Conventional lipid parameters may not adequately reflect coronary lesion complexity in myocardial infarction (MI), particularly in premature cases. Advanced lipid markers such as lipoprotein(a) [Lp(a)], apolipoprotein B (ApoB) and the ApoB/ApoA1 ratio may better represent atherogenic burden. To evaluate the association between lipid parameters and SYNTAX score in patients with premature MI. An exploratory age-stratified analysis comparing patients aged <45 years and 45-55 years was additionally performed. In this hospital-based cross-sectional study, consecutive MI patients aged ≤55 years with angiographically confirmed coronary artery disease (CAD) were enrolled. Blood samples were collected at admission prior to initiation of therapy for assessment of lipid profile, including Lp(a), ApoA1, ApoB and ApoB/ApoA1 ratio. SYNTAX score was categorized as low (≤22) or high (>22). Associations were analysed using Student's t-test, Spearman correlation, multivariate logistic regression and receiver operating characteristic (ROC) curve analysis. Among 100 patients (mean age 46.5 ± 6.2 years; 85% males), 37% had high SYNTAX scores as well as significantly higher Lp(a), ApoB and ApoB/ApoA1 ratio (p<0.01), while conventional lipid parameters were not significantly different. These associations appeared more pronounced among patients aged <45 years and formal interaction analysis provided additional evidence of an age-dependent relationship between Lp(a) and high SYNTAX score [interaction odds ratio (OR) 0.952, 95% confidence interval (CI) 0.917-0.989, p=0.011]. SYNTAX score correlated positively with Lp(a) (ρ=0.275, p=0.006), ApoB (ρ=0.347, p<0.001) and ApoB/ApoA1 ratio (ρ=0.352, p<0.001). In multivariable analysis, hypertension independently predicted high SYNTAX score (adjusted OR 3.46, p=0.012), whereas associations of advanced lipid markers were attenuated after multivariable adjustment. ROC analysis showed modest discriminative ability for Lp(a) (AUC 0.64, 95% CI: 0.52-0.77), with limited performance for ApoB and ApoB/ApoA1 ratio. Advanced lipid markers, particularly Lp(a) and ApoB/ApoA1 ratio, were associated with greater angiographic complexity in premature MI. Exploratory analyses suggested stronger associations among patients aged <45 years, particularly for Lp(a), and formal interaction analysis further supported an age-dependent relationship between Lp(a) and high SYNTAX score. However, their modest discriminative ability and lack of independent association after multivariable adjustment suggest that these markers should be considered adjunctive indicators of atherogenic burden rather than standalone predictors.
The anatomical synergy between percutaneous coronary intervention with TAXUS and cardiac surgery (SYNTAX) score remains a cornerstone for quantifying coronary artery disease complexity and guiding decisions between percutaneous coronary intervention and coronary artery bypass grafting. Developed from the SYNTAX trial in 2009, the score uses a standard methodological approach to systematically define coronary lesion attributes and yields an overall score that allows stratification of coronary complexity. A commonly accepted stratification divides patients into low (≤ 22), intermediate (23-32), and high (≥ 33) SYNTAX score, with higher categories associated with an increased risk of adverse cardiovascular events. This review article traces the history, evolution, and integration of the SYNTAX score in ESC and ACC/AHA guidelines. We also discuss its role in clinical trials and its contribution to Heart Team deliberations in patients with complex coronary artery disease. Patient benefits include adding precision for treatment selection with a historical potential to lower mortality in high-score cases by favoring coronary artery bypass grafting. Artificial intelligence and advanced imaging, such as coronary computed tomography angiography, are advancing automated, noninvasive SYNTAX score computation with superior accuracy. Future directions involve artificial intelligence-hybrid models for real-time, personalized assessments. This review article evaluates the enduring impact of the SYNTAX score and its evolving role in precision medicine.
Background: Lipoprotein metabolism, inflammation, and oxidative stress (OS) play interconnected roles in the pathogenesis of acute coronary syndrome (ACS). However, the relationship between oxidative stress biomarkers and coronary artery disease (CAD) complexity, particularly as assessed by the SYNTAX II score, remains incompletely understood. This study aimed to evaluate serum levels of oxidative stress-related biomarkers and to investigate their association with the SYNTAX II score in patients with newly diagnosed ACS. Methods: This was a retrospective, single-center observational study. A total of 60 patients with newly diagnosed ACS who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) were consecutively enrolled. Serum levels of superoxide dismutase (SOD), advanced oxidation protein products (AOPP), glutathione, catalase, and malondialdehyde (MDA) were measured using ELISA methods. Associations between oxidative stress markers and the SYNTAX II score were analyzed using correlation and regression analyses. Results: Median levels of SOD, AOPP, and glutathione were 261.0 (244.18-324.86) U/L, 23.81 (22.62-25.80) ng/mL, and 6.08 (5.28-11.46) ng/mL, respectively. Mean catalase and MDA levels were 339.07 ± 44.81 pg/mL and 0.66 ± 0.07 mmol/L. The SYNTAX II score was positively correlated with SOD, AOPP, glutathione, catalase, and MDA, as well as with age, female sex, and potassium levels, while it was negatively correlated with hemoglobin, creatinine clearance, and left ventricular ejection fraction (all p < 0.05). Patients with higher SYNTAX II scores demonstrated elevated levels of both oxidant and antioxidant biomarkers. Conclusions: Oxidative stress-related biomarkers were associated with the SYNTAX II score in patients with newly diagnosed ACS.
Historic cities, as carriers of urban culture and history, have spatial organizations and usage patterns that directly impact district vitality and sustainability.Addressing the common problems in historic cities of disconnection between public space functions and resident needs, along with insufficient spatial flexibility, this study takes Meizhou Ancient City in Guangdong, China, as an empirical case. It introduces space syntax theory to explore sustainable design pathways. This theory can effectively reveal the strengths and weaknesses of spatial structures. Combined with field research, it constructs data models to quantitatively analyze indicators such as integration, spatial symbiosis, and intelligibility, diagnosing core problems: single-function spaces, weak road network connectivity, and chaotic spatial cognition. Based on this, it proposes a strategy of "Inventory Integration-Functional Reconstruction Interface Optimization". The results show that after the intervention, the spatial symbiosis and ecological resilience of the ancient city were simultaneously enhanced, contributing to the sustainable development of historic cities. The research validates the scientific supporting role of space syntax theory in the design of public spaces for historic cities. The proposed strategy can effectively buffer disturbances from evolving social demands during the development of historic cities, promoting their sustainable and positive development, and providing a reference paradigm for the renewal of similar commercial-residential mixed historic cities.
When reading aloud mixed-language paragraphs, bilinguals occasionally produce language intrusions, that is, they translate written switch words to avoid producing them overtly. Intrusions provide evidence about the nature of language control, which refers to how bilinguals maintain control over which language they speak. The present study compared eye movements for successful versus unsuccessful switches during reading aloud of mixed-language paragraphs to reveal the cognitive mechanisms underlying language control failures. Forty-eight English-dominant Spanish-English bilinguals read aloud four stories four times (once each in English-only, Spanish-only, English mixed-language, and Spanish mixed-language conditions). Mixed-language paragraphs included ten language switches (five content words, five function words). Though they elicited the most intrusion errors, dominant-language function (but not content) words elicited more frequent regressive eye movements on successful switches versus intrusions, indicating heightened monitoring of the most error-prone switch targets. Additionally, there was no evidence that inattention to dominant-language switches drove their relatively larger elicitation of intrusions - bilinguals skipped and gazed at switch words to similar extents in both languages, and regressed more often to dominant-language than nondominant-language switches regardless of whether they switched successfully or not. These results confirm the vulnerability of dominant-language function words to language control failures, and reveal that these failures occur despite increased, but ultimately only partially successful, attempted monitoring. More broadly, these results reinforce proposals that different retrieval mechanisms underlie production of function versus content words, but challenge claims that function words cannot be monitored at the level of planned production prior to production of overt speech.
Previous research on communicative outcomes in children treated for nonsyndromic craniosynostosis (NSC) has yielded inconsistent findings, with reported prevalence rates of communicative difficulties varying widely. These discrepancies are attributable to small samples, heterogeneous age groups, and reliance on indirect or non-domain-specific outcome measures. There remains a need for systematic, age-specific screening using validated tools to clarify the nature and prevalence of communicative vulnerabilities in this population. The primary aim was to assess guardian-reported communicative abilities in a consecutive cohort of 5-year-old children treated for NSC and compare outcomes with normative data. Secondary aims were to examine whether reported difficulties were predominantly speech-language based or pragmatic, and to explore differences related to NSC subtype and timing of surgery. This cross-sectional study included 157 children treated for NSC at a national craniofacial centre in Sweden. Guardians completed the Children's Communication Checklist-2 (CCC-2) as part of routine 5-year follow-up. General Communication Composite (GCC) scores and subscale profiles were analysed and compared with published normative data. Group differences across synostosis type and surgical timing were examined using parametric and non-parametric statistical methods. Eighty-five percent of children scored within the normative range on the GCC. Fifteen percent scored below the clinical cut-off, a proportion not significantly different from the normative sample. Group-level differences were primarily observed in the domains of speech and language, with significantly lower scores in speech and syntax, while pragmatic difficulties were uncommon. No significant differences were found between craniosynostosis subtypes. Earlier surgery was associated with higher GCC scores in children with metopic NSC only. Most children treated for NSC demonstrate age-appropriate communicative abilities at 5 years of age. However, subtle vulnerabilities in speech and syntax were present in a subset of children. These findings support the use of screening in routine follow-up to identify children who may benefit from further assessment, while suggesting that broad language disorder-like profiles are uncommon in this population. What is already known on this subject Previous studies report highly variable rates of speech and language difficulties in children treated for nonsyndromic craniosynostosis (NSC), ranging from low to markedly elevated prevalence. What this study adds to the existing knowledge In a large consecutive cohort of 5-year-old children treated for NSC, 85% showed age-appropriate communicative abilities as rated by their guardians and did not differ significantly from normative data. Group-level differences were confined to speech- and language domains (speech and syntax), while pragmatic difficulties were uncommon. Earlier surgery was associated with higher communication scores in children with metopic NSC only. What are the potential or actual clinical implications of this study? Routine screening at follow-up is supported to identify speech- and language vulnerabilities in a minority of children treated for NSC. Broad language disorder-like profiles appear uncommon, suggesting that monitoring of speech and syntax may be more clinically relevant than global language screening alone. Most 5‐year‐old children treated for nonsyndromic craniosynostosis had guardian‐reported communication abilities within the normative range, and the proportion scoring below the CCC‐2 clinical cut‐off did not differ significantly from normative data. Communication vulnerabilities were mainly observed in speech and syntax, whereas pragmatic difficulties and broad language disorder–like profiles were uncommon. Systematic communication screening can support routine craniofacial follow‐up by identifying children who require comprehensive speech and language assessment, without subjecting all children to extensive assessment solely on the basis of their craniosynostosis diagnosis.
Patients with three-vessel coronary artery disease (3V-CAD) remain at heterogeneous risk for major adverse cardiovascular and cerebrovascular events (MACCE) after revascularization. Magnetocardiography (MCG) is a noncontact and radiation-free technique that may capture electrophysiological abnormalities not reflected by anatomical risk scores. This study evaluated the exploratory prognostic value of MCG-derived parameters in patients with 3V-CAD. This single-center prospective cohort study included 544 patients with 3V-CAD who underwent coronary revascularization. MCG recordings were obtained before revascularization using a 36-channel optically pumped magnetometer-based system. The primary endpoint was MACCE, defined as cardiac death, stroke, myocardial infarction, or unplanned revascularization. Cox regression models were constructed using clinical variables, SYNTAX score, and an MCG composite variable. Model performance was assessed using discrimination, calibration, decision curve analysis, and bootstrap internal validation. During a median follow-up of 725 days, 37 patients (6.8%) experienced MACCE. The SYNTAX score was independently associated with MACCE after adjustment for clinical variables and MCG score (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.04-1.12; p < 0.001). The MCG composite variable was also associated with MACCE after adjustment for clinical variables and SYNTAX score (HR, 2.74; 95% CI, 1.57-4.79; p < 0.001). Model discrimination increased from 0.596 for clinical variables alone to 0.682 after adding SYNTAX score and to 0.727 after adding MCG. However, the improvement from the clinical + SYNTAX model to the MCG-added model was not statistically significant (p = 0.17). Bootstrap validation showed an optimism-corrected C-index of 0.672. MCG-derived parameters were associated with MACCE and may provide complementary electrophysiological information for exploratory risk stratification in patients with 3V-CAD after revascularization. Larger multicenter studies with external validation are needed to confirm its complementary prognostic value. Chinese Clinical Trial Registry identifier: ChiCTR2200066942.
Language, as a uniquely human faculty, combines words into hierarchical phrases with diverse syntactic-semantic relations (e.g., subject-predicate and modifier-head phrases). These phrase types are theoretically generated through the labeling algorithm at the syntax-semantics interface. Nevertheless, previous research has focused predominantly on the syntactic system, whereas the neural basis and temporal dynamics of labeling remain poorly understood. To address this gap, we developed the Head-Anchored Labeling Manipulation approach. This method manipulates labeling by embedding the same Mandarin noun-verb dual-category words as heads in tightly controlled modifier-head constructions, where the head alone determines the phrase's grammatical type. The representational similarity analysis of EEG data revealed that labeling representations emerged during both the early and middle stages: 192-227, 290-318, 330-360, and 385-416 ms following the dual-category word. Labeling emerged as early as ~200 ms, concurrent with syntactic Merge, and continued into the N400 window. These results demonstrate that labeling dynamically links syntax to conceptual-intentional system and generates phrase types by determining the constituent head. Its early engagement challenges syntax-first models and supports parallel interactive accounts. Moreover, combinability representations (520-596 and 604-632 ms), together with a late event-related brain potential negativity (420-700 ms) elicited by the dual-category word in the baseline condition, reflect increased difficulty in reconciling semantic associations with atypical syntactic configurations. Together, these findings provide clear electrophysiological evidence for the temporal dynamics of labeling and elucidate the processes at the syntax-semantics interface.
Accurate risk stratification for patients with three-vessel coronary artery disease (3VD) undergoing percutaneous coronary intervention (PCI) remains important in contemporary practice. SYNTAX-based mortality prediction models require reassessment in modern PCI populations. This post-hoc analysis of the Multivessel TALENT trial evaluated the core and extended logistic clinical SYNTAX Score (LCSS) for predicting 1-year all-cause mortality. Discrimination was assessed using the area under the receiver-operating characteristic curve (AUC), and calibration using calibration intercept, calibration slope, graphical calibration, and the E-statistic. Prediction scores were calculated within each of 20 imputed datasets, with model performance evaluated within each imputation and summarised across imputations. Intercept-and-slope recalibration and decision curve analysis were also performed. At 1 year, 46 (3.0%) of 1,548 enrolled patients had died. The pooled AUCs were 0.716 for the LCSS core model and 0.744 for the extended model, compared with 0.629 for the anatomical SYNTAX Score and 0.632 for the functional SYNTAX Score. LCSS models systematically overestimated absolute risk, although observed mortality increased across predicted-risk quintiles. Decision curve analysis showed a positive net benefit for the original and recalibrated LCSS models across threshold probabilities of 1% to 10%, with numerically higher net benefit for the recalibrated extended model across much of the evaluated threshold range. In contemporary PCI for 3VD, the LCSS showed moderate discrimination for 1-year all-cause mortality while overestimating its absolute risk. Recalibration improved agreement with observed risk in this cohort and may inform future validation and model refinement.
Decoding the cis-regulatory syntax that controls gene expression is essential for improving our understanding of cell differentiation and disease. Deep learning based sequence-to-activity (S2A) models learn to identify regulatory motifs and their syntax through modeling chromatin accessibility. Previously, we developed AI-TAC, a S2A model that predicts chromatin accessibility across various immune cell types in multi-task fashion, effectively decoding the regulatory syntax underlying immune cell differentiation. While ATAC-seq is commonly used to measure regional accessibility, it also provides high-resolution profiles, the distribution of Tn5 insertion sites, that offer additional insights into the precise location and strength of TF binding sites. Here we present bpAI-TAC, a base-pair resolution ATAC-seq model, and demonstrate that modeling ATAC-seq profiles alongside accessibility consistently improves predictions of differential chromatin accessibility across cell types. Moreover, we find that multi-task learning across related immune cell types consistently outperforms single-task models. To understand what additional information bpAI-TAC learns from ATAC-seq profiles, we systematically compare sequence attributions from models trained with and without ATAC-seq profiles. We identify novel motifs with strong effect sizes that emerge when profile data is included. Our findings suggest that modeling ATAC-seq at base-pair resolution enables the model to learn a more nuanced and sensitive representation of the cis-regulatory syntax driving immune cell-specific chromatin landscapes.
Homocysteine (HCY) has been implicated in cardiovascular disease through adverse effects on vascular endothelium, oxidative stress, and thrombogenic pathways. Saudi Arabia has a young population and an increasing burden of cardiovascular disease, yet regional data on HCY and B-vitamin profiles in premature acute coronary syndrome (ACS) remain limited. This single-center cross-sectional exploratory study evaluated serum HCY, vitamins B12, B6, B1, and folate levels in 80 patients with premature ACS at King Fahd Military Medical Complex (KFMMC), Dhahran, Saudi Arabia. Premature ACS was defined as ACS occurring in men aged <=55 years and women aged <=65 years. Clinical, laboratory, electrocardiographic, echocardiographic, angiographic, and SYNTAX score II 2020 data were collected. Spearman correlation showed a weak but statistically significant inverse association between HCY and folate (rho = -0.254, p = 0.040; approximate R2 = 0.065), whereas correlations between HCY and vitamins B12, B1, and B6 were not statistically significant. Most patients had low SYNTAX score categories, and exploratory ordinal regression suggested associations between selected biomarkers/clinical variables and SYNTAX score category; however, these findings should be interpreted cautiously because of the small sample size, absence of a control group, and risk of model instability. The study provides preliminary descriptive data on HCY and B-vitamin status among Saudi patients with premature ACS and highlights the need for larger, controlled, multicenter studies incorporating dietary assessment and genetic determinants such as MTHFR polymorphisms.
A retrospective study included 171 patients with acute coronary syndrome who underwent primary percutaneous coronary intervention between 2019 and 2023. Elderly and long-lived patients with ST-ECS and NSTE-ACS are characterized by significant comorbidity, with significantly more severe coronary pathology, as measured by the Syntax Score. In-hospital and long-term mortality were significantly higher in patients over 75 years of age. However, the incidence of late stroke and bleeding did not differ statistically between the study groups. Patients 75 years and older are a complex, heterogeneous group with a very high risk of in-hospital and long-term mortality, requiring a balanced and individualized approach from medical personnel at all stages of treatment. В ретроспективное исследование был включен 171 пациент с острым коронарным синдромом (ОКС), которым в 2019–2023 гг. выполняли первичное чрескожное коронарное вмешательство. Пациенты старческого возраста и долгожители с ОКС с подъёмом сегмента ST и с ОКС без подъёма сегмента ST характеризуются выраженной коморбидностью со значительно более тяжёлой коронарной патологией по шкале Syntax Score. Госпитальная и отдалённая летальность статистически значимо выше у пациентов старше 75 лет. Однако частота отдалённых ОНМК и кровотечений в обследуемых группах статистически не отличалась. Пациенты 75 лет и старше — сложная гетерогенная группа очень высокого риска госпитальной и отдалённой летальности, что требует от медицинского персонала взвешенного и индивидуального подхода на всех этапах лечения.
Comparing angiographic findings of patients presenting with acute coronary syndrome (ACS) in the Middle East/Gulf (MEG) and North America (NA) may shed light onto how coronary artery disease (CAD) complexity at time of ACS presentation impacts immediate management and clinical outcomes. Therefore, we compared outcomes in concurrent ACS patients between MEG and NA. Consecutive patients with ACS were identified at 2 locations in an international health system. Extent of epicardial coronary disease was determined using Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score by trained investigators at both locations and compared using appropriate testing. In addition, in-hospital outcomes, including death, stroke and major bleeding were compared between the two groups. Between January and December 2017, 158 patients in MEG and 381 in NA were admitted with ACS. Patients in MEG were younger (57.3±11.5 vs. 65.0±12.1 years; P<0.001) than those in NA, more likely to have diabetes (51.9% vs. 28.9%; P<0.001). MEG patients had more complex CAD (SYNTAX score: 23.5±12.3 vs. 13.2±8.6; P<0.001) and were more likely to receive surgical or hybrid revascularization [odds ratio (OR) 2.1, 95% confidence interval (CI): 1.4-3.1] but less likely to receive percutaneous coronary interventions (OR 0.3, 95% CI: 0.2-0.5). These findings suggest that patients in the MEG present at the time of their first clinical event with more severe CAD, potentially driven by a higher prevalence and poorer control of diabetes. Further studies are needed to explore genetic, environmental, and metabolic factors contributing to rapid CAD progression in MEG populations.
Although existing approaches, such as Arden Syntax and Asbru, support computable medical knowledge representation, formalizing clinical practice guidelines (CGs) and their individual recommendations so that the logic is clear, consistent and usable, remains challenging. We propose a pre-structuring formalism based on Event-Condition-Action (ECA) - a well-established paradigm in computer science for modeling reactive systems, demonstrate its applicability to real-world examples and map it to Arden Syntax and Asbru. Our results show that this formalism provides a semantically coherent foundation that aligns with the structure of other formal guideline representations.
It is hard to efficiently revascularize high-risk patients with multivessel coronary disease, especially when conventional coronary artery bypass grafting is correlated with high perioperative risk and doing it percutaneously can be bigger issue for high-risk patients. Less invasive and modern alternative to OPCAB is Hybrid coronary revascularization. So we decided to compare this two methods and see which one will have better outcomes for high-risk patients. Our research involves comparing early (30 days) postoperative outcomes between Hybrid Coronary Revascularization (HCR) and Off-Pump Coronary Bypass surgery (OPCAB) in high surgical risk patients with coronary artery disease (EUROSCORE II > 6%, STS > 4% and SYNTAX SCORE > 32). In this single-centre retrospective study, we reviewed high-risk patients treated between Feb 18, 2024 and Dec 14, 2025. After applying predefined eligibility criteria, 87 patients were included, from 28 patients (Mean Age = 66.6 ± 10.7) underwent HCR and 59 (Mean Age = 76.6 ± 4.1) underwent off-pump open aorto-coronary bypass surgery via median sternotomy. We compared early (30 days) postoperative clinical outcomes between two groups. Statistical analysis was performed using IBM SPSS statistics, applying independent-samples t-test and chi-square test as appropriate. Hybrid Coronary Revascularisation (MIDCAB + PCI) required shorter operative time than Off-Pump Coronary Bypass surgery (OPCAB), but with higher in-hospital costs. HCR was also associated with shorter intubation duration (245.5 ± 51.2 min vs. 576.7 ± 97.3 min, P < 0.001), ICU stay (66.4 ± 15.5 h vs. 102.7 ± 12.7 h, P < 0.001), hospital length of stay (7.3 ± 0.8 days vs. 13.0 ± 3.7 days, P < 0.001), and lower thoracic drainage output (275.4 ± 74.1 ml vs. 615.3 ± 88.5 ml, P < 0.001). Blood transfusion requirements were higher in the HCR group (14.3% vs. 0.0%, P = 0.009). Wound infection occurred only in the OPCAB group (0.0% vs. 27.1%, P = 0.002). The composite 30-day MACCE rate was numerically lower in the HCR group (0.0% vs. 13.6%), but this difference did not reach statistical significance (P = 0.050). In high-risk patients with multivessel coronary artery disease, Hybrid Coronary Revascularization (MIDCAB + PCI), compared with traditional Off-Pump Coronary Artery Bypass surgery (OPCAB), was associated with a faster early-recovery profile, including shorter intubation time, ICU stay, and hospitalization, and lower chest-drain output. Multivariable analysis confirmed that these recovery benefits were independent of age, whereas the apparent advantage in overall complications was largely explained by the younger age of the HCR group. Differences in 30-day mortality and MACCE favoured HCR numerically but did not reach statistical significance in this underpowered cohort.Given the retrospective, non-randomized design with unequal group sizes and the absence of time-to-event follow-up, superiority of one strategy over the other cannot be established. Within these limitations, HCR appears to be a safe and feasible option that may be considered in selected elderly and high-risk patients (EUROSCORE II > 6%, STS > 4%, and SYNTAX SCORE > 32) with complex coronary anatomy. Larger, prospective, risk-adjusted studies with longer follow-up are warranted to confirm these findings. EC/NVU/PhD/26-001.
Feedback is essential in health professions education, yet its diversity makes it difficult to study and theorize beyond specific instances. Building on their prior theoretical framing of feedback, the authors undertook a focused pattern informed realist exploration of how it might work, for whom, and under what circumstances, in order to develop realist programme theories. A pattern informed rapid realist review of empirical studies on feedback was conducted using a recurring feedback pattern syntax as a guiding analytical lens. Through process mapping and context-mechanism-outcome configuration (CMOC) analysis, a convenience sample of articles describing feedback interventions across five modalities was reviewed. Causal explanations were refined into a series of realist programme theories. The authors reviewed 35 feedback interventions described in the literature. Analysis generated 34 CMOCs, and from these, 10 programme theories and 2 provisional program theories were developed in terms of patterns from the earlier study (patterns capitalised for clarity). The SENSOR pattern was essential across all interventions but varied in form and influence. OUTCOMES were shaped less by SENSOR type and more by their interplay with JUDGEMENT, RECURSION and INTERPRETATION. Although FREQUENCY and RECURSION were often conflated, recursive cycles and longitudinal facilitation were more consistently associated with performance change than frequency alone. ASSESSMENT conditioned how feedback was experienced and acted upon, sometimes enabling learning but at other times constraining it. This review developed and refined 10 programme theories along with 2 provisional programme theories. The findings suggest that feedback effectiveness arises from the interaction of elements, such as SENSORS, JUDGEMENT, RECURSION and FREQUENCY within specific contexts, rather than from any single feedback feature alone. The methods used in this study provide practical approaches for analysing heterogeneous feedback interventions, including the use of process mapping and PERFORMANCE MEASUREMENT-SENSOR-JUDGEMENT-ASSEMSSMENT (PmSJA) syntax, and offer some insight into where feedback cycles succeed, fail, and may be targeted for change.
Previous research has shown that people are sensitive to statistical regularities and will implicitly learn to bias attention toward locations and features frequently associated with search targets. However, most prior work has involved a single biasing contingency. In Experiment 1, we investigate whether individuals can simultaneously learn and implement two distinct contingencies: one based on location and another based on color. The results suggest that both contingencies are learned implicitly and exert independent effects on attentional allocation. Experiments 2 and 3 examine whether shifting one feature to the volitional system via endogenous cues affects the implicit learning and implementation of contingencies for the other feature. The findings indicate that endogenous cues for one feature do not block implicit learning of contingencies in the other. However, the influence of implicit contingencies on attentional allocation depends on the validity of the volitional cues: they are effective when cues are neutral or valid, but not when invalid. This pattern suggests that the implicit and volitional systems operate hierarchically, with the volitional system taking precedence. SIGNIFICANCE STATEMENT: Efficient attentional guidance is key to effective visual search. While both volitional control and statistical learning can guide attention, little is known about how attention is influenced when multiple guidance mechanisms compete. Using a task with competing statistical regularities, one for target location and one for color, we show that both statistical learning biases independently influence attention. Shifting a feature to the volitional control system does not disrupt the statistical learning of the other, but invalid volitional cues eliminate statistical learning effects, suggesting a hierarchical relationship. These findings offer new insight into how multiple guidance systems shape attentional allocation. OPEN PRACTICES STATEMENT: Subject level data and SPSS analysis syntax available on the Open Science Framework at: https://osf.io/5vt74/overview . The experiments were not preregistered, but the data, and analysis syntax are publicly available at https://osf.io/5vt74/overview .
Post-stroke spasticity is a frequent and disabling consequence of stroke, including when affecting the lower limbs, where it may impair stance, gait, balance, postural control, functional independence and quality of life. Botulinum toxin type A (BoNT-A) is widely used as a focal neuromodulatory treatment for post-stroke spasticity. However, the relationship between BoNT-A-induced reduction in muscle hypertonia, objective changes in spastic muscle's biomechanical properties, and functional outcomes such as mobility and balance remains insufficiently clarified. This systematic review aimed to synthesize recent evidence regarding the non-invasive assessment of spastic muscle properties following BoNT-A administration in post-stroke patients, with emphasis on mobility and balance outcomes. A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was performed in international electronic databases and included studies published between 1 January 2023 and 31 December 2025. The search strategy used specific keywords and keyword combinations/syntaxes, contextually, related to the topic of interest. A total of 32 studies met the eligibility criteria and were included in the final data analysis and synthesis, comprising 13 primary clinical studies-6 randomized or controlled interventional studies and 7 observational studies-together with 12 reviews or evidence syntheses, 3 technical or clinical framework papers, and 4 survey, epidemiological, health-services or health-economic studies. Overall, the included articles addressed BoNT-A treatment in post-stroke spasticity, with partial focus on muscle properties, gait, mobility, and functional outcomes. However, only a limited number of studies investigated objective non-invasive assessment methods, and few directly related muscle-property changes in balance and mobility outcomes. Formal risk-of-bias assessment and quantitative synthesis were not performed because of the substantial heterogeneity of the included evidence, with only two studies being potentially suitable for pooling and these addressing different muscle groups, interventions, and outcome domains. The reviewed literature confirms the clinical relevance of BoNT-A in the management of post-stroke spasticity. However, most studies assess treatment effects mainly through clinical scales, while objective evaluation of muscle stiffness, elasticity, viscoelastic properties, and their relationship with mobility and balance remains limited. Although some studies address gait, functional recovery, or muscle-related changes, the combined use of BoNT-A treatment, myotonometric assessment, and proprioceptive-stabilometric evaluation is largely absent. Therefore, current evidence highlights an important research gap and supports the need for future longitudinal studies integrating non-invasive biomechanical and balance assessment tools to better monitor treatment response and guide individualized neurorehabilitation in post-stroke patients.
Primary Progressive Aphasia (PPA) clinical syndromes do not align consistently with underlying pathology. This study aimed to identify language markers for specific neuropathologies using both standard clinical tests and narrative speech analysis. We analyzed data from 82 autopsy-confirmed PPA cases, including Alzheimer's disease (AD), transactive DNA-binding protein 43 (TDP-43) type C (TDP-C), Pick's disease, and 4R-tauopathies (progressive supranuclear palsy/ cortico-basal degeneration (PSP/CBD). Linear mixed-effects regression was used to analyze performance on standardized aphasia tests and narrative speech variables. TDP-C showed severe semantic deficits but high fluency, while AD was distinguished by impaired repetition. Narrative analysis differentiated 4R-Tauopathies: CBD patients demonstrated significantly poorer syntax and irregular verb inflection than PSP or Pick's, whereas PSP showed the lowest fluency. While standard tests effectively capture lexical-semantic features in AD and TDP-C, narrative measures reveal subtle grammatical and fluency differences critical for distinguishing specific tauopathies. This study outlines a more robust approach for predicting underlying pathology in PPA.
Tendon xanthomas, manifested as Achilles tendon (AT) thickening (ATT) or structural abnormalities, share pathogenic mechanisms with atherosclerosis such as cumulative exposure to low-density lipoprotein cholesterol; however, their association with the severity of systemic atherosclerosis remains unclear. This study sought to investigate the association between AT abnormalities assessed by ultrasound and the prevalence and severity of polyvascular disease (PVD) in patients undergoing percutaneous coronary intervention (PCI). This cross-sectional analysis used baseline data from a prospective multicenter observational study (Achilles Study: UMIN000053786). AT thickness and structural abnormalities were evaluated using ultrasonography. ATT was defined as ≥6.0 mm in men and ≥ 5.5 mm in women. AT structural abnormalities were defined as the presence of calcification, abnormal layer structure, or localized hypoechogenicity. Among 333 patients (median age 75 years; 83% male), ATT was observed in 109 patients (33%), and AT structural abnormalities were identified exclusively in patients with ATT (14%). The prevalence of PVD increased stepwise across patients with no AT abnormalities, those with ATT without structural abnormalities, and those with ATT with structural abnormalities (20% vs. 30% vs. 51%, p < 0.001). Maximum intima-media thickness of carotid artery and SYNTAX score were highest among patients with both ATT and structural abnormalities. These associations remained consistent in patients without familial hypercholesterolemia (FH). AT structural abnormalities assessed by ultrasound were significantly associated with the prevalence and severity of PVD in patients undergoing PCI. Assessment of AT abnormalities may serve as a useful marker for evaluating systemic atherosclerotic burden.