bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma for prevention and treatment of glycocalyx degradation in trauma and sepsis
Authors: Kravitz M. S. , Kattouf N. , Stewart I. J. , Ginde A. A. , Schmidt E. P. , Shapiro N. I. 
Published: July 2024

AbstractThe endothelial glycocalyx, a gel-like layer that lines the luminal surface of blood vessels, is composed of proteoglycans, glycoproteins, and glycosaminoglycans. The endothelial glycocalyx plays an essential role in vascular homeostasis, and its degradation in trauma and sepsis can lead to microvascular dysfunction and organ injury. While there are no proven therapies for preventing or treating endothelial glycocalyx degradation, some initial literature suggests that plasma may have a therapeutic role in trauma and sepsis patients. Overall, the literature suggesting the use of plasma as a therapy for endothelial glycocalyx degradation is non-clinical basic science or exploratory. Plasma is an established therapy in the resuscitation of patients with hemorrhage for restoration of coagulation factors. However, plasma also contains other bioactive components, including sphingosine-1 phosphate, antithrombin, and adiponectin, which may protect and restore the endothelial glycocalyx, thereby helping to maintain or restore vascular homeostasis. This narrative review begins by describing the endothelial glycocalyx in health and disease: we discuss the overlapping disease mechanisms in trauma and sepsis that lead to its damage and introduce plasma transfusion as a potential therapy for prevention and treatment of endothelial glycocalyx degradation. Second, we review the literature on plasma as an exploratory therapy for endothelial glycocalyx degradation in trauma and sepsis. Third, we discuss the safety of plasma transfusion by reviewing the adverse events associated with plasma and other blood product transfusions, and we examine modern transfusion precautions that have enhanced the safety of plasma transfusion. We conclude that the literature proposes that plasma may have the potential to prevent and treat endothelial glycocalyx degradation in trauma and sepsis, indicating the need for further research.
The multifactorial approach and the food allergen-specific substitutive diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: study protocol for a randomized controlled trial—the ALASKA study
Authors: Pantoja-Arévalo Lisset , Gesteiro Eva , Pérez-Ruiz Margarita , López-Seoane Jaime , Wusterhausen Patricia , Matthias Torsten , Urrialde Rafael , González-Gross Marcela 
Published: July 2024

Abstract
Background
Adverse reactions to foodstuffs (ARFS), specifically food allergy (FA) and food intolerance (FI), are increasing worldwide and represent a major public health concern. Thus, ARFS management, its identification, evaluation, and intervention, must provide a comprehensive solution.

Objectives
(a) To develop a multifactorial strategy for ARFS management in adults with FA and/or FI; (b) to describe the multiple influential variables in ARFS within the realm of ARFS management; and (c) to design a personalized food allergen-specific substitutive diet (FASSD), as a 6-month dietary treatment option for adults with ARFS and as a component of ARFS management.

Methods
The ALASKA study will consider the following main variables as part of the ARFS management: (1) demographics and clinical information; (2) symptomatology, food and beverages intake and physical activity; (3) hematobiochemical study; (4) immunology; (5) enzymatic activity; (6) anthropometry, body composition, and physical fitness; (7) QoL; (8) 6-month intervention; (9) end of the study; and (10) other assessments. The FASSD will be designed with special emphasis on the commonly lacking micronutrients in the ARFS population: niacin, Mg, K, P, Ca, Zn, B12, folate, Fe, and fiber.

Discussion
The ALASKA study protocol has been developed as a global strategy to manage and evaluate ARFS in Spanish adults older than 18 years of age. Approaching ARFS with multiple assessments, as influencing factors, will lead to a novel strategy for ARFS management. The FASSD has been designed as a personalized tool to avoid crucial micronutrient deficiencies that a current strict food allergen avoidance or elimination diet may provoke.

Trial registration
The protocol has been approved by the Ethics Committee of the UPM (REF.20200602) and registered on ClinicalTrials.gov (NCT05802017).
Comparative speed of kill provided by lotilaner (Credelio™), sarolaner (Simparica Trio™), and afoxolaner (NexGard™) to control Amblyomma americanum infestations on dogs
Authors: Reif Kathryn E. , Kollasch Todd M. , Neilson Jacqueline C. , Herrin Brian H. , Ryan William G. , Bell Marjorie C. , Beltz Mallory S. , Dryden Michael W. , Jesudoss Chelladurai Jeba R. J. , Miller Kamilyah R. , Sutherland Cameron J. 
Published: July 2024

﻿Abstract
Background
Canine acaricides with rapid onset and sustained activity can reduce pathogen transmission risk and enhance pet owner experience. This randomized, complete block design, investigator-masked study compared the speed of kill of Amblyomma americanum provided by three monthly-use isoxazoline-containing products.

Methods
Eight randomized beagles per group were treated (day 0), per label, with sarolaner (combined with moxidectin and pyrantel, Simparica Trio™), afoxolaner (NexGard™), or lotilaner (Credelio™), or remained untreated. Infestations with 50 adult A. americanum were conducted on days − 7, − 2, 21, and 28, and tick counts were performed on day − 5 (for blocking), and at 4, 8, 12, 24, 48, and 72 h following treatment and subsequent infestations. Efficacy calculations were based on geometric mean live tick counts. A linear mixed model was used for between-group comparisons.

Results
On day 0, only lotilaner significantly reduced an A. americanum infestation by 12 h (43.3%; P = 0.002). Efficacy of lotilaner and afoxolaner at 24 h post-treatment was 95.3% and 97.6%, respectively, both significantly different from sarolaner (74%) (P = 0.002, P < 0.001, respectively). On day 21, at 12 h postinfestation, lotilaner efficacy (59.6%) was significantly different from sarolaner (0.0%) (P < 0.001) and afoxolaner (6.3%) (P < 0.001). At 24 h, lotilaner efficacy (97.4%) was significantly different (P < 0.001) from sarolaner and afoxolaner (13.6% and 14.9%, respectively). On day 28, at 12 h postinfestation, lotilaner efficacy (47.8%) was significantly different from sarolaner (17.1%) (P = 0.020) and afoxolaner (9.0%) (P = 0.006). At 24 h, lotilaner efficacy (92.3%) was significantly different from sarolaner 4.9% (P < 0.001) and afoxolaner (0.0%) (P < 0.001). Speed of kill for sarolaner and afoxolaner, but not lotilaner, significantly declined over the study period. Following reinfestation on day 28, neither sarolaner nor afoxolaner reached 90% efficacy by 48 h. By 72 h, sarolaner efficacy was 97.4% and afoxolaner efficacy was 86.3%. Only lotilaner achieved ≥ 90% efficacy by 24 h post-treatment and 24 h postinfestation on days 21 and 28. Time to ≥ 90% efficacy following new infestations consistently occurred 24–48 h earlier for lotilaner compared with sarolaner or afoxolaner.

Conclusions
Credelio (lotilaner) has a more rapid onset of acaricidal activity against A. americanum than Simparica Trio (sarolaner-moxidectin-pyrantel) and NexGard (afoxolaner). Only lotilaner’s speed of tick kill is sustained throughout the dosing period.

Graphical Abstract
Developmental stages and molecular phylogeny of Hepatozoon fitzsimonsi (Dias 1953) (Adeleorina: Hepatozoidae) in tortoises Stigmochelys pardalis (Cryptodira: Testudinidae) and ticks of the genus Amblyomma (Acari: Ixodidae) from South Africa
Authors: Mofokeng Lehlohonolo S. , Netherlands Edward C. , Smit Nico J. , Cook Courtney A. 
Published: July 2024

Abstract
Background
Hepatozoon fitzsimonsi (Dias, 1953) is a frequently found haemogregarine of southern African tortoises. At the time of this species’ reassignment from the genus Haemogregarina to Hepatozoon, developmental stages such as sporocysts and sporozoites were observed in ticks associated with H. fitzsimonsi parasitised and non-parasitised tortoises. It was thus suggested that ticks may act as the potential vectors for this parasite. However, this earlier research was unable to confirm the identity of these sporogonic stages using molecular markers. In a separate study aimed at identifying tick species parasitising South African reptiles and molecularly screening these for the presence of Hepatozoon, that study identified H. fitzsimonsi in tortoise-associated ticks. Thus, the present study aimed to revisit the potential of ticks to act as vectors for H. fitzsimonsi in tortoises using a combined microscopy and molecular approach.

Methods
Specimens of Kinixys natalensis, Kinixys spekii, Kinixys zombensis and Stigmochelys pardalis were collected from Bonamanzi and Ndumo Game Reserve, South Africa. Upon capture, animals were examined for ticks, and these were collected along with blood and other tissues. Adult ticks were dissected and visceral impression slides were prepared along with thin blood and tissue smears on clean microscope slides. Smears and impression slides were stained with Giemsa, screened and micrographs of parasites were captured. Two primer sets were employed to target fragments of the 18S rRNA gene of parasites found in both tortoises and ticks and the resulting sequences were then compared with other known H. fitzsimonsi and haemogregarine sequences from the GenBank database.

Results
Peripheral blood gamont and liver merogonic stages were observed in S. pardalis, while the sporogonic stages were observed in the haemocoel of Amblyomma ticks. Gamont and sporocyst stages compared morphologically with previous descriptions of H. fitzsimonsi, identifying them as this species. Phylogenetic analysis revealed that the blood and tick sequences obtained in this study clustered in a monophyletic clade comprising known H. fitzsimonsi.

Conclusions
The present study provides further support for ticks acting as the vectors of H. fitzsimonsi by molecularly identifying and linking observed developmental stages in tortoises (S. pardalis) with those in the invertebrate host (Amblyomma spp.).

Graphical Abstract
Revealing the microbial composition changes and relationship with Fusarium caused by rot disease in the Crocus sativus L.
Authors: Song Jia , Xi Xiaoyuan , Qian Xiaodong , Li Jing , Tao Yuanyuan , Li Liqin , Zhou Guifen 
Published: July 2024

Abstract
Purpose
Rot disease caused by Fusarium poses a formidable threat to the growth of saffron (Crocus sativus L.), resulting in substantial damage to both yield and quality. It is paramount to delve into the root causes of rot disease in saffron to optimize both yield and quality. Existing preventive and treatment modalities have exerted deleterious effects on corms and the natural environment. Consequently, the quest for efficacious and eco-friendly methods such as biological control agents has become an urgent imperative.

Methods
The disparate distribution of microbial communities between rhizospheric microorganisms and saffron serves as the foundational exploration for uncovering the underlying causes of rot disease. Samples from various saffron organs and rhizosphere soil were gathered, and the sequencing data from the microbial communities were interpreted using 16S rRNA and ITS gene sequencing methods. This facilitated an in-depth examination of the composition and changes of microorganisms in both healthy and diseased saffron plants.

Results
The findings indicated rot disease reduced the abundance and diversity of microorganisms in saffron, and the fungal co-occurrence networks were less stable and their communities were more sensitive to rot disease than the bacterial community. Fusarium was the predominant genus in diseased samples, accounting for 99.19% and 89.77% of the communities in diseased leaves and corms. With corms and leaves displaying heightened susceptibility to infection compared to other plant organs. Some of the beneficial bacterial taxa enriched in the diseased plants were also identified in networks, they showed an antagonistic relationship with Fusarium, suggesting a potential for these bacteria to be used in biologically based control strategies against rot disease. These insights could prove invaluable for the development of biocontrol agents aimed at combating this plant ailment.

Conclusion
These findings significantly advance our understanding of saffron-microbiome interactions and could provide fundamental and important data for improving saffron yield and quality in the process of sustainable development.
Role of Th2, Th17 and Treg Cells and relevant cytokines in pathogenesis of allergic rhinitis
Authors: Guo Li-Ping , Yan Min , Niu Rui-Bing , Liu Lei , Yang Jing-Ru , Chen Rui-Lian , Duan Bao-Sheng , Li Cui-Cui , Li Jian-Xiong 
Published: July 2024

Abstract
Objective
To explore the role of different cells and molecules in the pathogenesis of allergic rhinitis (AR) with positive Artemisia allergen by detecting their expression levels.

Methods
From January 2021 to December 2022,200 AR patients diagnosed in the Otolaryngology Clinic of Ordos Central Hospital were selected as the AR group, and 50 healthy people who underwent physical examination in the hospital during the same period were randomly selected as the healthy control (HC) group. The levels of GATA-3mRNA, RORγtmRNA and FoxP3mRNA in peripheral blood mononuclear cells were detected by real-time fluorescence quantitative PCR (qRT-PCR). The proportions of Th2, Th17 and Treg cells were detected by flow cytometry. The concentrations of IL-4, IL-5, IL-17 and IL-10 in serum were detected by enzyme-linked immunosorbent assay. The differences of transcription gene level, immune cell ratio and cytokine concentration between the two groups were analyzed.

Results
There was no difference in age and gender between the two groups. The levels of GATA-3mRNA and RORγtmRNA transcription genes in peripheral blood mononuclear cells, the percentage of Th2, Th17 and Treg immune cells, the levels of eosinophils and basophils in peripheral blood, the concentrations of IL-4, IL-5, IL-17, IL-10 cytokines and IgE in serum of AR patients were significantly higher than those in HC group (P < 0.05). IL-4 and IL-17 were positively correlated with total IgE level.

Conclusion
The secretion of immune cells and cytokines in peripheral blood of AR patients is abnormal. Th2, Th17, Treg specific transcription factors and related cells and cytokines are involved in the occurrence and development of allergic rhinitis.
Severe distributive shock, neutrophilic dermatosis, and ST-elevation myocardial infarction in the setting of azathioprine hypersensitivity syndrome
Authors: Su Samuel , Wang Yu Ming , Zaborniak Karver , Hamza Sate , Jassal Davinder S. , Blouw Marcus 
Published: July 2024

Abstract
Background
Azathioprine is a purine synthesis inhibitor used as an immunosuppressive therapy for many immune-mediated diseases. Azathioprine hypersensitivity reaction is a rare, life-threatening adverse reaction characterized by a range of multisystem manifestations including fever, abdominal pain, arthralgias, erythematous cutaneous eruption, acute renal failure, neutrophilia, and more rarely, distributive shock. Although acute heart failure has been rarely described in association with azathioprine hypersensitivity syndrome, myocardial infarction has, to our knowledge, never been associated with this entity.

Case Presentation
We describe a case of a 59-year-old male with Crohn’s disease who developed severe azathioprine hypersensitivity syndrome that included distributive shock, neutrophilic dermatosis, and acute coronary syndrome with ST-elevation. Clinical improvement was seen after cessation of azathioprine and administration of glucocorticoid therapy.

Conclusion
Prompt recognition of azathioprine hypersensitivity syndrome, which can manifest as shock and neutrophilic dermatosis, is key to ensure rapid azathioprine cessation.
Fluid accumulation syndrome in sepsis and septic shock: pathophysiology, relevance and treatment—a comprehensive review
Authors: Pfortmueller Carmen Andrea , Dabrowski Wojciech , Wise Rob , van Regenmortel Niels , Malbrain Manu L. N. G. 
Published: July 2024

Abstract
In this review, we aimed to comprehensively summarize current literature on pathophysiology, relevance, diagnosis and treatment of fluid accumulation in patients with sepsis/septic shock. Fluid accumulation syndrome (FAS) is defined as fluid accumulation (any degree, expressed as percentage from baseline body weight) with new onset organ-failure. Over the years, many studies have described the negative impact of FAS on clinically relevant outcomes. While the relationship between FAS and ICU outcomes is well described, uncertainty exists regarding its diagnosis, monitoring and treatment. A stepwise approach is suggested to prevent and treat FAS in patients with septic shock, including minimizing fluid intake (e.g., by limiting intravenous fluid administration and employing de-escalation whenever possible), limiting sodium and chloride administration, and maximizing fluid output (e.g., with diuretics, or renal replacement therapy). Current literature implies the need for a multi-tier, multi-modal approach to de-resuscitation, combining a restrictive fluid management regime with a standardized early active de-resuscitation, maintenance fluid reduction (avoiding fluid creep) and potentially using physical measures such as compression stockings.

Trial registration: Not applicable.

Graphical Abstract
Recognition of target domain Japanese speech using language model replacement
Authors: Mori Daiki , Ohta Kengo , Nishimura Ryota , Ogawa Atsunori , Kitaoka Norihide 
Published: July 2024

AbstractEnd-to-end (E2E) automatic speech recognition (ASR) models, which consist of deep learning models, are able to perform ASR tasks using a single neural network. These models should be trained using a large amount of data; however, collecting speech data which matches the targeted speech domain can be difficult, so speech data is often used that is not an exact match to the target domain, resulting in lower performance. In comparison to speech data, in-domain text data is much easier to obtain. Thus, traditional ASR systems use separately trained language models and HMM-based acoustic models. However, it is difficult to separate language information from an E2E ASR model because the model learns both acoustic and language information in an integrated manner, making it very difficult to create E2E ASR models for specialized target domain which are able to achieve sufficient recognition performance at a reasonable cost. In this paper, we propose a method of replacing the language information within pre-trained E2E ASR models in order to achieve adaptation to a target domain. This is achieved by deleting the “implicit” language information contained within the ASR model by subtracting the source-domain language model trained with a transcription of the ASR’s training data in a logarithmic domain. We then integrate a target domain language model through addition in the logarithmic domain. This subtraction and addition to replace of the language model is based on Bayes’ theorem. In our experiment, we first used two datasets of the Corpus of Spontaneous Japanese (CSJ) to evaluate the effectiveness of our method. We then we evaluated our method using the Japanese Newspaper Article Speech (JNAS) and CSJ corpora, which contain audio data from the read speech and spontaneous speech domain, respectively, to test the effectiveness of our proposed method at bridging the gap between these two language domains. Our results show that our proposed language model replacement method achieved better ASR performance than both non-adapted (baseline) ASR models and ASR models adapted using the conventional Shallow Fusion method.
Epigenetic modification of PHLDA2 is associated with tumor microenvironment and unfavorable outcome of immune checkpoint inhibitor-based therapies in clear cell renal cell carcinoma
Authors: Zhao Junjie , Pan Xiuyi , Wang Zilin , Chen Yuntian , Liu Dingbang , Shen Yu , Wei Xinyuan , Xu Chenhao , Zhang Xingming , Hu Xu , Chen Junru , Zhao Jinge , Tang Bo , Sun Guangxi , Shen Pengfei , Liu Zhenhua , Zeng Hao , Liang Jiayu 
Published: July 2024

Abstract
Background
A substantial proportion of patients with metastatic clear cell renal cell carcinoma (ccRCC) cannot derive benefit from immune checkpoint inhibitor (ICI) plus anti-angiogenic agent combination therapy, making identification of predictive biomarkers an urgent need. The members of pleckstrin homology-like domain family A (PHLDA) play critical roles in multiple cancers, whereas their roles in ccRCC remain unknown.

Methods
Transcriptomic, clinical, genetic alteration and DNA methylation data were obtained for integrated analyses from TCGA database. RNA sequencing was performed on 117 primary tumors and 79 normal kidney tissues from our center. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis, gene set enrichment analysis were performed to explore transcriptomic features. Data from three randomized controlled trials (RCT), including CheckMate025, IMmotion151, JAVELIN101, were obtained for validation.

Results
Members of PHLDA family were dysregulated in pan-cancer. Elevated PHLDA2 expression was associated with adverse clinicopathologic parameters and worse prognosis in ccRCC. Aberrant DNA hypomethylation contributed to up-regulation of PHLDA2. An immunosuppressive microenvironment featured by high infiltrates of Tregs and cancer-associated fibroblasts, was observed in ccRCC with higher PHLDA2 expression. Utilizing data from three RCTs, the association of elevated PHLDA2 expression with poor therapeutic efficacy of ICI plus anti-angiogenic combination therapy was confirmed.

Conclusions
Our study revealed that elevated PHLDA2 expression regulated by DNA hypomethylation was correlated with poor prognosis and immunosuppressive microenvironment, and highlighted the role of PHLDA2 as a robust biomarker for predicting therapeutic efficacy of ICI plus anti-angiogenic agent combination therapy in ccRCC, which expand the dimension of precision medicine.