Testing ChatGPT's Ability to Provide Patient and Physician Information on Aortic Aneurysm.

Introduction: Our objective was to test the ability of ChatGPT 4.0 to provide accurate information for patients and physicians about abdominal aortic aneurysms (AAA) and to assess its alignment with Society for Vascular Surgery (SVS) clinical practice guidelines (CPG) for AAA care.

Material And Methods: Fifteen patient-level questions, 37 questions selected to reflect 28 SVS CPGs and 4 questions regarding AAA rupture risk were posed to ChatGPT 4.

Effects of dialysis on peripheral arterial disease.

End-stage renal disease is an independent risk factor for the development of peripheral arterial disease, with considerably worse outcomes in patients with concomitant diseases. It is important to realize the widespread, yet frequently asymptomatic, nature of peripheral arterial disease in patients with end-stage renal disease due to the presence of other comorbidities that decrease activity levels and sensation to allow for early recognition and timely medical management to try and mitigate otherwise poor outcomes. Despite their high risk, properly selected patients derive benefit from revascularization; both open and endovascular approaches provide similar outcomes in terms of overall survival, amputation-free survival, and limb salvage, with perhaps a slight preference toward open repair.

Impact of fixation duration on messenger RNA detectability in human formalin-fixed paraffin-embedded brain tissue.

Technologies to study mRNA in post-mortem human brain samples have greatly advanced our understanding of brain pathologies. With ongoing improvements, particularly in formalin-fixed paraffin-embedded tissue, these technologies will continue to enhance our knowledge in the future. Despite various considerations for tissue and mRNA quality, such as pre-mortem health status and RNA integrity, the impact of the tissue fixation time has not been addressed in a systemic fashion yet.

The Impact of Protease Reserved for Protein Evaluation of Ruminant Feed on Carbohydrase Activity during Co-Incubation.

For protein evaluation of feedstuffs for ruminants, the protease test provides a solely enzymatic method for estimating ruminal protein degradation. Since plant proteins are often structured in carbohydrate complexes, the use of carbohydrase during the test might improve its accuracy. It is advisable to co-incubate protease and carbohydrase, risking that the carbohydrase activity is reduced under the influence of the protease.

MYCT1 controls environmental sensing in human haematopoietic stem cells.

The processes that govern human haematopoietic stem cell (HSC) self-renewal and engraftment are poorly understood and challenging to recapitulate in culture to reliably expand functional HSCs. Here we identify MYC target 1 (MYCT1; also known as MTLC) as a crucial human HSC regulator that moderates endocytosis and environmental sensing in HSCs. MYCT1 is selectively expressed in undifferentiated human haematopoietic stem and progenitor cells (HSPCs) and endothelial cells but becomes markedly downregulated during HSC culture.

Cortical hyperexcitability in mouse models and patients with amyotrophic lateral sclerosis is linked to noradrenaline deficiency.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by the death of upper (UMN) and lower motor neurons (LMN) in the motor cortex, brainstem, and spinal cord. Despite decades of research, ALS remains incurable, challenging to diagnose, and of extremely rapid progression. A unifying feature of sporadic and familial forms of ALS is cortical hyperexcitability, which precedes symptom onset, negatively correlates with survival, and is sufficient to trigger neurodegeneration in rodents.

Probing cerebellar circuit dysfunction in rodent models of spinocerebellar ataxia by means of in vivo two-photon calcium imaging.

Purkinje neuron degeneration characterizes spinocerebellar ataxia type 1, yet the comprehension of the impact on the broader cerebellar circuit remains incomplete. We here detail simultaneous in vivo two-photon calcium imaging of diverse neuronal populations in the cerebellar cortex of Sca1 mice while they are navigating a virtual environment. We outline surgical procedures and protocols to chronically record from identical neurons, and we detail data post-processing and analysis to delineate disease-related alterations in neuronal activity and sensorimotor-driven response properties.

Human NMDAR autoantibodies disrupt excitatory-inhibitory balance, leading to hippocampal network hypersynchrony.

Anti-NMDA receptor autoantibodies (NMDAR-Abs) in patients with NMDAR encephalitis cause severe disease symptoms resembling psychosis and cause cognitive dysfunction. After passive transfer of patients' cerebrospinal fluid or human monoclonal anti-GluN1-autoantibodies in mice, we find a disrupted excitatory-inhibitory balance resulting from CA1 neuronal hypoexcitability, reduced AMPA receptor (AMPAR) signaling, and faster synaptic inhibition in acute hippocampal slices. Functional alterations are also reflected in widespread remodeling of the hippocampal proteome, including changes in glutamatergic and GABAergic neurotransmission.

Breast cancer patient-derived microtumors resemble tumor heterogeneity and enable protein-based stratification and functional validation of individualized drug treatment.

Despite tremendous progress in deciphering breast cancer at the genomic level, the pronounced intra- and intertumoral heterogeneity remains a major obstacle to the advancement of novel and more effective treatment approaches. Frequent treatment failure and the development of treatment resistance highlight the need for patient-derived tumor models that reflect the individual tumors of breast cancer patients and allow a comprehensive analyses and parallel functional validation of individualized and therapeutically targetable vulnerabilities in protein signal transduction pathways. Here, we introduce the generation and application of breast cancer patient-derived 3D microtumors (BC-PDMs).

Monitoring the macrophage response towards biomaterial implants using label-free imaging.

Understanding the immune system's foreign body response (FBR) is essential when developing and validating a biomaterial. Macrophage activation and proliferation are critical events in FBR that can determine the material's biocompatibility and fate in vivo. In this study, two different macro-encapsulation pouches intended for pancreatic islet transplantation were implanted into streptozotocin-induced diabetes rat models for 15 days.

Early molecular layer interneuron hyperactivity triggers Purkinje neuron degeneration in SCA1.

Toxic proteinaceous deposits and alterations in excitability and activity levels characterize vulnerable neuronal populations in neurodegenerative diseases. Using in vivo two-photon imaging in behaving spinocerebellar ataxia type 1 (Sca1) mice, wherein Purkinje neurons (PNs) degenerate, we identify an inhibitory circuit element (molecular layer interneurons [MLINs]) that becomes prematurely hyperexcitable, compromising sensorimotor signals in the cerebellum at early stages. Mutant MLINs express abnormally elevated parvalbumin, harbor high excitatory-to-inhibitory synaptic density, and display more numerous synaptic connections on PNs, indicating an excitation/inhibition imbalance.

Use of Ultrasound and Ki-67 Proliferation Index to Predict Breast Cancer Tumor Response to Neoadjuvant Endocrine Therapy.

Background: Prediction of tumor shrinkage and pattern of treatment response following neoadjuvant endocrine therapy (NET) for estrogen receptor positive (ER+), Her2 negative (Her2-) breast cancers have had limited assessment. We examined if ultrasound (US) and Ki-67 could predict the pathologic response to treatment with NET and how the pattern of response may impact surgical planning.

Methods: A total of 103 postmenopausal women with ER+, HER2- breast cancer enrolled on the FELINE trial had Ki-67 obtained at baseline, day 14, and surgical pathology.

TDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury.

Decreasing the activation of pathology-activated microglia is crucial to prevent chronic inflammation and tissue scarring. In this study, we used a stab wound injury model in zebrafish and identified an injury-induced microglial state characterized by the accumulation of lipid droplets and TAR DNA-binding protein of 43 kDa (TDP-43) condensates. Granulin-mediated clearance of both lipid droplets and TDP-43 condensates was necessary and sufficient to promote the return of microglia back to the basal state and achieve scarless regeneration.

Small Changes Make the Difference for SIRT2: Two Different Binding Modes for 3-Arylmercapto-Acylated Lysine Derivatives.

Sirtuins are protein deacylases regulating metabolism and stress responses and implicated in aging-related diseases. Modulators of the human sirtuins 1-7 are sought as chemical tools and potential therapeutics, for example, for treatment of cancer. We were able to show that 3-aryl-mercapto-succinylated- and 3-benzyl-mercapto-succinylated peptide derivatives yield selective Sirt5 inhibitors with low nM values.

Selective plasticity of callosal neurons in the adult contralesional cortex following murine traumatic brain injury.

Traumatic brain injury (TBI) results in deficits that are often followed by recovery. The contralesional cortex can contribute to this process but how distinct contralesional neurons and circuits respond to injury remains to be determined. To unravel adaptations in the contralesional cortex, we used chronic in vivo two-photon imaging.

Backbone and side chain resonance assignment of the intrinsically disordered human DBNDD1 protein.

The dysbindin domain-containing protein 1 (DBNDD1) is a conserved protein among higher eukaryotes whose structure and function are poorly investigated so far. Here, we present the backbone and side chain nuclear magnetic resonance assignments for the human DBNDD1 protein. Our chemical-shift based secondary structure analysis reveals the human DBNDD1 as an intrinsically disordered protein.

Astrogenesis in the murine dentate gyrus is a life-long and dynamic process.

Astrocytes are highly abundant in the mammalian brain, and their functions are of vital importance for all aspects of development, adaption, and aging of the central nervous system (CNS). Mounting evidence indicates the important contributions of astrocytes to a wide range of neuropathies. Still, our understanding of astrocyte development significantly lags behind that of other CNS cells.

Mapping human haematopoietic stem cells from haemogenic endothelium to birth.

The ontogeny of human haematopoietic stem cells (HSCs) is poorly defined owing to the inability to identify HSCs as they emerge and mature at different haematopoietic sites. Here we created a single-cell transcriptome map of human haematopoietic tissues from the first trimester to birth and found that the HSC signature RUNX1HOXA9MLLT3MECOMHLFSPINK2 distinguishes HSCs from progenitors throughout gestation. In addition to the aorta-gonad-mesonephros region, nascent HSCs populated the placenta and yolk sac before colonizing the liver at 6 weeks.

Cortical circuit dysfunction in a mouse model of alpha-synucleinopathy .

Considerable fluctuations in cognitive performance and eventual dementia are an important characteristic of alpha-synucleinopathies, such as Parkinson's disease and Lewy Body dementia and are linked to cortical dysfunction. The presence of misfolded and aggregated alpha-synuclein in the cerebral cortex of patients has been suggested to play a crucial role in this process. However, the consequences of a-synuclein accumulation on the function of cortical networks at cellular resolution are largely unknown.

Long-term dynamics of aberrant neuronal activity in awake Alzheimer's disease transgenic mice.

Alzheimer's disease (AD) is associated with aberrant neuronal activity, which is believed to critically determine disease symptoms. How these activity alterations emerge, how stable they are over time, and whether cellular activity dynamics are affected by the amyloid plaque pathology remains incompletely understood. We here repeatedly recorded the activity from identified neurons in cortex of awake APPPS1 transgenic mice over four weeks during the early phase of plaque deposition using in vivo two-photon calcium imaging.

Three Water Restriction Schedules Used in Rodent Behavioral Tasks Transiently Impair Growth and Differentially Evoke a Stress Hormone Response without Causing Dehydration.

Water restriction is commonly used to motivate rodents to perform behavioral tasks; however, its effects on hydration and stress hormone levels are unknown. Here, we report daily body weight and bi-weekly packed red blood cell volume and corticosterone (CORT) in adult male rats across 80 days for three commonly used water restriction schedules. We also assessed renal adaptation to water restriction using postmortem histologic evaluation of renal medulla.

Microglia contribute to the propagation of Aβ into unaffected brain tissue.

Microglia appear activated in the vicinity of amyloid beta (Aβ) plaques, but whether microglia contribute to Aβ propagation into unaffected brain regions remains unknown. Using transplantation of wild-type (WT) neurons, we show that Aβ enters WT grafts, and that this is accompanied by microglia infiltration. Manipulation of microglia function reduced Aβ deposition within grafts.

Continuous Sirtuin/HDAC (histone deacetylase) activity assay using thioamides as PET (Photoinduced Electron Transfer)-based fluorescence quencher.

Histone deacylase 11 and human sirtuins are able to remove fatty acid-derived acyl moieties from the ε-amino group of lysine residues. Specific substrates are needed for investigating the biological functions of these enzymes. Additionally, appropriate screening systems are required for identification of modulators of enzymatic activities of HDAC11 and sirtuins.