bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbapenemase Production and Epidemiological Characteristics of Carbapenem-Resistant Klebsiella pneumoniae in Western Chongqing, China
Authors: Huang Wan , Zhang Jisheng , Zeng Lingyi , Yang Chengru , Yin Lining , Wang Jianmin , Li Jie , Li Xinhui , Hu Kewang , Zhang Xiaoli , Liu Beizhong
Published: January 2022

Background

This study aimed to determine the molecular characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates in a hospital in western Chongqing, southwestern China.

Methods

A total of 127 unique CRKP isolates were collected from the Yongchuan Hospital of Chongqing Medical University, identified using a VITEK-2 compact system, and subjected to microbroth dilution to determine the minimal inhibitory concentration. Enterobacteriaceae intergenic repeat consensus polymerase chain reaction and multilocus sequence typing were used to analyze the homology among the isolates. Genetic information, including resistance and virulence genes, was assessed using polymerase chain reaction. The genomic features of the CRKP carrying gene blaKPC-2 were detected using whole-genome sequencing.

Results

ST11 was the dominant sequence type in the homology comparison. The resistance rate to ceftazidime-avibactam in children was much higher than that in adults as was the detection rate of the resistance gene blaNDM (p < 0.0001). Virulence genes such as mrkD (97.6%), uge (96.9%), kpn (96.9%), and fim-H (84.3%) had high detection rates. IncF (57.5%) was the major replicon plasmid detected, and sequencing showed that the CRKP063 genome contained two plasmids. The plasmid carrying blaKPC-2, which mediates carbapenem resistance, was located on the 359,625 base pair plasmid IncFII, together with virulence factors, plasmid replication protein (rep B), stabilizing protein (par A), and type IV secretion system (T4SS) proteins that mediate plasmid conjugation transfer.

Conclusion

Our study aids in understanding the prevalence of CRKP in this hospital and the significant differences between children and adults, thus providing new ideas for clinical empirical use of antibiotics.
Enhanced Proinflammatory Cytokine Production and Immunometabolic Impairment of NK Cells Exposed to Mycobacterium tuberculosis and Cigarette Smoke
Authors: Rao Yafei , Gai Xiaoyan , Le Yanqing , Xiong Jing , Liu Yujia , Zhang Xueyang , Wang Jundong , Cao Wenli , Sun Yongchang
Published: January 2022

Aim

Smoker COPD patients with chest radiological signs of prior tuberculosis (TB) showed more severe lung damage, but the mechanisms remain unclear. Emerging evidence has implicated NK cells in the pathogenesis of both COPD and TB. The purpose of this study was to delineate the profile and cytokine production of NK-cell subpopulations and their immunometabolic changes after exposure to both cigarette smoke (CS) and Mycobacterium tuberculosis(MTB).

Methods

We profiled NK-cell subpopulations in terms of percentage and cytokine production by flow cytometry in smoker patients with pulmonary TB (PTB). In an in vitro coexposure model, we investigated proinflammatory cytokine production, glycolytic influx, and oxidative phosphorylation of NK cells under CS extract (CSE) and PPD costimulation.

Results

Peripheral blood NK cells in smoker patients with active PTB (CS+PTB group) showed altered proportion of subpopulations and excessive proinflammatory cytokine expressions. In vitro, CSE- and PPD-coexposed NK-92 cells displayed enhanced proinflammatory cytokine production, concurrent with decreased glycolytic influx and oxidative phosphorylation.

Conclusion

Smoker patients with active PTB showed enhanced proinflammatory cytokine expression within altered NK cell subpopulations. CSE and PPD coexposure induced heightened cytokine production concurrent with impaired cell metabolism in NK cells. These novel data suggest a potential role of NK cells in the pathogenesis of lung injury in subjects with coexposure to CS and TB.
Perceptions of Live Donor Kidney Transplantation Using Segmentation Analysis and Perceptual Mapping to Understand Differences by Self-Reported Health Status in People on Dialysis
Authors: Bass Sarah Bauerle , Hollin Ilene L. , Kelly Patrick J. , Alhajji Mohammed , D’Avanzo Paul , Maurer Laurie , Gillespie Avrum , Schatell Dori , Gardiner Heather
Published: January 2022

Living donor kidney transplantation is a superior treatment option for those with end stage kidney disease, but most transplants are from deceased donors. Securing a living donor for living donor kidney transplantation requires effective, well-timed communication which many may find difficult or intimidating. This study uses segmentation analysis and an innovative marketing technique called perceptual mapping to create three dimensional models to compare living donor kidney transplant perceptions by self-reported health status in 160 end-stage kidney disease dialysis patients of two hospital-based dialysis units and an online forum through cross-sectional surveys. Findings indicate patients with poor self-reported health status are more concerned with not knowing what to say or being afraid a person would say no to living donor kidney transplantation. They are also concerned about the donor’s ability to care for family or donate in the future. They are, however, more likely to see benefits of living donor kidney transplantation, including the kidney lasting longer and having a greater quality of life. Findings reveal messages that could be emphasized in interventions to enhance the ability to ask for living donor kidney transplantation, especially in those assessed as having poor health status. Segmentation analysis and perceptual mapping methods can provide a more nuanced look at how best to develop intervention content to increase living donor kidney transplant.
The Effects of Fish Oil on Cardiovascular Diseases: Systematical Evaluation and Recent Advance
Authors: Liao Jia , Xiong Qingsong , Yin Yuehui , Ling Zhiyu , Chen Shaojie
Published: January 2022

Fish oil is rich in unsaturated fatty acids, i.e., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both of which are widely distributed in the body such as heart and brain. In vivo and in vitro experiments showed that unsaturated fatty acids may have effects of anti-inflammation, anti-oxidation, protecting vascular endothelial cells, thrombosis inhibition, modifying autonomic nerve function, improving left ventricular remodeling, and regulating blood lipid. Given the relevance to public health, there has been increasing interest in the research of potential cardioprotective effects of fish oil. Accumulated evidence showed that fish oil supplementation may reduce the risk of cardiovascular events, and, in specific, it may have potential benefits in improving the prognosis of patients with hypertension, coronary heart disease, cardiac arrhythmias, or heart failure; however, some studies yielded inconsistent results. In this article, we performed an updated systematical review in order to provide a contemporary understanding with regard to the effects of fish oil on cardiovascular diseases.
3D Convolution Conjugate Gradient Inversion of Potential Fields in Acoculco Geothermal Prospect, Mexico
Authors: Calderón José P. , Gallardo Luis A.
Published: January 2022

Potential field data have long been used in geophysical exploration for archeological, mineral, and reservoir targets. For all these targets, the increased search of highly detailed three-dimensional subsurface volumes has also promoted the recollection of high-density contrast data sets. While there are several approaches to handle these large-scale inverse problems, most of them rely on either the extensive use of high-performance computing architectures or data-model compression strategies that may sacrifice some level of model resolution. We posit that the superposition and convolutional properties of the potential fields can be easily used to compress the information needed for data inversion and also to reduce significantly redundant mathematical computations. For this, we developed a convolution-based conjugate gradient 3D inversion algorithm for the most common types of potential field data. We demonstrate the performance of the algorithm using a resolution test and a synthetic experiment. We then apply our algorithm to gravity and magnetic data for a geothermal prospect in the Acoculco caldera in Mexico. The resulting three-dimensional model meaningfully determined the distribution of the existent volcanic infill in the caldera as well as the interrelation of various intrusions in the basement of the area. We propose that these intrusive bodies play an important role either as a low-permeability host of the heated fluid or as the heat source for the potential development of an enhanced geothermal system.
Optimal Threshold of Homeostasis Model Assessment of Insulin Resistance to Identify Metabolic Syndrome in a Chinese Population Aged 45 Years or Younger
Authors: Lin Szu-Yu , Li Wen-Cheng , Yang Ting-An , Chen Yi-Chuan , Yu Wei , Huang Hsiung-Ying , Xiong Xue-Jie , Chen Jau-Yuan
Published: January 2022

Background

Metabolic syndrome (MetS) is regarded as a major risk factor for diabetes mellitus and cardiovascular disease (CVD). The optimal threshold of the homeostasis model assessment of insulin resistance (HOMA-IR) has been established for predicting MetS in diverse populations and for different ages. This study assessed the serum HOMA-IR level in a healthy Chinese population aged ≤45 years to determine its relationship with metabolic abnormalities.

Methods

Cross-sectional study data were collected from health checkup records of Chinese adults aged ≥18 years between 2013 and 2016 at Xiamen Chang Gung Hospital. Participants completed a standardized questionnaire, which was followed by a health examination and blood sample collection. Exclusion criteria were as follows: history of known CVDs; liver, kidney, or endocrine diseases or recent acute illness; hypertension; hyperlipidemia; and pregnancy or lactation.

Results

The clinical and laboratory characteristics of 5954 men and 4185 women were analyzed. Significant differences were observed in all assessed variables (all P < 0.05). The optimal cutoff point of HOMA-IR for predicting MetS was 1.7 in men and 1.78 in women.

Conclusions

We aimed to determine the optimal cutoff point of HOMA-IR for predicting MetS in a healthy Chinese population aged ≤45 years. The findings of this study would provide an evidence-based threshold for evaluating metabolic syndromes and further implementing primary prevention programs, such as lifestyle changes in the target population.
Pregnancy in Women With Monogenic Diabetes due to Pathogenic Variants of the Glucokinase Gene: Lessons and Challenges
Authors: Timsit José , Ciangura Cécile , Dubois-Laforgue Danièle , Saint-Martin Cécile , Bellanne-Chantelot Christine
Published: January 2022

Heterozygous loss-of-function variants of the glucokinase (GCK) gene are responsible for a subtype of maturity-onset diabetes of the young (MODY). GCK-MODY is characterized by a mild hyperglycemia, mainly due to a higher blood glucose threshold for insulin secretion, and an up-regulated glucose counterregulation. GCK-MODY patients are asymptomatic, are not exposed to diabetes long-term complications, and do not require treatment. The diagnosis of GCK-MODY is made on the discovery of hyperglycemia by systematic screening, or by family screening. The situation is peculiar in GCK-MODY women during pregnancy for three reasons: 1. the degree of maternal hyperglycemia is sufficient to induce pregnancy adverse outcomes, as in pregestational or gestational diabetes; 2. the probability that a fetus inherits the maternal mutation is 50% and; 3. fetal insulin secretion is a major stimulus of fetal growth. Consequently, when the fetus has not inherited the maternal mutation, maternal hyperglycemia will trigger increased fetal insulin secretion and growth, with a high risk of macrosomia. By contrast, when the fetus has inherited the maternal mutation, its insulin secretion is set at the same threshold as the mother’s, and no fetal growth excess will occur. Thus, treatment of maternal hyperglycemia is necessary only in the former situation, and will lead to a risk of fetal growth restriction in the latter. It has been recommended that the management of diabetes in GCK-MODY pregnant women should be guided by assessment of fetal growth by serial ultrasounds, and institution of insulin therapy when the abdominal circumference is ≥ 75th percentile, considered as a surrogate for the fetal genotype. This strategy has not been validated in women with in GCK-MODY. Recently, the feasibility of non-invasive fetal genotyping has been demonstrated, that will improve the care of these women. Several challenges persist, including the identification of women with GCK-MODY before or early in pregnancy, and the modalities of insulin therapy. Yet, retrospective observational studies have shown that fetal genotype, not maternal treatment with insulin, is the main determinant of fetal growth and of the risk of macrosomia. Thus, further studies are needed to specify the management of GCK-MODY pregnant women during pregnancy.
Harmonic Analysis and Neutral-Point Potential Control of Interleaved Parallel Three-Level Inverters for Flywheel Energy Storage System
Authors: Li Zhongrui , Nie Ziling , Xu Jie , Li Huayu , Ai Sheng
Published: January 2022

Flywheel energy storage system is a popular energy storage technology, in which inverters are the center of electrical energy conversion, directly affecting the power capacity. Parallel operation of three-level inverters is an effective approach to achieve larger motor drive power and the interleaved operation can improve the harmonic characteristics. However, harmonic analysis models of the interleaved parallel three-level inverters are rare in the literature and how the neutral-point potential imbalance affects the harmonics characteristics has not been discussed. This article establishes the harmonic calculation for balanced and unbalanced neutral-point potential through the five-level voltage capability of the interleaved parallel three-level inverters. Moreover, a neutral-point potential control method based on zero-sequence voltage injection is proposed. The implement process of the method is proposed, and how the operating frequency affect the ability of the neutral-point potential balance is studied. Finally, the simulation and experiment results verify the feasibility and practicability of the established harmonic analysis models and the neutral-point potential control method.
Whence Came These Plants Most Foul? Phylogenomics and Biogeography of Lowiaceae (Zingiberales)
Authors: Niissalo Matti A. , Gardner Elliot M. , Khew Gillian S. , Šída Otakar , Poulsen Axel Dalberg , Leong-Škorničková Jana
Published: January 2022

Lowiaceae (order Zingiberales) is a small family of forest herbs in Southeast Asia. All species belong to the genus Orchidantha. They are known for possessing orchid-like flowers that are smelly, apparently mimicking dead animals, feces, or mushrooms. Little is known of the biogeographic patterns or character evolution of the family. We sampled the family extensively, including many recently discovered species, and reconstructed the phylogeny of the family using HybSeq with Lowiaceae-specific RNA baits. Our phylogenetic reconstructions confirm that the family is most closely related to Strelitziaceae, and that species with dark, foul-smelling flowers form a grade in which a clade of species with paler flowers are embedded. The pale-flowered species produce a distinct odor, resembling edible mushrooms. Apart from a single species, the species from Borneo form a clade, and the same is true for Indochinese species. The remaining species form a more widespread clade. A biogeographic analysis shows that the distribution of Lowiaceae can explained by vicariance and gradual dispersal from a shared ancestral range of Borneo and Indochina. There is no evidence of long-distance dispersal, only a later extension in distribution to Peninsular Malaysia which coincides with the presence of a land bridge. Different directions of spread are possible, but none require long-distance dispersal. The results are consistent with the geological history of Southeast Asia. In particular, the relatively early isolation between Indochina and Borneo could be explained by the presence of a sea barrier that developed 10–15 MYA, and the continuous movement of plant species between Borneo and Peninsular Malaysia could be explained by a land bridge that existed until c. 5 MYA. The lack of an extensive land bridge with a suitable habitat may explain the absence of this genus from Sumatra and other Indonesian islands aside from Borneo. The strict reliance on a continuous habitat for the range expansion of Lowiaceae can be explained by their fruits and seeds, which lack obvious adaptations for long-distance dispersal. The inability to disperse to new areas may also explain why the extant species have very restricted distributions.
Comprehensive Analysis of Splicing Factor and Alternative Splicing Event to Construct Subtype-Specific Prognosis-Predicting Models for Breast Cancer
Authors: Zhang He , Han Baoai , Han Xingxing , Zhu Yuying , Liu Hui , Wang Zhiyong , Cui Yanfen , Tian Ran , Gao Zicong , Tian Ruinan , Ren Sixin , Zuo Xiaoyan , Tian Jianfei , Zhang Fei , Niu Ruifang
Published: January 2022

Recent evidence suggests that splicing factors (SFs) and alternative splicing (AS) play important roles in cancer progression. We constructed four SF-risk-models using 12 survival-related SFs. In Luminal-A, Luminal-B, Her-2, and Basal-Like BRCA, SF-risk-models for three genes (PAXBP1, NKAP, and NCBP2), four genes (RBM15B, PNN, ACIN1, and SRSF8), three genes (LSM3, SNRNP200, and SNU13), and three genes (SRPK3, PUF60, and PNN) were constructed. These models have a promising prognosis-predicting power. The co-expression and protein-protein interaction analysis suggest that the 12 SFs are highly functional-connected. Pathway analysis and gene set enrichment analysis suggests that the functional role of the selected 12 SFs is highly context-dependent among different BRCA subtypes. We further constructed four AS-risk-models with good prognosis predicting ability in four BRCA subtypes by integrating the four SF-risk-models and 21 survival-related AS-events. This study proposed that SFs and ASs were potential multidimensional biomarkers for the diagnosis, prognosis, and treatment of BRCA.
Filovirus VP24 Proteins Differentially Regulate RIG-I and MDA5-Dependent Type I and III Interferon Promoter Activation
Authors: He Felix B. , Khan Hira , Huttunen Moona , Kolehmainen Pekka , Melén Krister , Maljanen Sari , Qu Mengmeng , Jiang Miao , Kakkola Laura , Julkunen Ilkka
Published: January 2022

Filovirus family consists of highly pathogenic viruses that have caused fatal outbreaks especially in many African countries. Previously, research focus has been on Ebola, Sudan and Marburg viruses leaving other filoviruses less well studied. Filoviruses, in general, pose a significant global threat since they are highly virulent and potentially transmissible between humans causing sporadic infections and local or widespread epidemics. Filoviruses have the ability to downregulate innate immunity, and especially viral protein 24 (VP24), VP35 and VP40 have variably been shown to interfere with interferon (IFN) gene expression and signaling. Here we systematically analyzed the ability of VP24 proteins of nine filovirus family members to interfere with retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated antigen 5 (MDA5) induced IFN-β and IFN-λ1 promoter activation. All VP24 proteins were localized both in the cell cytoplasm and nucleus in variable amounts. VP24 proteins of Zaire and Sudan ebolaviruses, Lloviu, Taï Forest, Reston, Marburg and Bundibugyo viruses (EBOV, SUDV, LLOV, TAFV, RESTV, MARV and BDBV, respectively) were found to inhibit both RIG-I and MDA5 stimulated IFN-β and IFN-λ1 promoter activation. The inhibition takes place downstream of interferon regulatory factor 3 phosphorylation suggesting the inhibition to occur in the nucleus. VP24 proteins of Mengla (MLAV) or Bombali viruses (BOMV) did not inhibit IFN-β or IFN-λ1 promoter activation. Six ebolavirus VP24s and Lloviu VP24 bound tightly, whereas MARV and MLAV VP24s bound weakly, to importin α5, the subtype that regulates the nuclear import of STAT complexes. MARV and MLAV VP24 binding to importin α5 was very weak. Our data provides new information on the innate immune inhibitory mechanisms of filovirus VP24 proteins, which may contribute to the pathogenesis of filovirus infections.
Encephalomyelitis Caused by Balamuthia mandrillaris in a Woman With Breast Cancer: A Case Report and Review of the Literature
Authors: Hu Juan , Zhang Yiqi , Yu Yongwei , Yu Huili , Guo Siruo , Shi Ding , He Jianqin , Hu Chi , Yang Jiqi , Fang Xueling , Xiao Yonghong
Published: January 2022

Balamuthia mandrillaris is one cause of a rare and severe brain infection called granulomatous amoebic encephalitis (GAE), which has a mortality rate of >90%. Diagnosis of Balamuthia GAE is difficult because symptoms are non-specific. Here, we report a case of Balamuthia amoebic encephalomyelitis (encephalitis and myelitis) in a woman with breast cancer. She sustained trauma near a garbage dump 2 years ago and subsequently developed a skin lesion with a Mycobacterium abscessus infection. She experienced dizziness, lethargy, nausea and vomiting, inability to walk, and deterioration of consciousness. Next-generation sequencing of cerebrospinal fluid (CSF) samples revealed B. mandrillaris, and MRI of both brain and spinal cord showed abnormal signals. T-cell receptor (TCR) sequencing of the CSF identified the Top1 TCR. A combination of amphotericin B, flucytosine, fluconazole, sulfamethoxazole, trimethoprim, clarithromycin, pentamidine, and miltefosine was administrated, but she deteriorated gradually and died on day 27 post-admission.
Mechanistic and Biomarker Studies to Demonstrate Immune Tolerance in Multiple Sclerosis
Authors: Docampo María José , Lutterotti Andreas , Sospedra Mireia , Martin Roland
Published: January 2022

The induction of specific immunological tolerance represents an important therapeutic goal for multiple sclerosis and other autoimmune diseases. Sound knowledge of the target antigens, the underlying pathomechanisms of the disease and the presumed mechanisms of action of the respective tolerance-inducing approach are essential for successful translation. Furthermore, suitable tools and assays to evaluate the induction of immune tolerance are key aspects for the development of such treatments. However, investigation of the mechanisms of action underlying tolerance induction poses several challenges. The optimization of sensitive, robust methods which allow the assessment of low frequency autoreactive T cells and the long-term reduction or change of their responses, the detection of regulatory cell populations and their immune mediators, as well as the validation of specific biomarkers indicating reduction of inflammation and damage, are needed to develop tolerance-inducing approaches successfully to patients. This short review focuses on how to demonstrate mechanistic proof-of-concept in antigen-specific tolerance-inducing therapies in MS.
Obesity Increases Gene Expression of Markers Associated With Immunosenescence in Obese Middle-Aged Individuals
Authors: Brunelli Diego T. , Boldrini Vinicius O. , Bonfante Ivan L. P. , Duft Renata G. , Mateus Keryma , Costa Leonardo , Chacon-Mikahil Mara P. T. , Teixeira Ana M. , Farias Alessandro S. , Cavaglieri Cláudia R.
Published: January 2022

Recently, it has been argued that obesity leads to a chronic pro-inflammatory state that can accelerate immunosenescence, predisposing to the early acquisition of an immune risk profile and health problems related to immunity in adulthood. In this sense, the present study aimed to verify, in circulating leukocytes, the gene expression of markers related to early immunosenescence associated with obesity and its possible relationships with the physical fitness in obese adults with type 2 diabetes or without associated comorbidities. The sample consisted of middle-aged obese individuals (body mass index (BMI) between 30-35 kg/m²) with type 2 diabetes mellitus (OBD; n = 17) or without associated comorbidity (OB; n = 18), and a control group of eutrophic healthy individuals (BMI: 20 - 25 kg/m²) of same ages (E; n = 18). All groups (OBD, OB and E) performed the functional analyses [muscle strength (1RM) and cardiorespiratory fitness (VO2max)], anthropometry, body composition (Air Displacement Plethysmograph), blood collections for biochemical (anti-CMV) and molecular (gene expression of leptin, IL-2, IL-4, IL-6, IL-10, TNF-α, PD-1, P16ink4a, CCR7, CD28 and CD27) analyses of markers related to immunosenescence. Increased gene expression of leptin, IL-2, IL-4, IL-10, TNF-α, PD-1, P16ink4a, CCR7 and CD27 was found for the OBD and OB groups compared to the E group. Moreover, VO2max for the OBD and OB groups was significantly lower compared to E. In conclusion, obesity, regardless of associated disease, induces increased gene expression of markers associated with inflammation and immunosenescence in circulating leukocytes in obese middle-aged individuals compared to a eutrophic group of the same age. Additionally, increased adipose tissue and markers of chronic inflammation and immunosenescence were associated to impairments in the cardiorespiratory capacity of obese middle-aged individuals.
Discovery of Sex-Determining Genes in Portunus trituberculatus: A Comparison of Male and Female Transcriptomes During Early Developmental Stages
Authors: Zhang Wen , Lv Jianjian , Lan Weikang , Gao Baoquan , Liu Ping
Published: January 2022

Portunus trituberculatus is one of the main mariculture crabs of high economic value. To identify genes involved in sex determination, we first performed sex-specific transcriptome sequencing at six larval development stages using a DNA/RNA co-extraction method. A total of 907,952,938 and 828,774,880 reads were obtained from female and male crabs, respectively. 2,379 differentially expressed genes (DEGs) were found between females and males, and were mainly enriched in DNA replication, folate biosynthesis, and retinol metabolism pathways. Furthermore, transcription patterns of genes in the sex-determining region (SD) were analyzed based on the transcriptome data, and one Dmrt gene (PtDMY) was found to be exclusively expressed in males during early developmental stages. Notably, some known sex-related genes, including IAG, Dmrt11E, DmrtB1, and DmrtC2 were significantly down-regulated after knocking down PtDMY. Our results suggested that PtDMY is involved in sex determination and may be one of the key upstream regulators of the sex determination pathway. In addition, the massive volume of transcriptome data obtained in this study provided an important basis for the systematic study of sex determination mechanisms in P. trituberculatus.
Structural Mechanisms in Soft Fibrous Tissues: A Review
Authors: Sharabi Mirit
Published: January 2022

Through years of evolution, biological soft fibrous tissues have developed remarkable functional properties, unique hierarchical architectures, and -most notably, an unparalleled and extremely efficient deformation ability. Whereas the structure-function relationship is well-studied in natural hard materials, soft materials are not getting similar attention, despite their high prevalence in nature. These soft materials are usually constructed as fiber-reinforced composites consisting of diverse structural motifs that result in an overall unique mechanical behavior with large deformations. Biomimetics of their mechanical behavior is currently a significant bioengineering challenge. The unique properties of soft fibrous tissues stem from their structural complexity, which, unfortunately, also hinders our ability to generate adequate synthetic analogs, such that autografts remain the “gold standard” materials for soft-tissue repair and replacement. This review seeks to understand the structural and deformation mechanisms of soft collagenous tissues, with a particular emphasis on tendon and ligaments, the annulus fibrosus (AF) in the intervertebral disc (IVD), skin, and blood vessels. We examined and compared different mechanical and structural motifs in these different tissue types, which are subjected to complex and varied mechanical loads, to isolate the mechanisms of their deformation behavior. Herein, we focused on their composite structure from a perspective of the different building blocks, architecture, crimping patterns, fiber orientation, organization and their structure-function relationship. In the second part of the review, we presented engineered soft composite applications that used these structural motifs to mimic the structural and mechanical behavior of soft fibrous tissues. Moreover, we demonstrated new methodologies and materials that use biomimetic principles as a guide. These novel architectural materials have tailor-designed J-shaped large deformations behavior. Structural motifs in soft composites hold valuable insights that could be exploited to generate the next generation of materials. They actually have a two-fold effect: 1) to get a better understanding of the complex structure-function relationship in a simple material system using reverse biomimetics and 2) to develop new and efficient materials. These materials could revolutionize the future tailor-designed soft composite materials together with various soft-tissue repair and replacement applications that will be mechanically biocompatible with the full range of native tissue behaviors.
Identification of TRPM2 as a Marker Associated With Prognosis and Immune Infiltration in Kidney Renal Clear Cell Carcinoma
Authors: Sun Lei , Zhang Zijun , Zhao Hang , Qiu Miaoyun , Wen Ying , Yao Xiaoqiang , Tang Wai Ho
Published: January 2022

TRPM2 (transient receptor potential melastatin-2), a Ca2+ permeable, non-selective cation channel, is highly expressed in cancers and regulates tumor cell migration, invasion, and proliferation. However, no study has yet demonstrated the association of TRPM2 with the prognosis of cancer patients or tumor immune infiltration, and the possibility and the clinical basis of TRPM2 as a prognostic marker in cancers are yet unknown. In the current study, we first explored the correlation between the mRNA level of TRPM2 and the prognosis of patients with different cancers across public databases. Subsequently, the Tumor Immune Estimation Resource (TIMER) platform and the TISIDB website were used to assess the correlation between TRPM2 and tumor immune cell infiltration level. We found that 1) the level of TRPM2 was significantly elevated in most tumor tissues relative to normal tissues; 2) TRPM2 upregulation was significantly associated with adverse clinical characteristics and poor survival of kidney renal clear cell carcinoma (KIRC) patients; 3) the level of TRPM2 was positively related to immune cell infiltration. Moreover, TRPM2 was closely correlated to the gene markers of diverse immune cells; 4) a high TRPM2 expression predicted worse prognosis in KIRC based on different enriched immune cell cohorts; and 5) TRPM2 was mainly implemented in the T-cell activation process indicated by Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. In conclusion, TRPM2 can serve as a marker to predict the prognosis and immune infiltration in KIRC through the regulation of T-cell activation. The current data may provide additional information for further studies surrounding the function of TRPM2 in KIRC.
Decision-Making Process for the Management of Acute Stroke in Patients on Oral Anticoagulant: From Guidelines to Clinical Routine
Authors: Sibon Igor , Mazighi Mikael , Smadja Didier
Published: January 2022

Background: The occurrence of both ischaemic (IS) and haemorrhagic stroke in patients on anticoagulation is a major issue due to the frequency of their prescriptions in westernised countries and the expected impact of anticoagulant activity on recanalization during an IS or on the outcomes associated with intracerebral haemorrhage (ICH). Several guidelines are available but sometimes differ in their conclusions or regarding specific issues, and their application in routine emergency settings may be limited by particular individual issues or heterogeneous local specificities.

Methods: Based on the current guidelines and additional published data, the algorithms proposed in this paper aim to help the decision-making process regarding stroke management in the setting of concurrent anticoagulants by addressing specific clinical situations based on clinical variables commonly encountered in real-world practise.

Results: For patients on non–vitamin K oral anticoagulants, reversion can be achieved with specific antidotes, but only idarucizumab, the specific dabigatran antidote, is indicated in both IS and ICH. Due to the low risk of a prothrombotic effect, idarucizumab can be immediately used in IS patients eligible for thrombolysis before the dabigatran concentration is known. To optimise ICH management, the time since symptom onset, with thresholds proposed at 6 and 9 hours based on the expected timing of haematoma expansion, could also to be taken into account.

Conclusions: Anticoagulant reversal in patients presenting with a stroke remains a major issue, and algorithms based on a step-by-step approach may be useful for clinical practise. Real-life studies strongly support the benefits of idarucizumab availability in stroke units and emergency departments.
Lipopolysaccharide From E. coli Increases Glutamate-Induced Disturbances of Calcium Homeostasis, the Functional State of Mitochondria, and the Death of Cultured Cortical Neurons
Authors: Bakaeva Zanda , Lizunova Natalia , Tarzhanov Ivan , Boyarkin Dmitrii , Petrichuk Svetlana , Pinelis Vsevolod , Fisenko Andrey , Tuzikov Alexander , Sharipov Rinat , Surin Alexander
Published: January 2022

Lipopolysaccharide (LPS), a fragment of the bacterial cell wall, specifically interacting with protein complexes on the cell surface, can induce the production of pro-inflammatory and apoptotic signaling molecules, leading to the damage and death of brain cells. Similar effects have been noted in stroke and traumatic brain injury, when the leading factor of death is glutamate (Glu) excitotoxicity too. But being an amphiphilic molecule with a significant hydrophobic moiety and a large hydrophilic region, LPS can also non-specifically bind to the plasma membrane, altering its properties. In the present work, we studied the effect of LPS fromEscherichia colialone and in combination with the hyperstimulation of Glu-receptors on the functional state of mitochondria and Ca2+homeostasis, oxygen consumption and the cell survival in primary cultures from the rats brain cerebellum and cortex. In both types of cultures, LPS (0.1–10 μg/ml) did not change the intracellular free Ca2+concentration ([Ca2+]i) in resting neurons but slowed down the median of the decrease in [Ca2+]ion 14% and recovery of the mitochondrial potential (ΔΨm) after Glu removal. LPS did not affect the basal oxygen consumption rate (OCR) of cortical neurons; however, it did decrease the acute OCR during Glu and LPS coapplication. Evaluation of the cell culture survival using vital dyes and the MTT assay showed that LPS (10 μg/ml) and Glu (33 μM) reduced jointly and separately the proportion of live cortical neurons, but there was no synergism or additive action. LPS-effects was dependent on the type of culture, that may be related to both the properties of neurons and the different ratio between neurons and glial cells in cultures. The rapid manifestation of these effects may be the consequence of the direct effect of LPS on the rheological properties of the cell membrane.
Evidence-Based Challenges to the Continued Recommendation and Use of Peroxidatively-Susceptible Polyunsaturated Fatty Acid-Rich Culinary Oils for High-Temperature Frying Practises: Experimental Revelations Focused on Toxic Aldehydic Lipid Oxidation Products
Authors: Grootveld Martin
Published: January 2022

In this manuscript, a series of research reports focused on dietary lipid oxidation products (LOPs), their toxicities and adverse health effects are critically reviewed in order to present a challenge to the mindset supporting, or strongly supporting, the notion that polyunsaturated fatty acid-laden frying oils are “safe” to use for high-temperature frying practises. The generation, physiological fates, and toxicities of less commonly known or documented LOPs, such as epoxy-fatty acids, are also considered. Primarily, an introduction to the sequential autocatalytic peroxidative degradation of unsaturated fatty acids (UFAs) occurring during frying episodes is described, as are the potential adverse health effects posed by the dietary consumption of aldehydic and other LOP toxins formed. In continuance, statistics on the dietary consumption of fried foods by humans are reviewed, with a special consideration of French fries. Subsequently, estimates of human dietary aldehyde intake are critically explored, which unfortunately are limited to acrolein and other lower homologues such as acetaldehyde and formaldehyde. However, a full update on estimates of quantities derived from fried food sources is provided here. Further items reviewed include the biochemical reactivities, metabolism and volatilities of aldehydic LOPs (the latter of which is of critical importance regarding the adverse health effects mediated by the inhalation of cooking/frying oil fumes); their toxicological actions, including sections focussed on governmental health authority tolerable daily intakes, delivery methods and routes employed for assessing such effects in animal model systems, along with problems encountered with the Cramer classification of such toxins. The mutagenicities, genotoxicities, and carcinogenic potential of aldehydes are then reviewed in some detail, and following this the physiological concentrations of aldehydes and their likely dietary sources are considered. Finally, conclusions from this study are drawn, with special reference to requirements for (1) the establishment of tolerable daily intake (TDI) values for a much wider range of aldehydic LOPs, and (2) the performance of future nutritional and epidemiological trials to explore associations between their dietary intake and the incidence and severity of non-communicable chronic diseases (NCDs).
Association of Hypokalemia Incidence and Better Treatment Response in NSCLC Patients: A Meta-Analysis and Systematic Review on Anti-EGFR Targeted Therapy Clinical Trials
Authors: Zhou Jiawei , Bai Jianling , Yue Yuanping , Chen Xin , Lange Theis , You Dongfang , Zhao Yang
Published: January 2022

Background

This meta-analysis was designed to explore the relationship between the level of serum potassium and the treatment effect of epidermal growth factor receptor (EGFR) antagonist in advanced non-small cell lung cancer (aNSCLC).

Methods

We searched phase II/III prospective clinical trials on treatment with EGFR antagonists for aNSCLC patients. The objective response rate (ORR) and/or the disease control rate (DCR) and the incidence of hypokalemia of high grade (equal to or greater than grade 3) were summarized from all eligible trials. Heterogeneity, which was evaluated by Cochran’s Q-test and the I2 statistics, was used to determine whether a random effects model or a fixed effects model will be used to calculate pooled proportions. Subgroup analysis was performed on different interventions, line types, phases, and drug numbers.

Results

From 666 potentially relevant articles, 36 clinical trials with a total of 9,761 participants were included in this meta-analysis. The pooled ORR was 16.25% (95%CI = 12.45–21.19) when the incidence of hypokalemia was 0%–5%, and it increased to 34.58% (95%CI = 24.09–45.07) when the incidence of hypokalemia was greater than 5%. The pooled DCR were 56.03% (95%CI = 45.03–67.03) and 64.38% (95%CI = 48.60–80.17) when the incidence rates of hypokalemia were 0%–5% and greater than 5%, respectively. The results of the subgroup analysis were consistent with the results of the whole population, except for not first-line treatment, which may have been confounded by malnutrition or poor quality of life in long-term survival.

Conclusion

The efficacy of anti-EGFR targeted therapy was positively associated with the hypokalemia incidence rate. Treatment effects on the different serum potassium strata need to be considered in future clinical trials with targeted therapy.
Platinum-Based Neoadjuvant Chemotherapy Before Radical Prostatectomy for Locally Advanced Prostate Cancer With Homologous Recombination Deficiency: A Case Report
Authors: Zhuang Junlong , Zhang Shun , Qiu Xuefeng , Fu Yao , Ai Shuyue , Zhao Tingting , Yang Yining , Guo Hongqian
Published: January 2022

More emerging evidence showed that homologous recombination (HR) defect (HRD) may predict sensitivity to platinum agents in metastatic prostate cancer (PCa). Platinum-based neoadjuvant chemotherapy for PCa with HRD has not been reported. Here, we reported a man diagnosed as locally advanced PCa with high Gleason Score (5 + 5) and low PSA level (5.2 ng/ml). Next-generation sequencing (NGS) demonstrated HRD. He received six cycles of platinum-based neoadjuvant chemotherapy before radical prostatectomy (RP). Fifteen months after RP, his PSA level was still undetectable, and no imaging progression was found, indicating a potential role for platinum-based neoadjuvant chemotherapy in locally advanced PCa with HRD.
Characterization With KRAS Mutant Is a Critical Determinant in Immunotherapy and Other Multiple Therapies for Non-Small Cell Lung Cancer
Authors: Shen Mo , Qi Rongbin , Ren Justin , Lv Dongqing , Yang Haihua
Published: January 2022

Non-small cell lung cancer (NSCLC) is a frequent type of cancer, which is mainly characterized clinically by high aggressiveness and high mortality. KRAS oncoprotein is the most common molecular protein detected in NSCLC, accounting for 25% of all oncogenic mutations. Constitutive activation of the KRAS oncoprotein triggers an intracellular cascade in cancer cells, leading to uncontrolled cell proliferation of cancer cells and aberrant cell survival states. The results of multiple clinical trials have shown that different KRAS mutation subtypes exhibit different sensitivities to different chemotherapy regimens. Meanwhile, anti-angiogenic drugs have shown differential efficacy for different subtypes of KRAS mutated lung cancer. It was explored to find if the specificity of the KRAS mutation subtype would affect PD-L1 expression, so immunotherapy would be of potential clinical value for the treatment of some types of KRAS mutations. It was discovered that the specificity of the KRAS mutation affected PD-L1, which opened up immunotherapy as a potential clinical treatment option. After several breakthrough studies, the preliminary test data of many early clinical trials showed that it is possible to directly inhibit KRAS G12C mutation, which has been proved to be a targeted treatment that is suitable for about 10%–12% of patients with advanced NSCLC, having a significant impact on the prolongation of their survival and the improvement of their quality of life. This article reviews the latest progress of treatments for NSCLC with KRAS mutation, in order to gain insight into the biological diversity of lung cancer cells and their potential clinical implications, thereby enabling individualized treatment for patients with KRAS-mutant NSCLC.
Salivary Metabolomics for Prognosis of Oral Squamous Cell Carcinoma
Authors: Ishikawa Shigeo , Sugimoto Masahiro , Konta Tsuneo , Kitabatake Kenichiro , Ueda Shohei , Edamatsu Kaoru , Okuyama Naoki , Yusa Kazuyuki , Iino Mitsuyoshi
Published: January 2022

This study aimed to identify salivary metabolomic biomarkers for predicting the prognosis of oral squamous cell carcinoma (OSCC) based on comprehensive metabolomic analyses. Quantified metabolomics data of unstimulated saliva samples collected from patients with OSCC (n = 72) were randomly divided into the training (n = 35) and validation groups (n = 37). The training data were used to develop a Cox proportional hazards regression model for identifying significant metabolites as prognostic factors for overall survival (OS) and disease-free survival. Moreover, the validation group was used to develop another Cox proportional hazards regression model using the previously identified metabolites. There were no significant between-group differences in the participants’ characteristics, including age, sex, and the median follow-up periods (55 months [range: 3–100] vs. 43 months [range: 0–97]). The concentrations of 5-hydroxylysine (p = 0.009) and 3-methylhistidine (p = 0.012) were identified as significant prognostic factors for OS in the training group. Among them, the concentration of 3-methylhistidine was a significant prognostic factor for OS in the validation group (p = 0.048). Our findings revealed that salivary 3-methylhistidine is a prognostic factor for OS in patients with OSCC.
When Less Is More: Investigating Factors Influencing the Distraction Effect of Virtual Reality From Pain
Authors: Barcatta Katharina , Holl Elisabeth , Battistutta Layla , van der Meulen Marian , Rischer Katharina M.
Published: January 2022

Virtual reality (VR) is a powerful method of redirecting attention away from pain. Yet, little is known about which factors modulate the size of this distraction effect. The aim of this study was to investigate the role of cognitive load and inter-individual differences in the cognitive and affective domain on heat pain thresholds during a VR game. Ninety healthy participants (mean age ± SD: 23.46 ± 3.28; 50% identified as male and 50% as female) played a low and high load version of a VR game while heat pain thresholds and heart rate were recorded. The effects of cognitive load were assessed by computing the difference in pain thresholds between the high and low load condition for each participant. In addition, we computed the difference in heart rate variability (HRV) measures between both conditions to explore whether these would be correlated with the difference in heat pain thresholds. Prior to the VR session, participants completed questionnaires about their emotional distress, pain-related cognitions, and different executive functioning tasks. Contrary to our expectations, not all participants benefitted from a higher load in terms of distraction from pain. Logistic regression analysis revealed that participants who reported more emotional distress were more likely to exhibit higher pain thresholds in the low relative to the high load condition. Accordingly, these participants tended to show marginally higher HRV in the low compared to the high load condition. Our study demonstrates that the potential benefits of an increased cognitive load in VR on pain sensitivity depends on individual differences in affective state.