bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutual interaction of neurons and astrocytes derived from iPSCs with APP V717L mutation developed the astrocytic phenotypes of Alzheimer’s disease
Authors: Supakul Sopak , Murakami Rei , Oyama Chisato , Shindo Tomoko , Hatakeyama Yuki , Itsuno Maika , Bannai Hiroko , Shibata Shinsuke , Maeda Sumihiro , Okano Hideyuki 
Published: February 2024

Abstract
Background
The development of induced pluripotent stem cells (iPSCs) technology has enabled human cellular disease modeling for inaccessible cell types, such as neural cells in the brain. However, many of the iPSC-derived disease models established to date typically involve only a single cell type. These monoculture models are inadequate for accurately simulating the brain environment, where multiple cell types interact. The limited cell type diversity in monoculture models hinders the accurate recapitulation of disease phenotypes resulting from interactions between different cell types. Therefore, our goal was to create cell models that include multiple interacting cell types to better recapitulate disease phenotypes.

Methods
To establish a co-culture model of neurons and astrocytes, we individually induced neurons and astrocytes from the same iPSCs using our novel differentiation methods, and then co-cultured them. We evaluated the effects of co-culture on neurons and astrocytes using immunocytochemistry, immuno-electron microscopy, and Ca2+ imaging. We also developed a co-culture model using iPSCs from a patient with familial Alzheimer's disease (AD) patient (APPV717L mutation) to investigate whether this model would manifest disease phenotypes not seen in the monoculture models.

Results
The co-culture of the neurons and astrocytes increased the branching of astrocyte processes, the number of GFAP-positive cells, neuronal activities, the number of synapses, and the density of presynaptic vesicles. In addition, immuno-electron microscopy confirmed the formation of a tripartite synaptic structure in the co-culture model, and inhibition of glutamate transporters increased neuronal activity. Compared to the co-culture model of the control iPSCs, the co-culture model of familial AD developed astrogliosis-like phenotype, which was not observed in the monoculture model of astrocytes.

Conclusions
Co-culture of iPSC-derived neurons and astrocytes enhanced the morphological changes mimicking the in vivo condition of both cell types. The formation of the functional tripartite synaptic structures in the co-culture model suggested the mutual interaction between the cells. Furthermore, the co-culture model with the APPV717L mutation expressed in neurons exhibited an astrocytic phenotype reminiscent of AD brain pathology. These results suggest that our co-culture model is a valuable tool for disease modeling of neurodegenerative diseases.
Real-world use and clinical impact of an electronic patient-reported outcome tool in patients with solid tumors treated with immuno-oncology therapy
Authors: Dickson Natalie R , Beauchamp Karen D , Perry Toni S , Roush Ashley , Goldschmidt Deborah , Edwards Marie Louise , Blakely L Johnetta 
Published: February 2024

Abstract
Background
Utilization of electronic patient-reported outcome (ePRO) tools to monitor symptoms in patients undergoing cancer treatment has shown clinical benefits. Tennessee Oncology (TO) implemented an ePRO platform in 2019, allowing patients to report their health status online. We conducted a real-world, multicenter, observational, non-interventional cohort study to evaluate utilization of this platform in adults with solid tumors who initiated immuno-oncology (IO) therapy as monotherapy or in combination at TO clinics.

Methods
Patients initiating IO therapy prior to platform implementation were included in a historical control (HC) cohort; those initiating treatment after implementation were included in the ePRO cohort, which was further divided into ePRO users (platform enrollment ≤ 45 days from IO initiation) and non-users. Data were extracted from electronic medical records; patients were followed for up to 6 months (no minimum follow up). Outcomes included patient characteristics, treatment patterns, duration of therapy (DoT), and overall survival (OS).

Results
Data were collected for 538 patients in the HC and 1014 in the ePRO cohort; 319 in the ePRO cohort were ePRO users (uptake rate 31%). Baseline age was higher, more patients had stage IV disease at diagnosis, and more received monotherapy (82 vs 52%, respectively) in the HC vs the ePRO cohort. Median follow-up was 181.0 days (range 0.0–182.6) in the HC and 175.0 (0.0–184.0) in the ePRO cohort. Median DoT of index IO regimen was 5.1 months (95% confidence interval [CI], 4.4–NE) in the HC cohort vs not estimable (NE) in the ePRO cohort. Multivariable regression adjusting for baseline differences confirmed lower risk of treatment discontinuation in the ePRO vs HC cohort: hazard ratio (HR) 0.83 (95% CI, 0.71–0.97); p < 0.05. The estimated 6-month OS rate was 65.5% in the HC vs 72.4% in the ePRO cohort (p < 0 .01). Within the ePRO cohort, DoT of index IO regimen and OS did not differ between users and non-users. In ePRO users, patient platform use was durable over 6 months.

Conclusion
Improvements in DoT and OS were seen after ePRO platform implementation. Conclusions are limited by challenges in separating the impact of platform implementation from other changes affecting outcomes.
Viabahn stent graft for arterial injury management: safety, technical success, and long-term outcome
Authors: Brendel Jan M. , Mangold Tobias , Lescan Mario , Schmehl Jörg , Ghibes Patrick , Grimm Antonia , Greulich Simon , Krumm Patrick , Artzner Christoph , Grözinger Gerd , Estler Arne 
Published: February 2024

Abstract
Background
The Viabahn stent graft has emerged as an integral tool for managing vascular diseases, but there is limited long-term data on its performance in emergency endovascular treatment. This study aimed to assess safety, technical success, and long-term efficacy of the Viabahn stent graft in emergency treatment of arterial injury.

Methods
We conducted a retrospective single tertiary centre analysis of patients who underwent Viabahn emergency arterial injury treatment between 2015 and 2020. Indication, intraoperative complications, technical and clinical success, and major adverse events at 30 days were evaluated. Secondary efficacy endpoints were the primary and secondary patency rates assessed by Kaplan–Meier analysis.

Results
Forty patients (71 ± 13 years, 19 women) were analyzed. Indications for Viabahn emergency treatment were extravasation (65.0%), arterio-venous fistula (22.5%), pseudoaneurysm (10.0%), and arterio-ureteral fistula (2.5%). No intraoperative adverse events occurred, technical and clinical success rates were 100%. One acute stent graft occlusion occurred in the popliteal artery on day 9, resulting in a 30-day device-related major-adverse-event rate of 2.5%. Median follow-up was 402 days [IQR, 43–1093]. Primary patency rate was 97% (95% CI: 94–100) in year 1, and 92% (95% CI: 86–98) from years 2 to 6. One stent graft occlusion occurred in the external iliac artery at 18 months; successful revascularization resulted in secondary patency rates of 97% (95% CI: 94–100) from years 1 to 6.

Conclusion
Using Viabahn stent graft in emergency arterial injury treatment had 100% technical and clinical success rates, a low 30-day major-adverse-event rate of 2.5%, and excellent long-term patency rates.
Clinical and radiological results of high tibial of osteotomy over the age of 65 are comparable to that of under 55 at minimum 2-year follow-up: a propensity score matched analysis
Authors: Park Jae-Young , Kim Jae-Hwa , Cho Jin-woo , Kim Min soo , Choi Wonchul 
Published: February 2024

Abstract
Purpose
The results of medial open-wedge high tibial osteotomy (MOWHTO) according to age is inconclusive. This study aimed to compare the clinical outcomes and failure of MOWHTO in patients < 55 years and > 65 years.

Methods
Consecutive patients who underwent MOWHTO from July 2009 to August 2020 were retrospectively analyzed. 205 patients were considered for analysis. A 1-to-1 propensity score matched analysis to assess clinical outcomes scores including International Knee Documentation Committee (IKDC) subjective score and Lysholm score, radiologic outcomes, complication, and Total Knee Arthroplasty (TKA) conversion between patients > 65 years and patients < 55 years was performed. Radiologic outcomes included Hip-Knee-Ankle (HKA) angle, Weight Bearing Line ratio (WBLR), posterior tibial slope (PTS), and Insall-Salvati (IS) ratio before and after surgery.

Results
The follow-up period was 50.4 months in patients > 65 years and 55.3 months in patients < 55 years. There was no significant difference in the preoperative and postoperative HKA angle, WBLR, PTS, IS ratio, IKDC score and Lysholm score between the two groups. The arthroscopic evaluation of cartilage did not show any statistically significant differences between the two groups. Regarding Minimal clinically important differences (MCID), in the 26% of the older group exceeded MCID of IKDC score; 45% of the older group exceeded MCID of Lysholm score. In the younger group, 24% exceeded MCID of IKDC score and 35% exceeded MCID of Lysholm score. In older group, there were 7 (11.3%) cases of TKA conversion while no TKA conversion was recorded in the younger group. (P = 0.007) The average time to TKA conversion was 67 months. (42 months to 90 months) Kaplan–Meier analysis revealed that the survival rate was 95.2% at 4 years in the older group.

Conclusion
Similar clinical results were obtained in patients over 65 years of age that were eligible for MOWHTO at minimum 2-year follow-up as in patients under 55 years of age. MOWHTO may be a viable option in older patients if proper indications are met. However, the risk of TKA conversion must be considered preoperatively and discussed with patients.
Study Design: Cohort study; Level of evidence, 3.
Collision frequency measurement from optical reflectivity of laser indirect-driven CH/Al/diamond
Authors: Zhang Zhiyu , Hou Yong , Zhao Yang , Zhang Jiyan , Xu Tao , Jing Longfei , Qing Bo , Xiong Gang , Lv Min , Wang Feng , Du Huabing , Zhan Xiayu , Song Tianming , Huang Chengwu , Zhu Tuo , Zhang Yuxue , Zhao Yan , Zhang Lu , Li Liling , Yang Jiamin 
Published: February 2024

Abstract
A collision frequency measurement from the optical reflectivity of laser indirect-driven CH/Al/diamond on the SG-10kJ laser facility is presented. The optical reflectivity and the Al/diamond interface velocity were measured simultaneously by the velocity interferometer. The aluminum rear surface density was deduced from the interface velocity by analyzing the wave interaction. The deduced sample state was compared with the simulation and quite good agreement was found. The electron collision frequency was deduced by fitting the sample state to the optical reflectivity, and it is found that the experimental collision frequency agrees with a semi-empirical result within the error bar, but is larger than the simulated result based on the average-atom model with the hypernetted chain approximation.
Physical Activity, Sedentary Behavior, and Pancreatic Cancer Risk: A Mendelian Randomization Study
Authors: Gentiluomo Manuel , Dixon-Suen Suzanne C , Farinella Riccardo , Peduzzi Giulia , Canzian Federico , Milne Roger L , Lynch Brigid M , Campa Daniele 
Published: February 2024

Abstract
Pancreatic cancer is currently the seventh leading cause of cancer death worldwide. Understanding whether modifiable factors increase or decrease the risk of this disease is central to facilitating primary prevention. Several epidemiological studies have described the benefits of physical activity, and the risks associated with sedentary behavior, in relation to cancer. This study aimed to assess evidence of causal effects of physical activity and sedentary behavior on pancreatic cancer risk. We conducted a two-sample Mendelian randomization study using publicly available data for genetic variants associated with physical activity and sedentary behavior traits and genetic data from the Pancreatic Cancer Cohort Consortium (PanScan), the Pancreatic Cancer Case-Control Consortium (PanC4), and the FinnGen study for a total of 10 018 pancreatic cancer cases and 266 638 controls. We also investigated the role of body mass index (BMI) as a possible mediator between physical activity and sedentary traits and risk of developing pancreatic cancer. We found evidence of a causal association between genetically determined hours spent watching television (hours per day) and increased risk of pancreatic cancer for each hour increment (PanScan-PanC4 odds ratio = 1.52, 95% confidence interval 1.17-1.98, P = .002). Additionally, mediation analysis showed that genetically determined television-watching time was strongly associated with BMI, and the estimated proportion of the effect of television-watching time on pancreatic cancer risk mediated by BMI was 54%. This study reports the first Mendelian randomization-based evidence of a causal association between a measure of sedentary behavior (television-watching time) and risk of pancreatic cancer and that this is strongly mediated by BMI.
Summary: Pancreatic cancer is a deadly disease that is predicted to become the second leading cause of cancer-related deaths by 2030. Physical activity and sedentary behaviors have been linked to cancer risk and survival. However, there is limited research on their correlation with pancreatic cancer. To investigate this, we used a Mendelian randomization approach to examine the genetic predisposition to physical activity and sedentariness and their relation to pancreatic cancer risk, while excluding external confounders. Our findings revealed a causal link between the time spent watching television and an increased risk of pancreatic cancer. Additionally, we determined that over half of the effect of watching television on pancreatic risk is mediated by the individual's BMI.
Smad4 restricts injury-provoked biliary proliferation and carcinogenesis
Authors: Alexander William B. , Wang Wenjia , Hill Margaret A. , O'Dell Michael R. , Ruffolo Luis I. , Guo Bing , Jackson Katherine M. , Ullman Nicholas , Friedland Scott C. , McCall Matthew N. , Patel Ankit , Figueroa-Guilliani Nathania , Georger Mary , Belt Brian A. , Whitney-Miller Christa L. , Linehan David C. , Murphy Patrick J. , Hezel Aram F. 
Published: February 2024

ABSTRACT
Cholangiocarcinoma (CCA) is a deadly and heterogeneous type of cancer characterized by a spectrum of epidemiologic associations as well as genetic and epigenetic alterations. We seek to understand how these features inter-relate in the earliest phase of cancer development and through the course of disease progression. For this, we studied murine models of liver injury integrating the most commonly occurring gene mutations of CCA – including Kras, Tp53, Arid1a and Smad4 – as well as murine hepatobiliary cancer models and derived primary cell lines based on these mutations. Among commonly mutated genes in CCA, we found that Smad4 functions uniquely to restrict reactive cholangiocyte expansion to liver injury through restraint of the proliferative response. Inactivation of Smad4 accelerates carcinogenesis, provoking pre-neoplastic biliary lesions and CCA development in an injury setting. Expression analyses of Smad4-perturbed reactive cholangiocytes and CCA lines demonstrated shared enriched pathways, including cell-cycle regulation, MYC signaling and oxidative phosphorylation, suggesting that Smad4 may act via these mechanisms to regulate cholangiocyte proliferation and progression to CCA. Overall, we showed that TGFβ/SMAD4 signaling serves as a critical barrier restraining cholangiocyte expansion and malignant transformation in states of biliary injury.
Rethinking Cost-Sensitive Classification in Deep Learning via Adversarial Data Augmentation
Authors: Chen Qiyuan , Al Kontar Raed , Nouiehed Maher , Yang X. Jessie , Lester Corey 
Published: February 2024

Cost-sensitive classification is critical in applications where misclassification errors widely vary in cost. However, overparameterization poses fundamental challenges to the cost-sensitive modeling of deep neural networks (DNNs). The ability of a DNN to fully interpolate a training data set can render a DNN, evaluated purely on the training set, ineffective in distinguishing a cost-sensitive solution from its overall accuracy maximization counterpart. This necessitates rethinking cost-sensitive classification in DNNs. To address this challenge, this paper proposes a cost-sensitive adversarial data augmentation (CSADA) framework to make overparameterized models cost sensitive. The overarching idea is to generate targeted adversarial examples that push the decision boundary in cost-aware directions. These targeted adversarial samples are generated by maximizing the probability of critical misclassifications and used to train a model with more conservative decisions on costly pairs. Experiments on well-known data sets and a pharmacy medication image (PMI) data set, made publicly available, show that our method can effectively minimize the overall cost and reduce critical errors while achieving comparable overall accuracy. History: Nick Street served as the senior editor for this article. Funding: Research reported in this publication was supported by the National Library of medicine of the National Institutes of Health in the United States under award number R01LM013624. Data Ethics & Reproducibility Note: This paper abides by data ethics requirements. Data used are publicly available online at https://deepblue.lib.umich.edu/data/concern/data_sets/6d56zw997 . Codes to replicate the results of this paper are available on Code Ocean at https://doi.org/10.24433/CO.2139841.v1 and in the e-Companion to this article (available at https://doi.org/10.1287/ijds.2022.0033 ).
Case Article—Racial Bias in Automated Traffic Law Enforcement and the Price of Unjustness
Authors: Vogiatzis Chrysafis , Kontou Eleftheria 
Published: February 2024

This case study has been developed for students to practice their data analysis and optimization skills in a contemporary societal issue: that of injustice in automated traffic law enforcement. Specifically, this case study is for students of modern data analysis and statistical modeling courses that focus on hypothesis testing; it also has a component for students in optimization and mathematical modeling courses that focus on linear and network optimization. The case study has been used since Spring 2023 in a combination of two courses from the Industrial Engineering (Analysis of Data, an introduction to probability and statistics) and Civil Engineering (Transportation Systems, an introduction to mathematical modeling and optimization for civil engineers with a focus on transportation) curricula. History: This paper has been accepted for the INFORMS Transactions on Education Special Issue on DEI in ORMS Classrooms. Supplemental Material: The Teaching Note and data files are available at https://www.informs.org/Publications/Subscribe/Access-Restricted-Materials .
Case—Racial Bias in Automated Traffic Law Enforcement and the Price of Unjustness
Authors: Vogiatzis Chrysafis , Kontou Eleftheria 
Published: February 2024

This case study has been developed for students to practice their data analysis and optimization skills in a contemporary societal issue: that of injustice in automated traffic law enforcement. Specifically, this case study is for students of modern data analysis and statistical modeling courses that focus on hypothesis testing; it also has a component for students in optimization and mathematical modeling courses that focus on linear and network optimization. The case study has been used since Spring 2023 in a combination of two courses from the Industrial Engineering (Analysis of Data, an introduction to probability and statistics) and Civil Engineering (Transportation Systems, an introduction to mathematical modeling and optimization for civil engineers with a focus on transportation) curricula. History: This paper has been accepted for the INFORMS Transactions on Education Special Issue on DEI in ORMS Classrooms.
Enabling seamless migration of optical metro-urban networks to the multi-band: unveiling a cutting-edge 6D planning tool for the 6G era
Authors: Arpanaei Farhad , Rivas-Moscoso José Manuel , De Francesca Ivan , Hernández José Alberto , Sánchez-Macián Alfonso , Zefreh Mahdi Ranjbar , Larrabeiti David , Fernández-Palacios Juan Pedro 
Published: February 2024

The relentless demand for high-bandwidth services and applications in the beyond-5G/6G era necessitates optical networks to provide ample spectral resources to accommodate the increasing traffic loads. This requirement is especially pronounced in metro and regional segments, where a projected traffic compound annual growth rate (CAGR) of over 40%, driven by content delivery network (CDN) traffic concentrated near the end users, threatens to push the fiber capacity to its limits on a number of heavily utilized links in the short to medium term. This limitation cannot be circumvented despite the utilization of spectrally efficient modulation formats designed for short-distance transmission. Thus, it is imperative to explore migration strategies to solutions that allow the expansion of spectral resources beyond the current usage of the extended C-band (4.8 THz). In this article, we present a comprehensive evaluation of multi-homed edge-to-core routing, modulation-level selection, and spectrum assignment simulations conducted over reference metropolitan area networks (MANs) by leveraging on a novel network planner called 6D-MAN, which we have developed to adapt to heterogeneous multi-layer networks based on multi-band and multi-fiber transmission. Our simulations consider coherent transmission with flexible modulation format transponders operating at capacities ranging from 100 to 400 Gbps on the 50 GHz grid and explore link-by-link migration strategies restricted to the C+L-band, ensuring optimal performance in terms of the generalized signal-to-noise ratio (GSNR). The obtained results demonstrate that deploying L-band equipment on a selected number of links effectively extends the lifespan of existing networks, enabling congestion-free operation with minimal intervention. In their entirety, our findings underscore the importance of contemplating alternative spectral resources beyond the conventional C-band. They unequivocally accentuate the potential of L-band equipment strategic deployment to tackle capacity constraints in MANs, resulting in a 60% reduction in fiber length and a remarkable 45% decrease in new fiber-pair link deployment needs. The profound implications of efficient fiber capacity utilization manifest themselves in substantial OPEX and optical total cost of ownership savings, amounting to approximately 71% and 17%–27%, respectively, over a 10-year period. This research provides valuable insights for MAN operators seeking sustainable strategies to support the growing demands of future beyond-5G/6G services.