Romosozumab Efficacy in Postmenopausal Women With No Prior Fracture Who Fulfill Criteria for Very High Fracture Risk.

OBJECTIVE: We evaluated the efficacy of romosozumab in women from FRAME who had no prior fracture but met other criteria for very high fracture risk (VHFR). METHODS: In FRAME, postmenopausal women received romosozumab or placebo for 12 months (year 1) followed by denosumab for 12 months (year 2). In this post hoc analysis, we applied the following criteria from the American Association of Clinical Endocrinology to define VHFR: lumbar spine or total hip T-score <-3.0 and/or Fracture Risk Assessment Tool probability of major osteoporotic fracture >30% or hip fracture >4.5% to women with no fracture history at baseline (no fracture-VHFR [NF-VHFR]). Incidence of new vertebral, clinical, and nonvertebral fractures and mean bone mineral density (BMD) percentage change from baseline were assessed at years 1 and 2. RESULTS: Of the 7180 women in FRAME, 2825 were included in the NF-VHFR subgroup analysis. At year 1, romosozumab versus placebo reduced the incidence of new vertebral fracture (relative risk reduction [RRR]: 76%), clinical fracture (RRR: 60%), and nonvertebral fracture (RRR: 54%) (all P <.05). This fracture reduction was maintained through year 2 in women receiving the romosozumab-to-denosumab sequence versus the placebo-to-denosumab sequence for new vertebral, clinical, and nonvertebral fractures (RRR: 77%, 54%, and 46%, respectively; all P <.05). The mean BMD changes in both treatment groups were similar to those in the overall FRAME population at years 1 and 2. CONCLUSION: Romosozumab significantly reduced vertebral, clinical, and nonvertebral fracture risk and increased the BMD more than placebo in women at VHFR.

On the spurious resonance modes of time domain integral equations for analyzing acoustic scattering from penetrable objects.

The interior resonance problem of time domain integral equations (TDIEs) formulated to analyze acoustic field interactions on penetrable objects is investigated. Two types of TDIEs are considered: The first equation, which is termed the time domain potential integral equation (TDPIE), suffers from the interior resonance problem, i.e., its solution is replete with spurious modes that are excited at the resonance frequencies of the acoustic cavity in the shape of the scatterer. Numerical experiments demonstrate that, unlike the frequency-domain integral equations, the amplitude of these modes in the time domain could be suppressed to a level that does not significantly affect the solution. This is achieved by increasing the numerical solution accuracy through the use of a higher-order discretization in space and the band limited approximate prolate spheroidal wave function with high interpolation accuracy as basis function in time. The second equation is obtained by linearly combining TDPIE with its normal derivative. The solution of this equation, which is termed the time domain combined potential integral equation (TDCPIE), does not involve any spurious interior resonance modes but it is not as accurate as the TDPIE solution at non-resonance frequencies. In addition, TDCPIE's discretization calls for treatment of hypersingular integrals.

Crystallization and Structural Properties of Oleogel-Based Margarine.

Interest in oleogel as a promising alternative to traditional hydrogenated vegetable oil has increasingly grown in recent years due to its low content of saturated fatty acids and zero trans fatty acids. This study aimed to develop wax-based margarine to replace traditional commercial margarine. The wax-based margarine was prepared and compared with commercial margarine in texture, rheology, and microscopic morphology. The possibility of preparing margarine at room temperature (non-quenched) was also explored. The results showed that the hardness of oleogel-based margarine increased as the BW concentration increased. Denser droplets and crystal network structure were observed with the increase in BW content. XRD patterns of oleogel-based margarine with different content BW were quite similar and structurally to the ß' form. However, the melting temperature of oleogel-based margarine was over 40 °C at each concentration, which represented a poor mouth-melting characteristic. In addition, the unique, improved physical properties of oleogel-based margarine were obtained with binary mixtures of China lacquer wax (ZLW) and Beeswax (BW), due to the interaction of the ZLW and BW crystal network. The rapid cooling process improved the spreadability of oleogel-based margarine. The margarine prepared by 5% BW50:ZLW50 had similar properties to commercial margarine in texture and melting characteristics (37 °C), which had the potential to replace commercial margarine.

Canopy and understory nitrogen addition have different effects on fine root dynamics in a temperate forest: implications for soil carbon storage.

Elucidating the effects of atmospheric nitrogen (N) deposition on fine root dynamics and the potential underlying mechanisms is required to understand the changes in belowground and aboveground carbon storage. However, research on these effects in forests has mostly involved direct understory addition of N and has ignored canopy interception and processing of N. Here, we conducted a field experiment comparing the effects of canopy addition of N (CAN) with those of understory addition of N (UAN) at three N-addition rates (0, 25 and 50 kg N ha-1 yr-1 ) on fine root dynamics in a temperate deciduous forest. Fine root production and biomass were significantly higher with CAN than with UAN. At the same N-addition rate, increases in fine root production with CAN were at least two-fold greater than with UAN. At the high N-addition rate and relative to the control, fine root biomass was significantly increased by CAN (by 23.5%) but was significantly decreased by UAN (by 12.2%). Our results indicate that traditional UAN may underestimate the responses of fine root dynamics to atmospheric N deposition in forest ecosystems. Canopy N processes should be considered for more realistic assessments of the effects of atmospheric N deposition in forests.

Accuracy of digital complete dentures: A systematic review of in vitro studies.

STATEMENT OF PROBLEM: Reports on digital complete dentures (CDs) are increasing. However, systematic reviews on their accuracy and influencing factors are lacking. PURPOSE: The purpose of this systematic review was to evaluate the accuracy of digital CDs and to summarize influencing factors. MATERIAL AND METHODS: An electronic search of the English language literature from January 2009 to October 2019 was performed in the database PubMed/MEDLINE, with the results enriched by manual searches and citation mining. Factors investigated in the selected articles included the fabrication technique, type of computer-aided design and computer-aided manufacturing (CAD-CAM) system, shape of reference model, long-term service, analytical method, and statistical indicators. RESULTS: A total of 522 articles were identified, of which 14 in vitro articles met the inclusion criteria. Eight articles compared the adaptation of the denture base between digital and conventional methods, 4 studies evaluated the occlusal discrepancies, 4 compared the trueness or adaptation of the denture fabricated with CAD-CAM milling and 3D printing, 1 compared the denture adaptation with 4 different CAD-CAM systems, and 2 evaluated the adaptation of the denture base before and after incubation in artificial saliva. CONCLUSIONS: Most of the studies reported clinically acceptable values for the occlusal trueness and adaptation of digital CDs. The digital CDs showed similar or better adaptation than conventionally fabricated CDs, and the greatest misfit of the intaglio surface was reported in the posterior palatal seal area and border seal area. The fabrication technique, CAD-CAM system, and long-term service were statistically significant in relation to denture accuracy. Clarification is needed concerning the accuracy of digital CDs according to the shape of the cast, the parameters related to the CAD-CAM process, the analytical method, and the statistical indicators. No clear conclusions can be drawn about the superiority of CAD-CAM milling and 3D printing regarding denture accuracy.

Environmental and human health risk evaluation of heavy metals in ceramsites from municipal solid waste incineration fly ash.

Municipal solid waste incineration (MSWI) for power generation can reuse waste effectively, but it generates a large amount of fly ash enriched with heavy metals. If this fly ash cannot be treated properly, it can cause ecological damage and human health risk. According to the production of ceramsites from MSWI fly ash, an evaluation methodology is established, in which the influence of heavy metal stability on the environment is considered for the first time, and the health risks of heavy metals via different exposure pathways are distinguished. The results show that heavy metals in MSWI fly ash have moderate potential environmental risks to environment and have strong non-carcinogenic and carcinogenic risks both to children and adults. By contrast, heavy metals in ceramsites pose little risk to environment and human health. This paper explains some reasons of heavy metal content and leaching ratio change in ceramsite and also illustrates why stability is a concern through comparing the potential risk index method and the improved evaluation method. This evaluation system can be applied to different production processes of building materials using solid hazardous waste and provides a quantitative evaluation method for reducing environment and human health risks of heavy metals.

Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis.

BACKGROUND: Early clinical studies suggested that the anti-interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis. METHODS: In two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physician's global assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well as the superiority of brodalumab over ustekinumab at week 12 with respect to a 100% reduction in PASI score (PASI 100). RESULTS: At week 12, the PASI 75 response rates were higher with brodalumab at the 210-mg and 140-mg doses than with placebo (86% and 67%, respectively, vs. 8% [AMAGINE-2] and 85% and 69%, respectively, vs. 6% [AMAGINE-3]; P<0.001); the rates of sPGA scores of 0 or 1 were also higher with brodalumab (P<0.001). The week 12 PASI 100 response rates were significantly higher with 210 mg of brodalumab than with ustekinumab (44% vs. 22% [AMAGINE-2] and 37% vs. 19% [AMAGINE-3], P<0.001). The PASI 100 response rates with 140 mg of brodalumab were 26% in AMAGINE-2 (P=0.08 for the comparison with ustekinumab) and 27% in AMAGINE-3 (P=0.007). Rates of neutropenia were higher with brodalumab and with ustekinumab than with placebo. Mild or moderate candida infections were more frequent with brodalumab than with ustekinumab or placebo. Through week 52, the rates of serious infectious episodes were 1.0 (AMAGINE-2) and 1.3 (AMAGINE-3) per 100 patient-years of exposure to brodalumab. CONCLUSIONS: Brodalumab treatment resulted in significant clinical improvements in patients with moderate-to-severe psoriasis. (Funded by Amgen; AMAGINE-2 and AMAGINE-3 ClinicalTrials.gov numbers, NCT01708603 and NCT01708629.).

Contribution of the Covalent Component of the Hydrogen-Bond Network to the Properties of Liquid Water.

Many remarkable properties of liquid water originate from the ability of its molecules to form hydrogen bonds, each of which emerges as a combination of electrostatic, polarization, dispersion, and donor-acceptor or covalent interactions. In this work, ab initio molecular dynamics was tailored to isolate and switch off the covalent component of interactions between water molecules in simulations. Comparison of simulations with and without covalency shows that a small amount of intermolecular electron density transfer has a profound effect on the structure and dynamics of the hydrogen-bond network and thus on observable properties of room-temperature liquid water.

Communication: Compact orbitals enable low-cost linear-scaling ab initio molecular dynamics for weakly-interacting systems.

Today, ab initio molecular dynamics (AIMD) relies on the locality of one-electron density matrices to achieve linear growth of computation time with the system size, crucial in large-scale simulations. While Kohn-Sham orbitals strictly localized within predefined radii can offer substantial computational advantages over density matrices, such compact orbitals are not used in AIMD because a compact representation of the electronic ground state is difficult to find. Here, a robust method for maintaining compact orbitals close to the ground state is coupled with a modified Langevin integrator to produce stable nuclear dynamics for molecular and ionic systems. This eliminates a density matrix optimization and enables first orbital-only linear-scaling AIMD. An application to liquid water demonstrates that low computational overhead of the new method makes it ideal for routine medium-scale simulations, while its linear-scaling complexity allows us to extend first-principle studies of molecular systems to completely new physical phenomena on previously inaccessible length scales.

Charge Transport between Coupling Colloidal Perovskite Quantum Dots Assisted by Functional Conjugated Ligands.

Long alkyl-chain capping ligands are indispensable for preparing stable colloidal quantum dots. However, its insulating feature blocks efficient carrier transport among QDs, leading to inferior performance in light-emitting diodes (LEDs). The trade-off between conductivity and colloidal stability of QDs has now been overcome. Methylamine lead bromide (MAPbBr3 ) QDs with a conjugated alkyl-amine, 3-phenyl-2-propen-1-amine (PPA), as ligands were prepared. Owing to electron cloud overlapping and the delocalization effect of conjugated molecules, the conductivity and carrier mobility of PPA-QDs films increased almost 22 times over that of OA-QD films without compromising colloidal stability and photoluminescence. PPA-QDs LEDs exhibit a maximum current efficiency of 9.08 cd A-1 , which is 8 times of that of OA-QDs LEDs (1.14 cd A-1 ). This work provides critical solution for the poor conductivity of QDs in applications of energy-related devices.

Transcriptome analyses reveal SR45 to be a neutral splicing regulator and a suppressor of innate immunity in Arabidopsis thaliana.

BACKGROUND: Regulation of pre-mRNA splicing diversifies protein products and affects many biological processes. Arabidopsis thaliana Serine/Arginine-rich 45 (SR45), regulates pre-mRNA splicing by interacting with other regulatory proteins and spliceosomal subunits. Although SR45 has orthologs in diverse eukaryotes, including human RNPS1, the sr45-1 null mutant is viable. Narrow flower petals and reduced seed formation suggest that SR45 regulates genes involved in diverse processes, including reproduction. To understand how SR45 is involved in the regulation of reproductive processes, we studied mRNA from the wild-type and sr45-1 inflorescences using RNA-seq, and identified SR45-bound RNAs by immunoprecipitation. RESULTS: Using a variety of bioinformatics tools, we identified a total of 358 SR45 differentially regulated (SDR) genes, 542 SR45-dependent alternative splicing (SAS) events, and 1812 SR45-associated RNAs (SARs). There is little overlap between SDR genes and SAS genes, and neither set of genes is enriched for flower or seed development. However, transcripts from reproductive process genes are significantly overrepresented in SARs. In exploring the fate of SARs, we found that a total of 81 SARs are subject to alternative splicing, while 14 of them are known Nonsense-Mediated Decay (NMD) targets. Motifs related to GGNGG are enriched both in SARs and near different types of SAS events, suggesting that SR45 recognizes this motif directly. Genes involved in plant defense are significantly over-represented among genes whose expression is suppressed by SR45, and sr45-1 plants do indeed show enhanced immunity. CONCLUSION: We find that SR45 is a suppressor of innate immunity. We find that a single motif (GGNGG) is highly enriched in both RNAs bound by SR45 and in sequences near SR45- dependent alternative splicing events in inflorescence tissue. We find that the alternative splicing events regulated by SR45 are enriched for this motif whether the effect of SR45 is activation or repression of the particular event. Thus, our data suggests that SR45 acts to control splice site choice in a way that defies simple categorization as an activator or repressor of splicing.

Linking microbial community coalescence to ecological diversity, community assembly and species coexistence in a typical subhumid river catchment in northern China.

Community coalescence denotes the amalgamation of biotic and abiotic factors across multiple intact ecological communities. Despite the growing attention given to the phenomenon of coalescence, there remains limited investigation into community coalescence in single and multiple source habitats and its impact on microbial community assemblages in sinks. This study focused on a major river catchment in northern China. We investigated microbial community coalescence across different habitats (i.e., water, sediment, biofilm, and riparian soil) and seasons (i.e., summer and winter). Using 16S rRNA gene amplicon sequence variants, we examined the relationship between community coalescence and microbial diversity, assembly processes, and species coexistence. The results showed that the intensity of microbial community coalescence was higher in the same habitat pairs compared to disparate habitat pairs in both summer and winter. During the occurrence of microbial community coalescence, the assembly processes regulated the intensity of coalescence. When the microbial community exhibited strong heterogeneous selection (heterogeneous environmental conditions leading to more dissimilar community structures), the intensity of community coalescence was low. With the assembly process shifted towards stochasticity, coalescence intensity increased gradually. However, when homogeneous selection (homogeneous environmental conditions leading to more similar community structures) predominantly shaped microbial communities, coalescence intensity exceeded the threshold of 0.25-0.30. Moreover, the enhanced intensity of community coalescence could increase the complexity of microbial networks, thereby enhancing species coexistence. Furthermore, the assembly processes mediated the relationship between community coalescence and species coexistence, underscoring the pivotal role of intermediate intensity of community coalescence in maintaining efficient species coexistence. In conclusion, this study highlights the crucial role of community coalescence originating from single and multiple source habitats in shaping microbial communities in sinks, thus emphasizing its central importance in watershed ecosystems.

A prognostic and immune related risk model based on zinc homeostasis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The dysfunction of zinc homeostasis participates in the early and advancing malignancy of HCC. However, the prognostic ability of zinc homeostasis in HCC has not been clarified yet. Here, we showed a zinc-homeostasis related risk model in HCC. Five signature genes including ADAMTS5, PLOD2, PTDSS2, KLRB1, and UCK2 were screened out via survival analyses and regression algorithms to construct the nomogram with clinical characteristics. Experimental researches indicated that UCK2 participated in the progression of HCC. Patients with higher risk scores always had worse outcomes and were more associated with immune suppression according to the analyses of immune related-pathway activation, cell infiltration, and gene expression. Moreover, these patients were likely to exhibit more sensitivity to sorafenib and other antitumor drugs. This study highlights the significant prognostic role of zinc homeostasis and suggests potential treatment strategies in HCC.

Causal association of TSH with ischemic heart diseases and heart failure: A 2-sample Mendelian randomization study.

Thyroid dysfunction is associated with the risk of cardiovascular disease; however, whether plasma thyroid-stimulating hormone (TSH) levels in subjects with euthyroidism affect the risk of cardiovascular disease remains unclear. This study aimed to investigate the causal association between plasma TSH levels and cardiovascular diseases, particularly ischemic heart disease and heart failure (HF). Summary statistics from the Integrative Epidemiology Unit Open genome-wide association studies Project and FinnGen consortium were used to investigate the causal relationship between plasma TSH levels and the risk of cardiovascular diseases. Two-sample Mendelian randomization analysis using inverse-variance weighting as the primary method was performed. The MR Pleiotropy RESidual Sum and Outlier and leave-one-out methods were used to ensure the robustness of our findings. Genetically determined plasma TSH levels were associated with major coronary heart disease events (OR 1.0557, 95% CI 1.0141-1.0991), all-cause HF (OR 0.9587, 95% CI 0.9231-0.9956), and HF + non-ischemic cardiomyopathy (OR 0.9318, 95% CI 0.8786-0.9882). After the Bonferroni correction, the causation described above disappeared. In the secondary analysis, genetically determined higher TSH levels were associated with a higher risk for unstable angina pectoris (OR 1.0913, 95% CI 1.0350-1.1507), but were associated with a lower risk for HF + overweight (OR 0.9265, 95% CI 0.8821-0.9731). These results were further validated using sensitivity analysis. Our findings show that increased plasma TSH levels in patients with euthyroidism may increase the risk of unstable angina pectoris but reduce the risk of HF in overweight patients. This evidence indicates that plasma TSH levels may need to be carefully controlled in specific patients.

Reconstruction of Remodeling units reveals positive effects after 2 and 12 months of Romosozumab treatment.

Romosozumab treatment results in a transient early increase in bone formation and sustained decrease in bone resorption. Histomorphometric analyses revealed that the primary bone-forming effect of romosozumab is transient early stimulation of modeling-based bone formation on cancellous and endocortical surfaces; preclinical studies have demonstrated that romosozumab may affect changes in the remodeling unit resulting in positive bone balance. To further investigate the effects of romosozumab on bone balance, month 12 (M12) and M2 (to analyze early effects) unpaired bone biopsies from the FRAME clinical trial were analyzed using remodeling site reconstruction to assess whether positive changes in bone balance on cancellous/endocortical surfaces may contribute to the progressive improvement in bone mass/structure and reduced fracture risk in osteoporotic women at high fracture risk. At M12, bone balance was higher with romosozumab vs placebo on cancellous (+6.1 µm vs +1.5 µm; p = 0.012) and endocortical (+5.2 µm vs -1.7 µm; p = 0.02) surfaces; higher bone balance was due to lower final erosion depth (40.7 µm vs 43.7 µm; p = 0.05) on cancellous surfaces and higher completed wall thickness (50.8 µm vs 47.5 µm; p = 0.037) on endocortical surfaces. At M2, final erosion depth was lower on the endocortical surfaces (42.7 µm vs 50.7 µm; p = 0.021) and slightly lower on the cancellous surfaces (38.5 µm vs 44.6 µm; p = 0.11) with romosozumab vs placebo. Sector analysis of early endocortical formative sites revealed higher osteoid thickness (29.9 µm vs 19.2 µm; p = 0.005) and mineralized wall thickness (18.3 µm vs 11.9 µm; p = 0.004) with romosozumab vs placebo. These evolving bone packets may reflect early stimulation of bone formation that contributes to the increase in completed wall thickness at M12. These data suggest that romosozumab induces a positive bone balance due to its effects on bone resorption and formation at the level of the remodeling unit, contributing to the positive effects on bone mass, structure, and fracture risk.

Romosozumab treatment has a dual effect on bone, adding new bone and reducing bone loss. In the FRAME clinical trial, romosozumab increased bone mass and strength, and reduced fracture risk in postmenopausal women with osteoporosis. Addition of new bone occurs early in treatment and rapidly on cancellous and endocortical bone surfaces where bone resorption is not ongoing. However, it remains unclear if romosozumab affects bone loss or gain in areas where bone resorption is ongoing (remodeling units), contributing to a further positive bone balance. Here, we examined whether changes at the remodeling unit occur early (2 months) and/or late (12 months) in treatment, using bone biopsies from patients treated with romosozumab or placebo in FRAME. At month 2, a combination of lower bone resorption and higher bone gain on endocortical surfaces resulted in a positive bone balance with romosozumab versus placebo. At month 12, bone balance was positive with romosozumab versus placebo due to lower bone resorption on cancellous surfaces and greater bone gain on endocortical surfaces. This demonstrates that romosozumab induces a positive bone balance at remodeling units early in treatment leading to overall gains observed later, contributing to the positive effects of romosozumab on bone mass and structure.

3D-modeling from hip DXA shows improved bone structure with romosozumab followed by denosumab or alendronate.

Romosozumab treatment in women with postmenopausal osteoporosis increases bone formation while decreasing bone resorption, resulting in large BMD gains to reduce fracture risk within 1 yr. DXA-based 3D modeling of the hip was used to assess estimated changes in cortical and trabecular bone parameters and map the distribution of 3D changes in bone parameters over time in patients from 2 randomized controlled clinical trials: FRAME (romosozumab vs placebo followed by denosumab) and ARCH (romosozumab vs alendronate followed by alendronate). For each study, data from a subset of ~200 women per treatment group who had TH DXA scans at baseline and months 12 and 24 and had provided consent for future research were analyzed post hoc. 3D-SHAPER software v2.11 (3D-SHAPER Medical) was used to generate patient-specific 3D models from TH DXA scans. Percentage changes from baseline to months 12 and 24 in areal BMD (aBMD), integral volumetric BMD (vBMD), cortical thickness, cortical vBMD, cortical surface BMD (sBMD), and trabecular vBMD were evaluated. Data from 377 women from FRAME (placebo, 190; romosozumab, 187) and 368 women from ARCH (alendronate, 185; romosozumab, 183) with evaluable 3D assessments at baseline and months 12 and 24 were analyzed. At month 12, treatment with romosozumab vs placebo in FRAME and romosozumab vs alendronate in ARCH resulted in greater increases in aBMD, integral vBMD, cortical thickness, cortical vBMD, cortical sBMD, and trabecular vBMD (P < .05 for all). At month 24, cumulative gains in all parameters were greater in the romosozumab-to-denosumab vs placebo-to-denosumab sequence and romosozumab-to-alendronate vs alendronate-to-alendronate sequence (P < .05 for all). 3D-SHAPER analysis provides a novel technique for estimating changes in cortical and trabecular parameters from standard hip DXA images. These data add to the accumulating evidence that romosozumab improves hip bone density and structure, thereby contributing to the antifracture efficacy of the drug.

Osteoporosis is a chronic condition in which bones become weak and are more likely to break (fracture) with minimal force such as tripping or falling. A fracture, especially in the elderly, is a serious condition that affects daily activities and quality of life. Romosozumab, an approved medication for patients with osteoporosis, increases bone mass and bone strength thereby reducing fracture risk. In this study, 3D reproductions of patients' hip bones were generated from standard images of a bone density test with DXA from women in the FRAME clinical trial where they received romosozumab or placebo for 12 mo followed by 12 mo of denosumab or the ARCH clinical trial where they received romosozumab or alendronate for 12 mo, followed by 12 mo of alendronate. We found that patients treated with romosozumab for the first 12 mo had significantly greater increases in bone strength compared with those who received placebo or alendronate. After 24 mo, total gains in bone strength measurements were greater in patients treated with romosozumab first. Our study shows that DXA-based 3D modelling provides a novel technique for examining changes in bone strength and supports the use of romosozumab to improve hip bone strength and reduce fracture risk.

OBSERVE-5 interim analysis: an observational postmarketing safety registry of etanercept for the treatment of psoriasis.

BACKGROUND: Etanercept is approved for the treatment of chronic moderate to severe plaque psoriasis in adults. OBJECTIVE: We sought to evaluate the long-term safety of etanercept in a real-world clinical setting. Assessment of etanercept efficacy was a secondary objective. METHODS: OBSERVE-5 is a 5-year observational safety registry initiated in May 2006 at multiple sites in the United States and Canada. Data collection includes the number of serious adverse events, serious infectious events, and prespecified events of medical interest. Efficacy data include body surface area assessments, physician and patient global assessments of psoriasis, and the Dermatology Life Quality Index. This interim analysis presents data from the first 3 years of the follow-up period. RESULTS: A total of 2511 patients were enrolled. Of 1890 patients continuing in the registry after 3 years, 113 were inactive for 1 to 2 years, and 115 were inactive for longer than 2 years. The 3-year incidence proportions of serious adverse events and serious infectious events based on Kaplan-Meier methodology were 0.14 and 0.04, respectively. The observed numbers of patients experiencing lymphoma, serious infectious events requiring hospitalization, nonmelanoma skin cancer, and malignancies excluding nonmelanoma skin cancer were not higher than the expected number of cases estimated from a large US administrative health claims database. LIMITATIONS: The registry lacks a control group, and the study is too small to measure the frequency of rare events. CONCLUSION: Etanercept demonstrated good tolerability in patients with plaque psoriasis in the clinical setting in this interim analysis. No new or unexpected safety concerns were observed.

SuperUDF: Self-supervised UDF Estimation for Surface Reconstruction.

Learning-based surface reconstruction based on unsigned distance functions (UDF) has many advantages such as handling open surfaces. We propose SuperUDF, a self-supervised UDF learning which exploits a learned geometry prior for efficient training and a novel regularization for robustness to sparse sampling. The core idea of SuperUDF draws inspiration from the classical surface approximation operator of locally optimal projection (LOP). The key insight is that if the UDF is estimated correctly, the 3D points should be locally projected onto the underlying surface following the gradient of the UDF. Based on that, a number of inductive biases on UDF geometry and a pre-learned geometry prior are devised to learn UDF estimation efficiently. A novel regularization loss is proposed to make SuperUDF robust to sparse sampling. Furthermore, we also contribute a learning-based mesh extraction from the estimated UDFs. Extensive evaluations demonstrate that SuperUDF outperforms the state of the arts on several public datasets in terms of both quality and efficiency. Code will be released after accteptance.

Learning to Detect 3D Symmetry From Single-View RGB-D Images With Weak Supervision.

3D symmetry detection is a fundamental problem in computer vision and graphics. Most prior works detect symmetry when the object model is fully known, few studies symmetry detection on objects with partial observation, such as single RGB-D images. Recent work addresses the problem of detecting symmetries from incomplete data with a deep neural network by leveraging the dense and accurate symmetry annotations. However, due to the tedious labeling process, full symmetry annotations are not always practically available. In this work, we present a 3D symmetry detection approach to detect symmetry from single-view RGB-D images without using symmetry supervision. The key idea is to train the network in a weakly-supervised learning manner to complete the shape based on the predicted symmetry such that the completed shape be similar to existing plausible shapes. To achieve this, we first propose a discriminative variational autoencoder to learn the shape prior in order to determine whether a 3D shape is plausible or not. Based on the learned shape prior, a symmetry detection network is present to predict symmetries that produce shapes with high shape plausibility when completed based on those symmetries. Moreover, to facilitate end-to-end network training and multiple symmetry detection, we introduce a new symmetry parametrization for the learning-based symmetry estimation of both reflectional and rotational symmetry. The proposed approach, coupled symmetry detection with shape completion, essentially learns the symmetry-aware shape prior, facilitating more accurate and robust symmetry detection. Experiments demonstrate that the proposed method is capable of detecting reflectional and rotational symmetries accurately, and shows good generality in challenging scenarios, such as objects with heavy occlusion and scanning noise. Moreover, it achieves state-of-the-art performance, improving the F1-score over the existing supervised learning method by 2%-11% on the ShapeNet and ScanNet datasets.

RayMVSNet++: Learning Ray-Based 1D Implicit Fields for Accurate Multi-View Stereo.

Learning-based multi-view stereo (MVS) has by far centered around 3D convolution on cost volumes. Due to the high computation and memory consumption of 3D CNN, the resolution of output depth is often considerably limited. Different from most existing works dedicated to adaptive refinement of cost volumes, we opt to directly optimize the depth value along each camera ray, mimicking the range (depth) finding of a laser scanner. This reduces the MVS problem to ray-based depth optimization which is much more light-weight than full cost volume optimization. In particular, we propose RayMVSNet which learns sequential prediction of a 1D implicit field along each camera ray with the zero-crossing point indicating scene depth. This sequential modeling, conducted based on transformer features, essentially learns the epipolar line search in traditional multi-view stereo. We devise a multi-task learning for better optimization convergence and depth accuracy. We found the monotonicity property of the SDFs along each ray greatly benefits the depth estimation. Our method ranks top on both the DTU and the Tanks & Temples datasets over all previous learning-based methods, achieving an overall reconstruction score of 0.33 mm on DTU and an F-score of 59.48% on Tanks & Temples. It is able to produce high-quality depth estimation and point cloud reconstruction in challenging scenarios such as objects/scenes with non-textured surface, severe occlusion, and highly varying depth range. Further, we propose RayMVSNet++ to enhance contextual feature aggregation for each ray through designing an attentional gating unit to select semantically relevant neighboring rays within the local frustum around that ray. This improves the performance on datasets with more challenging examples (e.g., low-quality images caused by poor lighting conditions or motion blur). RayMVSNet++ achieves state-of-the-art performance on the ScanNet dataset. In particular, it attains an AbsRel of 0.058m and produces accurate results on the two subsets of textureless regions and large depth variation.