bluuebunny/crossref_metadata_2025_split huggingface dataset:
EDI3 knockdown in ER-HER2+ breast cancer cells reduces tumor burden and improves survival in two mouse models of experimental metastasis
Authors: Glotzbach Annika , Rohlf Katharina , Gonscharow Anastasia , Lüke Simon , Demirci Özlem , Begher-Tibbe Brigitte , Overbeck Nina , Reinders Jörg , Cadenas Cristina , Hengstler Jan G. , Edlund Karolina , Marchan Rosemarie 
Published: May 2024

Abstract
Background
Despite progress understanding the mechanisms underlying tumor spread, metastasis remains a clinical challenge. We identified the choline-producing glycerophosphodiesterase, EDI3 and reported its association with metastasis-free survival in endometrial cancer. We also observed that silencing EDI3 slowed cell migration and other cancer-relevant phenotypes in vitro. Recent work demonstrated high EDI3 expression in ER-HER2+ breast cancer compared to the other molecular subtypes. Silencing EDI3 in ER-HER2+ cells significantly reduced cell survival in vitro and decreased tumor growth in vivo. However, a role for EDI3 in tumor metastasis in this breast cancer subtype was not explored. Therefore, in the present work we investigate whether silencing EDI3 in ER-HER2+ breast cancer cell lines alters phenotypes linked to metastasis in vitro, and metastasis formation in vivo using mouse models of experimental metastasis.

Methods
To inducibly silence EDI3, luciferase-expressing HCC1954 cells were transduced with lentiviral particles containing shRNA oligos targeting EDI3 under the control of doxycycline. The effect on cell migration, adhesion, colony formation and anoikis was determined in vitro, and significant findings were confirmed in a second ER-HER2+ cell line, SUM190PT. Doxycycline-induced HCC1954-luc shEDI3 cells were injected into the tail vein or peritoneum of immunodeficient mice to generate lung and peritoneal metastases, respectively and monitored using non-invasive bioluminescence imaging. Metabolite levels in cells and tumor tissue were analyzed using targeted mass spectrometry and MALDI mass spectrometry imaging (MALDI-MSI), respectively.

Results
Inducibly silencing EDI3 reduced cell adhesion and colony formation, as well as increased susceptibility to anoikis in HCC1954-luc cells, which was confirmed in SUM190PT cells. No influence on cell migration was observed. Reduced luminescence was seen in lungs and peritoneum of mice injected with cells expressing less EDI3 after tail vein and intraperitoneal injection, respectively, indicative of reduced metastasis. Importantly, mice injected with EDI3-silenced cells survived longer. Closer analysis of the peritoneal organs revealed that silencing EDI3 had no effect on metastatic organotropism but instead reduced metastatic burden. Finally, metabolic analyses revealed significant changes in choline and glycerophospholipid metabolites in cells and in pancreatic metastases in vivo.

Conclusions
Reduced metastasis upon silencing supports EDI3’s potential as a treatment target in metastasizing ER-HER2+ breast cancer.
Long-term prosthetic-associated subclinical thrombotic events evaluation by cardiac CTA after transcatheter aortic valve implantation: incidence and outcomes
Authors: Zhou Qijing , Wen Jiaqi , Zhu Qifeng , Fan Jiaqi , Guan Xiaojun , Chen Xinyi , He Yuxin , Guo Yuchao , Jiang Jubo , Ding Xinfa , Pu Zhaoxia , Huang Zhaoxu , Li Cheng , Zhang Minming , Liu Xianbao , Xu Xiaojun , Wang Jian’an 
Published: May 2024

Abstract
Objective
To observe prosthetic-associated subclinical thrombotic events (PASTE) after transcatheter aortic valve implantation (TAVI) by cardiac CTA, and assess their impact on long-term patient outcomes.

Materials
We prospectively and consecutively enrolled 188 patients with severe aortic stenosis treated with TAVI from February 2014 to April 2017. At 5 years, 61 of 141 survived patients who had completed annual follow-up CTA (≥ 5 years) were included. We analyzed PASTE by CTA, including hypoattenuated leaflet thickening (HALT), sinus filling defect (SFD), and prosthesis filling defect (PFD). The primary outcome was a major adverse cardiovascular composite outcome (MACCO) of stroke, cardiac re-hospitalization, and bioprosthetic valve dysfunction (BVD); the secondary outcomes were bioprosthetic hemodynamics deterioration (PGmean) and cardiac dysfunction (LVEF).

Results
During a median follow-up time of 5.25 years, long-term incidence of HALT, SFD, and PFD were 54.1%, 37.7%, and 73.8%, respectively. In the primary outcome, SFD and early SFD were associated with the MACCO (SFD: p = 0.005; early SFD: p = 0.018), and SFD was a predictor of MACCO (HR: 2.870; 95% CI: 1.010 to 8.154, p = 0.048). In the secondary outcomes, HALT was associated with increased PGmean (p = 0.031), while persistent HALT was correlated with ΔPGmean (β = 0.38, p = 0.035). SFD was negatively correlated with ΔLVEF (β = −0.39, p = 0.041), and early SFD was negatively correlated with LVEF and ΔLVEF (LVEF: r = −0.50, p = 0.041; ΔLVEF: r = −0.53, p = 0.030).

Conclusions
PASTE were associated with adverse long-term outcomes, bioprosthetic hemodynamics deterioration, and cardiac dysfunction. In particular, SFD was a predictor of MACCO and may be a potential target for anticoagulation after TAVI (NCT02803294).

Registration
URL: https://www.clinicaltrials.gov; Unique identifier: NCT02803294.

Critical relevance statement
PASTE, especially SFD, after TAVI based on cardiac CTA findings impacts the long-term outcomes of patients which is a predictor of long-term major adverse outcomes in patients and may be a potential target for anticoagulation after TAVI.

Key Points

Transcatheter aortic valve implantation is being used more often; associated subclinical thromboses have not been thoroughly evaluated.

Prosthetic-associated subclinical thrombotic events were associated with adverse outcomes, bioprosthetic hemodynamics deterioration, and cardiac dysfunction.

Studies should be directed at these topics to determine if they should be intervened upon.

Graphical Abstract
MolScore: a scoring, evaluation and benchmarking framework for generative models in de novo drug design
Authors: Thomas Morgan , O’Boyle Noel M. , Bender Andreas , De Graaf Chris 
Published: May 2024

AbstractGenerative models are undergoing rapid research and application to de novo drug design. To facilitate their application and evaluation, we present MolScore. MolScore already contains many drug-design-relevant scoring functions commonly used in benchmarks such as, molecular similarity, molecular docking, predictive models, synthesizability, and more. In addition, providing performance metrics to evaluate generative model performance based on the chemistry generated. With this unification of functionality, MolScore re-implements commonly used benchmarks in the field (such as GuacaMol, MOSES, and MolOpt). Moreover, new benchmarks can be created trivially. We demonstrate this by testing a chemical language model with reinforcement learning on three new tasks of increasing complexity related to the design of 5-HT2a ligands that utilise either molecular descriptors, 266 pre-trained QSAR models, or dual molecular docking. Lastly, MolScore can be integrated into an existing Python script with just three lines of code. This framework is a step towards unifying generative model application and evaluation as applied to drug design for both practitioners and researchers. The framework can be found on GitHub and downloaded directly from the Python Package Index.Scientific ContributionMolScore is an open-source platform to facilitate generative molecular design and evaluation thereof for application in drug design. This platform takes important steps towards unifying existing benchmarks, providing a platform to share new benchmarks, and improves customisation, flexibility and usability for practitioners over existing solutions.
Graphical Abstract
Anatomy and size of Megateuthis, the largest belemnite
Authors: Klug Christian , Schweigert Günter , Hoffmann René , Fuchs Dirk , Pohle Alexander , Weis Robert , De Baets Kenneth 
Published: May 2024

AbstractBelemnite rostra are very abundant in Mesozoic marine deposits in many regions. Despite this abundance, soft-tissue specimens of belemnites informing about anatomy and proportions of these coleoid cephalopods are extremely rare and limited to a few moderately large genera like Passaloteuthis and Hibolithes. For all other genera, we can make inferences on their body proportions and body as well as mantle length by extrapolating from complete material. We collected data of the proportions of the hard parts of some Jurassic belemnites in order to learn about shared characteristics in their gross anatomy. This knowledge is then applied to the Bajocian genus Megateuthis, which is the largest known belemnite genus worldwide. Our results provide simple ratios that can be used to estimate belemnite body size, where only the rostrum is known.
The effectiveness of e-mental health interventions on stress, anxiety, and depression among healthcare professionals: a systematic review and meta-analysis
Authors: Zhang Zemiao , Hu Yinhuan , Liu Sha , Feng Xiandong , Yang Jinhong , Cheng Ling Jie , Ramazanu Sheena , Wu Xi Vivien 
Published: May 2024

Abstract
Background
Many healthcare professionals are experiencing psychological distress. Electronic mental health (e-mental health) interventions are convenient and multifunctional. This review aimed to examine the effectiveness of e-mental health interventions in enhancing the well-being of healthcare professionals and to identify moderating factors.

Methods
A comprehensive and systematic retrieval of randomized controlled trial (RCT) studies was conducted across eight databases. Population, intervention, comparison, and outcome (PICO) were used to define eligibility criteria. Stress, anxiety, and depression were included as the main outcomes. The overall effect was calculated based on the random effect model, and the effect size was presented using the standardized mean difference. The characteristics of the research design, intervention object, and intervention design were further selected as potential moderating factors for subgroup analysis. Meta-regression analyses were finally performed, incorporating intervention duration and sample size as independent variables.

Results
A total of 20 studies were included in the systematic review, and 17 were included in the meta-analysis. A large effect on relieving stress and anxiety and a small-to-medium effect on reducing depression were observed. Subgroup analyses showed that features including mindfulness approaches, online courses, computer use, group interventions, and professional guidance were more favorable in the design of services. Meta-regression revealed that intervention duration only affected anxiety symptoms. Caution should be exercised, as some subgroups had fewer studies and higher heterogeneity. For the secondary outcomes, a large effect on emotional exhaustion and a small-to-medium effect on well-being were observed.

Conclusion
In general, e-mental health interventions significantly improve the psychological health of healthcare staff. Future high-quality, large-scale studies targeting healthcare professionals and specific intervention scenarios are warranted.
How much online pornography is too much? A comparison of two theoretically distinct assessment scales
Authors: Vera Cruz Germano , Aboujaoude Elias , Liberacka-Dwojak Magdalena , Wiłkość-Dębczyńska Monika , Rochat Lucien , Khan Riaz , Khazaal Yasser 
Published: May 2024

Abstract
Background
Online pornography use, an ever more common activity, has raised myriad psychosocial and clinical concerns. While there is a need to screen for and measure its problematic dimension, there is a debate about the adequacy of existing assessment tools.

Objective
The study compares two instruments for measuring pathological online pornography use (POPU) that are based on different theoretical frameworks—one in line with DSM-5 criteria and the six-component addiction model and one in line with ICD-11 criteria.

Methods
An international sample of 1,823 adults (Mean age = 31.66, SD = 6.74) answered an online questionnaire that included the Short Version of the Problematic Pornography Consumption Scale (PPCS-6) and the Assessment of Criteria for Specific Internet-Use Disorders (ACSID-11). Factorial, correlational, and network analyses were conducted on the data.

Results
Both tools adequately screened for online “addictive” behavior, but the ACSID-11 was superior in assessing the degree of clinical risk.

Conclusion
Depending on the specific aim of the assessment (screening vs. clinical diagnostics), both online pornography measurement tools may be useful.
Thyroid Malignancy in Patients Who Underwent Thyroidectomy for Multinodular Goiter and Solitary Thyroid Nodule
Authors: Gedamu Desalew , Shimels Tariku , Kassie Daniel , Chanyalew Zewditu , Eyasu Mebrahtu 
Published: May 2024

PURPOSE Worldwide, incidence of thyroid malignancy is increasing. The purpose of this study was to evaluate the pattern and magnitude of nodule types. METHODS A cross-sectional retrospective study was performed at Saint Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia, among patients who underwent thyroidectomy from May 2018 to June 2022. Data were extracted using a structured format. Descriptive statistics were performed using SPSS version 26 software. Results were presented in terms of percentages and frequencies. RESULTS During a 4-year period, 1,476 patients had thyroidectomies and histopathologic information of 212 malignant cases was studied. Within multinodular goiter (MNG), thyroid cancer accounted for 69.8% (n = 148) of patients, whereas in solitary nodules, it accounted for 30.2%. From the total, 160 participants (75.5%) were female, and the female:male ratio was 3.1 (mean, 41.72; ± standard deviation [SD], 16.44) years, and age range of 12-88 years versus men, who have a mean of 44.71 (±SD, 14.91) years and an age range of 21-78 years. The mean age of male cases with solitary nodule and MNG was 40.6 and 46.5 years, respectively. The most frequent cancer in both types of nodules, accounting for 59% of patients, was papillary carcinoma, which was found in 64% of solitary nodules and 57.4% of multinodular nodules. Overall, 14.1% of tumors had multiple centers (17.4% in multinodular nodules and 6.9% in solitary nodules). In 7.1% of patients, microcarcinoma (<1 cm) was found, with papillary carcinoma accounting for 91.7% of the total. CONCLUSION Compared with men, women with cancer typically manifested at a younger age. Males with malignancy in solitary nodules had a lower mean age than those with MNGs. The most frequent and significant cause of multicentric presentation is papillary carcinoma.
Categorical Displacement
Authors: Moffett-Bateau Courtney 
Published: May 2024

Abstract
This article offers a history of Black thought as it has been represented or underrepresented in the university by tracing the phenomenon of the US American cultural wars to the Civil War. The article discusses the displacement of Black knowledges from predominantly white institutional structures as a categorical problem that spreads across all disciplines by identifying four formative aspects of the university: understanding the university as an institution, its relationship with society and literature, and the canon-building discourses that fuel a market demand for certain Black knowledges. Finding that the displacement of Black knowledges is facilitated by a logic of institutional discrimination, which cannot be reduced to only a problem of the university, this article argues that the displacement of Black knowledges is a central problem of American education and foundational to American society and history.
Sibling Availability, Sibling Sorting, and Subjective Health Among Chinese Adults
Authors: Wang Haowei , Verdery Ashton M. , Margolis Rachel 
Published: May 2024

Abstract
Despite rising numbers of only children in China, little is known about their family dynamics and well-being in adulthood—for example, how often they marry other only children and whether those in siblingless families have worse or better health than others. Theoretical expectations produce opposing predictions: siblings might provide social and emotional support and reduce parental caregiving pressures, but only children might receive more support from parents and grandparents. Using the 2010 China Family Panel Study, we examine marital sorting on Chinese adults’ number of siblings and test whether sibling availability and sibling sorting are associated with subjective physical and mental health. Despite general perceptions that China has an exceedingly high prevalence of adults with no siblings that might produce very small families, results demonstrate a low prevalence of siblingless couples (i.e., both spouses are only children). Married adults with no siblings or siblings-in-law have better subjective physical health but similar levels of subjective mental health relative to their counterparts with siblings. The health advantages of siblingless marital unions are greater for rural and female adults. Declining sibling prevalence in China will shape future family demographic dynamics but appears less detrimental to population health than sometimes assumed.
On Archipelagic Memory: A Conversation with Michael Rothberg and Vijaya Teelock
Authors: Raimondi Luca , Kabir Ananya Jahanara 
Published: May 2024

AbstractOn February 1, 2022, the online seminar “Conceptualising Archipelagic Memory” was organized as the curtain-raiser event for the Archipelagic Memory project and the international conference that took place in August of the same year. The seminar brought together Professors Michael Rothberg and Vijaya Teelock, in conversation with Ananya Kabir, to initiate a discussion on practices of memory-making in archipelagic spaces and through archipelagic structures, and on the meanings and possibilities embedded in the notion of “archipelagic memory.” In this annotated transcript of the conversation, Rothberg and Teelock reflect with Kabir on their research trajectories and expertise, provoking new models of analysis constitutive of an archipelagic approach to Indian Ocean cultural history.
Establishment and maintenance of random monoallelic expression
Authors: Kanata Eleni , Duffié Rachel , Schulz Edda G. 
Published: May 2024

ABSTRACT
This Review elucidates the regulatory principles of random monoallelic expression by focusing on two well-studied examples: the X-chromosome inactivation regulator Xist and the olfactory receptor gene family. Although the choice of a single X chromosome or olfactory receptor occurs in different developmental contexts, common gene regulatory principles guide monoallelic expression in both systems. In both cases, an event breaks the symmetry between genetically and epigenetically identical copies of the gene, leading to the expression of one single random allele, stabilized through negative feedback control. Although many regulatory steps that govern the establishment and maintenance of monoallelic expression have been identified, key pieces of the puzzle are still missing. We provide an overview of the current knowledge and models for the monoallelic expression of Xist and olfactory receptors. We discuss their similarities and differences, and highlight open questions and approaches that could guide the study of other monoallelically expressed genes.
An updated model of shoot apical meristem regulation by ERECTA family and CLAVATA3 signaling pathways in Arabidopsis
Authors: Uzair Muhammad , Urquidi Camacho Ricardo Andres , Liu Ziyi , Overholt Alex M. , DeGennaro Daniel , Zhang Liang , Herron Brittani S. , Hong Tian , Shpak Elena D. 
Published: May 2024

ABSTRACT
The shoot apical meristem (SAM) gives rise to the aboveground organs of plants. The size of the SAM is relatively constant due to the balance between stem cell replenishment and cell recruitment into new organs. In angiosperms, the transcription factor WUSCHEL (WUS) promotes stem cell proliferation in the central zone of the SAM. WUS forms a negative feedback loop with a signaling pathway activated by CLAVATA3 (CLV3). In the periphery of the SAM, the ERECTA family receptors (ERfs) constrain WUS and CLV3 expression. Here, we show that four ligands of ERfs redundantly inhibit the expression of these two genes. Transcriptome analysis confirmed that WUS and CLV3 are the main targets of ERf signaling and uncovered new ones. Analysis of promoter reporters indicated that the WUS expression domain mostly overlaps with the CLV3 domain and does not shift along the apical-basal axis in clv3 mutants. Our three-dimensional mathematical model captured gene expression distributions at the single-cell level under various perturbed conditions. Based on our findings, CLV3 regulates cellular levels of WUS mostly through autocrine signaling, and ERfs regulate the spatial expression of WUS, preventing its encroachment into the peripheral zone.
Investigating pulmonary neuroendocrine cells in human respiratory diseases with airway models
Authors: Candeli Noah , Dayton Talya 
Published: May 2024

ABSTRACT
Despite accounting for only ∼0.5% of the lung epithelium, pulmonary neuroendocrine cells (PNECs) appear to play an outsized role in respiratory health and disease. Increased PNEC numbers have been reported in a variety of respiratory diseases, including chronic obstructive pulmonary disease and asthma. Moreover, PNECs are the primary cell of origin for lung neuroendocrine cancers, which account for 25% of aggressive lung cancers. Recent research has highlighted the crucial roles of PNECs in lung physiology, including in chemosensing, regeneration and immune regulation. Yet, little is known about the direct impact of PNECs on respiratory diseases. In this Review, we summarise the current associations of PNECs with lung pathologies, focusing on how new experimental disease models, such as organoids derived from human pluripotent stem cells or tissue stem cells, can help us to better understand the contribution of PNECs to respiratory diseases.
Long-Run Effects of Incentivizing Work after Childbirth
Authors: Kuka Elira , Shenhav Na’ama 
Published: May 2024

This paper identifies the impact of increasing post-childbirth work incentives on mothers’ long-run careers. We exploit variation in work incentives across mothers based on the timing of a first birth and eligibility for the 1993 expansion of the Earned Income Tax Credit. Ten to nineteen years after a first birth, single mothers who were exposed to the expansion immediately after birth (“early”), rather than 3–6 years later (“late”), have 0.62 more years of work experience and 4.2 percent higher earnings conditional on working. We show that higher earnings are primarily explained by improved wages due to greater work experience. (JEL H24, H31, J16, J22, J31)