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Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by sterile ulcerative skin lesions. Multiple comorbidities and clinical features have been associated with PG, but no standardized guidelines exist for classifying PG phenotypes. To develop an expert-established classification framework for PG phenotypes to inform treatment guidelines and future research endeavors. In this modified Delphi consensus study that included 23 board-certified dermatologists and Medical Dermatology Society members with expertise in PG, panelists completed 5 rounds of anonymous, iterative online surveys that were administered from December 2023 through July 2025. Before the beginning of the consensus exercise, a literature review was performed by nonvoting researchers to summarize existing data on PG clinical associations and comorbidities. A PubMed search from inception to September 2023 identified observational studies, narrative reviews, systematic reviews, and meta-analyses describing PG clinical associations and comorbidities that were published in English. Experts indicated their agreement with proposed PG phenotypes and disease modifiers with a consensus threshold of 70% or greater. Anonymous comments and aggregated results were presented in each subsequent round. In the final round, a framework of PG phenotypes and disease modifiers was proposed for agreement. Twenty-three board-certified dermatologists and Medical Dermatology Society members with expertise in PG completed 5 rounds of iterative surveys. Consensus was reached on the final set of PG phenotypes and disease modifiers, with 83% of experts in agreement. PG phenotypes were overall classified into 2 major groups: PG with autoinflammatory syndromes and nonsyndromic PG. Nonsyndromic PG included 4 phenotypes: inflammatory bowel disease-associated PG, PG in association with hematologic cancers and blood dyscrasias, drug-induced PG, and other (including idiopathic) PG. Disease modifiers of PG phenotype presentations included involvement of special sites (head/neck, genitals, or peristomal skin) and extracutaneous manifestations. This expert-established, descriptive framework provides a standardized classification system for distinct PG phenotypes and its modifiers. This nomenclature may inform upcoming clinical guidelines and allow for consistency in reporting epidemiological research and outcomes among patients with PG.

Evaluating the benefit-risk profile of a medical product requires comprehensive evidence that integrates information across development stages. Technological advances and broader use of real-world data are enabling innovative quantitative paradigms characterized by greater efficiency, patient centricity, and sustainability. Despite regulatory recognition of model-informed drug development, disease progression modeling (DPM) remains underutilized compared with more established pharmacokinetic/pharmacodynamic modeling and simulation approaches. To inform adoption decisions by clinical, regulatory, and portfolio leaders, the Clinical Trials Transformation Initiative (CTTI) developed evidence-based, cross-sector recommendations that describe when and how to use DPM in medical product development and how to effectively communicate its impactful implementation across functions. In this article, we (i) define DPM and summarize its unique value in clinical development, (ii) describe CTTI's collaborative process to generate a set of nine DPM recommendations and a practical considerations framework, and (iii) present examples of strategic development questions showing how DPM can answer high-value questions about indication, population, endpoints, and dose selection. By providing a shared vocabulary and structured questions for decision makers and modelers, these recommendations may lower barriers to DPM implementation, support fit-for-purpose use of existing and new models, and enable more efficient, patient-focused, and sustainable clinical development.

Over the past two decades, cyborg insects have emerged as a promising alternative to artificial insect-scale mobile robots, owing to their low power consumption, resilient biological bodies with naturally integrated sensors, agile locomotion, and self-adaptability. However, most studies have focused primarily on autonomous control and hardware integration for search-oriented urban search-and-rescue operations following natural disasters such as earthquakes. This raises a crucial next-step challenge: beyond locating survivors, what life-saving interventions can cyborg insects perform? Here, we present paramedic cyborg insects (Paraborgs) equipped with a human-supervised auto-injection mechanism (AIM) and onboard camera, enabling needle-based in situ liquid-drug-delivery executed by multiple teleoperated cyborg cockroaches. The feasibility of Paraborg is demonstrated through three core innovations: (i) a compact auto-injection mechanism that launches an injector and delivers liquid drug to a target with an 90% success rate; a robust manual control strategy achieving 100% success in reaching designated checkpoints, 72% success in stabilizing cyborg cockroaches for targeted injection, and up to 95% close-range injection success within 150 mm of the target; and (iii) teamwork concept with multiple teleoperated cyborg insects for carrying out complex in situ functions. Together, these results demonstrate Paraborg as a prospective platform that extends cyborg insect swarm toward field-deployable medical intervention.

Juvenile Parkinson's disease (JPD) is a rare condition characterized by the onset of parkinsonian motor symptoms before the age of 21. Sixteen patients with JPD who presented to the Mayo Clinic between 1990-2020 were included. The median age of symptoms onset was 18.5 years, and six cases had pathogenic PRKN mutations. Resting tremor was the most frequent initial symptom (81.3%), and non-motor symptoms were notably common, including mild cognitive impairment (56.3%), anxiety (62.5%), and depression (56.3%). Levodopa responsiveness was suboptimal in 9 patients and 14 exhibited motor fluctuations. JPD demonstrates distinct clinical characteristics compared with early-onset and late-onset PD. A study of 16 patients who developed juvenile Parkinson's disease, analyzing symptoms, genetic causes, and treatment responseJuvenile Parkinson's disease (JPD) is a rare condition with Parkinson's disease-like symptoms occurring in young people. We reviewed all patients diagnosed with Parkinson's disease at the Mayo Clinic between 1990 and 2020 and focused on those whose symptoms began before age 21, gathering information from their medical records about their symptoms, family history, genetic tests, and treatments. We identified 16 patients. A total of 63% had family members with Parkinson's disease, and half carried a genetic mutation linked to the disease. Most began showing symptoms around age 18, and the most common first sign was a resting tremor. Beyond movement, many also had memory or thinking difficulties (63%), anxiety (63%), and depression (56%). All received standard Parkinson's medications, which helped at first but became less effective over time, and many developed treatment-related abnormal movements. Four patients underwent a surgical procedure called deep brain stimulation, which helped control their symptoms. Juvenile Parkinson's disease has distinct genetic and clinical features and requires early recognition, genetic testing, and care tailored to each person.

Sleep research has been limited by the lack of large, diverse polysomnography (PSG) datasets. Existing resources are often single-center, age-specific, or epidemiological in nature, restricting generalizability and large-scale clinical research. The objective of this study was to create a large, multi-center clinical PSG dataset to support scalable and broadly representative research in sleep medicine and clinical neuroscience. The Human Sleep Project (HSP) dataset comprises 119,234 overnight sleep recordings from more than 90,000 unique patients collected across five major U.S. institutions: Stanford University, Massachusetts General Brigham (MGB), Emory University, Beth Israel Deaconess Medical Center (BIDMC), and Boston Children's Hospital (BCH). Each study includes at least a standard attended PSG montage, along with clinical annotations and standardized automated sleep annotations. Data were harmonized using the Brain Imaging Data Structure (BIDS) framework and linked to de-identified demographic and electronic health record (EHR) data. The HSP spans the full human lifespan, from infancy to individuals over 90 years old, and includes diagnoses across 22 ICD-10 clinical categories. Analysis of the aggregated data demonstrates expected age-related trends in sleep architecture, including reduced total sleep time and N3 sleep and increased sleep fragmentation with advancing age. Standardization procedures successfully addressed technical and scoring variability across sites, creating a consistent and high-quality resource for large-scale analyses. The Human Sleep Project provides harmonized physiological signals, manual and automated annotations, and quality metadata for 119,234 sleep studies, including 115,129 PSGs and 4,105 home sleep apnea tests, enabling reproducible sleep research at an unprecedented scale.

Implant-associated infections caused by bacterial biofilms significantly limit the clinical utility of nickel-titanium (NiTi) alloys. Existing antimicrobial coatings often suffer from limited efficacy, poor biocompatibility, or non-selective killing mechanisms. To address these issues, a novel Cu3P-based film is fabricated on NiTi substrates through a combined approach of copper plasma immersion ion implantation and gas-phase phosphorization. This film can specifically cause bacterial metabolic collapse, which refers to ATP depletion caused by disrupted transmembrane proton motive force, and concurrently promote endogenous bacterial reactive oxygen species burst and glutathione depletion via controlled copper ion release. These synergistic effects can achieve over 99% eradication of both S. aureus and E. coli in vitro. Meanwhile, it exhibits excellent biocompatibility with mammalian cells due to the distinct mitochondrial energy metabolism pathway that distinguishes cells from bacteria. In vivo results from a rat subcutaneous infection model further confirm that the metal phosphide film effectively prevents infection and promotes tissue integration without causing inflammation or toxicity. This direct-contact and ion release synergistic antibacterial design concept provides theoretical insights for designing medical metallic implants with dual advantages of robust antibacterial performance and biosafety.

This study aimed to analyze the human papilloma virus (HPV) genotype distribution in vaginal intraepithelial neoplasia (VaIN) and its relationship with the anatomical location on the vaginal wall. A retrospective study was conducted on patients diagnosed with VaIN at the First Affiliated Hospital of Wenzhou Medical University between January 1, 2021, and December 31, 2024. A total of 1670 patients with low-grade VaIN and 259 patients with high-grade VaIN were included. Single HPV infection was the most prevalent type in VaIN cases. HPV52 was identified as the most common genotype in VaIN1 (25.0%), followed by HPV58 (15.7%), HPV53 (15.6%), and HPV16 (11.4%). In VaIN 2/3, the predominant genotypes were HPV16 (39.0%), HPV58 (22.4%), and HPV52 (15.1%). Multifocal lesions were observed in 34.7% of patients and were associated with both HPV co-infection and high-grade lesions. The diversity of HPV genotype was lower in the middle and lower segments of the vagina compared with the upper third and fornix. HPV16 was frequently and evenly detected across all vaginal segments in the specimen-level HSIL group (33.3%-47.2%). HPV52 was a leading genotype in the specimen-level LSIL group (17.6%-33.3%) and remained prevalent in the specimen-level HSIL group (10.3%-33.3%). HPV58 also accounted for a high proportion of infections. HPV exhibits distinct distribution patterns across different anatomical sites of the vaginal wall.

Criteria used by healthcare practitioners (HCPs) to set goals and assess when treatment was successful, met its goals, and/or should be ended has not been studied for men seeking treatment of premature ejaculation (PE). This study describes HCPs' priorities regarding treatment goals, assessment of success, and decisions to end treatment for men with PE, and examined whether HCP characteristics influenced these decisions. Overall, 240 medical and mental health professionals completed an online or in-person survey on treatment objectives and termination criteria in PE care. Results indicated that, according to HCP reports, patients' primary treatment goal was increased ejaculation latency, whereas HCPs themselves most strongly prioritized reducing distress and improving coping. For ejaculation latency, 44.7% of HCPs defined success according to the client's preferred level. Beyond latency, reduced stress and improved coping received the highest success rating, and 76.9% of HCPs reported moderate-to-high success in treating men with PE. Treatment termination was most often linked to increased sexual satisfaction and reduced distress. Professional training, identity, and PE treatment experience influenced goals, success assessment, and termination decisions. PE treatment requires explicit shared decision-making to align clinicians' biopsychosocial priorities with patients' symptom-specific expectations.

This cohort study examines the comorbidities and long-term outcomes associated with metabolic dysfunction–associated steatohepatitis (MASH) in patients on the liver transplant waiting list.

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Residual albuminuria remains a major clinical challenge in patients with type 2 diabetes mellitus and hypertension despite renin-angiotensin system inhibitor therapy. Esaxerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, reduces albuminuria; however, its effects on oxidative stress remain unclear. This 24-week, prospective, randomized, open-label, multicenter exploratory trial was conducted in Japan. Hypertensive patients with type 2 diabetes mellitus and albuminuria receiving standard-dose angiotensin II receptor blocker therapy were randomized to angiotensin II receptor blocker dose escalation or esaxerenone add-on therapy. Of 50 randomized patients, 47 were included in the full analysis set and 39 in the final analysis population (20 in the angiotensin II receptor blocker dose-escalation group and 19 in the esaxerenone add-on group). The primary endpoints were changes from baseline to Week 24 in urinary albumin-to-creatinine ratio and oxidative stress assessed by diacron-reactive oxygen metabolites. Esaxerenone add-on therapy produced a significantly greater reduction in log-transformed urinary albumin-to-creatinine ratio than angiotensin II receptor blocker dose-escalation therapy, with an adjusted between-group ratio of 0.71 (95% confidence interval, 0.58-0.87; p = 0.002). Systolic and diastolic blood pressures were significantly lower with esaxerenone. Estimated glomerular filtration rate decreased more with esaxerenone, whereas serum potassium levels did not differ significantly between groups. No significant between-group difference was observed in diacron-reactive oxygen metabolites. In hypertensive patients with type 2 diabetes mellitus and albuminuria, esaxerenone add-on therapy reduced albuminuria and blood pressure more effectively than angiotensin II receptor blocker dose escalation but did not significantly reduce oxidative stress.

People with psoriasis are at increased risk for nonmelanoma skin cancers (NMSC) and melanoma. Conventional immunosuppressants and TNF-α inhibitors may further increase skin malignancies, while the risks associated with other biologics are less clear. This study aimed to determine skin malignancy risks in psoriasis patients treated with cyclosporine, methotrexate, TNF-α inhibitors, IL-12/23, IL-17, and IL-23 inhibitors. Using the TriNetX database, psoriasis patients without skin cancer risk factors who received at least 2 years or at least 5 years of systemic treatment were compared with non-systemically treated psoriasis patients. Cyclosporine, methotrexate, and TNF-α inhibitors were also compared with other psoriasis biologics. NMSC and melanoma over 2 and 5 years were evaluated using multivariable Cox proportional hazards. Compared with non-systemically treated psoriasis patients, cyclosporine, methotrexate, TNF-α inhibitors, and the IL-12/23 inhibitor showed increased NMSC risk, whereas IL-17 inhibitors demonstrated a reduced risk. Compared with patients treated with cyclosporine, methotrexate, and TNF-α inhibitors, both IL-17 and IL-23 inhibitors demonstrated a reduced NMSC risk. Only cyclosporine was associated with elevated melanoma risk. The present study is limited by unmeasured factors, including psoriasis severity, ultraviolet radiation exposure, medication adherence, and dosing. Systemic therapies for psoriasis vary in skin malignancy risk, with IL-17 and IL-23 inhibitors having the lowest NMSC risk. &nbsp.

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The golden hamster, renowned for its representative PIWI-piRNA pathway profile among mammals, has emerged as a promising animal model for investigating female mammalian fertility. Prior research uncovered that the disruption of Piwil1 leads to complete infertility of female golden hamsters, with embryos derived from homozygous knockout (Piwil1-/-) females mated with wild-type males arresting at the two-cell stage. However, the underlying deep mechanisms remain unexplored. In the current study, we utilized highly sensitive single-cell mass spectrometry to generate proteome data of five developmental stages from oocytes to embryos in both wild-type (WT) and Piwil1-deficient golden hamsters, thus profiling the dynamic proteome landscape during oocyte-to-embryo transition (OET). Integrative analyses highlighted the temporal dynamics and complexity of hamster oocytes and embryos. Notably, we observed that classical maternal proteins in hamsters exhibit a more intricate pattern compared to mice, while PIWIL1 deficiency led to aberrant expression of proteins with diverse functions in oocytes and early embryos. Analysis of Multi-omics data indicated that PIWIL1 primarily regulates differentially expressed proteins at the post-translational level during OET. Specifically, the stability of TDRD1, essential for embryogenesis and gametogenesis, is modulated by PIWIL1, and could be its downstream target. Our study provides an extensive database that offers valuable insights into mammalian oocyte and early embryo development, and represents an invaluable resource for further mechanistic studies to deepen the understanding of developmental regulation.

Droplet-based 3D printing can fabricate complex structures, but quantitative regulation over droplet solidification and the mechanical performance of printed components remains essential for its load-bearing and multi-functional applications. Leveraging the intrinsic transparency of ice, we innovatively propose a nanoparticle-mediated strategy to suppress trapped air bubbles during water droplet solidification and thereby reinforce the mechanical performance of printed components. We develop a unified influencing factor to integrate the effects of nanoparticle concentration, diameter, and type on droplet nucleation and freezing characteristics. We uncover that the addition of nanoparticles raises nucleation temperature, refines ice dendrites, reduces freezing rate, and ultimately diminishes trapped air bubbles. These effects enable mechanical reinforcement of components and quantitative regulation of their compressive strength. The bubble volume fraction is reduced by ∼35% while the compressive strength is increased by up to 39%, exceeding the reported average values by more than two times. The low-cost strategy requires no external physical fields and introduces negligible changes to the hydrodynamic properties of raw printing materials. These findings elucidate the physical mechanisms governing nanoparticle-mediated bubble suppression during droplet solidification and further provide a viable pathway for the controllable fabrication of high-performance composite printing materials.