bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of circulating histone detection by mass spectrometry for early diagnosis, prognosis, and management of critically ill septic patients
Authors: García-Giménez José Luis , García-López Eva , Mena-Mollá Salvador , Beltrán-García Jesús , Osca-Verdegal Rebeca , Nacher-Sendra Elena , Aguado-Velasco Carmen , Casabó-Vallés Germán , Romá-Mateo Carlos , Rodriguez-Gimillo María , Antúnez Oreto , Ferreres José , Pallardó Federico V. , Carbonell Nieves 
Published: May 2023

Abstract
Background
As leading contributors to worldwide morbidity and mortality, sepsis and septic shock are considered a major global health concern. Proactive biomarker identification in patients with sepsis suspicion at any time remains a daunting challenge for hospitals. Despite great progress in the understanding of clinical and molecular aspects of sepsis, its definition, diagnosis, and treatment remain challenging, highlighting a need for new biomarkers with potential to improve critically ill patient management. In this study we validate a quantitative mass spectrometry method to measure circulating histone levels in plasma samples for the diagnosis and prognosis of sepsis and septic shock patients.

Methods
We used the mass spectrometry technique of multiple reaction monitoring to quantify circulating histones H2B and H3 in plasma from a monocenter cohort of critically ill patients admitted to an Intensive Care Unit (ICU) and evaluated its performance for the diagnosis and prognosis of sepsis and septic shock (SS).

Results
Our results highlight the potential of our test for early diagnosis of sepsis and SS. H2B levels above 121.40 ng/mL (IQR 446.70) were indicative of SS. The value of blood circulating histones to identify a subset of SS patients in a more severe stage with associated organ failure was also tested, revealing circulating levels of histones H2B above 435.61 ng/ml (IQR 2407.10) and H3 above 300.61 ng/ml (IQR 912.77) in septic shock patients with organ failure requiring invasive organ support therapies. Importantly, we found levels of H2B and H3 above 400.44 ng/mL (IQR 1335.54) and 258.25 (IQR 470.44), respectively in those patients who debut with disseminated intravascular coagulation (DIC). Finally, a receiver operating characteristic curve (ROC curve) demonstrated the prognostic value of circulating histone H3 to predict fatal outcomes and found for histone H3 an area under the curve (AUC) of 0.720 (CI 0.546–0.895) p < 0.016 on a positive test cut-off point at 486.84 ng/mL, showing a sensitivity of 66.7% and specificity of 73.9%.

Conclusions
Circulating histones analyzed by MS can be used to diagnose SS and identify patients at high risk of suffering DIC and fatal outcome.
Pyroptosis patterns influence the clinical outcome and immune microenvironment characterization in HPV-positive head and neck squamous cell carcinoma
Authors: Li Doudou , Ma Dong , Hou Yuxia 
Published: May 2023

Abstract
Background
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous tumor with diverse molecular pathological profiles. Recent studies have suggested the vital role of pyroptosis in tumor microenvironment. However, the expression patterns of pyroptosis in HPV-positive HNSCC are still unclear.

Methods
Unsupervised clustering analysis was used to identify the pyroptosis patterns based on the RNA-sequencing data of 27 pyroptosis-related genes (PRGs) in HPV-positive HNSCC samples. Random forest classifier and artificial neural network were performed to screen the signature genes associated with pyroptosis, which were verified in two independent external cohorts and qRT-PCR experiment. Principal component analysis was used to develop a scoring system, namely Pyroscore.

Results
The expression variations of 27 PRGs in HPV-positive HNSCC patients were analyzed from genomic and transcriptional domains. Two pyroptosis-related subtypes with distinct clinical outcomes, enrichment pathways and immune characteristics were identified. Next, six signature genes (GZMB, LAG3, NKG7, PRF1, GZMA and GZMH) associated with pyroptosis were selected for prognostic prediction. Further, a Pyroscore system was constructed to determine the level of pyroptosis in each patient. A low Pyroscore was featured by better survival time, increased immune cell infiltration, higher expression of immune checkpoint molecules and T cell-inflamed genes, as well as elevated mutational burden. The Pyroscore was also related to the sensitivity of chemotherapeutic agents.

Conclusions
The pyroptosis-related signature genes and Pyroscore system may be reliable predictors of prognosis and serve as mediators of immune microenvironment in patients with HPV-positive HNSCC.
PD-L1 expression, morphology, and molecular characteristic of a subset of aggressive uterine tumor resembling ovarian sex cord tumor and a literature review
Authors: Xiong Si-Ping , Luo Rong-Zhen , Wang Fang , Yang Xia , Lai Jun-Peng , Zhang Chao , Liu Li-Li 
Published: May 2023

Abstract
Background
Uterine tumors resembling ovarian sex cord tumor (UTROSCT) is a rare neoplasm of unknown etiology and has undetermined malignant potential. The emergence of recurrent UTROSCT case reports has led to its initial identification as a tumor of low malignancy potential. Owing to its low incidence, we currently lack any in-depth studies regarding the subset of UTROSCTs that may be aggressive in nature. Here, we sought to identify unique characteristics in aggressive UTROSCT.

Methods
19 cases of UTROSCT were collected. Their histologic and tumor immune microenvironment were evaluated by three gynecologic pathologists. The gene alteration was also detected by RNA sequencing. For later analyses regarding differences between benign and malignant tumors, we supplemented our 19 included cases with additional reports from the literature.

Results
Interestingly, we found PD-L1 expression in stromal tumor-infiltrating immune cells (stromal PD-L1) was markedly higher in aggressive UTROSCT. Patients with high stromal PD-L1 (≥ 22.5 cells/mm2) had worse prognosis. When our cases were added with previous cases identified in the literature, we discovered that aggressive UTROSCT was more likely to have significant mitotic activity and NCOA2 gene alterations than benign UTROSCT. Consistence with those results, patients with significant mitotic activity and gene alteration of NCOA2 had worse prognoses.

Conclusions
Collectively, high expression of stromal PD-L1, significant mitotic activity, and gene alteration of NCOA2 may be useful markers to predict aggressive UTROSCT.
Vascular response patterns to targeted therapies in murine breast cancer models with divergent degrees of malignancy
Authors: Hoffmann Emily , Gerwing Mirjam , Krähling Tobias , Hansen Uwe , Kronenberg Katharina , Masthoff Max , Geyer Christiane , Höltke Carsten , Wachsmuth Lydia , Schinner Regina , Hoerr Verena , Heindel Walter , Karst Uwe , Eisenblätter Michel , Maus Bastian , Helfen Anne , Faber Cornelius , Wildgruber Moritz 
Published: May 2023

Abstract
Background
Response assessment of targeted cancer therapies is becoming increasingly challenging, as it is not adequately assessable with conventional morphological and volumetric analyses of tumor lesions. The tumor microenvironment is particularly constituted by tumor vasculature which is altered by various targeted therapies. The aim of this study was to noninvasively assess changes in tumor perfusion and vessel permeability after targeted therapy in murine models of breast cancer with divergent degrees of malignancy.

Methods
Low malignant 67NR or highly malignant 4T1 tumor-bearing mice were treated with either the multi-kinase inhibitor sorafenib or immune checkpoint inhibitors (ICI, combination of anti-PD1 and anti-CTLA4). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with i.v. injection of albumin-binding gadofosveset was conducted on a 9.4 T small animal MRI. Ex vivo validation of MRI results was achieved by transmission electron microscopy, immunohistochemistry and laser ablation-inductively coupled plasma-mass spectrometry.

Results
Therapy-induced changes in tumor vasculature differed between low and highly malignant tumors. Sorafenib treatment led to decreased tumor perfusion and endothelial permeability in low malignant 67NR tumors. In contrast, highly malignant 4T1 tumors demonstrated characteristics of a transient window of vascular normalization with an increase in tumor perfusion and permeability early after therapy initiation, followed by decreased perfusion and permeability parameters. In the low malignant 67NR model, ICI treatment also mediated vessel-stabilizing effects with decreased tumor perfusion and permeability, while ICI-treated 4T1 tumors exhibited increasing tumor perfusion with excessive vascular leakage.

Conclusion
DCE-MRI enables noninvasive assessment of early changes in tumor vasculature after targeted therapies, revealing different response patterns between tumors with divergent degrees of malignancy. DCE-derived tumor perfusion and permeability parameters may serve as vascular biomarkers that allow for repetitive examination of response to antiangiogenic treatment or immunotherapy.
The Ras small GTPase RSR1 regulates cellulase production in Trichoderma reesei
Authors: Li Ni , Qiu Zhouyuan , Cai Wanchuan , Shen Yaling , Wei Dongzhi , Chen Yumeng , Wang Wei 
Published: May 2023

Abstract
Background
Lignocellulose is the most abundant renewable resource in the world and has attracted widespread attention. It can be hydrolyzed into sugars with the help of cellulases and hemicellulases that are secreted by filamentous fungi. Several studies have revealed that the Ras small GTPase superfamily regulates important cellular physiological processes, including synthesis of metabolites, sporulation, and cell growth and differentiation. However, it remains unknown how and to what extent Ras small GTPases participate in cellulase production.

Results
In this study, we found that the putative Ras small GTPase RSR1 negatively regulated the expression of cellulases and xylanases. Deletion of rsr1 (∆rsr1) significantly increased cellulase production and decreased the expression levels of ACY1-cAMP-protein kinase A (PKA) signaling pathway genes and the concentration of intracellular cyclic adenosine monophosphate (cAMP). Loss of acy1 based on ∆rsr1 (∆rsr1∆acy1) could further increase cellulase production and the expression levels of cellulase genes, while overexpression of acy1 based on ∆rsr1 (∆rsr1-OEacy1) significantly reduced cellulase production and transcriptional levels of cellulase genes. In addition, our results revealed that RSR1 negatively controlled cellulase production via the ACY1-cAMP-PKA pathway. Transcriptome analysis revealed significantly increased expression of three G-protein coupled receptors (GPCRs; tre62462, tre58767, and tre53238) and approximately two-fold higher expression of ACE3 and XYR1, which transcriptionally activated cellulases with the loss of rsr1. ∆rsr1∆ tre62462 exhibited a decrease in cellulase activity compared to ∆rsr1, while that of ∆rsr1∆tre58767 and ∆rsr1∆tre53238 showed a remarkable improvement compared to ∆rsr1. These findings revealed that GPCRs on the membrane may sense extracellular signals and transmit them to rsr1 and then to ACY1-cAMP-PKA, thereby negatively controlling the expression of the cellulase activators ACE3 and XYR1. These data indicate the crucial role of Ras small GTPases in regulating cellulase gene expression.

Conclusions
Here, we demonstrate that some GPCRs and Ras small GTPases play key roles in the regulation of cellulase genes in Trichoderma reesei. Understanding the roles of these components in the regulation of cellulase gene transcription and the signaling processes in T. reesei can lay the groundwork for understanding and transforming other filamentous fungi.
Comparison of 6-min walk test distance vs. estimated maximum oxygen consumption for predicting postoperative pulmonary complications in patients undergoing upper abdominal surgery: a prospective cohort study
Authors: Yin Xin , Wang Jingwen , Xu Zhibo , Qian Fuyong , Liu Songbin , Cai Yuxi , Jiang Zhaoshun , Zhang Xixue , Gu Weidong 
Published: May 2023

Abstract
Objective
The present study aims to evaluate the predictive ability of estimated maximum oxygen consumption (e$$\dot{V}$$

V
˙

O2max) and 6-min walk distance (6MWD) for postoperative pulmonary complications (PPCs) in adult surgical patients undergoing major upper abdominal surgery.

Method
This study was conducted by collecting data prospectively from a single center. The two predictive variables in the study were defined as 6MWD and e$$\dot{V}$$

V
˙

O2max. Patients scheduled for elective major upper abdominal surgery from March 2019 to May 2021 were included. The 6MWD was measured for all patients before surgery. e$$\dot{V}$$

V
˙

O2max was calculated using the regression model of Burr, which uses 6MWD, age, gender, weight, and resting heart rate (HR) to predict aerobic fitness. The patients were categorized into PPC and non-PPC group. The sensitivity, specificity, and optimum cutoff values for 6MWD and e$$\dot{V}$$

V
˙

O2max were calculated to predict PPCs. The area under the receiver operating characteristic curve (AUC) of 6MWD or e$$\dot{V}$$

V
˙

O2max was constructed and compared using the Z test. The primary outcome measure was the AUC of 6MWD and e$$\dot{V}$$

V
˙

O2max in predicting PPCs. In addition, the net reclassification index (NRI) was calculated to assess ability of e$$\dot{V}$$

V
˙

O2max compared with 6MWT in predicting PPCs.

Results
A total of 308 patients were included 71/308 developed PPCs. Patients unable to complete the 6-min walk test (6MWT) due to contraindications or restrictions, or those taking beta-blockers, were excluded. The optimum cutoff point for 6MWD in predicting PPCs was 372.5 m with a sensitivity of 63.4% and specificity of 79.3%. The optimum cutoff point for e$$\dot{V}$$

V
˙

O2max was 30.8 ml/kg/min with a sensitivity of 91.6% and specificity of 79.3%. The AUC for 6MWD in predicting PPCs was 0.758 (95% confidence interval (CI): 0.694–0.822), and the AUC for e$$\dot{V}$$

V
˙

O2max was 0.912 (95%CI: 0.875–0.949). A significantly increased AUC was observed in e$$\dot{V}$$

V
˙

O2max compared to 6MWD in predicting PPCs (P < 0.001, Z = 4.713). And compared with 6MWT, the NRI of e$$\dot{V}$$

V
˙

O2max was 0.272 (95%CI: 0.130, 0.406).

Conclusion
The results suggested that e$$\dot{V}$$

V
˙

O2max calculated from the 6MWT is a better predictor of PPCs than 6MWD in patients undergoing upper abdominal surgery and can be used as a tool to screen patients at risk of PPCs.
Amino acid profile, physico-chemical properties and fatty acids composition of some fruit seed kernels after detoxification
Authors: Mustafa Mustafa Abdel-Moneim , Sorour Mohamed Abdel-Hamid , Mehanni Abul-Hamd El‐Sayed , Hussien Saleh Mahmoud 
Published: May 2023

Abstract
Background
The use of food processing wastes and by-products, as well as the under-utilization of agricultural products, have recently received increased attention. Mango, apricot and peach are the three most significant fruits grown and processed in Egypt.

Results
This work aimed to evaluate the amino acid composition, physio-chemical properties and fatty acids content of mango, apricot, and peach seed kernels after removal antinutritional components. According to the results, mango kernel flour contained all the essential amino acids with levels higher than those of the FAO/WHO reference protein. In addition, total essential amino acids were 28.88, 26.78 and 36.46 g/100 g protein for apricot, peach and mango kernel flours, respectively. The highest essential amino acids value was leucine, while the highest non-essential amino acids value was glutamic in all kernel protein. All kernel oils showed adequate values for acid and peroxide value. The main unsaturated fatty acids in all kernel oils were oleic and linoleic acids. Oleic acid contents ranged between 41.76% and 59.87%. On the other hand, linoleic acid contents varied between 5.25% and 26.61%.

Conclusions
Mango, apricot, and peach kernels are by-products that present a novel potential source of excellent protein and oil that might be used for food and other industrial applications after reduction of antinutritional matter. As a result, detoxified kernel flour might be used to enhance high-value food products with economical, high-quality sources of protein and oil.

Graphical Abstract
Acetate and propionate effects in response to LPS in a porcine intestinal co-culture model
Authors: Andrani Melania , Borghetti Paolo , Ravanetti Francesca , Cavalli Valeria , Ferrari Luca , De Angelis Elena , Martelli Paolo , Saleri Roberta 
Published: May 2023

Abstract
Background
The interest in acetate and propionate as short chain fatty acids (SCFA) derives from research on alternative strategies to the utilization of antibiotics in pig farms. SCFA have a protective role on the intestinal epithelial barrier and improve intestinal immunity by regulating the inflammatory and immune response. This regulation is associated with an increase in intestinal barrier integrity, mediated by the enhancement of tight junction protein (TJp) functions, which prevent the passage of pathogens through the paracellular space. The purpose of this study was to evaluate the effect of in vitro supplementation with SCFA (5 mM acetate and 1 mM propionate) on viability, nitric oxide (NO) release (oxidative stress), NF-κB gene expression, and gene and protein expression of major TJp (occludin [OCLN], zonula occludens-1 [ZO-1], and claudin-4 [CLDN4]) in a porcine intestinal epithelial cell (IPEC-J2) and peripheral blood mononuclear cell (PBMC) co-culture model upon LPS stimulation, through which an acute inflammatory state was simulated.

Results
Firstly, the inflammatory stimulus induced by LPS evaluated in the IPEC-J2 monoculture was characterized by a reduction of viability, gene expression of TJp and OCLN protein synthesis, and an increase of NO release. The response evaluated in the co-culture showed that acetate positively stimulated the viability of both untreated and LPS-stimulated IPEC-J2 and reduced the release of NO in LPS-stimulated cells. Acetate also promoted an increase of gene expression of CLDN4, ZO-1, and OCLN, and protein synthesis of CLDN4, OCLN and ZO-1 in untreated and LPS-stimulated cells. Propionate induced a reduction of NO release in both untreated and LPS-stimulated IPEC-J2. In untreated cells, propionate induced an increase of TJp gene expression and of CLDN4 and OCLN protein synthesis. Contrarily, propionate in LPS-stimulated cells induced an increase of CLDN4 and OCLN gene expression and protein synthesis. PBMC were influenced by acetate and propionate supplementation, in that NF-κB expression was strongly downregulated in LPS-stimulated cells.

Conclusions
The present study demonstrates the protective effect of acetate and propionate upon acute inflammation by regulating epithelial tight junction expression and protein synthesis in a co-culture model, which simulates the in vivo interaction between epithelial intestinal cells and local immune cells.
Results from a randomised controlled pilot study of the Better Conversations with Primary Progressive Aphasia (BCPPA) communication partner training program for people with PPA and their communication partners
Authors: Volkmer A , Walton H , Swinburn K , Spector A , Warren J. D , Beeke S 
Published: May 2023

Abstract
Background
There has been a growing focus on functional communication interventions for primary progressive aphasia (PPA). These interventions aim to support individuals to participate in life situations. One such intervention, communication partner training (CPT) aims to change conversation behaviours in both the person with PPA and their communication partner (CP). CPT has a growing evidence base in stroke aphasia; however, these programmes are not designed to meet the needs of people with progressive communication difficulties. To address this, the authors developed a CPT program entitled Better Conversations with PPA (BCPPA) and undertook a pilot trial to establish for a future full trial; predicted recruitment rates, acceptability, an assessment of treatment fidelity and an appropriate primary outcome measure.

Methodology
This was a single-blind, randomised controlled pilot study comparing BCPPA to no treatment, delivered across 11 National Health Service Trusts in the UK. A random sample of eight recordings of local collaborators delivering the intervention were analysed to examine fidelity. Participants completed feedback forms reporting on acceptability. Pre- and post-intervention measures targeted conversation behaviours, communication goals and quality of life.

Results
Eighteen people with PPA and their CPs (9 randomised to BCPPA, 9 randomised to no treatment) completed the study. Participants in the intervention group rated BCPPA positively. Treatment fidelity was 87.2%. Twenty-nine of 30 intervention goals were achieved or over-achieved and 16 of 30 coded conversation behaviours demonstrated change in the intended direction. The Aphasia Impact Questionnaire was identified as the preferred outcome measure.

Conclusion
The first randomised controlled UK pilot study of a CPT program for people with PPA and their families demonstrates BCPPA is a promising intervention. The intervention was acceptable, treatment fidelity high and an appropriate measure identified. Results of this study indicate a future RCT of BCPPA is feasible.

Trial registration
Registered 28/02/2018 ISRCTN10148247.
Access to cardiovascular medicines in low- and middle-income countries: a mini review
Authors: Harrison Mark Amankwa , Marfo Afia Frimpomaa Asare , Annan Augustine , Ankrah Daniel Nii Amoo 
Published: May 2023

Abstract
Background
Many cardiovascular (CV) medicines are required for long term. However, with their limited resources, low- and middle-income countries (LMICs) may have challenges with access to cardiovascular medicines. The aim of this review was to provide a summary of available evidence on access to cardiovascular medicines in LMICs.

Methods
We searched PubMed and Google scholar for English language articles on access to cardiovascular medicines for the period 2010–2022. We also searched for articles reporting measures for challenges in access to CV medicines from 2007 to 2022. Studies conducted in LMICs, and reporting availability and affordability were included for review. We also reviewed studies reporting affordability or availability using the World Health Organisation/Health Action International (WHO/HAI) method. Levels of affordability and availability were compared.

Results
Eleven articles met the inclusion criteria for review on availability and affordability. Although availability appears to have improved, many countries did not meet the availability target of 80%. Between economies and within countries, there are equity gaps in access to CV medicines. Availability is lower in public health facilities than private facilities. Seven out of 11 studies reported availability less than 80%. Eight studies which investigated availability in the public sector reported less than 80% availability. Overall, CV medicines, especially combined treatments are not affordable in the majority of countries. Simultaneous achievement of availability and affordability target is low. In the studies reviewed, less than 1–53.5 days wages were required to purchase one month supply of CV medicines. Failure to meet affordability was 9–75%. Five studies showed that, on average 1.6 days’ wages of the Lowest-Paid Government Worker (LPGW) was required to purchase generic CV medicines in the public sector. Efficient forecasting and procurement, increased public financing and policies to improve generic use, among others are measures for improving availability and affordability.

Conclusions
Significant gaps exist in access to cardiovascular medicines in LMICs, and in many low—and lower middle—income countries access to cardiovascular medicines is low. To improve access and achieve the Global Action Plan on non-communicable diseases in these countries, policy interventions must be urgently instituted.