bluuebunny/crossref_metadata_2025_split huggingface dataset:
Durvalumab and guadecitabine in advanced clear cell renal cell carcinoma: results from the phase Ib/II study BTCRC-GU16-043
Authors: Zakharia Yousef , Singer Eric A. , Acharyya Satwik , Garje Rohan , Joshi Monika , Peace David , Baladandayuthapani Veera , Majumdar Annesha , Li Xiong , Lalancette Claudia , Kryczek Ilona , Zou Weiping , Alva Ajjai 
Published: February 2024

AbstractEpigenetic modulation is well established in hematologic malignancies but to a lesser degree in solid tumors. Here we report the results of a phase Ib/II study of guadecitabine and durvalumab in advanced clear cell renal cell carcinoma (ccRCC; NCT03308396). Patients received guadecitabine (starting at 60 mg/m2 subcutaneously on days 1-5 with de-escalation to 45 mg/m2 in case of dose limiting toxicity) with durvalumab (1500 mg intravenously on day 8). The study enrolled 57 patients, 6 in phase Ib with safety being the primary objective and 51in phase II, comprising 2 cohorts: 36 patients in Cohort 1 were treatment naive to checkpoint inhibitors (CPI) with 0-1 prior therapies and 15 patients in Cohort 2 were treated with up to two prior systemic therapies including one CPI. The combination of guadecitabine 45 mg/m2 with durvalumab 1500 mg was deemed safe. The primary objective of overall response rate (ORR) in cohort 1 was 22%. Sixteen patients (44%) experienced stable disease (SD). Secondary objectives included overall survival (OS), duration of response, progression-free survival (PFS), clinical benefit rate, and safety as well as ORR for Cohort 2. Median PFS for cohort 1 and cohort 2 were 14.26 and 3.91 months respectively. Median OS was not reached. In cohort 2, one patient achieved a partial response and 60% achieved SD. Asymptomatic neutropenia was the most common adverse event. Even though the trial did not meet the primary objective in cohort 1, the tolerability and PFS signal in CPI naive patients are worth further investigation.
HRDE-2 drives small RNA specificity for the nuclear Argonaute protein HRDE-1
Authors: Chen Shihui , Phillips Carolyn M. 
Published: February 2024

AbstractRNA interference (RNAi) is a conserved gene silencing process that exists in diverse organisms to protect genome integrity and regulate gene expression. In C. elegans, the majority of RNAi pathway proteins localize to perinuclear, phase-separated germ granules, which are comprised of sub-domains referred to as P granules, Mutator foci, Z granules, and SIMR foci. However, the protein components and function of the newly discovered SIMR foci are unknown. Here we demonstrate that HRDE-2 localizes to SIMR foci and interacts with the germline nuclear Argonaute HRDE-1 in its small RNA unbound state. In the absence of HRDE-2, HRDE-1 exclusively loads CSR-class 22G-RNAs rather than WAGO-class 22G-RNAs, resulting in inappropriate H3K9me3 deposition on CSR-target genes. Thus, our study demonstrates that the recruitment of unloaded HRDE-1 to germ granules, mediated by HRDE-2, is critical to ensure that the correct small RNAs are used to guide nuclear RNA silencing in the C. elegans germline.
Brain asymmetries from mid- to late life and hemispheric brain age
Authors: Korbmacher Max , van der Meer Dennis , Beck Dani , de Lange Ann-Marie G. , Eikefjord Eli , Lundervold Arvid , Andreassen Ole A. , Westlye Lars T. , Maximov Ivan I. 
Published: February 2024

AbstractThe human brain demonstrates structural and functional asymmetries which have implications for ageing and mental and neurological disease development. We used a set of magnetic resonance imaging (MRI) metrics derived from structural and diffusion MRI data in N=48,040 UK Biobank participants to evaluate age-related differences in brain asymmetry. Most regional grey and white matter metrics presented asymmetry, which were higher later in life. Informed by these results, we conducted hemispheric brain age (HBA) predictions from left/right multimodal MRI metrics. HBA was concordant to conventional brain age predictions, using metrics from both hemispheres, but offers a supplemental general marker of brain asymmetry when setting left/right HBA into relationship with each other. In contrast to WM brain asymmetries, left/right discrepancies in HBA are lower at higher ages. Our findings outline various sex-specific differences, particularly important for brain age estimates, and the value of further investigating the role of brain asymmetries in brain ageing and disease development.
Sustainability benefits of transitioning from current diets to plant-based alternatives or whole-food diets in Sweden
Authors: Bunge Anne Charlotte , Mazac Rachel , Clark Michael , Wood Amanda , Gordon Line 
Published: February 2024

AbstractPlant-based alternatives (PBAs) are increasingly becoming part of diets. Here, we investigate the environmental, nutritional, and economic implications of replacing animal-source foods (ASFs) with PBAs or whole foods (WFs) in the Swedish diet. Utilising two functional units (mass and energy), we model vegan, vegetarian, and flexitarian scenarios, each based on PBAs or WFs. Our results demonstrate that PBA-rich diets substantially reduce greenhouse gas emissions (30–52%), land use (20–45%), and freshwater use (14–27%), with the vegan diet showing the highest reduction potential. We observe comparable environmental benefits when ASFs are replaced with WFs, underscoring the need to reduce ASF consumption. PBA scenarios meet most Nordic Nutrition Recommendations, except for vitamin B12, vitamin D and selenium, while enhancing iron, magnesium, folate, and fibre supply and decreasing saturated fat. Daily food expenditure slightly increases in the PBA scenarios (3–5%) and decreases in the WF scenarios (4–17%), with PBA diets being 10–20% more expensive than WF diets. Here we show, that replacing ASFs with PBAs can reduce the environmental impact of current Swedish diets while meeting most nutritional recommendations, but slightly increases food expenditure. We recommend prioritising ASF reduction and diversifying WFs and healthier PBAs to accommodate diverse consumer preferences during dietary transitions.
Production vulnerability to wheat blast disease under climate change
Authors: Pequeno Diego N. L. , Ferreira Thiago B. , Fernandes José M. C. , Singh Pawan K. , Pavan Willingthon , Sonder Kai , Robertson Richard , Krupnik Timothy J. , Erenstein Olaf , Asseng Senthold 
Published: February 2024

AbstractWheat blast is a devastating disease caused by the fungal pathogen Magnaporthe oryzae pathotype Triticum that has spread to both neighbouring and distant countries following its emergence in Brazil in the 1980s. Under climate change conditions, wheat blast is predicted to spread primarily in tropical regions. Here we coupled a wheat crop simulation model with a newly developed wheat blast model, to provide quantitative global estimates of wheat blast vulnerability under current and future climates. Under current climatic conditions, 6.4 million hectares of arable land is potentially vulnerable to wheat blast. A more humid and warmer climate in the future (Representative Concentration Pathway 8.5) is likely to increase the area suitable for wheat blast infection, particularly in the Southern Hemisphere, and reduce global wheat production by 69 million tons per year (13% decrease) by mid-century. Impacts of climate change could be further exacerbated and food security problems increased.
Integrating transcriptomics and metabolomics to elucidate the mechanism by which taurine protects against DOX-induced depression
Authors: Li Yanan , Li Luxi , Wei Shanshan , Yao Jia , Liang Benhui , Chu Xue , Wang Lei , Liu Hui , Liao Dehua , Liu Daotong , Jiang Pei 
Published: February 2024

AbstractDoxorubicin (DOX) is an effective anticancer drug with potent antitumour activity. However, the application of DOX is limited by its adverse reactions, such as depression. Taurine can alleviate depression induced by multiple factors. However, it is still unclear whether and how taurine improves DOX-induced depression. To address this question, the aim of this study was to explore the potential mechanism by which taurine protects against DOX-induced depression. Mice were randomly divided into three groups (n = 8): (1) the control group, (2) the DOX group, and (3) the DOX + taurine group. The open field test (OFT), elevated plus maze test, and forced swim test (FST) were first performed to assess the effects of DOX and taurine on the behaviour of mice. Next, a combined transcriptomic and metabolomic analysis was performed to analyse the possible antidepressive effect of taurine. Taurine pretreatment increased the total distance travelled and speed of mice in the OFT, increased the number of entries into the open arm and the time spent in the open arm, and reduced the immobility time in the FST. In addition, 179 differential genes and 51 differentially abundant metabolites were detected in the DOX + taurine group compared to the DOX group. Furthermore, differential genes and differentially abundant metabolites were found to be jointly involved in 21 pathways, which may be closely related to the antidepressant effect of taurine. Taurine alleviated DOX-induced depressive behaviour. The various pathways identified in this study, such as the serotonergic synapse and the inflammatory mediator regulation of TRP channels, may be key regulatory pathways related to depression and antidepressant effects.
Minimum dietary diversity and associated determinants among children aged 6–23 months in Pakistan
Authors: Kumar Ramesh , Mahmood Tahir , Naeem Nawal , Khan Shahzad Ali , Hanif Mubashir , Pongpanich Sathirakorn 
Published: February 2024

AbstractPakistan is facing a high prevalence of malnutrition and Minimum Dietary Diversity (MDD) is one of the core indicators that remain below the recommended level. This study assesses MDD and its associated factors among children aged 6 to 23 months in Pakistan. The study uses a cross-sectional study using the dataset of the latest available Multiple Indicators Cluster Survey (MICS) for all provinces of Pakistan. Multistage sampling is used to select 18,699 children aged 6 to 23 months. The empirical method is the Logistic Regression Analysis and Chi-Square Test. The dataset is freely and publicly available with all identifier information removed, and no ethics approvals are required. About one-fifth (20%) of infants and young children aged 6 to 23 months had met MDD, this number varies from 17 to 29%, highest in Baluchistan and lowest in Punjab province of Pakistan. The age group (18–23) indicates a 2.45 times greater chance of having MDD. Age (< 0.001), diarrhea (0.01), prenatal care (0.06), mother’s education (< 0.001), computer access (< 0.001), wealth quantile (< 0.001), and residence (< 0.001) were significantly associated with meeting MDD. However, gender (0.6) and mother’s age (0.4) both were statistically insignificant in meeting MDD. Regarding mothers’ education, compared to no education, the chance of MDD is 1.45 times greater for highly educated mothers in the Punjab province. Dietary diversity among children aged 6 to 23 months in Pakistan is low. It is recommended that mothers should be aware and encouraged to use dietary diverse food for infants and younger children.
DNA demethylation and tri-methylation of H3K4 at the TACSTD2 promoter are complementary players for TROP2 regulation in colorectal cancer cells
Authors: Gehring A. , Huebner K. , Rani H. , Erlenbach-Wuensch K. , Merkel S. , Mahadevan V. , Grutzmann R. , Hartmann A. , Schneider-Stock R. 
Published: February 2024

AbstractTROP2 is a powerful cancer driver in colorectal cancer cells. Divergent epigenetic regulation mechanisms for the corresponding TACSTD2 gene exist such as miRNAs or DNA methylation. However, the role of TACSTD2 promoter hypermethylation in colorectal cancer has not been investigated yet. In this study, TROP2 expression strongly correlated with promoter methylation in different colorectal tumor cell lines. Treatment with 5-Azacytidine, a DNMT1 inhibitor, led to demethylation of the TACSTD2 promoter accompanied by an increase in TROP2 protein expression. TROP2 expression correlated with promoter methylation in vivo in human colon tumor tissue, thereby verifying promoter methylation as an important factor in the regulation of TROP2 expression in colorectal cancer. When performing a ChIP-Seq analysis in HCT116 and HT29 cells, we found that TACSTD2 promoter demethylation was accompanied by tri-methylation of H3K4. In silico analysis of GSE156613 data set confirmed that a higher binding of histone mark H3K4me3 around the TACSTD2 promoter was found in TACSTD2 high expressing tumors of colon cancer patients compared to the corresponding adjacent tumor tissue. Moreover, the link between TROP2 and the H3K4me3 code was even evident in tumors showing high intratumoral heterogeneity for TROP2 staining. Our data provide novel evidence for promoter demethylation and simultaneous gains of the active histone mark H3K4me3 across CpG-rich sequences, both being complementary mechanisms in the transcriptional regulation of TACSTD2 in colon cancer. The functional consequences of TROP2 loss in colorectal cancer needs to be further investigated.
Impact of the COVID-19 pandemic on the incidence and type of infections in hospitalized patients with cirrhosis: a retrospective study
Authors: Cuyàs Berta , Huerta Anna , Poca Maria , Alvarado-Tapias Edilmar , Brujats Anna , Román Eva , Guarner Carlos , Escorsell Àngels , Soriano German 
Published: February 2024

AbstractInfections are a major cause of morbidity and mortality in cirrhosis, especially those caused by multi-drug resistant bacteria. During the COVID-19 pandemic, the incidence and type of infection in these patients may have been influenced by the restrictive measures implemented. We aimed to compare the infections in patients with cirrhosis hospitalized before the COVID-19 pandemic versus those hospitalized during the pandemic. We retrospectively compared infections in patients with cirrhosis hospitalized in the hepatology unit during the pre-pandemic period (3/2019–2/2020) with infections in patients hospitalized during the pandemic (3/2020–2/2021). Baseline characteristics, type of infections, type of bacteria, antimicrobial resistance and mortality were evaluated. There were 251 hospitalizations in 170 patients during the pre-pandemic period and 169 hospitalizations in 114 patients during the pandemic period. One or more infections were identified in 40.6% of hospitalizations during the pre-pandemic period and 43.8% of hospitalizations during the pandemic, P = 0.52. We found 131 infections in the pre-pandemic period and 75 infections during the pandemic. The percentage of nosocomial infections decreased in the pandemic period (25.3% vs. 37.4% in the pre-pandemic period, P = 0.06). We found a non-significant trend to a higher incidence of infections by multi-drug resistant organisms (MDRO) in the pandemic period than in the pre-pandemic period (6.5% vs. 4%). The incidence of infections was similar in both periods. However, during the pandemic, we observed a trend to a lower incidence of nosocomial infections with a higher incidence of MDRO infections.
A Bronze Age lip-paint from southeastern Iran
Authors: Eskandari Nasir , De Carlo Eugenio , Zorzi Federico , Dall’Acqua Stefano , Furlan Claudio , Artioli Gilberto , Vidale Massimo 
Published: February 2024

AbstractA small chlorite vial, discovered among numerous artifacts looted and recovered in the Jiroft region of Kerman province, southeastern Iran, contains a deep red cosmetic preparation that is likely a lip-coloring paint or paste. Through analytical research involving XRD (X-ray diffraction), SEM–EDS (scanning electron microscopy-energy-dispersive spectroscopy), and HPLC–MS (high-performance liquid chromatography-mass spectrometry) analyses, the mineral components of the reddish substance were identified as hematite, darkened with manganite and braunite, and traces of galena and anglesite, mixed with vegetal waxes and other organic substances. The mixture, thus observed, bears a striking resemblance to the recipes of contemporary lipsticks. We also report the first radiocarbon date ever obtained from a Bronze age cosmetic in the ancient Near East: results place the pigment in the early 2nd millennium BCE, a date compatible with several mentions of the powerful eastern-iranian civilization of Marḫaši in coeval cuneiform texts of Mesopotamia, as well as with its currently emerging archaeological picture.
Energy storage and catalytic behaviour of cmWave assisted BZT and flexible electrospun BZT fibers for energy harvesting applications
Authors: Thirumalasetty Avanish Babu , Pamula Siva , Krishnan Thiyagarajan , Khade Vaishnavi , Sharief Pathan , Kota Venkata Siva Kumar , Adiraj Srinivas , Wuppulluri Madhuri 
Published: February 2024

AbstractHigh-performance lead-free Barium Zirconium Titanate (BZT) based ceramics have emerged as a potential candidate for applications in energy storage, catalysis for electro chemical energy conversion and energy harvesting devices as presented in this work. In the present study hybrid microwave sintered BZT are studied for dielectric, ferroelectric and phase transition properties. BZT ceramic exhibits tetragonal structure as confirmed by the Retvield refinement studies. XPS studies confirms the elemental composition of BZT and presence of Zr. Polarization versus electric field hysteresis loops confirms the ferroelectric behaviour of BZT ceramic. Encouragingly, the BZT showed a moderate energy storage efficiency of 30.7 % and relatively good electro chemical energy conversion (HER). Excellent catalytic activity observed for BZT electrode in acid medium with low Tafel slope 77 mV dec-1. Furthermore, electrospun nanofibers made of PVDF-HFP and BZT are used to make flexible piezoelectric nano generators (PENGs). FTIR studies show that the 16 wt% BZT composite ink exhibits a higher electroactive beta phase. The optimized open-circuit voltage and short circuit current of the flexible PENG exhibits 7Vpp and 750 nA under an applied force of 3N. Thus, flexible and self-powered BZT PENGs are alternative source of energy due to its reliability, affordability and environmental-friendly nature.
Design of modified reference phase modulation based boost chopper fed fifteen level stepped DC link hybrid converter
Authors: Uthirasamy R. , Kumar S. Vishnu , Ananth Christo , David Selvaraj , Aggarwal Shruti , Ansar Syed Anas , Mittal Nitin , Gupta Lipika , Gared Fikreselam 
Published: February 2024

AbstractA new fifteen-level stepped DC to AC hybrid converter is proposed for Solar Photovoltaic (SPV) applications. A boost chopper circuit is designed and interfaced with the fifteen-level hybrid converters specific to Electric Vehicles’ Brushless DC Motor (BLDC) drive systems. In chopper units, the output of solar panels is regulated and stepped up to obtain the nominal output voltage. In the stepped DC-link hybrid converter configuration, fifteen-level DC-link voltage is achieved by the series-operated DC-link modules with reduced electrical energy compression. From the comprehensive structure, it is anecdotal that the proposed topology has achieved minimum switching and power loss. Elimination of end passive components highlights the merits of the proposed hybrid systems. The reduction of controlled power semiconductor switches and gate-firing circuits has made the system more reliable than other hybrid converters. From the extensive analysis, the experimental setup has reported that 7% reduction in harmonics and a 54% reduction in controlled power switches than the existing fifteen-level converter topologies. Mitigation of power quality issues in the voltage profile of a fifteen-level multilevel hybrid converter is achieved through the implementation of dsPIC digital-controller-based gate triggering circuits.
Stronger genetic differentiation among within-population genetic groups than among populations in Scots pine provides new insights into within-population genetic structuring
Authors: Danusevičius Darius , Rajora Om P. , Kavaliauskas Darius , Baliuckas Virgilijus , Augustaitis Algirdas 
Published: February 2024

AbstractWe investigated the presence of spatial genetic groups within forest tree populations and determined if the genetic divergence among these groups is greater than that between populations using Scots pine (Pinus sylvestris) as a model species. We genotyped 890 adult trees of Scots pine in six natural populations in Lithuania at 11 nuclear microsatellite loci. We used a Bayesian clustering approach to identify the within-population genetic groups within each of the six populations. We calculated the differentiation indexes among the genetic groups within each population and among the six populations by ignoring the genetic groups. The Bayesian clustering revealed 2 to 6 distinct genetic groups of varying size as the most likely genetic structures within populations. The genetic differentiation indexes among the genetic groups within populations were nearly tenfold greater (FST = 0.012–0.070) than those between the populations (FST = 0.003). We conclude on the existence of markedly stronger structuring of genetic variation within populations than between populations of Scots pine in large forest tracts of northern Europe. Such genetic structures serve as a contributing factor to large within population genetic diversity in northern conifers. We assume that within population mating in Scots pine is not completely random but rather is stratified into genetic clusters. Our study provides pioneering novel key insights into structuring of genetic variation within populations. Our findings have implications for examining within-population genetic diversity and genetic structure, conservation, and management of genetic resources.
Serum biomarkers in patients with hand-arm vibration injury and in controls
Authors: Tekavec Eva , Nilsson Tohr , Dahlin Lars B. , Huynh Elizabeth , Axmon Anna , Nordander Catarina , Riddar Jakob , Kåredal Monica 
Published: February 2024

AbstractHand-arm vibration injury is a well-known occupational disorder that affects many workers globally. The diagnosis is based mainly on quantitative psychophysical tests and medical history. Typical manifestations of hand-arm vibration injury entail episodes of finger blanching, Raynaud’s phenomenon (RP) and sensorineural symptoms from affected nerve fibres and mechanoreceptors in the skin. Differences in serum levels of 17 different biomarkers between 92 patients with hand-arm vibration injury and 51 controls were analysed. Patients with hand-arm vibration injury entailing RP and sensorineural manifestations showed elevated levels of biomarkers associated with endothelial injury or dysfunction, inflammation, vaso- or neuroprotective compensatory, or apoptotic mechanisms: intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1); thrombomodulin (TM), heat shock protein 27 (HSP27); von Willebrand factor, calcitonin gene-related peptide (CGRP) and caspase-3. This study adds important knowledge on pathophysiological mechanisms that can contribute to the implementation of a more objective method for diagnosis of hand-arm vibration injury.