Cooperation of structural motifs controls drug selectivity in cyclin-dependent kinases: an advanced theoretical analysis.

Understanding drug selectivity mechanism is a long-standing issue for helping design drugs with high specificity. Designing drugs targeting cyclin-dependent kinases (CDKs) with high selectivity is challenging because of their highly conserved binding pockets. To reveal the underlying general selectivity mechanism, we carried out comprehensive analyses from both the thermodynamics and kinetics points of view on a representative CDK12 inhibitor. To fully capture the binding features of the drug-target recognition process, we proposed to use kinetic residue energy analysis (KREA) in conjunction with the community network analysis (CNA) to reveal the underlying cooperation effect between individual residues/protein motifs to the binding/dissociating process of the ligand. The general mechanism of drug selectivity in CDKs can be summarized as that the difference of structural cooperation between the ligand and the protein motifs leads to the difference of the energetic contribution of the key residues to the ligand. The proposed mechanisms may be prevalent in drug selectivity issues, and the insights may help design new strategies to overcome/attenuate the drug selectivity associated problems.

Final epidemic size of a two-community SIR model with asymmetric coupling.

Communities are commonly not isolated but interact asymmetrically with each other, allowing the propagation of infectious diseases within the same community and between different communities. To reveal the impact of asymmetrical interactions and contact heterogeneity on disease transmission, we formulate a two-community SIR epidemic model, in which each community has its contact structure while communication between communities occurs through temporary commuters. We derive an explicit formula for the basic reproduction number R 0 , give an implicit equation for the final epidemic size z, and analyze the relationship between them. Unlike the typical positive correlation between R 0 and z in the classic SIR model, we find a negatively correlated relationship between counterparts of our model deviating from homogeneous populations. Moreover, we investigate the impact of asymmetric coupling mechanisms on R 0 . The results suggest that, in scenarios with restricted movement of susceptible individuals within a community, R 0 does not follow a simple monotonous relationship, indicating that an unbending decrease in the movement of susceptible individuals may increase R 0 . We further demonstrate that network contacts within communities have a greater effect on R 0 than casual contacts between communities. Finally, we develop an epidemic model without restriction on the movement of susceptible individuals, and the numerical simulations suggest that the increase in human flow between communities leads to a larger R 0 .

Swiss chiropractic cohort (Swiss ChiCo) pilot study: feasibility for a musculoskeletal cohort study conducted within a nationwide practice-based research network.

PURPOSE: Practice-based research networks are collaborations between clinicians and researchers to advance primary care research. This study aims to assess the feasibility for longitudinal data collection within a newly established chiropractic PBRN in Switzerland. METHODS: A prospective observational cohort feasibility study was performed. PBRN participating chiropractors were asked to recruit patients seeking new conservative health care for musculoskeletal pain from March 28, 2022, to September 28, 2022. Participants completed clinically oriented survey questions and patient-reported outcome measures before the initial chiropractic assessment as well as 1 h, 2 weeks, 6 weeks, and 12 weeks thereafter. Feasibility was assessed through a variety of process, resource, and management metrics. Patient clinical outcomes were also assessed. RESULTS: A total of 76 clinicians from 35 unique primary care chiropractic clinics across Switzerland participated. A total of 1431 patients were invited to participate, of which 573 (mean age 47 years, 51% female) were enrolled. Patient survey response proportions were 76%, 64%, 61%, and 56%, at the 1-h, 2-, 6-, and 12-week survey follow-ups, respectively. Evidence of an association was found between increased patient age (OR = 1.03, 95%CI 1.01-1.04), patient from a German-speaking region (OR = 1.81, 95%CI 1.17-2.86), non-smokers (OR = 1.89, 95%CI 1.13-3.17), and increased pain impact score at baseline (OR = 1.18, 95%CI 1.01-1.38) and response to all surveys. CONCLUSION: The Swiss ChiCo pilot study exceeded its prespecified feasibility objectives. Nationwide longitudinal data capture was highly feasible. Similar to other practice-based cohorts, participant retention remains a challenge. Trial registration Swiss chiropractic cohort (Swiss ChiCo) pilot study (ClinicalTrials.gov identifier: NCT05116020).

Effects of community ecological network construction on physicochemical, microbial, and quality characteristics of inoculated northeast sauerkraut: A new insight in food fermentation processes.

The enhancement of the quality of northeast sauerkraut can be achieved by inoculation with lactic acid bacteria. However, a comprehensive ecological understanding of the intricate dynamic processes involved is currently lacking, which could yield valuable insights for regulating sauerkraut fermentation. This study compares spontaneously sauerkrauts with the sauerkrauts inoculated with autochthonous Lactiplantibacillus plantarum SC-MDJ and commercial L. plantarum, respectively. We examine their physicochemical properties, quality characteristics, bacterial community dynamics, and ecological network interactions. Inoculation with L. plantarum leads to reduced bacterial community richness and niche breadth, but an increase in robustness, interactions, and assembly processes. Notably, there appears to be a potential correlation between bacterial community structure and quality characteristics. Particularly, sauerkraut inoculated with L. plantarum SC-MDJ may produce a sourness more quickly, possibly attributed to the enhanced ecological role of L. plantarum SC-MDJ. This study establishes a foundation for the targeted regulation of sauerkraut fermentation.

Microbial redox cycling enhances ecosystem thermodynamic efficiency and productivity.

Microbial life in low-energy ecosystems relies on individual energy conservation, optimizing energy use in response to interspecific competition and mutualistic interspecific syntrophy. Our study proposes a novel community-level strategy for increasing energy use efficiency. By utilizing an oxidation-reduction (redox) reaction network model that represents microbial redox metabolic interactions, we investigated multiple species-level competition and cooperation within the network. Our results suggest that microbial functional diversity allows for metabolic handoffs, which in turn leads to increased energy use efficiency. Furthermore, the mutualistic division of labour and the resulting complexity of redox pathways actively drive material cycling, further promoting energy exploitation. Our findings reveal the potential of self-organized ecological interactions to develop efficient energy utilization strategies, with important implications for microbial ecosystem functioning and the co-evolution of life and Earth.

Universal Dynamics of Microbial Communities in Full-Scale Textile Wastewater Treatment Plants and System Prediction by Machine Learning.

The performance of full-scale biological wastewater treatment plants (WWTPs) depends on the operational and environmental conditions of treatment systems. However, we do not know how much these conditions affect microbial community structures and dynamics across systems over time and predictability of the treatment performance. For over a year, the microbial communities of four full-scale WWTPs processing textile wastewater were monitored. During temporal succession, the environmental conditions and system treatment performance were the main drivers, which explained up to 51% of community variations within and between all plants based on the multiple regression models. We identified the universality of community dynamics in all systems using the dissimilarity-overlap curve method, with the significant negative slopes suggesting that the communities containing the same taxa from different plants over time exhibited a similar composition dynamic. The Hubbell neutral theory and the covariance neutrality test indicated that all systems had a dominant niche-based assembly mechanism, supporting that the communities had a similar composition dynamic. Phylogenetically diverse biomarkers for the system conditions and treatment performance were identified by machine learning. Most of the biomarkers (83%) were classified as generalist taxa, and the phylogenetically related biomarkers responded similarly to the system conditions. Many biomarkers for treatment performance perform functions that are crucial for wastewater treatment processes (e.g., carbon and nutrient removal). This study clarifies the relationships between community composition and environmental conditions in full-scale WWTPs over time.

Robustness Evaluation of the Open Source Product Community Network Considering Different Influential Nodes.

With the rapid development of Internet technology, the innovative value and importance of the open source product community (OSPC) is becoming increasingly significant. Ensuring high robustness is essential to the stable development of OSPC with open characteristics. In robustness analysis, degree and betweenness are traditionally used to evaluate the importance of nodes. However, these two indexes are disabled to comprehensively evaluate the influential nodes in the community network. Furthermore, influential users have many followers. The effect of irrational following behavior on network robustness is also worth investigating. To solve these problems, we built a typical OSPC network using a complex network modeling method, analyzed its structural characteristics and proposed an improved method to identify influential nodes by integrating the network topology characteristics indexes. We then proposed a model containing a variety of relevant node loss strategies to simulate the changes in robustness of the OSPC network. The results showed that the proposed method can better distinguish the influential nodes in the network. Furthermore, the network's robustness will be greatly damaged under the node loss strategies considering the influential node loss (i.e., structural hole node loss and opinion leader node loss), and the following effect can greatly change the network robustness. The results verified the feasibility and effectiveness of the proposed robustness analysis model and indexes.

Are networks of trophic interactions sufficient for understanding the dynamics of multi-trophic communities? Analysis of a tri-trophic insect food-web time-series.

Resource-consumer interactions are considered a major driving force of population and community dynamics. However, species also interact in many non-trophic and indirect ways and it is currently not known to what extent the dynamic coupling of species corresponds to the distribution of trophic links. Here, using a 10-year data set of monthly observations of a 40-species tri-trophic insect community and nonlinear time series analysis, we compare the occurrence and strengths of both the trophic and dynamic interactions in the insect community. The matching between observed trophic and dynamic interactions provides evidence that population dynamic interactions reflect resource-consumer interactions in the many-species community. However, the presence of a trophic interaction does not always correspond to a detectable dynamic interaction especially for top-down effects. Moreover a considerable proportion of dynamic interactions are not attributable to direct trophic interactions, suggesting the unignorable role of non-trophic and indirect interactions as co-drivers of community dynamics.

Interaction between epidemic spread and collective behavior in scale-free networks with community structure.

Many real-world networks exhibit community structure: the connections within each community are dense, while connections between communities are sparser. Moreover, there is a common but non-negligible phenomenon, collective behaviors, during the outbreak of epidemics, are induced by the emergence of epidemics and in turn influence the process of epidemic spread. In this paper, we explore the interaction between epidemic spread and collective behavior in scale-free networks with community structure, by constructing a mathematical model that embeds community structure, behavioral evolution and epidemic transmission. In view of the differences among individuals' responses in different communities to epidemics, we use nonidentical functions to describe the inherent dynamics of individuals. In practice, with the progress of epidemics, individual behaviors in different communities may tend to cluster synchronization, which is indicated by the analysis of our model. By using comparison principle and Gers˘gorin theorem, we investigate the epidemic threshold of the model. By constructing an appropriate Lyapunov function, we present the stability analysis of behavioral evolution and epidemic dynamics. Some numerical simulations are performed to illustrate and complement our theoretical results. It is expected that our work can deepen the understanding of interaction between cluster synchronization and epidemic dynamics in scale-free community networks.

Predictors of Patients' Intention to Interact With Doctors in Web-Based Health Communities in China: Cross-Sectional Study.

BACKGROUND: Web-based health communities provide opportunities for doctors and patients to interact with each other and change the traditional communication mode between doctors and patients. However, little is known about the predictors of patients' intention to interact with doctors in Web-based health communities in China. OBJECTIVE: The purpose of this study was to investigate what are the predictors of patients' intention to interact with doctors in Web-based health communities in China. METHODS: On the basis of two-factor theory and service convenience theory, we propose that the attributes of Web-based health communities including ease of use and perceived synchronicity influence patients' intention to interact through convenience of Web-based health communities, whereas the attributes of physical health facilities such as inaccessibility and discontinuity affect patients' intention to interact through inconvenience of physical health facilities. We employed the survey method to validate our hypothesized relationships. Through developing the measurement instruments, we collected 334 valid answers from Web health community users and utilized partial least square to analyze the data. RESULTS: Ease of use (t311=2.924, P=.004) and perceived synchronicity (t311=2.353, P=.019) were found to influence convenience of Web-based health communities significantly, whereas inaccessibility (t311=3.189, P=.002) and discontinuity (t311=3.149, P=.002) were found to impact inconvenience of physical health facilities significantly. Meanwhile, both convenience of Web-based health communities (t311=2.353, P=.019) and inconvenience of physical health facilities (t311=2.787, P=.006) were found to affect patients' intention to interact with doctors in Web-based health communities significantly. Therefore, all the proposed hypotheses were supported. CONCLUSIONS: Through including factors from both Web-based health communities and physical health facilities, we can understand patients' intention to interact comprehensively. This study not only contributes to literature of doctor-patient interaction and Web-based health platforms but also provides implications to promote doctor-patient interaction online and offline.

Predictors of Patients' Loyalty Toward Doctors on Web-Based Health Communities: Cross-Sectional Study.

BACKGROUND: Web-based health communities provide means for patients to not only seek care but also to promote their relationship with doctors. However, little is known about the predictors of patients' loyalty toward doctors in Web-based health communities. OBJECTIVE: This study aimed to investigate the predictors of patients' loyalty toward doctors in Web-based health communities. METHODS: On the basis of sociotechnical systems theory and attachment theory, we propose that social factors including emotional interaction, perceived expertise, and social norm influence patients' loyalty through their emotional attachment, whereas technical factors including sociability, personalization, and perceived security affect patients' loyalty through functional dependence. To validate our proposed research model, we used the survey method and collected 373 valid answers. Partial least square was used to analyze the data. RESULTS: Our empirical analysis results showed that all the social factors including emotional interaction (beta=.257, t350=2.571; P=.01), perceived expertise (beta=.288, t350=3.412; P=.001), and social norm (beta=.210, t350=2.017; P=.04) affect patients' emotional attachment toward doctors significantly, whereas except sociability (beta=.110, t350=1.152; P=.25), technical factors such as personalization (beta=.242, t350=2.228; P=.03) and perceived security (beta=.328, t350=3.438; P=.001) impact functional dependence significantly. Considering the effect of working mechanisms, both emotional attachment (beta=.443, t350=4.518; P<.001) and functional dependence (beta=.303, t350=2.672; P=.008) influence patients' loyalty toward doctors in Web-based health communities significantly. CONCLUSIONS: Patients' loyalty toward doctors in Web-based health communities is important for the effectiveness of doctors' advice or service in Web-based health communities. The research results not only fill the gaps in the literature of the patient-doctor relationship and Web-based health communities but also has many implications for establishing patients' loyalty on Web-based health communities and in physical context.

What are the perceived added values and barriers of regulating long-term care in the home environment using a care network perspective: a qualitative study.

BACKGROUND: Changes in Dutch policy towards long-term care led to the Dutch Health and Youth Care Inspectorate testing a regulatory framework focusing on care networks around older adults living independently. This regulatory activity involved all care providers and the older adults themselves. METHODS: Semi-structured interviews with the older adults, and focus groups with care providers and inspectors were used to assess the perceived added value of, and barriers to the framework. RESULTS: The positive elements of this framework were the involvement of the older adults in the regulatory activity, the focus of the framework on care networks and the open character of the conversations with the inspectors. However, applying the framework requires a substantial investment of time. Care providers often did not perceive themselves as being part of a care network around one person and they expressed concerns about financial and privacy issues when thinking in terms of care networks. CONCLUSIONS: The experiences of the client were seen as important in regulating long-term care. Regulating care networks as a whole puts cooperation between care providers involved around one person on the agenda. However, barriers for this form of regulation were also perceived and, therefore, careful consideration when and how to regulate care networks is recommended.

Readying Community Water Fluoridation Advocates through Training, Surveillance, and Empowerment.

This paper describes the Community Water Fluoridation Advocacy Training Project that was designed to develop networks of community water fluoridation advocates in rural communities. The South Carolina (SC) Department of Health and Environmental Control Division of Oral Health staff and the SC Dental Association were responsible for developing and facilitating the training sessions for key policy influencers, which included medical and dental providers, early childhood educators, and water system operators and managers. Findings from the post-training survey indicate that participants increased their knowledge and skills to discuss the impact of water fluoridation on the dental health of community residents. Participants identified a need for online access to water fluoridation education and advocacy materials. Dental public health competencies illustrated: communication and collaboration with groups and individuals, and advocate, implement and evaluate public health policy, legislation and regulations.

Informed consent, community engagement, and study participation at a research site in Kigali, Rwanda.

People enroll in medical research for many reasons ranging from decisions regarding their own or family members' health situation to broader considerations including access to health and financial resources. In socially vulnerable communities the choice to participate is often based on a risk-benefit assessment that goes beyond the medical aspects of the research, and considers the benefits received. In this qualitative study, we examined the motivations of Rwandan women to participate in a non-commercial collaborative research study examining the safety, acceptability, and adherence of a contraceptive vaginal ring in Rwanda juxtaposed with the perceptions of the research within the community. 351 women attended the screening visit, four were excluded because they were not able to complete the assessment of understanding. The remaining participants' ages ranged from 17 to 38 and 80% had primary level of education or below. 120 were enrolled. Findings highlighted motivations for joining the study that were relayed both formally by the clinic (e.g. testing and treatment) and informally by the community including the positive aspects of the ring. There were also some negative rumors circulating regarding the research site, likely from excluded participants who faced potential stigma based on that exclusion. It was understood by most participants that they were enrolled in a research study and participants actively sought out enrollment in the research for a variety of reasons. The experiences demonstrate that although inequalities in access to health care may create conflicting situations around the study, it is possible to form partnerships between a research center and participants/their partners, for research about reproductive health.

Humpback Dolphins (Genus Sousa) in India: An Overview of Status and Conservation Issues.

This chapter aims to collate recent work done by different research teams along the Indian coast and presents research plans for the conservation and management of the genus Sousa in Indian waters. Humpback dolphins are the most common nearshore cetaceans found along the Indian coast. The taxonomy is confused, but two or more species of humpback dolphins may be present in India. Dedicated research on humpback dolphins and other cetaceans has been initiated only in the past few years and vast gaps in the ecology and conservation of the genus from the region remain. Dedicated and opportunistic research indicates that humpback dolphin presence is continuous along the west coast of India, owing to the contiguous favourable habitat of shallow nearshore waters, while along the east coast humpback dolphins are apparently found in pockets. Humpback dolphins are also the most numerous in incidental catch records from the coast, owing to the large overlap in space use with nearshore fisheries like small gillnets, trawls, shore seines and purse seines. Along many coastal sites, humpback dolphins are known to cause damage and depredation of fish catch of certain fishing gears, making them unpopular. At the same time, many fishers along the west coast have developed local dolphin-watching programmes as an alternate source of livelihood, providing positive impetus for conservation. However, research on the long-term effects of dolphin watching and its management is required. Some recommendations for more effective management of this species are made.

Effect of Age-Friendly Communities Action Plan on Trajectories of Older Canadians' Depressive Symptoms Between 2018 and 2020: Multilevel Results From the Canadian Longitudinal Study on Aging.

As the COVID-19 pandemic impacted mental health, this longitudinal study examined the effect of age-friendly communities (AFC) action plan on older adults' depressive symptoms. Using the CLSA, the CLSA COVID-19 Questionnaire study, survey of Canadian municipalities, and the census, the depressive symptoms trajectories were modeled with multilevel multinomial regressions. Most respondents (66.1%) had non-depressed trajectories, 28.1% experienced a moderate increase in depressive symptoms, and 5.8% had a depressed trajectory. AFC action plans did not have a protective effect on these trajectories. Being a female, greater loneliness, lower income, ≥2 chronic conditions, inferior social participation, weaker sense of belonging, COVID-19 infection, and pandemic stressors predicted a depressed trajectory. Neighborhood's deprivation had a weak protective effect on the declining trajectory. Although AFC action plans provided no benefits during the pandemic, volunteers facilitating resource access and social interactions could limit any increase in depressive symptoms.

An empirical study on social network analysis for small residential communities in Gangwon State, South Korea.

Social Network Analysis (SNA) provides a dynamic framework for examining interactions and connections within networks, elucidating how these relationships impact behaviors and outcomes. This study targeted small residential communities in Gangwon State, South Korea, to explore network formation theories and derive strategies for enhancing health promotion services in rural communities. Conducted in 12 small residential areas, the survey led to a network categorization model distinguishing networks as formal, informal, or non-existent. Key findings demonstrated that demographic and socio-economic factors, specifically age, income, living environment, leisure activities, and education level, significantly influence network formation. Importantly, age, environmental conditions, satisfaction with public transportation, and walking frequency were closely associated with the evolution of formal networks. These results highlight the importance of early community network assessments, which must consider distinct network traits to develop effective health promotion models. Utilizing SNA early in the assessment process can improve understanding of network dynamics and optimize the effectiveness of health interventions.

Field-aged rice hull biochar stimulated the methylation of mercury and altered the microbial community in a paddy soil under controlled redox condition changes.

Mercury (Hg) contaminated paddy soils are hot spots for methylmercury (MeHg) which can enter the food chain via rice plants causing high risks for human health. Biochar can immobilize Hg and reduce plant uptake of MeHg. However, the effects of biochar on the microbial community and Hg (de)methylation under dynamic redox conditions in paddy soils are unclear. Therefore, we determined the microbial community in an Hg contaminated paddy soil non-treated and treated with rice hull biochar under controlled redox conditions (< 0 mV to 600 mV) using a biogeochemical microcosm system. Hg methylation exceeded demethylation in the biochar-treated soil. The aromatic hydrocarbon degraders Phenylobacterium and Novosphingobium provided electron donors stimulating Hg methylation. MeHg demethylation exceeded methylation in the non-treated soil and was associated with lower available organic matter. Actinobacteria were involved in MeHg demethylation and interlinked with nitrifying bacteria and nitrogen-fixing genus Hyphomicrobium. Microbial assemblages seem more important than single species in Hg transformation. For future directions, the demethylation potential of Hyphomicrobium assemblages and other nitrogen-fixing bacteria should be elucidated. Additionally, different organic matter inputs on paddy soils under constant and dynamic redox conditions could unravel the relationship between Hg (de)methylation, microbial carbon utilization and nitrogen cycling.

'It looks like you just want them when things get rough': civil society perspectives on negative trial results and stakeholder engagement in HIV prevention trials.

Civil society organizations (CSOs) have significantly impacted on the politics of health research and the field of bioethics. In the global HIV epidemic, CSOs have served a pivotal stakeholder role. The dire need for development of new prevention technologies has raised critical challenges for the ethical engagement of community stakeholders in HIV research. This study explored the perspectives of CSO representatives involved in HIV prevention trials (HPTs) on the impact of premature trial closures on stakeholder engagement. Fourteen respondents from South African and international CSOs representing activist and advocacy groups, community mobilisation initiatives, and human and legal rights groups were purposively sampled based on involvement in HPTs. Interviews were conducted from February-May 2010. Descriptive analysis was undertaken across interviews and key themes were developed inductively. CSO representatives largely described positive outcomes of recent microbicide and HIV vaccine trial terminations, particularly in South Africa, which they attributed to improvements in stakeholder engagement. Ongoing challenges to community engagement included the need for principled justifications for selective stakeholder engagement at strategic time-points, as well as the need for legitimate alternatives to CABs as mechanisms for engagement. Key issues for CSOs in relation to research were also raised.

Development and Implementation of Diabetes Care by a Community Network Based on a Chronic Care Model.

INTRODUCTION: This participatory action research was conducted by the collaborative health-related team in a district, in Thailand. The community network jointly developed a care model for diabetic patients in primary care using the Chronic Care Model (CCM) and evaluated the effectiveness of implemented model. METHODS: Data was collected between October 2021 and March 2022 and involved 2 groups: 1) a community network of 25 people including representatives of the community hospital, primary care hospital, Sub-district administrative organization, community leaders, community representatives, representatives of diabetic patients, and representatives of caregivers of diabetic patients, and 2) 41 people with type 2 diabetes and 41 of their family caregivers. The research was conducted in 4 stages: planning, action, observation, and reflection. RESULTS: Both quantitative and qualitative data were collected, and the overall average knowledge scores of diabetic patients, family caregivers, and community representatives significantly increased from before (6.07 ± 2.11, 7.07 ± 1.98, P = .024, 5.74 ± 1.88, 7.37 ± 2.25, P < .001, 7.47 ± 2.44, 8.99 ± 1.72, P = .010) respectively. For satisfaction, diabetic patients were most satisfied with family caregiver support, while the community network representatives were most satisfied with their participation in planning a model for diabetic patients in primary care. After model implementation, the blood sugar-controlled patients (HbA1c < 7 mg%) significantly increased (0 and 9.76%, P = .045), although the fasting blood sugar (FBS) of diabetic patients did not improve. CONCLUSION: The development and implementation of diabetes care based on CCM, promoted community participation and involvement in diabetes care. This model mainly affected diabetic patients who could control their HbA1c level and the satisfaction of the community network.