Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment with 3-Aminobenzamide Negates the Radiofrequency-Induced Adaptive Response in Two Cell Models

In previous investigations, we demonstrated that pre-exposure of different cell cultures to radiofrequency fields can reduce the damage induced by genotoxic agents, an effect resembling the so-called adaptive response. In this study, we pre-exposed human peripheral blood lymphocytes and Chinese hamster lung fibroblast cell line to 1950 MHz, UMTS (Universal Mobile Telecommunication System) signal, for 20 h, and then treated cultures with Mitomycin-C. After confirming the induction of an adaptive response in terms of the reduction of micronuclei formation, we observed that such a response was negated by treatments with 3-aminobenzamide. Since 3-aminobenzamide is an inhibitor of poly (ADP-ribose) polymerase enzyme, which is involved in DNA repair, these results support the possible involvement of DNA repair mechanisms in radiofrequency-induced adaptive response.
Hyperpolarized Helium 3 MRI in Mild-to-Moderate Asthma: Prediction of Postbronchodilator Reversibility.

Background Longitudinal progression to irreversible airflow limitation occurs in approximately 10% of patients with asthma, but it is difficult to identify patients who are at risk for this transition. Purpose To investigate 6-year longitudinal changes in hyperpolarized helium 3 (3He) MRI ventilation defects in study participants with mild-to-moderate asthma and identify predictors of longitudinal changes in postbronchodilator forced expiratory volume in 1 second (FEV1) reversibility Materials and Methods Spirometry and hyperpolarized 3He MRI were evaluated in participants with mild-to-moderate asthma in two prospectively planned visits approximately 6 years apart. Participants underwent methacholine challenge at baseline (January 2010 to April 2011) and pre- and postbronchodilator evaluations at follow-up (November 2016 to June 2017). FEV1 and MRI ventilation defects, quantified as ventilation defect volume (VDV), were compared between visits by using paired t tests. Participants were dichotomized by postbronchodilator change in FEV1 at follow-up, and differences between reversible and not-reversible groups were determined by using unpaired t tests. Multivariable models were generated to explain postbronchodilator FEV1 reversibility at follow-up. Results Eleven participants with asthma (mean age, 42 years ± 9 [standard deviation]; seven men) were evaluated at baseline and after mean 78 months ± 7. Medications, exacerbations, FEV1 (76% predicted vs 76% predicted; P = .91), and VDV (240 mL vs 250 mL; P = .92) were not different between visits. In eight of 11 participants (73%), MRI ventilation defects at baseline were at the same location in the lung at follow-up MRI. In the remaining three participants (27%), MRI ventilation defects worsened at the same lung locations as depicted at baseline methacholine-induced ventilation. At follow-up, postbronchodilator FEV1 was not reversible in six of 11 participants; the concentration of methacholine to decrease FEV1 by 20% (PC20) was greater in FEV1-irreversible participants at follow-up (P = .01). In a multivariable model, baseline MRI VDV helped to predict postbronchodilator reversibility at follow-up (R 2 = 0.80; P < .01), but PC20, age, and FEV1 did not (R 2 = 0.63; P = .15). Conclusion MRI-derived, spatially persistent ventilation defects predict postbronchodilator reversibility 78 months ± 7 later for participants with mild-to-moderate asthma in whom there were no changes in lung function, medication, or exacerbations. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Stojanovska in this issue.
Prenatal socioeconomic status and social support are associated with neonatal brain morphology, toddler language and psychiatric symptoms

ABSTRACT Few studies have assessed the association of parental socioeconomic status (SES) with brain measures in neonates, at a time when exposure to the postnatal environment is minimal. Social support may buffer the adverse consequences of SES, and has been associated with better cognitive – emotional development in children. We studied the association of prenatal SES and social support with neonatal brain structure, and toddler cognition, and psychiatric symptoms. In a sample of 37 healthy neonates, we correlated a measure of SES and marital/partner status (an index of social support) with morphological features of the cerebral surface measured on high-resolution MRI scans between the 1st – 6th weeks of postnatal life. We then assessed how SES relates to cognitive and behavioral outcomes at age 24-months. We found that neonates born to mothers with lower SES had greater local volumes at the surface of the right occipital lobe, left temporal pole, and left inferior frontal and anterior cingulate regions. Partner status moderated the associations of SES on neonatal brain morphology. Lower SES was associated with poorer language scores and less severe ADHD and ODD symptoms. In summary, SES was associated with neonatal brain structure and language and behavioral outcomes at toddler age. Future studies with a greater sample size and longitudinal MRI scans will help to determine whether prenatal SES continues to relate to early brain development in the same or different brain regions.
Early Sex Differences in the Immune-Inflammatory Responses to Neonatal Ischemic Stroke

We recently reported that neonatal ischemia induces microglia/macrophage activation three days post-ischemia. We also found that female mice sustained smaller infarcts than males three months post-ischemia. The objective of our current study was to examine whether differential acute neuroinflammatory response and infiltrated immune cells occurs between male and females after three days post-ischemia. Permanent middle cerebral artery occlusion was induced in male and female postnatal 9-day-old (P9) mice, and mice were sacrificed three days after ischemia. Brains were analyzed for mRNA transcription after microglia magnetic cell sorting to evaluate M1 and M2 markers. FACS analysis was performed to assess myeloid infiltration and microglial expression of CX3 chemokine receptor 1 (CX3CR1). Inflammatory cytokine expression and microglia/macrophage activation were analyzed via in situ hybridization combined with immunofluorescence techniques. Lesion volume and cell death were measured. An increase in microglia/macrophages occurred in male versus female mice. The cells exhibited amoeboid morphology, and TNFα and ptgs2 (Cox-2) genes were more expressed in males. More myeloid cell infiltration was found in male versus female brains. However, we did not observe sex-dependent differences in the injured volume or cell death density. Our data show that sex differences in the acute microglial and immune responses to neonatal ischemia are likely both gene- and region-specific.
Factors Influencing Early Marginal Bone Loss around Dental Implants Positioned Subcrestally: A Multicenter Prospective Clinical Study

Early marginal bone loss (MBL) is a non-infective remodeling process of variable entity occurring within the first year after implant placement. It has a multifactorial etiology, being influenced by both surgical and prosthetic factors. Their impact remains a matter of debate, and controversial information is available, particularly regarding implants placed subcrestally. The present multicenter prospective clinical study aimed to correlate marginal bone loss around platform-switched implants with conical connection inserted subcrestally to general and local factors. Fifty-five patients were enrolled according to strict inclusion/exclusion criteria by four clinical centers. Single or multiple implants (AnyRidge, MegaGen, South Korea) were inserted in the posterior mandible with a one-stage protocol. Impressions were taken after two months of healing (T1), screwed metal-ceramic restorations were delivered three months after implant insertion (T2), and patients were recalled after six months (T3) and twelve months (T4) of prosthetic loading. Periapical radiographs were acquired at each time point. Bone levels were measured at each time point on both mesial and distal aspects of implants. Linear mixed models were fitted to the data to identify predictors associated with MBL. Fifty patients (25 male, 25 female; mean age 58.0 ± 12.8) with a total of 83 implants were included in the final analysis. The mean subcrestal position of the implant shoulder at baseline was 1.24 ± 0.57 mm, while at T4, it was 0.46 ± 0.59 mm under the bone level. Early marginal bone remodeling was significantly influenced by implant insertion depth and factors related to biological width establishment (vertical mucosal thickness, healing, and prosthetic abutment height). Deep implant insertion, thin peri-implant mucosa, and short abutments were associated with greater marginal bone loss up to six months after prosthetic loading. Peri-implant bone levels tended to stabilize after this time, and no further marginal bone resorption was recorded at twelve months after implant loading.
Fruit and Vegetable Consumption and Potential Moderators Associated with All-Cause Mortality in a Representative Sample of Spanish Older Adults

This study sought to determine the association between levels of fruit and vegetable consumption and time to death, and to explore potential moderators. We analyzed a nationally-representative sample of 1699 older adults aged 65+ who were followed up for a period of 6 years. Participants were classified into low (≤3 servings day), medium (4), or high (≥5) consumption using tertiles. Unadjusted and adjusted cox proportional hazard regression models (by age, gender, cohabiting, education, multimorbidity, smoking, physical activity, alcohol consumption, and obesity) were calculated. The majority of participants (65.7%) did not meet the recommendation of five servings per day. High fruit and vegetable intake increased by 27% the probability of surviving among older adults with two chronic conditions, compared to those who consumed ≤3 servings per day (HR = 0.38, 95%CI = 0.21–0.69). However, this beneficial effect was not found for people with none, one chronic condition or three or more, indicating that this protective effect might not be sufficient for more severe cases of multimorbidity. Given a common co-occurrence of two non-communicable diseases in the elderly and the low frequency of fruit and vegetable consumption in this population, interventions to promote consuming five or more servings per day could have a significant positive impact on reducing mortality.
CNS Correlates of "Objective" Neuropathy in Alcohol Use Disorder.

BACKGROUND Among the neurological consequences of alcoholism is peripheral neuropathy. Relative to HIV or diabetes-related neuropathies, neuropathy associated with Alcohol Use Disorders (AUD) is understudied. In both the diabetes and HIV literature, emerging evidence supports a CNS component to peripheral neuropathy. METHODS In seeking a central substrate for AUD-related neuropathy, the current study was conducted in 154 individuals with AUD (43 women, ages 21-74) and 99 healthy controls (41 women, ages 21-77) and explored subjective symptoms (self-report) and objective signs (perception of vibration, deep tendon ankle reflex, position sense, 2-point discrimination) of neuropathy separately. In addition to regional brain volumes, risk factors for AUD-related neuropathy, including age, sex, total lifetime ethanol consumed, nutritional indices (i.e., thiamine, folate), and measures of liver integrity (i.e., γ-glutamyl-transferase) were evaluated. RESULTS The AUD group described more subjective symptoms of neuropathy and were more frequently impaired on bilateral perception of vibration. From 5 correlates, the number of AUD-related seizures was most significantly associated with subjective symptoms of neuropathy. There were 15 correlates of impaired perception of vibration among the AUD participants: of these, age and volume of frontal precentral cortex were the most robust predictors. CONCLUSIONS This study supports CNS involvement in objective signs of neuropathy in AUD. This article is protected by copyright. All rights reserved.
Long-term Effects of Moderate versus High Durations of Aerobic Exercise on Biomarkers of Breast Cancer Risk: Follow-up to a Randomized Controlled Trial

Background: The optimal lifestyle for breast cancer prevention over the long term is unclear. We aimed to determine whether or not the amount of exercise prescribed in a year-long exercise intervention influences breast cancer biomarker levels 1 year later. Methods: We conducted a 24-month follow-up study (2012–2014) to the Breast Cancer and Exercise Trial in Alberta (BETA), a 12-month, two-armed (1:1), two-center randomized controlled trial of exercise in 400 cancer-free, postmenopausal women. The exercise prescription was moderate–vigorous aerobic exercise, 5 days/week (3 days/week supervised) for 30 minutes/session (MODERATE) or 60 minutes/session (HIGH). Participants were asked not to change their usual diet. We used linear mixed models to compare biomarker concentrations (C-reactive protein, insulin, glucose, HOMA-IR, estrone, sex hormone binding globulin, total estradiol, and free estradiol) over time (0, 12, and 24 months) by group (MODERATE, HIGH), using group–time interactions. Results: After 12 months of no intervention, 24-month fasting blood samples were available for 84.0% and 82.5% of MODERATE and HIGH groups, respectively (n = 333/400). We found no evidence that 0 to 24– or 12 to 24–month biomarker changes differed significantly between randomized groups (HIGH:MODERATE ratio of mean biomarker change ranged from 0.97 to 1.06, P values >0.05 for all). We found more favorable biomarker profiles among participants who experienced greater than the median fat loss during the trial. Conclusions: Prescribing aerobic exercise for 300 versus 150 minutes/week for 12 months to inactive, postmenopausal women had no effects on longer-term biomarkers. Impact: Exercise may lead to larger improvements in breast cancer biomarkers after intervention among women who also experience fat loss with exercise.
Disentangling the role of photosynthesis and stomatal conductance on rising forest water-use efficiency

Significance Forests remove about 30% of anthropogenic CO2 emissions through photosynthesis and return almost 40% of incident precipitation back to the atmosphere via transpiration. The trade-off between photosynthesis and transpiration through stomata, the water-use efficiency (WUE), is an important driver of plant evolution and ecosystem functioning, and has profound effects on climate. Using stable carbon and oxygen isotope ratios in tree rings, we found that WUE has increased by a magnitude consistent with estimates from atmospheric measurements and model predictions. Enhanced photosynthesis was widespread, while reductions in stomatal conductance were modest and restricted to moisture-limited forests. This result points to smaller reductions in transpiration in response to increasing atmospheric CO2, with important implications for forest–climate interactions, which remain to be explored. Multiple lines of evidence suggest that plant water-use efficiency (WUE)—the ratio of carbon assimilation to water loss—has increased in recent decades. Although rising atmospheric CO2 has been proposed as the principal cause, the underlying physiological mechanisms are still being debated, and implications for the global water cycle remain uncertain. Here, we addressed this gap using 30-y tree ring records of carbon and oxygen isotope measurements and basal area increment from 12 species in 8 North American mature temperate forests. Our goal was to separate the contributions of enhanced photosynthesis and reduced stomatal conductance to WUE trends and to assess consistency between multiple commonly used methods for estimating WUE. Our results show that tree ring-derived estimates of increases in WUE are consistent with estimates from atmospheric measurements and predictions based on an optimal balancing of carbon gains and water costs, but are lower than those based on ecosystem-scale flux observations. Although both physiological mechanisms contributed to rising WUE, enhanced photosynthesis was widespread, while reductions in stomatal conductance were modest and restricted to species that experienced moisture limitations. This finding challenges the hypothesis that rising WUE in forests is primarily the result of widespread, CO2-induced reductions in stomatal conductance.
Sleep restriction does not potentiate nocebo‐induced changes in pain and cortical potentials

The increased pain sensitivity following reduced sleep may be related to changes in cortical processing of nociceptive stimuli. Expectations shape pain perception and can inhibit (placebo) or enhance (nocebo) pain. Sleep restriction appears to enhance placebo responses; however, whether sleep restriction also affects nocebo responses remains unknown. The aim of the present study was to determine whether sleep restriction facilitates nocebo‐induced changes in pain and pain‐evoked cortical potentials.
Repurposing dasatinib for diffuse large B cell lymphoma

Significance Novel therapies are needed for ∼40% of patients with diffuse large B cell lymphoma (DLBCL) who do not respond to standard immunochemotherapy. Here we show that dasatinib, a drug used in B cell acute lymphoblastic leukemia and chronic myelogenous leukemia, may be repositioned for DLBCL therapy and combined with mTORC2 inhibitors for resistant cases. Our results can provide the basis for clinical trials using dasatinib for DLBCL as well as other lymphoid malignancies, which depend on cellular pathways targeted by dasatinib. To repurpose compounds for diffuse large B cell lymphoma (DLBCL), we screened a library of drugs and other targeted compounds approved by the US Food and Drug Administration on 9 cell lines and validated the results on a panel of 32 genetically characterized DLBCL cell lines. Dasatinib, a multikinase inhibitor, was effective against 50% of DLBCL cell lines, as well as against in vivo xenografts. Dasatinib was more broadly active than the Bruton kinase inhibitor ibrutinib and overcame ibrutinib resistance. Tumors exhibiting dasatinib resistance were commonly characterized by activation of the PI3K pathway and loss of PTEN expression as a specific biomarker. PI3K suppression by mTORC2 inhibition synergized with dasatinib and abolished resistance in vitro and in vivo. These results provide a proof of concept for the repurposing approach in DLBCL, and point to dasatinib as an attractive strategy for further clinical development in lymphomas.
Fatty degeneration and wnt10b expression in the supraspinatus muscle after surgical repair of torn rotator cuff tendon

Purpose: In the torn rotator cuff muscles, decreased expression of wnt10b prior to elevation of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) has previously been reported. The purpose of this study is to elucidate the expression profiles of these adipogenesis-related genes after rotator cuff detachment and reattachment in a rabbit model. Methods: We investigated gene expression profiles of PPARγ, C/EBPα, and wnt10b in different parts of rabbit supraspinatus (SSP) muscle after tendon detachment (n = 6 for each time point). In addition, we assessed expression of the same genes after SSP reattachment with different intervals from initial detachment (n = 6). Fatty degeneration of the SSP muscle was examined by Oil red-O staining. Gene expression profiles were examined by quantitative real-time polymerase chain reaction. Results: After SSP detachment, Oil red-O-positive oil deposits increased after 3 weeks. In the SSP reattachment model, numerous Oil red-O-positive cells were present at 5-week reattachment, following 2- and 3-week detachment. PPARγ and C/EBPα messenger ribonucleic acid expression exhibited a significant increase at 2 and 3 weeks after SSP detachment and remained increased at 5-week reattachment after 2- and 3-week detachment. A decreased expression of wnt10b was observed from 1 week after SSP detachment. Expression of wnt10b was recovered not in the central area of the SSP muscle but in the periphery after reattachment. Adipogenic change was not observed when SSP tendon was reattached after 1-week detachment. Conclusions: These results may suggest that once the adipogenic transcription factors, PPARγ and C/EBPα, were elevated, repair surgery after rotator cuff tear could not prevent the emergence of fat in the SSP muscle.
Arabidopsis Trichome Contains Two Plasma Membrane Domains with Different Lipid Compositions Which Attract Distinct EXO70 Subunits

Plasma membrane (PM) lipid composition and domain organization are modulated by polarized exocytosis. Conversely, targeting of secretory vesicles at specific domains in the PM is carried out by exocyst complexes, which contain EXO70 subunits that play a significant role in the final recognition of the target membrane. As we have shown previously, a mature Arabidopsis trichome contains a basal domain with a thin cell wall and an apical domain with a thick secondary cell wall, which is developed in an EXO70H4-dependent manner. These domains are separated by a cell wall structure named the Ortmannian ring. Using phospholipid markers, we demonstrate that there are two distinct PM domains corresponding to these cell wall domains. The apical domain is enriched in phosphatidic acid (PA) and phosphatidylserine, with an undetectable amount of phosphatidylinositol 4,5-bisphosphate (PIP2), whereas the basal domain is PIP2-rich. While the apical domain recruits EXO70H4, the basal domain recruits EXO70A1, which corresponds to the lipid-binding capacities of these two paralogs. Loss of EXO70H4 results in a loss of the Ortmannian ring border and decreased apical PA accumulation, which causes the PA and PIP2 domains to merge together. Using transmission electron microscopy, we describe these accumulations as a unique anatomical feature of the apical cell wall—radially distributed rod-shaped membranous pockets, where both EXO70H4 and lipid markers are immobilized.
NS2B/NS3 mutations enhance the infectivity of genotype I Japanese encephalitis virus in amplifying hosts

Genotype I (GI) virus has replaced genotype III (GIII) virus as the dominant Japanese encephalitis virus (JEV) in the epidemic area of Asia. The mechanism underlying the genotype replacement remains unclear. Therefore, we focused our current study on investigating the roles of mosquito vector and amplifying host(s) in JEV genotype replacement by comparing the replication ability of GI and GIII viruses. GI and GIII viruses had similar infection rates and replicated to similar viral titers after blood meal feedings in Culex tritaeniorhynchus. However, GI virus yielded a higher viral titer in amplifying host-derived cells, especially at an elevated temperature, and produced an earlier and higher viremia in experimentally inoculated pigs, ducklings, and young chickens. Subsequently we identified the amplification advantage of viral genetic determinants from GI viruses by utilizing chimeric and recombinant JEVs (rJEVs). Compared to the recombinant GIII virus (rGIII virus), we observed that both the recombinant GI virus and the chimeric rJEVs encoding GI virus-derived NS1-3 genes supported higher replication ability in amplifying hosts. The replication advantage of the chimeric rJEVs was lost after introduction of a single substitution from a GIII viral mutation (NS2B-L99V, NS3-S78A, or NS3-D177E). In addition, the gain-of-function assay further elucidated that rGIII virus encoding GI virus NS2B-V99L/NS3-A78S/E177E substitutions re-gained the enhanced replication ability. Thus, we conclude that the replication advantage of GI virus in pigs and poultry is the result of three critical NS2B/NS3 substitutions. This may lead to more efficient transmission of GI virus than GIII virus in the amplifying host-mosquito cycle.