bluuebunny/crossref_metadata_2025 huggingface dataset:
Busulfan or Treosulfan Conditioning Platform for Allogeneic Stem Cell Transplantation in Patients Aged >60 Y With Acute Myeloid Leukemia/Myelodysplastic Syndrome: A Subanalysis of the GITMO AlloEld Study
Authors: Malagola Michele , Polverelli Nicola , Martino Massimo , Patriarca Francesca , Bruno Benedetto , Giaccone Luisa , Grillo Giovanni , Bramanti Stefania , Bernasconi Paolo , De Gobbi Marco , Natale Annalisa , Terruzzi Elisabetta , Olivieri Attilio , Chiusolo Patrizia , Carella Angelo Michele , Casini Marco , Maffini Enrico , Nozzoli Chiara , Mazza Patrizio , Bassi Simona , Onida Francesco , Vacca Adriana , Falcioni Sadia , Luppi Mario , Iori Anna Paola , Pavone Vincenzo , Skert Cristina , Carluccio Paola , Borghero Carlo , Proia Anna , Selleri Carmine , Rubini Vicky , Sacchi Nicoletta , Oldani Elena , Bonifazi Francesca , Ciceri Fabio , Russo Domenico
Published: February 2023

Background.

The conditioning regimens with different alkylators at different doses can influence the outcome of allogeneic stem cell transplantation (SCT), but conclusive data are missing.

Methods.

With the aim to analyze real-life allogeneic SCTs performed in Italy between 2006 and 2017 in elderly patients (aged >60 y) with acute myeloid leukemia or myelodysplastic syndrome, we collected 780 first transplants data. For analysis purposes, patients were grouped according to the type of alkylator included in the conditioning (busulfan [BU]-based; n = 618; 79%; treosulfan [TREO]-based; n=162; 21%).

Results.

No significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival, although in the TREO-based group, we observed a greater proportion of elderly patients (P < 0.001); more active diseases at the time of SCT (P < 0.001); a higher prevalence of patients with either hematopoietic cell transplantation-comorbidity index ≥3 (P < 0.001) or a good Karnofsky performance status (P = 0.025); increased use of peripheral blood stem cells as graft sources (P < 0.001); and greater use of reduced intensity conditioning regimens (P = 0.013) and of haploidentical donors (P < 0.001). Moreover, the 2-y cumulative incidence of relapse with myeloablative doses of BU was significantly lower than that registered with reduced intensity conditioning (21% versus 31%; P = 0.0003). This was not observed in the TREO-based group.

Conclusions.

Despite a higher number of risk factors in the TREO group, no significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival according to the type of alkylator, suggesting that TREO has no advantage over BU in terms of efficacy and toxicity in acute myeloid leukemia and myelodysplastic syndrome.
Carotid Intima-Media Thickness (cIMT) and Cognitive Performance
Authors: Vibha Deepti , Prasad Kameshwar , Dwivedi Sada Nand , Kant Shashi , Pandit Awadh Kishor , Tiemeier Henning , Srivastava Achal Kumar , Karthikeyan Ganesan , Garg Ajay , Verma Vivek , Kumar Amit , Nehra Ashima , Ikram Arfan
Published: February 2023

Introduction:

Atherosclerosis has been shown to impact cognitive impairment, with most of the evidence originating from European, African, or East Asian populations that have employed carotid intima-media thickness (cIMT) as a biomarker for atherosclerosis. Vascular disease is related to dementia/cognitive decline. There is no community-based study from India that has looked at the association of cIMT with cognitive performance.

Methods:

In this cross-sectional study between December 2014 and 2019, we recruited 7505 persons [(mean age 64.6 (9.2) y) and 50.9% women] from a community-dwelling population in New Delhi. These persons underwent carotid ultrasound to quantify cIMT and a cognitive test battery that tapped into memory, processing speed, and executive function. We also computed the general cognitive factor (g-factor), which was identified as the first unrotated component of the principal component analysis and explained 37.4% of all variances in the cognitive tests. We constructed multivariate linear regression models adjusted for age, sex, education, and cardiovascular risk factors. Additional adjustment was made for depression, anxiety, and psychosocial support in the final model.

Results:

We found a significant association of higher cIMT with worse performance in general cognition (β=−0. 01(95% CI: −0.01; −0.01); P<0.001), processing speed (β=−0.20; 95% CI: −0.34; −0.07); P=0.003), memory (β=−0.29; 95% CI: −0.53; −0.05); P=0.016), and executive function (β=−0.54; 95% CI: −0.75; −0.33); P=<0.001). There was no statistically significant association of cIMT with Mini-Mental Status Examination score (β=0.02; 95% CI: −0.34; 0.40; 0.89).

Conclusion:

The cross-sectional study found significant associations of increased cIMT with worse performance in global cognition, information processing, memory, and executive function.
Nasu-Hakola Disease With Stroke-like Attack
Authors: Rashid Nezhad Azra , Olfati Nahid , Shoeibi Ali , Rezaei Talab Fariborz , Soltani Sabi Mohsen
Published: February 2023

Homozygous mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) gene are known to cause Nasu-Hakola disease, which is a rare cause of progressive presenile dementia.

A 36-year-old woman presented with repetitive seizures, a 5-year history of progressive behavioral and cognitive changes, and an affected sibling. Magnetic resonance imaging of the brain revealed an ischemic lesion in the left medial temporal lobe. Extensive evaluation of juvenile stroke revealed that viral and autoimmune encephalitides, serum lactate and pyruvate levels, and cerebrospinal fluid composition were all normal. Brain magnetic resonance imaging was notable of thinning of the corpus callosum and caudate and frontotemporal cortical atrophy, in addition to the ischemic lesion. Whole exome sequencing revealed a homozygous mutation (c.A257T; p.D86V) in TREM2.

The present case expands the clinical phenotype of Nasu-Hakola disease and further suggests that TREM2 pathway might have role in vessel wall health.
Quantifying the Prognostic Value of Preoperative Surgeon Intuition: Comparing Surgeon Intuition and Clinical Risk Prediction as Derived from the American College of Surgeons NSQIP Risk Calculator
Authors: Marwaha Jayson S , Beaulieu-Jones Brendin R , Berrigan Margaret , Yuan William , Odom Stephen R , Cook Charles H , Scott Benjamin B , Gupta Alok , Parsons Charles S , Seshadri Anupamaa J , Brat Gabriel A
Published: February 2023

Background:

Surgical risk prediction models traditionally use patient attributes and measures of physiology to generate predictions about postoperative outcomes. However, the surgeon’s assessment of the patient may be a valuable predictor, given the surgeon’s ability to detect and incorporate factors that existing models cannot capture. We compare the predictive utility of surgeon intuition and a risk calculator derived from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP).

Study Design:

From 10/1/2021 to 9/1/2022, surgeons were surveyed immediately before performing surgery to assess their perception of a patient’s risk of developing any postoperative complication. Clinical data were abstracted from ACS NSQIP. Both sources of data were independently used to build models to predict the likelihood of a patient experiencing any 30-day postoperative complication as defined by ACS NSQIP.

Results:

Preoperative surgeon assessment was obtained for 216 patients. NSQIP data were available for 9182 patients who underwent general surgery (1/1/17 to 9/1/22). A binomial regression model trained on clinical data alone had an AUC of 0.83 (95% CI: 0.80-0.85) in predicting any complication. A model trained on only preoperative surgeon intuition had an AUC of 0.70 (95% CI: 0.63-0.78). A model trained on surgeon intuition and a subset of clinical predictors had an AUC of 0.83 (95% CI: 0.77-0.89).

Conclusions:

Preoperative surgeon intuition alone is an independent predictor of patient outcomes; however, a risk calculator derived from ACS NSQIP is a more robust predictor of post-operative complication. Combining intuition and clinical data did not strengthen prediction.
Multiverruca sinensis gen. nov., sp. nov., a thermotolerant fungus isolated from soil in China
Authors: Wang Hai-Yan , Zhang Zhi-Yuan , Ren Yu-Lian , Shao Qiu-Yu , Li Xin , Chen Wan-Hao , Liang Jian-Dong , Liang Zong-Qi , Han Yan-Feng
Published: February 2023

During a survey of thermotolerant fungi in China, three isolates were obtained from soil samples. Phylogenetic analysis of a combined internal transcribed spacer and large subunit dataset showed that these isolates belong to the same species, which form a well-separated lineage distinct from the other genera in Latoruaceae. Morphologically, the isolates are characterized by having globose and smooth conidiogenous cells, verruculose mycelium and cymbiform conidia. Combining the phylogenetic analyses and morphological characteristics, Multiverruca gen. nov. is proposed and introduced to accommodate a single new species, Multiverruca sinensis sp. nov. Detailed descriptions, illustrations and notes are provided for the new genus and species.
Roseomonas acroporae sp. nov., isolated from coral Acropora digitifera
Authors: Xie Ziqiang , Wang Longsheng , Chen Bogui , Liao Baolin , Xiao Baohua , Sun Hao
Published: February 2023

A non-motile, rod-shaped, pink-pigmented bacterium NAR14T was isolated from coral Acropora digitifera from Daya Bay, Shenzhen, PR China. Cells were Gram-stain-negative, aerobic, catalase-positive and oxidase-negative. NAR14T grew with 0–6 % (w/v) NaCl (optimum, 2–4 %), at 10–41 °C (optimum, 28 °C) and at pH 4.0–9.5 (optimum, 5.0). The major respiratory quinone was Q-10. The predominant fatty acids (more than 10%) were summed feature 8 (65.6 %) and C16 : 0 (17.6%). The DNA G+C content of NAR14T was 73.6 %. The polar lipids of NAR14T comprised one diphosphatidylglycerol, one phosphatidylethanolamine, one phosphatidylglycerol, one phosphatidylcholine, one aminolipid and three unknown polar lipids. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that NAR14T formed a lineage within the genus

Roseomonas

of the family

Acetobacteraceae

, and it was distinct from the most closely related species

Roseomonas wooponensis

JCM 19527T and

Roseomonas riguiloci

JCM 17520T with the 16S rRNA gene sequence similarities of 94.61 and 93.98 %, respectively. Phenotypic characteristics (physiological, biochemical and chemotaxonomic) also supported the taxonomic novelty of this isolate. Thus, NAR14T is considered to represent a novel species within the genus

Roseomonas

, for which the name Roseomonas acroporae sp. nov. is proposed. The type strain is NAR14T (=KCTC 92174T = MCCC 1K07275T).
Upper respiratory tract microbiota dynamics following COVID-19 in adults
Authors: Rosas-Salazar Christian , Kimura Kyle S. , Shilts Meghan H. , Strickland Britton A. , Freeman Michael H. , Wessinger Bronson C. , Gupta Veerain , Brown Hunter M. , Boone Helen H. , Rajagopala Seesandra V. , Turner Justin H. , Das Suman Ranjan
Published: February 2023

To date, little is known about the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, on the upper respiratory tract (URT) microbiota over time. To fill this knowledge gap, we used 16S ribosomal RNA gene sequencing to characterize the URT microbiota in 48 adults, including (1) 24 participants with mild-to-moderate COVID-19 who had serial mid-turbinate swabs collected up to 21 days after enrolment and (2) 24 asymptomatic, uninfected controls who had mid-turbinate swabs collected at enrolment only. To compare the URT microbiota between groups in a comprehensive manner, different types of statistical analyses that are frequently employed in microbial ecology were used, including ⍺-diversity, β-diversity and differential abundance analyses. Final statistical models included age, sex and the presence of at least one comorbidity as covariates. The median age of all participants was 34.00 (interquartile range=28.75–46.50) years. In comparison to samples from controls, those from participants with COVID-19 had a lower observed species index at day 21 (linear regression coefficient=−13.30; 95 % CI=−21.72 to −4.88; q=0.02). In addition, the Jaccard index was significantly different between samples from participants with COVID-19 and those from controls at all study time points (PERMANOVA q<0.05 for all comparisons). The abundance of three amplicon sequence variants (ASVs) (one

Corynebacterium

ASV,

Frederiksenia canicola

, and one

Lactobacillus

ASV) were decreased in samples from participants with COVID-19 at all seven study time points, whereas the abundance of one ASV (from the family

Neisseriaceae

) was increased in samples from participants with COVID-19 at five (71.43 %) of the seven study time points. Our results suggest that mild-to-moderate COVID-19 can lead to alterations of the URT microbiota that persist for several weeks after the initial infection.
Variable disruption of epithelial monolayers by Neisseria meningitidis carriage isolates of the hypervirulent MenW cc11 and MenY cc23 lineages
Authors: Dave Neelam , Albiheyri Raed S. , Wanford Joseph J. , Green Luke R. , Oldfield Neil J. , Turner David P. J. , Martinez-Pomares Luisa , Bayliss Christopher D.
Published: February 2023

Colonization of mucosal tissues by

Neisseria meningitidis

requires adhesion mediated by the type IV pilus and multiple outer-membrane proteins. Penetration of the mucosa and invasion of epithelial cells are thought to contribute to host persistence and invasive disease. Using Calu-3 cell monolayers grown at an air–liquid interface, we examined adhesion, invasion and monolayer disruption by carriage isolates of two clonal complexes of

N. meningitidis

. Carriage isolates of both the serogroup Y cc23 and the hypervirulent serogroup W cc11 lineages exhibited high levels of cellular adhesion, and a variable disruption phenotype across independent isolates. Inactivation of the gene encoding the main pilus sub-unit in multiple cc11 isolates abrogated both adhesive capacity and ability to disrupt epithelial monolayers. Contrastingly, inactivation of the phase-variable opa or nadA genes reduced adhesion and invasion, but not disruption of monolayer integrity. Adherence of tissue-disruptive meningococci correlated with loss of staining for the tight junction protein, occludin. Intriguingly, in a pilus-negative strain background, we observed compensatory ON switching of opa genes, which facilitated continued adhesion. We conclude that disruption of epithelial monolayers occurs in multiple meningococcal lineages but can vary during carriage and is intimately linked to pilus-mediated adhesion.
Has the COVID-19 pandemic ended or not? opinions from the public in the U.S
Authors: Yang Yong
Published: February 2023

Recently President Joe Biden announced the end to the COVID-19 pandemic in the US but some scientists expressed different opinions. This study aimed to examine the view of the end of the COVID-19 pandemic among the public. Data were collected in September 2022 from an online crowdsourcing platform, and respondents answered if they believed that the pandemic has ended in the United States or not. Logistic regressions were used to estimate the likelihood of agreeing on the end of the pandemic, adjusted by demographics and several related variables. Among 2983 respondents, 78.1% believed that the COVID-19 pandemic had ended, and the percentage decreased to 66.5% after adding weights. Males, younger adults, Hispanics, those with higher levels of educational attainment, those with middle levels of household income, those living in suburban or rural areas, and those living in states that voted for the Republican party in the 2020 Presidential Election were more likely to believe that the pandemic had ended, compared with their counterparts. With about one-third of Americans did not agree that the pandemic had ended and marked demographical and geographical differences, the timing and the way of the pandemic end announcement should be deliberately cautious.
Risk of Second Primary Cancers After a Diagnosis of First Primary Cancer: A Pan-Cancer Analysis and Mendelian Randomization Study
Authors: Ruan Xiaohao , Huang Da , Zhan Yongle , Huang Jingyi , Huang Jinlun , NG Ada Tsui-Lin , TSU James Hok-Leung , Na Rong
Published: February 2023

Background

The risk of second primary cancers (SPC) is increasing after the first primary cancers (FPC) are diagnosed and treated. The underlying causal relationship remains unclear.

Methods

We conducted a pan-cancer association (26 cancers) study in the Surveillance, Epidemiology, and End Results (SEER) database. The standardized incidence ratio (SIR) was estimated as the risk of SPCs in cancer survivors based on the incidence in the general population. Furthermore, the causal effect was evaluated by two-sample Mendelian Randomization (MR, 13 FPCs) in the UK Biobank (UKB, n=459,136) and robust analysis (radial MR and Causal Analysis Using Summary Effect estimates, CAUSE).

Results

We found 11 significant cross-correlations among different cancers after harmonizing SIR and MR results. Whereas only 4 of them were confirmed by MR to have a robust causal relationship. In particular, patients initially diagnosed with oral pharyngeal cancer would have an increased risk of non-Hodgkin lymphoma (SIRSEER=1.18, 95%Confidence Interval [CI]:1.05-1.31, ORradial-MR=1.21, 95%CI:1.13-1.30,P=6.00×10−3; ORcause=1.17, 95%CI:1.05-1.31,P=8.90×10−3). Meanwhile, ovary cancer was identified to be a risk factor for soft tissue cancer (SIRSEER=1.72, 95%Confidence Interval [CI]:1.08-2.60, ORradial-MR=1.39, 95%CI:1.22-1.58,P=1.07×10−3; ORcause=1.36, 95%CI:1.16-1.58,P=0.01). And kidney cancer was likely to cause the development of lung cancer (SIRSEER=1.28, 95%Confidence Interval [CI]:1.22-1.35, ORradial-MR=1.17, 95%CI:1.08-1.27,P=6.60×10−3; ORcause=1.16, 95%CI:1.02-1.31,P=0.05) and myeloma (SIRSEER=1.54, 95%Confidence Interval [CI]:1.33-1.78, ORradial-MR=1.24, 95%CI:1.21-2.45,P=0.02; ORcause=1.49, 95%CI:1.04-2.34,P=0.02).

Conclusions

A certain type of primary cancer may cause another second primary cancer, and the profound mechanisms need to be studied in the future.

Funding

This work was in supported by grants from National Natural Science Foundation of China (Grant No. 81972645), Innovative research team of high-level local universities in Shanghai, Shanghai Youth Talent Support Program, intramural grant of The University of Hong Kong to Dr. Rong Na, and Shanghai Sailing Program (22YF1440500) to Dr. Da Huang.
Atherogenic index of plasma is associated with the risk of myocardial infarction: a prospective cohort study
Authors: Zhang Yijun , Wu Shouling , Tian Xue , Xu Qin , Xia Xue , Zhang Xiaoli , Li Jing , Chen Shuohua , Wang Anxin , Liu Fen
Published: February 2023

Background and aims

The atherogenic index of plasma (AIP) has been confirmed as a contributor of cardiovascular disease. But few evidence on the longitudinal pattern of AIP during follow-up. This study aimed to explore the associations between baseline and long-term AIP with the risk of myocardial infarction (MI).

Methods

A total of 98 861 participants without MI at baseline were included from the Kailuan study. The baseline AIP was calculated as log (triglyceride/high-density lipoprotein cholesterol). The long-term AIP was calculated as the updated mean AIP and the number of visits with high AIP. The updated mean AIP was calculated as the mean of AIP from baseline to the first occurrence of MI or to the end of follow-up. The number of visits with high AIP was defined as higher than the cutoff value at the first three visits. Univariable and multivariable Cox proportional hazard models were used to determine the association between AIP and the risk of MI.

Results

During a median follow-up of 12.80 years, 1804 participants developed MI. The multivariable models revealed that elevated levels of baseline and updated mean AIP increased the risk of MI, compared with quartile 1 the HR in quartile 4 was 1.63 (95% CI, 1.41-1.88) and 1.59 (95% CI, 1.37-1.83), respectively. Compared to those without high AIP, the risk of individuals with three times was 1.94 (95% CI,1.55-2.45).

Conclusions

Elevated levels of both baseline and long-term AIP displayed a higher risk of MI.
Surface sampling for SARS-CoV-2 in workplace outbreak settings in the UK, 2021-22
Authors: Nicholls Ian , Spencer Antony , Chen Yiqun , Bennett Allan , Atkinson Barry
Published: February 2023

Aims

To utilise environmental surface sampling to evaluate areas of SARS-CoV-2 contamination within workplaces to identify trends and improve local COVID-control measures.

Methods and Results

Surface sampling was undertaken at 12 workplaces that experienced a cluster of COVID-19 cases in the workforce between March 2021 and March 2022. 7.4% (61/829) of samples collected were positive for SARS-CoV-2 RNA by qPCR with only 1.8% (15/829) of samples identified with crossing threshold (Ct) values below 35.0. No sample returned whole genome sequence inferring RNA detected was degraded.

Conclusions

Few workplace surface samples were positive for SARS-CoV-2 RNA and positive samples typically contained low levels of nucleic acid. Although these data may infer a low probability of fomite transmission or other forms of transmission within the workplace, Ct values may have been lower at the time of contamination. Workplace environmental sampling identified lapses in COVID-control measures within individual sites and showed trends through the pandemic.

Significance and Impact of the Study

Prior to this study, few published reports investigated SARS-CoV-2 RNA contamination within workplaces experiencing cases of COVID-19. This report provides extensive data on environmental sampling identifying trends across workplaces and through the pandemic.
Acute infarct segmentation on diffusion-weighted image using deep learning algorithm and RAPID DWI: a comprehensive stroke center clinical validation study
Authors: Ryu Wi-Sun , Kang You-Ri , Noh Yoon-Gon , Park Jong-Hyeok , Kim Dongmin , Kim Byeong C. , Park Man-Seok , Kim Beom Joon , Kim Joon-Tae
Published: February 2023

Background

Accurate infarct volume measurement requires manual segmentation in diffusion weighted image (DWI) which is time-consuming and prone to variability. We compared two DWI infarct segmentation programs based on deep learning and the apparent diffusion coefficient threshold (JBS-01K and RAPID DWI, respectively) in a comprehensive stroke center.

Method

We included 414 patients whose DWI were evaluated using RAPID DWI and JBS-01K. We used the Bland-Altman plot to compare estimated and manually segmented infarct volumes. We compared R-squared, root mean squared error, Akaike information criterion, and log likelihood after linear regression of manually segmented infarct volumes.

Results

The mean age of included patients was 70,0±12.4 years, and 60.9% were male. The median time between the last known well and a DWI was 12.4 hours. JBS-01K segmented infarct volumes were more comparable to manually segmented volumes compared to RAPID DWI. JBS-01K had a lower root mean squared error (6.9 vs. 10.8) and log likelihood (p<0.001) compared to RAPID DWI. In addition, compared to RAPID DWI, JBS-01K more correctly classified patients according to the infarct volume threshold used in endovascular treatment trials (overall accuracy 98.1% vs. 94.0%; p = 0.002). In 35 patients who received DWI prior to endovascular treatment, JBS-01K infarct volume segmentation was more closely related to manual infarct volume segmentation.

Conclusion

We demonstrated that a deep learning method segmented infarct on DWI more accurately than one based on the apparent diffusion coefficient threshold.
Cellular protection from H2O2toxicity by Fv-Hsp70. Protection via catalase and gamma-glutamyl cysteine synthase
Authors: Hino Chris , Chan Grace , Jordaan Gwen , Chang Sophia S , Saunders Jacquelyn T , Bashir Mohammad T , Hansen James E , Gera Joseph , Weisbart Richard H , Nishimura Robert N
Published: February 2023

Heat shock proteins (HSPs), especially Hsp70 (HSPA1), have been associated with cellular protection from various cellular stresses including heat, hypoxia-ischemia, neurodegeneration, toxins, and trauma. Endogenous HSPs are often synthesized in direct response to these stresses but in many situations are inadequate in protecting cells. The present study addresses the transduction of Hsp70 into cells providing protection from acute oxidative stress by H2O2. The recombinant Fv-Hsp70 protein and two mutant Fv-Hsp70 proteins minus the ATPase domain, and minus the ATPase and terminal lid domains were tested at 0.5 and 1.0 uM concentrations after two different concentrations of H2O2treatment. All three recombinant proteins protected SH-SY5Y cells from acute H2O2toxicity. This data indicated that the protein binding domain was responsible for cellular protection. In addition, experiments pretreating cells with inhibitors of antioxidant proteins catalase and gamma-glutamylcysteine synthase (GGCS) before H2O2resulted in cell death despite treatment with Fv-Hsp70, implying that both enzymes were protected from acute oxidative stress after treatment with Fv-Hsp70. This study demonstrates that Fv-Hsp70 is protective in our experiments primarily by the protein-binding domain. The Hsp70 terminal lid domain was also not necessary for protection. Cellular protection was protective via the antioxidant proteins catalase and GGCS.
Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis
Authors: Vastrad Basavaraj , Vastrad Chanabasayya
Published: February 2023

Coronary artery disease (CAD) is the most common cardiovascular disorder and the leading cause of heart-related deaths in world. Increasing molecular targets have been discovered for CAD and CAD - related complications prognosis and therapy. However, there is still an urgent need to identify novel biomarkers. Therefore, we evaluated biomarkers that might help the diagnosis and treatment of CAD and CAD - related complications. We searched next generation sequencing (NGS) dataset (GSE202625) and identified differentially expressed genes (DEGs) by comparing CAD and normal control samples using DESeq2. Gene ontology (GO) and pathway enrichment analyses of the DEGs were performed using the g:Profiler online database. The protein-protein interaction (PPI) network was plotted with IMEx interactome and visualized using Cytoscape. Module analysis of the PPI network was done using PEWCC1. MiRNA - hub gene regulatory network and TF - hub gene regulatory network analysis was performed to identify the hub genes, miRNAs and TFs. Receiver operating characteristic (ROC) curve analysis was used to predict the diagnostic effectiveness of the hub genes. A total of 118 DEGs (479 up regulated genes and 479 down regulated genes) were detected. The GO enrichment analysis indicated that the DEGs most significantly enriched in cellular response to stimulus and biosynthetic process. The REACTOME pathway enrichment analysis revealed that the DEGs were most significantly enriched in immune system and eukaryotic translation elongation. PPI network, modules, miRNA - hub gene regulatory network and TF - hub gene regulatory network analysis demonstrated that EGR1, SIRT1, STAT1, LRRK2, HIF1A, CSNK2B, RPS3, RPS2, RPS4X and HDAC11 were the hub genes. On the whole, the findings of this study enhance our understanding of the potential molecular mechanisms of CAD and CAD-related complications, and provide potential targets for further research.
Epigenomic perturbation of novelEGFRenhancers reduces the proliferative and invasive capacity of glioblastoma and increases sensitivity to temozolomide
Authors: Vincent Craig A. , Nissen Itzel , Hörnblad Andreas , Remeseiro Silvia
Published: February 2023

Glioblastoma (GB) is the most aggressive of all primary brain tumours. Patients typically rely on radiotherapy with concurrent temozolomide (TMZ) treatment and face a median survival of ∼14 months. Alterations in the Epidermal Growth Factor Receptor gene (EGFR) are common in GB tumours, but therapies targeting EGFR have not shown significant clinical efficacy. Here, we investigated the influence of theEGFRregulatory genome on GB cells, and identified novelEGFRenhancers located in an intronic region nearby the GB-associated SNP rs723527. Epigenomic perturbation of this regulatory region using CRISPR-based methods decreasesEGFRexpression and reduces the proliferative and invasive capacity of glioblastoma cells, while increasing their sensitivity to TMZ. The enhancer-perturbed GB cells also undergo a metabolic reprogramming in favour of mitochondrial respiration and present increased apoptosis. Our findings demonstrate how epigenomic perturbation ofEGFRenhancers can ameliorate the aggressiveness of glioblastoma cells and enhance the efficacy of TMZ treatment.

SIGNIFICANCE

Our study demonstrates how CRISPR/Cas9-based perturbation of enhancers can be used to modulate the expression of key cancer genes, which can help improve the effectiveness of existing cancer treatments and potentially the prognosis of difficult-to-treat cancers such as glioblastoma.
Thermal and alkaline pre-treatments of inoculum halt methanogenesis and enables cheese whey valorization by batch acidogenic fermentation
Authors: Giulianetti de Almeida Maria Paula , Mondini Camille , Bruant Guillaume , Tremblay Julien , Weissbrodt David G. , Mockaitis Gustavo
Published: February 2023

Carboxylates like volatile fatty acids (VFAs) can be produced by acidogenic fermentation (AF) of dairy wastes like cheese whey, a massive residue produced at 160.67 million m3of which 42% are not valorized and impact the environment. In mixed-culture fermentations, selection pressures are needed to favor AF and halt methanogenesis. Inoculum pre-treatment was studied here as selective pressure for AF demineralized cheese whey in batch processes. Alkaline (NaOH, pH 8.0, 6 h) and thermal (90°C for 5 min, ice-bath until 23°C) pre-treatments, were tested together with batch operations run at initial pH 7.0 and 9.0, food-to-microorganism (F/M) ratios of 0.5 to 4.0 g COD g-1VS, and under pressurized and non-pressurized headspace, in experiments duplicated in two institutes. Acetic acid was highly produced (1.36 and 1.40 g CODAcOHL-1) at the expense of methanogenesis by combining a thermal pre-treatment of inoculum with a non-pressurized batch operation started at pH 9.0. Microbial communities comprised of VFAs and alcohol producers, such asClostridium,Fonticella, andIntestinimonas, and fermenters such asLongilineaandLeptolinea. Communities also presented the lipid-accumulating and bulk and foamingCandidatus Microthrixand the metanogenicMethanosaetaregardless of no methane production. An F/M ratio of 0.5 g COD g-1VS led to the best VFA production of 1,769.38 mg L-1. Overall, inoculum thermal pre-treatment, initial pH 9.0, and non-pressurized headspace acted as a selective pressure for halting methanogen and producing VFAs, valorizing cheese whey via batch acidogenic fermentation.
Early threat perception is independent of later cognitive and behavioral control. A virtual reality-EEG-ECG study
Authors: Lu Juanzhi , Kemmerer Selma K. , Riecke Lars , de Gelder Beatrice
Published: February 2023

Research on social threat has shown influences of various factors, such as agent characteristics, proximity and social interaction on social threat perception. An important, yet understudied aspect of threat experience concerns the ability to exert control over the thread. In this study, we used a Virtual Reality (VR) environment showing an approaching avatar that was either angry (threatening body expression) or neutral (neutral body expression) and informed participants to stop avatars from coming closer under five levels of control success (0, 25, 50, 75, or 100%) when they felt uncomfortable. Behavioral results revealed that social threat triggered faster reactions at a greater virtual distance from the participant than the neutral avatar. Event-related potentials (ERPs) revealed that the angry avatar elicited a larger N170/vertex positive potential (VPP) and a smaller N3 than the neutral avatar. The 100% control condition elicited a larger late positive potential (LPP) than the 75% control condition. In addition, we observed enhanced theta power and accelerated heart rate for the angry avatar vs. neutral avatar, suggesting that these measures index threat perception. Our results indicate that perception of social threat takes place in early to middle cortical processing stages, and control ability is associated with cognitive evaluation in middle to late stages.
CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth
Authors: Yang J , Bergdorf K , Yan C , Luo W , Chen SC , Ayers D , Liu Q , Liu X , Boothby M , Groves SM , Oleskie AN , Zhang X , Maeda DY , Zebala JA , Quaranta V , Richmond A
Published: February 2023

Background

Though the CXCR2 chemokine receptor is known to play a key role in cancer growth and response to therapy, a direct link between expression of CXCR2 in tumor progenitor cells during induction of tumorigenesis has not been established.

Methods

To characterize the role of CXCR2 during melanoma tumorigenesis, we generated tamoxifen-inducible tyrosinase-promoter drivenBrafV600E/Pten-/-/Cxcr2-/-andNRasQ61R/INK4a-/-/Cxcr2-/-melanoma models. In addition, the effects of a CXCR1/CXCR2 antagonist, SX-682, on melanoma tumorigenesis were evaluated inBrafV600E/Pten-/-andNRasQ61R/INK4a-/-mice and in melanoma cell lines. Potential mechanisms by whichCxcr2affects melanoma tumorigenesis in these murine models were explored using RNAseq, mMCP-counter, ChIPseq, and qRT-PCR; flow cytometry, and reverse phosphoprotein analysis (RPPA).

Results

Genetic loss ofCxcr2or pharmacological inhibition of CXCR1/CXCR2 during melanoma tumor induction resulted in key changes in gene expression that reduced tumor incidence/growth and increased anti-tumor immunity. Interestingly, afterCxcr2ablation,Tfcp2l1, a key tumor suppressive transcription factor, was the only gene significantly induced with a log2fold-change greater than 2 in these three different melanoma models.

Conclusions

Here, we provide novel mechanistic insight revealing how loss ofCxcr2expression/activity in melanoma tumor progenitor cells results in reduced tumor burden and creation of an anti-tumor immune microenvironment. This mechanism entails an increase in expression of the tumor suppressive transcription factor,Tfcp2l1,along with alteration in the expression of genes involved in growth regulation, tumor suppression, stemness, differentiation, and immune modulation. These gene expression changes are coincident with reduction in the activation of key growth regulatory pathways, including AKT and mTOR.
Enforced dimerization of CD45 by the adenovirus E3/49K protein inhibits T cell receptor signaling
Authors: Windheim Mark , Reubold Thomas F. , Gaestel Matthias , Burgert Hans-Gerhard
Published: February 2023

Human adenoviruses (HAdVs) are widespread pathogens that generally cause mild infections in immunocompetent individuals, but severe or even fatal diseases in immunocompromised patients. In order to counteract the host immune defenses HAdVs encode various immunomodulatory proteins in the early transcription unit 3 (E3). The E3/49K protein is a highly glycosylated type I transmembrane protein uniquely expressed by species D adenoviruses. Its N-terminal ectodomain sec49K is released by metalloprotease-mediated shedding at the cell surface and binds to the receptor-like protein tyrosine phosphatase CD45, a critical regulator of leukocyte activation and functions. It remained elusive which domains of CD45 and E3/49K are involved in the interaction and whether such an interaction can also occur on the cell surface with membrane-anchored full-length E3/49K. Here, we show that the two extracellular domains R1 and R2 of E3/49K bind to the same site in the domain d3 of CD45. This interaction enforces the dimerization of CD45 causing the inhibition of T cell receptor signaling. Intriguingly, the membrane-anchored E3/49K appears to be designed like a “molecular fishing rod” using an extended disordered region of E3/49K as a “fishing line” to bridge the distance between the plasma membrane of infected cells and the CD45 binding site on T cells to effectively position the domains R1 and R2 as baits for CD45 binding. This design strongly suggests that both the secreted sec49K and the membrane-anchored full-length E3/49K have immunomodulatory functions. The forced dimerization of CD45 may be applied as a therapeutic strategy in chronic inflammatory disorders and cancer.
Intracellular interaction of FNDC1/FN1/AR/cMYC in prostate cancer cells
Authors: Ghosh Priyanka , Ogunwobi Olorunseun O.
Published: February 2023

MicroRNAs play an important role in modulating normal cellular functions through protein-protein interaction in addition to regulating gene expression via mRNA degradation or translational repression.PVT1is a non-protein coding gene that encodes six annotated microRNAs (miRNAs), including miR-1207-3p, a demonstrated modulator in PCa. MiR-1207-3p is significantly underexpressed in PCa cells when compared to normal prostatic cells and directly targets fibronectin type III domain containing 1 (FNDC1), which was found to be overexpressed in PCa cells along with concomitant overexpression of fibronectin (FN1)/androgen receptor (AR)/c-MYC. To better understand the role of FNDC1/FN1/AR/c-MYC in PCa progression we examined the interaction between FNDC1/FN1/AR/c-MYC. Coimmunoprecipitation study showed direct physical interaction between FNDC1/FN1/AR/c-MYC in PCa cells and FN1/AR/cMYC in normal prostatic cell. Knockdown of FN1, AR and cMYC not only confirmed FN1/FNDC1/AR/cMYC interaction but also gave rise to the possibility of a complex. We also examined the spatial localization of the FNDC1/FN1/AR/c-MYC pathway by performing immunofluorescence staining in PCa cells. Single staining analysis revealed that FNDC1, AR and c-MYC localize to the nucleus and cytoplasm while FN1 localizes only to the cytoplasm in PCa cells but not in the non-tumorigenic prostate cells. However, our findings show that miR-1207-3p has no direct effect on the FNDC1/FN1/AR/cMYC interaction. Understanding this molecular interaction can reveal additional insights into the role of FNDC1/FN1/AR/cMYC interaction in PCa progression.
Structural and biochemical insights into PsEst3, a new GHSR-type esterase obtained from Paenibacillus sp. R4
Authors: Son Jonghyeon , Choi Woong , Kim Hyun , Kim Minseo , Lee Jun Hyuck , Shin Seung Chul , Kim Han-Woo
Published: February 2023

PsEst3, a psychrophilic esterase obtained from Paenibacillus sp. R4, which was isolated from the permafrost of Alaska, exhibits relatively high activity at low temperatures. Here, crystal structures of PsEst3 complexed with various ligands were generated and studied at atomic resolution, and biochemical studies were performed to analyze the structure–function relationship of PsEst3. Certain unique characteristics of PsEst3 distinct from those of other classes of lipases/esterases were identified. Firstly, PsEst3 contains a conserved GHSRA/G pentapeptide sequence in the GxSxG motif around the nucleophilic serine. Additionally, it contains a conserved HGFR/K consensus sequence in the oxyanion hole, which is distinct from that in other lipase/esterase families, as well as a specific domain composition (for example a helix–turn–helix motif) and a degenerative lid domain that exposes the active site to the solvent. Secondly, the electrostatic potential of the active site in PsEst3 is positive, which may cause unintended binding of negatively charged chemicals in the active site. Thirdly, the last residue of the oxyanion hole-forming sequence, Arg44, separates the active site from the solvent by sealing the acyl-binding pocket, suggesting that PsEst3 is an enzyme that is customized to sense an unidentified substrate that is distinct from those of classical lipases/esterases. Collectively, this evidence strongly suggests that PsEst3 belongs to a distinct family of esterases.
Synthesis, crystal structure and Hirshfeld surface analysis of bis[4-(2-aminoethyl)morpholine-κ2
N,N′]diaquanickel(II) dichloride
Authors: Chidambaranathan Balasubramanian , Sivaraj Settu , Vijayamathubalan Pandy , Selvakumar Shanmugam
Published: February 2023

The title coordination compound, [Ni(C6H14N2O)2(H2O)2]Cl2, was synthesized by mixing 4-(2-aminoethyl)morpholine and nickel chloride in double-distilled water. The asymmetric unit comprises one half of an NiII cation (located on an inversion centre), one 4-(2-aminoethyl)morpholine ligand, one coordinated water molecule and one chloride ion outside the metal coordination sphere. The nickel ion is in a octahedral environment of the N4O2 type, coordinating four N atoms from two 4-(2-aminoethyl)morpholine ligands and two trans-located O atoms from two water molecules. The morpholine ligand was found disordered over two positions with a site occupancy ratio of 0.708 (8):0.292 (8). The crystal structure is consolidated by N—H...Cl, N—H...O, C—H...Cl and C—H...O hydrogen bonds. Hirshfeld surface analysis confirms that van der Waals interactions are prevalent in the crystal packing of the synthesized complex.
Examining the effect of different knowledge aspects on information security awareness
Authors: Chua Hui Na , Khor Vi Vien , Wong Siew Fan
Published: February 2023

Purpose

The purpose of this paper is to identify the different aspects of knowledge and how they associate with information security awareness (ISA). The paper also explores how ISA differs based on demographic characteristics.

Design/methodology/approach

Survey data was collected from 609 respondents in Malaysia.

Findings

The results show that increasing access to informal, multimedia learning mediums, declarative, schematic and strategic knowledge positively impacts an individual's ISA, whereas textual learning medium decreases the ISA. Respondents with different education levels significantly prefer different types of knowledge. Males learn better for ISA with schematic and strategic knowledge compared to females.

Practical implications

The research provides implications for governments and organizations in designing effective ISA campaigns.

Originality/value

Studies show that ISA is crucial in improving information systems policy compliance behavior. The literature has examined various topics ranging from the factors influencing the ISA to how ISA impacts information security behavior. However, there is a lack of study on how different aspects of knowledge impact ISA. This study identified various knowledge aspects from the literature and grouped them into the source, type of knowledge, emotion toward knowledge and learning medium.
A hybrid approach to enhancing the performance of manufacturing organizations by optimal sequencing of value stream mapping tools
Authors: Kumar Sameer , Marawar Yogesh , Soni Gunjan , Jain Vipul , Gurumurthy Anand , Kodali Rambabu
Published: February 2023

Purpose

Lean manufacturing (LM) is prevalent in the manufacturing industry; thus, focusing on fast and accurate lean tool implementation is the new paradigm in manufacturing. Value stream mapping (VSM) is one of the many LM tools. It is understood that combining LM implementation with VSM tools can generate better outcomes. This paper aims to develop an expert system for optimal sequencing of VSM tools for lean implementation.

Design/methodology/approach

A proposed artificial neural network (ANN) model is based on the analytic network process (ANP) devised for this study. It will facilitate the selection of VSM tools in an optimal sequence.

Findings

Considering different types of wastes and their level of occurrence, organizations need a set of specific tools that will be effective in the elimination of these wastes. The developed ANP model computes a level of interrelation between wastes and VSM tools. The ANN is designed and trained by data obtained from numerous case studies, so it can predict the accurate sequence of VSM tools for any new case data set.

Originality/value

The design and use of the ANN model provide an integrated result of both empirical and practical cases, which is more accurate because all viable aspects are then considered. The proposed modeling approach is validated through implementation in an automobile manufacturing company. It has resulted in benefits, namely, reduction in bias, time required, effort required and complexity of the decision process. More importantly, according to all performance criteria and subcriteria, the main goal of this research was satisfied by increasing the accuracy of selecting the appropriate VSM tools and their optimal sequence for lean implementation.
The effect of supplier sustainability risk management strategies on supply chain performance
Authors: Silva C.W. Chathurani , Rathnayaka Dilini Dineshika , Fernando M.A.C.S. Sampath
Published: February 2023

Purpose

This study aims to evaluate the adoption of four types of supplier sustainability risk management (SSRM) strategies, namely, risk avoidance (RA), risk acceptance (RAC), collaboration-based risk mitigation (CBM) and monitoring-based risk mitigation (MBM) in Sri Lankan apparel and retail industries, and to investigate their effect on supply chain performance (SCP).

Design/methodology/approach

This study uses the dynamic capability view (DCV) to develop its hypotheses. Data collected from 89 firms were analysed using partial least square (PLS) structural equation modelling and PLS-based multiple group analysis.

Findings

Sri Lankan apparel and retail firms adopt RA and MBM strategies relatively more than CBM and RAC strategies, whereas there is no significant difference between the two industries in terms of the use of SSRM strategies. The path analysis revealed significant effects of RA and RAC strategies on SCP of both industries. The effect of CBM strategy on SCP is moderated by industry, while MBM has no significant impact.

Research limitations/implications

While managing supplier sustainability risks effectively, RA and RAC strategies provide more opportunities for managers to improve SCP. In achieving SCP, CBM strategies are proven to be more effective for retail industry compared with the apparel sector. Although MBM strategies offer sustainability advantages to firms, their contribution to improving the performance of apparel and retail supply chains is not significant. This research is limited to only two industries (apparel and retail) in Sri Lanka, where the evidence for the effects of SSRM strategies is not available for other contexts.

Originality/value

Either the effects of the four types of SSRM strategies on SCP or the moderating effect of industry on these effects have not been empirically confirmed in the literature. Evaluating the extent to which different strategies are implemented in Sri Lankan apparel and retail industries is another significant contribution of this research. Furthermore, this study contributes by using DCV to a sustainability-based supply chain risk management research.
A case of complete Melkersson‐Rosenthal syndrome: Possibly associated with Mycolicibacterium fortuitum from odontogenic origin
Authors: Zhang Wenqing , Yan Zhimin
Published: February 2023

Melkersson‐Rosenthal syndrome (MRS) is a neuromucocutaneous disease of unknown pathogenesis. With this communication, we describe a case of a 26‐year‐old woman with complete MRS in whom Mycolicibacterium fortuitum was detected in the swelling lip biopsy by next‐ generation sequencing. The patient's symptoms were slightly improved after intralesional corticosteroid injection combined with broad‐spectrum antibiotics, while they were significantly improved after further treatment of dental caries and removal of the residual root. This case provides insight into the possible microbial infection pathogenesis of MRS, and M. fortuitum was speculated to be related to granulomatous and neuronal disorders, most probably from odontogenic origin.