bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of long-term trends in genetic mean and variance after the introduction of genomic selection in layers: a simulation study
Authors: Pocrnic Ivan , Obšteter Jana , Gaynor R. Chris , Wolc Anna , Gorjanc Gregor
Published: May 2023

Nucleus-based breeding programs are characterized by intense selection that results in high genetic gain, which inevitably means reduction of genetic variation in the breeding population. Therefore, genetic variation in such breeding systems is typically managed systematically, for example, by avoiding mating the closest relatives to limit progeny inbreeding. However, intense selection requires maximum effort to make such breeding programs sustainable in the long-term. The objective of this study was to use simulation to evaluate the long-term impact of genomic selection on genetic mean and variance in an intense layer chicken breeding program. We developed a large-scale stochastic simulation of an intense layer chicken breeding program to compare conventional truncation selection to genomic truncation selection optimized with either minimization of progeny inbreeding or full-scale optimal contribution selection. We compared the programs in terms of genetic mean, genic variance, conversion efficiency, rate of inbreeding, effective population size, and accuracy of selection. Our results confirmed that genomic truncation selection has immediate benefits compared to conventional truncation selection in all specified metrics. A simple minimization of progeny inbreeding after genomic truncation selection did not provide any significant improvements. Optimal contribution selection was successful in having better conversion efficiency and effective population size compared to genomic truncation selection, but it must be fine-tuned for balance between loss of genetic variance and genetic gain. In our simulation, we measured this balance using trigonometric penalty degrees between truncation selection and a balanced solution and concluded that the best results were between 45° and 65°. This balance is specific to the breeding program and depends on how much immediate genetic gain a breeding program may risk vs. save for the future. Furthermore, our results show that the persistence of accuracy is better with optimal contribution selection compared to truncation selection. In general, our results show that optimal contribution selection can ensure long-term success in intensive breeding programs using genomic selection.
Current hotspot and study trend of innate immunity in COVID-19: a bibliometric analysis from 2020 to 2022
Authors: Lai Ping , Xu Shuquan , Xue Jin-hua , Zhang Hong-zhou , Zhong Yi-ming , Liao Yong-ling
Published: May 2023

Background

Since the coronavirus disease 2019 (COVID-19) has spread throughout the world, many studies on innate immunity in COVID-19 have been published, and great progress has been achieved, while bibliometric analysis on hotspots and research trends in this field remains lacking.

Methods

On 17 November 2022, articles and reviews on innate immunity in COVID-19 were recruited from the Web of Science Core Collection (WoSCC) database after papers irrelevant to COVID-19 were further excluded. The number of annual publications and the average citations per paper were analyzed by Microsoft Excel. Bibliometric analysis and visualization of the most prolific contributors and hotspots in the field were performed by VOSviewer and CiteSpace software.

Results

There were 1,280 publications that met the search strategy on innate immunity in COVID-19 and were published from 1 January 2020 to 31 October 2022. Nine hundred thirteen articles and reviews were included in the final analysis. The USA had the highest number of publications (Np) at 276 and number of citations without self-citations (Nc) at 7,085, as well as an H-index of 42, which contributed 30.23% of the total publications, followed by China (Np: 135, Nc: 4,798, and H-index: 23) with 14.79% contribution. Regarding Np for authors, Netea, Mihai G. (Np: 7) from the Netherlands was the most productive author, followed by Joosten, Leo A. B. (Np: 6) and Lu, Kuo-Cheng (Np: 6). The Udice French Research Universities had the most publications (Np: 31, Nc: 2,071, H-index: 13), with an average citation number (ACN) at 67. The journal Frontiers in Immunology possessed the most publications (Np: 89, Nc: 1,097, ACN: 12.52). “Evasion” (strength 1.76, 2021-2022), “neutralizing antibody” (strength 1.76, 2021-2022), “messenger RNA” (strength 1.76, 2021-2022), “mitochondrial DNA” (strength 1.51, 2021-2022), “respiratory infection” (strength 1.51, 2021-2022), and “toll-like receptors” (strength 1.51, 2021-2022) were the emerging keywords in this field.

Conclusion

The study on innate immunity in COVID-19 is a hot topic. The USA was the most productive and influential country in this field, followed by China. The journal with the most publications was Frontiers in Immunology. “Messenger RNA,” “mitochondrial DNA,” and “toll-like receptors” are the current hotspots and potential targets in future research.
Integration analysis of tumor metagenome and peripheral immunity data of diffuse large-B cell lymphoma
Authors: Zhang Yu , Han Shuiyun , Xiao Xibing , Zheng Lu , Chen Yingying , Zhang Zhijian , Gao Xinfang , Zhou Shujuan , Yu Kang , Huang Li , Fu Jiaping , Hong Yongwei , Jiang Jinhong , Qian Wenbin , Yang Haiyan , Shen Jianping
Published: May 2023

Background/purpose

It has been demonstrated that gut microbes are closely associated with the pathogenesis of lymphoma, but the gut microbe landscape and its association with immune cells in diffuse large B-cell lymphoma (DLBCL) remain largely unknown. In this study, we explored the associations between gut microbiota, clinical features and peripheral blood immune cell subtypes in DLBCL.

Method

A total of 87 newly diagnosed DLBCL adults were enrolled in this study. The peripheral blood samples were collected from all patients and then submitted to immune cell subtyping using full-spectral flow cytometry. Metagenomic sequencing was applied to assess the microbiota landscape of 69 of 87 newly diagnosed DLBCL patients. The microbiotas and peripheral blood immune cell subsets with significant differences between different National Comprehensive Center Network-International Prognostic Indexes (NCCN-IPIs) (low-risk, low-intermediate-risk, intermediate-high-risk, high-risk) groups were screened.

Results

A total of 10 bacterial phyla, 31 orders and 455 bacteria species were identified in 69 patients with newly diagnosed DLBCL. The abundances of 6 bacteria, including Blautia sp.CAG 257, Actinomyces sp.S6 Spd3, Streptococcus parasanguinis, Bacteroides salyersiae, Enterococcus faecalls and Streptococcus salivarius were significantly different between the low-risk, low-intermediate-risk, intermediate-high-risk and high-risk groups, among which Streptococcus parasanguinis and Streptococcus salivarius were markedly accumulated in the high-risk group. The different bacteria species were mostly enriched in the Pyridoxal 5’-phosphate biosynthesis I pathway. In addition, we found that 2 of the 6 bacteria showed close associations with the different immune cell subtypes which were also identified from different NCCN-IPIs. In detail, the abundance of Bacteroides salyersiae was negatively correlated with Treg cells, CD38+ nonrescue exhausted T cells, nature killer 3 cells and CD38+CD8+ effector memory T cells, while the abundance of Streptococcus parasanguinis was negatively correlated with HLA-DR+ NK cells, CD4+ Treg cells, HLA-DR+ NKT cells and HLA-DR+CD94+CD159c+ NKT cells.

Conclusion

This study first reveals the gut microbiota landscape of patients with newly diagnosed DLBCL and highlights the association between the gut microbiota and immunity, which may provide a new idea for the prognosis assessment and treatment of DLBCL.
Classification of inbound and outbound ships using convolutional neural networks
Authors: Guo Doudou , Gao Dazhi , Chen Zhuo , Li Yuzheng , Zhao Xiaojing , Song Wenhua , Li Xiaolei
Published: May 2023

In general, a single scalar hydrophone cannot determine the orientation of an underwater acoustic target. However, through a study of sea trial experimental data, the authors found that the sound field interference structures of inbound and outbound ships differ owing to changes in the topography of the shallow continental shelf. Based on this difference, four different convolutional neural networks (CNNs), AlexNet, visual geometry group, residual network (ResNet), and dense convolutional network (DenseNet), are trained to classify inbound and outbound ships using only a single scalar hydrophone. Two datasets, a simulation and a sea trial, are used in the CNNs. Each dataset is divided into a training set and a test set according to the proportion of 40% to 60%. The simulation dataset is generated using underwater acoustic propagation software, with surface ships of different parameters (tonnage, speed, draft) modeled as various acoustic sources. The experimental dataset is obtained using submersible buoys placed near Qingdao Port, including 321 target ships. The ships in the dataset are labeled inbound or outbound using ship automatic identification system data. The results showed that the accuracy of the four CNNs based on the sea trial dataset in judging vessels’ inbound and outbound situations is above 90%, among which the accuracy of DenseNet is as high as 99.2%. This study also explains the physical principle of classifying inbound and outbound ships by analyzing the low-frequency analysis and recording diagram of the broadband noise radiated by the ships. This method can monitor ships entering and leaving ports illegally and with abnormal courses in specific sea areas.
Biochemical and molecular characterization of novel keratinolytic protease from Bacillus licheniformis (KRLr1)
Authors: Rahimnahal Somayyeh , Meimandipour Amir , Fayazi Jamal , Asghar Karkhane Ali , Shamsara Mehdi , Beigi Nassiri Mohammadtaghi , Mirzaei Hamed , Hamblin Michael R. , Tarrahimofrad Hossein , Bakherad Hamid , Zamani Javad , Mohammadi Yahya
Published: May 2023

The keratin-degrading bacterium Bacillus licheniformis secretes a keratinase with potential industrial interest. Here, the Keratinase gene was intracellularly expressed in Escherichia coli BL21(DE3) using pET-21b (+) vector. Phylogenetic tree analysis showed that KRLr1 is closely related to Bacillus licheniformis keratinase that belongs to the serine peptidase/subtilisin-like S8 family. Recombinant keratinase appeared on the SDS-PAGE gel with a band of about 38 kDa and was confirmed by western blotting. Expressed KRLr1 was purified by Ni-NTA affinity chromatography with a yield of 85.96% and then refolded. It was found that this enzyme has optimum activity at pH 6 and 37°C. PMSF inhibited the KRLr1 activity and Ca2+ and Mg2+ increased the KRLr1 activity. Using keratin 1% as the substrate, the thermodynamic values were determined as Km 14.54 mM, kcat 912.7 × 10−3 (S−1), and kcat/Km 62.77 (M−1 S−1). Feather digestion by recombinant enzyme using HPLC method, showed that the amino acids cysteine, phenylalanine, tyrosine and lysine had the highest amount compared to other amino acids obtained from digestion. Molecular dynamics (MD) simulation of HADDOCK docking results exhibited that KRLr1 enzyme was able to interact strongly with chicken feather keratine 4 (FK4) compared to chicken feather keratine 12 (FK12). These properties make keratinase KRLr1 a potential candidate for various biotechnological applications.
Production of tailored hydroxylated prodiginine showing combinatorial activity with rhamnolipids against plant-parasitic nematodes
Authors: Kossmann D. F. , Huang M. , Weihmann R. , Xiao X. , Gätgens F. , Weber T. M. , Brass H. U. C. , Bitzenhofer N. L. , Ibrahim S. , Bangert K. , Rehling L. , Mueller C. , Tiso T. , Blank L. M. , Drepper T. , Jaeger K.-E. , Grundler F. M. W. , Pietruszka J. , Schleker A. S. S. , Loeschcke A.
Published: May 2023

Bacterial secondary metabolites exhibit diverse remarkable bioactivities and are thus the subject of study for different applications. Recently, the individual effectiveness of tripyrrolic prodiginines and rhamnolipids against the plant-parasitic nematode Heterodera schachtii, which causes tremendous losses in crop plants, was described. Notably, rhamnolipid production in engineered Pseudomonas putida strains has already reached industrial implementation. However, the non-natural hydroxyl-decorated prodiginines, which are of particular interest in this study due to a previously described particularly good plant compatibility and low toxicity, are not as readily accessible. In the present study, a new effective hybrid synthetic route was established. This included the engineering of a novel P. putida strain to provide enhanced levels of a bipyrrole precursor and an optimization of mutasynthesis, i.e., the conversion of chemically synthesized and supplemented monopyrroles to tripyrrolic compounds. Subsequent semisynthesis provided the hydroxylated prodiginine. The prodiginines caused reduced infectiousness of H. schachtii for Arabidopsis thaliana plants resulting from impaired motility and stylet thrusting, providing the first insights on the mode of action in this context. Furthermore, the combined application with rhamnolipids was assessed for the first time and found to be more effective against nematode parasitism than the individual compounds. To obtain, for instance, 50% nematode control, it was sufficient to apply 7.8 μM hydroxylated prodiginine together with 0.7 μg/ml (~ 1.1 μM) di-rhamnolipids, which corresponded to ca. ¼ of the individual EC50 values. In summary, a hybrid synthetic route toward a hydroxylated prodiginine was established and its effects and combinatorial activity with rhamnolipids on plant-parasitic nematode H. schachtii are presented, demonstrating potential application as antinematodal agents.
Graphical Abstract
MALDI-TOF Mass Spectrometry for interrogating ubiquitin enzymes
Authors: De Cesare Virginia
Published: May 2023

The attachment of ubiquitin to a substrate (ubiquitination or ubiquitylation) impacts its lifetime and regulates its function within the cell. Several classes of enzymes oversee the attachment of ubiquitin to the substrate: an E1 activating enzyme that makes ubiquitin chemically susceptible prior to the following stages of conjugation and ligation, respectively mediated by E2 conjugating enzymes (E2s) and E3 ligases (E3s). Around 40 E2s and more than 600 E3s are encoded in the human genome, and their combinatorial and cooperative behaviour dictate the tight specificity necessary for the regulation of thousands of substrates. The removal of ubiquitin is orchestrated by a network of about 100 deubiquitylating enzymes (DUBs). Many cellular processes are tightly controlled by ubiquitylation, which is essential in maintaining cellular homeostasis. Because of the fundamental role(s) of ubiquitylation, there is an interest in better understanding the function and specificity of the ubiquitin machinery. Since 2014, an expanding array of Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) Mass Spectrometry (MS) assays have been developed to systematically characterise the activity of a variety of ubiquitin enzymes in vitro. Here we recapitulate how MALDI-TOF MS aided the in vitro characterization of ubiquitin enzymes and the discovery of new and unexpected of E2s and DUBs functions. Given the versatility of the MALDI-TOF MS approach, we foreseen the use of this technology to further expand our understanding of ubiquitin and ubiquitin-like enzymes.
Clinical and genetic analysis of benign familial infantile epilepsy caused by PRRT2 gene variant
Authors: Gu Yu , Mei Daoqi , Wang Xiaona , Ma Ang , Kong Jinghui , Zhang Yaodong
Published: May 2023

Objective

This study presents the clinical phenotypes and genetic analysis of seven patients with benign familial infantile epilepsy (BFIE) diagnosed by whole-exome sequencing.

Methods

The clinical data of seven children with BFIE diagnosed at the Department of Neurology, Children’s Hospital Affiliated to Zhengzhou University between December 2017 and April 2022 were retrospectively analyzed. Whole-exome sequencing was used to identify the genetic causes, and the variants were verified by Sanger sequencing in other family members.

Results

The seven patients with BFIE included two males and five females ranging in age between 3 and 7 months old. The main clinical phenotype of the seven affected children was the presence of focal or generalized tonic–clonic seizures, which was well controlled by anti-seizure medication. Cases 1 and 5 exhibited predominantly generalized tonic–clonic seizures accompanied by focal seizures while cases 2, 3, and 7 displayed generalized tonic–clonic seizures, and cases 4 and 6 had focal seizures. The grandmother and father of cases 2, 6, and 7 had histories of seizures. However, there was no family history of seizures in the remaining cases. Case 1 carried a de novo frameshift variant c.397delG (p.E133Nfs*43) in the proline-rich transmembrane protein 2 (PRRT2) gene while case 2 had a nonsense variant c.46G > T (p.Glu16*) inherited from the father, and cases 3–7 carried a heterozygous frameshift variant c.649dup (p.R217Pfs*8) in the same gene. In cases 3 and 4, the frameshift variant was de novo, while in cases 5–7, the variant was paternally inherited. The c.397delG (p.E133Nfs*43) variant is previously unreported.

Conclusion

This study demonstrated the effectiveness of whole-exome sequencing in the diagnosis of BFIE. Moreover, our findings revealed a novel pathogenic variant c.397delG (p.E133Nfs*43) in the PRRT2 gene that causes BFIE, expanding the mutation spectrum of PRRT2.
Deep-learning segmentation of fascicles from microCT of the human vagus nerve
Authors: Buyukcelik Ozge N. , Lapierre-Landry Maryse , Kolluru Chaitanya , Upadhye Aniruddha R. , Marshall Daniel P. , Pelot Nicole A. , Ludwig Kip A. , Gustafson Kenneth J. , Wilson David L. , Jenkins Michael W. , Shoffstall Andrew J.
Published: May 2023

Introduction

MicroCT of the three-dimensional fascicular organization of the human vagus nerve provides essential data to inform basic anatomy as well as the development and optimization of neuromodulation therapies. To process the images into usable formats for subsequent analysis and computational modeling, the fascicles must be segmented. Prior segmentations were completed manually due to the complex nature of the images, including variable contrast between tissue types and staining artifacts.

Methods

Here, we developed a U-Net convolutional neural network (CNN) to automate segmentation of fascicles in microCT of human vagus nerve.

Results

The U-Net segmentation of ~500 images spanning one cervical vagus nerve was completed in 24 s, versus ~40 h for manual segmentation, i.e., nearly four orders of magnitude faster. The automated segmentations had a Dice coefficient of 0.87, a measure of pixel-wise accuracy, thus suggesting a rapid and accurate segmentation. While Dice coefficients are a commonly used metric to assess segmentation performance, we also adapted a metric to assess fascicle-wise detection accuracy, which showed that our network accurately detects the majority of fascicles, but may under-detect smaller fascicles.

Discussion

This network and the associated performance metrics set a benchmark, using a standard U-Net CNN, for the application of deep-learning algorithms to segment fascicles from microCT images. The process may be further optimized by refining tissue staining methods, modifying network architecture, and expanding the ground-truth training data. The resulting three-dimensional segmentations of the human vagus nerve will provide unprecedented accuracy to define nerve morphology in computational models for the analysis and design of neuromodulation therapies.
Impact of organic and integrated production systems on yield and seed quality of rainfed crops and on soil properties
Authors: Gopinath Kodigal A. , Venkatesh Govindarajan , Manjunath Mallappa , Jayalakshmi Mitnala , Prasad Telaprolu Venkata , Rajkumar Bollam , Venugopalan Visha Kumari , Raju Bellapukonda Murali Krishna , Prabhakar Mathyam , Chary Gajjala Ravindra , Singh Vinod Kumar
Published: May 2023

Mineral and vitamin deficiencies together affect a greater number of human populations in the world than does protein malnutrition. Organic farming is reported to improve nutritional quality of food grains while also improving soil health. However, sufficient scientific information on several aspects of organic farming based on long-term studies is lacking particularly under rainfed conditions of India. The purpose of this study was to assess the long-term impact of organic and integrated production systems on crops yield and quality, economic returns and soil properties. The study was conducted with three crops, sunflower (Helianthus annuusL.), pigeonpea (Cajanus cajanL.), and greengram [Vigna radiata(L.) Wilczek] under three different production systems, control (use of chemical inputs alone), organic and integrated. The results of the 10-year study revealed that, the average production of integrated system was on par with organic management and recorded significantly higher pigeonpea equivalent yield (PEY) (827 kg ha−1) compared to control (chemical inputs) (748 kg ha−1). In general, the yield gap between organic and integrated production systems declined from fourth year for greengram and eighth year for sunflower, during the 10-year experimental period whereas the pigeonpea yield was similar under both production systems from first year. Plots under organic management had significantly lower bulk density (1.18 mg m−3), higher water holding capacity (38.72%) and porosity (53.79%) compared to integrated production system and control (chemical inputs). The soil organic C (SOC) content in the plots under organic production system was 32.6% more than the initial organic carbon of the soil (0.43%), with higher soil N (205.2 kg ha−1). Plots under integrated production system, however, had higher soil P (26.5 kg ha−1) compared with other treatments. The dehydrogenase activity (5.86 μg TPF g−1soil h−1) and microbial biomass carbon (317.3 μg g−1soil) content was higher in the plots under organic production system than under other systems. Organically produced pigeonpea and greengram seeds had similar protein content with that of integrated system, and higher K and micronutrient (Fe, Zn, Cu, and Mn) contents than other treatments. The results show the potential of organic production system in improving crop yields, soil properties and produce quality in semiarid rainfed areas.
Inflammatory biomarkers as predictors of immune activation to different irradiated sites and short-term efficacy in advanced squamous cell esophageal carcinoma received radioimmunotherapy
Authors: Li Mengying , Cai Guoxin , Gao Zhenhua , Meng Xue , Han Xiao
Published: May 2023

Purpose

The present study aimed to compare immune activation among different irradiated sites and identify potential short-term efficacy prognostic factors in patients with advanced squamous cell esophageal carcinoma (ESCC) who received radiotherapy (RT) and immunotherapy.

Patients and methods

We recorded the clinical characteristics, blood cell counts, and derived blood index ratios, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), at three time points (before, during, and after RT) in 121 patients with advanced ESCC who had received RT and immunotherapy. Chi-square test and univariate and multivariate logistic regression analyses were used to calculate the relationships among inflammatory biomarkers (IBs), irradiated sites, and short-term efficacy.

Results

Delta-IBs were calculated as (medio-IBs - pre-IBs) ÷ pre-IBs. The medians of delta-LMR, and delta-ALC were the highest, whereas the median of delta-SII was the lowest in patients with brain radiation. Treatment responses were observed within 3 months after RT or until the beginning of the next line therapy, and the disease control rate (DCR) was 75.2%. The areas under the receiver operating characteristic curve (AUCs) for delta-NLR and delta-SII were 0.723 (p = 0.001) and 0.725 (p < 0.001), respectively. Multivariate logistic regression analysis showed that the treatment lines of immunotherapy (odds ratio [OR], 4.852; 95% confidence interval [CI], 1.595-14.759; p = 0.005) and delta-SII (OR, 5.252; 95% CI, 1.048-26.320; p = 0.044) were independent indicators of short-term efficacy.

Conclusion

In this study, we found that RT to the brain had a stronger immune activation effect than RT to extracranial organs. We also found that earlier-line immunotherapy plus RT and a decrease in SII during RT may generate better short-term efficacy in advanced ESCC.
Identification of abemaciclib derivatives targeting cyclin-dependent kinase 4 and 6 using molecular dynamics, binding free energy calculation, synthesis, and pharmacological evaluation
Authors: Zhou Yanting , Li Xiandeng , Luo Peifang , Chen Huiting , Zhou Yan , Zheng Xueting , Yin Yuan , Wei Haoche , Liu Hongji , Xia Wen , Shi Mingsong , Li Xiaoan
Published: May 2023

CDK4/6 plays a crucial role in various cancers and is an effective anticancer drug target. However, the gap between clinical requirements and approved CDK4/6 drugs is unresolved. Thus, there is an urgent need to develop selective and oral CDK4/6 inhibitors, particularly for monotherapy. Here, we studied the interaction between abemaciclib and human CDK6 using molecular dynamics simulations, binding free energy calculations, and energy decomposition. V101 and H100 formed stable hydrogen bonds with the amine-pyrimidine group, and K43 interacted with the imidazole ring via an unstable hydrogen bond. Meanwhile, I19, V27, A41, and L152 interacted with abemaciclib through π-alkyl interactions. Based on the binding model, abemaciclib was divided into four regions. With one region modification, 43 compounds were designed and evaluated using molecular docking. From each region, three favorable groups were selected and combined with each other to obtain 81 compounds. Among them, C2231-A, which was obtained by removing the methylene group from C2231, showed better inhibition than C2231. Kinase profiling revealed that C2231-A showed inhibitory activity similar to that of abemaciclib; additionally, C2231-A inhibited the growth of MDA-MB-231 cells to a greater extent than did abemaciclib. Based on molecular dynamics simulation, C2231-A was identified as a promising candidate compound with considerable inhibitory effects on human breast cancer cell lines.
Ondansetron: recommended antiemetics for patients with acute pancreatitis? a population-based study
Authors: Wu Ge , Ma Yifei , Wei Wanzhen , Zeng Jiahui , Han Yimin , Song Yiqun , Wang Zheng , Qian Weikun
Published: May 2023

Objective: Ondansetron administration is a common antemetic of acute pancreatitis therapy in the intensive care unit (ICU), but its actual association with patients’ outcomes has not been confirmed. The study is aimed to determine whether the multiple outcomes of ICU patients with acute pancreatitis could benefit from ondansetron.

Methods: 1,030 acute pancreatitis patients diagnosed in 2008–2019 were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database as our study cohort. The primary outcome we considered is the 90-day prognosis, and secondary outcomes included in-hospital survival and overall prognosis.

Results: In MIMIC-IV, 663 acute pancreatitis patients received ondansetron administration (OND group) during their hospitalization, while 367 patients did not (non-OND group). Patients in the OND group presented better in-hospital, 90-day, and overall survival curves than the non-OND group (log-rank test: in-hospital: p < 0.001, 90-day: p = 0.002, overall: p = 0.009). After including covariates, ondansetron was associated with better survival in patients with multiple outcomes (in-hospital: HR = 0.50, 90-day: HR = 0.63, overall: HR = 0.66), and the optimal dose inflection points were 7.8 mg, 4.9 mg, and 4.6 mg, respectively. The survival benefit of ondansetron was unique and stable in the multivariate analyses after consideration of metoclopramide, diphenhydramine, and prochlorperazine, which may also be used as antiemetics.

Conclusion: In ICU acute pancreatitis patients, ondansetron administration was associated with better 90-day outcomes, while results were similar in terms of in-hospital and overall outcomes, and the recommended minimum total dose might be suggested to be 4–8 mg.
Nanosecond pulse effectively ablated hepatocellular carcinoma with alterations in the gut microbiome and serum metabolites
Authors: Zou Yawen , Sun Ying , Chen Xinhua , Hong Liangjie , Dong Gang , Bai Xiwen , Wang Haiyu , Rao Benchen , Ren Zhigang , Yu Zujiang
Published: May 2023

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the world. Nanosecond pulsed electric fields (nsPEFs) have emerged as a new treatment for cancer. This study aims to identify the effectiveness of nsPEFs in the treatment of HCC and analyze the alterations in the gut microbiome and serum metabonomics after ablation.

Methods: C57BL/6 mice were randomly divided into three groups: healthy control mice (n = 10), HCC mice (n = 10), and nsPEF-treated HCC mice (n = 23). Hep1-6 cell lines were used to establish the HCC model in situ. Histopathological staining was performed on tumor tissues. The gut microbiome was analyzed by 16S rRNA sequencing. Serum metabolites were analyzed by liquid chromatography–mass spectrometry (LC-MS) metabolomic analysis. Spearman’s correlation analysis was carried out to analyze the correlation between the gut microbiome and serum metabonomics.

Results: The fluorescence image showed that nsPEFs were significantly effective. Histopathological staining identified nuclear pyknosis and cell necrosis in the nsPEF group. The expression of CD34, PCNA, and VEGF decreased significantly in the nsPEF group. Compared with normal mice, the gut microbiome diversity of HCC mice was increased. Eight genera including Alistipes and Muribaculaceae were enriched in the HCC group. Inversely, these genera decreased in the nsPEF group. LC-MS analysis confirmed that there were significant differences in serum metabolism among the three groups. Correlation analysis showed crucial relationships between the gut microbiome and serum metabolites that are involved in nsPEF ablation of HCC.

Conclusion: As a new minimally invasive treatment for tumor ablation, nsPEFs have an excellent ablation effect. The alterations in the gut microbiome and serum metabolites may participate in the prognosis of HCC ablation.
Characterization of pharmacogenomic variants in a Brazilian admixed cohort of elderly individuals based on whole-genome sequencing data
Authors: Bertholim-Nasciben Luciana , Scliar Marilia O. , Debortoli Guilherme , Thiruvahindrapuram Bhooma , Scherer Stephen W. , Duarte Yeda A. O. , Zatz Mayana , Suarez-Kurtz Guilherme , Parra Esteban J. , Naslavsky Michel S.
Published: May 2023

Introduction: Research in the field of pharmacogenomics (PGx) aims to identify genetic variants that modulate response to drugs, through alterations in their pharmacokinetics (PK) or pharmacodynamics (PD). The distribution of PGx variants differs considerably among populations, and whole-genome sequencing (WGS) plays a major role as a comprehensive approach to detect both common and rare variants. This study evaluated the frequency of PGx markers in the context of the Brazilian population, using data from a population-based admixed cohort from Sao Paulo, Brazil, which includes variants from WGS of 1,171 unrelated, elderly individuals.

Methods: The Stargazer tool was used to call star alleles and structural variants (SVs) from 38 pharmacogenes. Clinically relevant variants were investigated, and the predicted drug response phenotype was analyzed in combination with the medication record to assess individuals potentially at high-risk of gene-drug interaction.

Results: In total, 352 unique star alleles or haplotypes were observed, of which 255 and 199 had a frequency < 0.05 and < 0.01, respectively. For star alleles with frequency > 5% (n = 97), decreased, loss-of-function and unknown function accounted for 13.4%, 8.2% and 27.8% of alleles or haplotypes, respectively. Structural variants (SVs) were identified in 35 genes for at least one individual, and occurred with frequencies >5% for CYP2D6, CYP2A6, GSTM1, and UGT2B17. Overall 98.0% of the individuals carried at least one high risk genotype-predicted phenotype in pharmacogenes with PharmGKB level of evidence 1A for drug interaction. The Electronic Health Record (EHR) Priority Result Notation and the cohort medication registry were combined to assess high-risk gene-drug interactions. In general, 42.0% of the cohort used at least one PharmGKB evidence level 1A drug, and 18.9% of individuals who used PharmGKB evidence level 1A drugs had a genotype-predicted phenotype of high-risk gene-drug interaction.

Conclusion: This study described the applicability of next-generation sequencing (NGS) techniques for translating PGx variants into clinically relevant phenotypes on a large scale in the Brazilian population and explores the feasibility of systematic adoption of PGx testing in Brazil.
Forcing vine regrowth under different irrigation strategies: effect on polyphenolic composition and chromatic characteristics of cv. Tempranillo wines grown in a semiarid climate
Authors: Lavado Rodas Nieves , Uriarte Hernández David , Moreno Cardona Daniel , Mancha Ramírez Luis A. , Prieto Losada María Henar , Valdés Sánchez María Esperanza
Published: May 2023

One of the effects of climate change in warm areas is the asynchrony between the dates of the technological and the phenolic maturity of grapes. This is important because the quality and color stability of red wines are directly related to the content and distribution of phenolic compounds. A novel alternative that has been proposed to delay grape ripening and make it coincide with a seasonal period more favorable for the formation of phenolic compounds is crop forcing. This consists of severe green pruning after flowering, when the buds of the following year have already differentiated. In this way, the buds formed during the same season are forced to sprout, initiating a new delayed cycle. The aim of the present work is to study the effect on the phenolic composition and color of wines elaborated from vines fully irrigated (C), grown using conventional non-forcing (NF) and forcing (F) techniques (C-NF and C-F), and wines from vines subjected to regulated irrigation (RI), grown using NF and F techniques (RI-NF and RI-F). The trial was carried out in an experimental vineyard of the Tempranillo variety located in a semi-arid area (Badajoz, Spain) in the 2017–2019 seasons. The wines (four by treatment) were elaborated and stabilized according to the classic methodologies for red wine. All wines had the same alcohol content, and malolactic fermentation was not carried out in any of them. Anthocyanin profiles were analyzed by HPLC, and total polyphenolic content, anthocyanin content, catechin content, the contribution to color due to co-pigmented anthocyanins, and various chromatic parameters were also determined. Although a significant effect of year was found for almost all the parameters analyzed, a general increasing trend in F wines was found for most of them. The anthocyanin profile of F wines was found to differ from that of C wines, especially in delphinidin, cyanidin, petunidin, and peonidin content. These results indicate that by using the forcing technique it was possible to increase the polyphenolic content by ensuring that the synthesis and accumulation of these substances occurred at more suitable temperatures.
The cultivation of rye in marginal Alpine environments: a comparison of the agronomic, technological, health and sanitary traits of local landraces and commercial cultivars
Authors: Sardella Claudia , Capo Luca , Adamo Martino , Donna Matteo , Ravetto Enri Simone , Vanara Francesca , Lonati Michele , Mucciarelli Marco , Blandino Massimo
Published: May 2023

Rye is a secondary crop that is characterized by a higher tolerance to climatically less favorable conditions than other cereal species. For this reason, rye was historically used as a fundamental raw material for bread production and as a supply of straw in northern parts of Europe as well as in mountain environments, such as Alpine valleys, where locally adapted landraces have continued to be cultivated over the years. In this study, rye landraces collected in different valleys in the Northwest Italian Alps have been selected as the most genetically isolated within their geographical contexts and cultivated in two different marginal Alpine environments. The traits concerning their agronomy, mycotoxin contamination, bioactive content, as well as their technological and baking quality were assessed to characterize and compare rye landraces with commercial wheat and rye cultivars. Rye cultivars showed the same grain yield level as wheat in both environments. Only the genotype selected from the Maira Valley was characterized by tall and thin culms and a proneness to lodging, thereby resulting in a lower yield capacity. Among the rye cultivars, the hybrid one presented the highest yield potential, but also the highest susceptibility to the occurrence of ergot sclerotia. However, the rye cultivars, especially the landraces, were characterized by higher concentrations of minerals, soluble fibers, and soluble phenolic acids, and thus both their flours and breads had superior antioxidant properties. A 40% substitution of refined wheat flour with whole-grain rye flour led to a higher dough water absorption and a lower stability, thereby resulting in lower loaf volumes and darker products. Agronomically and qualitatively speaking, the rye landraces diverged significantly from the conventional rye cultivars, thus reflecting their genetic distinctiveness. The landrace from the Maira Valley shared a high content in phenolic acids and good antioxidant properties with the one from the Susa Valley and, when combined with wheat flour, turned out to be the most suitable for bread making. Overall, the results have highlighted the suitability of reintroducing historic rye supply chains, based on the cultivation of local landraces in marginal environments and the production of value-added bakery goods.
Cold stress resilience of Iranian olive genetic resources: evidence from autochthonous genotypes diversity
Authors: Karamatlou Issa , Navabpour Saeid , Nezhad Khalil Zaynali , Mariotti Roberto , Mousavi Soraya , Hosseini-Mazinani Mehdi
Published: May 2023

Olive (Olea europaea L.) is one of the most cultivated tree species in Iran. This plant is characterized by its tolerance to drought, salt, and heat stresses while being vulnerable to frost. During the last decade, periods of frost have occurred several times in Golestan Province, in the northeast of Iran, which caused severe damage to olive groves. This study aimed to evaluate and individuate autochthonous Iranian olive varieties with regard to frost tolerance and good agronomic performance. For this purpose, 218 frost-tolerant olive trees were selected from 150,000 adult olive trees (15–25 years old), following the last harsh autumn of 2016. The selected trees were reassessed at different intervals, i.e., 1, 4, and 7 months after the cold stress in field conditions. Using 19 morpho-agronomic traits, 45 individual trees with relatively stable frost-tolerance were reevaluated and selected for this research. Ten highly discriminating microsatellite markers were used for the genetic profiling of the 45 selected olive trees, and, ultimately, five genotypes with the highest tolerance among 45 selected ones were placed in a cold room at freezing temperatures for image analyses of cold damage. The results of morpho-agronomic analyses evidenced no bark splitting or symptoms of leaf drop in the 45 cold-tolerant olives (CTOs). The oil content of the cold-tolerant trees comprised almost 40% of the fruit dry weight, highlighting the potential of these varieties for oil production. Moreover, through molecular characterization, 36 unique molecular profiles were individuated among the 45 analyzed CTOs that were genetically more similar to the Mediterranean olive cultivars than the Iranian ones. The present study demonstrated the high potential of local olive varieties, which would be promising and more suitable than commercial olive varieties, with regard to the establishment of olive groves under cold climate conditions. This could be a valuable genetic resource for future breeding activities to face climate changes.
Identification and validation of two major QTLs for spikelet number per spike in wheat (Triticum aestivum L.)
Authors: Yi Xiaoyu , Ye Yingtong , Wang Jinhui , Li Zhen , Li Jiamin , Chen Yuqi , Chen Guoyue , Ma Jian , Pu Zhien , Peng Yuanying , Qi Pengfei , Liu Yaxi , Jiang Qiantao , Wang Jirui , Wei Yuming , Zheng Youliang , Li Wei
Published: May 2023

The total number of spikelets (TSPN) and the number of fertile spikelets (FSPN) affect the final number of grains per spikelet in wheat. This study constructed a high-density genetic map using 55K single nucleotide polymorphism (SNP) arrays from a population of 152 recombinant inbred lines (RIL) from crossing the wheat accessions 10-A and B39. Twenty-four quantitative trait loci (QTLs) for TSPN and 18 QTLs for FSPN were localized based on the phenotype in 10 environments in 2019–2021. Two major QTLs, QTSPN/QFSPN.sicau-2D.4 (34.43–47.43 Mb) and QTSPN/QFSPN.sicau-2D.5(32.97–34.43 Mb), explained 13.97%–45.90% of phenotypic variation. Linked kompetitive allele-specific PCR (KASP) markers further validated these two QTLs and revealed that QTSPN.sicau-2D.4 had less effect on TSPN than QTSPN.sicau-2D.5 in 10-A×BE89 (134 RILs) and 10-A×Chuannong 16 (192 RILs) populations, and one population of Sichuan wheat (233 accessions). The alleles combination haplotype 3 with the allele from 10-A of QTSPN/QFSPN.sicau-2D.5 and the allele from B39 of QTSPN.sicau-2D.4 resulted in the highest number of spikelets. In contrast, the allele from B39 for both loci resulted in the lowest number of spikelets. Using bulk-segregant analysis–exon capture sequencing, six SNP hot spots that included 31 candidate genes were identified in the two QTLs. We identified Ppd-D1a from B39 and Ppd-D1d from 10-A and further analyzed Ppd-D1 variation in wheat. These results identified loci and molecular markers with potential utility for wheat breeding and laid a foundation for further fine mapping and cloning of the two loci.
Long-term cold, freezing and drought: overlapping and specific regulatory mechanisms and signal transduction in tea plant (Camellia sinensis (L.) Kuntze)
Authors: Samarina Lidiia , Wang Songbo , Malyukova Lyudmila , Bobrovskikh Alexandr , Doroshkov Alexey , Koninskaya Natalia , Shkhalakhova Ruset , Matskiv Alexandra , Fedorina Jaroslava , Fizikova Anastasia , Manakhova Karina , Loshkaryova Svetlana , Tutberidze Tsiala , Ryndin Alexey , Khlestkina Elena
Published: May 2023

Introduction

Low temperatures and drought are two main environmental constraints reducing the yield and geographical distribution of horticultural crops worldwide. Understanding the genetic crosstalk between stress responses has potential importance for crop improvement.

Methods

In this study, Illumina RNA-seq and Pac-Bio genome resequencing were used to annotate genes and analyze transcriptome dynamics in tea plants under long-term cold, freezing, and drought.

Results

The highest number of differentially expressed genes (DEGs) was identified under long-term cold (7,896) and freezing (7,915), with 3,532 and 3,780 upregulated genes, respectively. The lowest number of DEGs was observed under 3-day drought (47) and 9-day drought (220), with five and 112 genes upregulated, respectively. The recovery after the cold had 6.5 times greater DEG numbers as compared to the drought recovery. Only 17.9% of cold-induced genes were upregulated by drought. In total, 1,492 transcription factor genes related to 57 families were identified. However, only 20 transcription factor genes were commonly upregulated by cold, freezing, and drought. Among the 232 common upregulated DEGs, most were related to signal transduction, cell wall remodeling, and lipid metabolism. Co-expression analysis and network reconstruction showed 19 genes with the highest co-expression connectivity: seven genes are related to cell wall remodeling (GATL7, UXS4, PRP-F1, 4CL, UEL-1, UDP-Arap, and TBL32), four genes are related to calcium-signaling (PXL1, Strap, CRT, and CIPK6), three genes are related to photo-perception (GIL1, CHUP1, and DnaJ11), two genes are related to hormone signaling (TTL3 and GID1C-like), two genes are involved in ROS signaling (ERO1 and CXE11), and one gene is related to the phenylpropanoid pathway (GALT6).

Discussion

Based on our results, several important overlapping mechanisms of long-term stress responses include cell wall remodeling through lignin biosynthesis, o-acetylation of polysaccharides, pectin biosynthesis and branching, and xyloglucan and arabinogalactan biosynthesis. This study provides new insight into long-term stress responses in woody crops, and a set of new target candidate genes were identified for molecular breeding aimed at tolerance to abiotic stresses.
Small cardamom genome: development and utilization of microsatellite markers from a draft genome sequence of Elettaria cardamomum Maton
Authors: Gaikwad Ambika Baldev , Kumari Ratna , Yadav Sheel , Rangan Parimalan , Wankhede Dhammaprakash Pandhari , Bhat KV.
Published: May 2023

Small cardamom (Elettaria cardamomum Maton), the queen of spices, is the third most expensive spice in the world after saffron and vanilla, valued highly for its aroma and taste. This perennial herbaceous plant is a native of coastal parts of Southern India and displays a significant amount of morphological diversity. Its genetic potential has not been exploited due to lack of genomic resources limiting our understanding of the genome and important metabolic pathways which give it the economic advantage in the spice industry. Here, we report upon the de novo assembled, draft whole genome sequence of cardamom variety, Njallani Green Gold. We used a hybrid assembly strategy using the reads from the Oxford Nanopore, Illumina and 10x Genomics GemCode sequencing chemistries. The assembled genome length was 1.06 Gb (gigabases) which is close to the estimated genome size of cardamom. More than 75% of the genome was captured in 8000 scaffolds with a N50 of 0.15 Mb. The genome appears to have a high repeat content and 68055 gene models were predicted. The genome is close to Musa species and displays an expansion and contraction in different gene families. The draft assembly was used for in silico mining of simple sequence repeats (SSRs). A total of 2,50,571 SSRs were identified of which 2,18,270 were perfect SSRs and 32,301 were compound SSRs. Among the perfect SSRs, trinucleotides were most abundant (1,25,329) and hexanucleotide repeats appear least (2,380). From the 2,50,571 SSRs mined, 2,27,808 primer pairs were designed based on flanking sequence information. Wet lab validation was performed for 246 SSR loci and based on their amplification profiles, 60 SSR markers were used for diversity analysis of a set of 60 diverse cardamom accessions. The average number of alleles detected per locus were 14.57 with a minimum of 4 and maximum of 30 alleles. Population structure analysis revealed the presence of high degree of admixtures which could primarily be due to cross-pollination prevalent in this species. The SSR markers identified would help in the development of gene or trait-linked markers which can be subsequently used for marker-assisted breeding for crop improvement in cardamom. The information on utilization of the SSR loci for generation of markers has been developed into a public database, ‘cardamomSSRdb’ that is freely available for use by the cardamom community.