Miracle-dz/UniFAR-FTUs huggingface dataset:
Nitric Oxide Disrupts H2O2-dependent Activation of Nuclear Factor κB

Tumor necrosis factor α (TNF-α) exerts its effect by two distinct signaling pathways. It can trigger cytotoxicity in sensitive target cells. TNF-α can also promote nuclear factor κB (NF-κB) activity and regulate the expression of genes that interfere with apoptosis and thus conferring resistance to several apoptotic stimuli. We have observed that interferon-γ (IFN-γ) sensitizes human ovarian carcinoma cell lines to TNF-α-mediated apoptosis and further, IFN-γ induces the expression of the inducible nitric-oxide synthase (iNOS) and the generation of nitric oxide (NO). This study examines the role of NO in the sensitization of the ovarian carcinoma cell line AD10 to TNF-α-mediated cytotoxicity. Treatment of AD10 cells with the NOS inhibitor l-NMA blocked the IFN-γ-dependent sensitization whereas NO donors (S-nitroso-N-acetylpenicillamine) sensitized these cells to TNF-α cytotoxicity. Analysis of the activation status of NF-κB upon treatment with NO donors confirmed the inhibitory role of NO on both the NF-κB DNA-binding property and its activation. Moreover, the inhibition of NF-κB nuclear translocation by NO donors directly correlated with the intracellular concentration of H2O2 and was reversed by the addition of exogenous H2O2. These findings show that NO might interfere with TNF-α-dependent NF-κB activation by interacting with O⨪2 and reducing the generation of H2O2, a potent NF-κB activator. Therefore, NO-mediated disruption of NF-κB activation results in the removal of anti-apoptotic/resistance signals and sensitizes tumor cells to cytotoxic cytokines like TNF-α.
Crystalline Red Phosphorus Nanoribbons: Large-Scale Synthesis and Electrochemical Nitrogen Fixation.

Two dimensional (2D) nanoribbons constitute an emerging nanoarchitecture for advanced microelectronics and energy conversion due to the stronger size confinement effects compared to traditional nanosheets. Triclinic crystalline red phosphorus (cRP) composed by a layered structure is a promising 2D phosphorus allotrope and the tube-like substructure is beneficial to the construction of nanoribbons. In this work, few-layer cRP nanoribbons are synthesized and the effectiveness in the electrochemical nitrogen reduction reaction (NRR) is investigated. An iodine-assisted chemical vapor transport (CVT) method is developed to synthesize ~10 g of bulk cRP lumps with a yield of over 99%. With the aid of probe ultrasonic treatment, high-quality cRP microcrystals are exfoliated into few-layer nanoribbons (cRP NRs) with large aspect ratios. As non-metallic materials, cRP NRs are suitable for the electrochemical nitrogen reduction reaction. The ammonia yield is 15.4 μg h -1 mg -1 cat. at -0.4 V vs. reversible hydrogen electrode in a neutral electrolyte under ambient conditions and the Faradaic efficiency is 9.4% at -0.2 V. Not only is cRP promising catalyst, but also the novel strategy expands the application of phosphorus-based 2D structures beyond that of traditional nanosheets.
JunB can enhance the transcription of IL‐8 in oral squamous cell carcinoma

Proteasome inhibitor MG132 was shown to enhance the secretion of interleukin 8 (IL‐8) by various cells. The enhancement is regulated by the transcription factor activator protein‐1 (AP‐1) at the transcriptional level. AP‐1 is a dimer formed by AP‐1 family proteins. The purpose of the present study was to explore the combinations of the AP‐1 family proteins that contribute to MG132‐driven IL‐8 secretion. Oral squamous cell carcinoma‐derived cell lines, Ca9‐22 and HSC3, were used to demonstrate their response to MG132. IL‐8 secretion was augmented by MG132 in both cell lines. c‐Jun expression was detected in both the cell lines, whereas c‐Fos expression was detected only in the HSC3. The influence of MG132 stimulation on c‐Jun and c‐Fos expression was further examined by western blot analysis. c‐Jun expression was increased by MG132 stimulation, whereas c‐Fos expression was not detected even after MG132 stimulation. As JunB is reported to inhibit the transcriptional activity of the AP‐1 complex, we speculated that the c‐Jun homodimer should contribute to IL‐8 enhancement. Expression vectors encoding wild type and c‐Jun mutants, M17 and M22‐23, respectively, were constructed and transfected into the Ca9‐22 cells. In contrast to our expectations, MG132‐induced IL‐8 secretion was significantly reduced in all the transfectants suggesting that other c‐Jun members might form homodimers with c‐Jun and contribute to IL‐8 enhancement. Transfection of the cells with c‐Jun or JunB small hairpin RNA (shRNA) reduced IL‐8 secretion up to 50% and 65% of the control shRNA transfectant. Furthermore, cotransfection of both shRNA almost completely inhibited the IL‐8 secretion. These results indicate that JunB not only inhibits but also enhances the transcription of c‐Jun targets in combination with c‐Jun.
Isolation and characterization of polymorphic microsatellite loci in the Chagas’ disease vector Triatoma infestans (Hemiptera: Reduviidae)

Microsatellites were identified and characterized from Triatoma infestans, the principal vector of Chagas’ disease in the Southern Cone of South American countries. Ninety-three microsatellite loci were isolated from partial genomic libraries, of which 30 were amplified and 10 were selected for genotyping. The degree of intrapopulation variation in these loci was determined using 34 specimens from the locality of Chancani (Cordoba, Argentina). The number of alleles per locus ranged from five to 19 and the expected heterozygosity ranged from 0.608 to 0.941. The variability of these microsatellite markers provides a valuable molecular tool for population genetic studies in T. infestans.
European species of subgenus Moerophora Foerster of Xorides Latreille (Hymenoptera: Ichneumonidae: Xoridinae), with descriptions of two new species

The European species of the subgenus Moerophora Foerster, 1869, of the genus Xorides Latreille, 1809 (= Xorides rufipes species-group, Wahl 1997) (Ichneumonidae: Xoridinae) are reviewed. A key to the species and notes on their distribution are provided. Seven species are recorded from Europe: X. (M.) austriacus (Clement), X. (M.) ephialtoides (Kriechbaumer), X. (M.) jakovlevi (Kokujev), X. (M.) rufipes (Gravenhorst), X. (M.) rusticus (Desvignes) and two new species, X. (M.) flavotibialis and X. (M.) ilignus, which are described. Macrosterotrichus bischoffi (Clement) is synonymized with Xylonomus rusticus Desvignes. Xorides (M.) rufipes is recorded as new to Croatia and Bosnia.
Seronegative occult hepatitis C infection among hemodialysis patients: A prevalence study

The aim of this study was to investigate the prevalence of occult hepatitis C virus (HCV) infection (OCI) among HD patients. Blood samples were taken from 79 HD patients and their sera were evaluated for the presence of anti‐HCV. Both the sera and peripheral blood mononuclear cells (PBMCs) were then checked for HCV RNA by nested reverse transcriptase‐polymerase chain reaction. Anti‐HCV was positive among 4/79 (5.1%) of the patients. From 75 patients who were negative for anti‐HCV, 71 (94.7%) patients were also negative for HCV RNA in sera samples but five of them were positive for HCV RNA in PBMCs. Totally, out of 79 patients, HCV RNA was detected in PBMCs of five (6.3%) patients, indicating that these patients had OCI. No significant difference was observed between the frequency of OCI and gender (P‐value = .6). HCV genotype in all five cases of OCI was genotype 3a. Our study showed prevalence rate of 6.3% OCI infection in HD patients. Regarding the serious complications and the clinical importance of OCI in HD patients, sensitive diagnostic methods for identifying HCV RNA in the PBMCs should be implemented for all HD patients.
Lung function monitoring in the era of respiratory pandemics

Oscillometry has been used in adjunct with spirometry in many studies and in clinical practice. Recent events with the spread of a viral respiratory pandemic has caused many clinics to stop using standard spirometry for the fear of aerosol transmission of virus. With recent experiences of our and other groups using oscillometry demonstrating its sensitivity, precision, and ease of use without any forced maneuvers, we suggest that it could be an alternative to spirometry while minimizing exhalation aerosol generation.
Effects of walnut intake on blood pressure: A systematic review and meta‐analysis of randomized controlled trials

The impact of walnuts on blood pressure (BP) is not a well‐established fact. Although several studies have assessed the effects of walnut consumption on BP, results are conflicting. Thus, we examined the effects of walnut doses and length of supplementation on BP. Biomedical databases were searched for published trials that compared walnut‐enhanced diet to control diet. Eighteen trials met eligibility criteria (n = 1,799). Overall, walnut consumption neither did alter SBP (weighted mean difference [WMD]: 0.08 mmHg; 95% CI: −0.69, 0.85) nor DBP (WMD: 0.08 CI: −0.26, 0.42). In subgroup analyses, walnut ingestion ≤40 g was statistically correlated with reduction in SBP (WMD: −0.53 mmHg, 95% CI: −0.79, −0.26) and DBP (WMD: −0.191 mmHg, 95% CI: −0.384, −0.034). Moreover, the length of intervention ≥8 weeks was linked to a significant reduction in SBP (WMD: −1.18 mmHg, 95% CI: −1.30, −1.06). Following dose–response evaluation, walnut intake significantly changed SBP (p = .015) and DBP (p = .026) through a nonlinear fashion at walnut dose up to 40 g/d. Nevertheless, these statistical results cannot be translated into clinical practice, once the changes expressed as WMD are slight taking into consideration the absolute values of BP categories. In conclusion, this meta‐analysis does not support walnut consumption as a BP‐lowering strategy.
Musical rhythm effects on visual attention are non-rhythmical: evidence against metrical entrainment

Abstract The idea that external rhythms synchronize attention cross-modally has attracted much interest and scientific inquiry. Yet, whether associated attentional modulations are indeed rhythmical in that they spring from and map onto an underlying meter has not been clearly established. Here we tested this idea while addressing the shortcomings of previous work associated with confounding (i) metricality and regularity, (ii) rhythmic and temporal expectations or (iii) global and local temporal effects. We designed sound sequences that varied orthogonally (high/low) in metricality and regularity and presented them as task-irrelevant auditory background in four separate blocks. The participants’ task was to detect rare visual targets occurring at a silent metrically aligned or misaligned temporal position. We found that target timing was irrelevant for reaction times and visual event-related potentials. High background regularity and to a lesser extent metricality facilitated target processing across metrically aligned and misaligned positions. Additionally, high regularity modulated auditory background frequencies in the EEG recorded over occipital cortex. We conclude that external rhythms, rather than synchronizing attention cross-modally, confer general, nontemporal benefits. Their predictability conserves processing resources that then benefit stimulus representations in other modalities.
Changing trend in mortality rate of multiple myeloma after introduction of novel agents: A population‐based study

Previously, the main treatment for multiple myeloma (MM) was cytotoxic chemotherapies, including autologous stem‐cell transplantation (ASCT), but survival benefit in the elderly was limited. More recently, clinical trials and practical experience with novel agents with superior efficacy have shown improved survival, including in the elderly. However, this improvement cannot be simply interpreted as a decline in mortality rate that is an important public health measure of progress against cancer. Here, we assessed the trends in mortality rates of MM in parallel with incidence rates in Japan and the U.S. We used national mortality data and population‐based cancer registry data in both countries from 1995 to 2015, during which 74 972 patients in Japan and 229 290 patients in the U.S. died of MM. Trends in mortality and incidence rates were characterized using joinpoint regression analysis. Despite upward trends in incidence, mortality rates showed a significant decrement after 2005 in Japan, with an annual percent change [APC (95% confidence interval)] of −2.5% (−2.9% to −2.1%), and after 2002 in the U.S., with an APC of −2.0% (−2.6% to −1.5%). In both countries, the change in mortality trend coincided with the introduction of the novel agents. Moreover, improvements in mortality were particularly large in patients aged 70 to 79 years, who cannot receive ASCT. Our results indicate that the benefits of novel agents for MM are appreciable at the population level and may encourage further development of novel agents for malignancies that can be widely applied to the patients.
Comparison of predicted and real propofol and remifentanil concentrations in plasma and brain tissue during target‐controlled infusion: a prospective observational study

Target‐controlled infusion systems are increasingly used to administer intravenous anaesthetic drugs to achieve a user‐specified plasma or effect‐site target concentration. While several studies have investigated the ability of the underlying pharmacokinetic‐dynamic models to predict plasma concentrations, there are no data on their performance in predicting drug concentrations in the human brain. We assessed the predictive performance of the Marsh propofol model and Minto remifentanil model for plasma and brain tissue concentrations. Plasma samples were obtained during neurosurgery from 38 patients, and brain tissue samples from nine patients. Propofol and remifentanil concentrations were measured using gas chromatography mass spectrometry and liquid chromatography tandem mass spectrometry. Data were analysed from the nine patients in whom both plasma and brain samples were simultaneously obtained. For the Minto model (five patients), the median performance error was 72% for plasma and −14% for brain tissue concentration predictions. The model tended to underestimate plasma remifentanil concentrations, and to overestimate brain tissue remifentanil concentrations. For the Marsh model (five patients), the median prediction errors for plasma and brain tissue concentrations were 12% and 81%, respectively. However, when the data from all blood propofol assays (36 patients) were analysed, the median prediction error was 11%, with overprediction in 15 (42%) patients and underprediction in 21 (58%). These findings confirm earlier reports demonstrating inaccuracy for commonly used pharmacokinetic‐dynamic models for plasma concentrations and extend these findings to the prediction of effect‐site concentrations.
The comparison of ibuprofen versus acetaminophen for blood pressure in preeclampsia: a meta-analysis of randomized controlled studies

Abstract Introduction The comparison of ibuprofen with acetaminophen for blood pressure (BP) in preeclampsia remains controversial. We conduct a systematic review and meta-analysis to compare the impact of ibuprofen versus acetaminophen on BP for preeclampsia. Methods We search PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases through October 2019 for randomized controlled trials (RCTs) assessing the effect of ibuprofen versus acetaminophen on BP for preeclampsia. This meta-analysis is performed using the random-effect model. Results Four RCTs are included in the meta-analysis. Overall in preeclampsia patients, ibuprofen and acetaminophen show similar systolic BP (SBP) (standard mean difference [SMD] = 0.04; 95% CI = −0.26–0.34; p= .81), diastolic BP (DBP) (SMD = 0.15; 95% CI = −0.18–0.48; p = 0.38), mean BP (MAP) (SMD = 0.02; 95% CI = −0.29–0.33; p = .91), severe range BP (SMD = −0.10; 95% CI = −0.40–0.19; p = .50), severe hypertension (SMD = 1.18; 95% CI = 0.85–1.62; p = .32), and satisfaction level (SMD = 1.2; 95% CI = 0.95–1.53; p = .13). Conclusions Ibuprofen and acetaminophen may have no significant influence on BP for preeclampsia.
Characterization of sleep habits and medication outcomes for sleep disturbance in children and adults with Angelman syndrome

The objectives of this study were to characterize the sleep habits of 50 clinically referred individuals with Angelman syndrome (AS) and to retrospectively compare the effectiveness/tolerability of the three most commonly prescribed sleep medications in the sample. An experienced physician assigned a Clinical Global Impressions‐Severity scale (CGI‐S) score for each subject's AS‐specific symptoms. Caregivers completed the Child Sleep Habits Questionnaire (CSHQ; screen for sleep problems in school‐aged [4–10 years] children), a screening assessment for sleep problems. Caregivers provided information about medication trials targeting disturbed sleep, with the physician assigning a CGI‐Improvement scale (CGI‐I) score for each trial. Linear regression showed significant negative association between age and CSHQ score. In their lifetime, 72% of participants had taken a medication for sleep, most commonly melatonin, clonidine and trazodone. The majority continued these for 6 months or longer. With these medications, many demonstrated significant improvement in sleep disturbances, with no difference in odds of improvement between medications. Disturbed sleep was common in this cohort and significantly worse in younger‐aged participants. The majority received at least one medication trial for disturbed sleep and each of the most commonly prescribed medication was effective for a substantial percentage of participants. Most participants remained on medication for at least 6 months, suggesting favorable tolerability.
Development of broadly reactive influenza vaccines by targeting the conserved regions of the hemagglutinin stem and head domains

ABSTRACT Introduction Influenza virus infections cause serious illness in millions of people each year. Although influenza virus vaccines are available, they are not optimally effective due to mismatches between the influenza virus strains used for the vaccine and the circulating strains. To improve protection by vaccines, a broadly protective or universal vaccine may be required. Strategies to develop universal vaccines aim to elicit broadly reactive antibodies, which target regions on the viral hemagglutinin (HA) protein which are conserved between strains. Broadly reactive antibodies have helped to identify such targets and can guide the design of such a vaccine. Areas covered The first part of this review provides an in-depth overview of broadly reactive anti-HA antibodies, discussing their origin, breadth and their mechanisms of protection. The second part discusses the technical design and mode of action of potential universal vaccine candidates that aim to elicit these broadly reactive antibodies and provide protection against a majority of influenza strains. Expert opinion While great strides have been made in the development of universal influenza vaccine candidates, real-life use still requires improvement of stability, enhancement of their breadth of protection and ease of production, while efficacies need to be determined in human trials.
Social isolation in mice: behavior, immunity, and tumor growth

Abstract The aim of this study was to investigate the behavioral, immunological, and neurological effects of long-term isolation in an animal model. Male C3H/eB mice wereraised in either social isolation or standard conditions for 6 weeks. At 10 weeks, each group was further divided into 3 sets. (A) Physical strength and behavior were evaluated with the grip strength, hot plate, staircase, and elevated plus-maze tests. Natural-killer cell activity and lymphocyte proliferation were measured. (B) Half the animals were subjected to electric shock with 3 reminders, and freezing time was evaluated at each reminder. Cortisone levels were evaluated after 16 weeks. (C)Mice were injected with 38 C-13 B lymphoma cells and followed for tumor size and survival. Strength evaluation yielded asignificantly lower body weight and grip strength in the socially isolated mice. Behavioral test results were similar in the two groups. The pattern of reactions to stress conditioning differed significantly, with the socially isolated mice showing an incline in freezing with each successive reminder, and the control mice showing a decline. The socially isolated mice had significantly attenuated tumor growth, with no significant difference in survival from control mice. There were no significant between-group differences in immunological parameters. In conclusion, social isolation serves as a model for chronic stress. It was associated with significant changes in stress conditioning reaction, resembling symptoms of post-traumatic stress disorder, and attenuated tumor development. No differences from controls were found in behavior tests, immune parameters, or survival after tumor cell inoculation. Lay summary This article explores biological and behavioral consequences of social isolation in a mice model. Our results show that social isolation leads to changes in the Hypothalamic-hypophyseal-adrenal axis, which in turn alter the response to stress. Additionally, social isolation was shown to impact tumor progression.
Volume Analysis of Brain Cognitive Areas in Alzheimer’s Disease: Interim 3-Year Results from the ASCOMALVA Trial

Background: Cerebral atrophy is a common feature of several neurodegenerative disorders, including Alzheimer’s disease (AD). In AD, brain atrophy is associated with loss of gyri and sulci in the temporal and parietal lobes, and in parts of the frontal cortex and cingulate gyrus. Objective: The ASCOMALVA trial has assessed, in addition to neuropsychological analysis, whether the addition of the cholinergic precursor choline alphoscerate to treatment with donepezil has an effect on brain volume loss in patients affected by AD associated with cerebrovascular injury. Methods: 56 participants to the randomized, placebo-controlled, double-blind ASCOMALVA trial were assigned to donepezil + placebo (D + P) or donepezil + choline alphoscerate (D + CA) treatments and underwent brain magnetic resonance imaging and neuropsychological tests every year for 4 years. An interim analysis of 3-year MRI data was performed by voxel morphometry techniques. Results: The D + P group (n = 27) developed atrophy of the gray and white matter with concomitant increase in ventricular space volume. In the D + CA group (n = 29) the gray matter atrophy was less pronounced compared to the D + P group in frontal and temporal lobes, hippocampus, and amygdala. These morphological data are consistent with the results of the neuropsychological tests. Conclusion: Our findings indicate that the addition of choline alphoscerate to standard treatment with the cholinesterase inhibitor donepezil counters to some extent the loss in volume occurring in some brain areas of AD patients. The observation of parallel less pronounced decrease in cognitive and functional tests in patients with the same treatment suggests that the morphological changes observed may have functional relevance.