Miracle-dz/UniFAR-FTUs huggingface dataset:
Successful Suicide Screening in the Pediatric Emergency Department: Youth, Parent, Researcher, and Clinician Perspectives

The purpose of this study was to include youth, parents, researchers, and clinicians in the identification of feasible and acceptable strategies for teen suicide screening in the pediatric emergency department (ED). Concept mapping methodology was used to elicit stakeholder responses. Regarding the most important result of suicide screening for teens in the pediatric ED, suicide prevention and education for parents, friends, and community members was rated easiest to implement, while short- and long-term follow-up and treatment was rated most important. In terms of successful suicide screening for teens in the pediatric ED, provision of resources and information was rated most feasible, and a safe, friendly, private screening environment was rated most important. The concept maps can be used to align suicide risk screening with the priorities and recommendations of pediatric ED stakeholders.
Developing a highly efficient and wildly adaptive CRISPR‐SaCas9 toolset for plant genome editing

The CRISPR- Streptococcus pyogenes Cas9 (SpCas9) system offers a rapid, simple and flexible genome editing approach. However, the targeting scope of the SpCas9 system is limited by the canonical NGG PAM. To broaden the editing range of the CRISPR system, several Cas orthologs recognized different PAM were isolated from diverse microbes and were engineered as powerful genome editing tools in eukaryotic cells (Murovec et al., 2017). One Cas9 ortholog, Staphylococcus aureus Cas9 (SaCas9), has a smaller size and comparable activity compared to SpCas9 (Kleinstiver et al., 2015a; Kleinstiver et al., 2015b). Previous studies reported that the SaCas9 could induce highly efficient targeted mutagenesis in Arabidopsis, citrus, tobacco and rice (Murovec et al., 2017). This article is protected by copyright. All rights reserved.
Long noncoding RNA CASC9 promotes LIN7A expression via miR‐758‐3p to facilitate the malignancy of ovarian cancer

The long noncoding RNA cancer susceptibility 9 (CASC9) has been reported to be a pivot modulator in growth and metastasis of breast cancer, liver cancer, esophageal squamous cell carcinoma, lung adenocarcinoma, gastric cancer, and nasopharyngeal cancer. However, its potential roles in ovarian cancer remain unclear. In this study, we aimed at its functions and molecular mechanism in ovarian cancer progression. We showed that CASC9 was highly expressed in ovarian cancer tissues and cell lines. An elevated level of CASC9 predicts an unfavorable prognosis in patients with ovarian cancer. Loss‐of‐function and gain‐of‐function assays illustrated that CASC9 promotes ovarian cancer cell proliferation, migration, and invasion in vitro, and accelerates tumor growth in vivo. We showed that CASC9 works as a competing endogenous RNA (ceRNA) for miR‐758‐3p which targets LIN7A. CASC9 inhibits the level of miR‐758‐3p, and in turn stimulates LIN7A expression in ovarian cancer. Overexpression of LIN7A reverses the suppressive roles of CASC9 depletion on ovarian cancer. In sum, our findings reveal a novel undefined regulatory signaling pathway, namely CASC9/miR‐758‐3p/LIN7A axis, involved in ovarian cancer progression.
Comparison of polyhexanide, cold atmospheric plasma and saline in the treatment of canine bite wounds.

OBJECTIVES To compare the efficacy of polyhexanide, cold argon plasma and saline in reducing bacterial bio-burden in dog bite wounds. MATERIALS AND METHODS Prospective blinded randomised clinical trial. Dogs were randomly assigned to one of the treatment groups by lottery and bacterial cultures obtained before and after treatment were compared. Bite wounds were surgically debrided and treated with polyhexanide, cold argon plasma or saline lavage. All wounds were cultured three times: directly after debridement, directly after prelavage with 2 mL/cm2 (saline in the saline and cold argon plasma group, or polyhexanide) and following the definitive lavage. Data were analysed using a generalised linear model for ordinal data. RESULTS A total of 85 dogs were enrolled in this study (polyhexanide n=29, cold argon plasma n=28, saline n=28). Positive bacterial culture results after debridement were obtained in 53/85 (62.3%) wounds. Polyhexanide and saline lavage significantly reduced the bio-burden, while cold argon plasma treatment did not. This effect was evident after prelavage when polyhexanide performed significantly better than saline and cold argon plasma as well as after final treatment. No significant differences were detected after prelavage or main treatment between saline and cold argon plasma. CLINICAL SIGNIFICANCE Polyhexanide lavage achieved the best immediate and ultimate decontamination of bite wounds.
Artemisinin inhibits breast cancer‐induced osteolysis by inhibiting osteoclast formation and breast cancer cell proliferation

In addition to being used to treat malaria, artemisinin (Art) can be used as an anti‐inflammatory and antitumor agent. In this study, we evaluated the effects of Art on osteoclast formation and activation and on the development of breast cancer cells in bone. To evaluate the effect of Art on osteoclast differentiation in vitro, we treated bone marrow‐derived macrophages (BMMs) with various concentrations of Art and evaluated the expression of genes and proteins involved in osteoclast formation. We also performed cell counting kit‐8 assays to evaluate the toxicity of Art in BMMs and MDA‐MB‐231 cells. We also performed Transwell assays, wound‐healing assays, colony formation assays, and cell apoptosis assays to evaluate the effect of Art in MDA‐MB‐231 cells. We also evaluated the effect of Art in an in vivo osteoclast bone resorption assay using a nude mouse model. We demonstrated that Art inhibits the differentiation and establishment of osteoclasts even though Art is not toxic to osteoclasts. In addition, Art reduced expression of genes involved in osteoclast formation and inhibited osteoclast bone resorption in a concentration‐dependent manner. Based on our data, we believe that Art can inhibit proliferation of breast cancer cells by activating apoptosis pathways, and inhibit osteoclast formation and differentiation by inhibiting activation of cathepsin K, ATPase H+ transporting V0 subunit D2, nuclear factor of activated T cells 1, calcitonin receptor, and tartrate‐resistant acid phosphatase and by inhibiting nuclear factor‐κB activation.
Exploiting correlated molecular-dynamics networks to counteract enzyme activity–stability trade-off

Significance Rigidifying flexible sites is a powerful method to improve enzyme stability. However, if the highly flexible regions form the active site, modifying them risks losing activity due to the activity–stability trade-off. We hypothesized here that regions outside the active site whose dynamics were highly correlated to flexible active sites, would provide good targets for stabilizing mutations. To test this hypothesis, six variants were constructed in the 3M variant of Escherichia coli transketolase. The best variant had a 10.8-fold improved half-life at 55 °C, and increased the Tm and Tagg by 3 °C and 4.3 °C, respectively. The variants even increased the activity, by up to threefold. This study highlights how protein engineering strategies could be potentially improved by considering long-range dynamics. The directed evolution of enzymes for improved activity or substrate specificity commonly leads to a trade-off in stability. We have identified an activity–stability trade-off and a loss in unfolding cooperativity for a variant (3M) of Escherichia coli transketolase (TK) engineered to accept aromatic substrates. Molecular dynamics simulations of 3M revealed increased flexibility in several interconnected active-site regions that also form part of the dimer interface. Mutating the newly flexible active-site residues to regain stability risked losing the new activity. We hypothesized that stabilizing mutations could be targeted to residues outside of the active site, whose dynamics were correlated with the newly flexible active-site residues. We previously stabilized WT TK by targeting mutations to highly flexible regions. These regions were much less flexible in 3M and would not have been selected a priori as targets using the same strategy based on flexibility alone. However, their dynamics were highly correlated with the newly flexible active-site regions of 3M. Introducing the previous mutations into 3M reestablished the WT level of stability and unfolding cooperativity, giving a 10.8-fold improved half-life at 55 °C, and increased midpoint and aggregation onset temperatures by 3 °C and 4.3 °C, respectively. Even the activity toward aromatic aldehydes increased up to threefold. Molecular dynamics simulations confirmed that the mutations rigidified the active-site via the correlated network. This work provides insights into the impact of rigidifying mutations within highly correlated dynamic networks that could also be useful for developing improved computational protein engineering strategies.
Body, Brain, Life for Cognitive Decline (BBL-CD): protocol for a multidomain dementia risk reduction randomized controlled trial for subjective cognitive decline and mild cognitive impairment

Background With no cure for dementia and the number of people living with the condition predicted to rapidly rise, there is an urgent need for dementia risk reduction and prevention interventions. Modifiable lifestyle risk factors have been identified as playing a major role in the development of dementia; hence, interventions addressing these risk factors represent a significant opportunity to reduce the number of people developing dementia. Relatively few interventions have been trialed in older participants with cognitive decline (secondary prevention). Objectives This study evaluates the efficacy and feasibility of a multidomain lifestyle risk reduction intervention for people with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Methods This study is an 8-week, two-arm, single-blind, randomized controlled trial (RCT) of a lifestyle modification program to reduce dementia risk. The active control group receives the following four online educational modules: dementia literacy and lifestyle risk, Mediterranean diet (MeDi), cognitive engagement and physical activity. The intervention group also completes the same educational modules but receives additional practical components including sessions with a dietitian, online brain training and sessions with an exercise physiologist to assist with lifestyle modification. Results Primary outcome measures are cognition (The Alzheimer’s Disease Assessment Scale-Cognitive-Plus [ADAS-Cog-Plus]) and a composite lifestyle risk factor score for Alzheimer’s disease (Australian National University – Alzheimer’s Disease Risk Index [ANU-ADRI]). Secondary outcome measures are motivation to change lifestyle (Motivation to Change Lifestyle and Health Behaviour for Dementia Risk Reduction [MCLHB-DRR]) and health-related quality of life (36-item Short Form Health Survey [SF-36]). Feasibility will be determined through adherence to diet (Mediterranean Diet Adherence Screener [MEDAS] and Australian Recommended Food Score [ARFS]), cognitive engagement (BrainHQ-derived statistics) and physical activity interventions (physical activity calendars). Outcomes are measured at baseline, immediately post-intervention and at 3- and 6-month follow-up by researchers blind to group allocation. Discussion If successful and feasible, secondary prevention lifestyle interventions could provide a targeted, cost-effective way to reduce the number of people with cognitive decline going on to develop Alzheimer’s disease (AD) and other dementias.
Gastrectomy and nigrostriatal dopaminergic depletion in de novo Parkinson's disease

Guido Alves, MD, PhD, Sampath Arepalli, MS, Dena G. Hernandez, PhD, Hirotaka Iwaki, MD, PhD, Mike A. Nalls, PhD, Andrew Singleton, PhD, Ole-Bjørn Tysnes, MD, PhD, Mathias Toft, MD, PhD, and Lasse Pihlstrøm, MD, PhD,* Institute of Clinical Medicine, University of Oslo, Oslo, Norway The Norwegian Center for Movement Disorders, Stavanger University Hospital, Stavanger, Norway The Centre for Organelle Research, University of Stavanger, Stavanger, Norway Department of Neurology, Stavanger University Hospital, Stavanger, Norway Department of Mathematics and Natural Sciences, University of Stavanger, Stavanger, Norway Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA Founder/Consultant with Data Tecnica International, Glen Echo, Maryland, USA Department of Neurology, Haukeland University Hospital, Bergen, Norway Department of Clinical Medicine, University of Bergen, Bergen, Norway Department of Neurology, Oslo University Hospital, Oslo, Norway
Segmentation of the Four-Layered Retinal Vasculature Using High-Resolution Optical Coherence Tomography Angiography Reveals the Microcirculation Unit.

Purpose To differentiate the four layers of the retinal vessel network in the human macula and examine their morphologic features using high-resolution optical coherence tomography angiography (HR-OCTA). Methods Macular areas measuring 464 × 464 pixels of 10 right eyes of 10 healthy subjects without ocular disease were scanned 10 times using a HR-OCTA device. Averaged OCTA images were created. Based on clear decorrelation signals, four vascular slabs were segmented, comprising one each in the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and top and bottom of the inner nuclear layer (INL). Qualitative features and quantitative measurements in each slab were compared with those in conventionally segmented slabs. Results HR-OCTA isolated four layers of vascular plexuses in the macula that followed the corresponding anatomic layers. Segmentations for the RNFL revealed that radial peripapillary capillaries (RPCs) extended to the central macular area. The RPCs followed relatively straight and long paths, with few apparent feed points and anastomoses. The GCL slab enhanced visualization of the capillary-free zones around the arteries and arterioles and helped to differentiate arterial and venous systems. The arterioles and venules were linked by capillaries that were arranged in a mesh-like fashion, with multiple arteriolar feed points and anastomoses. Vascular plexuses in the top and bottom of the INL consisted of capillaries in a vortex arrangement. The center of these vortex arrangements was consistent with the venules in the GCL. Conclusions HR-OCTA can differentiate the four layers of vascular plexuses in the human macula and elucidate their angiographic features.
Comparing two high correlation models to test the mechanical stability of americium-II

In this work two high density functional theory (DFT) correlation methodologies, the so called DFT+U (or GGA+U) implementation and the exact exchange of correlated electrons (EECE), hybrid DFT functional (or one case of hybrid DFT), are tested to determine the mechanical properties of americium-II. For each case, the numeric value of their principal parameter is chosen ( for the first case and for the second one) once the crystalline structure meets all the mechanical stability conditions. The results show that there is a range of values of and in which both methodologies generate a stable (experimentally correct) non-magnetic ground state, reaching approximately the same numeric value of the set of elastic constants of the cubic structure. However, only for the case of the hybrid functional results it is possible to show how the non-magnetic configuration is energetically favored, as compared to the ferromagnetic configuration. This happens around , a value in agreement with a previous analysis made under the same methodology for the metal case Am-I. Following a detailed and deep analysis, it is possible to find a close interrelation between the electronic properties of the metal: its distribution of states around the Fermi level, the energy difference between the two possible spin configurations, and the mechanical response of the crystal. Also, it is possible to conclude that the effect of alpha parameter on the electrons can be used as a parameter to simulate the presence of an external pressure over the structure. For the comparison, the calculations were performed within the LAPW approximation in DFT as implemented in the WIEN2k code, with a finite deformation method.
Identification of Drug-Side Effect Association via Semisupervised Model and Multiple Kernel Learning

Drug-side effect association contains the information on marketed medicines and their recorded adverse drug reactions. Traditional experimental method is time consuming and expensive. All associations of drugs and side-effects are seen as a bipartite network. Therefore, many computational approaches have been developed to deal with this problem, which are used to predict new potential associations. However, lots of methods did not consider multiple kernel learning (MKL) algorithm, which can integrate multiple sources of information and further improve prediction performance. In this study, we develop a novel predictor of drug-side effect association. First, we build multiple kernels from drug space and side-effect space. What is more, these corresponding kernels are linear weighted by MKL algorithm in drug space and side-effect space, respectively. Finally, a graph-based semisupervised learning is employed to construct drug-side effect predictor. Compared with existing methods, our method achieves better results on three benchmark data sets. The values of area under the precision recall curve are 0.668, 0.673, and 0.670 on three benchmark data sets, respectively. Our method is a useful tool for the side-effects prediction of drugs.
An interdomain bridge influences RNA binding of the human La protein

La proteins are RNA chaperones that perform various functions depending on distinct RNA-binding modes and their subcellular localization. In the nucleus, they help process UUU-3′OH–tailed nascent RNA polymerase III transcripts, such as pre-tRNAs, whereas in the cytoplasm they contribute to translation of poly(A)-tailed mRNAs. La accumulation in the nucleus and cytoplasm is controlled by several trafficking elements, including a canonical nuclear localization signal in the extreme C terminus and a nuclear retention element (NRE) in the RNA recognition motif 2 (RRM2) domain. Previous findings indicate that cytoplasmic export of La due to mutation of the NRE can be suppressed by mutations in RRM1, but the mechanism by which the RRM1 and RRM2 domains functionally cooperate is poorly understood. In this work, we use electromobility shift assays (EMSA) to show that mutations in the NRE and RRM1 affect binding of human La to pre-tRNAs but not UUU-3′OH or poly(A) sequences, and we present compensatory mutagenesis data supporting a direct interaction between the RRM1 and RRM2 domains. Moreover, we use collision-induced unfolding and time-resolved hydrogen–deuterium exchange MS analyses to study the conformational dynamics that occur when this interaction is intact or disrupted. Our results suggest that the intracellular distribution of La may be linked to its RNA-binding modes and provide the first evidence for a direct protein–protein interdomain interaction in La proteins.
Upregulation of KIF20A correlates with poor prognosis in gastric cancer

Background KIF20A is well known as one of the key proteins in mitosis. Recently, a number of studies illustrated that KIF20A might function as an oncogene in some carcinomas. However, its expression levels and clinical value remained unclear in gastric cancer (GC). Patients and methods In this study, we investigated the expression of KIF20A in samples from GC patients and cell lines by quantitative real-time PCR and Western blot. The function of KIF20A in cell proliferation of GC cell lines was examined via cell viability and colony formation assays. Immunohistochemistry assay based on a tissue microarray consisting of 146 cases was performed to evaluate the prognostic value of KIF20A. The overall survival rate of 122 GC patients based on KIF20A expression was analyzed as well. Finally, using KIF20A inhibitor, genistein, and combining it with cisplatin or fluorouracil, the antitumor effects were studied. Results Most GC samples (56.76%) showed higher KIF20A expression level compared to their corresponding normal specimens, which demonstrated the potential oncogenic role of KIF20A in GC. The functional studies elucidated the essential role of KIF20A in GC cell proliferation. Besides, tissue microarray result showed that the expression level of KIF20A was significantly related to the histological grades (P=0.036). Furthermore, we found the expression of KIF20A was related to poor overall survival rate, which is coincident with the results from Kaplan–Meier plotter database. In addition, we found that a KIF20A inhibitor, genistein, could enhance the antitumor activity of cisplatin and fluorouracil, which might be considered as a chemosensitive agent in GC. Conclusion KIF20A can promote cell proliferation in GC, which might be used as an independent prognostic factor and a potential therapeutic target.
Brain tissue iron quantification by MRI in intracerebral hemorrhage: Current translational evidence and pitfalls

Intracerebral hemorrhage (ICH) is a common subtype of hemorrhagic stroke with devastating consequences with no specific treatment. There is, however, substantial evidence for iron-mediated neurotoxicity in animal ICH models. Non-invasive quantification of the peri-hematomal tissue iron based on MRI has shown some promise in animal models and is being validated for clinical translation. This commentary reviews evidence for this approach and discusses potential pitfalls.
The Effects of Static and Moving Spectral Ripple Sensitivity on Unaided and Aided Speech Perception in Noise.

Purpose This study evaluated whether certain spectral ripple conditions were more informative than others in predicting ecologically relevant unaided and aided speech outcomes. Method A quasi-experimental study design was used to evaluate 67 older adult hearing aid users with bilateral, symmetrical hearing loss. Speech perception in noise was tested under conditions of unaided and aided, auditory-only and auditory-visual, and 2 types of noise. Predictors included age, audiometric thresholds, audibility, hearing aid compression, and modulation depth detection thresholds for moving (4-Hz) or static (0-Hz) 2-cycle/octave spectral ripples applied to carriers of broadband noise or 2000-Hz low- or high-pass filtered noise. Results A principal component analysis of the modulation detection data found that broadband and low-pass static and moving ripple detection thresholds loaded onto the first factor whereas high-pass static and moving ripple detection thresholds loaded onto a second factor. A linear mixed model revealed that audibility and the first factor (reflecting broadband and low-pass static and moving ripples) were significantly associated with speech perception performance. Similar results were found for unaided and aided speech scores. The interactions between speech conditions were not significant, suggesting that the relationship between ripples and speech perception was consistent regardless of visual cues or noise condition. High-pass ripple sensitivity was not correlated with speech understanding. Conclusions The results suggest that, for hearing aid users, poor speech understanding in noise and sensitivity to both static and slow-moving ripples may reflect deficits in the same underlying auditory processing mechanism. Significant factor loadings involving ripple stimuli with low-frequency content may suggest an impaired ability to use temporal fine structure information in the stimulus waveform. Support is provided for the use of spectral ripple testing to predict speech perception outcomes in clinical settings.