Search Results (2,449)

Melatonin occupies a paradoxical position in contemporary sleep medicine: despite its physiological role as a regulator of circadian timing, it is frequently used and perceived as a nonspecific “natural” hypnotic. Although melatonin demonstrates modest benefits for sleep initiation and clearer efficacy in circadian rhythm sleep–wake disorders, its clinical use is often undermined by diagnostic imprecision, inappropriate dosing, mistimed administration, inconsistent formulations, and inadequate patient counseling. Circadian disorders can be misclassified as primary insomnia, leading to symptomatic treatment approaches that fail to address the underlying phase misalignment. At the same time, supraphysiological doses and reflexive bedtime administration have become normalized despite evidence that melatonin acts primarily as a chronobiotic whose effects depend more on timing than dose. Regulatory inconsistencies and substantial variability in over-the-counter preparations further complicate safe and reproducible use. These factors contribute to avoidable treatment failure, inaccurate labeling of nonresponse, and persistent misconceptions regarding melatonin’s mechanism of action. Therefore, melatonin should be approached as a pharmacological intervention requiring the same diagnostic rigor, individualized dosing, and longitudinal assessment expected of other sleep therapeutics, particularly when integrated with behavioral and circadian interventions. Full article

Acute myeloid leukemia (AML) is a biologically heterogeneous malignancy in which therapeutic decision-making is increasingly guided by molecular and immunophenotypic diagnostics. Advances in genomic profiling and risk stratification have enabled the integration of targeted agents into frontline and relapsed/refractory treatment strategies. Among these, midostaurin, venetoclax, and gemtuzumab ozogamicin represent paradigm-shifting therapies whose clinical benefit depends on accurate and timely diagnosis. This review examines the diagnostic frameworks that inform the use of these agents and discusses their incorporation into contemporary AML management. Midostaurin has demonstrated improved outcomes in patients with FLT3-mutated AML when combined with intensive chemotherapy, underscoring the importance of early molecular testing. Venetoclax, a BCL-2 inhibitor, has expanded therapeutic options for older or unfit patients when used with hypomethylating agents or low-dose cytarabine, with emerging evidence linking response to cytogenetic and molecular features. Gemtuzumab ozogamicin, an anti-CD33 antibody–drug conjugate, illustrates the clinical relevance of immunophenotypic assessment and risk-adapted dosing strategies. We highlight current evidence supporting diagnosis-driven therapy selection, practical considerations for clinical implementation, and ongoing challenges, including resistance mechanisms and optimal sequencing. Integrating precise diagnostic tools with targeted therapies represents a critical step toward personalized AML care and improved patient outcomes. Full article

Longnan, located in Gansu Province, China, at the junction of Shaanxi, Gansu, and Sichuan provinces, represents one of the key corridors of the Northern Tea-Horse Ancient Road. This region preserves abundant traditional timber covered bridges with distinct local characteristics. This study employs ArcGIS spatial analysis and documentary research methods to explore the spatial distribution, spatiotemporal evolution, and influencing factors of these bridges. Spatial analyses (nearest neighbor index, kernel density, and standard deviational ellipse) are based on 71 bridges with traceable coordinates, while the temporal evolution analysis incorporates 80 bridges (64 with definite construction periods and 16 with unknown dates; the latter are handled through a sensitivity analysis as described later in this paper The results indicate that the timber covered bridges in Longnan exhibit a significantly clustered distribution, presenting a pattern of “dense in the southwest and sparse in the northeast”, with Wen County and Kang County as the core clustering areas. Temporally, they follow a unimodal evolution pattern: initiation in the Ming Dynasty, peak in the Qing Dynasty, decline in the Republic of China period, and near stagnation in modern times. The location and distribution of the covered bridges show a strong statistical association with natural conditions (e.g., topography, hydrology) and exhibit spatial coincidence with modern vegetation coverage—the latter treated solely as a contemporary context variable rather than a historical driver. Spatial coincidence with the ancient road is quantified (60.56% within a 2000 m buffer), while settlement proximity is only qualitatively noted as background. Socio-economic factors (e.g., population, transportation, and settlements) are examined qualitatively and display spatial coincidence rather than quantitatively measured influence; these factors cannot be directly compared with natural factors. Full article

The linguistic landscape is a significant aspect of the cultural landscape and heritage. Istria, a region and peninsula located in the Republic of Croatia, has experienced various influences over the years that have shaped language use, impacting the linguistic landscape and the identity of the local population. This paper aims to investigate how the linguistic and spatial identity of the people in Istria has been represented in the region’s cultural landscape during two comparative periods: the turn of the 20th century (the local population’s fight for their national language against the languages imposed by the European powers that governed this region—Italy and Austria) and the turn of the 21st century (the status of minorities in the present Croatian region of Istria). This diachronic research employs a cross-sectional method to compare findings and establish cause-and-effect relationships. This study involves analyzing linguistic data from historical postcards, conducting field studies, and using the pin placement feature on Google Maps to assess recent periods. This research identified Italian and Croatian as the dominant languages during different periods, with English being increasingly prevalent in contemporary times. The results demonstrated that the spatial identity of the Italian minority community is strongly reflected in the linguistic landscape, primarily due to bilateral interstate agreements. Full article

Automotive Noise, Vibration, and Harshness (NVH) has emerged as a critical interdisciplinary field influencing vehicle performance, passenger comfort, brand perception, and regulatory compliance. This thematic literature review synthesizes key research trends, methodological approaches, and technological developments shaping contemporary NVH studies. Drawing on 255 scholarly and industry sources, the review identifies five dominant themes: (1) sources and characterization of noise and vibration in internal combustion, hybrid, and electric vehicles; (2) advanced modeling and simulation techniques—including finite element analysis, statistical energy analysis, and machine learning–based prediction models; (3) materials, components, and structural optimization strategies for NVH mitigation; (4) the rapidly evolving landscape of electric and autonomous vehicle NVH; and (5) emerging active noise and vibration control technologies and data-driven diagnostics. The analysis highlights a definite shift toward holistic, data-driven, and multi-physics approaches, driven by lightweighting imperatives, widespread electrification, and increasingly stringent occupant comfort expectations. Key gaps in current research—including the need for unified evaluation metrics, real-time in-vehicle NVH monitoring, closer integration of subjective psychoacoustic perception with objective physical measurement, and validated simulation workflows for novel EV architectures—are identified and discussed. This review provides a consolidated and expanded framework for understanding contemporary NVH research directions and articulates opportunities for transformative innovation in next-generation vehicle development. Full article

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is a biologically heterogeneous disease. Beyond VHL inactivation, alterations in chromatin remodeling genes BAP1 and PBRM1 define distinct tumor phenotypes with prognostic implications. We sought to characterize the clinicopathological features and oncological outcomes associated with IHC-defined loss of these markers in a contemporary surgical cohort. Methods: We retrospectively analyzed 214 patients undergoing partial or radical nephrectomy for ccRCC (2010–2021). Loss of BAP1 and PBRM1 expression was assessed by automated immunohistochemistry. Tumors with retained expression were classified as wild-type and compared with those showing loss of at least one marker. Survival outcomes were evaluated using Kaplan–Meier analysis, multivariable Cox models, and Restricted Mean Survival Time (RMST). Results: IHC-defined loss was identified in 19 patients (8.9%): BAP1 in 12 (5.6%) and PBRM1 in 7 (3.3%). Tumors with IHC-defined loss showed more aggressive features, including larger size (7.7 vs. 4.7 cm; p = 0.009), higher necrosis (36.8% vs. 18.5%; p = 0.050), and more advanced stage (pT3–pT4: 47.4% vs. 16.4%; p < 0.001). Kaplan–Meier analysis demonstrated significantly worse survival outcomes in the IHC-loss group across all endpoints (p ≤ 0.011). RMST analysis at 60 months confirmed significantly worse outcomes across all endpoints (p ≤ 0.005). Conclusions: Loss of BAP1 or PBRM1 identifies a biologically aggressive ccRCC subset with worse oncological outcomes. IHC-based molecular profiling is a practical and accessible tool for risk stratification in surgically treated ccRCC. Full article

This paper addresses the contemporary challenge of religious disaffiliation and the “supermarket mentality” of liquid religion by proposing a prophetic paradigm shift in evangelisation and catechesis. Utilising Richard Osmer’s practical theological framework as a structure, the study identifies a historical shift from the lived apostolic kerygma (fides qua) toward an over-reliance on formal conciliar definitions and Magisterial formulae (fides quae). This diachronic analysis suggests that the current “apparent failure” of institutional engagement is rooted in a linguistic and methodological disconnect. Drawing on the visionary models of St Augustine and St Benedict, and grounded in Karl Rahner’s transcendental theology, the paper proposes a normative way forward: an inductive pedagogy of the heart. This model prioritises the art of accompaniment and the return to elementary, foundational concepts that address the experiential core of the human person. Ultimately, the study argues that restoring the balance between the lived tradition and the contents of the faith is a theological requirement for helping contemporary believers to live their faith in daily life. Full article

Background and Clinical Significance: Left ventricular free-wall rupture (LVFWR) is a rare but devastating mechanical complication of acute myocardial infarction (AMI), with reported in-hospital mortality approaching 90% without surgical intervention. Although its incidence has declined in the contemporary primary percutaneous coronary intervention (PCI) era, LVFWR remains an important cause of early post-infarction death, particularly after delayed reperfusion or fibrinolytic therapy. Subacute or contained “oozing” ruptures pose a unique diagnostic challenge because hemodynamic stability and nonspecific symptoms can mask the underlying catastrophe, and standard transthoracic echocardiography may fail to visualize a sealed defect. Contrast-enhanced cardiac computed tomography (CT) has emerged as a valuable adjunct in this setting, enabling early recognition and surgical planning. Case Presentation: We report a case of a 51-year-old male, a heavy smoker, with acute lateral ST-segment elevation myocardial infarction (STEMI) treated with thrombolysis at a referring hospital, followed by percutaneous coronary intervention (PCI) to the obtuse marginal branch. Despite reperfusion, he developed persistent pleuritic chest pain and a small pericardial effusion. Cardiac computed tomography (CT) demonstrated a contained (sealed) lateral-wall oozing-type left ventricular free-wall rupture (LVFWR) with thrombus sealing the defect. A multidisciplinary heart team initially opted for diligent observation with frequent echocardiography. Within the first 24 h, the pericardial effusion increased, and echocardiography showed circumferential effusion with lateral wall thickening and hematoma, prompting emergent sternotomy. Intraoperatively, a large posterolateral infarct with an oozing-type LV free-wall rupture was identified. Surgical repair was performed using interrupted pledgeted sutures, native pericardial patch, BioGlue, and an overlying Teflon patch, with intra-aortic balloon pump (IABP) support. This case demonstrates the complementary diagnostic value of multimodality imaging—echocardiography for serial monitoring of the pericardial effusion and regional wall changes, and cardiac CT for direct characterization of the contained (sealed) defect—and the timely transition from conservative to surgical management in oozing-type rupture. The patient recovered uneventfully and was discharged in stable condition. Conclusions: This case highlights the diagnostic value of multimodality imaging—particularly cardiac CT—in detecting contained (sealed) LVFWR when echocardiography is inconclusive. Early recognition and prompt surgical intervention enabled a successful outcome in this otherwise frequently fatal complication. Full article

Contemporary societies are characterized by increasing role multiplicity and accelerated social change, intensifying identity-related strain and inter-role conflict. Although role theory, narrative identity research, and psychological flexibility frameworks have independently advanced the understanding of psychological adaptation, an integrative structural model explaining how life domains are hierarchically organized and reorganized over time remains underdeveloped. This manuscript introduces Casa Vital (Vital House), a dynamic structural model that conceptualizes identity as a hierarchical architecture of interdependent life domains organized around a central integrative function. The model proposes three core constructs: structural coherence, structural modes (rigidity/flexibility) and self-directed agency, and argues that psychological adaptation depends not only on emotional regulation or narrative coherence but also on the capacity to reorganize domain hierarchies in alignment with personal values and contextual demands. By positioning identity at a meso-structural level of analysis, the framework integrates sociological, narrative, and contextual behavioral traditions while offering testable hypotheses and a falsifiable research agenda. Casa Vital expands the current models of adaptation by introducing hierarchical structural reorganization as a central component of identity functioning in complex contemporary contexts. Full article

This paper examines the role of Multimodal Journey Planners (MJPs) as a link between user-oriented personalization and the broader societal goals of sustainable urban mobility. In smart cities, MJPs may serve as digital decision-support tools that connect individual mobility choices with broader sustainability objectives. Although contemporary journey planners increasingly display multiple criteria, such as travel time, cost, CO₂ emissions, and number of transfers, they still generally rely on predefined and non-personalized criterion weights and rarely infer travellers’ actual preferences from observed choices. The paper therefore proposes a transparent methodological proof-of-concept that combines multicriteria decision-making and inverse optimization to discover individual preference weights and enable personalized, preference-aware planning of multimodal routes. The Weighted Sum Method (WSM) is adopted as the basic ranking framework, and the proposed approach is evaluated within a controlled methodological testbed based on multimodal journey scenarios in Vienna. The results indicate that, within the available methodological testbed, the preference-discovery-based model achieved closer in-sample agreement with user-provided route evaluations than the model based on explicitly rated criteria. This was observed in the ranking-agreement analysis, where a more favourable penalty-point ratio was obtained in 19/21 cases (90.5%) and in the numerical error comparison, where lower in-sample reconstruction errors were obtained for 18/21 users (85.71%) across all scenarios. The paper further considers the tension between individual and system-level goals, as well as a conceptual extension toward system-aware re-ranking of alternatives. Within the broader framework of smart mobility, the importance of interoperability and open data is also recognized, with National Access Points (NAPs) for multimodal travel information potentially representing an important precondition for the development of advanced and transparent MJP solutions. Full article

Most delinquent behavior occurs within age-homogeneous peer groups. Using incident-level data from the National Incident-Based Reporting System (NIBRS), this study reassesses the extent to which contemporary juvenile group offending reflects peer-only networks versus cross-age collaboration. Results show that while juvenile-only groups remain the dominant pattern, approximately one-third of co-offending incidents involve adult participants. Mixed-age groups are associated with group size, offense type, and situational context, and are especially common in serious offenses such as homicide, aggravated assault, and drug crimes. Mixed-age co-offending is also associated with greater offense severity, particularly higher odds of victim physical injury. These findings have important implications for the criminal justice system’s response to juvenile crime. While most juvenile offending diversion programs currently focus on interventions that counter peer influence and reduce the time spent with peers engaging in antisocial behavior, intervention strategies that also address the facilitating role of adult co-offenders may also be necessary. Full article

The traditionally accepted figure of 600,000 men departing Egypt during the Exodus is widely regarded as highly implausible by non-fundamentalist readers of the Torah. Biblical scholars have proposed alternative interpretations, beginning with W. M. Flinders Petrie, who argued in 1906 that the term elef, as used in passages enumerating potential soldiers leaving Egypt, should be understood not as “thousand” but rather as “a group.” This paper introduces two relatively underexplored considerations and examines their relevance for contemporary believers. First, a mathematical argument is presented that refines Petrie’s approach, providing further support for the improbability of a literal reading of these figures. Second, an additional calculation—based on the number of midwives mentioned in the Torah, also noted by Petrie—suggests that the population of Israelites may have been closer to 20,000. It should be emphasized that no argument of this kind can definitively establish any thesis regarding these numbers; rather, arguments can only render a given thesis more probable, depending on the assumptions employed to perform the calculations. Finally, the paper addresses the theological relevance of belief in the literal truth of the Exodus narrative. Drawing on the Buberian concept of saga and the approach of such thinkers as Louis Jacobs, it argues that, despite reinterpretations, it remains important for Jewish and other adherents to preserve belief in a kernel of historical truth within the Biblical narratives. At the same time, this residual core of literally true historical facts has been diminishing over time and remains subject to unpredictable further revision. Full article

Visual performance (VP) models have played a foundational role in architectural lighting design, informing illuminance standards intended to support safety, efficiency, and task performance across diverse occupant populations. This paper provides a critical historical review of VP models, tracing their development from early retinal response research and threshold visibility functions to contemporary applications in lighting standards. Key physiological and perceptual factors, including retinal illuminance, contrast, task size, and observer characteristics such as age, are examined through landmark studies that shaped suprathreshold VP modeling. Attention is given to the evolution and adoption of the Relative Visual Performance (RVP) model, which remains central to current Illuminating Engineering Society (IES) illuminance recommendations. The review further synthesizes theory-based, applied, and human-centered experimental approaches, highlighting how VP research expanded to include reaction time, reading performance, chromatic contrast, spectral power distribution, mesopic vision, and virtual reality environments. Despite this extensive body of work, VP models have seen limited revision in response to advances in lighting technology, digital displays, and LED spectral control. Based on gaps identified in prior research, this paper proposes a future modeling framework using linear mixed-effects models to independently assess and assign weights to factors influencing VP. Such an approach may support updated illuminance standards better aligned with modern lighting conditions, occupant needs, and energy efficiency goals. Full article

Non-ST-segment elevation myocardial infarction (NSTEMI) has become the predominant form of acute coronary syndrome (ACS) and is frequently associated with multivessel coronary artery disease (MVD). Patients presenting with NSTEMI and MVD represent a particularly high-risk population characterized by advanced age, comorbidities, and an increased atherosclerotic burden. Although advances in pharmacological therapy and early invasive management have improved prognosis, the optimal revascularization strategy in this setting remains uncertain. In contrast to ST-segment elevation myocardial infarction (STEMI), where randomized controlled trials consistently support complete revascularization, evidence in NSTEMI with MVD is limited and is largely derived from observational studies and registry data. This has generated ongoing debate regarding whether complete revascularization offers superior outcomes compared with culprit-only percutaneous coronary intervention (PCI), and whether non-culprit lesions should be treated during the index procedure (immediate strategy) or in a staged manner. Current data suggest that complete PCI is generally associated with reduced recurrent ischemia, reinfarction, and repeat revascularization, with potential long-term survival benefits. However, patient comorbidities, lesion complexity, and procedural risk continue to influence outcomes, highlighting the importance of individualized decision-making. This narrative review synthesizes contemporary evidence on PCI-based revascularization strategies in NSTEMI with MVD, focusing on two central aspects: the extent of revascularization (complete versus incomplete) and the timing of intervention (single-stage versus staged). By integrating findings from registries, randomized trials and guideline recommendations, the review identifies areas of consensus, persisting uncertainties, and key evidence gaps. Ultimately, it underscores the need for large, dedicated trials to guide practice and optimize outcomes for NSTEMI patients with multivessel coronary disease. Full article

A central question in contemporary bail reform is whether the different forms of monetary release used in large U.S. jurisdictions, commercial surety bonds, deposit bonds, full cash bonds, and property bonds, produce systematically different pretrial outcomes. The commercial bail industry has long defended its role on the grounds that bondsman-supervised release produces superior pretrial outcomes through a private enforcement function not available under alternative mechanisms. The present study tests this claim using data from the 2009 State Court Processing Statistics program on 5271 felony defendants released on financial conditions in 35 large urban counties. Logistic regression models with county fixed effects and cluster-robust standard errors estimate the association between release mechanism and two outcomes, pretrial rearrest and failure to appear (FTA), net of bail amount, prior criminal record, seriousness of offense, criminal justice status at arrest, time from arrest to release, type of legal representation, and demographic characteristics. Three findings emerge. First, defendants released on deposit bonds exhibit substantially lower odds of pretrial rearrest than otherwise comparable defendants released on commercial surety bonds, a finding that is robust across a battery of sensitivity analyses. Second, defendants released on full cash bonds exhibit substantially lower odds of FTA than otherwise comparable defendants released on commercial surety bonds, although this finding is somewhat sensitive to specification choice and is partly mediated by bail amount. Third, no specification supports the public-safety claim made on behalf of commercial bail because surety bonds do not outperform the alternatives for either outcome. These findings indicate that the principal empirical justification for the commercial bail industry is not supported by nationally representative data, and that a shift away from commercial bail toward court-administered alternatives is unlikely to impose behavioral costs and may produce modest public-safety gains. Full article