0.73; 95% CI = 0.57 to 0.92; heterogeneity: P = 0.276, I2 = 22.4%). The completeness of debulking removal (R0 rate) in the open laparotomy group was not statistically higher compared with the control group (RR = 1.07; 95% CI = 0.93 to 1.23; heterogeneity: P = 0.098, I2 = 52.3%), and no significant differences in residual disease of ≤1 cm (R1) (RR = 1.08; 95% CI = 0.91 to 1.28; heterogeneity: P = 0.330, I2 = 12.6%) and postoperative complications were found between the two groups (RR = 0.72; 95% CI = 0.34 to 1.54; heterogeneity: P = 0.055, I2 = 60.6%). Furthermore, the length of stays in hospital was significantly shorter in patients with OC treated with MIS than those treated with open laparotomy (Standard Mean Difference (SMD) = −1.21; 95% CI = −1.78 to −0.64; heterogeneity: P < 0.001, I2 = 92.7%].

Conclusions

For IDS after NACT in patients with advanced OC, complete cytoreductive surgery with MIS is another feasible and effective choice

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022298519, identifier CRD42022298519
Predictors predisposing to orocutaneous fistula occurrence following free flap reconstruction
Authors: Li Wenlu , Wu Shuang , Yuan Junhui , Meng Fan , Xu Chunmiao , Li Hailiang
Published: July 2022

Objectives

To explore the possible risk factors of orocutaneous fistula (OCF) development in free flap reconstruction of the tongue/floor of the mouth (TFOM).

Methods

Data of patients who underwent free flap reconstruction of the TFOM were retrospectively analyzed. The association between clinicopathologic variables and OCF occurrence was analyzed using univariate and multivariate analyses.

Results

Altogether, 469 patients were enrolled. OCF occurred in 43 patients with a rate of 9.2%. The univariate analysis revealed the negative effects of smoking, preoperative albumin level, cachexia, T4 stage, neck dissection, entire resection of the floor of the mouth (FOM), segmental mandibulectomy, and surgical site infection on OCF occurrence. The multivariate analysis confirmed the independence of cachexia (p<0.001, 4.386[1.883–9.472]), tumor stage (p<0.001, 2.738[1.482–6.629]), entire FOM resection (p<0.001, 6.332[2.110–14.432]), and surgical site infection (p<0.001, 5.376[1.998–11.218]) in affecting the OCF development.

Conclusions

OCF development following free flap reconstruction of the TFOM was relatively uncommon, but significantly associated with presence of cachexia, T4 stage, entire FOM resection, and surgical site infection.
Development and Validation of a 6-Gene Hypoxia-Related Prognostic Signature For Cholangiocarcinoma
Authors: Sun Qi , Wang Huxia , Xiao Baoan , Xue Dong , Wang Guanghui
Published: July 2022

Cholangiocarcinoma (CHOL) is highly malignant and has a poor prognosis. This study is committed to creating a new prognostic model based on hypoxia related genes. Here, we established a novel tumor hypoxia-related prognostic model consisting of 6 hypoxia-related genes by univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) algorithm to predict CHOL prognosis and then the risk score for each patient was calculated. The results showed that the patients with high-risk scores had poor prognosis compared with those with low-risk scores, which was verified as an independent predictor by multivariate analysis. The hypoxia-related prognostic model was validated in both TCGA and GEO cohorts and exhibited excellent performance in predicting overall survival in CHOL. The PPI results suggested that hypoxia-related genes involved in the model may play a central role in regulating the hypoxic state. In addition, the presence of IDH1 mutations in the high-risk group was high, and GSEA results showed that some metabolic pathways were upregulated, but immune response processes were generally downregulated. These factors may be potential reasons for the high-risk group with worse prognosis. The analysis of different immune regulation-related processes in the high- and low-risk groups revealed that the expression of genes related to immune checkpoints would show differences between these two groups. We further verified the expression of the oncogene PPFIA4 in the model, and found that compared with normal samples, CHOL patients were generally highly expressed, and the patients with high-expression of PPFIA4 had a poor prognosis. In summary, the present study may provide a valid prognostic model for bile duct cancer to inform better clinical management of patients.
Genetic Testing and Its Clinical Application in Prostate Cancer Management: Consensus Statements from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology
Authors: Chiu Peter K. F. , Lee Eric K. C. , Chan Marco T. Y. , Chan Wilson H. C. , Cheung M. H. , Lam Martin H. C. , Ma Edmond S. K. , Poon Darren M. C.
Published: July 2022

Background

In recent years, indications for genetic testing in prostate cancer (PC) have expanded from patients with a family history of prostate and/or related cancers to those with advanced castration-resistant disease, and even to early PC patients for determination of the appropriateness of active surveillance. The current consensus aims to provide guidance to urologists, oncologists and pathologists working with Asian PC patients on who and what to test for in selected populations.

Methods

A joint consensus panel from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology was convened over a series of 5 physical and virtual meetings. A background literature search on genetic testing in PC was performed in PubMed, ClinicalKey, EBSCOHost, Ovid and ProQuest, and three working subgroups were formed to review and present the relevant evidence. Meeting agendas adopted a modified Delphi approach to ensure that discussions proceed in a structured, iterative and balanced manner, which was followed by an anonymous voting on candidate statements. Of 5 available answer options, a consensus statement was accepted if ≥ 75% of the panelists chose “Accept Completely” (Option A) or “Accept with Some Reservation” (Option B).

Results

The consensus was structured into three parts: indications for testing, testing methods, and therapeutic implications. A list of 35 candidate statements were developed, of which 31 were accepted. The statements addressed questions on the application of PC genetic testing data and guidelines to Asian patients, including patient selection for germline testing, selection of gene panel and tissue sample, provision of genetic counseling, and use of novel systemic treatments in metastatic castration-resistant PC patients.

Conclusion

This consensus provides guidance to urologists, oncologists and pathologists working with Asian patients on indications for genetic testing, testing methods and technical considerations, and associated therapeutic implications.
Neonatal stunting and early childhood caries: A mini-review
Authors: Setiawan Arlette Suzy , Indriyanti Ratna , Suryanti Netty , Rahayuwati Laili , Juniarti Neti
Published: July 2022

The nutritional status of pregnant women greatly determines their newborn outcome. Deficiencies of several micronutrients are associated with stunting in early childhood, affecting health into adulthood. However, apart from the systemic disease that has been a concern so far, fetal undernutrition can also be associated with dental caries in a child's early life, especially since the primary teeth begin to form during the mother's gestation period. The important thing to underline regarding the intrauterine formation of primary teeth is especially in terms of enamel formation. One of the causes of developmental enamel defects that will contribute to the emergence of early childhood caries is the malnutrition of the pregnant mother. This mini-review aims to understand the linkage mechanism behind neonatal stunting to early childhood caries. This concept is expected to generate further research to help prevent both growth stunting and early childhood caries. In addition, with some evidence-based research, the importance of the first dental visit can be further promoted.