bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of microRNAs as diagnostic biomarkers for atrial fibrillation: a systematic review and meta-analysis
Authors: Rizal Ardian , Waranugraha Yoga , Wikananda Adhika Prastya , Yuniadi Yoga
Published: April 2023

Background

Genetic factors contribute to the AF pathophysiology by altering the structural and functional properties of proteins involved in different cellular activities. MicroRNAs (miRNAs), which take part in structural and electrical remodeling during the AF evolution, are important genetic elements that must be considered. The aim of study is to determine correlation between the expression of miRNAs and the development of AF, as well as to explain any potential importance of genetic factors in the AF diagnosis.

Methods and Results

Online scientific databases, including Cochrane, ProQuest, PubMed, and Web of Science were used to conduct the literature search. The keywords were associated with or characterized the relationship between miRNAs and AF. The pooled sensitivity and specificity statistical parameters were analyzed using a random-effects model. The miRNAs had a combined sensitivity and specificity of 0.80 (95% CI = 0.70–0.87) and 0.75 (95% CI = 0.64–0.83) for the diagnosis of AF, respectively. The area under the SROC was 0.84 (95% CI = 0.81–0.87). The DOR was 11.80 (95% CI = 6.79–20.50). This study also revealed that miRNAs had a pooled PLR of 3.16 (95% CI = 2.24–4.45) and NLR of 0.27 (95% CI = 0.18–0.39) for the diagnosis of AF. The miR-425-5p demonstrated the highest sensitivity (0.96, 95% CI, 0.89–0.99).

Conclusion

The meta-analysis revealed substantial connection between miRNA expression dysregulation and AF, supporting the potential diagnostic role of miRNAs. The miR-425-5p has potential role as a biomarker for AF.
Right ventricular failure: Current strategies and future development
Authors: Monteagudo-Vela María , Tindale Alexander , Monguió-Santín Emilio , Reyes-Copa Guillermo , Panoulas Vasileios
Published: April 2023

Right heart failure can be defined as a clinical syndrome consisting of signs and symptoms of heart failure resulting from right ventricular dysfunction. Function is normally altered due to three mechanisms: (1) pressure overload (2) volume overload, or (3) a decrease in contractility due to ischaemia, cardiomyopathy or arrythmias. Diagnosis is based upon a combination of clinical assessment plus echocardiographic, laboratory and haemodynamic parameters, and clinical risk assessment. Treatment includes medical management, mechanical assist devices and transplantation if recovery is not observed. Distinct attention to special circumstances such as left ventricular assist device implantation should be sought. The future is moving towards new therapies, both pharmacological and device centered. Immediate diagnosis and management of RV failure, including mechanical circulatory support where needed, alongside a protocolized approach to weaning is important in successfully managing right ventricular failure.
Specific correction of pyruvate kinase deficiency-causing point mutations by CRISPR/Cas9 and single-stranded oligodeoxynucleotides
Authors: Fañanas-Baquero Sara , Morín Matías , Fernández Sergio , Ojeda-Perez Isabel , Dessy-Rodriguez Mercedes , Giurgiu Miruna , Bueren Juan A. , Moreno-Pelayo Miguel Angel , Segovia Jose Carlos , Quintana-Bustamante Oscar
Published: April 2023

Pyruvate kinase deficiency (PKD) is an autosomal recessive disorder caused by mutations in the PKLR gene. PKD-erythroid cells suffer from an energy imbalance caused by a reduction of erythroid pyruvate kinase (RPK) enzyme activity. PKD is associated with reticulocytosis, splenomegaly and iron overload, and may be life-threatening in severely affected patients. More than 300 disease-causing mutations have been identified as causing PKD. Most mutations are missense mutations, commonly present as compound heterozygous. Therefore, specific correction of these point mutations might be a promising therapy for the treatment of PKD patients. We have explored the potential of precise gene editing for the correction of different PKD-causing mutations, using a combination of single-stranded oligodeoxynucleotides (ssODN) with the CRISPR/Cas9 system. We have designed guide RNAs (gRNAs) and single-strand donor templates to target four different PKD-causing mutations in immortalized patient-derived lymphoblastic cell lines, and we have detected the precise correction in three of these mutations. The frequency of the precise gene editing is variable, while the presence of additional insertions/deletions (InDels) has also been detected. Significantly, we have identified high mutation-specificity for two of the PKD-causing mutations. Our results demonstrate the feasibility of a highly personalized gene-editing therapy to treat point mutations in cells derived from PKD patients.
Visual analysis of the research hotspots in neoadjuvant therapy for patients with gastric cancer
Authors: Chen Tianxing , Liu Yating , Gao Jing , Zhang Dekui
Published: April 2023

Objective

This study aimed to analyze the research hotspots and frontiers in the field of neoadjuvant therapy for patients with gastric cancer (GC) using bibliometric and identify its developmental trends.

Methods

The literature related to neoadjuvant therapy for GC systematically retrieved between 1991 and 2021. Bibliometric methods were used to analysis the research hotspots and trends by CiteSpace and VOS-viewer software.

Results

The number of studies related to neoadjuvant therapies for GC showed an upward trend. Moreover, the current research directions were mostly focused on the clinical trials and applications of neoadjuvant therapies for GC. The frontier research directions included microsatellite instability, peritoneal metastasis, randomized controlled trials, multicenter studies, and regression analysis.

Conclusions

The interest and attention of researchers in this field are still growing. In the past five years, the literature related to neoadjuvant therapy and immunotherapy for gastric cancer has exploded. It is still an important period and a key stage for the development of neoadjuvant therapy for gastric cancer.
Identification of TREM2-positive tumor-associated macrophages in esophageal squamous cell carcinoma: implication for poor prognosis and immunotherapy modulation
Authors: Li Hongmu , Miao Yu , Zhong Leqi , Feng Songjie , Xu Yue , Tang Lu , Wu Chun , Zhang Xianzhou , Gu Ling , Diao Hengyi , Wang Huiyun , Wen Zhesheng , Yang Minglei
Published: April 2023

Background

It is now understood that the effectiveness of checkpoint immunotherapy can be impaired by immunosuppressive tumor-associated macrophages (TAMs). Nonetheless, the impact of different TAM subpopulations on the antitumor immune response remains unclear, mainly due to their heterogeneity. Herein, we identified a novel TAM subpopulation in esophageal squamous cell carcinoma (ESCC) that might contribute to poor clinical outcomes and immunotherapy modulation.

Methods and results

We analyzed two single-cell RNA sequencing (scRNA-seq) datasets (GSE145370 and GSE160269) of esophageal squamous cell carcinoma to identify a novel TREM2-positive TAM subpopulation characterized by upregulation of TREM2, C1QC, C1QB, C1QA, SPP1, and APOE. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) demonstrated that these genes were significantly overexpressed in ESCC. Multiplex immunofluorescence validated the infiltration of TREM2+ TAMs in ESCC tissues, which correlated with poorer overall survival (OS). The scRNA-seq analysis in dataset GSE120575 indicated significant enrichment of TREM2+ TAMs in melanoma patients (n=48) with poor immunotherapy response, which had an identical gene signature with TREM2+ TAMs from ESCC. Analysis of 29 bulk-RNA melanoma samples from dataset GSE78220 revealed that a gene signature of 40 genes associated with TREM2+ TAMs was upregulated in the transcriptome of melanomas that did not respond to anti-PD1 therapy. Validation in the TCGA ESCC cohort (n=80) showed that a high enrichment score of the TREM2+ TAM was associated with poor prognosis. In addition, 10 ESCC patients treated with anti-PD1 therapy suggested that patients who are not sensitive to immunotherapy have higher density of TREM2+TAMs infiltration.

Conclusion

Overall, TREM2+ TAM infiltration in ESCC is associated with poor prognosis and may serve as a biomarker for predicting outcomes and immunotherapy modulation in this patient population. modulation; single-cell RNA sequencing
Development of a high-resolution mass-spectrometry-based method and software for human leukocyte antigen typing
Authors: Wang Kun , Sun Zetao , Zhu Fei , Xu Yunping , Zhou Feng
Published: April 2023

Introduction

The human leukocyte antigen (HLA) system plays a critical role in the human immune system and is strongly associated with immune recognition and rejection in organ transplantation. HLA typing method has been extensively studied to increase the success rates of clinical organ transplantation. However, while polymerase chain reaction sequence-based typing (PCR-SBT) remains the gold standard, cis/trans ambiguity and nucleotide sequencing signal overlay during heterozygous typing present a problem. The high cost and low processing speed of Next Generation Sequencing (NGS) also render this approach inadequate for HLA typing.

Methods and materials

To address these limitations of the current HLA typing methods, we developed a novel typing technology based on nucleic acid mass spectrometry (MS) of HLA. Our method takes advantage of the high-resolution mass analysis function of MS and HLAMSTTs (HLA MS Typing Tags, some short fragment PCR amplification target products) with precise primer combinations.

Results

We correctly typed HLA by measuring the molecular weights of HLAMSTTs with single nucleotide polymorphisms (SNPs). In addition, we developed a supporting HLA MS typing software to design PCR primers, construct the MS database, and select the best-matching HLA typing results. With this new method, we typed 16 HLA-DQA1 samples, including 6 homozygotes and 10 heterozygotes. The MS typing results were validated by PCR-SBT.

Discussion

The MS HLA typing method is rapid, efficient, accurate, and readily applicable to typing of homozygous and heterozygous samples.
Who and how, DNA sensors in NETs-driven inflammation
Authors: Aubé Félix-Antoine , Bidias Amel , Pépin Geneviève
Published: April 2023

During infections, neutrophil extracellular traps act like a meshwork of molecules that captures microbes. In contrast, during sterile inflammation the presence of NETs is usually associated with tissue damage and uncontrolled inflammation. In this context, DNA acts both as activator of NETs formation and immunogenic molecule fueling inflammation within the injured tissue microenvironment. Pattern recognition receptors that specifically bind to and get activated by DNA such as Toll-like receptor-9 (TLR9), cyclic GMP-AMP synthase (cGAS), Nod-like receptor protein 3 (NLRP3) and Absence in Melanoma-2 (AIM2) have been reported to play a role in NETs formation and detection. However, how these DNA sensors contribute to NETs-driven inflammation is not well understood. Whether these DNA sensors have unique roles or on the contrary they are mostly redundant is still elusive. In this review, we summarize the known contribution of the above DNA sensors to the formation and detection of NETs in the context of sterile inflammation. We also highlight scientific gaps needed to be addressed and propose future direction for therapeutic targets.
The contrast in suspended particle dynamics at surface and near bottom on the river-dominated northern South China Sea shelf in summer: implication on physics and biogeochemistry coupling
Authors: Lee Jay , Liu James T. , Lin Yu-Shih , Chen Chen-Tung Arthur , Wang Bo-Shian
Published: April 2023

To understand the process-response relations among physical forcing and biogeochemical properties of suspended particles (SPs) in the river-dominated northern South China Sea shelf, a 5-day shipboard observation was conducted at a fixed location on the dispersal pathway of the Zhujiang (Pearl) River plume (ZRP) in the summer of 2016. Instrumented moorings were deployed near the sampling site to record the flow and wave fields every 10 minutes. Hydrographic properties were measured hourly to identify different water masses. Water and SPs samples at the surface (3 m) and near the bottom (3 m above the bed) were taken every 3 h for the analyses of nutrients, chlorophyll-a (Chl-a), and particulate organic matter (POM including POC, PN, and δ13CPOC). Meanwhile, the grain-size composition of SPs and seafloor sediment were also analyzed. Results showed that monsoon winds drove cold upwelling and ZRP waters at the surface. Both the upwelling and ZRP regimes contained newly produced marine phytoplankton based on low POC/Chl-a ratio (PC ratio) and enriched δ13CPOC. However, SPs in the ZRP regime were smaller (<153 µm), having denser particle bulk density, and less enriched δ13CPOC, indicating different bio-communities from the upwelling regime. EOF analysis of the surface data suggested that mixing processes and the dispersal of the ZRP regime were mainly controlled by far-field storm winds, tidal modulation, and strength of mixing. On the other hand, a bottom nepheloid layer (BNL) was observed, mainly consisting of SPs<63 μm with higher bulk density than SPs at the surface. POM in the BNL was degraded and δ13CPOC-depleted according to the PC ratio and δ13CPOC. EOF analysis of the near-bottom data indicated that the dominant physical processes influencing the biogeochemical properties of SPs in the BNL were jointly the upwelling-associated lateral transport (first order) and tide-related resuspension (second order). Our study identified the contrast between the surface and near-bottom regimes with the coupling patterns among physical forcing and physiochemical properties of SPs using good constraints on particle dynamics and particle sources.
Calibration of fish counts in video surveys: a case study from the Southeast Reef Fish Survey
Authors: Bacheler Nathan M. , Shertzer Kyle W. , Schobernd Zebulon H. , Coggins Lewis G.
Published: April 2023

Changes to sampling gears or vessels can influence the catchability or detectability of fish, leading to biased trends in abundance. Despite the widespread use of underwater video cameras to index fish abundance and the rapid advances in video technology, few studies have focused on calibrating data from different cameras used in underwater video surveys. We describe a side-by-side calibration study (N = 143 paired videos) undertaken in 2014 to account for a camera change in the Southeast Reef Fish Survey, a regional-scale, multi-species reef fish survey along the southeast United States Atlantic coast. Slope estimates from linear regression for the 16 species included in the analyses ranged from 0.21 to 0.98, with an overall mean of 0.57, suggesting that original cameras (Canon Vixia HF-S200) observed an average of 43% fewer fish than newer cameras (GoPro Hero 3+). Some reef fish species had limited calibration sample sizes, such that borrowing calibration information from related or unrelated species was justified in some cases. We also applied calibrations to 11-year video time series of relative abundance of scamp Mycteroperca phenax and red snapper Lutjanus campechanus (N = 13,072 videos), showing that calibrations were critical to separating changes in camera sightability from true changes in abundance. We recommend calibrating data from video cameras anytime changes occur, and pairing video cameras to the extent possible to control for the spatial and temporal variability inherent in fish populations and environmental conditions. Following these guidelines, researchers will be able to maintain the integrity of valuable long-term video datasets despite intentional or unavoidable changes to video cameras over time.
The impact of metakaolin on the hydration of tricalcium silicate: effect of C-A-S-H precipitation
Authors: Sowoidnich T. , Cölfen H. , Rößler C. , Damidot D. , Ludwig H.-M.
Published: April 2023

Introduction:Metakaolin (MK) is used as supplementary cementitious material to reduce the CO2footprint of Portland cements. However, the early hydration of Portland cement (OPC) is often retarded due to its use. The present work investigates the mechanisms of this retardation. Focus is laid on the interaction of MK with the main clinker phase C3S (Ca3SiO5, pure form of alite) that is known to govern the kinetics of early hydration of OPC.

Methods:Hydration reactions of MK and C3S were analysed by optical emission spectroscopy, electron microscopy, thermal analysis, X-ray diffraction and reaction calorimetry.

Results:Results on MK showed that compared to sodium ions the presence of calcium ions reduced the maximum amounts of silicate and aluminate ions released into solution by MK. For MK + C3S mixtures, C-A-S-H was formed at the surfaces of both C3S and MK within minutes with a composition of (CaO)1.3(SiO2)0.8(Al2O3)0.2(H2O)2.7. The solubility constant of (CaO)1.3(SiO2)0.8(Al2O3)0.2(H2O)2.7was determined.

Discussion:C-A-S-H appeared to be an unsuitable substrate for C-S-H nucleation. Therefore, its formation during early hydration is expected to play an important role in the retardation of C3S hydration. Indeed, when C-A-S-H seeds are formed, less C-S-H seeds are formed leading to lengthen the duration of the induction period. The presence of sulfate ions reduces the amount of C-A-S-H seeds as most aluminate ions are consumed to form ettringite. Consequently, sulfate ions induce an increase of the hydration kinetics such as observed in MK + C3S mixtures.
Strength of Onyx-based composite 3D printing materials according to fiber reinforcement
Authors: Lee Gyu-Wol , Kim Tae-Hyun , Yun Jong-Hwan , Kim Nam-Joo , Ahn Ki-Hwan , Kang Min-Soo
Published: April 2023

This study evaluates the mechanical strength of 3D-printed objects of composite material. The composite material considered in this study comprises onyx as the base material with glass fiber and carbon fiber as the internal reinforcements. 3D printing using composite materials generally involves laminating fiber reinforcements in the form of layers within the printed part. To analyze the effect of such reinforcements on the printed parts, specimens were prepared by varying the number of layers and arrangement conditions of the reinforcement. The analysis shows that the tensile strength of the composite increases with the number of reinforcement layers due to the effect of the fibers on the longitudinal direction and a larger bonding area between the internal Onyx and the fibers. Furthermore, higher tensile strength is observed when the reinforcements are laminated at regular intervals than when they are arranged in the center. This study serves as a database for 3D printing fiber-reinforced composites aiding future research in comparing and optimizing their strength according to the 3D printing conditions.
Pre-operative prognostic nutrition index and post-operative pneumonia in aneurysmal subarachnoid hemorrhage patients
Authors: Xu Manman , Zhang Liang , Wang Juan , Cheng Longyang , Chen Chunlei , Li Shaoya , Dai Haibin , Zhao Penglai , Hang Chunhua
Published: April 2023

Background and objective

Post-operative pneumonia (POP), a common complication, may be associated with prolonged hospitalization and long-term mortality in aneurysmal subarachnoid hemorrhage (aSAH) patients. This study aimed to explore the association between pre-operative prognostic nutrition index (PNI) and POP in aSAH patients.

Methods

A total of 280 aSAH patients were enrolled from Nanjing Drum Tower Hospital. PNI was calculated as follows: [10 × albumin(gr/dl)] + [0.005 × absolute pre-operative lymphocyte count (per mm3)]. We utilized multivariate analyses, restricted cubic spline, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) to elucidate the role of PNI in POP.

Results

Pre-operative PNI levels in the POP group were higher, compared with the non-POP group (41.0 [39.0, 45.4] vs. 44.4 [40.5, 47.3], P = 0.001). When we included PNI as a categorical variable in the multivariate analysis, the levels of PNI were associated with POP (odds ratio, 0.433; 95% confidence interval, 0.253–0.743; P=0.002). In addition, when we included PNI as a continuous variable in the multivariate analysis, the PNI levels were also associated with POP (odds ratio, 0.942; 95% confidence interval, 0.892–0.994; P = 0.028). The level of albumin was also a predictor of the occurrence of POP, with a lower diagnostic power than PNI [AUC: 0.611 (95% confidence interval, 0.549–0.682; P = 0.001) for PNI vs. 0.584 (95% confidence interval, 0.517–0.650; P = 0.017) for albumin]. Multivariable-adjusted spline regression indicated a linear dose–response association between PNI and POP in aSAH participants (P for linearity = 0.027; P for non-linearity = 0.130). Reclassification assessed by IDI and NRI was significantly improved with the addition of PNI to the conventional model of POP in aSAH patients (NRI: 0.322 [0.089–0.555], P = 0.007; IDI: 0.016 [0.001–0.031], P = 0.040).

Conclusion

The lower levels of pre-operative PNI may be associated with the higher incidence of POP in aSAH patients. Neurosurgeons are supposed to pay more attention to pre-operative nutrition status in aSAH patients.
Predictive model of recurrent ischemic stroke: model development from real-world data
Authors: Elhefnawy Marwa Elsaeed , Sheikh Ghadzi Siti Maisharah , Albitar Orwa , Tangiisuran Balamurugan , Zainal Hadzliana , Looi Irene , Sidek Norsima Nazifah , Aziz Zariah Abdul , Harun Sabariah Noor
Published: April 2023

Background

There are established correlations between risk factors and ischemic stroke (IS) recurrence; however, does the hazard of recurrent IS change over time? What is the predicted baseline hazard of recurrent IS if there is no influence of variable predictors? This study aimed to quantify the hazard of recurrent IS when the variable predictors were set to zero and quantify the secondary prevention influence on the hazard of recurrent ischemic stroke.

Methods

In the population cohort involved in this study, data were extracted from 7,697 patients with a history of first IS attack registered with the National Neurology Registry of Malaysia from 2009 to 2016. A time-to-recurrent IS model was developed using NONMEM version 7.5. Three baseline hazard models were fitted into the data. The best model was selected using maximum likelihood estimation, clinical plausibility, and visual predictive checks.

Results

Within the maximum 7.37 years of follow-up, 333 (4.32%) patients had at least one incident of recurrent IS. The data were well described by the Gompertz hazard model. Within the first 6 months after the index IS, the hazard of recurrent IS was predicted to be 0.238, and 6 months after the index attack, it reduced to 0.001. The presence of typical risk factors such as hyperlipidemia [HR, 2.22 (95%CI: 1.81–2.72)], hypertension [HR, 2.03 (95%CI: 1.52–2.71)], and ischemic heart disease [HR, 2.10 (95%CI: 1.64–2.69)] accelerated the hazard of recurrent IS, but receiving antiplatelets (APLTs) upon stroke decreased this hazard [HR, 0.59 (95%CI: 0.79–0.44)].

Conclusion

The hazard of recurrent IS magnitude differs during different time intervals based on the concomitant risk factors and secondary prevention.
Typical pantothenate kinase-associated neurodegeneration caused by compound heterozygous mutations in PANK2 gene in a Chinese patient: a case report and literature review
Authors: Tao Yilun , Zhao Chen , Han Dong , Wei Yiju , Wang Lihong , Song Wenxia , Li Xiaoze
Published: April 2023

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare genetic neurodegenerative disorder with brain iron accumulation characterized as dysarthria, spasticity, cognitive impairment, parkinsonism, and retinopathy. PKAN is caused by biallelic mutations in the mitochondrial pantothenate kinase 2 (PANK2) gene. Herein, we report a 4-year-old patient with PKAN from a Han Chinese family, who presented with developmental regression, progressive inability to walk, and limb tremors. Neuroimaging demonstrated “eye-of-the-tiger” sign. Whole exome sequencing (WES) identified compound heterozygous mutations of c.1213T>G (p.Tyr405Asp) and c.1502T>A (p.Ile501Asn) in PANK2 gene. In addition, a review of all known PANK2 variants observed in reported PKAN patients was conducted, to improve understanding of the genotype-phenotype associations that occur in PKAN patients.
Identifying the intervention mechanisms of polydatin in hyperuricemia model rats by using UHPLC-Q-Exactive Orbitrap mass spectroscopy metabonomic approach
Authors: Ge Xueli , Su Zhenguo , Wang Yuhao , Zhao Xue , Hou Kaifei , Zheng Shuna , Zeng Pengjiao , Shi Zhongqi , Hu Senhao , Wang Yuqing , Zhou Mengchen , Zhang Jiayu , Li Xiulian
Published: April 2023

Introduction

Polydatin is a biologically active compound found in mulberries, grapes, and Polygonum cuspidatum, and it has uric acid-lowering effects. However, its urate-lowering effects and the molecular mechanisms underlying its function require further study.

Methods

In this study, a hyperuricemic rat model was established to assess the effects of polydatin on uric acid levels. The body weight, serum biochemical indicators, and histopathological parameters of the rats were evaluated. A UHPLC-Q-Exactive Orbitrap mass spectrometry-based metabolomics approach was applied to explore the potential mechanisms of action after polydatin treatment.

Results

The results showed a trend of recovery in biochemical indicators after polydatin administration. In addition, polydatin could alleviate damage to the liver and kidneys. Untargeted metabolomics analysis revealed clear differences between hyperuricemic rats and the control group. Fourteen potential biomarkers were identified in the model group using principal component analysis and orthogonal partial least squares discriminant analysis. These differential metabolites are involved in amino acid, lipid, and energy metabolism. Of all the metabolites, the levels of L-phenylalanine, L-leucine, O-butanoylcarnitine, and dihydroxyacetone phosphate decreased, and the levels of L-tyrosine, sphinganine, and phytosphingosine significantly increased in hyperuricemic rats. After the administration of polydatin, the 14 differential metabolites could be inverted to varying degrees by regulating the perturbed metabolic pathway.

Conclusion

This study has the potential to enhance our understanding of the mechanisms of hyperuricemia and demonstrate that polydatin is a promising potential adjuvant for lowering uric acid levels and alleviating hyperuricemia-related diseases.
Bacterial lipopolysaccharide-related genes are involved in the invasion and recurrence of prostate cancer and are related to immune escape based on bioinformatics analysis
Authors: Che Bangwei , Zhang Wenjun , Li Wei , Tang Kaifa , Yin Jingju , Liu Miao , Xu Shenghan , Huang Tao , Yu Ying , Huang Kunyuan , Peng Zheng , Zha Cheng
Published: April 2023

Background

The composition of the tumor microbial microenvironment participates in the whole process of tumor disease. However, due to the limitations of the current technical level, the depth and breadth of the impact of microorganisms on tumors have not been fully recognized, especially in prostate cancer (PCa). Therefore, the purpose of this study is to explore the role and mechanism of the prostate microbiome in PCa based on bacterial lipopolysaccharide (LPS)-related genes by means of bioinformatics.

Methods

The Comparative Toxicogenomics Database (CTD) was used to find bacterial LPS- related genes. PCa expression profile data and clinical data were acquired from TCGA, GTEx, and GEO. The differentially expressed LPS-related hub genes (LRHG) were obtained by Venn diagram, and gene set enrichment analysis (GSEA) was used to investigate the putative molecular mechanism of LRHG. The immune infiltration score of malignancies was investigated using single-sample gene set enrichment analysis (ssGSEA). Using univariate and multivariate Cox regression analysis, a prognostic risk score model and nomogram were developed.

Results

6 LRHG were screened. LRHG were involved in functional phenotypes such as tumor invasion, fat metabolism, sex hormone response, DNA repair, apoptosis, and immunoregulation. And it can regulate the immune microenvironment in the tumor by influencing the antigen presentation of immune cells in the tumor. And a prognostic risk score and the nomogram, which were based on LRHG, showed that the low-risk score has a protective effect on patients.

Conclusion

Microorganisms in the PCa microenvironment may use complex mechanism and networks to regulate the occurrence and development of PCa. Bacterial lipopolysaccharide-related genes can help build a reliable prognostic model and predict progression-free survival in patients with prostate cancer.
Radiotherapy planning in a prostate cancer phantom model with intraprostatic dominant lesions using stereotactic body radiotherapy with volumetric modulated arcs and a simultaneous integrated boost
Authors: Skrobala Agnieszka , Kruszyna-Mochalska Marta , Graczyk Kinga , Ryczkowski Adam , Fundowicz Magdalena , Milecki Piotr , Malicki Julian
Published: April 2023

Aim

In the treatment of prostate cancer with radiation therapy, the addition of a simultaneous integrated boost (SIB) to the dominant intraprostatic lesions (DIL) may improve local control. In this study, we aimed to determine the optimal radiation strategy in a phantom model of prostate cancer using volumetric modulated arc therapy for stereotactic body radiotherapy (SBRT-VMAT) with a SIB of 1-4 DILs.

Methods

We designed and printed a three-dimensional anthropomorphic phantom pelvis to simulate individual patient structures, including the prostate gland. A total of 36.25 Gy (SBRT) was delivered to the whole prostate. The DILs were irradiated with four different doses (40, 45, 47.5, and 50 Gy) to assess the influence of different SIB doses on dose distribution. The doses were calculated, verified, and measured using both transit and non-transit dosimetry for patient-specific quality assurance using a phantom model.

Results

The dose coverage met protocol requirements for all targets. However, the dose was close to violating risk constraints to the rectum when four DILs were treated simultaneously or when the DILs were located in the posterior segments of the prostate. All verification plans passed the assumed tolerance criteria.

Conclusions

Moderate dose escalation up to 45 Gy seems appropriate in cases with DILs located in posterior prostate segments or if there are three or more DILs located in other segments.
Challenges in nodal peripheral T-cell lymphomas: from biological advances to clinical applicability
Authors: Zain Jasmine , Kallam Avyakta
Published: April 2023

T cell lymphomas are a heterogenous group with varying biological and clinical features that tend to have poor outcomes with a few exceptions. They account for 10-15% of all non-Hodgkin lymphomas (NHL), and 20% of aggressive NHL. There has been little change in the overall prognosis of T cell lymphomas over the last 2 decades. Most subtypes carry an inferior prognosis when compared to the B cell lymphomas, with a 5-year OS of 30%. Gene expression profiling and other molecular techniques has enabled a deeper understanding of these differences in the various subtypes as reflected in the latest 5th WHO and ICC classification of T cell lymphomas. It is becoming increasingly clear that therapeutic approaches that target specific cellular pathways are needed to improve the clinical outcomes of T cell lymphomas. This review will focus on nodal T cell lymphomas and describe novel treatments and their applicability to the various subtypes.
A prognostic model based on gene expression parameters predicts a better response to bortezomib-containing immunochemotherapy in diffuse large B-cell lymphoma
Authors: Mosquera Orgueira Adrián , Díaz Arías Jose Ángel , Serrano Martín Rocio , Portela Piñeiro Victor , Cid López Miguel , Peleteiro Raíndo Andrés , Bao Pérez Laura , González Pérez Marta Sonia , Pérez Encinas Manuel Mateo , Fraga Rodríguez Máximo Francisco , Vallejo Llamas Juan Carlos , Bello López José Luis
Published: April 2023

Diffuse Large B-cell Lymphoma (DLBCL) is the most common type of aggressive lymphoma. Approximately 60% of fit patients achieve curation with immunochemotherapy, but the remaining patients relapse or have refractory disease, which predicts a short survival. Traditionally, risk stratification in DLBCL has been based on scores that combine clinical variables. Other methodologies have been developed based on the identification of novel molecular features, such as mutational profiles and gene expression signatures. Recently, we developed the LymForest-25 profile, which provides a personalized survival risk prediction based on the integration of transcriptomic and clinical features using an artificial intelligence system. In the present report, we studied the relationship between the molecular variables included in LymForest-25 in the context of the data released by the REMoDL-B trial, which evaluated the addition of bortezomib to the standard treatment (R-CHOP) in the upfront setting of DLBCL. For this, we retrained the machine learning model of survival on the group of patients treated with R-CHOP (N=469) and then made survival predictions for those patients treated with bortezomib plus R-CHOP (N=459). According to these results, the RB-CHOP scheme achieved a 30% reduction in the risk of progression or death for the 50% of DLBCL patients at higher molecular risk (p-value 0.03), potentially expanding the effectiveness of this treatment to a wider patient population as compared with other previously defined risk groups.
Newer indications for neuromonitoring in critically ill neonates
Authors: Variane Gabriel F. T. , Pietrobom Rafaela F. R. , Noh Caroline Y. , Van Meurs Krisa P. , Chock Valerie Y.
Published: April 2023

Continuous neuromonitoring in the neonatal intensive care unit allows for bedside assessment of brain oxygenation and perfusion as well as cerebral function and seizure identification. Near-infrared spectroscopy (NIRS) reflects the balance between oxygen delivery and consumption, and use of multisite monitoring of regional oxygenation provides organ-specific assessment of perfusion. With understanding of the underlying principles of NIRS as well as the physiologic factors which impact oxygenation and perfusion of the brain, kidneys and bowel, changes in neonatal physiology can be more easily recognized by bedside providers, allowing for appropriate, targeted interventions. Amplitude-integrated electroencephalography (aEEG) allows continuous bedside evaluation of cerebral background activity patterns indicative of the level of cerebral function as well as identification of seizure activity. Normal background patterns are reassuring while abnormal background patterns indicate abnormal brain function. Combining brain monitoring information together with continuous vital sign monitoring (blood pressure, pulse oximetry, heart rate and temperature) at the bedside may be described as multi-modality monitoring and facilitates understanding of physiology. We describe 10 cases in critically ill neonates that demonstrate how comprehensive multimodal monitoring provided greater recognition of the hemodynamic status and its impact on cerebral oxygenation and cerebral function thereby informing treatment decisions. We anticipate that there are numerous other uses of NIRS as well as NIRS in conjunction with aEEG which are yet to be reported.
Noninvasive positive-pressure ventilation for children with acute asthma: a meta-analysis of randomized controlled trials
Authors: Dai Jiajia , Wang Libo , Wang Fang , Wang Lu , Wen Qingfen
Published: April 2023

Background

Noninvasive positive-pressure ventilation (NPPV) can be effective in children with acute asthma. However, clinical evidence remains limited. The objective of the meta-analysis was to systematically assess NPPV's effectiveness and safety in treating children with acute asthma.

Methods

Relevant randomized controlled trials were obtained from electronic resources, including PubMed, Embase, Cochrane's Library, Wanfang, and CNKI databases. The influence of potential heterogeneity was taken into account before using a random-effect model to pool the results.

Results

A total of 10 RCTs involving 558 children with acute asthma were included in the meta-analysis. Compared to conventional treatment alone, additional use of NPPV significantly improved early blood gas parameters such as the oxygen saturation (mean difference [MD]: 4.28%, 95% confidence interval [CI]: 1.51 to 7.04, p = 0.002; I2 = 80%), partial pressure of oxygen (MD: 10.61 mmHg, 95% CI: 6.06 to 15.16, p < 0.001; I2 = 89%), and partial pressure of carbon dioxide (MD: −6.29 mmHg, 95% CI: −9.81 to −2.77, p < 0.001; I2 = 85%) in the arterial blood. Moreover, NPPV was also associated with early reduced respiratory rate (MD: −12.90, 95% CI: −22.21 to −3.60, p = 0.007; I2 = 71%), improved symptom score (SMD: −1.85, 95% CI: −3.65 to −0.07, p = 0.04; I2 = 92%), and shortened hospital stay (MD: −1.82 days, 95% CI: −2.32 to −1.31, p < 0.001; I2 = 0%). No severe adverse events related to NPPV were reported.

Conclusions

NPPV in children with acute asthma is associated with improved gas exchange, decreased respiratory rates, a lower symptom score, and a shorter hospital stay. These results suggest that NPPV may be as effective and safe as conventional treatment for pediatric patients with acute asthma.
Targeting the formation of estrogens for treatment of hormone dependent diseases–current status
Authors: Rižner Tea Lanišnik , Romano Andrea
Published: April 2023

Local formation and action of estrogens have crucial roles in hormone dependent cancers and benign diseases like endometriosis. Drugs that are currently used for the treatment of these diseases act at the receptor and at the pre-receptor levels, targeting the local formation of estrogens. Since 1980s the local formation of estrogens has been targeted by inhibitors of aromatase that catalyses their formation from androgens. Steroidal and non-steroidal inhibitors have successfully been used to treat postmenopausal breast cancer and have also been evaluated in clinical studies in patients with endometrial, ovarian cancers and endometriosis. Over the past decade also inhibitors of sulfatase that catalyses the hydrolysis of inactive estrogen-sulfates entered clinical trials for treatment of breast, endometrial cancers and endometriosis, with clinical effects observed primarily in breast cancer. More recently, inhibitors of 17beta-hydroxysteroid dehydrogenase 1, an enzyme responsible for formation of the most potent estrogen, estradiol, have shown promising results in preclinical studies and have already entered clinical evaluation for endometriosis. This review aims to provide an overview of the current status of the use of hormonal drugs for the major hormone-dependent diseases. Further, it aims to explain the mechanisms behind the -sometimes- observed weak effects and low therapeutic efficacy of these drugs and the possibilities and the advantages of combined treatments targeting several enzymes in the local estrogen formation, or drugs acting with different therapeutic mechanisms.
Management and prediction of immune-related adverse events for PD1/PDL-1 immunotherapy in colorectal cancer
Authors: Sun Liting , Meng Cong , Zhang Xiao , Gao Jiale , Wei Pengyu , Zhang Jie , Zhang Zhongtao
Published: April 2023

Programmed cell death protein (PD-1) is an important immunosuppressive molecule, which can inhibit interaction between PD-1 and its ligand PD-L1, further enhancing the T cell response and anti-tumor activity, which is called immune checkpoint blockade. Immunotherapy, represented by immune checkpoint inhibitors, has opened up a new era of tumor treatment and is gradually being applied to colorectal cancer recently. Immunotherapy was reported could achieve a high objective response rate (ORR) for colorectal cancer with high microsatellite instability (MSI), thus opening up a new era of colorectal cancer immunotherapy. Along with the increasing use of PD1 drugs in colorectal cancer, we should pay more attention to the adverse effects of these immune drugs while seeing the hope. Immune-related adverse events (irAEs) caused by immune activation and immune homeostasis during anti-PD-1/PD-L1 therapy can affect multi-organ and even be fatal in serious cases. Therefore, understanding irAEs is essential for their early detection and appropriate management. In this article, we review the irAEs that occur during the treatment of colorectal cancer patients with PD-1/PD-L1 drugs, analyze the current controversies and challenges, and point out future directions that should be explored, including exploring efficacy predictive markers and optimizing the paradigm of individualized immunotherapy.
Association between arterial stiffness and orthostatic hypotension: A systematic review and meta-analysis
Authors: Saz-Lara Alicia , Cavero-Redondo Iván , Martínez-Vizcaíno Vicente , Lucerón-Lucas-Torres Maribel , Pascual-Morena Carlos , Sequí-Domínguez Irese
Published: April 2023

Background: Orthostatic hypotension, defined as a decrease in blood pressure on standing, is associated with an increased risk of mortality and cardiovascular events in the general population. In addition, it has recently been suggested that arterial stiffness is independently associated with orthostatic hypotension, which may be due to a loss of the buffering effect of the ascending aorta and an early return of pressure waves. However, the specific mechanisms underlying this association remain unclear. Thus, we aimed to evaluate the association between orthostatic hypotension and arterial stiffness in the adult population.

Methods: PubMed, Scopus, Web of Science, and Cochrane Library databases were searched from inception to 31 January 2022. The DerSimonian and Laird method was used to calculate pooled odds ratio (OR) estimates and their respective 95% confidence intervals (95% CI) for the association between orthostatic hypotension and arterial stiffness.

Results: Overall, 11 studies were included, with a total of 10,611 subjects. Our results showed that increased arterial stiffness raises the risk of orthostatic hypotension (OR: 1.40, 95% CI: 1.28–1.54), with a stronger association at central arterial stiffness (OR: 1.50, 95% CI: 1.34–1.68) than at peripheral arterial stiffness (OR: 1.29, 95% CI: 1.17–1.43).

Conclusion: Our findings showed that increased arterial stiffness raises the risk of orthostatic hypotension by 40% among the adult population. Considering that orthostatic hypotension, which is usually a consequence of antihypertensive treatment, has been widely associated with the risk of cardiovascular events, appropriate control of arterial stiffness could be a clinical strategy to prevent cardiovascular morbidity and mortality.
Altered motivation states for physical activity and ‘appetite’ for movement as compensatory mechanisms limiting the efficacy of exercise training for weight loss
Authors: Flack Kyle D. , Stults-Kolehmainen Matthew A. , Creasy Seth A. , Khullar Saumya , Boullosa Daniel , Catenacci Victoria A. , King Neil
Published: April 2023

Weight loss is a major motive for engaging in exercise, despite substantial evidence that exercise training results in compensatory responses that inhibit significant weight loss. According to the Laws of Thermodynamics and the CICO (Calories in, Calories out) model, increased exercise-induced energy expenditure (EE), in the absence of any compensatory increase in energy intake, should result in an energy deficit leading to reductions of body mass. However, the expected negative energy balance is met with both volitional and non-volitional (metabolic and behavioral) compensatory responses. A commonly reported compensatory response to exercise is increased food intake (i.e., Calories in) due to increased hunger, increased desire for certain foods, and/or changes in health beliefs. On the other side of the CICO model, exercise training can instigate compensatory reductions in EE that resist the maintenance of an energy deficit. This may be due to decreases in non-exercise activity thermogenesis (NEAT), increases in sedentary behavior, or alterations in sleep. Related to this EE compensation, the motivational states associated with the desire to be active tend to be overlooked when considering compensatory changes in non-exercise activity. For example, exercise-induced alterations in the wanting of physical activity could be a mechanism promoting compensatory reductions in EE. Thus, one’s desires, urges or cravings for movement–also known as “motivation states” or “appetence for activity”-are thought to be proximal instigators of movement. Motivation states for activity may be influenced by genetic, metabolic, and psychological drives for activity (and inactivity), and such states are susceptible to fatigue-or reward-induced responses, which may account for reductions in NEAT in response to exercise training. Further, although the current data are limited, recent investigations have demonstrated that motivation states for physical activity are dampened by exercise and increase after periods of sedentarism. Collectively, this evidence points to additional compensatory mechanisms, associated with motivational states, by which impositions in exercise-induced changes in energy balance may be met with resistance, thus resulting in attenuated weight loss.
Reciprocal relationships between parental and scholastic homework assistance and students’ academic functioning at elementary school
Authors: Benckwitz Lisa , Kohl Katharina , Roloff Janina , Lüdtke Oliver , Guill Karin
Published: April 2023

Homework assistance is provided both by parents and by institutions, for example, full-day schools. Previous research found evidence that the quality of homework assistance – measured by three dimensions derived from the self-determination theory, namely, responsiveness, structure, and control – is reciprocally related with students’ academic functioning (i.e., achievement and homework behavior). However, findings on parental homework assistance have been consistent only for the secondary level, whereas elementary school students have been studied less and previous results obtained for this population are inconclusive. Moreover, research on homework assistance that is given at school is scarce. Therefore, the present study aimed to investigate whether reciprocal associations between the quality of homework assistance and students’ academic functioning in elementary school can be found (1) for parental homework assistance and (2) for scholastic homework assistance. We calculated cross-lagged panel models based on longitudinal data from 335 German fourth graders collected in autumn 2019 (September and October) and winter 2020 (February and March). The analyses for scholastic homework assistance were based on a subsample of 112 students. Whereas responsiveness and structure did not predict students’ outcomes in the way we expected, control had unfavorable relationships in both homework settings. Moreover, parental control was reciprocally related with students’ mean grades in three subjects. The positive forms of homework assistance (responsiveness and structure) were predicted by different indicators of academic functioning in the two homework settings.