bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammation-related parameter serve as prognostic biomarker in esophageal squamous cell carcinoma
Authors: Xu Xiaoqin , Jing Jiexian 
Published: October 2022

ObjectiveThe aim of this study was to explore the predictive role of inflammation-related parameters in prognosis of esophageal squamous cell carcinoma (ESCC).MethodsA total of 370 ESCC patients subjected to curative surgery were enrolled. All patients had complete medical records and did not receive preoperative adjuvant therapy. Preoperative systemic immune-inflammation index (SII) was calculated as platelet count × neutrophil count/lymphocyte count, prognostic nutrition index (PNI) as albumin concentration (g/L) + 5 × total lymphocyte count (109/L), and systemic inflammation response index (SIRI) as neutrophil count × monocyte count/lymphocyte count. The optimal cut‐off values of preoperative SII, neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), PNI, and SIRI were determined via receiver operating characteristic (ROC) analysis, and their correlations with clinical parameters and survival analyzed.ResultsNLR was associated with gender (P = 0.022), and PLR (P = 0.037), PNI (P = 0.017) was associated with survival status, LMR was related with gender (P = 0.034) and survival status (P = 0.01), SIRI was correlated with gender (P = 0.000), smoking history (P = 0.000) and drinking history (P = 0.004). Survival analysis indicated that high PLR (P = 0.042), low LMR (P = 0.001), and low PNI (P = 0.007) were predictive of poor prognosis of ESCC. Stratified analysis revealed the prognostic predictor roles of distinct markers in different ESCC subgroups. SII and SIRI were predominantly correlated with the clinical outcome in the lymphatic metastasis subgroup. Further univariate analysis disclosed that T stage, smoking history, lymphatic metastasis, TNM staging, PLR, LMR, and PNI potentially serve as influencing factors(P &lt; 0.05). Multivariate analysis identified T stage (HR = 1.781, P = 0.002), TNM staging (HR = 8.617, P = 0.001) and LMR (HR = 0.504, P = 0.001) as independent predictors for outcomes of ESCC.ConclusionsLow LMR could serve as an independent marker of poor prognosis in patients with ESCC. Inflammation-related markers have distinct predictive roles in ESCC subgroups with different features.
Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis
Authors: Klotz Daniel Martin , Kuhlmann Jan Dominik , Link Theresa , Goeckenjan Maren , Hofbauer Lorenz C. , Göbel Andy , Rachner Tilman D. , Wimberger Pauline 
Published: October 2022

BackgroundNeuropilin (NRP) is a transmembrane protein, which has been shown to be a pro-angiogenic mediator and implicated as a potential driver of cancer progression. NRP-1 up-regulation in ovarian cancer tissue predicts poor prognosis. However, the clinical relevance of the soluble form of NRP-1 (sNRP-1) as a circulating biomarker in ovarian cancer patients is unknown.Methods/patients cohortsNRP-1 levels were quantified in a cohort of 88 clinically documented ovarian cancer patients by a commercially available sNRP-1 enzyme-linked immunosorbent assay (ELISA) kit (Biomedica, Vienna, Austria). Patients (81.8% with FIGOIII/IV) received primary cytoreductive surgery with the aim of macroscopic complete resection (achieved in 55.7% of patients) and the recommendation of adjuvant chemotherapy in line with national guidelines.ResultsHigher levels of sNRP-1 reflected more advanced disease (FIGO III/IV) and indicated a trend towards suboptimal surgical outcome, i.e. any residual tumor. sNRP-1 was neither related to the patients’ age nor the BRCA1/2 mutational status. Patients with higher sNRP-1 levels at primary diagnosis had a significantly reduced progression-free survival (PFS) (HR = 0.541, 95%CI: 0.304 - 0.963; p = 0.037) and overall survival (OS) (HR = 0.459, 95%CI: 0.225 - 0.936; p = 0.032). Principal component analysis showed that sNRP-1 levels were unrelated to the circulating hepatocyte growth factor (HGF) and the soluble ectodomain of its receptor the tyrosine kinase mesenchymal–epithelial transition (c-MET), suggesting that there is no proportional serological concentration gradient of soluble components of the NRP-1/HGF/c-MET signaling axis.ConclusionsIn line with the previously shown tissue-based prognostic role, we demonstrated for the first time that sNRP-1 can also act as a readily accessible, prognostic biomarker in the circulation of patients with ovarian cancer at primary diagnosis. Given its known role in angiogenesis and conferring resistance to the poly ADP-ribose polymerase (PARP) inhibitor olaparib in vitro, our results encourage more detailed investigation into sNRP-1 as a potential predictive biomarker for bevacizumab and/or PARP-inhibitor treatment.
Case report and literature review: Novel compound heterozygous FIG4 variants causing both of peripheral and central nervous system defects
Authors: Yu Yonglin , Yin Hongwei , Ma Changli , Jia Xiaoyi , Chen Wencong , Li Haifeng , Wu Ke 
Published: October 2022

BackgroundPathogenic variants in the FIG4 gene have been described to be associated with a diverse spectrum of syndromes, such as autosomal recessive bilateral temporooccipital polymicrogyria (OMIM 612691), autosomal dominant amyotrophic lateral sclerosis-11 (ALS11; OMIM 612577), autosomal recessive Charcot-Marie-Tooth disease, type 4J (CMT4J; OMIM 611228), and autosomal recessive Yunis-Varon syndrome (YVS; OMIM 216340). Heterozygous FIG4 variants are responsible for ALS11 characterized by progressive muscular weakness, atrophy, and bulbar palsy. CMT4J is a disorder of peripheral nervous system defects mainly presenting with a highly variable onset of proximal and/or distal muscle weakness. YVS is a disorder of severe neurological involvement with central nervous system (CNS) dysfunction and extensive skeletal anomalies.Case PresentationWe reported two Chinese siblings born with a weakness in all limbs. They experienced rapidly progressive weakness in distal limbs. At the age of 6 years, the elder brother presented with severe scoliosis and cervical kyphosis. They both had global developmental delay and a CNS involvement with cognitive deficits and swallowing problems. Genetic screening in the patients' family for inherited diseases was recommended. Novel compound heterozygous variants in the FIG4 gene (c.2148delTinsAA and c.317A &gt; G) were found by whole-exome sequencing in the patients. These variants were confirmed by Sanger sequencing in family members.ConclusionsHerein, we reported two Chinese male patients with CMT4J who presented with abnormal CNS features. CMT4J with CNS involvement has been very rarely reported. We hoped this study could expand the phenotypic and genetic spectrum of FIG4-related diseases. And we helped physicians to understand the genotype–phenotype correlation.
Abnormalities in microbial composition and function in infants with necrotizing enterocolitis: A single-center observational study
Authors: Huang Huan , Peng Qian , Zhang Yuli , Li Ying , Huang Nanqu , Duan Miao , Huang Bo 
Published: October 2022

ObjectiveTo investigate the features and functions of the intestinal microbiota in neonates with necrotizing enterocolitis (NEC) in a single center in China.MethodsWe collected clinical information and stool samples from 19 participants in our center, including 9 infants with necrotizing enterocolitis and 10 control infants. DNA was extracted from the samples, and 16S rRNA gene sequencing was used to analyse the participants' gut microbiota. Functional prediction was achieved using PICRUSt2.ResultsAlpha diversity analysis found that similar levels of bacterial richness and diversity were found in the gut microbiota of infants with NEC and control infants (P = 0.1800), whereas beta diversity analysis suggested that the overall structures of the gut microbiota were significantly different (P = 0.0020). The Mann–Whitney U test of bacterial composition and abundance analysis revealed that the abundance levels of Proteobacteria (P = 0.03049) and Firmicutes (P = 0.01011) significantly differed between the two groups at the phylum level. Proteobacteria was the most abundant phylum in the NEC group. At the genus level, the abundance levels of Enterococcus (P = 0.0003), Streptococcaceae (P = 0.0109) and Lactobacillales (P = 0.0171) were significantly decreased in infants with NEC. Furthermore, the linear discriminant analysis effect size (LEfSe) method showed 12 bacterial taxa with significant differences in relative abundances in the two groups. Interestingly, members of Proteobacteria were enriched in NEC samples. In addition, functional prediction suggested that the microbial changes observed in infants with NEC resulted in a decline in galactose metabolism, the pentose phosphate pathway, fructose and mannose metabolism, amino sugar and nucleotide sugar metabolism, glycolysis/gluconeogenesis, starch and sucrose metabolism, and phosphotransferase system (PTS) pathways (P &lt; 0.05).ConclusionsOur study shows the compositional and functional alterations of the intestinal microbiota in NEC, which will help demonstrate the relationship between the gut microbiota and NEC pathogenesis.
Safety and efficacy of compound methyl salicylate liniment for topical pain: A multicenter real-world study in China
Authors: Guo Jie , Hu Xiaolei , Wang Jing , Yu Bin , Li Juan , Chen Jianting , Nie Xiaoli , Zheng Zhijian , Wang Shixuan , Qin Qun 
Published: October 2022

Compound methyl salicylate liniment (Ammeltz) is composed of various components, such as methyl salicylate, menthol, camphor, chlorpheniramine maleate, and thymol. It was approved for listing in China in 2011. The purpose of this phase Ⅳ clinical trial was to evaluate the safety and efficacy of Ammeltz in a real-life environment in China. Adverse events and adverse drug reactions were used to assess the safety of the monitored drugs. Visual analog scale (VAS) scores were evaluated to assess the severity of pain and the pain relief rate was used to evaluate the efficacy of the study drug. Of 3,600 subjects enrolled, 3,515 (97.64%) subjects completed the study and 85 (2.36%) terminated the study prematurely. A total of 277 adverse events occurred in 258 subjects (7.28%). The most common adverse events included upper respiratory infections (130 cases, 3.67%), local pruritus (17 cases, 0.48%), and diarrhea (12 cases, 0.34%). A total of 50 (1.41%) subjects experienced 58 adverse drug reactions. The most common adverse drug reactions included local pruritus (17 cases, 0.48%), a burning sensation at the application site (10 cases, 0.28%), and irritation at the application site (local) (7 cases, 0.2%). No adverse reactions were identified as new adverse drug reactions. The majority of adverse drug reactions were mild (48 cases, 1.36%), and no severe adverse drug reactions occurred. The subjects experienced significant pain relief after using Ammeltz (mean VAS scores: 5.34 vs. 2.79; Day 7 ± 1 vs. Baseline; p &lt; 0.0001). The pain relief rate was 47.11% ± 23.13%, and in 2,769 cases (78.31%) the drug was effective in pain relief. After excluding subjects who used drugs that could affect the efficacy of the study drug, the subgroups of subjects experienced significant pain relief after using Ammeltz (mean VAS scores: 5.31 vs 2.77; Day 7 ± 1 vs Baseline; p &lt; 0.0001). The pain relief rate was 47.34% ± 23.00%, and 2,612 subjects (78.75%) experienced effective pain relief. In conclusion, Ammeltz is safe and effective in real-life use. It can significantly relieve soft tissue pain caused by shoulder and neck pain, back pain, or muscle pain. No new adverse drug reactions were found in our multicenter real-world study.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT05489939?cond=Safety+and+efficacy+of+compound+methyl+salicylate+liniment+for+topical+pain%3A+A+multicenter+real-world+study+in+China&amp;draw=2&amp;rank=1, identifier NCT05489939
Identification of the effect and mechanism of Yiyi Fuzi Baijiang powder against colorectal cancer using network pharmacology and experimental validation
Authors: Xiang Bin , Geng Ruiman , Zhang Zhengkun , Ji Xuxu , Zou Jiaqiong , Chen Lihong , Liu Ji 
Published: October 2022

Background: Yiyi Fuzi Baijiang powder (YFBP) is a traditional Chinese medicine used to treat colorectal cancer, although its bioactivity and mechanisms of action have not been studied in depth yet. The study intended to identify the potential targets and signaling pathways affected by YFBP during the treatment of colorectal cancer through pharmacological network analysis and to further analyze its chemical compositions and molecular mechanisms of action.Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID), HitPredict (HIT), and Search Tool for Interactions of Chemicals (STITCH) databases were used to screen the bioactive components and promising targets of YFBP. Targets related to colorectal cancer were retrieved from the GeneCards and Gene Ontology databases. Cytoscape software was used to construct the “herb–active ingredient–target” network. The STRING database was used to construct and analyze protein–protein interactions (PPIs). Afterward, the R packages clusterProfiler and Cytoscape Hub plug-in were used to perform Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of target genes. The results of the network pharmacological analysis were also experimentally validated.Results: In total, 33 active components and 128 target genes were screened. Among them, 46 target genes were considered potential therapeutic targets that crossed the CRC target genes. The network pharmacology analysis showed that the active components of YFBP were correlated positively with CRC inflammatory target genes such as TLR4, TNF, and IL-6. The inflammation-related signaling pathways affected by the active components included the TNF-α, interleukin-17, and toll-like receptor signaling pathways. The active ingredients of YFBP, such as luteolin, β-sitosterol, myristic acid, and vanillin, may exert anti-tumor effects by downregulating SMOX expression via anti-inflammatory signaling and regulation of the TLR4/NF-κB signaling pathway.Conclusion: In the present study, the potential active components, potential targets, and key biological pathways involved in the YFBP treatment of CRC were determined, providing a theoretical foundation for further anti-tumor research.
Non-carbonic buffer power of whole blood is increased in experimental metabolic acidosis: An in-vitro study
Authors: Krbec Martin , Waldauf Petr , Zadek Francesco , Brusatori Serena , Zanella Alberto , Duška František , Langer Thomas 
Published: October 2022

Non-carbonic buffer power (βNC) of blood is a pivotal concept in acid-base physiology as it is employed in several acid-base evaluation techniques, including the Davenport nomogram and the Van Slyke equation used for Base excess estimation in blood. So far, βNC has been assumed to be independent of metabolic acid-base status of blood, despite theoretical rationale for the contrary. In the current study, we used CO2 tonometry to assess βNC in blood samples from 10 healthy volunteers, simultaneously analyzing the electrolyte shifts across the red blood cell membrane as these shifts translate the action of intracellular non-carbonic buffers to plasma. The βNC of the blood was re-evaluated after experimental induction of metabolic acidosis obtained by adding a moderate or high amount of either hydrochloric or lactic acid to the samples. Moreover, the impact of βNC and pCO2 on the Base excess of blood was examined. In the control samples, βNC was 28.0 ± 2.5 mmol/L. In contrast to the traditional assumptions, our data showed that βNC rose by 0.36 mmol/L for each 1 mEq/l reduction in plasma strong ion difference (p &lt; 0.0001) and was independent of the acid used. This could serve as a protective mechanism that increases the resilience of blood to the combination of metabolic and respiratory acidosis. Sodium and chloride were the only electrolytes whose plasma concentration changed relevantly during CO2 titration. Although no significant difference was found between the electrolyte shifts in the two types of acidosis, we observed a slightly higher rate of chloride change in hyperchloremic acidosis, while the variation of sodium was more pronounced in lactic acidosis. Lastly, we found that the rise of βNC in metabolic acidosis did not induce a clinically relevant bias in the calculation of Base excess of blood and confirmed that the Base excess of blood was little affected by a wide range of pCO2.
Rainbow trout integrated response after recovery from short-term acute hypoxia
Authors: García-Meilán Irene , Tort Lluis , Khansari Ali Reza 
Published: October 2022

Overcoming a stress situation, such as hypoxia episodes, which involve an allostatic load, will depend on the ability of fish to modulate physiological and biochemical systems to maintain homeostasis. The aim of the study was to determine the integrated stress response after acute hypoxia of the rainbow trout considering the different elements and areas of the stress response: systemic and mucosal, local and global, and from the systemic hypothalamic–pituitary–interrenal axis to skin mucosa. For this purpose, trout were subjected to acute hypoxia (dissolved O2 down to 2 mg/L) for 1 h and then recovered and sampled at 1, 6, and 24 h after reoxygenation. Physiological responses were significantly affected by hypoxic stress and their interaction with time after the challenge, being significant for plasma lactate and cortisol levels, in both plasma and skin mucus. At the central brain level, only trh expression was modulated 1 h after hypoxia which indicates that brain function is not heavily affected by this particular stress. Unlike the brain, the head kidney and skin were more affected by hypoxia and reoxygenation. In the head kidney, an upregulation in the expression of most of the genes studied (gr, il1β, il6, tgfβ1, lysozyme, caspase 3, enolase, hif-1, myoglobin, sod2, gpx, gst, and gsr) took place 6 h after recovery, whereas only hsp70 and il10 were upregulated after 1 h. On the contrary, in the skin, most of the analyzed genes showed a higher upregulation during 1 h after stress suggesting that, in the skin, a local response took place as soon as the stressor was detected, thus indicating the importance of the skin in the building of a stress response, whereas the interrenal tissue participated in a later time point to help prevent further alteration at the central level. The present results also show that, even though the stressor is a physical/environmental stressor, all components of the biological systems participate in the regulation of the response process and the recovery process, including neuroendocrine, metabolism, and immunity.
Impression of foliar-applied folic acid on coriander (Coriandrum sativum L.) to regulate aerial growth, biochemical activity, and essential oil profiling under drought stress
Authors: Khan Muhammad Tajammal , Ahmed Shakil , Sardar Rehana , Shareef Muhammad , Abbasi Asim , Mohiuddin Muhammad , Ercisli Sezai , Fiaz Sajid , Marc Romina Alina , Attia Kotb , Khan Naeem , Golokhvast Kiril S. 
Published: October 2022

Drought is one of the major environmental limitations in the crop production sector that has a great impact on food security worldwide. Coriander (Coriandrum sativum L.) is an herbaceous angiosperm of culinary significance and highly susceptible to rootzone dryness. Elucidating the drought-induced physio-chemical changes and the foliar-applied folic acid (FA; vitamin B9)-mediated stress tolerance mechanism of coriander has been found as a research hotspot under the progressing water scarcity challenges for agriculture. The significance of folic acid in ameliorating biochemical activities for the improved vegetative growth and performance of coriander under the mild stress (MS75), severe stress (SS50), and unstressed (US100) conditions was examined in this study during two consecutive seasons. The results revealed that the plants treated with 50 mM FA showed the highest plant fresh biomass, leaf fresh biomass, and shoot fresh biomass from bolting stage to seed filling stage under mild drought stress. In addition, total soluble sugars, total flavonoids content, and chlorophyll content showed significant results by the foliar application of FA, while total phenolic content showed non-significant results under MS75 and SS50. It was found that 50 mM of FA upregulated the activity of catalase, superoxide dismutase, and ascorbate peroxidase enzymes in MS75 and SS50 plants compared with untreated FA plants. Thus, FA treatment improved the overall biological yield and economic yield regardless of water deficit conditions. FA-accompanied plants showed a decline in drought susceptibility index, while it improved the drought tolerance efficiency, indicating this variety to become stress tolerant. The optimum harvest index, essential oil (EO) percentage, and oil yield were found in MS75 followed by SS50 in FA-supplemented plants. The gas chromatography–mass spectrometry analysis revealed a higher abundance of linalool as the major chemical constituent of EO, followed by α-terpeniol, terpinene, and p-Cymene in FA-treated SS50 plants. FA can be chosen as a shotgun tactic to improve drought tolerance in coriander by delimiting the drastic changes due to drought stress.
Rapid prediction of winter wheat yield and nitrogen use efficiency using consumer-grade unmanned aerial vehicles multispectral imagery
Authors: Liu Jikai , Zhu Yongji , Tao Xinyu , Chen Xiaofang , Li Xinwei 
Published: October 2022

Rapid and accurate assessment of yield and nitrogen use efficiency (NUE) is essential for growth monitoring, efficient utilization of fertilizer and precision management. This study explored the potential of a consumer-grade DJI Phantom 4 Multispectral (P4M) camera for yield or NUE assessment in winter wheat by using the universal vegetation indices independent of growth period. Three vegetation indices having a strong correlation with yield or NUE during the entire growth season were determined through Pearson’s correlational analysis, while multiple linear regression (MLR), stepwise MLR (SMLR), and partial least-squares regression (PLSR) methods based on the aforementioned vegetation indices were adopted during different growth periods. The cumulative results showed that the reciprocal ratio vegetation index (repRVI) had a high potential for yield assessment throughout the growing season, and the late grain-filling stage was deemed as the optimal single stage with R2, root mean square error (RMSE), and mean absolute error (MAE) of 0.85, 793.96 kg/ha, and 656.31 kg/ha, respectively. MERIS terrestrial chlorophyll index (MTCI) performed better in the vegetative period and provided the best prediction results for the N partial factor productivity (NPFP) at the jointing stage, with R2, RMSE, and MAE of 0.65, 10.53 kg yield/kg N, and 8.90 kg yield/kg N, respectively. At the same time, the modified normalized difference blue index (mNDblue) was more accurate during the reproductive period, providing the best accuracy for agronomical NUE (aNUE) assessment at the late grain-filling stage, with R2, RMSE, and MAE of 0.61, 7.48 kg yield/kg N, and 6.05 kg yield/kg N, respectively. Furthermore, the findings indicated that model accuracy cannot be improved by increasing the number of input features. Overall, these results indicate that the consumer-grade P4M camera is suitable for early and efficient monitoring of important crop traits, providing a cost-effective choice for the development of the precision agricultural system.