bluuebunny/crossref_metadata_2025_split huggingface dataset:
ST-T segment changes in prehospital emergency physicians in the field: a prospective observational trial
Authors: Maleczek Mathias , Schebesta Karl , Hamp Thomas , Burger Achim Leo , Pezawas Thomas , Krammel Mario , Roessler Bernhard 
Published: July 2022

AbstractAimsDue to time-critical decision-making, physical strain and the uncontrolled environment, prehospital emergency management is frequently associated with high levels of stress in medical personnel. Stress has been known to cause ischemia like changes in electrocardiograms (ECGs), including arrhythmias and deviations in ST-T segments. There is a lack of knowledge regarding the occurrence of changes in ST-T segments in prehospital emergency physicians. We hypothesized that ST-T segment deviations occur in prehospital emergency physicians in the field.MethodsIn this prospective observational trial, ST-T segments of emergency physicians were recorded using 12-lead Holter ECGs. The primary outcome parameter was defined as the incidence of ST-T segment changes greater than 0.1 mV in two corresponding leads for more than 30 s per 100 rescue missions. The secondary outcomes included T-wave inversions and ST-segment changes shorter than 30 s or smaller than 0.1 mV. Surrogate parameters of stress were measured using the NASA-Task Load Index and cognitive appraisal, and their correlation with ST-T segment changes were also assessed.ResultsData from 20 physicians in 36 shifts (18 days, 18 nights) including 208 missions were analysed. Seventy percent of previously healthy emergency physicians had at least one ECG abnormality; the mean duration of these changes was 30 s. Significantly more missions with ECG changes were found during night than day shifts (39 vs. 17%, p < 0.001). Forty-nine ECG changes occurred between missions. No ST-T segment changes > 30 s and > 0.1 mV were found. Two ST-T segment changes < 30 s or < 0.1 mV (each during missions) and 122 episodes of T-wave inversions (74 during missions) were identified. ECG changes were found to be associated with alarms when asleep and NASA task load index.ConclusionECG changes are frequent and occur in most healthy prehospital emergency physicians. Even when occurring for less than 30 s, such changes are important signs for high levels of stress. The long-term impact of these changes needs further investigation.Trial registrationThe trial was registered at ClinicalTrials.gov (NCT04003883) on 1.7.2019: https://clinicaltrials.gov/ct2/show/NCT04003883?term=emergency+physician&rank=2
MiR-574-3p inhibits glucose toxicity-induced pancreatic β-cell dysfunction by suppressing PRMT1
Authors: Lv Lixia , Wang Xiumin , Shen Jinhua , Cao Ying , Zhang Qin 
Published: July 2022

Abstract
Background
Pancreatic β-cell dysfunction is commonly observed in patients with type 2 diabetes mellitus. Protein arginine methyltransferase 1 (PRMT1) plays an important role in pancreatic β-cell dysfunction. However, the detailed mechanisms remain largely unknown.

Methods
RT-qPCR, western blotting, and immunofluorescence assays were used to evaluate PRMT1 and miR-574-3p levels. Cell Counting Kit-8, Advanced Dlycation End products (AGEs), Reactive Oxygen Species (ROS), and glucose-stimulated insulin secretion were assayed, and flow cytometry and RT-qPCR were performed to detect the role of PRMT1 and miR-574-3p in MIN6 cells. Luciferase reporter assays were performed to determine the interactions between PRMT1 and miR-574-3p.

Results
High-glucose treatment resulted in the high expression of PRMT1. PRMT1 silencing could alleviate the reduced proliferation, insulin secretion, and GLUT1 level, in addition to suppressing the induced apoptosis, and AGEs and ROS levels, under high glucose conditions. MiR-574-3p was established as an upstream regulator of PRMT1 using luciferase reporter assays. More importantly, miR-574-3p reversed the effect of PRMT1 silencing in MIN6 cells.

Conclusions
miR-574-3p suppresses glucose toxicity-induced pancreatic β-cell dysfunction by targeting PRMT1.
Working toward improved monitoring of Cryptosporidium and Giardia (oo)cysts in water samples: testing alternatives to elution and immunomagnetic separation from USEPA Method 1623.1
Authors: Fradette Marie-Stéphanie , Charette Steve J. 
Published: July 2022

Abstract
Objective
This study was designed to find a method to enhance the recovery of Cryptosporidium spp. and Giardia spp. parasites from water samples for research purposes compared to the results that can be achieved with USEPA Method 1623.1. Four different approaches were used to test water samples that were artificially spiked with parasites. The approaches were: (i) Method 1623.1 itself, (ii) elution of Method 1623.1 combined with microfiltration, (iii) an elution technique based on grinding the filter membrane in a blender before the eluent was concentrated by immunomagnetic separation, and (iv) the blender elution followed by microfiltration. Fluorescence microscopy was used to determine which approach led to the highest parasite recovery rates.

Results
Method 1623.1 gave the best results for Giardia, while all four approaches were statistically equivalent for Cryptosporidium. We evaluated the costs and laboratory time requirements for each protocol to give readers a complete comparison of the methods tested. Elution of Method 1623.1 combined with microfiltration resulted in lower costs and less laboratory work time without compromising the recovery of the parasites.
Non-structural carbohydrates and morphological traits of leaves, stems and roots from tree species in different climates
Authors: Zhang Guangqi , Maillard Pascale , Mao Zhun , Brancheriau Loic , Engel Julien , Gérard Bastien , Fortunel Claire , Maeght Jean-Luc , Martínez-Vilalta Jordi , Ramel Merlin , Nourissier-Mountou Sophie , Fourtier Stéphane , Stokes Alexia 
Published: July 2022

Abstract
Objectives
Carbon fixed during photosynthesis is exported from leaves towards sink organs as non-structural carbohydrates (NSC), that are a key energy source for metabolic processes in trees. In xylem, NSC are mostly stored as soluble sugars and starch in radial and axial parenchyma. The multi-functional nature of xylem means that cells possess several functions, including water transport, storage and mechanical support. Little is known about how NSC impacts xylem multi-functionality, nor how NSC vary among species and climates. We collected leaves, stem and root xylem from tree species growing in three climates and estimated NSC in each organ. We also measured xylem traits linked to hydraulic and mechanical functioning.

Data description
The paper describes functional traits in leaves, stems and roots, including NSC, carbon, nitrogen, specific leaf area, stem and root wood density and xylem traits. Data are provided for up to 90 angiosperm species from temperate, Mediterranean and tropical climates. These data are useful for understanding the trade-offs in resource allocation from a whole-plant perspective, and to better quantify xylem structure and function related to water transportation, mechanical support and storage. Data will also give researchers keys to understanding the ability of trees to adjust to a changing climate.
Gel shift experiments with fragments of the Trypanosoma brucei RNA-binding protein RBP10
Authors: Liu Bin , Clayton Christine 
Published: July 2022

Abstract
Objective
Trypanosoma brucei is a parasite of mammals and Tsetse flies, and control of mRNA stability is critical for parasite survival in the two different hosts. T. brucei RBP10 is a protein with a single RNA Recognition Motif (RRM) which is expressed only in the mammalian (bloodstream) form. Numerous observations suggest that RBP10 binds to procyclic-specific mRNAs and targets them for destruction, and there is also some evidence for selective binding of RBP10 to RNAs containing the motif UA(U)6. We here investigated this binding further.

Results
We tested in vitro binding of RBP10 to two different probes in solution. One contained two copies of UA(U)6, and the other two copies of a mutant version, UACUCUCU, which is inactive in regulation. An N-terminal segment of RBP10, including the RRM domain and 90 residues to its C-terminus, could be produced as soluble protein. This could bind both probes in vitro with similar affinities in the low micromolar range, which is not atypical for a single RRM. Soluble RBP10 therefore did not distinguish between UA(U)6 and UACUCUCU. Since no other sequences were tested, the requirements for RBP10 RNA binding remain to be determined.
P-tau subgroups in AD relate to distinct amyloid production and synaptic integrity profiles
Authors: Wesenhagen Kirsten E. J. , Tijms Betty M. , Boonkamp Lynn , Hoede Patty L. , Goossens Julie , Dewit Nele , Scheltens Philip , Vanmechelen Eugeen , Visser Pieter Jelle , Teunissen Charlotte E. 
Published: July 2022

AbstractBackgroundWe previously identified four Alzheimer’s disease (AD) subgroups with increasingly higher cerebrospinal fluid (CSF) levels of tau phosphorylated at threonine 181 (p-tau). These subgroups included individuals across the cognitive spectrum, suggesting p-tau subgroups could reflect distinct biological changes in AD, rather than disease severity. Therefore, in the current study, we further investigated which potential processes may be related with p-tau subgroups, by comparing individuals on CSF markers for presynaptic structure [vesicle-associated membrane protein 2 (VAMP2)], postsynaptic structure [neurogranin (NRGN)], axonal damage [neurofilament light (NfL)], and amyloid production [beta-secretase 1 (BACE1) and amyloid-beta 1–40 (Aβ40)].MethodsWe selected 348 amyloid-positive (A+) individuals (53 preclinical, 102 prodromal, 193 AD dementia) and 112 amyloid-negative (A−) cognitively normal (CN) individuals from the Amsterdam Dementia Cohort (ADC). Individuals were labeled according to their p-tau subgroup (subgroup 1: p-tau ≤ 56 pg/ml; subgroup 2: 57–96 pg/ml; subgroup 3: 97–159 pg/ml; subgroup 4: > 159 pg/ml). CSF protein levels were measured with ELISA (NRGN, BACE1, Aβ40, NfL) or single-molecule array (Simoa) (VAMP2). We tested whether protein levels differed between the p-tau subgroups within A+ individuals with linear models corrected for age and sex and whether disease stage influenced these relationships.ResultsAmong A+ individuals, higher p-tau subgroups showed a higher percentage of AD dementia [subgroup 1:n= 41/94 (44%); subgroup 2:n= 81/147 (55%); subgroup 3:n= 59/89 (66%); subgroup 4:n= 7/11 (64%)]. Relative to controls, subgroup 1 showed reduced CSF levels of BACE1, Aβ40, and VAMP2 and higher levels of NfL. Subgroups 2 to 4 showed gradually increased CSF levels of all measured proteins, either across the first three (NfL and Aβ40) or across all subgroups (VAMP2, NRGN, BACE1). The associations did not depend on the clinical stage (interactionp-values ranging between 0.19 and 0.87).ConclusionsThe results suggest that biological heterogeneity in p-tau levels in AD is related to amyloid metabolism and synaptic integrity independent of clinical stage. Biomarkers reflecting amyloid metabolism and synaptic integrity may be useful outcome measures in clinical trials targeting tau pathology.
The current role and future directions of imaging in failed back surgery syndrome patients: an educational review
Authors: Witkam Richard L. , Buckens Constantinus F. , van Goethem Johan W. M. , Vissers Kris C. P. , Henssen Dylan J. H. A. 
Published: July 2022

AbstractBackgroundFailed back surgery syndrome (FBSS) is an umbrella term referring to painful sensations experienced by patients after spinal surgery, mostly of neuropathic nature. Adequate treatment of FBSS is challenging, as its etiology is believed to be multifactorial and still not fully clarified. Accurate identification of the source of pain is difficult but pivotal to establish the most appropriate treatment strategy. Although the clinical utility of imaging in FBSS patients is still contentious, objective parameters are highly warranted to map different phenotypes of FBSS and tailor each subsequent therapy.Main bodySince technological developments have weakened the applicability of prior research, this educational review outlined the recent evidence (i.e., from January 2005 onwards) after a systematic literature search. The state of the art on multiple imaging modalities in FBSS patients was reviewed. Future directions related to functional MRI and the development of imaging biomarkers have also been discussed.ConclusionBesides the fact that more imaging studies correlated with symptomatology in the postoperative setting are warranted, the current educational review outlined that contrast-enhanced MRI and MR neurography have been suggested as valuable imaging protocols to assess alterations in the spine of FBSS patients. The use of imaging biomarkers to study correlations between imaging features and symptomatology might hold future potential; however, more research is required before any promising hypotheses can be drawn.
Clinical trials of stem cell-based therapies for pediatric diseases: a comprehensive analysis of trials registered on ClinicalTrials.gov and the ICTRP portal site
Authors: Ji Yinwen , Hu Chuan , Chen Zuxing , Li Ying , Dai Jiayong , Zhang Jin , Shu Qiang 
Published: July 2022

Abstract
Background
Research on clinical trials that employ stem cells to treat children’s diseases is limited. The clinical trial registry database provides a unique window to us to get known about clinical trial researches with different statuses. However, few studies aimed to perform a comprehensive and thorough analysis of those registered trials in the aforementioned field based on ClinicalTrials.gov and the ICTRP portal site.

Methods
Our study covered the clinical researches about stem cell therapy enrolling subjects aged under 18 years old registered on ClinicalTrials.gov and WHO ICTRP before May 18, 2021. A cross-sectional study was implemented to comprehensively describe and analyze the included trials that met the criteria. Results were available on ClinicalTrials.gov, and publications related to the included trials were identified. All analyses were performed utilizing the SPSS 25.0 software.

Results
Eventually, 202 clinical trials were included and evaluated. The participant number of trials tended to be small; 71.3% were enrolled < 50. And 93.5% of the subjects were without gender restrictions. Till May 2020, 112 trials had been preliminary completed, of which only 39 trials had published papers or uploaded results. Most (73.6%) of 186 interventional trials were in phase 1 and phase 2, where 131 (70.4%) trials were conducted without masking, and 26.3% trials were randomized; 55.4% trials were performed single group assignment. Of 16 observational trials, case-only/series took up 37.5%. Hematopoietic stem cells (37.1%) and mesenchymal stem cells (36.1%) were mostly employed, while umbilical cord blood (UCB)-derived cells (24.3%) and bone marrow (BM)-derived cells (20.8%) were the major sources.

Conclusions
This study provided an overall picture of utilizing stem cells for treatment and management of childhood diseases. Since clinical trials in this area are insufficient in quantity and quality, there is an urgent need of larger, better-designed trials. Increased investment in clinical research of stem cell treatment products should be carried out to achieve the transformation of results as soon as possible. Moreover, it is important to optimize the management of the registration platform and shorten the time it takes for research results to be published.
Stem cells differentiation into insulin-producing cells (IPCs): recent advances and current challenges
Authors: Silva Isaura Beatriz Borges , Kimura Camila Harumi , Colantoni Vitor Prado , Sogayar Mari Cleide 
Published: July 2022

AbstractType 1 diabetes mellitus (T1D) is a chronic disease characterized by an autoimmune destruction of insulin-producing β-pancreatic cells. Although many advances have been achieved in T1D treatment, current therapy strategies are often unable to maintain perfect control of glycemic levels. Several studies are searching for new and improved methodologies for expansion of β-cell cultures in vitro to increase the supply of these cells for pancreatic islets replacement therapy. A promising approach consists of differentiation of stem cells into insulin-producing cells (IPCs) in sufficient number and functional status to be transplanted. Differentiation protocols have been designed using consecutive cytokines or signaling modulator treatments, at specific dosages, to activate or inhibit the main signaling pathways that control the differentiation of induced pluripotent stem cells (iPSCs) into pancreatic β-cells. Here, we provide an overview of the current approaches and achievements in obtaining stem cell-derived β-cells and the numerous challenges, which still need to be overcome to achieve this goal. Clinical translation of stem cells-derived β-cells for efficient maintenance of long-term euglycemia remains a major issue. Therefore, research efforts have been directed to the final steps of in vitro differentiation, aiming at production of functional and mature β-cells and integration of interdisciplinary fields to generate efficient cell therapy strategies capable of reversing the clinical outcome of T1D.
IL-37 overexpression promotes endometrial regenerative cell-mediated inhibition of cardiac allograft rejection
Authors: Qin Hong , Sun Chenglu , Zhu Yanglin , Qin Yafei , Ren Shaohua , Wang Zhaobo , Li Chuan , Li Xiang , Zhang Baoren , Hao Jingpeng , Li Guangming , Wang Hongda , Shao Bo , Zhang Jingyi , Wang Hao 
Published: July 2022

Abstract
Background
Endometrial regenerative cells (ERCs) play an important role in attenuation of acute allograft rejection, while their effects are limited. IL-37, a newly discovered immunoregulatory cytokine of the IL-1 family, can regulate both innate and adaptive immunity. Whether IL-37 overexpression can enhance the therapeutic effects of ERCs in inhibition of acute cardiac allograft rejection remains unknown and will be explored in this study.

Methods
C57BL/6 mice recipients receiving BALB/c mouse heterotopic heart allografts were randomly divided into the phosphate-buffered saline (untreated), ERC treated, negative lentiviral control ERC (NC-ERC) treated, and IL-37 overexpressing ERC (IL-37-ERC) treated groups. Graft pathological changes were assessed by H&E staining. The intra-graft cell infiltration and splenic immune cell populations were analyzed by immunohistochemistry and flow cytometry, respectively. The stimulatory property of recipient DCs was tested by an MLR assay. Furthermore, serum cytokine profiles of recipients were measured by ELISA assay.

Results
Mice treated with IL-37-ERCs achieved significantly prolonged allograft survival compared with the ERC-treated group. Compared with all the other control groups, IL-37-ERC-treated group showed mitigated inflammatory response, a significant increase in tolerogenic dendritic cells (Tol-DCs), regulatory T cells (Tregs) in the grafts and spleens, while a reduction of Th1 and Th17 cell population. Additionally, there was a significant upregulation of immunoregulatory IL-10, while a reduction of IFN-γ, IL-17A, IL-12 was detected in the sera of IL-37-ERC-treated recipients.

Conclusion
IL-37 overexpression can promote the therapeutic effects of ERCs to inhibit acute allograft rejection and further prolong graft survival. This study suggests that gene-modified ERCs overexpressing IL-37 may pave the way for novel therapeutic options in the field of transplantation.
Anti-fibrotic effect of a selective estrogen receptor modulator in systemic sclerosis
Authors: Kim Yena , Nam Yoojun , Rim Yeri Alice , Ju Ji Hyeon 
Published: July 2022

AbstractBackgroundThe rarity of systemic sclerosis (SSc) has hampered the development of therapies for this intractable autoimmune disease. Induced pluripotent stem cell (iPSC) can be differentiated into the key disease-affected cells in vitro. The generation of patient-derived iPSCs has opened up possibilities for rare disease modeling. Since these cells can recapitulate the disease phenotypes of the cell in question, they are useful high-throughput platforms for screening for drugs that can reverse these abnormal phenotypes.MethodsSSc iPSC was generated from PBMC by Sendai virus. Human iPSC lines from SSc patients were differentiated into dermal fibroblasts and keratinocytes. The iPSC-derived differentiated cells from the SSc patients were used on high-throughput platforms to screen for FDA-approved drugs that could be effective treatments for SSc.ResultsSkin organoids were generated from these cells exhibited fibrosis that resembled SSc skin. Screening of the 770-FDA-approved drug library showed that the anti-osteoporotic drug raloxifene reduced SSc iPSC-derived fibroblast proliferation and extracellular matrix production and skin fibrosis in organoids and bleomycin-induced SSc-model mice.ConclusionsThis study reveals that a disease model of systemic sclerosis generated using iPSCs-derived skin organoid is a novel tool for in vitro and in vivo dermatologic research. Since raloxifene and bazedoxifene are well-tolerated anti-osteoporotic drugs, our findings suggest that selective estrogen receptor modulator (SERM)-class drugs could treat SSc fibrosis.
A gene signature is critical for intrahepatic cholangiocarcinoma stem cell self-renewal and chemotherapeutic response
Authors: Huang Lifeng , Xu Dongwei , Qian Yawei , Zhang Xiaoqiang , Guo Han , Sha Meng , Hu Rui , Kong Xiaoni , Xia Qiang , Zhang Yi 
Published: July 2022

Abstract
Background
Improved understanding of the stemness regulation mechanism in intrahepatic cholangiocarcinoma (ICC) could identify targets and guidance for adjuvant transarterial chemoembolization (TACE).

Methods
TCGA database was excavated to identify the ICC stemness-associated genes. The pro-stemness effect of target genes was further analyzed by sphere formation assay, qRT-PCR, western blot, flow cytometric analysis, IHC, CCK8 assay and metabolomic analysis. Based on multivariate analysis, a nomogram for ICC patients with adjuvant TACE was established and our result was further confirmed by a validation cohort. Finally, the effect of dietary methionine intervention on chemotherapy was estimated by in vivo experiment and clinical data.

Results
In this study, we identified four ICC stemness-associated genes (SDHAF2, MRPS34, MRPL11, and COX8A) that are significantly upregulated in ICC tissues and negatively associated with clinical outcome. Functional studies indicated that these 4-key-genes are associated with self-renewal ability of ICC and transgenic expression of these 4-key-genes could enhance chemoresistance of cholangiocarcinoma cells. Mechanistically, the 4-key-genes-mediated pro-stemness requires the activation of methionine cycle, and their promotion on ICC stemness characteristic is dependent on MAT2A. Importantly, we established a novel nomogram to evaluate the effectiveness of TACE for ICC patients. Further dietary methionine intervene studies indicated that patients with adjuvant TACE might benefit from dietary methionine restriction if they have a relatively high nomogram score (≥ 135).

Conclusions
Our results show that four ICC stemness-associated genes could serve as novel biomarkers in predicting ICC patient’s response to adjuvant TACE and their pro-stemness ability may be attributed to the activation of the methionine cycle.