bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethanol causes cell death and neuronal differentiation defect during initial neurogenesis of the neural retina by disrupting calcium signaling in human retinal organoids
Authors: Gong Yu , Ge Lingling , Li Qiyou , Gong Jing , Chen Min , Gao Hui , Kang Jiahui , Yu Ting , Li Jiawen , Xu Haiwei
Published: May 2023

Background: Over 90% of children with fetal alcohol syndrome live with ocular aberration due to the susceptible and intricate human eye development process. Initial neurogenesis of the neural retina around six-week gestation is the critical period of human eye development while sustaining the highest risk of prenatal ethanol exposure because of ignorance of early pregnancy. However, the influence and mechanism of short-term ethanol exposure on this developmental process of the human neural retina remain largely unknown.
Methods: To faithfully recapitulate the initial retinal neurogenesis of human neural retina, human embryonic stem cell derived retinal organoids (hROs) were induced and identified by immunostaining. Morphological measurement was performed to primarily assess the influence of short-term ethanol exposure on the growth of neural retina. TUNNEL assay, immunostaining, and flow cytometry were utilized to detect cell death, retinal ganglion cell differentiation, and cell cycle progression in hROs. Bulk RNA-seq analysis and cnet plotting were performed to screen signaling pathway and regulated genes of ethanol treatment. GCaMP5G-expressing human embryonic stem cells were constructed by transduction of pLOV-CMV-GCaMP5G and fluorescence-activated cell sorting. Two-photon microscope live calcium imaging were utilized to reveal altered calcium signaling dynamics after ethanol treatment. Quantitative RT-PCR was performed to verify the expression of screened potential targeted genes of ethanol treatment.
Results: The hROs from D24 to D30 well recapitulate the initial neurogenesis of the human neural retina around six-week gestation in vivo at the histological, cellular, and molecular level. 1% (v/v) ethanol slowed the growth of hROs by inducing robust cell death and retinal ganglion cell differentiation defect. Calcium signaling dynamics was proved significantly altered and derived from ethanol-induced down-regulation of RYR1and CACNA1S. Moreover, the calcium-binding protein RET, one of the downstream effector genes of the calcium signaling pathway, synergistically integrates ethanol and calcium signals to abort neuron differentiation and cause cell death.
Conclusion: Our study demonstrated that short-term ethanol exposure greatly impaired the initial neurogenesis of hROs by disrupting the RYR1 related calcium signaling. These results may help us elaborate on more detailed principles of ethanol-induced teratogenesis and instruct the rational application of alcohol and ethanol-contained drugs during pregnancy.
Comprehensive analysis to identify age-associated genes in atherosclerosis and explore specific mechanisms
Authors: Ran Xianwen , Li Yongge , Liu Zhibo
Published: May 2023

Age is an independent risk factor for atherosclerosis. However, the precise mechanisms between them remain unclear, and this study combined aging and atherosclerosis genes in a comprehensive analysis. Gene expression profiles were obtained from the GEO database, and limma difference analysis and weighted correlation network analysis (WGCNA) were carried out on them respectively. Functional enrichment analysis and genomic enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) databases. The CIBERSORT algorithm was used to analyze the immune cell infiltration between the disease and control groups. The LASSO algorithm was used to obtain the hub gene and a diagnostic model was developed and finally validated in an external dataset. We identified that CCL3 expression is increased in senescent macrophages and regulates macrophage polarization by binding to CCR5. In this study, we analyzed the biological significance of aging-related genes in atherosclerosis and their correlation with immune infiltration, which may provide a new perspective for clinical treatment.
Management of prolonged second stage of labour in a rural setting in Malawi: a retrospective cohort study
Authors: Bakker Wouter , Dorp Elisabeth van , Phiri Timothy , Kazembe Misheck , Nkotola Alfred , Roosmalen Jos van , Akker Thomas van den
Published: May 2023

Objective
Prolonged second stage of labour potentially leads to maternal and perinatal complications. Options for clinical management are augmentation with oxytocin, instrumental vaginal birth or second-stage caesarean section. We aimed to describe incidence, management and outcome of prolonged second stage of labour in a low-resource setting in Malawi.
Methods
Retrospective analysis of medical records and partographs of all women who gave birth in 2015-2016 in a rural mission hospital in Malawi, comparing labour tracings with management protocols. Primary outcomes were incidence of prolonged second stage, instrumental vaginal birth and caesarean section. Furthermore, management and outcomes were assessed. Women arriving in hospital in the second stage of labour were compared to women arriving in an earlier stage of labour.
Results
Of all 3,426 women giving birth in the study period, 307 (9.0%) were diagnosed with prolonged second stage, based on their partographs. Of these women, 22 (7.2%) had labour augmented with oxytocin, 31 (10.1%) gave birth by vacuum extraction and 64 (20.9%) by caesarean section. Spontaneous vaginal birth occurred in 212 (69.0%). In total, 566/3,426 (16.5%) women were admitted whilst already in the second stage of labour of whom 538/566 (95.1%) had spontaneous vaginal births and 38/566 (6.7%) ended up having prolonged second stage registered in their partographs.
Conclusion
Prolonged second stage of labour is relatively common in this hospital, although diagnosis may be hampered by a very sizeable proportion of women arriving whilst already in the second stage, although a large majority of these women gave birth spontaneously. Caesarean section occurred twice as often as vacuum extraction, suggesting a role for additional training and decision-making during childbirth to support the use of vacuum extraction.
Association of endotoxaemia with low grade inflammation, metabolic syndrome and distinct response to lipopolysaccharide in type 1 diabetes
Authors: Fedulovs Aleksejs , Pahirko Leonora , Jēkabsons Kaspars , Kunrade Līga , Valeinis Jānis , Riekstiņa Una , Pīrāgs Valdis , Sokolovska Jelizaveta
Published: May 2023

Mechanisms of endotoxaemia as a source of low grade inflammation in type 1 diabetes (T1D) are not clear enough. We investigated the levels of lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP), endogenous anti-endotoxin core antibodies (EndoCAb IgG and IgM) and high sensitivity C reactive protein (hsCRP) in T1D. 74 patients with T1D and 33 control subjects were included. Higher levels of hsCRP and EndoCAb IgG were observed in T1D compared to control (p = 0.002 and p = 0.091, respectively). LBP (\(\beta\) = 0.29 (0.08; 0.50), p = 0.007), EndoCAb IgG (\(\beta\) = 0.25 (0.04; 0.46), p = 0.019) and LPS were significantly associated with hsCRP in T1D. In contrast to the situation in the control group, LPS did not correlate with LBP, EndoCAb, leukocytes and HDL in T1D. Within T1D group, patients with metabolic syndrome (MS) had higher level of LPS compared to patients without MS (MS 0.42 (0.35–0.56), no MS 0.34 (0.3–0.4), p = 0.009) and MS was associated with LPS (OR = 3.3 (1.6; 6.8), p = 0.001) and EndoCAb IgM (OR = 0.43 (0.20; 0.91), p = 0.027). To conclude, endotoxaemia is associated with low grade inflammation, MS and distinct response to LPS in T1D.
DNMT1 can induce primary germ layer differentiation through de novo DNA methylation
Authors: Tada Masako , Ito Takamasa , Kubiura-Ichimaru Musashi , Miura Fumihito , Yamaguchi Shinpei , Tajima Shoji , Surani M. Azim , Ito Takashi
Published: May 2023

DNA methyltransferases and TET enzymes dynamically regulate the DNA methylation-demethylation cycles during mouse embryonic development. DNMT1 maintains cell-specific DNA methylation after DNA replication. However, little is known about the physiological significance of the de novo methylation enzymatic potential of DNMT1, which has attracted much attention. Here, we show that the full-length DNMT1 and a mutant form without the N-terminal necessary for its maintenance activity potentially inhibit the differentiation of mouse pluripotent embryonic stem cells lacking Dnmt1, 3a and 3b into primitive endoderm cells. However, the mutant cells could differentiate into epiblast-like cells and beyond, leading to cell-autonomous mesendoderm differentiation. Strikingly, we found that in response to Nodal signalling and the increased concurrent access of DNMT1 and TET enzymes resulting from chromatin relaxation activated primordial germ cell-specific genes. With the precise target selectivity by its N-terminal region, DNMT1 may be involved in gene regulation leading to germline development.
The Metabolic Fate of Izencitinib, a Gut-selective Pan-JAK Inhibitor, in Humans. Identification of Unusual Fecal Metabolites and Implications for MIST Evaluation.
Authors: Yeola Suresh , Badagnani Ilaria , Huang Xiaojun , Segraves Nathanial L. , Rapta Miroslav , Borin Marie T. , Obedencio Glenmar P. , Fitch William L. , Baillie Thomas A. , Bourdet David L.
Published: May 2023

Izencitinib is a novel, orally administered pan-JAK inhibitor designed as a gut-selective therapy that was under development for the treatment of inflammatory bowel disease. The objectives of this study were to define the mass balance, routes and rates of excretion, and metabolic fate of izencitinib after oral administration of [14C]-izencitinib in humans. Six healthy adult male subjects were administered a single 100 mg (~ 300 mCi) oral dose of [14C]-izencitinib. Fecal excretion was the dominant route of elimination with > 90% of the administered dose recovered in the feces. Plasma concentrations of total radioactivity and izencitinib were low with the mean terminal half-life of total radioactivity (138 h) exceeding that of izencitinib (32.4 h). Izencitinib represented approximately 17% of the total circulating radioactivity, suggesting the presence of multiple circulating plasma metabolites. However, no metabolites exceeded 10% of total drug-related material in plasma. The major metabolites in feces, M18 and M9, were found to have unusual structures that reflected the presence of a nucleophilic carbon center in the naphthyridine ring of izencitinib. Proposed mechanisms for the formation of these metabolites involved oxidation and rearrangement (M18) and a one-carbon addition, potentially occurring through reaction with endogenous formaldehyde (M9). Given the gut-selective properties of izencitinib, it is proposed that these novel fecal metabolites are the most relevant for evaluating the impact of metabolism on the pharmacological and toxicological properties of izencitinib, and that the circulating plasma metabolite profile is of little consequence in the assessment of the safety characteristics of izencitinib metabolites.
Analysis of Biomass as feedstock in a CLC-based polygeneration process for CO2 valorization
Authors: Sunkara Sushma , Pankhedkar Nimish , Dwivedi Abhishek , Gudi Ravindra , Biswas Pratim , Bhargava Suresh
Published: May 2023

From the viewpoint of circular economy, the utilization of biomass as a preferred feedstock for power generation with carbon capture has become prevalent. Biomass utilization leads to a negative global carbon balance by leveraging its inherent carbon which was absorbed from the atmosphere. While Chemical Looping Combustion (CLC) has been a promising carbon capture technology for solid fuels such as coal, this paper further explores the feasibility of using biomass as fuel in CLC along with the valorization of CO2 to useful chemicals. In light of the same, a polygeneration approach utilizing biomass has been proposed to produce power and value-added chemicals (Methanol and DME). Biomass has a significant amount of oxygen and a higher H:C ratio in comparison with conventional fuels like coal. The effect of the same has been evaluated by developing novel process configurations and comparing both feedstocks. Detailed techno-feasibility analysis on the schemes, and optimization studies to maximize the performance of the system in terms of Energetics, CO2 mitigation, and profitability have been carried out. From the analysis, it has been identified that the usage of biomass in CLC configuration results in higher chemical production rates and higher profits with lesser CO2 emissions in comparison to coal. The above analysis and evaluation have been carried out through simulations using Aspen Plus ® software.
‘People that suffer or have been through it know the answers’: Stakeholders’ perspectives on improving healthcare systems for end-of-life care in chronic obstructive airways disease
Authors: Landers Amanda , Pitama Suzanne G , Palmer Suetonia C , Beckert Lutz
Published: May 2023

Background: Chronic obstructive pulmonary disease (COPD) is a progressive and disabling lung condition with a high mortality. Our research has shown that health care for end-of-life COPD is poorly integrated. Involving people with end-of-life COPD, their support people and health professionals in the design of healthcare services may improve the delivery of care for advanced COPD, including informing system-level quality improvement.
Design: We conducted a focus group study involving stakeholders of healthcare services: people with end-of life COPD, support people, bereaved support people, and community- and hospital-based health care professionals.
Methods: We conducted qualitative analysis using deductive structural coding, and then inductive descriptive and pattern coding. Analyses were triangulated by investigators. The research positioned people with end-of-life COPD, their support people and health professionals as experts in healthcare services. Critical theory and Actor-Network theory informed the analysis.
Results: Seven focus groups involving 74 participants reported their experiences of end-of-life care for COPD. Five themes related to healthcare systems responses to improving care quality were identified: governance, system integration, resource design and development, standardisation of processes, and communication.
Conclusion: Stakeholders provided multiple healthcare system-level responses to end-of-life care in COPD that could inform healthcare service design and clinical quality improvement.
Clinical study on ultrasonic artificial intelligence-assisted diagnosis of developmental hip dysplasia in children
Authors: Zhang Si-Cheng , Ma Hai-Long , Sun Xi-Wei , Wu Qing-Jie , Xu Jing-Yuan , Sun Jun
Published: May 2023

Background:Developmental hip dysplasia(DDH) is a common pediatric disease.For patients younger than 6 months of age,ultrasound diagnosis is more suitable for screening and assessment of hip development.At present,there is an urgent need for a reproducible and reliable ultrasound screening method for DDH diagnosis.
Purpose: To construct and verify an artificial intelligence-assisted deep learning system for ultrasound diagnosis of developmental hip dysplasia in children.
Materials and Methods: 2021 standard sections were selected from January 2019 to January 2021. All standard sections were annotated using unified standards through the image transmedia data annotation and audit system.1753 images were randomly selected to train the deep learning system,the remaining 268 were used to test the system.
Results:
268 patients were tested. The AUC for diagnosing hip joint maturity was 0.941, (sensitivity 90.5%, specificity 97.8%),while the AUC for Graf classification was 0.685(sensitivity 45.3% specificity 91.7%),compared with clinicians’ measurements. According to the Bland–Altman method, the 95% limits of agreement of α angle was-6.426°~4.811°(Bias=-0.8075,P < 0.001), that of β angle was -5.545°~6.507°(Bias=0.4812,P=0.057). 7 key points measured by AI were statistically different from the clinician values.
Conclusions: The artificial intelligence system could quickly and accurately measure the Graf correlation index of standard hip joint ultrasound images.
A wearable stethoscope for accurate real-time lung sound monitoring and automatic wheezing detection based on an AI algorithm
Authors: Lee Soo Hyun , Lee Kyoung-Ryul , Kim Taewi , Im Sunghoon , Lee Yi Jae , Jeong Seongeun , Shin Hanho , Kim Minho , Lee Jingoo , Kim Dohyeong , Choi Gil-Soon , Kang Daeshik , Seo Sungchul
Published: May 2023

The various bioacoustics signals obtained with auscultation contain complex clinical information used as traditional biomarkers, however it is not widely used in clinical for long-term studies due to spatiotemporal limitations. Here, we developed a wearable stethoscope for skin-attachable, continuous and real-time auscultation using a lung sound monitoring patch (LSMP). The LSMP can monitor respiratory function through mobile app and classify normal and adventitious breathing by comparing the unique acoustic characteristics they produced. Heart and breathing sounds from humans can be distinguished from complex sound consisting of a mixture of the bioacoustic signal and external noise. The performance was further demonstrated with pediatric asthma and elderly chronic obstructive pulmonary disease (COPD) patients. We implemented a counting algorithm to identify wheezing events in real-time regardless of the respiratory cycle. As a result, the AI-based adventitious breathing event counter distinguished over 80% of events, especially wheezing events, in long-term clinical application.
A pan-cancer analysis indicates the cuproptosis-related SLC31A1 gene is a potential prognostic and immunotherapy biomarker in various cancers including colon adenocarcinoma
Authors: Chen Zhaowei , Kang Lili , Yang Zhenze , Cai Yaoqing , Yu Shuyong , Li Ping , Song Jian
Published: May 2023

Background Abnormal expression of cuproptosis-related regulators is closely related to the development of various cancers. However, the role of cuproptosis-related SLC31A1 (solid carrier family 31 member 1) gene, as a high-affinity copper transporter, in the prognosis and immunotherapy of multiple different cancers remains unclear.Methods Based on the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases, the expression level of SLC31A1 was analyzed in tumors and normal tissues, and the survival value of SLC31A1 was evaluated by Cox regression analysis. Then, we explored the relationship between SLC31A1 expression and genetic alterations, DNA methylation, and immune cell infiltration. And the biological function of SLC31A1 in pan-cancer was further clarified by Gene Set Enrichment Analysis (GSEA). Additionally, in colon adenocarcinoma (COAD), we deeply explored the relationship between SLC31A1 expression and clinicopathological stages, immune infiltration types, RNAss, DNAss, and tumor microenvironment scores, and the specific biological process of SLC31A1 was investigated through GO enrichment analysis.Results The expression level of SLC31A1 varied considerably with cancers, and its high expression had significant prognostic value in LIHC, KIRC, THYM, UCS, ACC, LGG, MESO, BLCA, TGCT, KICH, COAD, STAD, PCPG, and BRCA. SLC31A1 expression was significantly correlated with genetic alterations, DNA methylation, and immune cell infiltration. GSEA further indicated that SLC31A1 was mainly related to immune regulation signals in various cancers. In COAD, SLC31A1 expression was remarkably related to RNAss and immune scores, and GO analysis revealed that SLC31A1 was mainly associated with DNA and RNA replication, activity, and binding.Conclusion Our research first systematically revealed the potential value of SLC31A1 in prognosis and immunotherapy in multiple cancers, especially in COAD, suggesting that it will become a new target in the prognosis and treatment of cancers.
The Value of Oral Selective Estrogen Receptor Degraders in Patients with HR-Positive, HER2-Negative Advanced Breast Cancer after Progression on ≥ 1 Line of Endocrine Therapy: Systematic Review and Meta-analysis
Authors: Huang Xiewei , Yu Yushuai , Luo Shiping , Fu Wenfen , Zhang Jie , Song Chuangui
Published: May 2023

Background: Currently, the value of oral selective estrogen receptor degraders (SERDs) for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (aBC) after progression on ≥ 1 line of endocrine therapy (ET) remains controversial. We conducted a meta-analysis to evaluate progression-free survival (PFS) and safety benefits in several clinical trials.
Materials and methods: Cochrane Library, Embase, PubMed, and conference proceedings (SABCS, ASCO, ESMO, and ESMO Breast) were searched systematically and comprehensively. Random effects model or fixed effects models were used to assess pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for oral SERDs versus standard of care.
Results: A total of four studies involving 1,290 patients were included in our analysis. The hazard ratio (HR) of PFS showed that the oral SERDs regimen is better than the standard of carein patients with HR+/HER2- aBC after progression on ≥ 1 line of ET (HR: 0.75, 95% CI: 0.62-0.91, p = 0.004). In patients with ESR1 mutations, the oral SERDs regimen obtained better PFS than those treated with the standard of care (HR: 0.58, 95% CI: 0.47-0.71, p <0.00001). For patients with disease progression following previous use of CDK4/6 inhibitors, arms of the oral SERDs still obtain PFS profit versus the standard of care (HR: 0.75, 95% CI: 0.64-0.87, p = 0.0002).
Conclusions: Oral SERDs regimen has a significant PFS benefit compared to standard-of-care ET in patients with HR+/HER2- aBC after progression on ≥ 1 line of ET. In particular, we recommend oral SERDs as a preferred choice for those patients with ESR1m, and it could be a potential replacement for fulvestrant. Oral SERDs regimen also benefits after the progression of CDK4/6 inhibitors combined with endocrine therapy.
Simulation Analysis and Test of Gap Squeeze Gear Type Fertilizer Discharger for Granular Fertilizer Containing Caking
Authors: Dun Guoqiang , Mao Ning , Ji Xinxin , Zhang Fuli
Published: May 2023

Precision fertilizer application technology is necessary to improve fertilizer utilization efficiency in agricultural production. To achieve precision fertilizer application and solve problems in production practice that contain the structure problem of the traditional mechanical fertilization systems, and the fertilizer discharger is blocked and can not achieve uniform fertilization because the fertilizer contains caking fertilizer in response to the characteristics of conventional fertilizers containing caking fertilizers, innovative design and system experimental simulation studies were carried out. A gap squeeze gear-type fertilizer dis-charger was designed, and fertilizer caking crushing was achieved by configuring the gear gap squeezing method. Combined with engineering practice, two mixed fertilizers (granular fertilizer with caking fertilizer) were constructed and blended by using BPM (Hertz Mindlin with bonding) discrete element, the fertilizer discharger was used as the object of study to simulate and experimentally investigate the process of crushing and discharging of mixed fertilizer and the process of uniform discharging of mixed fertilizer. The simulation test model of the separation device with vibration screen of the caking fertilizer and granular fertilizer after fertilizing was established to study the crushing rate of the caking fertilizer, and the simulation model with collection plate of the uniformity of the mixed fertilizer discharge was based on to explore the uniformity of the mixed fertilizer. The L9 (34) orthogonal test was carried out under the conditions with the number of teeth, pressure angle, and fertilization gap as test factors and the fertilizer crushing rate and fertilizer uniformity coefficient as test indicators. The test results showed that the number of teeth and pressure angle had significant effects (0.01 < P < 0.05) on the crushing fertilizer rate and fertilizer uniformity, and the fertilization gap had no significant impact (P༞0.05) on the crushing fertilizer rate and fertilizer uniformity. In the optimal combination of parameters, the number of teeth 6, pres-sure angle 15 °, fertilization gap 6mm operation, the coefficient of uniformity of crushing fertilizer rate and fertilizer uniformity were 74.89% and 17.21%, respectively. The bench test results compared with the outer groove wheeled fertilizer drainer showed that the optimized gap squeeze gear type fertilizer discharger has higher fertilizer crushing quality at different speeds, and the fertilizer crushing rate and uniformity were79.69% and 18.56%, respectively, within the error range. The simulation results are in general agreement. This study provides evidence for fertilizer discharger structure design and enhances the effect of fertilizer discharger crushing.
A cytomegalovirus inflammasome inhibitor curbs proinflammatory cytokine release and pyroptosis
Authors: Brune Wolfram , Deng Yingqi , Ostermann Eleonore
Published: May 2023

In response to viral infection, cells can initiate programmed cell death (PCD), leading to a reduction in the release of viral progeny. Viruses have therefore evolved specific mechanisms to curb PCD. Cytomegaloviruses (CMVs) are particularly sophisticated manipulators of cellular defenses and are known to encode potent inhibitors of apoptosis and necroptosis. However, a CMV inhibitor of pyroptosis, the third major PCD form, has not been identified. Encoding such an inhibitor should be important for the virus as the three PCD pathways are not separate entities but interconnected pathways. Here we identify the murine CMV M84 protein as an inhibitor of pyroptosis and proinflammatory cytokine release. M84 interacts with the pyrin domain of the inflammasome components AIM2 and ASC to block Caspase-1 activation, release of interleukin 1β (IL-1β) and IL-18, cleavage of Gasdermin D, and pyroptosis of macrophages. Growth attenuation of an M84-deficient MCMV in macrophages was rescued by knockout of either Aim2 or Asc or by treatment with a Caspase-1 inhibitor, and its attenuation in infected mice was partially rescued in Asc knockout mice. These results demonstrate that viral inhibition of the inflammasome-pyroptosis pathway is important to promote viral replication and dissemination in vivo.
Contrasting germination behavior of nodding broomrape towards soybean seeds- and sprouts-extract is associated with their corresponding phytohormones, sugars and isoflavones contents
Authors: Manoharlal Raman , Saiprasad G.V.S.
Published: May 2023

In the present study, a comparative study involving soybean (Glycine max L.) seeds- (SPE) and sprouts-extract (SSE) as a pre-conditioning media was performed to evaluate their allelopathic impact on nodding broomrape (Orobanche cernua L.) germination. Contrasting germination behaviour of broomrape, characterised by respective inhibition and induction in its germination was observed in response to an optimised concentration of SPE and SSE. Further study was conducted to explore the phyto-constituents of soybean seed- (SSP) and sprout-flour (SSF) responsible for differential germination of broomrape. Plant-growth regulators quantification revealed a relative enhanced bioactive gibberellin (GA4) to abscisic acid (ABA) ratio (GA4 : ABA) in SSF. Carbohydrates analysis revealed a relative reduced content of soluble-sugars, starch, sucrose (SUC) and raffinose-family oligosaccharides (RFOs) in concomitant with relative enhanced levels of reducing-sugars, glucose (GLU) and galactose (GAL) in SSF. The isoflavone content (IFC) analysis revealed a relative enhanced level of total IFC and individual bioactive aglycones [viz. daidzein, glycitein and genistein (GEN)] in SSF. Exogenous applications of GA3, ABA and its antagonists (viz. uniconazole and fluridone), mono- (viz. GLU and GAL), oligo-saccharides (viz. SUC and RFOs), SPE50 and SSE50 pre-treated with enzyme-mix harbouring RFOs- and SUC-metabolizing enzymes (viz. α-galactosidase + invertase) and GEN as a pre-conditioning media of broomrape were also in agreement with the aforesaid observations. To the best of our knowledge, this is first report mentioning the contrasting germination behavior of broomrape towards SPE and SSE. Overall, these findings could be explored to formulate the ‘Green’ methods for the control of parasitic-weed infestation in agonomically important crops.
Chromatin conformation dynamics during CD4+ T cell activation implicates autoimmune disease-associated genes and regulatory elements
Authors: Wells Andrew , Pahl Matthew , Sharma Prabhat , Thomas Rajan , Thompson Zachary , Mount Zachary , Pippin James , Morawski Peter , Campbell Daniel , Grant Struan , Su Chun
Published: May 2023

Genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with autoimmune disease, but the causal variants and their contribution to immune dysregulation remain largely unknown. We measured the dynamics of chromosome conformation, chromatin accessibility, and gene transcription across three phases of naive human CD4+ T cell activation and co-localized active cis-regulatory elements with the 95% credible set of variants from 15 autoimmune GWAS. Reorganization of chromosome structure placed these elements in direct contact with ~1,200 protein-coding genes, at least one-third of which were dynamically regulated by stimulation. The set of implicated genes is enriched for high-throughput CRISPR screen targets that control multiple aspects of CD4+ T cell activation, and we pharmacologically validated eight novel gene products as potent regulators of T cell proliferation. These maps also allowed the identification and functional validation of a novel stretch of intergenic enhancers whose activity is required for IL2 gene expression and is influenced by autoimmune-associated genetic variation. This study represents a powerful strategy and resource for assigning physiologic relevance to autoimmune-risk variants and identifying novel genes that control T cell activation and function.
TVIE-based fault-tolerant model predictive control for trajectory tracking of mobile robot
Authors: Zhu Jun-Wei , Ying Liang-Huan , Wang Xin
Published: May 2023

This paper investigates the trajectory tracking control issue for linear parameter-varying (LPV) system of wheeled mobile robot (WMR) with actuator fault and constraints, where a time-varying intermediate estimator (TVIE)-based fault-tolerant model predictive control (MPC) method is proposed. A new estimation-based predictive model is designed by introducing the estimations of error state and fault from the TVIE. Moreover, compared with the existing traditional IE or extended state observer(ESO), the estimation performance of TVIE whose gain is optimized online based on an objective function is better. To guarantee stability and recursive feasibility, the bimodal MPC strategy is used, where a terminal penalty and a terminal constraint are included. Finally, the effectiveness and superiority of the proposed approach is illustrated by two experiments.
A Novel MALT1-related Immune Prognostic Signature and Targeted Drug Screening for Glioblastoma
Authors: Li Hui , Du Zhishan , Lu Han , Wang Zhenhua , Xi Jianxin , Chen Jun , Li Yutang , Zhong Sheng
Published: May 2023

As the most common intracranial malignancy in adults, glioblastoma (GBM) has limited improvement in prognosis with traditional treatment methods, such as surgery, chemotherapy, and radiotherapy. Currently, immunotherapy has revolutionized treatment outcomes for many cancers. However, special immunosuppressive microenvironment of GBM results in patients’ resistance to immunotherapy and poor prognosis. The mucosa-associated lymphoid tissue translocation gene 1 (MALT1) was reported to be involved in NF-κB activation and promote cancer cell’s proliferation and migration. And inhibition of MALT1 could attenuate the mesenchymal phenotype of GBM. Therefore, uncovering the role of MALT1 in the immunosuppressive microenvironment of GBM is of great importance. In this study, RNA-seq data of 169 GBM patients were downloaded from TCGA (The Cancer Genome Atlas) database and divided into MALT1_H (MALT1_High) and MALT1_L (MALT1_Low) groups based on MALT1’s expression level. First, the enrichment levels of the 29-immune signature were quantified in every GBM patient of MALT1_H and MALT1_L. Next, DEIGs (differentially expressed immune genes) were identified and used to establish an IPS (immune prognostic signature) by the LASSO (Least Absolute Shrinkage and Selection Operator) Cox regression analysis. PDYN was first found to be associated with GBM prognosis and was identified as a potential target of GBM. Based on three-gene IPS, we developed a predictive nomogram model to assess the prognosis of GBM patients. Additionally, MALT1 were proved to be a potential ideal therapeutic target for GBM. So, series of computer-aided technology were applied to screen favorable inhibitors of MALT1. In summary, we explored role of MALT1 in the suppressive immune microenvironment of GBM, established a novel MALT1-related nomogram model for prognostic prediction, and developed the targeted therapy for GBM in this study.
Application of Machine Learning to the Prediction of Cancer-Associated Venous Thromboembolism
Authors: Mantha Simon , Chatterjee Subrata , Singh Rohan , Cadley John , Poon Chester , Chatterjee Avijit , Kelly Daniel , Sterpi Michelle , Soff Gerald , Zwicker Jeffrey , Soria José , Ruiz Magdalena , Muñoz Andres , Arcila Maria
Published: May 2023

Venous thromboembolism (VTE) is a common and impactful complication of cancer. Several clinical prediction rules have been devised to estimate the risk of a thrombotic event in this patient population, however they are associated with limitations. We aimed to develop a predictive model of cancer-associated VTE using machine learning as a means to better integrate all available data, improve prediction accuracy and allow applicability regardless of timing for systemic therapy administration. A retrospective cohort was used to fit and validate the models, consisting of adult patients who had next generation sequencing performed on their solid tumor for the years 2014 to 2019. A deep learning survival model limited to demographic, cancer-specific, laboratory and pharmacological predictors was selected based on results from training data for 23,800 individuals and was evaluated on an internal validation set including 5,951 individuals, yielding a time-dependent concordance index of 0.72 (95% CI = 0.70–0.74) for the first 6 months of observation. Adapted models also performed well overall compared to the Khorana Score (KS) in two external cohorts of individuals starting systemic therapy; in an external validation set of 1,250 patients, the C-index was 0.71 (95% CI = 0.65–0.77) for the deep learning model vs 0.66 (95% CI = 0.59–0.72) for the KS and in a smaller external cohort of 358 patients the C-index was 0.59 (95% CI = 0.50–0.69) for the deep learning model vs 0.56 (95% CI = 0.48–0.64) for the KS. The proportions of patients accurately reclassified by the deep learning model were 25% and 26% respectively. In this large cohort of patients with a broad range of solid malignancies and at different phases of systemic therapy, the use of deep learning resulted in improved accuracy for VTE incidence predictions. Additional studies are needed to further assess the validity of this model.
Prevalence and factors associated with Acute Kidney Injury among children aged 6month- 12years passing dark urine admitted at Soroti Regional Referral Hospital: A cross-sectional study
Authors: Nakuya Margaret , Batte Anthony , Musiime Victor
Published: May 2023

Introduction: Acute Kidney Injury (AKI) is associated with a high mortality yet survivors are at risk for Hypertension, chronic kidney disease, long term neurocognitive and behavioural problems. Early recognition of patients with possible AKI is crucial for better treatment outcome, hence a need for evidence to guide targeted screening of patients with a risk factor for AKI. We sought to determine the prevalence and factors associated with AKI among children passing dark urine since haemoglobinuria, which presents as dark urine is a known risk factor for AKI.
Methodology: This was a cross sectional study conducted at Soroti Regional Referral Hospital, among children aged 6month to 12years, who presented with dark urine. Urine colour was assessed using the Hammer Smith colour urine chart, only children with urine colour grade ≥ 5 were recruited. Serum creatinine analysis was done on the day of admission, within 48 hours and at day 7 or discharge. AKI was defined as a ≥ 1.5-fold increase in serum creatininefrom the baseline. Bivariate and multivariate analysis was used to determine factors associates with AKI with p values <0.05 level of significance.
Results: Between January 2022 – July 2022, we enrolled a total of 255 participantswith median age of 4.0 (IQR, 2.0-6.58) years. About two thirds of the participants were males 157 (61.6%) and majority 111 (43.5%) presented with grade 8 of the urine colour. The prevalence of AKI was 38% (95% CI 32.3% - 44.2%). The factors found to be associated with AKI were grade of the urine colour ≥ 9 (aOR, 3.120 (95% CI 1.34-6.78) and reduced urine output (aOR, 3.226 (95% CI 1.10-9.81)
Conclusion; The prevalence of AKI among children passing dark urine was high (38%). AKI was more likely to occur if the child was passing urine that is profoundly black and if there is history of reduced urine output. These findings reiterate the need for close monitoring of urine output of hospitalized children particularly those passing dark urine. Screening of those with profoundly black urine or reduced urine output should be done.
Unraveling the Genetic Drivers of Heart Failure from Cardiac Endothelial Cells via Single-Cell RNA-Sequencing Data and Machine Learning Model
Authors: Zhong Jisheng , Wu Dongdong , Chen Junquan , Liu Aijun , Li Gang , Su Junwu , Liu Yu
Published: May 2023

Background
Heart failure is a complex syndrome that hinders the heart's ability to provide oxygen to the tissues and is a significant cause of death globally. Given that left ventricular failure is more common than left atrial failure, this study utilizes single-cell RNA-sequencing data to detect differentially expressed genes (DEGs) between the endothelial cells of the two chambers and examines whether these DEGs are related to heart failure development.
Method
The analysis of a healthy human dataset was performed using Seurat, an R package, to identify differentially expressed genes (DEGs) between endothelial cells from the left ventricle and the left atrium of the heart. These findings were validated using two datasets that included both humans and mice with and without heart disease. The overlapped DEGs from the datasets were then utilized to develop a risk prediction model by using linear regression, which can determine an individual's risk for heart failure based on the expression levels of the overlapped DEGs.
Results
Seven genes, including MYL3, MYH6, TNNC1, FN1, B2M, MYL2, and SAT1, were identified with a significant p-value in all three datasets. Enrichment analysis has shown that these genes play a critical role in muscle contraction and heart regulation, and mutations in these genes have been linked to cardiomyopathy. The risk prediction model had a high accuracy rate of 85% in an independent validation dataset.
Conclusion
This study has successfully identified significant genes in endothelial cells that are associated with heart failure and may explain the difference in morbidity between the left ventricle and left atrium.
Investigations on Confederated Unified Power Quality Conditioner with Three-Phase Photovoltaic System
Authors: Mudgal Yashvi , Singh Gurpinder
Published: May 2023

The photovoltaic (PV) system put on a roof has attracted a lot of attention because of its ability to generate clean energy while having a negligible effect on the natural environment. PV energy sources' intermittent operation causes voltage quality issues, and advances in semiconductor technology tend to raise current harmonic distortion levels. The most prevalent source of imbalance between the transmission and generating sides of the system is a problem with power quality at the load side. Unified Power Quality Conditioner (UPQC) is a method for improving power quality that may be employed when power quality issues take on new forms. The MATLAB-Simulink program stimulates a dynamic model of a confederated Three-Phase PV-UPQC study. The developed unified power quality conditioner with solar array successfully reduces the current and voltage harmonics, as shown by the MATLAB simulation results.
Demographic, Clinical, and Immunological features in Combined Immunodeficiency Patients with Pulmonary Complications: A Retrospective Multicenter Study from Iran
Authors: Khanbabaee Ghamartaj , Pourghasem Matin , Jamee Mahnaz , Tabatabaii Seyed Ahmad , Khalili Mitra , Mesdaghi Mehrnaz , Sadeghi-Shabestari Mahnaz , Shirvani Armin , Sadr Saeid , Zahmatkesh Arefeh , Delavari Samaneh , Eslami Narges , Farahbakhsh Nazanin , Mansouri Mahboubeh , Tabiei Ebrahim , Modarresi Seyedeh Zalfa , Behbahani Abdolhamid Taghizadeh , Eslamian Golnaz , Fallahi Mazdak , Enayat Javad , Fallah Shahrzad , Pourghasem Mahsa , Aghamohammadi Asghar , Chavoshzadeh Zahra
Published: May 2023

Background: Combined immunodeficiency (CID) is characterized by profound defects in the development and function of both B and T cells. We aimed to investigate clinical and immunological phenotype in CID patients with and without pulmonary complications.Methods: This retrospective study was performed on patients with established diagnosis of CID registered between 2009 and 2020, who had available thoracic computed tomography scan in their medical records. Patients were divided into two groups based on the development of pulmonary complications, and their demographic, clinical, and laboratory characteristics were compared. All data were analyzed by SPSS software, and a P-value < 0.05 was considered as a significant difference.Results: 53 patients [56.6% male and 43.4% females] were enrolled in the study and divided into two groups of patients with (n = 43) and without (n = 10) pulmonary abnormality in the HRCT. In patients with pulmonary complications, skin lesions, failure to thrive, and autoimmunity, were three top high provenances, and anemia was significantly presented in patients with complicated HRCT. Findings of thoracic high resolution computed topographies (HRCTs) included pneumonia (n = 15, 28.3%), bronchiectasis (n = 10, 18.9%), pulmonary nodules (n = 1, 1.9%), atelectasis (n = 2, 3.8%), interstitial lung disease (n = 2, 3.8%). Dead patients had significantly lower level of platelet (183000 cell/µL, P-value = 0.031), IgG (501 mg/dl, P-value = 0.037) and IgE (1.5 IU/ml, P-value = 0.046) compare to alive patients. The mortality rate was higher in patients with pulmonary complications compared to the other group (18.9% vs. 1.9%, p = 0.667).Conclusion: Respiratory disorders in CID are common and require early periodic monitoring by respiratory tests and HRCT to avoid irreversible injuries.
Risk-Benefits Assessment of Calcium Supplementation Based on Multi- Dimensional Nutritional Profiles in the Hungarian Population
Authors: Mirani Sara , Horváth László , Vecsernyés Miklós , Tóth Béla E.
Published: May 2023

Background Calcium intake is an essential component of a healthy diet and has been linked to numerous health benefits, including the prevention of osteoporosis and reduction of fracture risk in children and adults. The most plausible consequence of insufficient calcium intake can lead to osteoporosis over decades, which is a significant cause of morbidity and mortality with high burden of disease. However, attention should be given to the risk of potential overdoses, since some trials have linked excessive calcium supplementation to increased risk of health complications.Methods Our study aimed to evaluate the possible factors influencing the participants’ calcium profile through a “dietary intake specific questionnaire” to achieve the optimal calcium and vitamin D intake in the prevention of or during therapies for osteoporosis. A comprehensive multi-dimensional dietary survey was administered to evaluate various aspects of the participants' diets, including dietary and supplemented calcium intake, vitamin D exposure, vitamin supplementation profile, and relevant lifestyle parameters. In this article, we specifically analyzed the calcium intake profiles and pharmacovigilance aspects of the study participants.Results We received 478 evaluable datasets. The dietary calcium intake, on average, was close to optimal in the general public. Supplementation safety concerns were raised for the public in less than 7% of patients, who were reported to have a potential overload in daily calcium intake. Albeit, one-third (34%) of the population had a significant deficiency (average: 544 mg/day), and this effect was more relevant among ≤ 25-years old individuals, of them only less than 37% of the responders had an optimal calcium intake. More than half (52%) of the dietary calcium deficient participants did not take any additional calcium supplements. Although, in 73% of general population, most calcium supplementation dosage in use was equal to or below 200 mg/day.Conclusion Our study highlights the importance to implement a “Patient Focused Motivation Strategy” as a broader approach in pharmaceutical care for increasing the patient’s knowledge, understanding the needs of supplementation, and selecting the correct form and dose of the available non-prescription products. It is important to maintain motivation and adherence to the recommended therapy to achieve optimal health outcomes.
A Novel Approach to Biomarker Discovery: Four Key Genes as High-Performance Biomarkers for Colorectal Cancer
Authors: Liu Yongjun , Xu Yuqing , Li Xiaoxing , Chen Mengke , Wang Xueqin , Zhang Ning , Zhang Heping , Zhang Zhengjun
Published: May 2023

Objectives The goal of this study was to use a new machine-learning framework based on max-linear competing risk factor models to identify a parsimonious set of differentially expressed genes (DEGs) that play a pivotal role in the development of colorectal cancer (CRC).Methods Transcriptome data from six public datasets were analyzed, and a new Chinese cohort was collected to validate the findings.Results The study discovered a set of four critical DEGs - CXCL8, PSMC2, APP, and SLC20A1 - that exhibit high accuracy in detecting CRC in diverse populations and ethnicities. Notably, PSMC2 and CXCL8 appear to play a central role in CRC, and CXCL8 alone could potentially serve as an early-stage marker for CRC.Conclusions This work represents a pioneering effort in applying the max-linear competing risk factor model to identify critical genes for human malignancies, and the reproducibility of the results across diverse populations suggests that the four DEGs identified can provide a comprehensive description of the transcriptomic features of CRC. The practical implications of this research include the potential for personalized risk assessment and tailored treatment plans for patients.