Abstract: Hop (Humulus lupulus L.) is recognised as a valuable source of bioactive compounds; however, the phytochemical composition and biological potential of wild Romanian hops remain insufficiently characterized. In this study, the bioactive profile of wild hop cones was evaluated using an integrated phytochemical, biological, and in silico ap-proach. The hydroethanolic extract was characterized by a total phenolic content of 25.61 mg GAE/g DW and a total flavonoid content of 3.20 mg RE/g DW, with α-acids predominating (8.77%) and β-acids detected only at trace levels (0.15%). Hydrodistil-lation yielded 0.613 ± 0.11% essential oil, which was rich in sesquiterpene hydrocar-bons (64.61%), mainly α-humulene, β-caryophyllene oxide, selina-3,7-diene, and ger-macrene B. The hydroethanolic extract exhibited strong antioxidant activity (IC₅₀ = 5.03 µg GAE/mL), whereas the essential oil showed a moderate but dose-dependent radi-cal-scavenging capacity (IC₅₀ = 0.44% v/v). In addition, the essential oil displayed pronounced antibacterial and antibiofilm activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, with the highest antibiofilm inhibition observed for Pseudomonas aeruginosa (96.44%). Molecular docking analysis suggested that the major volatile constituents may interact with S. aureus Sortase A, providing a plausible mechanistic basis for the observed antibiofilm effects. Overall, these findings indicate that wild Romanian hop cones represent a promising source of antioxidant and anti-microbial bioactive compounds, supporting their potential applications in pharmaceu-tical, food, and cosmetic formulations, as well as in natural product–based drug discovery.

Abstract: The WHOQOL-BREF questionnaire is widely used globally in research that requires the assessment of quality of life. Its official status, broad availability in multiple languages, and the fact that it is free to use are the primary reasons it is selected by researchers and clinicians. However, the quality of particular language versions and the lack of standardization raise concerns about the quality of data collected in different countries and thus their comparability. In this study, 17 country versions published on the WHO website were analyzed. Each translation was compared to the model English questionnaire in terms of visual layout, inclusion of instructions for respondents, timeframe of measurement, and additional elements. Moreover, selected versions were reviewed by native speakers and with use of LLM to assess the accuracy of the question and scale translations. The results of the analysis revealed significant discrepancies between translations in all analyzed fields. Some translation errors were so severe that responses to certain questions could not be meaningfully compared. The study concludes that the WHOQOL-BREF questionnaire translations should be reviewed across all evaluated elements to ensure its consistency and comparability. Additionally, specific language versions developed by various academic institutions should be closely scrutinized by the WHO team. A common practice of adding a note that a particular version is not an official WHO translation will not suffice, as these tools are treated de facto as officially approved by researchers and medical specialists.

Abstract:

Background/Objectives: Sarcopenia, obesity, and sarcopenic obesity (SO) are common in older adults and may be associated with functional limitations in basic (ADL) and instrumental (IADL) activities of daily living. This study aimed to evaluate the association between body composition phenotypes and ADL/IADL limitations among older adults. Methods: A cross-sectional study included 440 community-dwelling adults aged ≥60 years (281 women, 159 men; mean age 74.7 ± 7.8 years). Sarcopenia was diagnosed according to EWGSOP2 criteria, obesity was defined as percent body fat >42% in women and >30% in men, and SO was classified based on the ESPEN/EASO recommendations. Participants without obesity or sarcopenia were categorized as ‘normal’ phenotype. Functional status was evaluated using the Katz and Lawton scales, with limitations defined as ADL ≤5 and IADL ≤26 points, respectively. Multivariate logistic regression analysis was performed to determine factors associated with ADL and IADL limitations. Results: Over half of the participants (57.1%) had abnormal body composition: 31.6% obesity, 11.4% sarcopenia, and 13.2% SO. SO was associated with a nearly threefold higher risk of ADL limitations (OR = 2.86; p = 0.003) and a 3.7-fold higher risk of IADL limitations (OR = 3.68; p < 0.001) compared to the normal phenotype. Sarcopenia was associated with IADL limitations in the unadjusted model (OR = 2.44; p = 0.010). Independent predictors of ADL and IADL limitations included reduced muscle strength, a higher number of chronic diseases, and a worse nutritional status. Conclusions SO was linked to higher risk of both ADL and IADL limitations, while sarcopenia was associated only with IADL deficits. Obesity severity may be relevant, but its impact on daily functioning in older adults requires further study.

Abstract:

Background: Street sex workers (SSWs) experience some of the highest levels of health inequality in the UK yet face persistent barriers to accessing NHS healthcare. These barriers are shaped by structural disadvantage, stigma, and the complex realities of their lives. Despite significant health needs, engagement with services remains low, and existing models of care often fail to accommodate the lived experiences of this population. Aims: This study explores how SSWs access, experience, and navigate NHS healthcare. It aims to understand the barriers and enablers of access, identify areas for improvement, and offer recommendations to inform the development of more inclusive service provision. Methods: An ethnographic approach was undertaken within a South Yorkshire charitable organisation. Data collection involved participant observation and an arts-based scrapbook intended to facilitate trauma-informed, flexible engagement. Thematic analysis was used to analyse the data, organised around a dynamic, processual access using the candidacy framework. Findings: Barriers to care were present across all stages of healthcare engagement, including minimisation of health needs, administrative exclusion, lack of continuity, and stigma from professionals. Participants frequently described systems as inaccessible. Key enablers included supportive organisational staff, and consistent, trusted relationships with specific providers. Areas for Improvement and Recommendations: Findings highlight the need to simplify registration processes, provide in-person options, and reduce reliance on digital communication. Greater continuity of care and gender-sensitive, trauma-informed approaches were consistently requested. Services should not be evaluated solely by uptake but by how well they accommodate marginalised users. Healthcare settings that prioritise safety, trust, and consistency were shown to improve engagement. SW spoke of the work of access of care which for many way too hard to gain. Conclusions: SSWs are not disengaged from healthcare but are routinely excluded by systems that fail to meet their needs. Service redesign must begin from the realities of those most marginalised through co-production, to reduce health inequity and build meaningful access.

Abstract:

Breast cancer remains a major global health challenge, strongly influenced by inequities in access to high-cost antibody-based diagnostic and therapeutic technologies. Because their manufacturing requires complex and expensive bioproduction systems, many regions, particularly in Latin America, face limited availability of tools essential for early detection and targeted treatment. This gap has highlighted the need for cost-effective and scalable theranostic alternatives, driving interest in aptamers, synthetic DNA or RNA oligomers selected through SELEX technology that fold into functional structures with high affinity, low immunogenicity, and reproducible chemical synthesis. Aptamers have expanded the landscape of diagnostic platforms by enabling sensitive aptasensors, liquid biopsy strategies, and nanomedicine-based imaging systems. They also contribute to targeted therapy by recognizing cancer biomarkers with precision and enabling controlled drug delivery. This review critically integrates advances in aptamer-based theranostics for breast cancer, examining their molecular mechanisms, including structural folding, selective ligand binding, and nanomaterial interfacing. We also discuss their application in extracellular vesicle capture, cancer stem cell detection, and therapeutic conjugates, emphasizing their advantages and limitations relative to antibody-based approaches. By consolidating current evidence, this work positions aptamers as emerging tools capable of democratizing precision oncology, particularly in regions where access to advanced technologies remains limited.

Abstract:

Background: Immersive virtual reality (VR) has emerged as a promising tool to enhance neuroplasticity, motivation, and engagement during post-stroke motor rehabilitation. However, evidence on its feasibility and data-driven integration into clinical practice remains limited. Objective: This pilot study aimed to evaluate the feasibility, usability, and short-term motor outcomes of an immersive VR-assisted rehabilitation program using the Travee-VR system. Methods: Fourteen adults with post-stroke upper-limb paresis completed a 10-day hybrid rehabilitation program combining conventional therapy with immersive VR sessions. Feasibility and tolerability were assessed through adherence, adverse events, the System Usability Scale (SUS), and the Simulator Sickness Questionnaire (SSQ). Motor outcomes included active and passive range of motion (AROM, PROM) and a derived GAP index (PROM–AROM). Correlations between clinical changes and in-game performance metrics were explored to identify potential digital biomarkers of recovery. Results: All participants completed the program without adverse events. Usability was rated as high (mean SUS = 79 ± 11.3), and cybersickness remained mild (SSQ < 40). Significant improvements were observed in shoulder abduction (+7.3°, p < 0.01) and elbow flexion (+5.8°, p < 0.05), with moderate-to-large effect sizes. Performance gains in the Fire and Fruits games correlated with clinical improvement in shoulder AROM (ρ = 0.45, p = 0.041). Cluster analysis identified distinct responder profiles, reflecting individual variability in neuroplastic adaptation. Conclusions: The Travee-VR system proved feasible, well tolerated, and associated with measurable short-term improvements in upper-limb function. By linking clinical outcomes with real-time kinematic data, this study supports the role of immersive, feedback-driven VR as a catalyst for data-informed neuroplastic recovery. These results lay the groundwork for adaptive, clinic-to-home rehabilitation models integrating clinical and digital biomarkers.

Abstract: Background/Objectives: Acute Pancreatitis (AP) is an unpredictable inflammatory disease associated with high morbidity and significant mortality, particularly in severe forms. Early death is primarily linked to Systemic Inflammatory Response Syndrome (SIRS) and Multi-Organ Failure (MOF). The objective of this study was to identify objective clinical and laboratory predictors of early and one-year mortality in AP patients and to evaluate the prognostic accuracy of commonly used severity scoring systems. Methods: This prospective, observational study enrolled 50 adult patients admitted to the Intensive Care Unit (ICU) at the University Hospital Center Bežaniska Kosa. Patients with chronic pancreatitis, trauma-induced AP, or late presentation were excluded. Severity scores (APACHE II, BISAP, Ranson, Pancreas) and biomarkers (C-reactive protein, Procalcitonin) were collected at admission (0h) and dynamically at 48-72h and day 7. Endpoints were early (in-hospital) and one-year mortality. Results: Overall mortality was 16% (n=8). Mortality was significantly associated with sepsis/septic shock (p&lt;0.001), severe AP ($p=0.001$), prolonged mechanical ventilation, and ICU stay. At admission, APACHE II (AUROC 0.813) and BISAP (AUROC 0.807) showed good accuracy. Reassessment at 48 hours markedly improved prediction: APACHE II achieved excellent value (AUROC 0.917), and the Ranson score became a strong predictor (p&lt;0.001). Procalcitonin (PCT) was identified as a significant and superior predictor of mortality from 48 hours onwards (p&lt;0.001), outperforming CRP. One-year survival was significantly shorter among patients with sepsis, septic shock, severe AP, and prolonged ICU stay. Conclusions: Dynamic assessment using clinical scoring systems, particularly APACHE II and BISAP within the first 48 hours, provides reliable mortality prediction in acute pancreatitis. The presence of sepsis, severe disease, and the need for prolonged organ support are key mortality determinants. Serial PCT monitoring offers sensitive, incremental value for risk stratification and guiding intensive care decisions in both short- and long-term outcomes.

Abstract: Abstract: Background: Academic health sciences libraries face organizational challenges because medical and health sciences schools are part of integrated academic health systems, yet there remains a lack of systematic guidance on structuring these libraries. Purpose: To create a mission-driven analytical framework that examines library organizational models within academic health systems, focusing on service delivery throughout the educational continuum and utilizing hub-spoke organizational principles from healthcare. Methods: We conducted a systematic literature review, thematic analysis, and iterative framework development grounded in organizational theory and healthcare delivery principles to develop a mission-driven decision framework. Results: Analysis reveals three main organizational models: independent (school-based), integrated (university library system), and hub-spoke (distributed). There is no single best model—success depends on institutional context, goals, resources, and stakeholder needs. Mission alignment should guide organizational design, with cost and feasibility considerations coming into play only after mission objectives are met. Hub-spoke models offer benefits for geographically dispersed systems, requiring higher initial investment but providing a strong return through reduced duplication and increased efficiency. Supporting the educational continuum from undergraduate to continuing medical education demands careful organizational planning to address service fragmentation during transitional phases. Conclusions: Choosing an organizational model involves a systematic, mission-driven analysis that aligns institutional missions with service needs and matches these needs to suitable organizational structures. This framework is the first to offer a comprehensive analytical method for making managerial decisions in complex academic health system environments, including practical guidance for implementation and economic validation. It shows that structures aligned with the mission can lead to positive returns on institutional investment.

Abstract: Permanently increasing incidence of chronic diseases is challenging for healthcare worldwide being directly associated with physical inactivity considered an important cause of most chronic diseases. In contrast, physical exercise is proven as a powerful instrument of healthcare to protect individuals against health-to-disease transition and against disease progression. Nonetheless, a number of studies warn against inappropriate high-intensity and/or unaccustomed exercise which exceed an individual physical capacity. Indeed, an extensive cardiac output during prolonged exercise leads to significantly increased cardiac dimensions triggering cardiac complications which may result in arrythmogenic sudden cardiac death. Remarkable plasticity of mitochondria allows these organelles for sensing and adapting to a variety of stressors and responding to stimuli by molecular signalling, regulating bioenergetics and cellular homeostasis decisive for repair machinery, proliferation and apoptosis, tissue regeneration versus degeneration with whole body outcomes. Mitochondria act as biosensors in human body: they are reactive towards stimuli and protective against health-to-disease transition. For performing this life-important function throughout the life, mitochondria need supportive measures including physical activity considered an essential pillar of the mitochondrial medicine. This article highlights reciprocity between the quality of mitochondrial health and homeostasis on one hand and physical fitness and exercise intervention on the other hand. The proposed novelty relates to monitoring of mitochondrial homeostasis strongly recommended for creating individualised training programmes and monitoring exercise efficacy during and after the programme performed. To this end, patient friendly non-invasive approach is already established utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation.

Abstract: Objectives: Aim of the study was to compare in two groups of male swimmers, divid-ed into master (MS) and leisure (LS), a series of anthropometric and metabolic parame-ters evaluated before (T0) and after six months training (T6). Method: For MS training protocols were administered by a certified swimming coach and entailed 3 days a week of swimming practice which had as a final goal the competition season. LS were in-stead regular swimmers involved in a recreational workout without any supervision and any specific goal other than keeping themselves physically fit. Results: At T6 both groups performed the test with a significant increase of their total time (TT; MS = 11.9 ± 13.4%; LS = 8.3 ± 15.5%; p>0.05) and maximum speed reached (Spmax; MS= 6.5 ± 9.3%; LS = 2.1 ± 10.6%; p>0.05). Maximal aerobic capacity in MS increased by 12.6 ±14 while in LS 2.5 ± 5.4% (p<0.05). VO2 consumption at anaerobic threshold was increased by 16.8 ± 16.8% for MS and 2.5 ± 5.4% for LS (p< 0.05). Conclusions: Our results show that only the coach-assisted training was able to evoke significant physiological ad-justments in parameters related to aerobic capacity such as VO₂max increase and VO₂AT.

Abstract: This article critically examines the limitations of current large language model (LLM) benchmarks, particularly in healthcare and clinical evaluation. While standardised leaderboards and benchmarks have driven rapid technical progress and shaped industry perceptions, they are increasingly undermined by issues like benchmark data contamination and narrow assessment criteria. The article explains that benchmark leakage can overstate results, and traditional evaluation using multiple-choice questions does not reflect the complexity of clinical practice. Specialised medical benchmarks, though more targeted, still overlook essential attributes such as reliability, calibration, and safety, and often lack representation of diverse healthcare contexts and languages. A shift toward real-world evaluation frameworks, emphasising scenario-based simulations, multisite validation, and comprehensive translational assessment, is required. The Translational Evaluation of Healthcare AI (TEHAI) framework is presented as a robust alternative that integrates technical, utility, and adoption criteria and explicitly addresses ethical and contextual factors. Genuine clinical benefit and patient safety can be ensured only through continuous, context-specific evaluation that transcends traditional benchmarking.

Abstract: Next-generation sequencing (NGS) and antisense oligonucleotide (ASO) technologies are converging to transform the diagnosis and treatment of rare monogenic disorders. NGS enables comprehensive, single-test molecular diagnoses through targeted panels, whole-exome (WES), and whole-genome sequencing (WGS), which together reveal pathogenic variants across coding, intronic, and structural domains. Integration with transcriptomic analyses, including RNA sequencing, further refines genotype–phenotype correlations and identifies splicing aberrations amenable to correction by ASOs. Therapeutic advances now span RNase H-dependent gapmers for transcript knockdown, splice-modulating phosphorodiamidate morpholino oligomers (PMOs), and peptide/antibody-conjugated PMOs that enhance muscle and cardiac delivery. These platforms underpin the rise of N-of-1 ASO therapies—customized drugs developed for individual patients with unique pathogenic variants. Landmark cases such as Milasen, Valeriasen, and Atipeksen illustrate the clinical feasibility and ethical complexities of personalized RNA therapeutics, while updated FDA guidance supports expedited, patient-specific investigational pathways. Despite progress, challenges persist in delivery efficiency, long-term efficacy, and equitable access. Emerging approaches—including long-read sequencing, AI-driven oligo design, and improved nanoparticle delivery—promise to extend ASO precision and reach. This review synthesizes current advances linking genomic diagnosis to individualized RNA-targeted interventions, outlining how integrated NGS-ASO pipelines are reshaping the therapeutic landscape for rare genetic diseases.

Abstract: Background. Frailty is a multifactorial condition that significantly impacts older adults' health and independence, which can be mitigated through training. This study examined the effects of a 12-week progressive strength training (PST) program on frailty status and short-term autonomic compensatory responses during postural transitions. Methods: Eight older adults (60-79 years) classified as pre-frail or frail according to the frailty index (FI) participated in a 12-week PST program. Time and frequency-domain heart rate varia-bility (HRV) in the supine position, cardiac parasympathetic modulation (CPM) deter-mined from the HR 30:15 ratio (longest RR interval around the 30th heartbeat divided by the shortest RR interval around the 15th heartbeat after standing), and cardiac baroreceptor gain (CBG) assessed as the ratio of heart rate change to systolic blood pressure drop (ΔHR/ΔSBP) at 30, 60, 180, and 420 seconds after standing were assessed at pre-test, 8 weeks and 12 weeks (autonomic function outcomes). The level of physical activity (LPA), handgrip strength (HGS), and gait speed (GS) were assessed, and orthostatic intolerance (OI) symptoms were self-reported at pre-test, 8 weeks and 12 weeks. Results: After 12 weeks of PST, FI scores decreased from 0.18 to 0.04 (78% reduction). LPA, HGS, and GS improved by 152%, 13%, and 11%, respectively. Three of eight participants reported OI symptoms at pre-test, with no reported symptoms at week 12. Despite this, PST did not enhance short-term autonomic responses. Conclusion: PST counteracted frailty and im-proved physical and muscular function but did not enhance indices of short-term auto-nomic regulation in frail older people.

Abstract: Background/objectives: Studies evaluating the longitudinal impact (beyond a decade) of Antibiotic stewardship programs (ASP) strategies on the volume/quality of antibiotic prescriptions, as well as impact on antimicrobial resistance are lacking. Since 2008, the ASP at Singapore General Hospital had implemented various strategies in the following phases: 1) initiation; 2) expansion; 3) optimisation; and 4) innovation. In this study, we aim to evaluate the impact of ASP on the volume/quality of antibiotic prescribing and susceptibility trends of clinically significant Gram-negative bacilli (GNB). Methods: We conducted a single-center, retrospective observational study from 2011 to 2024. Antibiotic consumption, appropriateness and susceptibility trends of 6 GNBs to 7 commonly used antibiotics were analysed using Kendall tau test. Results: We demonstrated sustained improvement in appropriateness of 7 broad-spectrum IV antibiotics, accompanied by significant reductions in IV ciprofloxacin, cefepime and, ertapenem use (p &lt; 0.05). Hospital-wide susceptibility of 6 GNBs to all evaluated antibiotics improved significantly (p &lt; 0.05), except for E. coli susceptibility to ertapenem and Enterobacterales susceptibility to ciprofloxacin. Conclusion: An evolving multi-pronged antibiotic stewardship approach improved antibiotic prescribing and GNB susceptibility towards majority of the antibiotics. In a rapidly evolving healthcare landscape, ASPs must remain agile, continually refining priorities and employing innovative strategies.

Abstract: Our growing knowledge of the complex roles of the endogenous mutagenic deaminases in human disease is fueling the development of a fundamentally new generation of drugs that are likely to revolutionize medicine. These new drugs and drug development opportunities are designed to harness therapeutic benefits by modulating deaminase behavior. The fact that the deaminases are endogenous enzymes playing crucial roles in inflammation-linked diseases makes them powerful agents for forging this new frontier in drug development. While only a few deaminase modulating drugs are approved for clinical use, many are in development. We provide examples to highlight how we can unlock the healing power harnessed by this amazing orchestra of enzymes. We also identify the challenges and new opportunities not currently being acted upon.

Abstract: Automatic radiology report generation (ARRG) has emerged as a promising application of deep learning (DL) with the potential to alleviate reporting workload and improve diagnostic consistency. However, despite rapid methodological advances, the field re-mains technically fragmented and not yet mature for routine clinical adoption. This systematic review maps the current ARRG research landscape by examining DL archi-tectures, multimodal integration strategies, and evaluation practices from 2015 to April 2025. A PRISMA-compliant search identified 89 eligible studies, revealing a marked predominance of chest radiography datasets (87.6%), largely driven by their public availability and the accelerated development of automated tools during the COVID-19 pandemic. Most models employed hybrid architectures (73%), particularly CNN–Transformer pairings, reflecting a shift toward systems capable of combining local feature extraction with global contextual reasoning. Although these approaches have achieved measurable gains in textual and semantic coherence, several challenges per-sist, including limited anatomical diversity, weak alignment with radiological reason-ing, and evaluation metrics that insufficiently reflect diagnostic adequacy or clinical impact. Overall, the findings indicate a rapidly evolving but clinically immature field, underscoring the need for validation frameworks that more closely reflect radiological practice and support future deployment in real-world settings.

Abstract: Background: Chest, abdominal, and pelvic computed tomography (CT) with intrave-nous contrast is widely used for tumor staging, treatment planning, and therapy mon-itoring. The integration of artificial intelligence (AI) services is expected to improve diagnostic accuracy across multiple anatomical regions simultaneously. Purpose: To evaluate the diagnostic accuracy of a multi-target AI service in detecting 16 pathological features on chest and abdominal CT images. Methods: We conducted a retrospective study using anonymized CT data from an open dataset. A total of 229 CT scans were independently interpreted by four radiologists with more than 5 years of experience and analyzed by the AI service. Sixteen pathological features were assessed. AI errors were classified as minor, intermediate, or clinically significant. Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve (AUC). Re-sults: Across 229 CT scans, the AI service made 423 errors (11.5% of all evaluated fea-tures, n = 3664). False positives accounted for 262 cases (61.9%) and false negatives for 161 (38.1%). Most errors were minor (62.9%) or intermediate (31.7%), while clinically significant errors comprised only 5.4%. The overall AUC of the AI service was 0.88 (95% CI: 0.87–0.89), compared with 0.78–0.81 for radiologists. For clinically significant find-ings, the AI AUC was 0.90 (95% CI: 0.71–1.00). Diagnostic accuracy was unsatisfactory only for urolithiasis. Conclusions: The multi-target AI service demonstrated high di-agnostic accuracy for chest and abdominal CT interpretation, with most errors being clinically negligible; performance was limited for urolithiasis.

Abstract: Determining the postmortem interval remains one of the most persistent and fragmented challenges in forensic science. Conventional approaches—thermal, biochemical, molecular, or entomological—capture only isolated fragments of a single physical reality: the irreversible drift of a once-living system toward equilibrium. This Perspective proposes a unifying paradigm in which death is understood as a progressive rise in entropy, encompassing the loss of biological order across thermal, chemical, structural, and ecological domains. Each measurable postmortem variable—temperature decay, metabolite diffusion, macromolecular breakdown, tissue disorganization, and microbial succession—represents a distinct expression of the same universal law. Within this framework, entropy becomes a dimensionless index of disorder that can be normalized and compared across scales, transforming scattered empirical data into a coherent continuum. A Bayesian formulation further integrates these entropic signals according to their temporal reliability, yielding a probabilistic, multidomain equation for PMI estimation. By merging thermodynamics, information theory, and biology, the concept of death as rising entropy offers a comprehensive physical description of the postmortem process and a theoretical foundation for future computational, imaging, and metabolomic models in forensic time analysis.

Abstract: Palliative care (PC) is a multidimensional approach to end-of-life care aimed at alleviating suffering and enhancing the quality of life for individuals and their families. A key aspect of PC is managing symptoms such as pain, dyspnea, and psychological distress. This study assesses the links between PC reception, those three symptoms, and the ex-post rating of end-of-life care, this before and during the COVID-19 pandemic. It relies on data from the Survey of Health, Ageing, and Retirement in Europe (SHARE). A person who knew the deceased was interviewed on various aspects of the last year of life of a former respondent (6,641 individuals from nineteen European countries and Israel, who died between 2006 and March 2020, and 2,596 who died during the COVID-19 pandemic). Before COVID-19, receiving PC improved the rating of care; however, the improvement was significant only in case of dyspnea or psychological distress, not when the person had suffered only from pain. During COVID-19, the global beneficial effect of PC became less significant.

Abstract: This manuscript examines the historical underpinnings of two prominent genres in biomedical literature: the individualized case report and the systematically averaged clinical trial. Although both are fundamental to clinical science, their intellectual origins reflect divergent approaches to the study of nature. Tracing these approaches back to classical antiquity, we find Hippocratic medicine valuing detailed observations of individual patients, a focus later enriched by the Renaissance fascination with wonders and anomalies, known as paradoxography. In contrast, medieval Aristotelian science, with its emphasis on the regularities and universal laws of nature, provided a philosophical foundation for the development of population-based methodologies. We argue that these two traditions—one celebrating the exceptional case, the other seeking aggregate evidence—continued to shape scientific inquiry through the Middle Ages and into the Scientific Revolution. The dialectic between them can still be observed in modern biomedical writing: case reports give voice to rarities and novel phenomena, while clinical trials aim for reproducible, generalized knowledge. By exploring the historical, philosophical, and methodological roots of these genres, we gain insight into how scientific culture has balanced the importance of singular marvels with the necessity of robust statistical evidence. This balance remains central to contemporary medical research and practice.