bluuebunny/crossref_metadata_2025_split huggingface dataset:
High expression of phosphoglycerate dehydrogenase predicts poor outcome in patients with high-grade serous ovarian cancer
Authors: van Wagensveld Lilian , Van Nyen Tom , Annibali Daniela , Sonke Gabe S , Kruitwagen Roy F P M , Amant Frederic , Horlings Hugo M 
Published: June 2024

Abstract

Introduction
High-grade serous ovarian cancer (HGSOC) is characterized by high mortality and prevalent recurrences. This study investigates the prognostic value of phosphoglycerate dehydrogenase (PHGDH) in HGSOC which has been linked to metabolic reprogramming and recurrences in other cancers.

Methods
Data from 306 patients with advanced-stage HGSOC treated between 2008 and 2015 were analyzed. PHGDH expression levels were determined using immunohistochemistry and categorized as “low” or “high.”

Results
PHGDH-high was associated with higher FIGO stage and increased use of neoadjuvant chemotherapy. Patients with PHGDH-high tumors had significantly worse survival than PHDH-low, even after adjusting for confounding factors.
Bioengineering secreted proteases converts divergent Rcr3 orthologs and paralogs into extracellular immune co-receptors
Authors: Kourelis Jiorgos , Schuster Mariana , Demir Fatih , Mattinson Oliver , Krauter Sonja , Kahlon Parvinderdeep S , O’Grady Ruby , Royston Samantha , Bravo-Cazar Ana Lucía , Mooney Brian C , Huesgen Pitter F , Kamoun Sophien , van der Hoorn Renier A L 
Published: June 2024

Abstract
Secreted immune proteases “Required for Cladosporium resistance-3” (Rcr3) and “Phytophthora-inhibited protease-1” (Pip1) of tomato (Solanum lycopersicum) are both inhibited by Avirulence-2 (Avr2) from the fungal plant pathogen Cladosporium fulvum. However, only Rcr3 acts as a decoy co-receptor that detects Avr2 in the presence of the Cf-2 immune receptor. Here, we identified crucial residues in tomato Rcr3 that are required for Cf-2-mediated signaling and bioengineered various proteases to trigger Avr2/Cf-2-dependent immunity. Despite substantial divergence in Rcr3 orthologs from eggplant (Solanum melongena) and tobacco (Nicotiana spp.), minimal alterations were sufficient to trigger Avr2/Cf-2-mediated immune signaling. By contrast, tomato Pip1 was bioengineered with 16 Rcr3-specific residues to initiate Avr2/Cf-2-triggered immune signaling. These residues cluster on one side of the protein next to the substrate-binding groove, indicating a potential Cf-2 interaction site. Our findings also revealed that Rcr3 and Pip1 have distinct substrate preferences determined by two variant residues and that both are suboptimal for binding Avr2. This study advances our understanding of Avr2 perception and opens avenues to bioengineer proteases to broaden pathogen recognition in other crops.
Filling the gaps on root hair development under salt stress and phosphate starvation using current evidence coupled with a meta-analysis approach
Authors: Ibeas Miguel Angel , Salinas-Grenet Hernán , Johnson Nathan R , Pérez-Díaz Jorge , Vidal Elena A , Alvarez José Miguel , Estevez José M 
Published: June 2024

Abstract
Population expansion is a global issue, especially for food production. Meanwhile, global climate change is damaging our soils, making it difficult for crops to thrive and lowering both production and quality. Poor nutrition and salinity stress affect plant growth and development. Although the impact of individual plant stresses has been studied for decades, the real stress scenario is more complex due to the exposure to multiple stresses at the same time. Here we investigate using existing evidence and a meta-analysis approach to determine molecular linkages between 2 contemporaneous abiotic stimuli, phosphate (Pi) deficiency and salinity, on a single plant cell model, the root hairs (RHs), which is the first plant cell exposed to them. Understanding how these 2 stresses work molecularly in RHs may help us build super-adaptable crops and sustainable agriculture in the face of global climate change.
Cucumber JASMONATE ZIM-DOMAIN 8 interaction with transcription factor MYB6 impairs waterlogging-triggered adventitious rooting
Authors: Pan Jiawei , Sohail Hamza , Sharif Rahat , Hu Qiming , Song Jia , Qi Xiaohua , Chen Xuehao , Xu Xuewen 
Published: June 2024

Abstract
Waterlogging is a serious abiotic stress that drastically decreases crop productivity by damaging the root system. Jasmonic acid (JA) inhibits waterlogging-induced adventitious root (AR) formation in cucumber (Cucumis sativus L.). However, we still lack a profound mechanistic understanding of how JA governs AR formation under waterlogging stress. JASMONATE ZIM-DOMAIN (JAZ) proteins are responsible for repressing JA signaling in a transcriptional manner. In this study, we showed that overexpressing CsJAZ8 inhibited the formation of ARs triggered by waterlogging. Molecular analyses revealed that CsJAZ8 inhibited the activation of the R2R3-MYB transcription factor CsMYB6 via direct interaction. Additionally, silencing of CsMYB6 negatively impacted AR formation under waterlogging stress, as CsMYB6 could directly bind to the promoters of 1-aminocyclopropane-1-carboxylate oxidase 2 gene CsACO2 and gibberellin 20-oxidase gene CsGA20ox2, facilitating the transcription of these genes. The overexpression of CsACO2 and CsGA20ox2 led to increased levels of ethylene and gibberellin, which facilitated AR formation under waterlogging conditions. On the contrary, silencing these genes resulted in contrasting phenotypes of AR formation. These results highlight that the transcriptional cascade of CsJAZ8 and CsMYB6 plays a critical role in regulating hormonal-mediated cucumber waterlogging-triggered AR formation by inhibiting ethylene and gibberellin accumulation. We anticipate that our findings will provide insights into the molecular mechanisms that drive the emergence of AR in cucumber plants under waterlogging stress.
Unthinkable actions
Authors: Steinberg Etye 
Published: June 2024

Abstract
For each person, some actions are unthinkable: performing them requires crossing a line that one's conscience cannot allow crossing. This article explores what such unthinkability is. In doing so, it introduces a novel categorization of theories of action and practical reason. The article argues that an action is unthinkable if and only if the agent judges that she should never treat any consideration as a reason in favor of performing this action. This view meets two important tests. The first is ‘Failure’: a theory of unthinkable action must allow for the conceptual possibility of doing the unthinkable and explain what is special about the failure implicated in doing the unthinkable, especially in comparison to the failure implicated in akratic action. The second is ‘Incapacity’: a theory of unthinkability must distinguish between not doing something because it is unthinkable and not doing something because of an extremely negative psychological reaction.
Asymptotic Weak Gravity Conjecture in M-theory on K3× K3
Authors: Charkaoui M , Sammani R , Saidi E H , Laamara R Ahl 
Published: June 2024

Abstract
The Asymptotic Weak Gravity Conjecture (WGC) has been proposed as a special case of the Tower WGC that probes infinite distances in the moduli space corresponding to weakly coupled gauge regimes. The conjecture has been studied in M-theory on a Calabi–Yau threefold (CY3) with finite volume inducing a 5D effective quantum field theory. In this paper, we extend the scope of the previous study to encompass lower dimensions, particularly we generalize the obtained 5D Asymptotic WGC to the effective field theory (EFT$_{3D}$) coupled to 3D gravity that descends from M-theory compactified on a Calabi–Yau fourfold with an emphasis on $K3\times K3$. We find that the CY4 has three fibration structures labeled as line Type-$\mathbb {T}^{2}$, surface Type-$\mathbb {S}$, and bulk Type-$\mathbb {V}$. The emergent EFT$_{3D}$ is shown to have 2+2 towers of particle states termed as the BPS $\mathcal {T}_{M_{\mathrm{k}}\rightarrow 0}^{\rm{{\small BPS}}}$ and $\mathcal {T}_{M_{\mathrm{k}}\rightarrow \infty }^{\rm{{\small BPS}}}$ as well as the non-BPS $\mathcal {T}_{M_{\mathrm{k}}\rightarrow 0}^{\rm{{\small N-BPS}}}$ and $\mathcal {T}_{M_{\mathrm{k}}\rightarrow \infty }^{\rm{{\small N-BPS}}}$. To ensure the viability of the 3D Asymptotic WGC, we give explicit calculations to thoroughly test the Swampland constraint for both the weakly and strongly gauge coupled regimes. Additional aspects, including the gauge symmetry breaking and duality symmetry, are also investigated.
Firm Networks and Asset Returns
Authors: Ramírez Carlos A 
Published: June 2024

Abstract
Changes in the propagation of shocks along firm networks are important to understanding aggregate and cross-sectional features of stock returns. When calibrated to match key characteristics of supplier–customer networks in the United States, a model in which firms are interlinked via enduring relationships generates long-run consumption risks, high and volatile risk premiums, and a small and stable risk-free rate. The model also matches cross-sectional patterns of portfolio returns sorted by firm centrality, a feature unaccounted for by standard asset pricing models. (JEL C67, E30, G12, L14)
The Managerial Family? Family Care Work in Germany and Spain
Authors: Lüth Laura , Zimmermann Katharina 
Published: June 2024

Abstract
This article engages with scholarly debates on the emergence of market logics in family life. By deploying qualitative data from couple interviews in Germany and Spain, we show how the existence of a so-called managerial family is salient among interviewees in both countries. Couples might introduce weekly family planning meetings or follow investment strategies when organizing childcare and housework. Drawing on the theoretical concept of moral economies, the article adds a macro-level institutional perspective to this picture of entrepreneurial family life by linking how couples justify their managerial practices to macro-level moral ideas and the institutional setup in which they live.
Investigation of the diversity, equity, inclusion, and belonging within the undergraduate student population within the Department of Animal Science at Iowa State University
Authors: Carlson Kelsi A , Bundy Jennifer M , Martin Michael J , Smalley Scott W , Johnson Anna K 
Published: June 2024

Abstract
Iowa State University (ISU) provides resources for diversity, equity, inclusion, and belonging (DEI-B) to provide students with a comfortable academic home regardless of their demographics or prior experiences. The objective of this study was to investigate undergraduate students’ DEI-B perspectives in the Department of Animal Science at ISU. One survey instrument was developed containing 14 questions that covered demographics, feelings of inclusion, comfort-seeking tools, and ways to improve DEI-B. Answer choices were either multiple choice, 1 to 5 sliding scale, or a specified text sliding scale. Eligible participants were undergraduate students enrolled in Animal or Dairy Science (n = 974). Demographics and comfort-seeking tools will be presented descriptively. Inclusion at the start and after 2 yr were compared using six different linear models. A variable was deemed significant if the P-value was ≤ 0.05. A total of 383 students (88% of total respondents) completed 50% or more of the inclusion questions. Seniors had the highest response rate. More students reported coming from a rural background. Primary species of interest was companion animals. There were no observed differences in feelings of inclusion in classes, with peers, or with faculty for hometown, admission type, ethnic group, and first generation when students started (P ≥ 0.067). There was a difference for primary species of interest (P ≤ 0.011) and with female students feeling less included (P ≤ 0.039). There were no observed differences after 2 yr in classes, with peers, or with faculty for classification year, admission type, or first generation (P ≥ 0.088). Suburban students felt the least included in classes compared to rural and urban students (P ≤ 0.036). Female students felt less included in all three categories (P ≤ 0.017). The majority of students reported having companion animal experience but almost half reported having no experience with livestock prior to ISU. A total of 51% of students said they never considered transferring to another major and 48% indicated that they plan to pursue a career in veterinary medicine. A total of 75% of students felt inclusion could be improved by creating more hands-on opportunities and 60% suggested the department provide more study space. In conclusion, the Department of Animal Science at ISU has some effective inclusion practices but needs to evolve and improve in its DEI-B practices for the undergraduate student population.
Chromatographic purification of the plasmin‐like enzyme from clamworm (Perinereis aibuhitensis Grub) and its fibrinolytic activity by metal ions
Authors: Song Tuo , Han Xinyuan , Jiang Tingting , Pu Xinyi , Wei Mingjun , Zhu Yuping , Wu Wenhui 
Published: June 2024

AbstractIn this study, fibrinolytic protease was isolated and purified from Perinereis aibuhitensis Grub, and the extraction process was optimized. The properties of the enzyme, such as the amino acid composition, thermal stability, optimal temperature, and pH, were investigated. After detoxification, proteins collected from fresh Clamworm (Perinereis aibuhitensis Grub) were concentrated via ammonium sulfate precipitation. The crude protease was purified using gel filtration resin (Sephadex G‐100), anion exchange resin (DEAE‐Sepharose FF), and hydrophobic resin (Phenyl Sepharose 6FF). The molecular weight of the protease was determined by polyacrylamide gel electrophoresis (SDS‐PAGE). The optimum temperature and optimum pH of the protease were determined. The activity of crude protease in the 40–60% salt‐out section was the highest, reaching 467.53 U/mg. The optimal process for purifying crude protein involved the application of DEAE‐Sepharose FF and Phenyl Sepharose 6FF, which resulted in the isolation of a single protease known as Asp60‐D1‐P1 with the highest fibrinolytic activity; additionally, the enzyme activity was measured at 3367.76 U/mg. Analysis by Native‐PAGE and SDS‐PAGE revealed that the molecular weight of Asp60‐D1‐P1 was 44.5 kDa, which consisted of two subunits with molecular weights of 6.5 and 37.8 kDa, respectively. The optimum temperature for Asp60‐D1‐P1 was 40°C, and the optimal pH was 8.0.
Treatment options in refractory chronic spontaneous urticaria
Authors: Pathania Yashdeep Singh 
Published: June 2024

Purpose of review
Chronic spontaneous urticaria (CSU) patients sometimes do not respond to second-generation antihistamine, and 10–50% patients do not even respond to four-fold the usual dose of nonsedating H1 antihistamine, which further leads to repeated courses of oral corticosteroids to abate the symptoms. There are third-line agents approved by EAACI guidelines, which include omalizumab and cyclosporine. Certain patients are even resistant to the third-line agents. In this review, various other treatment options will be discussed in patients of refractory CSU.

Recent findings
Recently, we demonstrated azathioprine as a possible third-line option, which was found noninferior to cyclosporine in antihistamine refractory CSU. There have been trials, studies, case series and reports, which suggest other putative options for refractory CSU management.

Summary
Studies on the management of refractory CSU are accumulating thereby expanding the armamentarium of dermatologists and allergologist against difficult-to-treat urticaria patients.
Reimagining Initial Certification as a Process That Begins During Residency to Support Continuous Development Across Training and Practice
Authors: Carraccio Carol , Schumacher Daniel J. , ten Cate Olle 
Published: June 2024

Abstract
In the United States, initial board certification remains focused on a high-stakes knowledge examination after completion of training. A more contemporary view supports a program of assessment that includes multiple types and sources of data with an emphasis on direct workplace observation to get the best picture of an individual’s performance. In this article, the authors reimagine initial certification as a continuous assessment for learning that begins in residency, focuses on both knowledge acquisition and its application, and interdigitates intentionally with the first cycle of maintenance of certification to advance learning and smooth the transition from training to practice. A more expanded view of competence, as a 3-layered construct (canonical, contextual, and personalized), supports this proposal. Canonical competence (context-independent knowledge)—best assessed through examinations of knowledge—is most heavily weighted and assessed during medical school but remains critical throughout one’s career. Contextual competence (context-dependent knowledge) is best assessed in the workplace and is key during residency and fellowship as trainees navigate a myriad of clinical work environments. Personalized competence, representing the totality of one’s unique areas of expertise, is best demonstrated during the practice years when deliberate practice experience supports the growth of personalized expertise and discoveries that advance the field. Shifting initial board certification from relying on an anxiety-provoking, high-stakes, often single moment in time-standardized examination to a nuanced approach that is part of an individual trainee’s program of assessment offers a more just and robust decision about readiness for unsupervised practice. Such a model would also sow the seeds of meaningful individualization of learning needs that begins in training, continues through practice, and lays the foundation for improving the quality of care for patients within a given practice as well as shifting the current contiguous phases of training and practice into a true continuum.
Current management of giant cell arteritis and its complications
Authors: Galli Elena , Muratore Francesco , Warrington Kenneth J. 
Published: June 2024

Purpose of the review
This review provides an update on current management strategies for giant cell arteritis (GCA), emphasizing the need for alternative therapies to reduce disease relapses and mitigate glucocorticoid (GC)-related morbidity.

Recent Findings
The standard of care for GCA has traditionally involved prolonged use of GC, and recent studies are exploring faster GC tapering regimens in an effort to reduce adverse effects while maintaining disease control. Randomized clinical trials have highlighted the efficacy of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, in reducing disease flares and sparing GCs. However, the optimal treatment duration with TCZ is unknown and patients remain at risk of relapse after treatment discontinuation. An unmet therapeutic need persists for patients who are not candidates for TCZ, and for those who have inadequate response to this biologic. Therefore, investigations into alternative therapies such as targeting interleukin-17A, blocking T-cell activation or inhibiting the Janus kinase–signal transducer and activator of transcription pathway, showcase potential avenues for tailored treatments.

Summary
While GCs remain the cornerstone of therapy, TCZ emerges as a promising GC-sparing agent. Ongoing research targeting different pathways implicated in GCA pathogenesis have led to encouraging results. However, the preliminary nature of these findings necessitates larger randomized controlled trials to establish their efficacy conclusively.
Accuracy of Phantomless Calibration of Routine Computed Tomography Scans for Opportunistic Osteoporosis Screening in the Spine Clinic
Authors: Cetik Riza M. , Crawford Charles H. , Glassman Steven D. , Dimar John R. , Gum Jeffrey L. , Djurasovic Mladen , Carreon Leah Y. 
Published: June 2024

Study Design.
Diagnostic accuracy study

Objective.
To establish a simple method of phantomless bone mineral density (BMD) measurement by using preoperative lumbar Computed Tomography (CT) scans, and compare the accuracy of reference tissue combinations to diagnose low BMD against uncalibrated Hounsfield units (HUs).

Summary of Background Data.
HUs are used as a measure of BMD; however, associations between HU and T-scores vary widely. Quantitative CT (qCT) scans are more accurate, but they require density calibration with an object of known density (phantom), which limits feasibility. As an emerging technique, phantomless (internal) calibration of routine CT scans may provide a good opportunity for screening.

Methods.
Patients who were scheduled to undergo lumbar surgery, with a preoperative CT scan, and a dual-energy x-ray absorptiometry (DXA) scan within six months were included. Four tissues were selected for calibration: subcutaneous adipose (A), erector spinae (ES), psoas (P) and aortic blood (AB). The HUs of these tissues were used in linear regression against ground-truth values. Calibrations were performed by using two different internal tissues at a time to maintain simplicity and in-office applicability.
Volumetric bone mineral densities (vBMD) derived from internally calibrated CT scans were analyzed for new threshold values for low bone density. Areas under the curve (AUC) were calculated with 95% confidence intervals (CI).

Results.
45 patients were included (M/F=10/35, mean age:63.3). Calibrated vBMDs had stronger correlations with DXA T-scores when compared with HUs, with L2 exhibiting the highest coefficients. Calibration by using A and ES with the threshold of 162 mg/cm3 had a sensitivity of 90% in detecting low BMD (AUC=0.671).

Conclusions.
This novel method allows simple, in-office calibration of routine preoperative CT scans without the use of a phantom. Calibration using adipose and erector spinae with a threshold of 162 mg/cm3 is proposed for low bone density screening with high sensitivity (90%).

Level of Evidence.
Level III