Miracle-dz/UniFAR-FTUs huggingface dataset:
Financial burden among US households affected by cancer at the end of life

Economic burden on families coping with end‐stage cancer remains poorly understood. Advanced malignancy threatens financial stability of families, and interventions are needed to buffer them from impoverishment. This study examined the relationship between subjective and objective assessments of financial burden on families (financial strain and stress, respectively) and identified potentially modifiable factors to inform intervention efforts.
Cell Culture System for Analysis of Genetic Heterogeneity Within Hepatocellular Carcinomas and Response to Pharmacologic Agents.

BACKGROUND & AIMS No targeted therapies have been found to be effective against hepatocellular carcinoma (HCC), possibly due to the large degree of intratumor heterogeneity. We performed genetic analyses of different regions of HCCs to evaluate levels of intratumor heterogeneity and associate alterations with responses to different pharmacologic agents. METHODS We obtained samples of HCCs (associated with hepatitis B virus infection) from 10 patients undergoing curative resection, before adjuvant therapy, at hospitals in China. We collected 4-9 spatially distinct samples from each tumor (55 regions total), performed histologic analyses, isolated cancer cells, and carried them low-passage culture. We performed whole-exome sequencing, copy-number analysis, and high-throughput screening of the cultured primary cancer cells. We tested responses of an additional 105 liver cancer cell lines to a fibroblast growth factor receptor (FGFR) 4 inhibitor. RESULTS We identified a total of 3670 non-silent mutations (3192 missense, 94 splice-site variants, and 222 insertions or deletions) in the tumor samples. We observed considerable intratumor heterogeneity and branched evolution in all 10 tumors; the mean percentage of heterogeneous mutations in each tumor was 39.7% (range, 12.9%-68.5%). We found significant mutation shifts toward C>T and C>G substitutions in branches of phylogenetic trees among samples from each tumor (P < .0001). Of note, 14 of the 26 oncogenic alterations (53.8%) varied among subclones that mapped to different branches. Genetic alterations that can be targeted by existing pharmacologic agents (such as those in FGF19, DDR2, PDGFRA, and TOP1) were identified in intratumor subregions from 4 HCCs and were associated with sensitivity to these agents. However, cells from the remaining subregions, which did not have these alterations, were not sensitive to these drugs. High-throughput screening identified pharmacologic agents to which these cells were sensitive, however. Overexpression of FGF19 correlated with sensitivity of cells to an inhibitor of FGFR 4; this observation was validated in 105 liver cancer cell lines (P = .0024). CONCLUSIONS By analyzing genetic alterations in different tumor regions of 10 HCCs, we observed extensive intratumor heterogeneity. Our patient-derived cell line-based model, integrating genetic and pharmacologic data from multiregional cancer samples, provides a platform to elucidate how intratumor heterogeneity affects sensitivity to different therapeutic agents.
Dipeptidyl Peptidase‐4 Inhibitor Anagliptin Prevents Intracranial Aneurysm Growth by Suppressing Macrophage Infiltration and Activation

Background Chronic inflammation plays a key role in the pathogenesis of intracranial aneurysms (IAs). DPP‐4 (dipeptidyl peptidase‐4) inhibitors have anti‐inflammatory effects, including suppressing macrophage infiltration, in various inflammatory models. We examined whether a DPP‐4 inhibitor, anagliptin, could suppress the growth of IAs in a rodent aneurysm model. Methods and Results IAs were surgically induced in 7‐week‐old male Sprague Dawley rats, followed by oral administration of 300 mg/kg anagliptin. We measured the morphologic parameters of aneurysms over time and their local inflammatory responses. To investigate the molecular mechanisms, we used lipopolysaccharide‐treated RAW264.7 macrophages. In the anagliptin‐treated group, aneurysms were significantly smaller 2 to 4 weeks after IA induction. Anagliptin inhibited the accumulation of macrophages in IAs, reduced the expression of MCP‐1 (monocyte chemotactic protein 1), and suppressed the phosphorylation of p65. In lipopolysaccharide‐stimulated RAW264.7 cells, anagliptin treatment significantly reduced the production of tumor necrosis factor α, MCP‐1, and IL‐6 (interleukin 6) independent of GLP‐1 (glucagon‐like peptide 1), the key mediator in the antidiabetic effects of DPP‐4 inhibitors. Notably, anagliptin activated ERK5 (extracellular signal–regulated kinase 5), which mediates the anti‐inflammatory effects of statins, in RAW264.7 macrophages. Preadministration with an ERK5 inhibitor blocked the inhibitory effect of anagliptin on MCP‐1 and IL‐6 expression. Accordingly, the ERK5 inhibitor also counteracted the suppression of p65 phosphorylation in vitro. Conclusions A DPP‐4 inhibitor, anagliptin, prevents the growth of IAs via its anti‐inflammatory effects on macrophages.
Phytoplankton Diversity and Community Composition along the Estuarine Gradient of a Temperate Macrotidal Ecosystem: Combined Morphological and Molecular Approaches

Microscopical and molecular analyses were used to investigate the diversity and spatial community structure of spring phytoplankton all along the estuarine gradient in a macrotidal ecosystem, the Baie des Veys (eastern English Channel). Taxa distribution at high tide in the water column appeared to be mainly driven by the tidal force which superimposed on the natural salinity gradient, resulting in a two-layer flow within the channel. Lowest taxa richness and abundance were found in the bay where Teleaulax-like cryptophytes dominated. A shift in species composition occurred towards the mouth of the river, with the diatom Asterionellopsis glacialis dramatically accumulating in the bottom waters of the upstream brackish reach. Small thalassiosiroid diatoms dominated the upper layer river community, where taxa richness was higher. Through the construction of partial 18S rDNA clone libraries, the microeukaryotic diversity was further explored for three samples selected along the surface salinity gradient (freshwater - brackish - marine). Clone libraries revealed a high diversity among heterotrophic and/or small-sized protists which were undetected by microscopy. Among them, a rich variety of Chrysophyceae and other lineages (e.g. novel marine stramenopiles) are reported here for the first time in this transition area. However, conventional microscopy remains more efficient in revealing the high diversity of phototrophic taxa, low in abundances but morphologically distinct, that is overlooked by the molecular approach. The differences between microscopical and molecular analyses and their limitations are discussed here, pointing out the complementarities of both approaches, for a thorough phytoplankton community description.
Microscope-Integrated Optical Coherence Tomography Angiography in the Operating Room in Young Children With Retinal Vascular Disease

Importance Intraoperative optical coherence tomography (OCT) has gained traction as an important adjunct for clinical decision making during vitreoretinal surgery, and OCT angiography (OCTA) has provided novel insights in clinical evaluation of retinal diseases. To date, these two technologies have not been applied in combination to evaluate retinal vascular disease in the operating suite. Objective To conduct microscope-integrated, swept-source OCTA (MIOCTA) in children with retinal vascular disease. Design, Setting, and Participants In this case report analysis, OCT imaging in pediatric patients, MIOCTA images were obtained during examination under anesthesia from a young boy with a history of idiopathic vitreous hemorrhage and a female infant with familial exudative vitreoretinopathy. Main Outcomes and Measures Side-by-side comparison of research MIOCT angiograms and clinically indicated fluorescein angiograms. Results In 2 young children with retinal vascular disease, the MIOCTA images showed more detailed vascular patterns than were visible on the fluorescein angiograms although within a more posterior field of view. The MIOCTA system allowed visualization of small pathological retinal vessels in the retinal periphery that were obscured in the fluorescein angiograms by fluorescein staining from underlying, preexisting laser scars. Conclusions and Relevance This is the first report to date of the use of MIOCTA in the operating room for young children with retinal vascular disease. Further optimization of this system may allow noninvasive detailed evaluation of retinal vasculature during surgical procedures and in patients who could not cooperate with in-office examinations.
The impact of multiple sclerosis severity on health state utility values: Evidence from Australia

Background: The measurement of health state utility values (HSUVs) for a representative sample of Australian people with multiple sclerosis (MS) has not previously been performed. Objectives: Our main aim was to quantify the HSUVs for different levels of disease severities in Australian people with MS. Method: HSUVs were calculated by employing a ‘judgement-based’ method that essentially creates EQ-5D-3L profiles based on WHOQOL-100 responses and then applying utility weights to each level in each dimension. A stepwise linear regression was used to evaluate the relationship between HSUVs and disease severity, classified as mild (Expanded Disability Status Scale (EDSS) levels: 0–3.5), moderate (EDSS levels: 4–6) and severe (EDSS levels: 6.5–9.5). Results: Mean HSUV for all people with MS was 0.53 (95% confidence interval (CI): 0.52–0.54). Utility decreased with increasing disease severity: 0.61 (95% CI: 0.60–0.62), 0.51 (95% CI: 0.50–0.52) and 0.40 (95% CI: 0.38–0.43) for mild, moderate and severe disease, respectively. Adjusted differences in mean HSUV between the three severity groups were statistically significant. Conclusion: For the first time in Australia, we have quantified the impact of increasing severity of MS on health utility of people with MS. The HSUVs we have generated will be useful in further health economic analyses of interventions that slow progression of MS.
Single-molecule imaging reveals dynamic biphasic partition of RNA-binding proteins in stress granules

Stress granules (SGs) are cytosolic, nonmembranous RNA–protein complexes. In vitro experiments suggested that they are formed by liquid–liquid phase separation; however, their properties in mammalian cells remain unclear. We analyzed the distribution and dynamics of two paradigmatic RNA-binding proteins (RBPs), Ras GTPase-activating protein SH3-domain–binding protein (G3BP1) and insulin-like growth factor II mRNA-binding protein 1 (IMP1), with single-molecule resolution in living neuronal cells. Both RBPs exhibited different exchange kinetics between SGs. Within SGs, single-molecule localization microscopy revealed distributed hotspots of immobilized G3BP1 and IMP1 that reflect the presence of relatively immobile nanometer-sized nanocores. We demonstrate alternating binding in nanocores and anomalous diffusion in the liquid phase with similar characteristics for both RBPs. Reduction of low-complexity regions in G3BP1 resulted in less detectable mobile molecules in the liquid phase without change in binding in nanocores. The data provide direct support for liquid droplet behavior of SGs in living cells and reveal transient binding of RBPs in nanocores. Our study uncovers a surprising disconnect between SG partitioning and internal diffusion and interactions of RBPs.
Accounting For Patients' Socioeconomic Status Does Not Change Hospital Readmission Rates.

There is an active public debate about whether patients' socioeconomic status should be included in the readmission measures used to determine penalties in Medicare's Hospital Readmissions Reduction Program (HRRP). Using the current Centers for Medicare and Medicaid Services methodology, we compared risk-standardized readmission rates for hospitals caring for high and low proportions of patients of low socioeconomic status (as defined by their Medicaid status or neighborhood income). We then calculated risk-standardized readmission rates after additionally adjusting for patients' socioeconomic status. Our results demonstrate that hospitals caring for large proportions of patients of low socioeconomic status have readmission rates similar to those of other hospitals. Moreover, readmission rates calculated with and without adjustment for patients' socioeconomic status are highly correlated. Readmission rates of hospitals caring for patients of low socioeconomic status changed by approximately 0.1 percent with adjustment for patients' socioeconomic status, and only 3-4 percent fewer such hospitals reached the threshold for payment penalty in Medicare's HRRP. Overall, adjustment for socioeconomic status does not change hospital results in meaningful ways.
Biomass Allocation Patterns across China’s Terrestrial Biomes

Root to shoot ratio (RS) is commonly used to describe the biomass allocation between below- and aboveground parts of plants. Determining the key factors influencing RS and interpreting the relationship between RS and environmental factors is important for biological and ecological research. In this study, we compiled 2088 pairs of root and shoot biomass data across China’s terrestrial biomes to examine variations in the RS and its responses to biotic and abiotic factors including vegetation type, soil texture, climatic variables, and stand age. The median value of RS (RSm) for grasslands, shrublands, and forests was 6.0, 0.73, and 0.23, respectively. The range of RS was considerably wide for each vegetation type. RS values for all three major vegetation types were found to be significantly correlated to mean annual precipitation (MAP) and potential water deficit index (PWDI). Mean annual temperature (MAT) also significantly affect the RS for forests and grasslands. Soil texture and forest origin altered the response of RS to climatic factors as well. An allometric formula could be used to well quantify the relationship between aboveground and belowground biomass, although each vegetation type had its own inherent allometric relationship.
The Capacity of Mycobacterium tuberculosis To Survive Iron Starvation Might Enable It To Persist in Iron-Deprived Microenvironments of Human Granulomas

ABSTRACT This study was conducted to investigate the role of iron deprivation in the persistence of Mycobacterium tuberculosis. We present evidence of iron restriction in human necrotic granulomas and demonstrate that under iron starvation M. tuberculosis persists, refractive to antibiotics and capable of restarting replication when iron is made available. Transcriptomics and metabolomic analyses indicated that the persistence of M. tuberculosis under iron starvation is dependent on strict control of endogenous Fe utilization and is associated with upregulation of pathogenicity and intrinsic antibiotic resistance determinants. M. tuberculosis mutants compromised in their ability to survive Fe starvation were identified. The findings of this study advance the understanding of the physiological settings that may underpin the chronicity of human tuberculosis (TB) and are relevant to the design of effective antitubercular therapies. IMPORTANCE One-third of the world population may harbor persistent M. tuberculosis, causing an asymptomatic infection that is refractory to treatment and can reactivate to become potentially lethal tuberculosis disease. However, little is known about the factors that trigger and maintain M. tuberculosis persistence in infected individuals. Iron is an essential nutrient for M. tuberculosis growth. In this study, we show, first, that in human granulomas the immune defense creates microenvironments in which M. tuberculosis likely experiences drastic Fe deprivation and, second, that Fe-starved M. tuberculosis is capable of long-term persistence without growth. Together, these observations suggest that Fe deprivation in the lung might trigger a state of persistence in M. tuberculosis and promote chronic TB. We also identified vulnerabilities of iron-restricted persistent M. tuberculosis, which can be exploited for the design of new antitubercular therapies. IMPORTANCE One-third of the world population may harbor persistent M. tuberculosis, causing an asymptomatic infection that is refractory to treatment and can reactivate to become potentially lethal tuberculosis disease. However, little is known about the factors that trigger and maintain M. tuberculosis persistence in infected individuals. Iron is an essential nutrient for M. tuberculosis growth. In this study, we show, first, that in human granulomas the immune defense creates microenvironments in which M. tuberculosis likely experiences drastic Fe deprivation and, second, that Fe-starved M. tuberculosis is capable of long-term persistence without growth. Together, these observations suggest that Fe deprivation in the lung might trigger a state of persistence in M. tuberculosis and promote chronic TB. We also identified vulnerabilities of iron-restricted persistent M. tuberculosis, which can be exploited for the design of new antitubercular therapies.
Hydraulic and hydrological aspects of an evapotranspiration-constructed wetland combined system for household greywater treatment

ABSTRACT Constructed wetlands systems demand preliminary and primary treatment to remove solids present in greywater (GW) to avoid or reduce clogging processes. The current paper aims to assess hydraulic and hydrological behavior in an improved constructed wetland system, which has a built-in anaerobic digestion chamber (AnC), GW is distributed to the evapotranspiration and treatment tank (CEvaT), combined with a subsurface horizontal flow constructed wetland (SSHF-CW). The results show that both the plants present in the units and the AnC improve hydraulic and volumetric efficiency, decrease short-circuiting and improve mixing conditions in the system. Moreover, the hydraulic conductivity measured on-site indicates that the presence of plants in the system and the flow distribution pattern provided by the AnC might reduce clogging in the SSHF-CW. It is observed that rainfall enables salt elimination, thus increasing evapotranspiration (ET), which promotes effluent reduction and enables the system to have zero discharge when reuse is unfeasible.
A Scientific Approach to Improve Physiological Capacity of an Elite Cyclist.

Previous studies in endurance athletes have indicated that block periodization (BP) can be a good alternative to the more traditional organization of training despite the fact that the total volume and intensity of the training are similar. However, these studies usually last only 4-12 wk. The aim of the present single-case study was to investigate the consequences of 58 wk with systematic BP of low-intensity training (LIT), moderate-intensity training (MIT), and high-intensity interval training (HIT) including incorporation of heavy strength training. It is important that a maintenance stimulus on the nonprioritized training modalities was added in the different training blocks. Performance-related variables were tested regularly during the intervention. The studied cyclist started with a maximal oxygen uptake (VO2max) of 73.8 mL · kg-1 · min-1, peak aerobic power (Wmax) of 6.14 W/kg, and a power output at 3 mmol/L blood lactate concentration (Power3la-) of 3.6 W/kg. Total training volume during the 58-wk intervention was 678 h, of which 452 h were LIT (67%), 124 h were MIT (18%), 69 h were HIT (10%), and 34 h were heavy strength training (5%). The weekly training volume had a large range depending on the focus of the training block. After the intervention the cyclist's VO2max was 87 mL · kg-1 · min-1, Wmax was 7.35 W/kg, and Power3la- was 4.9 W/kg. This single case indicates that the present training program can be a good alternative to the more traditional organization of long-term training of endurance athletes. However, a general recommendation cannot be given based on this single-case study.
Computer-aided detection of prostate cancer in T2-weighted MRI within the peripheral zone

In this paper we propose a prostate cancer computer-aided diagnosis (CAD) system and suggest a set of discriminant texture descriptors extracted from T2-weighted MRI data which can be used as a good basis for a multimodality system. For this purpose, 215 texture descriptors were extracted and eleven different classifiers were employed to achieve the best possible results. The proposed method was tested based on 418 T2-weighted MR images taken from 45 patients and evaluated using 9-fold cross validation with five patients in each fold. The results demonstrated comparable results to existing CAD systems using multimodality MRI. We achieved an area under the receiver operating curve (Az) values equal to 90.0%±7.6%, 89.5%±8.9%, 87.9%±9.3% and 87.4%±9.2% for Bayesian networks, ADTree, random forest and multilayer perceptron classifiers, respectively, while a meta-voting classifier using average probability as a combination rule achieved 92.7%±7.4%.
Tissue characterization with depth-resolved attenuation coefficient and backscatter term in intravascular optical coherence tomography images

Abstract. An important application of intravascular optical coherence tomography (IVOCT) for atherosclerotic tissue analysis is using it to estimate attenuation and backscatter coefficients. This work aims at exploring the potential of the attenuation coefficient, a proposed backscatter term, and image intensities in distinguishing different atherosclerotic tissue types with a robust implementation of depth-resolved (DR) approach. Therefore, the DR model is introduced to estimate the attenuation coefficient and further extended to estimate the backscatter-related term in IVOCT images, such that values can be estimated per pixel without predefining any delineation for the estimation. In order to exclude noisy regions with a weak signal, an automated algorithm is implemented to determine the cut-off border in IVOCT images. The attenuation coefficient, backscatter term, and the image intensity are further analyzed in regions of interest, which have been delineated referring to their pathology counterparts. Local statistical values were reported and their distributions were further compared with a two-sample t-test to evaluate the potential for distinguishing six types of tissues. Results show that the IVOCT intensity, DR attenuation coefficient, and backscatter term extracted with the reported implementation are complementary to each other on characterizing six tissue types: mixed, calcification, fibrous, lipid-rich, macrophages, and necrotic core.
Network Analysis Reveals Ecological Links between N-Fixing Bacteria and Wood-Decaying Fungi

Nitrogen availability in dead wood is highly restricted and associations with N-fixing bacteria are thought to enable wood-decaying fungi to meet their nitrogen requirements for vegetative and generative growth. We assessed the diversity of nifH (dinitrogenase reductase) genes in dead wood of the common temperate tree species Fagus sylvatica and Picea abies from differently managed forest plots in Germany using molecular tools. By incorporating these genes into a large compilation of published nifH sequences and subsequent phylogenetic analyses of deduced proteins we verified the presence of diverse pools corresponding to functional nifH, almost all of which are new to science. The distribution of nifH genes strongly correlated with tree species and decay class, but not with forest management, while higher fungal fructification was correlated with decreasing nitrogen content of the dead wood and positively correlated with nifH diversity, especially during the intermediate stage of wood decay. Network analyses based on non-random species co-occurrence patterns revealed interactions among fungi and N-fixing bacteria in the dead wood and strongly indicate the occurrence of at least commensal relationships between these taxa.