bluuebunny/crossref_metadata_2025 huggingface dataset:
An in silico investigation on the binding site preference of PD-1 and PD-L1 for designing antibodies for targeted cancer therapy
Authors: Abdolmaleki Sarah , Ganjalikhani hakemi Mazdak , Ganjalikhany Mohamad Reza
Published: July 2024

Cancer control and treatment remain a significant challenge in cancer therapy and recently immune checkpoints has considered as a novel treatment strategy to develop anti-cancer drugs. Many cancer types use the immune checkpoints and its ligand, PD-1/PD-L1 pathway, to evade detection and destruction by the immune system, which is associated with altered effector function of PD-1 and PD-L1 overexpression on cancer cells to deactivate T cells. In recent years, mAbs have been employed to block immune checkpoints, therefore normalization of the anti-tumor response has enabled the scientists to develop novel biopharmaceuticals. In vivo affinity maturation of antibodies in targeted therapy has sometimes failed, and current experimental methods cannot accommodate the accurate structural details of protein-protein interactions. Therefore, determining favorable binding sites on the protein surface for modulator design of these interactions is a major challenge. In this study, we used the in silico methods to identify favorable binding sites on the PD-1 and PD-L1 and to optimize mAb variants on a large scale. At first, all the binding areas on PD-1 and PD-L1 have been identified. Then, using the RosettaDesign protocol, thousands of antibodies have been generated for 11 different regions on PD-1 and PD-L1 and then the designs with higher stability, affinity, and shape complementarity were selected. Next, molecular dynamics simulations and MM-PBSA analysis were employed to understand the dynamic, structural features of the complexes and measure the binding affinity of the final designs. Our results suggest that binding sites 1, 3 and 6 on PD-1 and binding sites 9 and 11 on PD-L1 can be regarded as the most appropriate sites for the inhibition of PD-1-PD-L1 interaction by the designed antibodies. This study provides comprehensive information regarding the potential binding epitopes on PD-1 which could be considered as hotspots for designing potential biopharmaceuticals. We also showed that mutations in the CDRs regions will rearrange the interaction pattern between the designed antibodies and targets (PD-1 and PD-L1) with improved affinity to effectively inhibit protein-protein interaction and block the immune checkpoint.
Longitudinal evidence over 2 years of the pandemic shows that poor mental health in people living with obesity may be underestimated
Authors: Vowels Matthew J. , Vowels Laura M. , Gibson-Miller Jilly
Published: July 2024

It is well-documented that people living with obesity are at greater risk of poorer mental health outcomes. The aim of our study was twofold: First, to examine the longitudinal trajectories of depression and anxiety in people living with obesity over two years across eight waves of a UK national COVID-19 survey (March 2020-March 2022) using smoothing-splines mixed-effects models. Second, to investigate participation effects via a missingness analysis to check whether survey attrition over time was related to participant characteristics. Trajectory models showed that those living with overweight and obesity consistently reported significantly higher rates of anxiety and depression compared to those in normal weight categories over two years. Our missingness analysis revealed that depression and anxiety predicted the likelihood of responding to the survey over time, whereby those reporting higher rates of depression and anxiety were less likely to respond to the survey. Our findings add to the literature surrounding the (long-term) link between living with obesity and poor mental health. Notably, our results suggest that people who have poorer mental health were less likely to participate in the survey. Thus, we conclude that it is likely that longitudinal population survey studies potentially underreport mental health problems over time and therefore the realistic impact of obesity on mental health outcomes may be underestimated.
Assessing the accuracy of spectral indices obtained from Sentinel images using field research to estimate land degradation
Authors: Ebrahimi Akhtar , Zolfaghari Farhad , Ghodsi Marzieh , Narmashiri Fatemeh
Published: July 2024

Wind erosion resulting from soil degradation is a significant problem in Iran’s Baluchistan region. This study evaluated the accuracy of remote sensing models in assessing degradation severity through field studies. Sentinel-2 Multispectral Imager’s (MSI) Level-1C satellite data was used to map Rutak’s degradation severity in Saravan. The relationship between surface albedo and spectral indices (NDVI, SAVI, MSAVI, BSI, TGSI) was assessed. Linear regression establishes correlations between the albedo and each index, producing a degradation severity map categorized into five classes based on albedo and spectral indices. Accuracy was tested with 100 ground control points and field observations. The Mann-Whitney U-Test compares remote sensing models with field data. Results showed no significant difference (P > 0.05) between NDVI, SAVI, and MSAVI models with field data, while BSI and TGSI models exhibited significant differences (P ≤ 0.001). The best model, BSI-NDVI, achieves a regression coefficient of 0.86. This study demonstrates the advantage of remote sensing technology for mapping and monitoring degraded areas, providing valuable insights into land degradation assessment in Baluchistan. By accurately identifying severity levels, informed interventions can be implemented to mitigate wind erosion and combat soil degradation in the region.
Unraveling the molecular landscape of breast muscle development in domestic Yuzhong pigeons and European meat pigeon: Insights from Iso-seq and RNA-seq analysis
Authors: Yang Pengkun , Song Xinghui , Zhang Liheng , Wang Xinlei , Han Zhanbing , Wang Runzhi , Yang Mingjun , Liu Peiyao , Zhang Zhen
Published: July 2024

The mechanisms governing gene regulation in domestic Yuzhong pigeon breast muscle development remain largely elusive. Here, we conducted a comparative analysis using Iso-seq and RNA-seq data from domestic Yuzhong pigeons and European meat pigeons to uncover signaling pathways and genes involved in breast muscle development. The Iso-seq data from domestic Yuzhong pigeons yielded 131,377,075 subreads, resulting in 16,587 non-redundant high-quality full-length transcripts post-correction. Furthermore, utilizing pfam, CPC, PLEK, and CPAT, we predicted 5575, 4973, 2333, and 4336 lncRNAs, respectively. Notably, several genes potentially implicated in breast muscle development were identified, including tropomyosin beta chain, myosin regulatory light chain 2, and myosin binding protein C. KEGG enrichment analysis revealed critical signaling pathways in breast muscle development, spanning carbon metabolism, biosynthesis of amino acids, glycolysis/gluconeogenesis, estrogen signaling, PI3K-AKT signaling, protein processing in the endoplasmic reticulum, oxidative phosphorylation, pentose phosphate pathway, fructose and mannose metabolism, and tight junctions. These findings offer insights into the biological processes driving breast muscle development in domestic Yuzhong pigeon, contributing to our understanding of this complex phenomenon.
Spatial transcriptomic profiling of isolated microregions in tissue sections utilizing laser-induced forward transfer
Authors: Ye Kaiqiang , Chang Wanqing , Xu Jitao , Guo Yunxia , Qin Qingyang , Dang Kaitong , Han Xiaofeng , Zhu Xiaolei , Ge Qinyu , Cui Qiannan , Xu Yun , Zhao Xiangwei
Published: July 2024

Profiling gene expression while preserving cell locations aids in the comprehensive understanding of cell fates in multicellular organisms. However, simple and flexible isolation of microregions of interest (mROIs) for spatial transcriptomics is still challenging. We present a laser-induced forward transfer (LIFT)-based method combined with a full-length mRNA-sequencing protocol (LIFT-seq) for profiling region-specific tissues. LIFT-seq demonstrated that mROIs from two adjacent sections could reliably and sensitively detect and display gene expression. In addition, LIFT-seq can identify region-specific mROIs in the mouse cortex and hippocampus. Finally, LIFT-seq identified marker genes in different layers of the cortex with very similar expression patterns. These genes were then validated using in situ hybridization (ISH) results. Therefore, LIFT-seq will be a valuable and efficient technique for profiling the spatial transcriptome in various tissues.
Blood glucose and lactate levels as early predictive markers in patients presenting with cardiogenic shock: A retrospective cohort study
Authors: Billig Hannah , Al Zaidi Muntadher , Quacken Florian , Görtzen-Patin Jan , Goody Philip Roger , Gräff Ingo , Nickenig Georg , Zimmer Sebastian , Aksoy Adem
Published: July 2024

Lactate and glucose are widely used biochemical parameters in current predictive risk scores for cardiogenic shock. Data regarding the relationship between lactate and glucose levels in cardiogenic shock are limited. Thus, we aimed to analyze glucose and lactate as early markers for in-hospital mortality in cardiogenic shock. In this retrospective cohort study, 312 patients presenting with cardiogenic shock to a tertiary-care hospital between 2016 and 2018 were included. Apparent cardiogenic shock was defined as hypoperfusion with hemodynamic compromise and biochemical marker increase due to diminished tissue perfusion, corresponding to SCAI shock stages. In-hospital mortality was assessed as the primary endpoint. The median age of the study population was 71 (60–79) years and the etiology of cardiogenic shock was acute myocardial infarction in 45.8%. Overall in-hospital mortality was 67.6%. In the receiver operating curve analysis, the area under the receiver-operating curve (AUC) for prediction of in-hospital mortality was higher for lactate (AUC: 0.757) than for glucose (AUC: 0.652). Both values were significantly associated with outcome (groups created with best cutoff values obtained from the Youden index). Correlation analysis showed a significant non-linear association of both values. In a multivariable stepwise Cox regression analysis, lactate remained an independent predictor for in-hospital mortality, whilst glucose, despite being implicated in energy metabolism, was not independently predictive for mortality. Together, these data suggest that lactate at admission is superior for mortality prediction in patients with apparent cardiogenic shock. Glucose was not independently predictive for mortality.
MICT ameliorates hypertensive nephropathy by inhibiting TLR4/NF-κB pathway and down-regulating NLRC4 inflammasome
Authors: Dong Wenyu , Luo Minghao , Li Yun , Chen Xinhua , Li Lingang , Chang Qing
Published: July 2024

Background

Hypertensive nephropathy (HN) is one of the main causes of end-stage renal disease (ESRD), leading to serious morbidity and mortality in hypertensive patients. However, existing treatment for hypertensive nephropathy are still very limited. It has been demonstrated that aerobic exercise has beneficial effects on the treatment of hypertension. However, the underlying mechanisms of exercise in HN remain unclear.

Methods

The spontaneously hypertensive rats (SHR) were trained for 8 weeks on a treadmill with different exercise prescriptions. We detected the effects of moderate intensity continuous training (MICT) and high intensity interval training (HIIT) on inflammatory response, renal function, and renal fibrosis in SHR. We further investigated the relationship between TLR4 and the NLRC4 inflammasome in vitro HN model.

Results

MICT improved renal fibrosis and renal injury, attenuating the inflammatory response by inhibiting TLR4/NF-κB pathway and the activation of NLRC4 inflammasome. However, these changes were not observed in the HIIT group. Additionally, repression of TLR4/NF-κB pathway by TAK-242 inhibited activation of NLRC4 inflammasome and alleviated the fibrosis in Ang II-induced HK-2 cells.

Conclusion

MICT ameliorated renal damage, inflammatory response, and renal fibrosis via repressing TLR4/NF-κB pathway and the activation of NLRC4 inflammasome. This study might provide new references for exercise prescriptions of hypertension.
The performance of ChatGPT and Bing on a computerized adaptive test of verbal intelligence
Authors: Klein Balázs , Kovacs Kristof
Published: July 2024

We administered a computerized adaptive test of vocabulary three times to assess the verbal intelligence of chatGPT (GPT 3.5) and Bing (based on GPT 4). There was no difference between their performance; both performed at a high level, outperforming approximately 95% of humans and scoring above the level of native speakers with a doctoral degree. In 42% of test items that were administered more than once these large language models provided different answers to the same question in different sessions. They never engaged in guessing, but provided hallucinations: answers that were not among the options. Such hallucinations were not triggered by the inability to answer correctly as the same questions evoked correct answers in other sessions. The results implicate that psychometric tools developed for humans have limitations when assessing AI, but they also imply that computerised adaptive testing of verbal ability is an appropriate tool to critically evaluate the performance of large language models.
Magnitude and associated factors of sexual violence among female housemaids attending night school in Bahir Dar City, Northwest Ethiopia: Institution-Based Cross-Sectional Study, 2022
Authors: Gebremariam Seble Asheber , Gebey Mulugeta Yaze , Yadita Zemenu Shiferaw , Bekele Yibeltal Alemu
Published: July 2024

Background

Sexual violence is a major public health problem that affects the health and well-being of millions of young people. Housemaids are the most vulnerable group to sexual violence due to their nature of work. It leads to various physical, mental, sexual, and reproductive health problems, especially in our country’s context. However, they have limited information regarding the magnitude and the factors associated with sexual violence among housemaids. As a result, the purpose of this study was to determine the magnitude and risk factors for sexual violence among female housemaids attending night school in Bahir Dar, Northwest Ethiopia, in 2022.

Method

An institution-based cross-sectional study design was conducted among 340 housemaids attending night school in Bahir Dar city from May 15 to June 20, 2022. Participants were selected using simple random sampling through computer-generated techniques. An interviewer-administered, structured questionnaire was used. Data were entered, coded, and cleaned using EPI Data version 4.6.0.2, and exported to SPSS version 26 for further analysis. Both bivariable and multivariable logistic regression were done to identify factors associated with sexual violence. P-value and 95% confidence interval were used to declare the statistical association.

Result

The magnitude of sexual violence after being a housemaid was 30.3% with a 95% confidence interval (25.3–35.38). Ever had sex [Adjusted Odds Ratio(AOR) = 4.67; 95%; Confidence Interval(CI) (2.60, 8.39)], no discussion of sexual and reproductive issues [Adjusted Odds Ratio(AOR) = 2.32; 95%; Confidence Interval(CI) (1.29, 4.16)], poor social support [Adjusted Odds Ratio(AOR) = 2.69; 95%; Confidence Interval(CI) (1.32, 5.52)], were identified as factors associated with sexual violence among housemaids. Similarly, academic performance [Adjusted Odds Ratio (AOR) = 0.96; 95%; Confidence Interval (CI) (0.93, 0.99)], and distance to reach school [Adjusted Odds Ratio (AOR) = 2.04; 95%; Confidence Interval (CI) (1.19, 3.48)] were identified as factors associated with sexual violence among housemaids.

Conclusion

This study identified that the magnitude of sexual violence among housemaids was high. Housemaids who ever had sex, no discussion of sexual and reproductive health (SRH) with anyone, poor social support, poor academic performance, and distance to reach school were factors associated with sexual violence. Therefore, creating a sexual and reproductive health (SRH) discussion session for housemaids is important for securing their sexual rights.
Genetic diversity analysis of big-bracted dogwood (Cornus florida and C. kousa) cultivars, interspecific hybrids, and wild-collected accessions using RADseq
Authors: Moreau Erin L. P. , Medberry Ava N. , Honig Josh A. , Molnar Thomas J.
Published: July 2024

Big-bracted dogwoods are popular ornamental trees known for their beautiful spring blooms with showy bracts and four-season appeal. The two most widely grown species are Cornus florida and Cornus kousa, native to Eastern North America and East Asia. Despite their horticultural prominence, there is little information available regarding genetic diversity, population structure, relatedness, and subspecies origins of dogwood cultivars. In this study, 313 cultivars, wild-collected plants, and Rutgers University breeding selections, focusing on C. florida, C. kousa, and interspecific hybrids, were genotyped using restriction-site associated DNA sequencing (RADseq) generating thousands of single nucleotide polymorphism (SNP) and insertion deletion (Indel) markers. The research results showed high genetic diversity among C. florida and C. kousa wild-collected plants and cultivars. For C. florida, pink-bracted plants formed a distinct clade from those with white-bracts with the Mexican C. florida ssp. urbiniana forming an outgroup. For C. kousa, Chinese-collected plants (ssp. chinensis) were a distinct subspecies with clear separation from Japanese and Korean accessions (ssp. kousa) and cultivars were designated as ssp. chinensis, ssp. kousa, or ssp. hybrid. Using this information, a Kompetitive allele specific PCR (KASP) assay genotyping panel was designed to determine C. kousa trees’ subspecies makeup. Results revealed many cases of genetically identical cultivars being sold under different names, especially for pink-bracted cultivars of both species. Additionally, reported parent-progeny relationships were evaluated and either validated or discredited. Finally, the hybrid germplasm analysis validated pedigrees of interspecific F1 hybrids and found many of the recent Rutgers breeding selections contain small regions of pacific dogwood (C. nuttallii) DNA introgressed into C. kousa backgrounds. This diversity study elucidates origins, diversity, and relationships of a large population of big-bracted dogwoods. The results can inform plant breeders, arboreta, and the ornamental plant industry, as most modern cultivars and popular historic cultivars are represented.
Public conservation connection and support between ocean and terrestrial systems in the United States
Authors: Froehlich Halley E. , Mizuta Darien D. , Wilson Jono R.
Published: July 2024

Terrestrial and ocean ecosystems are increasingly under threat from an array of anthropogenic pressures. And while threats mount, how people view and value nature is changing. In the United States (U.S.) in particular, there is a shift away from viewing nature as something to ‘dominate,’ as evidenced in the decline in hunting. However, it is unclear if or how opinions around environmental issues and conservation need might differ when comparing ocean versus terrestrial ecosystems, especially given the prevalence and continued importance of wild capture fishing in the U.S. We employed two national parallel surveys, one focused on oceans, the other land, receiving responses from nearly every state in the U.S. (N = 1,973). While we found only slight, but statistically significant more concern for ocean habitats and animals over terrestrial ecosystems, this did not translate to increased willingness to monetarily support more ocean conservation actions. Using Random Forest models, we also found the best predictor of conservation need was feeling most impacted by environmental issues personally (self and/or community), regardless of ecosystem type. In fact, land versus sea (survey) had the lowest rank in the models, underscoring the importance of general nature-based interactions. Instead, the number of outdoor recreational activities was a highly ranked variable explaining the level of reported impact to self/community, with people who participate in 2 or more activities scoring higher levels of impact, on average. Notably, people who hunt and fish, versus only do one or the other, reported higher levels of impact and participated in more activities overall, providing a more nuanced finding regarding the nature ‘dominance hypothesis.’ Voting, not political affiliation, was also important in explaining responses, and governmental mechanisms to fund conservation were favored over voluntary. Overall, our results add to the strong existing literature that access and connection to nature is key, but uniquely broad connection may “float all boats,” especially when diversified.
Phylogenetic diversity and virulence gene characteristics of Escherichia coli from pork and patients with urinary tract infections in Thailand
Authors: Ketkhao Pramualchai , Utrarachkij Fuangfa , Parikumsil Nattaya , Poonchareon Kritchai , Kerdsin Anusak , Ekchariyawat Peeraya , Narongpun Pawarut , Nakajima Chie , Suzuki Yasuhiko , Suthienkul Orasa
Published: July 2024

Extraintestinal pathogenic Escherichia coli (ExPEC), especially uropathogenic E. coli (UPEC) are responsible for urinary tract infections (UTIs), while diarrheagenic E. coli (DEC) cause foodborne illnesses. These pathogenic E. coli are a serious threat to human health and a public concern worldwide. However, the evidence on pork E. coli (PEC) harboring UPEC virulence-associated genes is currently limited. Therefore, this study aimed to determine the phylogroups, virulence genes, and their association between PEC and UPEC from UTI patients. In this study, 330 E. coli were obtained from archived stock culture isolated from pork (PEC; n = 165) and urine of patients with UTIs (UPEC; n = 165) during 2014–2022. Phylogroups, UPEC- and diarrheagenic E. coli (DEC) associated virulence genes were assessed using PCR assays. The results showed that phylogroups A (50.3%), and B1 (32.1%) were commonly found among PEC whereas phylogroups B2 (41.8%), and C (25.5%) were commonly detected in the UPEC. PEC and UPEC carried similar virulence-associated genes with different percentages. The most frequent UPEC virulence-associated gene among UPEC, and PEC strains was fimH, (93.3%, and 92.1%), followed by iucC (55.2%, and 12.7%), papC (21.8%, and 4.2%), afaC (22.4%, and 0%), hlyCA (17%, and 0.6%), cnf (16.4%, and 0.6%), and sfa/focDE (8.5%, and 4.8%). Additionally, 6 of 27 UPEC virulence-associated gene patterns were found in both PEC and UPEC strains regardless of phylogroups. Furthermore, the DEC virulence-associated genes were found in only 3 strains, one from PEC harboring eae, and two from UPEC carried fimH-bfpA or afaC-CVD432 indicating hybrid strains. Cluster analysis showed a relationship between PEC and UPEC strains and demonstrated that PEC harboring UPEC virulence-associated genes in pork may be associated with UPEC in humans. Food safety and hygiene practices during pork production chain are important procedures for minimizing cross-contamination of these strains that could be transmitted to the consumers.
Reliability and minimal detectable change of dynamic temporal summation and conditioned pain modulation using a single experimental paradigm
Authors: Vincenot Matthieu , Beaulieu Louis-David , Gendron Louis , Marchand Serge , Léonard Guillaume
Published: July 2024

Background

Quantitative sensory tests (QST) are frequently used to explore alterations in somatosensory systems. Static and dynamic QST like pain threshold and temporal summation (TS) and conditioned pain modulation (CPM) are commonly used to evaluate excitatory and inhibitory mechanisms involved in pain processing. The aim of the present study was to document the reliability and the minimal detectable change (MDC) of these dynamic QST measurements using a standardized experimental paradigm.

Material and methods

Forty-six (46) pain-free participants took part in 2 identical sessions to collect TS and CPM outcomes. Mechanical (pressure pain threshold [PPT]) and thermal (constant 2-minute heat pain stimulation [HPS]) nociceptive stimuli were applied as test stimuli, before and after a cold-water bath (conditioning stimulus). TS was interpreted as the change in pain perception scores during HPS. CPM were determined by calculating the difference in pain perception between pre- and post- water bath for both PPT and HPS. Relative and absolute reliability were analyzed with intra-class correlation coefficient (ICC2, k), standard error of the measurements (SEMeas) and MDC.

Results

Results revealed a good to excellent relative reliability for static QST (ICC ≥ 0.73). For TS, a poor to moderate relative reliability depending on the calculation methods (ICC = 0.25 ≤ ICC ≤ 0.59), and a poor relative reliability for CPM (ICC = 0.16 ≤ ICC ≤ 0.37), both when measured with mechanical stimulation (PPT) and thermal stimulation (HPS). Absolute reliability varied from 0.73 to 7.74 for static QST, 11 to 22 points for TS and corresponded to 11.42 points and 1.56 points for thermal and mechanical-induced CPM, respectively. MDC analyses revealed that a change of 1.58 to 21.46 point for static QST, 31 to 52 points for TS and 4 to 31 points for CPM is necessary to be interpreted as a real change.

Conclusion

Our approach seems well-suited to clinical use. Although our method shows equivalent relative and absolute reliability compared to other protocols, we found that the reliability of endogenous pain modulation mechanisms is vulnerable, probably due to its dynamic nature.
Evaluation of superficial xenograft volume estimation by ultrasound and caliper against MRI in a longitudinal pre-clinical radiotherapeutic setting
Authors: Roth Daniel , Safi Marcella , Vilhelmsson Timmermand Oskar , Sereti Evangelia , Molendowska Malwina , Gottschalk Michael , Bjartell Anders , Ceberg Crister , Szczepankiewicz Filip , Strand Joanna
Published: July 2024

Background

Accurate tumor volume estimation is important for evaluating the response to radionuclide therapy and external beam radiotherapy as well as to other pharmaceuticals. A common method for monitoring the growth of subcutaneous tumors in pre-clinical models and assessing the treatment response is to measure the tumor length and width by external calipers to estimate its volume. This procedure relies on an assumption of a spheroidal tumor shape wherein the tumor depth equals the width and can yield considerably inaccuracies. Ultrasound imaging is a non-invasive technique that can measure all three axes of the tumor and might be an alternative to caliper measurement with potentially greater accuracy and comparable ease-of-use and throughput. Both 2D and 3D ultrasound imaging are possible, the former offering short scan times without the need for anesthesia and heating—valuable factors for longitudinal studies in large animal cohorts. Nevertheless, tumor volume estimation accuracy by 2D ultrasound imaging has seen limited investigation. In this study we have evaluated the accuracy of tumor volume estimation by caliper and 2D ultrasound with comparisons to reference measurements by magnetic resonance imaging (MRI) in a pre-clinical model of prostate cancer treated with either external beam radiotherapy, radionuclide therapy, or no treatment.

Results

Tumor volumes were measured longitudinally in 29 mice by caliper, ultrasound, and MRI before and after external beam radiotherapy, [177Lu]Lu-PSMA-617 radionuclide therapy, or no treatment. Caliper measurements had a marked bias, overestimating the tumor volumes by a median of 150% compared to MRI. Ultrasound measurements were markedly more accurate, with a median bias of -21% compared to MRI.

Conclusion

Ultrasound imaging is a reliable and accurate method for tumor volume estimation in pre-clinical models of radiotherapy, whereas caliper measurements are prone to overestimation.
Wind power density in areas of Northeastern Brazil from Regional Climate Models for a recent past
Authors: Gurgel Augusto de Rubim Costa , Sales Domingo Cassain , Lima Kellen Carla
Published: July 2024

Investments in renewable energy sources are increasing in several countries, especially in wind energy, as a response to global climate change caused by the burning of fossil fuels for electricity generation. Thus, it is important to evaluate the Regional Climate Models that simulate wind speed and wind power density in promising areas for this type of energy generation with the least uncertainty in recent past, which is essential for the implementation of wind farms. Therefore, this research aims to calculate the wind power density from Regional Climate Models in areas at Northeast of Brazil from 1986 to 2005. Initially, the ECMWF-ERA5 reanalysis data was validated against observed data obtained from Xavier. The results were satisfactory, showing a strong correlation in areas of Ceará and Rio Grande do Norte (except during the SON season), and some differences in relation to the wind intensity registered by observed data, particularly during the JJA season. Then, the Regional Climate Models RegCM4.7, RCA4 and Remo2009 were validated against the ECMWF-ERA5 reanalysis data, with all models successfully representing the wind speed pattern, especially from December to May. Four specific areas in Northeast of Brazil were selected for further study. In these areas, the RCMs simulations were evaluated to identify the RCM with the best statistical indices and consequently the lowest associated uncertainty for each area. The selected RCMs were: RegCM4.7_HadGEM2 (northern coastal of Ceará and northern coastal of Rio Grande do Norte) and RCA4_Miroc (Borborema and Central Bahia). Finally, the wind power density was calculated from the selected RCM for each area. The northern regions of Rio Grande do Norte and Ceará exhibited the highest wind power density.
Vitamin K2 sensitizes the efficacy of venetoclax in acute myeloid leukemia by targeting the NOXA-MCL-1 pathway
Authors: Tauchi Tetsuzo , Moriya Shota , Okabe Seiichi , Kazama Hiromi , Miyazawa Keisuke , Takano Naoharu
Published: July 2024

Promising outcomes have been reported in elder patients with acute myeloid leukemia (AML) using combined therapy of venetoclax (VEN) and azacytidine (AZA) in recent years. However, approximately one-third of patients appear to be refractory to this therapy. Vitamin K2 (VK2) shows apoptosis-inducing activity in AML cells, and daily oral VK2 (menaquinone-4, GlakayR) has been approved for patients with osteoporosis in Japan. We observed a high response rate to AZA plus VEN therapy, with no 8-week mortality in the newly diagnosed AML patients consuming daily VK2 in our hospital. The median age of the patients was 75.9 years (range 66–84) with high-risk features. Patients received AZA 75 mg/m2 on D1-7, VEN 400 mg on D1-28, and daily VK2 45 mg. The CR/CRi ratio was 94.7% (18/19), with a CR rate of 79%. Complete cytogenetic CR was achieved in 15 of 19 (79%) patients, and MRD negativity in 2 of 15 (13%) evaluable CR patients. Owing to the extremely high response rate in clinical settings, we further attempted to investigate the underlying mechanisms. The combination of VK2 and VEN synergistically induced apoptosis in all five AML cell lines tested. VK2, but not VEN, induced mitochondrial reactive oxygen species (ROS), leading to the transcriptional upregulation of NOXA, followed by MCL-1 repression. ROS scavengers repressed VK2 induced-NOXA expression and led to the cancellation of pronounced apoptosis and the downregulation of MCL-1 by VK2 plus VEN. Additionally, knockdown and knockout of NOXA resulted in abrogation of the MCL-1 repression as well as enhanced cytotoxicity by the two-drug combination, indicating that VK2 suppresses MCL-1 via ROS-mediated NOXA induction. These data suggest that the dual inhibition of BCL-2 by VEN and MCL-1 by VK2 is responsible for the remarkable clinical outcomes in our patients. Therefore, large-scale clinical trials are required.
Natural convection in the cytoplasm: Theoretical predictions of buoyancy-driven flows inside a cell
Authors: Desai Nikhil , Liao Weida , Lauga Eric
Published: July 2024

The existence of temperature gradients within eukaryotic cells has been postulated as a source of natural convection in the cytoplasm, i.e. bulk fluid motion as a result of temperature-difference-induced density gradients. Recent computations have predicted that a temperature differential of ΔT ≈ 1 K between the cell nucleus and the cell membrane could be strong enough to drive significant intracellular material transport. We use numerical computations and theoretical calculations to revisit this problem in order to further understand the impact of temperature gradients on flow generation and advective transport within cells. Surprisingly, our computations yield flows that are an order of magnitude weaker than those obtained previously for the same relative size and position of the nucleus with respect to the cell membrane. To understand this discrepancy, we develop a semi-analytical solution of the convective flow inside a model cell using a bi-spherical coordinate framework, for the case of an axisymmetric cell geometry (i.e. when the displacement of the nucleus from the cell centre is aligned with gravity). We also calculate exact solutions for the flow when the nucleus is located concentrically inside the cell. The results from both theoretical analyses agree with our numerical results, thus providing a robust estimate of the strength of cytoplasmic natural convection and demonstrating that these are much weaker than previously predicted. Finally, we investigate the ability of the aforementioned flows to redistribute solute within a cell. Our calculations reveal that, in all but unrealistic cases, cytoplasmic convection has a negligible contribution toward enhancing the diffusion-dominated mass transfer of cellular material.
Achieving cervical cancer elimination: The simulated impacts of HPV vaccination and transitioning from liquid-based cytology to HPV-based screening test
Authors: Balqis-Ali Nur Zahirah , Anis-Syakira Jailani , Fun Weng Hong , Mohd Said Zakiah , Abdul Samad Shazimah , Zainal Abidin Norhaslinda , Zulkepli Jafri , Ahmad Norazura , Mohd Abas Mohd Norazam , Yong Chee Meng , Yusof Siti Norbayah , Daud Nur Adila , Sararaks Sondi
Published: July 2024

The Ministry of Health Malaysia aims to fully replace liquid-based cytology (LBC) with Human Papillomavirus (HPV) tests and increase the screening coverage from a baseline of 25% to 40% by 2023, followed by a 10% yearly increment until 70% coverage. This transition requires proper planning, including the number of tests needed and budget allocation. This study aims to simulate different transition strategies involving the shift from LBC to HPV testing with expanded screening coverage to predict their impact on cervical cancer elimination in Malaysia. A system dynamics model was developed to simulate the transition from LBC to HPV testing and HPV vaccination coverage in Malaysia. The dynamic model utilised local epidemiological data, published research, and expert opinion when data was unavailable. The simulation showed that a combination of high HPV vaccination coverage and transitioning fully to five-yearly HPV testing by 2030, coupled with a 70% screening uptake by 2040, would accelerate cancer elimination in Malaysia by 18 years with an estimated screening cost of MYR1.81 billion equivalent to USD 411 millions compared to the baseline of using LBC as the primary screening method (MYR1.39 billion, USD 315 millions). Sustained, it would lead to averting 6,000 new cancer cases by 2070. Alternatively, conducting HPV screenings twice before age 50 would advance cervical cancer elimination by 14 years and prevent approximately 1000 new cases by 2070, with an estimated cost of MYR1.13 billion equivalent to USD 257 millions. A delay in achieving the full transition prolonged the elimination more than a delay in increasing the screening coverage. In all scenarios, yearly vaccination of 90% of girls age 13 is crucial to achieving elimination. In the Malaysian context, where HPV vaccination coverage has reached considerable levels, the evidence advocates for a full transition from LBC to HPV testing, ideally by 2030. While expanding screening coverage remains a critical factor in this endeavour, the findings unequivocally endorse prioritising the transition process.

Trial registration: Trial registration number: NMRR ID-22-00187-DJU.
Unraveling dynamics of paramyxovirus-receptor interactions using nanoparticles displaying hemagglutinin-neuraminidase
Authors: Wu Xuesheng , Goebbels Maite , Debski-Antoniak Oliver , Marougka Katherine , Chao Lemeng , Smits Tony , Wennekes Tom , Kuppeveld Frank J. M. van , Vries Erik de , de Haan Cornelis A. M.
Published: July 2024

Sialoglycan-binding enveloped viruses often possess receptor-destroying activity to avoid being immobilized by non-functional decoy receptors. Sialic acid (Sia)-binding paramyxoviruses contain a hemagglutinin-neuraminidase (HN) protein that possesses both Sia-binding and -cleavage activities. The multivalent, dynamic receptor interactions of paramyxovirus particles provide virion motility and are a key determinant of host tropism. However, such multivalent interactions have not been exhaustively analyzed, because such studies are complicated by the low affinity of the individual interactions and the requirement of high titer virus stocks. Moreover, the dynamics of multivalent particle-receptor interactions are difficult to predict from Michaelis-Menten enzyme kinetics. Therefore, we here developed Ni-NTA nanoparticles that multivalently display recombinant soluble HN tetramers via their His tags (HN-NPs). Applying this HN-NP platform to Newcastle disease virus (NDV), we investigated using biolayer interferometry (BLI) the role of important HN residues in receptor-interactions and analyzed long-range effects between the catalytic site and the second Sia binding site (2SBS). The HN-NP system was also applicable to other paramyxoviruses. Comparative analysis of HN-NPs revealed and confirmed differences in dynamic receptor-interactions between type 1 human and murine parainfluenza viruses as well as of lab-adapted and clinical isolates of human parainfluenza virus type 3, which are likely to contribute to differences in tropism of these viruses. We propose this novel platform to be applicable to elucidate the dynamics of multivalent-receptor interactions important for host tropism and pathogenesis, particularly for difficult to grow sialoglycan-binding (paramyxo)viruses.
A evolução da informação visual jornalística a partir da infografia
Authors: Uliana Barboza Eduardo Fernando
Published: July 2024

Este artigo versa especificamente sobre a evolução da informação visual jornalística a partir do contexto histórico, os conceitos e as classificações da infografia impressa à multimídia apresentados por autores como Alberto Cairo, Jaime Serra, José Luis Valero Sancho, José Manuel de Pablos, Gonzalo Peltzer, Ary Moraes e Tattiana Teixeira. O artigo trata ainda sobre a infografia multimídia e suas possibilidades informativas na comunicação online.
Promessas de campanha nas eleições presidenciais de 2022
Authors: Diniz Simone , Alves Mércia
Published: July 2024

Este artigo trata das promessas de campanha do PT, PL, MDB e PDT expressas nos programas de governo e apresentados ao Tribunal Superior Eleitoral para as eleições presidenciais de 2022. Por meio da análise de conteúdo, trabalhamos com a codificação das promessas em duas variáveis: 1) promessas passíveis de serem verificadas caso o proponente viesse a vencer as eleições; e 2) promessas retóricas. O objetivo é verificar que tipo de promessa predominou nas candidaturas supra mencionadas; quais os conteúdos temáticos apresentados pelas candidaturas; e em que medida, diferenças no posicionamento ideológico dos partidos pautam o tipo de promessa e o conteúdo temático abordado nos programas de governo.
Triton X-100 Mediated Electron Transfer Reactions between Iron(III) Polypyridyl Complexes and Phenylsulfinylacetic Acids
Authors: Rathnakumari R. Jeevi Esther , Kavitha C. , Jaba Rose J. Janet Sylvia , Subramaniam P. , Vetriselvi V.
Published: July 2024

Oxidative decarboxylation of phenylsulfinylacetic acids (PSAAs) by iron(III) polypyridyl complexes in non-ionic surfactant Triton X-100 medium has been investigated spectrophotometrically. An initial intermediate formation between PSAA and [Fe(NN)3]3+ is confirmed from the observed Michaelis–Menten kinetics and fractional order dependence on PSAA. Applying the Hammett substituent constants to the overall rate constants obtained in TX-100 medium gives non-linear concave upward Hammett plots. A suitable mechanism involving the formation of diphenyl sulphone as product has been proposed. The observed increase in rate with increase in concentration of TX-100 at low concentration range, clearly shows that the reaction takes place in micellar medium and both the reactants are associated or incorporated into micellar phase.
Synthesis, In silico Study and Cytotoxicity Evaluation of Some Newly Synthesized Stilbene Derivatives
Authors: Pirgal Dimple , Karki Subhas S. , Kumar Sujeet , Metikurki Basavraj
Published: July 2024

A series of 12 stilbene derivatives (23-34) were synthesized by reacting benzyl-triphenylphosphonium chlorides (9-14) and hydrochloride salt of 3,5-disubstituted-4-hydroxybenzaldehydes (21-22). The synthesized molecules were tested against the human breast cancer cell line MCF7 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in 10% Dulbecco’s modified Eagle Medium (DMEM). Compound 23 exhibited significant cytotoxicity, with 1.11% viability at a concentration of 200 µM, compared to the reference standard resveratrol (15.14%) and 5-fluorouracil (51.86%). All the synthesized derivatives demonstrated equipotency to 5-fluorouracil (5-FU) at all the tested concentrations. The docking study was conducted on the tyrosine-protein kinase/Janus Kinase 2(JAK2) receptor using Autodock Vina. The results of the docking study suggest that, with the exception of compounds 29 (-6.7 kcal/mol) and 32 (-7.1 kcal/mol), most of the synthesized derivatives have exhibited glide scores greater than the standard resveratrol (-7.8 kcal/mol). This implies that these compounds 23-34 have a strong binding affinity to the JAK2 receptor, which is relevant in the context of cancer research, as JAK2 is associated with various signaling pathways involved in cell proliferation and survival.
Synthesis, X-Ray Crystal Structure, Solid State Electrical and Optical Properties of New Copper(II) Complex with 1,10-Phenanthroline Ligand
Authors: Sarkar Saikat , Sarkar Avijit , Aydogdu Yildirim , Dagdelen Fethi , Sarkar Sougata , Chattopadhyay Krishna
Published: July 2024

A new ionic copper(II) complex of 1,10-phenanthroline was synthesized and structurally characterized by elemental and spectroscopic analyses, molar conductance and magnetic moment measurements. The crystal structure of complex was also investigated through single crystal X-ray diffraction analysis and suggestted a distorted octahedral geometry around copper(II), where one N atom from 1,10-phenanthroline and three O atoms from three H2O molecules occupying the basal plane while another Nphen and one Cl atom remain at the apical positions. Thus, the presence of three coordinated waters and chloride group along with the counter chloride ion and water of crystallization is responsible for extensive hydrogen bonding present in the molecule. Thus, the complex forms a 3D gigantic H-bonded network. The two types of intermolecular O–H···Cl and O–H···O hydrogen bonding play the pivotal role in crystal packing and plausible conductivity mechanism through the π-π interacting supports. The electrical conductivity and optical properties were also measured and the results focus on the semiconducting nature of the complex with optical band gap (Egd) value 1.23 eV.
Synthesis and Characterization of Novel Indole Containing 1,2,3-Triazole Linked 1,3,4-Thiadiazole Hybrids: Evaluation of Anticancer Activity and Molecular Docking Studies
Authors: Perike Nagaraju , Edigi Praveen Kumar , Gurrapu Nirmala , Nagulapally Sridhara Devi , Bujji Sushmitha , Subhashini N.J.P.
Published: July 2024

Novel scaffolds containing indole, 1,2,3-triazole linked thiadiazole derivatives (9a-l) were synthesized and confirmed with analytical techniques like 1H NMR, 13C NMR and LC-MS. All the compounds were further screened for their anticancer activity against two cancer cell lines A-549 and MCF-7 by making use of MTT assay and doxorubicin as standard drug. Among the compounds 9c, 9d and 9e demonstrated prominent activity against the tested cancer cell lines A-549 and MCF-7 cell lines compared to doxorubicin. Auto dock Vina of PyRx tool was employed in order to perform molecular docking studies on ERK2. Interestingly, the binding energies and interactions acquired from docking results of compounds are in accordance with the investigatory data.
Effect of phyto-additives on proximate composition and lipid profile of eggs stored for 6 weeks
Authors: Idowu Adijat Oyeyemi , Ojebiyi Olusegun Ojeniyi , Shittu Muritala Daniel , Ojediran Taiwo Kayode , Abolaji Oluwaseun Ezekiel , Salahudeen Yusirat Oladunni
Published: July 2024

This study was conducted to examine the effect of supplementing layers’ diet with three phyto-additives; Black seeds (BS), African Nutmeg (AN), and Negro pepper (NP) on the chemical composition of stored table eggs. Isa Brown pullets were used and allotted into 7 treatments of 4 replicates with 6 birds each to make a total of 24 birds per treatment in a completely randomized design experiment. The treatments were T1 - control (given antibiotics), T2 - 0.5% BS, NP T3 – 1.0% BS, T4 – 0.5% AN, T5 – 1.0% AN, T6 – 0.5% NP and T7 – 1.0%. Collection of data started eight weeks after the birds were placed on experimental diets; 3 eggs were selected from each replicate to make a total of 12 eggs per treatment. They were stored for 6 weeks before taking to the laboratory for chemical analysis. Eggs from birds given diets supplemented with 0.5% black seed had the highest dry matter (26.79%), crude protein (12.08%), crude fat (11.26%), ash (1.22%) and gross energy (1.47 Kcal/g-1) while eggs of birds on Treatment 3 (0.5% African nutmeg) and Treatment 4 (0.5% Negro pepper) had the highest percentage carbohydrate (3.22 and 3.27%). Total cholesterol and low-density lipoprotein (LDL) were significantly (p < 0.05) reduced in eggs fed diet supplemented with 0.5% black seed and also gave the best high-density lipoprotein. It can be concluded from this study that supplementing layers diet with these phytoadditives enhanced the proximate composition and reduced the total cholesterol of stored eggs.