bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a novel immune-related gene signature for prognosis and the tumor microenvironment in patients with uveal melanoma combining single-cell and bulk sequencing data
Authors: Wang Wanpeng , Zhao Han , Wang Sha
Published: January 2023

Introduction

Uveal melanoma (UVM) is the most invasive intraocular malignancy in adults with a poor prognosis. Growing evidence revealed that immune-related gene is related to tumorigenesis and prognosis. This study aimed to construct an immune-related prognostic signature for UVM and clarify the molecular and immune classification.

Methods

Based on The Cancer Genome Atlas (TCGA) database, single-sample gene set enrichment (ssGSEA) and hierarchical clustering analysis were performed to identify the immune infiltration pattern of UVM and classify patients into two immunity clusters. Then, we proposed univariate and multivariate Cox regression analysis to identify immune-related genes that related to overall survival (OS) and validated in the Gene Expression Omnibus (GEO) external validation cohort. The molecular and immune classification in the immune-related gene prognostic signature defined subgroups were analyzed.

Results

The immune-related gene prognostic signature was constructed based on S100A13, MMP9, and SEMA3B genes. The prognostic value of this risk model was validated in three bulk RNA sequencing datasets and one single-cell sequencing dataset. Patients in the low-risk group had better OS than those in the high-risk group. The receiver-operating characteristic (ROC) analysis revealed its strong predictive ability for UVM patients. Lower expression of immune checkpoint genes was presented in the low-risk group. Functional studies showed that S100A13 knockdown via siRNA inhibited UVM cell proliferation, migration, and invasion in vitro, with the increased expression of reactive oxygen species (ROS) related markers in UVM cell lines.

Discussion

The immune-related gene prognostic signature is an independent predictive factor for the survival of patients with UVM and provides new information about cancer immunotherapy in UVM.
SRA inhibition improves antitumor potency of antigen-targeted chaperone vaccine
Authors: Qian Jie , Yu Xiaofei , Liu Zheng , Cai Jinyang , Manjili Masoud H. , Yang Hu , Guo Chunqing , Wang Xiang-Yang
Published: January 2023

We have previously demonstrated that scavenger receptor A (SRA) acts as an immunosuppressive regulator of dendritic cell (DC) function in activating antitumor T cells. Here we investigate the potential of inhibiting SRA activity to enhance DC-targeted chaperone vaccines including one that was recently evaluated in melanoma patients. We show that short hairpin RNA-mediated SRA silencing significantly enhances the immunogenicity of DCs that have captured chaperone vaccines designed to target melanoma (i.e., hsp110-gp100) and breast cancer (i.e., hsp110-HER/Neu-ICD). SRA downregulation results in heightened activation of antigen-specific T cells and increased CD8+ T cell-dependent tumor inhibition. Additionally, small interfering RNA (siRNA) complexed with the biodegradable, biocompatible chitosan as a carrier can efficiently reduce SRA expression on CD11c+ DCs in vitro and in vivo. Our proof-of-concept study shows that direct administration of the chitosan-siRNA complex to mice promotes chaperone vaccine-elicited cytotoxic T lymphocyte (CTL) response, culminating in improved eradication of experimental melanoma metastases. Targeting SRA with this chitosan-siRNA regimen combined with the chaperone vaccine also leads to reprogramming of the tumor environment, indicated by elevation of the cytokine genes (i.e., ifng, il12) known to skew Th1-like cellular immunity and increased tumor infiltration by IFN-γ+CD8+ CTLs as well as IL-12+CD11c+ DCs. Given the promising antitumor activity and safety profile of chaperone vaccine in cancer patients, further optimization of the chitosan-siRNA formulation to potentially broaden the immunotherapeutic benefits of chaperone vaccine is warranted.
Performance characteristics optimization of CRDI engine fuelled with a blend of sesame oil methyl ester and diesel fuel using response surface methodology approach
Authors: Kumar Manish , Gautam Raghvendra , Ansari Naushad Ahmad
Published: January 2023

The primary aim of this experiment was to use response surface methodology (RSM) to optimize engine operating parameters for optimal performance and emission characteristics of a common rail direct injection (CRDI) diesel engine fuelled with sesame oil methyl ester (SOME)/diesel blends. The experiments were carried out on a water-cooled common rail direct injection engine with a 4-stroke, single-cylinder connected to an eddy current dynamometer. As input variables, the SOME% (0%–20%), fuel injection pressure (FIP) (500–600 bar), EGR rates (0%–14%), and engine load (0–12 kg) were used. The optimization method is utilized to maximize brake thermal efficiency (BTE) while minimizing BSFC, CO, HC, and NOx emissions. Experimental research data were used to create the RSM model through DoE (Design of experiments). The most relevant factors impacting the responses were identified using an ANOVA analysis. According to the optimization findings, the engine’s optimum working parameters were found to be a 20% SOME ratio, 577.5 bar FIP, 5.26% EGR rates, and 5.12 kg engine load. Under these operating circumstances, the optimal responses were determined to be 18.92% BTE, 0.3705 kg/kWh BSFC, 0.03190% vol. CO, 13 ppm HC, and 447.5 ppm NOx emission. At the same time, R2 values were 96.35%, 87.54%, 91.57%, 95.87%, and 93.73% for BTE, BSFC, CO, HC, and NOx respectively.
Mixture formation of OME3−5 and 1-Octanol in comparison with diesel-like Dodecane under ECN Spray A conditions
Authors: Strauß Lukas , Rieß Sebastian , Wensing Michael
Published: January 2023

In order to be able to use the full potential of regenerative fuels, a comprehensive characterization is necessary to identify the differences between conventional fuels and regenerative fuels. In the current work, we compare OME3−5 and 1-Octanol with diesel-like Dodecane in terms of mixture formation under ECN Spray A conditions for single and multi-injection. To determine the mixtures, i.e., the mass distribution and the resulting air-fuel equivalence ratio, Naber and Siebers’ model as well as Musculus and Kattke’s model are used, which are based on experimental data. For this work, the mass flow rates and also the liquid and gaseous penetration depths of the fuel spray are measured. Results show that the mass ratios for the quasi-steady state of a single main injection for all three fuels are nearly the same, whereas the air-fuel equivalence ratios are very different. In addition, multiple injections are used to show that the fuel influences the opening and closing behavior of the injector. In the transient case of multiple injections, completely different mixtures result. In summary, it can be stated that OME3−5 and also 1-Octanol show a clearly different physio-chemical behavior from Dodecane and cannot simply be used as a drop-in fuel. Therefore, a simple exchange is not possible without major adaptations.
Utilization of ethanolamine phosphate phospholyase as a unique astrocytic marker
Authors: Tsujioka Hiroshi , Yamashita Toshihide
Published: January 2023

Astrocytes play diverse roles in the central nervous system (CNS) in both physiological and pathological conditions. Previous studies have identified many markers of astrocytes to analyze their complicated roles. Recently, closure of the critical period by mature astrocytes has been revealed, and the need for finding mature astrocyte-specific markers has been growing. We previously found that Ethanolamine phosphate phospholyase (Etnppl) was almost not expressed in the developing neonatal spinal cord, and its expression level slightly decreased after pyramidotomy in adult mice, which showed weak axonal sprouting, suggesting that its expression level negatively correlates with axonal elongation. Although the expression of Etnppl in astrocytes in adult is known, its utility as an astrocytic marker has not yet been investigated in detail. Here, we showed that Etnppl was selectively expressed in astrocytes in adult. Re-analyses using published RNA-sequencing datasets revealed changes in Etnppl expression in spinal cord injury, stroke, or systemic inflammation models. We produced high-quality monoclonal antibodies against ETNPPL and characterized ETNPPL localization in neonatal and adult mice. Expression of ETNPPL was very weak in neonatal mice, except in the ventricular and subventricular zones, and it was heterogeneously expressed in adult mice, with the highest expression in the cerebellum, olfactory bulb, and hypothalamus and the lowest in white matter. Subcellular localization of ETNPPL was dominant in the nuclei with weak expression in the cytosol in the minor population. Using the antibody, astrocytes in adult were selectively labeled in the cerebral cortex or spinal cord, and changes in astrocytes were detected in the spinal cord after pyramidotomy. ETNPPL is expressed in a subset of Gjb6+ astrocytes in the spinal cord. The monoclonal antibodies we created, as well as fundamental knowledge characterized in this study, will be valuable resources in the scientific community and will expand our understanding of astrocytes and their complicated responses in many pathological conditions in future analyses.
Lupus nephropathy beyond immunosuppression: Searching for nephro and cardioprotection
Authors: Morales Enrique , Sandino Justo , Galindo María
Published: January 2023

Renal involvement in systemic lupus erythematosus (SLE) represents one of the most frequent organ manifestations, often leading to end-stage kidney disease (ESKD). Several therapies have been tested in patients with lupus nephritis (LN) to prevent further organ damage. The effectiveness of immunosuppressive therapy as a treatment for LN is abundant, supported by multiple clinical trials that have shown its efficacy in preventing the development of chronic kidney disease (CKD). In addition to immunosuppressive therapy, several traditional and recent therapies aimed at nephroprotection in patients with proteinuric chronic kidney disease are gaining importance in the setting of LN. Thus, immunosuppressive therapy should be accompanied by nephro- and cardioprotective measures to control cardiovascular risk factors and proteinuria to ensure a better renal prognosis. Despite this, the literature on these specific measures is relatively scarce, with recommendations focused on the blockade of the renin-angiotensin-aldosterone system (RAAS). This review explores the pharmacological options available for cardiovascular and renal protection outside the usual treatment schemes.
Tubridge flow diverter for the treatment of small and medium aneurysms
Authors: Xie Dajiang , Yang Heng , Zhao Li , Ye Xin , Yang Shuxu , Gao Chao , Tian Yanlong , Ni Wei , Gu Yuxiang
Published: January 2023

Background

Tubridge flow diverter is a widely used device aimed at reconstructing parent arteries and occluding complex aneurysms in China. The experience of Tubridge in treating small and medium aneurysms is still limited. In this study, we aimed to evaluate the safety and efficacy of the Tubridge flow diverter for the treatment of the two types of aneurysms.

Methods

We reviewed the clinical records of aneurysms treated with a Tubridge flow diverter between 2018 and 2021 in a national cerebrovascular disease center. Cases were divided into small and medium aneurysms according to aneurysm size. The therapeutic process, occlusion rate, and clinical outcome were compared.

Results

In total, 57 patients and 77 aneurysms were identified. The patients were divided into two groups: small aneurysms (39 patients, 54 aneurysms) and medium aneurysms (18 patients, 23 aneurysms). There were 19 patients with tandem aneurysms (a total of 39 aneurysms) in the two groups, among which 15 patients (30 aneurysms) were in the small aneurysm group and four patients (nine aneurysms) were in the medium aneurysm group. The results show that the mean maximal diameter/neck in the small and medium aneurysms was 3.68/3.25 and 7.61/6.24 mm, respectively. In total, 57 Tubridge flow diverters were successfully implanted without unfolding failure, and there were six patients with new mild cerebral infarction in the small aneurysm group. The complete occlusion rate on the last angiographic follow-up was achieved in 88.46% of the small aneurysms group and 81.82% of the medium aneurysms group. The complete occlusion rate of patients with tandem aneurysms in the last angiographic follow-up was 86.67% (13/15) of the small aneurysms group and 50% (2/4) of the medium aneurysm group. Intracranial hemorrhage was nonencountered in the two groups.

Conclusion

Our preliminary experience suggests that the Tubridge flow diverter might be a safe and effective treatment for small and medium aneurysms along the internal carotid artery. Long stents may increase the risk of cerebral infarction. Adequate evidence is required to clarify the definite indications and complications in a multicenter randomized controlled trial with a long-term follow-up.
Importance of nutritional assessment tools in the critically ill patient: A systematic review
Authors: Domenech-Briz Vicente , Gea-Caballero Vicente , Czapla Michal , Chover-Sierra Elena , Juárez-Vela Raúl , Santolalla Arnedo Ivan , Villanueva-Blasco Víctor J. , Sánchez-González Juan Luis , Martínez-Sabater Antonio
Published: January 2023

Background

Among the risks of the critically ill patient, one of the aspects to be taken into account is the high probability of occurrence of malnutrition risk (40–50%). This process leads to increased morbimortality and worsening. The use of assessment tools allows the individualization of care.

Objective

To analyze the different nutritional assessment tools used during the admission of critically ill patients.

Methods

Systematic review of the scientific literature related to the nutritional assessment of critically ill patients. Between January 2017 and February 2022, articles were rescued from the electronic databases “Pubmed,” “Scopus,” “CINAHL” and “The Cochrane Library”; which will analyze which instruments are used during nutritional assessment in the ICU, as well as their impact on mortality and comorbidity of patients.

Results

The systematic review was made up of 14 scientific articles that met the selection criteria, obtained from seven different countries. The instruments described were: mNUTRIC, NRS 2002, NUTRIC, SGA, MUST and the ASPEN and ASPEN criteria. All the included studies demonstrated beneficial effects after nutritional risk assessment. mNUTRIC was the most widely used assessment instrument, with the best predictive validity for mortality and adverse outcomes.

Conclusion

The use of nutritional assessment tools makes it possible to know the real situation of patients, and by objectifying situations, to allow different interventions to improve the nutritional level of patients. The best effectiveness has been achieved using tools such as mNUTRIC, NRS 2002 and SGA.
Development of a population pharmacokinetics and pharmacodynamics model of glucarpidase rescue treatment after high-dose methotrexate therapy
Authors: Fukaya Yutaka , Kimura Toshimi , Hamada Yukihiro , Yoshimura Kenichi , Hiraga Hiroaki , Yuza Yuki , Ogawa Atsushi , Hara Junichi , Koh Katsuyoshi , Kikuta Atsushi , Koga Yuhki , Kawamoto Hiroshi
Published: January 2023

Introduction

Glucarpidase (CPG2) reduces the lethal toxicity of methotrexate (MTX) by rapid degradation.

Methods

In this study, a CPG2 population pharmacokinetics (popPK) analysis in healthy volunteers (phase 1 study) and a popPK-pharmacodynamics (popPK-PD) analysis in patients (phase 2 study, n = 15) who received 50 U/kg of CPG2 rescue for delayed MTX excretion were conducted. In the phase 2 study, the first CPG2 treatment at a dose of 50 U/kg was intravenously administered for 5 min within 12 h after the first confirmation of delayed MTX excretion. The second dose of CPG2, with a plasma MTX concentration >1 μmol/L, was administered to the patient more than 46 h after the start of CPG2 administration.

Results

The population mean PK parameters (95% CI) of MTX, obtained from the final model post hoc, were estimated as follows: CLrMTX = 2.424 L/h (95% CI: 1.755–3.093), VcMTX = 12.6 L (95% CI: 10.8–14.3), VpMTX = 2.15 L (95% CI: 1.60–2.70), and α = 8.131 x 105 (4.864 x 105-11.398 x 105). The final model, including covariates, was CLrMTX (L/h): 3.248 x Body Weight/Serum creatinine/60 (CV 33.5%), VcMTX (L): 0.386 x Body Weight/body surface area (CV 29.1%), VpMTX (L):3.052 x Body Weight/60 (CV 90.6%), and α (L/h): 6.545 x 105 (CV 79.8%).

Discussion

These results suggest that the pre-CPG2 dose and 24 h after CPG2 dosing were the most important sampling points in the Bayesian estimation of plasma MTX concentration prediction at 48 h. These CPG2-MTX popPK analysis and Bayesian estimation of rebound in plasma MTX concentrations are clinically important to estimate >1.0 μmol/L 48 h after the first CPG2 dosing.

Clinical trial registration

https://dbcentre3.jmacct.med.or.jp/JMACTR/App/JMACTRS06/JMACTRS06.aspx?seqno=2363, identifier JMA-IIA00078 and https://dbcentre3.jmacct.med.or.jp/JMACTR/App/JMACTRS06/JMACTRS06.aspx?seqno=2782, identifier JMA-IIA00097.
Expression and significance of m6A-RNA-methylation in oral cancer and precancerous lesion
Authors: Qin Zhiming , Bai Jiaying , He Huiying , Li Binbin
Published: January 2023

Background

Oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) are a series of related pathologic and molecular events involving simple epithelial hyperplasia, mild to severe dysplasia and canceration. N6-methyladenosine RNA methylation, as the most common modification of both coding mRNA and non-coding ncRNA in eukaryotes, participates in the regulation of the occurrence and development of various malignant tumors in human. However, its role in oral epithelial dysplasia (OED) and OSCC remain unclear.

Materials and methods

In this study, multiple public databases were used for bioinformatics analysis of 23 common m6A methylation regulators in head and neck squamous cell carcinoma (HNSCC). Protein expressions of IGF2BP2 and IGF2BP3 were verified accordingly in clinical cohort samples of OED and OSCC.

Results

Patients with high expression of FTO、HNRNPC、HNRNPA2B1、LRPPRC、IGF2BP1、IGF2BP2、IGF2BP3 had a poor prognosis. IGF2BP2 had a relatively high mutation rate in HNSCC, and its expression was significantly positively correlated with tumor purity, and significantly negatively correlated with the infiltration level of B cells and CD8+T cells. The expression of IGF2BP3 was significantly positively correlated with tumor purity and CD4+T cells. Immunohistochemistrically, the expression of IGF2BP2 and IGF2BP3 in oral simple epithelial hyperplasia, OED and OSCC increased gradually. Both were strongly expressed in OSCC.

Conclusion

IGF2BP2 and IGF2BP3 were the potential biological prognostic indicators of OED and OSCC.
The efficacy and safety of epirubicin and cyclophosphamide combined with pyrotinib in neoadjuvant treatment for HER2-positive breast cancer: A real-world study
Authors: Li Fu , Liang Yimin , Luo Ming , Shen Jiayue , Zhou Taosheng , Liang Yajing , Tang Xiaoqi , Yuan Huiming , Zeng Jian
Published: January 2023

Purpose

Long-term survival benefit of anthracyclines for human epidermal growth factor receptor 2 (HER2)-positive breast cancer is clear. In the neoadjuvant treatment, compared with the monoclonal antibody such as trastuzumab and pertuzumab, the clinical benefit of pyrotinib, a new small-molecule tyrosine kinase inhibitor (TKI), as the main anti-HER2 strategy currently requires more research to determine. Our real-world study is the first prospective observational study in China to evaluate the efficacy and safety of epirubicin (E) and cyclophosphamide (C) with pyrotinib as anti-HER2 therapy in the neoadjuvant setting of patients with stage II-III HER2-positive breast cancer.

Methods

From May 2019 to December 2021, 44 untreated patients with HER2-positive nonspecific invasive breast cancer who received 4 cycles of neoadjuvant EC with pyrotinib. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included the overall clinical response, breast pathological complete response rate (bpCR), the rate of axillary lymph nodes pathological negativity and adverse events (AEs). Other objective indicators were the rate of surgical breast-conserving, the negative conversion ratios of tumor markers.

Results

Thirty-seven (84.1%) of 44 patients completed this neoadjuvant therapy, and 35 (79.5%) had surgery and were included in the primary endpoint assessment. The objective response rate (ORR) of 37 patients was 97.3%. Two patients reached clinical complete response, 34 obtained clinical partial response, 1 sustained stable disease, and no one had progressive disease. Eleven (31.4%) of 35 patients who had surgery achieved bpCR and the rate of axillary lymph nodes pathological negativity was 61.3%. The tpCR rate was 28.6% (95% CI: 12.8-44.3%). Safety was evaluated in all 44 patients. Thirty-nine (88.6%) had diarrhea, and 2 developed grade 3 diarrhea. Four (9.1%) patients had grade 4 leukopenia. All grade 3-4 AEs could be improved after symptomatic treatment.

Conclusion

The regimen of 4 cycles of EC combined with pyrotinib presented some feasibility in the neoadjuvant setting for HER2-positive breast cancer with manageable safety. New regimens with pyrotinib should be evaluated for higher pCR in future.

Trial registration

chictr.org Identifier: ChiCTR1900026061.
Review of the status of neoadjuvant therapy in HER2-positive breast cancer
Authors: Dowling Gavin P. , Keelan Stephen , Toomey Sinead , Daly Gordon R. , Hennessy Bryan T. , Hill Arnold D. K.
Published: January 2023

Purpose

The development of human epidermal growth factor receptor 2 (HER2)-directed therapies has revolutionized the treatment of HER2-positive breast cancer. The aim of this article is to review the continually evolving treatment strategies in the neoadjuvant setting of HER2-positive breast cancer, as well as the current challenges and future perspectives.

Methods

Searches were undertaken on PubMed and Clinicaltrials.gov for relevant publications and trials.

Findings

The current standard of care in high-risk HER2-positive breast cancer is to combine chemotherapy with dual anti-HER2 therapy, for a synergistic anti-tumor effect. We discuss the pivotal trials which led to the adoption of this approach, as well as the benefit of these neoadjuvant strategies for guiding appropriate adjuvant therapy. De-escalation strategies are currently being investigated to avoid over treatment, and aim to safely reduce chemotherapy, while optimizing HER2-targeted therapies. The development and validation of a reliable biomarker is essential to enable these de-escalation strategies and personalization of treatment. In addition, promising novel therapies are currently being explored to further improve outcomes in HER2-positive breast cancer.
Discordance between germline genetic findings and abnormal tumor immunohistochemistry staining of mismatch repair proteins in individuals with suspected Lynch syndrome
Authors: Pan Shujuan , Cox Hannah , Willmott Jamie , Mundt Erin , Gorringe Heidi , Landon Michelle , Bowles Karla R. , Coffee Bradford , Roa Benjamin B. , Mancini-DiNardo Debora
Published: January 2023

Background and Aims

Tumor immunohistochemical staining (IHC) of DNA mismatch repair (MMR) proteins is often used to guide germline genetic testing and variant classification for patients with suspected Lynch syndrome. This analysis examined the spectrum of germline findings in a cohort of individuals showing abnormal tumor IHC.

Methods

We assessed individuals with reported abnormal IHC findings and referred for testing with a six-gene syndrome-specific panel (n=703). Pathogenic variants (PVs) and variants of uncertain significance (VUS) in MMR genes were designated expected/unexpected relative to IHC results.

Results

The PV positive rate was 23.2% (163/703; 95% confidence interval [CI], 20.1%-26.5%); 8.0% (13/163; 95% CI, 4.3%-13.3%) of PV carriers had a PV in an unexpected MMR gene. Overall, 121 individuals carried VUS in MMR genes expected to be mutated based on IHC results. Based on independent evidence, in 47.1% (57/121; 95% CI, 38.0%-56.4%) of these individuals the VUSs were later reclassified as benign and in 14.0% (17/121; 95% CI, 8.4%-21.5%) of these individuals the VUSs were reclassified as pathogenic.

Conclusions

Among patients with abnormal IHC findings, IHC-guided single-gene genetic testing may miss 8% of individuals with Lynch syndrome. In addition, in patients with VUS identified in MMR genes predicted to be mutated by IHC, extreme caution must be taken when the IHC results are considered in variant classification.
Circulating tumour DNA as biomarker for rectal cancer: A systematic review and meta-analyses
Authors: van Rees Jan M. , Wullaert Lissa , Grüter Alexander A. J. , Derraze Yassmina , Tanis Pieter J. , Verheul Henk M. W. , Martens John W. M. , Wilting Saskia M. , Vink Geraldine , van Vugt Jeroen L. A. , Beije Nick , Verhoef Cornelis
Published: January 2023

Background

Circulating tumour DNA (ctDNA) has been established as a promising (prognostic) biomarker with the potential to personalise treatment in cancer patients. The objective of this systematic review is to provide an overview of the current literature and the future perspectives of ctDNA in non-metastatic rectal cancer.

Methods

A comprehensive search for studies published prior to the 4th of October 2022 was conducted in Embase, Medline, Cochrane, Google scholar, and Web of Science. Only peer-reviewed original articles and ongoing clinical trials investigating the association between ctDNA and oncological outcomes in non-metastatic rectal cancer patients were included. Meta-analyses were performed to pool hazard ratios (HR) for recurrence-free survival (RFS).

Results

A total of 291 unique records were screened, of which 261 were original publications and 30 ongoing trials. Nineteen original publications were reviewed and discussed, of which seven provided sufficient data for meta-analyses on the association between the presence of post-treatment ctDNA and RFS. Results of the meta-analyses demonstrated that ctDNA analysis can be used to stratify patients into very high and low risk groups for recurrence, especially when detected after neoadjuvant treatment (HR for RFS: 9.3 [4.6 – 18.8]) and after surgery (HR for RFS: 15.5 [8.2 – 29.3]). Studies investigated different types of assays and used various techniques for the detection and quantification of ctDNA.

Conclusions

This literature overview and meta-analyses provide evidence for the strong association between ctDNA and recurrent disease. Future research should focus on the feasibility of ctDNA-guided treatment and follow-up strategies in rectal cancer. A blueprint for agreed-upon timing, preprocessing, and assay techniques is needed to empower adaptation of ctDNA into daily practice.
Comparison of somatostatin receptor expression in patients with neuroendocrine tumours with and without somatostatin analogue treatment imaged with [18F]SiTATE
Authors: Eschbach Ralf S. , Hofmann Markus , Späth Lukas , Sheikh Gabriel T. , Delker Astrid , Lindner Simon , Jurkschat Klaus , Wängler Carmen , Wängler Björn , Schirrmacher Ralf , Tiling Reinhold , Brendel Matthias , Wenter Vera , Dekorsy Franziska J. , Zacherl Mathias J. , Todica Andrei , Ilhan Harun , Grawe Freba , Cyran Clemens C. , Unterrainer Marcus , Rübenthaler Johannes , Knösel Thomas , Paul Tanja , Boeck Stefan , Westphalen Christoph Benedikt , Spitzweg Christine , Auernhammer Christoph J. , Bartenstein Peter , Unterrainer Lena M. , Beyer Leonie
Published: January 2023

Purpose

Somatostatin analogues (SSA) are frequently used in the treatment of neuroendocrine tumours. Recently, [18F]SiTATE entered the field of somatostatin receptor (SSR) positron emission tomography (PET)/computed tomography (CT) imaging. The purpose of this study was to compare the SSR-expression of differentiated gastroentero-pancreatic neuroendocrine tumours (GEP-NET) measured by [18F]SiTATE-PET/CT in patients with and without previous treatment with long-acting SSAs to evaluate if SSA treatment needs to be paused prior to [18F]SiTATE-PET/CT.

Methods

77 patients were examined with standardised [18F]SiTATE-PET/CT within clinical routine: 40 patients with long-acting SSAs up to 28 days prior to PET/CT examination and 37 patients without pre-treatment with SSAs. Maximum and mean standardized uptake values (SUVmax and SUVmean) of tumours and metastases (liver, lymphnode, mesenteric/peritoneal and bones) as well as representative background tissues (liver, spleen, adrenal gland, blood pool, small intestine, lung, bone) were measured, SUV ratios (SUVR) were calculated between tumours/metastases and liver, likewise between tumours/metastases and corresponding specific background, and compared between the two groups.

Results

SUVmean of liver (5.4 ± 1.5 vs. 6.8 ± 1.8) and spleen (17.5 ± 6.8 vs. 36.7 ± 10.3) were significantly lower (p < 0.001) and SUVmean of blood pool (1.7 ± 0.6 vs. 1.3 ± 0.3) was significantly higher (p < 0.001) in patients with SSA pre-treatment compared to patients without. No significant differences between tumour-to-liver and specific tumour-to-background SUVRs were observed between both groups (all p > 0.05).

Conclusion

In patients previously treated with SSAs, a significantly lower SSR expression ([18F]SiTATE uptake) in normal liver and spleen tissue was observed, as previously reported for 68Ga-labelled SSAs, without significant reduction of tumour-to-background contrast. Therefore, there is no evidence that SSA treatment needs to be paused prior to [18F]SiTATE-PET/CT.
Outcome of patients with tetralogy of Fallot with pulmonary atresia
Authors: Sames-Dolzer Eva , Fahrnberger Anna , Kreuzer Michaela , Mair Roland , Gierlinger Gregor , Tulzer Andreas , Gitter Roland , Prandstetter Christoph , Tulzer Gerald , Mair Rudolf
Published: January 2023

Objective

Tetralogy of Fallot patients with pulmonary atresia (TOFPA) have a largely varying source of pulmonary perfusion with often hypoplastic and even absent central pulmonary arteries. A retrospective single center study was undertaken to assess outcome of these patients regarding type of surgical procedures, long-term mortality, achievement of VSD closure and analysis of postoperative interventions.

Methods

76 consecutive patients with TOFPA operated between 01.01.2003 and 31.12.2019 are included in this single center study. Patients with ductus dependent pulmonary circulation underwent primary single stage full correction including VSD closure and right ventricular to pulmonary conduit implantation (RVPAC) or transanular patch reconstruction. Children with hypoplastic pulmonary arteries and MAPCAs without double supply were predominantly treated by unifocalization and RVPAC implantation. The follow up period ranges between 0 and 16,5 years.

Results

31 patients (41%) underwent single stage full correction at a median age of 12 days, 15 patients could be treated by a transanular patch. 30 days mortality rate in this group was 6%. In the remaining 45 patients the VSD could not be closed during their first surgery which was performed at a median age of 89 days. A VSD closure was achieved later in 64% of these patients after median 178 days. 30 days mortality rate after the first surgery was 13% in this group. The estimated 10-year-survival rate after the first surgery is 80,5% ± 4,7% showing no significant difference between the groups with and without MAPCAs (p > 0,999). Median intervention-free interval (surgery and transcatheter intervention) after VSD closure was 1,7 ± 0,5 years [95% CI: 0,7–2,8 years].

Conclusions

A VSD closure could be achieved in 79% of the total cohort. In patients without MAPCAs this was possible at a significant earlier age (p < 0,01). Although patients without MAPCAs predominantly underwent single stage full correction at newborn age, the overall mortality rate and the interval until reintervention after VSD closure did not show significant differences between the two groups with and without MAPCAs. The high rate of proven genetic abnormalities (40%) with non-cardiac malformations did also pay its tribute to impaired life expectancy.
Environmental factors related to differences in the microbiota in the upper respiratory tract in young children: Focusing on the impact of early nursery attendance
Authors: Abushawish Asmaa , Haro Kaoru , Hoshina Takayuki , Kitajima Naoko , Kusuhara Koichi
Published: January 2023

Background

Microbial colonization of the upper respiratory tract (URT) during the first years of life differs significantly according to environmental factors. We investigated the association between early nursery attendance, URT infection (URTI) and drugs used for its treatment and the differences in the URT microbiota.

Methods

This prospective study included 33 young children (11 and 22 with and without nursery attendance during their infancy, respectively). URT secretions were collected from the nasopharynx of these children at 2, 4, 6, 12, 18 and 24 months old. Clinical information after the latest sampling, including histories of URTI and the uses of antibiotics or cold medicines, was collected from all children. URT bacteria were identified by a clone library analysis of the 16S rRNA gene.

Results

In the diversity of URT microbiota using the Shannon index, we did not detect any associations between variations in the URT microbiota and environmental factors (nursery attendance, development of URTIs, or the uses of antibiotics or cold medicines). However, in a clustering analysis, the proportion of the samples classified as Corynebacterium propinquum-dominant cluster was significantly lower in children ≥6 months old with nursery attendance than in those without nursery attendance. In addition, the URT microbiota was significantly different between samples from children ≥6 months old with and without a history of ≥3 URTI episodes after the first sampling. Furthermore, the URT microbiota was also significantly different between samples from these children with and without antibiotic use between the previous and present samplings.

Conclusion

Early nursery attendance and its related factors, including the frequency of URTI and antibiotic treatment, may be associated with the differences in the URT flora in young children.
Salvianolate injection for hypertensive nephropathy patients who were using valsartan: A systematic review and meta-analysis
Authors: Xu Qiyao , Shen Yuehong , Zhao Jianqiao , Shen Jianping
Published: January 2023

Background: The treatment of hypertensive nephropathy has remained unchanged for many years. Salvianolate is the main active component extracted from Salvia Miltiorrhiza. The current studies seem to suggest that salvianolate has a certain therapeutic effect on hypertensive nephropathy.

Objective: The purpose of this meta-analysis is to evaluate the effect and safety of salvianolate on hypertensive nephropathy under the condition of standardized use of valsartan.

Methods: We conducted a systematic search (unlimited initial date to 22 October 2022) in PubMed, Web of Science, the Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Data knowledge service platform, China Science and Technology Journal Database, China Biomedical Literature Service System. Searching for the study of salvianolate on hypertensive nephropathy. Two reviewers independently included the study that met the inclusion criteria, and extracted data, evaluated the quality of the study. We use RevMan5.4 and stata15 software for this meta-analysis. We use GRADEprofiler 3.2.2 software for evidence quality assessment.

Results: This meta-analysis included seven studies (525 patients). Compared with the use of valsartan combined with conventional treatment, salvianolate combined with valsartan and conventional treatment can further improve the efficacy (RR = 1.28, 95%CI:1.17 to 1.39), reduce blood pressure [systolic blood pressure (MD = 8.98, 95%CI:−12.38 to −5.59); diastolic blood pressure (MD = 5.74, 95%CI:−7.20 to −4.29)], serum creatinine (MD = −17.32, 95%CI:−20.55 to −14.10), blood urea nitrogen (MD = −1.89, 95%CI:−3.76 to −0.01), urine microalbumin (MD = −23.90, 95%CI:−26.54 to −21.26), and urinary protein to creatinine ratio (MD = −1.92, 95%CI:−2.15 to −1.69), cystatin C (MD = −1.04, 95%CI: −1.63 to −0.45) and increase calcitonin gene-related peptide (MD = 18.68, 95%CI:12.89 to 24.46) without increasing adverse reactions (RR = 2.20, 95%CI:0.52 to 9.40). But it has no additional effect on endothelin-1 and malondialdehyde. The quality of evidence ranged from moderate to very low.

Conclusion: This meta-analysis shows that the salvianolate can further improve renal function of hypertensive nephropathy patients based on valsartan was used. Therefore, salvianolate can be used as a clinical supplement for hypertensive nephropathy. However, the quality of the evidence is not high due to the uneven quality of the included studies and the insufficient sample size, we still need a lot of large sample size studies with more perfect design to confirm these results.

Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373256, identifier CRD42022373256
AF driver detection in pulmonary vein area by electropcardiographic imaging: Relation with a favorable outcome of pulmonary vein isolation
Authors: Fambuena-Santos Carlos , Hernández-Romero Ismael , Molero Rubén , Atienza Felipe , Climent Andreu M. , Guillem M S.
Published: January 2023

Pulmonary vein isolation (PVI) is the most successful treatment for atrial fibrillation (AF) nowadays. However, not all AF patients benefit from PVI. In this study, we evaluate the use of ECGI to identify reentries and relate rotor density in the pulmonary vein (PV) area as an indicator of PVI outcome. Rotor maps were computed in a set of 29 AF patients using a new rotor detection algorithm. The relationship between the distribution of reentrant activity and the clinical outcome after PVI was studied. The number of rotors and proportion of PSs in different atrial regions were computed and compared retrospectively in two groups of patients: patients that remained in sinus rhythm 6 months after PVI and patients with arrhythmia recurrence. The total number of rotors obtained was higher in patients returning to arrhythmia after the ablation (4.31 ± 2.77 vs. 3.58 ± 2.67%, p = 0.018). However, a significantly higher concentration of PSs in the pulmonary veins was found in patients that remained in sinus rhythm (10.20 ± 12.40% vs. 5.19 ± 9.13%, p = 0.011) 6 months after PVI. The results obtained show a direct relationship between the expected AF mechanism and the electrophysiological parameters provided by ECGI, suggesting that this technology offers relevant information to predict the clinical outcome after PVI in AF patients.
Insights into the control and consequences of breathing adjustments in fishes-from larvae to adults
Authors: Perry Steve F. , Pan Yihang K. , Gilmour Kathleen M.
Published: January 2023

Adjustments of ventilation in fishes to regulate the volume of water flowing over the gills are critically important responses to match branchial gas transfer with metabolic needs and to defend homeostasis during environmental fluctuations in O2 and/or CO2 levels. In this focused review, we discuss the control and consequences of ventilatory adjustments in fish, briefly summarizing ventilatory responses to hypoxia and hypercapnia before describing the current state of knowledge of the chemoreceptor cells and molecular mechanisms involved in sensing O2 and CO2. We emphasize, where possible, insights gained from studies on early developmental stages. In particular, zebrafish (Danio rerio) larvae have emerged as an important model for investigating the molecular mechanisms of O2 and CO2 chemosensing as well as the central integration of chemosensory information. Their value stems, in part, from their amenability to genetic manipulation, which enables the creation of loss-of-function mutants, optogenetic manipulation, and the production of transgenic fish with specific genes linked to fluorescent reporters or biosensors.
Short-term isolation effects on the brain, cognitive performance, and sleep—The role of exercise
Authors: Klein Timo , Braunsmann Leonard , Koschate Jessica , Hoffmann Uwe , Foitschik Tina , Krieger Stephanie , Crucian Brian , Schneider Stefan , Abeln Vera
Published: January 2023

Isolation is stressful and negatively affects sleep and mood and might also affect the structure and function of the brain. Physical exercise improves brain function. We investigated the influence of physical exercise during isolation on sleep, affect, and neurobehavioral function. N = 16 were isolated for 30 days with daily exercise routines (ISO100) and n = 16 isolated for 45 days with every second day exercise (ISO50). N = 27 were non-isolated controls who either exercised on a daily basis (CTRLEx) or refused exercise (CTRLNonEx) for 30 days. At the beginning and the end of each intervention, intravenous morning cortisol, melatonin, brain-derived neurotrophic factor and IGF-1, positive and negative affect scales, electroencephalography, cognitive function, and sleep patterns (actigraphy) were assessed. High levels of cortisol were observed for the isolated groups (p < .05) without negative effects on the brain, cognitive function, sleep, and mood after 4 to 6 weeks of isolation, where physical exercise was performed regularly. An increase in cortisol and impairments of sleep quality, mood, cognitive function, and neurotrophic factors (p < .05) were observed after 4 weeks of absence of physical exercise in the CTRLNonEx group. These findings raise the assumption that regular physical exercise routines are a key component during isolation to maintain brain health and function.
Credibility assessment of cold adaptive Pseudomonas jesenni MP1 and P. palleroniana N26 on growth, rhizosphere dynamics, nutrient status, and yield of the kidney bean cultivated in Indian Central Himalaya
Authors: Khan Amir , Singh Ajay Veer , Pareek Navneet , Arya Pratima , Upadhayay Viabhav Kumar , Kumar Jugran Arun , Kumar Mishra Pankaj , Goel Reeta
Published: January 2023

Kidney bean (Phaseolus vulgaris) productivity and nutritional quality are declining due to less nutrient accessibility, poor soil health, and indigent agronomic practices in hilly regions, which collectively led to a fall in farmer’s income, and to malnutrition in consumers. Addressing such issues, the present investigation was designed to assess the impact of Pseudomonas jesenii MP1 and Pseudomonas palleroniana N26 treatment on soil health, microbial shift, yield, and nutrient status of the kidney bean in the Harsil and Chakrata locations of Indian Central Himalaya. P. jesenii MP1 and P. palleroniana N26 were characterized as cold adaptive PGPR as they possessed remarkable in vitro plant growth promoting traits. Further, field trial study with PGPR treatments demonstrated remarkable and prolific influence of both strains on yield, kidney bean nutrient status, and soil health at both geographical locations, which was indicated with improved grain yield (11.61%–23.78%), protein (6.13%–24.46%), and zinc content (21.86%–61.17%) over control. The metagenomic study revealed that use of bioinoculants also concentrated the nutrient mobilizing and plant beneficial microorganisms in the rhizosphere of the kidney bean. Moreover, correlation analysis also confirmed that the plant growth-promoting traits of P. jesenii MP1 and P. palleroniana N26 are the basis for improved yield and nutrient status of the kidney bean. Further, cluster and principal component analysis revealed that both P. jesenii MP1 and P. palleroniana N26 exhibited pronounced influence on yield attributes of the kidney bean at both the locations. At the Harsil location, the P. jesenii MP1-treated seed demonstrated highest grain yield over other treatments, whereas at Chakarata, P. jesenii MP1, and P. palleroniana N26 treatment showed almost equal enhancement (~23%) in grain yield over control. The above results revealed that these bioinoculants are efficient plant growth promoters and nutrient mobilizers; they could be used as green technology to improve human health and farmer’s income by enhancing soil health, yield, and nutrient status of the kidney bean at hilly regions.
Investigating phenotypic relationships in persimmon accessions through integrated proteomic and metabolomic analysis of corresponding fruits
Authors: De Pascale Sabrina , Troise Antonio Dario , Petriccione Milena , Nunziata Angelina , Cice Danilo , Magri Anna , Salzano Anna Maria , Scaloni Andrea
Published: January 2023

Together with phenological and genomic approaches, gel-based and label-free proteomic as well metabolomic procedures were separately applied to plants to highlight differences between ecotypes, to estimate genetic variability within/between organism populations, or to characterize specific mutants/genetically modified lines at metabolic level. To investigate the possible use of tandem mass tag (TMT)-based quantitative proteomics in the above-mentioned contexts and based on the absence of combined proteo-metabolomic studies onDiospyros kakicultivars, we here applied integrated proteomic and metabolomic approaches to fruits from Italian persimmon ecotypes with the aim to characterize plant phenotypic diversity at molecular level. We identified 2255 proteins in fruits, assigning 102 differentially represented components between cultivars, including some related to pomological, nutritional and allergenic characteristics. Thirty-three polyphenols were also identified and quantified, which belong to hydroxybenzoic acid, flavanol, hydroxycinnamic acid, flavonol, flavanone and dihydrochalcone sub-classes. Heat-map representation of quantitative proteomic and metabolomic results highlighted compound representation differences in various accessions, whose elaboration through Euclidean distance functions and other linkage methods defined dendrograms establishing phenotypic relationships between cultivars. Principal component analysis of proteomic and metabolomic data provided clear information on phenotypic differences/similarities between persimmon accessions. Coherent cultivar association results were observed between proteomic and metabolomic data, emphasizing the utility of integrating combinedomicapproaches to identify and validate phenotypic relationships between ecotypes, and to estimate corresponding variability and distance. Accordingly, this study describes an original, combined approach to outline phenotypic signatures in persimmon cultivars, which may be used for a further characterization of other ecotypes of the same species and an improved description of nutritional characteristics of corresponding fruits.
tRNA-derived small RNAs in plant response to biotic and abiotic stresses
Authors: Wang Chaojun , Chen Weiqiang , Aili Maimaiti , Zhu Lei , Chen Yan
Published: January 2023

tRNA-derived small RNAs (tsRNAs) represent a novel category of small non-coding RNAs and serve as a new regulator of gene expression at both transcriptional and post-transcriptional levels. Growing evidence indicates that tsRNAs can be induced by diverse stimuli and regulate stress-responsive target genes, allowing plants to adapt to unfavorable environments. Here, we discuss the latest developments about the biogenesis and classification of tsRNAs and highlight the expression regulation and potential function of tsRNAs in plant biotic and abiotic stress responses. Of note, we also collect useful bioinformatics tools and resources for tsRNAs study in plants. Finally, we propose current limitations and future directions for plant tsRNAs research. These recent discoveries have refined our understanding of whether and how tsRNAs enhance plant stress tolerance.