bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new Neu—a syngeneic model of spontaneously metastatic HER2-positive breast cancer
Authors: Baugh Aaron G. , Gonzalez Edgar , Narumi Valerie H. , Kreger Jesse , Liu Yingtong , Rafie Christine , Castanon Sofi , Jang Julie , Kagohara Luciane T. , Anastasiadou Dimitra P. , Leatherman James , Armstrong Todd , Chan Isaac , Karagiannis George S. , Jaffee Elizabeth M. , MacLean Adam , Roussos Torres Evanthia T. 
Published: May 2024

AbstractMetastatic disease results from the dissemination of tumor cells beyond their organ of origin to grow in distant organs and is the primary cause of death in patients with advanced breast cancer. Preclinical murine models in which primary tumors spontaneously metastasize are valuable tools for studying metastatic progression and novel cancer treatment combinations. Here, we characterize a novel syngeneic murine breast tumor cell line that provides a model of spontaneously metastatic neu-expressing breast cancer with quicker onset of widespread metastases after orthotopic mammary implantation in immune-competent NeuN mice. The NT2.5-lung metastasis (-LM) cell line was derived from serial passaging of tumor cells that were macro-dissected from spontaneous lung metastases after orthotopic mammary implantation of parental NT2.5 cells. Within one week of NT2.5-LM implantation, metastases are observed in the lungs. Within four weeks, metastases are also observed in the bones, spleen, colon, and liver. We demonstrate that NT2.5-LM metastases are positive for NeuN—the murine equivalent of human epidermal growth factor 2 (HER2). We further demonstrate altered expression of markers of epithelial-to-mesenchymal transition (EMT), suggestive of their enhanced metastatic potential. Genomic analyses support these findings and reveal enrichment in EMT-regulating pathways. In addition, the metastases are rapidly growing, proliferative, and responsive to HER2-directed therapy. The new NT2.5-LM model provides certain advantages over the parental NT2/NT2.5 model, given its more rapid and spontaneous development of metastases. Besides investigating mechanisms of metastatic progression, this new model may be used for the rationalized development of novel therapeutic interventions and assessment of therapeutic responses.
Reifying actions into artifacts: process–object duality from an embodied perspective on mathematics learning
Authors: Shvarts Anna , Bos Rogier , Doorman Michiel , Drijvers Paul 
Published: May 2024

AbstractGrasping mathematical objects as related to processes is often considered critical for mathematics understanding. Yet, the ontology of mathematical objects remains under debate. In this paper, we theoretically oppose internalist approaches that claim mental entities as the endpoints of process–object transitions and externalist approaches that stress mathematical artifacts—such as physical manipulatives and formulas—as constituting mathematical objects. We search for a view on process–object duality that overcomes the dualism of mind and body. One such approach is commognition that describes mathematical objects as discursive entities. This paper expands the nature of mathematical objects beyond discourse and highlights the role of learners’ interaction with the environment by adopting ecological onto-epistemology. We develop a functional dynamic systems perspective on process–object duality in mathematics learning emphasizing embodied actions and the re-invention of artifacts’ affordances. As a main result, we reconsider process﻿–object duality as a reification of repetitive actions into a cultural artifact that consists of two steps: (1) forming a new sensory-motor coordination that brings new perception to the fore and (2) crystallizing a new artifact in a mathematical environment that captures this new perception. An empirical example from research on embodied action-based design for trigonometry illustrates our theoretical ideas.
Graphical abstract
Prospective benchmarking of an observational analysis in the SWEDEHEART registry against the REDUCE-AMI randomized trial
Authors: Matthews Anthony A. , Dahebreh Issa J. , MacDonald Conor J. , Lindahl Bertil , Hofmann Robin , Erlinge David , Yndigegn Troels , Berglund Anita , Jernberg Tomas , Hernán Miguel A. 
Published: May 2024

AbstractProspective benchmarking of an observational analysis against a randomized trial increases confidence in the benchmarking process as it relies exclusively on aligning the protocol of the trial and the observational analysis, while the trials findings are unavailable. The Randomized Evaluation of Decreased Usage of Betablockers After Myocardial Infarction (REDUCE-AMI, ClinicalTrials.gov ID: NCT03278509) trial started recruitment in September 2017 and results are expected in 2024. REDUCE-AMI aimed to estimate the effect of long-term use of beta blockers on the risk of death and myocardial following a myocardial infarction with preserved left ventricular systolic ejection fraction. We specified the protocol of a target trial as similar as possible to that of REDUCE-AMI, then emulated the target trial using observational data from Swedish healthcare registries. Had everyone followed the treatment strategy as specified in the target trial protocol, the observational analysis estimated a reduction in the 5-year risk of death or myocardial infarction of 0.8 percentage points for beta blockers compared with no beta blockers; effects ranging from an absolute reduction of 4.5 percentage points to an increase of 2.8 percentage points in the risk of death or myocardial infarction were compatible with our data under conventional statistical criteria. Once results of REDUCE-AMI are published, we will compare the results of our observational analysis against those from the trial. If this prospective benchmarking is successful, it supports the credibility of additional analyses using these observational data, which can rapidly deliver answers to questions that could not be answered by the initial trial. If benchmarking proves unsuccessful, we will conduct a “postmortem” analysis to identify the reasons for the discrepancy. Prospective benchmarking shifts the investigator focus away from an endeavour to use observational data to obtain similar results as a completed randomized trial, to a systematic attempt to align the design and analysis of the trial and the observational analysis.
Sandy beach erosion: impacts and adaptation strategies in Thailand
Authors: Thepsiriamnuay Hiripong , Pumijumnong Nathsuda 
Published: May 2024

AbstractThis paper focuses on sandy beach erosion as a result of rising sea levels, including adaptation option analysis in Thailand. Twenty-seven beaches in the provinces of Rayong, Nakhon Si Thammarat, and Trang were selected as study areas with high rates of erosion. The major scientific challenge entailed determining the relevance and contribution of rising sea levels (including storms) to beach erosion. The SimCLIM/CoastCLIM model was utilized to forecast changes in sea level and shoreline during the period of 1940–2100. A cost–benefit analysis (CBA) was conducted to evaluate adaptation options in terms of economics. The main outcome was a relevant contribution to knowledge on sea-level rise (including storm alteration) and its effects on sandy beach erosion, in terms of loss of sandy beach area and population migration. The results indicate that Mae Phim, Ban Ko Fai, and Pak Meng beaches are all threatened by erosion, and 8.02 and 23.26% of the erosion are attributed to storms and sea-level rise. Future scenarios (in 2100) showed 124.38 cm rise in 2100 sea level (compared to the 1995 baseline) leading to 507.90 m of eroded beaches, 2.15 km2 of sand loss and 873 people migrating. The results of CBA show that scenario 2 (beach nourishment) is not proper for application as an adaptation option on sandy beaches with high amounts of erosion (Ban Ko Fai and Pak Meng beach), while the option of beach nourishment alone is likely to be applied on Mae Phim beach due to its lower rate of erosion.
Determinants of thermal homeostasis in the preimplantation embryo: a role for the embryo’s central heating system?
Authors: Leese Henry J. , Sturmey Roger G. 
Published: May 2024

AbstractA number of factors may impinge on thermal homeostasis in the early embryo. The most obvious is the ambient temperature in which development occurs. Physiologically, the temperature in the lumen of the female tract is typically lower than the core body temperature, yet rises at ovulation in the human, while in an IVF setting, embryos are usually maintained at core body temperature. However, internal cellular developmental processes may modulate thermal control within the embryo itself, especially those occurring in the mitochondria which generate intracellular heat through proton leak and provide the embryo with its own ‘central heating system’. Moreover, mitochondrial movements may serve to buffer high local intracellular temperatures. It is also notable that the preimplantation stages of development would generate proportionally little heat within their mitochondria until the blastocyst stage as mitochondrial metabolism is comparatively low during the cleavage stages. Despite these data, the specific notion of thermal control of preimplantation development has received remarkably scant consideration. This opinion paper illustrates the lack of reliable quantitative data on these markers and identifies a major research agenda which needs to be addressed with urgency in view of laboratory conditions in which embryos are maintained as well as climate change–derived heat stress which has a negative effect on numerous clinical markers of early human embryo development.
Aluminum-doped zinc oxide thickness controllable wavelengths in visible light and high responsivity devices using interrupted flow atomic layer deposition
Authors: Tseng Po-Hsien , Lai Yu-Sheng , Huang Cheng-Ming , Tsai Shang-Yu , Ko Fu-Hsiang 
Published: May 2024

AbstractIn this study, we develop a highly sensitive visible light photodetector that utilizes a thin-film structure composed of low-cost aluminum-doped zinc oxide (AZO) and n-type silicon. The AZO thickness can be adequately controlled to fit the different wavelengths of interest for photodetectors in the visible light range using interrupted flow atomic layer deposition (ALD). This in situ aluminum doping method ensures a uniform aluminum distribution within the AZO thin films and effectively increases the internal film reflections and photoresponsivity. The Schottky interface with n-type silicon is created by degenerated AZO due to the lower Fermi level, and visible light can effectively penetrate the underlying depletion zone. Optical simulation of the high conductivity of AZO indicated that the optimal thickness was 54.6, 65.8, and 91.7 nm for devices illuminated with 450 nm blue, 525 nm green and 700 nm red light, respectively. Hall effect measurements confirmed that the AZO film can achieve a low resistivity of 5 × 10–4Ω-cm and high carrier concentration of 3 × 1020 cm−3at a suitable precursor ratio. Additionally, AZO films offer multifunctionality by providing optical antireflective properties and forming Schottky junctions with n-type silicon to enable photoelectric conversion. This multifunctional role of AZO was experimentally validated through electrical, optical, and optical-to-electrical experiments, which showed that the optimized device can reach an optical responsivity of approximately 10.7 AW−1at specific visible light wavelengths. The significant photoelectrical conversion efficiency and simple thin-film structure design facilitate future applications in light intensity measurement, such as in colorimetry or fluorometry.
MiR-99a-3p downregulates TRIM21 to promote gastric cancer development
Authors: He Ling , Zhou Jiaoli , Ding Doukun , Jiang Yongjing , Yang Rui , Li Zhiming 
Published: May 2024

Abstract
Gastric cancer (GC) stands as one of the most formidable malignancies worldwide. It is well-established that miRNAs play a crucial role in the initiation and progression of various human cancers. Among these, miR-99a-3p has been implicated in the pathogenesis of GC. In the context of our study, we embarked on the comprehensive examination of miR-99a-3p expression in GC cells. Additionally, we sought to establish a correlation between miR-99a-3p expression levels and the overall survival (OS) of GC patients, and our findings hinted at its potential role in predicting an unfavorable prognosis. To further investigate the functional implications of miR-99a-3p in GC, we conducted a series of cell-based experiments after successfully knocking down miR-99a-3p. These investigations uncovered a substantial inhibition of cellular events associated with tumor progression. Moreover, employing TargetScan, we identified Tripartite motif-containing protein 21 (TRIM21) as a putative target with a binding site for miR-99a-3p. Subsequent dual-luciferase reporter gene assay confirmed the direct interaction between miR-99a-3p and TRIM21. Western blot analysis validated the alteration in TRIM21 expression levels, revealing an upregulation upon miR-99a-3p knockdown. Building on these molecular findings, we extended our investigations to human GC tissues, where we observed a downregulation of TRIM21, which, notably, correlated with shorter overall survival. Lastly, to further solidify our conclusions, we conducted a series of in vitro and in vivo rescue experiments, collectively suggesting that miR-99a-3p promoted the progression of GC cells through the downregulation of TRIM21. In summary, our study comprehensively explored the role of miR-99a-3p in GC, revealing its association with unfavorable patient outcomes, functional implications in tumor progression, and a direct regulatory relationship with TRIM21. These findings collectively underscore the significance of miR-99a-3p in the pathogenesis of GC and present a potential therapeutic avenue for further investigation.
A Prototype-Based Neural Network for Image Anomaly Detection and Localization
Authors: Huang Chao , Kang Zhao , Wu Hong 
Published: May 2024

AbstractImage anomaly detection and localization perform not only image-level anomaly classification but also locate pixel-level anomaly regions. Recently, it has received much research attention due to its wide application in various fields. This paper proposes ProtoAD, a prototype-based neural network for image anomaly detection and localization. First, the patch features of normal images are extracted by a deep network pre-trained on nature images. Then, the prototypes of the normal patch features are learned by non-parametric clustering. Finally, we construct an image anomaly localization network (ProtoAD) by appending the feature extraction network with L2 feature normalization, a $$1\times 1$$

1
×
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convolutional layer, a channel max-pooling, and a subtraction operation. We use the prototypes as the kernels of the $$1\times 1$$

1
×
1

convolutional layer; therefore, our neural network does not need a training phase and can conduct anomaly detection and localization in an end-to-end manner. Extensive experiments on two challenging industrial anomaly detection datasets, MVTec AD and BTAD, demonstrate that ProtoAD achieves competitive performance compared to the state-of-the-art methods with a higher inference speed. The code and pre-trained models are publicly available at https://github.com/98chao/ProtoAD.
Relative Performance of Volume of Distribution Prediction Methods for Lipophilic Drugs with Uncertainty in LogP Value
Authors: Coutinho Ana L. , Cristofoletti Rodrigo , Wu Fang , Al Shoyaib Abdullah , Dressman Jennifer , Polli James E. 
Published: May 2024

Abstract
Purpose
The goal was to assess, for lipophilic drugs, the impact of logP on human volume of distribution at steady-state (VDss) predictions, including intermediate fut and Kp values, from six methods: Oie-Tozer, Rodgers-Rowland (tissue-specific Kp and only muscle Kp), GastroPlus, Korzekwa-Nagar, and TCM-New.

Method
A sensitivity analysis with focus on logP was conducted by keeping pKa and fup constant for each of four drugs, while varying logP. VDss was also calculated for the specific literature logP values. Error prediction analysis was conducted by analyzing prediction errors by source of logP values, drug, and overall values.

Results
The Rodgers-Rowland methods were highly sensitive to logP values, followed by GastroPlus and Korzekwa-Nagar. The Oie-Tozer and TCM-New methods were only modestly sensitive to logP. Hence, the relative performance of these methods depended upon the source of logP value. As logP values increased, TCM-New and Oie-Tozer were the most accurate methods. TCM-New was the only method that was accurate regardless of logP value source. Oie-Tozer provided accurate predictions for griseofulvin, posaconazole, and isavuconazole; GastroPlus for itraconazole and isavuconazole; Korzekwa-Nagar for posaconazole; and TCM-New for griseofulvin, posaconazole, and isavuconazole. Both Rodgers-Rowland methods provided inaccurate predictions due to the overprediction of VDss.

Conclusions
TCM-New was the most accurate prediction of human VDss across four drugs and three logP sources, followed by Oie-Tozer. TCM-New showed to be the best method for VDss prediction of highly lipophilic drugs, suggesting BPR as a favorable surrogate for drug partitioning in the tissues, and which avoids the use of fup.
Strangers in the Homeland? The Academic Performance of U.S.-Born Children of Return Migrants in Mexico
Authors: Hoffmann Nathan I. 
Published: May 2024

AbstractThe number of return migrants from the U.S. to Mexico has swelled in recent years, yet we know little about the academic performance of the over 500,000 U.S.-born children who have accompanied them. This study compares Programme for International Student Assessment (PISA) test scores of U.S.-born children of return migrants in Mexico to two groups: Mexican-born students in Mexico and students in the U.S. born to Spanish-speaking immigrant parents. While previous work often highlights the struggles these children face in adapting to schools in Mexico, at age 15 they attain slightly higher PISA scores than their Mexican-born counterparts. However, these adolescents’ scores are much lower than similar youths’ in the U.S. Results for both comparisons change little in models controlling for variables related to immigrant selection and are consistent across possible individual moderators, including age at migration. This paper highlights the importance of a cross-border perspective and attention to institutional context in studies of immigrant education.
The medium is the message: toxicity declines in structured vs unstructured online deliberations
Authors: Klein Mark , Majdoubi Nouhayla 
Published: May 2024

AbstractHumanity needs to deliberate effectively at scale about highly complex and contentious problems. Current online deliberation tools—such as email, chatrooms, and forums—are however plagued by levels of discussion toxicity that deeply undercut the willingness and ability of the participants to engage in thoughtful, meaningful, deliberations. This has led many organizations to either shut down their forums or invest in expensive, frequently unreliable, and ethically fraught moderation of people's contributions in their forums. This paper includes a comprehensive review on online toxicity, and describes how a structured deliberation process can substantially reduce toxicity compared to current approaches. The key underlying insight is that unstructured conversations create, especially at scale, an “attention wars” dynamic wherein people are often incented to resort to extremified language in order to get visibility for their postings. A structured deliberation process wherein people collaboratively create a compact organized collection of answers and arguments removes this underlying incentive, and results, in our evaluation, in a 50% reduction of high-toxicity posts.
Gender differences in obstructive sleep apnea syndrome: a pilot study
Authors: Fabozzi Antonio , Pasqualotto Federico , Laguardia Marianna , Natuzzi Pietro Francesco , Capone Rosaria , Steffanina Alessia , Pellegrino Daniela , Olmati Federica , Antonaglia Caterina , Palange Paolo 
Published: May 2024

Abstract
Purpose
OSAS is a syndrome that often presents clinically differently between men and women. The aim of this study was to assess the clinical presentation, nocturnal home sleep cardiorespiratory monitoring and therapeutic adherence to CPAP in both sexes to identify the most frequent patterns.

Methods
Data from the first visit, the nocturnal home sleep cardiorespiratory monitoring and follow-up visit of 74 OSA patients were collected. Exclusion criteria included other respiratory and/or neuromuscular diseases (including Obesity hypoventilation syndrome) and other non-respiratory sleep disorders.

Results
Men were older and had a higher supine AHI and ODI compared to women. In addition, BMI and age correlated positively with AHI in males. Women had a higher hypopneas frequency and better therapeutic adherence to CPAP.

Conclusions
Men were associated with a higher AHI when sleeping in the supine position and this may be useful to look for new therapeutic options in combination with or as an alternative to CPAP. BMI correlated positively with AHI in men and this should be considered to stimulate weight loss as the main treatment to reduce the number of apneas/hypopneas, as men also had less therapeutic adherence to CPAP in our study. Females presented a significantly higher frequency of hypopneas than men, as well as a lower number of desaturation events per hour (ODI): these differences in the nocturnal home sleep cardiorespiratory monitoring could reflect different pathophysiological mechanisms of OSAS onset between the two sexes, which should be investigated in future scientific studies.
Assessment of EHR Efficiency Tools and Resources Associated with Physician Time Spent on the Inbox
Authors: Bundy Richa , Moses Adam , Stambaugh Elisabeth , Stewart Paschal , Witek Lauren , Carlasare Lindsey , Rosenthal Gary , Sinsky Christine , Dharod Ajay 
Published: May 2024

Abstract
Background
Physicians are experiencing an increasing burden of messaging within the electronic health record (EHR) inbox. Studies have called for the implementation of tools and resources to mitigate this burden, but few studies have evaluated how these interventions impact time spent on inbox activities.

Objective
Explore the association between existing EHR efficiency tools and clinical resources on primary care physician (PCP) inbox time.

Design
Retrospective, cross-sectional study of inbox time among PCPs in network clinics affiliated with an academic health system.

Participants
One hundred fifteen community-based PCPs.

Main Measures
Inbox time, in hours, normalized to eight physician scheduled hours (IB-Time8).

Key Results
Following adjustment for physician sex as well as panel size, age, and morbidity, we observed no significant differences in inbox time for physicians with and without message triage, custom inbox QuickActions, encounter specialists, and message pools. Moreover, IB-Time8 increased by 0.01 inbox hours per eight scheduled hours for each additional staff member resource in a physician’s practice (p = 0.03).

Conclusions
Physician inbox time was not associated with existing EHR efficiency tools evaluated in this study. Yet, there may be a slight increase in inbox time among physicians in practices with larger teams.