bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity tracker-based intervention to increase physical activity in patients with type 2 diabetes and healthy individuals: study protocol for a randomized controlled trial
Authors: Mähs M. , Pithan J. S. , Bergmann I. , Gabrys L. , Graf J. , Hölzemann A. , Van Laerhoven K. , Otto-Hagemann S. , Popescu M. L. , Schwermann L. , Wenz B. , Pahmeier I. , Teti A. 
Published: July 2022

Abstract
Background
One relevant strategy to prevent the onset and progression of type 2 diabetes mellitus (T2DM) focuses on increasing physical activity. The use of activity trackers by patients could enable objective measurement of their regular physical activity in daily life and promote physical activity through the use of a tracker-based intervention. This trial aims to answer three research questions: (1) Is the use of activity trackers suitable for longitudinal assessment of physical activity in everyday life? (2) Does the use of a tracker-based intervention lead to sustainable improvements in the physical activity of healthy individuals and in people with T2DM? (3) Does the accompanying digital motivational intervention lead to sustainable improvements in physical activity for participants using the tracker-based device?

Methods
The planned study is a randomized controlled trial focused on 1642 participants with and without T2DM for 9 months with regard to their physical activity behavior. Subjects allocated to an intervention group will wear an activity tracker. Half of the subjects in the intervention group will also receive an additional digital motivational intervention. Subjects allocated to the control group will not receive any intervention. The primary outcome is the amount of moderate and vigorous physical activity in minutes and the number of steps per week measured continuously with the activity tracker and assessed by questionnaires at four time points. Secondary endpoints are medical parameters measured at the same four time points. The collected data will be analyzed using inferential statistics and explorative data-mining techniques.

Discussion
The trial uses an interdisciplinary approach with a team including sports psychologists, sports scientists, health scientists, health care professionals, physicians, and computer scientists. It also involves the processing and analysis of large amounts of data collected with activity trackers. These factors represent particular strengths as well as challenges in the study.

Trial Registration
The trial is registered at the World Health Organization International Clinical Trials Registry Platform via the German Clinical Studies Trial Register (DRKS), DRKS00027064. Registered on 11 November 2021.
Bioinformatics analysis and experimental verification of Notch signalling pathway-related miRNA–mRNA subnetwork in extracellular vesicles during Echinococcus granulosus encystation
Authors: Gao Jian , Zhou Xuan , Liu Ling , Lv Guodong , Hou Qiulian , Zhang Xiaofan , Shen Yujuan 
Published: July 2022

Abstract
Background
Encystation of the protoscoleces (PSCs) of Echinococcus granulosus is the main cause of secondary hydatid dissemination in the intermediate host. Extracellular vesicles (EVs) can transfer miRNAs into parasite cells to regulate mRNA expression. However, loading of developmental pathway-related miRNAs, such as those related to the Notch signalling pathway in EVs is unclear. Thus, we screened the miRNA-mRNA subnetwork involved in the Notch pathway during E. granulosus encystation in vitro and assessed changes in expression in the parasite and EVs.

Methods
mRNAs and miRNAs differentially expressed (DE) between PSCs and microcysts (MCs) were screened using high-throughput sequencing. DE mRNAs obtained from transcriptome analysis were intersected with mRNAs predicted to be targets of the conserved DE miRNAs of a small RNA library. DE miRNA functions were analysed using public databases, and a miRNA–mRNA subnetwork related to the Notch pathway was established. Notch pathway-related mRNA and miRNA expression of worms and EVs at different times was verified.

Results
In total, 1445 DE mRNAs between MCs and PSCs were screened after the intersection between 1586 DE mRNAs from the transcriptome and 9439 target mRNAs predicted using 39 DE miRNAs from the small RNA library. The DE mRNAs were clustered into 94 metabolic pathways, including the Notch pathway. Five DE miRNAs, including the most significantly expressed new DE miRNA, egr-new-mir0694-3p, corresponding to four target mRNAs (EgrG_000892700, EgrG_001029400, EgrG_001081400 and EgrG_000465800) were all enriched in the Notch pathway. The expression of the above mRNAs and miRNAs was consistent with the results of high-throughput sequencing, and the expression of each miRNA in EVs was verified. Annotated as ADAM17/TACE in the Notch pathway, EgrG_000892700 was down-regulated during PSC encystation. egr-miR-4989-3p and egr-miR-277a-3p expression in EVs after encystation was nearly five times that in EVs before encystation, which might regulate the expression of EgrG_000892700.

Conclusions
Five miRNAs corresponding to four target mRNAs may be involved in regulating the Notch pathway during the PSC encystation. EVs may regulate the expression of EgrG_000892700 in PSCs because of continuous targeting of egr-miR-4989-3p and egr-miR-277a-3p and participate in the regulation the Notch pathway. The study might expand new ideas for blocking the secondary infection of E. granulosus PSCs via EVs miRNAs.

Graphical Abstract
Classified metabolic power-based measures in professional football players: comparison between playing positions and match period
Authors: Akyildiz Zeki , Çene Erhan , Parim Coşkun , Çetin Onat , Turan Çağatay , Yüksel Yılmaz , Silva Rui , Silva Ana Filipa , Nobari Hadi 
Published: July 2022

Abstract
Objective
The aim of this study was (i) provide reference data of metabolic power-based measures during professional football matches; and to (ii) analyze the between-position and between-halves differences of power-based measures during professional football matches.

Methods
Forty-six professional male players from two Turkish Super League teams were observed during two seasons, and 58 matches were analyzed. Total distance, equivalent distance, Low Power (LP), Intermediate Power (IP), High Power (HP), Elevated Power (EP), Max Power (MP) and power metabolic measures Pmet at different match moments were considered.

Results
Significant between-position differences were observed for IP (p: 0.000; d: 0.284), HP (p ≤ 0.001; d = 0.45), EP (p ≤ 0.001; d = 0.44), and for MP (p ≤ 0.001; d = 0.56), with the central defenders (CD) showing the lower values, and the central midfielders (CM) showing the higher values for the overall measures.

Conclusion
Power-based measures are dependent on playing positions. While the CD have lower Pmet values when compared to all positions, the CM have the greatest values. Training and recovery strategies must be ensured for CM players, especially those who have greater match participation.
Acute hepatitis-like presentation with cholestasis of CBFB–MYH11-positive acute myeloid leukemia in an adult male: a case report
Authors: Spinelli Irene , De Santis Adriano , Cesini Laura , Riminucci Mara , Corsi Alessandro , Forlino Mariana , Perrone Elio Pietro , Minotti Clara , Cartoni Claudio 
Published: July 2022

Abstract
Background
Liver involvement in adults with acute myeloid leukemia is uncommon. Most of the case reports describe acute liver failure or obstructive jaundice, while acute hepatitis is rarely mentioned. We report a patient with acute myeloid leukemia who presented with clinical, biochemical, and radiological signs of acute hepatitis that totally regressed after chemotherapy.

Case presentation
A 38-year-old Caucasian man presented with fever, cough, and mild fatigue. Laboratory workup showed anemia, thrombocytopenia, severe leukocytosis, transaminitis, and hyperbilirubinemia. Imaging of the abdomen (ultrasound and magnetic resonance) showed hepatomegaly, splenomegaly, upper limits portal veins diameters, increased thickness of the gallbladder wall, and significant abdominal lymph nodes. Peripheral blood smear and bone marrow evaluation were consistent with acute myeloid leukemia, and liver biopsy showed massive sinusoidal and portal infiltration by leukemic cells. After remission-inducing chemotherapy, there was complete normalization of liver function tests, and liver, spleen, and portal vein size.

Conclusions
This case highlights the importance of taking acute myeloid leukemia into account as a possible cause of liver damage to make a rapid diagnosis and start appropriate treatment that may lead to hematological remission and hepatic dysfunction resolution.
The roles of long noncoding RNAs in the regulation of OCT4 expression
Authors: Zhou Rui-Ting , Ni Yi-Ran , Zeng Fan-Jun 
Published: July 2022

AbstractOCT4 is a major transcription factor that maintains the pluripotency of stem cells, including embryonic stem cells, induced pluripotent stem cells and cancer stem cells. An increasing number of long noncoding RNAs have been reported to participate in the regulation of OCT4 expression through various mechanisms, including binding with the OCT4 gene promoter to regulate local methylation; promoting chromosomal spatial folding to form an inner ring, thereby aggregating OCT4 cis-acting elements scattered in discontinuous sites of the chromosome; competitively binding microRNAs with OCT4 to upregulate OCT4 expression at the posttranscriptional level; and sharing a promoter with OCT4. Moreover, the transcription of some long noncoding RNAs is regulated by OCT4, and certain long noncoding RNAs form feedback regulatory loops with OCT4. In this review, we summarized the research progress of the long noncoding RNAs involved in the regulation of OCT4 expression.
Advances in cell therapies using stem cells/progenitors as a novel approach for neurovascular repair of the diabetic retina
Authors: Lechner Judith , Medina Reinhold J. , Lois Noemi , Stitt Alan W. 
Published: July 2022

Abstract
Background
Diabetic retinopathy, a major complication of diabetes mellitus, is a leading cause of sigh-loss in working age adults. Progressive loss of integrity of the retinal neurovascular unit is a central element in the disease pathogenesis. Retinal ischemia and inflammatory processes drive interrelated pathologies such as blood retinal barrier disruption, fluid accumulation, gliosis, neuronal loss and/or aberrant neovascularisation. Current treatment options are somewhat limited to late-stages of the disease where there is already significant damage to the retinal architecture arising from degenerative, edematous and proliferative pathology. New preventive and interventional treatments to target early vasodegenerative and neurodegenerative stages of the disease are needed to ensure avoidance of sight-loss.

Main body
Historically, diabetic retinopathy has been considered a primarily microvascular disease of the retina and clinically it is classified based on the presence and severity of vascular lesions. It is now known that neurodegeneration plays a significant role during the pathogenesis. Loss of neurons has been documented at early stages in pre-clinical models as well as in individuals with diabetes and, in some, even prior to the onset of clinically overt diabetic retinopathy. Recent studies suggest that some patients have a primarily neurodegenerative phenotype. Retinal pigment epithelial cells and the choroid are also affected during the disease pathogenesis and these tissues may also need to be addressed by new regenerative treatments.
Most stem cell research for diabetic retinopathy to date has focused on addressing vasculopathy. Pre-clinical and clinical studies aiming to restore damaged vasculature using vasoactive progenitors including mesenchymal stromal/stem cells, adipose stem cells, CD34+ cells, endothelial colony forming cells and induced pluripotent stem cell derived endothelial cells are discussed in this review. Stem cells that could replace dying neurons such as retinal progenitor cells, pluripotent stem cell derived photoreceptors and ganglion cells as well as Müller stem cells are also discussed. Finally, challenges of stem cell therapies relevant to diabetic retinopathy are considered.

Conclusion
Stem cell therapies hold great potential to replace dying cells during early and even late stages of diabetic retinopathy. However, due to the presence of different phenotypes, selecting the most suitable stem cell product for individual patients will be crucial for successful treatment.
The therapeutic potential of Camel Wharton jelly mesenchymal stem cells (CWJ-MSCs) in canine chronic kidney disease model
Authors: El Miniawy Hala M. F. , Farghali Haithem A. , Khattab Marwa S. , Emam Ibrahim A. , Ibrahem Essam M. , Sabry Dina , Ismail Tahany A. 
Published: July 2022

AbstractBackgroundChronic kidney disease (CKD) is a worldwide health problem that its incidence increases nowadays with the increase in the risk of environmental pollution. CKD can progress to end-stage renal disease (ESRD) which usually ends fatally. This study aimed to examine the therapeutic potential of Camel Wharton jelly-mesenchymal stem cells (CWJ-MSCs) in chronic kidney disease model induced in dogs.MethodsCWJ-MSCs were injected directed to the kidney with ultrasonographic guidance in dogs with 5/6 nephrectomy to evaluate its therapeutic potency in such cases. Analysis of variance was applied in normally distributed quantitative variables while a non-parametric Mann–Whitney test was used for non-normally distributed quantitative variables.ResultsThe serum urea and creatinine in the treated group were significantly decreased transferring dogs in the treated group from stage 3 to stage 2 CKD according to the IRIS staging system. Histopathology of renal tissue revealed improving CKD lesions by increasing regeneration of degenerated tubules, maintaining the integrity of glomeruli. New vascularization with blood vessels remodeling were common findings. Periodic acid Schiff stain of renal tissue showed the integrity of renal tubules and thickness of the glomerular basement membrane. Fibrosis of cortex and medulla was lower in the treated group than in the CKD model as monitored by Mallory’s trichrome stain (MTC). NGAL and KIM-1 genes expression were decreased while VEGF and EGF genes expression were increased indicating renal tissue repair.ConclusionsCWJ-MSCs have a therapeutic potential in the CKD model induced in dogs.
Hyaluronan supports the limbal stem cell phenotype during ex vivo culture
Authors: Puri Sudan , Moreno Isabel Y. , Sun Mingxia , Verma Sudhir , Lin Xiao , Gesteira Tarsis F. , Coulson-Thomas Vivien J. 
Published: July 2022

Abstract
Background
Hyaluronan (HA) has previously been identified as an integral component of the limbal stem cell niche in vivo. In this study, we investigated whether a similar HA matrix is also expressed in vitro providing a niche supporting limbal epithelial stem cells (LESCs) during ex vivo expansion. We also investigated whether providing exogenous HA in vitro is beneficial to LESCs during ex vivo expansion.

Method
Human LESCs (hLESCs) were isolated from donor corneas and a mouse corneal epithelial progenitor cell line (TKE2) was obtained. The HA matrix was identified surrounding LESCs in vitro using immunocytochemistry, flow cytometry and red blood exclusion assay. Thereafter, LESCs were maintained on HA coated dishes or in the presence of HA supplemented in the media, and viability, proliferation, cell size, colony formation capabilities and expression of putative stem cell markers were compared with cells maintained on commonly used coated dishes.

Results
hLESCs and TKE2 cells express an HA-rich matrix in vitro, and this matrix is essential for maintaining LESCs. Further supplying exogenous HA, as a substrate and supplemented to the media, increases LESC proliferation, colony formation capabilities and the expression levels of putative limbal stem cell markers.

Conclusion
Our data show that both exogenous and endogenous HA help to maintain the LESC phenotype. Exogenous HA provides improved culture conditions for LESC during ex vivo expansion. Thus, HA forms a favorable microenvironment for LESCs during ex vivo expansion and, therefore, could be considered as an easy and cost-effective substrate and/or supplement for culturing LESCs in the clinic.
Knockout of integrin β1 in induced pluripotent stem cells accelerates skin-wound healing by promoting cell migration in extracellular matrix
Authors: Ren Yansong , Liu Jinbo , Xu Huijun , Wang Shun , Li Shirui , Xiang Meng , Chen Sifeng 
Published: July 2022

Abstract
Background
Induced pluripotent stem cells (iPSCs) have the potential to promote wound healing; however, their adhesion to the extracellular matrix (ECM) might decrease iPSC migration, thereby limiting their therapeutic potential. Integrin β1 (Itgb1) is the major integrin subunit that mediates iPSC-ECM adhesion, suggesting that knocking out Itgb1 might be an effective method for enhancing the therapeutic efficacy of iPSCs.

Methods
We knocked out Itgb1 in mouse iPSCs and evaluated its effects on the therapeutic potential of topically applied iPSCs, as well as their underlying in vivo and in vitro mechanisms.

Results
The Itgb1-knockout (Itgb1-KO) did not change iPSC pluripotency, function, or survival in the absence of embedding in an ECM gel but did accelerate wound healing, angiogenesis, blood perfusion, and survival in skin-wound lesions. However, embedding in an ECM gel inhibited the in vivo effects of wild-type iPSCs but not those of Itgb1-knockout iPSCs. Additionally, in vitro results showed that Itgb1-knockout decreased iPSC-ECM adhesion while increasing ECM-crossing migration. Moreover, ECM coating on the culture surface did not change cell survival, regardless of Itgb1 status; however, the in vivo and in vitro functions of both Itgb1-knockout and wild-type iPSCs were not affected by the presence of agarose gel, which does not contain integrin-binding sites. Knockout of Integrin α4 (Itga4) did not change the above-mentioned cellular and therapeutic functions of iPSCs.

Conclusions
Itgb1-knockout increased iPSCs migration and the wound-healing-promoting effect of topically applied iPSCs. These findings suggest the inhibition of Itgb1 expression is a possible strategy for increasing the efficacy of iPSC therapies.
Toward in vivo proof of binding of 18F-labeled inhibitor [18F]TRACK to peripheral tropomyosin receptor kinases
Authors: Wuest Melinda , Bailey Justin J. , Dufour Jennifer , Glubrecht Darryl , Omana Vanessa , Johnston Tom H. , Brotchie Jonathan M. , Schirrmacher Ralf 
Published: July 2022

Abstract
Background
Tropomyosin receptor kinases (TrkA, TrkB, TrkC) are a family of tyrosine kinases primarily expressed in neuronal cells of the brain. Identification of oncogenic alterations in Trk expression as a driver in multiple tumor types has increased interest in their role in human cancers. Recently, first- and second-generation 11C and 18F-labeled Trk inhibitors, e.g., [18F]TRACK, have been developed. The goal of the present study was to analyze the direct interaction of [18F]TRACK with peripheral Trk receptors in vivo to prove its specificity for use as a functional imaging probe.

Methods
In vitro uptake and competition experiments were carried out using the colorectal cancer cell line KM12. Dynamic PET experiments were performed with [18F]TRACK, either alone or in the presence of amitriptyline, an activator of Trk, entrectinib, a Trk inhibitor, or unlabeled reference compound TRACK in KM12 tumor-bearing athymic nude mice as well as B6129SF2/J and corresponding B6;129S2-Ntrk2tm1Bbd/J mice. Western blot and immunohistochemistry experiments were done with KM12 tumors, brown adipose tissue (BAT), and brain tissue samples.

Results
Uptake of [18F]TRACK was increasing over time reaching 208 ± 72% radioactivity per mg protein (n = 6/2) after 60 min incubation time. Entrectinib and TRACK competitively blocked [18F]TRACK uptake in vitro (IC50 30.9 ± 3.6 and 29.4 ± 9.4 nM; both n = 6/2). [18F]TRACK showed uptake into KM12 tumors (SUVmean,60 min 0.43 ± 0.03; n = 6). Tumor-to-muscle ratio reached 0.9 (60 min) and 1.2 (120 min). In TrkB expressing BAT, [18F]TRACK uptake reached SUVmean,60 min 1.32 ± 0.08 (n = 7). Activation of Trk through amitriptyline resulted in a significant radioactivity increase of 21% in KM12 tumor (SUVmean,60 min from 0.53 ± 0.01 to 0.43 ± 0.03; n = 6; p < 0.05) and of 21% in BAT (SUVmean,60 min from 1.32 ± 0.08; n = 5 to 1.59 ± 0.07; n = 6; p < 0.05) respectively. Immunohistochemistry showed TrkB > TrkA expression on BAT fat cells, but TrkA > TrkB in whole brain. WB analysis showed sevenfold higher TrkB expression in BAT versus KM12 tumor tissue.

Conclusion
The present data show that radiotracer [18F]TRACK can target peripheral Trk receptors in human KM12 colon cancer as well as brown adipose tissue as confirmed through in vitro and in vivo blocking experiments. Higher TrkB versus TrkA protein expression was detected in brown adipose tissue of mice confirming a peripheral functional role of brain-derived neurotrophic factor in adipose tissue.
Characterization of a novel chitinolytic Serratia marcescens strain TC-1 with broad insecticidal spectrum
Authors: Tao Aili , Wang Tan , Pang Fahu , Zheng Xueling , Ayra-Pardo Camilo , Huang Siliang , Xu Ruxin , Liu Fengqin , Li Jiakang , Wei Yibin , Wang Zhiqing , Niu Qiuhong , Li Dandan 
Published: July 2022

AbstractThe Gram-negative rod-shaped bacterium Serratia marcescens is an opportunistic pathogen of many organisms, including insects. We report the identification and optimal in vitro chitinase production conditions of a novel chitinolytic S. marcescens strain TC-1 isolated from a naturally infected white grub (Anomala corpulenta) collected from a peanut field at Nanyang city, Henan province, China. Strain identification was conducted by morphological, physiological, biochemical and molecular analyses. The amplified 16S rRNA gene of TC-1 showed a similarity greater than 99% with multiple strains of S. marcescens. Based on Neighbor-joining phylogenetic tree analysis of bacterial 16S rRNA gene sequences, TC-1 formed a clade with S. marcescens, clearly separated from other Serratia spp. The strain TC-1 showed larvicidal activities against five insect species (A. corpulenta, Plutella xylostella, Spodoptera exigua, Helicoverpa armigera, Bombyx mori) and the nematode Caenorhabditis elegans, but not against S. litura. The operating parameters of chitinase production by TC-1 were optimized by response surface methodology using a three-factor, three-level Box-Behnken experimental design. The effects of three independent variables i.e. colloidal chitin concentration (7–13 g l−1), incubation time (24–72 h) and incubation temperature (24–32 °C) on chitinase production by TC-1 were investigated. A regression model was proposed to correlate the independent variables for an optimal chitinase activity predicted as 20.946 U ml−1, using a combination of colloidal chitin concentration, incubation time and incubation temperature of 9.06 g l−1, 63.83 h and 28.12 °C, respectively. The latter agreed well with a mean chitinase activity of 20.761 ± 0.102 U ml−1 measured in the culture supernatants of TC-1 grown under similar conditions with a colloidal chitin concentration, incubation time and incubation temperature of 9 g l−1, 64 h and 28 °C, respectively. Our study revealed the S. marcescens strain TC-1 with potential as a biocontrol agent of insect pests and nematodes and demonstrated the proposed regression model's potential to guide chitinase production by this strain.