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A novel approach for automated counting of tumor cell colonies

Background and Objective The heterogeneous response of cancer cells to radiation necessitates comprehensive investigations into cell survival, which are often conducted using clonogenic assays. These assays involve laborious and subjective manual enumeration of cell colonies. This paper presents an innovative digital image processing technique for automated cell colony counting. Methods This research focused on HT-29 cells (colon cancer). The methodology uses Hough techniques to achieve precise detection, mathematical morphology, and establishment of the optimal minimum colony size using ROC curve. This approach seamlessly integrated into ImageJ software as a ColCounter plugin. Results Images with resolution of 1200*1200 pixels achieved sensitivity and specificity of 92.88% and 92.62%, respectively. To determine the software´s effectiveness of image analysis of different resolutions compared with manual counting, an evaluation of the automated method’s reliability was conducted. The findings revealed an overall intraclass correlation coefficient (ICC) of 0.89 (95% CI: 0.81–0.93). The limits of agreement were determined using the Bland-Altman method. Conclusions The proposed methodology demonstrated interchangeability with the conventional manual enumeration technique. The results confirm the software’s elevated performance, even in altered contexts. ColCounter offers manual editing function, enhancing its utility as a streamlined, rapid, and precise tool for quantifying tumor cell colonies in clonogenic assays.

Planetary-mass exosatellite detected around the substellar companion of a star

Measurement of sludge-water interface based on adjustable peak point of ultrasonic echo energy

To address the escalating water resources consumption, the need for intelligent automation in urban sewage treatment has become imperative. However, existing ultrasonic sludge interface instruments have been found to exhibit poor environmental noise suppression and low identification accuracy of mud-water interface, thereby necessitating a new approach. This paper analyzes the problems and proposes a mud-water interface monitoring method based on extraction of ultrasonic energy peak point. The method involves an array ultrasonic system structure comprising multiple ultrasonic transmitting and receiving elements, median value average filtering to suppress peak noise interference, and interval maximum method to separate the target peak point from residual noise. The proposed method was tested using a high-precision ultrasonic probe in Beijing Ma-Fang Sewage Treatment Plant and corrected using a fault diagnosis method with 3σ threshold. Results demonstrated a high measurement accuracy with a mean deviation of less than 2% and a precision variance below ±0.02 m. Compared to conventional ultrasonic and optical methods, this approach exhibited superior robustness in turbid environments, fully meeting the technical requirements of sludge thickness monitoring.

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The anxious society’s fertility problem: The promoting effect of physical exercise on mental health—An empirical analysis using CGSS data

The declining willingness to have children is significantly influenced by underlying psychological constraints that cannot be ignored. Providing psychological health support and interventions for the reproductive-age population is crucial for enhancing fertility intentions. Based on data from the 2021 China General Social Survey, this research explores the association between the psychological benefits of physical exercise on individuals’ willingness to bear children. The results indicate a positive correlation between engagement in physical exercise and individual fertility intentions. Specifically, a one-unit higher in level of physical exercise is associated with a 0.099-unit higher level of fertility willingness. Mechanistically, participation in physical exercise is associated with psychological well-being ( β  = 0.0133, P  < 0.001) and social engagement( β  = 0.011, P  < 0.001),these factors are, in turn, associated with higher fertility intentions. Heterogeneity analysis reveals that the positive association between physical exercise and fertility intentions is more pronounced among single individuals with higher educational attainment and income levels (β = 0.092, β = 0.109, β = 0.095; P < 0.001), suggesting potential implications for addressing the “fertility-income paradox.”.

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Biodiversity of Eucalyptus endophytic fungi across different climates in Iran

Endophytic fungi are crucial for plant health, but the relative importance of climate versus host factors in shaping their communities is not fully understood. This study investigates the hypothesis that macro-climate is one of the primary drivers of endophytic fungal diversity and composition in Eucalyptus camaldulensis across different regions in Iran. A total of 712 fungal isolates were isolated from leaves, branches, and fruits across five provinces (Alborz, Isfahan, Mazandaran, Qom, and Tehran) spanning arid to humid climates. Cultivation and morphological/molecular identification revealed a clear diversity gradient, with the highest species richness, Shannon diversity, and colonization frequency in the humid province of Mazandaran, and the lowest in the semi-arid and arid provinces of Alborz and Qom, respectively. Community composition shifted significantly along this climatic gradient: arid sites were dominated by stress-tolerant generalists (e.g., Alternaria ), while the humid site supported a balanced community of specialists (e.g., Neofusicoccum ). Across all climates, tissue type was a consistent secondary filter, with leaves harboring the most diverse communities, followed by branches and fruits. These results demonstrate a hierarchical assembly where climate filters the regional species pool, and host tissue type then fine-tunes the local community. This study provides the first comprehensive baseline of E. camaldulensis endophytes in Iran and highlights the vulnerability of these symbiotic systems to climate change, while also identifying them as a valuable resource for biotechnology.

Identifying academic success and underperformance: The discriminative power of very short answer questions and multiple-choice questions

Background Multiple-choice questions (MCQs) are widely used in medical education, but are criticized for cueing and guessing. Very short answer questions (VSAQs), which require students to generate responses independently, may better assess knowledge. While VSAQs demonstrate higher item discrimination within individual exams, their effectiveness in distinguishing academic performance across multiple assessments remains unclear – representing a key gap in the validation of VSAQs under Messick’s framework, specifically the category of “ relations to other variables ”. This study examines whether VSAQs or MCQs more effectively distinguish students of varying performance levels across multiple summative examinations. Methods We analyzed retrospective data from six mixed-format examinations with VSAQs and MCQs of three cohorts of first- and second-year medical students. Academic performance was measured using grade point average (GPA) across assessments. Linear regression assessed the relationship of each question format with GPA, while ROC curves and C-statistics evaluated their ability to identify poor and excellent performing students (lowest and highest quintile of GPA). Results VSAQs showed higher item discrimination (R ir -values) than MCQs in all exams. VSAQs also had a stronger positive association with GPA compared to MCQs, and higher C-statistics, indicating superior discriminative ability. Conclusion VSAQs outperform MCQs in distinguishing academic performance levels across multiple assessments. Their integration into examinations enhances discriminative ability and may facilitate earlier identification of poor and excellent performing students, enabling targeted interventions and support of students.

Insomnia and psychological disintegration: Evidence from a transdiagnostic network analysis

Insomnia is commonly conceptualized in terms of hyperarousal or symptom amplification; however, less attention has been paid to the structural organization and integration of psychological processes underlying sleep disturbance. This study examined whether insomnia is associated with reduced integration among psychological domains rather than elevated symptom activation alone. A comparative network analysis was conducted on 27 transdiagnostic psychological markers in a sample of 391 Iranian university students (169 poor sleepers, 222 good sleepers). Gaussian graphical models were estimated using graphical LASSO regularization with EBIC model selection. Network structure, expected influence, and node predictability were examined, and Network Comparison Tests were used to assess structural and global strength differences between groups. Compared with good sleepers, poor sleepers exhibited markedly sparser network structures, a greater number of isolated nodes, and substantially lower node predictability. No significant differences were observed in global network strength between groups. Several cognitive variables tended to show higher centrality in good sleepers, suggesting context-dependent roles within more integrated psychological systems. These findings indicate that insomnia may be characterized by reduced integration among psychological processes rather than uniformly elevated symptom activation, reflecting a systems-level characteristic of psychological functioning associated with sleep disturbance.

The current status of health literacy among caregivers of lung cancer patients:A cross-sectional survey

Aim This exploratory, hypothesis-generating study aimed to investigate the current status of cancer health literacy among lung cancer caregivers and to identify factors associated with their health literacy levels. The primary hypothesis was that caregivers would demonstrate sub optimal cancer health literacy. The primary endpoint was the total score on the Chinese Cancer Health Literacy Scale (C-CHLS). Secondary endpoints included scores on the Health Literacy of Caregivers Scale-Cancer (HLCS-C) and the identification of factors associated with caregivers’ health literacy. Background Health literacy, defined as an individual’s ability to acquire, comprehend, and utilize health-related information to make informed decisions for maintaining health, is a critical factor in cancer prevention and treatment. It significantly impacts individual health outcomes.While existing research primarily focuses on cancer patients,there is limited exploration into the health literacy of cancer caregivers, who play a vital role in patient support and care. Design A cross-sectional study. Methods Using convenience sampling, 198 caregivers of lung cancer patients receiving treatment at a tertiary hospital in Sichuan Province, China, from October 2024 to December 2024 were recruited. Data were collected using a general information questionnaire,health literacy of caregivers scale-cancer and Chinese cancer prevention and control literacy questionnaire. Data entry was performed using Microsoft Excel 2016, and statistical analysis was conducted using SPSS 26.0. Results Only 48.48% (n = 96) of caregivers demonstrated adequate health literacy. Multivariable analysis identified seven factors significantly associated with cancer health literacy (all p  < 0.05): younger age (β = 0.187, t = 3.189), higher education level (β = 0.209, t = 2.784), professional occupation (β = 0.169, t = 2.144), better self-rated health (β = 0.186, t = 3.091), non-smoking status (β = 0.175, t = 2.514), non-alcohol consumption (β = 0.163, t = 2.412), and higher perceived cancer risk (β = 0.286, t = 4.274). Conclusion The suboptimal health literacy levels among lung cancer caregivers observed in this sample underscore the potential need for tailored educational interventions. Future programs may consider addressing modifiable factors, particularly focusing on older, less-educated caregivers with health-risk behaviors. These findings provide preliminary evidence for developing targeted strategies to improve caregiver health literacy in similar clinical settings.

Direct medical costs of respiratory infections in adults: A multicenter retrospective analysis in Thai Nguyen, Vietnam

Background Respiratory infections remain a significant health and economic burden in low- and middle-income countries, including Vietnam. This study aimed to estimate the direct medical costs of respiratory infections among adults in Thai Nguyen, Vietnam and identify some influencing factors. Methods In this retrospective study, we analyzed direct medical costs of inpatient aged ≥18 discharged with respiratory infections (ICD-10 codes: J00 – J22) in seven hospitals in Thai Nguyen, Vietnam. Records of patients admitted between 11 November 2022 and 30 June 2025 were included. A generalized gamma linear mixed model with log-link function was used to identify influencing factors, including patient demographics and infection-related characteristics. All costs are expressed in US$, adjusted to 2025 levels. Results The analysis included 25,081 inpatients with 28,016 respiratory infection episodes. Most were female (54.3%), Kinh ethnicity (70.0%), and aged ≥60 (58.1%). Pneumonia (J18) was the most common primary diagnosis (58.5%), followed by bacterial pneumonia (J15, 18.7%). Common secondary diagnoses included hypertension (27.1%), gastro-oesophageal reflux disease (7.8%), and type 2 diabetes (6.9%). The median total medical cost per inpatient episode was US$174.9 (IQR 104.7–243.3), mainly driven by hospital bed days (median US$83.5), followed by medicine costs (US$52.7), and laboratory tests (US$12.7). Pneumonia was the most expensive disease, with median costs of US$218.8 (J15), US$1,179.4 (J16), and US$181.5 (J18). Primary diagnosis, age, gender, hospital level, length of stay, and additional secondary diagnosis were associated with higher direct medical costs. Conclusion Hospitalized adults with respiratory infections incurred a median direct medical cost of US$174.9 in Thai Nguyen, Vietnam. Costs were substantially higher for lower respiratory tract infections and were influenced by hospital level, length of stay, and comorbidities. These findings highlight the need for preventive measures and efficient hospital resource allocation in Vietnam.

Eligibility to donate blood under an individual donor assessment policy: A national cross-sectional study of gay, bisexual and other men who have sex with men in Aotearoa, New Zealand

Background To protect the blood supply, many countries defer higher-risk donors such as men who have had sex with men (MSM) in the last 3 months. However, this may be unnecessarily restrictive and increase non-compliance risks. New Zealand (NZ) has shifted from this approach to individual donor assessment (IDA), but the potential impact is poorly understood. We aimed to estimate the increase in blood donor eligibility and examine the characteristics of newly eligible MSM. Methods We used data from SPOTS, a large national cross-sectional online survey of MSM. Items included socio-demographics, blood donation history, views and preferences about blood donation, sexual behaviours and drug use. We described blood donation engagement and estimated the proportion eligible to donate blood under three scenarios (previous NZ policy; UK-style: IDA with chemsex deferral; Canada-style; IDA without chemsex deferral). We then examined the characteristics of potentially newly eligible MSM donors. Results Of the 3,235 participants, 43.1% had ever donated blood, 82.0% were interested in donating, 86.1% preferred an IDA-style policy, and 80.6% intended to donate, should they become eligible. We estimated 13% were eligible to donate under the previous NZ policy, rising to 37% under a UK-style IDA, and 41% under NZ’s new IDA policy. In NZ’s new IDA policy, 30% of currently ineligible participants will become eligible. Compared to participants currently eligible, newly eligible MSM were more likely to be aged 30–44 (OR 1.8, 1.4–2.4), tertiary educated (OR 1.4, 1.1–1.8), spend a lot of their free time with gay men (OR 4.3, 3.2–5.9), and identify as gay only (OR 2.5, 1.96–3.2). As expected, a high proportion of newly eligible MSM were in a regular same-sex relationship. Conclusions NZ could triple eligible MSM donors with its new IDA policy. Findings from this research are relevant internationally as blood services plan IDA implementation.

Cognitive flexibility, impulsivity, and compulsivity in problematic consumption behaviours

Different studies have identified cognitive inflexibility, impulsivity and compulsivity in substance use and gambling disorder, but it is unclear whether these deficits are present in other possible addictive behaviours. In this study, we evaluated cognitive inflexibility, as measured by the Probabilistic Reversal Learning Task (PRLT), impulsivity across UPPS-P model and the compulsivity in regular gamblers, buyers, video gamers, consumers of pornography and control group. Multivariate analysis was performed to evaluate the five groups, revealing higher scores across several impulsivity and compulsivity domains in the buyers group compared to the other groups. On the overall measure of cognitive flexibility using the PRLT, buyers performed worse than gamers and pornography users, suggesting a relative disadvantage in adapting to changing reward contingencies even before trial-level learning patterns were examined. To further evaluate patterns of cognitive flexibility across groups, a GLME model was developed. The results showed that phase-group interactions were generally weak, and none of the contrasts related to reversal differed between groups. This indicates that the cost of adapting to contingency reversals was similar across all five groups, with no evidence that any particular group would exhibit greater inflexibility during reversal phases. Finally, the findings show that impulsivity and compulsivity can manifest themselves differently in these activities, which has implications for the development of more personalised intervention strategies that take into account both the nature of the disorder and the specific cognitive deficits involved.

Global lung cancer burden, trends, and projections from 2010 to 2050: A population-level severity framework integrating DALYs-per-case and mortality-to-incidence ratio

Background Lung cancer remains the leading cause of cancer mortality worldwide. While incidence and mortality describe population burden, they do not fully capture disease severity at the level of the individual patient. This study quantified the contemporary global burden, temporal trends, and future trajectory of tracheal, bronchus, and lung (TBL) cancer, and applied a multidimensional severity framework integrating fatal and non-fatal outcomes. Methods A global ecological analysis was conducted across 185 countries and territories using harmonized data from GLOBOCAN 2022, the Global Burden of Disease (GBD) 2023 study, and the UN World Population Prospects 2024. Contemporary burden was assessed using incident cases, deaths, age-standardized incidence and mortality rates (ASIR/ASMR), disability-adjusted life years (DALYs), mortality-to-incidence ratio (MIR), and DALYs per incident case. Temporal trends in ASIR and ASMR (2010–2023) were estimated using log-linear regression to derive average annual percent change (AAPC). Projections to 2050 were generated under two scenarios: (1) constant 2022 rates reflecting demographic change only, and (2) trend-based projections extrapolating country-specific AAPCs. Disease severity was evaluated using a two-dimensional framework combining MIR and DALYs-per-case, which captures average lifetime health loss per diagnosed individual independent of population size or age structure. Results In 2022, an estimated 2.48 million new TBL cancer cases and 1.82 million deaths occurred globally, corresponding to ASIR and ASMR of 23.6 and 16.8 per 100,000, respectively. Global DALYs reached 46.7 million, yielding 18.8 DALYs per case, with substantially higher burden in males and in higher-SDI regions. From 2010-2023, age-standardized rates increased in most low- and middle-income countries and declined predominantly in high-income settings. By 2050, demographic change alone is projected to drive large increases in burden in many low-resource countries, with further amplification under trend-based scenarios. DALYs-per-case showed a moderate positive correlation with MIR (Spearman’s r_s = 0.46), revealing marked heterogeneity in severity profiles across countries. Conclusions Global lung cancer burden is projected to rise substantially in many regions despite declining rates in high-income settings. Integrating DALYs-per-case with MIR provides a complementary severity lens that highlights inequities not captured by incidence and mortality alone and supports more targeted prevention, treatment, and survivorship strategies.

Completeness of death registration in Ghana: An evaluation of multiple data sources and methods

Introduction The lack of a robust and comprehensive civil registration system undermines efforts to develop policies that address emerging health issues in a population. While Ghana has made significant strides in birth registration, progress in death registration has lagged despite the system’s introduction in 1888. Death records are dispersed across institutions and hampered by weak coordination and inconsistent data sharing. The study aims to evaluate the completeness of death registration using both demographic and empirical methods. Methods We assessed the quality of mortality data using demographic methods and further applied Death Distribution Methods (DDM) as well as the Empirical Completeness Method (ECM) to evaluate the completeness of death registration from the 2022 mortality register and two rounds of population and housing censuses. Findings Age reporting ranged between fairly accurate and rough, with noticeable under-reporting of under-five deaths. Death registration completeness was estimated at 28.7 percent and 56 percent using the ECM and DDM, respectively. DDM results reveal that male completeness was highest (101%) in the Volta Region and lowest (42%) in the Western Region, while female completeness was highest in Upper East (89%) and lowest in Western (35%) regions. Sub-national variations in completeness were further highlighted by the ECM, with completeness ranging from nearly 70 percent in Greater Accra to barely 8 percent in the Oti Region. Conclusions The study revealed that completeness of death registration remains low and incomplete, with minimal improvement over the past two decades. The findings underscore the urgent need to adopt innovative, targeted and coordinated approaches to improve completeness, ensuring Ghana can meet international commitments such as SDG 17.19.2.

Expression of Concern: How does social support influence autonomous physical learning in adolescents? Evidence from a chain mediation and latent profile analysis

Influence of salinity on growth, nutrient utilization, and gene expression of giant freshwater prawn (Macrobrachium rosenbergii)

Salinity is one of the most influential eco-hydrological factors that affect the molting, growth, and other physico-biochemical responses of crustaceans. A 56-day in vivo experiment was conducted to assess the effects of variable salinities on growth attributes, feed utilization, and gene expression profile of Macrobrachium rosenbergii. Juveniles of M. rosenbergii that were exposed to salinities of 0, 3, 6, 9, and 12 ppt in triplicate, and designated as control, T1, T2, T3, and T4, respectively. Higher weight gain (WG), %WG, specific growth rate (SGR), feed conversion ratio (FCR), and protein efficiency ratio (PER) were recorded at 3 ppt than at other salinities. A salinity of 3 ppt also showed higher values of condition factor (CF), and survival of M. rosenbergii . A polynomial regression analysis indicated that the optimal salinity for WG and SGR of M. rosenbergii were 3.12 and 3.80, respectively. A significant decrease in the molt-inhibiting hormone (MIH) and an increase in the chitinase (CHIT) gene expression were documented at 3 ppt compared to control. The mRNA transcripts of stress response genes were significantly downregulated, and immune-related genes were upregulated at 3 ppt salinity, compared to the other salinities. Although the expression of antioxidant-related genes was upregulated when rearing at 3 ppt salinity, no significant differences were found relative to other salinities. Our findings suggest that M. rosenbergii reared at 3 ppt salinity show promising improvements in growth attributes by modulating the expression profile of physico-biochemical response genes reared at low temperature.

Cardiometabolic risk pathways in adults with disabilities: A structural equation model of diet quality and functional ability

Background Adults with disabilities experience increased cardiometabolic risk, yet the pathways linking nutrition, functional ability, and environmental factors remain insufficiently defined. This study examined these relationships using a structural equation modeling framework. Methods A cross-sectional study was conducted among 123 adults with disabilities in Palestine (mean age 31.9 years). Data included anthropometric measures, two non‑consecutive 24-hour dietary recalls, disability severity (Disability Rating Scale), functional ability (Barthel Index), psychosocial environment, and socioeconomic indicators. Dietary quality and adequacy were assessed using the Diet Quality Index (DQI) and Mean Adequacy Ratio (MAR). Seven latent constructs were specified and tested using confirmatory factor analysis and structural equation modeling. Results Indicators of cardiometabolic risk were prevalent: 58.5% overweight/obese and 51.2% had inadequate intake. Disability severity correlated with reduced muscle mass and poorer diet quality. Nutritional adequacy positively predicted body composition (β = 0.274) and functional ability (β = 0.185). Functional ability and physical activity were inversely associated with adiposity, while sedentary behavior moderated the relationship between diet quality and waist circumference. Mental illness specifically impaired diet quality, but not caloric intake. Urban residence and lower education predicted poorer dietary outcomes. The model explained 63.7% of variance in body composition and 94.4% in functional ability. Conclusions Cardiometabolic risk in adults with disabilities is shaped by interrelated pathways involving disability severity, nutrition, functional capacity, and psychosocial factors. Lower anthropometric measures may reflect muscle loss rather than reduced risk. Interventions should focus on improving nutritional adequacy, supporting functional independence, addressing mental health, and reducing environmental barriers.

HLA-DRB1 and HLA-DQB1 genetic polymorphisms and susceptibility to coronary atherosclerosis in a Northeast Chinese Population: A case-control study

Atherosclerosis is a chronic inflammatory disease with increasing prevalence in Northeast China, where HLA class II molecules play an important immunoregulatory role. However, the contribution of specific HLA-DRB1 and HLA-DQB1 alleles to AS susceptibility in this population remains incompletely characterized, necessitating novel biomarkers for early detection. In this case-control study of 209 participants, HLA-DRB1 and HLA-DQB1 allele and phenotypic haplotype distributions were compared using odds ratios with 95% confidence intervals and Bonferroni correction for multiple comparisons. A total of 28 HLA-DRB1 and 12 HLA-DQB1 alleles were analyzed. The lowest P value for HLA-DRB1 was observed for DRB1*07:01 ( P  = 0.077, corrected P  = 1.000; OR = 1.994, 95% CI: 0.955–4.164), and that for HLA-DQB1 was observed for DQB1*02:02 ( P  = 0.150, corrected P  = 1.000; OR = 1.739, 95% CI: 0.850–3.558). Neither reached statistical significance, though both trended upward in the AS-susceptible group (DRB1*07:01: 12.59% vs. 6.76%; DQB1*02:02: 12.22% vs. 7.43%). The DRB1*07:01-DQB1*02:02 phenotypic haplotype was more frequent in the AS-susceptible group than in the control group (22.22% vs. 10.81%), with an OR of 2.357 (95% CI: 1.019–5.452). Although the association did not survive Bonferroni correction (corrected P  = 1.000), the effect size suggested the signal was unlikely to be a trivial statistical artifact. In conclusion, the DRB1*07:01-DQB1*02:02 phenotypic haplotype was identified as a candidate risk marker for AS in the Northeast Chinese population, warranting validation in larger cohorts.

Balancing adaptations and fidelity of implementation strategies to optimize primary healthcare in Ethiopia: Lessons from embedded implementation research

Background Optimizing Ethiopia’s Health Extension Program (HEP) has been critical to enhancing primary healthcare (PHC) service delivery, particularly in remote and underserved settings. Embedded implementation research (EIR) strengthens PHC systems by positioning implementers and local managers at the center of addressing operational bottlenecks, enabling adaptive, context-specific refinement of interventions and strategies while maintaining high fidelity to their core components. This study evaluates the implementation fidelity, adaptation of strategies, and lessons to address challenges in equitable access, quality, and accountability through the “Improve Primary Health Care Service Delivery” project. Method A participatory pragmatic EIR approach was applied to co-design and pressure test the implementation strategies to optimize the HEP roadmap (2020–2035). Fourteen woredas from agrarian and pastoral contexts were selected to pressure test HEP optimization strategies. Continuous adaptation tracking and fidelity monitoring were conducted throughout the project implementation period from April 2022 to September 2024. The HEP optimization implementation strategies, adaptations, and modifications were guided by frameworks such as Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies to ensure interventions fit local contexts. Results The adaptations of implementation strategies resulted in implementation fidelity, which improved maternal and child health service coverage, strengthened community health program units, enhanced referral systems through Networks of Care (NoCs), and contextualization of service delivery for pastoralist communities. While most strategies were retained and repackaged for scale, others—including performance-based incentives and governance restructuring—were deprioritized because of feasibility, policy, and sustainability considerations. Adaptations were guided through iterative learning and stakeholder engagement and clustered into four broad areas: contextualization of service delivery models, strengthening community engagement, streamlining quality improvement and NoCs approaches, and refining accountability mechanisms. Stakeholder engagement was pivotal in balancing fidelity with contextual adaptations, fostering trust and sustainability. Despite challenges such as resource constraints, sociocultural barriers, and infrastructure limitations, systematic monitoring and iterative learning processes facilitated the refinement of scale-up strategies. Conclusions Adaptive implementation science effectively optimizes health programs in complex and dynamic contexts. Participatory co-design, stakeholder engagement, and systematic frameworks facilitated the development and refinement of strategies that improved service quality, access, and accountability in diverse PHC settings.