bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shaping immunity: The influence of natural selection on population immune diversity
Authors: Randolph Haley E. , Aracena Katherine A. , Lin Yen‐Lung , Mu Zepeng , Barreiro Luis B. 
Published: April 2024

SummaryHumans exhibit considerable variability in their immune responses to the same immune challenges. Such variation is widespread and affects individual and population‐level susceptibility to infectious diseases and immune disorders. Although the factors influencing immune response diversity are partially understood, what mechanisms lead to the wide range of immune traits in healthy individuals remain largely unexplained. Here, we discuss the role that natural selection has played in driving phenotypic differences in immune responses across populations and present‐day susceptibility to immune‐related disorders. Further, we touch on future directions in the field of immunogenomics, highlighting the value of expanding this work to human populations globally, the utility of modeling the immune response as a dynamic process, and the importance of considering the potential polygenic nature of natural selection. Identifying loci acted upon by evolution may further pinpoint variants critically involved in disease etiology, and designing studies to capture these effects will enrich our understanding of the genetic contributions to immunity and immune dysregulation.
Effect of low uterine segment involvement on prognosis of early stage endometrial cancer
Authors: Akdöner Aslı , Kurt Sefa , Yavuz Onur , Bayram Emre , Üresin Merve , Ulukuş Emine Çağnur 
Published: April 2024

AbstractAimOur aim is to investigate the effect of uterine lower segment involvement on prognosis of early‐stage endometrial cancer cases diagnosed and treated in our clinic.Materials and MethodsThe file records of 316 cases reviewed retrospectively.Only stage I (a and b, n=209) cases were investigated, because they were more homogeneous group.ResultsThe lymphovascular invasion rate was found to be higher in patients with stage Ia and uterine lower segment involvement (p < 0.001). Adjuvant treatment requirement was higher in patients with stage Ia and uterine lower segment involvement (p < 0.001). Among stage Ia cases, the recurrence rate between 1 and 3 years was found to be higher in cases with uterine lower segment involvement (p = 0.001). Among the stage Ib cases, lymphovascular invasion was found to be higher in cases with uterine lower segment involvement (p < 0.001). The recurrence rate between 1 and 3 years was found to be higher in stage Ib compared to Ia (p = 0.01). Uterine lower segment involvement was found to be associated with high lymphovascular invasion rate in all stage I cases (p < 0.001). It was determined that the need for adjuvant treatment was higher in cases with uterine lower segment involvement (p < 0.001). It was determined that the probability of recurrence between 1 and 3 years was higher in cases with uterine lower segment involvement (p = 0.007).ConclusionUterine lower segment involvement is associated with increased lymphovascular invasion even in the early stages. It is an important risk factor for systemic spread such as lymphovascular invasion, myometrial invasion, and lymph node involvement.
Honokiol regulates ovarian cancer cell malignant behavior through YAP/TAZ pathway modulation
Authors: Liu Fang , Zhang Yufang , Xia Xinyi , Han Jing , Cao Linyan 
Published: April 2024

AbstractBackgroundOvarian cancer (OVCA) stands as one of the most fatal gynecological malignancies. Honokiol (HNK) has been substantiated by numerous studies for its anti‐tumor activity against malignancies including OVCA. Consequently, this work was designed to elucidate the impact of HNK‐mediated modulation of the YAP/TAZ pathway on the biological functions of OVCA cells.MethodsOVCA cells were subjected to treatment with varying concentrations (0, 25, 50, 75, and 100 μM) of HNK, concomitant with the administration of YAP agonist (XMU). Assessment of cellular viability was executed employing the CCK‐8 assay, while quantification of cellular proliferation transpired via colony formation assays. Apoptosis was ascertained using flow cytometry, and expression of apoptosis‐related proteins (caspase‐3, Bcl‐2, Bax), EMT‐related proteins (E‐cadherin, N‐cadherin), migration‐associated proteins (MMP‐2, MMP‐9), and YAP/TAZ pathway‐related proteins was evaluated by western blot. Transwell experiments were conducted to assess cellular migratory and invasive propensities. Xenograft tumor models were built to observe tumor growth (volume and weight), apoptosis was assessed by TUNEL staining, and Ki67 expression was evaluated through IHC.ResultsHNK exerted inhibitory effects on the viability and proliferative capacity of OVCA cells, elicited apoptotic responses, curtailed the migratory and invasive tendencies of cells, and downregulated the YAP/TAZ pathway. Stimulation with YAP agonist (XMU‐MP‐1) partially attenuated the impacts of HNK on OVCA cell biology. Experiments in vivo confirmed that HNK inhibited OVCA tumor growth.ConclusionThe outcomes of this investigation conclusively established that HNK orchestrated the modulation of the YAP/TAZ pathway, thereby exerting control over the malignant phenotypic manifestations of OVCA cells. The ascertained function of HNK in restraining cellular proliferation and tumor progression provided novel evidence of its anti‐proliferative activity within OVCA cells.
In vitro digestibility and solubility of phosphorus of three plant‐based meat analogues
Authors: Wehrmaker Ariane Maike , de Groot Wouter , Jan van der Goot Atze , Keppler Julia Katharina , Bosch Guido 
Published: April 2024

AbstractInterest in plant‐based meat analogues has increased and can be expected to be applied to pet foods, which necessitates the understanding of the nutrient supply in those foods. Our primary aim was to advance our understanding of the digestive properties of sterilized plant‐based meat analogues. The impact of the preparatory processing steps on the solubility of meat analogues was studied. Meat analogues were made by mixing water, salt, and wheat gluten with soy protein isolate, pea protein isolate, or faba bean concentrate. Mixed materials were processed into model meat analogues using shear cell technology. Products were canned in water or gravy and sterilized. An animal‐based canned pet food was made as a reference. Products sampled at the processing steps (mixing, shearing, sterilization) were digested in vitro. Samples of digestate were taken at the gastric phase (0 and 120 min) and small intestinal phase (120, 200, 280, and 360 min) for analysis of protein hydrolysis. The extent digestion of nitrogen and dry matter was determined at the end of incubation. Total phosphorus, soluble phosphorus after acid treatment, and after acid and enzymatic treatment were determined. The degree of hydrolysis after gastric digestion was low but increased immediately in the small intestinal phase; products based on pea had the highest values (56%). Nitrogen digestibility was above 90% for all materials at each processing step, indicating that bioactive compounds were absent or inactivated in the protein isolates and concentrate. Phytate seemed to play a minor role in meat analogues, but phosphorus solubility was influenced by processing. Shearing decreased soluble phosphorus, but this effect was partly reversed by sterilization. Nutrient digestibility as well as phosphorus solubility in plant‐based products was higher than or comparable with the reference pet food. These findings show that the digestive properties of the tested plant‐based meat analogues do not limit the supply of amino acids and phosphorus.
The first MASH drug therapy on the horizon: Current perspectives of resmetirom
Authors: Petta Salvatore , Targher Giovanni , Romeo Stefano , Pajvani Utpal B. , Zheng Ming‐Hua , Aghemo Alessio , Valenti Luca V. C. 
Published: April 2024

AbstractThe rising prevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD) poses a significant global health challenge, affecting over 30% of adults worldwide. MASLD is linked to increased mortality rates and substantial healthcare costs, primarily driven by its progression to metabolic dysfunction‐associated steatohepatitis (MASH), which can lead to severe liver complications including cirrhosis and hepatocellular carcinoma. Despite its growing burden, effective pharmacotherapy for MASLD/MASH has been lacking until the recent conditional approval of resmetirom by the FDA. Resmetirom, a liver‐targeted thyroid hormone receptor‐β selective drug, has shown promise in clinical trials for treating non‐cirrhotic MASH with moderate to advanced fibrosis. It has demonstrated efficacy in reducing hepatic fat content, improving liver histology (both MASH resolution and fibrosis improvement), and ameliorating biomarkers of liver damage without significant effects on body weight or glucose metabolism. Notably, resmetirom also exhibits favourable effects on circulating lipids, potentially reducing cardiovascular risk in MASLD/MASH patients. The safety profile of resmetirom appears acceptable, with gastrointestinal adverse events being the most common, though generally mild or moderate. However, long‐term surveillance is warranted to monitor for potential risks related to thyroid, gonadal, or bone diseases. Clinical implementation of resmetirom faces challenges in patient selection and monitoring treatment response, and will heavily rely on non‐invasive tests for liver fibrosis assessment. Nonetheless, resmetirom represents a landmark breakthrough in MASLD/MASH treatment, paving the way for future therapeutic strategies aiming to mitigate the multifaceted risks associated with this complex metabolic liver disease.
Changing landscape of alcohol‐associated liver disease in younger individuals, women, and ethnic minorities
Authors: Arab Juan P , Dunn Winston , Im Gene , Singal Ashwani K. 
Published: April 2024

AbstractAlcohol use is the most important determinant of the development of alcohol‐associated liver disease (ALD) and of predicting long‐term outcomes in those with established liver disease. Worldwide, the amount, type, and pattern of use of alcohol vary. Alcohol use and consequent liver disease have been increasing in certain ethnic groups especially Hispanics and Native Americans, likely due to variations in genetics, cultural background, socio‐economic status, and access to health care. Furthermore, the magnitude and burden of ALD have been increasing especially in the last few years among females and young adults who are at the prime of their productivity. It is critical to recognize the problem and care for these patients integrating cultural aspects in liver clinics. At the federal level, a societal approach is needed with the implementation of public health policies aiming to reduce alcohol consumption in the community. By addressing these challenges and promoting awareness, we can strive to reduce the burden of ALD, especially in high‐risk demographic groups to improve their long‐term health outcomes. Finally, we need studies and quality research examining these changing landscapes of demographics in ALD as a basis for developing therapeutic targets and interventions to reduce harmful drinking behaviours in these high‐risk demographic groups.
Genetic legacies of mega‐landslides: Cycles of isolation and contact across flank collapses in an oceanic island
Authors: Noguerales Víctor , Arjona Yurena , García‐Olivares Víctor , Machado Antonio , López Heriberto , Patiño Jairo , Emerson Brent C. 
Published: April 2024

AbstractCatastrophic flank collapses are recognized as important drivers of insular biodiversity dynamics, through the disruption of species ranges and subsequent allopatric divergence. However, little empirical data supports this conjecture, with their evolutionary consequences remaining poorly understood. Using genome‐wide data within a population genomics and phylogenomics framework, we evaluate how mega‐landslides have impacted evolutionary and demographic history within a species complex of weevils (Curculionidae) within the Canary Island of Tenerife. We reveal a complex genomic landscape, within which individuals of single ancestry were sampled in areas characterized by long‐term geological stability, relative to the timing of flank collapses. In contrast, individuals of admixed ancestry were almost exclusively sampled within the boundaries of flank collapses. Estimated divergence times among ancestral populations aligned with the timings of mega‐landslide events. Our results provide first evidence for a cyclical dynamic of range fragmentation and secondary contact across flank collapse landscapes, with support for a model where this dynamic is mediated by Quaternary climate oscillations. The context within which we reveal climate and topography to interact cyclically through time to shape the geographic structure of genetic variation, together with related recent work, highlights the importance of topoclimatic phenomena as an agent of diversification within insular invertebrates.
Supporting and rejecting the populist radical right: Evidence from contemporary Chile
Authors: Rovira Kaltwasser Cristóbal , Salas‐Lewin Rocío , Zanotti Lisa 
Published: April 2024

AbstractAlthough the populist radical right (PRR) has become a global phenomenon, most studies of it focus on Europe. Moreover, extant research has centred on analysing those who support rather than reject the PRR. To address this twofold research gap, we rely on novel public opinion data to examine those who both ‘love’ and ‘hate’ the PRR in contemporary Chile. We demonstrate not only that those in favour of the Chilean PRR are a homogeneous constituency with similar characteristics to their European brethren (e.g., xenophobic attitudes) but also that those at odds with the Chilean PRR make up a relatively large and heterogeneous constituency. In summary, this contribution seeks to broaden comparative studies on the PRR and to show the relevance of studying support as well as rejection of the PRR, particularly in countries with runoff elections; since then, large segments of the electorate vote for the lesser evil.
The effects of using heel protectors on the prevention of heel pressure injuries and plantar flexion contractures
Authors: Arslan Kubra , Ates Sebahat 
Published: April 2024

AbstractBackgroundImmobilization in the intensive care unit can lead to pressure injuries and plantar flexion contractures.AimThis study was conducted to evaluate the effectiveness of heel protectors applied for the prevention of heel pressure injuries and plantar flexion contractures in intensive care units.MethodsThis study was conducted as a randomized controlled trial in two adult intensive care units of a teaching and research hospital. The study sample consisted of 84 patients admitted to intensive care units between January 2022 and December 2022. Patients who had been in the intensive care unit for at least 5 days, scored 16 or less on the Braden Pressure Ulcer Risk Assessment Scale and scored 4 or more on the Ramsey Sedation Scale, were included in the study. Heel protector boots were applied to the heels of the patients in the intervention group, while standard positioning with a pillow and ROM exercises were continued in the control group. A sociodemographic data form, the Ramsey Sedation Scale and the Braden Pressure Ulcer Risk Assessment Scale were used to collect data. While pressure injuries were evaluated with the International NPUAP‐EPUAP Pressure Ulcer Classification System, goniometric measurements were made to evaluate joint ROM.ResultsIn the intervention group, heel pressure injuries did not develop during the study, whereas five patients in the control group developed heel pressure injuries. The risk of pressure injury development that was seen in the control group was 1.7 times higher compared with the risk for the intervention group (log 95% CI: 0.91–2.59). There were significant differences between the right foot (99%; F = 99.229; p = .000) and left foot (99%; F = 100.519; p = .000) in range of motion measurement values of the patients in the intervention group according to the measurement times. According to the results of the multiple comparison test (Bonferroni) performed to determine the range of motion measurement periods showing significant differences, it was observed that each measurement for both feet yielded lower results than the previous measurement (seven measurements from day 1 to day 13).ConclusionThe use of heel protector boots was found to be effective in preventing the development of heel pressure injuries and plantar flexion contractures in intensive care unit patients.Relevance for Clinical PracticeThis study provides evidence that intensive care nurses can use heel protector boots to prevent the development of heel pressure injuries and plantar flexion contractures.
Improving perioperative acetaminophen administration for safer and cost‐effective multimodal analgesia in pediatric surgery: A QI initiative
Authors: Mahon Richard M. , Rajbhandari Prabi , Brown Todd A. , Engler Laurie J. , Bhalla Tarun 
Published: April 2024

AbstractBackgroundThe use of acetaminophen in the perioperative period has emerged as an attractive option for providing safer and cost‐effective analgesia in children.AimsThe primary aim of our project was to increase the use of acetaminophen (both oral and intravenous) in the perioperative period from a baseline of 39.5% to 50% for all surgical patients within 24 months. The secondary aim was to increase the use of enteral acetaminophen from 10% to 52.5% during the same period.MethodsA multidisciplinary team was formed, and model for improvement was chosen as the QI methodology. The primary measure was the total percentage of surgical patients receiving any form of perioperative acetaminophen, while our secondary measure was the percentage use of oral acetaminophen administration. We also tracked the average maximum PACU (Post Anesthesia Care Unit) pain scores and the percentage of patients receiving IV opioids. Multiple interventions were conducted, including education, increasing the availability of acetaminophen, and optimizing the electronic medical record (EMR). Monthly data was collected using an automated report in the EMR.ResultsWe successfully achieved our goal, increasing the use of acetaminophen from 39.5% to 70% within four months. Despite some fluctuations, by the end of 24 months, we not only met but surpassed our goal, with 63% of patients receiving perioperative acetaminophen. Similarly, the usage of oral acetaminophen increased from a baseline of 10% to 78%. Our average maximum PACU pain scores improved from 5.4 to 5.2, and the percentage of patients receiving rescue opioids decreased from 15.4 to 13.1.ConclusionWe successfully achieved and sustained our goals of improving acetaminophen use for our surgical patients without worsening pain scores or worsening use of intravenous opioids. Future directions include further refining our strategies and exploring additional opportunities to optimize pain management in pediatric perioperative settings.
A viral protein competitively bound to rice CIPK23 inhibits potassium absorption and facilitates virus systemic infection in rice
Authors: Jing Xinxin , Wang Pengyue , Liu Jianjian , Xiang Meirong , Song Xia , Wang Chaonan , Li Pengbai , Li Honglian , Wu Zujian , Zhang Chao 
Published: April 2024

SummaryPotassium (K+) plays a crucial role as a macronutrient in the growth and development of plants. Studies have definitely determined the vital roles of K+ in response to pathogen invasion. Our previous investigations revealed that rice plants infected with rice grassy stunt virus (RGSV) displayed a reduction in K+ content, but the mechanism by which RGSV infection subverts K+ uptake remains unknown. In this study, we found that overexpression of RGSV P1, a specific viral protein encoded by viral RNA1, results in enhanced sensitivity to low K+ stress and exhibits a significantly lower rate of K+ influx compared to wild‐type rice plants. Further investigation revealed that RGSV P1 interacts with OsCIPK23, an upstream regulator of Shaker K+ channel OsAKT1. Moreover, we found that the P1 protein recruits the OsCIPK23 to the Cajal bodies (CBs). In vivo assays demonstrated that the P1 protein competitively binds to OsCIPK23 with both OsCBL1 and OsAKT1. In the nucleus, the P1 protein enhances the binding of OsCIPK23 to OsCoilin, a homologue of the signature protein of CBs in Arabidopsis, and facilitates their trafficking through these CB structures. Genetic analysis indicates that mutant in oscipk23 suppresses RGSV systemic infection. Conversely, osakt1 mutants exhibited increased sensitivity to RGSV infection. These findings suggest that RGSV P1 hinders the absorption of K+ in rice plants by recruiting the OsCIPK23 to the CB structures. This process potentially promotes virus systemic infection but comes at the expense of inhibiting OsAKT1 activity.
Flavour improvement in early generations of fresh market tomatoes (Solanum lycopersicum): I. Identification of QTL for sensory attributes, physicochemical measurements and volatile compounds
Authors: Hagenguth Julia , Kanski Larissa , Kahle Hannah , Becker Heiko C. , Horneburg Bernd 
Published: April 2024

AbstractHuman sensory analysis is the most appropriate method for assessing the flavour of fresh market tomatoes, but it is very labour and time consuming. Therefore, sensory attributes are often neglected in early generations of breeding programmes and genetic studies, although there is a demand for tomatoes with improved flavour. In this study, the recently developed Breeders' Sensory Test was applied to an F2mapping population derived from two parents with superior flavour. Sensory attributes, physicochemical measurements, volatiles and fruit weight were assessed in organic low‐input and hydroponic cultivation. A linkage map spanning 1070 cM was developed. In total, 71 quantitative trait loci (QTL) were detected for the means of both cultivation systems, 61 for organic and 46 for hydroponic cultivation. A proportion of 27% of the loci were co‐localized between both cultivation systems. Nine distinct QTL clusters for flavour‐related traits were identified, including a large cluster on chromosome 6 comprising five sensory and nine volatile QTL. The sensory QTL on chromosomes 2, 5, 6, 10 and 11, partly within clusters, are recommended for marker‐assisted selection.
Histone variant H2A.Z is required for plant salt response by regulating gene transcription
Authors: Miao Rongqing , Zhang Yue , Liu Xinxin , Yuan Yue , Zang Wei , Li Zhiqi , Yan Xiufeng , Pang Qiuying , Zhang Aiqin 
Published: April 2024

AbstractAs a well‐conserved histone variant, H2A.Z epigenetically regulates plant growth and development as well as the interaction with environmental factors. However, the role of H2A.Z in response to salt stress remains unclear, and whether nucleosomal H2A.Z occupancy work on the gene responsiveness upon salinity is obscure. Here, we elucidate the involvement of H2A.Z in salt response by analysing H2A.Z disorder plants with impaired or overloaded H2A.Z deposition. The salt tolerance is dramatically accompanied by H2A.Z deficiency and reacquired in H2A.Z OE lines. H2A.Z disorder changes the expression profiles of large‐scale of salt responsive genes, announcing that H2A.Z is required for plant salt response. Genome‐wide H2A.Z mapping shows that H2A.Z level is induced by salt condition across promoter, transcriptional start site (TSS) and transcription ending sites (−1 kb to +1 kb), the peaks preferentially enrich at promoter regions near TSS. We further show that H2A.Z deposition within TSS provides a direct role on transcriptional control, which has both repressive and activating effects, while it is found generally H2A.Z enrichment negatively correlate with gene expression level response to salt stress. This study shed light on the H2A.Z function in salt tolerance, highlighting the complex regulatory mechanisms of H2A.Z on transcriptional activity for yielding appropriate responses to particularly environmental stress.