Miracle-dz/UniFAR-FTUs huggingface dataset:
A 60 Hz uniform electromagnetic field promotes human cell proliferation by decreasing intracellular reactive oxygen species levels

Previously, we showed that exposure of human normal and cancer cells to a 6 mT, 60 Hz gradient electromagnetic field (EMF) induced genotoxicity. Here, we investigated the cellular effects of a uniform EMF. Single or repetitive exposure to a 6 mT, 60 Hz uniform EMF neither induced DNA damage nor affected cell viability in HeLa and primary IMR-90 fibroblasts. However, continuous exposure of these cells to an EMF promoted cell proliferation. Cell viability increased 24.4% for HeLa and 15.2% for IMR-90 cells after a total 168 h exposure by subculture. This increase in cell proliferation was directly correlated with EMF strength and exposure time. When further incubated without EMF, cell proliferation slowed down to that of unexposed cells, suggesting that the proliferative effect is reversible. The expression of cell cycle markers increased in cells continuously exposed to an EMF as expected, but the distribution of cells in each stage of the cell cycle did not change. Notably, intracellular reactive oxygen species levels decreased and phosphorylation of Akt and Erk1/2 increased in cells exposed to an EMF, suggesting that reduced levels of intracellular reactive oxygen species play a role in increased proliferation. These results demonstrate that EMF uniformity at an extremely low frequency (ELF) is an important factor in the cellular effects of ELF-EMF.
Phosphodiesterase 2 inhibition preferentially promotes NO/guanylyl cyclase/cGMP signaling to reverse the development of heart failure

Significance The morbidity and mortality associated with heart failure (HF) are unacceptably high. Cyclic guanosine-3′,5′-monophosphate (cGMP) plays a key role in preserving cardiac structure and function, and therapeutically targeting cGMP in HF has shown promise in experimental models and patients. Phosphodiesterases (PDEs) metabolize and curtail the actions of cGMP (and cAMP), and increased PDE activity is thought to contribute to HF pathogenesis. Herein, we show that inhibition of one specific isoform, PDE2, enhances the salutary effects of cGMP in the context of HF, and that this beneficial action facilitates a distinct pathway, driven by nitric oxide, that is impaired in this disorder. These observations validate PDE2 inhibitors as a demonstrable means of boosting cardiac cGMP and advancing HF therapy. Heart failure (HF) is a shared manifestation of several cardiovascular pathologies, including hypertension and myocardial infarction, and a limited repertoire of treatment modalities entails that the associated morbidity and mortality remain high. Impaired nitric oxide (NO)/guanylyl cyclase (GC)/cyclic guanosine-3′,5′-monophosphate (cGMP) signaling, underpinned, in part, by up-regulation of cyclic nucleotide-hydrolyzing phosphodiesterase (PDE) isozymes, contributes to the pathogenesis of HF, and interventions targeted to enhancing cGMP have proven effective in preclinical models and patients. Numerous PDE isozymes coordinate the regulation of cardiac cGMP in the context of HF; PDE2 expression and activity are up-regulated in experimental and human HF, but a well-defined role for this isoform in pathogenesis has yet to be established, certainly in terms of cGMP signaling. Herein, using a selective pharmacological inhibitor of PDE2, BAY 60-7550, and transgenic mice lacking either NO-sensitive GC-1α (GC-1α−/−) or natriuretic peptide-responsive GC-A (GC-A−/−), we demonstrate that the blockade of PDE2 promotes cGMP signaling to offset the pathogenesis of experimental HF (induced by pressure overload or sympathetic hyperactivation), reversing the development of left ventricular hypertrophy, compromised contractility, and cardiac fibrosis. Moreover, we show that this beneficial pharmacodynamic profile is maintained in GC-A−/− mice but is absent in animals null for GC-1α or treated with a NO synthase inhibitor, revealing that PDE2 inhibition preferentially enhances NO/GC/cGMP signaling in the setting of HF to exert wide-ranging protection to preserve cardiac structure and function. These data substantiate the targeting of PDE2 in HF as a tangible approach to maximize myocardial cGMP signaling and enhancing therapy.
Efficacy and Safety of Continuous Subcutaneous Insulin Infusion vs. Multiple Daily Injections on Type 1 Diabetes Children: A Meta-Analysis of Randomized Control Trials

Objective: This meta-analysis was performed to evaluate the efficacy and safety of continuous subcutaneous insulin infusion (CSII) vs. multiple daily injections (MDI) in children with type 1 diabetes. Methods: A literature search was conducted on databases including PubMed and Embase up to June 2017. The pooled weighted mean difference or risk ratio as well as 95% confidence intervals were calculated using RevMan 5.3 software. Results: Eight studies involving 310 children with type 1 diabetes were included. Results showed that HbA1c (%) was significantly lower (p=0.007) after CSII compared with MDI in children with type 1 diabetes. In addition, there was no significant difference between groups in HbA1c (%) change, total daily insulin doses, change of total daily insulin doses and incidence of ketoacidosis and severe hypoglycemia. However, subgroup analyses indicated that age, treatment duration and study design were influenced the efficacy of CSII and MDI in children with type 1 diabetes. Conclusion: CSII is associated with lower HbA1c levels in children with type 1 diabetes but appears to have no effect on insulin requirement or incidence of ketoacidosis and severe hypoglycemia.
The TMEM16A channel mediates the fast polyspermy block in Xenopus laevis

In externally fertilizing animals, such as sea urchins and frogs, prolonged depolarization of the egg immediately after fertilization inhibits the entry of additional sperm – a phenomenon known as the fast block to polyspermy. In the African clawed frog, Xenopus laevis, this depolarization is driven by a Ca2+-activated Cl− efflux. Although the prominent Ca2+-activated Cl− currents generated by immature X. laevis oocytes are conducted by xTMEM16A channels, little is known about which channels contribute to fertilization-competency in mature eggs. Moreover, the gamete undergoes a gross transformation as it matures from an immature oocyte into a fertilization-competent egg. Here we report the results of our approach to identify the Ca2+-activated Cl− channel that triggers the fast block. Querying published proteomics and RNA-seq data, we identified two Ca2+-activated Cl− channels expressed in fertilization-competent X. laevis eggs: xTMEM16A and xBEST2A. Furthermore, transcripts for these channels increase in abundance during gamete maturation. To determine if either of these mediates the fast block, we characterized exogenously expressed xTMEM16A and xBEST2A using pharmacologic inhibitors. None of the inhibitors tested blocked xBEST2A currents specifically. However, Ani9 and MONNA each reduced xTMEM16A currents by more than 70%, while only nominally inhibiting those generated by xBEST2A. Using whole-cell recordings during fertilization, we found that Ani9 and MONNA effectively diminished fertilization-evoked depolarizations. These results indicate that fertilization activates TMEM16A channels in X. laevis eggs and induces the earliest known event triggered by fertilization: the fast block to polyspermy. HIGHLIGHTS Protein for the channels xBEST2A and xTMEM16A is present in X. laevis eggs. The inhibitors MONNA and Ani9 effectively block xTMEM16A compared to xBEST2A. Xenopus laevis fertilization opens TMEM16A to trigger egg depolarization. The TMEM16A-mediated depolarization is critical for the fast block to polyspermy.
In their own words: developing the Parent Experiences Questionnaire following neonatal brain injury using participatory design

ABSTRACT Primary objective: This study aimed to create a specific questionnaire (Parent Experiences Questionnaire) about early experiences, service involvement, and needs of children and parents following neonatal brain injury that could be used to inform clinical care and needed interventions. Research design and methods: A mixed-method design was utilized, engaging in both qualitative and quantitative methods across three phases. Phase 1 employed participatory design involving 12 parent and clinician participants in semi-structured interviews to address main topics, item importance, and overall impressions of the questionnaire. In phase 2, the questionnaire was piloted by 32 parents. Post hoc revisions added four questions to address current parent and child therapeutic needs in phase 3. Main outcomes and results: The final questionnaire yielded 24 items addressing topics of early communication between parent and clinicians, early intervention services, efficacy, and barriers in optimizing the child’s development and parents’ experience. The questionnaire was reviewed positively by a group of parents in phase 2 and demonstrated good acceptance, online feasibility, stability, and association with current parental mental health and child development. Conclusions: This investigation offers a valuable new questionnaire to inform clinical care regarding discussions with parents about neonatal brain injury, evaluate the perceived efficacy of early intervention services, and guide relevant future intervention efforts.
Abnormal Low-Frequency Oscillations Reflect Trait-Like Pain Ratings in Chronic Pain Patients Revealed through a Machine Learning Approach

Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a sensitive and reliable metric for studying pathological brain mechanisms across various chronic pain patient populations. However, the relationship between pathological brain activity and clinical symptoms are not well defined. Therefore, we used regional BOLD signal variability/amplitude of low-frequency oscillations (LFOs) to identify functional brain abnormalities in the dynamic pain connectome in chronic pain patients that are related to chronic pain characteristics (i.e., pain intensity). Moreover, we examined whether there were sex-specific attributes of these functional brain abnormalities and whether functional brain abnormalities in patients is related to pain intensity characteristics on different time scales. We acquired resting-state functional MRI and quantified frequency-specific regional LFOs in chronic pain patients with ankylosing spondylitis. We found that patients exhibit frequency-specific aberrations in LFOs. Specifically, lower-frequency (slow-5) abnormalities were restricted to the ascending pain pathway (thalamus and S1), whereas higher-frequency abnormalities also included the default mode (i.e., posterior cingulate cortex; slow-3, slow-4) and salience (i.e., mid-cingulate cortex) networks (slow-4). Using a machine learning approach, we found that these abnormalities, in particular within higher frequencies (slow-3), can be used to make generalizable inferences about patients' average pain ratings (trait-like pain) but not current (i.e., state-like) pain levels. Furthermore, we identified sex differences in LFOs in patients that were not present in healthy controls. These novel findings reveal mechanistic brain abnormalities underlying the longer-lasting symptoms (trait pain intensity) in chronic pain. SIGNIFICANCE STATEMENT Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a reliable metric for studying functional brain associated with chronic pain. The current results demonstrate that dysfunction in these intrinsic fluctuations/oscillations in the ascending pain pathway, default mode network, and salience network during resting state display sex differences and can be used to make inferences about trait-like pain intensity ratings in chronic pain patients. These results provide robust and generalizable implications for investigating brain mechanisms associated with longer-lasting/trait-like chronic pain symptoms.
Acceptance and Commitment Therapy for Psychosis and Trauma: Investigating Links between Trauma Severity, Attachment and Outcome

Background: Although Acceptance and Commitment Therapy (ACT) may be effective for individuals with psychosis and a history of childhood trauma, little is known about predictors of treatment response among such patients. Aims: The current study examined: (1) whether severity of trauma predicted treatment response, and (2) profiles of patients with regard to their responses to treatment. Method: Fifty participants with psychosis and childhood trauma history were recruited and randomized to take part in either eight sessions of group-based ACT, or to be on a waiting list for the ACT group (i.e. treatment as usual group). The entire sample was used for the first part of the analyses (aim 1), whereas subsequent subsample analyses used only the treatment group (n = 30 for aim 2). Results: It was found that trauma severity did not moderate the effectiveness of ACT on symptom severity, participants’ ability to regulate their emotional reactions, or treatment compliance with regard to help-seeking. In addition, among those receiving ACT, the results revealed three distinct and clinically relevant change profiles. Avoidant attachment style and number of sessions attended were predictive of belonging to the different clusters or profiles. Patients in the profile representing the least amount of clinical change attended an average of two sessions less than those in the other change profiles. Conclusion: ACT offered in a group format appears to be a promising treatment for those with psychosis and history of trauma regardless of trauma severity. Given the brevity of the intervention, patients should be encouraged to attend each session to obtain maximum benefit.
Ferrite-Tuned Resonant Cavities

The case of a dominant-mode rectangular cavity with a slab of ferrite against one side wall is treated. Use is made of the change in effective rf permeability of the ferrite in response to changes in the applied static magnetic field. Experimental results on an X-band cavity show a 10 per cent tuning range with an unloaded Q of 1,000 or more at 9,000 megacycles. Calculation of the Q of the cavity from the loss tangents of the ferrite material is outlined.
Was that my name? Infants’ listening in conversational multi-talker backgrounds

Abstract This study tested infants’ ability to segregate target speech from a background of ecologically valid multi-talker speech at a 10 dB SNR. Using the Headturn Preference Procedure, 72 English-learning 5-, 9-, and 12-month-old monolinguals were tested on their ability to detect and perceive their own name. At all three ages infants were able to detect the presence of the target speech, but only at 9 months did they show sensitivity to the phonetic details that distinguished their own name from other names. These results extend previous findings on infants’ speech perception in noise to more naturalistic forms of background speech.
Increase in circulating cells coexpressing M1 and M2 macrophage surface markers in patients with systemic sclerosis

Alterations in macrophage polarisation are recognised among the possible immune system abnormalities contributing to systemic sclerosis (SSc) pathogenesis.1 Macrophages have been classified as classically (M1) or alternatively (M2) activated, although growing evidence indicates that they may exhibit characteristics shared by more than one of the described phenotypes.2–5 An M2 pre-eminent phenotype has been postulated for SSc monocytes/macrophages.2 The aim of the study was to widen a phenotype characterisation (M1, M2 and mixed M1/M2) of circulating monocytes/macrophages in patients with SSc and healthy subjects (HSs) through flow cytometry analysis. Fifty-eight consecutive patients with SSc (38 limited and 20 diffuse SSc) and 27 age-matched and gender-matched HSs were enrolled after signing informed consent. SSc diagnosis was based on the 2013 American College of Rheumatology/European League Against Rheumatism criteria (online supplementary file 1). 6 For flow cytometry analysis, peripheral blood was collected and anti-CD14 and anti-CD45 antibodies were used to identify the monocyte/macrophage lineage; macrophage scavenger receptors (CD204, CD163) and mannose receptor 1 (CD206) were used as M2 phenotype markers; and co-stimulatory molecules (CD80, CD86) and Toll-like receptors (TLR4, TLR2) were used as M1 phenotype markers. CD66b was used to distinguish granulocytes (Miltenyi Biotech, Germany). Flow c ytometry analysis was performed using the Navios flow cytometer and Kaluza analysis software (Beckman Coulter). A total of 5 × 10 6 cells were evaluated and more than 30 events were detected in the smallest subset investigated, according to the consensus guidelines for minimal residual disease. Results were expressed in percentages over total circulating leu c ocytes, unless otherwise specified. The non-parametric al Mann-Whitney U test was used for statistical analysis and any p value lower than 0.05 was considered statistically significant. Two initial gating strategies were used to study circulating M2-like monocytes/macrophages, the first gated CD14+cells and the second gated CD204 …
In Vitro Antiviral Activity of Cabotegravir against HIV-2

We examined the antiviral activity of the integrase inhibitor (INI) cabotegravir against HIV-2 isolates from INI-naive individuals. HIV-2 was sensitive to cabotegravir in single-cycle and spreading-infection assays, with 50% effective concentrations (EC50s) in the low to subnanomolar range; comparable results were obtained for HIV-1 in both assay formats. ABSTRACT We examined the antiviral activity of the integrase inhibitor (INI) cabotegravir against HIV-2 isolates from INI-naive individuals. HIV-2 was sensitive to cabotegravir in single-cycle and spreading-infection assays, with 50% effective concentrations (EC50s) in the low to subnanomolar range; comparable results were obtained for HIV-1 in both assay formats. Our findings suggest that cabotegravir should be evaluated in clinical trials as a potential option for antiretroviral therapy and preexposure prophylaxis in HIV-2-prevalent settings.
Coherent Detection of Frequency-Hopped Quadrature Modulations in the Presence of Jamming - Part I: QPSK and QASK Modulations

This paper examines the performance of coherent QPSK and QASK systems combined with FH or FH/PN spread spectrum techniques in the presence of partial-band multitone or noise jamming. The worst-case jammer and worst-case performance are determined as functions of the signal-to-background noise ratio (SNR) and signal-to-jammer power ratio (SJR). Asymptotic results for high SNR are shown to have a linear dependence between the jammer's optimal power allocation and the system error probability performance.
Impact of Adult Scoliosis on Roussouly Sagittal Shape Classification

Study Design. A retrospective analysis of data collected prospectively in an adult spine deformity multicenter database. Objective. The aim of this study was to determine the impact of adult scoliosis (AS) on the type of Roussouly sagittal shape in terms of classification applicability, scoliosis modification of a patient theoretical sagittal shape, and coronal-sagittal deformity associations. Summary of Background Data. Roussouly described a four-type sagittal shape classification in healthy individuals, which has been also applied to patients with degenerative spinal disease. However, it remains uncertain if its principles can be applied to AS patients. Methods. AS patients recorded in a prospective multicenter database of adult spinal deformity were included. Preoperative sagittal radiographs were analyzed using the KEOPS software to measure pelvic parameters, global sagittal alignment, and the various criteria used for the Roussouly classification. The different sagittal shape types were compared using the Chi-square and McNemars tests, and analysis of variance with Bonferroni correction. Results. The classification was applicable to all of the 190 analyzed AS patients. In addition to Roussouly criteria, two parameters helped differentiate the different shapes: T10-L2 angle (24° ± 19 type-1; 14° ± 15 type-2; 3° ± 15 type-3; 0.4° ± 14 type-4; P < 0.001), and lordosis distribution index (90% ± 17 type-1; 83% ± 16 type-2; 73% ± 21 type-3; 63% ± 16 type-4; P < 0.001). AS changed the theoretical shape in 34% of the patients (P < 0.001). Curve etiology and curve pattern were not associated with any particular type of sagittal shape (P > 0.05). Type-1 was associated with older patients (P = 0.02), degenerative curves (P = 0.02), and greater PI-LL mismatch (P = 0.012). Types 3 to 4 were associated with younger age and idiopathic etiology (P < 0.001). Conclusion. Roussouly four-type sagittal shape classification could be applied to AS patients. AS modified the theoretical type in one of every three patients. No particular association was found between the sagittal types and specific coronal deformities. Sagittal shape recognition in patients with AS will help restore the appropriate theoretical shape through surgery, which can eventually lead to better surgical outcomes Level of Evidence: 2
APC2 associates with the actin cortex through a multipart mechanism to regulate cortical actin organization and dynamics in the Drosophila ovary

The actin cortex that lines the plasma membrane of most eukaryotic cells resists external mechanical forces and plays critical roles in a variety of cellular processes including morphogenesis, cytokinesis, and cell migration. Despite its ubiquity and significance, we understand relatively little about the composition, dynamics, and structure of the actin cortex. Adenomatous polyposis coli (APC) proteins regulate the actin and microtubule cytoskeletons through a variety of mechanisms, and in some contexts, APC proteins are cortically enriched. Here we show that APC2 regulates cortical actin dynamics in the follicular epithelium and the nurse cells of the Drosophila ovary and in addition affects the distribution of cortical actin at the apical side of the follicular epithelium. To understand how APC2 influences these properties of the actin cortex, we investigated the mechanisms controlling the cortical localization of APC2 in S2 cultured cells. We previously showed that the N‐terminal half of APC2 containing the Armadillo repeats and the C‐terminal 30 amino acids (C30) are together necessary and sufficient for APC2's cortical localization. Our work presented here supports a model that cortical localization of APC2 is governed in part by self‐association through the N‐terminal APC Self‐Association Domain (ASAD) and a highly conserved coiled‐coil within the C30 domain.