bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy and Exergy Analysis of a Nuclear Power Plant
Authors: Benčin Tim , Avsec Jurij , Novosel Urška
Published: November 2024

Nuclear power plant can be a key pillar of a country’s energy supply. In their operation, it is necessary to follow the efficient use of the primary energy source. Using the thermodynamic analysis of energy and exergy flows in a nuclear power plant, we calculated the energy and exergy efficiency. With comparison of final electrical energy and internal energy of nuclear fuel we hand the energy efficiency for chosen power station. This has significant meaning. However, a nuclear power plant is an example of power station, that operates generally on principle of heat transfer. At that irreversibility and thus loss of exergy occur, so a clearer and more meaningful picture of the efficient use of nuclear fuel is shown by exergy efficiency. This is describing relationship between exergy of output electric current and exergy of nuclear fuel. The main goal of our research work was to observe the energy and exergy flows and their loses on the built model of the nuclear power plant. Based on the findings, we gave energy and exergy efficiency for individual assembly and the whole plant. By comparing the two efficiency evaluation criteria, we researched where deviations occur between energy and exergy efficiency. The essence of such an analysis is the data that clearly show us the places where we lose energy or exergy. With such knowledge, we can discuss on theoretical possibilities of improvements on individual assemblies of power station, which would upgrade the existing efficiency of the entire nuclear power plant. For the set model in our research, the energy efficiency was found to be 33.7% and the exergy efficiency 46.8%.
Optical Performance of a Novel Tube-Bundle Cavity Receiver for Solar Parabolic Trough Collectors
Authors: Ebadi Hossein , Kamfiroozi Shahdad , Cammi Antonio , Savoldi Laura
Published: November 2024

Solar parabolic trough collectors (PTC) are one of the mature technologies that have increased the share of solar energy in the power sector. Having a working temperature in the range of 200 to 500 °C, PTC systems can be integrated whether as a direct steam generator using water as the heat transfer fluid or with a Rankine cycle turbine by means of a heat exchanger and other heat transfer fluids such as air, molten salts, oils and nanofluid. In this research, a novel concept of a tube-bundle cavity receiver is investigated using optical simulations through SolTrace software. The obtained results proved that the tube-bundle cavity absorber will increase the average and the peak flux reaching the receiving area by near 100%. Then the optical modelling was validated for the parabolic trough solar collector of LS-2 and the results showed a very good agreement with the literature, concerning the optical criteria.
Thermodynamic Analysis and Optimization of Molten Salt Reactors Coupled With Desalination Solutions
Authors: Alcorn Isabella , Louis Ethan , Gonzales Robert , Aguilar Diego , Kimber Mark
Published: November 2024

In recent years, Molten Salt Reactor (MSR) technology has received significant attention. Its low pressure makes the MSR a low-risk option which, when coupled with its high temperature, makes it a highly beneficial choice for power generation and suggests the ease of integration with other systems such as desalination. It is worthwhile with the growing interest in MSRs, to develop a simulation tool that can predict performance in a multi-faceted MSR-based flow loop. This study focuses on MSR applications, namely clean water production utilizing a specific optimized combination of FLiNaK and supercritical carbon dioxide (SCO2) cycles. It addresses the growing worldwide need to decarbonize our energy production and simultaneously provide clean water. The results of optimized MSR-desalination configurations exhibit promising implications for the production of abundant amounts of clean water while also maintaining ample power supply to the electrical grid. They show that a design for a coupled MSR and desalination plant are not only possible but that the components and design are scalable for 50–250 MWth power input.
Effect of Porous Walls and Nanofluids on the Thermo-Hydraulic Performance of Tapered Double-Layered Microchannel Heat Sink
Authors: Kumar Avinash , Bakli Chirodeep
Published: November 2024

The present study investigates the effect of porous walls on the thermo-hydraulic characteristics of tapered Double Layer Microchannel Heat Sink (DL-MCHS). Three tapered DL-MCHS with different porous walls arrangements is simulated and compared for varying tapering of the channel and Reynolds number considering water and nanofluid as coolant. The fluid flow through porous media and micro-channel is modeled using the Darcy-Brinkman-Forchheimer equation and Navier-Stokes equation respectively. The above two equations coupled with continuity and energy equations are solved numerically to depict the thermo-hydraulic characteristics of DL-MCHS. It is demonstrated that the porous walls reduce the pressure losses along with a reduction in cooling performance of tapered DL-MCHS making the use of porous walls non-viable. However, incorporating porous walls in either bottom or top channel enhances the thermal performance and the overall performance making the use of porous walls viable. Also, the use of Al2O3-H2O nanofluid enhances the performance of a heat sink further by 11% as compared to water. It is found that incorporating porous walls only in the bottom channel gives the best performance among all three porous arrangements. Finally, through an optimization study, the enhancement in thermal performance by 22.7% is reported considering TF = 0.5, Re = 600, and nanofluid as coolant making it an optimum viable design.
Generalization of RELAP5-3D Molecular Diffusion Model to a Noncondensable Gas Primary Coolant
Authors: Mesina George , Martin Robert P.
Published: November 2024

The molecular diffusion model [1, 2] was developed within RELAP5-3D [3, 4] in 2005. Its objective was to implement the capability of calculating the ingress of air into a particular Very Hight Temperature gas-cooled Reactor (VHTR) by molecular diffusion following an accident, such as a large break in the primary coolant system, resulting in a complete loss of flow and depressurization. The existing coding was verified and validated [4]. However, the implementation was confined to only two different gases for the primary fluid, water vapor and helium. It has become of interest to implement other gases as the primary coolant, primarily for modeling designs for new Small Modular Reactors (SMR) and microreactors. This project adds the capability to specify, through use input, a variety of noncondensable (NC) gases as the primary coolant.

The approach for molecular diffusion modeling has two parts. The first part solves the diffusion equation at each time step to calculate the various components of gas added or subtracted from each RELAP5-3D control volume due to molecular diffusion during the time step. The second part modifies the RELAP5-3D field equations with the molecular diffusion calculations so that the overall fluid behavior modeling accounts for molecular diffusion. The theory, algorithm, coding implementation and verification are given, and some numerical validation and calculational results are given.
Running Through the Haze: How Wildfire Smoke Affects Physical Activity and Mental Well-Being
Authors: Giles Luisa V. , Thomson Cynthia J. , Lesser Iris , Brandenburg Jason P.
Published: November 2024

Background: With a warming climate, extreme wildfires are more likely to occur, which may adversely affect air quality, physical activity (PA), and therefore, mental well-being. Methods: We assessed PA engagement and mental well-being between periods with and without wildfire smoke, and whether there were associations between changes in PA behavior and mental well-being. Questionnaires on PA and mental well-being during a period of wildfire smoke were completed by 348 participants; of these participants, 162 also completed a follow-up PA and mental well-being questionnaire during a period without wildfire smoke. Data were analyzed using generalized/linear mixed models. Relationships between mental well-being and PA were analyzed using repeated-measures correlations. Results: Leisure-time walking, moderate PA, and vigorous PA were all significantly lower during periods of smoke compared to periods without smoke. Participants also experienced significantly higher symptoms of stress (11.63 [1.91] vs 10.20 [1.70], P = .039), anxiety (7.75 [2.24] vs 4.38 [1.32], P < .001), and depression (9.67 [0.90] vs 7.27 [0.76], P < .001) during the period of wildfire smoke. Vigorous PA, the proportion of PA time spent outdoors, and the sum of PA during leisure time, were significantly negatively correlated with mental well-being, therefore, it is possible that PA could be used as a tool during times of wildfire smoke. Conclusions: These data suggest that PA and mental well-being are adversely impacted during wildfire smoke events. Future research should consider the impact of strategies to support PA during wildfire events on PA and mental well-being.
Physical experiments of waves generated by submerged steam eruptions with applications to volcanic tsunamis
Authors: Shen Yaxiong , Whittaker Colin N. , Lane Emily M. , White James D. L. , Power William
Published: November 2024

The tsunamigenic potential of underwater volcanic eruptions is not well understood, even though eruption-generated tsunamis can be devastating. To address how erupted steam bursts from underwater volcanoes generate tsunamis, we present the experiments, using pressurized steam injected vertically into a water tank. Results over various eruption conditions identify three eruption regimes, namely, shallow-, intermediate-, and deep-water eruptions, according to the combined effects of water depths, source strengths, and source durations. The transition between shallow and intermediate eruptions is characterized by critical depths maximizing tsunami wave heights, while the transition between intermediate and deep eruptions is characterized by containment depths inhibiting surface disturbances. Water depth and source intensity are the dominant factors controlling maximum wave amplitudes, more so than aspects of jet duration and condensation. These experiments and supporting dimensional analysis improve our understanding of how underwater volcanic eruptions form tsunamis, while also providing a complete dataset for advancing tsunami generation models.
Anthropogenic warming has ushered in an era of temperature-dominated droughts in the western United States
Authors: Zhuang Yizhou , Fu Rong , Lisonbee Joel , Sheffield Amanda M. , Parker Britt A. , Deheza Genoveva
Published: November 2024

Historically, meteorological drought in the western United States (WUS) has been driven primarily by precipitation deficits. However, our observational analysis shows that, since around 2000, rising surface temperature and the resulting high evaporative demand have contributed more to drought severity (62%) and coverage (66%) over the WUS than precipitation deficit. This increase in evaporative demand during droughts, mostly attributable to anthropogenic warming according to analyses of both observations and climate model simulations, is the main cause of the increased drought severity and coverage. The unprecedented 2020–2022 WUS drought exemplifies this shift in drought drivers, with high evaporative demand accounting for 61% of its severity, compared to 39% from precipitation deficit. Climate model simulations corroborate this shift and project that, under the fossil-fueled development scenario (SSP5-8.5), droughts like the 2020–2022 event will transition from a one-in-more-than-a-thousand-year event in the pre-2022 period to a 1-in-60-year event by the mid-21st century and to a 1-in-6-year event by the late-21st century.
Quantification of electrochemically accessible iridium oxide surface area with mercury underpotential deposition
Authors: Edgington Jane , Vispute Sejal , Li Ruihan , Deberghes Adrien , Seitz Linsey C.
Published: November 2024

Research drives development of sustainable electrocatalytic technologies, but efforts are hindered by inconsistent reporting of advances in catalytic performance. Iridium-based oxide catalysts are widely studied for electrocatalytic technologies, particularly for the oxygen evolution reaction (OER) for proton exchange membrane water electrolysis, but insufficient techniques for quantifying electrochemically accessible iridium active sites impede accurate assessment of intrinsic activity improvements. We develop mercury underpotential deposition and stripping as a reversible electrochemical adsorption process to robustly quantify iridium sites and consistently normalize OER performance of benchmark IrO

x

electrodes to a single intrinsic activity curve, where other commonly used normalization methods cannot. Through rigorous deconvolution of mercury redox and reproportionation reactions, we extract net monolayer deposition and stripping of mercury on iridium sites throughout testing using a rotating ring disk electrode. This technique is a transformative method to standardize OER performance across a wide range of iridium-based materials and quantify electrochemical iridium active sites.
Dysregulation of zebrin-II cell subtypes in the cerebellum is a shared feature across polyglutamine ataxia mouse models and patients
Authors: Bartelt Luke C. , Switonski Pawel M. , Adamek Grażyna , Longo Fabiana , Carvalho Juliana , Duvick Lisa A. , Jarrah Sabrina I. , McLoughlin Hayley S. , Scoles Daniel R. , Pulst Stefan M. , Orr Harry T. , Hull Court , Lowe Craig B. , La Spada Albert R.
Published: November 2024

Spinocerebellar ataxia type 7 (SCA7) is a genetic neurodegenerative disorder caused by a CAG-polyglutamine repeat expansion. Purkinje cells (PCs) are central to the pathology of ataxias, but their low abundance in the cerebellum underrepresents their transcriptomes in sequencing assays. To address this issue, we developed a PC enrichment protocol and sequenced individual nuclei from mice and patients with SCA7. Single-nucleus RNA sequencing in SCA7-266Q mice revealed dysregulation of cell identity genes affecting glia and PCs. Specifically, genes marking zebrin-II PC subtypes accounted for the highest proportion of DEGs in symptomatic SCA7-266Q mice. These transcriptomic changes in SCA7-266Q mice were associated with increased numbers of inhibitory synapses as quantified by immunohistochemistry and reduced spiking of PCs in acute brain slices. Dysregulation of zebrin-II cell subtypes was the predominant signal in PCs of SCA7-266Q mice and was associated with the loss of zebrin-II striping in the cerebellum at motor symptom onset. We furthermore demonstrated zebrin-II stripe degradation in additional mouse models of polyglutamine ataxia and observed decreased zebrin-II expression in the cerebella of patients with SCA7. Our results suggest that a breakdown of zebrin subtype regulation is a shared pathological feature of polyglutamine ataxias.
A peptide targeting outer membrane protein A of
Acinetobacter baumannii
exhibits antibacterial activity by reducing bacterial pathogenicity
Authors: Zhao Hui , Hu Yue , Nie Dan , Li Na , Chen Zhou , Zhou Shan , Li Mingkai , Xue Xiaoyan
Published: November 2024

The World Health Organization has classified multidrug-resistant (MDR)
Acinetobacter baumannii
as a significant threat to human health, necessitating the urgent discovery of new antibacterial drugs to combat bacterial resistance. Outer membrane protein A of
A. baumannii
(AbOmpA) is an outer membrane-anchored β-barrel-shaped pore protein that plays a critical role in bacterial adhesion, invasion, and biofilm formation. Therefore, AbOmpA is considered a key virulence factor of
A. baumannii
. Herein, we screened three phage display peptide libraries targeting AbOmpA and identified several peptides. Among them, P92 (amino acid sequence: QMGFMTSPKHSV) exhibited the highest binding affinity with AbOmpA, with a KD value of 7.84 nM.
In vitro
studies demonstrated that although P92 did not directly inhibit bacterial growth, it significantly reduced the invasion and adhesion capabilities of multiple clinical isolates of MDR
A. baumannii
and concentration-dependently inhibited biofilm formation by acting on OmpA. Furthermore, the polymerase chain reaction results confirmed a significant positive correlation between the antibacterial effect of P92 and OmpA expression levels. Encouragingly, P92 also displayed remarkable therapeutic efficacy against
A. baumannii
infection in various models, including an
in vitro
cell infection model, a mouse skin infection model, and a mouse sepsis model. These results highlight P92 as a novel and highly effective antimicrobial molecule specifically targeting the virulence factor AbOmpA.
Therapeutic drug monitoring of posaconazole delayed-release tablets and injections in pediatric patients
Authors: Wu Juan , Chen Changcheng , Luo Chengjuan , Ning Botao , Liu Yue , Li Zhuo , Zhang Shunguo , Li Zhiling
Published: November 2024

This study aimed to investigate the dose and trough concentration (
C
min
) of posaconazole delayed-release tablets and injections, and their correlation with efficacy and safety in pediatric patients. Patients younger than 18 years old received posaconazole delayed-release tablets or injections for prophylaxis or treatment of invasive fungal disease (IFD). Blood samples were collected to determine the plasma
C
min
s, and dose regimen adjustments were made if necessary. Clinical data were collected. A total of 210
C
min
s of 113 pediatric patients were detected. The median
C
min
s were 1.0 and 1.3 mg/L for tablets and injections, respectively (
P
< 0.05). The median doses required to achieve the target
C
min
were about 6.0 mg/kg of body weight/day, and no statistical difference was observed between different age groups, formulations, or indications (
P
> 0.05). Concomitant treatment of tacrolimus and diarrhea were found to affect
C
min
s of tablets, while age, gender, and BMI were found to be correlated with
C
min
s of injections. IFD breakthrough occurred in 9.2% of patients with a median
C
min
s of 0.74 mg/L for prophylaxis, and infection progression occurred in 43.2% of patients with a median
C
min
s of 0.97 mg/L for treatment, respectively. Transaminitis was the most common adverse event. Posaconazole delayed-release tablets and injections are safe for prophylaxis and treatment of IFD in pediatric patients. An empirical initial dose of 6.0 mg/kg of body weight/day is appropriate for prophylaxis, while a higher dose should be required for the treatment of IFD. It is necessary to adjust the dose regimen according to the results of therapeutic drug monitoring.

This study is registered with
chictr.gov.cn
under identifier ChiCTR2300070008.
In vivo
emergence of resistance to ceftazidime/avibactam through modification of chromosomal AmpC β-lactamase in
Klebsiella aerogenes
Authors: Rodríguez-Pallares Salud , Blanco-Martín Tania , Lence Emilio , Aja-Macaya Pablo , Sánchez-Peña Lucía , González-Pinto Lucía , Rodríguez-Mayo María , Fernández-González Ana , Galán-Sánchez Fátima , Beceiro Alejandro , González-Bello Concepción , Bou Germán , Arca-Suárez Jorge
Published: November 2024

We describe the
in vivo
emergence of resistance to ceftazidime/avibactam via modification of AmpC in a clinical
Klebsiella aerogenes
isolate during therapy with this combination. Paired ceftazidime/avibactam-susceptible/resistant isolates were obtained before and during ceftazidime/avibactam treatment. Whole genome sequencing revealed a differential mutation in AmpC (R148W) in the ceftazidime/avibactam-resistant isolate. Molecular cloning and structural studies confirmed the impact of this substitution, which affects the architecture of the H10 helix, on the evolved resistant phenotype.
Does strain-level persistence of lactobacilli in long-term back-slopped sourdoughs inform on domestication of food-fermenting lactic acid bacteria?
Authors: Pham Vi D. , Xu Zhaohui S. , Simpson David J. , Zhang Justina S. , Gänzle Michael G.
Published: November 2024

Sourdoughs are maintained by back-slopping over long time periods. To determine strain-level persistence of bacteria, we characterized four sourdoughs from bakeries over a period of 3.3, 11.0, 18.0, and 19.0 years. One sourdough included isolates of
Levilactobacillus
spp. and
Fructilactobacillus
spp. that differed by fewer than 10 single-nucleotide polymorphisms (SNPs) from the isolates obtained 3.3 years earlier and thus likely represent the same strain. Isolates of
Levilactobacillus parabrevis
differed by 200–300 SNPs; their genomes were under positive selection, indicating transmission from an external source. In two other sourdoughs, isolates of
Fructilactobacillus sanfranciscensis
that were obtained 11 and 18 years apart differed by 19 and 29 SNPs, respectively, again indicating repeated isolation of the same strain. The isolate of
Fl. sanfranciscensis
from the fourth sourdough differed by 45 SNPs from the isolate obtained 19 years previously. We thus identified strain-level persistence in three out of four long-term back-slopped sourdoughs, making it possible that strains persisted over periods that are long enough to allow bacterial speciation and domestication.

IMPORTANCE

The assembly of microbial communities in sourdough is shaped by dispersal and selection. Speciation and domestication of fermentation microbes in back-slopped food fermentations have been documented for food-fermenting fungi including sourdough yeasts but not for bacteria, which evolve at a slower rate. Bacterial speciation in food fermentations requires strain-level persistence of fermentation microbes over hundreds or thousands of years. By documenting strain-level persistence in three out of four sourdoughs over a period of up to 18 years, we demonstrate that persistence over hundreds or thousands of years is possible, if not likely. We thus not only open a new perspective on fermentation control in bakeries but also support the possibility that all humans, despite their cultural diversity, share the same fermentation microbes.
Future Research Directions for an Afrocentric E-Learning System
Authors: Chan Gerry , Ataguba Grace , Banire Bilikis , Frempong George , Orji Rita
Published: November 2024

In this article, we present the iterative design of an Afrocentric e-learning system. To ensure cultural inclusivity and promote effective student learning, gamification principles, frameworks, and theories are integrated into the design. So far, an interactive prototype has been created and a user evaluation is on the research agenda. This work contributes to designing for underrepresented populations and serves as a lens to examine user preferences when user behaviours are tracked during user evaluation. This is the first step towards developing an AI-driven adaptive and socio-culturally sensitive e-learning system that uses machine learning models to control personalized content delivery, learning adaptation, and user engagement.
Integrated Deep Learning Model for the Detection, Segmentation, and Morphologic Analysis of Intracranial Aneurysms Using CT Angiography
Authors: Yang Yi , Chang Zhenyao , Nie Xin , Wu Jun , Chen Jingang , Liu Weiqi , He Hongwei , Wang Shuo , Zhu Chengcheng , Liu Qingyuan
Published: November 2024

An integrated deep learning model was developed and validated for the detection, segmentation, and morphologic measurement of intracranial aneurysms on head CT angiography images.
Prostate Cancer Knowledge and Attitude Toward Screening Practices Among Men 40 and Over in the Jazan Region, Saudi Arabia
Authors: Elyas Anas , Mahfouz Mohamed Salih , Suwaydi Abdulkarim Zain Ahmed , Alotayf Osama Ali , Tayri Abdullah Omar , Daghriri Bandar Fahad , Daghreeri Abdulrahman Abdu , Hattan Faisal Ahmed , Akkam Mohammed Maqbul
Published: November 2024

Background: Prostate cancer (PCa) is the second most prevalent malignancy among males and ranks as the fifth primary cause of mortality worldwide, underscoring its substantial impact on public health. Notably, there is a lack of research focused on PCa within the context of Saudi Arabia. Consequently, this study endeavours to elucidate the knowledge, attitudes, and screening practices related to PCa among males in Jazan, Saudi Arabia.

Methodology: A cross‐sectional survey was carried out on males over 40 years old in the Jazan region of Saudi Arabia between December 2022 and March 2023. The survey used a web‐based questionnaire containing questions about sociodemographic characteristics, PCa knowledge, and attitudes toward screening practices. Descriptive and inferential statistical analysis evaluated the participants’ knowledge and attitudes toward PCa screening.

Results: Out of the 468 male participants aged over 40 years, approximately 44% demonstrated limited awareness about PCa. Intriguingly, 60.3% of participants showed a positive attitude toward PCa screening. Moreover, 35.7% reported consulting a urologist for screening purposes. Furthermore, 25.6% had undergone a prostate‐specific antigen (PSA) test, with the predominant rationale (25.8%) being medical advice. Multivariate analysis revealed that being married (adjusted odds ratio (AOR) = 4.5, p = 0.011) and having a family history of PCa (AOR = 4.6, p = 0.001) were significant predictors of heightened PCa awareness. Concurrently, a history of PCa (AOR = 6.8, p = 0.001) and holding a postgraduate qualification (AOR = 5.5, p = 0.024) emerged as significant determinants of proactive practices toward PCa.

Conclusion: The results revealed a significant lack of knowledge regarding PCa and the screening practices associated with it among the study participants. These results emphasize the urgent need to provide men with comprehensive information about the benefits and limitations of PCa screening in order to enable them to make more informed decisions.
Translation and Cross‐Cultural Adaptation of the Toronto Extremity Salvage Score (TESS) for Latin American Spanish–Speaking Patients With Limb Sarcoma
Authors: Ceballos Oscar , Cabrolier Jorge , Chehade Begoña , Hardoy Francisco , Cortes Francisco , Tolosa Ricardo , Wevar Orlando
Published: November 2024

Background and Objectives: This study aims to translate and culturally adapt the Toronto Extremity Salvage Score (TESS) for Latin American Spanish–speaking patients, enhancing the tool’s accessibility for evaluating postsurgical functional outcomes in sarcoma patients across Latin America.

Methods: The TESS questionnaires for lower extremity (LE) and upper extremity (UE) were translated and adapted following international guidelines. The process included forward and backward translation, expert committee review, and pretesting with cognitive interviewing. Patients treated for bone or soft tissue tumors in LE or UE were recruited to complete the adapted questionnaires. Test–retest reliability was evaluated by having participants complete the questionnaire again 2 weeks after the initial assessment.

Results: A total of 89 participants completed the questionnaires. The study found high internal consistency, with Cronbach’s alpha values reaching 0.9437 for LE and 0.9402 for UE. An agreement rate of 98.4% for the global score of TESS‐LE (95% confidence interval [CI]: 0.909–1.059) and 93.9% for TESS‐UE (95% CI: 0.882–0.995) was observed, demonstrating strong test–retest reliability.

Conclusions: The Latin American Spanish version of TESS for both lower and upper extremities is a reliable and culturally appropriate tool for assessing physical function in limb sarcoma patients. Further validation across diverse Latin American populations is encouraged to strengthen its broad applicability.
Supplementary Figure S1 from NAD+ Metabolic Enzyme Inhibitor as Radiosensitizer for Malignant Meningioma and its Modulation of P53 Expression
Authors: Lv Yifan , Deng Yuxuan , Feng Jie , Liu Jinqiu , Yang Mingxu , Pu Zhuonan , Zhang Shaodong , Wu Zhen , Ji Nan , Park Deric M. , Hao Shuyu
Published: November 2024

Supplementary Figure S1
Supplementary Table 2 from Spatial Multiomics Reveals Intratumoral Immune Heterogeneity with Distinct Cytokine Networks in Lung Cancer Brain Metastases
Authors: Christensson Gustav , Bocci Matteo , Kazi Julhash U. , Durand Geoffroy , Lanzing Gustav , Pietras Kristian , Gonzalez Velozo Hugo , Hagerling Catharina
Published: November 2024

Descriptive statistics of the distances from each tumor core (TC) region of interest and the nearest immune infiltrate, measured using QuPath on the digital scan of the microscope slide. All distances are given in micrometers.
Supplementary Table 1 from Spatial Multiomics Reveals Intratumoral Immune Heterogeneity with Distinct Cytokine Networks in Lung Cancer Brain Metastases
Authors: Christensson Gustav , Bocci Matteo , Kazi Julhash U. , Durand Geoffroy , Lanzing Gustav , Pietras Kristian , Gonzalez Velozo Hugo , Hagerling Catharina
Published: November 2024

Molecular characteristics of the primary tumor and the brain metastases in our patient cohort (first sheet), as well as PDL1 expression and details of treatment for the patients in our lung cancer brain metastasis cohort (second sheet). BrM, Brain Metastasis; KRAS, Kirsten rat sarcoma virus; PDL1, Programmed death-ligand; PT, Primary Tumor; TP53, Tumor protein P53; RefSeq, NCBI Reference Sequence Database; HGCS, Guman Gene Connectome Server; HGVS, Human Genome Variation Society; c, reference sequence based on a protein coding RNA; p, reference sequence based on a protein (amino acid) sequence.
Supplementary Figure S8 from Spatial Multiomics Reveals Intratumoral Immune Heterogeneity with Distinct Cytokine Networks in Lung Cancer Brain Metastases
Authors: Christensson Gustav , Bocci Matteo , Kazi Julhash U. , Durand Geoffroy , Lanzing Gustav , Pietras Kristian , Gonzalez Velozo Hugo , Hagerling Catharina
Published: November 2024

S8. Differentially Expressed Genes between TI and TC ROIs.
Supplementary Figure S4 from Spatial Multiomics Reveals Intratumoral Immune Heterogeneity with Distinct Cytokine Networks in Lung Cancer Brain Metastases
Authors: Christensson Gustav , Bocci Matteo , Kazi Julhash U. , Durand Geoffroy , Lanzing Gustav , Pietras Kristian , Gonzalez Velozo Hugo , Hagerling Catharina
Published: November 2024

S4. Immune signatures in the lung cancer brain metastasis cohort.
Figure 3 from Spatial Multiomics Reveals Intratumoral Immune Heterogeneity with Distinct Cytokine Networks in Lung Cancer Brain Metastases
Authors: Christensson Gustav , Bocci Matteo , Kazi Julhash U. , Durand Geoffroy , Lanzing Gustav , Pietras Kristian , Gonzalez Velozo Hugo , Hagerling Catharina
Published: November 2024

Immune and metastatic tumor cell interactions. A, Representative images showing the nearest MTC to each CD8+ and CD68+ cell visualized using PhenoptrReports. B, Boxplot of distance to nearest MTC for each immune cell calculated using SPIAT, grouped by immune cell type and patient. n = 2 applies to all patients except for patient 24, in which case n = 3. The central line of the boxplot includes the median; the boundaries of the box correspond to the first and third quartiles (25th and 75th percentiles). The length of the whisker corresponds to at most 1.5 multiplied by the IQR, measured from the edge of the hinge. Outliers are shown as crosses.
Figure 2 from Spatial Multiomics Reveals Intratumoral Immune Heterogeneity with Distinct Cytokine Networks in Lung Cancer Brain Metastases
Authors: Christensson Gustav , Bocci Matteo , Kazi Julhash U. , Durand Geoffroy , Lanzing Gustav , Pietras Kristian , Gonzalez Velozo Hugo , Hagerling Catharina
Published: November 2024

Lymphoid and myeloid segregation. A, Representative images depicting one TC for each of the four patients. The cores have been stained for CD20 (B cells, in yellow), CD4 (CD4+ T cells, in green), CD8 (CD8+ T cells, in red), CD68 (macrophages, in magenta), FOXP3 (regulatory T cells, in orange), Pan-CK (MTCs, in white), and 4′,6-diamidino-2-phenylindole (nuclei, in blue). B, Abundances of immune cell populations in stroma regions are shown as a percentage of all stroma cells. Each dot corresponds to one TC (n = 9). C, Mean percentage of CIN between reference (y-axis) and target (x-axis) populations across the whole core (tumor and stroma) for each patient, using a search radius of 30 μm. n = 2 applies to all observations except for patient 24, in which case n = 3. D, NMSs for reference (y-axis) and target (x-axis) populations for the whole core. The values are displayed as a mean of the different TCs and a search radius of 30 μm. Gray squares indicate that the NMS was unable to be calculated. DAPI, diamidino-2-phenylindole.
Data from Spatial Multiomics Reveals Intratumoral Immune Heterogeneity with Distinct Cytokine Networks in Lung Cancer Brain Metastases
Authors: Christensson Gustav , Bocci Matteo , Kazi Julhash U. , Durand Geoffroy , Lanzing Gustav , Pietras Kristian , Gonzalez Velozo Hugo , Hagerling Catharina
Published: November 2024

Abstract
The tumor microenvironment of brain metastases has become a focus in the development of immunotherapeutic drugs. However, countless patients with brain metastasis have not experienced clinical benefit. Thus, understanding the immune cell composition within brain metastases and how immune cells interact with each other and other microenvironmental cell types may be critical for optimizing immunotherapy. We applied spatial whole-transcriptomic profiling with extensive multiregional sampling (19–30 regions per sample) and multiplex IHC on formalin-fixed, paraffin-embedded lung cancer brain metastasis samples. We performed deconvolution of gene expression data to infer the abundances of immune cell populations and inferred spatial relationships from the multiplex IHC data. We also described cytokine networks between immune and tumor cells and used a protein language model to predict drug–target interactions. Finally, we performed deconvolution of bulk RNA data to assess the prognostic significance of immune–metastatic tumor cellular networks. We show that immune cell infiltration has a negative prognostic role in lung cancer brain metastases. Our in-depth multiomics analyses further reveal recurring intratumoral immune heterogeneity and the segregation of myeloid and lymphoid cells into distinct compartments that may be influenced by distinct cytokine networks. By using computational modeling, we identify drugs that may target genes expressed in both tumor core and regions bordering immune infiltrates. Finally, we illustrate the potential negative prognostic role of our immune–metastatic tumor cell networks. Our findings advocate for a paradigm shift from focusing on individual genes or cell types toward targeting networks of immune and tumor cells.
Significance:
Immune cell signatures are conserved across lung cancer brain metastases, and immune–metastatic tumor cell networks have a prognostic effect, implying that targeting cytokine networks between immune and metastatic tumor cells may generate more precise immunotherapeutic approaches.
Thrasymachus’ government: an analogy with Machiavelli’s Prince
Authors: Menezes Luiz Maurício Bentim da Rocha
Published: November 2024

In Book I of Plato's Republic, Thrasymachus' proposal opens an important field of analysis within political philosophy, as it is through his discourse that justice becomes associated with the existing government policy in cities, given that, regardless of the political constitution, force always belongs to the governments and it is these who make the laws that it is fair for the governed to obey. This work aims, first, to analyze Thrasymachus' proposal for the whole of political philosophy and, second, to relate this proposal with Machiavelli's The Prince.
Por outro amanhã: a história comparada e novos caminhos para construir o futuro. GRAEBER, David; WENGROW, David. O despertar de tudo: Uma nova história da humanidade. São Paulo: Companhia das Letras, 2022.
Authors: Ramos Gabriela
Published: November 2024

A presente resenha tem como objetivo destacar as principais ideias da obra "O despertar de tudo: Uma nova história da humanidade", evidenciando a influência que a antropologia clássica exerce no trabalho e questionando aspectos contraditórios entre o que defendem os autores de forma geral e pressupostos inseridos de forma desconexa. Apesar da crítica, no atual momento de incerteza e desesperança causadas pela crise ambiental e social que vivemos, a leitura da obra se mostra essencial, especialmente na medida em que nos apresenta novos modos de pensar a sociedade, nos expondo a outras possibilidades de futuro para além do fim do mundo.
As semelhanças e diferenças no discurso sobre História nas plataformas “Brasil Paralelo” e “Guia do Politicamente Incorreto”
Authors: Spinola Marina de Almeida
Published: November 2024

A História passa por constantes mudanças e interpretações. Assim, são construídos revisionismos historiográficos para contemplar os vários debates possíveis. Porém, surgem os revisionismos ideológicos que, em vez de contribuir para reflexões, servem como propaganda para ideais de um grupo ou para o apagamento de responsabilidades sobre violências passadas. O Guia do Politicamente Incorreto e o Brasil Paralelo são duas plataformas de revisionismo ideológico da direita; porém, apesar de terem posicionamentos parecidos, defendem discursos diferentes. Desse modo, é essencial entendermos suas diferenças e semelhanças nos discursos a fim de compreender as intenções e públicos de cada produção.
O iluminismo experimental da Grã-Bretanha
Authors: J. Corfield Penelope , Balieiro Marcos
Published: November 2024

Trata-se de apresentar um panorama geral do iluminismo, tal como ocorreu na Grã-Bretanha dezoitista. Ao longo do texto, esse movimento será mostrado não apenas no que diz respeito a seus aspectos filosóficos, mas também no que toca ao trabalho de cientistas e literatos em geral. O quadro que emergirá a partir daí será o de um período preocupado não apenas com a racionalidade, mas, também, com a inovação, pautada por um conhecimento de matizes fortemente experimentais. Serão apresentadas considerações não apenas acerca de autores e cientistas relevantes, mas, também, acerca da sociedade da época, e da maneira como a prática e as descobertas científicas e intelectuais se influenciavam mutuamente.
A Ilustração Alemã
Authors: Cacciola Maria Lúcia
Published: November 2024

Busca-se apresentar uma discussão sobre as origens do iluminismo alemão, contrapondo os avanços que teriam realizado Leibniz Crusius e Wolff. Salienta-se o elemento particular da sociedade alemã do século XVII e XVIII, de modo a compreender as especificidades da proposta kantiana, a qual se mostra como um processo em desenvolvimento e não acabado de liberdade e autonomia.
O discurso iconográfico como signo das Luzes: o frontispicio da Encyclopédie e a obra de Mestre Ataíde
Authors: França Lilian Cristina Monteiro
Published: November 2024

French Enlightenment thought developed its own iconography. Mestre Ataíde, a prominent Brazilian artist from the colonial period, had engraving manuals in his library, including plates from the Encyclopédie. A comparative analysis of the compositional structure and lines of force of the Frontispiece of the Encyclopédie (Cochin, 1675) and the works Ascension of Christ (1806) and Assumption of the Virgin (1804), both by Mestre Ataíde, suggests the potential presence of Enlightenment symbols in their iconography. Based on this premise, it is expected to contribute to studies that connect French Enlightenment ideals to Brazil in the 19th century.
Le crime d’encyclopédisme: ideias ilustradas e insurreição no Brasil do Século XVIII
Authors: Menezes Edmilson
Published: November 2024

In 18th century Brazil, possessing certain books could be an indication of a transgression. Sharing certain ideas was enough to characterize a sui generis crime: le crime d’encyclopédisme. Luís Vieira da Silva, one of the members of the Insurreição Mineira, was incriminated because of his books. The objective of the work is to present what happened to his library as an important record of both Portuguese policy towards the colonies in America and the aversion to free thought defended, notably, by Enlightenment authors, considered worthy of censorship due to the revolutionary and critical influence of they exercised.
Tocqueville: sobre a erosão do solo social e político democrático
Authors: Reis Helena Esser dos
Published: November 2024

Tocqueville considera que formas autoritárias de governo podem encontrar apoio entre os cidadãos dos “tempos democráticos”. Argumenta que a erosão das condições sociais e políticas não é fruto de uma ação opressiva externa, mas algo que atravessa as relações sociais e políticas. Mantendo formalmente, ou em aparência, certas condições de igualdade e liberdade, que se coadunam aos interesses dos indivíduos, a própria democracia pode abrir espaço para o surgimento de diversas formas de desigualdade e a opressão.  Com base no autor, propomos discutir esse fenômeno que tende a fazer emergir desde dentro da própria democracia formas sociais e políticas violadoras.
Impact of a Chronic Total Occlusion on Outcomes After FFR-Guided PCI or Coronary Bypass Surgery: A FAME 3 Substudy
Authors: Otsuki Hisao , Takahashi Kuniaki , Zimmermann Frederik M. , Mavromatis Kreton , Aminian Adel , Jagic Nikola , Dambrink Jan-Henk E. , Kala Petr , MacCarthy Philip , Witt Nils , Kobayashi Yuhei , Takahashi Tatsunori , Woo Y. Joseph , Yeung Alan C. , De Bruyne Bernard , Pijls Nico H.J. , Fearon William F. ,   on behalf of the FAME 3 Trial Investigators
Published: November 2024

BACKGROUND:

The clinical impact of a chronic total occlusion (CTO) in patients with 3-vessel coronary artery disease undergoing fractional flow reserve–guided percutaneous coronary intervention (PCI) with current-generation drug-eluting stents or coronary artery bypass grafting (CABG) is unclear.

METHODS:

The FAME 3 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 3) compared fractional flow reserve–guided PCI with CABG in patients with 3-vessel coronary artery disease. The primary end point was major adverse cardiac and cerebrovascular events, a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. In this substudy, the 3-year outcomes were analyzed in patients with or without a CTO.

RESULTS:

Of the patients randomized to PCI or CABG in the FAME 3 trial, 305 (21%) had a CTO. In the PCI arm, revascularization of the CTO was attempted in 61% with a procedural success rate of 88%. The incidence of major adverse cardiac and cerebrovascular events at 3 years was not significantly different between those with or without a CTO in both the PCI (15.2% versus 20.1%; adjusted hazard ratio, 0.62 [95% CI, 0.38–1.03];
P
=0.07) and the CABG (13.0% versus 12.9%; adjusted hazard ratio, 0.96 [95% CI, 0.55–1.66];
P
=0.88) arms. In those without a CTO, PCI was associated with a significantly higher risk of major adverse cardiac and cerebrovascular events compared with CABG (adjusted hazard ratio, 1.61 [95% CI, 1.20–2.17];
P
<0.01) but not in those with a CTO (adjusted hazard ratio, 1.21 [95% CI, 0.64–2.28];
P
=0.56;
P
interaction
=0.31).

CONCLUSIONS:

The presence of a CTO did not significantly impact the treatment effect of PCI versus CABG at 3 years in patients with 3-vessel coronary artery disease.

CLINICAL TRIAL REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02100722.
Risk of Major Adverse Cardiovascular Outcomes in Families With MASLD: A Population-Based Multigenerational Cohort Study
Authors: Ebrahimi Fahim , Ebrahimi Ramin , Hagström Hannes , Sundström Johan , Sun Jiangwei , Bergman David , Forss Anders , Ludvigsson Jonas F.
Published: November 2024

BACKGROUND:

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a risk factor for cardiovascular disease. However, whether family members of individuals with MASLD also share an increased cardiovascular risk is unknown.

METHODS:

We created a nationwide multigenerational cohort study identifying all family members of Swedish adults diagnosed with biopsy-proven MASLD (1969−2017) and of matched general population comparators (by age, sex, calendar year, and county of residence). We calculated incidence rates and used Cox models to calculate adjusted hazard ratios (aHRs) and 95% CIs for incident major adverse cardiovascular events (MACE), including acute myocardial infarction, stroke, hospitalization for heart failure, or cardiovascular death. Cox models were adjusted for education, country of birth, diabetes, hypertension, obesity, dyslipidemia, chronic kidney disease, chronic obstructive pulmonary disease, and the Charlson comorbidity index.

RESULTS:

We identified 22 267 MASLD first-degree relatives (FDRs; parents, siblings, and offspring) and 5687 MASLD spouses, as well as 118 056 comparator FDRs and 29 389 comparator spouses without earlier cardiovascular disease. Overall, the mean age was 41.8 years (SD, 18.0), and 51.5% were females. Over a median of 24.6 years, the incidence rate for MACE was higher in MASLD FDRs than in comparator FDRs (65.0 versus 62.5/10 000 person-years; aHR, 1.06 [95% CI, 1.01−1.11]). MASLD FDRs had higher rates of acute myocardial infarction (23.0 versus 20.9/10 000 person-years; aHR, 1.09 [95% CI, 1.01−1.18]) and cardiovascular death (aHR, 1.09 [95% CI, 1.01−1.18]). Across generations of FDRs, the risk of MACE was uniformly increased with no differences by relationship (ie, parents, siblings, and offspring;
P
interaction
>0.05). MASLD spouses were also at an increased risk of MACE (117.6 versus 103.5/10 000 person-years; aHR, 1.09 [95% CI, 1.01−1.18]).

CONCLUSIONS:

First-degree relatives of individuals with biopsy-proven MASLD are at slightly higher risk of incident MACE, but absolute risks do not support early screening for cardiovascular disease. Shared lifestyle factors may be the main contributors, as spouses of MASLD patients also had higher risks of MACE.
Stakeholder Perspectives on a Heart Failure With Reduced Ejection Fraction Polypill: A Multi-Center Mixed Methods Study
Authors: Chen Justin C. , DeJong Colette , Agarwal Mansi , Hairston Amaris M. , Durstenfeld Matthew S. , McKay Virginia , Huffman Mark D. , Hsue Priscilla Y. , Agarwal Anubha
Published: November 2024

BACKGROUND:

A polypill containing all 4 classes of guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF) has been proposed to change the heart failure treatment paradigm. The acceptability, appropriateness, and feasibility of a HFrEF polypill-based strategy are unknown. The purpose of this study was to elicit patients’ and providers’ priorities in the design of HFrEF polypills.

METHODS:

From April 2023 to December 2023, we conducted a convergent parallel mixed-methods study at Washington University in St. Louis, the University of California, San Francisco, and the American College of Cardiology. We administered physician surveys containing adapted implementation outcome measures to elicit physicians’ perspectives on the acceptability, feasibility, and appropriateness of a HFrEF polypill (Likert scale ranging from 1 [low] to 5 [high]). We used a purposive sampling frame to select patients and physicians for in-depth interviews. Using semi-structured interview guides, we elicited participants’ perspectives on current HFrEF care, HFrEF polypill design, and supportive strategies. The Consolidated Framework for Implementation Research v2.0 guided thematic analysis.

RESULTS:

Of the 214 survey respondents across the United States, physicians agreed that HFrEF polypills are highly acceptable (mean [SD], 4.2 [0.7]), highly appropriate (4.1 [0.8]), and highly feasible (4.1 [0.7]). Key themes from 9 patient and 22 provider interviews included the following: (1) current determinants of HFrEF care, including medication adherence, variations in clinical practice, and health care access, (2) provider-level differences in preferred HFrEF polypill design, (3) cost and equity considerations in the implementation of HFrEF polypills, and (4) research priorities for evaluating polypill effectiveness and implementation.

CONCLUSIONS:

A HFrEF polypill-based strategy was viewed as highly acceptable, appropriate, and feasible by patients and physicians. Participants described key priorities in HFrEF polypill design, titratability, and potential impacts on health equity that will directly inform future randomized controlled trials.