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Key message: Embryo abortion at the heart-shaped stage is the main reason for the failure of interspecific hybridization of hydrangea, and salicylic acid plays a key role during embryo abortion. Difficulties in obtaining seeds from interspecific hybridization between Hydrangea macrophylla and H. arborescens had severely restricted the process of breeding new hydrangea varieties. To clarify the cause of reproductive barriers, an interspecific hybridization was made between H. macrophylla 'Endless Summer' (female parent) and H. arborescens 'Annabelle' (male parent). The results showed that both parents’ floral organs developed normally, 'Annabelle' had high pollen viability (84.83% at 8 h after incubation), and the pollen tube could enter into the ovule of 'Endless Summer' at 72 h after pollination. Therefore, the pre-fertilization barrier was not the main reason for the failure of interspecific hybridization. However, observation of the embryo development by paraffin sections showed that the embryo was aborted at the heart-shaped stage. In addition, salicylic acid (SA) content was significantly higher (fourfold, P < 0.01) at 21 days after pollination (DAP) as compared to that of 17 DAP, which means SA may be closely correlated with embryo development. A total of 957 metabolites were detected, among which 78 were significantly different. During the embryo abortion, phenylpropanoids and polyketides were significantly down-regulated, while organic oxygen compounds were significantly up-regulated. Further analysis indicated that the metabolic pathway was enriched in the shikimic acid biosynthesis pathway, which suggests that more SA was synthesized. Taken together, it can be reasonably speculated that SA plays a key role leading to embryo abortion underlying the interspecific hybridization between Hydrangea macrophylla and H. arborescens. The result is helpful to direct the breeding of hydrangea through distant hybridization. [ABSTRACT FROM AUTHOR]

Ruzotolimod (Toll‐like receptor 7 (TLR7) agonist, RG7854) is an oral, small molecule immuno‐modulator activating the TLR 7 and is being evaluated in patients with CHB. As with other TLR7 agonists, the study drug‐related adverse events of flu‐like symptoms have been reported in some participants during phase I studies with ruzotolimod. An exploratory analysis of the relationship between pharmacokinetic (PK)/pharmacodynamic (PD) and flu‐like symptoms was performed in participants from two phase I studies including both healthy volunteers and NUC‐suppressed CHB patients who received either single or multiple ascending doses of orally administered ruzotolimod. Linear and logistic regression were used to explore potential relationships between dose, flu‐like symptoms, PK, and PD. Generalized linear regression was performed to predict the probability of flu‐like symptoms of all intensities at different RO7011785 (the active metabolite of the double prodrug ruzotolimod) PK exposure. This analysis showed that single or multiple doses of ruzotolimod at ⩾100 mg, the immune PD (IFN‐α, neopterin, IP‐10, and the transcriptional expression of ISG15, OAS‐1, MX1, and TLR7) responses increase with the RO7011785 PK exposure, which increases linearly with the doses from 3 mg to 170 mg of ruzotolimod. The analysis also showed that the probability of flu‐like symptoms occurrence increases with PD responses (IFN‐α and IP‐10). Dose reduction of ruzotolimod can be an effective way to reduce the magnitude of PD response, thus reducing the probability of study drug‐related flu‐like symptoms occurrence at all intensity in the participants who are highly sensitive to PD activation and intolerant to flu‐like symptoms. [ABSTRACT FROM AUTHOR]

In this study, multiple instrumental observations including Global Navigation Satellite System total electron content (TEC), plasma drift velocity measured by Sanya (18.3°N, 109.6°E, dip latitude 12.6°N) Incoherent Scatter Radar (SYISR) and F2‐layer peak electron density (NmF2) and peak height (hmF2) from ionosonde and SYISR have been used to investigate ionospheric responses during a minor yet highly geo‐effective geomagnetic storm on 26–27 May 2021. Our findings revealed a significant time delay in the post‐sunset plasma density enhancement peak across different latitudes over East Asia, that is, the lower the geographic latitude, the earlier the peak appeared. The plasma density enhancement was accompanied by a decrease in hmF2 prior to NmF2 peak around sunset. The newly built SYISR measurements around sunset verified that the field‐aligned drift decreased the ionosphere with a notable time delay at latitude, beneficial to electron density enhancements at lower altitudes within the 16–30°N latitudinal band but a small TEC change. While at 30–50°N, it is possible that the competition between storm‐induced equatorward winds and downward field‐aligned drift depressed hmF2 decline and the buildup increased both NmF2 and TEC. The ICON observations suggested that the meridional wind during this minor storm event modulated the direction of plasma transport near sunset, playing a dominant role in post‐sunset plasma density enhancement from low to middle latitudes. These results provide fresh insight into the electrodynamic mechanisms of post‐sunset enhancements at middle and low latitudes over East Asia, and also enhance our understanding of the intricate behaviors within the ionosphere‐thermosphere system in response to a minor storm. Key Points: The local time of post‐sunset plasma density enhancement peak had a notable time delay with increasing latitude during a minor stormThe plasma drift during postsunset hours observed by Sanya incoherent scatter radar exhibited strong response to the minor geomagnetic stormThe meridional winds changing from equatorward to poleward explained the post‐sunset enhancement from low to middle latitudes [ABSTRACT FROM AUTHOR]

Introduction: Laparoscopic duodenal web resection surgery remains safe in neonates. The pearls in laparoscopic duodenal web excision are a proper and stable duodenal exposure. Herein, we present a modified duodenal traction technique, which can improve operative field exposure in laparoscopic surgery. Material and Methods: This modified technique was performed in 54 patients during laparoscopic duodenal web resection surgery at our center. It was performed using a 5-0 PDS-II suture, which was introduced percutaneously at 1–2 cm under either side of the costal margin at the anterior axillary line, respectively, to retract the duodenum. Results: Perioperative data of these patients and short-term follow-up data of duodenal web patients were retrospectively reviewed. All 54 procedures were completed without conversion to open surgery or requiring additional ports. Patients' mean age at surgery was 5 days (range 2–30 days), and the median weight at the time of surgery was 3.25 kg (range 2.52–3.88 kg). Eight patients (14.8%) had complete membranes, whereas 46 (85.2%) had a membrane with a hole. The mean time required for this technique was 336 (range 216–416) seconds and the mean duration of the entire surgery was 77 (range 65–89) minutes. The mean postoperative hospital stay was 16 (range 9–90) days and no postoperative complication related to the suspension procedure occurred. Conclusion: Our outcomes demonstrated the modified duodenal traction technique is a feasible and ideal method during laparoscopic duodenal web resection surgery. [ABSTRACT FROM AUTHOR]

A new incoherent scattering radar established at Sanya (18.3°N, 109.6°E; SYISR) has made it possible to directly measure the fine structure of the ionospheric E‐F valley. An intriguing phenomenon termed "ionospheric drizzle" was revealed by the month‐long continuous observation of complete ionospheric profiles with a temporal and vertical resolution of 0.8 s and 4.5 km. It manifests as weak plasma "streaks" in the strength of ∼103–104 cm−3 that detach from the F‐layer base and extends downward to the sporadic E (Es) layer during pre‐dawn hours, with an apparent descent speed of ∼10–20 m/s. The frequently observed "ionospheric drizzle" provides additional plasma to enhance the Es layer. Subsequent testing particle simulations were performed, revealing the critical role of the neutral winds in the plasma descent. This downward coupling process enhancing the Es layer is thus supposed to be important in communication and navigation. Key Points: Using the Sanya ISR, "ionospheric drizzle", a phenomenon linking the F‐layer and sporadic E layer at pre‐dawn hours, was revealedStreak‐like plasma detaches from the F‐layer base with a descent speed of ∼10–20 m/s and significantly enhances the Es layer at ∼120 kmTest particle simulations are performed to explain the critical role of neutral winds in the "ionospheric drizzle" formation [ABSTRACT FROM AUTHOR]

Measuring the plasma motion vector field accurately is beneficial to understanding the physical processes in the ionosphere. As a newly built advanced modular phase array Incoherent Scatter Radar in Sanya (SYISR), SYISR can measure the line‐of‐sight (LOS) velocity of ion drift in multiple directions, potentially yielding the spatial distribution of ionospheric plasma drift at low latitudes in East Asia. Compared to the traditional ISR, it can operate continuously for a long‐time and perform with fast and flexible scanning. This paper evaluates different beam configurations and inversion methods for vector ion velocity detection by comparing the vector ion velocities input in the forward modeling and derived by inversion. For the mono‐static SYISR, the all‐sky scan mode is suitable for observing the distribution of vector ion velocity with height, and the fine scan mode is suitable for observing the spatial distribution of two components of vector ion drift perpendicular to the magnetic field in the northern region of SYISR's non‐grating lobe. For the future tri‐static SYISR, it could simultaneously observe the spatial distribution of all three components of the vector ion velocity. Besides, the inversion method based on Bayesian estimation shows good accuracy and stability in deriving the vector ion velocity, especially when the LOS ion velocity has a large error. These results will benefit the design and optimization of the actual experiments for the vector ion velocity measurement and inversion using the SYISR system. Key Points: A procedure is constructed to guide and evaluate the detection of the vector ion velocity by the Incoherent Scatter Radar in Sanya (SYISR) systemThe ion velocity inversion method based on Bayesian estimation shows good accuracy and stability in deriving the vector ion velocityMono‐static and tri‐static SYISR can be used to detect the height profile of vector ion velocity and spatial distribution, respectively [ABSTRACT FROM AUTHOR]

As the first advanced modular phase array incoherent scatter radar (ISR) established in the Eastern Hemisphere at low latitudes, Sanya ISR (SYISR) can measure the line-of-sight (LOS) velocity of ion drift in multiple directions, potentially yielding the spatial distribution of ionospheric plasma drift. Three beam-scanning modes are designed for plasma drift detection: meridian, zonal and cross-shaped (both meridian and zonal) plane, which will provide the distribution of plasma drift in latitude/longitude as well as altitude. The altitude profile of plasma drift and the first presented distribution of low latitude plasma drift in the meridian plane for March to May 2021 are inversed through LOS velocity using cross-shaped and meridian beam-scanning modes, respectively. A statistical correlation coefficient between the v p n and crest-to-trough ratio (CTR) of equatorial ionization anomaly (EIA) TEC and a case study of magnetic storm response in plasma drift show that the inversed plasma drift can be a good indicator in response to the changes in atmospheric tide and solar wind at different time scales and explain the corresponding ionospheric electron density variations at low and equatorial latitudes. This study proves that the SYISR-measured plasma drift is reliable and will play an important role in the atmosphere-ionosphere-magnetospheric coupling study in the East Asian region. [ABSTRACT FROM AUTHOR]

In the present work, the momentum fluxes of gravity wave (GW) around the mesopause are estimated, using the decadal continuous observations by meteor radar at Mohe (53.5°N, 122.3°E). Applying the Hocking's (2005) approach with the modified-composite-day (MCD) analysis, the GW momentum fluxes of short-periods (less than 2 h) are estimated month by month. As the first step, several experiments are designed to evaluate the accuracy and uncertainty in the estimation. The results show that Mohe meteor radar has the ability to give reasonable estimations on the GW momentum fluxes at a height of 82–94 km, in which errors are generally less than 5 m2/s2. The uncertainty induced by different angular information of the detected meteor in each month achieves ~2 m2/s2. It is inferred that the variability of the GW momentum fluxes over 2 m2/s2 can be distinguished in the observation. The interannual variation of the estimated GW momentum fluxes show a significant enhancement in 2012, and a depression in 2013, with a fluctuation over ±10 m2/s2 at 82 km. However, no obvious quasi-biennial oscillation (QBO) -like signal has been found in the Lomb–Scargle periodogram. [ABSTRACT FROM AUTHOR]

Introduction: Neuromyelitis optica spectrum disorders (NMOSD), mainly mediated by B cells and AQP4 antibody, has a high rate of recurrence. Telitacicept is a novel drug specifically targeting the upstream signaling for the activation of B cell with its following production of autoimmune antibodies. Thus, it may be a promising approach. Our study preliminarily explored the potential safety and effectiveness of Telitacicept following plasma exchange in the treatment of recurrent NMOSD. Methods: This was a single‐center, single‐arm, open‐label study enrolling eight patients with recurrent NMOSD in China. All patients received plasma exchange three times, followed by Telitacicept 240 mg every week for 46 times. The primary endpoint was the time of first recurrence after enrollment. Secondary end points included: changes in Expanded Disability Status Scale score, Optic Spinal Impairment Scale score, Hauser Ambulation Index, number of lesions on MRI, retinal nerve fiber layer thickness measured by optical coherence tomography, latency and amplitude of visual evoked potential, titer of AQP4 antibody, and immune parameters of blood. Safety was also assessed. The study was registered with Chictr.org.cn (ChiCTR1800019427). Results: Eight eligible patients were enrolled. Relapse occurred in two patients (25%) and five patients (63%) remained relapse free after 48 weeks of treatment. The time to first recurrence was prolonged and the number of recurrences was reduced (p < 0.001, power of test = 1). One patient withdrew from the study due to low neutrophil count. No serious adverse events occurred. Conclusions: In this small, uncontrolled study, Telitacicept following plasma exchange has the potential to be a safe treatment for patients with recurrent NMOSD. It may prolong the recurrence interval and reduces the annual count of recurrences. A multicenter randomized controlled study with a larger sample is thus feasible and needed to further assess its safety and efficacy. [ABSTRACT FROM AUTHOR]

A new incoherent scatter radar (ISR) has recently been dedicated at Sanya (SYISR), China (geographic 18.34°N and 109.62°E) to detect the low‐latitude ionospheric plasma by conducting continuous operation and electronic beam steering on a pulse‐to‐pulse basis. This paper provides an overview of the processing procedure of SYISR ion line data and presents some preliminary observational results under various transmitting signal schemes and different working modes, such as the zenith‐directed mode and meridional and zonal scanning modes, with comparison to the international reference ionosphere model (IRI‐2016), ionosonde and Ionospheric Connections Explorer (ICON) satellite measurements. The diurnal and altitude versus latitude variation characteristics of electron density (Ne), electron temperature (Te), and ion temperature (Ti) are in accordance with those of other ISR measurements in mid‐low latitudes, and IRI shows some discrepancies with SYISR observations, including the sunrise and sunset enhancement in SYISR_Ti and the overestimated IRI_Te. The comparison between the daytime SYISR_Ti and ICON_Ti shows good consistency based on 31 observational samples. The measurement of line‐of‐sight velocity (Vi) for long pulse can reveal the properties of the medium scale traveling ionospheric disturbances manifesting the radar's potential to study the mesoscale ionospheric variation in the Sanya area. The derived vector velocities with a better measurement accuracy during the day are generally in line with ionospheric plasma physics. The results show that SYISR can obtain continuous ionospheric parameters through multi‐beam scanning measurements at ∼700 km horizontal scale, which provides important information for studying the atmosphere‐ionosphere‐magnetosphere coupling and ionospheric scintillation at low latitudes in East Asia. Plain Language Summary: China's first phased‐array incoherent scatter radar was completed in 2021 in Sanya, which is called SYISR. SYISR aims to investigate fundamental scientific problems in the ionosphere, including atmosphere‐ionosphere‐magnetosphere coupling, regional ionospheric properties and ionospheric irregularities in southern China. SYISR can directly measure electron density, electron and ion temperature, and drift velocity of the ionospheric plasma and can be used to indirectly obtain the temperature of the neutral atmosphere, wind field and irregularity information. This paper describes in detail the data processing from the IQ signal to the derived ionospheric parameters for SYISR. Ionospheric experiments in various scanning modes have been performed, mainly including a single beam in zenith‐directed mode and multiple beams in meridian and zonal scanning modes, and the obtained results are evaluated. These experimental results are evaluated through comparison with the IRI‐2016 model, digital ionosonde and Ionospheric Connections Explorer satellite. The comparison results indicate that SYISR is able to provide reliable, unique, and important ionospheric information for the study of ionospheric science at low latitudes in East Asia. Key Points: Sanya incoherent scatter radar (SYISR) is a new phased array system dedicated to the ionospheric observations at low latitudes in Asia sectorSYISR is operational, providing high‐quality ionospheric measurements in multiple radar scanning modes and radio pulse schemes modesData processing procedures and initial ion‐line results using typical experiment modes are reported [ABSTRACT FROM AUTHOR]

Background: Biliary atresia (BA) is the most common cholestatic liver disease in neonates. Herein, we aimed at characterizing the gut microbiota and fecal bile acid profiles of BA patients, defining the correlations between them, and evaluating the relationship between the clinical pathogenesis and changes in the gut microbiota and bile acid profiles. Methods: A total of 84 fecal samples from BA patients (n = 46) and matched healthy controls (HCs, n = 38) were subjected to sequencing by 16S rRNA gene amplification, and fecal bile acid were analyzed by targeted metabolomics. Findings: Compared with the controls, a structural separation of the intestinal flora of BA patients was uncovered, which was accompanied by changes in the composition of fecal bile acids. In the BA group, Actinobacillus , Monoglobus , and Agathobacter were enriched in patients without cholangitis (p < 0.05). Selenomonadaceae and Megamonas were more abundant in patients without recurrent cholangitis episodes (p < 0.05), while Lachnospiraceae and Ruminococcaceae were enriched in patients with multiple recurrences of cholangitis (p < 0.05). Postoperative jaundice clearance was associated with Campylobacter and Rikenellaceae (p < 0.05), and tauroursodeoxycholic acid was associated with jaundice clearance (p < 0.001). Conclusion: BA patients are characterized by different compositions of gut microbiota and bile acids, and their interaction is involved in the process of liver damage in BA, which may be closely related to the occurrence of postoperative cholangitis and jaundice clearance. [ABSTRACT FROM AUTHOR]

The objectives of this phase I study are to assess the safety, tolerability, and pharmacokinetics (PKs) of RO7049389 in healthy Chinese volunteers (HVs) and evaluate potential ethnic differences in the safety and PKs using data from this study and the first‐in‐human study (in which most of the HVs were non‐Asian). HVs randomly received a single dose of 200–600 mg of RO7049389 or a placebo in a single ascending dose (n = 28) or multiple doses of 200–400 mg of RO7049389 or a placebo in multiple ascending doses (n = 24). Safety and tolerability were monitored throughout the study. Serial blood samples were collected for PK analysis. RO7049389 was safe and well‐tolerated in the HVs. The time to maximum concentration ranged from 1.5 to 3.0 h, and terminal half‐life ranged from 3.66 to 14.6 h. A single dose of 200–600 mg and multiple doses of 200–400 mg exhibited nonlinear PKs. In general, the safety profiles were comparable between non‐Asian and Asian HVs, but the plasma exposure of RO7049389 in Chinese HVs was higher than that in non‐Asian HVs. The data generated from this study will provide guidance for future clinical studies on RO7049389 in Chinese/Asian patients with hepatitis B virus. [ABSTRACT FROM AUTHOR]

A special F2 layer stratification structure named F3 layer occurs frequently in equatorial and low latitude ionosphere during summer daytime. In this study, a new phenomenon of decreasing occurrence of the F3 layer, and narrowing differences of virtual heights between the F3 and F2 layers in the recovery phase of geomagnetic storms is reported. We named this phenomenon as the inhibition of F3 layer event (IFLE). Using the ionosonde observations during summer of 2012–2015 at Sanya (18.3°N, 109.6°E, dip latitude 12.6°N), we found that IFLE occurred during 14 geomagnetic storms (−127 nT ≤ Dstmin ≤ −22 nT), which was accompanied by the thinning and lowering bottom ionosphere, and decreasing the crest‐to‐trough ratio of total electron content (TEC). Together with the ion drift data measured by Defense Meteorological Satellite Program F18, we suggest that the IFLE is mainly caused by the westward disturbance dynamo electric field (DDEF; downward drift velocity), taking disadvantage of the formation of the F3 layer. The observed decrease in the crest‐to‐trough ratio of TEC also indicates that the westward DDEF should prompt IFLE by providing less plasma from the equatorial region to the low latitude. Hence, IFLE then can be a good indicator to show how the magnetosphere‐ionospheric coupling process affects the low and equatorial ionosphere. Notably, the results also indicate that even a very weak geomagnetic storm can generate significant changes in ionospheric state at low latitude. Key Points: A new phenomenon of the inhibition of F3 layer over Sanya during recovery phase of geomagnetic storms in summer is reportedEven weak geomagnetic storms can produce significant changes in the low latitude ionosphere over Sanya in the recovery phaseInhibition of F3 layer event is mainly caused by the westward disturbance dynamo electric field [ABSTRACT FROM AUTHOR]

Coproporphyrins (CP‐I and CP‐III) in plasma are considered potential markers for assessing liver organic anion‐transporting polypeptide transporter OATP1B activity and monitoring OATP1B‐mediated drug‐drug interactions (DDIs) in clinical settings. However, the effect of altered renal clearance (CLrenal) on CP‐I and CP‐III plasma exposure has rarely been examined. Therefore, the purpose of this study is to further evaluate CP‐I and CP‐III as clinical endogenous markers for OATP1B activity and to investigate the impact of CLrenal on DDI assessments for the first time. In this study, 18 healthy participants were recruited to receive RO7049389 (a potential inhibitor of OATP1B) 800 mg twice daily for 6 days and a single dose of pitavastatin (a probe drug of OATP1B) before and after RO7049389 treatment. Plasma concentrations of pitavastatin, CP I, CP III, and the amounts of CP‐I and CP‐III excreted in urine were measured. Seventeen healthy participants completed the study. After multiple doses of RO7049389, the area under the plasma concentration–time curve from time 0 to 12 hours of pitavastatin increased 1.95‐fold (90% confidence interval [CI], 1.58‐2.41), while for CP‐I and CP‐III it increased 3.00‐fold (90%CI, 2.35‐3.82) and 2.84‐fold (90%CI, 2.22‐3.65), respectively. Concurrently, the CLrenal of CP‐I decreased by 31% (90%CI, 23%‐39%), and that of CP‐III decreased by 70% (90%CI, 61%‐77%). In conclusion, CP‐I and CP‐III in plasma display the potential to be applied as endogenous markers for the evaluation of OATP1B inhibition in clinical trials. While renal transporters contribute significantly to the CLrenal of CP‐III, it would be better to investigate the impact of the CLrenal on plasma exposure of CP‐III during clinical DDI assessments. [ABSTRACT FROM AUTHOR]

The pharmacokinetics (PK) of RO7049389, a new hepatitis B virus (HBV) core protein allosteric modulator of class I, and of its active metabolite M5 were studied in fasted and fed conditions after single and multiple once‐a‐day and twice‐a‐day doses in healthy subjects and patients with HBV. The nonlinearity of the pharmacokinetics, the large variability, the small sample size per dose arms, the higher plasma exposure in Asians, and the heterogeneity in patient baseline characteristics seen in phase I studies made the ethnic sensitivity assessment and the selection of the recommended phase II dose difficult. A population PK model, simultaneously modeling RO7049389 and M5, was developed to characterize the complex PK, quantify ethnicity (i.e., Asian vs. non‐Asian) and gender effects on the PK of RO7049389 and M5, and infer the quantity of RO7049389 in liver relative to plasma. Exposures in the liver are of particular importance for dose selection since the liver is the site of action of the compound. The model described and reproduced the population PK profiles as well as the between‐subject variability of RO7049389 and its metabolite. It could show that the PK is similar between healthy subjects and in HBV patients, once the ethnicity and gender effects are accounted for. The model predicts that, despite a large difference in the plasma exposure of RO7049389 between Asians and non‐Asians, the exposure in the liver is comparable, allowing the use of the same dose to treat Asian and non‐Asian patients. This model provides a valuable basis to develop this new anti‐HBV drug and to define optimal dosing. [ABSTRACT FROM AUTHOR]

Hepatitis B virus RNA (HBV RNA)–containing particles are encapsidated pre‐genomic RNA (pgRNA) detectable in chronically infected patients in addition to virions (HBV DNA) that have been suggested as a marker of the treatment efficacy. This makes promising the use of core protein allosteric modulators, such as RG7907, which disrupt the nucleocapsid assembly and profoundly reduce HBV RNA. Here, we developed a multiscale model of HBV extending the standard viral dynamic models to analyse the kinetics of HBV DNA and HBV RNA in 35 patients treated with RG7907 for 28 days. We compare the predictions with those obtained in patients treated with the nucleotide analog tenofovir. RG7907 blocked 99.3% of pgRNA encapsidation (range: 92.1%–99.9%) which led to a decline of both HBV DNA and HBV RNA. As a consequence of its mode of action, the first phase of decline of HBV RNA was rapid, uncovering the clearance of viral particles with half‐life of 45 min. In contrast, HBV DNA decline was predicted to be less rapid, due to the continuous secretion of already formed viral capsids (t1/2 = 17 ± 6 h). After few days, both markers declined at the same rate, which was attributed to the loss of infected cells (t1/2 ≅ 6 ± 0.8 days). By blocking efficiently RNA reverse transcription but not its encapsidation, nucleotide analog in contrast was predicted to lead to a transient accumulation of HBV RNA both intracellularly and extracellularly. The model brings a conceptual framework for understanding the differences between HBV DNA and HBV RNA dynamics. Integration of HBV RNA in viral dynamic models may be helpful to better quantify the treatment effect, especially in viral‐suppressed patients where HBV DNA is no longer detectable. [ABSTRACT FROM AUTHOR]

The effects of the 13–14 March 1989 great magnetic storm on the East Asian ionosphere have been re‐investigated using ground‐based and satellite measurements as well as theoretical simulation. Within introduction of new data like the Chinese ionosondes and DMSP F8 and F9 and low‐equatorial magnetometer data, we are able to track the ionospheric response at both the bottomside and topside ionosphere from middle to low latitude to obtain an overall understanding of storm‐time ionospheric change. Through the comparative study of different longitude bands, we found that the East‐Asian ionosphere was characterized by a strong westward electron density gradient persisting over a day at both the bottomside and topside ionosphere at mid‐low latitudes during the main and recovery phases of the storm. This feature was not studied in the previous literature for this event at this area. We then examine the effect through a numerical simulation work from the Thermosphere Ionosphere Electrodynamics General Circulation Model under Apex and Dipole geomagnetic fields. It is seen that the model well reproduces the zonal gradients during this event under realistic geomagnetic field model. The conditions favor for this structure requires a hemispheric asymmetry response of storm thermosphere as well as background condition and also the storm development which requires further investigation. This study shows that even very close stations would manifest totally different storm behaviors during the superstorm event suggesting a great challenge in the space weather prediction. Key Points: Use dense ionosonde network to study the east‐west differences of the ionospheric response to the March 1989 stormReveal a long‐duration strong zonal gradient in ionospheric electron density during superstorm event in the East Asian regionPropose that north‐south asymmetry of the geomagnetic configuration may cause the zonal gradient in the East Asian region in equinox [ABSTRACT FROM AUTHOR]

Hypertension control rate in the US is low with the current clinical practice (JNC 7) and cardiovascular disease (CVD) remain is the leading cause of morbidity and mortality. A 6-month clinical trial simulation case study testing different virtual clinical practice strategies was performed in an attempt to increase the control rate. The CVD risk was calculated using the Framingham CVD risk model at baseline and 6 months post-treatment. The estimated CVD events for the baseline patient sample without any treatment was 998 (95 % CI: 967-1,026) over 6 months in 100,000 patients. Treating these patients for 6 months with current clinical practice, high dose strategy, high dose with low target BP strategy resulted in a reduction in CVD events of 191(95 % CI: 169-205), 284 (95 % CI: 261-305), and 353 (95 % CI: 331-375), respectively. Hence the two alternative strategies resulted in an increase in treatment effect by 49 % (95 %CI: 44-59 %) and 85 % (95 %CI: 79-99 %), respectively. The increased safety with the current low dose strategy may potentially be offset by increased CVD risk in the time necessary to control hypertension. [ABSTRACT FROM AUTHOR]

Treatment decisions for hypertension using sphygmomanometer based measurements and the current clinical practice paradigm do not account for the timing of blood pressure (BP) measurement. This study aimed to evaluate the clinical implications of discordance between measured and true BP, to quantify BP misclassification rate at a typical clinical visit in current clinical practice, and to propose a BP calibration system to decrease the impact of timing of BP measurement. A clinical trial simulation case study was performed using an in silico Monte Carlo Simulation approach. The time-courses of BPs with and without an antihypertensive treatment effect were simulated from a baseline BP model combined with an antihypertensive PK/PD model. Virtual subject characteristics were sampled from the FDA internal database. The baseline BP model was qualified using observed 24 h ambulatory BP monitoring (ABPM) data from 225 subjects by a visual predictive check as well as a global sensitivity analysis. First of all, our results showed that the measured cuff BP in current typical clinical practice deviated from the true values. (1) Cuff BP deviated from the true values by more than 5 mmHg in 57 % (95 % CI: 54-61 %) of patients and more than 10 mmHg in 26 % (95 % CI: 22-32 %) of patients respectively. (2) These discordances were reduced to 28 % (deviation ≥5 mmHg, 95 % CI: 18-40 %) and 9 % (deviation ≥10 mmHg, 95 % CI: 4-18%) of patients assuming perfect sphygmomanometer measurement and thus represent the contribution of ignoring the daily circadian rhythm of BP. Secondly, our results showed 23-32 % of patients were misclassified to an incorrect BP category for a casual clinical visit based on JNC 7 guideline. In addition, the accuracy of the measured cuff BP varied by time of clinic visit. Specifically, 11:00 AM to 3:00 PM was identified to be the better time frame, while times before 9:00 AM were the worst time frame. Therefore, clinic visit time may need to be adjusted accordingly. Finally, we proposed an easy BP calibration method for clinic use to adjust for time of day differences due to circadian variability in case that the desirable clinic visit time cannot be tailored for practical reasons. [ABSTRACT FROM AUTHOR]