bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phillyrin improves myocardial remodeling in salt-sensitive hypertensive mice by reducing endothelin1 signaling
Authors: Luo Qingman , Liu Qiao , Tang Kecheng , Zhong Bin , Yang Shengqian , Li Xiaohui 
Published: March 2024

Abstract

Objectives
Prolonged exposure to chronic hypertension places the heart under excessive strain, resulting in myocardial remodeling. Phillyrin, derived from the natural plant Forsythia suspensa, has been found to possess cardioprotective properties. The objective of this study is to investigate the role and mechanism of phillyrin in hypertension-induced myocardial remodeling in mice.

Methods
We constructed a mouse model of salt-sensitive hypertension. The mice were treated with varying doses of phillyrin, and their blood pressure, cardiac function, cardiac hypertrophy, fibrosis, inflammation, and other conditions were assessed.

Key findings
Our research findings demonstrated that phillyrin has the potential to lower blood pressure, enhance cardiac function, and mitigate cardiac hypertrophy, fibrosis, and inflammatory responses in deoxycorticosterone acetate-salt hypertension mice. In hypertensive mice, there was an elevated expression of endothelin1 (ET-1) in heart tissue, which can be reduced by phillyrin. Additionally, phillyrin effectively reduced the hypertrophy of H9c2 cells induced by ET-1 stimulation.

Conclusions
Our research highlights the therapeutic capabilities of phillyrin in the treatment of myocardial remodeling through the reduction of ET-1 signaling. These results contribute to the advancement of novel applications for phillyrin and establish a solid conceptual basis for future investigations in this area.
Safe testing
Authors: Grünwald Peter , de Heide Rianne , Koolen Wouter 
Published: March 2024

Abstract
We develop the theory of hypothesis testing based on the e-value, a notion of evidence that, unlike the p-value, allows for effortlessly combining results from several studies in the common scenario where the decision to perform a new study may depend on previous outcomes. Tests based on e-values are safe, i.e. they preserve type-I error guarantees, under such optional continuation. We define growth rate optimality (GRO) as an analogue of power in an optional continuation context, and we show how to construct GRO e-variables for general testing problems with composite null and alternative, emphasizing models with nuisance parameters. GRO e-values take the form of Bayes factors with special priors. We illustrate the theory using several classic examples including a 1-sample safe t-test and the 2×2 contingency table. Sharing Fisherian, Neymanian, and Jeffreys–Bayesian interpretations, e-values may provide a methodology acceptable to adherents of all three schools.
Usefulness of serial testing for the diagnosis of malaria in cases of fever upon return from travel
Authors: Lydia Slack , Blaise Genton 
Published: March 2024

Abstract

Background
When malaria is suspected in case of fever after travel in endemic areas, the current recommendation is to repeat the malaria test at 24-hour intervals, with up to two additional tests, as long as the test result is negative. A retrospective analysis was conducted to investigate the appropriateness of this recommendation by determining the proportion of tests with negative result at first and subsequently with a positive one at second or third attempt.

Methods
A retrospective study was conducted at the Centre for Primary Care and Public Health, Lausanne, covering a period of 15 years. All patients tested once for malaria were included. Testing included microscopy thick and thin films as well as malaria rapid diagnostic test used in combination. The main outcome measure was the proportion of patients with a first negative test result, subsequently positive on second or third test over the total patients with suspected malaria assessed. Demographic, travel, clinical, and laboratory variables were collected from patients’ records to identify potential predictors of an initially negative and then positive test result.

Results
Four thousand nine hundred seventy-two patients were included. Of those, 4557 (91.7%) had definitive negative test results, and 415 (8.3%) had a positive result on the first test [332/415 (80%) Plasmodium falciparum, 40/415 (9.6%) P. vivax, 21/415 (5.1%) P. ovale, 12/415 (2.9%) P. vivax/ovale, 9/415 (2.2%) P. malariae and 1/415 (0.2%) P. knowlesi], and 3/4972 (0.06%) had a positive result on the second test after a first negative result, 1/4972(0.02%) had a positive test result after 2 negative results, all with P. falciparum. One of the four patients that were positive after their initial negative test was pregnant. The very small number of patients with an initially negative test result and secondarily positive did not allow for risk factor analysis.

Conclusions
The current recommendation of serial malaria testing is not supported by the present study, a fortiori for those who do not present with a strong clinical or laboratory predictor of malaria.
Stress response membrane protein OsSMP2 negatively regulates rice tolerance to drought
Authors: Wang Wei , Li Yaqi , Yang Songjin , Wu Jiacheng , Ma Chuan , Chen Yulin , Sun Xingzhuo , Wu Lingli , Liang Xin , Fu Qiuping , Xu Zhengjun , Li Lihua , Huang Zhengjian , Zhu Jianqing , Jia Xiaomei , Ye Xiaoying , Chen Rongjun 
Published: March 2024

Abstract
In a gene chip analysis, rice (Oryza sativa) OsSMP2 gene expression was induced under various abiotic stresses, prompting an investigation into its role in drought resistance and abscisic acid signaling. Subsequent experiments, including qRT–PCR and β-glucuronidase activity detection, affirmed the OsSMP2 gene’s predominant induction by drought stress. Subcellular localization experiments indicated the OsSMP2 protein primarily localizes to the cell membrane system. Overexpressing OsSMP2 increased sensitivity to exogenous abscisic acid, reducing drought resistance and leading to reactive oxygen species accumulation under drought stress. Conversely, in simulated drought experiments, OsSMP2-silenced transgenic plants showed significantly longer roots compared with the wild-type Nipponbare. These results suggest that OsSMP2 overexpression negatively affects rice drought resistance, offering valuable insights into molecular mechanisms, and highlight OsSMP2 as a potential target for enhancing crop resilience to drought stress.
When synthetic biology meets medicine
Authors: Feng Yuge , Su Cong , Mao Guobin , Sun Baoting , Cai Yizhi , Dai Junbiao , Ma Yingxin 
Published: March 2024

Abstract
In recent years, the world has faced significant challenges with the coronavirus disease 2019 (COVID-19) pandemic, as well as other infectious diseases such as Zika and Ebola. Furthermore, the rapid rise of non-communicable diseases such as diabetes, heart disease, and cancer has placed tremendous strain on healthcare resources and systems. Unfortunately, advancements in drug development, diagnostics, and therapeutics have struggled to keep pace with the emergence and progression of diseases, necessitating the exploration of new technologies for the discovery and development of biomedicines and biotherapies. Synthetic biology, a revolutionary field in modern science, holds great promise in advancing drug development and disease treatment. This review provides a comprehensive overview of recent developments in the application of synthetic biology to medicine, with a specific focus on its role in drug discovery, drug production, and the diagnosis and treatment of various diseases.
Evaluation of the drug–drug interaction between triazole antifungals and cystic fibrosis transmembrane conductance regulator modulators in a real-life cohort
Authors: Jansen Anouk M E , Eggermont Margot N , Wilms Erik B , Aziz Sami , Reijers Monique , Roukema Jolt , Warris Adilia , Brüggemann Roger J M , van der Meer Renske 
Published: March 2024

Abstract
Limited data on the clinical management of drug–drug interactions between triazoles and Cystic Fibrosis transmembrane conductance regulator (CFTR) modulators are available. We retrospectively evaluated azole target attainment and dose adaptations in patients from two Dutch CF centres concomitantly receiving triazoles and CFTR modulators. In total, 21 patients with 59 triazole trough concentrations were evaluated. Subtherapeutic concentrations were frequently observed, especially for itraconazole and voriconazole. Of the investigated antifungal agents, posaconazole appears the most preferable option. Our results emphasize the importance of adequate management of this interaction and underpin the added value of therapeutic drug monitoring of triazoles in this population.
Rapid variability of Markarian 421 during extreme flaring as seen through the eyes of XMM–Newton
Authors: Gokus A , Wilms J , Kadler M , Dorner D , Nowak M A , Kreikenbohm A , Leiter K , Bretz T , Schleicher B , Markowitz A G , Pottschmidt K , Mannheim K , Kreykenbohm I , Langejahn M , McBride F , Beuchert T , Dauser T , Kreter M , Abhir J , Baack D , Balbo M , Biland A , Brand K , Buss J , Eisenberger L , Elsaesser D , Günther P , Hildebrand D , Linhoff M , Paravac A , Rhode W , Sliusar V , Hasan S , Walter R 
Published: March 2024

ABSTRACT
By studying the variability of blazars across the electromagnetic spectrum, it is possible to resolve the underlying processes responsible for rapid flux increases, so-called flares. We report on an extremely bright X-ray flare in the high-peaked BL Lacertae object Markarian 421 (Mrk 421) that occurred simultaneously with enhanced γ-ray activity detected at very high energies by First G-APD Cherenkov Telescope on 2019 June 9. We triggered an observation with XMM–Newton, which observed the source quasi-continuously for 25 h. We find that the source was in the brightest state ever observed using XMM–Newton, reaching a flux of 2.8 × 10−9 $\mathrm{erg\, cm^{-2}\, s^{-1}}$ over an energy range of 0.3–10 keV. We perform a spectral and timing analysis to reveal the mechanisms of particle acceleration and to search for the shortest source-intrinsic time-scales. Mrk 421 exhibits the typical harder-when-brighter behaviour throughout the observation and shows a clock-wise hysteresis pattern, which indicates that the cooling dominates over the acceleration process. While the X-ray emission in different sub-bands is highly correlated, we can exclude large time lags as the computed z-transformed discrete correlation functions are consistent with a zero lag. We find rapid variability on time-scales of 1 ks for the 0.3–10 keV band and down to 300 s in the hard X-ray band (4–10 keV). Taking these time-scales into account, we discuss different models to explain the observed X-ray flare, and find that a plasmoid-dominated magnetic reconnection process is able to describe our observation best.
The nature of compact radio-loud AGN: a systematic look at the LOFAR AGN population
Authors: Chilufya J , Hardcastle M J , Pierce J C S , Croston J H , Mingo B , Zheng X , Baldi R D , Röttgering H J A 
Published: March 2024

ABSTRACT
We investigate the nature of low-luminosity radio-loud active galactic nuclei (RLAGN) selected from the LOFAR Two-metre Sky Survey (LoTSS) first data release (DR1). Using optical, mid-infrared, and radio data, we have conservatively selected 55 radiative AGN candidates from DR1 within the redshift range 0.03 &lt; z &lt; 0.1. We show using high-frequency Karl G. Jansky Very Large Array (VLA) observations that 10 out of 55 objects show radio emission on scales &gt;1–3 kpc, 42 are compact at the limiting resolution of 0.35 arcsec (taking an upper limit on the projected physical size, this corresponds to less than 1 kpc), and three are undetected. The extended objects display a wide range of radio morphologies: two-jet (5), one-jet (4), and double-lobed (1). We present the radio spectra of all detected radio sources which range from steep to flat/inverted and span the range seen for other compact radio sources such as compact symmetric objects (CSOs), compact steep spectrum (CSS) sources, and gigahertz peaked-spectrum (GPS) sources. Assuming synchrotron self-absorption (SSA) for flat/inverted radio spectrum sources, we predict small physical sizes for compact objects to range between 2 and 53 pc. Alternatively, using free–free absorption (FFA) models, we have estimated the free electron column depth for all compact objects, assuming a homogeneous absorber. We find that these objects do not occupy a special position on the power/linear size (P − D) diagram but some share a region with radio-quiet quasars (RQQs) and the so-called ‘FR0’ sources in terms of radio luminosity and linear size.
The distance to CRL 618 through its radio expansion parallax
Authors: Cerrigone Luciano , Umana Grazia , Trigilio Corrado , Menten Karl M , Bordiu Cristobal , Ingallinera Adriano , Leto Paolo , Buemi Carla S , Bufano Filomena , Cavallaro Francesco , Loru Sara , Riggi Simone 
Published: March 2024

ABSTRACT
CRL 618 is a post-Asymptotic Giant Branch star that has started to ionize its ejecta. Its central H ii region has been observed over the last 40 yr and has steadily increased in flux density at radio wavelengths. In this paper, we present data that we obtained with the Very Large Array in its highest frequency band (43 GHz) in 2011 and compare these with archival data in the same frequency band from 1998. By applying the so-called expansion-parallax method, we are able to estimate an expansion rate of 4.0 ± 0.4 mas yr−1 along the major axis of the nebula and derive a distance of 1.1 ± 0.2 kpc. Within errors, this distance estimation is in good agreement with the value of ∼900 pc derived from the expansion of the optical lobes.
Integrating Patient-Reported Outcomes Into Prognostication in Gastroesophageal Cancer: Results of a Population-Based Retrospective Cohort Analysis
Authors: Baccili Cury Megid Thais , Sharma Divya , Baskurt Zeynep , Xiaolu Ma Lucy , Wang Xin , Barron Carly C , Jang Raymond Woo-Jun , Chen Eric Xueyu , Swallow Carol Jane , Mesci Aruz , Yeung Jonathan , Wong Rebecca K S , Brar Savtaj Singh , Veit-Haibach Patrick , Kim John , Bach Yvonne , Aoyama Hiroko , Elimova Elena 
Published: March 2024

Abstract

Background
Patient-reported outcomes measures (PROM) are self-reflections of an individual’s physical functioning and emotional well-being. The Edmonton Symptom Assessment Scale (ESAS) is a simple and validated PRO tool of 10 common symptoms and a patient-reported functional status (PRFS) measure. The prognostic value of this tool is unknown in patients with gastroesophageal cancer (GEC). In this study, we examined the association between the ESAS score and overall survival (OS) in patients with GEC, the prognostication difference between ESAS and Eastern Cooperative Oncology Group (ECOG), and assessed the correlation between PRFS and the physician-reported ECOG performance status (PS).

Methods
The study was a retrospective cohort study of 211 patients with GEC with localized (stages I-III) and metastatic disease who completed at least one baseline ESAS prior to treatment. Patients were grouped into 3 cohorts based on ESAS score. OS was assessed using the Kaplan-Meier method, and the concordance index (c-index) was calculated for ESAS and physician-reported ECOG. The agreement between PRFS and physician-ECOG was also assessed.

Results
In total, 211 patients were included. The median age was 60.8 years; 90% of patients were ECOG PS 0-1; 38% of patients were stages I-III, while 62% were de novo metastatic patients. Median OS in low, moderate, high symptom burden (SB) patients’ cohorts was 19.17 m, 16.39 mm, and 12.68 m, respectively (P &lt; .04). The ability to predict death was similar between physician-ECOG and ESAS (c-index 0.56 and 0.5753, respectively) and PRFS and physician-ECOG (c-index of 0.5615 and 0.5545, respectively). The PS agreement between patients and physicians was 50% with a weighted Kappa of 0.27 (95% CI: 0.17-0.38).

Conclusion
Patient’s SB seems to carry a prognostic significance. ESAS and physician-reported ECOG exhibit comparable prognostic values. Physicians and patients can frequently have divergent opinions on PS. ESAS takes a patient-centered approach and should be encouraged in practice among patients with GEC as an additional tool for prognostication.
Two Hematological Markers Predicting the Efficacy and Prognosis of Neoadjuvant Chemotherapy Using Lobaplatin Against Triple-Negative Breast Cancer
Authors: Wang Cheng , Shi Qiyun , Zhang Guozhi , Wu Xiujuan , Yan Wenting , Wan Andi , Xiong Siyi , Yuan Long , Tian Hao , Ma Dandan , Jiang Jun , Qi Xiaowei , Zhang Yi 
Published: March 2024

Abstract

Background
Our previous work indicated that the addition of lobaplatin to combined therapy with taxane and anthracycline can improve the pathological complete response rate of neoadjuvant therapy for triple-negative breast cancer (TNBC) and lengthen long-term survival significantly, but the therapeutic markers of this regimen are unclear.

Methods
Eighty-three patients who met the inclusion criteria were included in this post hoc analysis. We analyzed the association between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) before neoadjuvant chemotherapy with the efficacy and prognosis after treatment with docetaxel, epirubicin, and lobaplatin neoadjuvant chemotherapy regimen. χ2 test and Cox regression were used to analyze the association between PLR and NLR with total pathologic complete response (tpCR), as well as the association between PLR and NLR with event-free survival (EFS) and overall survival (OS), respectively.

Results
The tpCR rate in the PLR− group was 49.0% (25/51), which was significantly higher than that in the PLR+ group (25.0% [8/32], P = .032). The tpCR rate in the NLR− group was 49.1% (26/53), which was significantly higher than that in the NLR+ group (23.3% [7/30], P = .024). The tpCR rate of the PLR−NLR− (PLR− and NLR−) group was 53.7% (22/41), which was significantly higher than that of the PLR+/NLR+ (PLR+ or/and NLR+) group (26.1% [11/42]; P = .012). EFS and OS in the NLR+ group were significantly shorter than those in the NLR− group (P = .028 for EFS; P = .047 for OS). Patients in the PLR−NLR− group had a longer EFS than those in the PLR+/NLR+ group (P = .002).

Conclusion
PLR and NLR could be used to predict the efficacy of neoadjuvant therapy with the taxane, anthracycline, and lobaplatin regimen for patients with TNBC, as patients who had lower PLR and NLR values had a higher tpCR rate and a better long-term prognosis.
Pleiotropic Effects of miR5504 Underlying Plant Height, Grain Yield and Quality in Rice
Authors: Wang Huihui , Wang Xin , Li Yangyang , Cui Ying , Yan Xin , Gao Jiadong , Ouyang Jiexiu , Li Shaobo 
Published: March 2024

Abstract
MicroRNAs (miRNAs) are known to play critical roles in regulating rice agronomic traits through mRNA cleavage or translational repression. Our previous study indicated that miR5504 regulates plant height by affecting cell proliferation and expansion. Here, the two independent homozygous mir5504 mutants (CR1 and CR2) and overexpression lines (OE1 and OE2) were further used to investigate the functions of miR5504. The panicle length, 1000-grain weight and grain yield per plant of miR5504-OE lines were identical to those of Nipponbare (NIP), but the 1000-grain weight of mir5504 mutants was reduced by about 10% and 9%, respectively. Meanwhile, the grain width and thickness of mir5504 mutants decreased significantly by approximately 10% and 11%, respectively. Moreover, the cytological results revealed a significant decrease in cell number along grain width direction and cell width in spikelet in mir5504, compared with those in NIP. In addition, several major storage substances of the rice seeds were measured. Compared to NIP, the amylose content of the mir5504 seeds was noticeably decreased, leading to an increase of nearly 10 mm in gel consistency (GC) in mir5504 lines. Further investigation confirmed that LOC_Os08g16914 was the genuine target of miR5504: LOC_Os08g16914 over-expression plants phenocopied the mir5504 mutants. This study provides insights into the role of miR5504 in rice seed development.
Light signaling in plants—a selective history
Authors: Huq Enamul , Lin Chentao , Quail Peter H 
Published: March 2024

Abstract
In addition to providing the radiant energy that drives photosynthesis, sunlight carries signals that enable plants to grow, develop and adapt optimally to the prevailing environment. Here we trace the path of research that has led to our current understanding of the cellular and molecular mechanisms underlying the plant's capacity to perceive and transduce these signals into appropriate growth and developmental responses. Because a fully comprehensive review was not possible, we have restricted our coverage to the phytochrome and cryptochrome classes of photosensory receptors, while recognizing that the phototropin and UV classes also contribute importantly to the full scope of light-signal monitoring by the plant.
Natural polymorphisms in ZMET2 encoding a DNA methyltransferase modulate the number of husk layers in maize
Authors: Wang Zi , Xia Aiai , Wang Qi , Cui Zhenhai , Lu Ming , Ye Yusheng , Wang Yanbo , He Yan 
Published: March 2024

Abstract
DNA methylation affects agronomic traits and the environmental adaptability of crops, but the natural polymorphisms in DNA methylation–related genes and their contributions to phenotypic variation in maize (Zea mays) remain elusive. Here, we show that a polymorphic 10-bp insertion/deletion variant in the 3′UTR of Zea methyltransferase2 (ZMET2) alters its transcript level and accounts for variation in the number of maize husk layers. ZMET2 encodes a chromomethylase and is required for maintaining genome-wide DNA methylation in the CHG sequence context. Disruption of ZMET2 increased the number of husk layers and resulted in thousands of differentially methylated regions, a proportion of which were also distinguishable in natural ZMET2 alleles. Population genetic analyses indicated that ZMET2 was a target of selection and might play a role in the spread of maize from tropical to temperate regions. Our results provide important insights into the natural variation of ZMET2 that confers both global and locus-specific effects on DNA methylation, which contribute to phenotypic diversity in maize.
Maize requires arogenate dehydratase 2 for resistance to Ustilago maydis and plant development
Authors: Ren Ru Chang , Kong Ling Guang , Zheng Guang Ming , Zhao Ya Jie , Jiang Xin , Wu Jia Wen , Liu Cuimei , Chu Jinfang , Ding Xin Hua , Zhang Xian Sheng , Wang Guan Feng , Zhao Xiang Yu 
Published: March 2024

Abstract
Maize (Zea mays) smut is a common biotrophic fungal disease caused by Ustilago maydis and leads to low maize yield. Maize resistance to U. maydis is a quantitative trait. However, the molecular mechanism underlying the resistance of maize to U. maydis is poorly understood. Here, we reported that a maize mutant caused by a single gene mutation exhibited defects in both fungal resistance and plant development. maize mutant highly susceptible to U. maydis (mmsu) with a dwarf phenotype forms tumors in the ear. A map-based cloning and allelism test demonstrated that 1 gene encoding a putative arogenate dehydratase/prephenate dehydratase (ADT/PDT) is responsible for the phenotypes of the mmsu and was designated as ZmADT2. Combined transcriptomic and metabolomic analyses revealed that mmsu had substantial differences in multiple metabolic pathways in response to U. maydis infection compared with the wild type. Disruption of ZmADT2 caused damage to the chloroplast ultrastructure and function, metabolic flux redirection, and reduced the amounts of salicylic acid (SA) and lignin, leading to susceptibility to U. maydis and dwarf phenotype. These results suggested that ZmADT2 is required for maintaining metabolic flux, as well as resistance to U. maydis and plant development in maize. Meanwhile, our findings provided insights into the maize response mechanism to U. maydis infection.