Photo- or Electrochemical Cyclization of Dienes with Diselenides to Access Seleno-Benzo[b]azepines.

A cascade selenylation/cyclization of dienes with diselenides has been realized under visible-light irradiation or electrolysis conditions. Employing O2 or electricity as a "green" oxidant, this protocol provides a green and efficient method for an array of biologically important seleno-benzo[b]azepine derivatives in moderate to good yields. The direct sunlight irradiation and gram-scale reaction render the approach practical and attractive.

Asthma does not influence the severity of COVID-19: a meta-analysis.

OBJECTIVE: Previous studies have reported a correlation between coronavirus disease-2019 (COVID-19) and asthma. However, data on whether asthma constitutes a risk factor for COVID-19 and the prevalence of asthma in COVID-19 cases still remain scant. Here, we interrogated and analyzed the association between COVID-19 and asthma. METHODS: In this study, we systematically searched PubMed, Embase, and Web of Science databases for studies published between January 1 and August 28, 2020. We included studies that reported the epidemiological and clinical features of COVID-19 and its prevalence in asthma patients. We excluded reviews, animal trials, single case reports, small case series and studies evaluating other coronavirus-related illnesses. Raw data from the studies were pooled into a meta-analysis. RESULTS: We analyzed findings from 18 studies, including asthma patients with COVID-19. The pooled prevalence of asthma in COVID-19 cases was 0.08 (95% CI, 0.06-0.11), with an overall I2 of 99.07%, p < 0.005. The data indicated that asthma did not increase the risk of developing severe COVID-19 (odds ratio [OR] 1.04 (95% CI, 0.75-1.46) p = 0.28; I2=20%). In addition, there was no significant difference in the incidence of asthma with age in COVID-19 infections [OR] 0.77(95% CI, 0.59-1.00) p = 0.24; I2=29%). CONCLUSION: Taken together, our data suggested that asthma is not a significant risk factor for the development of severe COVID-19.

The Association between Allergic Rhinitis and COVID-19: A Systematic Review and Meta-Analysis.

Objective: Previous studies have yielded conflicting results regarding the association of coronavirus disease 2019 (COVID-19) with allergic rhinitis (AR). Data on AR prevalence in COVID-19 patients are limited. Consequently, whether AR is a harmful or protective factor for COVID-19 patients remains controversial. Therefore, we analyzed the relationship between COVID-19 and AR. Methods: We systematically searched PubMed, Embase, Cochrane, and Web of Science databases for studies published between January 1, 2020 and January 11, 2022. We included studies reporting the epidemiological and clinical characteristics of COVID-19 and its incidence in patients with AR. We excluded letters, case reports, literature review articles, non-English language article, and non-full-text articles. The raw data from these studies were pooled into a meta-analysis. Results: We analyzed the results of nine studies. The prevalence of AR in patients with COVID-19 was 0.13 (95% confidence interval [CI] 0.04-0.25), with an overall I 2 of 99.77%, P=0.24. COVID-19 patients with AR are less prone to severe disease (odds ratio [OR] = 0.79, 95% CI, 0.52-1.18, P=0.25) and hospitalization (OR = 0.23, 95%CI, 0.02-2.67, P ≤ 0.0001) than patients without AR. Conclusion: Our data suggest that allergic rhinitis is a protective factor in patients with COVID-19.

Organocatalytic Reaction of Chromone-Oxindole Synthon: Access to Chromanone-Based Spirocyclohexaneoxindoles with Five Adjacent Stereocenters.

An efficient strategy for stereo-controlled synthesis of potential biological and structurally complex chromanone-based spirocyclohexaneoxindoles via an organocatalytic domino formal double Michael cycloaddition of bifunctional chromone-oxindole synthons and nitroolefins is reported. These products possessing five adjacent stereocenters including one spiro quaternary carbon center, were smoothly afforded in up to 85% yield, >99% ee, and >20:1 dr. This strategy benefits from the intramolecular nature of the second Michael reaction step, through counterbalancing the lower electrophilicity of these unactivated chromones to facilitate the reaction.

A Mechanistic Investigation of Methylene Blue and Heparin Interactions and Their Photoacoustic Enhancement.

We recently reported a real-time method to measure heparin in human whole blood based on the photoacoustic change of methylene blue (MB). Intriguingly, the MB behaved unlike other "turn on" photoacoustic probes-the absorbance decreased as the photoacoustic signal increased. The underlying mechanism was not clear and motivated this study. We studied the binding mechanism of MB and heparin in water and phosphate buffer saline (PBS) with both experimental and computational methods. We found that the photoacoustic enhancement of the MB-heparin mixture was a result of MB-heparin aggregation due to charge neutralization and resulting sequestration of MB in these aggregates. The sequestration of MB in the MB-heparin aggregates led to decreased absorbance-there was simply less free dye in solution to absorb light. The highest photoacoustic signal and aggregation occurred when the number of negatively charged sulfate groups on heparin was approximately equal to the number of positively charged MB molecule. The MB-heparin aggregates dissociated when there were more sulfated groups from heparin than MB molecules because of the electrostatic repulsion between negatively charged sulfate groups. PBS facilitated MB dimer formation regardless of heparin concentration and reprecipitated free MB in aggregates due to ionic strength and ionic shielding. Further molecular dynamics experiments found that binding of heparin occurred at the sulfates and glucosamines in heparin. Phosphate ions could interact with the heparin via sodium ions to impair the MB-heparin binding. Finally, our model found 3.7-fold more MB dimerization upon addition of heparin in MB solution confirming that heparin facilitates MB aggregation. We conclude that the addition of heparin in MB decreases the absorbance of the sample because of MB-heparin aggregation leading to fewer MB molecules in solution; however, the aggregation also increases the PA intensity because the MB molecules in the MB-heparin aggregate have reduced degrees of freedom and poor heat transfer to solvent.

Switchable Photoacoustic Intensity of Methylene Blue via Sodium Dodecyl Sulfate Micellization.

The interaction between methylene blue (MB) and sodium dodecyl sulfate (SDS) has been widely studied spectroscopically, but details about their interactions remain unclear. Here, we combined photoacoustic (PA) imaging with nanoparticle tracking analysis (NTA) and spectroscopy to further elucidate this interaction. PA imaging of 0.05 mM MB showed a 492-fold increase in intensity upon the addition of 3.47 mM SDS. Higher concentrations above SDS's critical micelle concentration (CMC) at 8.67 mM decreased the PA intensity by 54 times. Relative quantum yield measurements indicated that PA intensity increased as a result of fluorescence quenching. Meanwhile, NTA indicated an increased number of nonmicellar MB/SDS clusters at SDS concentrations below the CMC varying in size from 80 to 400 nm as well as a decreased number above the CMC. This trend suggested that MB/SDS clusters are responsible for the PA intensity enhancement. Comparison of PA intensities and spectral shifts with MB/hexadecyltrimethylammonium bromide, MB/sodium octyl sulfate, and MB/sodium chloride demonstrated that MB was bound to the sulfate moiety of SDS before and after micellization. Our observations suggest that MB forms aggregates with SDS at premicellar concentrations, and the MB aggregates disassociate as monomers that are bound to the sulfate moiety of SDS at micellar concentrations. These findings further clarify the process by which MB and SDS interact and demonstrate the potential for developing MB-/SDS-based contrast agents.

A Nanoscale Tool for Photoacoustic-Based Measurements of Clotting Time and Therapeutic Drug Monitoring of Heparin.

Heparin anticoagulation therapy is an indispensable feature of clinical care yet has a narrow therapeutic window and is the second most common intensive care unit (ICU) medication error. The active partial thromboplastin time (aPTT) monitors heparin but suffers from long turnaround times, a variable reference range, limited utility with low molecular weight heparin, and poor correlation to dose. Here, we describe a photoacoustic imaging technique to monitor heparin concentration using methylene blue as a simple and Federal Drug Administration-approved contrast agent. We found a strong correlation between heparin concentration and photoacoustic signal measured in phosphate buffered saline (PBS) and blood. Clinically relevant heparin concentrations were detected in blood in 32 s with a detection limit of 0.28 U/mL. We validated this imaging approach by correlation to the aPTT (Pearson's r = 0.86; p < 0.05) as well as with protamine sulfate treatment. This technique also has good utility with low molecular weight heparin (enoxaparin) including a blood detection limit of 72 µg/mL. We then used these findings to create a nanoparticle-based hybrid material that can immobilize methylene blue for potential applications as a wearable/implantable heparin sensor to maintain drug levels in the therapeutic window. To the best of our knowledge, this is the first use of photoacoustics to image anticoagulation therapy with significant potential implications to the cardiovascular and surgical community.

SU-8 nanoimprint fabrication of wire-grid polarizers using deep-UV interference lithography.

We describe a new fabrication method for making wire-grid polarizers for the visible and near-IR based on deep-UV interference lithography, nanoimprint, and glancing angle deposition. We fabricated aluminum wire grids with periods ranging from 375 to 230 nm with heights from 145 to 110 nm, respectively. The measured extinction ratio was as high as 220:1 at 1064 nm. The performance of the polarizer is limited by the roughness and porosity of the Al film and the underlying SU-8 structure. This method allows patterning of wire grids on any substrate material, which makes this an attractive method for fabricating wire-grid micropolarizers in a timely and cost-effective manner.

Boosting the effectiveness of UV filters and sunscreen formulations using photostable, non-toxic inorganic platelets.

We have studied the size-dependent optical scattering of aqueous suspensions containing Mg2Al-LDH platelets, which exhibit high total- and side-scatterings. By incorporating 3 wt% Mg2Al-LDH platelets (280 nm) in a commercial sunscreen formulation, we achieved a twofold Sun Protection Factor boost, providing a promising, high-efficient and non-toxic strategy to enhance sunscreen effectiveness.

Low-Spin Fe Redox-Based Prussian Blue with excellent selective dual-band electrochromic modulation and energy-saving applications.

Dual-band electrochromic materials (DBEMs) are of utmost importance for smart windows to realize independent control of the visible (VIS) and near-infrared (NIR) light. However, very few single-component DBEMs are capable of independently and effectively controlling both VIS and NIR light. Here, we present Prussian blue (PB) with remarkable performance to replace the composite DBEMs that require deliberate design and complicated preparation. Excellent durability and capacity were achieved simultaneously due to the activated low-spin Fe in PB. A dual-band electrochromic device (DBED) by using PB thin films as electrochromic layers was constructed, exhibiting superior dual-band electrochromic performance, energy storage performance and memory effect. We show that the energy-saving DBED can be bleached without applying any external bias potential, and can be colored by using a commercial photovoltaic solar panel under ambient solar irradiation. The stored energy during coloration can be further used to light up the lights. Finally, the coloration mechanism of the DBED was studied by the density functional theory calculations, to shed light on the large optical transmittance modulation in both VIS and NIR regions. The new insights will advance the design of efficient and durable DBEMs and the development of bi-functional smart windows.

An explainable deep learning framework for characterizing and interpreting human brain states.

Deep learning approaches have been widely adopted in the medical image analysis field. However, a most of existing deep learning approaches focus on achieving promising performances such as classification, detection, and segmentation, and much less effort is devoted to the explanation of the designed models. Similarly, in the brain imaging field, many deep learning approaches have been designed and applied to characterize and predict human brain states. However, these models lack interpretation. In response, we propose a novel domain knowledge informed self-attention graph pooling-based (SAGPool) graph convolutional neural network to study human brain states. Specifically, the dense individualized and common connectivity-based cortical landmarks system (DICCCOL, structural brain connectivity profiles) and holistic atlases of functional networks and interactions system (HAFNI, functional brain connectivity profiles) are integrated with the SAGPool model to better characterize and interpret the brain states. Extensive experiments are designed and carried out on the large-scale human connectome project (HCP) Q1 and S1200 dataset. Promising brain state classification performances are observed (e.g., an average of 93.7% for seven-task classification and 100% for binary classification). In addition, the importance of the brain regions, which contributes most to the accurate classification, is successfully quantified and visualized. A thorough neuroscientific interpretation suggests that these extracted brain regions and their importance calculated from self-attention graph pooling layer offer substantial explainability.

Intrabasal Plane Defect Formation in NiFe Layered Double Hydroxides Enabling Efficient Electrochemical Water Oxidation.

Defect engineering has proven to be one of the most effective approaches for the design of high-performance electrocatalysts. Current methods to create defects typically follow a top-down strategy, cutting down the pristine materials into fragmented pieces with surface defects yet also heavily destroying the framework of materials that imposes restrictions on the further improvements in catalytic activity. Herein, we describe a bottom-up strategy to prepare free-standing NiFe layered double hydroxide (LDH) nanoplatelets with abundant internal defects by controlling their growth behavior in acidic conditions. Our best-performing nanoplatelets exhibited the lowest overpotential of 241 mV and the lowest Tafel slope of 43 mV/dec for the oxygen evolution reaction (OER) process, superior to the pristine LDHs and other reference cation-defective LDHs obtained by traditional etching methods. Using both material characterization and density functional theory (DFT) simulation has enabled us to develop relationships between the structure and electrochemical properties of these catalysts, suggesting that the enhanced electrocatalytic activity of nanoplatelets mainly results from their defect-abundant structure and stable layered framework with enhanced exposure of the (001) surface.

Instruction-based learning: A review.

Humans are able to learn to implement novel rules from instructions rapidly, which is termed "instruction-based learning" (IBL). This remarkable ability is very important in our daily life in both learning individually or working as a team, and almost every psychology experiment starts with instructing participants. Many recent progresses have been made in IBL research both psychologically and neuroscientifically. In this review, we discuss the role of language in IBL, the importance of the first trial performance in IBL, why IBL should be considered as a goal-directed behavior, intelligence and IBL, cognitive flexibility and IBL, how behaviorally relevant information is processed in the lateral prefrontal cortex (LPFC), how the lateral frontal cortex (LFC) networks work as a functional hierarchy during IBL, and the cortical and subcortical contributions to IBL. Finally, we develop a neural working model for IBL and provide some sensible directions for future research.

Visualizing Research Trends and Identifying Hotspots of Traditional Chinese Medicine (TCM) Nursing Technology for Insomnia: A 18-Years Bibliometric Analysis of Web of Science Core Collection.

Objective: To explore the research hotspot and frontier direction of TCM nursing of insomnia and provide reference for the follow-up study of the optimal scheme of TCM nursing of insomnia. Background: Insomnia is a common sleep-wake disorder, affects 6-10% of adults and was associated with independent higher risks of cardiovascular disease and diabetes. TCM Nursing Techniques of insomnia has a long history and has shown a definite impact. However, it's still lack of analysis in the field of the most commonly used and effective techniques, as well as the co-morbidities associated with insomnia. Therefore, the database was searched and analyzed to find effective TCM Nursing Techniques for insomnia and related diseases related to insomnia. Method: Randomized controlled trials on the intervention of TCM Nursing Techniques in insomnia were retrieved from Web of Science Core Collection and imported into CiteSpace 5.6.R5 visualization software. The works of literature were co-cited by keywords authors and institutions for visual analysis, and the co-morbidities associated with insomnia of TCM Nursing Techniques in literature was extracted manually. The symptoms of co-morbidities associated with insomnia were imported into Cytoscape 3.9.0 software and clustered by CytoHubba. Result: As of October 20, 2021, the literature published in the last 20 years from Web of Science Core Collection was screened, and the publication period of the included literature was from 2004 to 2021. From 2016 to now, the total number of articles has been increasing. A total of 146 articles were included, and the highest production year was 2020. There is little cooperation between states, institutions, and authors. China (including Hong Kong and Taiwan) and Hong Kong Polytech University are leading countries and institutions in this area. MYUNGHAENG HUR is the most cited author, and J ALTERN COMPLEM MED is the most cited journal. According to cluster analysis and keyword frequency, auricular therapy, aromatherapy, and acupressure are the three most commonly used techniques. While the top five co-morbidities are fatigue, anxiety, depression, pain and hemodialysis. The three frontier topics and the main research directions are sleep quality, comorbid insomnia and clinical trial design. Conclusion: We found that acupressure, aromatherapy, and auricular acupoint therapy are the most commonly used nursing methods of TCM to intervene in insomnia. However, these studies have limitations such as small sample size, lack of objectivity in evaluating sleep quality, and high heterogeneity of intervention measures, which are not conducive to forming TCM clinical nursing guidelines. Therefore, it is necessary to adopt objectified sleep quality evaluation methods, select suitable acupoints according to TCM theories, and design multi-center large-sample clinical trials based on the safety principle of randomized blind control. This study provides an in-depth perspective for insomnia research on TCM Nursing Techniques and includes information for follow-up research on TCM Nursing Techniques of insomnia.

Rosai-Dorfman disease originating from nasal septal mucosa and presenting with nasal dorsum collapse: A case report with literature review.

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is an uncommon histiocytic disease with idiopathic etiology and unique pathology. Extra-nodal RDD that occurs in the nasal cavity is extremely unusual and the characteristic clinical features are unknown. Herein, we report a case of nasal septum RDD, with intermittent epistaxis from the left nasal cavity, which led to collapse of the nasal bridge. The patient underwent surgical biopsy, and a diagnosis of nasal septum RDD was established. No further treatment was performed. An enlarged mass was found in the second postoperative year which was treated by surgical excision in the third postoperative year. To improve the current diagnostic and therapeutic approach of extra-nodal RDD, we incorporate previous reports from the literature to discuss the pathological characteristics, pathogenesis, clinical manifestations, diagnosis, and therapy for this rare disease.

Application and prospect of quasi-targeted metabolomics in age-related hearing loss.

Age-related hearing loss (ARHL) is a common sensory deficit in the elderly, which seriously affects physical and mental health. Therefore, understanding its underlying molecular mechanisms and taking interventions to treat ARHL are urgently needed. In our study, cochlea of 4-week-old C57BL/6 mice as the Youth group (n = 6) and 48-week-old cochlea as the Old group (n = 6) were subjected to quasi-targeted metabolomics analysis by Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). In total, 208 differential metabolites were identified in 12 cochlea samples, which highlighted the following discriminant compounds: tryptophan, piperidine, methionine, L-arginine, histamine, serotonin, acetylcholine, and 4-aminobutyric acid. Differentially expressed metabolites were identified which were involved in KEGG pathways related to the digestion and absorption of oxidative stress associated amino acids, Synaptic vesicle cycle of serotonin, Pantothenate and CoA Biosynthesis. These findings are a first step toward elucidating the pathophysiological pathways involved in the etiology of ARHL and provide the possibility to further explore the mechanisms of ARHL using metabolomic analysis.

Differentiate preterm and term infant brains and characterize the corresponding biomarkers via DICCCOL-based multi-modality graph neural networks.

Preterm birth is a worldwide problem that affects infants throughout their lives significantly. Therefore, differentiating brain disorders, and further identifying and characterizing the corresponding biomarkers are key issues to investigate the effects of preterm birth, which facilitates the interventions for neuroprotection and improves outcomes of prematurity. Until now, many efforts have been made to study the effects of preterm birth; however, most of the studies merely focus on either functional or structural perspective. In addition, an effective framework not only jointly studies the brain function and structure at a group-level, but also retains the individual differences among the subjects. In this study, a novel dense individualized and common connectivity-based cortical landmarks (DICCCOL)-based multi-modality graph neural networks (DM-GNN) framework is proposed to differentiate preterm and term infant brains and characterize the corresponding biomarkers. This framework adopts the DICCCOL system as the initialized graph node of GNN for each subject, utilizing both functional and structural profiles and effectively retaining the individual differences. To be specific, functional magnetic resonance imaging (fMRI) of the brain provides the features for the graph nodes, and brain fiber connectivity is utilized as the structural representation of the graph edges. Self-attention graph pooling (SAGPOOL)-based GNN is then applied to jointly study the function and structure of the brain and identify the biomarkers. Our results successfully demonstrate that the proposed framework can effectively differentiate the preterm and term infant brains. Furthermore, the self-attention-based mechanism can accurately calculate the attention score and recognize the most significant biomarkers. In this study, not only 87.6% classification accuracy is observed for the developing Human Connectome Project (dHCP) dataset, but also distinguishing features are explored and extracted. Our study provides a novel and uniform framework to differentiate brain disorders and characterize the corresponding biomarkers.

Inhibitory Control in Aging: The Compensation-Related Utilization of Neural Circuits Hypothesis.

As one of the core executive functions, inhibitory control plays an important role in human life. Inhibitory control refers to the ability to suppress task irrelevant information both internally and externally. Modern cognitive neuroscience has extensively investigated the neural basis of inhibitory control, less is known about the inhibitory control mechanisms in aging. Growing interests in cognitive declines of aging have given raise to the compensation-related utilization of neural circuits hypothesis (CRUNCH). In this review, we survey both behavioral, functional, and structural changes relevant to inhibitory control in aging. In line with CRUNCH, we found that older adults engage additional brain regions than younger adults when performing the same cognitive task, to compensate for declining brain structures and functions. Moreover, we propose CRUNCH could well take functional inhibitory deficits in older adults into account. Finally, we provide three sensible future research directions.

Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of HNSCC with or without HPV infection.

Head and neck squamous cell carcinoma (HNSCC) are the sixth most common cancer type in the world. Human papillomavirus (HPV) infection is an emerging risk factor for HNSCC. Immune infiltration of HNSCC is linked to therapeutic results. This article aimed to decide whether variations in HPV status affect immune infiltration, molecular mechanism, and how these results vary in HNSCC patients. We investigated the tumor-infiltrating immune cells (TIICs) and immune-related gene differences between HPV (+) and HPV (-) HNSCC. The gene expression quantification data of HNSCC and their clinical information were download from the TCGA database. Immune-related genes have been linked to the ImmPort platform. After analyzed of 22 TIICs in the HNSCC tumor environment by CIBERSORT and further assessment, lower memory B cell and higher T cell regulatory were connected with better HPV (-) HNSCC outcome, higher activated memory CD4 T cell, higher T cell regulatory, and lower activated NK cell were linked with better HPV (+) result. We finally got five forms of immune genes (CAMP, EDNRB, NTS, CXCL9, LHB) associated with HNSCC progression. Higher expressions of CAMP, EDNRB, and NTS were associated with increased overall survival in HPV (-) patients. Higher expression of CXCL9 and lower expression of LHB contributed to increased overall survival of HPV (+) patients. There tend to be discrepancies in the cell structure of TIICs and immune-related genes in HPV (-) and HPV (+) HNSCC. These variances are typically too crucial for the therapeutic outcome of the patient and the development of the tumor. In specific, our sample established these candidate immune cells and immune-related genes as candidate reservoirs for further researches.

Shared Decision-Making in Breast Reconstruction for Breast Cancer Patients: A Scoping Review.

For most breast cancer (BC) patients who have undergone a mastectomy, the decision whether to proceed with breast reconstruction (BR) is complicated and requires deliberation. Shared decision-making (SDM) helps to address those needs and promote informed value-based decisions. However, little is known about the SDM status for BR in BC patients. This scoping review describes: 1) basic characteristics of studies on BR SDM in BC patients; 2) factors influencing BR SDM in BC patients; 3) experience and perception of BR SDM in BC patients; and 4) outcome measures reported. This review was performed in accordance with the Arksey and O'Malley methodology. A total of 5 English and 4 Chinese databases were searched, as well as different sources from grey literature. The data extraction form was developed by referring to the objectives and the Ottawa Decision Support Framework (ODSF). Data was analyzed using thematic analysis, framework analysis and descriptive statistics, with findings presented in the tables and diagrams. A total of 1481 records were retrieved and 42 of these included after screening. In 21 (21/42, 50%) of the studies, patient decision aids (PDAs) were utilized, and in 17 (17/42, 40.48%) of the studies, the factors influencing the implementation of SDM were explored. Of these 17 studies, the factors influencing the implementation of SDM were categorized into the following: the patient level (17/17, 100%), the healthcare level (2/17, 11.76%) and the organizational and system level (7/17, 41.18%). A total of 8 (19.05%) of the 42 studies focused on patients' experiences and perceptions of SDM, and all studies used qualitative research methods. Of these 8 studies, a total of 7 (7/8, 87.50%) focused on patients' experiences of SDM participation, and 4 (4/8, 50.00%) focused on patients' perceptions of SDM. A total of 24 studies (24/42, 57.14%) involved quantitative outcome measures, where 49 items were divided into three classifications according to the outcomes of ODSF: the quality of the decision (17/24, 70.83%), the quality of the decision-making process (20/24, 83.33%), and impact (13/24, 54.17%). Although researchers have paid less attention to other research points in the field of SDM, compared to the design and application of SDM interventional tools, the research team still presents some equally noteworthy points through scoping review. For instance, the various factors influencing BC patients' participation in SDM for BR (especially at the healthcare provider level and at the organizational system level), patients' experiences and perceptions. Systematic reviews (SRs) should be conducted to quantify the impact of these different factors on BR SDM. Implementation of scientific theories and methods can inform the exploration and integration of these factors.