bluuebunny/crossref_metadata_2025 huggingface dataset:
Prophylactic IL-23 blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy
Authors: Ju Mingyi , Zhang Jiaojiao , Deng Zhuoyuan , Wei Minjie , Ma Lianghua , Chen Ting , Zhao Lin
Published: August 2024

Background

Immune-related adverse events (irAEs), characterized by targeted inflammation, occur in up to 60% of patients with melanoma treated with immune checkpoint inhibitors (ICIs). Evidence proved that the baseline peripheral blood profiles of patients at risk for severe irAEs development paralleled clinical autoimmunity. Interleukin (IL)-23 blockade with risankizumab is recommended for cases that are suffering from autoimmune disease, such as autoimmune colitis. However, currently, the role of IL-23 in irAEs onset and severity remains poorly understood.

Methods

The pro-inflammatory cytokines most associated with severe irAEs onset were identified by retrospective analysis based on GSE186143 data set. To investigate the efficacy of prophylactic IL-23 blockade administration to prevent irAEs, refer to a previous study, we constructed two irAEs murine models, including dextran sulfate sodium salt (DSS)-induced colitis murine model and a combined-ICIs-induced irAEs murine model. To further explore the applicability of our findings, murine models with graft-versus-host disease were established, in which Rag2−/−Il2rg−/−mice were transferred with human peripheral blood mononuclear cells and received combined cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed cell death protein-1 (PD-1) treatment. Human melanoma cells were xenografted into these mice concomitantly.

Results

Here we show that IL-23 was upregulated in the serum of patients suffering from irAEs after dual anti-CTLA-4 and anti-PD-1 treatment, and increased as a function of irAEs severity. Additionally, Augmented CD4+Tems may preferentially underlie irAEs onset. Treating mice with anti-mouse IL-23 antibody concomitantly with combined CTLA-4 and PD-1 immunotherapy ameliorates colitis and, in addition, preserves antitumor efficacy. Moreover, in xenografted murine models with irAEs, prophylactic blockade of human IL-23 using clinically available IL-23 inhibitor (risankizumab) ameliorated colitis, hepatitis and lung inflammation, and moreover, immunotherapeutic control of tumors was retained. Finally, we also provided a novel machine learning-based computational framework based on two blood-based features—IL-23 and CD4+Tems—that may have predictive potential for severe irAEs and ICIs response.

Conclusions

Our study not only provides clinically feasible strategies to dissociate efficacy and toxicity in the use of combined ICIs for cancer immunotherapy, but also develops a blood-based biomarker that makes it possible to achieve a straightforward and non-invasive, detection assay for early prediction of irAEs onset.
Evolving role of the health system CIO: perspectives from 33 health systems
Authors: Kim Dae Hyun , Lemak Christy , Jones Douglas , Pena Dalton
Published: August 2024

Objectives

This study explores the evolving position of the health system chief information officer (CIO) by identifying new core roles for success.

Methods

An advisory board of industry executives and system leaders guided the study. Purposeful sampling was used to invite chief executive officer and CIOs from 65 not-for-profit US health systems to participate. Interviews were conducted with 51 executives from 33 different systems, using a comprehensive interview topic guide. Interview transcripts were analysed using NVivo software, focusing on themes related to the evolving role of the health system CIO.

Results

Analyses revealed three main themes, with the CIO as (1) enabler of strategic change and transformation, (2) strategic developer of technology and leadership talent and (3) driver of organisational culture.

Discussion

The role of CIO has undergone transformation from technology and information system management to strategic leadership within the broader health system context. It highlights the importance of comprehensive business knowledge for CIOs and the need for other C-suite executives to have a deeper understanding of information and technology.

Conclusion

As healthcare continues to evolve, the role of the CIO is expected to expand further, requiring a blend of technical and strategic business skills. This evolution presents opportunities for health systems to enhance their leadership development programmes, preparing leaders for the complexities of the contemporary health system sector.
Delayed development of spinal stenosis at the spinal cord stimulator percutaneous lead entry point: case report and literature review
Authors: Leech Hunter Xavier , Provenzano David Anthony , DeRiggi Leonard , Oliver-Smith David
Published: August 2024

Background

Spinal cord stimulation (SCS) is an efficacious treatment for various refractory chronic pain syndromes. Serious complications including spinal cord compression (SCC) are rare with 19 previous reports which are mainly attributed to fibrotic scar tissue formation at the distal end of the leads at the location of the contacts. We report a case of SCC following SCS implantation at the lead entry location secondary to a delayed progression of spinal canal stenosis.

Case presentation

A patient in her early 70s underwent SCS implantation with adequate therapeutic benefit for approximately 2 years before citing complaints of increasing lower back pain and lower extremity radicular pain. Lumbar spine X-rays excluded lead migration as a causative factor. An MRI of the lumbar spine obtained 30 months following SCS implantation demonstrated a marked interval progression of central canal stenosis secondary to facet and ligamentous hypertrophy manifesting in compression of the spinal cord at the lead entry location. An L1–L2 decompressive laminectomy with hardware removal resulted in the resolution of her symptoms. A literature search conducted with the PubMed database identified previously published cases of SCC following SCS implantation which highlighted the rarity of this complication.

Conclusion

Our case report urges physicians of SCS patients, noting a loss of therapeutic benefit with their device, to investigate new pathologies including SCC. Furthermore, our case highlights clinical symptoms and surgical treatments of SCC. Paddle leads are more commonly implicated in published cases of SCC than percutaneous leads. Lastly, MRI conditionality is critical to identifying cases of SCC.
Lactoferrin in the treatment of interstitial cystitis: a retrospective pilot study
Authors: Rosa Luigi , Cutone Antimo , Ianiro Giusi , Valenti Piera , Paesano Rosalba
Published: August 2024

Interstitial cystitis (IC), defined as a painful bladder syndrome (PBS), is a chronic condition that manifests itself as a suprapubic pain associated with an enhancing of frequency/urgency of urination, and for which there is no cure. Here, we present a retrospective pilot study on women affected from IC/PBS and treated with bovine lactoferrin (bLf). A total of 31 women, affected (20) or unaffected (11) from hereditary thrombophilia (HT), presented the median of 6 episodes of IC/PBS during the 6 months before the study. Treatment consisted of 17 weeks of orally administered Valpalf® capsules, containing bLf plus sodium bicarbonate and citrate. Out of 31 patients, only 3 women had one episode of IC/PBS during the follow-up period, while no episode was observed in 28 women. In the HT group, a significant decrease in both serum IL-6 and D-dimers was found after Valpalf® treatment. Moreover, in Valpalf®-treated women, cystoscopy revealed a global improvement in the appearance of the bladder, especially in term of inflammation/irritation and presence of Hunner ulcers. Even if our results must be corroborated by randomized double-blinded controlled trials on a larger number of patients, our observations indicate that bLf treatment is efficient in relieving IC/PBS symptoms, without side effects.
Building risk assessment methodology for explosive and non-conventional terrorist attacks
Authors: Carbonelli Marco , Quaranta Riccardo , Gaudio Pasquale , Di Giovanni Daniele , Xerri Grace P. , Malizia Andrea , Gratta Laura
Published: August 2024

An original methodology suitable for the assessment of the risk of a terrorist attack in a given site/building is proposed and illustrated for the case of an explosive or non-conventional (Chemical, Biological, Radiological, Nuclear and explosive—CBRNe) attack. The Building Risk Assessment Methodology discussed in this paper represents the arrival point of a detailed analysis and research carried out during the past 5 years and provides the synthesis of different results obtained for the assessment of Building Threats and Building Vulnerabilities. These two assessments were discussed in detail in other already published papers. The effort presented in this work is to deploy a risk and impact assessment technique for buildings that can be adopted in any operating scenario in the presence of explosive or non-conventional threats. The main target of the methodology is to provide a sufficiently accurate estimate of the risk in a simple fashion. The methodology allows to manage the different kinds of risk related to the explosive and non-conventional threats, and it is useful for identifying a ranking of risks for different buildings in different portions of territory and for prioritizing actions and investments in preparedness, protection and resilience of critical areas and critical infrastructures. In the paper, the results of two different case studies for three different threats will be considered, analyzed and compared.
Effect of Track Spectrum on the Dynamic Responses of Passenger–Train–Bridge System
Authors: Wang Shaoqin , Wan Xing , Xu Chuanqiang , Qiao Hong
Published: August 2024

To study the influence of the Chinese high-speed railway ballastless track spectrum and the German low-interference spectrum on riding comfort, a long-span highway-railway suspension bridge is studied as an example, and a passenger–train–bridge coupling model is established based on the structural dynamics. The vibration responses of the passenger–train–bridge system during the CRH2C train running on the bridge are studied by a combination of the self-written computer program and general finite element software, considering the hunting movement, and the riding comfort of trains and passengers is evaluated using [Formula: see text] and ISO-2631 standard, respectively. The results show that track irregularity has a few effects on the lateral vibration of the bridge. Compared with the German low-interference spectrum, the Chinese high-speed railway ballastless track spectrum has less exciting effects on the vibration of the passenger–train–bridge system and better riding comfort. Passengers in the middle of the train and on the middle seats of the same train have better riding comfort, and with the increase of train speed, the riding comfort of passengers will gradually reduce. Instead of passenger responses, the riding comfort classification based on the car body is overestimated.
Elastic–Plastic Buckling of Scaled Model of Radial Ring-Stiffened Shallow Spherical Shells Based on Energy Method
Authors: Yu Wei , Guo Xincheng , Yang Yanguo , Zhang Lu , Zhao Shenghua , Zhu Wanxu
Published: August 2024

Stiffened shallow spherical shell has the advantages including high strength and light weight, which allows it to be widely applied in areas including aerospace, submarine and civil engineering. For the design of scaled model for elastic–plastic buckling of a large radially–circumferentially stiffened shallow spherical shell under uniformly distributed pressure and for the purpose of similarity prediction, the similarity relation of the elastic–plastic buckling coefficient of the shell is derived; then by using the dense stiffening theory and considering the dual nonlinearity of geometry and materials, the energy increment formula for the structure under uniformly distributed external pressure is established; next, based on the similarity transformation of the energy increment of the structural system, the generalized similarity condition and similarity relation of elastic–plastic buckling of the structure under uniformly distributed external pressure are identified. Based on the scaling and equivalence of tensile–compressive stiffness and bending stiffness, the distortion scaled model for the prototype is designed. Through numerical simulation, the distortion similarity prediction for elastic–plastic buckling under uniformly distributed pressure of the radially–circumferentially stiffened shallow spherical shell that has square-shaped dimple defects has been conducted; based on the derived similarity relation of elastic–plastic buckling of stiffened plate, the similarity prediction for the elastic–plastic buckling of orthogonally stiffened plate in the plane under unidirectional uniformly distributed pressure has been conducted. The results indicate that the load–displacement curve, buckling load, and buckling mode of the distortion similarity scaled model, combined with the established radial displacement scaling factor expression, the scaling relation of tension–compression stiffness, and the similarity relation of buckling mode, can effectively predict the elastic–plastic buckling characteristics of its prototype structure. The research results can provide theoretical reference for the design and test of the scaled model with distortion of elastic–plastic buckling of similar stiffened large shell structures.
Stochastic Vibration Responses of Functionally Graded Three-Stage Conical–Cylindrical Combined Shell Structure Subjected to Various Stationary Stochastic Excitations
Authors: Ni Bo , Xi Lifeng
Published: August 2024

This paper proposed a theoretical model for analyzing the stochastic vibration responses of functionally graded three-stage conical–cylindrical combined shell structure (FG-TSCCCSS) subjected to various stationary stochastic excitations. The theoretical model is established by employing the differential quadrature method in conjunction with pseudo excitation method (PEM) in the framework of FSDT. The material property parameters of FG-TSCCCSS along the thickness direction are ascertained based on four-parameter power–law distributions in terms of volume fractions of constituents of FGMs. The FG-TSCCCSS mainly consists of three conical shell segments with different tapers and one cylindrical shell segment. The coupling between adjacent shell segments is achieved by means of common nodes. The various boundary conditions of FG-TSCCCSS are simulated by applying the penalty function method. Based on the above model, the convergence analysis of the established model for determining the value of the penalty factor and the number of differential quadrature nodes first. Then, the precision and reliability of the proposed numerical model are verified by comparing the present solutions with the results of literature works and finite element software. Finally, the stochastic vibration response analysis of FG-TSCCCSS is carried out by investigating the influences of power–law distribution, power–law exponent, boundary condition, stochastic excitation type and taper angle on the natural frequency and PSD acceleration response of FG-TSCCCSS. The paper can provide the theoretical reference and numerical tool for the random vibration response evaluation of combined shell structures of various engineering application fields.
Scalar shell dynamics of quantum-corrected Schwarzschild black hole surrounded by quintessence field
Authors: Hussain Arif , Javed Faisal , Fatima Ghulam , Tchier Fairouz , Nozima Shoakhmedova , Mustafa Ghulam
Published: August 2024

With a Kiselev spacetime around Schwarzschild black holes that have undergone quantum correction, the goal of this work is to examine the geometric structure of a thin-shell. In order to do so, we take into consideration black hole solutions and match the inner Minkowski spacetime using a cut and paste method. Our findings indicate that the use of a phantom-like equation of state, such as quintessence, dark energy, and phantom energy, in the linearized radial perturbation technique shows stable thin-shell configurations that lie beyond the outer manifold’s predicted position of the event horizon. Moreover, we discover that the characteristics of the black hole solutions have a significant impact on the thin-shell stability. We examine the behavior of a thin-shell configuration with massless and massive scalar fields by using Klein–Gordon’s equation of motion. According to our findings, the thin-shell system dynamics are significantly influenced by the scalar field, resulting in interesting phenomena including expansion and collapse. These results provide fresh light on the behavior of black hole solutions by providing important insights into the interaction between quantum correction factors related to scalar fields and thin-shell dynamics. In particular, our research suggests that the quantum correction parameter decreases the stable configuration of a Schwarzschild black hole encircled by a quintessence field.
Design of Nonlinear Delay Differential System for Analyzing Vulnerabilities in Nanoscale Hardware Implants: A Deep Dive into Intelligent Computing Networks
Authors: Asif Raja Muhammad Junaid Ali , Masood Zaheer , Hussain Ijaz , Zameer Aneela , Mehmood Ammara , Raja Muhammad Asif Zahoor
Published: August 2024

In the annals of contemporary innovation, the study of miniature marvels nanoscale hardware implants emerged as a pivotal instrument, scarcely perceptible to the naked eye, embodies a prowess of cutting-edge technologies and clandestine intrigue. The objective of this research is to introduce a time delay nonlinear system for nanoscale hardware implants vulnerabilities that portray the exploitation of a system by utilizing the stupendous knacks of advanced deep bidirectional long short-term memory (LSTM) networks for time series predictions. Firmware-level bugs present the potential for escalating privileges and executing of code remotely beneath the operating system, allowing for infiltration or complete intervention within a computer system. The designed deep bidirectional LSTM is configured to precisely predict and forecast the dynamic states of time delay differential system, offering a robust framework for mimicking delays that commonly manifest in the real cyber-physical systems. To orchestrate the system compromises in real scenarios through the activation of bugged hardware, time delay factors [Formula: see text] and [Formula: see text] are introduced to account the time delays necessary for exploiting the bugged and patched nodes, respectively. Synthetic data is generated to train the LSTM network for all scenarios of the model for the dynamics of bugged, compromised, patched nodes and these acquired information is used for training, testing and validation purposes regarding exploitation of the bugged hardware. Comparative analysis on exhaustive simulations revealed a minimal difference between the LSTM’s predictions and those from the numerical outcomes with MSE in the range of [Formula: see text], underscoring the network’s effectiveness, robustness and stability in modeling complex system dynamics of hardware vulnerabilities.
The impulsive vaccination in an SVIS diffusive model
Authors: Luo Zipeng , Ahn Inkyung , Lin Zhigui
Published: August 2024

This paper examines a reaction-diffusion problem with impulses, which presents a susceptible-vaccinated-infected-susceptible (SVIS) epidemic model with impulsive vaccination. First, the existence and uniqueness of the global solution and the disease-free periodic solution have been established. Second, by considering the principal eigenvalue, the asymptotic behavior of the disease-free periodic solution and the sufficient condition for the persistence of diseases are given, in addition, the mono-tonicity of the principal eigenvalue is investigated. Third, the periodic state of the endemic disease has been explored when vaccination is not completely effective. Finally, the numerical simulations presented reveal the impacts of the infection rate and impulses, and demonstrate that effective vaccination is a reliable way to control the spread of diseases.
Coexistence states for a Lotka–Volterra competitive model with aggressive movement strategy
Authors: Dong Yaying , Zhou Xueqian , Li Shanbing
Published: August 2024

This paper is concerned with a model of reaction–diffusion–advection equations arising in ecology. The equations model a situation in which the foreign species and the native species are both assumed to be competing for space in the same ecological niche, and the foreign species is just random diffusion while the native species is “braver” — a combination of random diffusion and a directed movement up the gradient of the foreign species. Our aim is to give the necessary and sufficient conditions for the coexistence of the foreign species and native species. For this, we first establish an a priori estimate result. Then we apply eigenvalue theory and homogenization principle to derive the necessary conditions for the coexistence. Finally, the sufficient conditions for the coexistence are given by using a global bifurcation method.
Dynamics of Nicholson’s blowflies system with spatial heterogeneity, nonlocal operator and delay
Authors: Cao Jianzhi , Li Qiuying , Ma Hongyan
Published: August 2024

In this paper, some properties of the solutions for Nicholson’s blowflies system with nonlocal operator and delay are performed in heterogeneous environment. First of all, the existence and uniqueness of the positive steady-state solution are studied by Lyapunouv–Schmidt reduction method and implicit function theorem. Moreover, the asymptotic behaviors of trivial and nontrivial positive steady-state solutions to the system are also researched through the sub-supersolution method and iterative method. This paper ends with conclusion and discussion.
Identification of Hub Genes and Potential Drugs in Neurofibromatosis 1: An Integrated Bioinformatics Analysis
Authors: Adnan Zoha , Rasheed Muhammad Asif , Khan Sami Ullah , Irfan Areeba , Awwad Fuad A. , Ismail Emad A. A. , Ijaz Khan M. , Kamolova Nargiza
Published: August 2024

Background: Neurofibromatosis Type 1 (NF1) is an autosomal dominant benign tumor predisposition syndrome. Till date very little is known about the pathogenesis and underlying mechanisms of NF1.

Objective: The aim of this study is to use integrated bioinformatics approaches to explore the pathways involved in NF1 onset by identifying hub genes and potential drugs.

Methods: Microarray profiling datasets were used to obtain Differentially Expressed Genes (DEGs) by analyzing in GEO2R. 1730 DEGs were found and STRING analysis revealed Protein–Protein Interaction (PPI) network of these DEGs. Molecular Complex was detected using MCODE plugin of Cytoscape. CytoHubba plugin of Cytoscape was used to declare hub genes based on their degree of connectivity. Lastly, Drug–Gene Interaction Database (DGIdb) and Gene Expression Profiling Interactive Analysis (GEPIA) servers were used to find potential drugs and survival analysis of hub gene, respectively.

Results: Degree of connectivity revealed 10 hub genes out of 1730 DEGs. The survival analysis of these hub genes resulted in three specific genes that are altered in NF1 patients. These three genes are named as BRCA1, KIF11 and LAMA1. Furthermore, 13 potential drugs were also predicted to influence BRCA1, KIF11 and LAMA1 and have therapeutic potential against NF1.

Conclusion: This research opens ways to understanding the pathogenesis of NF1. All three genes are key biological markers and potential drug targets that can be confirmed by further experiments. Moreover, 13 potential drugs were found to work against the disease.
Using Generative AI in Finance, and the Lack of Emergent Behavior in LLMs
Authors: Bhattacharya Ranjeeta , Aoun Mario Antoine
Published: August 2024

In each issue of
Communications
, we publish selected posts or excerpts from the many blogs on our website. The views expressed by bloggers are their own and not necessarily held by
Communications
or the Association for Computing Machinery.

Read more blogs and join the discussion at https://cacm.acm.org/blog.

https://cacm.acm.org/blog

Ranjeeta Bhattacharya on using generative AI to navigate complex regulations, and Mario Antoine Aoun on why there are no emergent properties in large language models.
Syllabus Makeover: Engaging students with multimedia syllabus abstracts
Authors: Samuel Anita
Published: August 2024

Course syllabi are often long, text-heavy documents that learners find difficult to engage with. This paper proposes a syllabus abstract--a one-page infographic-style syllabus that summarizes key course elements and includes interactive elements such as audio and video explanations. This approach aims to make syllabi more visually appealing and accessible for learners.
Pseudomyxoma Peritonei in a Case of Carcinoma Cervix: Subtle Finding With Implications on Management and Prognosis
Authors: Kumari Sarita , Singh Suvidya
Published: August 2024

Pseudomyxoma peritonei (PMP) is a well‐known entity in gastrointestinal and ovarian tumors of mucinous histology. It has important implications on prognosis depending on whether seen in conjunction with a benign or a malignant tumor. In the current report, we describe a case of PMP in a case of advanced endocervical adenocarcinoma of the cervix which was managed surgically.
Solar PV System for Thailand’s International Airport: Site Configuration, Energy Production, and Glare Effect
Authors: Sirisamphanwong Chattariya , Velmurugan Karthikeyan , Ngoenmeesri Rattaporn , Wiengmoon Buntoon , Chindaruksa Sirinuch , Ramachandran Tholkappiyan , Kuppusamy Madhan , Sirisamphanwong Chatchai
Published: August 2024

In this study, Khon Kaen and Phuket International Airports are chosen to analyze the glare effect using ForgeSolar and economic viability. Simulation is performed with fixed tilt and orientation as this study aims to provide glare‐free solar photovoltaic (PV) sites for stakeholders without negotiating the energy generation. The solar site at Khon Kaen International Airport, a potential for temporary afterimage, occurred on KKC‐PV‐F1, KKC‐PV‐G3, KKC‐PV‐G4, KKC‐PV‐G5, KKC‐PV‐G7, KKC‐PV‐G10 for 3,564 min (flight path receptor (FPR)), 2,206 min (air traffic control (ATC)), 1,199 min (ATC), 438 min (ATC), 8,616 min (FPR), 1,743 min (FPR). Following that, low potential for temporary afterimage occurred on KKC‐PV‐G4 and KKC‐PV‐G7 for 2,589 min (ATC) and 5,850 min (FPR), respectively. Apart from these, KKC‐PV‐F1, KKC‐PV‐G1, KKC‐PV‐G2, KKC‐PV‐G6, KKC‐PV‐G8, KKC‐PV‐G9, and KKC‐PV‐G11 are naturally free from the glare effect for FPR and ATC. The Phuket International Airport, HKT‐PV‐G2, HKT‐PV‐G5, HKT‐PV‐R1, and HKT‐PV‐R2 solar PV sites are free from the glare effect. Overall, it is concluded that 3,350 kWp (KKC) and 4,300 kWp (HKT) solar PV systems are qualified as per Federal Aviation Administration (FAA) regulations. Further, economic analysis shows that the payback period of the system is 8.34–9.65 years and the overall benefit of 3,462.11 M฿.
Mosquito Control Strategies and Insecticide Resistance of the Malaria Vector in Urbanized Land Use Types in Suame Municipality, Ghana
Authors: Oppong Jennifer , Avicor Silas Wintuma , Baidoo Philip Kweku , Addo-Fordjour Patrick , Larbi John Asiedu , Akowuah Carlos Frimpong , Boateng Akosua , Essien Isaac Prince , Mensah Gloria
Published: August 2024

Modified landscapes could create breeding habitats for mosquitoes and affect their community structure and susceptibility with implications for their management. Hence, in this study, household mosquito control methods in two urbanized landscapes; industrial and residential human settlements, in Ghana and insecticide susceptibility of the inhabiting Anopheles populations were assessed. Household knowledge and usage pattern of mosquito control methods in the modified landscapes were obtained using a questionnaire. Female adult Anopheles mosquitoes were also subjected to susceptibility tests using mosquito coils (0.08% meperfluthrin, 0.03% dimefluthrin, and 0.3% transfluthrin) and World Health Organization (WHO) insecticide test papers (0.05% deltamethrin, 4% DDT, 0.1% bendiocarb, 0.25% pirimiphos‐methyl, and 5% malathion). Although insecticide‐treated nets and aerosols were used for mosquito control, mosquito coils were the most common and widely preferred household method. The Anopheles mosquitoes were resistant to all the insecticides (mosquito coils and WHO test papers) except pirimiphos‐methyl. Land use type did not affect insecticide resistance, but the insecticide type did. The findings indicate the effect of household insecticide usage practices on local mosquito populations and their implications for effective vector management and disease control in modified landscapes.
Performance Evaluation of High Current Density (HCD) Solid Oxide Electrolysis Cell (SOEC) Hydrogen Production System in Endothermic Mode: An Energy and Exergy Perspective
Authors: Shamsi Syed Shaheryar Ali , Muhammad Hafiz Ali , Song Rak-Hyun , Park Seok-Joo , Lee Seung-Bok , Hong Jong-Eun , Kim Hye-Sung , Joh Dong Woo , Bang Hyung-Joon , Lim Tak-Hyoung , Lee Young Duk
Published: August 2024

Solid oxide electrolysis cell (SOEC) systems operating at high current densities (HCD) are emerging as sustainable and efficient solutions for hydrogen production. However, the performance of the HCD SOEC systems in endothermic mode, which requires significant external energy, is underexplored. Existing studies often lack comprehensive exergy analyses and effective energy management strategies. Accordingly, this study bridges these gaps by developing a 10 kW HCD SOEC system using Aspen HYSYS software and analyzing five different cases with varying fuel composition, external steam utilization, and fuel recirculation. The cases were systematically evaluated using energy and exergy models to assess their potential and operational possibilities in endothermic mode. Simulation results indicated that all designed cases achieved a hydrogen production rate of 0.076 g s−1. Systems without external steam and recirculation exhibited low overall performance. However, integrating external steam and recirculation strategies significantly boosted the overall performance (Case 5 (E‐DR)), achieving the highest lower heating value LHV‐based overall energy and exergy efficiencies of 78.2% and 77.6%, respectively, making it the best configuration under HCD endothermic conditions. In‐depth exergy analysis revealed that the SOEC stack and fuel superheater (FS) units experienced the highest energy dissipation in all cases and presented the highest improvement potential. Additionally, parametric analysis showed that Case 5 (E‐DR) outperformed all other designed cases when operating with higher external steam temperature, external steam factor, and a recirculation ratio of 0.5. This case maintained superior performance up to 54% steam utilization. Beyond this point, the external steam‐supported system without recirculation (Case 3 (NRE‐H)) exhibited superior performance, thus offering a simpler design by eliminating the need for recirculation. Overall, these insights pave the way for the advancements in SOEC technology under HCD endothermic conditions.
A Status Update and the Development Progress of the HTR Code Package
Authors: Zhang Jiaxuan , Liu Chunyu , Li Jiaming , Macián-Juan Rafael
Published: August 2024

As a critical component of the energy sector, the high‐temperature gas‐cooled reactor (HTR) system plays an important role on the road to carbon neutrality. As a flagship of the safety analysis codes, the HTR code package (HCP) has been developed to provide a comprehensive modeling and simulation platform of the HTR system under operational and accidental conditions, especially for pebble bed reactors. A variety of individual legacy HTR computer codes were integrated into a consistent code package using flexible and efficient programing techniques and standards, and the know‐how gained over decades in HTR safety studies was preserved. This paper gives a state‐of‐the‐art overview in HTR studies and presents the new flexible curtain‐based control rod system that has been recently implemented. This method involves flexible manipulation of isotope concentrations and utilizes C++ object‐oriented programing principles while incorporating the legacy codes. Comparative analyses with established codes such as Serpent and ATHLET underscore the precision and reliability of the HCP, thereby enhancing its applicability in HTR design and safety evaluations. Finally, the paper outlines prospective avenues for further advancing the HCP, underscoring its evolving role in shaping the future of HTR development and analysis.
Relationship Between Glycosylated Hemoglobin Variability and the Severity of Coronary Artery Disease in Patients With Type 2 Diabetes Mellitus
Authors: Liu Xinyan , Yang Xiyao , Wu Na
Published: August 2024

Background: Glycosylated hemoglobin (HbA1c) variability is a risk factor for cardiovascular complications in patients with Type 2 diabetes mellitus (T2DM), but its relationship with the severity of coronary artery disease (CAD) is unclear.

Methods: Patients with T2DM who underwent coronary angiography due to angina were enrolled. HbA1c variability was expressed as coefficient of variation (CV), standard deviation (SD), variability independent of mean (VIM), and time in range (TIR). The severity of CAD was expressed by the number of involved vessels and Gensini score. Multivariate regression models were constructed to test the relationship between HbA1c variability, number of involved vessels, and the Gensini score, followed by linear regression analysis.

Results: A total of 147 patients were included. In multivariate analysis, VIM‐HbA1c (OR = 2.604; IQR: 1.15, 5.90; r = 0.026) and HbA1cTIR (OR = 0.13; IQR: 0.04, 0.41; r < 0.001) were independent risk factors for the number of involved vessels. After adjustment, HbA1cTIR (OR = 0.01; IQR: 0.002, 0.04; r < 0.001), SD‐HbA1c (OR = 4.12, IQR: 1.64, 10.35; r = 0.001), CV‐HbA1c (OR = 1.41, IQR: 1.04, 1.92; r = 0.007), and VIM‐HbA1c (OR = 3.26; IQR: 1.43, 7.47; r = 0.003) were independent risk factors for the Gensini score. In the linear analysis, the Gensini score was negatively correlated with HbA1cTIR (β = −0.629; r < 0.001) and positively correlated with SD‐HbA1c (β = 0.271; r = 0.001) and CV‐HbA1c (β = 0.176; r = 0.033). After subgroup analysis, HbA1cTIR was a risk factor for the number of involved vessels. The Gensini score was negatively correlated with HbA1cTIR and positively correlated with SD‐HbA1c at subgroups of subjects with a mean HbA1c ≤ 7%.

Conclusions: Our analysis indicates that HbA1c variability, especially HbA1cTIR, plays a role for the severity of CAD in patients with T2DM. HbA1c variability may provide additional information and require management even at the glycemic target.

Translational Aspects: Studies have shown that HbA1c variability is related to cardiovascular complications. Further, we explore the correlation between HbA1c variability and the severity of CAD. HbA1c variability is a risk factor for coronary stenosis in T2DM. It may be a potential indicator reflecting glycemic control for the prevention and treatment of cardiovascular complications.
Supplementary Figure 6 from Human 3D Ovarian Cancer Models Reveal Malignant Cell–Intrinsic and –Extrinsic Factors That Influence CAR T-cell Activity
Authors: Joy Joash D. , Malacrida Beatrice , Laforêts Florian , Kotantaki Panoraia , Maniati Eleni , Manchanda Ranjit , Annibaldi Alessandro , Hopkins Sarah , Garrobo-Calleja Ianire , Gautrot Julien , Balkwill Frances R.
Published: August 2024

CCL2 produced by fibroblasts activated CCR2/4+ CAR-T cells to induce antigen-dependent cytotoxicity.
Supplementary Figure 4 from Human 3D Ovarian Cancer Models Reveal Malignant Cell–Intrinsic and –Extrinsic Factors That Influence CAR T-cell Activity
Authors: Joy Joash D. , Malacrida Beatrice , Laforêts Florian , Kotantaki Panoraia , Maniati Eleni , Manchanda Ranjit , Annibaldi Alessandro , Hopkins Sarah , Garrobo-Calleja Ianire , Gautrot Julien , Balkwill Frances R.
Published: August 2024

Primary omental fibroblasts induced CAR-T cell cytotoxicity against G164 cells in suspension spheroids.
Figure 4 from Human 3D Ovarian Cancer Models Reveal Malignant Cell–Intrinsic and –Extrinsic Factors That Influence CAR T-cell Activity
Authors: Joy Joash D. , Malacrida Beatrice , Laforêts Florian , Kotantaki Panoraia , Maniati Eleni , Manchanda Ranjit , Annibaldi Alessandro , Hopkins Sarah , Garrobo-Calleja Ianire , Gautrot Julien , Balkwill Frances R.
Published: August 2024

CCL2 produced by fibroblasts activated CCR2/4+ CAR T cells to induce antigen-dependent cytotoxicity. A, Cytokine profile of FB-, G164-, and OvCAR3-conditioned medium using proteome profiler array. FBs from two donors were used for this experiment. Each cytokine is in duplicate. Dots that are not labeled are reference points. B, ELISA showing CCL2 concentrations in monolayers and spheroids of malignant cells with and without FB. Two FB donors were used for this experiment. Data plotted as mean ± SD of two replicates. C and D, IFNγ concentration measured by ELISA (C) and Incucyte CAR T-cell killing assay of G164 spheroids with no treatment (NT) or with recombinant CCL2 (D). E and F, ELISA data showing IFNγ concentration (E) and Incucyte killing assay of G164 spheroids cultured in FB-M with anti-CCL2 (aCCL2) antibody (F). G, Fold change analysis of the expression of T-cell activation markers HLA-DR and CD69 on CCR2+ (top) and CCR4+ (bottom) CAR T cells after CCL2, FB-M, or FB-M with aCCL2 treatments. C, E, and G, Data plotted as mean ± SD for three CAR T-cell donors. Statistics performed using two-way (C and E) and one-way ANOVA (G). D and F, Data shown for one CAR T-cell donor. Representative images at day 3 (left) and quantification (right). Red, dead cells. Scale bar, 400 μm.
Data from Estrogen Induces LCAT to Maintain Cholesterol Homeostasis and Suppress Hepatocellular Carcinoma Development
Authors: He Wenzhi , Wang Min , Zhang Xuechun , Wang Yilan , Zhao Dongli , Li Wenhua , Lei Fang , Peng Min , Zhang Zhonglin , Yuan Yufeng , Huang Zan
Published: August 2024

Abstract
Hepatocellular carcinoma (HCC) is an aggressive disease that occurs predominantly in men. Estrogen elicits protective effects against HCC development. Elucidation of the estrogen-regulated biological processes that suppress HCC could lead to improved prevention and treatment strategies. Here, we performed transcriptomic analyses on mouse and human liver cancer and identified lecithin cholesterol acyltransferase (LCAT) as the most highly estrogen-upregulated gene and a biomarker of favorable prognosis. LCAT upregulation inhibited HCC in vitro and in vivo and mediated estrogen-induced suppression of HCC in an ESR1-dependent manner. LCAT facilitated high-density lipoprotein cholesterol production and uptake via the LDLR and SCARB1 pathways. Consistently, high HDL-C levels corresponded to a favorable prognosis in HCC patients. The enhanced HDL-C absorption induced by LCAT impaired SREBP2 maturation, which ultimately suppressed cholesterol biosynthesis and dampened HCC cell proliferation. HDL-C alone inhibited HCC growth comparably to the cholesterol-lowering drug lovastatin, and SREBF2 overexpression abolished the inhibitory activity of LCAT. Clinical observations and cross-analyses of multiple databases confirmed the correlation of elevated LCAT and HDL-C levels to reduced cholesterol synthesis and improved HCC patient prognosis. Furthermore, LCAT deficiency mimicked whereas LCAT overexpression abrogated the tumor growth–promoting effects of ovariectomy in HCC-bearing female mice. Most importantly, HDL-C and LCAT delayed the development of subcutaneous tumors in nude mice, and HDL-C synergized with lenvatinib to eradicate orthotopic liver tumors. Collectively, this study reveals that estrogen upregulates LCAT to maintain cholesterol homeostasis and to dampen hepatocarcinogenesis. LCAT and HDL-C represent potential prognostic and therapeutic biomarkers for targeting cholesterol homeostasis as a strategy for treating HCC.

Significance: Estrogen mediates the sex differences in hepatocellular carcinoma development by reducing cholesterol biosynthesis through activation of an LCAT/HDL-C axis, providing strategies for improving liver cancer prevention, prognosis, and treatment.
Supplementary Table S3 from Molecular Subtypes of High-Grade Serous Ovarian Cancer across Racial Groups and Gene Expression Platforms
Authors: Davidson Natalie R. , Barnard Mollie E. , Hippen Ariel A. , Campbell Amy , Johnson Courtney E. , Way Gregory P. , Dalley Brian K. , Berchuck Andrew , Salas Lucas A. , Peres Lauren C. , Marks Jeffrey R. , Schildkraut Joellen M. , Greene Casey S. , Doherty Jennifer A.
Published: August 2024

SchildkrautB derived expression data
Supplemental Table 4 from Association of Urinary Biomarkers of Tobacco Exposure with Lung Cancer Risk in African American and White Cigarette Smokers in the Southern Community Cohort Study
Authors: Murphy Sharon E. , Guillermo Cherie , Thomson Nicole M. , Carmella Steven G. , Wittmann Milo , Aldrich Melinda C. , Cai Qiuyin , Sullivan Shannon M. , Stram Daniel O. , Le Marchand Loïc , Hecht Stephen S. , Blot William J. , Park S. Lani
Published: August 2024

Supplemental Table 4. Characteristics for study participants in Southern Community Cohort, by race
Table S13 from Prostate Cancer Diagnosis Rates among Insured Men with and without HIV in South Africa: A Cohort Study
Authors: Ruffieux Yann , Fernández Villalobos Nathalie V. , Didden Christiane , Haas Andreas D. , Chinogurei Chido , Cornell Morna , Egger Matthias , Maartens Gary , Folb Naomi , Rohner Eliane
Published: August 2024

Table S13 shows hazard ratios for the association of different factors with an incident prostate cancer diagnosis, including men with a single C61 ICD-10 code.
Table S1 from Prostate Cancer Diagnosis Rates among Insured Men with and without HIV in South Africa: A Cohort Study
Authors: Ruffieux Yann , Fernández Villalobos Nathalie V. , Didden Christiane , Haas Andreas D. , Chinogurei Chido , Cornell Morna , Egger Matthias , Maartens Gary , Folb Naomi , Rohner Eliane
Published: August 2024

Table S1 shows degrees of freedom chosen for the natural spline bases in the Royston-Parmar flexible parametric survival models.
Data from Genetic Risk of Second Malignant Neoplasm after Childhood Cancer Treatment: A Systematic Review
Authors: Ducos Claire , Aba Naïla , Rosselli Filippo , Fresneau Brice , Al Ahmad Nachar Baraah , Zidane Monia , de Vathaire Florent , Benhamou Simone , Haddy Nadia
Published: August 2024

Abstract
Second malignant neoplasm (SMN) is one of the most severe long-term risks for childhood cancer survivors (CCS), significantly impacting long-term patient survival. While radiotherapy and chemotherapy are known risk factors, the observed inter-individual variability suggests a genetic component contributing to the risk of SMN. This article aims to conduct a systematic review of genetic factors implicated in the SMN risk among CCS. Searches were performed in PubMed, Scopus, and Web of Sciences. Eighteen studies were included (eleven candidate gene studies, three genome-wide association studies, and four whole exome/genome sequencing studies). The included studies were based on different types of first cancers, investigated any or specific types of SMN, and focused mainly on genes involved in drug metabolism and DNA repair pathways. These differences in study design and methods used to characterize genetic variants limit the scope of the results and highlight the need for further extensive and standardized investigations. However, this review provides a valuable compilation of SMN risk-associated variants and genes, facilitating efficient replication and advancing our understanding of the genetic basis for this major risk for CCS.
Promise and Perils of Primary HPV Testing
Authors: Spencer Jennifer C. , Wheeler Cosette M.
Published: August 2024

Cervical cancer screening has reduced morbidity and mortality in many countries, but efforts to optimize screening modalities and schedules are ongoing. Using data from a randomized trial conducted in British Columbia, Canada, in conjunction with a provincial screening registry, Gottschlich and colleagues demonstrated that the estimated risk for precancerous disease (cervical intraepithelial neoplasia grades 2 or worse) at 8 years following a negative human papillomavirus (HPV) test was similar to the current standard of care (Pap testing after 3 years). The study supports extending screening intervals for those with a negative HPV test beyond currently recommended 5-year intervals. In an ideal world, the resources saved through less frequent routine cervical screening could be redirected to increasing screening uptake and follow-up of abnormalities to improve equity in cervical cancer prevention. However, implementation of extending screening intervals remains less than straightforward in settings with fragmented healthcare systems that lack information systems to support patient call/recall, such as the United States. To achieve the full promise of primary HPV testing, stakeholders at every level must commit to identifying and addressing the diverse spectrum of barriers that undergird existing inequities in care access, appropriately resource implementation strategies, and improve health information systems.

See related article by Gottschlich et al., p. 904
Supplementary Figure 1 from Mapping the Single-Cell Differentiation Landscape of Osteosarcoma
Authors: Truong Danh D. , Weistuch Corey , Murgas Kevin A. , Admane Prasad , King Bridgette L. , Chauviere Lee Jes , Lamhamedi-Cherradi Salah-E. , Swaminathan Jyothishmathi , Daw Najat C. , Gordon Nancy , Gopalakrishnan Vidya , Gorlick Richard G. , Somaiah Neeta , Deasy Joseph O. , Mikos Antonios G. , Tannenbaum Allen , Ludwig Joseph
Published: August 2024

MTL differentiation images
Supplementary Table S3 from Clinical Implications and Molecular Features of Extracellular Matrix Networks in Soft Tissue Sarcomas
Authors: Pankova Valeriya , Krasny Lukas , Kerrison William , Tam Yuen B. , Chadha Madhumeeta , Burns Jessica , Wilding Christopher P. , Chen Liang , Chowdhury Avirup , Perkins Emma , Lee Alexander T.J. , Howell Louise , Guljar Nafia , Sisley Karen , Fisher Cyril , Chudasama Priya , Thway Khin , Jones Robin L. , Huang Paul H.
Published: August 2024

Supplementary Table S3: Reactome enriched pathways in soft tissue sarcoma (STS) matrisome and adhesome clusters. Tables for each cluster showing enriched term description and false discovery rate (FDR). Top 10 hits with FDR < 0.001 are shown for each cluster.