Development and validation of HPV-associated and HPV-independent penile squamous cell carcinoma prognostic nomogram.

OBJECTIVE: The aim of this study was to introduce HPV-associated and HPV-independent histologic classifications to analyze prognostic factors and develop a prognostic nomogram for patients with penile squamous cell carcinoma (PSCC). METHODS: Data of 1502 PSCC patients between 2010 and 2020 were accessed from the SEER database, and the patients were randomly divided into a training set and a validation set. Independent risk factors for PSCC patients prognosis were analyzed by using univariate and multivariate COX proportional hazards regression, and was used for the construction of the nomogram, and the predictive performance of the model was evaluated by C-index, calibration curve and ROC curve. Kaplan-Meier analysis was applied to explore the impact of HPV-related factors on patient survival, while propensity score matching (PSM) and inverse probability treatment weighting (IPTW) techniques were used to balance other confounding factors like individual clinical and pathological factors, and to evaluate the differences in overall survival (OS) and cause-specific survival (CSS) between subgroups. RESULT: The results indicated that histologic type, Grade classification, T/M stage, surgical methods and chemotherapy were independent risk factors affecting OS and CSS in PSCC patients. In addition, age and marital status were significantly associated with OS, while lymph node metastasis was an independent prognostic factor for CSS, the validation results of the model showed that the nomogram had a superior predictive performance compared with the American Joint Committee on Cancer staging system. In addition, subgroup analyses prior to and after IPTW and PSM adjustments showed that HPV-associated group had better OS and CSS than HPV-independent group. CONCLUSION: Our study developed and validated a nomogram using a novel histologic classification and achieved satisfactory results, which can better help clinicians to predict the prognosis of penile squamous cell carcinoma patients.

Insights into Chitin-Degradation Potential of Shewanella khirikhana JW44 with Emphasis on Characterization and Function of a Chitinase Gene SkChi65.

Chitin, a polymer of ß-1,4-linked N-acetylglucosamine (GlcNAc), can be degraded into valuable oligosaccharides by various chitinases. In this study, the genome of Shewanella khirikhana JW44, displaying remarkable chitinolytic activity, was investigated to understand its chitin-degradation potential. A chitinase gene SkChi65 from this strain was then cloned, expressed, and purified to characterize its enzymatic properties and substrate hydrolysis. Genome analysis showed that, of the 14 genes related to chitin utilization in JW44, six belonged to glycoside hydrolase (GH) families because of their functional domains for chitin binding and catalysis. The recombinant chitinase SkChi65, consisting of 1129 amino acids, was identified as a member of the GH18 family and possessed two chitin-binding domains with a typical motif of [A/N]KWWT[N/S/Q] and one catalytic domain with motifs of DxxDxDxE, SxGG, YxR, and [E/D]xx[V/I]. SkChi65 was heterologously expressed as an active protein of 139.95 kDa best at 37 °C with 1.0 mM isopropyl-ß-d-thiogalactopyranoside induction for 6 h. Purified SkChi65 displayed high stability over the ranges of 30-50 °C and pH 5.5-8.0 with optima at 40 °C and pH 7.0. The kinetic parameters Km, Vmax, and kcat of SkChi65 towards colloidal chitin were 27.2 µM, 299.2 µMs-1, and 10,203 s-1, respectively. In addition to colloidal chitin, SkChi65 showed high activity towards glycol chitosan and crystalline chitin. After analysis by thin-layer chromatography, the main products were N,N'-diacetylchitobiose, and GlcNAc with (GlcNAc)2-6 used as substrates. Collectively, SkChi65 could exhibit both exo- and endochitinase activities towards diverse substrates, and strain JW44 has a high potential for industrial application with an excellent capacity for chitin bioconversion.

Discovery of 2,3-Dihydro[1,4]dioxino[2,3-g]benzofuran Derivatives as Protease Activated Receptor 4 (PAR4) Antagonists with Potent Antiplatelet Aggregation Activity and Low Bleeding Tendency.

Patients with arterial embolic disease have benefited greatly from antiplatelet therapy. However, hemorrhage risk of antiplatelet agents cannot be ignored. Herein, we describe the discovery of 2,3-dihydro[1,4]dioxino[2,3-g]benzofuran compounds as novel PAR4 antagonists. Notably, the isomers 36 and 37 with the chemotype of phenoxyl methylene substituted on the 2,3-dihydro-1,4-dioxine ring exhibited potent in vitro antiplatelet activity (IC50 = 26.13 nM for 36 and 14.26 nM for 37) and significantly improved metabolic stability in human liver microsomes (T1/2 = 97.6 min for 36 and 11.1 min for BMS-986120). 36 also displayed good oral PK profiles (mice: T1/2 = 7.32 h and F = 45.11%). Both of them showed overall potent ex vivo antiplatelet activity at concentrations of 6 and 12 mg/kg, with no impact on the coagulation system and low bleeding liability. Our work will facilitate development of novel PAR4 antagonists as a safer therapeutic option for arterial embolism.

Recapitulating and reversing human brain ribosomopathy defects via the maladaptive integrated stress response.

Animal or human models recapitulating brain ribosomopathies are incomplete, hampering development of urgently needed therapies. Here, we generated genetic mouse and human cerebral organoid models of brain ribosomopathies, caused by mutations in small nucleolar RNA (snoRNA) SNORD118. Both models exhibited protein synthesis loss, proteotoxic stress, and p53 activation and led to decreased proliferation and increased death of neural progenitor cells (NPCs), resulting in brain growth retardation, recapitulating features in human patients. Loss of SNORD118 function resulted in an aberrant upregulation of p-eIF2α, the mediator of integrated stress response (ISR). Using human iPSC cell-based screen, we identified small-molecule 2BAct, an ISR inhibitor, which potently reverses mutant NPC defects. Targeting ISR by 2BAct mitigated ribosomopathy defects in both cerebral organoid and mouse models. Thus, our SNORD118 mutant organoid and mice recapitulate human brain ribosomopathies and cross-validate maladaptive ISR as a key disease-driving mechanism, pointing to a therapeutic intervention strategy.

Home Triad: A New Exploration of Home for People Living With Dementia Based on Lefebvre's Spatial Triad.

OBJECTIVES: This article examines a novel theoretical framework, which we term Home Triad, for research and practice involving people living with dementia (PLWD). BACKGROUND: Most of the existing home-related research on PLWD focuses on interior modifications, home care interventions and models, place attachment, and/or institutional homelike environments. However, limited studies have examined the meaning of home from PLWD's perspective, and even fewer have simultaneously considered the individual experience of PLWD, the external power (e.g., the role of design), and their interaction dynamics in the meaning-making process. METHODS: We developed home triad based on Lefebvre's spatial triad. Inspired by Chaudhury's home story structure, we conducted a life story analysis of a person living with dementia, "Kai," under four contexts-childhood home, neighborhood and city, daily routine, and attachment-within home triad. RESULTS: Home triad abstracts "home" with a dialectically interconnected relationship of the conceived, perceived, and lived home. Through PLWD's everyday life, the essence of home is primarily shaped by the interaction between their lived and perceived homes. However, a person's experiences of and participation in home living activities are also planned and/or regulated by different groups of people (caregivers, designers, and policymakers), who play important roles in the conceived home. Critically examining how PLWD's lived and perceived home is constrained or enabled through the conceived home deserves greater future research efforts. CONCLUSION: A systematic examination of the essence of home for PLWD using home triad can facilitate subsequent research and practice that promote PLWD's health, well-being, and quality of life.

Ribosome biogenesis controls cranial suture MSC fate via the complement pathway in mouse and human iPSC models.

Disruption of global ribosome biogenesis selectively affects craniofacial tissues with unclear mechanisms. Craniosynostosis is a congenital craniofacial disorder characterized by premature fusion of cranial suture(s) with loss of suture mesenchymal stem cells (MSCs). Here we focused on ribosomopathy disease gene Snord118, which encodes a small nucleolar RNA (snoRNA), to genetically disturb ribosome biogenesis in suture MSCs using mouse and human induced pluripotent stem cell (iPSC) models. Snord118 depletion exhibited p53 activation, increased cell death, reduced proliferation, and premature osteogenic differentiation of MSCs, leading to suture growth and craniosynostosis defects. Mechanistically, Snord118 deficiency causes translational dysregulation of ribosomal proteins and downregulation of complement pathway genes. Further complement pathway disruption by knockout of complement C3a receptor 1 (C3ar1) exacerbated MSC and suture defects in mutant mice, whereas activating the complement pathway rescued MSC cell fate and suture growth defects. Thus, ribosome biogenesis controls MSC fate via the complement pathway to prevent craniosynostosis.

Chemical crosslinking and ligation methods for in vivo analysis of RNA structures and interactions.

RNA structures and interactions in living cells drive a variety of biological processes and play critical roles in physiology and disease states. However, studies of RNA structures and interactions have been challenging due to limitations in available technologies. Direct determination of structures in vitro has been only possible to a small number of RNAs with limited sizes and conformations. We recently introduced two chemical crosslink-ligation techniques that enabled studies of transcriptome-wide secondary and tertiary structures and their dynamics. In a dramatically improved version of the psoralen analysis of RNA interactions and structures (PARIS2) method, we detailed the synthesis and use of amotosalen, a highly soluble psoralen analogue, and enhanced enzymology for higher efficiency duplex capture. We also introduced spatial 2'-hydroxyl acylation reversible crosslinking (SHARC) with exonuclease (exo) trimming, a method which utilizes a novel crosslinker class that targets the 2'-OH to capture three-dimensional (3D) structures. Both are powerful orthogonal approaches for solving in vivo RNA structure and interactions, integrating crosslinking, exo trimming, proximity ligation, and high throughput sequencing. In this chapter, we present a detailed protocol for the methods and highlight steps that outperform existing crosslink-ligation approaches.

A snoRNA-tRNA modification network governs codon-biased cellular states.

The dynamic balance between tRNA supply and codon usage demand is a fundamental principle in the cellular translation economy. However, the regulation and functional consequences of this balance remain unclear. Here, we use PARIS2 interactome capture, structure modeling, conservation analysis, RNA-protein interaction analysis, and modification mapping to reveal the targets of hundreds of snoRNAs, many of which were previously considered orphans. We identify a snoRNA-tRNA interaction network that is required for global tRNA modifications, including 2'-O-methylation and others. Loss of Fibrillarin, the snoRNA-guided 2'-O-methyltransferase, induces global upregulation of tRNA fragments, a large group of regulatory RNAs. In particular, the snoRNAs D97/D133 guide the 2'-O-methylation of multiple tRNAs, especially for the amino acid methionine (Met), a protein-intrinsic antioxidant. Loss of D97/D133 snoRNAs in human HEK293 cells reduced target tRNA levels and induced codon adaptation of the transcriptome and translatome. Both single and double knockouts of D97 and D133 in HEK293 cells suppress Met-enriched proliferation-related gene expression programs, including, translation, splicing, and mitochondrial energy metabolism, and promote Met-depleted programs related to development, differentiation, and morphogenesis. In a mouse embryonic stem cell model of development, knockdown and knockout of D97/D133 promote differentiation to mesoderm and endoderm fates, such as cardiomyocytes, without compromising pluripotency, consistent with the enhanced development-related gene expression programs in human cells. This work solves a decades-old mystery about orphan snoRNAs and reveals a function of snoRNAs in controlling the codon-biased dichotomous cellular states of proliferation and development.

The Application of Fully Immersive Virtual Reality on Reminiscence Interventions for Older Adults: Scoping Review.

BACKGROUND: The increasing number of older adults with mental, behavioral, and memory challenges presents significant public health concerns. Reminiscence is one type of nonpharmacological intervention that can effectively evoke memories, stimulate mental activities, and improve psychological well-being in older adults through a series of discussions on previous experiences. Fully immersive virtual reality (FIVR) may be a useful tool for reminiscence interventions because it uses realistic virtual environments connected to a person's significant past stories. OBJECTIVE: This review aims to examine empirical evidence regarding the application of FIVR in reminiscence interventions, its usability and acceptability, and its effectiveness in assisting the intervention to achieve optimal outcomes. METHODS: We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach for scoping reviews. The PubMed, PsycINFO, Embase, CINAHL, Web of Science, ACM, and IEEE Xplore electronic databases were used for the search. We included peer-reviewed studies that used FIVR as an assistive tool for reminiscence interventions; were published between January 1, 2000, and August 1, 2022; reported empirical research; involved older adults as participants; and addressed health- and behavior-related outcomes or the feasibility and usability of FIVR. We used Endnote X9 to organize the search results and Microsoft Excel for data extraction and synthesis. RESULTS: Of the 806 articles collected from the databases and other resources, 11 were identified. Most of the studies involved participants aged between 70 and 90 years. Only 1 study did not involve those with cognitive impairments, whereas 3 specifically targeted people living with dementia. The results indicated that FIVR reminiscence interventions enhanced engagement and reduced fatigue. Although some studies have observed positive effects on anxiety, apathy, depression, cognitive functions, and caregiver burden reduction, these findings were inconsistent across other research. In addition, FIVR showed overall usability and acceptability with manageable side effects among older adults across various health conditions during reminiscence sessions. However, 1 study reported adverse feelings among participants, triggered by unpleasant memories evoked by the virtual reality content. CONCLUSIONS: The role of FIVR in reminiscence interventions remains nascent, with limited studies evaluating its impacts on older adults. Many of the reviewed studies had notable limitations: small sample sizes, absence of rigorous research design, limited assessment of long-term effects, lack of measures for health and behavior outcomes, and quality of life. Beyond these limitations, this review identified a list of future research directions in 6 categories. On the basis of the review findings, we provide practical recommendations to enhance FIVR reminiscence interventions, covering topics such as virtual reality content, device choice, intervention types, and the role and responsibility of facilitators.

Thalidomide Alleviates Apoptosis, Oxidative Damage and Inflammation Induced by Pemphigus Vulgaris IgG in HaCat Cells and Neonatal Mice Through MyD88.

Purpose: Thalidomide (Tha) can be used as a selective treatment for mild pemphigus vulgaris (PV). However, the specific mechanism of action remains unclear. Patients and Methods: PV IgG extracted from patients' serum was cocultured with HaCaT cells to construct a PV cell model, and different concentrations of Tha were used to screen the drug effect. The expression level of MYD88 was assessed in skin lesions of PV patients. Intracellular Ca2+ concentration, reactive oxygen species level, DSG3, PG, MYD88, apoptosis-related proteins (Caspase-3, Bcl-2, and Bax), NF-κB pathway-related proteins (IκBα, p-IκBα, p50, and p65), NLRP3, IFN-γ, TNF-α, IL-6, and IL-8 levels were measured. PV IgG was subcutaneously injected into C57BL/6 neonatal mice to construct the animal model. Immunofluorescence was used to detect IgG deposition in the mouse epidermis, whereas immunohistochemistry and TUNEL methods were used to detect the expression of MYD88 and NLRP3 as well as cell apoptosis level in the mouse epidermis. Results: Tha reversed the decrease in Dsg3 and PG caused by PV IgG. The expression of MyD88 increased in the patients' skin, PV cell model, and PV mouse model. The increase in MyD88 expression level in PV cell models and PV newborn mouse models was inhibited by Tha. Overexpression of MyD88 induced a decrease in the expression levels of Dsg3 and PG in Hacat cells. Overexpression of MyD88 inhibited Tha effects on Dsg3 and PG expressions and blocked Tha effects on Ca2+, apoptosis, Bax, Bcl-2, and Caspase-3 expressions, oxidative damage, and inflammatory response in HaCat cells. Tha alleviated acantholysis induced by PV IgG in model mice. Conclusion: Through MYD88, Tha attenuated apoptosis of HaCat cells, modulated NF-κB to hamper the oxidative damage and inflammatory response in the PV cell models, and alleviated acantholysis, IgG deposition, and epidermal cell apoptosis induced by PV IgG in model mice.

Frustrated Radical Pairs in Organic Synthesis.

Frustrated radical pairs (FRPs) describe the phenomenon that two distinct radicals─which would otherwise annihilate each other to form a closed-shell covalent adduct─can coexist in solution, owing to steric repulsion or weak bonding association. FRPs are typically formed via spontaneous single-electron transfer between two sterically encumbered precursors─an oxidant and a reductant─under ambient conditions. The two components of a FRP exhibit orthogonal chemical properties and can often act in cooperativity to achieve interesting radical reactivities. Initially observed in the study of traditional frustrated Lewis pairs, FRPs have recently been shown to be capable of homolytically activating various chemical bonds. In this Perspective, we will discuss the discovery of FRPs, their fundamental reactivity in chemical bond activation, and recent developments of their use in synthetic organic chemistry, including in C-H bond functionalization. We anticipate that FRPs will provide new reaction strategies for solving challenging problems in modern organic synthesis.

Influences of High School Physical Learning Environments on Students' Anxiety in China.

BACKGROUND: High school students are at an increased risk of developing generalized anxiety disorder (GAD) due to significant pressure to achieve academic success. AIM: Although it is known that a school's physical learning environment can influence students' GAD, there is limited research examining this relationship. To fill this knowledge gap, a cross-sectional study was conducted among 230 students from two high schools in China. METHODS: A survey questionnaire captured students' GAD self-evaluations (dependent variables), perceptions/preferences of their school physical environment (independent variables), and social and personal conditions (confounding variables). Bivariate analysis showed that students' GAD scores were associated with multiple factors related to the learning environment, physical activities, and personal characteristics. The multivariate analysis examined the relationship between GAD scores and physical learning environment variables while controlling for confounding variables. RESULTS: The results indicated that adequate lighting (B = -0.154, p = .029) and perceived effectiveness of using self-service cafeterias in reducing anxiety (B = -0.138, p = .044) were significantly associated with GAD scores. CONCLUSIONS: These findings provide evidence for the importance of designing high schools with students' mental health in mind. Specifically, school administrators and designers should consider how to improve the physical learning environment by incorporating natural light, a self-service cafeteria, and spaces for physical activities to promote students' mental well-being.

Regioselective aliphatic C-H functionalization using frustrated radical pairs.

Frustrated Lewis pairs (FLPs) are well documented for the activation of small molecules such as dihydrogen and carbon dioxide1-4. Although canonical FLP chemistry is heterolytic in nature, recent work has shown that certain FLPs can undergo single-electron transfer to afford radical pairs5. Owing to steric encumbrance and/or weak bonding association, these radicals do not annihilate one another, and they have thus been named frustrated radical pairs (FRPs). Notable preliminary results suggest that FRPs may be useful reagents in chemical synthesis6-8, although their applications remain limited. Here we demonstrate that the functionalization of C(sp3)-H bonds can be accomplished using a class of FRPs generated from disilazide donors and an N-oxoammonium acceptor. Together, these species undergo single-electron transfer to generate a transient and persistent radical pair capable of cleaving unactivated C-H bonds to furnish aminoxylated products. By tuning the structure of the donor, it is possible to control regioselectivity and tailor reactivity towards tertiary, secondary or primary C-H bonds. Mechanistic studies lend strong support for the formation and involvement of radical pairs in the target reaction.

Chemical RNA Cross-Linking: Mechanisms, Computational Analysis, and Biological Applications.

In recent years, RNA has emerged as a multifaceted biomolecule that is involved in virtually every function of the cell and is critical for human health. This has led to a substantial increase in research efforts to uncover the many chemical and biological aspects of RNA and target RNA for therapeutic purposes. In particular, analysis of RNA structures and interactions in cells has been critical for understanding their diverse functions and druggability. In the last 5 years, several chemical methods have been developed to achieve this goal, using chemical cross-linking combined with high-throughput sequencing and computational analysis. Applications of these methods resulted in important new insights into RNA functions in a variety of biological contexts. Given the rapid development of new chemical technologies, a thorough perspective on the past and future of this field is provided. In particular, the various RNA cross-linkers and their mechanisms, the computational analysis and challenges, and illustrative examples from recent literature are discussed.

A Framework to Develop an Immersive Virtual Reality Simulation Tool for Postpartum Hemorrhage Management Nurse Training.

ABSTRACT: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality and morbidity. Effective nurse training for PPH management can reduce negative health impacts on childbearing women. This article discusses a framework for the development of an innovative immersive virtual reality simulator for PPH management training. The simulator should consist of: 1) a virtual world, including virtual physical and social environments, and simulated patients, and 2) a smart platform, providing automatic instructions, adaptive scenarios, and intelligent performance debriefing and evaluations. This simulator will provide a realistic virtual environment for nurses to practice PPH management and promote women's health.

Electrochemical reactor dictates site selectivity in N-heteroarene carboxylations.

Pyridines and related N-heteroarenes are commonly found in pharmaceuticals, agrochemicals and other biologically active compounds1,2. Site-selective C-H functionalization would provide a direct way of making these medicinally active products3-5. For example, nicotinic acid derivatives could be made by C-H carboxylation, but this remains an elusive transformation6-8. Here we describe the development of an electrochemical strategy for the direct carboxylation of pyridines using CO2. The choice of the electrolysis setup gives rise to divergent site selectivity: a divided electrochemical cell leads to C5 carboxylation, whereas an undivided cell promotes C4 carboxylation. The undivided-cell reaction is proposed to operate through a paired-electrolysis mechanism9,10, in which both cathodic and anodic events play critical roles in altering the site selectivity. Specifically, anodically generated iodine preferentially reacts with a key radical anion intermediate in the C4-carboxylation pathway through hydrogen-atom transfer, thus diverting the reaction selectivity by means of the Curtin-Hammett principle11. The scope of the transformation was expanded to a wide range of N-heteroarenes, including bipyridines and terpyridines, pyrimidines, pyrazines and quinolines.

Habitat quality assessment of wintering migratory birds in Poyang Lake National Nature Reserve based on InVEST model.

Poyang Lake National Nature Reserve (PLNNR) is an important resting place for wintering migratory birds on the East Asian-Australasian Flyway (EAAF). In recent years, due to human activities and climate change, the area of wetlands has shown a downward trend, and the number and habitat of wintering migratory birds have been threatened. It is urgent to evaluate the habitat quality of wintering migratory birds in PLNNR. Therefore, the InVEST model and landscape index were used to evaluate the habitat quality of wintering migratory birds, and the grey correlation theory was used to reveal the response of typical wintering migratory bird population to habitat quality. The results showed that the habitat quality of the PLNNR was still at a high level, but showed a downward trend, with the average index of habitat quality decreasing from 0.872 to 0.817. The area of the highest quality habitat decreased by 3394.92 hm2, the area of the lowest, low, and medium quality habitats increased by 3112.11 hm2, and the area of the high quality habitat remained stable. The lowest, low, and medium quality habitat expanded from the middle to the south of the PLNNR mainly because of the expansion of construction land and cultivated land. The area with deterioration in habitat quality was 10,477.53 hm2, mainly concentrated in the center and south of the PLNNR. The area with restoration in habitat quality was 6148.26 hm2, mainly concentrated in the Bang Lake and Dacha Lake. The area with no change in habitat quality remained stable. The fragmentation degree and shape complexity of highest and high quality habitats increased, dominance degree and connectivity decreased, and the landscape pattern of habitat quality showed a downward trend. Typical wintering migratory birds have a strong correlation with highest, high, and low habitat quality, and there is a downward trend with the deterioration of habitat quality. Finally, this paper puts forward constructive suggestions on the degradation of habitat quality caused by land-use change.

Seeing Is Believing: Using Eye-Tracking Devices in Environmental Research.

OBJECTIVES: This article aims to provide methodological guidance for research that uses eye-tracking devices (ETDs) to study environment and behavior relationships. BACKGROUND: Vision is an important human sense through which people acquire a large amount of environmental information. ETDs are tools for detecting eye/gaze behaviors, facilitating better understanding about how people collect visual information and how such information is related to emotions and psychological states. However, there is a lack of guidance for the application of ETDs to environment and behavior studies. METHODS: A literature review was conducted on articles reporting empirical studies that used ETDs. The data were extracted and compiled, including information such as research questions, research design, types of ETDs, variables measured, types of physical environment (or visual stimuli), stimuli durations, data analysis methods, and so on. RESULTS: Fifty articles were identified. The main research topics were related to urban and landscape environments, and architecture and interior spaces. Most of the research designs were experimental or quasi-experimental designs, with a few cross-sectional studies. The majority types of ETDs were screen-based ETDs, followed by mobile ETDs (glasses). Main variables were gaze fixations, fixation durations, and scan paths. Typical types of stimuli included images, videos, virtual reality, and real environments and/or objects. CONCLUSIONS: Guidance for eye-tracking research on environment and behavior was developed based on the literature review results, to provide direction for determining research questions, selecting appropriate research designs, establishing participant inclusion and/or excluding criteria, collecting and analyzing data, and interpreting research results.

Does public health policy quality foster state innovation capacity? Evidence from a global panel data.

The design and implementation of public health policy may shape state innovation capacity with governance effectiveness, political stability, and government integrity. Previous studies, however, failed to incorporate these relationships simultaneously. This study aims to combine two distinct scholarships to examine whether the quality of policies in the public health sector contributes to state innovation capacity. We extracted data from the WHO international health regulatory dataset covering the WHO Member States between 2010 and 2017 to investigate the relationship (N = 145). Our fixed-effects models and regression discontinuity design (RDD) suggest a positive impact of public health policy quality on state innovation capacity. There are several contributions to the study of the relationship between public health and innovation in this study. Firstly, it fills a theoretical void concerning the relationship between policy development and implementation in the public health sector and country-specific innovations. Second, it provides an empirical quantitative analysis of policy quality in the public health sector. Third, this study contributes evidence that public health plays an important role in fostering state innovation beyond urbanization, investment in science and technology, and foreign trade. Furthermore, our quasi-experimental evidence found that this mechanism may be significant only between the more politically stable countries and the most politically stable countries. These contributions have empirical implications for governments across the world that seek to balance public health and innovation capacity in the context of the post-pandemic era.

Physical Activity Impacts of an Activity-Friendly Community: A Natural Experiment Study Protocol.

Background: Stakeholders from multiple sectors are increasingly aware of the critical need for identifying sustainable interventions that promote healthy lifestyle behaviors. Activity-friendly communities (AFCs) have been known to provide opportunities for engaging in physical activity (PA) across the life course, which is a key to healthy living and healthy aging. Purpose: Our purpose is to describe the study protocol developed for a research project that examines: (a) the short- and long-term changes in total levels and spatial and temporal patterns of PA after individuals move from non-AFCs to an AFC; and (b) what built and natural environmental factors lead to changes in PA resulting from such a move, either directly or indirectly (e.g., by affecting psychosocial factors related to PA). Methods: This protocol is for a longitudinal, case-comparison study utilizing a unique natural experiment opportunity in Austin, Texas, USA. Case participants were those adults who moved from non-AFCs to an AFC. Matching comparison participants were residents from similar non-AFCs who did not move during the study period. Recruitment venues included local businesses, social and print media, community events, and individual referrals. Objectively measured moderate-to-vigorous PA and associated spatial and temporal patterns served as the key outcomes of interest. Independent (e.g., physical environments), confounding (e.g., demographic factors), and mediating variables (e.g., psychosocial factors) were captured using a combination of objective (e.g., GIS, GPS, Tanita scale) and subjective measures (e.g., survey, travel diary). Statistical analyses will be conducted using multiple methods, including difference-in-differences models, repeated-measures linear mixed models, hierarchical marked space-time Poisson point pattern analysis, and hierarchical linear mixed models. Conclusion: Natural experiment studies help investigate causal relationships between health and place. However, multiple challenges associated with participant recruitment, extensive and extended data collection activities, and unpredictable intervention schedules have discouraged many researchers from implementing such studies in community-based populations. This detailed study protocol will inform the execution of future studies to explore how AFCs impact population health across the life course.