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In this case series, the authors aim to illustrate a technique for reinforcing tissue above deep-brain stimulator (DBS) surgical sites to prevent wound breakdown and decrease postoperative infectious risks. Twelve patients were implanted with DBS electrodes and an implantable pulse generator. Fish acellular dermal matrix was utilized following successful placement and tunneling of DBS leads to reinforce the surgical wound closure above the DBS cranial burr hole cover. This matrix was placed under the galea and above the pericranium in each patient before standard galea and skin closure techniques after the implants were placed. Eleven of 12 patients had the implant placed during surgery. One patient was excluded due to an allergy to the graft material. No patients at any point during the follow-up period showed any clinically significant signs of wound breakdown or infection at the surgical site. There was one report of suture extrusion without any associated infection or wound breakdown. In this case series, the authors demonstrate that the use of fish skin acellular dermal matrix is a safe and effective strategy that can be utilized during DBS placement to further bolster the skin above DBS burr hole covers to aid in wound healing and decrease postoperative surgical site infections.

High-electron-mobility transistors (HEMTs) based on wide bandgap (WBG) materials like gallium nitride (GaN) are vital for next-generation power electronics and high-frequency applications, offering high breakdown voltage, electron mobility, and power density. The global shift toward electrification and sustainability is driving demand for GaN and silicon carbide (SiC) power devices. However, challenges such as current collapse and increased channel resistance under high-power conditions hinder performance. To address these limitations, numerous solutions have been explored, with simulation emerging as an indispensable starting point. Technology Computer-Aided Design (TCAD) simulations play a critical role by enabling accurate modeling, performance optimization, and reduced experimental effort. This paper reviews key and advanced physical models in TCAD simulations of GaN HEMTs, covering mechanisms such as carrier transport, thermal effects, and impact ionization. Mobility models-FLDMOB, Albrecht, Gansat, Yamaguchi, Brooks-Herring, and Conwell-Weisskopf-are analyzed for capturing velocity saturation and nonlocal transport. Recombination models like Shockley-Read-Hall and Auger are discussed in relation to carrier lifetime, while impact ionization models, including van-Overstraeten-de-Man, Selberherr, and Okuto-Crowell, are evaluated for breakdown prediction. Emphasis is placed on choosing models suited to specific structures and conditions to ensure simulation accuracy. Advanced modeling enhances TCAD's predictive power, supporting innovation in GaN-based power electronics.

This paper applies principles and perspectives emerging from free energy neuroscience to the psychoanalytic concept of the death drive. The aim is to offer a contemporary reappraisal of this controversial aspect of psychoanalytic theory and its link to psychosis. The paper begins with a review of the death drive as proposed by Sigmund Freud, before proceeding to briefly outline Karl Friston's free energy principle. Building on proposals from Gustaw Sikora and Bernard Penot, it then explores how the combined and coordinating processes of minimising [binding] free energy and dismantling [unbinding] inexpedient generative models of reality may be understood as essential to life, growth, and adaptation. The question is thus raised: if a periodic unbinding-even destruction and demise-of generative models is vital to adaptive living, how might the death drive be conceptualised? The paper then proceeds to develop the notion that what Freud identified as the (defused) death drive may reflect a critical breakdown in the reciprocal ebb and flow of binding free energy/unbinding generative models of reality. Two illustrations-both of which concern psychotic phenomena-are given in an attempt to depict how the death drive in defused form may be recognised as manifesting both as arrested unbinding and/or interminable binding. The discussion explores how such a breakdown in the vital rhythms of life and self-organisation can sabotage the ability to think, compromise the mind's capacity to function as a container, and produce a boundless infinitisation of experience therein.

A silicon single-photon avalanche diode (SPAD) fabricated in a 40 nm CMOS image sensor (CIS) technology is reported. An N-well/deep P-well (DPW) structure on a CIS epitaxial wafer is employed, where the N-well and lightly doped epitaxial layer form a virtual guard ring that suppresses edge breakdown. The device exhibits a breakdown voltage of 22.7 V, a peak photon detection probability (PDP) of 89.4% at 660 nm and 3 V excess bias voltage, and a median dark count rate (DCR) of 0.6 cps/µm². A timing jitter of 144 ps full width at half maximum and an afterpulsing probability below 0.3% are achieved. Temperature-dependent measurements show a pronounced PDP redshift at 60 °C, accompanied by enhanced peak and long-wavelength PDP. The SPAD is suitable for high-performance low-light visible imaging applications.

The breakdown and recycling of carrion is a crucial ecological process that largely relies on a community of necrophagous insects and microbes. Recent work has shown that a specialized microbial network, likely dispersed throughout the environment by insects, assembles during cadaver decomposition to break down flesh regardless of climate and geography. Because of their broad distribution and successional nature, decomposer microbes have been used in machine learning models to predict the postmortem interval (PMI) of human remains, an important contribution to the field of forensics. How factors such as an indoor environment, which alters insect activity, impact the composition of microbial communities decomposing human remains is unclear. Here, we investigate the effects of enclosed shelter on microbial community assembly and successional patterns during human decomposition and provide important considerations for PMI modeling. Compared to outdoor cadavers, we show that indoor cadavers experienced delayed colonization of key decomposer microbes over the course of decomposition due to restricted insect access. Consequently, machine learning models trained on outdoor cadavers frequently underestimated the PMI of cadavers decomposing indoors. Delayed colonization by blow fly maggots (Diptera: Calliphoridae) was correlated with higher PMI prediction errors, suggesting that insects are an important source of microbial decomposers that drive PMI model predictions. Incorporating microbial data from indoor cadavers and insect activity into PMI models significantly improved prediction capabilities for both indoor and outdoor decomposition environments. Ultimately, we demonstrate the important role insects play in the maintenance and distribution of microbes that help to recycle vertebrate remains.IMPORTANCEMicrobes are critical for the decomposition and recycling of organic matter. Recently, microbiome-based models have shown promising performance in estimating the postmortem interval (PMI). However, many deaths occur indoors, yet no studies have investigated the impact of enclosed shelter on the cadaver microbiome in a controlled setting. Here, cadavers were decomposed indoors, and we found that blow fly maggots serve as an important source of decomposer taxa that significantly alter the cadaver microbiome following infestation. Notably, PMI estimation models trained on outdoor data sets failed to accurately predict the PMI when insect colonization was delayed. We show that incorporating 16S rRNA amplicon data from cadavers decomposing indoors, along with environmental variables, significantly improves PMI estimates, suggesting a microbiome-based forensic tool may be feasible across decomposition environments. Importantly, this research demonstrates the critical ecological role insects play in the dispersal of specialized microbes that are involved in the breakdown and recycling of vertebrate remains.

Two-dimensional (2D) semiconductors enable atomically thin channels and attractive electrostatics, but practical scaling increasingly hinges on gate-dielectric integration rather than channel performance. A key challenge is forming high-quality dielectrics on chemically inert, dangling-bond-free 2D surfaces while pushing equivalent oxide thickness to the sub-nanometer regime without excessive leakage, traps, or electrical breakdown. This review addresses the materials and process physics that govern dielectric formation in 2D devices, with an emphasis on atomic layer deposition nucleation, surface pretreatment and functionalization, and the use of seed and buffer layers for conformal high-κ oxides. The roles of layered insulators, such as hexagonal boron nitride, are discussed in terms of interface quality, electrostatic scaling limits, and transport limitations. The impact of dielectrics and processing on leakage mechanisms, defect generation, device-to-device variability, and reliability metrics, including time-dependent dielectric breakdown, bias-temperature instability, hysteresis, and threshold-voltage drift, is examined. Finally, we highlight van der Waals dry integration and dielectric transfer approaches that reduce process-induced damage and support wafer-scale uniformity, as well as opportunities for mixed-dimensional and 3D stacked architectures across logic, memory, and emerging functional systems. [Image: see text]

Diabetic retinopathy (DR) is a leading cause of preventable vision loss, yet current therapies primarily address late, VEGF-driven vascular complications rather than early upstream drivers. Emerging evidence indicates that early DR originates from metabolic stress within the retinal neurovascular unit, where dysregulated lipid metabolism, oxidative stress, and inflammation precede visible microvascular damage. Disturbances in polyunsaturated fatty acid (PUFA) metabolism, together with related metabolic stressors such as elevated homocysteine (Hcy), drive lipid dysregulation, oxidative stress, and inflammation preceding visible microvascular damage, promoting endothelial dysfunction and blood-retinal barrier (BRB) breakdown. Hyperglycemia shifts retinal lipid composition toward oxidation-prone omega-6 PUFAs and activates lipoxygenase (LOX), cyclooxygenase (COX), and cytochrome P450 (CYP450) eicosanoid pathways. LOX-derived metabolites such as 12- and 15-HETE stimulate NADPH oxidase, disrupt tight junctions, and promote inflammatory signaling in endothelial and Müller cells. COX-2-driven prostaglandin E2 signaling increases vascular permeability, while CYP450 metabolites and their soluble epoxide hydrolase (sEH) derived products exert context-dependent effects on vascular integrity. Elevated Hcy further enhances oxidative stress and NF-κB activation, amplifying PUFA-mediated inflammatory signaling. These mechanisms identify modifiable upstream targets that complement glycemic control. Higher dietary omega-3 intake and lower omega-6:omega-3 ratios are associated with reduced DR risk, particularly in well-controlled diabetes. Omega-3-rich diets, exercise, and correction of folate and B-vitamin deficiencies may help improve systemic inflammation and retinal barrier integrity. Integrating lipid pathway modulation, nutritional support, and metabolic control with careful ocular monitoring may help slow the progression of DR before irreversible blindness occurs.

Osteoarthritis (OA) is a prevalent, chronic joint disorder characterized by cartilage degradation, synovial inflammation, and extracellular matrix (ECM) remodeling, yet disease-modifying therapies remain elusive. Emerging evidence implicates ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, and cellular senescence, characterized by growth arrest and a senescence-associated secretory phenotype (SASP), as central contributors to OA pathogenesis. Ferroptotic chondrocytes release reactive lipid species and damage-associated molecular patterns (DAMPs) that induce paracrine senescence in neighboring cells, while senescent cells amplify oxidative stress and ferroptotic susceptibility, forming a self-perpetuating feed-forward loop that accelerates tissue degeneration. Histological, molecular, and in vivo studies demonstrate iron accumulation, lipid peroxidation, glutathione peroxidase 4 (GPX4) depletion, and SASP factor secretion in human OA cartilage, synovium, and animal models, linking these processes to ECM breakdown and joint inflammation. Targeted interventions, alone or in combination, can disrupt this pathological loop, preserve chondrocyte viability, reduce SASP-mediated inflammation, and mitigate cartilage damage. Integration of biomarker-guided patient stratification, advanced imaging, and spatial transcriptomic profiling may enable precision-targeted, disease-modifying therapies. Therefore, elucidating the crosstalk between ferroptosis and senescence offers a conceptual and translational framework for shifting OA management from symptomatic relief toward preservation of joint integrity and long-term disease modification.

For the past half-century, psychiatric drug development has largely focused on tweaking neurotransmitter receptors and chemical pathways. Yet despite billions of dollars invested and major advances in neuroscience, truly innovative treatments for mental illness remain scarce. Disorders like depression, schizophrenia, and post-traumatic stress disorder (PTSD) continue to be managed with drugs discovered decades ago that often provide only partial relief, with remission rates of approximately 30-40% for treatment-resistant depression and 60-70% of schizophrenia patients experiencing persistent symptoms despite medication. This stagnation has prompted a paradigm shift - what if the key to treating mental illness is not just which receptor a drug targets, but how it changes the brain's processing of sensory information? In this treatise, I propose that many psychiatric conditions stem from breakdowns in the brain's sensory filtering mechanisms, the neural circuits that gate irrelevant stimuli before they consume valuable processing resources, and that effective therapies must restore these filtering functions. While computational psychiatry has long recognized that mental illness may reflect failures in predictive filtering, the specific neural substrate implementing this gating remains underspecified. Here the cerebellum emerges as a critical hub: neuroanatomically positioned to perform bottom-up sensory gating before cortical processing, housing more than half the brain's neurons in an architecture ideally suited for distilling signal from noise and showing state-dependent disruption of cerebellar-cortical connectivity during symptom provocation in PTSD. Intriguingly, psychedelic drugs may act as recalibration triggers for these neural filters, acutely disrupting entrenched filtering architectures and reopening windows of plasticity through which maladaptive sensory weightings can be reset. This cerebellar filtering framework offers a neuroanatomically specified extension of predictive processing theory, generates falsifiable predictions, and suggests novel therapeutic targets for conditions that have resisted a half-century of receptor-focused drug development.

Aging leads to degenerative changes in lung structural and mechanical properties that may impact breathing. Relatively little is known about how age-related alterations in lung mechanical properties impact expiratory duration (TE) and residual volume (RV). The present study tested three hypotheses: 1) alveolar airspace increases with age due to alveolar wall breakdown, 2) lung elastic recoil decreases, slowing expiratory flow (E-flow), and 3) airway compliance (Caw) decreases, promoting air trapping reflected by increased RV. To test these hypotheses, we evaluated changes in alveolar size using histological assessments, mechanical properties using forced oscillation perturbations with a programmable mechanical ventilator and breathing parameters using plethysmography in young (6 months) and old (24 months) Fischer 344 rats. Mean linear intercept (Lm) was higher in old (65 ± 10 µm) compared to young (55 ± 5 µm) rats, indicating alveolar airspace increase. In old rats, decreased elastic recoil was indicated by increased parameter K (0.178 ± 0.010 vs. 0.167 ± 0.013 in young) and higher V₁₀/TLC (80.7 ± 1.2% vs. 78.5 ± 2.5% in young). In addition, RV was higher in old rats (0.41 ± 0.10 mL vs. 0.27 ± 0.05 mL in young), consistent with air trapping. These mechanical changes were associated with increased E-flow (~30%) in old rats, attributable to increased tidal volume (2.08 ± 0.41 mL vs. 1.53 ± 0.36 mL in young) as TE was unchanged. These results indicate important changes in the lung parenchyma, causing alteration in passive and active properties of the respiratory system in aging rats.

Olanzapine is an atypical antipsychotic used to treat chronic schizophrenia and bipolar I disorder, including mixed/manic episodes. It is a BCS class II medication, and thus there is a potential for sublingual administration allowing rapid absorption. This may potentially result in a faster onset of action compared to oral tablets. The aim of this work was to formulate a fast-dissolving sublingual film of olanzapine with rapid disintegration. Hydroxypropyl methylcellulose E5, polyethylene glycol 400, and Transcutol HP were optimized using a QBD approach based on disintegration time, folding endurance, weight variation, content uniformity, and in vitro drug release of films. The drug was completely soluble with the above-mentioned ingredients. Optimized film was further evaluated for drug content, pH, and dissolution studies. The optimized film disintegrated within 30 s, showed smooth surfaces on SEM and AFM analysis. The drug content was found to be 88% for optimized film formulation, and the in vitro dissolution studies estimated the release to be 94.79% in 10 min. This novel approach may offer a promising alternative in terms of reduced dosage; however, further investigations and in vivo assessment of the film are warranted to prove enhanced permeation indicating quicker absorption sublingually, leading to an increase in bioavailability. Olanzapine is a medicine used to treat people with schizophrenia and mania. It is sold in the form of tablets, which breakdown in the mouth, and as injections. However, some people may find it difficult to swallow tablets and hence may prefer a simpler way of taking this medicine. To solve this problem, we have tried to make a film containing olanzapine which is to be placed just under the tongue. The film was designed using robust techniques, both mathematically and technically. The film was checked for properties including how well the medicine dissolved in the film, how quickly the film breaks down when kept under the tongue, and how rapidly the medicine comes out of the film. The film showed the desired performance in the laboratory. This study shows that it is possible to prepare a film to be kept under the tongue for medicines needed for treating schizophrenia, rather than being swallowed like a tablet and yet get same or even better results. Although the study is promising in the laboratory, further testing of the film is required on humans to check how it fares after administering the film to actual patients.

Autoimmune thyroid diseases (AITDs), including Hashimoto's thyroiditis and Graves' disease, arise from thyroid-specific autoimmunity driven by a breakdown of immune tolerance and dysregulated T-cell responses. Within this immune network, imbalance between T helper 17 (Th17) cells and regulatory T (Treg) cells has emerged as a major determinant of persistent inflammation and defective immune restraint. These two subsets are supported by distinct but interconnected metabolic programs. Th17 cells preferentially engage glycolytic and anabolic pathways to sustain inflammatory activity, whereas Treg cells rely more strongly on oxidative metabolism and mitochondrial fitness to preserve lineage stability and suppressive function. In AITDs, these intracellular programs are further reshaped by disease-associated microenvironmental cues, including excess iodine, oxidative stress, lactate accumulation, inflammatory cytokines, and tissue-derived stromal signals. This review summarizes how glucose, lipid, mitochondrial, and amino acid metabolism collectively regulate Th17 and Treg differentiation and function. We further examine how these pathways are altered in AITDs and distorted in thyroid and orbital tissues to amplify immune disequilibrium. Finally, we discuss emerging therapeutic strategies aimed at targeting immune metabolic circuits to restore immune homeostasis.

Diabetic retinopathy (DR) is a microvascular complication of diabetes characterized by blood-retinal barrier (BRB) disruption and progressive endothelial dysfunction. Disturbances in one-carbon metabolism, particularly hyperhomocysteinemia (HHcy), have been implicated as biologically plausible modifiers of retinal endothelial vulnerability. To synthesize mechanistic, preclinical, and clinical evidence linking HHcy and one-carbon metabolism to BRB dysfunction in DR, and to explore translational implications for endothelial risk assessment. Narrative review of experimental, observational, and translational studies examining homocysteine metabolism, endothelial regulation, BRB integrity, and diabetes-induced metabolic perturbations. Evidence was prioritized based on mechanistic relevance, in vitro and in vivo models, and human correlates. Elevated homocysteine promotes oxidative stress, tight junction destabilization, N-methyl-d-aspartate receptor activation, mitochondrial dysfunction, and impaired mitophagy in retinal endothelial cells. Diabetes amplifies these pathways, lowering the threshold for VEGF-mediated BRB breakdown. Observational studies associate HHcy with DR severity, but causality remains unproven. Cardiovascular trials demonstrate plasma homocysteine lowering without consistent macrovascular benefit, suggesting HHcy functions primarily as a biomarker or modifier. Emerging data indicate potential intersections with innate immune signaling and ferroptotic vulnerability, offering mechanistic hypotheses for translational research. Integrative frameworks considering glycemic control, one-carbon metabolic status, and endothelial signaling may inform future early-intervention strategies, though clinical validation is pending. HHcy represents a mechanistic modifier of retinal endothelial stress in DR rather than a validated therapeutic target. Anti-VEGF therapy and glycemic optimization remain the only proven interventions. Further studies clarifying intracellular one-carbon metabolism and BRB integrity may refine risk stratification and identify early-intervention opportunities.