bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastric cancer-derived exosomal miR-519a-3p promotes liver metastasis by inducing intrahepatic M2-like macrophage-mediated angiogenesis
Authors: Qiu Shengkui , Xie Li , Lu Chen , Gu Chao , Xia Yiwen , Lv Jialun , Xuan Zhe , Fang Lang , Yang Jing , Zhang Lu , Li Zheng , Wang Weizhi , Xu Hao , Li Bowen , Xu Zekuan 
Published: October 2022

Abstract
Background
Liver metastasis (LM) is a major obstacle to the prognosis of gastric cancer (GC) patients, but the molecular mechanism underlying gastric cancer liver metastasis (GC-LM) remains unknown. Exosomes have been identified as an important mediator of communication between tumor cells and the microenvironment. Therefore, we sought to investigate the effects of primary GC cells on the liver microenvironment and the role of exosomal microRNAs (exo-miRNA) in GC-LM.

Methods
Sequential differential centrifugation, transmission electron microscopy and NanoSight analysis were used to extract and characterize exosomes. MicroRNA sequencing in GC-derived exosomes and mRNA sequencing in PMA-treated THP-1 cells were used to identify differentially expressed miRNAs in exosomes and the functional targets of exosomal miR-519a-3p (exo-miR-519a-3p) in macrophages, respectively. Tracing and internalization of exosomes and transfer of exo-miR-519a-3p were observed by immunofluorescence. Tubule formation assays, aortic ring assays, and exosome-educated GC-LM model were used to investigate the roles of GC-derived exosomes and exo-miR-519a-3p in angiogenesis and GC-LM. Luciferase reporter assay, qRT-PCR, Western blot, ELISA, flow cytometry and immunofluorescence were used to investigate the regulatory mechanism of exo-miR-519a-3p at GC-LM.

Results
The expression level of miR-519a-3p in serum exosomes was significantly higher in GC-LM patients than in patients without LM, and high expression of exo-miR-519a-3p indicates a worse prognosis. GC-derived exosomes are mainly accumulated in the liver and internalized by intrahepatic macrophages. Mechanistically, exo-miR-519a-3p activates the MAPK/ERK pathway by targeting DUSP2, thereby causing M2-like polarization of macrophages. M2-like polarized macrophages accelerate GC-LM by inducing angiogenesis and promoting intrahepatic premetastatic niche formation.

Conclusions
Our results indicate that exo-miR-519a-3p plays a critical role in mediating crosstalk between primary GC cells and intrahepatic macrophages and is a potential therapeutic target for GC-LM.
In silico optimization of RNA–protein interactions for CRISPR-Cas13-based antimicrobials
Authors: Park Ho-min , Park Yunseol , Berani Urta , Bang Eunkyu , Vankerschaver Joris , Van Messem Arnout , De Neve Wesley , Shim Hyunjin 
Published: October 2022

AbstractRNA–protein interactions are crucial for diverse biological processes. In prokaryotes, RNA–protein interactions enable adaptive immunity through CRISPR-Cas systems. These defence systems utilize CRISPR RNA (crRNA) templates acquired from past infections to destroy foreign genetic elements through crRNA-mediated nuclease activities of Cas proteins. Thanks to the programmability and specificity of CRISPR-Cas systems, CRISPR-based antimicrobials have the potential to be repurposed as new types of antibiotics. Unlike traditional antibiotics, these CRISPR-based antimicrobials can be designed to target specific bacteria and minimize detrimental effects on the human microbiome during antibacterial therapy. In this study, we explore the potential of CRISPR-based antimicrobials by optimizing the RNA–protein interactions of crRNAs and Cas13 proteins. CRISPR-Cas13 systems are unique as they degrade specific foreign RNAs using the crRNA template, which leads to non-specific RNase activities and cell cycle arrest. We show that a high proportion of the Cas13 systems have no colocalized CRISPR arrays, and the lack of direct association between crRNAs and Cas proteins may result in suboptimal RNA–protein interactions in the current tools. Here, we investigate the RNA–protein interactions of the Cas13-based systems by curating the validation dataset of Cas13 protein and CRISPR repeat pairs that are experimentally validated to interact, and the candidate dataset of CRISPR repeats that reside on the same genome as the currently known Cas13 proteins. To find optimal CRISPR-Cas13 interactions, we first validate the 3-D structure prediction of crRNAs based on their experimental structures. Next, we test a number of RNA–protein interaction programs to optimize the in silico docking of crRNAs with the Cas13 proteins. From this optimized pipeline, we find a number of candidate crRNAs that have comparable or better in silico docking with the Cas13 proteins of the current tools. This study fully automatizes the in silico optimization of RNA–protein interactions as an efficient preliminary step for designing effective CRISPR-Cas13-based antimicrobials.
Identification of target genes regulated by encystation-induced transcription factor Myb2 using knockout mutagenesis in Giardia lamblia
Authors: Kim Juri , Park Eun-Ah , Shin Mee Young , Park Soon-Jung 
Published: October 2022

Abstract
Background
Encystation is one of the two processes comprising the life cycle of Giardia lamblia, a protozoan pathogen with tetraploid genome. Giardia lamblia Myb2 (GlMyb2) is a distinct encystation-induced transcription factor whose binding sites are found in the promoter regions of many encystation-induced genes, including its own.

Methods
Two sequential CRISPR/Cas9 experiments were performed to remove four glmyb2 alleles. The expression level of G. lamblia cyst wall protein 1 (GlCWP1), a well-known target gene of GlMyb2, was measured via western blotting and immunofluorescence assays. Chromatin immunoprecipitation experiments using anti-GlMyb2 antibodies were performed on the encysting G. lamblia cells. Quantitative real-time PCR was performed to confirm an expression of candidate GlMyb2-regulated genes by comparing the transcript level for each target candidate in wild-type and knockout mutant Giardia. The promoter region of glcwp1 was analyzed via deletion and point mutagenesis of the putative GlMyb2 binding sites in luciferase reporters.

Results
Characterization of the null glmyb2 mutant indicated loss of functions related to encystation, i.e. cyst formation, and expression of GlCWP1. The addition of the wild-type glmyb2 gene to the null mutant restored the defects in encystation. Chromatin immunoprecipitation experiments revealed dozens of target genes. Nineteen genes were confirmed as GlMyb2 regulons, which include the glmyb2 gene, six for cyst wall proteins, five for signal transduction, two for transporter, two for metabolic enzymes, and three with unknown functions. Detailed analysis on the promoter region of glcwp1 defined three GlMyb2 binding sites important in its encystation-induced expression.

Conclusions
Our data confirm that GlMyb2 acts as a transcription activator especially during encystation by comparing the glmyb2 knockout mutant with the wild type. Further investigation using glmyb2 null mutant will provide knowledge regarding transcriptional apparatus required for the encystation process of G. lamblia.

Graphical Abstract
The influence of physical performance on technical and tactical outcomes in the UEFA Champions League
Authors: Modric Toni , Malone James J. , Versic Sime , Andrzejewski Marcin , Chmura Paweł , Konefał Marek , Drid Patrik , Sekulic Damir 
Published: October 2022

AbstractBackgroundTo clarify does physical performance affect success in highest-level soccer, the purpose of the present study was to identify differences in technical-tactical performance (TP) between teams covering high and low running performance (RP) during the UEFA Champions League (UCL) matches.MethodsThe RP and TP data were collected from UCL group stage matches in the 2020/21 season. RP variables included total distance covered (TD), high intensity running (HIR), total distance when in ball possession (TDB), and high intensity running when in ball possession (HIRB). TP variables included goal chances, shots, shots on target, passes, accurate passes, key passes, key passes accurate, crosses, crosses accurate, counter attacks, counter attacks with a shot, high pressing, high pressing successful, low pressing, low pressing successful, tackles, tackles successful, entrances to the opponent’s box, total actions, and successful actions. K-means cluster analysis method was used to classify teams covering (i) low and high TD, (ii) low and high HIR, (iii) low and high TDB, (iv) low and high and HIRB. Linear mixed models were used to identify differences in teams’ TP according to their RP. Pearson’s correlations were used to establish direct association between team TP and RP.ResultsSimilar TP were observed whether teams covering high or low TD/HIR. Teams covering greater TDB/HIRB had more goal chances, shots, shots on target, passes, accurate passes, key passes, accurate key passes, crosses, successful high pressing, entrances to the opponent’s box, total actions, and successful actions were observed (all moderate to very large effect sizes. Significant association between specific TP variables and TDB/HIRB were evidenced (Pearson’s r = 0.35–0.96, allp < 0.05).ConclusionCovering greater TDB and HIRB may allow more frequent execution of fundamental TP which are considered essential for match success, indicating that RP when team has ball in possession is important determinant of success in highest-level soccer. This study shows that physical performance affect success in highest-level soccer.
Altered basal forebrain function during whole-brain network activity at pre- and early-plaque stages of Alzheimer’s disease in TgF344-AD rats
Authors: van den Berg Monica , Adhikari Mohit H. , Verschuuren Marlies , Pintelon Isabel , Vasilkovska Tamara , Van Audekerke Johan , Missault Stephan , Heymans Loran , Ponsaerts Peter , De Vos Winnok H. , Van der Linden Annemie , Keliris Georgios A. , Verhoye Marleen 
Published: October 2022

AbstractBackgroundImbalanced synaptic transmission appears to be an early driver in Alzheimer’s disease (AD) leading to brain network alterations. Early detection of altered synaptic transmission and insight into mechanisms causing early synaptic alterations would be valuable treatment strategies. This study aimed to investigate how whole-brain networks are influenced at pre- and early-plague stages of AD and if these manifestations are associated with concomitant cellular and synaptic deficits. MethodsTo this end, we used an established AD rat model (TgF344-AD) and employed resting state functional MRI and quasi-periodic pattern (QPP) analysis, a method to detect recurrent spatiotemporal motifs of brain activity, in parallel with state-of-the-art immunohistochemistry in selected brain regions.ResultsAt the pre-plaque stage, QPPs in TgF344-AD rats showed decreased activity of the basal forebrain (BFB) and the default mode-like network. Histological analyses revealed increased astrocyte abundance restricted to the BFB, in the absence of amyloid plaques, tauopathy, and alterations in a number of cholinergic, gaba-ergic, and glutamatergic synapses. During the early-plaque stage, when mild amyloid-beta (Aβ) accumulation was observed in the cortex and hippocampus, QPPs in the TgF344-AD rats normalized suggesting the activation of compensatory mechanisms during this early disease progression period. Interestingly, astrogliosis observed in the BFB at the pre-plaque stage was absent at the early-plaque stage. Moreover, altered excitatory/inhibitory balance was observed in cortical regions belonging to the default mode-like network. In wild-type rats, at both time points, peak activity in the BFB preceded peak activity in other brain regions—indicating its modulatory role during QPPs. However, this pattern was eliminated in TgF344-AD suggesting that alterations in BFB-directed neuromodulation have a pronounced impact in network function in AD.ConclusionsThis study demonstrates the value of rsfMRI and advanced network analysis methods to detect early alterations in BFB function in AD, which could aid early diagnosis and intervention in AD. Restoring the global synaptic transmission, possibly by modulating astrogliosis in the BFB, might be a promising therapeutic strategy to restore brain network function and delay the onset of symptoms in AD.
Severe hyponatremia in an infant with epidermolysis bullosa: a case report
Authors: Dehghani Soheil , Akbarzadeh Pasha Boshra , Karimi Amirali , Afshin Azadeh 
Published: October 2022

Abstract
Background
Epidermolysis bullosa is a rare inherited connective tissue disorder compromising cellular junctions. Blister formation is the first manifestation of epidermolysis bullosa. As cellular adhesion is affected, it can affect many organs. Due to compromised skin integrity, water loss and electrolyte imbalances are prevalent in these patients. However, hypernatremia is the usual observed sodium imbalance rather than hyponatremia.

Case presentation
The patient was a 48-day-old Iranian male infant born near term. He was diagnosed with epidermolysis bullosa at 1 month of age. The patient was brought to the pediatrics center with apnea and respiratory distress, and was intubated and admitted to the pediatric intensive care unit. His symptoms started 4 days before the admission with vomiting and poor feeding, and the patient later developed loss of consciousness. Vital signs revealed a pulse rate of 154 beats per minute, respiratory rate of 70 per minute, a temporal temperature of 36.5 °C, nondetectable blood pressure, and oxygen saturation of 96%. The patient was anuric at presentation and was rehydrated. Physical examination showed bolus eruptions all over the body but not in mucosal membranes. Important laboratory findings were white blood cell count of 41,000/mm3 with 68% neutrophils, hemoglobin of 10.8 g/dL, platelet count of 856,000/mm2, negative C-reactive protein (CRP), blood sugar of 514 mg/dL, urea of 129 mg/dL, sodium of 98 mg/dL, corrected sodium of 105 mg/dL, potassium of 5.5 mg/dL, serum creatinine of 1.7 mg/dL, and serum procalcitonin of more than 75 ng/mL. Urine analysis revealed many red blood cells. Brain computed tomography demonstrated loss of differentiation between gray and white matter and effacement of cortical sulci suggesting severe cytotoxic edema.
We administered 3% hypertonic saline and corrected the plasma sodium levels, and provided the patient with multiple doses of mannitol as well as antibiotics due to the leukocytosis. Subsequently, after 3 days in pediatric intensive care unit, the symptoms of brain edema resolved, and after 4 days, he was weaned from the ventilator and extubated. Later he was discharged from the pediatric intensive care unit.

Conclusion
This study illustrates the possibility of severe hyponatremia in patients with epidermolysis bullosa to clinicians. Although uncommon, knowledge on such possibilities is vital due to the possible detrimental outcomes for patients.
Pre-cooling with ingesting a high-carbohydrate ice slurry on thermoregulatory responses and subcutaneous interstitial fluid glucose during heat exposure
Authors: Naito Takashi , Saito Tatsuya , Morito Akihisa , Yamada Satoshi , Shimomasuda Masatsugu , Nakamura Mariko 
Published: October 2022

AbstractThe purpose of this study was to compare the effects of ingesting ice slurries with two different carbohydrate contents on body temperatures and the subcutaneous interstitial fluid glucose level during heat exposure. Seven physically active men underwent one of three interventions: the ingestion of 7.5 g/kg of a control beverage (CON: 26°C), a normal-carbohydrate ice slurry (NCIS: −1°C), or a high-carbohydrate ice slurry (HCIS: −5°C). The participants were monitored for a 120-min period that included 10 min of rest, 25 min of exposure to the experimental cooling intervention (during which the beverage was ingested), and 85 min of seated rest in a climate chamber (36°C, 50% relative humidity). The rectal temperature in the HCIS and NCIS trials was lower than that in the CON trial from 40 to 75 min. The infrared tympanic temperature was also lower in the HCIS and NCIS trials than in the CON trial from 20 to 50 min, whereas the deep thigh or mean skin temperatures were not significantly different among the three groups. From 90 to 120 min, the subcutaneous interstitial fluid glucose level in the NCIS trial was lower than that at 65 min; however, reductions were not seen in the HCIS and CON trials. These findings suggest that both HCIS ingestion and conventional NCIS ingestion were effective cooling strategies for reducing thermal strain, while HCIS ingestion may also enable a higher subcutaneous interstitial fluid glucose level to be maintained, ensuring an adequate supply of required muscle substrates.
Biomimetic anti-inflammatory and osteogenic nanoparticles self-assembled with mineral ions and tannic acid for tissue engineering
Authors: Byun Hayeon , Jang Gyu Nam , Hong Min-Ho , Yeo Jiwon , Shin Hyunjung , Kim Won Jong , Shin Heungsoo 
Published: October 2022

AbstractBone healing involves complex processes including inflammation, induction, and remodeling. In this context, anti-inflammatory and osteoconductive multi-functional nanoparticles have attracted considerable attention for application in improved bone tissue regeneration. In particular, nanoparticles that promote suppression of inflammatory response after injury and direction of desirable tissue regeneration events are of immense interest to researchers. We herein report a one-step method to prepare multi-functional nanoparticles using tannic acid (TA) and simulated body fluid (SBF) containing multiple mineral ions. Mineral-tannic acid nanoparticles (mTNs) were rapidly fabricated in 10 min, and their size (around 250–350 nm) and chemical composition were controlled through the TA concentration. In vitro analysis using human adipose derived stem cells (hADSCs) showed that mTNs effectively scavenged reactive oxygen species (ROS) and enhanced osteogenesis of hADSCs by inducing secretion of alkaline phosphatase. mTNs also increased osteogenic marker gene expression even in the presence of ROS, which can generally arrest osteogenesis (OPN: 1.74, RUNX2: 1.90, OCN: 1.47-fold changes relative to cells not treated with mTNs). In vivo analysis using a mouse peritonitis model revealed that mTNs showed anti-inflammatory effects by decreasing levels of pro-inflammatory cytokines in blood (IL-6: 73 ± 4, TNF-α: 42 ± 2%) and peritoneal fluid (IL-6: 78 ± 2, TNF-α: 21 ± 6%). We believe that this one-step method for fabrication of multi-functional nanoparticles has considerable potential in tissue engineering approaches that require control of complex microenvironments, as required for tissue regeneration.
Investigating the teacher’s perceptions of classroom management and teaching self-efficacy during Covid-19 pandemic in the online EFL courses
Authors: Farkhani Zahra Akbarzade , Badiei Ghazal , Rostami Farzad 
Published: October 2022

AbstractDuring the coronavirus pandemic, online education continued to expand across varied educational factors. Therefore, the teachers had to develop and change some of the strategies used in their classes previously. Online classroom management is a synchronous-based online learning environment in education that is worthwhile to modify. For this purpose, the current study sought to understand the perceptions of classroom management and teaching self-efficacy by Iranian EFL teachers during the Covid-19 pandemic. Concerning sampling, 100 male and female English teachers constituted the study sample. Data were collected via Online Teaching Self–Efficacy Inventory questionnaire through different online platforms. The findings reflected that EFL teachers could select appropriate classroom management during online and face-to-face classes. In addition, the teachers had a positive attitude toward managing the classroom during the Covid-19 pandemic. The implications of this study may open up new perspectives into successful pedagogy for, teachers and students in outbreak days.
Anterior knee pain post-multiple surgeries for tibia fracture effectively managed with infrapatellar fat pad injection: a case report
Authors: Obara Shinju , Oishi Rieko , Nakano Yuko , Kurosawa Shin , Inoue Satoki 
Published: October 2022

Abstract
Background
The anterior knee compartment is filled by the infrapatellar fat pad (IFP) and has been emphasized as a source of anterior knee pain (AKP).

Case presentation
A 51-year-old woman sustained a right tibial plateau and open diaphyseal fracture 2 years earlier. She remained with chronic AKP after undergoing bone fixations. Increased anterior portion of the IFP brightness and decreased adipose tissue gliding with flexion and extension compared to the unaffected side was shown on ultrasonography. An injection of 0.2% lidocaine between the patellar tendon and IFP, and into the IFP under ultrasound guidance, immediately relieved the pain. The pain kept recurring although injections were effective for a while; thus, surgery was scheduled. Scar tissue on the IFP surface was endoscopically excised and her pain dramatically reduced.

Conclusion
This is the first report in which the detection of increased brightness on ultrasound of IFP and the injections into the IFP triggered an additional surgical intervention. Ultrasound evaluation and injection may be beneficial in pain clinic patients presenting with AKP and may provide an opportunity for diagnosis.
Sex of household head and other household determinants of childhood anaemia among households in Ghana: regression analysis of the 2019 Malaria Indicator Survey
Authors: Klu Desmond , Agordoh Percival Delali 
Published: October 2022

Abstract
Background
Childhood anaemia is still a major public health concern. Although the prevalence of anaemia among children under age five is reducing in Ghana, the severity level is still worsening. This study sought to examine and compare household factors affecting the anaemia status of children under age five living in male- and female-headed households in Ghana.

Methods
The study used a weighted sample of 5,799 household heads from the 2019 Ghana Malaria Indicator Survey (GMIS). A binary logistic regression analysis was used to examine the effect of sex of household heads and other household factors on the anaemia status of children under the age of five in male- and female-headed households in Ghana. All analyses were conducted at the 95% confidence level.

Results
The results showed that a higher proportion (83.0%) of children under age five are not anaemic in households in Ghana. However, the probability of a child being anaemic is higher in male-headed households (aOR = 1.28; C.I:1.08–1.51), in the poorest (aOR = 2.41; CI: 1.59–3.65), poorer (aOR = 2.04; C.I:1.41–2.94) and middle (aOR = 1.78; C.I:1.29–2.46) household wealth category. Higher likelihood of anaemia was found among children in households that used charcoal (aOR = 1.51; C.I:1.15–1.99) and fuelwood (aOR = 1.44; C.I:1.02–2.02) for cooking. Similarly, there is a high probability of childhood anaemia in households with 5–10 members (aOR = 4.49; C.I: 3.78–5.34), 11 or more members (aOR = 7.21; C.I: 4.60–11.31) and household residing in northern part of Ghana (aOR = 1.40; C.I:1.07–1.83). The lower odds of being anaemic were recorded among children whose household heads were aged 40 years and older, household using other cooking fuels (aOR = 0.49; C.I: 0.21–0.78) and household with no bednets (aOR = 0.57; C.I: 0.44–0.74).

Conclusions
The GMIS data suggest that anaemia and its severity are higher among children living in MHH than among those living in FHH. The results indicate that poverty, a higher number of household members, relatively younger male household heads and the type of cooking fuel used were factors accounting for the differences in childhood anaemia in MHH and FHH. Equal attention should be given to MHH and FHH in terms of programmes and interventions aimed towards preventing and reducing childhood anaemia in Ghana.