bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum levels of soluble urokinase plasminogen activator receptor in juvenile idiopathic arthritis: a single-center Swedish case-control study
Authors: Lewander Per , Wirestam Lina , Dahle Charlotte , Wetterö Jonas , Sjöwall Christopher 
Published: May 2023

Abstract
Objectives
Reliable biomarkers in the early stages of idiopathic arthritis (JIA) are scarce and the disease heterogeneity makes it clinically challenging to predict the risk of joint damage. Biomarkers with prognostic potential are warranted in order to individualize treatment and follow-up in JIA. The soluble urokinase plasminogen activator receptor (suPAR) has been reported as an easily measurable biomarker for prognosis and severity in several rheumatic diseases but it has never been studied in JIA.

Methods
Sera from 51 well-characterized patients with JIA and 50 age- and sex-matched control subjects were collected and stored for later analysis of suPAR. Patients were carefully followed clinically over 3 years and analysis of erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (anti-CCP) were analyzed as part of clinical routine. Signs of joint erosions were evaluated by radiography.

Results
Overall, the levels of suPAR did not differ significantly between JIA patients and controls but those with polyarticular involvement showed higher suPAR (p = 0.013). In addition, elevated suPAR were associated with joint erosions (p = 0.026). Two RF/anti-CCP negative individuals with erosions showed high levels of suPAR.

Conclusions
We present new data on the biomarker suPAR in JIA. Our results indicate that, apart from RF and anti-CCP, analysis of suPAR could be of additional value in assessing the risk of erosions. Analysis of suPAR early could potentially guide treatment decision-making in JIA, but our observations should be confirmed in prospective studies.
Experimental hepatic encephalopathy causes early but sustained glial transcriptional changes
Authors: Claeys Wouter , Van Hoecke Lien , Lernout Hannah , De Nolf Clint , Van Imschoot Griet , Van Wonterghem Elien , Verhaege Daan , Castelein Jonas , Geerts Anja , Van Steenkiste Christophe , Vandenbroucke Roosmarijn E. 
Published: May 2023

AbstractHepatic encephalopathy (HE) is a common complication of liver cirrhosis, associated with high morbidity and mortality, for which no brain-targeted therapies exist at present. The interplay between hyperammonemia and inflammation is thought to drive HE development. As such, astrocytes, the most important ammonia-metabolizing cells in the brain, and microglia, the main immunomodulatory cells in the brain, have been heavily implicated in HE development. As insight into cellular perturbations driving brain pathology remains largely elusive, we aimed to investigate cell-type specific transcriptomic changes in the HE brain. In the recently established mouse bile duct ligation (BDL) model of HE, we performed RNA-Seq of sorted astrocytes and microglia at 14 and 28 days after induction. This revealed a marked transcriptional response in both cell types which was most pronounced in microglia. In both cell types, pathways related to inflammation and hypoxia, mechanisms commonly implicated in HE, were enriched. Additionally, astrocytes exhibited increased corticoid receptor and oxidative stress signaling, whereas microglial transcriptome changes were linked to immune cell attraction. Accordingly, both monocytes and neutrophils accumulated in the BDL mouse brain. Time-dependent changes were limited in both cell types, suggesting early establishment of a pathological phenotype. While HE is often considered a unique form of encephalopathy, astrocytic and microglial transcriptomes showed significant overlap with previously established gene expression signatures in other neuroinflammatory diseases like septic encephalopathy and stroke, suggesting common pathophysiological mechanisms. Our dataset identifies key molecular mechanisms involved in preclinical HE and provides a valuable resource for development of novel glial-directed therapeutic strategies.
Graphical Abstract
Comparison of different dose accumulation strategies to estimate organ doses after stereotactic magnetic resonance-guided adaptive radiotherapy
Authors: Regnery Sebastian , Leiner Lukas , Buchele Carolin , Hoegen Philipp , Sandrini Elisabetta , Held Thomas , Deng Maximilian , Eichkorn Tanja , Rippke Carolin , Renkamp C. Katharina , König Laila , Lang Kristin , Adeberg Sebastian , Debus Jürgen , Klüter Sebastian , Hörner-Rieber Juliane 
Published: May 2023

Abstract
Introduction
Re-irradiation is frequently performed in the era of precision oncology, but previous doses to organs-at-risk (OAR) must be assessed to avoid cumulative overdoses. Stereotactic magnetic resonance-guided online adaptive radiotherapy (SMART) enables highly precise ablation of tumors close to OAR. However, OAR doses may change considerably during adaptive treatment, which complicates potential re-irradiation. We aimed to compare the baseline plan with different dose accumulation techniques to inform re-irradiation.

Patients & methods
We analyzed 18 patients who received SMART to lung or liver tumors inside prospective databases. Cumulative doses were calculated inside the planning target volumes (PTV) and OAR for the adapted plans and theoretical non-adapted plans via (1) cumulative dose volume histograms (DVH sum plan) and (2) deformable image registration (DIR)-based dose accumulation to planning images (DIR sum plan). We compared cumulative dose parameters between the baseline plan, DVH sum plan and DIR sum plan using equivalent doses in 2 Gy fractions (EQD2).

Results
Individual patients presented relevant increases of near-maximum doses inside the proximal bronchial tree, spinal cord, heart and gastrointestinal OAR when comparing adaptive treatment to the baseline plans. The spinal cord near-maximum doses were significantly increased in the liver patients (D2% median: baseline 6.1 Gy, DIR sum 8.1 Gy, DVH sum 8.4 Gy, p = 0.04; D0.1 cm³ median: baseline 6.1 Gy, DIR sum 8.1 Gy, DVH sum 8.5 Gy, p = 0.04). Three OAR overdoses occurred during adaptive treatment (DIR sum: 1, DVH sum: 2), and four more intense OAR overdoses would have occurred during non-adaptive treatment (DIR sum: 4, DVH sum: 3). Adaptive treatment maintained similar PTV coverages to the baseline plans, while non-adaptive treatment yielded significantly worse PTV coverages in the lung (D95% median: baseline 86.4 Gy, DIR sum 82.4 Gy, DVH sum 82.2 Gy, p = 0.006) and liver patients (D95% median: baseline 87.4 Gy, DIR sum 82.1 Gy, DVH sum 81.1 Gy, p = 0.04).

Conclusion
OAR doses can increase during SMART, so that re-irradiation should be planned based on dose accumulations of the adapted plans instead of the baseline plan. Cumulative dose volume histograms represent a simple and conservative dose accumulation strategy.
Non-T-depleted haploidentical transplantation with post-transplant cyclophosphamide in patients with secondary versus de novo AML in first complete remission: a study from the ALWP/EBMT
Authors: Nagler Arnon , Labopin Myriam , Blaise Didier , Raiola Anna Maria , Corral Lucia Lopez , Bramanti Stefania , Sica Simona , Kwon Mi , Koc Yener , Pavlu Jiri , Kulagin Alexander , Busca Alessandro , Rodríguez Arancha Bermúdez , Reményi Péter , Schmid Christoph , Brissot Eolia , Sanz Jaime , Bazarbachi Ali , Giebel Sebastian , Ciceri Fabio , Mohty Mohamad 
Published: May 2023

AbstractWe compared outcomes of adult patients with secondary acute myeloid leukemia (sAML) versus de novo AML after non-T-depleted haploidentical stem cell transplant (HaploSCT) with post-transplant cyclophosphamide (PTCy). Seventeen hundred and eleven AML patients (sAML-231, de novo-1480) in first complete remission transplanted from 2010 to 2021, were included. Patients with de novo AML were younger, median age 55.8 versus 60.8 years, p < 0.0001, had better transplantation comorbidity index (HCT-CI) ≥ 3 21.3% versus 40.8%, p < 0.0001 and Karnofsky performance status (KPS) with KPS ≥ 90 in 78% versus 68.5%, respectively, p = 0.002. The two patient groups did not differ with respect to gender, cytomegalovirus serostatus, and cell source. Median time from diagnosis to HaploSCT was 5.2 versus 4.9 months, respectively, p = 0.005. Fewer sAML patients received myeloablative conditioning 35.1% versus 50.1%, p < 0.0001. Two hundred and eleven sAML and 410 de novo AML patients were included in the matched-pair analysis matching two de novo AML with each sAML. No significant difference was observed in any transplantation outcome parameter between the sAML versus de novo AML groups. Two-year non-relapse mortality and relapse incidence did not differ with HaploSCT for de novo versus sAML; 21.4% versus 21%, hazard ratio (HR) = 0.98, p = 0.9 and 23.4% versus 20.6%, HR = 0.92, p = 0.67, respectively. Two-year leukemia-free survival, overall survival, and graft-versus-host disease (GVHD)-free, relapse-free survival were also not different between the de novo AML and sAML groups 55.2% versus 58.4%, HR = 0.95, p = 0.67; 61.4% versus 66.4%, HR = 0.91, p = 0.51 and 46.3% versus 48.2%, HR = 0.92, p = 0.48, respectively. Similarly, the incidence of engraftment as well as acute and chronic GVHD was similar between the 2 cohorts. In conclusion, HaploSCT with PTCy may be able to overcome the bad prognosis of sAML as results are not significantly different to those of HaploSCT in de novo AML.
BCAS2 regulates granulosa cell survival by participating in mRNA alternative splicing
Authors: Yao Xiaohong , Wang Chaofan , Sun Longjie , Yan Lu , Chen Xuexue , Lv Zheng , Xie Xiaomei , Tian Shuang , liu Wenbo , Li Lei , Zhang Hua , Liu Jiali 
Published: May 2023

Abstract
Background
Granulosa cell proliferation and differentiation are essential for follicle development. Breast cancer amplified sequence 2 (BCAS2) is necessary for spermatogenesis, oocyte development, and maintaining the genome integrity of early embryos in mice. However, the function of BCAS2 in granulosa cells is still unknown.

Results
We show that conditional disruption of Bcas2 in granulosa cells caused follicle development failure; the ratio of the positive cells of the cell proliferation markers PCNA and Ki67 were unchanged in granulosa cells. Specific deletion of Bcas2 caused a decrease in the BrdU-positive cell ratio, cell cycle arrest, DNA damage, and an increase in apoptosis in granulosa cells, and RPA1 was abnormally stained in granulosa cells. RNA-seq results revealed that knockout of Bcas2 results in unusual expression of cellular senescence genes. BCAS2 participated in the PRP19 complex to mediate alternative splicing (AS) of E2f3 and Flt3l mRNA to inhibit the cell cycle. Knockout of Bcas2 resulted in a significant decrease in the ratio of BrdU-positive cells in the human granulosa-like tumour (KGN) cell line.

Conclusions
Our results suggest that BCAS2 may influence the proliferation and survival of granulosa cells through regulating pre-mRNA splicing of E2f3 and Flt3l by forming the splicing complex with CDC5L and PRP19.
An online, peer-mentored food allergy education program improves children’s and parents’ confidence
Authors: Dhanjal Ranjit , Dine Kyle , Gerdts Jennifer , Merrill Kaitlyn , Frykas Tara Lynn M , Protudjer Jennifer LP 
Published: May 2023

Abstract
Background
Children with food allergy, and their families experience substantial burdens because of efforts necessary to minimize the risk of anaphylaxis. To this end, peer-to-peer education is paramount. Food Allergy Canada offers an online, peer-to-peer mentoring program. However, the impact of this program has not previously been formally evaluated.

Objective
To determine if Allergy Pals, an online, peer-to-peer mentoring program, for children aged 7–11 years, increased child and parental food allergy competency, and confidence. Our secondary aim was to qualitatively describe the experiences of the program.

Methods
From May 2020-May 2021, children and their parents were invited to participate in an online, anonymous survey about Allergy Pals, at pre-program, and post-program. Primary outcomes, which were described and compared using chi2 or t-tests, as appropriate for the respective variables, included food allergy competence (epinephrine carriage, signs and symptoms of anaphylaxis) and food allergy confidence (e.g. comfort asking other for food allergy-related support). Secondary outcomes included child and parent perceptions of the program, which were analysed thematically.

Results
Overall, 17 children completed the pre-program, and 11 completed the post-program survey. Corresponding numbers for parents were 25 and 23. Food allergy competence was high pre-program, and remained so post-program. Food allergy confidence improved from pre-program to post-program. E.g. Children tended to feel less left out (5/12, 41.7%; 3/10; 30.0%, respectively), a finding that was reflected also in parents’ scores. Themes identified for child and parent perceptions further supported improved food allergy confidence.

Conclusion
Although food allergy competence was high pre-program, Allergy Pals improved food allergy confidence.
Acute pancreatitis during valproic acid administration in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms: a case report
Authors: Yanaga Mako , Okamoto Naomichi , Hashimoto Reia , Igata Ryohei , Konishi Yuki , Ikenouchi Atsuko , Isomoto Naoki , Shinkai Takahiro , Harada Masaru , Yoshimura Reiji 
Published: May 2023

Abstract
Background
Valproic acid (VPA) is a relatively safe drug widely used for the treatment of epileptic seizures and mania in bipolar disorder, as well as the prevention of migraine headaches. Here, we present a case of VPA-induced pancreatitis in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms. He had no distinctive abdominal symptoms.

Case presentation
A 66-year-old Japanese man was treated with VPA for agitation and violent behavior due to vascular dementia, epileptic seizures, and psychiatric symptoms. During admission, he experienced a sudden decrease in consciousness and blood pressure. Abdominal findings were unremarkable; however, blood tests showed an inflammatory response and elevated amylase levels. Contrast-enhanced abdominal computed tomography showed diffuse pancreatic enlargement and inflammation extending to the subrenal pole. VPA-induced acute pancreatitis was diagnosed, VPA was discontinued, and high-dose infusions were administered. Acute pancreatitis resolved after treatment initiation.

Conclusions
Clinicians should be aware of this relatively rare side effect of VPA. Diagnosis may be challenging in elderly people and patients with dementia as they may present with non-specific symptoms. Clinicians should consider the risk of acute pancreatitis when using VPA in patients who cannot report spontaneous symptoms. Blood amylase and other parameters should be measured accordingly.
Intravenous injection of human umbilical cord-derived mesenchymal stem cells ameliorates not only blood glucose but also nephrotic complication of diabetic rats through autophagy-mediated anti-senescent mechanism
Authors: Li Xinyue , Guo Le , Chen Jingan , Liang Haowei , Liu Yi , Chen Wei , Zhou Li , Shan Letian , Wang Hui 
Published: May 2023

Abstract
Background
Diabetic nephropathy (DN) is one of the most severe complications of diabetes mellitus, which is characterized by early occurrence of albuminuria and end-stage glomerulosclerosis. Senescence and autophagy of podocytes play an important role in DN development. Human umbilical cord-derived mesenchymal stem cells (hucMSCs) have potential in the treatment of diabetes and its complications. However, the role of hucMSCs in the treatment of DN and the underlying mechanism remain unclear.

Methods
In vivo, a streptozotocin-induced diabetic male Sprague Dawley rat model was established to determine the renoprotective effect of hucMSCs on DN by biochemical analysis, histopathology, and immunohistochemical staining of renal tissues. And the distribution of hucMSCs in various organs in rats within 168 h was analyzed. In vitro, CCK8 assay, wound healing assay, and β-galactosidase staining were conducted to detect the beneficial effects of hucMSCs on high glucose-induced rat podocytes. Real-time PCR and western blot assays were applied to explore the mechanism of action of hucMSCs.

Results
The in vivo data revealed that hucMSCs were distributed into kidneys and significantly protected kidneys from diabetic damage. The in vitro data indicated that hucMSCs improved cell viability, wound healing, senescence of the high glucose-damaged rat podocytes through a paracrine action mode. Besides, the altered expressions of senescence-associated genes (p16, p53, and p21) and autophagy-associated genes (Beclin-1, p62, and LC3) were improved by hucMSCs. Mechanistically, hucMSCs protected high glucose-induced injury in rat podocytes by activating autophagy and attenuating senescence through the AMPK/mTOR pathway.

Conclusions
In conclusion, hucMSCs might be a promising therapeutic strategy for the clinical treatment of DN-induced renal damages.
Human bone marrow-derived mesenchymal stem overexpressing microRNA-124-3p inhibit DLBCL progression by downregulating the NFATc1/cMYC pathway
Authors: Zhao Xiaoxuan , Xu Mingxi , Hu Xuemeng , Ding Xiaolei , Zhang Xian , Xu Liye , Li Li , Sun Xiuhua , Song Jincheng 
Published: May 2023

Abstract
Background
Exosomes play important roles in intercellular communication by delivering microRNAs (miRNAs) that mediate tumor initiation and development, including those in diffuse large B cell lymphoma (DLBCL). To date, however, limited studies on the inhibitory effect of exosomes derived from human bone marrow mesenchymal stem cells (hBMSCs) on DLBCL progression have been reported. Therefore, this study aimed to investigate the role of hBMSC exosomes carrying microRNA-124-3p in the development of DLBCL.

Methods
Microarray-based expression analysis was adopted to identify differentially expressed genes and regulatory miRNAs, which revealed the candidate NFATc1. Next, the binding affinity between miR-124-3p and NFATc1 was detected by luciferase activity assays. The mechanism underlying NFATc1 regulation was investigated using lentiviral transfections. Subsequently, DLBCL cells were cocultured with exosomes derived from hBMSCs transfected with a miR-124-3p mimic or control. Proliferation and apoptosis were measured in vitro. Finally, the effects of hBMSC-miR-124-3p on tumor growth were investigated in vivo.

Results
MiR-124-3p was expressed at low levels, while NFATc1 was highly expressed in DLBCL cells. MiR-124-3p specifically targeted and negatively regulated the expression of NFATc1 in DLBCL cells, upregulated miR-124-3p-inhibited DLBCL cell proliferation and promoted apoptosis. The miR-124-3p derived from hBMSCs inhibits tumor growth both in vivo and in vitro via downregulation of the NFATc1/cMYC pathway.

Conclusion
Human bone marrow-derived mesenchymal stem cell overexpressing microRNA-124-3p represses the development of DLBCL through the downregulation of NFATc1.
Light in the box—photobiological examination chamber with light trap ventilation system for studying fungal surface cultures illustrated with Metarhizium brunneum and Beauveria brongniartii
Authors: Vrabl Pamela , Zottele Maria , Colleselli Lucia , Schinagl Christoph Walter , Mayerhofer Laura , Siewert Bianka , Strasser Hermann 
Published: May 2023

AbstractDue to their versatile way of life as saprophytes, endophytes, and entomopathogens, fungi of the genera Metarhizium and Beauveria are exposed to varying illumination conditions in their natural habitats, which makes a thorough adaptation to light very likely. While the few available studies for these genera support this assumption, research in this field is still in its infancy and the data material restricted to only a few fungal species. Thus, the aim of this work was to explore how light influences growth, conidial production and secondary metabolite formation of two industrial relevant strains of M. brunneum (MA 43, formerly M. anisopliae var. anisopliae BIPESCO 5/F52) and B. brongniartii (BIPESCO 2). To achieve this, we constructed an easily adjustable illumination device for highly standardized photophysiological studies of fungi on Petri dishes, the so-called LIGHT BOX. With the aid of this device, M. brunneum and B. brongniartii were grown on S4G or S2G agar at 25 °C for 14 days either in complete darkness or under constant illumination with red light (λpeak = 635 nm), green light (λpeak = 519 nm) or blue light (λpeak = 452 nm). In addition, for each wavelength the effect of different illumination intensities was tested, i.e., intensities of red light ranging from 22.1 ± 0.1 to 136.5 ± 0.3 µW cm-2, green light from 16.5 ± 0.1 to 96.2 ± 0.1 µW cm-2, and blue light from 56.1 ± 0.2 to 188.9 ± 0.6 µW cm-2. Both fungi strongly responded in terms of growth, conidial production, pigmentation and morphology to changes in the wavelength and irradiation intensity. The wavelength-dependent production of the well-known secondary metabolite oosporein which is secreted by the genus Beauveria in particular, was also increased under green and blue light exposure. The established LIGHT BOX system allows not only to optimize conidial production yields with these biotechnologically relevant fungi, but also allows the photobiological exploration of other fungi.
Management of regional citrate anticoagulation for continuous renal replacement therapy: guideline recommendations from Chinese emergency medical doctor consensus
Authors: Liu Shu-Yuan , Xu Sheng-Yong , Yin Lu , Yang Ting , Jin Kui , Zhang Qiu-Bin , Sun Feng , Tan Ding-Yu , Xin Tian-Yu , Chen Yu-Guo , Zhao Xiao-Dong , Yu Xue-Zhong , Xu Jun ,   Emergency Medical Doctor Branch of the Chinese Medical Doctor Association, Chen Xu-Feng , Chen Zhi , Dou Qing-Li , Guan Jian , Gui Yao-Song , Huang Zhong-Wei , Li Xiao-Min , Liu Dan-Ping , Lv Jing-Jun , Liu Yong , Qian Chuan-Yun , Shan Yi , Shi Yan , Sun Ming , Wu Hai-Ying , Xia Jian , Xu Feng , Xu Tie , Yan Xian-Liang , Yang Jian-Zhong , Yu Yong-Wu , Zhang Jin-Song , Zhang Mao , Zhang Wei , Zhao Hong-Yu , Zheng Dong-Hui , Zhou Ping , Zhu Bao-Feng , Zhu Hua-Dong , Shen Shi-Qian , Prowle John , Bellgardt Martin 
Published: May 2023

AbstractContinuous renal replacement therapy (CRRT) is widely used for treating critically-ill patients in the emergency department in China. Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT. Regional citrate anticoagulation (RCA) has been shown to potentially be safer and more effective and is now recommended as the preferred anticoagulant method for CRRT. However, there is still a lack of unified standards for RCA management in the world, and there are many problems in using this method in clinical practice. The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association (CMDA) organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues, including the advantages and disadvantages of RCA in CRRT anticoagulation, the principle of RCA, parameter settings for RCA, monitoring of RCA (mainly metabolic acid–base disorders), and special issues during RCA. Based on the latest available research evidence as well as the paneled experts’ clinical experience, considering the generalizability, suitability, and potential resource utilization, while also balancing clinical advantages and disadvantages, a total of 16 guideline recommendations were formed from the experts’ consensus.