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The Curiosity rover explored the region between the orbitally defined phyllosilicate-bearing Glen Torridon trough and the overlying layered sulfate-bearing unit, called the "clay-sulfate transition region." Samples were drilled from the top of the fluviolacustrine Glasgow member of the Carolyn Shoemaker formation (CSf) to the eolian Contigo member of the Mirador formation (MIf) to assess in situ mineralogical changes with stratigraphic position. The Sample Analysis at Mars-Evolved Gas Analysis (SAM-EGA) instrument analyzed drilled samples within this region to constrain their volatile chemistry and mineralogy. Evolved H 2 O consistent with nontronite was present in samples drilled in the Glasgow and Mercou members of the CSf but was generally absent in stratigraphically higher samples. SO 2 peaks consistent with Fe sulfate were detected in all samples, and SO 2 evolutions consistent with Mg sulfate were observed in most samples. CO 2 and CO evolutions were variable between samples and suggest contributions from adsorbed CO 2 , carbonates, simple organic salts, and instrument background. The lack of NO and O 2 in the data suggest that oxychlorines and nitrates were absent or sparse, and evolved HCl was consistent with the presence of chlorides in all samples. The combined rover data sets suggest that sediments in the upper CSf and MIf may represent similar source material and were deposited in lacustrine and eolian environments, respectively. Rocks were subsequently altered in briny solutions with variable chemical compositions that resulted in the precipitation of sulfates, carbonates, and chlorides. The results suggest that the clay-sulfate transition records progressively drier surface depositional environments and saline diagenetic fluid, potentially impacting habitability., (© 2024. The Author(s).)

Complexification of macrobiomolecules, such as homodimer to heterodimer transitions, are common during evolution. Is such complexification always adaptive? Using large-scale experiments and in-depth biochemical analyses, Després et al. recently demonstrated that an obligate heterodimer can evolve from a homodimer through neutral, nonadaptive events, and quantified key parameters required for such transitions., Competing Interests: Declaration of interests A-R.C. is a member of the Scientific Advisory Board for ProFound Therapeutics. The remaining authors have no interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To compare dual task cost (DTC) during gait initiation (GI) between a population of patients with persistent concussion symptoms (PCS) and age-matched healthy participants., Design: Cohort study., Setting: University research center., Participants: A cohort sample including 15 participants with PCS (43.9±11.7y, 73.3% female) and 23 age-matched healthy participants (42.1±10.3y, 65.2% female) as controls., Interventions: Participants were tested on a single occasion where they performed 5 trials of single task and 5 trials of dual task GI with 12-camera motion capture and 3 force plates., Main Outcome Measures: The dependent variables of interest were the DTC for the center of pressure (COP) displacement and velocity during the anticipatory postural adjustment (APA) phase, the COP-center of mass (COP-COM) separation, and the response accuracy during the auditory cognitive tasks., Results: There were significant group differences with worse DTC for the PCS participants in anterior (A)/posterior (P) displacement (PCS, -37.5±22.1%; Control, -9.7±39.2%; P=.016, d=0.874), APA medial (M)/lateral (L) velocity (PCS, -34.8±28.8%; Control, -17.0±40.21%; P=.041, d=0.866), and the peak COP-COM separation (PCS, -7.3±6.7%; Control, 0.6±6.5%; P=.023, d=1.200). There were no significant group differences in the APA A/P velocity (PCS, -38.8±33.1%; Control, -19.8±43.9%; P=.094), APA M/L displacement (PCS, -34.8±21.8%; Control, -10.6±25.3%; P=.313), or cognitive task performance (PCS, -2.7±10.8%; Control, -0.2±4.3%; P=.321)., Conclusions: PCS participants had greater (worse) DTC during both the planning and execution of the task, with large effect sizes (d>0.80). PCS participants also used a posture-second strategy whereby attentional resources were inappropriately allocated to the cognitive task. These deficits may challenge a patient's ability to complete activities of daily living and limit their functional independence., (Copyright © 2024 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Patient-reported outcome measures (PROMs) are used in orthopaedic surgery to measure aspects of musculoskeletal function that are important to patients, such as disability and pain. However, current assessments of function using PROMs do not necessarily consider a patient's functional demands in detail. A patient's functional demands could serve as a confounder to their perception of their functional ability. Hence, functional demands may need to be adjusted for when PROMs are used to measure musculoskeletal function., Methods: We conducted a cross-sectional study in which new orthopaedic patients completed a questionnaire regarding demographics, function [Patient-Reported Outcomes Measurement Information System], functional demand (Tegner Activity Level Scale), pain self-efficacy, and symptoms of depression. 169 eligible patients with diverse orthopaedic conditions were enrolled in the study from an orthopaedic clinic, and 19 were excluded for incomplete questionnaires., Results: The mean Patient-Reported Outcomes Measurement Information System score was 36.5 ± 9.1, and the mean Tegner score was 2.6 ± 2.0. In the multivariable regression model, patient-reported function was significantly associated with functional demand (β = 0.17, P < 0.001). Significant associations were observed for pain self-efficacy (β = 0.15, P < 0.001), acuity (β = -0.10, P = 0.004), and age 80 years or older (β = -0.16, P = 0.004). No notable association was observed with depression or age 65 to 79 years., Discussion: Higher patient-reported physical function is associated with higher levels of functional demand when controlling for psychosocial factors, acuity, and age. Because of its confounding effect on measuring physical function, functional demand should be assessed and included in models using PROMs before and after surgery. For example, payment models using improvements in PROMs, such as the short form of the Hip dysfunction and Osteoarthritis Outcome Score and the Knee injury and Osteoarthritis Outcome Score after joint arthroplasty, should include functional demand in the model when assessing quality of care., Level of Evidence: Level II., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Chronic hepatitis B (CHB) represents a significant unmet medical need with few options beyond lifelong treatment with nucleoside analogues, which rarely leads to a functional cure. Novel agents that reduce levels of HBV DNA, RNA and other viral antigens could lead to better treatment outcomes. The capsid assembly modulator (CAM) class of compounds represents an important modality for chronic suppression and to improve functional cure rates, either alone or in combination. GLP-26 is a potent CAM, which in this work was optimized for potency, safety, and other drug-like properties leading to ALG-001075 . ALG-001075 was further advanced through clinical development as the highly soluble prodrug ALG-000184 . ALG-000184 is currently being explored in multiple clinical trials in HBV-infected subjects where unprecedented reductions in HBV DNA, RNA and other viral antigens have been observed, making ALG-000184 a promising candidate to become a cornerstone for future chronic suppressive and combination treatment regimens for CHB.

Dry reforming of methane (DRM), the catalytic conversion of CH 4 and CO 2 into syngas (H 2 +CO), is an important process closely correlated to the environment and chemical industry. NiAl-based catalysts have been reported to exhibit excellent activity, low cost, and environmental friendliness. At the same time, the rapid deactivation caused by carbon deposition, Ni sintering, and phase transformation exerts great challenges for its large-scale applications. This review summarizes the recent advances in NiAl-based catalysts for DRM, particularly focusing on the strategies to construct efficient and stable NiAl-based catalysts. Firstly, the thermodynamics and elementary steps of DRM, including the activation of reactants and coke formation and elimination, are summarized. The roles of Al 2 O 3 and its mixed oxides as the support, and the influences of the promoters employed in NiAl-based catalysts over the DRM performance, are then illustrated. Finally, the design of anti-coking and anti-sintering NiAl-based catalysts for DRM is suggested as feasible and promising by tailoring the structure and states of Ni and the modification of Al-based supports including small Ni size, high Ni dispersion, proper basicity, strong metal-support interaction (SMSI), active oxygen species as well as high phase stability., (© 2024 Wiley-VCH GmbH.)

Photo-sono therapy (PST) is an innovative anti-vascular approach based on cavitation-induced spallation. Currently, passive cavitation detection (PCD) is the prevalent technique for cavitation monitoring during treatment. However, the limitations of PCD are the lack of spatial information of bubbles and the difficulty of integration with the PST system. To address this, we proposed a new, to the best of our knowledge, cavitation mapping method that integrates Doppler optical coherence tomography (OCT) with PST to visualize bubble dynamics in real time. The feasibility of the proposed system has been confirmed through experiments on vascular-mimicking phantoms and in vivo rabbit ear vessels, and the results are compared to high-speed camera observations and PCD data. The findings demonstrate that Doppler OCT effectively maps cavitation in real time and holds promise for guiding PST treatments and other cavitation-related clinical applications.

Background: Patient-reported outcome measures (PROMs) were originally developed as research tools; however, there is increasing interest in using PROMs to inform clinical care. Prior work has shown the benefits of implementing PROMs at the point of care, but a patient's health numeracy (their ability to understand and work with numbers) may affect their ability to interpret PROM results., Materials and Methods: We recruited patients presenting to an outpatient orthopedic clinic. Forty-nine patients completed a survey that included demographic information, the short-form General Health Numeracy Test, and accuracy questions about four PROM displays (bar graph, table, line graph, pictograph) that indicated the same PROM results., Results: Patients with higher health numeracy answered all display accuracy questions correctly ( P =.016). Patients who preferred using the table were more likely to answer display accuracy questions incorrectly (odds ratio, 0.013, P =.024). The two most frequently preferred PROM formats were bar graphs and tables, and most patients preferred to learn about their PROM function scores via a combination of displays and verbal discussions., Conclusion: Patient health numeracy is associated with the ability to correctly interpret visual displays of PROMs. Implementation of PROMs at point of care currently does not account for health numeracy. Efforts to account for health numeracy when using PROMs at point of care may improve the efficacy of using PROMs to improve outcomes in orthopedic surgery. [ Orthopedics . 2024;47(5):e255-e260.].

There have been numerous studies using effect-directed analysis (EDA) to identify key toxic substances present in source and drinking water, but none of these studies have considered the effects of metabolic activation. This study developed a comprehensive method including a pretreatment process based on an in vitro metabolic activation system, a comprehensive biological effect evaluation based on concentration-dependent transcriptome (CDT), and a chemical feature identification based on nontarget chemical analysis (NTA), to evaluate the changes in the toxic effects and differences in the chemical composition after metabolism. Models for matching metabolites and precursors as well as data-driven identification methods were further constructed to identify toxic metabolites and key toxic precursor substances in drinking water samples from the Yangtze River. After metabolism, the metabolic samples showed a general trend of reduced toxicity in terms of overall biological potency (mean: 3.2-fold). However, metabolic activation led to an increase in some types of toxic effects, including pathways such as excision repair, mismatch repair, protein processing in endoplasmic reticulum, nucleotide excision repair, and DNA replication. Meanwhile, metabolic samples showed a decrease (17.8%) in the number of peaks and average peak area after metabolism, while overall polarity, hydrophilicity, and average molecular weight increased slightly (10.3%). Based on the models for matching of metabolites and precursors and the data-driven identification methods, 32 chemicals were efficiently identified as key toxic substances as main contributors to explain the different transcriptome biological effects such as cellular component, development, and DNA damage related, including 15 industrial compounds, 7 PPCPs, 6 pesticides, and 4 natural products. This study avoids the process of structure elucidation of toxic metabolites and can trace them directly to the precursors based on MS spectra, providing a new idea for the identification of key toxic pollutants of metabolites.

This study presents a miniaturized head-mount optical coherence tomography (OCT) system tailored for high-resolution brain imaging in freely moving mice, providing an advanced noninvasive imaging tool in neuroscience research. Leveraging optical coherence tomography technology, the system enables depth-resolved imaging and integrates functional OCT extensions, including angiography and Doppler imaging. Remarkably lightweight at 1.5 g, the device allows for the preservation of natural mouse behavior during imaging sessions. With a maximum 4 × 4 mm field of view and 7.4 μm axial resolution, the system offers reliable imaging capabilities. Noteworthy features include focal adjustability, rotary joint integration for fiber-twist-free operation, and a high-speed swept-source OCT laser at 200 kHz, facilitating real-time imaging. By providing insights into brain mechanisms and neurological disorders without disrupting natural behavior, this innovative system holds promise as a powerful tool in neuroscience research. Its compact design and comprehensive imaging capabilities make it well-suited for studying various brain regions and dynamic processes, contributing significantly to our understanding of brain function and pathology., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Facing the great threats to ecosystems and human health posed by the continuous release of chemicals into aquatic environments, effect-directed analysis (EDA) has emerged as a powerful tool for identifying causative toxicants. However, traditional EDA shows problems of low-coverage, labor-intensive and low-efficiency. Currently, a number of high-efficiency techniques have been integrated into EDA to improve toxicant identification. In this review, the latest progress and current limitations of high-efficiency EDA, comprising high-coverage effect evaluation, high-resolution fractionation, high-coverage chemical analysis, high-automation causative peak extraction and high-efficiency structure elucidation, are summarized. Specifically, high-resolution fractionation, high-automation data processing algorithms and in silico structure elucidation techniques have been well developed to enhance EDA. While high-coverage effect evaluation and chemical analysis should be further emphasized, especially omics tools and data-independent mass acquisition. For the application status in aquatic environments, high-efficiency EDA is widely applied in surface water and wastewater. Estrogenic, androgenic and aryl hydrocarbon receptor-mediated activities are the most concerning, with causative toxicants showing the typical structural features of steroids and benzenoids. A better understanding of the latest progress and application status of EDA would be beneficial to further advance in the field and greatly support aquatic environment monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Greater pain self-efficacy (PSE) is associated with reduced pain, fewer limitations, and increased quality of life after treatment for orthopedic conditions. The aims of this study were to (1) assess if PSE improves during a visit with an orthopedic surgeon and (2) identify modifiable visit factors that are associated with an increase in PSE., Materials and Methods: We performed a prospective observational study of orthopedic clinic visits at a multispecialty clinic from February to May 2022. New patients who presented to one of six orthopedic surgeons were approached for the study. Patients who provided consent completed a pre-visit questionnaire including the Pain Self-Efficacy Questionnaire (PSEQ) and demographic questions. A trained research member recorded the five-item Observing Patient Involvement in Decision Making Instrument (OPTION-5) score, number of questions asked, and visit duration. Immediately after the visit, patients completed a post-visit questionnaire consisting of the PSEQ and Perceived Involvement in Care Scale (PICS)., Results: Of 132 patients enrolled, 61 (46%) had improved PSE after the orthopedic visit, with 38 (29%) having improvement above a clinically significant threshold. There were no significant differences between patients with increased PSE and those without increased PSE when comparing the PICS, OPTION-5, questions asked, or visit duration., Conclusion: Almost half of the patients had improvement in PSE during an orthopedic visit. The causal pathway to how to improve PSE and the durability of the improved PSE have implications in strategies to improve patient outcomes in orthopedic surgery, such as communication methods and shared decision-making. Future research can focus on studying different interventions that facilitate improving PSE. [ Orthopedics . 2024;47(4):e197-e203.].

Objective: The aim of this study was to investigate the diagnostic potential of Krebs von den Lungen-6 (KL-6) in differentiating between malignant pleural effusion (MPE) induced by non-small cell lung cancer (NSCLC) and benign pleural effusion (BPE)., Methods: We collected 143 pleural effusion samples from August 2018 to March 2021. The samples included 91 cases of MPE and 52 cases of BPE. The KL-6 and other indicators in pleural effusion were detected., Results: The level of pleural effusion KL-6 (pKL-6) in the MPE group was significantly higher than in the BPE group (Mann-Whitney U = 442.500, P = .000). The area under the curve (AUC) of pKL-6/pleural effusion adenosine deaminase (pADA) + pleural effusion carcinoembryonic antigen (pCEA)/pADA (AUC = 0.992) in diagnosing MPE was higher than that of pKL-6 alone (AUC = 0.903), with a sensitivity of 93.26% and specificity of 100%., Conclusion: The measurement of pKL-6 can differentiate NSCLC-induced MPE from BPE. Furthermore, the combined detection of pKL-6/pADA and pCEA/pADA can significantly improve the diagnostic efficiency for distinguishing NSCLC-induced MPE., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Lung cancer is a highly prevalent tumor with a lack of biological markers that reflect its progression. Mast cell surface membrane protein 1 (MCEMP1, also known as C19ORF59) has not been reported in lung adenocarcinoma (LUAD)., Objective: We aimed to investigate the role of MCEMP1 in LUAD., Methods: MCEMP1 expression in LUAD was analyzed using The Cancer Genome Atlas (TCGA) data, and conducted univariate and multivariate Cox regression analyses to evaluate the prognostic significance of MCEMP1 expression in TCGA. Tumor Immune Estimation Resource (TIMER) was used for examining the correlation between MCEMP1 expression and immune cell infiltration in LUAD. Furthermore, proliferation, migration, invasion, and colony-forming ability were investigated using LUAD cell lines., Results: MCEMP1 had low expression in LUAD patient tissues and was correlated with lymph node metastasis, differentiation level, and tumor status. The Area under Curve (AUC) value of MCEMP1 for the Receiver Operating Characteristic (ROC) curve analysis was 0.984. The immune infiltration analysis revealed a correlation between MCEMP1 expression and the extent of macrophages and neutrophil infiltration in LUAD. Additionally, MCEMP1 has low expression in clinical samples, MCEMP1 overexpressed in LUAD cells substantially reduced cell growth, migration, and invasion of malignant cells., Conclusion: Low expression MCEMP1 promotes LUAD progression, which provides new insights and a potential biological target for future LUAD therapies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Many organic pollutants were detected in tap water (TW) and source water (SW) along the Yangtze River. However, the potential toxic effects and the high-concern organics (HCOs) which drive the effect are still unknown. Here, a non-targeted toxicity testing method based on the concentration-dependent transcriptome and non-targeted LC-HRMS analysis combining tiered filtering were used to reveal the overall biological effects and chemical information. Subsequently, we developed a qualitative pathway-structure relationship (QPSR) model to effectively match the biological and chemical information and successfully identified HCOs in TW and SW along the Yangtze River by potential substructures of HCOs. Non-targeted toxicity testing found that the biological potency of both TW and SW was stronger in the downstream of the Yangtze River, and disruption of the endocrine system and cancer were the main drivers of the effect. In addition, non-targeted LC-HRMS analysis combined with retention time prediction results identified 3220 and 631 high-confidence compound structures in positive and negative ion modes, respectively. Then, QPSR model was further implied and identified a total of 103 HCOs, containing 35 industrial chemicals, 30 PPCPs, 26 pesticides, and 12 hormones in TW and SW, respectively. Among them, the neuroactive and hormonal compounds oxoamide, 8-iso-16-cyclohexyl-tetranor prostaglandin E2, E Keppra, and Tocris-0788 showed the highest frequency of detection, which were identified in more than 1/3 of the samples. The strategy of combining non-targeted toxicity testing and non-targeted LC-HRMS analysis will support comprehensive biological effect assessment, identification of HCOs, and risk control of mixtures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The search for life beyond Earth necessitates a rigorous and comprehensive examination of biosignatures, the types of observable imprints that life produces. These imprints and our ability to detect them with advanced instrumentation hold the key to our understanding of the presence and abundance of life in the universe. Biosignatures are the chemical or physical features associated with past or present life and may include the distribution of elements and molecules, alone or in combination, as well as changes in structural components or physical processes that would be distinct from an abiotic background. The scientific and technical strategies used to search for life on other planets include those that can be conducted in situ to planetary bodies and those that could be observed remotely. This chapter discusses numerous strategies that can be employed to look for biosignatures directly on other planetary bodies using robotic exploration including those that have been deployed to other planetary bodies, are currently being developed for flight, or will become a critical technology on future missions. Search strategies for remote observations using current and planned ground-based and space-based telescopes are also described. Evidence from spectral absorption, emission, or transmission features can be used to search for remote biosignatures and technosignatures. Improving our understanding of biosignatures, their production, transformation, and preservation on Earth can enhance our search efforts to detect life on other planets.

While Earth contains the only known example of life in the universe, it is possible that life elsewhere is fundamentally different from what we are familiar with. There is an increased recognition in the astrobiology community that the search for life should steer away from terran-specific biosignatures to those that are more inclusive to all life-forms. To start exploring the space of possibilities that life could occupy, we can try to dissociate life from the chemistry that composes it on Earth by envisioning how different life elsewhere could be in composition, lifestyle, medium, and form, and by exploring how the general principles that govern living systems on Earth might be found in different forms and environments across the Solar System. Exotic life-forms could exist on Mars or Venus, or icy moons like Europa and Enceladus, or even as a shadow biosphere on Earth. New perspectives on agnostic biosignature detection have also begun to emerge, allowing for a broader and more inclusive approach to seeking exotic life with unknown chemistry that is distinct from life as we know it on Earth.

The Astrobiology Primer 3.0 (ABP3.0) is a concise introduction to the field of astrobiology for students and others who are new to the field of astrobiology. It provides an entry into the broader materials in this supplementary issue of Astrobiology and an overview of the investigations and driving hypotheses that make up this interdisciplinary field. The content of this chapter was adapted from the other 10 articles in this supplementary issue and thus represents the contribution of all the authors who worked on these introductory articles. The content of this chapter is not exhaustive and represents the topics that the authors found to be the most important and compelling in a dynamic and changing field.

Extreme bradycardia, extreme tachycardia, ventricular flutter fib, and ventricular tachycardia are four malignant arrhythmias (MAs) that lead to sudden cardiac death. It is very important to detect them in daily life. The arterial blood pressure (ABP) signal contains abundant pathological information about four MAs and is easy to be recorded under domestic conditions. Thus, a synthesis-by-analysis (SA) modeling method for ABP signal was proposed to detect the four MAs in this study. The average models of MAs and healthy subjects were obtained by SA modeling, and the change of each ABP wave was quantitively described by twelve parameters of wave models. Then, the probabilistic neural network (PNN) and random forest (RF) are trained to detect the MAs. The experimental data were employed from Fantasia and the 2015 PhysioNet/CinC Challenge databases. The SA modeling results show that some pathological and physiological changes could be extracted from the average models. The two-sample ks-test results between different groups are markedly different (h = 1, p < 0.05). The detection results show that the performances of PPN classifiers are less than that of RF. The kappa coefficients (KC) for the RF classifiers are 97.167 ± 1.46 %, 97.888 ± 0.808 %, 99.895 ± 0.545 %, 98.575 ± 1.683 % and 92.241 ± 1.517 %, respectively. The mean KC is 97.083 ± 0.67 %. Compared to the performance of some existing studies, the proposed method has better performance and is potential to diagnose MAs in m-health., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 IPEM. Published by Elsevier Ltd. All rights reserved.)

Pulse rate variability (PRV) signals are extracted from pulsation signal can be effectively used for cardiovascular disease monitoring in wearable devices. Permutation entropy (PE) algorithm is an effective index for the analysis of PRV signals. However, PE is computationally intensive and impractical for online PRV processing on wearable devices. Therefore, to overcome this challenge, a fast permutation entropy (FPE) algorithm is proposed based on the microprocessor data updating process in this paper, which can analyze PRV signals with single-sample recursive. The simulation data and PRV signals extracted from pulse signals in "Fantasia database" were utilized to verify the performance and accuracy of the improved methods. The results show that the speed of FPE is 211 times faster than PE and maintain the accuracy of algorithm (Root Mean Squared Error = 0) for simulation data with a length of 10,000 samples and embedded dimension m = 5, time delay τ = 5, buffer length Lw = 512. For the RRV signals with 3000∼5000 samples, the result show that the consumption of FPE is less than 0.2 s, which is 175 times faster than PE. This indicates that FPE has better application performance than PE. Furthermore, a low-cost wearable signal detection system is developed to verify the proposed method, the result show that the proposed method can calculate the FPE of PRV signal online with single-sample recursive calculation. Subsequently, entropy-based features are used to explore the performance of decision trees in identifying life-threatening arrhythmias, and the method resulted in a classification accuracy of 85.43%. It can therefore be inferred that the proposed method has great potential in cardiovascular disease., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 IPEM. Published by Elsevier Ltd. All rights reserved.)

The identification and management of high-risk contaminants have raised great concern from governments. Facing the growing amount of data on the occurrence of emerging contaminants (ECs) in surface water, a deep mining and quality control strategy was developed to integrate data on all reported ECs in Chinese surface water over the past decade, and an exposure and effect database was further built. In addition, multilevel risk characterization was carried out to prioritize high-risk areas, contaminants and endpoints. A total of 1038 ECs, mainly pharmaceutical and personal care products (PPCPs) and industrial chemicals, were curated, with concentrations ranging from 0.02 pg/L to 533 µg/L. For individual risk, all the provinces had acceptable risks except for Henan, which was characterized with a medium chronic risk. Nine ECs, including 4-nonylphenol and estrone, dominated individual risks. Conversely, for multisubstance risk, 76.20% and 73.87% of aquatic organisms were affected acutely and chronically at the national level, with acute and chronic risks exceeding the safety threshold of 5% in 11 and 19 provinces, respectively. Nineteen ECs, including sitosterol and chyfluthrin, dominated the multisubstance risk. In addition, 9 MoAs mainly inducing electron transfer inhibition, neurotoxicity and narcosis toxicity are high-risk endpoints. The study revealed the ecological risk status and key risk entities of Chinese surface waters, which provided the latest data to support the control of ECs in China., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

DNA and RNA nanostructures are being investigated as therapeutics, vaccines, and drug delivery systems. These nanostructures can be functionalized with guests ranging from small molecules to proteins with precise spatial and stoichiometric control. This has enabled new strategies to manipulate drug activity and to engineer devices with novel therapeutic functionalities. Although existing studies have offered encouraging in vitro or pre-clinical proof-of-concepts, establishing mechanisms of in vivo delivery is the new frontier for nucleic-acid nanotechnologies. In this review, we first provide a summary of existing literature on the in vivo uses of DNA and RNA nanostructures. Based on their application areas, we discuss current models of nanoparticle delivery, and thereby highlight knowledge gaps on the in vivo interactions of nucleic-acid nanostructures. Finally, we describe techniques and strategies for investigating and engineering these interactions. Together, we propose a framework to establish in vivo design principles and advance the in vivo translation of nucleic-acid nanotechnologies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To evaluate for disparities in peripartum toxicology testing among maternal-infant dyads across a hospital network and subsequent child protective services (CPS) involvement., Methods: Retrospective chart review of 59,425 deliveries at 5 hospitals in Massachusetts between 2016 and 2020. We evaluated associations between maternal characteristics, toxicology testing, and child welfare involvement with disproportionality risk ratios and hierarchical logistical regression., Results: Toxicology testing was performed on 1959 (3.3%) dyads. Younger individuals and individuals of color were more likely to be tested for cannabis use or maternal medical complications compared to white non-Hispanic individuals. Among those without a substance use disorder, age <25 (adjusted odds ratio [aOR] 2.81; 95% confidence interval [CI], 2.43-3.26), race and ethnicity (non-Hispanic Black (aOR 1.80; 95% CI, 1.52-2.13), Hispanic (aOR 1.23; 95% CI, 1.05-1.45), mixed race/other (aOR 1.40; 95% CI, 1.04, 1.87), unavailable race (aOR 1.92; 95% CI, 1.32-2.79), and public insurance (Medicaid [aOR 2.61; 95% CI, 2.27-3.00], Medicare [aOR 13.76; 95% CI, 9.99-18.91]) had increased odds of toxicology testing compared to older, white non-Hispanic, and privately insured individuals. The disproportionality ratios in testing were greater than 1.0 for individuals under 25 years old (3.8), Hispanic individuals (1.6), non-Hispanic Black individuals (1.8), individuals of other race (1.2), unavailable race (1.8), and individuals with public insurance (Medicaid 2.6; Medicare 10.6). Among dyads tested, race and ethnicity was not associated with CPS involvement., Conclusions: Peripartum toxicology testing is disproportionately performed on non-white, younger, and poorer individuals and their infants, with cannabis use and medical complications prompting testing more often for patients of color than for white non-Hispanic individuals., (Copyright © 2023 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Sample entropy is an effective nonlinear index for analyzing pulse rate variability (PRV) signal, but it has problems with a large amount of calculation and time consumption. Therefore, this study proposes a fast sample entropy calculation method to analyze the PRV signal according to the microprocessor process of data updating and the principle of sample entropy. The simulated data and PRV signal are employed as experimental data to verify the accuracy and time consumption of the proposed method. The experimental results on simulated data display that the proposed improved sample entropy can improve the operation rate of the entropy value by a maximum of 47.6 times and an average of 28.6 times and keep the entropy value unchanged. Experimental results on PRV signal display that the proposed improved sample entropy has great potential in the real-time processing of physiological signals, which can increase approximately 35 times., (© 2023. International Federation for Medical and Biological Engineering.)

Coral reefs in the Central Indo-Pacific region comprise some of the most diverse and yet threatened marine habitats. While reef monitoring has grown throughout the region in recent years, studies of coral reef benthic cover remain limited in spatial and temporal scales. Here, we analysed 24,365 reef surveys performed over 37 years at 1972 sites throughout East Asia by the Global Coral Reef Monitoring Network using Bayesian approaches. Our results show that overall coral cover at surveyed reefs has not declined as suggested in previous studies and compared to reef regions like the Caribbean. Concurrently, macroalgal cover has not increased, with no indications of phase shifts from coral to macroalgal dominance on reefs. Yet, models incorporating socio-economic and environmental variables reveal negative associations of coral cover with coastal urbanisation and sea surface temperature. The diversity of reef assemblages may have mitigated cover declines thus far, but climate change could threaten reef resilience. We recommend prioritisation of regionally coordinated, locally collaborative long-term studies for better contextualisation of monitoring data and analyses, which are essential for achieving reef conservation goals., (© 2023. The Author(s).)

Studies of psychrophilic life on Earth provide chemical clues as to how extraterrestrial life could maintain viability in cryogenic environments. If living systems in ocean worlds ( e.g., Enceladus) share a similar set of 3-mer and 4-mer peptides to the psychrophile Colwellia psychrerythraea on Earth, spaceflight technologies and analytical methods need to be developed to detect and sequence these putative biosignatures. We demonstrate that laser desorption mass spectrometry, as implemented by the CORALS spaceflight prototype instrument, enables the detection of protonated peptides, their dimers, and metal adducts. The addition of silicon nanoparticles promotes the ionization efficiency, improves mass resolving power and mass accuracies via reduction of metastable decay, and facilitates peptide de novo sequencing. The CORALS instrument, which integrates a pulsed UV laser source and an Orbitrap™ mass analyzer capable of ultrahigh mass resolving powers and mass accuracies, represents an emerging technology for planetary exploration and a pathfinder for advanced technique development for astrobiological objectives. Teaser: Current spaceflight prototype instrument proposed to visit ocean worlds can detect and sequence peptides that are found enriched in at least one strain of microbe surviving in subzero icy brines via silicon nanoparticle-assisted laser desorption analysis.

Introduction: Geroscience studies of low-dose rapamycin in laboratory species have identified numerous benefits, including reversing age-related cardiac dysfunction. Cardiovascular benefits have been observed in dogs with 10 weeks of treatment, raising questions about possible benefits and adverse effects of long-term use of low-dose rapamycin. The objectives of this study were to assess the impact of 6 months of low-dose rapamycin on echocardiographic indices of cardiac function in healthy dogs and to document the occurrence of adverse events., Methods: Seventeen client-owned dogs aged 6-10 years, weighing 18-36 kg, and without significant systemic disease were included in a prospective, randomized, placebo-controlled, masked clinical trial. Low-dose rapamycin (0.025 mg/kg) or placebo was administered three times per week for 6 months. Baseline, 6-month, and 12-month evaluation included physical examination, cardiology examination, and clinicopathology. Three-month evaluation included physical examination and clinicopathology. Owners completed online questionnaires every 2 weeks., Results: There were no statistically significant differences in echocardiographic parameters between rapamycin and placebo groups at 6 or 12 months. No clinically significant adverse events occurred. In 26.8% of the bi-weekly surveys owners whose dogs received rapamycin reported perceived positive changes in behavior or health, compared to 8.1% in the placebo group ( p  = 0.04)., Discussion: While no clinically significant change in cardiac function was observed in dogs treated with low-dose rapamycin, the drug was well-tolerated with no significant adverse events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Barnett, Wesselowski, Gordon, Saunders, Promislow, Schwartz, Chou, Evans, Kaeberlein and Creevy.)

Translation is the process by which ribosomes synthesize proteins. Ribosome profiling recently revealed that many short sequences previously thought to be noncoding are pervasively translated. To identify protein-coding genes in this noncanonical translatome, we combine an integrative framework for extremely sensitive ribosome profiling analysis, iRibo, with high-powered selection inferences tailored for short sequences. We construct a reference translatome for Saccharomyces cerevisiae comprising 5,400 canonical and almost 19,000 noncanonical translated elements. Only 14 noncanonical elements were evolving under detectable purifying selection. A representative subset of translated elements lacking signatures of selection demonstrated involvement in processes including DNA repair, stress response, and post-transcriptional regulation. Our results suggest that most translated elements are not conserved protein-coding genes and contribute to genotype-phenotype relationships through fast-evolving molecular mechanisms., Competing Interests: Declaration of interests A.-R.C. is a member of the Scientific Advisory Board for Flagship Labs 69, Inc. (ProFound Therapeutics)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The coordination and the directional order of ciliary metachronal waves are the major factors that determine the effectiveness of mucociliary clearance (MCC). Even though metachronal waves play an essential part in immune response, clinical diagnostic tools and imaging techniques that can reliably and efficiently capture their spatial distribution and function are currently limited., Methods: We present label-free high-speed visualization of ciliary metachronal wave propagations in freshly-excised tracheal explants using a spectrally-encoded interferometric microscope over a two-dimensional (2D) plane of 0.5 mm × 0.5 mm at an acquisition rate of 50 frame-per-second. Furthermore, phase-resolved enhanced dynamic (PHRED) analysis of time-series doppler images was performed, where spatial-temporal characteristics of cilia metachronal wave motions are revealed through frequency component analysis and spatial filtering., Results: The PHRED analysis of phase-resolved Doppler (PRD) images offers a capability to distinguish the propagation direction of metachronal waves, and quantitatively assess amplitude and dominant frequency of cilia beating at each spatial location. Compared to the raw PRD images, the phase-resolved dynamic wavefront imaging (PRDWI) method showed the direction and coordination of collective cilia movement more distinctively., Conclusions: The PRDWI technique can have broad application prospects for the diagnosis of human respiratory diseases and evaluation of the curative effect of treatments and open new perspectives in biomedical sciences., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-439/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Recently, numerous organic pollutants have been detected in water environment. The safety of our drinking water has attracted widespread attention. Effective methods to screen and identify high-concern substances are urgently needed. In this study, the combined workflow for the detection and identification of high-concern organic chemicals was established and applied to tap water samples from the Yangtze River Basin. The solid phase extraction (SPE) sorbents were compared and evaluated and finally the HLB cartridge was selected as the best one for most of the contaminants. Based on target, suspect and non-target analysis, 3023 chemicals/peaks were detected. Thirteen substances such as diundecyl phthalate (DUP), 2-hydroxyatrazine, dioxoaminopyrine and diethyl-2-phenylacetamide were detected in drinking water in the Yangtze River Basin for the very first time. Based on three kinds of prioritization principles, 49 ubiquitous, 103 characteristic chemicals and 13 inefficiently removed chemicals were selected as high-concern substances. Among them, 8, 31, 9, 3, 4 substances overlapped with the toxic, risky or high-concern chemicals lists in China, America, European Union, Japan, Korea, respectively. Specific management and removal strategies were further recommended. The workflow is efficient for identification of key pollutants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

➤: There are a growing number of opportunities within the field of orthopaedic surgery to address climate change and investigate ways to promote sustainability., ➤: Orthopaedic surgeons can take a proactive role in addressing climate change and its impacts within the areas of operating-room waste, carbon emissions from transportation and implant manufacturing, anesthetic gases, and water usage., ➤: Future studies are needed to further these initiatives on quantifying and decreasing environmental impact and furthering sustainable use of our resources., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H297 )., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

We estimated the total life expectancy (TLE), frailty-free life expectancy (FFLE), frail life expectancy (FLE), pre-frail life expectancy (PFLE), and FLE with and without disability among 2,000 Mexican Americans aged ≥67 years over an 18-year period. Frailty was defined as the presence of ≥2 criteria (weight loss, weakness, self-reported exhaustion, slowness). We used the Markov chain method to estimate the TLE, FFLE, FLE, PFLE, and FLE with and without disability by age and gender. TLE at age 67 was 17.49 years (women) and 15.54 years (men); FFLE was 6.50 years (women) and 6.45 years (men); PFLE was 6.48 years (women) and 5.42 years (men); FLE was 4.51 years (women) and 3.67 years (men); and FLE with disability was 2.13 years (women) and 1.13 years (men). In conclusion, Mexican American older women had fewer years of non-frail LE, more pre-frail or frail years, and more years with disability than men., Competing Interests: All authors declare no Conflicts of Interest related to this manuscript.

More and more contaminants in dust have been found to be glucocorticoid receptor (GR) disrupting chemicals. However, little is known about the related potency and responsible toxicants, especially for the main bioaccessible ones in dust. An effect-directed analysis (EDA)-based workflow was developed, including solvent-based exhaustive extraction/tenax-assisted bioaccessible extraction (TBE), high-throughput bioassays, suspect and non-target analysis, as well as in silico candidate selection, for a more realistic identification of responsible contaminants in dust. None of the 39 dust samples from 23 cities in China exhibited GR agonistic activity, while GR antagonistic potencies were detected in 34.8% of samples, being significantly different from the high detection frequency of GR agonistic activities in other environmental media. The GR antagonistic potencies of the dust samples were all reduced after bioaccessible extraction. The mean bioaccessibility of GR antagonistic potency compared with the related exhaustive extracts was 36.8%, and the lowest value was 9%. By using in silico candidate selection, greater than 99% candidate chemical structures which were found by a non-target screening strategy were removed. Di- n -butyl phthalate (D n BP), diisobutyl phthalate (DiBP), and nicotine (NIC) were responsible for the activities of the exhaustive extracts of dust, contributing up to 91% potencies. DiBP and D n BP were also responsible for the bioaccessible activities, contributing up to 79% potencies. However, the contribution from NIC decreased significantly and can be ignored because of its low bioaccessibility. This study suggests that the improved workflow combining extraction, reporter gene bioassays, suspect and non-target analysis, as well as in silico candidate selection is useful for EDA analysis in dust samples. In addition, exhaustive extraction may overestimate the risk of contaminants, while bioaccessibility evaluation based on bioaccessible extraction is essential in both effect evaluation and toxicant identification.

Objective: Peri-implantitis is characterized by peri-implant mucositis and alveolar bone resorption. This study investigated cholecystokinin ( CCK ) expression and the mechanism underlying its involvement in peri-implantitis., Methods: mRNA sequencing was performed using the Gene Expression Omnibus database GSE106090. Human bone marrow mesenchymal stem cells (hBMSCs) were pretreated with various concentrations of CCK (0, 10, 30, or 100 nM) for 1 hour before induction in osteogenic differentiation medium for 2 weeks. Alkaline phosphatase (ALP) activity was determined, and the cells were stained with alizarin red. The expression levels of TNFα and the osteogenic markers ALP , RUNX2 , and OCN were measured using quantitative real-time PCR. TNFα, phosphorylated P65, and total P65 levels were determined by western blot., Results: Compared with healthy individuals, 262 and 215 genes were up- and down-regulated, respectively, in the periodontal tissues of patients with peri-implantitis. CCK expression was significantly upregulated in patients with peri-implantitis. CCK reduced ALP activity, osteogenic differentiation, and levels of the osteogenic markers ALP , RUNX2 , and OCN . Moreover, CCK promoted levels of TNFα and phosphorylated P65, which is a marker of activation for the NF-κB inflammatory pathway., Conclusions: CCK regulates osteogenic differentiation through the TNFα/NF-κB axis in peri-implantitis.

Photo-mediated Ultrasound Therapy (PUT), as a new anti-vascular technique, can promote cavitation activity to selectively destruct blood vessels with a significantly lower amount of energy when compared to energy level required by other laser and ultrasound treatment therapies individually. Here, we report the development of a high speed PUT system based on a 50-kHz pulsed laser to achieve faster treatment, decreasing the treatment time by a factor of 20. Furthermore, we integrated it with optical coherence tomography angiography (OCTA) for real time monitoring. The feasibility of the proposed OCTA-guided PUT was validated through in vivo rabbit experiments. The addition of OCTA to PUT allows for quantitative prescreening and real time monitoring of treatment response, thereby enabling implementation of individualized treatment strategies., (© 2022. The Author(s).)

Background: The need for multidisciplinary care of patients with advanced limb threat is well established. We examined patient reported outcomes and health-related quality of life (HR-QoL) for those who completed a multidisciplinary extremity preservation program (EPP) at our institution., Methods: Patients with advanced limb threat, who had previously failed standard management at a tertiary-care center, were referred to EPP for evaluation by a multidisciplinary panel of vascular, plastic, orthopedic and podiatric surgeons, along with infectious disease, prosthetics, orthotics, imaging, palliative care, social work and wound nursing specialists. HR-QoL was quantified before and after EPP participation with the RAND-36 questionnaire. The validated RAND-36 assesses physical function, role limitations caused by physical and emotional health problems, social functioning, emotional well-being, energy, pain and general health perceptions., Results: From 2018 to 2020, 185 patients were referred to EPP. After review by the multidisciplinary panel, 120 were accepted into the program, 63 of whom completed their course of care; 9 were one-time consultations. The median number of EPP in-person care visits was 23 (13-54) per participant; 87.3% of patients received one or more surgical procedure, including operative debridement (73%), revascularization (44%), soft-tissue reconstruction or transplantation (46%), as well as hyperbaric oxygen therapy (11%) during their course of treatment. 85.7% of patients achieved complete wound healing, 41.5% occurring within 6 months. Ultimately, 14.3% required a major amputation. Graduates noted improvement in all categories of the HR-QoL upon completion, including those undergoing major amputation. On adjusted multivariate regression analysis, patients with immunocompromised status were more likely to show greater improvement in their social function (OR: 10.1; P < 0.044) and emotional role limitation (OR: 8.1; P = 0.042), while, patients with larger wound volume at presentation were more likely to have greater improvement in their general health (OR: 1.1; P < 0.049). Conversely, patients with a smoking history had less improvement in energy level (OR: 0.4; P = 0.044) and patients with dialysis-dependence had less improvement in social function (OR: 0.2; P = 0.034)., Conclusions: Coordinated, multidisciplinary extremity preservation program improves HR-QoL of patients with complex limb threat, including those who are immunocompromised with impaired social function and emotional role limitations. Furthermore, study is warranted to better characterize the generalizability of this approach, including considerations of cost-effectiveness, wound recidivism, and limiting the number of in-person visits required to achieve complete healing., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Although pain is common in osteoarthritis, most people fail to achieve adequate analgesia. Increasing acknowledgement of the contribution of pain sensitisation has resulted in the investigation of medications affecting pain processing with central effects. Antidepressants contribute to pain management in other conditions where pain sensitisation is present., Objectives: To assess the benefits and harms of antidepressants for the treatment of symptomatic knee and hip osteoarthritis in adults., Search Methods: We used standard, extensive Cochrane search methods. The latest search was January 2021., Selection Criteria: We included randomised controlled trials of adults with osteoarthritis that compared use of antidepressants to placebo or alternative comparator. We included trials that focused on efficacy (pain and function), treatment-related adverse effects and had documentation regarding discontinuation of participants. We excluded trials of less than six weeks of duration or had participants with concurrent mental health disorders., Data Collection and Analysis: We used standard Cochrane methods. Major outcomes were pain; responder rate; physical function; quality of life; and proportion of participants who withdrew due to adverse events, experienced any adverse events or had serious adverse events. Minor outcomes were proportion meeting the OARSI (Osteoarthritis Research Society International) Response Criteria, radiographic joint structure changes and proportion of participants who dropped out of the study for any reason. We used GRADE to assess certainty of evidence., Main Results: Nine trials (2122 participants) met the inclusion criteria. Seven trials examined only knee osteoarthritis. Two also included participants with hip osteoarthritis. All trials compared antidepressants to placebo, with or without non-steroidal anti-inflammatory drugs. Trial sizes were 36 to 388 participants. Most participants were female, with mean ages of 54.5 to 65.9 years. Trial durations were 8 to 16 weeks. Six trials examined duloxetine. We combined data from nine trials in meta-analyses for knee and hip osteoarthritis. One trial was at low risk of bias in all domains. Five trials were at risk of attrition and reporting bias. High-certainty evidence found that antidepressants resulted in a clinically unimportant improvement in pain compared to placebo. Mean reduction in pain (0 to 10 scale, 0 = no pain) was 1.7 points with placebo and 2.3 points with antidepressants (mean difference (MD) -0.59, 95% confidence interval (CI) -0.88 to -0.31; 9 trials, 2122 participants). Clinical response was defined as achieving a 50% or greater reduction in 24-hour mean pain. High-certainty evidence demonstrated that 45% of participants receiving antidepressants had a clinical response compared to 28.6% receiving placebo (RR 1.55, 95% CI 1.32 to 1.82; 6 RCTs, 1904 participants). This corresponded to an absolute improvement in pain of 16% more responders with antidepressants (8.9% more to 26% more) and a number needed to treat for an additional beneficial effect (NNTB) of 6 (95% CI 4 to 11). High-certainty evidence showed that the mean improvement in function (on 0 to 100 Western Ontario and McMaster Universities Arthritis Index, 0 = best function) was 10.51 points with placebo and 16.16 points with antidepressants (MD -5.65 points, 95% CI -7.08 to -4.23; 6 RCTs, 1909 participants). This demonstrates a small, clinically unimportant response. Moderate-certainty evidence (downgraded for imprecision) showed that quality of life measured using the EuroQol 5-Dimension scale (-0.11 to 1.0, 1.0 = perfect health) improved by 0.07 points with placebo and 0.11 points with antidepressants (MD 0.04, 95% CI 0.01 to 0.07; 3 RCTs, 815 participants). This is clinically unimportant. High-certainty evidence showed that total adverse events increased in the antidepressant group (64%) compared to the placebo group (49%) (RR 1.27, 95% CI 1.15 to 1.41; 9 RCTs, 2102 participants). The number needed to treat for an additional harmful outcome (NNTH) was 7 (95% CI 5 to 11). Low-certainty evidence (downgraded twice for imprecision for very low numbers of events) found no evidence of a difference in serious adverse events between groups (RR 0.94, 95% CI 0.46 to 1.94; 9 RCTs, 2101 participants). The NNTH was 1000.  Moderate-certainty evidence (downgraded for imprecision) showed that 11% of participants receiving antidepressants withdrew from trials due to an adverse event compared to 5% receiving placebo (RR 2.15, 95% CI 1.56 to 2.97; 6 RCTs, 1977 participants). The NNTH was 17 (95% CI 10 to 35)., Authors' Conclusions: There is high-certainty evidence that use of antidepressants for knee osteoarthritis leads to a non-clinically important improvement in mean pain and function. However, a small number of people will have a 50% or greater important improvement in pain and function. This finding was consistent across all trials. Pain in osteoarthritis may be due to a variety of causes that differ between individuals. It may be that the cause of pain that responds to this therapy is only present in a small number of people. There is moderate-certainty evidence that antidepressants have a small positive effect on quality of life with heterogeneity between trials. High-certainty evidence indicates antidepressants result in more adverse events and moderate-certainty evidence indicates more withdrawal due to adverse events. There was little to no difference in serious adverse events (low-certainty evidence due to low numbers of events). This suggests that if antidepressants were being considered, there needs to be careful patient selection to optimise clinical benefit given the known propensity for adverse events with antidepressant use. Future trials should include alternative antidepressant agents or phenotyping of pain in people with osteoarthritis, or both., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Extreme bradycardia (EB), extreme tachycardia (ET), ventricular tachycardia (VT), and ventricular flutter (VF) are the four types of life-threatening arrhythmias, which are symptoms of cardiovascular diseases. Therefore, in this study, a method of life-threatening arrhythmia recognition is proposed based on pulse rate variability (PRV). First, noise and interference are wiped out from the arterial blood pressure (ABP), and the PRV signal is extracted. Then, 19 features are extracted from the PRV signal, and 15 features with highly important and significant variation were selected by random forest (RF). Finally, the back-propagation neural network (BPNN), extreme learning machine (ELM), and decision tree (DT) are used to build, train, and test classifiers to detect life-threatening arrhythmias. The experimental data are obtained from the MIMIC/Fantasia and the 2015 Physiology Net/CinC Challenge databases. The experimental results show that the DT classifier has the best average performance with accuracy and kappa coefficient ( kappa ) of 98.76 ± 0.08% and 97.59 ± 0.15%, which are higher than those of the BPNN ( accuracy = 94.85 ± 1.33% and kappa = 89.95 ± 2.62%) and ELM ( accuracy = 95.05 ± 0.14% and kappa = 90.28 ± 0.28%) classifiers. The proposed method shows better performance in identifying four life-threatening arrhythmias compared to existing methods and has potential to be used for home monitoring of patients with life-threatening arrhythmias., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chou, Liu, Gong and Chou.)

Disrupting the interplay between programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) is a powerful immunotherapeutic approach to cancer treatment. Herein, spherical nucleic acid (SNA) liposomal nanoparticle conjugates that incorporate a newly designed antisense DNA sequence specifically against PD-L1 (immune checkpoint inhibitor SNAs, or IC-SNAs) are explored as a strategy for blocking PD-1/PD-L1 signaling within the tumor microenvironment (TME). Concentration-dependent PD-L1 silencing with IC-SNAs is observed in MC38 colon cancer cells, where IC-SNAs decrease both surface PD-L1 (sPD-L1) and total PD-L1 expression. Furthermore, peritumoral administration of IC-SNAs in a syngeneic mouse model of MC38 colon cancer leads to reduced sPD-L1 expression in multiple cell populations within the TME, including tumor cells, dendritic cells, and myeloid derived suppressor cells. The treatment effectively increases CD8 + T cells accumulation and functionality in the TME, which ultimately inhibits tumor growth and extends animal survival. Taken together, these data show that IC-SNA nanoconstructs are capable of disrupting the PD-1/PD-L1 interplay via gene regulation, thereby providing a promising avenue for cancer immunotherapy., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Here we describe the development and evaluation of a survey instrument to assess the research suitability of veterinary electronic medical records (EMRs) through the conduct of two studies as part of the Dog Aging Project (DAP). In study 1, four reviewers used the instrument to score a total of 218 records in an overlapping matrix of pairs to assess inter-rater agreement with respect to appropriate format (qualification), identification match (verification), and record quality. Based upon the moderate inter-rater agreement with respect to verification and the relatively large number of records that were incorrectly rejected the instrument was modified and more specific instructions were provided. In study 2, a modified instrument was again completed by four reviewers to score 100 different EMRs. The survey scores were compared to a gold standard of board-certified specialist review to determine receiver operating curve statistics. The refined survey had substantial inter-rater agreement across most qualification and verification questions. The cut-off value identified had a sensitivity of 95 and 96% (by reviewer 1 and reviewer 2, respectively) and a specificity of 82% and 91% (by reviewer 1 and reviewer 2, respectively) to predict gold standard acceptance or rejection of the record. Using just qualification and verification questions within the instrument (as opposed to full scoring) minimally impacted sensitivity and specificity and resulted in substantial time savings in the review process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Praczko, Tinkle, Arkenberg, McClelland, Creevy, Tolbert, Barnett, Chou, Evans, McNulty, Dog Aging Project Consortium and Levine.)

Aim: This in vitro study aimed to investigate the roles of aspirin (ASA) and its concentrations on the odontogenesis of human dental pulp cells (HDPCs) and to investigate the influence of ASA on TGF- β 1 liberation from dentin. Methodology . HDPCs were cultured in a culture medium with 25, 50, 75, 100, and 200  μ ·g/mL ASA and 0  μ ·g/mL ASA as a control. The mitochondrial activity of HDPCs was assessed using an MTT assay. Crystal violet staining and triton were used to evaluate cell proliferation rates. ALP activity was measured with a fluorometric assay. Expressions of DSP and RUNX2 were determined with the ELISA. DSP and RUNX2 mRNA levels were measured with RT-qPCR. Alizarin red staining was conducted to evaluate the mineralized nodule formation. Dentin slices were submerged in PBS (negative control), 17% EDTA (positive control), and ASA before collecting the solution for TGF- β 1 quantification by the ELISA. The data were analyzed by the t- tests and ANOVA, followed by the Tukey post hoc tests. P values < 0.05 were considered statistically significant., Results: The results showed that 25-50  μ ·g/mL ASA promoted mitochondrial activity of HDPCs at 72 h ( P < 0.05) and yielded significantly higher proliferation rates of HDPCs than the control at 14d and 21d ( P < 0.001). All concentrations of ASA promoted odontogenic differentiation of HDPCs by enhancing the levels of DSP and RUNX2, their mRNA expression, and mineralization in a dose-dependent manner. Also, ASA yielded significantly higher TGF- β 1 liberation after conditioning dentin for 5 min (25, 200  μ ·g/mL; P < 0.001) and 10 min (200  μ ·g/mL; P < 0.05)., Conclusions: This in vitro study demonstrated that ASA, especially in high concentrations, promoted the odontogenesis of HDPCs and TGF- β 1 liberation from dentin, showing the potential of being incorporated into the novel pulp capping materials for dental tissue regeneration., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 V. Khampatee et al.)

The influence of health literacy on involvement in decision-making in orthopedic surgery has not been analyzed and could inform processes to engage patients. The goal of this study was to determine the relationship between health literacy and the patient's preferred involvement in decision-making. We conducted a cross-sectional observational study of patients presenting to a multispecialty orthopedic clinic. Patients completed the Literacy in Musculoskeletal Problems (LiMP) survey to evaluate their health literacy and the Control Preferences Scale (CPS) survey to evaluate their preferred level of involvement in decision-making. Statistical analysis was performed with Pearson's correlation and multivariable logistic regression. Thirty-seven percent of patients had limited health literacy (LiMP score <6). Forty-eight percent of patients preferred to share decision-making with their physician equally (CPS score=3), whereas 38% preferred to have a more active role in decision-making (CPS score≤2). There was no statistically significant correlation between health literacy and patient preference for involvement in decision-making ( r =0.130; P =.150). Among patients with orthopedic conditions, there is no significant relationship between health literacy and preferred involvement in decision-making. Results from studies in other specialties that suggest that limited health literacy is associated with a preference for less involvement in decision-making are not generalizable to orthopedic surgery. Efforts to engage patients to be informed and participatory in decision-making through the use of decision aids and preference elicitation tools should be directed toward variation in preference for involvement in decision-making, but not toward patient health literacy. [ Orthopedics . 2022;45(4):227-232.].

Background: Osteochondral lesions of the talus (OLTs) have been traditionally treated with bone marrow stimulation techniques such as microfracture. However, conventional microfracture results in a biomechanically weaker repair tissue of predominantly type I collagen. Acellular micronized cartilage matrix (MCM) serves as a bioactive scaffold to restore hyaline cartilage. The purpose was to compare short-term outcomes after microfracture with and without augmentation with MCM for medial-sided OLTs., Methods: A retrospective review was performed between 2010-2019 for medial-sided OLTs undergoing treatment with either microfracture augmented with MCM or isolated microfracture. The MCM was hydrated with either bone marrow aspirate concentrate (BMAC) or platelet-rich plasma (PRP). Outcomes included visual analogue scale (VAS) pain scores, Foot and Ankle Activity Measure (FAAM) scores, return-to-daily activities, and return-to-sport., Results: 48 patients (14 MCM with PRP, 6 MCM with BMAC; 28 isolated microfracture) with average age 35.5 years (range: 13.8-67.2 years) and mean follow-up 4.0 ± 3.4 years (range,.13-10.7) were included. There was no difference in average lesion size between MCM and microfracture groups (64.0 ± 49.4 mm 2 versus 57.3 ± 44.2 mm 2 , P = .63) and a trend toward larger lesion size for BMAC compared to PRP (106.5 ± 59.2 versus 45.9 ± 32.1 mm 2 , P = .056). There was no difference in time to return-to-activity (83.5 ± 18.8 versus 87.3 ± 49.1 days) or return-to-sports (151.9 ± 62.2 versus 165 ± 99.2 days) with MCM versus isolated microfracture. However, the MCM group had a significantly greater improvement in VAS pain score at final follow-up (4.9 ± 2.2 versus 2.7 ± 2.6, P = .0032) and significantly higher post-operative FAAM-Activities of Daily Living subscale scores (97.2 ± 8.2 versus 79.7 ± 32.8, P = .033)., Conclusions: Augmenting microfracture with MCM hydrated with PRP or BMAC may result in beneficial changes in pain scores and activities of daily living, but similar return-to-activities and return-to-sport times compared to microfracture alone in management of medial OLT., Level of Evidence: IV., (Copyright © 2021 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Continuous blood pressure (BP) measurement is crucial for long-term cardiovascular monitoring, especially for prompt hypertension detection. However, most of the continuous BP measurements rely on the pulse transit time (PTT) from multiple-channel physiological acquisition systems that impede wearable applications. Recently, wearable and smart health electronics have become significant for next-generation personalized healthcare progress. This study proposes an intelligent single-channel bio-impedance system for personalized BP monitoring. Compared to the PTT-based methods, the proposed sensing configuration greatly reduces the hardware complexity, which is beneficial for wearable applications. Most of all, the proposed system can extract the significant BP features hidden from the measured bio-impedance signals by an ultra-lightweight AI algorithm, implemented to further establish a tailored BP model for personalized healthcare. In the human trial, the proposed system demonstrates the BP accuracy in terms of the mean error (ME) and the mean absolute error (MAE) within 1.7 ± 3.4 mmHg and 2.7 ± 2.6 mmHg, respectively, which agrees with the criteria of the Association for the Advancement of Medical Instrumentation (AAMI). In conclusion, this work presents a proof-of-concept for an AI-based single-channel bio-impedance BP system. The new wearable smart system is expected to accelerate the artificial intelligence of things (AIoT) technology for personalized BP healthcare in the future.

Background: Many named species as defined in current bacterial taxonomy correspond to species complexes. Uncertainties regarding the organization of their genetic diversity challenge research efforts. We utilized the Agrobacterium tumefaciens species complex (a.k.a. Agrobacterium biovar 1), a taxon known for its phytopathogenicity and applications in transformation, as a study system and devised strategies for investigating genome diversity and evolution of species complexes., Results: We utilized 35 genome assemblies, including 14 newly generated ones, to achieve a phylogenetically balanced sampling of A. tumefaciens. Our genomic analysis suggested that the 10 genomospecies described previously are distinct biological species and supported a quantitative guideline for species delineation. Furthermore, our inference of gene content and core-genome phylogeny allowed for investigations of genes critical in fitness and ecology. For the type VI secretion system (T6SS) involved in interbacterial competition and thought to be conserved, we detected multiple losses and one horizontal gene transfer. For the tumor-inducing plasmids (pTi) and pTi-encoded type IV secretion system (T4SS) that are essential for agrobacterial phytopathogenicity, we uncovered novel diversity and hypothesized their involvement in shaping this species complex. Intriguingly, for both T6SS and T4SS, genes encoding structural components are highly conserved, whereas extensive diversity exists for genes encoding effectors and other proteins., Conclusions: We demonstrate that the combination of a phylogeny-guided sampling scheme and an emphasis on high-quality assemblies provides a cost-effective approach for robust analysis in evolutionary genomics. We show that the T6SS VgrG proteins involved in specific effector binding and delivery can be classified into distinct types based on domain organization. The co-occurrence patterns of VgrG-associated domains and the neighboring genes that encode different chaperones/effectors can be used to infer possible interacting partners. Similarly, the associations between plant host preference and the pTi type among these strains can be used to infer phenotype-genotype correspondence. Our strategies for multi-level investigations at scales that range from whole genomes to intragenic domains and phylogenetic depths from between- to within-species are applicable to other bacteria. Furthermore, modularity observed in the molecular evolution of genes and domains is useful for inferring functional constraints and informing experimental works., (© 2022. The Author(s).)

Background & Aims: Fecal microbiota transplantation (FMT) is an emerging treatment modality for ulcerative colitis (UC). Several randomized controlled trials have shown efficacy for FMT in the treatment of UC, but a better understanding of the transferable microbiota and their immune impact is needed to develop more efficient microbiome-based therapies for UC., Methods: Metagenomic analysis and strain tracking was performed on 60 donor and recipient samples receiving FMT for active UC. Sorting and sequencing of immunoglobulin (Ig) A-coated microbiota (called IgA-seq) was used to define immune-reactive microbiota. Colonization of germ-free or genetically engineered mice with patient-derived strains was performed to determine the mechanism of microbial impact on intestinal immunity., Results: Metagenomic analysis defined a core set of donor-derived transferable bacterial strains in UC subjects achieving clinical response, which predicted response in an independent trial of FMT for UC. IgA-seq of FMT recipient samples and gnotobiotic mice colonized with donor microbiota identified Odoribacter splanchnicus as a transferable strain shaping mucosal immunity, which correlated with clinical response and the induction of mucosal regulatory T cells. Colonization of mice with O splanchnicus led to an increase in Foxp3 + /RORγt + regulatory T cells, induction of interleukin (IL) 10, and production of short chain fatty acids, all of which were required for O splanchnicus to limit colitis in mouse models., Conclusions: This work provides the first evidence of transferable, donor-derived strains that correlate with clinical response to FMT in UC and reveals O splanchnicus as a key component promoting both metabolic and immune cell protection from colitis. These mechanistic features will help enable strategies to enhance the efficacy of microbial therapy for UC. Clinicaltrials.gov ID NCT02516384., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Developing low-cost and highly efficient catalysts toward the efficient oxygen evolution reaction (OER) is highly desirable for photoelectrochemical (PEC) water splitting. Herein, we demonstrated that N-incorporation could efficiently activate NiFeO x catalysts for significantly enhancing the oxygen evolution activity and stability of BiVO 4 photoanodes, and the photocurrent density has been achieved up to 6.4 mA cm -2 at 1.23 V (vs. reversible hydrogen electrode (RHE), AM 1.5 G). Systematic studies indicate that the partial substitution of O sites in NiFeO x catalysts by low electronegative N atoms enriched the electron densities in both Fe and Ni sites. The electron-enriched Ni sites conversely donated electrons to V sites of BiVO 4 for restraining V 5+ dissolution and improving the PEC stability, while the enhanced hole-attracting ability of Fe sites significantly promotes the oxygen-evolution activity. This work provides a promising strategy for optimizing OER catalysts to construct highly efficient and stable PEC water splitting devices., (© 2021. The Author(s).)