Adverse Events During Pregnancy Associated With Entecavir and Adefovir: New Insights From a Real-World Analysis of Cases Reported to FDA Adverse Event Reporting System

Background: Due to the embryotoxicity found in animal studies and scarce clinical data in pregnant women, it is still controversial whether entecavir (ETV) and adefovir dipivoxil (ADV) are safe during human pregnancy. This is of paramount importance when counseling pregnant women with hepatitis B virus (HBV) on risks and benefits to their offspring.Objective: To quantify the association between administration of ETV and ADV in pregnant women and occurrence of adverse events (AEs) during pregnancy (AEDP).Methods: Pregnancy reports from the FDA Adverse Event Reporting System (FAERS) were used to perform a retrospective analysis of AEDP associated with ETV or ADV. Disproportionality analysis estimating the reporting odds ratio (ROR) was conducted to identify the risk signals. A signal was defined as ROR value >2, and lower limit of 95% confidence interval (CI)> 1.Results: A total of 1,286,367 reports involving AEDP were submitted to FAERS by healthcare professionals. Of these, there were 547 cases reporting ETV and 242 cases reporting ADV as primary suspected drugs. We found a moderate or strong signal for increased risk of spontaneous abortion when comparing ETV with tenofovir disoproxil fumarate (TDF) and telbivudine (LdT), with RORs equal to 1.58 (95% CI, 1.09–2.30) and 2.13 (95% CI, 1.04–4.36), respectively. However, when the included reports were limited to indication containing HBV infection, no signals for increased AEDP were detected. Futhermore, a strong signal for increased risk of spontaneous abortion was identified in patients with HBV infection when comparing ETV or ADV with lamivudine (LAM), with RORs of 3.55 (95% CI, 1.54–8.18) and 2.85 (95% CI, 1.15–7.08), respectively.Conclusion: We found a strong signal for increased risk of spontaneous abortion in patients with HBV infection taking ETV or ADV, in comparison with those prescribed with LAM. Moreover, no obvious signal association of human teratogenicity with exposure to ETV or ADV was identified in fetuses during pregnancy. Nevertheless, owing to the limitations of a spontaneous reporting database, which inevitably contains potential biases, there is a pressing need for well-designed comparative safety studies to validate these results in clinical practice.

Public Distrust in Disputed Elections: Evidence from Latin America

The comparative literature on democratization has shown that election trust depends as much on subjective factors as on the objective conditions of the process. This literature, however, has thus far overlooked the consequences of candidates refusing to concede an electoral defeat. This letter argues that a disputed electoral outcome further inflames negative perceptions of electoral integrity among voters who supported a losing candidate. We bring support for this claim from a multilevel regression that includes data from the AmericasBarometer surveys on almost 100,000 respondents across 49 elections in 18 Latin American countries. We combine these responses with an original database of disputed elections in the region. The empirical findings demonstrate the eroding effect of challenged election outcomes on voters' election trust, particularly among those who voted for a losing candidate. The findings underscore an intuitive yet untested pattern: candidates' refusal to accept the electoral outcome is a strong signal among their supporters, increasing their distrust on the integrity of the process.

Second-harmonic generation from green printed selenium structures

Plenary large-scale efficient second-harmonic generation sources remains a challenge in micro-/nanoscale research. In this work, we demonstrate the strong second-harmonic generation in arrays of selenium particles fabricated by green printing method at the pumping wavelength of 1047 nm. Second-harmonic generation mapping shows the strong signal over the whole area of selenium particle. We propose, that such structures can be a perspective platform for efficient frequency conversion systems and nonlinear sensing applications.

Residue-resolved monitoring of protein hyperpolarization at sub-second time resolution

Signal-enhancement techniques for NMR spectroscopy are important to amplify the weak resonances provided by nuclear spins. Recently, ‘hyperpolarization’ techniques have been intensively investigated. These provide nuclear spin states far from equilibrium yielding strong signal boosts up to four orders of magnitude. Here we propose a method for real-time NMR of ‘hyperpolarized’ proteins at residue resolution. The approach is based on dissolution dynamic nuclear polarization (d-DNP), which enables the use of hyperpolarized buffers that selectively boost NMR signals of solvent-exposed protein residues. The resulting spectral sparseness and signal enhancements enable recording of residue-resolved spectra at a 2 Hz sampling rate. Thus, we monitor the hyperpolarization level of different protein residues simultaneously under near-physiological conditions. We aim to address two points: 1) NMR experiments are often performed under conditions that increase sensitivity but are physiologically irrelevant; 2) long signal accumulation impedes fast real-time monitoring. Both limitations are of fundamental relevance to ascertain pharmacological relevance and study protein kinetics.

“Warm cover”: precursory strong signals for haze pollution hidden in the middle troposphere

Eastern China (EC), located in the downstream region of the Tibetan Plateau (TP), is a large area with frequent haze pollution. In addition to air pollutant emissions, meteorological conditions are a key inducement for air pollution episodes. Based on the study of the Great Smog of London in 1952 and haze pollution in EC over recent decades, it is found that the abnormal “warm cover” (air–temperature anomalies) in the middle troposphere, as a precursory strong signal, could be connected to severe air pollution events. The convection and vertical diffusion in the atmospheric boundary layer (ABL) were suppressed by a relatively stable structure of warm cover in the middle troposphere leading to ABL height decreases, which were favorable for the accumulation of air pollutants in the ambient atmosphere. The anomalous structure of the troposphere's warm cover not only exist in heavy haze pollution on the daily scale, but also provide seasonal, interannual and interdecadal strong signals for frequently occurring regional haze pollution. It is revealed that a close relationship existed between interannual variations of the TP's heat source and the warm cover strong signal in the middle troposphere over EC. The warming TP could lead to anomalous warm cover in the middle troposphere from the plateau to the downstream EC region and even the entire East Asian region, thus causing frequent winter haze pollution in EC region.

The Optimization of PCI Interference in the 4G LTE Network in Padang

With the growth of the customers and the expansion of the 4G LTE network in the area of Padang City, a PCI (Physical cell identity) modulo interference spot has been detected. PCI modulo interference occurs when an area is covered by two or more cells, which have a strong signal, and these cells have the same PCI modulo value. Based on the measurement results by the driving test method, the network conditions were not optimal because the SINR percentage (Signal to Interference Noise Ratio) in the good category was still low, at 9.47%, and the download throughput in the good category was 18.94%. This indicated that the interference in the area was quite high. Thus, it was necessary to do optimization action. The optimization action was taken by rotating the PCI on the site by considering the modulo value of each site so that the PCI with the same modulo did not merely lead to one location. Besides, action was taken to change the azimuth direction of cells that were too dominant. Based on the optimization process that has been carried out and the driving test activities that have been carried out again, the performance in the existing conditions has increased. The SINR percentage in the good category increased by 10%, so it became 19.47%, and the download throughput in the good category increased by 44.74% and became 63.68%.

Neutron darkfield imaging of fiber composites

While X-ray based darkfield imaging with grating interferometers is already widely used, darkfield imaging with neutrons has still a relatively small user community focused mostly on magnetic materials. Here, we demonstrate the application of neutron darkfield imaging byTalbot-Lau type grating interferometry to fiber reinforced plastics. Common carbon and glass fiber composites have been investigated including characteristic damage structures. The darkfield images show a strong signal response caused by fiber delamination, suitable fiber direction, particles, pores and cracks. The basic principles of neutron darkfield imaging applied to fiber composites are highlighted.

Votes in eastern EU cities will reflect rural divide

Significance The electoral success of activists, political entrepreneurs, more liberal-minded or pro-EU politicians in capital cities is not a strong signal that attitudes and voting patterns are shifting at the national level. Many Central-East European (CEE) citizens still have strong preferences for socially conservative policies and politicians, despite economic preferences increasingly leaning leftwards. Impacts The European Commission will have more supporters in key places to push for more climate change awareness and Green policies. Newcomers into the system will challenge entrenched corruption and clientelism. Firms allied to mainstream parties will resist losing advantageous contracts. Nationalist or anti-EU parties will moderate their rhetoric and adapt their strategies so as not to alienate their urban supporters further.

Online Learning during Covid-19: What is the Most Effective Platform for Teaching and Learning Mathematics?

The purpose of this research was to find how the first online learning implementation in the Department of Mathematics Education in The Islamic State Institute of Bengkulu during the Covid-19 pandemic. This research was qualitative research which was conducted in July as an evaluation of the first online learning from March until July. 90 students were chosen by purposive sampling and then given an online questionnaire. The results showed that there were some mathematical courses students took in the Even Semester 2019/2020. The platforms used by lecturers while teaching Mathematics were 39.6% WhatsApp Group, 22% Google Classroom, 13.2% Cisco Webex, and 25.2 % others. Platforms that were felt effective as online learning applications were 52.7% Cisco Webex, 26.4 % WhatsApp Group, 9.9% Zoom meeting, 5.5% Google Classroom, and 5.5% others. This is felt to be effective because it does not consume a lot of data packages, has a strong signal, and can be accessed at any time (WhatsApp Group and Google Classroom). In addition, this platform can be used for live conferencing / video calls using whiteboards which are deemed effective for teaching math material (Cisco Webex). However, several obstacles were found during the implementation of online learning, namely difficulties in obtaining sufficient internet data packages; limited network; difficult assignments and assessments; less effective teaching methods; and use of multiple applications.

Anatomy and Histochemistry of Seed Coat Development of Wild (Pisum sativum subsp. elatius (M. Bieb.) Asch. et Graebn. and Domesticated Pea (Pisum sativum subsp. sativum L.)

In angiosperms, the mature seed consists of embryo, endosperm, and a maternal plant-derived seed coat (SC). The SC plays a role in seed filling, protects the embryo, mediates dormancy and germination, and facilitates the dispersal of seeds. SC properties have been modified during the domestication process, resulting in the removal of dormancy, mediated by SC impermeability. This study compares the SC anatomy and histochemistry of two wild (JI64 and JI1794) and two domesticated (cv. Cameor and JI92) pea genotypes. Histochemical staining of five developmental stages: 13, 21, 27, 30 days after anthesis (DAA), and mature dry seeds revealed clear differences between both pea types. SC thickness is established early in the development (13 DAA) and is primarily governed by macrosclereid cells. Polyanionic staining by Ruthenium Red indicated non homogeneity of the SC, with a strong signal in the hilum, the micropyle, and the upper parts of the macrosclereids. High peroxidase activity was detected in both wild and cultivated genotypes and increased over the development peaking prior to desiccation. The detailed knowledge of SC anatomy is important for any molecular or biochemical studies, including gene expression and proteomic analysis, especially when comparing different genotypes and treatments. Analysis is useful for other crop-to-wild-progenitor comparisons of economically important legume crops.