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Fania (Fanny) Kaplan and the attempted assassination of Vladimir Lenin: Ophthalmologic considerations
No full textFania (Fanny) Kaplan (1890-1918), who was reportedly visually impaired, confessed to the attempted assassination of Soviet leader Vladimir Lenin (1870-1924) in 1918 by shooting him with a pistol. The precise nature of her visual loss is unknown and raises doubts about whether she had sufficient visual function to perform the act.
Historical documents were reviewed.
The cause of Kaplan's visual loss is uncertain but occurred following a bomb blast in 1906. If the explosion was the cause, then she most likely had bilateral closed-globe, blast-related injuries, perhaps with additional functional visual loss. She reportedly received treatment at a medical centre in Kharkov (now Kharkiv), then led by the prominent ophthalmologist Leonard Girshman (1839-1921). An informal estimate of the minimum visual acuity required to shoot an adult at 10 feet (3 m) with a pistol is approximately 1.2 logMAR (Snellen equivalent 20/320 or 6/96).
Based on available historical documents, Kaplan's visual function was most likely sufficient to carry out the assassination attempt, although her visual impairment may have contributed to the attempt being unsuccessful
Antileukemic therapies for older adults with AML ineligible for conventional therapy: systematic review & meta-analysis
No full text•In older adults with AML ineligible for conventional chemotherapy, HMA or LDAC plus VEN probably reduces mortality and improves remission.•Evidence from 47 studies informed eight recommendations in the updated 2025 ASH AML guidelines.
Older adults with newly diagnosed acute myeloid leukemia (AML) are often ineligible for conventional “7+3” induction chemotherapy. Despite recent drug approvals, treatment outcomes remain poor in this population. We conducted an updated systematic review to inform the 2025 American Society of Hematology (ASH) AML update guidelines in older adults. This review compared the efficacy and safety of low-dose cytarabine (LDAC), azacitidine (AZA), 5- and 10-day decitabine (DEC), and gemtuzumab ozogamicin, alone or combined with drugs such as venetoclax (VEN), in older adults with AML ineligible for conventional chemotherapy. We included randomized controlled trials (RCTs) and non-randomized studies (NRS) of adults aged ≥55 years with AML, and synthesized evidence on mortality, remission, quality of life (QoL), functional status, and severe toxicity. We applied GRADE to assess the certainty of evidence. We included 47 studies (30 RCTs, 17 NRS). AZA or LDAC combined with VEN probably reduces mortality and improves remission and QoL. AZA plus isocitrate dehydrogenase-1 (IDH1) inhibitors may reduce 1-year mortality and improve remission and survival in patients with IDH1-mutated AML. Compared with DEC alone, combining DEC with other agents showed inconsistent effects with mostly low certainty of conclusions. VEN combinations showed promising effects on mortality and remission but lacked data on QoL and functional status. In older adults with AML ineligible for conventional therapy, evidence suggests that hypomethylating agents (HMAs) or LDAC combined with VEN likely improves survival and remission outcomes. Treatment decisions should consider patient goals and functional status. These findings informed eight recommendations in updated ASH-AML guidelines
Longitudinal associations between depression, substance use, and immune activation and inflammation: A secondary analysis of men who have sex with men living with HIV in Brazil (HPTN 063)
No full text•Depressive symptoms predicted changes in inflammation and immune activation over one year among men with HIV in Brazil.•Depression and alcohol use showed high within-person variability across time; stimulant use was mostly stable.•Studies should investigate if interventions targeting depression can improve immune function among men with HIV in Brazil.
Limited research has examined the longitudinal interplay of depression, substance use, and immune dysregulation among men with HIV.
We analyzed longitudinal data from 100 men who have sex with men (MSM) living with HIV enrolled in the HPTN 063 cohort (2011–2013) in Brazil. Depressive symptom severity, alcohol use severity, and recent illicit stimulant use were assessed quarterly over 12 months. Soluble markers of immune activation (sCD14) and inflammation (IL-6) were measured at baseline and at a 12-month visit.
Depressive symptom severity and alcohol use severity showed substantial within-person variability across time, whereas stimulant use remained relatively stable. These psychosocial factors were weakly intercorrelated. Controlling for baseline IL-6, the odds of having detectable IL-6 at 12 months increased by 2 % for each point increase in the proportion of visits with elevated depression, 7 % for each point increase in mean depressive severity across visits, 5 % for each point increase in depressive severity at nine months, and 6 % for each point increase in depressive severity at 12 months. Effects persisted after controlling for baseline HIV viral load. Controlling for baseline sCD14, estimated 12-month sCD14 increased 8 ng/mL for each point increase in 12-month depressive severity and 20 ng/mL for each point increase in 12-month alcohol use severity. The alcohol–sCD14 association was attenuated when adjusting for HIV viral load. Neither baseline IL-6 nor sCD14 strongly predicted future depressive symptoms or substance use.
Depressive symptoms predicted future inflammation and current immune activation. Research should examine if interventions to treat depression can improve immune functioning
Development of a quadruple-conjugated carbon dot nanomodel for targeted glioma therapy
No full textHigh-grade gliomas are devastating cancers with dismal prognosis, largely because current chemotherapeutics fail to cross the blood-brain barrier and lack tumor-cell specificity. Nanotechnology aims to overcome these limitations through targeted drug delivery. Here, a quadruple-conjugated nanomodel was synthesized using carbon dots (C-dots) as biocompatible nanocarriers via a one-pot reaction that covalently links two targeting peptides and two anticancer agents. The short peptide (shPep-1) targets the tumor-restricted receptor IL13Rα2, whereas the long peptide (lnPep-1) contains a nuclear localization signal for enhanced intracellular trafficking. Therapeutic cargo consists of epirubicin and the temozolomide metabolite 5-aminoimidazole-4-carboxamide. This nanomodel displays potent cytotoxicity in multiple high-grade glioma cell lines at 50 nM while remaining relatively non-toxic to normal cells (IC₅₀ > 2 µM). Despite a lower drug-loading capacity than single-peptide formulations, it induced greater glioma cell death, underscoring the enhanced therapeutic synergy of its dual-peptide, dual-drug design. Fluorescence studies confirm superior uptake and nuclear delivery, establishing C-dots as a stable, cost-effective, modular platform for next-generation personalized cancer nanotherapies
Patients With Bw4 and Bw6 Antibodies Can Participate in Clinical Xenotransplantation Trials
No full textWith clinical xenotransplantation now underway, optimal patient selection is critical for achieving successful outcomes. Candidates with antibodies targeting Bw4 and Bw6 epitopes on HLA molecules often experience prolonged wait times for allotransplantation because of high calculated panel reactive antibody levels. We investigated whether these antibodies cross-react with class I swine leukocyte antigen (SLA) molecules and could therefore pose a barrier to xenotransplantation.
We performed sequence alignment and structural modeling to assess the presence of Bw4 and Bw6 epitopes in class I SLA proteins. Human sera containing anti-Bw4 or anti-Bw6 antibodies were tested for reactivity against SLA molecules encoded by 5 haplotypes from pigs we study in xenotransplantation. Genetically engineered pig renal endothelial cells and a prototype panel of SLA-coated beads served as antigenic targets in flow cytometry assays.
Structural analysis confirmed the absence of Bw4 and the presence of modified Bw6 motifs in SLA molecules. Despite the potential epitope conservation, anti-Bw6 sera showed no significant IgG binding to SLA, possibly because of residues adjacent to the canonical epitope. One anti-Bw4 patient showed IgG reactivity to SLA alleles lacking Bw4 or Bw6, implicating a distinct epitope. IgM reactivity was broadly observed across sera.
These findings indicate that the SLA of at least some pigs will not exhibit cross-reactivity with anti-Bw4 and anti-Bw6 antibodies. Incorporating detailed, epitope-level histocompatibility testing may allow these highly sensitized patients, access to xenotransplantation
The Illiquidity of Water Markets
No full textWe investigate the efficiency of a market relative to a non-market institution—an auction relative to a quota—as allocation mechanisms in the presence of frictions. We use data from water markets in southeastern Spain and explore a specific change in the institutions to allocate water. On the one hand, frictions arose because poor farmers were liquidity constrained. On the other hand, farmers who were part of the wealthy elite were not liquidity constrained. We estimate a structural dynamic demand model by taking advantage of the fact that water demand for both types of farmers is determined by the technological constraint imposed by the crop's production function. This approach allows us to differentiate liquidity constraints from unobserved heterogeneity. We show that the institutional change from an auction to a quota increased total efficiency for the farmers considered. Welfare increased by 23.4 real pesetas per farmer per tree, a 6 percent increase in total production relative to the market
Variations in Managing Acute Spinal Cord Injury in the North American Clinical Trials Network and Partner Institutes
No full textStudy DesignSurvey based study.ObjectivesTo evaluate current patterns for managing SCI among spine surgeons in North America.MethodsA survey of the North American Clinical Trials Network (NACTN) and other institutions collected institutional demographics and specific practices on acute SCI management. Variables included trauma level designation, annual case volumes (patient number, spine fracture and surgery performed), steroid usage, emergent cervical traction, magnetic resonance imaging (MRI) access, surgical decompression timing, intraoperative ultrasound and neuromonitoring use, mean arterial pressure (MAP) and spinal cord perfusion pressure (SCPP) targets, lumbar drain use, and the influence of American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade on decision-making.ResultsThirty surgeons from 23 institutions responded (93.3% Level 1 trauma centers). Most centers (93.3%) had immediate MRI access; about 70% of physicians did not use steroids. Emergent cervical traction was used by 60%. An aim of surgical decompression within 24 h was reported by 90%, with 20% operating immediately upon arrival. MAP goals were used by 93.3%, most targeting 85-90 mmHg for ≥5 days. Lumbar drains for SCPP optimization were used in 30%, typically targeting intrathecal pressure (ITP) 60 mmHg. Management varied by AIS grade in 43.4%.ConclusionDespite agreement in the general scope of acute SCI care, significant implementation heterogeneity exists across North American spine centers. Variability was pronounced in steroid use, timing of decompression (90% within 24 h), cervical traction, and lumbar drain utilization. These findings call for evidence-based protocols to guide acute SCI management and reduce inter-institutional practice variation
Abstract WP134: Predictive Models for 30-Day Readmission After Stroke: A Systematic Review and Meta-Analysis
No full textBackground: Stroke readmissions highlight gaps in post-discharge care that require urgent action. In the United States, 18.2% of stroke patients are readmitted within 30 days of discharge, with a 12.4% readmission rate for ischemic stroke. While several predictive models have been developed to identify factors associated with readmission, evidence on their performance and clinical utility remains limited We aimed to evaluate and compare the performance of logistic regression and machine learning models for predicting all cause and stroke-specific 30-day readmissions using data from existing literature.
Methods: Following the PRISMA guidelines, we systematically searched PubMed, Embase, Web of Science, and Google Scholar for studies published between January 2021 and July 2025. Of 292 records identified, 13 studies met inclusion criteria. We evaluated model quality using rehospitalization rates and AUC, performed subgroup analysis comparing of all-cause (AC) versus stroke-specific (SS) readmissions using logistic regression (4) and machine learning methods (13) approaches.
Results: Total number of subjects were 203,399 (SS readmissions = 280; AC readmissions = 20340). 17 models provided AUCs for meta-analysis: SS readmission models (n = 2; pooled readmission rate: 2.0%), and AC readmission models (n = 15; readmission rate: 8.0%). Chen et.al.2022 demonstrated the highest AUCs for AC readmissions (0.94 and 0.89) despite low readmission rates, followed by Hu et al. (2025) with an AUC of 0.91 and Lv et al. (2023) with an AUC of 0.80. The overall readmission proportion across all studies was 11% (95% CI: 7%-16%), with a weighted combined proportion of 6.8%, based on subgroup contribution of 80% AC and 20% SS. The AUC across studies was 0.72 (95% CI: 0.67-0.78). Subgroup-specific AUCs were 0.67 (95% CI: 0.54-0.79) for SS and 0.70 (95% CI: 0.69-0.70) for AC. (Figure) Between-study heterogeneity was considerable (Q = 829.35, p < 0.001; I2=98.07%; τ2 = 0.01).
Conclusion: Our results suggest that overall predictive accuracy of 30-day readmissions remain limited, regardless of strong potential of some models. The high level of heterogeneity indicates that methodological and population differences influence performance, emphasizing the need for external validation and standardization of modeling approaches. Future studies should focus on developing robust, generalizable readmission risk models refined and multi-site validation and transparent reporting standards
Targeting SMPDL3B to Ameliorate Radiation- and Cisplatin-Induced Renal Toxicity
No full textWhat are the main findings? Combined radiation + cisplatin reduces podocyte SMPDL3B, driving podocyte loss, GBM thickening, mesangial expansion, fibrosis, albuminuria, and accumulation of long-chain C1P linked to inflammation/cell death. Podocyte-specific SMPDL3B overexpression protects kidney structure and function after genotoxic injury and normalizes abnormal C1P accumulation. What are the implications of the main findings? SMPDL3B is a key regulator of podocyte survival and sphingolipid balance during cancer therapy-associated kidney stress, making it a promising target to prevent nephrotoxicity. Enhancing SMPDL3B activity/expression may expand the therapeutic window for radiotherapy and platinum chemotherapy, improving tumor control while preserving long-term kidney health. Kidney toxicity remains a major dose-limiting complication of radiation therapy and platinum-based chemotherapy, yet the molecular determinants of renal susceptibility and resilience to these genotoxic treatments are incompletely understood. Podocytes are particularly vulnerable to such insults, and emerging evidence implicates lipid dysregulation in podocyte injury. This study investigated the role of sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B), a podocyte-enriched lipid-modulating enzyme, in radiation- and cisplatin-induced nephrotoxicity. Using a doxycycline-inducible, podocyte-specific SMPDL3B transgenic mouse model, renal injury was assessed following focal kidney irradiation, cisplatin administration, or their combination through functional assays, histopathology, ultrastructural analysis, immunofluorescence, and targeted lipidomics. Combined radiation and cisplatin exposure markedly reduced podocyte SMPDL3B expression, accompanied by podocyte depletion, glomerular basement membrane remodeling, proteinuria, and impaired renal function. These structural and functional abnormalities were associated with the selective accumulation of long-chain ceramide-1-phosphate species. In contrast, podocyte-specific induction of SMPDL3B preserved glomerular architecture, maintained renal function, and prevented pathological ceramide-1-phosphate elevation. Collectively, these findings identify SMPDL3B as a key regulator of podocyte stability and lipid homeostasis during chemoradiation stress. Enhancing SMPDL3B activity may represent a mechanistically grounded strategy to mitigate treatment-induced kidney injury while preserving anticancer efficacy
The Role of the Boston Keratoprosthesis in Severe Ocular Surface Disease and Autoimmune Diseases
No full textTo synthesize contemporary evidence on Boston KPro outcomes in autoimmune cohorts and outline practical strategies to improve anatomic retention and visual results.
A review.
The Boston keratoprosthesis (KPro) is the most widely implanted artificial cornea and a critical option for visual rehabilitation in patients at high risk of graft failure. Autoimmune disorders, including Stevens-Johnson syndrome (SJS), Sjögren's disease (SjD), ocular mucous membrane pemphigoid (OMMP), and ocular graft-versus-host disease (oGVHD), create highly inflammatory, cicatricial ocular surface environments characterized by severe dry eye, limbal stem cell deficiency, and corneal neovascularization, all of which undermine conventional keratoplasty. While selected patients with a relatively "wet" and medically quiet surface can benefit from Type 1 KPro, most end-stage cicatricial phenotypes are better served by Type 2 KPro or alternative mucous-membrane-covered devices. Across studies, autoimmune etiology is consistently associated with higher rates of tissue melt, infectious/sterile keratitis, retroprosthetic membrane, glaucoma, and vitreoretinal complications compared with non-autoimmune eyes. A structured perioperative bundle, systemic disease quiescence for ≥3 months, rheumatology co-management, prophylactic glaucoma drainage devices when indicated, long-term bandage contact lens wear, and intensified antibiotic ± antifungal prophylaxis appear to mitigate risk. Emerging approaches (biologics, donor-carrier crosslinking, γ-irradiated tissue, and newer KPro designs) show promise but require standardized endpoints and multicenter registries.
Despite substantial challenges, the Boston KPro remains a vision-restoring option for carefully selected autoimmune patients when performed within multidisciplinary programs using rigorous preventive protocols