bluuebunny/crossref_metadata_2025_split huggingface dataset:
A small library of chalcones induce liver cancer cell death through Akt phosphorylation inhibition
Authors: Sahin Irem Durmaz , Christodoulou Michael S. , Guzelcan Ece Akhan , Koyas Altay , Karaca Cigdem , Passarella Daniele , Cetin-Atalay Rengul 
Published: July 2020

AbstractHepatocellular carcinoma (HCC) ranks as the fifth most common and the second deadliest cancer worldwide. HCC is extremely resistant to the conventional chemotherapeutics. Hence, it is vital to develop new treatment options. Chalcones were previously shown to have anticancer activities in other cancer types. In this study, 11 chalcones along with quercetin, papaverin, catechin, Sorafenib and 5FU were analyzed for their bioactivities on 6 HCC cell lines and on dental pulp stem cells (DPSC) which differentiates into hepatocytes, and is used as a model for untransformed control cells. 3 of the chalcones (1, 9 and 11) were selected for further investigation due to their high cytotoxicity against liver cancer cells and compared to the other clinically established compounds. Chalcones did not show significant bioactivity ($$\hbox {IC}_{50}>20\upmu \hbox {M}$$IC50>20μM) on dental pulp stem cells. Cell cycle analysis revealed that these 3 chalcone-molecules induced SubG1/G1 arrest. Akt protein phosphorylation was inhibited by these molecules in PTEN deficient, drug resistant, mesenchymal like Mahlavu cells leading to the activation of p21 and the inhibition of NF$$ \kappa $$κB-p65 transcription factor. Hence the chalcones induced apoptotic cell death pathway through NF$$ \kappa $$κB-p65 inhibition. On the other hand, these molecules triggered p21 dependent activation of Rb protein and thereby inhibition of cell cycle and cell growth in liver cancer cells. Involvement of PI3K/Akt pathway hyperactivation was previously described in survival of liver cancer cells as carcinogenic event. Therefore, our results indicated that these chalcones can be considered as candidates for liver cancer therapeutics particularly when PI3K/Akt pathway involved in tumor development.
Anisotropic and nonlinear magnetodielectric effects in orthoferrite ErFeO3 single crystals
Authors: Oh Dong Gun , Kim Jong Hyuk , Shin Hyun Jun , Choi Young Jai , Lee Nara 
Published: July 2020

AbstractIn rare-earth orthoferrites, strongly correlated order parameters have been thoroughly investigated, which aims to find multiple functionalities such as multiferroic or magnetoelectric properties. We have discovered highly anisotropic and nonlinear magnetodielectric effects from detailed measurements of magnetoelectric properties in single-crystalline orthoferrite, ErFeO3. Isothermal dielectric constant varies in shapes and signs depending on the relative orientations between the external electric and magnetic fields, which may be ascribed to the spin-phonon couplings. In addition, a dielectric constant with both electric and magnetic fields along the c axis exhibits two symmetric sharp anomalies, which are closely relevant to the spin-flop transition, below the ordering temperature of Er3+ spins, TEr = 3.4 K. We speculate that the magnetostriction from the exchange couplings between Er3+ and Fe3+ magnetic moments would be responsible for this relationship between electric and magnetic properties. Our results present significant characteristics of the orthoferrite compounds and offer a crucial guide for exploring suitable materials for magnetoelectric functional applications.
Effects of progranulin on the pathological conditions in experimental myocardial infarction model
Authors: Sasaki Takahiro , Shimazawa Masamitsu , Kanamori Hiromitsu , Yamada Yoshihisa , Nishinaka Anri , Kuse Yoshiki , Suzuki Genjiro , Masuda Tomomi , Nakamura Shinsuke , Hosokawa Masato , Minatoguchi Shinya , Hara Hideaki 
Published: July 2020

AbstractProgranulin is a secreted growth factor associated with multiple physiological functions in ischemic pathophysiology. However, it is still not fully understood how progranulin is involved in ischemic lesion and cardiac remodeling after myocardial infarction (MI). In this study, we investigated the effects of progranulin on myocardial ischemia and reperfusion injury. We investigated progranulin expression using Western blotting and immunostaining after permanent left coronary artery (LCA) occlusion in mice. Infarct size and the number of infiltrating neutrophils were measured 24 h after permanent LCA occlusion. Recombinant mouse progranulin was administered before LCA occlusion. In addition, we evaluated cardiac function using cardiac catheterization and echocardiography, and fibrosis size by Masson’s trichrome staining after myocardial ischemia/reperfusion in rabbits. Recombinant human progranulin was administered immediately after induction of reperfusion. Progranulin expression increased in the myocardial ischemic area 1, 3, and 5 days after permanent LCA occlusion in mice. The administration of recombinant mouse progranulin significantly attenuated infarct size and infiltrating neutrophils 24 h after permanent LCA occlusion in mice. We also found that administration of recombinant human progranulin ameliorated the deterioration of cardiac dysfunction and fibrosis after myocardial ischemia/reperfusion in rabbits. These findings suggest that progranulin may protect myocardial ischemia/reperfusion injury.
Influence of ventilation use and occupant behaviour on surface microorganisms in contemporary social housing
Authors: Sharpe T. , McGill G. , Dancer S. J. , King M.-F. , Fletcher L. , Noakes C. J. 
Published: July 2020

AbstractIn the context of increasingly airtight homes, there is currently little known about the type and diversity of microorganisms in the home, or factors that could affect their abundance, diversity and nature. In this study, we examined the type and prevalence of cultivable microorganisms at eight different sites in 100 homes of older adults located in Glasgow, Scotland. The microbiological sampling was undertaken alongside a household survey that collated information on household demographics, occupant behaviour, building characteristics, antibiotic use and general health information. Each of the sampled sites revealed its own distinct microbiological character, in both species and number of cultivable microbes. While some potential human pathogens were identified, none were found to be multidrug resistant. We examined whether the variability in bacterial communities could be attributed to differences in building characteristics, occupant behaviour or household factors. Sampled sites furnished specific microbiological characteristics which reflected room function and touch frequency. We found that homes that reported opening windows more often were strongly associated with lower numbers of Gram-negative organisms at indoor sites (p < 0.0001). This work offers one of the first detailed analysis of cultivable microbes in homes of older adults and their relationship with building and occupancy related factors, in a UK context.
Maternal total cell-free DNA in preeclampsia with and without intrauterine growth restriction
Authors: Kwak Dong Wook , Kim Shin Young , Kim Hyun Jin , Lim Ji Hyae , Kim Young-Han , Ryu Hyun Mee 
Published: July 2020

AbstractElevation of total cell-free DNA (cfDNA) in patients with preeclampsia is well-known; however, whether this change precedes the onset of symptoms remains inconclusive. Here, we conducted a nested case–control study to determine the elevation of cfDNA levels in women who subsequently developed preeclampsia. Methylated HYP2 (m-HYP2) levels were determined in 68 blood samples collected from women with hypertensive disorders of pregnancy, along with 136 control samples, using real-time quantitative PCR. The measured m-HYP2 levels were converted to multiples of the median (MoM) values for correction of maternal characteristics. The m-HYP2 levels and MoM values in patients with preeclampsia were significantly higher than in controls during the third trimester (P < 0.001, both), whereas those for women who subsequently developed preeclampsia did not differ during the second trimester. However, when patients with preeclampsia were divided based on the onset-time of preeclampsia or 10th percentile birth weight, both values were significantly higher in women who subsequently developed early-onset preeclampsia (P < 0.05, both) and preeclampsia with small-for-gestational-age (SGA) neonate (P < 0.01, both) than controls. These results suggested that total cfDNA levels could be used to predict early-onset preeclampsia or preeclampsia with SGA neonate.
Response of spike-wave discharges in aged APP/PS1 Alzheimer model mice to antiepileptic, metabolic and cholinergic drugs
Authors: Jin Nanxiang , Ziyatdinova Sofya , Gureviciene Irina , Tanila Heikki 
Published: July 2020

AbstractEpileptic nonconvulsive spike-wave discharges (SWDs) are commonly seen in amyloid plaque bearing transgenic mice but only rarely in their wild-type littermates. To shed light on their possible treatment options, we assessed the effect of drugs with variable and known mechanisms of action on the occurrence of SWDs in aged APPswe/PS1dE9 mice. The treatments included prototypic antiepileptic drugs (ethosuximide and levetiracetam), donepezil as the typical Alzheimer drug and atropine as an antagonistic effect, GABABantagonist CGP-35348, and alternate energy substrates beta-hydroxybutyrate (BHB), pyruvate and lactate on the occurrence of SWDs in aged APPswe/PS1dE9 mice. All agents were administered by single intraperitoneal injections at doses earlier documented to be effective and response was assessed by recording 3 h of video-EEG. Atropine at 25 mg/kg significantly decreased SWD occurrence in all behavioral states, and also resulted in altered frequency composition of SWDs and general EEG slowing during sleep. Ethosuximide at 200 mg/kg and levetiracetam at 75 mg/kg effectively suppressed SWDs only during a period of mixed behavioral states, but levetiracetam also increased SWDs in sleep. BHB at 1 g/kg decreased SWDs in sleep, while both pyruvate and lactate at the same dose tended to increase SWD number and total duration. Unexpectantly, donepezil at 0.3 mg/kg CGP-35348 at 100 mg/kg had no effect on SWDs. These findings call for re-evaluation of some prevailing theories on neural circuit alternations that underlie SWD generation and show the utility of APP/PS1 mice for testing potential new treatments for nonconvulsive epileptic activity related to Alzheimer pathology.
Uniaxial compression testing and Cauchy stress modeling to design anatomical silicone replicas
Authors: Hattab Georges , Ahlfeld Tilman , Klimova Anna , Koepp Alexander , Schuerer Michael , Speidel Stefanie 
Published: July 2020

AbstractAnatomically realistic organ replicas or phantoms allow for accurate studies and reproducible research. To recreate a human kidney, mimicry of the elastic properties of the human kidney is crucial. However, none of the related work addressed the design and development of a kidney phantom using only silicone as material. In contrast to paraffin and hydrogel, silicone is an ideal variant for its extended shelf life, soft-tissue-like feeling, and viscoelastic modularity. To this end, we conducted Uniaxial Compression testing and Cauchy stress modeling. Results indicate that none of the available manufacturer silicone brands are suitable for the task of creating a realistic kidney phantom. Indeed, the tested silicone mixtures in low and high strain fall outside the required approximate target compressive moduli of 20 kPa and 500 kPa, respectively. This work provides a frame of reference for future work by avoiding the pitfalls of the selected ready-made silicones and reusing the reported theoretical and experimental setup to design a realistic replica of the kidney organ.
Cumulative live-birth, perinatal and obstetric outcomes for POSEIDON groups after IVF/ICSI cycles: a single-center retrospective study
Authors: Abdullah Raed K. , Liu Nenghui , Zhao Yuhao , Shuang Yang , Shen Zhang , Zeng Hong , Wu Jielei 
Published: July 2020

AbstractRecently, perinatal outcomes and cumulative live birth rate (CLBR) have widely been utilized to assess the fertility outcomes and safety of assisted reproductive technology (ART), but more robust research is needed to address the success rates of live-healthy births resulting from this procedure, particularly for patients with low prognosis. This study aims to assess and comparative perinatal outcomes and CLBR per cycle of in vitro fertilization/Intracytoplasmic sperm injection (IVF/ICSI) between four groups of low prognosis characterized by POSEIDON criteria. A retrospective assessment was done among infertile women with a low prognosis undergoing IVF/ICSI at a reproductive center in China. Data were collected between January 2011 and December 2015 with a follow-up of at least two years, and censoring was defined by three-cycle completion, discontinuation, or having a live birth. Participants were grouped into 4 groups according to the POSEIDON classification (POSEIDON1, POSEIDON2, POSEIDON3, and POSEIDON4). The main outcomes were perinatal and obstetric outcomes with CLBR per cycle after IVF/ICSI procedure. And IVF/ICSI-technique outcomes as a secondary outcome. Statistical analyses were performed by SPSS, and a p value of < 0.05 was considered significant. A total of 461 eligible participants underwent a total of 825 IVF/ICSI cycles. POSEIDON1 had the best perinatal outcomes in terms of live births (≥ 28w) (54.8%). POSEIDON4 had a higher risk for perinatal and obstetric complications with abortion rate (9.8%); LBW (11.7%), PTD (23.5%), PROM (11.7%), and gestational diabetes (17.6%). POSEIDON2 had a high rate for malpresentation (14.2%), and cesarean delivery(57.2%), while POSEIDON3 was much associated with the occurrences of placenta previa (9.3%) compared to other groups (p value = 0.001). After adjusting odds ratio by age and BMI, POSEIDON4 had the least odds for biochemical pregnancy (p value = 0.019); and the least odds for clinical pregnancy (p value = 0.001) of the four groups. CLBR per cycle was better in POSEIDON1 and increased with an increasing number of cycles in all groups during the three cycles. Conservative CLBR after three complete cycles were 77.27%, 42.52%, 51.4% and 22.34%, while optimistic CLBR were 79.01%, 51.19%, 58.59% and 34.46% in POSEIDON1 to POSEIDON4, respectively. Younger women with low prognosis and normal ovarian reserve have a higher probability for live births and better perinatal outcomes compared with older women with poor or normal ovarian reserve. Besides, young women with low prognosis, despite ovarian reserve status, can increase their probability of conception and get relatively higher CLBR by undergoing multiple cycles of IVF/ICSI. Age is therefore considered as a critical parameter in predicting the perinatal outcome and CLBR.
Walking characteristics including mild motor paralysis and slow walking speed in post-stroke patients
Authors: Mizuta Naomichi , Hasui Naruhito , Nakatani Tomoki , Takamura Yusaku , Fujii Shintaro , Tsutsumi Masako , Taguchi Junji , Morioka Shu 
Published: July 2020

AbstractWalking speed is strongly influenced by the severity of motor paralysis in post-stroke patients. Nevertheless, some patients with mild motor paralysis still walk slowly. Factors associated with this difference in walking speed have not been elucidated. To confirm walking characteristics of patients with mild motor paralysis and slow walking speed, this study identified patient subgroups based on the association between the severity of motor paralysis and walking speed. Fugl-Meyer assessment synergy score (FMS) and the walking speed were measured (n = 42), and cluster analysis was performed based on the association between FMS and walking speed to identify the subgroups. FMS and walking speed were associated (ρ = 0.50); however, some patients walked slowly despite only mild motor paralysis. Cluster analysis using FMS and walking speed as the main variables classified patients into subgroups. Patients with mild motor paralysis (FMS: 18.4 ± 2.09 points) and slow walking speed (0.28 ± 0.14 m/s) exhibited poorer trunk stability, increased co-contraction of the shank muscle, and increased intramuscular coherence in walking compared to other clusters. This group was identified by their inability to fully utilize the residual potential of motor function. In walking training, intervention in instability and excessive cortical control may be effective.
A PIP2 substitute mediates voltage sensor-pore coupling in KCNQ activation
Authors: Liu Yongfeng , Xu Xianjin , Gao Junyuan , Naffaa Moawiah M. , Liang Hongwu , Shi Jingyi , Wang Hong Zhan , Yang Nien-Du , Hou Panpan , Zhao Wenshan , White Kelli McFarland , Kong Wenjuan , Dou Alex , Cui Amy , Zhang Guohui , Cohen Ira S. , Zou Xiaoqin , Cui Jianmin 
Published: July 2020

AbstractKCNQ family K+ channels (KCNQ1-5) in the heart, nerve, epithelium and ear require phosphatidylinositol 4,5-bisphosphate (PIP2) for voltage dependent activation. While membrane lipids are known to regulate voltage sensor domain (VSD) activation and pore opening in voltage dependent gating, PIP2 was found to interact with KCNQ1 and mediate VSD-pore coupling. Here, we show that a compound CP1, identified in silico based on the structures of both KCNQ1 and PIP2, can substitute for PIP2 to mediate VSD-pore coupling. Both PIP2 and CP1 interact with residues amongst a cluster of amino acids critical for VSD-pore coupling. CP1 alters KCNQ channel function due to different interactions with KCNQ compared with PIP2. We also found that CP1 returned drug-induced action potential prolongation in ventricular myocytes to normal durations. These results reveal the structural basis of PIP2 regulation of KCNQ channels and indicate a potential approach for the development of anti-arrhythmic therapy.
PRIME-3D2D is a 3D2D model to predict binding sites of protein–RNA interaction
Authors: Xie Juan , Zheng Jinfang , Hong Xu , Tong Xiaoxue , Liu Shiyong 
Published: July 2020

AbstractProtein-RNA interaction participates in many biological processes. So, studying protein–RNA interaction can help us to understand the function of protein and RNA. Although the protein–RNA 3D3D model, like PRIME, was useful in building 3D structural complexes, it can’t be used genome-wide, due to lacking RNA 3D structures. To take full advantage of RNA secondary structures revealed from high-throughput sequencing, we present PRIME-3D2D to predict binding sites of protein–RNA interaction. PRIME-3D2D is almost as good as PRIME at modeling protein–RNA complexes. PRIME-3D2D can be used to predict binding sites on PDB data (MCC = 0.75/0.70 for binding sites in protein/RNA) and transcription-wide (MCC = 0.285 for binding sites in RNA). Testing on PDB and yeast transcription-wide data show that PRIME-3D2D performs better than other binding sites predictor. So, PRIME-3D2D can be used to predict the binding sites both on PDB and genome-wide, and it’s freely available.
Properties of Lexical Diversity in the Narratives of Children With Typical Language Development and Developmental Language Disorder
Authors: Charest Monique , Skoczylas Melissa J. , Schneider Phyllis 
Published: July 2020

Purpose
We examined four measures of lexical diversity in the narratives of children with typical language development (TLD) and developmental language disorder (DLD) that comprised the normative sample of the Edmonton Narrative Norms Instrument (Schneider et al., 2005). The purpose was to document the properties of each measure with respect to variations in utterance and sample length, developmental trends, and group differences.

Method

The sample consisted of 377 picture-elicited, story generation transcripts from children with TLD (
n
= 300) and DLD (
n
= 77) aged 4–9 years. We extracted the moving-average type–token ratio (MATTR) and the number of different words from the full sample, from samples equated for the number of utterances, and from samples equated for the total number of words.

Results
MATTR was the only measure to show no relationships to utterance or sample length. All measures showed significant positive growth with age and significant groupwise differences between children with TLD and DLD. However, the magnitude of age effects and differentiation between groups varied considerably across measures. Across measures, there were significant differences in the number of children with DLD who were identified with low lexical diversity relative to their same-age peers in the TLD group.

Conclusion
The results of this study support the view that different measures of lexical diversity may be appropriate for different clinical purposes. It is important for clinicians to understand how measures of lexical diversity function in order to make educated choices among measures and ensure appropriate interpretation.
The Importance of Morphological Awareness in Bilingual Language and Literacy Skills: Clinical Implications for Speech-Language Pathologists
Authors: Fumero Keisey , Tibi Sana 
Published: July 2020

PurposeThis clinical focus article will highlight the importance and role of morphological awareness (MA) across orthographies, in particular, the role it plays in reading development, specifically with bilingual populations. MA supports reading acquisition and development beyond other predictors of reading, such as phonological awareness, orthographic knowledge, and rapid automatic naming to name a few. While MA aids in the development of decoding fluency, vocabulary development, and reading comprehension, explicit morphological instruction does not occur regularly in reading intervention. For English learners (ELs), instruction should focus on improving MA, semantic awareness, and orthographic processing, which in turn would exert a positive influence on reading accuracy, fluency, and comprehension. This clinical focus article aims to provide speech-language pathologists with applicable tasks to measure MA and strategies to guide explicit morphological instruction.MethodThe role of MA in reading development will be described with regard to its importance beyond other predictors and the role it plays in theoretical models of reading development. Then, MA will be described across orthographies, with a focus on cross-linguistic influences. Finally, measurement tasks will be described, and clinical implications will be discussed in terms of using different strategies and tools to explicitly address MA.ConclusionClinical implications of morphological instruction should be further explored and incorporated in current practices. With regard to ELs, it is important that we provide effective and specific instruction to better bridge the academic achievement gaps and increase overall language and literacy skills. Morphological instruction should be explicit and provided in conjunction with other domains of language. Equally important is leveraging families of ELs to promote their children's oral language and literacy in their first language.