Search Results (6,490)

The rapid transition toward electrified mobility and climate neutrality has prioritized the structural and environmental optimization of battery electric vehicle (BEV) subsystems. While vehicle lightweighting enhances operational efficiency, the production phase of structural enclosures and battery cells frequently introduces severe environmental and economic impacts and supply chain vulnerabilities. This study presents a comprehensive cradle-to-gate environmental life cycle assessment (LCA), life cycle costing (LCC), and semi-quantitative social assessment of alternative battery housing materials and battery cell architectures. To achieve a functionally accurate comparison, alternative materials, including a novel recyclable thermoplastic acrylic sheet molding compound (SMC), commercial thermoset SMCs, aluminum (AlMg₃), and stainless steel, are evaluated using an analytical stiffness- and strength-equivalent methodology across three real-world geometric demonstrators. Simultaneously, lithium iron phosphate (LFP) liquid electrolyte prismatic cells and solid-state polymer pouch cells are assessed. Material-level results indicate that, while aluminum minimizes the structural mass, primary aluminum manufacturing exhibits the highest global warming potential and processing costs. Conversely, Polytec SMC and Elium SMC achieve the lowest environmental impacts alongside competitive total production costs. At the cell level, prismatic LFP architectures display superior environmental performance compared to solid-state pouch cells, which suffer from energy-intensive processing and lower volumetric capacity normalization. Demonstrator-level aggregation reveals that the electrochemical cells heavily dominate the environmental and economic footprint of the complete assembly, with the housing accounting for less than 5% of the total global warming potential (GWP) and 1% of the total costs. The social assessment reveals moderate and comparable performance across all systems, with slight advantages for thermoplastic composite-based configurations in terms of circularity potential and innovation perception. Overall, the study highlights the critical importance of the cell architecture and manufacturing processes in determining battery system sustainability, while demonstrating the relevance of lightweight composite housings in reducing the structural mass with a minimal environmental penalty. Full article

Background: Cancer is one of the leading causes of morbidity and mortality worldwide, and epidemiological projections indicate that its incidence will continue to increase. Gastrointestinal cancers are among the most frequently diagnosed malignant neoplasms. Quality of life is a key component of oncology care and is significantly influenced by nutritional status and dietary habits. Methods: The study included 52 adult patients diagnosed with gastrointestinal cancer. Data were collected using an anonymous questionnaire based on the QEB (Questionnaire of Eating Behaviour) and WHOQOL-BREF (World Health Organization Quality of Life—BREF) instruments, supplemented with questions regarding changes in dietary habits and the use of dietary counseling following diagnosis. Nutritional knowledge, dietary habits, and quality of life across four domains (physical, psychological, social, and environmental) were assessed. Statistical analysis was performed using descriptive statistics and appropriate tests of statistical significance. Results: Cancers of the colon and rectum—reported either as unspecified colorectal cancer or as separately specified colon or rectal cancer—together accounted for the largest share of diagnoses (26 diagnoses, representing 44.8% of the 58 total reported diagnoses). Quality-of-life assessment revealed the lowest scores in the physical domain and the highest scores in the social domain. The youngest participants achieved the highest scores in the psychological domain, whereas the lowest scores across all domains were observed among individuals aged over 60 years. Following diagnosis, 63.5% of participants reported reviewing and modifying their dietary habits; however, the majority had not received dietary counseling. Women reported higher fruit and vegetable consumption than men, while higher educational attainment was associated with greater self-assessed nutritional knowledge. Conclusions: Among patients with gastrointestinal cancers surveyed in this study, the physical domain of quality of life had the lowest WHOQOL-BREF score. Most participants reported modifying their dietary habits after diagnosis, although most had not received formal dietary counseling. Higher educational attainment was associated with higher self-assessed nutritional knowledge. Given the small convenience sample and cross-sectional design, these findings should be considered exploratory. Full article

Steel production contributes significantly to global resource consumption and accounts for nearly 8% of worldwide CO₂ emissions. As the construction industry moves toward decarbonization, the reuse of structural steel has emerged as a highly impactful strategy for reducing embodied carbon and extending material life cycles. However, most end-of-life structures are still demolished using conventional methods that prioritize recycling for scrap value rather than recovering reusable steel components, resulting in the loss of high-quality material and reduced environmental and economic benefits. Despite growing interest in circular construction, systematic analyses of real-world structural steel reuse projects remain limited. This restricts the understanding of the practical conditions required for scalable implementation. Moreover, there is a lack of structured approaches for identifying the factors influencing deconstruction and large-scale structural steel reuse across reverse supply chains. This study addresses these gaps by developing a framework of factors affecting efficient deconstruction and structural steel reuse, identified through a thematic analysis of the literature and structured around structure attributes, business attributes, value chain activities, project management, and regulations. Fifteen case studies were analyzed: two from North America, twelve from Europe, and one from Asia. A structural steel reuse classification model is introduced to support cross-case comparison of coordination demands, implementation barriers, and scalability potential within reverse supply chains. The results demonstrate that reuse pathways differ substantially in coordination requirements, implementation complexity, and scalability outcomes. They further indicate that the dominant challenges to structural steel reuse are no longer primarily technical, but instead stem from system-level coordination gaps, limited information availability, and insufficient integration across reverse supply chains. Based on these findings, targeted solutions are identified, including improved dismantling strategies, enhanced documentation systems, dedicated storage infrastructure, and stronger regulatory alignment. This study provides a structured analytical approach and practical recommendations to support decision-making, stakeholder coordination, and the scalable implementation of structural steel reuse. Full article

Background/Objectives: To evaluate classification of improvement and agreement of walking-ability improvement criteria derived from outcome measures of walking capacity and performance among inpatients with spinal cord injury (SCI). Methods: Retrospective analysis of admission and discharge data from adults with SCI in the single-centre database from years 2020 to 2023: Six-minute Walk Test (6MWT), Ten-metre Walk Test (10MWT), Walking Index for Spinal Cord Injury; selected items of Spinal Cord Independence Measure (SCIM-III), and Functional Independence Measure; Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI) Walking Mobility subscale. Twenty-three criteria for assessing walking-ability improvement including distribution-based change threshold (DBCT) and provisional milestones for in-home or in-the-community walking (derived from stroke population) and/or related independence were evaluated. Proportion of patients who progressed according to each criterion and agreement between criteria were calculated. Results: Data from 281 individuals were analysed (median 2 months since SCI). Improvement in SCIM-III Mobility Categories was achieved in 47%. Estimated DBCT of 6MWT (69 m) was exceeded in 46%, and DBCT of 10MWT at comfortable speed (CS) in 42% of participants. Forty-two percent of participants improved in provisional Walking Ability Categories (WACs) based on 6MWT or 10MWT_CS, 39% on SCIM-III-Stairs criterion, and 36% on the SCI-FAI criterion. Conclusions: The estimated DBCT and the WACs for 6MWT and 10MWT_CS are promising criteria to assess improvement in walking capacity after rehabilitation in patients with SCI; however, they require prospective validation against patient-centred and real-world mobility anchors. SCIM-III Mobility Categories and Stairs are recommended for assessing improvement in walking-related independence, and the SCI-FAI criterion for walking performance in everyday life. Full article

Ticks are prominent hosts for many viruses that are pathogenic to humans on almost every continent. Despite the documented historical association of ticks with viral disease in humans, clinical case reports are low, likely due to under-recognition of these pathogens. A key feature of understanding tick-borne virus transmission to humans lies in the natural invertebrate and vertebrate hosts supporting ecological maintenance. As humans are often infected as incidental hosts during the tick–virus life cycle, determining relevant ticks and mammals involved in maintenance can inform prevention strategies, surveillance priorities, and diagnostic assay development. This review aims to cover common trends in tick-borne virus ecology, including the wide breadth of implicated tick species, an unclear role for definitive vertebrate reservoirs, and the focal distributions of these viruses closely linked to these host ecological features. Here we also provide examples of prominent tick-borne viruses causing human disease between the Old (Africa, Asia, Europe) and New (Americas) Worlds, highlighting parallels in initial discoveries, vectors, and vertebrates including tick-borne encephalitis, Crimean–Congo hemorrhagic fever, severe fever with thrombocytopenia syndrome, Colorado Tick fever, and Powassan, Heartland, and Bourbon viruses. Full article

The article reflects on the care for the work of creation within Benedictine spirituality and within the broader tradition of the Cistercian Order. It seeks to demonstrate that monastic spirituality, though developed in a pre-modern context, contains enduring theological and ethical intuitions that remain relevant for contemporary ecological reflection. The starting point of the analysis is the Rule of Saint Benedict written by Benedict of Nursia, which, although it does not employ the modern vocabulary of ecology or environmental ethics, nevertheless articulates a coherent vision of human life characterized by reverence, moderation, and responsibility toward the created world. Particular attention is given to key spiritual and anthropological dimensions of the Benedictine tradition, such as attentive listening (obsculta), humility, moderation, stability, and responsible work, expressed synthetically in the principle ora et labora. These elements are interpreted not only as monastic disciplines shaping individual and communal life, but also as forming a relational anthropology in which the human person is understood as fundamentally embedded within a network of relationships with God, other people, and creation. In this sense, Benedictine spirituality already implies a non-exploitative attitude toward the natural world. The article then examines how concern for creation has been deepened and concretized in the spirituality, institutional practice, and historical development of the Cistercian Order. Drawing on selected Cistercian documents as well as contemporary monastic reflections, the study shows that care for the natural environment is inseparably linked with spiritual attentiveness to God, interior silence, openness of heart, and readiness to serve. The Cistercian tradition, with its emphasis on simplicity of life, manual labor, and harmonious integration with the surrounding environment, develops these Benedictine intuitions in a particularly concrete and historically embodied form. From this perspective, a pro-ecological attitude is not interpreted merely as a reactive response to contemporary environmental crises, but rather as a structural consequence of a theologically grounded vision of reality. It emerges from a deep relationship with God as Creator and from a sense of entrusted responsibility for creation understood as a gift rather than as an object of domination. Ecological sensitivity is thus presented as an intrinsic dimension of monastic spirituality rather than an external adaptation to modern concerns. The main research question of the article is: to what extent and in what way do Benedictine and Cistercian spiritual traditions provide theological, anthropological, and ethical foundations for an ecological attitude toward creation within the framework of contemporary integral ecology. To address this problem, the study employs qualitative research methods grounded in theological inquiry. The primary method is textual analysis of the Rule of Saint Benedict and selected Cistercian documents, complemented by theological–hermeneutical interpretation aimed at identifying key spiritual principles and their implicit ecological implications. In addition, the study applies a historical–critical perspective in order to situate monastic sources within their original cultural and theological context, as well as a comparative theological approach, which enables a dialogue between classical monastic spirituality and contemporary ecological theology. These methods are used not only to reconstruct historical meanings, but also to interpret monastic texts in light of contemporary debates on integral ecology, sustainability, and the ethics of responsibility for our common home. In this way, the article highlights a significant continuity between monastic wisdom and modern ecological reflection, showing their mutual capacity for enrichment. Full article

Autochthonous mucocutaneous leishmaniasis caused by Leishmania infantum is an under-recognised but established manifestation of endemic leishmaniasis in Spain. This review identified 65 confirmed autochthonous cases reported since 1990, showing a relatively consistent clinical pattern. Most patients were adults, predominantly men in the fifth or sixth decade of life. Nearly half were immunosuppressed, mainly due to HIV infection, corticosteroid use, biologic therapy, autoimmune diseases, or solid organ transplantation, although immunocompetent individuals were also affected. The laryngeal, nasal, and oral mucosa were the most commonly involved sites, with occasional tracheal and bronchial disease. Clinical presentation was typically chronic and non-specific, including ulcerative, nodular, polypoid, or tumour-like lesions that frequently mimicked malignancy or inflammatory disorders, often delaying diagnosis. Unlike classical New World mucocutaneous leishmaniasis, Spanish cases generally lacked a preceding cutaneous lesion, supporting recognition as a distinct form of L. infantum infection. Diagnosis required microbiological confirmation, ideally with species identification through culture or molecular methods, while serology showed limited reliability. Treatment approaches varied considerably, reflecting the absence of standardised protocols, although systemic therapy (particularly liposomal amphotericin B) was most commonly used. Improved recognition, surveillance, and inclusion in clinical guidelines are needed to reduce diagnostic delay and therapeutic variability. Full article

Background: The growing awareness of breast cancer’s molecular diversity has not changed the technical foundations of surgery itself, but it has profoundly reshaped how surgeons think about surgery. Rather than molecular biology prescribing specific surgery, it is the surgeon’s interpretation of biological behavior—tumor subtype, genomic risk, treatment responsiveness—that influences surgical timing, extent, and feasibility. This is particularly important in the developing world, where mastectomy continues to be the default surgery, not always because it is required, but because biological nuance is underutilized in surgical planning. This review integrates existing evidence, guidelines, and real-world clinical experience to show how a surgeon who understands tumor biology can meaningfully expand safe breast conservation, de-escalate axillary surgery, and align operative choices with systemic therapy. In essence, molecular biology becomes a lens through which surgeons can practice more personalized, precise, and less invasive surgery, without compromising oncologic safety. Recent findings: We present evidence-based algorithms focusing on Luminal A, Luminal B, HER2-positive, and triple-negative subtypes, while discussing the nuances of multifocal and multicentric disease, metaplastic histologies, and discordant lesion management. The review addresses axillary management in the molecular era, specifying the appropriateness of sentinel lymph node biopsy, targeted axillary dissection, or completion axillary dissection, and how subtype-specific nodal responses to neoadjuvant therapy can guide de-escalation strategies. Through clinical vignettes, we exemplify how molecular integration into surgical planning can modify clinical courses, enabling oncoplastic conservation in downstaged tumors and justifying definitive resection in chemo-resistant cases. We examine the implications of germline and somatic genetic testing on surgical decision-making, particularly in relation to BRCA1/2 and PALB2 mutation carriers, alongside ethical and practical counseling considerations. Additionally, we review emerging biomarkers—such as circulating tumor DNA and immune and radiomic signatures—and propose research priorities for their incorporation into surgical trials. Conclusions: Effective implementation necessitates enhanced surgeon education, standardized assays, and multidisciplinary coordination to promote equitable access, consistent utilization of biology-driven algorithms, and rigorous quality oversight. This review furnishes breast surgeons with a pragmatic framework for translating molecular knowledge into multidisciplinary, patient-centered care pathways that optimize oncological safety, aesthetic outcomes, and overall quality of life. Full article

Background/Objectives: Regular participation in physical activity is essential for maintaining health and well-being and plays a key role in disease prevention and quality of life, both in the general population and among people with disabilities, who represent approximately 16% of the global population. Martial arts-based physical activity programs incorporating safe-falling techniques may contribute to improving physical fitness, reducing fall-related injuries, and supporting adherence to the World Health Organization physical activity recommendations. This systematic review primarily aimed to identify martial arts-based fall-training programs, particularly judo-based interventions, and examine their effects on health and well-being in individuals with intellectual disability. As a secondary objective, evidence from other populations and martial arts disciplines was considered to identify relevant fall-training protocols and transferability. Methods: The research question was formulated using the PEO framework. Eligibility criteria included: people with intellectual and developmental disabilities or special educational needs; exposure to exercise programs involving martial arts, combat sports, or judo; and outcomes related to safe falling, falls, balance, motor skills, and physical condition. A systematic literature search was conducted between December 2025 and April 2026 on the Web of Science Core Collection, Scopus, PubMed, and SPORTDiscus in accordance with PRISMA guidelines. Results: From a total of 658 records identified, 27 studies met the inclusion criteria, encompassing 1892 participants with various disabilities, including intellectual disability, autism spectrum disorder, visual impairment, and deafness. The interventions involved different martial arts modalities, such as judo, taekwondo, karate, tai chi, and capoeira. Overall, the available evidence suggests beneficial effects on physical fitness, motor abilities, balance, psychosocial outcomes, and safe-falling skills across different populations; however, substantial clinical and methodological heterogeneity was observed among the included studies. Conclusions: No studies investigating structured martial arts-based fall-training programs in individuals with intellectual disability were identified. Although evidence from other populations is promising, it remains heterogeneous. Further high-quality studies are needed to evaluate these interventions in individuals with intellectual disabilities. Full article

Background: Biological treatment of psoriasis has revolutionized the therapy of this disease, in most cases enabling complete remission of skin lesions. Methods: This study aimed to analyze real-world evidence from 165 patients (mean age 38.1 ± 5.66) treated with 11 biological drugs at our Dermatology Department. Results: Skin lesion severity, expressed by Psoriasis Area and Severity Index (PASI) and Body Surface Area (BSA), improved significantly throughout the treatment, along with the quality of life, expressed by Dermatology Life Quality Index (DLQI) (all p < 0.0001). We observed a statistically significantly higher reduction in skin lesion severity and life quality improvement with IL-23 and IL-17 inhibitors compared to TNFα inhibitors (both p < 0.0001). Secondary loss of response was observed in 26.7% of patients treated with anti-TNF agents, compared to 15.0% in the anti-IL-23 group and 8.3% in the anti-IL-17 group (χ² test, p = 0.0683). Patients who had been treated in the past with biologics had significantly higher PASI and BSA at week 16 of therapy compared to those who were bio-naïve. A positive correlation was demonstrated between PASI at 16 weeks and BMI (R = 0.15; p = 0.0396). There was no correlation between the duration of psoriasis, sex, or age of patients when introducing biologics and PASI at any of the timepoints (p > 0.05). The most frequent side effects were infections, occurring mainly in patients on anti-TNFα agents and bimekizumab. Conclusions: IL-17 and IL-23 inhibitors demonstrated superior efficacy compared to TNFα inhibitors, with higher rates of complete skin clearance and a lower tendency toward loss of response. The worst efficacy and the highest rate of loss of response were observed in case of adalimumab. These findings support the increasing role of IL-17 and IL-23 inhibitors as preferred therapeutic options in psoriasis. Previous biologic exposure and higher BMI seem to be associated with poorer therapeutic outcomes. Overall, biological treatment is an effective, rapid, and safe therapeutic option. Full article

Background: The World Health Organization recommends exclusive breastfeeding for the first six months of life, with continued breastfeeding alongside complementary feeding up to two years or beyond. However, many mothers are unable to meet their breastfeeding expectations, resulting in a significant emotional impact shaped by social, cultural, and occupational factors. Objective: The aim of this study was to explore mothers’ perceptions and experiences of desired but unattained breastfeeding, with particular attention to its cultural–religious dimension. Methods: A qualitative descriptive study within an interpretivist paradigm was conducted between September 2024 and February 2025. Thirty women (15 Christian and 15 Muslim) receiving care from a primary care midwife in a Spanish city in North Africa participated. Data were collected through semi-structured interviews and analysed using inductive thematic analysis following Braun and Clarke’s approach. Results: Four main themes were identified: (1) emotional experiences and feelings, (2) reasons for breastfeeding discontinuation, (3) contextual and structural barriers, and (4) the influence of the social environment and support networks. Although both groups shared emotions such as guilt, frustration, and sadness, some differences were observed in how breastfeeding discontinuation was interpreted and experienced within this sample. Several Muslim participants expressed distress in relation to maternal identity and perceived maternal inadequacy, whereas several Christian participants more frequently emphasised contextual factors such as perceived lack of support or social pressure. Conclusions: The experience of desired but unattained breastfeeding is complex and may be shaped by cultural–religious context alongside individual, social, and structural factors. Integrating a transcultural approach into healthcare provision may improve emotional support and help reduce the burden of guilt and distress associated with breastfeeding discontinuation. Full article

Background/Objectives: Benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS) affects up to 60% of men by age 90. With Singapore’s aging population, minimally invasive surgical therapies (MIST) have emerged as effective alternatives for patients unsuitable for traditional surgery. We sought to evaluate real-world outcomes of MIST procedures: Water Vapor Thermal Therapy (WVTT) and Prostatic Urethral Lift (PUL) in treating BPH-related LUTS. Methods: This is a retrospective analysis of 62 MIST patients treated at a tertiary hospital in Singapore between August 2021 and February 2025, with a minimum of three-month follow-up. Primary outcomes included improvements in maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and Quality of Life (QoL) scores. Secondary outcomes included complications, re-treatment rates, and healthcare utilization metrics. Results: Thirty-six patients underwent WVTT, and 26 underwent PUL. Median age was 67 years, with a mean prostate volume of 61 cm³. At three months, both procedures showed improvements: Qmax increased by 4.28 mL/s (WVTT, p < 0.001) and 3.46 mL/s (PUL, p = 0.06); IPSS decreased by 12.8 (WVTT, p < 0.001) and 12.5 (PUL, p < 0.001); QoL scores improved by 2.53 (WVTT, p < 0.001) and 3.31 (PUL, p < 0.001). The complication rate was 32.3%, with complications being predominantly Clavien–Dindo grades 1–2. Day surgery was achieved in 83.9% of cases, with only 4.8% requiring readmission within 30 days. At three months, 98.4% were catheter-free, and excluding prior catheter-dependent patients, 82.4% were medication-free. At a median follow-up of 5.9 months, the re-treatment rate was 3.2%. Conclusions: MIST procedures are safe and effective for BPH-LUTS, showing comparable outcomes between WVTT and PUL while optimizing healthcare resource utilization. Full article

Background/Objectives: Isocitrate Dehydrogenase (IDH)1/2-mutant diffuse gliomas represent a biologically distinct subgroup of adult brain tumors in which eary metabolic reprogramming and accumulation of the oncometabolite D-2-hydroxyglutarate (D-2HG) drive epigenetic, immunologic, and clinical characteristics, including a high burden of glioma-associated epilepsy. This review summarizes the molecular and metabolic consequences of IDH mutations, their role in glioma-associated epilepsy, and the evolving impact of mutant IDH-targeted therapies in contemporary neuro-oncology. Methods: We conducted a narrative review of key molecular, translational, imaging, and clinical studies on IDH-mutant diffuse gliomas. The literature included the 2021 (World Health Organization) WHO Classification of Tumours of the Central Nervous System, studies investigating D-2HG biology and glioma-associated epilepsy, and prospective clinical trials and real-world evidence evaluating IDH-targeted therapies and contemporary antiseizure management. Particular emphasis was placed on vorasidenib, advanced metabolic imaging, and emerging liquid biopsy approaches. Results: IDH mutations are early driver events that promote D-2HG accumulation, resulting in widespread epigenetic reprogramming, metabolic dysregulation, and an immunosuppressive tumor microenvironment. D-2HG has also been implicated in the development of glioma-associated epilepsy, although the underlying mechanisms remain incompletely understood. Advances in integrated histomolecular diagnostics, magnetic resonance spectroscopy, amino acid positron emission tomography, and cerebrospinal fluid liquid biopsy have improved disease classification and treatment monitoring. Mutant IDH inhibitors, particularly vorasidenib, prolong progression-free survival, delay the need for subsequent treatment, and reduce intratumoral D-2HG concentrations, and have shown encouraging early signals of improved seizure control and preserved health-related quality of life in patients with grade 2 IDH-mutant gliomas, although this evidence remains preliminary and requires confirmation in larger prospective studies. Conclusions: IDH-mutant diffuse gliomas exemplify precision neuro-oncology, in which a single metabolic alteration informs diagnosis, disease monitoring, and targeted therapeutic approach. Additionally, ongoing studies are expected to further define the role of IDH inhibition across different disease stages and in combination with immunotherapy and standard treatments. Lastly, future clinical trials should systematically incorporate seizure outcomes, neurocognitive function, patient-reported outcomes, and immunologic endpoints to optimize both tumor control and quality of life. Full article

This paper proposes that the origin of life may be understood as a cascade of dynamical integration events governed by Painlevé transcendental equations—a class of nonlinear differential equations arising widely in physics, from quantum mechanics to general relativity. Four prebiotic subsystems (mineral catalysts, information polymers, free-energy transducers, and lipid membranes) undergo progressive coupling, tracing a stepwise cascade ($\mathrm{PVI}\to \mathrm{PV}\to {\mathrm{PIII}}^{D_6}\to {\mathrm{PIII}}^{D_7}\to {\mathrm{PIII}}^{D_8}$) along the Chekhov confluence diagram, culminating in the LUCA (Last Universal Common Ancestor). Each step corresponds to a specific biochemical integration event. The Painlevé framework is explicitly phenomenological: it classifies dynamical regimes of subsystem coupling rather than deriving biochemical mechanisms from first principles. A central quantitative feature is a characteristic separation parameter (${\Delta }_{\min }\approx 0.15$) between effective subsystem rates ($r_i={\tau }_i^{-1}$), with oscillation frequencies scaling as $\omega \propto r^{1/2}{\Delta }^{-1/2}$. Several prospective test systems are identified, including the Belousov–Zhabotinsky reaction, the formose reaction, and chemically monitored extreme environments. Existing literature is used to define operational protocols, but no retrospective dataset is treated here as an independent validation of the proposed value of ${\Delta }_{\min }\approx 0.15$. In particular, the formose calculation below is explicitly an illustrative model calculation whose parameters remain to be measured. The framework offers a potential unification of the RNA World, Metabolism-First, and Protocell theories as sequential stages of a single cascade; provides an indicative timeline (4.4–3.5 Ga) anchored to geological constraints; and makes quantitative, falsifiable predictions. A dedicated Scope and Limitations section discusses what the approach does and does not claim. Full article

Background/Objectives: Allergic rhinoconjunctivitis (AR) induced by house dust mites (HDMs) is a common condition that impairs quality of life, and allergen immunotherapy is the only treatment accepted to modify its natural course. However, real-world evidence on polymerized HDM subcutaneous immunotherapy (SCIT) remains limited. We evaluated the up to 24-month effectiveness of polymerized HDM SCIT and examined how baseline symptom burden affects the measured response. Methods: In a retrospective, single-arm, real-world cohort, 353 patients (mean age 15.9 (12.3) years) with HDM-induced AR with/without asthma (asthma subpopulation, n = 112) initiated polymerized SCIT (ALXOID^®, Inmunotek S.L., Spain) with an extract of house dust mites (Dermatophagoides pteronyssinus, D. farinae, Blomia tropicalis). Patients were followed for up to 24 months; 139 contributed an observation at month 12 and 67 at month 24. The primary outcome was the Rhinoconjunctivitis Combined Symptom–Medication Score (RCSMS); secondary outcomes were a visual analog scale (VAS) and the ESPRINT-15 quality-of-life questionnaire. Effectiveness was estimated using mixed models for repeated measures. The pre-specified primary-analysis population was restricted to a baseline RCSMS ≥ 2 to avoid floor effects and regression to the mean at low baseline scores. Results: At month 24, the RCSMS decreased by 0.938 points (−35.3%) in the full cohort and by 48.3% in the baseline RCSMS ≥ 2 population; in the full cohort, the VAS and ESPRINT-15 improved by 50.6% and 69.7%, respectively (all p < 0.001; within-subject effect sizes were small for the full-cohort RCSMS and medium for all other outcomes). The shape of the improvement trajectory did not differ by age group, and all age groups exceeded the minimal clinically important difference; the age analysis was exploratory. Patients with baseline RCSMS < 2 showed continued improvement in VAS and ESPRINT-15 scores. In contrast, the RCSMS increased, a pattern consistent with a statistical floor effect, suggesting limited responsiveness of the score at low baseline values. Conclusions: Up to 24 months, polymerized HDM SCIT was associated with clinically meaningful improvements in symptoms, medication use, and quality of life, most clearly in patients with a baseline RCSMS ≥ 2. Baseline symptom severity should be considered when interpreting combined symptom–medication outcomes in allergen immunotherapy. The single-arm design precludes causal inference. Full article