bluuebunny/crossref_metadata_2025 huggingface dataset:
Greek Literary Papyri Dating Benchmark
Authors: Paparrigopoulou Asimina , Kougia Vasiliki , Konstantinidou Maria , Pavlopoulos John
Published: May 2023

Dating papyri accurately is crucial not only to editing their texts but also for our understanding of palaeography and the history of writing, ancient scholarship, material culture, networks in antiquity, etc. Most ancient manuscripts offer little evidence regarding the time of their production, forcing papyrologists to date them on palaeographical grounds, a method often criticized for its subjectivity. In this work, with data obtained from the \href{https://www.baylor.edu/classics/index.php?id=958430}{Collaborative Database of Dateable Greek Bookhands, Baylor University}, an online collection of objectively dated Greek papyri, we created a dataset of literary papyri, which can be used for computational papyri dating. We provide an experimental benchmark on this dataset, by fine-tuning four convolutional neural networks (CNNs) pre-trained on generic images.
Resolution effects on ox-bow lake mapping and inundation consistency analysis in moribund deltaic flood plain of India
Authors: Pal Swades , Ghosh Ripan
Published: May 2023

Research on investigating spatial resolution effect on image-based wetland mapping was done and found finer resolution image has more efficiency but how is it useful for spectral water indices based delineation of partially vegetation shaded ox-bow lake, a cut-off channels of a river, and mapping inundation frequency? In order to obtain these answers, the present study used Landsat and Sentinel images and computed spectral indices like Normalized differences water index (NDWI), Modified NDWI (MNDWI), Re-modified NDWI (RmNDWI) and ensemble Vegetation inclusive aggregated water index (ViAWI). For obtaining inundation consistency character, water presence frequency (WPF) approach was adopted. A set of accuracy matrices was applied for validating the resolution effect. The study revealed that finer resolution sentinel images are more effective in ox-bow lake mapping and characterising inundation frequency but it was not significantly better. Accuracy difference between them was very minimum. Therefore, the study recommended that in a Sentinel image sparse condition, Landsat images could alternatively be used. Among the used indices MNDWI was found suitable for ox-bow lake mapping but vegetation-shaded ox-bow lake was mapped using ensemble ViAWI. Inundation frequency analysis exhibited that about 70% area is consistent in water presence and therefore be hydro-ecologically viable and economically remunerative.
Common patterns and drivers of healthcare system reforms across the OECD nations
Authors: Farkas Brenlea , Moss Stephana J , Stelfox Henry T , Quinn Amity , Drummond Rachelle , Columbus Melanie , Madubueze Ada , Clement Fiona
Published: May 2023

BackgroundChanging health care needs, growing public expectations for high quality and cost-effective care, a burned out and strained healthcare workforce, and market competitions are pushing countries to re-evaluate the efficiency, sustainability, and performance of their health systems. The aims of this study were to: 1) identify the prominent drivers of reforms and 2) examine the common patterns of health system reforms across multiple dimensions.MethodsWe conducted a targeted search of grey and peer-reviewed literature focusing on health system reforms across the 38 Organization for Economic Cooperation and Development (OECD) member countries. A thematic framework was developed by adapting an existing health system framework expanded to five dimensions: 1) financing; 2) population coverage; 3) governance; 4) service delivery; and 5) service coverage. Data were indexed and charted deductively by a single reviewer (NVivo 12).ResultsReforms were most often undertaken at times of economic crises (e.g., recession, war), changes to the nation’s political climate (e.g., change in political party or system), or a drastic change in population needs (e.g., aging population, epidemic). Despite a variety in evolutionary paths to present day health systems, some common patterns emerged across the five dimensions with reform continual in most nations.ConclusionHealth system reforms have historically been driven by the economic, political, and social context; a context similar to the current one. Therefore, policy makers could leverage the current context to call for structural reform to healthcare systems.
Has the Opening of High-speed Railway in China Promoted Urban Low-Carbon Transformation Along the Route: Re-estimation Based on Staggered DID Robust Estimators
Authors: Wang Qiaoru , Chen Leyi , Liu Tingyu
Published: May 2023

Considering the opening of high-speed railway (HSR) as a quasi-natural experiment, this paper explores the emission reduction effect of HSR opening and its mechanisms and heterogeneity characteristics based on the panel data of 272 cities in China from 2006 to 2019 by Staggered DID model and the mediating effect model. It is found that:(1)the opening of HSR significantly reduces the carbon emission level of cities, and the conclusion still holds after controlling the endogeneity issue and a series of robustness tests;(2) Bancon decomposition and negative weight diagnostics both show that the estimated average treatment effect bias is small and the robust estimators are more robust;(3) by reducing production costs and promoting inter-regional industrial division of labor, the opening of HSR promotes intra-industrial structural transformation and inter-industrial structural transformation respectively, thus reducing urban carbon emissions. At the same time, HSR achieves urban carbon emission reduction by promoting free movement of population and human capital agglomeration;(4) further study finds that there is regional heterogeneity in the emission reduction effect of HSR opening, and the carbon reduction effect is mainly reflected in large and medium-sized cities, near provincial capitals, non-resource-based cities, and cities with scarce educational resources, which indicates that the location of future HSR should be combined with the city's own characteristics and be tailored to the city.
Microscale acoustic metamaterials as conformal sonotransparent skull prostheses
Authors: Kim Gunho , Rabut Claire , Ling Bill , Shapiro Mikhail , Daraio Chiara
Published: May 2023

Functional ultrasound imaging enables sensitive, high-resolution imaging of neural activity in freely behaving animals and human patients. However, the skull acts as an aberrating and absorbing layer for sound waves, leading to most functional ultrasound experiments being conducted after skull removal. In pre-clinical settings, craniotomies are often covered with a polymethylpentene film, which offers limited longitudinal imaging, due to the film’s poor conformability, and limited mechanical protection, due to the film’s low stiffness. Here, we introduce a skull replacement consisting of a microstructured, conformal acoustic window based on mechanical metamaterials, designed to offer high stiffness-to-density ratio and sonotransparency. We test the acoustic window in vivo, via terminal and survival experiments on small animals. Long-term biocompatibility and lasting signal sensitivity are demonstrated over a long period of time (> 4 months) by conducting ultrasound imaging in mouse models implanted with the metamaterial skull prosthesis.
Altered structural connectivity in olfactory disfunction after mild COVID-19 using probabilistic tractography
Authors: Bispo Diógenes Diego de Carvalho , Brandão Pedro Renato de Paula , Pereira Danilo Assis , Maluf Fernando Bisinoto , Dias Bruna Arrais , Paranhos Hugo Rafael , von Glehn Felipe , de Oliveira Augusto César Penalva , Soares Alexandre Anderson Sousa Munhoz , Descoteaux Maxime , Regattieri Neysa Aparecida Tinoco
Published: May 2023

We aimed to investigate changes in olfactory bulb volume and brain network in the white matter (WM) in patients with persistent olfactory disfunction (OD) following COVID-19. A cross-sectional study evaluated 38 participants with OD after mild COVID-19 and 24 controls, including Sniffin' Sticks identification test (SS-16), MoCA, and brain magnetic resonance imaging. Network-Based Statistics (NBS) and graph theoretical analysis were used to explore the WM. The COVID-19 group had reduced olfactory bulb volume compared to controls. In NBS, COVID-19 patients showed increased structural connectivity in a subnetwork comprising parietal brain regions. Regarding global network topological properties, patients exhibited lower global and local efficiency and higher assortativity than controls. Concerning local network topological properties, patients had reduced local efficiency (left lateral orbital gyrus and pallidum), increased clustering (left lateral orbital gyrus), increased nodal strength (right anterior orbital gyrus), and reduced nodal strength (left amygdala). SS-16 test score was negatively correlated with clustering of whole-brain WM in the COVID-19 group. Thus, patients with OD after COVID-19 had relevant WM network dysfunction with increased connectivity in the parietal sensory cortex. Reduced integration and increased segregation are observed within olfactory-related brain areas might be due to compensatory plasticity mechanisms devoted to recovering olfactory function.
Insight into the mechanism of a novel heterotrophic nitrifying – aerobic denitrifying bacterium, Bacillus subtilis strain H1, and its application potential in mariculture wastewater treatment
Authors: Xie Yumeng , Tian Xiangli , Liu Yang , Zhao Kun , Li Yongmei , Luo Kai , Wang Bo , Dong Shuanglin
Published: May 2023

The nitrogen removal performance and mechanisms of Bacillus subtilis H1 isolated from a mariculture environment were investigated. Strain H1 efficiently removed NH4+-N, NO2−-N, and NO3−-N in simulated wastewater with removal efficiencies of 85.61%, 90.58%, and 57.82%, respectively. Strain H1 also efficiently degraded mixed nitrogen and had removal efficiencies ranging from 82.39–89.54%. Nitrogen balance analysis revealed that inorganic nitrogen was degraded by heterotrophic nitrification–aerobic denitrification (HN-AD) and assimilation. 15N isotope tracing indicated N2O was the product of the HN-AD process, while N2 as the final product was only detected during the reduction of 15NO2−-N. The nitrogen assimilation and dissimilation pathways by strain H1 were further clarified using complete genome sequencing, nitrification inhibitor addition, and enzymatic activity measurement, and the ammonium oxidation process was speculated as NH4+→ NH2OH→ NO→ N2O. These results showed the application prospect of B. subtilis H1 in treating mariculture wastewater.
Recent functional decline and outpatient follow-up after hospital discharge: A cohort study
Authors: Bogler Orly , Kirkwood David , Austin Peter C. , Jones Aaron , Sinn Chi-Ling Joanna , Okrainec Karen , Costa Andrew , Lapointe-Shaw Lauren
Published: May 2023

Background: Functional decline is common following acute hospitalization and is associated with hospital readmission, institutionalization, and mortality. Early physician follow-up has the potential to prevent poor outcomes and is integral to high-quality transitional care. Our study sought to determine whether functional decline was associated with post-discharge follow-up and whether this association changed following COVID-19, given that both functional decline and COVID-19 may affect access to post-discharge care.
Method: We conducted a retrospective cohort study using health administrative data from Ontario, Canada. We included patients over 65 who were discharged from an acute care facility during March 1st, 2019 – January 31st, 2020 (pre-COVID-19 period), and March 1st, 2020 – January 31st, 2021 (COVID-19 period), and who were assessed for home care while in hospital. Patients with and without functional decline were compared. Our primary outcome was any physician follow-up visit within 7 days of discharge.
Results:
Our study included 21,771 (pre-COVID) and 17,248 (COVID) hospitalized patients, of whom 15,637 (71.8%) and 12,965 (75.2%) had recent functional decline. Our propensity-weighted cohorts included 15637/15810 patients with/without function decline in the pre-COVID-19 period and 12965/13132 with/without functional decline in the COVID-19 period. Pre-COVID, there was no difference in physician follow-up within 7 days of discharge (Exposed 45.0% vs Unexposed 44.0%; RR=1.02, 95% CI 0.98 – 1.06). These results did not change in the COVID-19 period (Exposed 51.1% vs. Unexposed 49.4%; RR=1.03, 95% CI 0.99-1.08, Z-test for interaction p=0.72). In the COVID-19 cohort, functional decline was associated with having a 7-day physician virtual visit (RR 1.15; 95% CI 1.08 – 1.24) and a 7-day physician home visit (RR 1.64; 95% CI 1.10 – 2.43).
Conclusions: Functional decline was not associated with reduced 7-day post-discharge physician follow-up in either the pre-COVID-19 or COVID-19 periods. In the COVID-19 period, functional decline was positively associated with 7-day virtual and home-visit follow-up.
Transcriptomic analysis of ipsilateral spinal cord in rats after bone fracture
Authors: Wang Shen , Deng Jin , Yuan Shaoxun , Lu Qingguo , Gu Xinyi , Huang Chen , Guo Shuhang , Yu Dehong , Yin Xiaofeng
Published: May 2023

Backgroud: A large amount of research has shown that spinal cord injury causes bone loss and increases fracture risk, while spinal cord injuries caused by fractures and their underlying molecular mechanisms still need further investigation.Methods To investigate the specific changes in the spinal cord after bone fractures, we obtained L4-L5 spinal cord segments from the same side of SD rats with tibial fractures at 0, 3, 7, 14, and 28 days after the fracture. Gene Ontology (GO) enrichment analysis, KEGG pathway analysis, and Ingenuity Pathway Analysis(IPA) were used to analyze the differential gene expression of the genes at different time points .Results Our sequencing results showed that the transcriptional changes in the spinal cord after fracture developed towards the direction of restoring normal physiological function. At 3 and 7 days after fracture, the same-side L4-L5 spinal cord segment showed significant activation of neurodegeneration and central nervous system development, with neurodegeneration activation being most significant at 3 days after fracture and the spinal cord also showing activation of cell survival regulation effects after 7 days of bone fracture. At 14 days after bone fracture, the spinal cord showed significant enrichment in the myelin sheath formation signaling pathway, activation of cell death in the central nervous system, GO terms relating to synaptic function were also significantly enriched. The spinal cord had active gene transcription, protein synthesis, and degradation metabolism processes at these three time points after fracture. At 28 days after fracture, the spinal cord showed recovery of motor function. In addition, a series of important genes in the spinal cord after fracture were differentially expressed, including PCP4 and Krit1. Rictor, TEAD1, torin1, DDX5, CAB39L, and Ngf in the spinal cord may act as upstream master regulators to play a role in fracture repair.Conclusions We speculate that local injury stimulation of the fracture through DRG enters the intermediate neurons of the spinal cord dorsal horn, triggering a series of adaptive changes including activation of neurodegeneration and central nervous system development in the spinal cord, among other changes. With the involvement of important molecules such as PCP4 and Krit1, the physiological function of the spinal cord gradually recovers after fracture, reducing the risk of disuse osteoporosis and promoting fracture repair. This study provides an understanding of the transcriptome changes in the spinal cord following fracture at different time points, and the changes observed across these time points, and screens for important genes that might participate in the regulation of spinal cord fracture healing, providing a sequencing basis for exploring the bidirectional relationship between fracture and the spinal cord.
Phonological Awareness Mediates the Relationship between DCDC2 and Reading Performance with the Influence of Home Environment
Authors: Li Miao , DeMille Mellissa , Lovett Maureen , Bosson-Heenan Joan , Frijters Jan , Gruen Jeffrey
Published: May 2023

Proficient reading requires critical phonological processing skill that interact with both genetic and environmental factors. However, the precise nature of the relationships between phonological processing and genetic and environmental factors are poorly understood. We analyzed data from the Genes, Reading and Dyslexia (GRaD) Study on 1,419 children ages 8 to 14 years from African-American and Hispanic-American family backgrounds living in North America. The analyses showed that phonological awareness mediated the relationship between DCDC2-READ1 and reading outcomes when parental education and socioeconomic status was low. The association between READ1 and reading performance is complex, whereby mediation by phonological awareness was significantly moderated by both parental education and socioeconomic status. These results show the importance of home environment and phonological skills when determining associations between READ1 and reading outcomes. This will be an important consideration in the development of genetic screening for risk of reading disability.
Explore the possible pathway of improving liver and heart injury in diabetes nephropathy based on bioinformatics analysis
Authors: Yang Ye , Wang Qin , Wang Xiaobei , Wang Xinling
Published: May 2023

Background This study explore the possible pathway of MicroRNA-130a, TXNIP, CD44 and TGF-β1 improving liver and heart injury in diabetes nephropathy based on bioinformatics ananlysis.Methods Screening Key Genes Using Bioinformatics Analysis. The biochemical index and serum levels of MicroRNA-130a, TXNIP, CD44 and TGF-β1 were detected and analyzed by Pearson correlation analysis in 100 DN patients and 50 healthy controls. The rats model were randomly divided into two groups. The expression of MicroRNA-130a, TXNIP, CD44 and TGF-β1 in liver and heart and the morphological changes was detected.Results Screening and Analysis of Differentially Expressed Genes MicroRNA-130a and TXNIP, CD44 and TGFBI Involved in diabetes Nephropathy by Bioinformatics Methods. Compared to healthy controls, serum levels of MicroRNA-130a were decreased, while levels of TXNIP, CD44 and TGF-β1 were elevated in DN patients. Moreover, MicroRNA-130a was negatively correlated with TXNIP, CD44 and TGF-β1. In DN rats, the levels of TXNIP, CD44 and TGF-β1 in the liver and heart tissues were significantly elevated, while MicroRNA-130a levels were significantly decreased, compared to the NC group.Conclusion Upregulate MicroRNA-130a and decrease TXNIP, CD44 and TGF-β1 may participate in liver and heart injury pathway of diabetes nephropathy.
IFNα induces CCR5 in CD4+ T-cells, causing its anti- HIV inefficiency and its subsequent pathogenic elevation, partially controlled by anti-HIV therapy
Authors: Gallo Robert , Buanec Hélène , Schiavon Valérie , Mérandet Marine , Howkit Alexandre , SONG HONGSHUO , Bergerat David , C Fombellida Lopez , Bensussan Armand , Bouaziz Jean-David , Burny Arsène , Darcis Gilles , Sajadi Mohammad , Kottilil Shyamasundaran , Zagury Daniel
Published: May 2023

Like EC, we find that ART-treated patients control serum IFNα concentration and show few immune cell alterations enabling a healthy but fragile medical status. However, treatment interruption leads to elevated IFNα reflecting virus production indicating that like EC, ART does not achieve a virological cure. The immune system becomes overwhelmed by multiple immune cell abnormalities as found in untreated patients. These are chiefly mediated by elevated IFNα inducing signaling checkpoints abnormalities, including PD1, in cytotoxic immune cells. Importantly, during acute infection, elevated IFNα correlated with HIV load, and we found that IFNα enhances CCR5, the HIV coreceptor in CD4+ T-cells, impairing its antiviral response and accounting for the pathogenic vicious cycle: HIV → IFNα ↗ → infected CD4+ T-cells ↗ →HIV ↗. This study opens immunotherapeutic perspectives showing the need to control IFNα in order to convert ART patients into EC.
Industry applications of identifying spot laser welded nugget for automatic ESS manufacturing process
Authors: Chen Youshyang , Chang Jieh-Ren , Mohammad Ashraf , Kuo Fang-Chang
Published: May 2023

Recent advancements in energy storage along with power electronic technology have made battery energy storage systems (ESS) a feasible alternative for current power applications. Battery packs with lithium-ion (Li-ion) pouch cells are the main source of ESS. However, it is a big trouble that improper voltage and impedance of laser welding significantly affect the whole battery module during battery pack manufacturing stages, causing the cell imbalance inside and eventually resulting in a thermal runaway of battery pack and non-durable use. Importantly, the formation of nuggets welded can be classified as good (GD) and not-good (NG) based on the labels after peeling off the flyer of Li-ion pouch cell. Interestingly, it is usually a standard practice in this industry to include substantial numbers of redundant welds to gain confidence in the structural stability of the welded component. Thus, a non-destroyed and low-cost detection for identifying the nuggets is absolutely necessary. An effective methodology is motivated and proposed with three procedures for the identification of laser-welded nuggets. At first, the nuggets are detected and separated from a grayscale image. Image features are extracted to train the nugget images on the advanced detector model constructed to identify the GD and NG nuggets. Second, this research develops five models for achieving this purpose of detector; one is called the nugget model developed in convolution neural network (CNN) technique, and the others use the transfer learning of the most popular pre-trained models. From the comparative studies, it is found that the residual network (ResNet) model more effectively classifies the nuggets with 100% accuracy rate than that of the other listed models. Finally, this research has significant application contributions of battery manufacturing industries to produce highly efficient welded nugget products by overcoming the cost-ineffective problems of manual inspection; thus, it further helps this industry simultaneously reduce productive inspection time and increase the manufacturing efficiency of ESS at a lower cost without human intervention than the past.
Compassion Focused Therapy (CFT) for the reduction of the self-stigma of mental disorders : The COMpassion for Psychiatric disorders And Self-Stigma (COMPASS) study protocol for a randomized controlled study.
Authors: Riebel Marie , Rohmer Odile , Charles Emilie , Lefebvre François , Weibel Sébastien , Weiner Luisa
Published: May 2023

Background:
People with mental disorders face frequent stigmatizing attitudes and behaviors from others. Importantly, they can internalize such negative attitudes and thus self-stigmatize. Self-stigma is involved in diminished coping skills leading to social avoidance and difficulties in adhering to care. Reducing self-stigma and its emotional corollary, shame, is thus crucial to attenuate the negative outcomes associated with mental illness. Compassion Focused Therapy (CFT) is a third wave cognitive behavioral therapy that targets shame reduction and hostile self-to-self relationship and allows for symptom improvement while increasing self-compassion. Although shame is a prominent part of the concept of self-stigma, the efficacy of CFT has never been evaluated in individuals with high levels of self-stigma. The purpose of this study is to evaluate the efficacy and acceptability of a group-based CFT program on self-stigma, compared to a psychoeducation program for self-stigma (Ending Self-Stigma) and to treatment as usual (TAU). We hypothesize that diminished shame and emotional dysregulation and increased self-compassion will mediate the relationship between self-stigma improvements post-therapy in the experimental group.
Methods:
This seven-center trial will involve 336 participants diagnosed with a severe mental illness and reporting high levels of self-stigma. Participants will be randomized into one of three treatment arms: 12 week-treatment of Compassion-Focused Therapy (experimental arm), 12 week-treatment of Psychoeducation (active control arm), and TAU (treatment as usual - passive control arm). The primary outcome is the decrease of self-stigma scores on a self-report scale, i.e., ISMI, at 12 weeks.
Secondary endpoints include sustainability of self-stigma scores (ISMI) and self-reported scores regarding target psychological dimensions, e.g., shame and emotional regulation, social functioning and psychiatric symptoms. Assessments are scheduled at pretreatment, post-treatment (at 12 weeks), and at 6-month follow-up. Acceptability will be evaluated via (i) the Credibility and Expectancy Questionnaire at T0, the Consumer Satisfaction Questionnaire for Psychotherapeutic Services posttreatment and at 6-month follow-up, (iii) attendance and (iv) dropout rates.
Discussion:
This study will evaluate the potential efficacy and acceptability of a group-based CFT program on the decrease of self-stigma, and thereby contribute to the continuing development of evidence-based therapeutic interventions for the internalized stigma of mental disorders. `
Trial registration:
This trial has been registered on January 26, 2023: clinicaltrials.gov NCT05698589 https://www.clinicaltrials.gov/ct2/show/NCT05698589
Isolation of bioactive phytochemicals from Crinum asiaticum along with their cytotoxic and TRAIL-resistance abrogating prospect assessment
Authors: Rakhi Sharmin , Hara Yasumasa , Islam Md. , Manome Teruhisa , Alam Safaet , Emon Nazim , Al-Mansur Muhammad , Kuddus Md , Sarkar Md. , Ishibashi Masami , Ahmed Firoj
Published: May 2023

Crinum asiaticum L. (Amaryllidaceae) is a perennial bulbous herb, locally utilized for possessing multifaceted pharmacological properties including anticancer, immune-stimulating, analgesic, antiviral, antimalarial, antibacterial, and antifungal, in addition to their popularity as an aesthetic plant. Separation of MeOH extract of C. asiaticum leaves yielded three known compounds as cycloneolitsol (1), hippeastrine (2) and β-sitosterol (3). Among these, compounds 1 and 2 were subjected to the cytotoxic assay and found that 1 decreased cell viability to 45% and 8% against HCT116 cells; 15% and 9% against DU145 cells; 63% and 23% against Huh7 cells at 100 µM and 200 µM concentrations, respectively. Similarly, 2 decreased cell viability to 10% and 7% against HCT116 cells; 25% and 15% against DU145 cells; 26% and 18% against Huh7 cells at 100 µM and 200 µM concentrations, respectively. When tested for TRAIL-resistance abrogating activity, 1 (100 µM) along with TRAIL (100 ng/mL) showed moderate activity in AGS cells producing 25% more inhibition than the agent alone. Whereas (20 and 30 µM) in combination with TRAIL (100 ng/mL) exhibited strong activity in abrogating TRAIL-resistance and caused 34 and 36% more inhibition in AGS cells, respectively. The in-silico studies of compounds 1 and 2 revealed high docking hits in the TRAIL and other cancer-associated proteins which indicates a good correlation with the cell-based assay. It is still recommended to conduct further investigations to understand their exact molecular mechanism.
Pyruvate dehydrogenase complex integrates the metabolome and epigenome in CD8+ memory T cell differentiation in vitro
Authors: Tarasenko Tatiana , Banerjee Payal , Gomez-Rodriguez Julio , Gildea Derek , Zhang Suiyuan , Wolfsberg Tyra , Jenkins Lisa , Program NISC Comparative Sequencing , McGuire Peter
Published: May 2023

Modulation of metabolic flux through pyruvate dehydrogenase complex (PDC) plays an important role in T cell activation and differentiation. PDC sits at the transition between glycolysis and the tricarboxylic acid cycle and is a major producer of acetyl-CoA, marking it as a potential metabolic and epigenetic node. To understand the role of pyruvate dehydrogenase complex in T cell differentiation, we generated mice deficient in T cell pyruvate dehydrogenase E1A (Pdha) subunit using a CD4-cre recombinase-based strategy. Herein, we show that genetic ablation of PDC activity in T cells (TPdh-/-) leads to marked perturbations in glycolysis, the tricarboxylic acid cycle, and OXPHOS. TPdh-/- T cells became dependent upon substrate level phosphorylation via glycolysis, secondary to depressed OXPHOS. Due to the block of PDC activity, histone acetylation was also reduced, including H3K27, a critical site for CD8+ TM differentiation. Transcriptional and functional profiling revealed abnormal CD8+ TM differentiation in vitro. Collectively, our data indicate that PDC integrates the metabolome and epigenome in CD8+ memory T cell differentiation. Targeting this metabolic and epigenetic node can have widespread ramifications on cellular function.
The Impact of CFTR Modulator Triple Therapy on Type 2 Inflammatory Response in Patients with Cystic Fibrosis
Authors: Mehta Ajay , Lee Irene , Li Galvin , Jones Marieke , Hanson Lydia , Lonabaugh Kevin , List Rhonda , Borish Larry , Albon Dana
Published: May 2023

Background
Treatment of cystic fibrosis (CF) has been revolutionized by the use of cystic fibrosis transmembrane conductance regulator (CFTR) protein modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) triple therapy. Prior studies support a role for type 2 (T2) inflammation in many people with CF (PwCF) and CF-asthma overlap syndrome (CFAOS) is considered a separate clinical entity. It is unknown whether initiation of ETI therapy impacts T2 inflammation in PwCF. We hypothesized that ETI initiation decreases T2 inflammation in PwCF.
Methods
A single center retrospective chart review was conducted for adult PwCF. As markers of T2 inflammation, absolute eosinophil count (AEC) and total immunoglobulin E (IgE) data were collected longitudinally 12 months prior to ETI therapy initiation and 12 months following therapy initiation. Multivariable analyses adjusted for the age, gender, CFTR mutation, disease severity, inhaled steroid use, and microbiological colonization.
Results
There was a statistically significant reduction (20.10%, p < 0.001) in 12-month mean IgE following ETI initiation; this change remained statistically significant in the multivariate model. The longitudinal analysis demonstrated no change in AEC following therapy initiation.
Conclusion
This study shows reduction in IgE but no change in AEC after ETI therapy initiation. We think that the lack of influence on AEC argues against an impact on previously established T2 inflammation and that the reduction in IgE is likely related to antigen load reduction post ETI. Further studies are warranted to determine the underlying mechanism of ETI impact on T2 inflammation and possible role for asthma immunomodulator therapy post ETI initiation in CFAOS.
Importance of Anemia in Heart Failure over Blood Pressure Variability
Authors: Kiuchi Shunsuke , Hisatake Shinji , Kabuki Takayuki , Dobashi Shintaro , Murakami Yoshiki , Ikeda Takanori
Published: May 2023

The evaluation of arteriosclerosis (vascular function) is important when treating heart failure (HF). Vascular dysfunction is associated with anemia through renal function and endothelial nitric oxide synthase, and many patients with HF have anemia. Additionally, blood pressure variability (BPV) caused by vascular dysfunction is also associated with HF prognosis. However, how anemia and BPV may affect HF prognosis is unclear. Between January 2012 and July 2018, 214 patients with HF were hospitalized, the cardio-ankle vascular index (CAVI) as an index of arteriosclerosis of whom was measured. According to the CAVI, the patients were divided into the elevated and preserved CAVI groups. Furthermore, we investigated the factors related to major adverse cardiovascular events (MACE). MACE was defined as cardiovascular death or rehospitalization within 1 year after discharge. In the elevated CAVI group, significant differences in body mass index (BMI), BPV, left ventricular dimension, and hemoglobin levels were observed between patients with MACE and those without MACE. Meanwhile, in the preserved CAVI group, significant differences in BMI, diastolic/mean blood pressure values, and hemoglobin levels were observed. The multivariate analysis showed an independent association between hemoglobin level and MACE occurrence in both the elevated and preserved CAVI groups (elevated CAVI group: hazard ratio [HR] = 0.800, P = 0.045; preserved CAVI group: HR = 0.783, P = 0.049 {model 1}, and HR = 0.752, P = 0.023 {model 2}). Anemia was independently associated with HF prognosis with or without arteriosclerosis. In HF with arteriosclerosis, BPV may also be useful for evaluating the prognosis.
Development, chlorophyll content and nutrient accumulation in in vitro shoots of Melaleuca alternifolia under light-wavelengths and benzylaminopurine (BAP)
Authors: Gonzales-Alvarado Antony Cristhian , Cardoso Jean Carlos
Published: May 2023

In vitro growing of the Melaleuca could contribute to the cloning of superior genotypes. The studies of factors that affect the micropropagation are necessary, especially by the use of recent technologies, such as the use of light-emitting diodes (LEDs). This study aimed at better understanding the effects of wavelengths on the development and physiology of melaleuca cultivated in vitro, as well as the interaction of LEDs with the main cytokinin used in micropropagation, the N6-Benzylaminopurine (BAP). The BAP and wavelengths, as well as the interaction between them, had a strong influence on most of the variables analyzed, altering the in vitro development, chlorophyll concentrations in the plants, as well as changing the different variables analyzed from the culture medium, such as pH, EC, quantities of Ca2+, Mg2+ and P in the culture media and the nutrient accumulation in the shoots. The results demonstrate that the main effects of the addition of BAP in the in vitro cultivation of melaleuca are: the increase in the number of shoots which resulted in greater increase in fresh and dry mass; reduction of height and chlorophyll contents; completely inhibition of adventitious rooting; higher consumption of Mg and lower consumption of Ca and P from the culture media; higher contents of Fe and lower contents of P, S, Mn, Cu and B in the in vitro tissues.
New Drug Discovery of Cardiac Anti-Arrhythmic Drugs: Insights in Animal Models
Authors: Sharma Ashish Kumar , Singh Shivam , Bhat Mehvish , Gill Kartik , Tantray Junaid , Jose Divyamol , Gupta Rashmi , Sharma Rajesh , Sahu Sanjay Kumar , Rathore Gulshan , Chandolia Priyanka , Singh Mithilesh , Mishra Anurag , Raj Shobhit , Gupta Archita , Agarwal Mohit , Gupta Anamika , Gupta Prashant , Vashist Ankit , Vaibhav Parth , Kathuria Nancy , Yadav Vipin , Singh Ravindra Pal , Garg Arun , Zaid Mohammad , Kifayat Sumaiya , Yangzom Tsering , Kumar Sachin , Shakya Anjali
Published: May 2023

In the normal heart cardiac rhythm is controlled by microscopic and macroscopic structures. Abnormality of pacemaker or electrical conduction aberrations causes arrhythmic disorders. Cardiac Arrhythmias may be fortunate, typical, threatening and eventually fatal. Cardio-vascular arrhythmia happens commonly in clinical practise affecting drastically to the patients on digitalis, anaesthesia and acute myocardial infarction. Both traditional and genetic animal models of arrhythmias, their characteristics, and their significance are summarized as: In Vitro Models: Isolated guinea pig papillary muscles, Action potential and refractory period in isolated guinea pig papillary muscle, Langendorff technique & Acetylcholine or potassium induced arrhythmia. In Vivo Models- Chemically induced arrhythmia: Aconitine antagonism in rats, Digoxin induced arrhythmia in rats, Strophanthin/ouabain induced arrhythmia, Adrenaline induced arrhythmia & Calcium induced arrhythmia. Electrically induced arrhythmia: Ventricular fibrillation electrical threshold, Programmed electrical stimulation induced arrhythmia & Sudden coronary death models in dogs. Exercise induced ventricular fibrillation. Mechanically induced arrhythmia: Reperfusion arrhythmia in rats, Reperfusion arrhythmia in dogs & Two stage coronary ligation in dogs. Genetic models of arrhythmias. Conclusion: Experimental models of cardiac arrhythmias, traditional and genetic gives quick summary of the most popular animal models, their characteristics, and their significance for new drug discovery of antiarrhythmic agents.
EGFR, and VEGFR inhibitory activities of the crude extract from marine algae Dictyopteris acrostichoides supported by in silico analysis and metabolic profiling
Authors: Attia Eman Zekry , Abdel-Rahman Iman A. M. , Aly Omar M. , Saber Hani , Rushdi Mohammed Ismael , Abdelmohsen Usama Ramadan
Published: May 2023

Ethanol extracts of Caulerpa racemosa, Dictyopteris acrostichoides, Halimeda opuntia and Polycladia myrica, were tested for their cytotoxicity against HepG2 (human hepatoma), MCF-7 (human breast adenocarcinoma), and Caco-2 (human colon adenocarcinoma) cells. Dictyopteris acrostichoides displayed cytotoxicity against HepG2, MCF-7 and Caco-2 with IC50 values of 11.65, 9.28 and 16.86 µg/mL, respectively in comparison to doxorubicin as a positive control, (IC50 = 5.72, 5.17 and 5.81 µg/mL, respectively). LC-HR-ESI-MS metabolic profiling of the D. acrostichoides extract characterized seventeen metabolites (1–17). In silico analysis indicated 1-(3-oxo-undecyldisulfanyl)-undecan-3-one (16) was the most active EGFR inhibitor, while 1-(3-Oxo-undecyldisulfanyl)-undecan-3-one (16) and di(3-acetoxy-5-undecenyl) disulfide (17) were the most active VEGFR inhibitors. Furthermore, the ethanol extract of D. acrostichoides was tested against epidermal growth factor receptor (EGFR) kinase (IC50 = 0.11 µg/mL) compared to lapatinib as a positive control, (IC50 = 0.03µg/mL) and against vascular endothelial growth factor (VEGF) (IC50 = 0.276 µg/mL) compared to sorafenib as a positive control, (IC50 = 0.049 µg/mL).
Robinin inhibits pancreatic cancer cell proliferation, EMT and inflammation via regulating TLR2-PI3k-AKT signaling pathway
Authors: Zhang wenwen , Liu Wenting , Hu Xingchen
Published: May 2023

Purpose To investigate the anti-tumor effect of Robinin (Toll-like receptor 2 inhibitor) in pancreatic cancer cells via regulating tumor microenvironment.Methods The effects of Robinin on cell proliferation or migration in Mia-PACA2 and PANC-1 were determined, using CCK8 or wound healing assay, respectively. The typical markers of EMT (αSMA and snail) and the inflammation markers (IL-6 and TNF-α) were all detected by western blot. CU-T12-9 (TLR2 agonist) was used to rescue Robinin’s effect. PI3k-p85α and Phosphorylated-AKT (p-AKT) were evaluated, compared to the β-actin and AKT, using western blot.Results Robinin significantly inhibited cell proliferation and migration in Mia-PACA2 and PANC-1, compared to HPNE (**P < 0.01). Robinin also attenuated the expression of α-SMA and snail in Mia-PACA2, and PANC-1 (**P < 0.01). Besides, it was found that expression of IL-6 and TNF-α were diminished in presence of Robinin in Mia-PACA2, and PANC-1 (**P < 0.01). Western blot confirmed that Robinin could target on TLR2, and further downregulated PI3k-AKT signaling pathway to exert biological function.Conclusions Robinin exerts anti-tumor effect perhaps via downregulating inflammation and EMT in pancreatic cancer cell through inhibiting TLR2-PI3k-AKT signaling pathway. Robinin may be a novel agent in adjuvant therapy of pancreatic cancer.
Synthesis, Characterization, and In Vitro Evaluation of Alpha-amylase and Alpha- glucosidase Studies of 2,3,4-triimidazole Derivatives
Authors: Abbas Sawsan K , Al-Saadi Narjis Hadi , Hanoon H. D.
Published: May 2023

In medicinal chemistry, employing privileged scaffolds provides researchers with a jump start in their search for novel and improved therapeutic agents. The imidazole ring, which has a variety of derivatives that have shown a broad range of biological functions, is one of these scaffolds. A new imidazole(4a-4e) derivatives were synthesized under reflex conditions or ultrasonic irradiation, and identified, by using melting point, FTIR, 1HNMR, 13CMR and mass spectra. The ultrasonic-assisted reactions were compared with the reactions under traditional heating conditions. Then the prepared compounds were investigated in vitro as antidiabetic agents using α-amylase and α- glucosidase assays with the reference drug acarbose at different concentrations (50,100,150,200 and 250µg/mL). All evaluated compounds were found to be more active than acarbose (32% − 63%) against α-amylase with percentage inhibition in the range of (49% -82%).In vitro assays of α-glucosidase activity showed a percentage inhibition ranging from ( 26%-47% ) for 4a ( 21%- 34%) for 4b (24%-44%) for 4c ( 27%-52%) for 4d and ( 29%-48%) for 4e which were lower than that of acarbose (43%-61%) at the concentration (50–200µg/mL), whereas at concentration 250µg/mL the percentage inhibition of 4a,4c and 4d with 56%,58 and 61% respectively, was closer to acarbose 66%. As a result, the investigated compounds may have α-amylase and α-glucosidase inhibitory activity and may be utilized as anti-diabetes agents.
FakeNewsDetection using Soft Computing
Authors: S AKSHAYAMATHI , B PREETHI , M KEERTHANA , S AYYASAMY
Published: May 2023

Reports have been around for a while and were accepted as having real results. The negative impact of rumors has increased due to the quick development of online media, so it is critical to spot them as soon as possible. Several methods have been used before offers distinct reviews based on the information's content or social context. In any event, the majority of current approaches ignore or fail to explore effectively the instance of information generating in online media, including the grouping of collaborations of internetbased media users with information through time. In this paper, we provide a novel strategy. we provide a cutting-edge method for communicating identification that is based on in-depth learning. Our approach makes use of the dynamics of how news spreads by studying how customers are portrayed and how their responses vary around the world. We want to give our customers the ability to verify the rumors and fake news they come across on social media platforms like Twitter and Facebook. The clients can get verifiable facts and continually search for the sources of information occurrences. Official organizations can conform to a situation and participants in the flow by using the constant movement variables. Experiments conducted on the Twitter and Weibo datasets demonstrate the suggested technique's execution at the decreasing edge.
The Usefulness of Mannan Antigen and Anti-mannan Anti-body in the Diagnosis of Candidemia
Authors: Akın Hicran , Cilo Burcu Dalyan , Ener Beyza , Kazak Esra , Akalın Halis
Published: May 2023

Background
Candida species are among the important nosocomial infection agents. Since morbidity and mortality are high in invasive candidiasis, early diagnosis is crucial. Hence, rapid serologic tests are needed for diagnosis. One of these methods is the detection of mannan antigen (Mn) and anti-mannan antibody (A-Mn) in the blood.
Objectives
In this study, we aimed to evaluate the performance of Mn and A-Mn testing in the diagnosis of candidemia.
Methods
Seventy-two patients with candidemia, 30 patients with bacteremia, 26 individuals without infection as the control group were included in the study. Candida Mn and A-Mn levels were measured by the ELISA method. Sensitivity, specificity, and negative and positive predictive values were calculated to evaluate the performance of the tests.
Results
The sensitivity and specificity of the Mn in patients with candidemia were 31.9% and 78.7%, respectively. Mn positivity was significantly higher in neutropenic candidemia patients compared with non-neutropenic candidemia patients (p = 0.026). In the A-Mn test, sensitivity and specificity were 81.9% and 42.6%, respectively, and there was no significant difference between the candidemia and bacteremia groups. It was found that the specificity increased (90.2%) when both tests were used together.
Conclusions
It was determined that the use of Mn and A-Mn tests alone did not contribute significantly to the diagnosis of candidemia, and the combined use of Mn/ A-Mn tests may be useful. It was concluded that the Mn is a more valuable diagnostic tool in the neutropenic patient group, and regular weekly Mn screening can be recommended in these patients.
Sexual Behavior, Self-declaration of Sexual Orientation, and Violence Experience: National Health Survey, Brazil, 2019
Authors: Szwarcwald Celia Landmann , Pascom Ana Roberta Pati , Júnior Paulo Roberto Borges Souza , Damacena Giseli Nogueira , Castilho Euclides Ayres
Published: May 2023

Background Population surveys involving the monitoring of high-risk sexual behavior have been recognized as important public health tools to control the HIV epidemic and other sexually transmitted infections (STIs).Methods Using data from the Knowledge, Attitudes, and Practices survey (PCAP-2013) and from the National Health Survey (PNS), indicators of sexual behavior were compared according to sociodemographic characteristics, including size (%) estimates of men who have sex with men (MSM) and women who have sex with women (WSW). To compare PCAP and PNS proportional distributions, the Pearson's chi-square test, adjusted by the Rao-Scott’s correction, was applied. Using data from the PNS-2019, experience of violence (verbal, physical, and sexual) was analyzed according to sexual orientation. Odds ratios (OR) were estimated by logistic regression models using each type of violence as the response variable and sexual orientation (heterosexual, homosexual/bisexual) as the independent variable.Results Size (%) estimates of MSM and WSW, obtained by direct questions from the PCAP-2013, showed lower homosexuality prevalence estimates than those resulting from the PNS-2019 self-declared sexual orientation. Significant differences were found between the MSM proportions according to the PCAP-2013 (3.7%; 95% CI 3.1–4.4%) and to the PNS-2019 (2.2%; 95% CI 1.9–2.5), and between the WSW proportions (4.6%; 95% CI 4.0-5.4%) and (2.1%; 95% CI 1.8–2.4), respectively. Regarding condom use at last sexual intercourse, no differences between the PCAP-2013 and the PNS-2019 estimates were found at the national level, but significant improvements were found for MSM, people aged 18–24 and 25–34 years, and individuals not living with a partner. Violence-related indicators showed that over 40% of homosexual/bisexual men and women have suffered some type of violence in the past 12 months. Regarding sexual violence, at least once in a lifetime, prevalence was 18.1% among MSM, with 10-fold greater odds (9.9; 95% CI 6.7–14.8) than that of heterosexual men. Among WSW, prevalence was 25.6%, with an estimated OR of 3.3 (95% CI 2.4–4.3).Conclusions The findings emphasize the importance of monitoring HIV/STI risk-related practices and violence experienced by sexual minorities at subnational levels in order to strengthen public policies focused on overcoming the persistent homophobic prejudice in the Brazilian society.