This manuscript reconceives debates about life and death by integrating conceptual clarification, methodological innovation, comparative exegesis, and an actionable empirical-normative protocol. Motivated by persistent clinical, legal, and cross-cultural conflicts; most visibly in controversies over brain-death determinations and organ procurement, this paper advances two interlocking contributions. The first is a clarified and operationalized theoretical instrument: The Three-Sense Taxonomy (physiological, organismal, social/interest-based), reworked as a policy-ready diagnostic tool with explicit indicators, institutional consequences, and safeguards. The second is a novel methodological innovation, the Integrative Deliberative Empirical-Normative (IDEN) framework which prescribes how mixed empirical methods, structured public deliberation, and explicit normative synthesis should be combined to generate legitimate and implementable policy in plural societies. After a focused literature review drawing on contemporary clinical guidelines, empirical studies of relatives' dilemmas, and comparative philosophical sources, the paper applies the taxonomy and IDEN to three case studies: brain death and transplantation in Western medicine, familial decision-making in Confucian contexts, and soteriological considerations in Indian contexts (Advaita Vedānta and Buddhist frameworks). Each case demonstrates how conceptual ambiguity and institutional opacity produce moral harms, and how IDEN-guided pilots can produce transparent, defensible compromises (an organismal legal default plus bounded, deliberatively ratified accommodations). The paper concludes with detailed pilot designs, evaluation metrics, ethical safeguards, and a research agenda. It argues that conceptual rigor without democratic legitimacy is brittle, and legitimacy without conceptual clarity is muddled; the IDEN framework seeks the necessary marriage of the two.

Postmortem human temporal bones provide an irreplaceable resource for studying the cochlea and vestibular labyrinth in their native anatomic context, as the tissues of these organs cannot be non-destructively biopsied. However, temporal bone procurement using an intracranial circular saw blade remains technically challenging, with intermittent blade fractures despite iterative optimization of blade materials and design. Because specimens are rare, efficient collection of biologic materials, including perilymph, further increases the value of each autopsy. We qualitatively assessed modifiable and non-modifiable factors contributing to blade fracture risk during five postmortem temporal bone collections by three operators and evaluated refinements for perilymph collection. Potential contributors, based on direct observation and operator-reported experience, included irregular middle cranial fossa (MCF) topography, angle of saw blade engagement with bone, cortical scoring technique, and operator body mechanics. Modifiable factors included maintaining an orthogonal saw axis relative to the MCF, performing cortical scoring before complete osteotomy, and repositioning of the operator to improve ergonomic alignment with the saw axis. Non-modifiable factors included the irregular surface of the MCF, temporal bone asymmetry, and physical constraints limiting orthogonal saw alignment. These observations informed a refined saw blade design intended to accommodate non-modifiable anatomic and ergonomic constraints. Perilymph workflow refinements enabled timely recovery of low-volume samples before temporal bone fixation. After optimization, trainee procurement duration averaged 8.0 ± 2.5 min across five serial sessions, whereas experienced operators retrospectively self-reported ~5 min per temporal bone. These refinements are intended to improve the robustness, reproducibility, speed, and accessibility of postmortem temporal bone collection for human otopathology studies.

High-energy LiNi0.6Co0.1Mn0.3O2 (NCM613) ||silicon/carbon (Si/C) full cells undergo pronounced interfacial chemomechanical degradation under high-voltage and high-temperature conditions, as repeated Si volume fluctuation, electrolyte decomposition, and transition-metal (TM) dissolution accelerate cell failure. Although monoanhydride additives such as succinic anhydride (SA) can scavenge acidic impurities, their limited reactive sites and insufficient structural adaptability restrict long-term interphase stabilization. To address these limitations, 1,2,4,5-cyclohexanetetracarboxylic dianhydride (HPMDA) is introduced as a multifunctional electrolyte additive, extending additive design from monoanhydride to dianhydride. Relative to SA, the dual-anhydride framework of HPMDA provides four carbonyl-active sites, enabling enhanced H2O/HF scavenging and more effective regulation of Li[+] solvation, while the cyclohexane backbone imparts conformational flexibility for mechanically compliant interphases. HPMDA regulates the electrolyte solvation structure toward an aggregate-rich configuration and facilitates the preferential decomposition of fluoroethylene carbonate (FEC), thereby promoting the formation of thin and uniform solid electrolyte interphase (SEI) and cathode electrolyte interphase (CEI) layers that accommodate Si volume fluctuation and suppress cathode corrosion. Consequently, the coupled chemical-mechanical degradation is markedly suppressed, leading to improved cycling stability of NCM613||Si/C full cells, with capacity retentions of 80% after 400 cycles at 45 °C, 82% after 200 cycles at 55 °C, and 80% after 300 cycles at 4.6 V. These results reveal the structure-function relationship underlying the transition from monoanhydride to dianhydride additives and provide a molecular basis for electrolyte design that couples bulk chemistry, solvation structure, and interphase mechanics.

The genus Cyphellophora belongs to the order Chaetothyriales, family Cyphellophoraceae, and accommodates various species that have previously been reported as a cause of infection in humans. Here, we report a case of presumptive dermal phaeohyphomycosis of the elbow from a patient in Adelaide, Australia. Biopsies showed fungal growth on culture but subsequent molecular identification by ITS sequencing could not resolve the identity, with a low similarity match to Cyphellophora pauciseptata (89.3% similarity) observed. Hence, the isolate was subjected to nanopore genome sequencing to enable multi-gene phylogenetic analysis. The de novo genome assembly was found to consist of 23 nuclear fragments (size range 16,678-4716,474 bp) totalling 26,281,485 bp with a coverage of 17X, the mitochondrial genome was 29,902 bp in size and had a coverage of 277X. Ab initio gene annotation reported 11,251 genes and a GC-content of 54.17%. To define the phylogenetic placement, the ITS and LSU ribosomal DNA, BT2 and RPB1 loci were extracted from the assembled genome and compared to available sequence data from NCBI GenBank. The isolate was found to represent a distinct genetic lineage within the Cyphellophora, which we describe here as a new species, Cyphellophora adelaidensis.

Human gastrointestinal anatomy evolved under conditions of food scarcity, low-caloric-density diets, and high physical activity. In this context, a relatively gastric-accommodation stomach capacity conferred a survival advantage by allowing consumption of large volumes of fibrous, low-energy foods, buffering seasonal shortages, and maximizing intake during rare periods of abundance. Modern food environments, characterized by constant access to energy-dense foods and sedentary lifestyles, have reversed these selective pressures, creating an evolutionary mismatch between ancestral digestive physiology and contemporary diets. This narrative review explores how a digestive architecture shaped by scarcity may become maladaptive in modern high-calorie conditions and examines stomach capacity as an under-recognized contributor to obesity and metabolic disease. Evidence was synthesized from evolutionary biology, anthropology, gastroenterology, and metabolic medicine using literature identified in PubMed, Scopus, and Web of Science (1990-2024). Evolutionary and anthropological evidence suggests that increased gastric volume was advantageous in both pre-agrarian and agrarian societies. In contrast, in modern environments this trait may promote excessive energy intake, delayed satiety, and metabolic dysfunction, particularly in the presence of ultra-processed foods. Clinical observations from bariatric surgery support this framework, as surgical reduction of gastric volume induces rapid metabolic improvements, often preceding significant weight loss. Gastric accommodation capacity, once adaptive, may now contribute to metabolic disease in obesogenic environments, reframing obesity as a predictable consequence of evolutionary mismatch.

Cytochrome P450 enzymes form a large superfamily of monooxygenases capable of oxidising diverse substrates. Among them, members of the CYP108 family are recognised for their role in monoterpenoid oxidation. In this study, we report the identification and characterisation of a new CYP108 family member, CYP108D18, from a metagenome-assembled genome derived from microbial communities in a geothermal hot spring located in northern Queensland, Australia. Taxonomic binning associated CYP108D18 with a Novosphingobium species, a genus well-known for its bioremediation potential. CYP108D18 was heterologously expressed in Escherichia coli, yielding 640 nmol L[-1] of culture, and purified to homogeneity. The enzyme exhibited moderate thermostability, with a [15]T50 value of 47°C ± 1°C. Spectroscopic substrate binding assays revealed that while CYP108D18 bound monoterpenoids similarly to other CYP108 enzymes, it showed higher affinity and pronounced larger heme spin-state shifts with aromatic hydrocarbons such as phenylcyclohexane and phenanthrene. Subsequent in silico docking and spectral-binding studies also suggested that CYP108D18 may accommodate larger plant-derived sesquiterpenes, indicating a potential role in their metabolism. Reconstitution of CYP108D18 with spinach ferredoxin and ferredoxin reductase resulted in the oxidation of phenylcyclohexane to trans-4-phenylcyclohexanol. Molecular dynamics simulations and ONIOM (QM/MM) calculations supported selective hydrogen abstraction at the cyclohexane C4 position, rationalising trans-4-phenylcyclohexanol as the predominant product. The high-resolution crystal structure of substrate-free CYP108D18 revealed a bound dioxygen ligand positioned above the heme iron, an unusual feature among P450 structures. Both substrate-free and phenylcyclohexane-bound structures revealed a persistent open conformation, suggesting the absence of a canonical open-to-closed transition upon ligand binding. Spectroelectrochemical analysis showed a heme redox potential of -451 mV versus NHE for the substrate-free CYP108D18, shifting subtly to -409 mV upon phenylcyclohexane binding, which contributes to reduced activity with non-native [2Fe-2S] ferredoxins.

Exposure and response prevention (ERP) remains a first-line psychological treatment for obsessive compulsive disorder (OCD), yet a clinically meaningful subset of patients cannot initiate, tolerate, or complete an adequate ERP dose even after step up in format, frequency, pharmacotherapy augmentation, or level of care. These failures are often interpreted as noncompliance, but they more often reflect a persistent capacity gap that limits between-session exposure practice and response prevention. This conceptual analysis positions ketogenic metabolic therapy (KMT) as a candidate adjunct when low capacity prevents delivery of an adequate ERP trial or persists after nonresponse. OCD evidence for KMT remains limited to case level reports that include standardized symptom measures and describe remission during nutritional ketosis, including one report in which KMT preceded successful ERP completion. These observations support a narrower clinical question that centers on capacity restoration rather than direct symptom treatment. ERP readiness is conceptualized across clinical, functional, and psychosocial domains that shape distress tolerance, cognitive efficiency, daily feasibility, and accommodation. Measurement-based care anchors decision points using adherence to between session exposure practice, completion of an adequate ERP dose, and established response and remission thresholds on validated symptom and global severity measures. Stepped care and staging checkpoints define pragmatic windows to test whether KMT increases ERP engagement, reduces refusal and drop out, and improves symptom severity and functioning beyond usual escalation alone.

Family communication dysfunction significantly impacts HIV medication adherence and mental health outcomes among adolescents in sub-Saharan Africa, yet evidence-based family interventions remain scarce in resource-limited settings. This qualitative descriptive study examined family communication transformation following culturally adapted Multiple Family Group Therapy (MFGT) for adolescents living with HIV and their families in rural Ghana. Focus group discussions were conducted with 20 caregivers and 19 adolescents who completed the 11-session intervention. All core therapeutic content was delivered across sessions 1 through 10; the 11th session comprised a graduation ceremony and sustainability planning. Reflexive thematic analysis revealed four major themes: preintervention dysfunction (public shaming, adolescent defiance, spousal teknonymy, extended family triangulation); MFGT-facilitated skills (tone modulation, privacy-preserving correction, active listening); postintervention transformation (caregiver behavioral consolidation, adolescent reciprocal adaptation, spousal reconnection); and sustaining mechanisms (observational learning, metacognitive awareness, positive reinforcement, peer accountability). Communication improvements occurred bidirectionally, with caregiver changes catalyzing adolescent adaptations. Findings are theoretically interpreted through family systems theory, communication accommodation theory, social cognitive theory, and self-determination theory. Culturally adapted MFGT successfully transformed communication patterns while preserving traditional authority structures, suggesting potential for integration within HIV care systems in resource-limited settings.

Achieving general asymmetric catalytic manifolds that accommodate broad substrate diversity remains a long-standing and highly sought-after goal in synthetic chemistry. Herein, we report an efficient cobalt-catalyzed desymmetric hydrogenation of structurally diverse cyclic 1,2- and 1,3-diacid anhydrides, enabling access to pharmaceutically relevant chiral γ- and δ-lactones with broad substrate scope and excellent enantioselectivity (up to 99% ee). The reaction is readily scalable, as demonstrated by gram-scale synthesis of several representative products. Notably, this 3d-metal catalytic platform represents a rare example that outperforms platinum-group-metal-based counterparts in both generality and stereoselectivity. DFT studies identify a catalytically active d[7] Co(II) dihydride complex with an outer-sphere hydride transfer mechanism, wherein a relatively flexible chiral pocket underlies the broad substrate compatibility of this catalytic system.