bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and external validation of machine learning-based models to predict patients with cellulitis developing sepsis during hospitalisation
Authors: Chen Xilingyuan , Hu Li , Yu Rentao 
Published: July 2024

ObjectiveCellulitis is the most common cause of skin-related hospitalisations, and the mortality of patients with sepsis remains high. Some stratification models have been developed, but their performance in external validation has been unsatisfactory. This study was designed to develop and compare different models for predicting patients with cellulitis developing sepsis during hospitalisation.DesignThis is a retrospective cohort study.SettingThis study included both the development and the external-validation phases from two independent large cohorts internationally.Participants and methodsA total of 6695 patients with cellulitis in the Medical Information Mart for Intensive care (MIMIC)-IV database were used to develop models with different machine-learning algorithms. The best models were selected and then externally validated in 2506 patients with cellulitis from the YiduCloud database of our university. The performances and robustness of selected models were further compared in the external-validation group by area under the curve (AUC), diagnostic accuracy, sensitivity, specificity and diagnostic OR.Primary outcome measuresThe primary outcome of interest in this study was the development based on the Sepsis-3.0 criteria during hospitalisation.ResultsPatient characteristics were significantly different between the two groups. In internal validation, XGBoost was the best model, with an AUC of 0.780, and AdaBoost was the worst model, with an AUC of 0.585. In external validation, the AUC of the artificial neural network (ANN) model was the highest, 0.830, while the AUC of the logistic regression (LR) model was the lowest, 0.792. The AUC values changed less in the boosting and ANN models than in the LR model when variables were deleted.ConclusionsBoosting and neural network models performed slightly better than the LR model and were more robust in complex clinical situations. The results could provide a tool for clinicians to detect hospitalised patients with cellulitis developing sepsis early.
Infliximab in steroid-refractory immune-related hepatitis does not demonstrate hepatotoxicity and may shorten time on steroids
Authors: Burri Elias , Mangana Joanna , Cheng Phil F , Schneider Alia , Weber Achim , Dummer Reinhard , Ramelyte Egle 
Published: July 2024

BackgroundImmune-related hepatitis (irHepatitis) is a relatively common immune-related adverse event (irAE) of checkpoint inhibitors. Often, it responds well to steroids; however, in refractory cases, further therapy is needed. Anti-tumor necrosis factor (TNF) antibodies are used for management of multiple irAEs, but there are little data in irHepatitis. Here, we report on safety and efficacy of infliximab in 10 cases of steroid-refractory irHepatitis.MethodsWe retrospectively reviewed patients treated with infliximab for steroid-refractory grade ≥3 irHepatitis at the Department of Dermatology, University Hospital Zurich. The positive response to infliximab was defined as no further increase in alanine aminotransferase (ALT)/aspartate aminotransferase (AST) above 50% than at the time of first infliximab infusion and control of irHepatitis without therapies other than steroids and infliximab.Results10 patients with steroid-resistant irHepatitis grade ≥3 were treated with infliximab 5 mg/kg, of whom 7 (70%) responded positively. In two cases, the liver values increased over 50% before the irHepatitis could be controlled. In another case, therapies other than infliximab and steroids were given. At the median follow-up of 487 days, 90% of the patients demonstrated resolved irHepatitis without AST/ALT elevation following infliximab infusions.ConclusionsTreatment of irHepatitis with infliximab did not result in hepatotoxicity and led to long-lasting positive response in 9 of 10 of the cases. Further research is needed to evaluate the role of anti-TNF antibodies in management of irHepatitis.
TCF1-positive and TCF1-negative TRM CD8 T cell subsets and cDC1s orchestrate melanoma protection and immunotherapy response
Authors: De León-Rodríguez Saraí G , Aguilar-Flores Cristina , Gajón Julián A , Juárez-Flores Ángel , Mantilla Alejandra , Gerson-Cwilich Raquel , Martínez-Herrera José Fabián , Villegas-Osorno Diana Alejandra , Gutiérrez-Quiroz Claudia T , Buenaventura-Cisneros Sergio , Sánchez-Prieto Mario Alberto , Castelán-Maldonado Edmundo , Rivera Rivera Samuel , Fuentes-Pananá Ezequiel M , Bonifaz Laura C 
Published: July 2024

BackgroundMelanoma, the most lethal form of skin cancer, has undergone a transformative treatment shift with the advent of checkpoint blockade immunotherapy (CBI). Understanding the intricate network of immune cells infiltrating the tumor and orchestrating the control of melanoma cells and the response to CBI is currently of utmost importance. There is evidence underscoring the significance of tissue-resident memory (TRM) CD8 T cells and classic dendritic cell type 1 (cDC1) in cancer protection. Transcriptomic studies also support the existence of aTCF7+ (encoding TCF1) T cell as the most important for immunotherapy response, although uncertainty exists about whether there is a TCF1+TRM T cell due to evidence indicating TCF1 downregulation for tissue residency activation.MethodsWe used multiplexed immunofluorescence and spectral flow cytometry to evaluate TRM CD8 T cells and cDC1 in two melanoma patient cohorts: one immunotherapy-naive and the other receiving immunotherapy. The first cohort was divided between patients free of disease or with metastasis 2 years postdiagnosis while the second between CBI responders and non-responders.ResultsOur study identifies two CD8+TRM subsets, TCF1+ and TCF1−, correlating with melanoma protection. TCF1+TRM cells show heightened expression of IFN-γ and Ki67 while TCF1− TRM cells exhibit increased expression of cytotoxic molecules. In metastatic patients, TRM subsets undergo a shift in marker expression, with the TCF1− subset displaying increased expression of exhaustion markers. We observed a close spatial correlation between cDC1s and TRMs, with TCF1+TRM/cDC1 pairs enriched in the stroma and TCF1− TRM/cDC1 pairs in tumor areas. Notably, these TCF1− TRMs express cytotoxic molecules and are associated with apoptotic melanoma cells. Both TCF1+ and TCF1− TRM subsets, alongside cDC1, prove relevant to CBI response.ConclusionsOur study supports the importance of TRM CD8 T cells and cDC1 in melanoma protection while also highlighting the existence of functionally distinctive TCF1+ and TCF1− TRM subsets, both crucial for melanoma control and CBI response.
Using microfluidic shear to assess transfusion requirements in trauma patients
Authors: Vuoncino Leslie H , Robles Anamaria J , Barnes Ashli C , Ross James T , Graeff Leonardo W , Anway Taylor L , Vincent Nico T , Tippireddy Nithya , Tanaka Kimi M , Mays Randi J , Callcut Rachael A 
Published: July 2024

BackgroundViscoelastic assays have widely been used for evaluating coagulopathies but lack the addition of shear stress important toin vivoclot formation. Stasys technology subjects whole blood to shear forces over factor-coated surfaces. Microclot formation is analyzed to determine clot area (CA) and platelet contractile forces (PCFs). We hypothesize the CA and PCF from this novel assay will provide information that correlates with trauma-induced coagulopathy and transfusion requirements.MethodsBlood samples were collected on adult trauma patients from a single-institution prospective cohort study of high-level activations. Patient and injury characteristics, transfusion data, and outcomes were collected. Thromboelastography, coagulation studies, and Stasys assays were run on paired samples collected at admission. Stasys CA and PCFs were quantified as area under the curve calculations and maximum values. Normal ranges for Stasys assays were determined using healthy donors. Data were compared using Kruskal-Wallis tests and simple linear regression.ResultsFrom March 2021 to January 2023, 108 samples were obtained. Median age was 37.5 (IQR 27.5–52) years; patients were 77% male. 71% suffered blunt trauma, 26% had an Injury Severity Score of ≥25. An elevated international normalized ratio significantly correlated with decreased cumulative PCF (p=0.05), maximum PCF (p=0.05) and CA (p=0.02). Lower cumulative PCF significantly correlated with transfusion of any products at 6 and 24 hours (p=0.04 and p=0.05) as well as packed red blood cells (pRBCs) at 6 and 24 hours (p=0.04 and p=0.03). A decreased maximum PCF showed significant correlation with receiving any transfusion at 6 (p=0.04) and 24 hours (p=0.02) as well as transfusion of pRBCs, fresh frozen plasma, and platelets in the first 6 hours (p=0.03, p=0.03, p=0.03, respectively).ConclusionsAssessing coagulopathy in real time remains challenging in trauma patients. In this pilot study, we demonstrated that microfluidic approaches incorporating shear stress could predict transfusion requirements at time of admission as well as requirements in the first 24 hours.Level of evidenceLevel II.
A comprehensive forecast for cosmological parameter estimation using joint observations of gravitational waves and short $$\gamma $$-ray bursts
Authors: Han Tao , Jin Shang-Jie , Zhang Jing-Fei , Zhang Xin 
Published: July 2024

AbstractIn the third-generation (3G) gravitational-wave (GW) detector era, multi-messenger GW observation for binary neutron star (BNS) merger events can exert great impacts on exploring cosmic expansion history. In this work, we comprehensively explore the potential of 3G GW standard siren observations in cosmological parameter estimations by considering 3G GW detectors and the future short $$\gamma $$
γ
-ray burst (GRB) detector THESEUS-like telescope joint observations. Based on a 10-year observation of different detection strategies, we predict that the numbers of detectable GW-GRB events are 334–674 with the redshifts $$z<3.5$$

z
<
3.5

and the inclination angles $$\iota <15^{\circ }$$

ι
<

15
∘

. For the cosmological analysis, we consider the $$\Lambda $$
Λ
CDM, wCDM, $$w_0w_a$$

w
0

w
a

CDM, and interacting dark energy (IDE) models. We find that GW can tightly constrain the Hubble constant with precision of 0.345–0.065%, but does not perform well in constraining other cosmological parameters. Fortunately, GW detection could effectively break the cosmological parameter degeneracies generated by the mainstream EM observations, CMB + BAO + SN (CBS). When combining mock GW data with CBS data, CBS + GW can tightly constrain the equation of state of dark energy w with a precision of 1.26%, close to the standard of precision cosmology. Meanwhile, the addition of GW to CBS could improve constraints on cosmological parameters by 34.2–94.9%. In conclusion, GW standard siren observations from 3G GW detectors could play a crucial role in helping solve the Hubble tension and probe the fundamental nature of dark energy.
Can the induced increase in the angular velocity prevent the overspinning of BTZ black holes?
Authors: Düztaş Koray 
Published: July 2024

AbstractPreviously we showed that nearly extremal Bañados–Teitelboim–Zanelli (BTZ) black holes can be overspun by test bodies and fields, following the work of Rocha and Cardoso for the extremal case. The naked singularities in AdS space-times correspond to states rotating faster than light in the Ads/CFT correspondence. Therefore, overspinning turns out to be a drastic problem in a (2 + 1) dimensional AdS space-time, where one cannot invoke backreaction effects. Here, we consider the induced increase in the angular velocity of the event horizon which modifies the condition to allow the absorption of the perturbations satisfying the null energy condition. We show that its magnitude is sufficiently large to prevent the absorption of the challenging modes both for test bodies and scalar fields. We bring a solution to the notorious overspinning problem which does not involve any reference to self-energy or gravitational radiation
Accumulated laser-photoneutron generation
Authors: Cohen Itamar , Cohen Tamir , Levinson Aviv , Elkind Michael , Rakovsky Yonatan , Levanon Assaf , Michaeli David , Cohen Erez , Beck Arie , Pomerantz Ishay 
Published: July 2024

AbstractWe present repeated generation of photoneutrons by double-pulse irradiation of ultrathin foils. A ~ mJ prepulse turns a foil into a 100-μm scale plasma plume from which a beam of MeV electrons is generated by the main pulse. Neutrons are generated in a secondary metal target placed downstream to the electron beam. We utilize an automated target system capable of delivering ultrathin foils to the laser focus at an average rate of 0.1 Hz. With 153 consecutive laser shots taken over the course of 24 min, we generated a total 2.6 × 107 neutrons. We present a method for evaluating how the number of photoneutrons scales with the laser intensity in this experimental scenario, which we validate against the measured yields.
ShNFN: Shepard Neuro-Fuzzy Network for Intrusion Detection in Fog Computing
Authors: Ganeshan R , Sravani Meesala , Kalidindi Archana , Om Prakash P G 
Published: July 2024

Fog computing is a type of distributed computing that makes data storage and computation closer to the network edge. While fog computing offers numerous advantages, it also introduces several challenges, particularly in terms of security. Intrusion Detection System (IDS) plays a crucial role in securing fog computing environments by monitoring network traffic and system activities for signs of malicious behavior. Several techniques can be employed to enhance intrusion detection in fog computing environments. Accordingly, this paper proposes a Shepard Neuro-Fuzzy Network (ShNFN) for intrusion detection in fog computing. Initially, in the cloud layer, the input data are passed to data transformation to transform the unstructured data into structured form. Here, data transformation is done employing the Box-Cox transformation. Following this, the feature selection is done in terms of information gain and symmetric uncertainty process and it is used to create a relationship between two variables. After that, the data are classified by employing the proposed ShNFN. The ShNFN is attained by fusing two networks, such as Cascade Neuro-Fuzzy Network (Cascade NFN) and Shepard Convolutional Neural Networks (ShCNN). After this, the physical process is executed at the endpoint layer. Finally, intrusion detection is accomplished in the fog layer by the proposed ShNFN method. The performance of the intrusion detection using ShNFN is calculated by the metrics of recall, F-measure and precision. The proposed method achieves the values of 93.3%, 92.5% and 94.8% for recall, F-measure, and precision, respectively.
SoK: Fully Homomorphic Encryption Accelerators
Authors: Zhang Junxue , Cheng Xiaodian , Yang Liu , Hu Jinbin , Liu Ximeng , Chen Kai 
Published: July 2024

Fully Homomorphic Encryption (FHE) is a key technology enabling privacy-preserving computing. However, the fundamental challenge of FHE is its inefficiency, due primarily to the underlying polynomial computations with high computation complexity and extremely time-consuming ciphertext maintenance operations. To tackle this challenge, various FHE accelerators have recently been proposed by both research and industrial communities. This article takes the first initiative to conduct a systematic study on the 14 FHE accelerators: cuHE/cuFHE, nuFHE, HEAT, HEAX, HEXL, HEXL-FPGA, 100×, F1, CraterLake, BTS, ARK, Poseidon, FAB, and TensorFHE. We first make our observations on the evolution trajectory of these existing FHE accelerators to establish a qualitative connection between them. Then, we perform testbed evaluations of representative open-source FHE accelerators to provide a quantitative comparison on them. Finally, with the insights learned from both qualitative and quantitative studies, we discuss potential directions to inform the future design and implementation for FHE accelerators.
Unveiling Cellular Identities and Gene Expression Pathways in Overlapping Myocarditis and Myositis
Authors: Fankhauser Reilly G. , Johnson Douglas B. , Moslehi Javid J. , Balko Justin M. 
Published: July 2024

Immune checkpoint therapies can drive antitumor responses and benefit patients but can also induce life-threatening immune-related adverse events such as myocarditis and myositis. These immune-related adverse events are rare but carry substantial morbidity and mortality. In this issue, Siddiqui and colleagues use single-cell RNA and T-cell receptor sequencing to identify novel cellular subsets and propose various mechanisms that could contribute to the pathogenesis of immune checkpoint inhibitor–associated myocarditis and myositis. These new insights should help move the field toward the development of improved treatment and prevention options, ultimately improving patient outcomes.See related article by Siddiqui et al., p. 964 (1)
How unique structural adaptations support and coordinate the complex function of von Willebrand factor
Authors: Lenting Peter J. , Denis Cécile V. , Christophe Olivier D. 
Published: July 2024

Abstract
von Willebrand factor (VWF) is a multimeric protein consisting of covalently linked monomers, which share an identical domain architecture. Although involved in processes such as inflammation, angiogenesis, and cancer metastasis, VWF is mostly known for its role in hemostasis, by acting as a chaperone protein for coagulation factor VIII (FVIII) and by contributing to the recruitment of platelets during thrombus formation. To serve its role in hemostasis, VWF needs to bind a variety of ligands, including FVIII, platelet-receptor glycoprotein Ib-α, VWF-cleaving protease ADAMTS13, subendothelial collagen, and integrin α-IIb/β-3. Importantly, interactions are differently regulated for each of these ligands. How are these binding events accomplished and coordinated? The basic structures of the domains that constitute the VWF protein are found in hundreds of other proteins of prokaryotic and eukaryotic organisms. However, the determination of the 3-dimensional structures of these domains within the VWF context and especially in complex with its ligands reveals that exclusive, VWF-specific structural adaptations have been incorporated in its domains. They provide an explanation of how VWF binds its ligands in a synchronized and timely fashion. In this review, we have focused on the domains that interact with the main ligands of VWF and discuss how elucidating the 3-dimensional structures of these domains has contributed to our understanding of how VWF function is controlled. We further detail how mutations in these domains that are associated with von Willebrand disease modulate the interaction between VWF and its ligands.
A phase 1 clinical trial of NKTR-255 with CD19-22 CAR T-cell therapy for refractory B-cell acute lymphoblastic leukemia
Authors: Srinagesh Hrishikesh , Jackson Clayton , Shiraz Parveen , Jeyakumar Nikeshan , Hamilton Mark , Egeler Emily , Mavroukakis Sharon , Kuo Adam , Cancilla Juancarlos , Sahaf Bita , Agarwal Neha , Kanegai Alyssa , Kramer Anne Marijn , Arai Sally , Bharadwaj Sushma , Dahiya Saurabh , Hosoya Hitomi , Johnston Laura , Kennedy Vanessa , Liedtke Michaela , Lowsky Robert , Mikkilineni Lekha , Negrin Robert , Rezvani Andrew , Sidana Surbhi , Shizuru Judith , Smith Melody , Weng Wen-Kai , Feldman Steven , Frank Matthew J. , Lee Zachary , Tagliaferri Mary , Marcondes A. Mario , Miklos David , Mackall Crystal , Muffly Lori 
Published: July 2024

Abstract
Although chimeric antigen receptor (CAR) T-cell (CAR-T) therapy has revolutionized the treatment of B-cell malignancies, many patients relapse and therefore strategies to improve antitumor immunity are needed. We previously designed a novel autologous bispecific CAR targeting CD19 and CD22 (CAR19-22), which was well tolerated and associated with high response rates but relapse was common. Interleukin-15 (IL15) induces proliferation of diverse immune cells and can augment lymphocyte trafficking. Here, we report the results of a phase 1 clinical trial of the first combination of a novel recombinant polymer-conjugated IL15 receptor agonist (NKTR-255), with CAR19-22, in adults with relapsed/refractory B-cell acute lymphoblastic leukemia. Eleven patients were enrolled, 9 of whom successfully received CAR19-22 followed by NKTR-255. There were no dose-limiting toxicities, with transient fever and myelosuppression as the most common possibly related toxicities. We observed favorable efficacy with 8 of 9 patients (89%) achieving measurable residual disease–negative remission. At 12 months, progression-free survival for NKTR-255 was double that of historical controls (67% vs 38%). We performed correlative analyses to investigate the effects of IL15 receptor agonism. Cytokine profiling showed significant increases in IL15 and the chemokines CXCL9 and CXCL10. The increase in chemokines was associated with decreases in absolute lymphocyte counts and CD8+ CAR T cells in the blood and 10-fold increases in cerebrospinal fluid CAR-T cells, suggesting lymphocyte trafficking to tissue. Combining NKTR-255 with CAR19-22 was safe, feasible, and associated with high rates of durable responses. This trial was registered at www.clinicaltrials.gov as #NCT03233854.
Novel MAGIC composite scores using both clinical symptoms and biomarkers best predict treatment outcomes of acute GVHD
Authors: Akahoshi Yu , Spyrou Nikolaos , Weber Daniela , Aguayo-Hiraldo Paibel , Ayuk Francis , Chanswangphuwana Chantiya , Choe Hannah K. , Eder Matthias , Etra Aaron M. , Grupp Stephan A. , Hexner Elizabeth O. , Hogan William J. , Kitko Carrie L. , Kraus Sabrina , Al Malki Monzr M. , Merli Pietro , Qayed Muna , Reshef Ran , Schechter Tal , Ullrich Evelyn , Vasova Ingrid , Wölfl Matthias , Zeiser Robert , Baez Janna , Beheshti Rahnuma , Eng Gilbert , Gleich Sigrun , Katsivelos Nikolaos , Kowalyk Steven , Morales George , Young Rachel , Chen Yi-Bin , Nakamura Ryotaro , Levine John E. , Ferrara James L. M. 
Published: July 2024

Abstract
Acute graft-versus-host disease (GVHD) grading systems that use only clinical symptoms at treatment initiation such as the Minnesota risk identify standard and high-risk categories but lack a low-risk category suitable to minimize immunosuppressive strategies. We developed a new grading system that includes a low-risk stratum based on clinical symptoms alone and determined whether the incorporation of biomarkers would improve the model’s prognostic accuracy. We randomly divided 1863 patients in the Mount Sinai Acute GVHD International Consortium (MAGIC) who were treated for GVHD into training and validation cohorts. Patients in the training cohort were divided into 14 groups based on similarity of clinical symptoms and similar nonrelapse mortality (NRM); we used a classification and regression tree (CART) algorithm to create three Manhattan risk groups that produced a significantly higher area under the receiver operating characteristic curve (AUC) for 6-month NRM than the Minnesota risk classification (0.69 vs 0.64, P = .009) in the validation cohort. We integrated serum GVHD biomarker scores with Manhattan risk using patients with available serum samples and again used a CART algorithm to establish 3 MAGIC composite scores that significantly improved prediction of NRM compared to Manhattan risk (AUC, 0.76 vs 0.70, P = .010). Each increase in MAGIC composite score also corresponded to a significant decrease in day 28 treatment response (80% vs 63% vs 30%, P &lt; .001). We conclude that the MAGIC composite score more accurately predicts response to therapy and long-term outcomes than systems based on clinical symptoms alone and may help guide clinical decisions and trial design.