Effectiveness of Fosphenytoin and Levetiracetam to Prevent Posttraumatic Seizures in Young Children with Accidental or Abusive Traumatic Brain Injury.

BACKGROUND: Seizures occur frequently in pediatric patients with traumatic brain injury (TBI), particularly abusive head trauma (AHT). There are limited data on the effectiveness of fosphenytoin and levetiracetam to prevent posttraumatic seizures. METHODS: We performed a retrospective single center cohort study of children < 3 years old admitted with mild [Glasgow Coma Scale (GCS) score 13-15], moderate (GCS 9-12), and severe (GCS 3-8) TBI at a level I trauma center from 2011 to 2021. Antiseizure medications were used at the discretion of the treating physicians. Nonparametric tests were used to compare antiseizure medication prophylaxis and TBI etiology. RESULTS: A total of 717 patients (263 with AHT, 454 with accidental TBI) were included, of whom 135 (19%) received fosphenytoin, 152 (21%) received levetiracetam, and 430 (60%) did not receive any seizure prophylaxis. Over the study period, the use of fosphenytoin prophylaxis decreased (R2 = 0.67, p = 0.004), whereas the use of levetiracetam increased (R2 = 0.51, p = 0.008). Additionally, the occurrence of early posttraumatic seizures decreased (R2 = 0.58, p = 0.006). Children with AHT were more likely to receive any seizure prophylaxis than those with accidental TBI (52% vs. 27%; p < 0.001) and were more likely to have ≥ 1 seizure during hospitalization (22% vs. 4%; p < 0.001). Among children who received seizure prophylaxis, those who received fosphenytoin had a higher occurrence of seizures than those who received levetiracetam (33% vs.18%; p = 0.004). After controlling for age, admission year, TBI mechanism, and severity of injury, we observed no differences in seizure occurrence between groups. CONCLUSIONS: In children < 3 years old with TBI, no differences were observed in occurrence of seizures between patients who received fosphenytoin and patients who received levetiracetam prophylaxis after controlling for patient factors including severity of injury. Levetiracetam may be an equally effective alternative to fosphenytoin for seizure prophylaxis for early posttraumatic seizure prevention in this age group.

Larger Than Life? Body Mass Records of Zoo-Managed Giant Anteaters (Myrmecophaga tridactyla).

It has been suggested repeatedly that zoo-kept giant anteaters (Myrmecophaga tridactyla) have higher body masses than their free-ranging conspecifics. Here, we assess this hypothesis by comparing body mass data of 184 female and 173 male individuals kept in zoos to published and unpublished data of free-ranging animals (n = 215). In zoos, the average adult body mass of all individuals was 45.9 ± 9.6 kg (range 19.2-72.6 kg), whereas body mass for free-ranging specimens was 33.0 ± 2.3 kg (21-45.5 kg). Among those zoo animals in which a sufficient number of subsequent intra-annual measures had been taken, we assessed visually whether regular, annual fluctuations in body mass were evident. We observed regular, likely seasonal, cycles in body mass, which (i) may be plausibly attributed to ambient temperature changes that affect the body temperature of anteaters, and (ii) would likely not have occurred if the animals were affected by obesity. Additionally, we explain our hypothesis that in the case of giant anteaters, the discrepancy in body mass between natural habitats and zoos most likely is not indicative of a generally obese population in zoos, as is typically concluded in the case of similar comparisons in primates, but represents an unleashing of the full growth potential of the species by conditions of optimal energy and nutrient provision. Future recording of not only body mass but also body dimensions is recommended to better compare the body condition of free-ranging and zoo-managed individuals.

Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes.

Progressive supranuclear palsy (PSP), a rare Parkinsonian disorder, is characterized by problems with movement, balance, and cognition. PSP differs from Alzheimer's disease (AD) and other diseases, displaying abnormal microtubule-associated protein tau by both neuronal and glial cell pathologies. Genetic contributors may mediate these differences; however, the genetics of PSP remain underexplored. Here we conduct the largest genome-wide association study (GWAS) of PSP which includes 2779 cases (2595 neuropathologically-confirmed) and 5584 controls and identify six independent PSP susceptibility loci with genome-wide significant (P < 5 × 10-8) associations, including five known (MAPT, MOBP, STX6, RUNX2, SLCO1A2) and one novel locus (C4A). Integration with cell type-specific epigenomic annotations reveal an oligodendrocytic signature that might distinguish PSP from AD and Parkinson's disease in subsequent studies. Candidate PSP risk gene prioritization using expression quantitative trait loci (eQTLs) identifies oligodendrocyte-specific effects on gene expression in half of the genome-wide significant loci, and an association with C4A expression in brain tissue, which may be driven by increased C4A copy number. Finally, histological studies demonstrate tau aggregates in oligodendrocytes that colocalize with C4 (complement) deposition. Integrating GWAS with functional studies, epigenomic and eQTL analyses, we identify potential causal roles for variation in MOBP, STX6, RUNX2, SLCO1A2, and C4A in PSP pathogenesis.

Prominent loss of striatal dopamine transporter binding in frontotemporal lobar degeneration with the MAPT N279K mutation present as early as at prodromal stage without parkinsonism.

Our research found out, from 123I-FP-CIT SPECT scans of three familial frontotemporal dementia (fFTD) individuals with MAPT N279K mutation and similar autopsy findings of frontotemporal degeneration with severe neuronal loss in the substantia nigra, that prominent decrease of dopamine transporter binding (z-score < -5.0) was present at prodromal fFTD without parkinsonism.

Modeling Lewy body disease with SNCA triplication iPSC-derived cortical organoids and identifying therapeutic drugs.

Aggregated α-synuclein (α-SYN) proteins, encoded by the SNCA gene, are hallmarks of Lewy body disease (LBD), affecting multiple brain regions. However, the specific mechanisms underlying α-SYN pathology in cortical neurons, crucial for LBD-associated dementia, remain unclear. Here, we recapitulated α-SYN pathologies in human induced pluripotent stem cells (iPSCs)-derived cortical organoids generated from patients with LBD with SNCA gene triplication. Single-cell RNA sequencing, combined with functional and molecular validation, identified synaptic and mitochondrial dysfunction in excitatory neurons exhibiting high expression of the SNCA gene, aligning with observations in the cortex of autopsy-confirmed LBD human brains. Furthermore, we screened 1280 Food and Drug Administration-approved drugs and identified four candidates (entacapone, tolcapone, phenazopyridine hydrochloride, and zalcitabine) that inhibited α-SYN seeding activity in real-time quaking-induced conversion assays with human brains, reduced α-SYN aggregation, and alleviated mitochondrial dysfunction in SNCA triplication organoids and excitatory neurons. Our findings establish human cortical LBD models and suggest potential therapeutic drugs targeting α-SYN aggregation for LBD.

Relationships between regional burden of tau pathology and age at death and disease duration in PSP.

BACKGROUND: A definitive diagnosis of progressive supranuclear palsy (PSP) can only be established through neuropathological evaluations where four cardinal tau lesions are identified. Relationships between regional tau burden and disease duration/age at death is unclear. OBJECTIVE: To investigate relationships between tau burden in different brain regions and disease duration and age at death in PSP and determine whether association are influenced by PSP subtype (subcortical/cortical) or co-pathologies. METHODS: We identified 45 patients with definite PSP who were evaluated at Mayo Clinic between 2009 and 2023, died and underwent histopathological evaluation. We performed semi-quantitative lesion count for each of four cardinal lesions (pretangles/globose neurofibrillary tangles, threads, tufted astrocytes, and coiled bodies) across 10 brain regions. We fit Bayesian linear hierarchical regression models to estimate the relationship between total pathological burden, and disease duration and age at death by region and the influence of subtype and co-pathologies. RESULTS: Of the 45 patients, 18 (40 %) were female. Median age at death was 75 (56-87) years and median disease duration was 8 (3,15) years. Younger age at death was associated with greater total tau burden in the pallidum, red nucleus, striatum, and subthalamic nucleus (all p ≤ 0.01). Shorter disease duration was associated with greater total tau burden in the red nucleus (p = 0.05). There was no evidence for a difference in association between lesion types. PSP subtype and co-pathologies did not influence associations. CONCLUSIONS: The findings from this study suggest that age and disease duration influence burden of tau pathology in subcortical regions in PSP.

Structural and Functional Characterization of the Most Frequent Pathogenic PRKN Substitution p.R275W.

Mutations in the PINK1 and PRKN genes are the most frequent genetic cause of early-onset Parkinson disease. The pathogenic p.R275W substitution in PRKN is the most frequent substitution observed in patients, and thus far has been characterized mostly through overexpression models that suggest a possible gain of toxic misfunction. However, its effects under endogenous conditions are largely unknown. We used patient fibroblasts, isogenic neurons, and post-mortem human brain samples from carriers with and without PRKN p.R275W to assess functional impact. Immunoblot analysis and immunofluorescence were used to study mitophagy activation, and mitophagy execution was analyzed by flow cytometry of the reporter mitoKeima. The functional analysis was accompanied by structural investigation of PRKN p.R275W. We observed lower PRKN protein in fibroblasts with compound heterozygous p.R275W mutations. Isogenic neurons showed an allele-dose dependent decrease in PRKN protein. Lower PRKN protein levels were accompanied by diminished phosphorylated ubiquitin and decreased MFN2 modification. Mitochondrial degradation was also allele-dose dependently impaired. Consistently, PRKN protein levels were drastically reduced in human brain samples from p.R275W carriers. Finally, structural simulations showed significant changes in the closed form of PRKN p.R275W. Our data suggest that under endogenous conditions the p.R275W mutation results in a loss-of-function by destabilizing PRKN.

Patterns of glucose hypometabolism can help differentiate FTLD-FET from other types of FTLD.

INTRODUCTION: FTLD-FET is a newly described subtype of frontotemporal lobar degeneration (FTLD characterized by pathologic inclusions of FET proteins: fused in sarcoma (FUS), Ewing sarcoma, and TATA-binding protein-associated factor 2N (TAF15)). Severe caudate volume loss on MRI has been linked to FTLD-FUS, yet glucose hypometabolism in FTLD-FET has not been studied. We assessed [18F] fluorodeoxyglucose PET (FDG-PET) hypometabolism in FTLD-FET subtypes and compared metabolism to FTLD-tau and FTLD-TDP. METHODS: We retrospectively reviewed medical records of 26 autopsied FTLD patients (six FTLD-FET, ten FTLD-Tau, and ten FTLD-TDP) who had completed antemortem FDG-PET. We evaluated five regions, caudate nucleus, medial frontal cortex, lateral frontal cortex, and medial temporal using a 0-3 visual rating scale and validated our findings quantitatively using CORTEX-ID suite Z scores. RESULTS: Of the six FTLD-FET cases (three females) with median age at onset = 36, three were atypical FTLD-U (aFTLD-U) and three were neuronal intermediate filament inclusion disease (NIFID). bvFTD was the most common presentation. Four of the six FTLD cases (3 aFTLD-U + 1 NIFID) showed prominent caudate hypometabolism relatively early in the disease course. FTLD-tau and FTLD-TDP did not show early prominent caudate hypometabolism. Hypometabolism in medial and lateral temporal cortex was associated with FTLD-TDP, while FTLD-tau had normal-minimal regional metabolism. DISCUSSION: Prominent caudate hypometabolism, especially early in the disease course, appears to be a hallmark feature of the aFTLD-U subtype of FTLD-FET. Assessing caudate and temporal hypometabolism on FDG-PET will help to differentiate FTLD-FET from FTLD-tau and FTLD-TDP.

MAPT haplotype-associated transcriptomic changes in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative movement and cognitive disorder characterized by abnormal accumulation of the microtubule-associated protein tau in the brain. Biochemically, inclusions in PSP are enriched for tau proteoforms with four microtubule-binding domain repeats (4R), an isoform that arises from alternative tau pre-mRNA splicing. While preferential aggregation and reduced degradation of 4R tau protein is thought to play a role in inclusion formation and toxicity, an alternative hypothesis is that altered expression of tau mRNA isoforms plays a causal role. This stems from the observation that PSP is associated with common variation in the tau gene (MAPT) at the 17q21.31 locus which contains low copy number repeats flanking a large recurrent genomic inversion. The complex genomic structural changes at the locus give rise to two dominant haplotypes, termed H1 and H2, that have the potential to markedly influence gene expression. Here, we explored haplotype-dependent differences in gene expression using a bulk RNA-seq dataset derived from human post-mortem brain tissue from PSP (n = 84) and controls (n = 77) using a rigorous computational pipeline, including alternative pre-mRNA splicing. We found 3579 differentially expressed genes in the temporal cortex and 10,011 in the cerebellum. We also found 7214 differential splicing events in the temporal cortex and 18,802 in the cerebellum. In the cerebellum, total tau mRNA levels and the proportion of transcripts encoding 4R tau were significantly increased in PSP compared to controls. In the temporal cortex, the proportion of reads that expressed 4R tau was increased in cases compared to controls. 4R tau mRNA levels were significantly associated with the H1 haplotype in the temporal cortex. Further, we observed a marked haplotype-dependent difference in KANSL1 expression that was strongly associated with H1 in both brain regions. These findings support the hypothesis that sporadic PSP is associated with haplotype-dependent increases in 4R tau mRNA that might play a causal role in this disorder.

Endowing Three-Dimensional Porous Wood with Hydrophobicity/Superhydrophobicity Based on Binary Silanization.

Wood, as a natural biomass material, has long been a research focus. Superhydrophobic modified wood, in particular, has shown great promise in a myriad of engineering applications such as architecture, landscape, and shipbuilding. However, commercial development has encountered significant resistance due to preparation difficulties and sometimes unsatisfactory performance. In this study, hydrophobic/superhydrophobic wood comodified with methyltrimethoxysilane (MTMS) and 1H,1H,2H,2H-perfluorodecyltrimethoxysilane (PFDTMS) was fabricated by a one-step sol-gel method that uses an in situ growth process. Low-molecular-weight MTMS was allowed to permeate the three-dimensional porous wood interior. Then, acid-base catalysts were used to regulate the hydrolytic condensation process of MTMS and PFDTMS composite silanes to generate micro/nano hierarchical structures with low surface energy on the wood surface. The physicochemical characteristics of modified wood were investigated and the reaction mechanism established. The modified wood displayed excellent internal hydrophobicity/surface superhydrophobicity, water-moisture resistance, and dimensional stability at low fluorine concentrations. The resulting superhydrophobic surface provided stain resistance, self-cleaning ability, and loading capacity in water while exhibiting good mechanochemical stability; wood mechanical strength was also enhanced. This methodology created a superhydrophobic surface and bulk hydrophobization of wood in one step. Beyond wood, this approach is expected to provide a promising approach for functional modification of other porous composite materials.

Melody Valve Implantation in the Tricuspid Position After Pediatric Heart Transplantation-A Case Report.

Tricuspid regurgitation (TR) is common after a heart transplant and is associated with worse clinical outcomes. The incidence ranges from 34% immediately after transplant to 20% by 10 years. Most patients can be managed medically; however, severe TR and symptomatic right heart failure warrant tricuspid valve replacement. The use of Melody transcatheter pulmonary valve in the tricuspid position is previously described. We report a unique case of posttransplant severe TR treated with surgical bioprosthetic tricuspid valve replacement who subsequently underwent successful transcatheter Melody valve placement in tricuspid position for progressive bioprosthetic valve stenosis with 11 years of follow-up.

Bridging the gap: Multi-omics profiling of brain tissue in Alzheimer's disease and older controls in multi-ethnic populations.

INTRODUCTION: Multi-omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked Black Americans (BA) and Latin Americans (LA), who are disproportionately affected by AD. METHODS: To bridge this gap, Accelerating Medicines Partnership in Alzheimer's Disease (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors. RESULTS: We generated multi-omics data and curated and harmonized phenotypic data from BA (n = 306), LA (n = 326), or BA and LA (n = 4) brain donors plus non-Hispanic White (n = 252) and other (n = 20) ethnic groups, to establish a foundational dataset enriched for BA and LA participants. This study describes the data available to the research community, including transcriptome from three brain regions, whole genome sequence, and proteome measures. DISCUSSION: The inclusion of traditionally underrepresented groups in multi-omics studies is essential to discovering the full spectrum of precision medicine targets that will be pertinent to all populations affected with AD. HIGHLIGHTS: Accelerating Medicines Partnership in Alzheimer's Disease Diversity Initiative led brain tissue profiling in multi-ethnic populations. Brain multi-omics data is generated from Black American, Latin American, and non-Hispanic White donors. RNA, whole genome sequencing and tandem mass tag proteomicsis completed and shared. Multiple brain regions including caudate, temporal and dorsolateral prefrontal cortex were profiled.

Transcatheter Pulmonary Valve Replacement in Middle and Late Adulthood.

Transcatheter pulmonary valve replacement (TPVR) is now frequently performed in patients with adult congenital heart disease. As the life expectancy of the population with adult congenital heart disease continues to improve, more patients will require pulmonary valve intervention. This study details the short-term and midterm clinical outcomes of patients aged ≥40 years who underwent TPVR. We performed an institutional retrospective cohort study that included patients aged ≥40 years who underwent TPVR (and clinical follow-up) from January 1, 2012 to January 1, 2024. Descriptive analyses, Kaplan-Meier survival analysis, and Cox proportional hazard modeling were used to determine outcomes and risk factors affecting survival. The study included 67 patients, and median age at TPVR was 48 years (43 to 57). Median hospital length of stay after TPVR was 1 day (1 to 3); periprocedural complications occurred in 5 patients, and acute kidney injury occurred in 1 patient. Median duration of follow-up was 3.5 years (0.1 to 9.7). There were 9 total deaths, and 1-, 3-, and 5-year Kaplan-Meier survival after TPVR was 95%, 91%, and 82%, respectively. Moderate or worse right ventricular dysfunction was present in 22 patients before TPVR and in 20 patients after TPVR. Inpatient status before TPVR negatively affected survival (hazard ratio 24.7, 3.3 to 186.1, p = 0.002). In conclusion, TPVR was performed in patients aged ≥40 years with favorable periprocedural and midterm follow-up outcomes including survival, but right ventricular dysfunction did not improve, and further exploration of the ideal timing of TPVR in this age group is warranted.

Impact of a Multidisciplinary Service Line and Program for Transcatheter Device Closure of the Neonatal Ductus Arteriosus.

Outline a quality initiative establishing an institutional service line for neonatal transcatheter device closure of the patent ductus arteriosus (TDC-PDA). A retrospective descriptive observational study surrounds programmatic approach to TDC-PDA in premature neonates with process measure spanning education, implementation, referral, and post-procedural care. Metrics tracked pre- and post-program creation with statistical analyses performed. Neonatal TDC-PDA referrals increased exponentially since program inception (n = 13 in year prior; n = 42 year 1; n = 74 year 2), especially in patients weighing less than 1.3 kg (12.5%; 55%; 50%), and were associated with an increased procedural success rate (81%; 95%; 99%). Procedural checklist creation decreased procedural "out of isolette" time (median 93 min; 59; 52), and procedural-related complication or clinical sequelae (19%; 12%; 4%). A multidisciplinary service line and program dedicated to neonatal TDC-PDA can result in a significant increase in referrals as well as procedural efficacy and safety for this medically fragile population.

Flortaucipir PET uncovers relationships between tau and amyloid-ß in primary age-related tauopathy and Alzheimer's disease.

[18F]-Flortaucipir positron emission tomography (PET) is considered a good biomarker of Alzheimer's disease. However, it is unknown how flortaucipir is associated with the distribution of tau across brain regions and how these associations are influenced by amyloid-ß. It is also unclear whether flortaucipir can detect tau in definite primary age-related tauopathy (PART). We identified 248 individuals at Mayo Clinic who had undergone [18F]-flortaucipir PET during life, had died, and had undergone an autopsy, 239 cases of which also had amyloid-ß PET. We assessed nonlinear relationships between flortaucipir uptake in nine medial temporal and cortical regions, Braak tau stage, and Thal amyloid-ß phase using generalized additive models. We found that flortaucipir uptake was greater with increasing tau stage in all regions. Increased uptake at low tau stages in medial temporal regions was only observed in cases with a high amyloid-ß phase. Flortaucipir uptake linearly increased with the amyloid-ß phase in medial temporal and cortical regions. The highest flortaucipir uptake occurred with high Alzheimer's disease neuropathologic change (ADNC) scores, followed by low-intermediate ADNC scores, then PART, with the entorhinal cortex providing the best differentiation between groups. Flortaucipir PET had limited ability to detect PART, and imaging-defined PART did not correspond with pathologically defined PART. In summary, spatial patterns of flortaucipir mirrored the histopathological tau distribution, were influenced by the amyloid-ß phase, and were useful for distinguishing different ADNC scores and PART.

A single-cell atlas deconstructs heterogeneity across multiple models in murine traumatic brain injury and identifies novel cell-specific targets.

Traumatic brain injury (TBI) heterogeneity remains a critical barrier to translating therapies. Identifying final common pathways/molecular signatures that integrate this heterogeneity informs biomarker and therapeutic-target development. We present the first large-scale murine single-cell atlas of the transcriptomic response to TBI (334,376 cells) across clinically relevant models, sex, brain region, and time as a foundational step in molecularly deconstructing TBI heterogeneity. Results were unique to cell populations, injury models, sex, brain regions, and time, highlighting the importance of cell-level resolution. We identify cell-specific targets and previously unrecognized roles for microglial and ependymal subtypes. Ependymal-4 was a hub of neuroinflammatory signaling. A distinct microglial lineage shared features with disease-associated microglia at 24 h, with persistent gene-expression changes in microglia-4 even 6 months after contusional TBI, contrasting all other cell types that mostly returned to naive levels. Regional and sexual dimorphism were noted. CEREBRI, our searchable atlas (https://shiny.crc.pitt.edu/cerebri/), identifies previously unrecognized cell subtypes/molecular targets and is a leverageable platform for future efforts in TBI and other diseases with overlapping pathophysiology.

Clinicopathologic and Neuroimaging Correlations of Nonverbal Oral Apraxia in Patients With Neurodegenerative Disease.

BACKGROUND AND OBJECTIVES: Nonverbal oral apraxia (NVOA) is the inability to plan, sequence, and execute voluntary oromotor movements in the absence of weakness. In the context of neurodegenerative disease, it remains unclear whether it is linked to a specific underlying pathologic, clinical, or neuroimaging finding. Thus, we aimed to assess the clinicopathologic and neuroimaging associations of NVOA. METHODS: We conducted a retrospective study of autopsy-confirmed patients previously assessed through an NVOA evaluation tool with a previously published cutpoint to screen for NVOA. We compared demographic and clinical characteristics and postmortem pathology between those who developed NVOA and those who did not. We also compared clinicopathologic characteristics in mild vs greater than mild NVOA and early vs late-emerging NVOA. SPM12 was used to assess patterns of gray matter loss in NVOA vs non-NVOA with age and sex included as covariates. RESULTS: A total of 104 patients (median age at symptom onset 63 years, 43% female) were included in the study. 63 (60.6%) developed NVOA. NVOA appeared at a median of 4.3 years from symptom onset. 29% developed NVOA within the first 3 years. Primary progressive apraxia of speech and the nonfluent variant of primary progressive aphasia were the most common baseline diagnoses in the NVOA group while progressive supranuclear palsy (PSP) syndrome and logopenic progressive aphasia (LPA) were the most common in patients without NVOA. Atrophy of the left lateral and medial posterior frontal cortex was related to NVOA. The most common pathologies associated with NVOA were PSP (36.5%) and corticobasal degeneration (CBD) (33.3%). In patients without NVOA, PSP (26.8%) and other pathologies (26.8%) were the most frequent. 11% of patients with NVOA had persistently mild NVOA and were more likely to have baseline diagnoses of LPA, PSP syndrome, or semantic dementia. The most frequent pathologies in this group were Alzheimer disease and PSP. The pathologic associations of greater than mild NVOA were CBD and PSP. DISCUSSION: NVOA is present in several clinical syndromes. It is most associated with PSP and CBD. NVOA is a manifestation of left lateral and medial posterior frontal cortex damage rather than a particular pathology.

Temporary sinus node dysfunction following ablation of atrial fibrillation in patients with aberrancy of the sinus node artery: a case series.

OBJECTIVES: Our goal was to investigate sinus node dysfunction (SND) as a rare complication following surgical and catheter atrial fibrillation (AF) ablation in patients with an aberrant sinus node artery (SNA). METHODS: We used a retrospective analysis of 3 patients with an aberrant SNA who underwent different AF ablation procedures: 1 concomitant to aortic valve replacement, 1 thoracoscopic hybrid AF ablation and 1 catheter AF ablation. RESULTS: All patients experienced temporary SND perioperatively. In the first patient, sinus rhythm (SR) recovered by postoperative day 6. In the second patient, SR returned by postoperative day 14. The third patient had a sinus arrest during ablation that restored to SR immediately post-procedure. All patients had normal SR at the 3-month follow-up. CONCLUSIONS: Awareness of SNA anatomy can help to prevent iatrogenic SND during AF ablation. If SND occurs, a wait-and-see approach is recommended, given that sinus node function seems to recover. Because SND recovers, the benefits of posterior wall isolation could outweigh the disadvantages of temporary SND.

Evaluating the efficacy of few-shot learning for GPT-4Vision in neurodegenerative disease histopathology: A comparative analysis with convolutional neural network model.

AIMS: Recent advances in artificial intelligence, particularly with large language models like GPT-4Vision (GPT-4V)-a derivative feature of ChatGPT-have expanded the potential for medical image interpretation. This study evaluates the accuracy of GPT-4V in image classification tasks of histopathological images and compares its performance with a traditional convolutional neural network (CNN). METHODS: We utilised 1520 images, including haematoxylin and eosin staining and tau immunohistochemistry, from patients with various neurodegenerative diseases, such as Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We assessed GPT-4V's performance using multi-step prompts to determine how textual context influences image interpretation. We also employed few-shot learning to enhance improvements in GPT-4V's diagnostic performance in classifying three specific tau lesions-astrocytic plaques, neuritic plaques and tufted astrocytes-and compared the outcomes with the CNN model YOLOv8. RESULTS: GPT-4V accurately recognised staining techniques and tissue origin but struggled with specific lesion identification. The interpretation of images was notably influenced by the provided textual context, which sometimes led to diagnostic inaccuracies. For instance, when presented with images of the motor cortex, the diagnosis shifted inappropriately from AD to CBD or PSP. However, few-shot learning markedly improved GPT-4V's diagnostic capabilities, enhancing accuracy from 40% in zero-shot learning to 90% with 20-shot learning, matching the performance of YOLOv8, which required 100-shot learning to achieve the same accuracy. CONCLUSIONS: Although GPT-4V faces challenges in independently interpreting histopathological images, few-shot learning significantly improves its performance. This approach is especially promising for neuropathology, where acquiring extensive labelled datasets is often challenging.

Expanding the empirical study of virtual reality beyond empathy to compassion, moral reasoning, and moral foundations.

This study utilizes a controlled experimental design to investigate the influence of a virtual reality experience on empathy, compassion, moral reasoning, and moral foundations. With continued debate and mixed results from previous studies attempting to show relationships between virtual reality and empathy, this study takes advantage of the technology for its ability to provide a consistent, repeatable experience, broadening the scope of analysis beyond empathy. A systematic literature review identified the most widely used and validated moral psychology assessments for the constructs, and these assessments were administered before and after the virtual reality experience. The study is comprised of two pre-post experiments with student participants from a university in the United States. The first experiment investigated change in empathy and moral foundations among 44 participants, and the second investigated change in compassion and moral reasoning among 69 participants. The results showed no significant change in empathy nor compassion, but significant change in moral reasoning from personal interest to post-conventional stages, and significant increase in the Care/harm factor of moral foundations. By testing four of the primary constructs of moral psychology with the most widely used and validated assessments in controlled experiments, this study attempts to advance our understanding of virtual reality and its potential to influence human morality. It also raises questions about our self-reported assessment tools and provides possible new insights for the constructs examined.