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Automated quantification of tumor-infiltrating lymphocytes by machine learning reveals prognostic and immunogenomic features in lung cancer

Deep neural network-based coupling model of inter-organizational knowledge flow and agent collaborative decision-making

Sepsis insult generates different vascular response phenotypes: an unsupervised time-series clustering preclinical study

Haplotype-level analysis of environmental DNA metabarcoding revealed the biogeography and phylogeography of freshwater fishes in Korean Peninsula

Bioactive galloylquinic acids from Copaifera lucens as dual inhibitors of SARS-CoV-2 Spike and RdRp proteins

Accessibility features in executive function apps and user performance post-stroke

Fecal metabolic signals are associated with changes in microbiota and systemic metabolic pathways in Crohn’s disease

Research on the power of non-state-owned shareholders in the board and state-owned enterprises’ innovation investment

In the deepening stage of the reform of mixed ownership of state-owned enterprises from “mixed equity” to “reform mechanism”, how to stimulate the vitality of enterprise innovation through effective reform of corporate governance mechanism has become a core issue related to the success or failure of the reform. Existing research mostly focuses on the equity structure of non-state-owned shareholders, but generally ignores the power allocation of the board of directors, which is a key link in transforming equity advantages into governance efficiency. Based on the perspective of board functions, this paper discusses the impact and mechanism of the board of directors’ board power on the innovation investment of state-owned enterprises from 2008 to 2022. The research finds that the power of non-state-owned shareholders in the board has a significant promotion effect on SOEs’ innovation investment. The results of the robustness test show that such a finding holds. According to mechanism analysis, the interplay intensity in the board serves as sort of mediator for the impacts of the power of non-state-owned shareholders in the board on SOEs’ innovation investment. The power of state-owned shareholders in the board plays an inverted U-shaped role in the positive promotion exerted by the power of non-state-owned shareholders in the board on SOEs’ innovation investment, that is, along with the expansion of the power of state-owned shareholders in the board, the positive impacts of the power of non-state-owned shareholders in the board on innovation investment are reinforced before being inhibited.

Machine learning for the diagnosis of fibromyalgia based on magnetic resonance imaging

The clinical diagnosis of fibromyalgia (FM), a syndrome characterized by generalized pain, is challenging due to its unknown etiology and frequent comorbidity with other diseases. As a noninvasive modality, functional magnetic resonance imaging has been extensively employed in investigating the pathogenesis of FM. This study proposes a novel diagnostic approach utilizing resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) combined with a machine learning algorithm with the objective of enhancing the clinical diagnostic efficiency of FM. Two-sample t tests revealed differences between FM patients and healthy controls in rs-fMRI and DTI corresponding to brain image indices, mainly in the temporal lobe and frontal lobe. In addition, an effective diagnostic classification model was developed based on the single variable feature selection method by applying a support vector and random forest classifier combined with different brain image indicators. Our study demonstrated that the integration of DTI features with a support vector machine model yields superior diagnostic outcomes.

Thoracic surgeons’ practice and attitude towards surgical antimicrobial prophylaxis in VATS lung surgery: A survey within a large medical consortium

Background and objectives Surgical site infections (SSIs) are a significant post-surgery complication, impacting mortality, morbidity, and healthcare costs. Surgical antimicrobial prophylaxis (SAP) is pivotal in SSIs prevention. This study aimed to evaluate the current use of SAP in video-assisted thoracoscopic surgery (VATS) lung surgery in China. Methods A descriptive, cross-sectional survey study was conducted among thoracic surgeons within a large medical consortium in order to assess their practice and attitude about SAP. A three-section multiple-choice online questionnaire was designed and distributed via WeChat software to thoracic surgeons. The surgeons’ answers were considered consistent when they were in accordance to clinical guidelines. Results 89 thoracic surgeons were requested to participate in this study and their response rate was 73.03%. Preoperatively, 60.00% administered antimicrobials, predominantly within 0.5 to 1 hour before surgery, with cefuroxime as the preferred agent. Intraoperatively, 32.31% did not administer additional antimicrobials, and postoperatively, 90.77% prescribed them, often continuing until drainage tube removal. Surgeons frequently upgraded prophylaxis, especially postoperatively. Deviations from guidelines were common, particularly in postoperative SAP duration (76.92%), intraoperative redosing decisions (58.33%), and preoperative SAP administration (40.00%). Departmental habits significantly influenced SAP practices. The primary reason for inconsistencies was the absence of patient-specific considerations in the guidelines, affecting nearly half of the cases. Experienced surgeons were more likely to cite this lack of patient-specific attention as a reason for deviation. Conclusion The study underscores the need for updated, multidisciplinary guidelines for VATS lung surgery, emphasizing the importance of a collaborative approach among healthcare professionals to optimize individualized SAP.

A hybrid color emotional experience approach: Integrating the pleasure-arousal-dominance model with fuzzy grey relational analysis

Color schemes are a crucial component of modern product design and user experience, closely linked to users’ emotional needs. However, emotional experiences with product colors are inherently complex and abstract. Accurately capturing these emotional tendencies and translating them into effective color schemes has long been a challenge in emotional design. This study proposes an emotional experience-based approach to product color matching, grounded in Kansei Engineering (KE). To establish a robust closed-loop between design and evaluation, both forward and reverse KE models were developed, accompanied by comprehensive evaluation methods ranging from color factor analysis to the optimization of final schemes. Given the vagueness and complexity of the experiential data obtained from 216 questionnaires, the Pleasure-Arousal-Dominance (PAD) model was integrated with fuzzy Grey Relational Analysis (GRA) to extract nuanced and meaningful insights. Using the color design of a household hair dryer as a case study, the feasibility of the framework was demonstrated. Comparative results showed that, the proposed PAD–fuzzy GRA approach produces more stable and discriminative evaluation outcomes for intermediate schemes. Moreover, the resulting rankings exhibited a higher degree of consistency with independent eye-tracking measurements, indicating a closer alignment with users’ actual visual attention and emotional perception. The proposed methodology effectively captures users’ emotional responses to specific color schemes without relying on overly complex calculations or experimental conditions. It aligns with subjective visual preferences and identifies color combinations that evoke positive emotions. By incorporating practical design psychology methods, this hybrid design and evaluation framework offers an intuitive and applicable reference for emotional experience, extending beyond conventional color matching.

Skin-related adverse events and their associated factors among Diabetic patients on insulin therapy

Background More than 530 million individuals globally are afflicted with diabetes mellitus (DM), and the prevalence continues to escalate. Insulin remains the cornerstone of DM management across the globe. Nevertheless, existing literature indicates that individuals utilizing insulin are susceptible to developing abscesses and scar formation at injection sites. These complications may undermine therapeutic adherence, thereby adversely impacting the intended clinical outcomes. This study aimed to evaluate the prevalence of abscesses and scar formation at injection sites, along with their associated factors, among diabetic patients undergoing insulin therapy in Dar es Salaam, Tanzania. Methods A hospital-based analytical cross-sectional study was conducted from the 28th of February 2024 to the 25th of May 2024. A total of 428 patients diagnosed with diabetes mellitus and undergoing insulin therapy were enrolled from four selected hospitals in Dar es Salaam. A validated case report form (CRF) was employed to gather socio-demographic characteristics and clinical data pertinent to the formation of abscesses and scars following insulin therapy. Data were analyzed utilizing Stata version 15.0 software, with findings summarized as frequencies and percentages. Factors associated with the development of abscesses and scarring were evaluated using modified Poisson regression, and a p-value of less than 0.05 was deemed statistically significant. Results Of 428 participants, the prevalence of abscesses and scar formation at the insulin injection site was 22.2% and 46.7%, respectively. Factors positively associated with abscesses were improper injection technique (adjusted Prevalence Ratio [aPR] = 1.11; 95% CI: 1.02–1.21, p = 0.009) and poor injection site rotation (aPR = 2.7; 95% CI: 1.13–6.45, p = 0.025). In contrast, the use of an insulin pen was negatively associated with abscesses (aPR = 0.13; 95% CI: 0.04–0.48, p = 0.002). Scar formation was positively associated with improper injection site rotation (aPR = 1.63; 95% CI: 1.03–2.32, p = 0.037) and uncontrolled blood glucose levels (aPR = 1.69; 95% CI: 1.01–2.84, p = 0.049). Conclusion This study indicates that skin complications at insulin injection sites are highly prevalent. The findings suggest that improper injection technique, poor site rotation, and uncontrolled blood glucose are significant modifiable risk factors. The use of insulin pens may help reduce the risk of abscesses. Therefore, targeted patient education on correct injection practices and glycemic control is crucial to minimize these complications.

Temporal trends and health inequalities in global, regional, and national years lived with disability of severe periodontitis from 1990 to 2021

This study evaluates changes in cross-national disparities in the burden of severe periodontitis between 1990 and 2021. All data on severe periodontitis used in this study were derived from the 2021 Global Burden of Disease (GBD) study. Annual years lived with disability (YLDs) and their estimated annual percentage changes (EAPCs) were calculated and stratified by year, age, geographical region, and socio-demographic index (SDI) at global, regional, and national levels. Decomposition analysis assessed the contributions of demographic and epidemiological factors to the evolving burden of severe periodontitis. A frontier analysis identified areas for improvement and disparities among countries based on development levels. Distributional inequalities were measured using the slope index of inequality (SII) and concentration index. The autoregressive integrated moving average model (ARIMA) was used to project the disease burden up to 2036. In 2021, there were 6,903.28 thousand YLDs (95% uncertainty interval [UI]: 2,772.28−14,106.18 thousand) attributed to severe periodontitis globally. Between 1990 and 2021, the global age-standardized rate (ASR) of YLDs showed a stable trend, increasing slightly from 79.62 (95% UI: 31.46–169.62) to 80.89 (95% UI: 32.47–165.37) with an EAPC of 0.08% (95% confidence interval [CI]: −0.03 to 0.18). Population growth accounted for 66.73% of the global increase in YLDs. SII values rose from 12.72 (95% CI: 1.92–23.52) in 1990 to 44.99 (95% CI: 31.14–58.85) in 2021, while the concentration index decreased from 0.05 (95% CI: −0.04 to 0.13) in 1990 to 0.035 (95% CI: −0.06 to 0.13). According to the forecasts, the global ASR of YLDs for severe periodontitis is projected to show a slight decline over the next 15 years. Significant potential exists for reducing the burden of severe periodontitis across countries, irrespective of their development levels. Severe periodontitis remains a significant global health challenge, with substantial cross-country disparities that persist despite overall stable trends in global YLDs. Targeted interventions and policies are urgently needed to address these disparities, focusing on improving oral health outcomes across all countries, regardless of their socio-demographic development levels.

Model-free prognostication of non-linear time series

Objective The COVID-19 pandemic has highlighted the importance of studying the course of infectious progression. Similar needs exist for time series of other origins. While models are commonly devised and fitted to the observed data, we recently demonstrated the feasibility to directly evaluate the noisy non-linear time series that characterize the occurrence. However, for practical utility, analytics alone has limited value. The requirement of forecasting – at least in the short term – needs to be met. Methods We initially utilized normalized new infections per day (7-day moving average for cases per million inhabitants) from Our World in Data. We then validated our method in unrelated non-linear time series of stock markets and blowfly populations. We studied a novel model-independent time series approach, time lagged analyses, and feature-space plots incorporating the time-lagged data. Results 1) Machine learning on the basis of correlation coefficient, utilizing about 80% of the time series as training sets, was able to generate excellent predictions for progression. 2) Feature-space plots of normalized new cases versus autocorrelation and average mutual information required a form of dynamic calibration to correct for differences in scale among the axes. With that adjustment, the maximum local Lyapunov exponent displayed sharp spikes concomitantly with peaks of infectious spread. 3) The average mutual information over various time lags and wave lengths displayed divergence and sums of absolute values that were anticipatory to peaks in new infections. Conclusion The study of non-linear time series with available techniques for observed complex data can extract characteristics that enable short-range forecasting without the need for model-building. Time-lagged analysis provides one suitable foundation. Among various approaches, machine learning achieved the best prognosticative results.

Virological failure and risk factors among people living with HIV taking second-line ART in Addis Ababa, Ethiopia

Background Virological failure (VF) presents significant challenges in the emergence of drug resistance, and elevated risk of transmission, higher mortality rates, and a diminished quality of life. Various factors contribute to VF, but documented information on this issue is lacking in Ethiopia. Therefore, this study aimed to assess the prevalence of VF and identify the risk factors among people living with HIV who are on second-line antiretroviral treatment (ART). Methods A concurrent mixed-method study using quantitative and qualitative data was conducted at selected hospitals in Addis Ababa, Ethiopia. The analysis was conducted using SPSS version 28, Stata version 18.5, and R for quantitative data and thematic analysis with Atlas.ti version 24 software was used for qualitative data. Result Among 369 adults living with HIV taking second-line ART enrolled in the study, 191 (52%) were male with a median age of 44 years. The prevalence of VF was 55 (14.9%, 95% CI: 11, 19), with an incidence density of 27.2 per 10,000 person months (95% CI 21.1, 35.5). Lost to follow-up significantly increased VF risk [AHR: 2.52 (95% CI: 1.35, 4.69, p-value: 0.004)]. Patients transferred from other health facilities were two times at higher risk of VF compared to those receiving ART at the same facility [AHR: 1.97 (95% CI: 1.07, 3–64, p-value: 0.029)]. Likewise, clients with a history of regimen change were at a higher risk of VF [AHR = 2.05, (95% CI: 1.08, 3.88, p-value = 0.027)]. The qualitative data also supported these findings. Conclusion This study underscores the need for improved ART adherence and consistent care to reduce virological failure in PLHIV to improve the quality of life.

Making community-based health planning and services work: Staffing, accountability and digital integration for quality primary health care in Northern Ghana

Background Strengthening primary health care through Ghana’s Community-based Health Planning and Services (CHPS) strategy depends on functional community structures, responsiveness, and integration into health information systems. However, the extent to which CHPS zones use the Ghana Community Scorecard (CSC) to promote accountability, equity, and service improvement remains unclear. We assessed CHPS staff categories and functionality in Northern region of Ghana and their ability to support Community Health Management Committees (CHMCs) in health facility assessments, Community Health Action Plans, and updating of results into existing digital platforms. Method A cross-sectional design combined quantitative surveys and qualitative interviews across 86 CHPS zones in six districts between March 13–20, 2024. Analysis focused on staff categories, functionality, CSC trainings, facility assessment, utilization of results, feedback mechanisms, and service improvements. Qualitative data explored barriers and enablers shaping CHPS performance. Results The 86 CHPS zones employed 549 health workers, predominantly female (51%). Categories included Community Health Officers (5%), midwives (17%), registered nurses (14%), enrolled nurses (33%), community health nurses (27%) and others (5%). Overall, 96% of CHPS zones were functional based on staff, CHMCs, volunteers, equipment, and service provision. About 88% had basic equipment. Services include outreach, home visits, minor illness treatment, antenatal care, and referrals. CSC training reached 41% of Community Health Officers and other health workers. Only 36% of the CHPS zones uploaded facility assessment results to existing digital platforms, and 46.5% implemented improvements from CSC recommendations. High-performing districts benefitted from adequate staffing, training, Non-Governmental Organization support, and community mobilization. Barriers included limited training coverage, exclusion of midwives and nurses from training, and persistent Gender, Equity and Social Inclusion (GESI) gaps. Conclusion CHPS zones show functionality but face challenges in staff capacity, training, and digital integration. Gaps in inclusivity and equipment provision limit effectiveness. Scaling-up training, strengthening human resources, improving basic equipment provision, and embedding GESI are essential to ensure CHPS zones deliver equitable, accountable, and quality services.

In-silico characterization of deleterious non-synonymous SNPs in the human S1PR1 gene reveals structural instability and altered ligand affinity

S1PR1 is a G protein-coupled receptor that plays a key role in regulating lymphocyte trafficking, immune response, cardiovascular system function, cell proliferation and survival, tumor angiogenesis, and metastasis. It is also recognized as a pharmacotherapeutic target for the treatment of autoimmune diseases like relapsing multiple sclerosis and ulcerative colitis. This study aimed to identify deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) in the S1PR1 gene that may impact its functional properties and pharmacotherapeutic responses though in-silico approaches. A total of 3,259 SNPs were identified in the human S1PR1 gene, with 6.51% being non-synonymous (nsSNPs). Functional predictions from eight computational tools prioritized 25 deleterious variants. Further structural and evolutionary evaluation highlighted R120P, F125S, C184Y, Y198C, and L275P as the most damaging nsSNPs. These mutations were found to cluster within the seven-transmembrane (7-TM) domain (residues 46–322), directly affecting receptor stability and signaling. Structural modeling revealed disrupted hydrogen bonds, void formations, and loss of critical disulfide bonding (C184Y), severely compromising folding. Conservation analysis confirmed R120P, F125S, and C184Y as highly conserved (score 9), underscoring their functional importance. Molecular docking and dynamics simulations showed that R120P and F125S weaken binding affinity for natural agonist sphingosine-1-phosphate (S1P) and FTY720P, while antagonist W146 retained strong binding. Our analysis further revealed significant changes in binding interactions and protein-ligand complex stability under simulated physiological conditions. Collectively, these findings identified high-risk nsSNPs in S1PR1 gene with potential structural and functional implications, particularly in diseases involving impaired receptor signaling. These findings enhanced our understanding of how specific nsSNPs can influence disease susceptibility, drug response, and receptor function, paving the way for precision medicine approaches in treating autoimmune and inflammatory disorders.

A fractional-order approach to predator-prey interactions: Modeling fear and disease dynamics with memory effects

The dynamical behaviors of a predator-prey model with fear effect and disease on prey are studied by employing the fractional-order derivative with a power-law kernel as the operator. The proposed model introduces four novel aspects: the impact of fear on a constant recruitment rate, previously unexplored in the literature; reinfection dynamics where infected prey can re-acquire the disease; selective predation by predators on infected prey due to pathogen-induced vulnerability; and the used of Caputo fractional derivative to include the memory effect. A deterministic approach is provided to establish the mathematical model including its validity by showing the existence, uniqueness, non-negativity, and boundedness. Three types of equilibrium points are obtained which represent the extinction of disease and predator, the predator-free, and the co-existence points. The local dynamics are investigated using Matignon’s condition and generalized Routh-Hurwitz criterion for the Caputo fractional-order model. The Volterra, quadratic, and linear functions are utilized to construct the Lyapunov function, as well as the LaSalle invariance principle, to show global dynamics. Some phenomena are provided namely forward and Hopf bifurcations to show the change of the dynamics when a parameter is varied. These results are supported by numerical ways using the predictor-corrector scheme.

Complex excitability and “flipping" of granule cells: An experimental and computational study

In response to prolonged depolarizing current steps, different classes of neurons display specific firing characteristics (i.e., excitability class), such as a regular train of action potentials with more or less adaptation, delayed responses, or bursting. In general, one or more specific ionic transmembrane currents underlie the different firing patterns. Here, we sought to investigate the influence of artificial sodium-like (Na channels) and slow potassium-like (KM channels) voltage-gated channels conductances on firing patterns and transition to depolarization block (DB) in Dentate Gyrus granule cells with dynamic clamp - a computer-controlled real-time closed-loop electrophysiological technique, which allows to couple mathematical models simulated in a computer with biological cells. Our findings indicate that the mimicked extra Na/KM channels significantly affect the firing rate of low-frequency cells, but not that of high-frequency cells. Moreover, we have observed that 44 percent of recorded cells exhibited what we have called a “flipping” behavior. This means that these cells were able to overcome the DB and generate trains of action potentials at higher current injection steps. We have developed a mathematical model of “flipping" cells to explain this phenomenon. Based on our computational model, we conclude that the appearance of “flipping" is linked to the number of states for the sodium channel of the model.

Evidence of prevailing practice of home slaughter in Iran revealed by bioeconomic modeling of small ruminants slaughtered in and outside registered abattoirs

Home slaughter seems to be a prevailing practice in developing countries, and presents a potential public health risk and animal welfare problem for the societies all over the world. Nevertheless, the nature and extent of this practice is poorly understood in many countries. The objective of this study was to estimate the number of sheep and goats slaughtered outside registered abattoirs in Iran and to discuss the possible determinants of this practice. Number of live and slaughtered animals, human population, and per capita red meat consumption were extracted from FAOSTAT and the Statistical Center of Iran (SCI). Per capita red meat consumption and bio-economic modeling of flock compositions were used to estimate non-abattoir slaughter numbers. Based on per capita meat consumption and the bio-economic models, it was estimated that 7,937,725 (42.3%) and 12,809,170 (54.1%) of sheep and goats were slaughtered either at home or in unregulated abattoirs during 2017. Home slaughter is a neglected problem in numerous countries and communities. Additional studies are needed to clarify the nature and extent of this human and livestock health challenge. An integrated One Health surveillance system is needed to address this practice in developing countries.