bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma, urine, and stool metabolites in response to dietary rice bran and navy bean supplementation in adults at high-risk for colorectal cancer
Authors: Hill Emily B. , Baxter Bridget A. , Pfluger Brigitte , Slaughter Caroline K. , Beale Melanie , Smith Hillary V. , Stromberg Sophia S. , Tipton Madison , Ibrahim Hend , Rao Sangeeta , Leach Heather , Ryan Elizabeth P.
Published: February 2023

Introduction

Dietary intake of whole grains and legumes and adequate physical activity (PA) have been associated with reduced colorectal cancer (CRC) risk. A single-blinded, two-arm, randomized, placebo-controlled pilot trial was implemented to evaluate the impact of a 12-week dietary intervention of rice bran + navy bean supplementation and PA education on metabolite profiles and the gut microbiome among individuals at high risk of CRC.

Methods

Adults (n=20) were randomized 1:1 to dietary intervention or control. All participants received PA education at baseline. Sixteen study foods were prepared with either heat-stabilized rice bran + navy bean powder or Fibersol®-2 as a placebo. Intervention participants consumed 30 g rice bran + 30 g navy bean powder daily; those in the control group consumed 10 g placebo daily. Non-targeted metabolite profiling was performed by UPLC-MS/MS to evaluate plasma, urine, and stool at 0, 6, and 12 weeks. Stool was also analyzed for primary and secondary bile acids (BAs) and short chain fatty acids (SCFAs) by UPLC-MS/MS and microbial community structure via 16S amplicon sequencing. Two-way ANOVA was used to compare differences between groups for metabolites, and mixed models were used to compare differences between groups for BAs, SCFAs, and alpha and beta diversity measures of microbial community structure.

Results

Across biological matrices, the intervention resulted in changes to several amino acid and lipid metabolites, compared to control. There was a 2.33-fold difference in plasma (p<0.001) and a 3.33-fold difference in urine (p=0.008) for the amino acid S-methylcysteine at 12 weeks. Fold-differences to 4-methoxyphenol sulfate in plasma and urine after 6 and 12 weeks (p<0.001) was a novel result from this combined rice bran and navy bean intervention in people. A 2.98-fold difference in plasma (p=0.002) and a 17.74-fold difference in stool (p=0.026) was observed for the lipid octadecenedioylcarnitine at 12 weeks. For stool BAs, 3-oxocholic acid was increased at 12 weeks compared to control within a subset of individuals (mean difference 16.2 ug/uL, p=0.022). No significant differences were observed between groups for stool SCFAs or microbial community structure.

Discussion

Dietary intake of rice bran + navy beans demonstrates beneficial modulation of host and gut microbial metabolism and represents a practical and affordable means of increasing adherence to national guidelines for CRC control and prevention in a high-risk population.
Case report: Unusual development of hepatocellular carcinoma during immunosuppressive treatments against rheumatoid arthritis overlapping Sjögren’s syndrome; cirrhotic steatohepatitis with liver inflammation and fibrosis lurks in autoimmune disorders
Authors: Yoshida Shuhei , Fujita Masashi , Ishigame Teruhide , Kobayashi Yasuyuki , Sumichika Yuya , Saito Kenji , Matsumoto Haruki , Temmoku Jumpei , Fujita Yuya , Matsuoka Naoki , Asano Tomoyuki , Sato Shuzo , Watanabe Hiroshi , Yoshida Hiroshi , Marubashi Shigeru , Hashimoto Yuko , Ohira Hiromasa , Migita Kiyoshi
Published: February 2023

The sequential progression from chronic liver disease to cirrhosis may be a risk factor for hepatocellular carcinoma (HCC) development. Although HCC originates from hepatitis B virus- or hepatitis C virus-associated liver cirrhosis, it has recently been reported in patients with non-alcoholic steatohepatitis (NASH) with advanced fibrosis. However, little is known about the pathophysiological mechanisms linking HCC to rheumatic disorders, including rheumatoid arthritis (RA). Herein, we describe the case of HCC with NASH complicated by RA and Sjögren’s syndrome (SS). A fifty-two-year-old patient with RA and diabetes was referred to our hospital for further examination of a liver tumor. She received methotrexate (4 mg/week) for 3 years and adalimumab (40 mg/biweekly) for 2 years. On admission, laboratory data showed mild thrombocytopenia and hypoalbuminemia, with normal hepatitis virus markers or liver enzymes. Anti-nuclear antibodies were positive with high titers (x640), and anti-SS-A/Ro (187.0 U/ml; normal range [NR]: ≤6.9 U/mL) and anti-SS-B/La (320 U/ml; NR: ≤6.9 U/mL) antibodies were also high. Abdominal ultrasonography and computed tomography revealed liver cirrhosis and a tumor in the left lobe (S4) of the liver. She was diagnosed with HCC based on imaging findings, and elevated levels of protein induced by vitamin K absence- II (PIVKA-II) were detected. She underwent laparoscopic partial hepatectomy, and histopathological examination revealed steatohepatitis HCC with background liver cirrhosis. The patient was discharged on the 8th day post-operation without any complications. At the 30 months follow-up, no significant evidence of recurrence was observed. Our case suggests that clinical screening for HCC is needed in patients with RA who are at a high risk of NASH, as they may progress to HCC even without elevated liver enzymes.
Toll-like receptors 7 and 9 regulate the proliferation and differentiation of B cells in systemic lupus erythematosus
Authors: Wen Luyao , Zhang Bei , Wu Xinfeng , Liu Rongzeng , Fan Hua , Han Lei , Zhang Zhibo , Ma Xin , Chu Cong-Qiu , Shi Xiaofei
Published: February 2023

Systemic lupus erythematosus (SLE) is an autoimmune illness marked by the loss of immune tolerance and the production of autoantibodies against nucleic acids and other nuclear antigens (Ags). B lymphocytes are important in the immunopathogenesis of SLE. Multiple receptors control abnormal B-cell activation in SLE patients, including intrinsic Toll-like receptors (TLRs), B-cell receptors (BCRs), and cytokine receptors. The role of TLRs, notably TLR7 and TLR9, in the pathophysiology of SLE has been extensively explored in recent years. When endogenous or exogenous nucleic acid ligands are recognized by BCRs and internalized into B cells, they bind TLR7 or TLR9 to activate related signalling pathways and thus govern the proliferation and differentiation of B cells. Surprisingly, TLR7 and TLR9 appear to play opposing roles in SLE B cells, and the interaction between them is still poorly understood. In addition, other cells can enhance TLR signalling in B cells of SLE patients by releasing cytokines that accelerate the differentiation of B cells into plasma cells. Therefore, the delineation of how TLR7 and TLR9 regulate the abnormal activation of B cells in SLE may aid the understanding of the mechanisms of SLE and provide directions for TLR-targeted therapies for SLE.
Immune-related risk score: An immune-cell-pair-based prognostic model for cutaneous melanoma
Authors: Li Mingjia , Long Xinrui , Bu Wenbo , Zhang Guanxiong , Deng Guangtong , Liu Yuancheng , Su Juan , Huang Kai
Published: February 2023

Background

Melanoma is among the most malignant immunologic tumor types and is associated with high mortality. However, a considerable number of melanoma patients cannot benefit from immunotherapy owing to individual differences. This study attempts to build a novel prediction model of melanoma that fully considers individual differences in the tumor microenvironment.

Methods

An immune-related risk score (IRRS) was constructed based on cutaneous melanoma data from The Cancer Genome Atlas (TCGA). Single-sample gene set enrichment analysis (ssGSEA) was used to calculate immune enrichment scores of 28 immune cell signatures. We performed pairwise comparisons to obtain scores for cell pairs based on the difference in the abundance of immune cells within each sample. The resulting cell pair scores, in the form of a matrix of relative values of immune cells, formed the core of the IRRS.

Results

The area under the curve (AUC) for the IRRS was over 0.700, and when the IRRS was combined with clinical information, the AUC reached 0.785, 0.817, and 0.801 for the 1-, 3-, and 5-year survival, respectively. Differentially expressed genes between the two groups were enriched in staphylococcal infection and estrogen metabolism pathway. The low IRRS group showed a better immunotherapeutic response and exhibited more neoantigens, richer T-cell receptor and B-cell receptor diversity, and higher tumor mutation burden.

Conclusion

The IRRS enables a good prediction of prognosis and immunotherapy effect, based on the difference in the relative abundance of different types of infiltrating immune cells, and could provide support for further research in melanoma.
Repeatability of metabolic tumor burden and lesion glycolysis between clinical readers
Authors: Choi Jung W. , Dean Erin A. , Lu Hong , Thompson Zachary , Qi Jin , Krivenko Gabe , Jain Michael D. , Locke Frederick L. , Balagurunathan Yoganand
Published: February 2023

The Metabolic Tumor Volume (MTV) and Tumor Lesion Glycolysis (TLG) has been shown to be independent prognostic predictors for clinical outcome in Diffuse Large B-cell Lymphoma (DLBCL). However, definitions of these measurements have not been standardized, leading to many sources of variation, operator evaluation continues to be one major source. In this study, we propose a reader reproducibility study to evaluate computation of TMV (& TLG) metrics based on differences in lesion delineation. In the first approach, reader manually corrected regional boundaries after automated detection performed across the lesions in a body scan (Reader M using a manual process, or manual). The other reader used a semi-automated method of lesion identification, without any boundary modification (Reader A using a semi- automated process, or auto). Parameters for active lesion were kept the same, derived from standard uptake values (SUVs) over a 41% threshold. We systematically contrasted MTV & TLG differences between expert readers (Reader M & A). We find that MTVs computed by Readers M and A were both concordant between them (concordant correlation coefficient of 0.96) and independently prognostic with a P-value of 0.0001 and 0.0002 respectively for overall survival after treatment. Additionally, we find TLG for these reader approaches showed concordance (CCC of 0.96) and was prognostic for over -all survival (p ≤ 0.0001 for both). In conclusion, the semi-automated approach (Reader A) provides acceptable quantification & prognosis of tumor burden (MTV) and TLG in comparison to expert reader assisted measurement (Reader M) on PET/CT scans.
Standard ecological and molecular research methods and techniques for Labyrinthula spp.
Authors: Sullivan Brooke K. , Martin Daniel L. , Yoshioka Reyn M. , Brakel Janina , Jakobsson-Thor Stina , Eisenlord Morgan , Trevathan-Tackett Stacey M.
Published: February 2023

Labyrinthula are unicellular protists occupying diverse spatial and functional niches, including various roles in host and ecological function, fatty acid production, pandemic marine disease and saprobic decomposition. Labyrinthula species span tropical and temperate climates and have been isolated from each marine coastal ecosystem tested. Our understanding of primary cellular and molecular functions of Labyrinthula has substantially progressed through a combination of increased global investments, research interest and technological advances. Recent advances in molecular techniques provide a toolkit for advancing ecological questions in marine infectious disease in seagrass meadows around the world. Here we provide a comprehensive review of relevant ecological and molecular techniques used in long-term research and the progression of Labyrinthula scholarship. Our aims in preparing this review are to: 1) share, compare and advance global Labyrinthula protocols, 2) increase accessibility to robust methodology to encourage the uptake of Labyrinthula-based questions into marine studies of molecular and ecological qualities of Labyrinthula and 3) encourage uptake of robust Labyrinthula-based questions into coastal marine studies, while also encouraging international collaborative networks across multiple fields. Lastly, we discuss gaps in the over 100 years of Labyrinthula research and opportunities for expanding research on this model marine organism.
Present and future perspectives in early diagnosis and monitoring for progressive fibrosing interstitial lung diseases
Authors: Stanel Stefan Cristian , Rivera-Ortega Pilar
Published: February 2023

Progressive fibrosing interstitial lung diseases (PF-ILDs) represent a group of conditions of both known and unknown origin which continue to worsen despite standard treatments, leading to respiratory failure and early mortality. Given the potential to slow down progression by initiating antifibrotic therapies where appropriate, there is ample opportunity to implement innovative strategies for early diagnosis and monitoring with the goal of improving clinical outcomes. Early diagnosis can be facilitated by standardizing ILD multidisciplinary team (MDT) discussions, implementing machine learning algorithms for chest computed-tomography quantitative analysis and novel magnetic-resonance imaging techniques, as well as measuring blood biomarker signatures and genetic testing for telomere length and identification of deleterious mutations in telomere-related genes and other single-nucleotide polymorphisms (SNPs) linked to pulmonary fibrosis such as rs35705950 in the MUC5B promoter region. Assessing disease progression in the post COVID-19 era also led to a number of advances in home monitoring using digitally-enabled home spirometers, pulse oximeters and other wearable devices. While validation for many of these innovations is still in progress, significant changes to current clinical practice for PF-ILDs can be expected in the near future.
Association between perioperative plasma transfusion and in-hospital mortality in patients undergoing surgeries without massive transfusion: A nationwide retrospective cohort study
Authors: Xu Xiaohan , Zhang Yuelun , Tang Bo , Yu Xuerong , Huang Yuguang
Published: February 2023

Background

An aggressive plasma transfusion is associated with a decreased mortality in traumatic patients requiring massive transfusion (MT). However, it is controversial whether non-traumatic or non-massively transfused patients can benefit from high doses of plasma.

Methods

We performed a nationwide retrospective cohort study using data from Hospital Quality Monitoring System, which collected anonymized inpatient medical records from 31 provinces in mainland China. We included the patients who had at least one record of surgical procedure and received red blood cell transfusion on the day of surgery from 2016 to 2018. We excluded those receiving MT or diagnosed with coagulopathy at admission. The exposure variable was the total volume of fresh frozen plasma (FFP) transfused, and the primary outcome was in-hospital mortality. The relationship between them was assessed using multivariable logistic regression model adjusting 15 potential confounders.

Results

A total of 69319 patients were included, and 808 died among them. A 100-ml increase in FFP transfusion volume was associated with a higher in-hospital mortality (odds ratio 1.05, 95% confidence interval 1.04–1.06,p< 0.001) after controlling for the confounders. FFP transfusion volume was also associated with superficial surgical site infection, nosocomial infection, prolonged length of hospital stay, ventilation time, and acute respiratory distress syndrome. The significant association between FFP transfusion volume and in-hospital mortality was extended to the subgroups of cardiac surgery, vascular surgery, and thoracic or abdominal surgery.

Conclusions

A higher volume of perioperative FFP transfusion was associated with an increased in-hospital mortality and inferior postoperative outcomes in surgical patients without MT.
Fluorescence molecular optomic signatures improve identification of tumors in head and neck specimens
Authors: Chen Yao , Streeter Samuel S. , Hunt Brady , Sardar Hira S. , Gunn Jason R. , Tafe Laura J. , Paydarfar Joseph A. , Pogue Brian W. , Paulsen Keith D. , Samkoe Kimberley S.
Published: February 2023

Background

Fluorescence molecular imaging using ABY-029, an epidermal growth factor receptor (EGFR)-targeted, synthetic Affibody peptide labeled with a near-infrared fluorophore, is under investigation for surgical guidance during head and neck squamous cell carcinoma (HNSCC) resection. However, tumor-to-normal tissue contrast is confounded by intrinsic physiological limitations of heterogeneous EGFR expression and non-specific agent uptake.

Objective

In this preliminary study, radiomic analysis was applied to optical ABY-029 fluorescence image data for HNSCC tissue classification through an approach termed “optomics.” Optomics was employed to improve tumor identification by leveraging textural pattern differences in EGFR expression conveyed by fluorescence. The study objective was to compare the performance of conventional fluorescence intensity thresholding and optomics for binary classification of malignant vs. non-malignant HNSCC tissues.

Materials and Methods

Fluorescence image data collected through a Phase 0 clinical trial of ABY-029 involved a total of 20,073 sub-image patches (size of 1.8 × 1.8 mm2) extracted from 24 bread-loafed slices of HNSCC surgical resections originating from 12 patients who were stratified into three dose groups (30, 90, and 171 nanomoles). Each dose group was randomly partitioned on the specimen-level 75%/25% into training/testing sets, then all training and testing sets were aggregated. A total of 1,472 standardized radiomic features were extracted from each patch and evaluated by minimum redundancy maximum relevance feature selection, and 25 top-ranked features were used to train a support vector machine (SVM) classifier. Predictive performance of the SVM classifier was compared to fluorescence intensity thresholding for classifying testing set image patches with histologically confirmed malignancy status.

Results

Optomics provided consistent improvement in prediction accuracy and false positive rate (FPR) and similar false negative rate (FNR) on all testing set slices, irrespective of dose, compared to fluorescence intensity thresholding (mean accuracies of 89% vs. 81%, P = 0.0072; mean FPRs of 12% vs. 21%, P = 0.0035; and mean FNRs of 13% vs. 17%, P = 0.35).

Conclusions

Optomics outperformed conventional fluorescence intensity thresholding for tumor identification using sub-image patches as the unit of analysis. Optomics mitigate diagnostic uncertainties introduced through physiological variability, imaging agent dose, and inter-specimen biases of fluorescence molecular imaging by probing textural image information. This preliminary study provides a proof-of-concept that applying radiomics to fluorescence molecular imaging data offers a promising image analysis technique for cancer detection in fluorescence-guided surgery.
Shifts in intestinal microbiota and improvement of sheep immune response to resist Salmonella infection using Toll-like receptor 4 (TLR4) overexpression
Authors: Xu Xue-Ling , Zhao Yue , Chen Ming-Ming , Li Yan , Li Yao , Wu Su-Jun , Zhang Jin-Long , Zhang Xiao-Sheng , Yu Kun , Lian Zheng-Xing
Published: February 2023

Introduction

Toll-like receptor 4 (TLR4) identifies Gram-negative bacteria or their products and plays a crucial role in host defense against invading pathogens. In the intestine, TLR4 recognizes bacterial ligands and interacts with the immune system. Although TLR4 signaling is a vital component of the innate immune system, the influence of TLR4 overexpression on innate immune response and its impact on the composition of the intestinal microbiota is unknown.

Methods

Here, we obtained macrophages from sheep peripheral blood to examine phagocytosis and clearance of Salmonella Typhimurium (S. Typhimurium) in macrophages. Meanwhile, we characterized the complex microbiota inhabiting the stools of TLR4 transgenic (TG) sheep and wild-type (WT) sheep using 16S ribosomal RNA (rRNA) deep sequencing.

Results

The results showed that TLR4 overexpression promoted the secretion of more early cytokines by activating downstream signaling pathways after stimulation by S. Typhimurium. Furthermore, diversity analysis demonstrated TLR4 overexpression increased microbial community diversity and regulated the composition of intestinal microbiota. More importantly, TLR4 overexpression adjusted the gut microbiota composition and maintained intestinal health by reducing the ratio of Firmicutes/Bacteroidetes and inflammation and oxidative stress-producing bacteria (Ruminococcaceae, Christensenellaceae) and upregulating the abundance of Bacteroidetes population and short-chain fatty acid (SCFA)-producing bacteria, including Prevotellaceae. These dominant bacterial genera changed by TLR4 overexpression revealed a close correlation with the metabolic pathways of TG sheep.

Discussion

Taken together, our findings suggested that TLR4 overexpression can counteract S. Typhimurium invasion as well as resist intestinal inflammation in sheep by regulating intestinal microbiota composition and enhancing anti-inflammatory metabolites.
The role of the cerebellum in sequencing and predicting social and non-social events in patients with bipolar disorder
Authors: Siciliano Libera , Olivito Giusy , Lupo Michela , Urbini Nicole , Gragnani Andrea , Saettoni Marco , Delle Chiaie Roberto , Leggio Maria
Published: February 2023

Introduction

Advances in the operational mode of the cerebellum indicate a role in sequencing and predicting non-social and social events, crucial for individuals to optimize high-order functions, such as Theory of Mind (ToM). ToM deficits have been described in patients with remitted bipolar disorders (BD). The literature on BD patients’ pathophysiology reports cerebellar alterations; however, sequential abilities have never been investigated and no study has previously focused on prediction abilities, which are needed to properly interpret events and to adapt to changes.

Methods

To address this gap, we compared the performance of BD patients in the euthymic phase with healthy controls using two tests that require predictive processing: a ToM test that require implicit sequential processing and a test that explicitly assesses sequential abilities in non-ToM functions. Additionally, patterns of cerebellar gray matter (GM) alterations were compared between BD patients and controls using voxel-based morphometry.

Results

Impaired ToM and sequential skills were detected in BD patients, specifically when tasks required a greater predictive load. Behavioral performances might be consistent with patterns of GM reduction in cerebellar lobules Crus I-II, which are involved in advanced human functions.

Discussion

These results highlight the importance of deepening the cerebellar role in sequential and prediction abilities in patients with BD.
Healthy lifestyles and wellbeing reduce neuroinflammation and prevent neurodegenerative and psychiatric disorders
Authors: Kip Elodie , Parr-Brownlie Louise C.
Published: February 2023

Since the mid-20th century, Western societies have considered productivity and economic outcomes are more important than focusing on people’s health and wellbeing. This focus has created lifestyles with high stress levels, associated with overconsumption of unhealthy foods and little exercise, which negatively affect people’s lives, and subsequently lead to the development of pathologies, including neurodegenerative and psychiatric disorders. Prioritizing a healthy lifestyle to maintain wellbeing may slow the onset or reduce the severity of pathologies. It is a win-win for everyone; for societies and for individuals. A balanced lifestyle is increasingly being adopted globally, with many doctors encouraging meditation and prescribing non-pharmaceutical interventions to treat depression. In psychiatric and neurodegenerative disorders, the inflammatory response system of the brain (neuroinflammation) is activated. Many risks factors are now known to be linked to neuroinflammation such as stress, pollution, and a high saturated and trans fat diet. On the other hand, many studies have linked healthy habits and anti-inflammatory products with lower levels of neuroinflammation and a reduced risk of neurodegenerative and psychiatric disorders. Sharing risk and protective factors is critical so that individuals can make informed choices that promote positive aging throughout their lifespan. Most strategies to manage neurodegenerative diseases are palliative because neurodegeneration has been progressing silently for decades before symptoms appear. Here, we focus on preventing neurodegenerative diseases by adopting an integrated “healthy” lifestyle approach. This review summarizes the role of neuroinflammation on risk and protective factors of neurodegenerative and psychiatric disorders.
Isotopic composition of serum zinc and copper in healthy children and children with autism spectrum disorder in North America
Authors: Miller Kerri , Day Patrick L. , Behl Supriya , Stromback Lindsay , Delgado Adriana , Jannetto Paul J. , Wieser Michael E. , Mehta Sunil Q. , Pandey Mukesh K.
Published: February 2023

To better understand zinc and copper regulation and their involvement in various biochemical pathways as it relates to autism spectrum disorder (ASD), isotopic composition of serum zinc and copper were evaluated in both healthy children and children with ASD in North America. No significant difference in isotopic composition of serum zinc or copper with respect to healthy controls and ASD children were identified. However, the isotopic composition of serum copper in boys was found to be enriched in 65Cu in comparison to previously published healthy adult copper isotopic composition. Furthermore, in both boys and girls, the average isotopic composition of serum zinc is heavier than previously published healthy adult isotopic zinc composition. There was also a negative association between total zinc concentrations in serum and the zinc isotopic composition of serum in boys. Finally, children with heavier isotopic composition of copper also showed a high degree of variability in their zinc isotopic composition. While numerous studies have measured the isotopic composition of serum zinc and copper in adults, this is one of the first studies which measured the isotopic composition of serum copper and zinc in children, specifically those diagnosed with ASD. The results of this study showed that age and gender specific normal ranges of isotopic composition must be established to effectively use isotopic composition analysis in studying various diseases including ASD.
Biotransformation of gluten-free composite flour mediated by probiotics via solid-state fermentation process conducted under different moisture contents
Authors: Koyum Kareem Adebayo , Foo Hooi Ling , Ramli Norhayati , Loh Teck Chwen
Published: February 2023

Staple foods produced from composite flour are considered feasible to alleviate protein-energy malnutrition (PEM). However, one of the major limitations of composite flour is poor protein digestibility. The biotransformation process mediated by probioticsviasolid-state fermentation (SSF) holds a promising potential to address the poor protein digestibility in composite flour. Yet, there is no report established in this regard to the best of our knowledge. Therefore, 4 strains ofLactiplantibacillus plantarumandPediococcus pentosaceusUP2 isolated from Malaysian foods that were previously reported to produce versatile extracellular hydrolytic enzymes were employed to biotransform gluten-free composite flour derived from rice, sorghum, and soybean. The SSF process was performed under 30–60% (v/w) moisture content for 7 days, where samples were withdrawn at 24 h intervals for various analyses such as pH, total titratable acidity (TTA), extracellular protease activity, soluble protein concentration, crude protein content, andin vitroprotein digestibility. The pH of the biotransformed composite flour showed a significant reduction from the initial range of pH 5.98–6.67 to the final pH of 4.36–3.65, corresponding to the increase in the percentage of TTA in the range of 0.28–0.47% to 1.07–1.65% from days 0 to 4 and remained stable till day 7 of the SSF process. The probiotics strains exhibited high extracellular proteolytic activity (0.63–1.35 U/mg to 4.21–5.13 U/mg) from days 0 to 7. In addition, the treated composite flour soluble protein increased significantly (p≤ 0.05) (0.58–0.60 mg/mL to 0.72–0.79 mg/mL) from days 0 to 7, crude protein content (12.00–12.18% to 13.04–14.39%) and protein digestibility (70.05–70.72% to 78.46–79.95%) from days 0 to 4 of SSF. The results of biotransformation of 50% (v/w) moisture content were mostly comparable to 60% (v/w) moisture content, implying 50% (v/w) moisture content was the most suitable moisture content for the effective biotransformation of gluten-free composite flour mediated by probioticsviaSSF since flour quality is better at lower moisture content. As for the overall performance,L. plantarumRS5 was ranked the best strain, attributed to the general improvement in the physicochemical properties of composite flour.
Application of nanomedicine in radiotherapy sensitization
Authors: Song Xiaoyu , Sun Zhenkun , Li Li , Zhou Lu , Yuan Shuanghu
Published: February 2023

Radiation therapy is an important component of cancer treatment. As research in radiotherapy techniques advances, new methods to enhance tumor response to radiation need to be on the agenda to enable enhanced radiation therapy at low radiation doses. With the rapid development of nanotechnology and nanomedicine, the use of nanomaterials as radiosensitizers to enhance radiation response and overcome radiation resistance has attracted great interest. The rapid development and application of emerging nanomaterials in the biomedical field offers good opportunities to improve the efficacy of radiotherapy, which helps to promote the development of radiation therapy and will be applied in clinical practice in the near future. In this paper, we discuss the main types of nano-radiosensitizers and explore their sensitization mechanisms at the tissue level, cellular level and even molecular biology and genetic level, and analyze the current status of promising nano-radiosensitizers and provide an outlook on their future development and applications.
The relationship between single nucleotide polymorphisms and skin cancer susceptibility: A systematic review and network meta-analysis
Authors: Zhang Lu , Pozsgai Éva , Song Yongan , Macharia John , Alfatafta Huda , Zheng Jia , Li Zhaoyi , Liu Hongbo , Kiss István
Published: February 2023

Background

Single nucleotide polymorphisms (SNPs) interfere with the function of certain genes and thus may influence the probability of skin cancer. The correlation between SNPs and skin cancer (SC) lacks statistical power, however. Therefore, the purpose of this study was to identify the gene polymorphisms involved in skin cancer susceptibility using network meta-analysis and to determine the relationship between SNPs and SC risk.

Methods

PubMed, Embase, and Web of Science were searched for articles including “SNP” and different types of SC as keywords between January 2005 and May 2022. The Newcastle-Ottawa Scale was used to assess bias judgments. The odds ratio (ORs) and their 95% confidence intervals (CIs) were determined to estimate heterogeneity within and between studies. Meta-analysis and network meta-analysis were carried out to identify the SNPs associated with SC. The P-score of each SNP was compared to obtain the rank of probability. Subgroup analyses were performed by cancer type.

Results

A total of 275 SNPs from 59 studies were included in the study. Two subgroup SNP networks using the allele model and dominant model were analyzed. The alternative alleles of rs2228570 (FokI) and rs13181 (ERCC2) were the first-ranking SNPs in both subgroups one and two of the allele model, respectively. The homozygous dominant genotype and heterozygous genotype of rs475007 in subgroup one and the homozygous recessive genotype of rs238406 in subgroup two were most likely to be associated with skin cancer based on the dominant model.

Conclusions

According to the allele model, SNPs FokI rs2228570 and ERCC2 rs13181 and, according to the dominant model, SNPs MMP1 rs475007 and ERCC2 rs238406 are closely linked to SC risk.
Hemolytic uremic syndrome in the setting of COVID-19 successfully treated with complement inhibition therapy: An instructive case report of a previously healthy toddler and review of literature
Authors: Matošević Matija , Kos Ivanka , Davidović Maša , Ban Maja , Matković Hana , Jakopčić Ivan , Vuković Brinar Ivana , Szilágyi Ágnes , Csuka Dorottya , Sinkovits György , Prohászka Zoltán , Vrljičak Kristina , Lamot Lovro
Published: February 2023

Introduction

As the global pandemic continues, new complications of COVID-19 in pediatric population have turned up, one of them being hemolytic uremic syndrome (HUS), a complement-mediated thrombotic microangiopathy (CM-TMA) characterized by triad of thrombocytopenia, microangiopathic hemolytic anemia and acute kidney injury (AKI). With both multisystem inflammatory syndrome in children (MIS-C) and HUS sharing complement dysregulation as one of the key factors, the aim of this case report is to highlight differences between these two conditions and also emphasize the importance of complement blockade as a treatment modality.

Case report

We describe a 21-month-old toddler who initially presented with fever and confirmed COVID-19. His condition quickly deteriorated and he developed oliguria, accompanied with diarrhea, vomiting and oral intake intolerance. HUS was suspected, supported with compelling laboratory findings, including decreased platelets count and C3 levels, elevated LDH, urea, serum creatinine and sC5b-9 and presence of schistocytes in peripheral blood, negative fecal Shiga toxin and normal ADAMTS13 metalloprotease activity. The patient was given C5 complement blocker Ravulizumab and started to display rapid improvement.

Conclusion

Although reports of HUS in the setting of COVID-19 continue to pour in, the questions of exact mechanism and similarities to MIS-C remain. Our case for the first time accentuates the use of complement blockade as a valuable treatment option in this scenario. We sincerely believe that reporting on HUS as a complication of COVID-19 in children will give rise to improved diagnosis and treatment, as well as better understanding of both of these intricating diseases.
Case report: Accelerated regression of giant cardiac rhabdomyomas in neonates with low dose everolimus
Authors: Hurtado-Sierra Daniel , Ramos Garzón Judy Ximena , Rojas Lyda Z. , Fernández-Gómez Oscar , Manrique-Rincón Francisco
Published: February 2023

Cardiac rhabdomyoma (CRHM) is the principal cardiac tumor in children and is most often associated with tuberous sclerosis complex (TSC). Mutations in the TSC1 and TSC2 genes cause the overactivation of the mammalian Target of Rapamycin (mTOR). This protein family is responsible for abnormal cell proliferation leading to the formation of CRHMs and hamartomas in other organs. Despite the tendency for spontaneous regression, some CRHMs can cause heart failure and intractable arrhythmias, requiring surgical resection. In recent years, the use of everolimus and sirolimus (mTOR inhibitors) in the treatment of CRHMs has been reported. We report two cases of neonates with giant rhabdomyomas, with hemodynamic repercussions treated with low-dose everolimus (4.5 mg/m2/week). In both cases, we obtained an approximate decrease of 50% in the total area of the mass after three weeks of treatment. Despite rebound growth after stopping the drug, we were able to evidence that the use of low doses of everolimus immediately after birth is effective and safe in the treatment of giant CRHMs, avoiding surgical resection of the tumor and associated morbidity and mortality.
The impact of key monitoring policy on the usage of policy-related drugs in Hubei Province, China
Authors: Wen Xiaotong , Wang Yue , Chen Xiaoze , Liu Yuxin , Mao Zongfu
Published: February 2023

Introduction: This study evaluated quantitatively the impact of the first batch of the catalog of Key Monitoring and Rational Use Drugs (KMRUD) in Hubei Province on policy-related drug use and expenditures.

Methods: This study is aimed to provide a basis for the successful implementation of subsequent catalogs of KMRUD, which may promote the standardization of clinical application of related drugs and effectively reduce drug expenses of the patients. Data on the procurement records of policy-related drugs from January 2018 to June 2021 were obtained from the Drug Centralized Procurement Platform of the Public Resources Trading Center in Hubei Province. Interrupted time-series (ITS) analysis was used in this study.

Results: After the implementation of the first batch of the catalog of KMRUD, the consumption of policy-related drugs decreased by 83.29% in 2020. The spending on policy-related drugs decreased by 83.93% in 2020. The introduction of the first batch of the catalog of KMRUD was associated with a significant decrease in the spending on policy-related drugs in the level (p = 0.001). Before the implementation of the KMRUD catalog policy, the Defined Daily Doses (DDDs) (β1 = -32.26 p < 0.001) and spending (β1 = -3662.19 p < 0.001) on policy-related drugs showed a downward trend. In the aggregated ITS analysis, the Defined Daily Dose cost (DDDc) of policy-related drugs decreased significantly in the trend (p < 0.001). After the implementation of the KMRUD catalog policy, the monthly procurement volume of 10 policy-related drugs have a significant downward trend (p < 0.05), and 4 policy-related drugs have a significant upward trend (p < 0.05).

Conclusion: After the policy intervention, the total DDDc on policy-related drugs indicated sustained reductions. The KMRUD policy overall achieved the goal of limiting policy-related drug use and controlling cost increases. And it is recommended that the health department quantify the usage indicator of adjuvant drugs, uniform standards, and apply prescription reviews and dynamic supervision, and other measures to strengthen supervision.
Prognosis and personalized treatment prediction in lung adenocarcinoma: An in silico and in vitro strategy adopting cuproptosis related lncRNA towards precision oncology
Authors: Ma Chao , Li Feng , He Zhanfeng , Zhao Song , Yang Yang , Gu Zhuoyu
Published: February 2023

Background: There is a rapid increase in lung adenocarcinomas (LUAD), and studies suggest associations between cuproptosis and the occurrence of various types of tumors. However, it remains unclear whether cuproptosis plays a role in LUAD prognosis.

Methods: Dataset of the TCGA-LUAD was treated as training cohort, while validation cohort consisted of the merged datasets of the GSE29013, GSE30219, GSE31210, GSE37745, and GSE50081. Ten studied cuproptosis-related genes (CRG) were used to generated CRG clusters and CRG cluster-related differential expressed gene (CRG-DEG) clusters. The differently expressed lncRNA that with prognosis ability between the CRG-DEG clusters were put into a LASSO regression for cuproptosis-related lncRNA signature (CRLncSig). Kaplan–Meier estimator, Cox model, receiver operating characteristic (ROC), time-dependent AUC (tAUC), principal component analysis (PCA), and nomogram predictor were further deployed to confirm the model’s accuracy. We examined the model’s connections with other forms of regulated cell death, including apoptosis, necroptosis, pyroptosis, and ferroptosis. The immunotherapy ability of the signature was demonstrated by applying eight mainstream immunoinformatic algorithms, TMB, TIDE, and immune checkpoints. We evaluated the potential drugs for high risk CRLncSig LUADs. Real-time PCR in human LUAD tissues were performed to verify the CRLncSig expression pattern, and the signature’s pan-cancer’s ability was also assessed.

Results: A nine-lncRNA signature, CRLncSig, was built and demonstrated owning prognostic power by applied to the validation cohort. Each of the signature genes was confirmed differentially expressed in the real world by real-time PCR. The CRLncSig correlated with 2,469/3,681 (67.07%) apoptosis-related genes, 13/20 (65.00%) necroptosis-related genes, 35/50 (70.00%) pyroptosis-related genes, and 238/380 (62.63%) ferroptosis-related genes. Immunotherapy analysis suggested that CRLncSig correlated with immune status, and checkpoints, KIR2DL3, IL10, IL2, CD40LG, SELP, BTLA, and CD28, were linked closely to our signature and were potentially suitable for LUAD immunotherapy targets. For those high-risk patients, we found three agents, gemcitabine, daunorubicin, and nobiletin. Finally, we found some of the CRLncSig lncRNAs potentially play a vital role in some types of cancer and need more attention in further studies.

Conclusion: The results of this study suggest our cuproptosis-related CRLncSig can help to determine the outcome of LUAD and the effectiveness of immunotherapy, as well as help to better select targets and therapeutic agents.
Kinematics and muscle activity of the lower limb during single-leg stance on the two sides of the Togu Jumper
Authors: Mayer Petra , Sebesi Balázs , Vadász Kitty , Laczkó József , Zentai Norbert , Balázs Bence , Váczi Márk
Published: February 2023

Purpose: Togu Jumper is a both sides utilized balance training device, which consists of an inflated rubber hemisphere attached to a rigid platform. It has been shown to be effective in improving postural control but there are no recommendations for the usage of the sides. Our aim was to examine leg muscle activity and kinematics in response to a single-leg stance on the two sides of the Togu Jumper and the floor.

Methods: In 14 female subjects, linear acceleration of leg segments, segmental angular sway, and myoelectric activity of 8 leg muscles were recorded in the three stance conditions.

Results: Except gluteus medius and gastrocnemius medialis, all muscles were more active when balancing on either Togu Jumper side compared to the floor (p < 0.001), but there was no difference between the two sides in any muscles. Linear acceleration was the greatest in the frontal plane on the flat Togu side in the case of the foot (p < 0.001). Pelvis acceleration was unaffected by the balance conditions. Segmental angular sway was the greatest in the frontal plane, on the bladder side in the foot segment (p < 0.001). No difference was found among the three conditions (all p > 0.05) in the case of the shank, thigh, and pelvis.

Conclusion: The use of the two Togu Jumper sides produced different balance strategies in the foot segment and induced no difference in equilibrium procedures at the level of the pelvis.
Neuroplasticity in F16 fighter jet pilots
Authors: Radstake Wilhelmina E. , Jillings Steven , Laureys Steven , Demertzi Athena , Sunaert Stefan , Van Ombergen Angelique , Wuyts Floris L.
Published: February 2023

Exposure to altered g-levels causes unusual sensorimotor demands that must be dealt with by the brain. This study aimed to investigate whether fighter pilots, who are exposed to frequent g-level transitions and high g-levels, show differential functional characteristics compared to matched controls, indicative of neuroplasticity. We acquired resting-state functional magnetic resonance imaging data to assess brain functional connectivity (FC) changes with increasing flight experience in pilots and to assess differences in FC between pilots and controls. We performed whole-brain exploratory and region-of-interest (ROI) analyses, with the right parietal operculum 2 (OP2) and the right angular gyrus (AG) as ROIs. Our results show positive correlations with flight experience in the left inferior and right middle frontal gyri, and in the right temporal pole. Negative correlations were observed in primary sensorimotor regions. We found decreased whole-brain functional connectivity of the left inferior frontal gyrus in fighter pilots compared to controls and this cluster showed decreased functional connectivity with the medial superior frontal gyrus. Functional connectivity increased between the right parietal operculum 2 and the left visual cortex, and between the right and left angular gyrus in pilots compared to controls. These findings suggest altered motor, vestibular, and multisensory processing in the brains of fighter pilots, possibly reflecting coping strategies to altered sensorimotor demands during flight. Altered functional connectivity in frontal areas may reflect adaptive cognitive strategies to cope with challenging conditions during flight. These findings provide novel insights into brain functional characteristics of fighter pilots, which may be of interest to humans traveling to space.
Impact of different ground-based microgravity models on human sensorimotor system
Authors: Saveko Alina , Bekreneva Maria , Ponomarev Ivan , Zelenskaya Inna , Riabova Alexandra , Shigueva Tatiana , Kitov Vladimir , Abu Sheli Nelly , Nosikova Inna , Rukavishnikov Ilya , Sayenko Dimitry , Tomilovskaya Elena
Published: February 2023

This review includes current and updated information about various ground-based microgravity models and their impact on the human sensorimotor system. All known models of microgravity are imperfect in a simulation of the physiological effects of microgravity but have their advantages and disadvantages. This review points out that understanding the role of gravity in motion control requires consideration of data from different environments and in various contexts. The compiled information can be helpful to researchers to effectively plan experiments using ground-based models of the effects of space flight, depending on the problem posed.
Fundus image classification using Inception V3 and ResNet-50 for the early diagnostics of fundus diseases
Authors: Pan Yuhang , Liu Junru , Cai Yuting , Yang Xuemei , Zhang Zhucheng , Long Hong , Zhao Ketong , Yu Xia , Zeng Cui , Duan Jueni , Xiao Ping , Li Jingbo , Cai Feiyue , Yang Xiaoyun , Tan Zhen
Published: February 2023

Purpose: We aim to present effective and computer aided diagnostics in the field of ophthalmology and improve eye health. This study aims to create an automated deep learning based system for categorizing fundus images into three classes: normal, macular degeneration and tessellated fundus for the timely recognition and treatment of diabetic retinopathy and other diseases.

Methods: A total of 1,032 fundus images were collected from 516 patients using fundus camera from Health Management Center, Shenzhen University General Hospital Shenzhen University, Shenzhen 518055, Guangdong, China. Then, Inception V3 and ResNet-50 deep learning models are used to classify fundus images into three classes, Normal, Macular degeneration and tessellated fundus for the timely recognition and treatment of fundus diseases.

Results: The experimental results show that the effect of model recognition is the best when the Adam is used as optimizer method, the number of iterations is 150, and 0.00 as the learning rate. According to our proposed approach we, achieved the highest accuracy of 93.81% and 91.76% by using ResNet-50 and Inception V3 after fine-tuned and adjusted hyper parameters according to our classification problem.

Conclusion: Our research provides a reference to the clinical diagnosis or screening for diabetic retinopathy and other eye diseases. Our suggested computer aided diagnostics framework will prevent incorrect diagnoses caused by the low image quality and individual experience, and other factors. In future implementations, the ophthalmologists can implement more advanced learning algorithms to improve the accuracy of diagnosis.