The prognostic role of changes in body fat in patients with idiopathic pulmonary fibrosis (IPF) remains underexplored. We investigated the association between changes in body fat during the first ...year post-diagnosis and outcomes in patients with IPF.
This single-center, retrospective study included IPF patients with chest CT scan and pulmonary function test (PFT) at diagnosis and a one-year follow-up between January 2010 and December 2020. The fat area (cm
, sum of subcutaneous and visceral fat) and muscle area (cm
) at the T12-L1 level were obtained from chest CT images using a fully automatic deep learning-based software. Changes in the body composition were dichotomized using thresholds dividing the lowest quartile and others, respectively (fat area: -52.3 cm
, muscle area: -7.4 cm
). Multivariable Cox regression analyses adjusted for PFT result and IPF extent on CT images and the log-rank test were performed to assess the association between the fat area change during the first year post-diagnosis and the composite outcome of death or lung transplantation.
In total, 307 IPF patients (69.3 ± 8.1 years; 238 men) were included. During the first year post-diagnosis, fat area, muscle area, and body mass index (BMI) changed by -15.4 cm
, -1 cm
, and - 0.4 kg/m
, respectively. During a median follow-up of 47 months, 146 patients had the composite outcome (47.6%). In Cox regression analyses, a change in the fat area < -52.3 cm
was associated with composite outcome incidence in models adjusted with baseline clinical variables (hazard ratio HR, 1.566, P = .022; HR, 1.503, P = .036 in a model including gender, age, and physiology GAP index). This prognostic value was consistent when adjusted with one-year changes in clinical variables (HR, 1.495; P = .030). However, the change in BMI during the first year was not a significant prognostic factor (P = .941). Patients with a change in fat area exceeding this threshold experienced the composite outcome more frequently than their counterparts (58.4% vs. 43.9%; P = .007).
A ≥ 52.3 cm
decrease in fat area, automatically measured using deep learning technique, at T12-L1 in one year post-diagnosis was an independent poor prognostic factor in IPF patients.
Current pharmacological treatments for Parkinson’s disease (PD) are focused on symptomatic relief, but not on disease modification, based on the strong belief that PD is caused by irreversible ...dopaminergic neuronal death. Thus, the concept of the presence of dormant dopaminergic neurons and its possibility as the disease-modifying therapeutic target against PD have not been explored. Here we show that optogenetic activation of substantia nigra pars compacta (SNpc) neurons alleviates parkinsonism in acute PD animal models by recovering tyrosine hydroxylase (TH) from the TH-negative dormant dopaminergic neurons, some of which still express DOPA decarboxylase (DDC). The TH loss depends on reduced dopaminergic neuronal firing under aberrant tonic inhibition, which is attributed to excessive astrocytic GABA. Blocking the astrocytic GABA synthesis recapitulates the therapeutic effect of optogenetic activation. Consistently, SNpc of postmortem PD patients shows a significant population of TH-negative/DDC-positive dormant neurons surrounded by numerous GABA-positive astrocytes. We propose that disinhibiting dormant dopaminergic neurons by blocking excessive astrocytic GABA could be an effective therapeutic strategy against PD.
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•Reactive astrocytes in SNpc produce excessive GABA via MAO-B in animal models of PD•Aberrant tonic inhibition causes reduced DA production in neurons and motor deficits•Dormant neurons are rescued by MAO-B inhibition or optogenetic neuronal activation
Heo et al. report that astrocytic GABA-mediated aberrant tonic inhibition of DA neurons leads to a reduction in TH expression and dopamine production, causing dormant DA neurons and motor deficits. Blocking astrocytic GABA synthesis by MAO-B inhibition or optogenetic activation of dormant DA neurons reverses PD pathology.
Objectives
To determine the incidence, risk factors, and prognostic indicators of symptomatic air embolism after percutaneous transthoracic lung biopsy (PTLB) by conducting a systematic review and ...pooled analysis.
Methods
We searched the EMBASE and OVID-MEDLINE databases to identify studies that dealt with air embolism after PTLB and had extractable outcomes. The incidence of air embolism was pooled using a random effects model, and the causes of heterogeneity were investigated. To analyze risk factors for symptomatic embolism and unfavorable outcomes, multivariate logistic regression analysis was performed.
Results
The pooled incidence of symptomatic air embolism after PTLB was 0.08% (95% confidence interval CI, 0.048–0.128%;
I
2
= 45%). In the subgroup analysis and meta-regression, guidance modality and study size were found to explain the heterogeneity. Of the patients with symptomatic air embolism, 32.7% had unfavorable outcomes. The presence of an underlying disease (odds ratio OR, 5.939; 95% CI, 1.029–34.279;
p
= 0.046), the use of a ≥ 19-gauge needle (OR, 10.046; 95% CI, 1.103–91.469;
p
= 0.041), and coronary or intracranial air embolism (OR, 19.871; 95% CI, 2.725–14.925;
p
= 0.003) were independent risk factors for symptomatic embolism. Unfavorable outcomes were independently associated with the use of aspiration biopsy rather than core biopsy (OR, 3.302; 95% CI, 1.149–9.492;
p
= 0.027) and location of the air embolism in the coronary arteries or intracranial spaces (OR = 5.173; 95% CI = 1.309–20.447;
p
= 0.019).
Conclusion
The pooled incidence of symptomatic air embolism after PTLB was 0.08%, and one-third of cases had sequelae or died. Identifying whether coronary or intracranial emboli exist is crucial in suspected cases of air embolism after PTLB.
Key Points
•
The pooled incidence of symptomatic air embolism after percutaneous transthoracic lung biopsy was 0.08%, and one-third of patients with symptomatic air embolism had sequelae or died.
•
The risk factors for symptomatic air embolism were the presence of an underlying disease, the use of a ≥ 19-gauge needle, and coronary or intracranial air embolism.
•
Sequelae and death in patients with symptomatic air embolism were associated with the use of aspiration biopsy and coronary or intracranial locations of the air embolism.
This study was conducted to confirm the Cs-137 and Sr-90 adsorption properties of illite. In the experimental method, illite was added to Cs-137 and Sr-90 solutions and stirred. And Following the ...completion of the adsorption reaction, the solid/liquid phase was separated using a centrifuge, and the adsorption rate was calculated by measuring the radioactivity concentration of the separated liquid phase using a gamma nuclide analyzer, Liquid Scintillation Count (LSC). As a result of the experiment, after reacting for 30 min, 94% of Cs-137 was adsorbed. And 84.26% of Sr-90 was adsorbed.
The mammalian brain comprises structurally and functionally distinct regions. Each of these regions has characteristic molecular mechanisms that mediate higher-order tasks, such as memory, learning, ...emotion, impulse, and motor control. Many genes are involved in neuronal signaling and contribute to normal brain development. Dysfunction of essential components of neural signals leads to various types of brain disorders. Autism spectrum disorder is a neurodevelopmental disorder characterized by social deficits, communication challenges, and compulsive repetitive behaviors. Long-term genetic studies have uncovered key genes associated with autism spectrum disorder, such as SH3 and multiple ankyrin repeat domains 3, methyl-CpG binding protein 2, neurexin 1, and chromodomain helicase DNA binding protein 8. In addition, disease-associated networks have been identified using animal models, and the understanding of the impact of these genes on disease susceptibility and compensation is deepening. In this review, we examine rescue strategies using key models of autism spectrum disorder.
Abstract
The measured response of cell population is often delayed relative to drug injection, and individuals in a population have a specific age distribution. Common approaches for describing the ...delay are to apply transit compartment models (TCMs). This model reflects that all damaged cells caused by drugs suffer transition processes, resulting in death. In this study, we present an extended TCM using Coxian distribution, one of the phase-type distributions. The cell population attacked by a drug is described via age-structured models. The mortality rate of the damaged cells is expressed by a convolution of drug rate and age density. Then applying to Erlang and Coxian distribution, we derive Erlang TCM, representing the existing model, and Coxian TCMs, reflecting sudden death at all ages. From published data of drug and tumor, delays are compared after parameter estimations in both models. We investigate the dynamical changes according to the number of the compartments. Model robustness and equilibrium analysis are also performed for model validation. Coxian TCM is an extended model considering a realistic case and captures more diverse delays.
We evaluated the prognostic efficiency of the European Leukemia Net (ELN) 2017 criteria on the post-transplant outcomes of 174 patients with intermediate (INT; n = 108, 62%) or adverse (ADV) risk (n ...= 66, 38%) of acute myeloid leukemia; these patients had received the first allogeneic hematopoietic stem-cell transplantation (HSCT) at remission. After a median follow-up period of 18 months, the 2 year OS, RFS, and CIR after HSCT were estimated to be 58.6% vs. 64.4% (p = 0.299), 50.5% vs. 53.7% (p = 0.533), and 26.9% vs. 36.9% (p = 0.060) in the INT and ADV risk groups, respectively. Compared to the ELN 2017 stratification, pre-HSCT WT1 levels (cutoff: 250 copies/104 ABL) more effectively segregated the post-HSCT outcomes of INT risk patients compared to ADV risk patients regarding their 2 year OS (64.2% vs. 51.5%, p = 0.099), RFS (59.4% vs. 32.4%, p = 0.003), and CIR (18.9% vs. 60.0% p < 0.001). Indeed, high WT1 levels were more prominent in INT risk patients than in ADV risk patients. Notably, FLT3-ITD had the greatest impact on post-HSCT outcomes among all the ELN 2017 criteria components; patients in the FLT3-ITD mutant subgroups exhibited the worst outcomes regardless of their allelic ratios or NPM1 status compared to the pre-HSCT WT1 level of other INT and ADV risk patients.
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•A 3D interconnected structure-based cathode with high sulfur loading was fabricated.•For the 3D anode, molten Li was infused into the porous Ni networks.•The Li-infused Ni sponge ...anodes exhibited a stable cyclic performance.•The 3D structure improved the rate and cyclic performance of Li–S cells.•Li–S cells with 3D structure electrodes can enhance the cell energy density.
Lithium–sulfur (Li–S) batteries have attracted extensive attention as competitive candidates for next-generation high-energy–density batteries because of their excellent theoretical energy density, and the abundance and low cost of sulfur. In this study, a high-energy–density Li–S battery based on a porous metal–carbon composite cathode with a three-dimensional (3D) structure and high sulfur loading, and a metal sponge skeleton–Li composite anode was fabricated. The 3D metal composite electrodes provided a highly robust conductive pathway that improved the electrical/ionic transport. In particular, the 3D sponge–Li anode exhibited stable stripping and plating performance in symmetric cell tests owing to the high electron conductivity provided by the interconnected metal networks. In addition, well-designed full cells with 3D Al–multi-walled carbon nanotube on sulfur cathodes and 3D Ni sponge/Li anodes demonstrated excellent electrochemical performance owing to their high sulfur loading (>8 mg cm−2). The weight of the anode was reduced to less than half of that of a typical Li anode. Further, the cell exhibited an excellent rate capability and improved cyclability. Therefore, our 3D interconnected structure can effectively achieve high sulfur loading and energy densities, thereby addressing the limitations of conventional Li–S cells and achieving notable advances in electrochemical energy storage.
•Zeolitic metal–organic framework (ZIF-8) films were deposited by supersonic spraying.•This supersonic spray method produced textured crystalline films on copper and glass substrates.•Addition of ...high-boiling-point solvents in ZIF-8 pores resulted in preferred crystal orientations.•The produced films are microstructurally compact and strongly adherent to substrates.
We describe the first use of high-rate supersonic spray coating to deposit thin films of ZIF-8, a zeolitic metal–organic framework (MOF), adopting a sodalite architecture. This cold-spray technique is versatile and scalable, with tunable processing parameters capable of generating either a textured crystalline film or a randomly oriented polycrystalline coating on both metallic and non-metallic substrates. We provide evidence that guest occupancy by organic solvents (dimethylformamide, dimethylacetamide, and dimethylsulfoxide) in the sodalite cage of ZIF-8 structurally stabilizes the framework against high-velocity impact, resulting in the preferred orientations observed. Moreover, we show that amorphous ZIF-8 films can be straightforwardly obtained at high air pressure exceeding 7bars in which the particle velocity is ∼500m/s. It is anticipated that this high-throughput approach can be adapted to fabricate microstructurally compact and strongly adhered ZIF-8 films.
There are limited data on second stem cell transplantation (SCT2) outcomes with alternative donors for relapsed AML after the first stem cell transplantation (SCT1). We analyzed the outcomes of 52 ...adult AML patients who received SCT2 from haploidentical donors (HIT,
= 32) and double-cord blood (dCBT,
= 20) between 2008 and 2021. The HIT group received T-cell-replete peripheral blood stem cells after reduced-toxicity conditioning with anti-thymocyte globulin (ATG), while the dCBT group received myeloablative conditioning. For a median follow-up of 64.9 months, the HIT group, compared to the dCBT group, had earlier engraftment, superior 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) with similar relapse. Multivariate analysis demonstrated that HIT was significantly associated with better OS, DFS, and lower NRM than dCBT. Both longer remission duration after SCT1 and complete remission at SCT2 were significantly associated with a lower relapse rate. In addition, bone marrow
measurable residual disease (MRD) positivity was significantly associated with inferior OS and higher relapse. This study suggests that T-cell-replete HIT with ATG-based GVHD prophylaxis may be preferred over dCBT as SCT2 for relapsed AML and that
-MRD negativity may be warranted for better SCT2 outcomes.
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