bluuebunny/crossref_metadata_2025 huggingface dataset:
Terminal Ediacaran–Late Ordovician evolution of the NE Laurentia palaeocontinent: rift–drift–onset of Taconic Orogeny, sea-level change and ‘Hawke Bay’ onlap (not offlap)
Authors: Landing Ed , Webster Mark , Bowser Samuel S.
Published: June 2023

Rodinia break-up with late Ediacaran rifting defined a NE Laurentia triple junction (New York Promontory–Ottawa–Bonnechere aulacogen (OBA)–Quebec Reentrant). Rifting persisted to
c.
510 Ma. The oldest passive-margin shelf units (Forestdale Marble and Moosalamoo Phyllite) underlie a sandstone (Cheshire) commonly regarded as the oldest passive unit. Late Dyeran–Middle Cambrian rifting led to the oldest OBa sedimentation and formed the Franklin Basin (NW Vermont). Cambrian–Darriwillian shelf–slope facies are linked eustatically – not Taconic Orogeny onset. Onlap and shelf carbonates are coeval with black slope mud; and lowstand shelf unconformities with green, oxic slope mud. Early–middle Dyeran eustatic change defined slope units: (1) Browns Pond Formation dysoxic–anoxic (d–a) interval with debrite cap (Holcombville Member, new); (2) Middle Granville Formation Oxic Interval (new); and (3) lower Hatch Hill Formation d–a interval. Our analysis leads to two controversial conclusions: (i) the existence of the Dashwoods and other micro-continental blocks due to hyperextension is not supported by cover sequences linking Laurentia to proposed Dashwoods areas (i.e. Green Mountains) and an arc origin of the type Dashwoods; and (ii) ‘Hawke Bay Event(s)’, widely interpreted as Cambrian global regressive event(s), is a local highstand systems tract facies with shelf sand bypass onto the Hatch Hill Formation slope in its NE Laurentia type region.
Search-based Time-aware Graph-enhanced Recommendation with Sequential Behavior Data
Authors: Zheng Lei , Chai Huacan , Chen Xianyu , Jin Jiarui , Zhang Weinan , Yu Yong , Guo Xiaodong , Ge Can , Feng Ziming
Published: June 2023

Extending from sequential recommendation models, in this article, we present a novel framework named Search-based Time-Aware Recommendation (STARec), which first retrieves the historical behaviors of the given user through a search-based retriever and then captures the user’s evolving demands over time through a time-aware sequential network. We notice that the key insight of STARec is to use the feature and labels to augment the representations, and thus the effectiveness of STARec relies on the acquisition of rich browsing records of the target user and powerful representation of each browsed item and thus its performance could heavily drop regarding long-tail users and items. To this end, we extend STARec by constructing a graph upon the user–item interactions and leveraging the graph structure to enhance the representation learning. We call this extended version Search-based Time-Aware Graph-Enhanced Recommendation (STAGE). We conduct extensive experiments on three real-world datasets and STARec achieves consistent superiority. We further compare STAGE against STARec long-tail users and our results demonstrate that STAGE could outperform STARec at most cases. Results of online A/B tests show that STARec and STAGE achieve an average click-through rate improvement of around 6% and 1.5% in the two main item recommendation scenarios, respectively.

1
Bias and Extrapolation in Markovian Linear Stochastic Approximation with Constant Stepsizes
Authors: Huo Dongyan (Lucy) , Chen Yudong , Xie Qiaomin
Published: June 2023

We consider Linear Stochastic Approximation (LSA) with constant stepsize and Markovian data. Viewing the joint process of the data and LSA iterate as a time-homogeneous Markov chain, we prove its convergence to a unique limiting and stationary distribution in Wasserstein distance and establish non-asymptotic, geometric convergence rates. Furthermore, we show that the bias vector of this limit admits an infinite series expansion with respect to the stepsize. Consequently, the bias is proportional to the stepsize up to higher order terms. This result stands in contrast with LSA under i.i.d. data, for which the bias vanishes. In the reversible chain setting, we provide a general characterization of the relationship between the bias and the mixing time of the Markovian data, establishing that they are roughly proportional to each other.

Polyak-Ruppert averaging reduces the variance of the LSA iterates but does not affect the bias. The above characterization allows us to show that the bias can be reduced using Richardson-Romberg extrapolation with m≥ 2 stepsizes, which eliminates the m-1 leading terms in the bias expansion. This extrapolation scheme leads to an exponentially smaller bias and an improved mean squared error, both in theory and empirically. Our results immediately apply to the Temporal Difference learning algorithm with linear function approximation, Markovian data, and constant stepsizes.
Gacha Game Analysis and Design
Authors: Chen Canhui , Fang Zhixuan
Published: June 2023

Gacha game is a special opaque selling approach, where the seller is selling gacha pulls to the buyer. Each gacha pull provides a certain probability for the buyer to win the gacha game reward. The gacha game has been enthusiastically embraced in numerous online video games and has a wide range of potential applications. In this work, we model the complex interaction between the seller and the buyer as a Stackelberg game, where the sequential decision of the buyer is modeled as a Markov Decision Process (MDP). We define the whale property in the context of gacha games. Then, we show that this is the necessary condition to achieve optimal revenue. Moreover, we provide the revenue-optimal gacha game design and show that it is equivalent to the single-item single-bidder Myerson auction. We further explore two popular multi-item gacha games, namely, the sequential multi-item gacha game and the banner-based multi-item gacha game. We also discuss the subsidies in the gacha game and demonstrate how subsidies may encourage the buyer to engage in grinding behavior. Finally, we provide a case study on blockchain systems as gacha games.
Optimistic No-regret Algorithms for Discrete Caching
Authors: Mhaisen Naram , Sinha Abhishek , Paschos Georgios , Iosifidis George
Published: June 2023

We take a systematic look at the problem of storing whole files in a cache with limited capacity in the context of optimistic learning, where the caching policy has access to a prediction oracle. The successive file requests are assumed to be generated by an adversary, and no assumption is made on the accuracy of the oracle. We provide a universal lower bound for prediction-assisted online caching and proceed to design a suite of policies with a range of performance-complexity trade-offs. All proposed policies offer sublinear regret bounds commensurate with the accuracy of the oracle. In this pursuit, we design, to the best of our knowledge, the first optimistic Follow-the-Perturbed leader policy, which generalizes beyond the caching problem. We also study the problem of caching files with different sizes and the bipartite network caching problem.
PEACH: Proactive and Environment Aware Channel State Information Prediction with Depth Images
Authors: Ayvasik Serkut , Mehmeti Fidan , Babaians Edwin , Kellerer Wolfgang
Published: June 2023

Up-to-date and accurate prediction of Channel State Information (CSI) is of paramount importance in Ultra-Reliable Low-Latency Communications (URLLC), specifically in dynamic environments where unpredictable mobility is inherent. CSI can be meticulously tracked by means of frequent pilot transmissions, which on the downside lead to an increase in metadata (overhead signaling) and latency, which are both detrimental for URLLC. To overcome these issues, in this paper, we take a fundamentally different approach and propose PEACH, a machine learning system which utilizes environmental information with depth images to predict CSI amplitude in beyond 5G systems, without requiring metadata radio resources, such as pilot overheads or any feedback mechanism. PEACH exploits depth images by employing a convolutional neural network to predict the current and the next 100 ms CSI amplitudes. The proposed system is experimentally validated with extensive measurements conducted in an indoor environment. We prove that environmental information can be instrumental towards proactive CSI amplitude acquisition of both static and mobile users on base stations, while completely avoiding the dependency on feedback and pilot transmission for both downlink and uplink CSI information. Furthermore, compared to demodulation reference signal based traditional pilot estimation, in ideal conditions without interference, our experimental results show that PEACH yields the similar performance in terms of average bit error rate. More importantly, in the realistic cases with interference taken into account, our experiments demonstrate considerable improvements introduced by PEACH in terms of normalized mean square error of CSI amplitude estimation when compared to traditional approaches.
Switching in the Rain: Predictive Wireless x-haul Network Reconfiguration
Authors: Kadota Igor , Jacoby Dror , Messer Hagit , Zussman Gil , Ostrometzky Jonatan
Published: June 2023

4G, 5G, and smart city networks often rely on microwave and millimeter-wave x-haul links. A major challenge associated with these high frequency links is their susceptibility to weather conditions. In particular, precipitation may cause severe signal attenuation, which significantly degrades the network performance. In this paper, we develop a Predictive Network Reconfiguration (PNR) framework that uses historical data to predict the future condition of each link and then prepares the network ahead of time for imminent disturbances. The PNR framework has two components: (i) an Attenuation Prediction (AP) mechanism; and (ii) a Multi-Step Network Reconfiguration (MSNR) algorithm. The AP mechanism employs an encoder-decoder Long Short-Term Memory (LSTM) model to predict the sequence of future attenuation levels of each link. The MSNR algorithm leverages these predictions to dynamically optimize routing and admission control decisions aiming to maximize network utilization, while preserving max-min fairness among the nodes using the network (e.g., base-stations) and preventing transient congestion that may be caused by switching routes. We train, validate, and evaluate the PNR framework using a dataset containing over 2 million measurements collected from a real-world city-scale backhaul network. The results show that the framework: (i) predicts attenuation with high accuracy, with an RMSE of less than 0.4 dB for a prediction horizon of 50 seconds; and (ii) can improve the instantaneous network utilization by more than 200% when compared to reactive network reconfiguration algorithms that cannot leverage information about future disturbances. The full paper associated with this abstract can be found at https://doi.org/10.1145/3570616.
Predation in a Microbial World: Mechanisms and Trade-Offs of Flagellate Foraging
Authors: Kiørboe Thomas
Published: June 2023

Heterotrophic nanoflagellates are the main consumers of bacteria and picophytoplankton in the ocean and thus play a key role in ocean biogeochemistry. They are found in all major branches of the eukaryotic tree of life but are united by all being equipped with one or a few flagella that they use to generate a feeding current. These microbial predators are faced with the challenges that viscosity at this small scale impedes predator–prey contact and that their foraging activity disturbs the ambient water and thus attracts their own flow-sensing predators. Here, I describe some of the diverse adaptations of the flagellum to produce sufficient force to overcome viscosity and of the flagellar arrangement to minimize fluid disturbances, and thus of the various solutions to optimize the foraging–predation risk trade-off. I demonstrate how insights into this trade-off can be used to develop robust trait-based models of microbial food webs.
Accurate LLI and LAMPE Estimation Using the Mechanistic Modeling Approach with Layered Oxides
Authors: Dubarry Matthieu , Agrawal Vishal , Hüske Martin , Kuipers Matthias
Published: June 2023

In the past decade and half since their introduction, multiple frameworks of mechanistic models were made available to enable the quantification of loss of lithium inventory and loss of active materials. They usually come either with capacity/state of charge- or lithiation-based matching for the electrodes. While both approaches were believed to be equivalent, the present work will show that they are not when used with materials that are not fully delithiated at end-of-charge because they differ on how they account for inaccessible lithium. Herein, we will explain these discrepancies and propose new equations to improve both types of frameworks.
Reproducibly Defining Electrode Area of Carbon Paper Electrodes via Machine Cutting and High-Throughput Waxing
Authors: Gerulskis Rokas , Minteer Shelley D.
Published: June 2023

Carbon paper is one of the most common carbon electrode materials employed in electrochemical research due to its low cost, disposability, and controllable dimensions and scaling. Carbon paper is usually hand cut and a variety of strategies are used to define electrode area. This procedure is tedious, imprecise, and inaccurate, yielding coefficients of variation in peak current output as high as 20%. Imprecision in hand-preparation translates directly to poor reproducibility in electrochemical data leading to challenges in directly comparing data across research groups and research fields. This work introduces an inexpensive and precise method to automatically cut and rapidly wax carbon paper electrodes, circumventing laborious traditional preparation and substantially improving precision in electrochemical data.
Decreased miR-17-92 cluster correlates with senescence features, disrupted oxidative homeostasis, and impaired therapeutic efficacy of mesenchymal stem cells
Authors: Cen Yelei , Qi Jinjin , Chen Liang , Xia Caixia , Zheng Min , Liu Yanning , Lou Guohua
Published: June 2023

We reported for the first time that c-Myc-regulated miR-17-92 contributed to increased p21 expression and redox system dysregulation during AMSC senescence and was associated with the reduced therapeutic effects of senescent AMSCs on ALF. Moreover, modifying the expression of the miR-17-92 cluster members, especially miR-17 and/or miR-20a, could reverse AMSC senescence. Thus, miR-17-92 cluster can be used both as an index for evaluating and as a modification strategy for improving the therapeutic potential of AMSCs.
DAGLβ is the principal synthesizing enzyme of 2-AG and promotes aggressive phenotype of intrahepatic cholangiocarcinoma via AP-1/DAGLβ/miR4516 feedforward circuitry
Authors: Ma Mingjian , Zeng Guangyan , Tan Bingyan , Zhao Guangyin , Su Qiao , Zhang Wenhui , Song Yan , Liang Jiahua , Xu Borui , Wang Zicheng , Chen Jiancong , Hou Mengjun , Yang Chuntao , Yun Jingping , Huang Yuhua , Lin Yansong , Chen Demeng , Han Yuyan , DeMorrow Sharon , Liang Lijian , Lai Jiaming , Huang Li
Published: June 2023

Dysregulated endocannabinoid system (ECS) had been confirmed in various liver diseases. However, regulation and function of 2-arachidonoyl glycerol (2-AG) and diacylglycerol lipase β (DAGLβ) in intrahepatic cholangiocarcinoma (ICC) remain to be elucidated. Here, we demonstrated that 2-AG was enriched in ICC, and DAGLβ was the principal synthesizing enzyme of 2-AG in ICC. DAGLβ promotes tumorigenesis and metastasis in ICC via a novel activator protein-1 (AP-1)/DAGLβ/miR4516 feedforward circuitry.
Tobacco smoking is associated with combined pulmonary fibrosis and emphysema and worse outcomes in interstitial lung disease
Authors: Douglas Dylan , Keating Layne , Strykowski Rachel , Lee Cathryn T. , Garcia Nicole , Selvan Kavitha , Kaushik Neha , Bauer Ventura Iazsmin , Jablonski Renea , Vij Rekha , Chung Jonathan H. , Bellam Shashi , Strek Mary E. , Adegunsoye Ayodeji
Published: June 2023

Smoking in ILD is associated with combined pulmonary fibrosis and emphysema and worse clinical outcomes.
Competitiveness of the Exotic Silphium perfoliatum against the Native Urtica dioica: A Field Experiment
Authors: Ende L. Marie , Schwarzer Sophie-Juliane , Ebner Alexandra , Lauerer Marianne
Published: June 2023

Silphium perfoliatum (cup plant) is native to North America and is increasingly used as a bioenergy crop in Germany. Spontaneous occurrences of this species have already been detected in several European countries. To assess the possible risk to biodiversity by spreading of S. perfoliatum, we investigated the competitiveness of this species against the native and highly competitive Urtica dioica over four years in a field experiment in Bayreuth (Germany). S. perfoliatum grew well among U. dioica, although its biomass was strongly reduced by surrounding U. dioica. Projection area, plant height, and reproductive potential were less or similarly reduced by surrounding U. dioica as by the intraspecific competition. Moreover, S. perfoliatum significantly suppressed the growth of the competitive U. dioica. A settlement and establishment of S. perfoliatum in the native flora of Central Europe and a suppression of uncompetitive plant species are therefore conceivable.
Supplementary Data from CD19-specific CAR T Cells that Express a PD-1/CD28 Chimeric Switch-Receptor are Effective in Patients with PD-L1–positive B-Cell Lymphoma
Authors: Liu Hui , Lei Wen , Zhang Chaoting , Yang Chunmei , Wei Juying , Guo Qunyi , Guo Xiaojun , Chen Zhilu , Lu Ying , Young Ken H. , Lu Zheming , Qian Wenbin
Published: June 2023

Supplementary Data from CD19-specific CAR T Cells that Express a PD-1/CD28 Chimeric Switch-Receptor are Effective in Patients with PD-L1–positive B-Cell Lymphoma
Data from A Phase 1/2 Multicenter Randomized Trial of Local Ablation Plus Toripalimab Versus Toripalimab Alone for Previously Treated Unresectable Hepatocellular Carcinoma
Authors: Zhou Chunhui , Li Yan , Li Jiaping , Song Botian , Li Hanfeng , Liang Bin , Gu Shanzhi , Li Haiping , Chen Changyong , Li Sai , Peng Changli , Liu Fei , Xiao Juxiong , Long Xueying , Li Ping , Xiong Zhengping , Yi Xiaoping , Liao Weihua , Shi Liangrong
Published: June 2023

Abstract
Purpose: To assess the safety and efficacy of local ablation plus PD-1 inhibitor toripalimab in previously treated unresectable hepatocellular carcinoma (HCC). Patients and Methods: In the multicenter, two-stage, and randomized phase 1/2 trial, patients were randomly assigned to receive toripalimab alone (240mg, every 3 weeks), subtotal local ablation followed by toripalimab starting on post-ablation day 3 (Schedule D3) or on post-ablation day 14 (Schedule D14). The first endpoint of stage 1 was to determine which combination schedule could continue and progression-free survival (PFS) as the primary endpoint for stage 1/2. Results: A total of 146 patients were recruited. During stage 1, Schedule D3 achieved numerically higher objective response rate than Schedule D14 for non-ablation lesions (37.5% versus 31.3%), and was chosen for stage 2 evaluation. For the entire cohort of both stages, patients with Schedule D3 had a significantly higher objective response rate than with toripalimab alone (33.8% versus 16.9%, P = 0.027). Moreover, patients with Schedule D3 had improved median PFS (7.1 months versus 3.8 months, P ﹤0.001) and median overall survival (18.4 months versus 13.2 months, P = 0.005), as compared with toripalimab alone. In addition, six (9%) patients with toripalimab, 8 (12%) with Schedule D3, and 4 (25%) with Schedule D14 developed grade 3 or 4 adverse events, and one patient (2%) with Schedule D3 manifested grade 5 treatment-related pneumonitis. Conclusions: In patients with previously treated unresectable HCC, subtotal ablation plus toripalimab improved the clinical efficacy as compared with toripalimab alone with an acceptable safety profile.
Data from CD19-specific CAR T Cells that Express a PD-1/CD28 Chimeric Switch-Receptor are Effective in Patients with PD-L1–positive B-Cell Lymphoma
Authors: Liu Hui , Lei Wen , Zhang Chaoting , Yang Chunmei , Wei Juying , Guo Qunyi , Guo Xiaojun , Chen Zhilu , Lu Ying , Young Ken H. , Lu Zheming , Qian Wenbin
Published: June 2023

AbstractPurpose:
CD19-specific chimeric antigen receptor (CAR) T-cell therapy is effective against refractory or relapsed (R/R) B-cell lymphoma, but the efficacy is hindered by the existence of PD-1/PD-L1 pathway.
Patients and Methods:
Here, we generated a novel anti-CD19 CAR-expressing PD-1/CD28 chimeric switch-receptor (CD19-PD-1/CD28-CAR). We then conducted a phase Ib study to evaluate safety and efficacy of CD19-PD-1/CD28-CAR T cells in the treatment of PD-L1+ B-cell lymphoma.
Results:
We found that CD19-PD-1/CD28-CAR T cells had superior T-cell proliferation, cytokine production, and sequentially capability of killing PD-L1+ B-cell lymphoma cells in vitro and in vivo relative to the prototype, CD19-CAR T cells. Among 17 adult patients with R/R lymphoma who received the CAR T therapy, 10 patients had objective response (58.8%), including seven patients with complete remission (41.2%). At a median follow-up 15 months, median overall survival for all patients was not reached. Remarkably, no severe neurologic toxicity or cytokine release syndrome was observed.
Conclusions:
This first-in-human study demonstrates the tolerability, safety, and encouraging efficacy of CD19-PD-1/CD28-CART in PD-L1+ large B-cell lymphoma.
Data from Comparative Genomic Analysis of Pancreatic Acinar Cell Carcinoma (PACC) and Pancreatic Ductal Adenocarcinoma (PDAC)Unveils New Actionable Genomic Aberrations in PACC
Authors: Florou Vaia , Elliott Andrew , Bailey Matthew H. , Stone David , Affolter Kajsa , Soares Heloisa P. , Nevala-Plagemann Chris , Scaife Courtney , Walker Phillip , Korn W. Michael , Lou Emil , Shroff Rachna T. , Hosein Peter J. , Garrido-Laguna Ignacio
Published: June 2023

Abstract
Purpose: Pure pancreatic acinar cell carcinomas (PACC) are rare malignancies with no established treatment. PACC demonstrates significant genetic intertumoral heterogeneity with multiple pathways involved, suggesting using targeted cancer therapeutics to treat this disease. We aggregated one of the largest datasets of pure PACC to examine the genomic variability and explore patient-specific therapeutic targets. Experimental Design: PACC specimens (n=51) underwent next-generation sequencing (NGS) of DNA (n=29) or whole exome [n=22]) and RNA (whole transcriptome, n=29) at a commercial laboratory. We performed comparative analyses of a genomic cohort of pancreatic ductal adenocarcinomas (PDAC, n=4205). In parallel, we conducted a retrospective review patients with PACC treated at Huntsman Cancer Institute (HCI). Results: The real-world dataset included samples from 51 patients with PACC. We found key molecular differences between pure PACC and PDAC, highlighting the unique characteristics of pure PACC. Major differences in PACC include lower MAPK signaling and less stromal cell abundance compared to PDAC. Pure PACC showed genomic loss-of-heterozygosity to largely coincide with mutations in BRCA1, BRCA2, and PALB2. Of the seven patients treated at HCI, one had a tumor that harbored a BRAF-V600E mutation. Leveraging precision oncology, this patient is being treated with encorafenib plus binimetinib, achieving an exceptionally durable and ongoing complete response of more than three years. Conclusions: There are major differences between PACC and PDAC, including downregulation of the MAPK signaling pathway, and less stromal cell abundance. In addition, genomic characterization of pure PACC revealed frequent targetable alterations, which can guide patient treatment.
A Targeted Thorium-227 Conjugate Demonstrates Efficacy in Preclinical Models of Acquired Drug Resistance and Combination Potential with Chemotherapeutics and Antiangiogenic Therapies
Authors: Zitzmann-Kolbe Sabine , Kristian Alexander , Zopf Dieter , Kamfenkel Claudia , Politz Oliver , Ellingsen Christine , Hilbig Jochen , Juul Mark U. , Fonslet Jesper , Nielsen Carsten H. , Schatz Christoph A. , Bjerke Roger M. , Cuthbertson Alan S. , Mumberg Dominik , Hagemann Urs B.
Published: June 2023

Targeted alpha therapies (TAT) are an innovative class of therapies for cancer treatment. The unique mode-of-action of TATs is the induction of deleterious DNA double-strand breaks. Difficult-to-treat cancers, such as gynecologic cancers upregulating the chemoresistance P-glycoprotein (p-gp) and overexpressing the membrane protein mesothelin (MSLN), are promising targets for TATs. Here, based on the previous encouraging findings with monotherapy, we investigated the efficacy of the mesothelin-targeted thorium-227 conjugate (MSLN-TTC) both as monotherapy and in combination with chemotherapies and antiangiogenic compounds in ovarian and cervical cancer models expressing p-gp. MSLN-TTC monotherapy showed equal cytotoxicity in vitro in p-gp–positive and -negative cancer cells, while chemotherapeutics dramatically lost activity on p-gp–positive cancer cells. In vivo, MSLN-TTC exhibited dose-dependent tumor growth inhibition with treatment/control ratios of 0.03–0.44 in various xenograft models irrespective of p-gp expression status. Furthermore, MSLN-TTC was more efficacious in p-gp–expressing tumors than chemotherapeutics. In the MSLN-expressing ST206B ovarian cancer patient-derived xenograft model, MSLN-TTC accumulated specifically in the tumor, which combined with pegylated liposomal doxorubicin (Doxil), docetaxel, bevacizumab, or regorafenib treatment induced additive-to-synergistic antitumor efficacy and substantially increased response rates compared with respective monotherapies. The combination treatments were well tolerated and only transient decreases in white and red blood cells were observed. In summary, we demonstrate that MSLN-TTC treatment shows efficacy in p-gp–expressing models of chemoresistance and has combination potential with chemo- and antiangiogenic therapies.
Urinary N-Terminal Pro-Brain Natriuretic Peptide Predicts Acute Kidney Injury and Severe Disease in COVID-19
Authors: Vogel Manuel Julian , Leininger Simon B , Staudner Stephan T , Hubauer Ute , Wallner Stefan , Mustroph Julian , Hanses Frank , Zimmermann Markus , Lehn Petra , Burkhardt Ralph , Maier Lars S , Hupf Julian , Jungbauer Carsten G
Published: June 2023

Introduction: The ongoing COVID-19 pandemic is placing an extraordinary burden on our health care system with its limited resources. Accurate triage of patients is necessary to ensure medical care for those most severely affected. In this regard, biomarkers could contribute to risk evaluation. The aim of this prospective observational clinical study was to assess the relationship between urinary N-terminal pro-brain natriuretic peptide (NT-proBNP) and acute kidney injury (AKI) as well as severe disease in patients with COVID-19. Methods: 125 patients treated with an acute respiratory infection in the emergency department of the University Hospital Regensburg were analyzed. These patients were divided into a COVID-19 cohort (n = 91) and a cohort with infections not caused by severe acute respiratory syndrome-coronavirus-2 (n = 34). NT-proBNP was determined from serum and fresh urine samples collected in the emergency department. Clinical endpoints were the development of AKI and a composite one consisting of AKI, intensive care unit admission, and in-hospital death. Results: 11 (12.1%) COVID-19 patients developed AKI during hospitalization, whereas 15 (16.5%) reached the composite endpoint. Urinary NT-proBNP was significantly elevated in COVID-19 patients who suffered AKI or reached the composite endpoint (each p < 0.005). In a multivariate regression analysis adjusted for age, chronic kidney disease, chronic heart failure, and arterial hypertension, urinary NT-proBNP was identified as independent predictor of AKI (p = 0.017, OR = 3.91 [CI: 1.28–11.97] per standard deviation [SD]), as well as of the composite endpoint (p = 0.026, OR 2.66 [CI: 1.13–6.28] per SD). Conclusion: Urinary NT-proBNP might help identify patients at risk for AKI and severe disease progression in COVID-19.
Granulomatosis with Polyangiitis Complicated by Severe Exudative Retinal Detachment and Orbital Granuloma Successfully Controlled with Rituximab: A Case Report
Authors: Sugisawa Keigo , Takase Hiroshi , Sugihara Takahiko , Saito Tetsuya , Iwasaki Yuko , Kamoi Koju , Kawaguchi Tatsushi , Yasuda Shinsuke , Ohno-Matsui Kyoko
Published: June 2023

We report a rare case of severe exudative retinal detachment with orbital granuloma associated with granulomatosis with polyangiitis (GPA). A 42-year-old man developed bilateral conjunctival hyperemia and eye pain 15 months before presenting to us. Because vitreous cells and retinal detachment were detected in his left eye, he was referred to us for further evaluation. The left eye showed scleral edema, cells in the anterior chamber and anterior vitreous, exudative retinal detachment, and elevated white subretinal lesions from the nasal to the inferior parts of the eye fundus. Orbital contrast-enhanced magnetic resonance imaging revealed a granulomatous lesion, retinal detachment, and fluid retention in the left eyeball. Comprehensive rheumatological evaluation revealed proteinase 3 anti-neutrophil cytoplasmic antibody positivity and a history of otitis media, leading to a GPA diagnosis. Methylprednisolone 1,000 mg/day was administered intravenously for 3 days, followed by oral prednisolone and intravenous cyclophosphamide. Although the retinal detachment decreased, scleritis and choroidal detachment relapse were observed in the left eye after the fifth cyclophosphamide administration. After switching from cyclophosphamide to rituximab, the scleritis and choroidal detachment resolved. Remission was successfully maintained with biannual rituximab administration. In this case, we conclude that rituximab was important to re-induce and maintain remission after recurrence. Collaboration with a rheumatologist is essential for proper treatment in related cases. This is the first report of ultra-widefield and multimodal imaging for retinal detachment associated with GPA.
Global, Regional, and National Advances Toward the Management of Rheumatic Heart Disease Based on the Global Burden of Disease Study 2019
Authors: Ruan Renjie , Liu Xiaozhu , Zhang Yunrui , Tang Ming , He Bo , Zhang Qing‐Wei , Shu Tingting
Published: June 2023

Background

Population growth, aging, and major alterations in epidemiologic trends inadvertently modulate the status of rheumatic heart disease (RHD) epidemiology. This investigation predicted RHD burden pattern and temporal trends to provide epidemiologic evidence.

Methods and Results

Prevalence, mortality, and disability‐adjusted life‐years data for RHD were obtained from the GBD (Global Burden of Disease) study. We performed decomposition analysis and frontier analysis to assess variations and burden in RHD from 1990 to 2019. In 2019, there were >40.50 million RHD cases worldwide, along with nearly 0.31 million RHD‐related deaths and 10.67 million years of healthy life lost to RHD. The RHD burden was commonly concentrated within lower sociodemographic index regions and countries. RHD primarily affects women (22.52 million cases in 2019), and the largest age‐specific prevalence rate was at 25 to 29 years in women and 20 to 24 years in men. Multiple reports demonstrated prominent downregulation of RHD‐related mortality and disability‐adjusted life‐years at the global, regional, and national levels. Decomposition analysis revealed that the observed improvements in RHD burden were primarily due to epidemiological alteration; however, it was negatively affected by population growth and aging. Frontier analysis revealed that the age‐standardized prevalence rates were negatively linked to sociodemographic index, whereas Somalia and Burkina Faso, with lower sociodemographic index, showed the lowest overall difference from the frontier boundaries of mortality and disability‐adjusted life‐years.

Conclusions

RHD remains a major global public health issue. Countries such as Somalia and Burkina Faso are particularly successful in managing adverse outcomes from RHD and may serve as a template for other countries.
Electron Leak From the Mitochondrial Electron Transport Chain Complex I at Site I
Q
Is Crucial for Oxygen Sensing in Rabbit and Human Ductus Arteriosus
Authors: Read Austin D. , Bentley Rachel E. T. , Martin Ashley Y. , Mewburn Jeffrey D. , Alizadeh Elahe , Wu Danchen , Lima Patricia D. A. , Dunham‐Snary Kimberly J. , Thébaud Bernard , Sharp Willard , Archer Stephen L.
Published: June 2023

Background

As partial pressure of oxygen (pO
2
) rises with the first breath, the ductus arteriosus (DA) constricts, diverting blood flow to the pulmonary circulation. The DA's O
2
sensor resides within smooth muscle cells. The DA smooth muscle cells’ mitochondrial electron transport chain (ETC) produces reactive oxygen species (ROS) in proportion to oxygen tension, causing vasoconstriction by regulating redox‐sensitive ion channels and enzymes. To identify which ETC complex contributes most to DA O
2
sensing and determine whether ROS mediate O
2
sensing independent of metabolism, we used electron leak suppressors, S1QEL (suppressor of site I
Q
electron leak) and S3QEL (suppressor of site III
Qo
electron leak), which decrease ROS production by inhibiting electron leak from quinone sites I
Q
and III
Qo
, respectively.

Methods and Results

The effects of S1QEL, S3QEL, and ETC inhibitors (rotenone and antimycin A) on DA tone, mitochondrial metabolism, O
2
‐induced changes in intracellular calcium, and ROS were studied in rabbit DA rings, and human and rabbit DA smooth muscle cells. S1QEL's effects on DA patency were assessed in rabbit kits, using micro computed tomography. In DA rings, S1QEL, but not S3QEL, reversed O
2
‐induced constriction (
P
=0.0034) without reducing phenylephrine‐induced constriction. S1QEL did not inhibit mitochondrial metabolism or ETC‐I activity. In human DA smooth muscle cells, S1QEL and rotenone inhibited O
2
‐induced increases in intracellular calcium (
P
=0.02 and 0.001, respectively), a surrogate for DA constriction. S1QEL inhibited O
2
‐induced ROS generation (
P
=0.02). In vivo, S1QEL prevented O
2
‐induced DA closure (
P
<0.0001).

Conclusions

S1QEL, but not S3QEL, inhibited O
2
‐induced rises in ROS and DA constriction ex vivo and in vivo. DA O
2
sensing relies on pO
2
‐dependent changes in electron leak at site I
Q
in ETC‐I, independent of metabolism. S1QEL offers a therapeutic means to maintain DA patency.
3/4 of a Monster: On Mixed Shifty Agreement in Telugu
Authors: Messick Troy
Published: June 2023

Within the typology of embedded pronouns, there are languages that allow for non–first person pronouns to apparently control first person agreement morphology when in certain embedded contexts. This type of agreement displays some degree of optionality: it is also possible for the pronoun to control the expected agreement morphology given the pronoun’s own overt morphological features. This squib provides new data from the Dravidian language Telugu showing that when the embedded pronoun controls agreement on two separate targets, agreement may be uniform across the two targets or the two targets can mismatch in one direction, but crucially not the other. I show how this paradigm can be accounted for using the assumptions that the pronouns in question are similar to so-called hybrid nouns and that agreement features are restricted in principled ways.
Addressing (In)Equality in Redress: Human Rights-Led Reform of the Investor-State Dispute Settlement Mechanism
Authors: Deva Surya , Van Ho Tara
Published: June 2023

In the context of ongoing debates concerning the reform of the investor-State dispute settlement (ISDS) mechanism, this article critiques the widely-accepted approach that seeks to fit international human rights law (IHRL) into the existing structure of ISDS and argues that IHRL should at least be treated as ‘primus inter pares’ vis-à-vis international investment law. Testing ISDS on the touchstone of the human rights to equality, non-discrimination, and an effective remedy, the authors demonstrate that ISDS is incompatible with IHRL. Considering various structural and systemic problems, abolishing ISDS is perhaps the only normatively sound solution to address this incompatibility with IHRL. However, as this may not be politically feasible in the near future, this article articulates eight principles for a human-rights compatible international dispute settlement mechanism. We argue that these principles should inform the current efforts to reform the ISDS mechanism to avoid the risk of making only cosmetic changes.
Alone in paradise: a new genus and species of Hirmoneurini tangle-veined flies (Diptera, Nemestrinidae) in South America
Authors: PUJOL-LUZ JOSÉ ROBERTO , LAMAS CARLOS JOSÉ EINICKER
Published: June 2023

A new genus and new species of tangle-veined flies of the tribe Hirmoneurini (Nemestrinidae), Bernardia xenomorpha gen. et sp. nov., is described from the highland savannas of Brazil. This represents the first record of this tribe from the Southern Hemisphere. The new taxon is compared with the related genera and species of Hirmoneurinae. Bernardia xenomorpha gen. et sp. nov. fits perfectly in the diagnosis of the subfamily, especially by the reduction of the hypandrium and by having the proboscis reduced and, in the tribe Hirmoneurini, by having the frons projected forward and covered by dense pilosity. Bernardia xenomorpha gen. et sp. nov. is distinguished from the other species of Hirmoneurinae, mainly by the length of the proboscis, which reaches the first pair of coxae, while in the other species the proboscis does not exceed the length of the head and, by the U-shaped genital fork, with simple (not bifurcate) arms. An identification key for the American subfamilies, tribes, and genera of Nemestrinidae is also included.
Models in Microeconomic Theory
Authors: Osborne Martin J. , Rubinstein Ariel
Published: June 2023

Models in Microeconomic Theory covers basic models in current microeconomic theory. Part I (Chapters 1-7) presents models of an economic agent, discussing abstract models of preferences, choice, and decision making under uncertainty, before turning to models of the consumer, the producer, and monopoly. Part II (Chapters 8-14) introduces the concept of equilibrium, beginning, unconventionally, with the models of the jungle and an economy with indivisible goods, and continuing with models of an exchange economy, equilibrium with rational expectations, and an economy with asymmetric information. Part III (Chapters 15-16) provides an introduction to game theory, covering strategic and extensive games and the concepts of Nash equilibrium and subgame perfect equilibrium. Part IV (Chapters 17-20) gives a taste of the topics of mechanism design, matching, the axiomatic analysis of economic systems, and social choice.

The book focuses on the concepts of model and equilibrium. It states models and results precisely, and provides proofs for all results. It uses only elementary mathematics (with almost no calculus), although many of the proofs involve sustained logical arguments. It includes about 150 exercises.

With its formal but accessible style, this textbook is designed for undergraduate students of microeconomics at intermediate and advanced levels.
Extensive games
Authors: Osborne Martin J. , Rubinstein Ariel
Published: June 2023

A market is currently served by a single incumbent. A competitor is considering entering the market. The incumbent wants to remain alone in the market and thus wishes to deter the competitor from entering. If the competitor enters, the incumbent can start a price war or can act cooperatively. A price war is the worst outcome for both parties; cooperative behavior by the incumbent is best for the competitor, and for the incumbent is better than a price war but worse than the competitor’s staying out of the market. We can model this situation as a strategic game.
Preferences and utility
Authors: Osborne Martin J. , Rubinstein Ariel
Published: June 2023

This chapter discusses a model of preferences over an arbitrary set of alternatives. We regard an individual’s preferences as a description of her mental attitude, outside the context of any choice. This chapter investigates an individual’s preference relation, a formal concept that describes her mental attitude to all relevant alternatives.
A market with asymmetric information
Authors: Osborne Martin J. , Rubinstein Ariel
Published: June 2023

This chapter discusses an equilibrium concept that differs from the notions of competitive equilibrium discussed in Chapters 9–12. The models in the earlier chapters specify the precise set of economic agents who operate in the market, and an equilibrium specifies the terms of trade (prices) for which the aggregate demand and supply of these agents are equal. The model we study in this chapter does not explicitly specify the set of agents. As a consequence, the equilibrium notion is more abstract. A set of contracts is an equilibrium if no agent who offers a contract wants to withdraw it, and no agent can profit by adding a contract.

We illustrate the concept by applying it to a model central to the economics of information. The problems at the end of the chapter demonstrate the use of the concept to study other economic interactions.
Mechanism design
Authors: Osborne Martin J. , Rubinstein Ariel
Published: June 2023

Consider the following problem. Some individuals in a society are X’s and others are Y ’s. Every individual of each type has to be matched with one and only one individual of the other type. For example, managers have to be matched with assistants, or pilots have to be matched with copilots. Each X has preferences over the Y ’s and each Y has preferences over the X’s. Every individual prefers to be matched than to remain unmatched. We look for matching methods that result in sensible outcomes given any preferences.
Socialism
Authors: Osborne Martin J. , Rubinstein Ariel
Published: June 2023

Consider a society in which each individual can produce the same consumption good, like food, using a single input, like land. Each individual is characterized by his productivity. The higher an individual’s productivity, the more output she produces with any given amount of the input.

An economic system can be thought of as a rule that specifies the output produced by the entire society and the allocation of this output among the individuals as a function of the individuals’ productivities. Should individuals with high productivity get more output than ones with low productivity? Should two individuals with the same productivity receive the same amount of output? Should an increase in an individual’s productivity result in him receiving more output?

The design of an economic system requires an answer to such questions. The approach in this chapter (like those in Chapters 3 and 20) is axiomatic. The central result specifies conditions capturing efficiency and fairness that are satisfied only by an economic system that resembles the socialist ideal.
P-Type Processes and Predictability: The Winter Precipitation Type Research Multiscale Experiment (WINTRE-MIX)
Authors: Minder Justin R. , Bassill Nick , Fabry Frédéric , French Jeffrey R. , Friedrich Katja , Gultepe Ismail , Gyakum John , Kingsmill David E. , Kosiba Karen , Lachapelle Mathieu , Michelson Daniel , Nichman Leonid , Nguyen Cuong , Thériault Julie M. , Winters Andrew C. , Wolde Mengistu , Wurman Joshua
Published: June 2023

During near-0°C surface conditions, diverse precipitation types (p-types) are possible, including rain, drizzle, freezing rain, freezing drizzle, ice pellets, wet snow, snow, and snow pellets. Near-0°C precipitation affects wide swaths of the United States and Canada, impacting aviation, road transportation, power generation and distribution, winter recreation, ecology, and hydrology. Fundamental challenges remain in observing, diagnosing, simulating, and forecasting near-0°C p-types, particularly during transitions and within complex terrain. Motivated by these challenges, the field phase of the Winter Precipitation Type Research Multiscale Experiment (WINTRE-MIX) was conducted from 1 February to 15 March 2022 to better understand how multiscale processes influence the variability and predictability of p-type and amount under near-0°C surface conditions. WINTRE-MIX took place near the U.S.–Canadian border, in northern New York and southern Quebec, a region with plentiful near-0°C precipitation influenced by terrain. During WINTRE-MIX, existing advanced mesonets in New York and Quebec were complemented by deployment of 1) surface instruments, 2) the National Research Council Convair-580 research aircraft with W- and X-band Doppler radars and in situ cloud and aerosol instrumentation, 3) two X-band dual-polarization Doppler radars and a C-band dual-polarization Doppler radar from the University of Illinois, and 4) teams collecting manual hydrometeor observations and radiosonde measurements. Eleven intensive observing periods (IOPs) were coordinated. Analysis of these WINTRE-MIX IOPs is illuminating how synoptic dynamics, mesoscale dynamics, and microscale processes combine to determine p-type and its predictability under near-0°C conditions. WINTRE-MIX research will contribute to improving nowcasts and forecasts of near-0°C precipitation through evaluation and refinement of observational diagnostics and numerical forecast models.
First case of very late-onset FHL2 in Spain with two variants in the PRF1 gene
Authors: Sienes Bailo Paula , Goñi Ros Nuria , Menéndez Jándula Bárbara , Álvarez Alegret Ramiro , González Gómez Eduardo , González Tarancón Ricardo , Izquierdo Álvarez Silvia
Published: June 2023

Hemophagocytic lymphohistiocytosis (HLH) is a rare but fatal disorder characterized by the proliferation and infiltration of macrophages and hyperactivated T lymphocytes that escape from the physiological control pathways and favour the existence of an environment of excessive inflammation and tissue destruction. HLH has been classified into two types: a primary or familial autosomal recessive form, caused by mutations in genes encoding proteins involved in the granule-dependent cytotoxic pathway (familial hemophagocytic lymphohistiocytosis [FHL] types 1–5); and other secondary or acquired form, generally associated with infections, malignancy, autoimmune diseases, metabolic disorders or primary immunodeficiencies. Since the first familial hemophagocytic lymphohistiocytosis-2 (FHL2) causative mutation in the PRF1 gene was described in 1999, more than 200 mutations have been identified to date. Here, we report the first case of very late-onset FHL2 in a Spanish 72-year-old female with splenomegaly, hypertriglyceridemia, hypofibrinogenemia, pancytopenia and marrow hemophagocytosis harbouring in heterozygosity two PRF1 variants proposed as causative in this study. The heterozygous mutation c.445G>A (p.Gly149Ser) identified in the exon 2 results in a missense mutation previously described as a probable pathogenic variant associated with the development of FHL2. Affecting the same exon, c.272C>T (p.Ala91Val) is the most prevalent variant of this gene. Although it was initially classified as benign, recent studies support its potential pathogenic role, considering it a variant of uncertain significance associated with a risk of developing FHL2. The genetic confirmation of FHL made possible an adequate counselling to the patient and direct relatives and provided important information for her control and follow-up.
Eloquence and Wisdom in an Age of Authenticity: The Three Dimensions of Preaching
Authors: Sandercock-Brown Grant
Published: June 2023

In our current age, authenticity is a highly regarded virtue which has very real implications for preachers in how they present themselves to their hearers and how they craft their homilies. The work of Charles Taylor will help us explore these implications. Building on an understanding of preaching as testimony and combining Taylor's insight with Augustine's timeless advice on preaching, we can then construct a three-dimensional framework for contemporary preaching in a Western context. We then reflect on the practical implications of a dimension of authenticity understood as appropriate self-disclosure. An exploration and critique of authenticity will lay the groundwork for an enhanced understanding of the contemporary preaching enterprise.