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Human induced pluripotent stem cell-derived sensory neuron (iPSC-dSN) models are a valuable resource for the study of neurotoxicity but are affected by poor replicability and reproducibility, often due to a lack of optimization. Here, we identify experimental factors related to culture conditions that substantially impact cellular drug response in vitro and determine optimal conditions for improved replicability and reproducibility. Treatment duration and cell seeding density were both found to be significant factors, while cell line differences also contributed to variation. A replicable dose–response in viability was demonstrated after 48-h exposure to docetaxel or paclitaxel. Additionally, a replicable dose-dependent reduction in neurite outgrowth was demonstrated, demonstrating the applicability of the model for the examination of additional phenotypes. Overall, we have established an optimized iPSC-dSN model for the study of taxane-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (LncRNAs) have been implicated as critical regulators of cancer tumorigenesis and progression. However, their functions and molecular mechanisms in colorectal cancer (CRC) still remain to be further elucidated. Methods: LINC00460 was identified by differential analysis between human CRC and normal tissues and verified by in situ hybridization (ISH) and qRT-PCR. We investigated the biological functions of LINC00460 in CRC by in vitro and in vivo experiments. We predicted the mechanism and downstream functional molecules of LINC00460 by bioinformatics analysis, and confirmed them by dual luciferase reporter gene assay, RNA immunoprecipitation (RIP), RNA pull-down, etc. Results: LINC00460 was found to be significantly overexpressed in CRC and associated with poor prognosis. Overexpression of LINC00460 promoted CRC cell immune escape and remodeled a suppressive tumor immune microenvironment, thereby promoting CRC proliferation and metastasis. Mechanistic studies showed that LINC00460 served as a molecular sponge for miR-186-3p, and then promoted the expressions of MYC, CD47 and PD-L1 to facilitate CRC cell immune escape. We also demonstrated that MYC upregulated LINC00460 expression at the transcriptional level and formed a positive feedback loop. Conclusions: The LINC00460/miR-186-3p/MYC feedback loop promotes CRC cell immune escape and subsequently facilitates CRC proliferation and metastasis. Our findings provide novel insight into LINC00460 as a CRC immune regulator, and provide a potential therapeutic target for CRC patients. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies shed light on the potential role of secure parental attachment in mitigating the effects of child sexual abuse (CSA) on the survivors' long-term psychological distress. However, few studies have explored both approach and avoidance coping strategies as mediators of the link between parental attachment and psychological distress in a nonclinical sample. The purpose of this study was to examine the respective mediating effects of approach coping and avoidance coping on the relationship between perceived parental attachment, CSA severity, and psychological distress. Method: Our sample included 427 adults with a history of CSA. Participants were recruited from various social media websites (e.g., Facebook, Craigslist, discussion board, university announcement board). We conducted a mediation analysis with bootstrapping. Results: We found that parental attachment significantly predicted CSA survivors' psychological distress. Additionally, both approach coping and avoidance coping mediated the effect of perceived parental attachment on psychological distress. CSA severity was found to be a nonsignificant predictor of psychological distress. Conclusion: These findings may help develop interventions that enhance CSA survivors' effective copings strategies to ultimately reduce psychological distress. [ABSTRACT FROM AUTHOR]

This paper investigates the thermo-elastoplastic sliding frictional contact and wear problem of a functionally graded material (FGM) coated homogeneous half-plane subjected to a rigid cylindrical punch. The coating has arbitrarily varying material properties including elastic modulus, Poisson's ratio, thermal expansion coefficient, wear coefficient, etc. The graded layer is modeled using a thermo-elastoplastic constitutive model of FGM to evaluate the contact pressure, in-plane stress, and temperature field. A modified Archard model is used to characterize the wear behavior of FGM coating, and the influence of wear on the stress and strain behavior is considered. The constitutive model and wear model are implemented in the finite element method (FEM) to study the thermo-elastoplastic sliding frictional contact and wear behavior of FGM coating. After the validation of the numerical approach, the effects of plasticity, wear, cycle number, gradient index, and gradient form are discussed. Simulation results show that changing the gradient form and gradient index can prevent contact damage and reduce frictional wear. [ABSTRACT FROM AUTHOR]

A resource allocation strategy for the low earth orbit (LEO) satellite Internet based on terminal traffic prediction was proposed to address the problems of blind coverage spots in ground network and the low resource utilization of satellite network. An improved LSTM-ARIMA algorithm was proposed with real datasets by the strategy to accurately predict the data traffic generated in the ground area over a certain period of time in the future. Two communication models, differentiated data transmission and task offloading were constructed through Stackelberg games, taking into the data processing latency and energy consumption account. By solving the Nash equilibrium, the optimal ratio for users to transmit data or unload tasks through the LEO satellite Internet, as well as the optimal pricing for satellites to provide network services, were obtained. Extensive simulation results verify that the proposed strategy can increase the revenue by approximately 40% in data transmission services and 50% in task offloading services. [ABSTRACT FROM AUTHOR]

Soil moisture monitoring is a significant aspect of environmental and agricultural studies, and Global Navigation Satellite System Interferometric Reflectometry (GNSS-IR) has emerged as a promising technology for this purpose. Traditionally, GNSS-IR is mainly employed for bare soil experiments, and the effectiveness of bare soil retrieval algorithm will be reduced due to the influence of vegetation and meteorological, etc. To address the limitations of the bare-soil retrieval algorithm, a multi-feature soil moisture retrieval approach was proposed. This approach integrated multiple factors including GNSS signals, cumulative precipitation, effective reflection height, and Normalized Microwave Reflection Index (NMRI), and then multi-layer perceptron (MLP) was employed to build retrieval models. In this study, measurements from the Plate Boundary Observatory (PBO) H2O networks and a self-built site in Henan, China were used for experiments and validation, and the geographical environment of stations are various. The experimental results demonstrated several key findings: (1) The delay phase is not sensitive to the variations in soil moisture before and after precipitation, but by integrating the cumulative precipitation data, the accuracy of the model could be improved. (2) The introduction of NMRI and reflection height can help remove the influence of vegetation and penetration depth. (3) Compared between three retrieval models (i.e., unary linear regression, multiple linear regression, and MLP), the decrease in the mean absolute error (MAE) of MLP is up to 96% most and the mean coefficient of determination (R2) is all above 0.98. Meanwhile, this study proved that the proposed method could fully utilize satellite reflection signals from all directions and better reflect the fluctuation of soil moisture. [ABSTRACT FROM AUTHOR]

Recurrence posed an important challenge to pulmonary tuberculosis (PTB) control in China. The prospective study aimed to identify potential risk factors and to explore the value of QuantiFERON-TB Gold Plus (QFT-Plus) in identifying at-risk individuals with treated prior PTB history. All eligible individuals aged ≥18 years who had been diagnosed with PTB before 2016 in Zhongmu County, where with an average level of TB prevalence in China, were included and received baseline survey including chest radiography, QuantiFERON-TB Gold In-Tube (QFT-GIT) and QFT-Plus, then PTB recurrence was tracked through a 2-year follow-up. Half of 1068 (52.34%, 559/1068) included eligible participants were QFT-Plus positive at baseline and 21 of them recurred active TB in 2-year follow-up. Individuals aged ≥ 60 years, who had a recent history of TB and smokers were associated with increased risk of TB recurrence with an adjusted odds ratio (aOR) of 3.97 (95% confidence interval (CI): 1.29–12.24), 7.71 (95% CI: 1.74–34.25) and 4.56 (95% CI: 1.62–12.83), respectively. Compared to QFT-Plus negatives, those who were TB2+/TB1- (aOR = 15.34) exhibited stronger association with the risk of TB recurrence than those who were TB1+/TB2+ (aOR = 6.06). A dose response relationship was also found between the risk of TB recurrence with the baseline level of TB2-TB1 (p for trend < 0.001). High burden of TB infection and high risk of PTB recurrence were observed in the study population. Those with recent onset of prior TB, elderly smokers and QFT-Plus positives especially with TB2 single positive deserved further attention in active TB surveillance. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab is a beneficial therapy in several advanced cancer types. Predictive biomarkers to better understand which patients are destined to benefit or experience toxicity are needed. Associations between bevacizumab induced hypertension and survival have been reported but with conflicting conclusions. Methods: We performed post-hoc analyses to evaluate the association in 3124 patients from two phase III adjuvant breast cancer trials, E5103 and BEATRICE. Differences in invasive disease-free survival (IDFS) and overall survival (OS) between patients with hypertension and those without were compared. Hypertension was defined as systolic blood pressure (SBP) ≥ 160 mmHg (n = 346) and SBP ≥ 180 mmHg (hypertensive crisis) (n = 69). Genomic analyses were performed to evaluate germline genetic predictors for the hypertensive crisis. Results: Hypertensive crisis was significantly associated with superior IDFS (p = 0.015) and OS (p = 0.042), but only IDFS (p = 0.029; HR = 0.28) remained significant after correction for prognostic factors. SBP ≥ 160 mmHg was not associated with either IDFS or OS. A common single-nucleotide polymorphism, rs6486785, was significantly associated with hypertensive crisis (p = 8.4 × 10−9; OR = 5.2). Conclusion: Bevacizumab-induced hypertensive crisis is associated with superior outcomes and rs6486785 predicted an increased risk of this key toxicity. [ABSTRACT FROM AUTHOR]

Purpose: Child sexual abuse (CSA) has short-term and long-term effects on survivors, but distress after the abuse varies widely and not all survivors show a significant degree of distress. Factors contributing to the variations of CSA outcomes need to be further investigated. The present study examines the moderating role of childhood attachment in the relationship between the experience of CSA and adult attachment, psychological distress, and self-esteem. Methods: Seven hundred and sixty-seven adults participated in this study, of which 427 (55.67%) reported a history of CSA. Participants were recruited from various social media websites (e.g., Facebook, Craigslist, discussion board, university announcement board). To examine the moderating role of childhood attachment between the experience of CSA and adult attachment, we conducted path analysis. Results: Childhood attachment significantly predicted adult attachment, psychological distress, and self-esteem in adulthood and moderated the relation between CSA and anxious adult attachment; CSA survivors with more secure childhood attachment were less likely to develop anxious attachment in adulthood. Additionally, CSA survivors reported less secure adult attachment, more psychological distress, and lower self-esteem than did individuals without a history of CSA. Furthermore, secure childhood attachment was significantly associated with secure adult attachment, lower levels of psychological distress, and higher levels of self-esteem. Conclusions: The results suggested that secure childhood attachment at least partially protected against negative long-term effects of CSA and fostered healthier intrapersonal and interpersonal adjustment in CSA survivors. [ABSTRACT FROM AUTHOR]

In recent years, smartphones have emerged as the primary terminal for navigation and location services among mass users, owing to their universality, portability, and affordability. However, the highly integrated antenna design within smartphones inevitably introduces interference from internal signal sources, leading to a misalignment between the antenna phase center (APC) and the antenna geometric center. Accurately determining a smartphone's APC can mitigate system errors and enhance positioning accuracy, thereby meeting the increasing demand for precise and reliable user positioning. This paper delves into a detailed analysis of the generation of Global Navigation Satellite System (GNSS) receiver antenna phase center errors and proposes a method for correcting the receiver antenna phase center. Subsequently, a smartphone positioning experiment was conducted by placing the smartphone on an observation column with known coordinates. The collected observations were processed in static relative positioning mode, referencing observations from geodetic-grade equipment, and the accuracy of the static relative positioning fixed solution was evaluated. Following weighted estimation, we determined the antenna phase center of the Xiaomi Mi8 and corrected the APC. A comparison of the positioning results of the Xiaomi Mi8 before and after APC correction revealed minimal impact on the standard deviations (STDs) but significant influence on the root mean square errors (RMSEs). Specifically, the RMSEs in the E/N/U direction were reduced by 59.6%, 58.5%, and 42.0%, respectively, after APC correction compared to before correction. Furthermore, the integer ambiguity fixing rate slightly improved after the APC correction. In conclusion, the determination of a smartphone's APC can effectively reduce system errors in the plane direction of GNSS positioning, thereby enhancing smartphone positioning accuracy. This research holds significant value for advancing high-precision positioning studies related to smartphones. [ABSTRACT FROM AUTHOR]

3,4-Bis(3-nitrofurazan-4-yl)furoxan (DNTF) is a novel energetic material with an excellent performance and has attracted considerable attention. Motivated by recent theories and experiments, we had carried out experimental and theoretical studies on the high-pressure responses of vibrational characteristics, in conjunction with structural and electronic characteristics. It is found that all observed infrared spectra peaks seem to shift towards higher frequencies. And the peaks attributed to N–Oc (coordinated oxygen atom) stretching vibrations become broader due to the decrease of lattice constants and the free region of DNTF crystals with the increase of pressure, where the a-direction is more sensitive to pressure. In addition, the non-covalent interaction between adjacent DNTF molecules in the same layer changes from the van der Waals interaction to the steric effect with the increase of pressure, and that between layers also changes from the van der Waals interaction to the π–π stacking interaction. More importantly, these results highlight that the increase of pressure may lead to the stability decrease and impact the sensitivity increase of DNTF. This study can deepen the understanding of the energetic material DNTF under high pressure and is of great significance for blasting and detonation applications of DNTF. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid carcinoma (PTC) is the most common malignant endocrine tumour, and its incidence and prevalence are increasing considerably. Cellular heterogeneity in the tumour microenvironment is important for PTC prognosis. Spatial transcriptomics is a powerful technique for cellular heterogeneity study. Methods: In conjunction with a clinical pathologist identification method, spatial transcriptomics was employed to characterise the spatial location and RNA profiles of PTC‐associated cells within the tissue sections. The spatial RNA‐clinical signature genes for each cell type were extracted and applied to outlining the distribution regions of specific cells on the entire section. The cellular heterogeneity of each cell type was further revealed by ContourPlot analysis, monocle analysis, trajectory analysis, ligand–receptor analysis and Gene Ontology enrichment analysis. Results: The spatial distribution region of tumour cells, typical and atypical follicular cells (FCs and AFCs) and immune cells were accurately and comprehensively identified in all five PTC tissue sections. AFCs were identified as a transitional state between FCs and tumour cells, exhibiting a higher resemblance to the latter. Three tumour foci were shared among all patients out of the 13 observed. Notably, tumour foci No. 2 displayed elevated expression levels of genes associated with lower relapse‐free survival in PTC patients. We discovered key ligand–receptor interactions, including LAMB3–ITGA2, FN1–ITGA3 and FN1–SDC4, involved in the transition of PTC cells from FCs to AFCs and eventually to tumour cells. High expression of these patterns correlated with reduced relapse‐free survival. In the tumour immune microenvironment, reduced interaction between myeloid‐derived TGFB1 and TGFBR1 in tumour focus No. 2 contributed to tumourigenesis and increased heterogeneity. The spatial RNA‐clinical analysis method developed here revealed prognosis‐associated cellular heterogeneity in the PTC microenvironment. Conclusions: The occurrence of tumour foci No. 2 and three enhanced ligand–receptor interactions in the AFC area/tumour foci reduced the relapse‐free survival of PTC patients, potentially leading to improved prognostic strategies and targeted therapies for PTC patients. [ABSTRACT FROM AUTHOR]

Purpose: Consensus molecular subtypes (CMS) are mainly used for biological interpretability and clinical stratification of colorectal cancer (CRC) in primary tumors (PT) but few in metastases. The heterogeneity of CMS distribution in metastases and the concordance of CMS between PT and metastases still lack sufficient study. We used CMS to classify CRC metastases and combine it with histopathological analysis to explore differences between PT and distant metastases. Patients and Methods: We obtained gene expression profiles for 942 PT samples from TCGA database (n=376) and GEO database (n=566), as well as 442 metastasis samples from GEO database. Among these, 765 PT samples and 442 metastasis samples were confidently identified with CMS using the "CMS classifier" and enrolled for analysis. Clinicopathological manifestation and CMS classification of CRC metastases were assessed with data from GEO, TCGA, and cBioPortal. Overall, 105 PT-metastasis pairs were extracted from 10 GEO datasets to assess CMS concordance. Tumor microenvironment (TME) features between PT and metastases were analyzed by immune-stromal infiltration with ESTIMATE and xCell algorithms. Finally, TME features were validated with multiplex immunohistochemistry in 27 PT-metastasis pairs we retrospectively collected. Results: Up to 64% of CRC metastases exhibited concordant CMS groups with matched PT, and the TME of metastases was similar to that of PT. For most common distant metastases, liver metastases were predominantly CMS2 and lung and peritoneal metastases were mainly CMS4, highlighting "seed" of tumor cells of different CMS groups had a preference for metastasis to "soil" of specific organs. Compared with PT, cancer-associated fibroblasts (CAF) reduced in liver metastases, CD4+T cells and M2-like macrophages increased in lung metastases, and M2-like macrophages and CAF increased in peritoneal metastases. Conclusion: Our findings underscore the importance of CMS-guided specific organ monitoring and treatment post-primary tumor surgery for patients. Differences in immune-stromal infiltration among different metastases provide targeted therapeutic opportunities for metastatic CRC. [ABSTRACT FROM AUTHOR]

Given the widespread misinformation problem in societies across the globe, scholars aiming to combat misinformation wish to change verification behaviors at the individual level. To map what is known about media users' verification behaviors, this study reviewed 52 articles and analyzed how verification research has progressed so far. The results indicate that verification research has been conducted since 2000 but has increased considerably in recent years. However, a clear definition and a standard measure of verification behaviors were missing. Theories and methodologies from different disciplines have been adopted to investigate verification behaviors. The examined variables are diverse, but the overall understanding of the findings is fragmented. Interestingly, the COVID-19 pandemic boosted the number of studies on media users' verification behaviors and brought changes to the direction of the research. This review calls for a better conceptualization and validated measures of verification behaviors and examinations of verification in more diverse contexts. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal tract (GIT) nematodes prefer to live in the intestines of wild animals, causing damage and even death, and posing a zoonotic risk. The polyparasitism of GIT nematodes results in the complex dynamics of the nematode communities that occur naturally in wild animals. However, the nematode community in captive wild animals is poorly understood. Methods: We combined microscopic examination and amplicon sequencing for community diversity. Results: We characterized GIT nematode assemblages to one order, one family, four genera, and ten species, in 512 fecal samples of 121 species from captive wild animals in southern China. The positive rate of GIT nematodes was 20.7% (106/512), including 42.3% (11/26) in reptiles, 26.5% (39/147) in herbivores, 25.0% (25/100) in non-human primates, 20.0% (5/25) in omnivores, 12.2% (9/74) in carnivores, and 12.1% (17/140) in avians. The dominant nematodes were Haemonchus contortus in herbivores and Trichuris species in primates. The nematode communities of arboreal primates differed from their terrestrial counterparts, reflecting both host phylogeny and ecological constraints. Soil-transmitted Strongyloides species were widespread throughout the herbivore, primate, avian, and carnivore communities, and tended to infect omnivorous primates and terrestrial herbivores. In addition, new Trichuris and Heterakis species were found in the nematode communities of captive porcupines and peafowls. Conclusion: This study highlights the variation in the composition of the GIT nematode community and strengthens the attention to the harms induced by zoonotic nematodes and co-infective nematodes with low species richness. [ABSTRACT FROM AUTHOR]

A joint user association and dynamic resource allocation algorithm was proposed for the slicing scenario of ultra dense low earth orbit-radio access network (LEO-RAN) in order to address the efficient utilization of resources of the integrated terrestrial-satellite network for 6G .Considering the constraints of the minimum rate, maximum delay and resource proportion of different slices, a joint optimization problem of user association and resource allocation was established to maximize the weighted sum of the SE and the differentiated SLA of different slices as the optimization objective. A network slicing algorithm based on multi-agent deep deterministic policy gradient (MADDPG) was proposed to determine the proportion of slicing resources, a Lagrange dual based user association algorithm was proposed to determine the optimal user association policy and the resources were allocated to users by using the round-robin scheduling mechanism. The simulation results show that the proposed algorithm can effectively improve SE while satisfying the differentiated SLA of different slices. Compared with MADDPG-RA, MATD3-LG, MATD3-RA, MASAC-LG and MASAC-RA algorithms, the system utility of the proposed algorithm is improved by 2.0%, 2.3%, 5.7%, 8.7% and 9.4%, respectively. [ABSTRACT FROM AUTHOR]

Pangolins are susceptible to a variety of gastrointestinal nematodes due to their burrowing lifestyle and feeding habits, and few parasitic nematodes have been reported. Here, a Chinese pangolin with old wounds on its leg and tail was rescued from the Heyuan City, Guangdong Province. The cox1 and SSU rRNA of the worms from the intestine of the Chinese pangolin had the highest sequence identity of 89.58% and 97.95% to the species in the infraorder Spiruromorpha. The complete mitogenome of the worm was further assembled by next-generation sequencing, with a size of 13,708 bp and a GC content of 25.6%. The worm mitogenome had the highest sequence identity of 78.56% to that of Spirocerca lupi, sharing the same gene arrangement with S. lupi and some species in other families under Spiruromorpha. However, the mitogenome between the worm and S. lupi showed differences in codon usage of PCGs, sequences of NCR, and tRNA secondary structures. Phylogenetic analysis showed that the worm mitogenome was clustered with S. lupi in the family Thelaziidae to form a separate branch. However, it is still difficult to identify the worm in the family Thelaziidae because the species in the family Thelaziidae are confused, specifically S. lupi and Thelazia callipaeda in the family Thelaziidae were separated and grouped with species from other families. Thus, the parasitic nematode from the Chinese pangolin may be a novel species in Spiruromorpha and closely related to S. lupi. This study enriches the data on gastrointestinal nematodes in the Chinese pangolin. [ABSTRACT FROM AUTHOR]

The full design of a liquid neutron reflectometer for China spallation neutron source is reported. The horizontal sample geometry enables studies on both solid and liquid samples. A neutron beam with a wavelength range from 1 to 10 Å and neutron flux intensity of 4 × 107 n/cm2/s was optimized for the classical specular reflection. A multi-blade detector with high detection efficiency and a high neutron counting rate was used to ensure the performance of neutron detection. Data acquisition and reduction routines were demonstrated to confirm the reliability of the measurements. The design and algorithms developed in this study pave the way for the future construction of liquid reflectometry for high-performance neutron scattering measurements. [ABSTRACT FROM AUTHOR]

Summary: This paper is concerned with the adaptive neural network event‐triggered control (ETC) problem for stochastic nonlinear systems with output constraint. The influence of stochastic disturbance inevitably exists in many practical systems, which leads to system instability. Meanwhile, a novel tan type barrier Lyapunov function (Tan‐BLF) structure is proposed to deal with the constraint requirements of stochastic systems. In the sense of probability, the output constraints will not be violated during the operation of the system. In addition, the ETC strategy is adopted to reduce the burden of communication. The asymptotic stability of the closed‐loop system is guaranteed without violating output constraints. Meanwhile, the tracking error converges to a small region of the origin. Two simulations results demonstrate the effectiveness of theoretical analysis. [ABSTRACT FROM AUTHOR]

The preparation methods for refining kraft pulp into dissolving pulp are generally limited by an aggressive chemical input and overlook the valorization of the xylan component. This work demonstrated an integrated process involving deep eutectic solvent (DES) pretreatment followed by mechanical refining and enzymatic hydrolysis (DME) for the preparation of the dissolving pulp and co-production of two xylo-oligosaccharides (XOSs). The technical feasibility of the DME process was assessed with typical bleached bamboo and poplar kraft pulp. It was shown that the employed aqueous alkaline DES consisting of choline hydroxide and urea (40% concentration) could initially purify cellulose while selectively extracting alkali-soluble XOSs by the unique bonding behavior of the DES. The resulting dissolving pulp showed considerably high cellulose contents of 94.3% and 91.1% for the bleached bamboo pulp and bleached poplar pulp, respectively. The overall cascade process significantly improved the cellulose reactivity and quality (α-cellulose > 90%, S10/S18 < 8%), which could meet the high criterion for commercial dissolving pulp while extracting 69.4% of the content of high-purity XOSs. When 100 g bleached pulp was subjected to this technology route, a high yield of over 80 g cellulose was obtained for both the substrates while simultaneously producing the alkaline and water-soluble XOSs (approximately 10 g). It was proposed that the strong hydrogen-bonding-accepting ability of the ChOH-urea DES system could purify cellulose through XOS selective solubilization while swelling cellulose to ease the subsequent mechanical fibrillation. Subsequently, the mechanically treated cellulose with enhanced accessibility to xylanase provided an additional technique for further cellulose purification through a facile enzymatic hydrolysis. Therefore, this proposed integrated technique could refine bleached kraft pulp into dissolving pulp with enhanced cellulose reactivity while co-producing high-purity XOS product streams. [ABSTRACT FROM AUTHOR]

Biochar always suffers from low porosity and/or poor surface functionality, which limit its performances. Among various surface engineering strategies, air oxidation favors both pore development and surface oxygenation for biochar. However, there is still a lack of systematic knowledge and critical perspective on air oxidation in surface engineering of biochar-based materials for various applications. Herein, this review analyzed the mechanisms of air oxidation, summarized the routes of air oxidation in surface engineering of biochar-based materials, investigated the impacts of controlling factors (including operation parameters and intrinsic biochar structure) on pore development and surface oxygenation during air oxidation, and discussed the performances of the resultant materials in pollution control, biomass catalytic conversion and energy storage. This review suggested that air oxidation could be conducted in oxidative torrefaction/pyrolysis, and applied as post-modification or pretreatment processes. Interestingly, air oxidation is efficient in enriching the heteroatoms in the heteroatom-doped biochar, and promoting the doping of metal species on biochar by enriching the anchor sites. This review also highlighted the future challenges concerning air oxidation in the surface engineering of biochar-based materials. Finally, this review was intended to attract broad attention and inspire new discoveries for promoting the application of air oxidation in surface engineering of biochar-based materials for various advanced applications. Highlights: • Air oxidation favors pore development and/or surface oxygenation for biochar. • Air oxidation can be conducted in oxidative torrefaction/pyrolysis, and applied as post-modification or pretreatment processes. • Mechanisms and controlling factors for air oxidation were analyzed, and future challenges were highlighted. [ABSTRACT FROM AUTHOR]

Room‐temperature sodium–sulfur batteries are potential candidate for sustainable large‐scale energy storage systems due to their high energy density and low cost. However, the shuttling effect of high‐order polysulfides (Na2Sn, 4 < n ≤ 8) usually leads to rapid capacity fading, while the reaction kinetics of low‐order polysulfides (Na2Sn, 1 ≤ n ≤ 4) are slow. In this work, microporous‐mesoporous carbon derived from mangosteen peels is reported as cathode materials for RT Na–S batteries. The designed micro‐mesoporous structure not only effectively suppresses the shuttling effect of sodium polysulfides (NaPS), but also has high electrical conductivity and porosity, which facilitates electron/ion diffusion. Oxygen functional groups on the surface provide high catalytic activity for efficient low‐order NaPS conversion. The obtained Na–S battery exhibits high reversible capacity with excellent long‐term cycle performance (526.1 mAh g−1 at 4 A g−1 after 1000 cycles) and outstanding rate performance (676.59 mAh g−1 at 16 A g−1). This work demonstrates a novel activation strategy of biomass‐derived carbons for high‐performance Na–S batteries. [ABSTRACT FROM AUTHOR]

The Global Navigation Satellite System Interferometric Reflectometry (GNSS-IR) technique provides a new remote sensing method that shows great potential for soil moisture detection and vegetation growth, as well as for climate research, water cycle management, and ecological environment monitoring. Considering that the land surface is always covered by vegetation, it is essential to take into account the impacts of vegetation growth when detecting soil moisture (SM). In this paper, based on the GNSS-IR technique, the SM was retrieved from multi-GNSS and multi-frequency data using a machine learning model, accounting for the impact of the vegetation moisture content (VMC). Both the signal-to-noise ratio (SNR) data that was used to retrieve SM and the multipath data that was used to eliminate the vegetation influence were collected from a standard geodetic GNSS station located in Nanjing, China. The normalized microwave reflectance index (NMRI) calculated by multipath data was mapped to a normalized difference vegetation index (NDVI), which was derived from Sentinel-2 data on the Google Earth Engine platform to estimate and eliminate the influence of VMC. Based on the characteristic parameters of amplitude and phase extracted from detrended SNR signals and NDVI derived from multipath data, three machine learning methods, including random forest (RF), multiple linear regression (MLR), and multivariate adaptive regression spline (MARS), were employed for data fusion. The results show that the vegetation effect can be well eliminated using the NMRI method. Comparing MLR and MARS, RF is more suitable for GNSS-IR SM inversion. Furthermore, the SM reversed from amplitude and phase fusion is better than only those from either amplitude fusion or phase fusion. The results prove the feasibility of the proposed method based on a multipath approach to characterize the vegetation effect, as well as the RF model to fuse multi-GNSS and multi-frequency data to retrieve SM with vegetation error-correcting. [ABSTRACT FROM AUTHOR]

Deep learning brought boosts to auto diabetic retinopathy (DR) diagnosis, thus, greatly helping ophthalmologists for early disease detection, which contributes to preventing disease deterioration that may eventually lead to blindness. It has been proved that convolutional neural network (CNN)‐aided lesion identifying or segmentation benefits auto DR screening. The key to fine‐grained lesion tasks mainly lies in: (1) extracting features being both sensitive to tiny lesions and robust against DR‐irrelevant interference, and (2) exploiting and re‐using encoded information to restore lesion locations under extremely imbalanced data distribution. To this end, we propose a CNN‐based DR diagnosis network with attention mechanism involved, termed lesion‐aware network, to better capture lesion information from imbalanced data. Specifically, we design the lesion‐aware module (LAM) to capture noise‐like lesion areas across deeper layers, and the feature‐preserve module (FPM) to assist shallow‐to‐deep feature fusion. Afterward, the proposed lesion‐aware network (LANet) is constructed by embedding the LAM and FPM into the CNN decoders for DR‐related information utilization. The proposed LANet is then further extended to a DR screening network by adding a classification layer. Through experiments on three public fundus datasets with pixel‐level annotations, our method outperforms the mainstream methods with an area under curve of 0.967 in DR screening, and increases the overall average precision by 7.6%, 2.1%, and 1.2% in lesion segmentation on three datasets. Besides, the ablation study validates the effectiveness of the proposed sub‐modules. [ABSTRACT FROM AUTHOR]

Background: This study explores and compares the influences of family communication patterns (conversation orientation and conformity orientation) on family discussion and preventive behaviors for older parents and their adult children in the context of the early COVID-19 outbreak. Methods: A total of 248 participants, including 117 parents and 131 adult children, participated in an online survey in February 2020. Participants reported family communication patterns, family discussions related to COVID-19, and their preventive behaviors. Results: Conversation orientation was positively associated with information sharing and scientific discussion for older parents and adult children. Our results revealed the differential influences of conformity orientation on older parents and adult children. Conformity orientation was positively associated with scientific discussion for older parents but was not significantly associated with any form of family discussion reported by adult children. There was a significant interaction effect of conversation orientation and conformity orientation on disputed communication within the family, suggesting that conflicts may arise in COVID-related discussions when parents and adult children value conversation and conformity. Scientific discussion was found to mediate the relationships between family communication patterns and preventive behaviors. The effects of scientific discussions were stronger for older parents than for adult children. Conclusions: Family communication patterns can be associated with preventive behaviors through different forms of family discussion about COVID-19. Conversation orientation is a strong facilitator for positive behavioral effects and scientific discussion is the most benign form of family health discussion. Health communication efforts should enhance the agency role of the family and motivate scientific discussion in health practices. [ABSTRACT FROM AUTHOR]

Background: Triple negative breast cancer (TNBC) represents a significant clinical challenge. Chemotherapy remains the mainstay for a large part of TNBC patients, whereas drug resistance and tumor recurrence frequently occur. It is in urgent need to identify novel molecular targets for TNBC and develop effective therapy against the aggressive disease. Methods: Immunohistochemistry was performed to examine the expression of HER3 in TNBC samples. Western blots were used to assess protein expression and activation. Cell proliferation and viability were determined by cell growth (MTS) assays. TCGA databases were analyzed to correlate HER3 mRNA expression with the clinical outcomes of TNBC patients. Specific shRNA was used to knockdown HER3 expression. IncuCyte system was utilized to monitor cell growth and migration. LIVE/DEAD Cell Imaging was to detect live and dead cells. HER3 recognition by our anti-HER3 monoclonal antibody (mAb) 4A7 was verified by ELISA, flow cytometry, and co-immunoprecipitation assays. Orthotopic tumor models were established in nude mice to determine the capability of TNBC cells forming tumors and to test if our mAb 4A7 could potentiate the antitumor activity of paclitaxel in vivo. Results: Elevated expression of HER3 was observed in approximately half of the TNBC specimens and cell lines tested. Analyses of TCGA databases found that the TNBC patients with high HER3 mRNA expression in the tumors showed significantly worse overall survival (OS) and relapse-free survival (RFS) than those with low HER3 expression. Specific knockdown of HER3 markedly inhibited TNBC cell proliferation and mammosphere formation in vitro and tumor growth in vivo. Our mAb 4A7 abrogated heregulin (a ligand for HER3), but not SDF-1 (a ligand for CXCR4)-induced enhancement of TNBC cell migration. Combinations of 4A7 and the EGFR-tyrosine kinase inhibitor (TKI) gefitinib dramatically decreased the levels of phosphorylated HER3, EGFR, Akt, and ERK1/2 in TNBC cells and potently induced growth inhibition and cell death. Moreover, 4A7 in combination with paclitaxel exerted significant antitumor activity against TNBC in vitro and in vivo. Conclusions: Our data demonstrate that increased HER3 is an effective therapeutic target for TNBC and our anti-HER3 mAb (4A7) may enhance the efficacy of gefitinib or paclitaxel in TNBC. [ABSTRACT FROM AUTHOR]

Background: Individuals in close contact with active pulmonary tuberculosis (TB) patients showed a high risk of recent infection and, once infected, higher risk of developing active TB in the following years post-exposure. But the peak time of active disease onset is unclear. This study aims to estimate post exposure TB incidence risk among close contacts to provide reference for clinical and public health strategies. Methods: We searched PubMed, Web of Science, and EMBASE for articles published until December 1, 2022. The incidence rates were quantitatively summarized by means of meta-analysis using the random-effect model. Results: Of the 5616 studies, 31 studies included in our analysis. For baseline close contacts results, the summarized prevalence of Mycobacterium tuberculosis (MTB) infection and active TB was found to be 46.30% (95% CI: 37.18%-55.41%) and 2.68% (95% CI: 2.02%-3.35%), respectively. During the follow-up, the 1-year, 2-year and 5-year cumulative incidence of TB in close contacts were 2.15% (95% CI: 1.51%-2.80%), 1.21% (95% CI: 0.93%-1.49%) and 1.11% (95% CI: 0.64%-1.58%), respectively. Individuals with a positive result of MTB infection testing at baseline showed significantly higher cumulative TB incidence as compared to those negatives (3.80% vs. 0.82%, p < 0.001). Conclusions: Individuals with close contact to active pulmonary TB patients are bearing significant risk of developing active TB, particularly within the first-year post-exposure. Population with recent infections should be an important priority for active case finding and preventive intervention worldwide. [ABSTRACT FROM AUTHOR]

In vehicular edge computing (VEC) networks, the rapid expansion of intelligent transportation and the corresponding enormous numbers of tasks bring stringent requirements on timely task offloading. However, many tasks typically appear within a short period rather than arriving simultaneously, which makes it difficult to realize effective and efficient resource scheduling. In addition, some key information about tasks could be learned due to the regular data collection and uploading processes of sensors, which may contribute to developing effective offloading strategies. Thus, in this paper, we propose a model that considers the deterministic demand of multiple tasks. It is possible to generate effective resource reservations or early preparation decisions in offloading strategies if some feature information of the deterministic demand can be obtained in advance. We formulate our scenario as a 0‐1 programming problem to minimize the average delay of tasks and transform it into a convex form. Finally, we proposed an efficient optimal offloading algorithm that uses the interior point method. Simulation results demonstrate that the proposed algorithm has great advantages in optimizing offloading utility. [ABSTRACT FROM AUTHOR]

Background: Individuals in close contact with active pulmonary tuberculosis (TB) patients showed a high risk of recent infection and, once infected, higher risk of developing active TB in the following years post-exposure. But the peak time of active disease onset is unclear. This study aims to estimate post exposure TB incidence risk among close contacts to provide reference for clinical and public health strategies. Methods: We searched PubMed, Web of Science, and EMBASE for articles published until December 1, 2022. The incidence rates were quantitatively summarized by means of meta-analysis using the random-effect model. Results: Of the 5616 studies, 31 studies included in our analysis. For baseline close contacts results, the summarized prevalence of Mycobacterium tuberculosis (MTB) infection and active TB was found to be 46.30% (95% CI: 37.18%-55.41%) and 2.68% (95% CI: 2.02%-3.35%), respectively. During the follow-up, the 1-year, 2-year and 5-year cumulative incidence of TB in close contacts were 2.15% (95% CI: 1.51%-2.80%), 1.21% (95% CI: 0.93%-1.49%) and 1.11% (95% CI: 0.64%-1.58%), respectively. Individuals with a positive result of MTB infection testing at baseline showed significantly higher cumulative TB incidence as compared to those negatives (3.80% vs. 0.82%, p < 0.001). Conclusions: Individuals with close contact to active pulmonary TB patients are bearing significant risk of developing active TB, particularly within the first-year post-exposure. Population with recent infections should be an important priority for active case finding and preventive intervention worldwide. [ABSTRACT FROM AUTHOR]

Polyploidization can provide a wealth of genetic variation for adaptive evolution and speciation, but understanding the mechanisms of subgenome evolution as well as its dynamics and ultimate consequences remains elusive. Here, we report the telomere-to-telomere (T2T) gap-free reference genome of allotetraploid horseradish (Armoracia rusticana) sequenced using a comprehensive strategy. The (epi)genomic architecture and 3D chromatin structure of the A and B subgenomes differ significantly, suggesting that both the dynamics of the dominant long terminal repeat retrotransposons and DNA methylation have played critical roles in subgenome diversification. Investigation of the genetic basis of biosynthesis of glucosinolates (GSLs) and horseradish peroxidases reveals both the important role of polyploidization and subgenome differentiation in shaping the key traits. Continuous duplication and divergence of essential genes of GSL biosynthesis (e.g., FMOGS-OX, IGMT, and GH1 gene family) contribute to the broad GSL profile in horseradish. Overall, the T2T assembly of the allotetraploid horseradish genome expands our understanding of polyploid genome evolution and provides a fundamental genetic resource for breeding and genetic improvement of horseradish. Horseradish is a spicy root vegetable and it also produces horseradish peroxidase, an enzyme widely used in biochemistry applications. Here, the authors report its telomere-to-telomere reference genome, reveal subgenome diversification and the effect on the biosynthesis of glucosinolates and horseradish peroxidases. [ABSTRACT FROM AUTHOR]

Despite limited biomonitoring studies suggesting extensive antibiotic exposure in general population, the body burden of antibiotics in young children and their potential health risks remain unclear. To assess the antibiotic exposure levels in young children, 508 preschoolers aged 3–6 years were recruited from eastern China in 2022, and a total of 50 representative antibiotics from 8 categories, including 17 human antibiotics (HAs), 4 antibiotics preferred as HAs (PHAs), 16 veterinary antibiotics (VAs), and 13 antibiotics preferred as VAs (PVAs), were analyzed by UPLC-MS/MS. Hazard quotient (HQ) and hazard index (HI) were calculated to evaluate the health risks, and multivariate logistic regression was applied to examine diet with antibiotic exposure. Our results showed that there were 41 antibiotics detected in children's urine, and the overall detection frequency was as high as 100%. Sulfonamides, macrolides, β-lactams, quinolones, and azoles were the predominant categories of antibiotic detected. Among the studied children, 6.5% had a sum of estimated daily intake (EDI) of all VAs and PVAs larger than 1 μg/kg/day. Notably, 10.0% of the children had a microbiological HI value exceeding 1, primarily contributed by ciprofloxacin. Children with higher consumption of seafood had a relatively increased exposure to multiple categories of antibiotics, including HAs, VAs, quinolones, azoles, and others. Principal component analysis suggested that "Aquatic products and viscera preferred dietary pattern" scores were positively correlated with the exposure levels of ciprofloxacin (OR: 1.23; 95% CI: 1.02–1.47) and carbadox (OR: 1.32; 95% CI: 1.10–1.59), and a relatively increased exposure of PHAs was realized in children with higher "Meat-egg preferred dietary pattern" scores (OR: 1.24; 95% CI: 1.03–1.50). In conclusion, there was a widespread exposure to antibiotics among preschool children from eastern China, and children who consumed more animal-derived foods may had an increased exposure to antibiotics. [ABSTRACT FROM AUTHOR]

The Asteraceae (daisy family) is one of the largest families of plants. The genetic basis for its high biodiversity and excellent adaptability has not been elucidated. Here, we compare the genomes of 29 terrestrial plant species, including two de novo chromosome-scale genome assemblies for stem lettuce, a member of Asteraceae, and Scaevola taccada, a member of Goodeniaceae that is one of the closest outgroups of Asteraceae. We show that Asteraceae originated ~80 million years ago and experienced repeated paleopolyploidization. PII, the universal regulator of nitrogen-carbon (N-C) assimilation present in almost all domains of life, has conspicuously lost across Asteraceae. Meanwhile, Asteraceae has stepwise upgraded the N-C balance system via paleopolyploidization and tandem duplications of key metabolic genes, resulting in enhanced nitrogen uptake and fatty acid biosynthesis. In addition to suggesting a molecular basis for their ecological success, the unique N-C balance system reported for Asteraceae offers a potential crop improvement strategy. Asteraceae is the largest family of flowering plants. Here, the authors assemble the genomes of stem lettuce (within Asteraceae) and beach cabbage (within Goodeniaceae) for evolutionary genomics analyses and reveal the absence of the core regulatory gene of nitrogen and carbon assimilation in Asteraceae. [ABSTRACT FROM AUTHOR]

Background: Individuals in close contact with active pulmonary tuberculosis (TB) patients showed a high risk of recent infection and, once infected, higher risk of developing active TB in the following years post-exposure. But the peak time of active disease onset is unclear. This study aims to estimate post exposure TB incidence risk among close contacts to provide reference for clinical and public health strategies. Methods: We searched PubMed, Web of Science, and EMBASE for articles published until December 1, 2022. The incidence rates were quantitatively summarized by means of meta-analysis using the random-effect model. Results: Of the 5616 studies, 31 studies included in our analysis. For baseline close contacts results, the summarized prevalence of Mycobacterium tuberculosis (MTB) infection and active TB was found to be 46.30% (95% CI: 37.18%-55.41%) and 2.68% (95% CI: 2.02%-3.35%), respectively. During the follow-up, the 1-year, 2-year and 5-year cumulative incidence of TB in close contacts were 2.15% (95% CI: 1.51%-2.80%), 1.21% (95% CI: 0.93%-1.49%) and 1.11% (95% CI: 0.64%-1.58%), respectively. Individuals with a positive result of MTB infection testing at baseline showed significantly higher cumulative TB incidence as compared to those negatives (3.80% vs. 0.82%, p < 0.001). Conclusions: Individuals with close contact to active pulmonary TB patients are bearing significant risk of developing active TB, particularly within the first-year post-exposure. Population with recent infections should be an important priority for active case finding and preventive intervention worldwide. [ABSTRACT FROM AUTHOR]

Regenerated cellulose fibers (RCFs) are widely used biodegradable and eco-friendly materials made from woody biomass that can replace synthetic fibers. In this work, we explored the feasibility of fabricating RCFs using phosphoric acid with hydrogen peroxide (PHP)-treated wheat straw in an N, N-dimethylacetamide/lithium chloride (DMAc/LiCl) solvent system. The effects of upstream pretreatment conditions on the obtained cellulose-enriched fraction (CEF), the solubility of CEF in DMAc/LiCl, the mechanical properties of RCFs, and the interfacial interaction of residual lignin were systematically studied. CEF could be completely dissolved in DMAc/LiCl, and its wet spun RCFs had tensile strengths of 184 MPa and toughness values of 25 MJ/m3; it demonstrated remarkable wet strength (84 MPa), wet toughness (11 MJ/m3), and dyeing properties. The existence of residual lignin negatively affected the RCF mechanical properties; however, it enhanced its resistance to water infiltration. The present work provided a new approach for producing RCFs from woody biomass. [ABSTRACT FROM AUTHOR]

Resonant ultrasound spectroscopy (RUS) is a nondestructive technique, and one of its applications is to determine the elastic constants of a solid by measuring its free-vibration resonant frequencies. For dissipative materials, the vibration spectrum peaks are broad and strongly overlapped, and in some cases, the resonant frequencies extracted by a linear prediction filter are considered to be false positive frequencies that cannot be paired with theoretical resonant frequencies. The inverse identification of elastic constants is also seriously influenced when these false positive frequencies are wrongly paired with theoretical resonant frequencies. In this paper, a new selection index and an extraction process for RUS resonant frequencies are studied to discard false positive frequencies. The change in the relative error between the theoretical and extracted frequencies was employed to update the traditional frequency selection index. An extraction process was proposed by combining a trial-and-error method and a Bayesian method. A bone-mimicking material (quality factor, Q ≈ 30) and the simulated resonant spectra were adopted to validate the proposed method. The performance of identifying false positive frequencies was effectively improved by using the new selection index. Moreover, the proposed process can be applied to enhance the pairing and estimation accuracy for RUS. Calculations of the elastic constants for distinct specimens presented good consistency. The new method proposed in this paper provides a better analysis of the elastic constants in highly dissipative materials and can help to extend the application range of RUS. [ABSTRACT FROM AUTHOR]

Ni2In-type hexagonal compounds MM′X (M, M′ = transition metals, X = main element) involving magnetostructural transition (MST) have attracted much attention due to their giant magnetocaloric effect (MCE). Physical pressure, as an effective method, has been used to adjust the MST and the resultant MCE. Enhanced and diminished MCEs by hydrostatic pressure were both reported previously, but the underlying mechanism is unclear. Here, we report our neutron diffraction study on MST and MCE regulated by hydrostatic pressure in MnNi1 – xFexSi1 – yGey alloys. Careful refinements indicate that the martensitic phase shows a linear ferromagnetic structure with spin moment confined on Mn sites, which remains almost unchanged at pressures lower than 5 kbar even though slight compressions of Mn–Mn bond lengths can be identified. The MST keeps sharp under pressures lower than 5 kbar, while the derived volume change (ΔV/V) across MST reduces 7%, i.e., from 2.84% (0 kbar) to 2.63% (2.1 kbar), due to the effect of pressure on two-phase coexistence. Accordingly, the estimated lattice entropy change (ΔSLatt) based on the Debye approximation reduces by 10% from 37.1 J/kg K (0 kbar) to 33.5 J/kg K (2.1 kbar). These ΔSLatt values, driven by temperature, are all somewhat larger than the magnetic entropy change driven by a 5 T magnetic field. This result may imply that a magnetic field of 5 T is not sufficient for the MST to complete. As the pressure reaches 5 kbar, the MST notably slows down. This may originate from the extended temperature region of two-phase coexistence but not the decoupling of MST. [ABSTRACT FROM AUTHOR]

This study proposes a moderated mediation model to understand how social media use influences political polarization through two competing mechanisms and how such mechanisms are conditioned by political tolerance. The model was tested with a survey of 1,200 Hong Kong residents after the prolonged Anti-Extradition Law Amendment Bill movement. We found that social media use was positively correlated with attitudinal and affective polarization. Such polarizing effects were channeled through politically motivated selective avoidance, but there were noticeable depolarizing effects induced by increased network heterogeneity. More importantly, political tolerance could further amplify the depolarizing effects of social media use. In contrast, political tolerance cannot counteract the polarizing effect of social media use channeled through selective avoidance. [ABSTRACT FROM AUTHOR]

Background: Individuals in close contact with active pulmonary tuberculosis (TB) patients showed a high risk of recent infection and, once infected, higher risk of developing active TB in the following years post-exposure. But the peak time of active disease onset is unclear. This study aims to estimate post exposure TB incidence risk among close contacts to provide reference for clinical and public health strategies. Methods: We searched PubMed, Web of Science, and EMBASE for articles published until December 1, 2022. The incidence rates were quantitatively summarized by means of meta-analysis using the random-effect model. Results: Of the 5616 studies, 31 studies included in our analysis. For baseline close contacts results, the summarized prevalence of Mycobacterium tuberculosis (MTB) infection and active TB was found to be 46.30% (95% CI: 37.18%-55.41%) and 2.68% (95% CI: 2.02%-3.35%), respectively. During the follow-up, the 1-year, 2-year and 5-year cumulative incidence of TB in close contacts were 2.15% (95% CI: 1.51%-2.80%), 1.21% (95% CI: 0.93%-1.49%) and 1.11% (95% CI: 0.64%-1.58%), respectively. Individuals with a positive result of MTB infection testing at baseline showed significantly higher cumulative TB incidence as compared to those negatives (3.80% vs. 0.82%, p < 0.001). Conclusions: Individuals with close contact to active pulmonary TB patients are bearing significant risk of developing active TB, particularly within the first-year post-exposure. Population with recent infections should be an important priority for active case finding and preventive intervention worldwide. [ABSTRACT FROM AUTHOR]

Bone metastasis is one of the most important factors associated with poor prognosis for patients with prostate, breast, thyroid, and lung cancer. In the past two decades, 651 clinical trials, including 554 interventional trials, were being registered in ClinicalTrials.gov and pharma.id.informa.com to combat bone metastases from different perspectives. In this review, we comprehensively analyzed, regrouped, and discussed all the interventional trials on bone metastases. Clinical trials were re-grouped into bone-targeting agents, radiotherapy, small molecule targeted therapy, combination therapy, and others, based on the different mechanisms of action including modifying the bone microenvironment and preventing the growth of cancer cells. We also discussed the potential strategies that might improve overall survival and progression-free survival of patients with bone metastases in the future. [ABSTRACT FROM AUTHOR]

Purpose: Among all ischemic stroke patients, more than half are mild and rapidly improving acute ischemic stroke (MaRAIS) patients. However, many MaRAIS patients do not recognize the disease early on, and thus they delay access to the treatment that would be most effective if provided earlier. This is especially true in rural areas. The aim of this study was to develop and validate a late hospital arrival risk nomogram in a rural Chinese population of patients with MaRAIS. Methods: We developed a prediction model based on a training dataset of 173 MaRAIS patients collected from September 9, 2019 to May 13, 2020. Data analyzed included demographics and disease characteristics. A least absolute shrinkage and selection operator (LASSO) regression model was used to optimize feature selection for the late hospital arrival risk model. Multivariable logistic regression analysis was applied to build a prediction model incorporating the features selected in the LASSO regression models. The discrimination, calibration, and clinical usefulness of the prediction model were assessed using the C-index, calibration plot, and decision curve analysis, respectively. Internal validation was then assessed using bootstrapping validation. Results: Variables contained in the prediction nomogram included transportation mode, history of diabetes, knowledge of stroke symptoms, and thrombolytic therapy. The model had moderate predictive power with a C-index of 0.709 (95% confidence interval: 0.636– 0.783) and good calibration. In the internal validation, the C-index reached 0.692. The risk threshold was 30– 97% according to the analysis of the decision curve, and the nomogram could be applied in clinical practice. Conclusion: This novel nomogram, which incorporates transportation mode, history of diabetes, knowledge of stroke symptoms, and thrombolytic therapy, was conveniently applied to facilitate individual late hospital arrival risk prediction among MaRAIS patients in a rural area of Shanghai, China. [ABSTRACT FROM AUTHOR]