Biodiversity mitigates drought effects in the decomposer system across biomes.

Multiple facets of global change affect the earth system interactively, with complex consequences for ecosystem functioning and stability. Simultaneous climate and biodiversity change are of particular concern, because biodiversity may contribute to ecosystem resistance and resilience and may mitigate climate change impacts. Yet, the extent and generality of how climate and biodiversity change interact remain insufficiently understood, especially for the decomposition of organic matter, a major determinant of the biosphere-atmosphere carbon feedbacks. With an inter-biome field experiment using large rainfall exclusion facilities, we tested how drought, a common prediction of climate change models for many parts of the world, and biodiversity in the decomposer system drive decomposition in forest ecosystems interactively. Decomposing leaf litter lost less carbon (C) and especially nitrogen (N) in five different forest biomes following partial rainfall exclusion compared to conditions without rainfall exclusion. An increasing complexity of the decomposer community alleviated drought effects, with full compensation when large-bodied invertebrates were present. Leaf litter mixing increased diversity effects, with increasing litter species richness, which contributed to counteracting drought effects on C and N loss, although to a much smaller degree than decomposer community complexity. Our results show at a relevant spatial scale covering distinct climate zones that both, the diversity of decomposer communities and plant litter in forest floors have a strong potential to mitigate drought effects on C and N dynamics during decomposition. Preserving biodiversity at multiple trophic levels contributes to ecosystem resistance and appears critical to maintain ecosystem processes under ongoing climate change.

A Visual Measurement Method for Deep Holes in Composite Material Aerospace Components.

The visual measurement of deep holes in composite material workpieces constitutes a critical step in the robotic assembly of aerospace components. The positioning accuracy of assembly holes significantly impacts the assembly quality of components. However, the complex texture of the composite material surface and mutual interference between the imaging of the inlet and outlet edges of deep holes significantly challenge hole detection. A visual measurement method for deep holes in composite materials based on the radial penalty Laplacian operator is proposed to address the issues by suppressing visual noise and enhancing the features of hole edges. Coupled with a novel inflection-point-removal algorithm, this approach enables the accurate detection of holes with a diameter of 10 mm and a depth of 50 mm in composite material components, achieving a measurement precision of 0.03 mm.

Error Analysis of Normal Surface Measurements Based on Multiple Laser Displacement Sensors.

The robotic drilling of assembly holes is a crucial process in aerospace manufacturing, in which measuring the normal of the workpiece surface is a key step to guide the robot to the correct pose and guarantee the perpendicularity of the hole axis. Multiple laser displacement sensors can be used to satisfy the portable and in-site measurement requirements, but there is still a lack of accurate analysis and layout design. In this paper, a simplified parametric method is proposed for multi-sensor normal measurement devices with a symmetrical layout, using three parameters: the sensor number, the laser beam slant angle, and the laser spot distribution radius. A normal measurement error distribution simulation method considering the random sensor errors is proposed. The measurement error distribution laws at different sensor numbers, the laser beam slant angle, and the laser spot distribution radius are revealed as a pyramid-like region. The influential factors on normal measurement accuracy, such as sensor accuracy, quantity and installation position, are analyzed by a simulation and verified experimentally on a five-axis precision machine tool. The results show that increasing the laser beam slant angle and laser spot distribution radius significantly reduces the normal measurement errors. With the laser beam slant angle ≥15° and the laser spot distribution radius ≥19 mm, the normal measurement error falls below 0.05°, ensuring normal accuracy in robotic drilling.

[Cloning and functional analysis of flavanone synthase â ¡ from Dendrobium huoshanense].

Flavonoid C-glycosides are a class of natural products that are widely involved in plant defense responses and have diverse pharmacological activities. They are also important active ingredients of Dendrobium huoshanense. Flavanone synthase Ⅱ has been proven to be a key enzyme in the synthesis pathway of flavonoid C-glycosides in plants, and their catalytic product 2-hydroxyflavanone is the precursor compound for the synthesis of various reported flavonoid C-glycosides. In this study, based on the reported amino acid sequence of flavanone synthase Ⅱ, a flavanone synthase Ⅱ gene(DhuFNSⅡ) was screened and verified from the constructed D. huoshanense genome localization database. Functional validation of the enzyme showed that it could in vitro catalyze naringenin and pinocembrin to produce apigenin and chrysin, respectively. The open reading frame(ORF) of DhuFNSⅡ was 1 644 bp in length, encoding 547 amino acids. Subcellular localization showed that the protein was localized on the endoplasmic reticulum. RT-qPCR results showed that DhuFNSⅡ had the highest expression in stems, followed by leaves and roots. The expression levels of DhuFNSⅡ and other target genes in various tissues of D. huoshanense were significantly up-regulated after four kinds of abiotic stresses commonly encountered in the growth process, but the extent of up-regulation varied among treatment groups, with drought and cold stress having more significant effects on gene expression levels. Through the identification and functional analysis of DhuFNSⅡ, this study is expected to contribute to the elucidation of the molecular mechanism of the formation of quality metabolites of D. huoshanense, flavonoid C-glycosides, and provide a reference for its quality formation and scientific cultivation.

Unraveling temporal and spatial biomarkers of epithelial-mesenchymal transition in colorectal cancer: insights into the crucial role of immunosuppressive cells.

The occurrence and progression of tumors can be established through a complex interplay among tumor cells undergoing epithelial-mesenchymal transition (EMT), invasive factors and immune cells. In this study, we employed single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (ST) to evaluate the pseudotime trajectory and spatial interactive relationship between EMT-invasive malignant tumors and immune cells in primary colorectal cancer (CRC) tissues at different stages (stage I/II and stage III with tumor deposit). Our research characterized the spatiotemporal relationship among different invasive tumor programs by constructing pseudotime endpoint-EMT-invasion tumor programs (EMTPs) located at the edge of ST, utilizing evolution trajectory analysis integrated with EMT-invasion genes. Strikingly, the invasive and expansive process of tumors undergoes remarkable spatial reprogramming of regulatory and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), regulatory T cells (Treg), and exhausted T cells (Tex). These EMTP-adjacent cell are linked to EMT-related invasion genes, especially the C-X-C motif ligand 1 (CXCL1) and CXCL8 genes that are important for CRC prognosis. Interestingly, the EMTPs in stage I mainly produce an inflammatory margin invasive niche, while the EMTPs in stage III tissues likely produce a hypoxic pre-invasive niche. Our data demonstrate the crucial role of regulatory and immunosuppressive cells in tumor formation and progression of CRC. This study provides a framework to delineate the spatiotemporal invasive niche in CRC samples.

Implementing digital systems to facilitate genetic testing for hereditary cancer syndromes: An observational study of 4 clinical workflows.

PURPOSE: National efforts have prioritized the identification of effective methods for increasing case ascertainment and delivery of evidence-based health care for individuals at elevated risk for hereditary cancers. METHODS: This study examined the uptake of genetic counseling and testing following the use of a digital cancer genetic risk assessment program implemented at 27 health care sites in 10 states using 1 of 4 clinical workflows: (1) traditional referral, (2) point-of-care scheduling, (3) point-of-care counseling/telegenetics, and (4) point-of-care testing. RESULTS: In 2019, 102,542 patients were screened and 33,113 (32%) were identified as at high risk and meeting National Comprehensive Cancer Network genetic testing criteria for hereditary breast and ovarian cancer, Lynch syndrome, or both. Among those identified at high risk, 5147 (16%) proceeded with genetic testing. Genetic counseling uptake was 11% among the sites with workflows that included seeing a genetic counselor before testing, with 88% of patients proceeding with genetic testing after counseling. Uptake of genetic testing across sites varied significantly by clinical workflow (6% referral, 10% point-of-care scheduling, 14% point-of-care counseling/telegenetics, and 35% point-of-care testing, P < .0001). CONCLUSION: Study findings highlight the potential heterogeneity of effectiveness attributable to different care delivery approaches for implementing digital hereditary cancer risk screening programs.

Discovery of a highly potent CECR2 bromodomain inhibitor with 7H-pyrrolo[2,3-d] pyrimidine scaffold.

Cat eye syndrome chromosome region candidate 2 (CECR2) bromodomain is a module of CECR2-containing remodeling factor (CERF), which is a chromatin remodeling complex correlating with transcriptional control and adjustment of chromatin architecture. Potent chemical probes would be beneficial to gain insights into the biochemical and pharmacological functions of CECR2 BRD. Herein, we report the discovery of a series of CECR2 BRD inhibitors with 7H-pyrrolo[2,3-d] pyrimidine scaffold based on molecular docking model of TP-248 and CECR2 BRD. The most potent inhibitor of this series, DC-CBi-22 with IC50 of 8.0 ± 1.4 nM against CECR2 BRD and selectivity over BPTF BRD up to 24.9-fold. The SARs were detailed according to molecular docking. DC-CBi-22 would serve as a useful chemical probe for the study of CECR2.

The association between changes in multifidus muscle morphology and back pain scores following discectomy surgery for lumbar disc herniation: a systematic review and meta-analysis.

PURPOSE: To evaluate the impact of discectomy on back muscles (e.g. multifidus muscle (MM)) morphology in patients with lumbar disc herniation (LDH) following discectomy surgery, address the association of back muscles morphology with pain score preoperatively and post-operatively, and investigate the relationships between the changes from pre- to post-operative back muscles measurements and pain score (primary outcome) and disability score (secondary outcome) change following discectomy if any. METHODS: We searched three online databases for randomized controlled trials (RCTs) and observational studies. In LDH patients, eligible for discectomy surgery, pre- and post-operative and the changes from pre- to post-operative of back and/or leg pain with Visual Analogue Scale (VAS) and multifidus muscle morphology, were considered as primary outcomes. Cochrane Risk-of-Bias 2 tool and Newcastle-Ottawa Scale (NOS) were used to assess the methodological quality of RCTs and observational studies, respectively. Standardize mean difference (SMD) with 95% confidence intervals (CI) was evaluated. A meta-regression analysis was conducted. GRADE approach was used to summarize the strength of evidence. RESULTS: One RCT and five observational studies were included in the analysis of 489 patients with LDH undergoing discectomy surgery. The mean overall follow-up was 64.9 weeks (6 to 148.7 weeks). There was a significant negative relationship between the change from pre- to post-operative cross-sectional area (CSA) in MM and change in VAS back pain [regression coefficient = -0.01, (95% CI = -0.02, -0.01), p = 0.044] after discectomy surgery. No significant relationship between preoperative CSA in MM and preoperative/post-operative clinical (any of the follow-up periods) scores could be established. CONCLUSION: The results of this study found very low-quality grade evidence for an association between higher reduction of CSA in MM and less reductions of back pain scores following discectomy surgery for patients with LDH. Due to the heterogeneity and methodological limitations, further studies will improve understanding and aid preoperative counselling.

Discovery of a novel 53BP1 inhibitor through AlphaScreen-based high-throughput screening.

Tumor suppressor p53-binding protein 1 (53BP1), a tantem tudor domain (TTD) protein, takes part in DNA Damage Repair (DDR) pathways through the specific recognition of lysine methylation on histones. The dysregulation of 53BP1 is closely related to the development of many diseases including cancer. Moreover, recent studies found that deficiency of 53BP1 could increase the efficiency of precise CRISPR/Cas9 genome editing. Thus, discovery of inhibitor is beneficial to the study of biological functions of 53BP1 and the application of CRISPR/Cas9 genome editing. UNC2170 and its derivatives have been reported as 53BP1 targeted small molecular inhibitors with modest activities. Hence, to discover better 53BP1 inhibitors, we conducted an AlphaScreen assay based high-throughput screening (HTS) and identified a novel and effective 53BP1-TTD inhibitor DP308 which disrupts the binding between 53BP1 and H4K20me2 peptide with an IC50 value of 1.69 ± 0.73 µM. Both Microscale Themophoresis (MST) and Surface Plasmon Resonance (SPR) assays confirmed the direct binding between DP308 and 53BP1-TTD protein with binding affinity (Kd) of about 2.7 µM. Molecular docking studies further suggested that DP308 possibly occupies the H4K20me2 binding pocket of the 53BP1-TTD aromatic cage. These results demonstrated that DP308 is a promising small molecule inhibitor for further optimization towards a more potent chemical probe of 53BP1. Additionally, it could be a potential valuable tool for applying to gene editing therapy by increasing the efficiency of CRISPR/Cas9 genome editing.

Phenotypic and genetic effects of season on milk production traits in dairy cattle in the Netherlands.

Milk production systems in several countries show considerable differences between seasons. For example, in the Netherlands, cows are kept inside and fed silage in winter, whereas they are on pasture in summer. The differences between seasons affect milk yield and composition and might influence the genetic background of milk production traits. The objective of this study was to estimate phenotypic and genetic effects of season on milk production traits. For this purpose, 19,286 test-day milk production records of 1,800 first-parity Dutch Holstein-Frisian cows were available, and these cows were genotyped using a 50K SNP panel. Phenotypic effects of season were significant for all milk production traits. Effects of season were large for milk fat yield, fat content, and protein content. Genetic correlations between milk production traits in different seasons showed that genotype by season interaction effects were relatively small for most milk production traits. The genetic background of protein content and lactose content seems to be sensitive to seasonal effects. Furthermore, the genetic correlations between spring and autumn differed significantly from unity for almost all milk production traits. A genome-wide association study for genotype by season interaction identified chromosomal regions on BTA3, BTA14, BTA20, and BTA25 that showed genotype by season interaction effects, including a region containing DGAT1, which showed interaction effects for fat content and protein content.

[Comparison of planting modes of Dendrobium huoshanense and analysis of advantages of simulated cultivation].

Dendrobium huoshanense is a precious medicinal plant belonging to Dendrobium of Orchidaceae. It is a special medicinal material and extremely scarce in Huoshan county, Anhui province. At present, D. huoshanense has been greatly protected, which also makes it possible to industrialize relying on tissue culture and artificial cultivation technology. Three main planting methods were utilized for cultivating D. huoshanense including facility cultivation, under forest cultivation and simulative habitat cultivation. Firstly, the three cultivation modes and technical characteristics of D. huoshanense were compared and analyzed, and it was found that the ecological environment of D. huoshanense cultivated in the simulated environment was closer to that of wild D. huoshanense. Secondly, based on comparing the characters and quality of three cultivation modes, the results showed that the shape of D. huoshanense cultivated in simulated environment was more similar to that of "grasshopper thigh" recorded in Bencao Jing Jizhu, and its quality was better than that of facilities and under forest cultivation. The comprehensive benefit comparison of three modes showed that the simulated cultivation had high income, the lowest input-output ratio and significant economic benefit. The quality of cultivated D. huoshanense was further evaluated from four aspects of "excellent environment" "excellent shape" "high quality" "excellent effect", which summarized the comprehensive advantages of simulative habitat cultivation of D. huoshanense as follows: the original habitat and site environment of simulated wild D. huoshanense, the closer shape to the wild, the more content of main medicinal components, and higher economic benefit and better efficacy. The quality of D. huoshanense was improved by the use of simulative habitat cultivation, which has practical significance to guide its large-scale cultivation.

Phenotypic and genetic effects of pregnancy on milk production traits in Holstein-Friesian cattle.

Pregnancy is a prerequisite for the initiation of lactation and for maintaining the milk production cycle. Pregnancy affects milk production and therefore should be accounted for in the genetic evaluation. Furthermore, there might be genetic differences in pregnancy effects on milk composition. The objective of this study was to estimate phenotypic and genetic effects of pregnancy on milk production traits. For this purpose, test-day records and conception dates of 1,359 first-parity Holstein-Friesian cows were analyzed. Significant effects of pregnancy on all milk production traits were detected except somatic cell score (e.g., the cumulative effects of pregnancy on milk yield were -247 kg). The pregnancy effects on milk yield, lactose yield, protein yield, fat yield, and fat content were small during early gestation (<150 d) and substantially increased in late gestation. The effects of pregnancy on milk protein yield were relatively stronger than those on fat yield. The effects of pregnancy on milk production traits differed for DGAT1 genotypes. Milk yield, lactose yield, protein yield, and fat yield of DGAT1 AA cows were more affected by pregnancy than that of DGAT1 KK cows (e.g., the cumulative effects of pregnancy on milk yield were negligible for DGAT1 KK cows and were -443 kg for DGAT1 AA cows). These results suggest that DGAT1 KK cows may be more suitable for shortening or omitting the dry period than DGAT1 AA cows.

Genome-wide association study for genotype by lactation stage interaction of milk production traits in dairy cattle.

Substantial evidence demonstrates that the genetic background of milk production traits changes during lactation. However, most GWAS for milk production traits assume that genetic effects are constant during lactation and therefore might miss those quantitative trait loci (QTL) whose effects change during lactation. The GWAS for genotype by lactation stage interaction are aimed at explicitly detecting the QTL whose effects change during lactation. The purpose of this study was to perform GWAS for genotype by lactation stage interaction for milk yield, lactose yield, lactose content, fat yield, fat content, protein yield, and somatic cell score to detect QTL with changing effects during lactation. For this study, 19,286 test-day records of 1,800 first-parity Dutch Holstein cows were available and cows were genotyped using a 50K SNP panel. A total of 7 genomic regions with effects that change during lactation were detected in the GWAS for genotype by lactation stage interaction. Two regions on Bos taurus autosome (BTA)14 and BTA19 were also significant based on a GWAS that assumed constant genetic effects during lactation. Five regions on BTA4, BTA10, BTA11, BTA16, and BTA23 were only significant in the GWAS for genotype by lactation stage interaction. The biological mechanisms that cause these changes in genetic effects are still unknown, but negative energy balance and effects of pregnancy may play a role. These findings increase our understanding of the genetic background of lactation and may contribute to the development of better management indicators based on milk composition.

Application of 3D reconstruction for midline glossectomy in OSA patients.

OBJECTIVE: To explore the application of three-dimensional (3D) reconstruction technology for midline glossectomy in patients with obstructive sleep apnea (OSA). METHODS: Fifteen patients with OSA were included in this study. Each of them received computed tomography angiography (CTA) examination of lingual arteries in the resting tongue position and fully extended tongue position respectively. The two-dimensional CTA images were converted to 3D models using 3D reconstruction technology. We simulated the midline glossectomy in different tongue positions with a safe margin of 3 mm. The differences in the distances between bilateral lingual arteries, the depths of the lingual arteries and the surgical resectable volumes of the tongue were compared between different tongue positions in 3D models. RESULTS: The depths of the lingual arteries, the distances between bilateral lingual arteries based on three measuring sections and the surgical resectable volumes of the tongue in the fully extended tongue position were significantly smaller than those in the resting tongue position (P < 0.01 or 0.05). CONCLUSION: The 3D reconstruction technology can show the course of lingual artery stereoscopically and visually, and can be more beneficial to guide surgery than two-dimensional examination. Lingual artery examination in the fully extended tongue position has higher specificity in displaying intraoperative actual situation.

MiR-130b increases fibrosis of HMC cells by regulating the TGF-ß1 pathway in diabetic nephropathy.

Basement membrane thickening, glomerular hypertrophy, and deposition of multiple extracellular matrix characterize the pathological basis of diabetic nephropathy (DN), a condition which ultimately leads to glomerular and renal interstitial fibrosis. Here, we identified a novel microRNA, miR-130b, and investigated its role and therapeutic efficacy in alleviating DN. Introduction of miR-130b dramatically increased cell growth and fibrosis in DN cells. We found that transforming growth factor (TGF)-ß1 was a functional target of miR-130b in human glomerular mesangial cells (HMCs) and overexpression of miR-130b increased expressions of the downstream signaling molecules of TGF-ß1, t-Smad2/3, p-Smad2/3, and SMAD4. An ectopic application of miR-130b increased messenger RNA and protein expressions of collagen type I (colI), colIV, and fibronectin, whose expression levels were correlated with the expression of miR-130b. Taken together, the findings of this study reveal that miR-130b in HMC cells plays an important role in fibrosis regulation and may thus be involved with the pathogenesis of DN. Therefore, miR-130b may serve as a novel therapeutic target for the prevention and the treatment of DN.

Genome-wide association studies for genetic effects that change during lactation in dairy cattle.

Genetic effects on milk production traits in dairy cattle might change during lactation. However, most genome-wide association studies (GWAS) for milk production traits assume that genetic effects are constant during lactation. This assumption might lead to missing these quantitative trait loci (QTL) whose effects change during lactation. This study aimed to screen the whole genome specifically for QTL whose effects change during lactation. For this purpose, 4 different GWAS approaches were performed using test-day milk protein content records: (1) separate GWAS for specific lactation stages, (2) GWAS for estimated Wilmink lactation curve parameters, (3) a GWAS using a repeatability model where SNP effects are assumed constant during lactation, and (4) a GWAS for genotype by lactation stage interaction using a repeatability model and accounting for changing genetic effects during lactation. Separate GWAS for specific lactation stages suggested that the detection power greatly differs between lactation stages and that genetic effects of some QTL change during lactation. The GWAS for estimated Wilmink lactation curve parameters detected many chromosomal regions for Wilmink parameter a (protein content level), whereas 2 regions for Wilmink parameter b (decrease in protein content toward nadir) and no regions for Wilmink parameter c (increase in protein content after nadir) were detected. Twenty chromosomal regions were detected with effects on milk protein content; however, there was no evidence that their effects changed during lactation. For 5 chromosomal regions located on chromosomes 3, 9, 10, 14, and 27, significant evidence was observed for a genotype by lactation stage interaction and thus their effects on milk protein content changed during lactation. Three of these 5 regions were only identified using a GWAS for genotype by lactation stage interaction. Our study demonstrated that GWAS for genotype by lactation stage interaction offers new possibilities to identify QTL involved in milk protein content. The performed approaches can be applied to other milk production traits. Identification of QTL whose genetic effects change during lactation will help elucidate the genetic and biological background of milk production.

Dual silencing of EGFR and HER2 enhances the sensitivity of gastric cancer cells to gefitinib.

Gefitinib exhibits very limited efficacy in gastric cancer (GC). Indeed, the limited clinical results obtained with gefitinib alone justify investigation of additional therapeutic strategies. Here, we demonstrate the importance of EGFR and HER2 in GC malignancy using RNA interference (RNAi). Additionally, we explored the ability of RNAi targeting EGFR and HER2 to enhance the sensitivity of GC cells to gefitinib. Specific small interfering RNAs (siRNAs) significantly inhibited mRNA and protein expression of target genes. EGFR-specific siRNA, EGFR/HER2 siRNAs, and gefitinib inhibited growth and induced apoptosis in GC cell lines in a dose-dependent manner. In contrast, resistance to HER2-siRNA-induced growth inhibition and apoptosis was linked to compensatory activation of EGFR. Moreover, gefitinib dramatically reduced p-EGFR and p-HER2 levels in the cell lines tested, and sensitivity to gefitinib was enhanced through dual silencing of EGFR and HER2 via suppression of AKT and ERK activation. These findings are in agreement with the profound inhibitory effect of gefitinib on activation of both EGFR and HER2. Overall, EGFR/HER2 knockdown by siRNAs further decreased the growth of GC cells treated with gefitinib alone, confirming that single-agent drug targeting does not achieve a maximal biological effect. The combination of gefitinib with EGFR/HER2 siRNAs should be further investigated as a new strategy for the treatment of GC and other EGFR/HER2-dependent cancers.

Freeze-dried and irradiated allograft bone combined with fresh autologous coagula promotes angiogenesis in an ectopic bone allograft implantation model.

BACKGROUND: Freeze-dried and irradiated allograft bone (FIAB) is more easily impacted than fresh-frozen allograft bone (FAB), but has weaker incorporation efficiency. We combined FIAB with fresh autologous coagula to enhance donor-host incorporation after impaction during hip revision. METHODS: Thirty adult male Sprague-Dawley (SD) rats were sacrificed for bone allograft harvesting, and nine male rats were subjected to ectopic bone allograft implantation. For each rat, the container on the left (study) side was filled with freeze-dried allograft bone powder and fresh autologous blood coagula, whereas the right (control) side was filled with freeze-dried allograft bone powder and physiological saline. The extent of angiogenesis (VEGFα) was investigated at postoperative weeks 1, 4, and 8. The deformability of the material was evaluated by performing a confined-impaction mechanical test. RESULTS: At postoperative weeks 4 and 8, angiogenesis within FIAB on the left side was more pronounced than that on the right side. At postoperative week 1, the left side showed significantly higher VEGFα expression than that on the right side. The delta ratios of compression of the allografts were found to be influenced by bone height and impaction frequency, but not by stiffness or elastic modulus (EM). CONCLUSION: Supplementation with fresh autologous coagula promoted angiogenesis within the FIABs. Moreover, FIABs were equivalent to FABs in terms of deformability.

Racial Disparities in Accessing Care along the Continuum of Cancer Genetic Service Delivery.

BACKGROUND: Public health calls to ensure equity in genomics and precision medicine necessitate a closer examination of how these efforts might differentially affect access to genetic services across demographic subgroups. This study set out to examine racial/ethnic disparities along the cancer genetic service delivery continuum. METHODS: Retrospective data are drawn from 15 clinical sites across 6 U.S. States. Individuals who screened at-risk for hereditary cancer were: (i) referred/scheduled to see a genetic counselor (referral workflow), or (ii) offered genetic testing at the point-of-care (POC testing workflow). Logistic regression analyses evaluated the associations between race/ethnicity and several outcomes including appointment scheduling, genetic counseling, and genetic testing, controlling for demographics, clinical factors, and county-level covariates. RESULTS: A total of 14,527 patients were identified at-risk. Genetic testing uptake was significantly higher at POC sites than referral sites (34% POC vs. 11% referral, P < 0.001). Race/ethnicity was significantly associated with testing uptake among all sites, with non-Hispanic Blacks having lower odds of testing compared with non-Hispanic Whites [aOR = 0.84; 95% confidence interval (CI), 0.71-1.00; P = 0.049]. Moreover, this disparity was observed at referral sites, but not POC sites. Among patients scheduled, non-Hispanic Blacks had lower odds of counseling (aOR = 0.28; 95% CI, 0.17-0.47; P < 0.001). CONCLUSIONS: Findings suggest that factors influencing genetic counseling show rates may be driving disparities in genetic testing. IMPACT: Strategies to reduce barriers to seeing a genetic counselor, including modifications to clinical workflow, may help mitigate racial/ethnic disparities in genetic testing.

Output-Feedback Consensus Maneuvering of Uncertain MIMO Strict-Feedback Multiagent Systems Based on a High-Order Neural Observer.

In this article, a distributed output-feedback consensus maneuvering problem is investigated for a class of uncertain multiagent systems with multi-input and multi-output (MIMO) strict-feedback dynamics. The followers are subject to immeasurable states and external disturbances. A distributed neural observer-based adaptive control method is designed for consensus maneuvering of uncertain MIMO multiagent systems. The method is based on a modular structure, resulting in the separation of three modules: 1) a variable update law for the parameterized path; 2) a high-order neural observer; and 3) an output-feedback consensus maneuvering control law. The proposed distributed neural observer-based adaptive control method ensures that all followers agree on a common motion guided by a desired parameterized path, and the proposed method evades adopting the adaptive backstepping or dynamic surface control design by reformulating the dynamics of agents, thereby reducing the complexity of the control structure. Combined with the cascade system analysis and interconnection system analysis, the input-to-state stability of the consensus maneuvering closed loop is established in the Lyapunov sense. A simulation example is presented to demonstrate the performance of the proposed distributed neural observer-based adaptive control method for output-feedback consensus maneuvering.