bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombotic events associated with low baseline direct oral anticoagulant levels in atrial fibrillation: the MAS study
Authors: Testa Sophie , Palareti Gualtiero , Legnani Cristina , Dellanoce Claudia , Cini Michela , Paoletti Oriana , Ciampa Antonio , Antonucci Emilia , Poli Daniela , Morandini Rossella , Tala Maurizio , Chiarugi Paolo , Santoro Rita Carlotta , Iannone Angela Maria , De Candia Erica , Pignatelli Pasquale , Faioni Elena Maria , Chistolini Antonio , Esteban Maria del Pilar , Marietta Marco , Tripodi Armando , Tosetto Alberto 
Published: February 2024

Abstract
Although effective and safe, treatment with direct oral anticoagulants (DOAC) in atrial fibrillation (AF) is still associated with thrombotic complications. Whether the measurement of DOAC levels may improve treatment efficacy is an open issue. We carried out the observational, prospective, multicenter Measure and See (MAS) study. Blood was collected 15 to 30 days after starting DOAC treatment in patients with AF who were followed-up for 1 year. Plasma samples were centralized for DOAC level measurement. Patients’ DOAC levels were converted into drug/dosage standardized values to allow a pooled analysis in a time-dependent, competitive-risk model. The measured values were transformed into standardized values (representing the distance of each value from the overall mean) by subtracting the DOAC-specific mean value from the original values and dividing by the standard deviation. Trough and peak DOAC levels were assessed in 1657 and 1303 patients, respectively. In total, 21 thrombotic complications were recorded during 1606 years of follow-up (incidence of 1.31% of patients per year). Of 21 thrombotic events, 17 occurred in patients whose standardized activity levels were below the mean of each DOAC (0); the incidence was the highest (4.82% of patients per year) in patients whose standardized values were in the lowest class (−1.00 or less). Early measurement of DOAC levels in patients with AF allowed us to identify most of the patients who, having low baseline DOAC levels, subsequently developed thrombotic complications. Further studies are warranted to assess whether thrombotic complications may be reduced by measuring baseline DOAC levels and modifying treatment when indicated. This trial was registered at www.ClinicalTrials.gov as #NCT03803579.
Tribological Behaviors of Electroless Nickel-Boron Coating on Titanium Alloy Surface
Authors: Jia Yao , Lai Jianping , Yu Jiaxin , Qi Huimin , Zhang Yafeng , He Hongtu 
Published: February 2024

AbstractTitanium alloys are excellent structural materials in engineering fields, but their poor tribological properties limit their further applications. Electroless plating is an effective method to enhance the tribological performance of alloys, but it is difficult to efficiently apply to titanium alloys, due to titanium alloy’s strong chemical activity. In this work, the electroless Nickel-Boron (Ni-B) coating was successfully deposited on the surface of titanium alloy (Ti-6AL-4V) via a new pre-treatment process. Then, linearly reciprocating sliding wear tests were performed to evaluate the tribological behaviors of titanium alloy and its electroless Ni-B coatings. It was found that the Ni-B coatings can decrease the wear rate of the titanium alloy from 19.89×10−3 mm3 to 0.41×10−3 mm3, which attributes to the much higher hardness of Ni-B coatings. After heat treatment, the hardness of Ni-B coating further increases corresponding to coating crystallization and hard phase formation. However, heat treatment does not improve the tribological performance of Ni-B coating, due to the fact that higher brittleness and more severe oxidative wear exacerbate the damage of heat-treated coatings. Furthermore, the Ni-B coatings heat-treated both in air and nitrogen almost present the same tribological performance. The finding of this work on electroless coating would further extend the practical applications of titanium alloys in the engineering fields.
Alteration of chromosome structure impacts gene expressions implicated in pancreatic ductal adenocarcinoma cells
Authors: Han Wenrui , Shi Detong , Yang Qiu , Li Xinxin , Zhang Jian , Peng Cheng , Yan Fang 
Published: February 2024

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a five-year survival rate of approximately 10%. Genetic mutations are pivotal drivers in PDAC pathogenesis, but recent investigations also revealed the involvement of non-genetic alterations in the disease development. In this study, we undertook a multi-omics approach, encompassing ATAC-seq, RNA-seq, ChIP-seq, and Hi-C methodologies, to dissect gene expression alterations arising from changes in chromosome accessibility and chromatin three-dimensional interactions in PDAC.

Results
Our findings indicate that chromosomal structural alterations can lead to abnormal expressions on key genes during PDAC development. Notably, overexpression of oncogenes FGFR2, FOXA2, CYP2R1, and CPOX can be attributed to the augmentation of promoter accessibility, coupled with long-range interactions with distal elements. Additionally, our findings indicate that chromosomal structural alterations caused by genomic instability can lead to abnormal expressions in PDACs. As an example, by analyzing chromosomal changes, we identified a putative oncogenic gene, LPAR1, which shows upregulated expression in both PDAC cell lines and clinical samples. The overexpression is correlated with alterations in LPAR1-associated 3D genome structure and chromatin state. We further demonstrated that high LPAR1 activity is required for enhanced PDAC cell migration in vitro.

Conclusions
Collectively, our findings reveal that the chromosomal conformational alterations, in addition to the well-known genetic mutations, are critical for PDAC tumorigenesis.
Genome assembly of Medicago truncatula accession SA27063 provides insight into spring black stem and leaf spot disease resistance
Authors: Botkin Jacob R. , Farmer Andrew D. , Young Nevin D. , Curtin Shaun J. 
Published: February 2024

AbstractMedicago truncatula, model legume and alfalfa relative, has served as an essential resource for advancing our understanding of legume physiology, functional genetics, and crop improvement traits. Necrotrophic fungus, Ascochyta medicaginicola, the causal agent of spring black stem (SBS) and leaf spot is a devasting foliar disease of alfalfa affecting stand survival, yield, and forage quality. Host resistance to SBS disease is poorly understood, and control methods rely on cultural practices. Resistance has been observed in M. truncatula accession SA27063 (HM078) with two recessively inherited quantitative-trait loci (QTL), rnpm1 and rnpm2, previously reported. To shed light on host resistance, we carried out a de novo genome assembly of HM078. The genome, referred to as MtHM078 v1.0, is comprised of 23 contigs totaling 481.19 Mbp. Notably, this assembly contains a substantial amount of novel centromere-related repeat sequences due to deep long-read sequencing. Genome annotation resulted in 98.4% of BUSCO fabales proteins being complete. The assembly enabled sequence-level analysis of rnpm1 and rnpm2 for gene content, synteny, and structural variation between SBS-resistant accession SA27063 (HM078) and SBS-susceptible accession A17 (HM101). Fourteen candidate genes were identified, and some have been implicated in resistance to necrotrophic fungi. Especially interesting candidates include loss-of-function events in HM078 because they fit the inverse gene-for-gene model, where resistance is recessively inherited. In rnpm1, these include a loss-of-function in a disease resistance gene due to a premature stop codon, and a 10.85 kbp retrotransposon-like insertion disrupting a ubiquitin conjugating E2. In rnpm2, we identified a frameshift mutation causing a loss-of-function in a glycosidase, as well as a missense and frameshift mutation altering an F-box family protein. This study generated a high-quality genome of HM078 and has identified promising candidates, that once validated, could be further studied in alfalfa to enhance disease resistance.
Physical symptoms and anxiety and depression in older patients with advanced cancer in China: a network analysis
Authors: Tang Mo , Su Zhongge , He Yi , Pang Ying , Zhou Yuhe , Wang Yu , Lu Yongkui , Jiang Yu , Han Xinkun , Song Lihua , Wang Liping , Li Zimeng , Lv Xiaojun , Wang Yan , Yao Juntao , Liu Xiaohong , Zhou Xiaoyi , He Shuangzhi , Zhang Yening , Song Lili , Li Jinjiang , Wang Bingmei , Tang Lili 
Published: February 2024

Abstract
Background
Little is understood about the association between psychosomatic symptoms and advanced cancer among older Chinese patients.

Methods
This secondary analysis was part of a multicenter cross-sectional study based on an electronic patient-reported outcome platform. Patients with advanced cancer were included between August 2019 and December 2020 in China. Participants (over 60 years) completed the MD Anderson Symptom Inventory (MDASI) and Hospital Anxiety and Depression Scale (HADS) to measure symptom burden. Network analysis was also conducted to investigate the network structure, centrality indices (strength, closeness, and betweenness) and network stability.

Results
A total of 1022 patients with a mean age of 66 (60–88) years were included; 727 (71.1%) were males, and 295 (28.9%) were females. A total of 64.9% of older patients with advanced cancer had one or more symptoms, and up to 80% had anxiety and depression. The generated network indicated that the physical symptoms, anxiety and depression symptom communities were well connected with each other. Based on an evaluation of the centrality indices, ‘distress/feeling upset’ (MDASI 5) appears to be a structurally important node in all three networks, and ‘I lost interest in my own appearance’ (HADS-D4) had the lowest centrality indices. The network stability was relatively high (> 0.7).

Conclusion
The symptom burden remains high in older patients with advanced cancer in China. Psychosomatic symptoms are highly interactive and often present as comorbidities. This network can be used to provide targeted interventions to optimize symptom management in older patients with advanced cancer in China.

Trial registration
Chinese Clinical Trial Registry (ChiCTR1900024957), registered on 06/12/2020.
The severity of andropause symptoms and its relationship with social well-being among retired male nurses: a preliminary cross-sectional study
Authors: Nikjou Roya , Ajri-Khameslou Mehdi , Jegargoosheh Shiva , Momeni Parisa , Nemati-Vakilabad Reza 
Published: February 2024

AbstractBackgroundAndropause is a syndrome that occurs due to decreased androgen levels in men. Various aspects of health, such as social well-being, can affect andropause status during men’s retirement. This study aimed to determine the severity of andropause symptoms and its relationship with social well-being among retired male nurses.MethodsThis preliminary cross-sectional study was conducted on 284 retired male nurses in Ardabil (northwest of Iran). The participants were selected through the census sampling method. Data were collected using a demographic information form, the Male Andropause Symptoms Self-Assessment Questionnaire (MASSQ), and the Social Well-Being Scale (SWBS). Data were analyzed using SPSS software (version 22.0).ResultsThe study found that the overall mean scores of the severity of andropause symptoms and social well-being among retired male nurses were 57.24 ± 12.62 (range = 35–91) and 94.54 ± 12.77 (range = 75–123), respectively. The highest and lowest mean scores between dimensions of social well-being were related to social contribution (20.26 ± 2.47) and social acceptance (15.26 ± 2.77), respectively. Multiple linear regression analysis revealed that subscales of social well-being, age, marital status, and spouse’s menopause were predictors of the severity of andropause symptoms among retired male nurses. The selected predictors accounted for 53.1% of the total variance in severity of andropause symptoms (F = 36.613,p < 0.001).ConclusionThe results showed a moderate to severe prevalence of andropause among retired male nurses and a significant association between andropause and social well-being. The study suggests further research to examine sexual orientation and other factors that may affect andropause in retired male nurses.
Clinical success of anti-infective combination therapy compare to monotherapy in patients with carbapenem-resistant Pseudomonas aeruginosa infection: a 10-years retrospective study
Authors: Chen Jialong , Lin Jing , Weng Jianzhen , Ju Yang , Li Yanming 
Published: February 2024

Abstract
Background
Carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection has become a major public health concern. The recommendations for monotherapy and combination therapy in the current guidelines lack sufficient evidence to support them. The primary objective of this study is to determine the effectiveness of anti-Infective combination therapy compared to monotherapy in achieving clinical success in patients with CRPA infection and risk factors of clinical failure of monotherapy.

Methods
A retrospective study from Medical Information Mart for Intensive Care IV (MIMIC-IV) was conducted. We included adults with infections caused by CRPA. The outcomes of this study were clinical success, complete clinical success, and 28-day all-cause mortality.

Results
A total of 279 subjects were finally enrolled. The rate of clinical success for combination therapy was higher than that for monotherapy (73.1% versus 60.4%, p=0.028). Compared to clinical failure patients, patients in the clinical success group were more likely to die within 28 days after CRPA was found (48.3% versus 3.6%, p<0.001). In a multivariate logistic regression analysis, monotherapy was found to be significantly correlated with clinical success (OR, 0.559, 95% CI, 0.321-0.976; p = 0.041).

Conclusion
Combination therapy is more effective for CRPA infection patients, especially those whose SOFA score is ≥ 2 or whose Charlson comorbidity index is ≥ 6.
A clinical 3D pointing test differentiates spatial memory deficits in dementia and bilateral vestibular failure
Authors: Gerb J. , Brandt T. , Dieterich M. 
Published: February 2024

Abstract
Background
Deficits in spatial memory, orientation, and navigation are often neglected early signs of cognitive impairment or loss of vestibular function. Real-world navigation tests require complex setups. In contrast, simple pointing at targets in a three-dimensional environment is a basic sensorimotor ability which provides an alternative measure of spatial orientation and memory at bedside. The aim of this study was to test the reliability of a previously established 3D-Real-World Pointing Test (3D-RWPT) in patients with cognitive impairment due to different neurodegenerative disorders, bilateral vestibulopathy, or a combination of both compared to healthy participants.

Methods
The 3D-RWPT was performed using a static array of targets in front of the seated participant before and, as a transformation task, after a 90-degree body rotation around the yaw-axis. Three groups of patients were enrolled: (1) chronic bilateral vestibulopathy (BVP) with normal cognition (n = 32), (2) cognitive impairment with normal vestibular function (n = 28), and (3) combined BVP and cognitive impairment (n = 9). The control group consisted of age-matched participants (HP) without cognitive and vestibular deficits (n = 67). Analyses focused on paradigm-specific mean angular deviation of pointing in the azimuth (horizontal) and polar (vertical) spatial planes, of the preferred pointing strategy (egocentric or allocentric), and the resulting shape configuration of the pointing array relative to the stimulus array. Statistical analysis was performed using age-corrected ANCOVA-testing with Bonferroni correction and correlation analysis using Spearman’s rho.

Results
Patients with cognitive impairment employed more egocentric pointing strategies while patients with BVP but normal cognition and HP used more world-based solutions (pBonf 5.78 × 10-3**). Differences in pointing accuracy were only found in the azimuth plane, unveiling unique patterns where patients with cognitive impairment showed decreased accuracy in the transformation tasks of the 3D-RWPT (pBonf < 0.001***) while patients with BVP struggled in the post-rotation tasks (pBonf < 0.001***). Overall azimuth pointing performance was still adequate in some patients with BVP but significantly decreased when combined with a cognitive deficit.

Conclusion
The 3D-RWPT provides a simple and fast measure of spatial orientation and memory. Cognitive impairment often led to a shift from world-based allocentric pointing strategy to an egocentric performance with less azimuth accuracy compared to age-matched controls. This supports the view that cognitive deficits hinder the mental buildup of the stimulus pattern represented as a geometrical form. Vestibular hypofunction negatively affected spatial memory and pointing performance in the azimuth plane. The most severe spatial impairments (angular deviation, figure frame configuration) were found in patients with combined cognitive and vestibular deficits.
Causal effects of endometriosis on SLE, RA and SS risk: evidence from meta-analysis and Mendelian randomization
Authors: Tang Tianyou , Zhong Yi , Xu Sipei , Yu Huilin 
Published: February 2024

Background
Endometriosis is an underdiagnosed disorder that affects an estimated 6-10% of women of reproductive age. Endometriosis has been reported in epidemiological studies to be associated with autoimmune diseases. However, the relationship remains controversial.

Methods
A meta-analysis of observational studies was undertaken to evaluate the risk of autoimmune diseases in patients with endometriosis. The relevant studies were retrieved via the databases Medline, Embase and Web of Science until July 20, 2023. Mendelian randomization (MR) was subsequently utilized to scrutinize the causal influence of genetic predisposition toward endometriosis on three autoimmune diseases.

Results
The meta-analysis findings revealed a relationship between endometriosis and the onset of SLE (cohort studies: RR = 1.77, 95% confidence interval (CI): 1.47–2.13, I2 = 0%; Case-control and cross-sectional studies: OR = 5.23, 95% CI: 0.74–36.98, I2 = 98%), RA (cohort studies: RR = 2.18, 95% CI: 1.85–2.55, I2 = 92%; Case-control and cross-sectional studies: OR = 1.40, 95% CI: 1.19–1.64, I2 = 0%) and SS (cohort studies: RR = 1.49, 95% CI: 1.34–1.66, I2 = 0%). Similarly, in our MR study, the results of the inverse-variance-weighted (IVW) model suggested that genetic predisposition to endometriosis was causally associated with an increased risk for SLE (OR = 1.915, 95% CI: 1.204–3.045, p = 0.006) and RA (OR = 1.005, 95% CI: 1.001–1.009, p = 0.014).

Conclusions
Both our meta-analysis and MR study indicate that endometriosis increases the risk of autoimmune diseases. These findings not only broaden our understanding of the genetic mechanisms underlying the comorbidity of endometriosis and autoimmune diseases, but also offer a new strategy for autoimmune disease prevention.
Social factors and age play a significant role in cervical cancer and advanced-stage disease among Danish women
Authors: Bønløkke Sara , Blaakær Jan , Steiniche Torben , Iachina Maria 
Published: February 2024

Abstract
Background
For cervical cancer (CC), the implementation of preventive strategies has the potential to make cervical cancer occurrence and death largely avoidable. To better understand the factors possibly responsible for cervical cancer, we aimed to examine possible differences in age and social parameters as well as screening status between women with low- or high-stage cervical cancer and matched controls.

Methods
Through the Danish Cancer Registry (DCR), women diagnosed with cervical cancer in Denmark between 1987 and 2016 were included. These were age- and residence-matched in a 1:5 ratio with controls from the general female population. The study population was sub grouped into a low-stage subpopulation with women with early-stage cervical cancer and matched controls and a high-stage subpopulation with women with late-stage cervical cancer and matched controls. Age and social parameters were compared within the subpopulations as well as between low- and high-stage cases. For part of the study population, screening attendance was examined to compare differences in adherence.

Results
Overall, we found that the risk of cervical cancer is significantly increased in socially disadvantaged women and not least non-attenders in screening. Interestingly, the high-stage subpopulation was significantly older than the low-stage subpopulation (p < 0.001), and when examining the impact of age further, we found that for cervical cancer cases, the risk of having low-stage disease decreases significantly with increasing age, whereas the risk of having high-stage disease increases significantly with increasing age. In the screening cohort, significantly less cases than controls were attenders in screening with the most pronounced differences seen in the old subpopulation (women aged 50–64 years) and in the high-stage subpopulation (p-values all < 0.001). Interestingly, when examining the risk of CC for attenders and non-attenders, we demonstrated that many social parameters continue to influence the risk of cervical cancer, even in women attending screening.

Conclusions
Older women, socially disadvantaged women, and non-attenders in screening are particularly vulnerable in terms of developing cervical cancer, especially high-stage disease. Therefore, improvements in the participating rate in screening as well as a revision of the current screening guidelines are needed.
Surrogacy of one-year survival for overall survival in advanced hepatocellular carcinoma
Authors: Jin Yuzhi , Ren Hui , Yue Qianhua , Wu Wei , Liu Chuan , Guo Yixuan , Zhao Peng 
Published: February 2024

Abstract
Background
The increasing number of sequential treatments complicates the evaluation of overall survival (OS) in clinical trials for hepatocellular carcinoma (HCC), therefore, reliable surrogate endpoints (SEs) are required. This study aimed to evaluate the surrogacy of progression-free survival (PFS) and one-year (1-yr) milestone survival for OS in HCC trials.

Methods
We systematically searched databases for randomized clinical trials that evaluated systemic treatments for advanced HCC. Individual patient data were reconstructed to calculate the 1-yr survival rate. We adopted a two-stage meta-analytic validation model to evaluate the correlation between SEs and OS, and the correlation between treatment effects on SEs and OS. The hazard ratio (HR) was calculated to assess the treatment effects on PFS and OS, and the 1-yr survival ratio was calculated to evaluate the treatment effects on the 1-yr milestone survival.

Results
Thirty-two HCC trials involving 13,808 patients were included. A weak correlation was detected between the median PFS and median OS (R2 = 0.32), whereas the correlation improved between PFS HR and OS HR (R2 = 0.58). We identified strong correlations between the 1-yr survival rate and median OS and between the 1-yr survival ratio and OS HR (R2 = 0.74 and 0.65, respectively). In subgroup analyses, PFS HR strongly correlated with OS HR in trials relevant to immune checkpoint inhibitors (ICIs). Although the correlation remained weak between PFS and OS even in trials with PFS HR ≤ 0.6, the 1-yr survival rate and 1-yr survival ratio were strong surrogates for median OS and OS HR, respectively (R2 = 0.77 and 0.75).

Conclusions
One-year milestone survival outperformed PFS as a SE for OS in HCC, indicating the application of 1-yr survival as a secondary endpoint. In particular, PFS HR was a potential SE for OS HR in the ICI trials.