bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D Collagen Vascular Tumor-on-a-Chip Mimetics for Dynamic Combinatorial Drug Screening
Authors: Wan Li , Yin Jun , Skoko John , Schwartz Russell , Zhang Mei , LeDuc Philip R. , Neumann Carola A. 
Published: March 2021

Abstract
Disease models, including in vitro cell culture and animal models, have contributed significantly to developing diagnostics and treatments over the past several decades. The successes of traditional drug screening methods were generally hampered by not adequately mimicking critical in vivo features, such as a 3D microenvironment and dynamic drug diffusion through the extracellular matrix (ECM). To address these issues, we developed a 3D dynamic drug delivery system for cancer drug screening that mimicks drug dissemination through the tumor vasculature and the ECM by creating collagen-embedded microfluidic channels. Using this novel 3D ECM microsystem, we compared viability of tumor pieces with traditionally used 2D methods in response to three different drug combinations. Drug diffusion profiles were evaluated by simulation methods and tested in the 3D ECM microsystem and a 2D 96-well setup. Compared with the 2D control, the 3D ECM microsystem produced reliable data on viability, drug ratios, and combination indeces. This novel approach enables higher throughput and sets the stage for future applications utilizing drug sensitivity predicting algorithms based on dynamic diffusion profiles requiring only minimal patient tissue. Our findings moved drug sensitivity screening closer to clinical implications with a focus on testing combinatorial drug effects, an option often limited by the amount of available patient tissues.
Targeted Therapy to β3 Integrin Reduces Chemoresistance in Breast Cancer Bone Metastases
Authors: Fox Gregory C. , Su Xinming , Davis Jennifer L. , Xu Yalin , Kwakwa Kristin A. , Ross Michael H. , Fontana Francesca , Xiang Jingyu , Esser Alison K. , Cordell Elizabeth , Pagliai Kristen , Dang Ha X. , Sivapackiam Jothilingam , Stewart Sheila A. , Maher Christopher A. , Bakewell Suzanne J. , Fitzpatrick James A.J. , Sharma Vijay , Achilefu Samuel , Veis Deborah J. , Lanza Gregory M. , Weilbaecher Katherine N. 
Published: March 2021

Abstract
Breast cancer bone metastases are common and incurable. Tumoral integrin β3 (β3) expression is induced through interaction with the bone microenvironment. Although β3 is known to promote bone colonization, its functional role during therapy of established bone metastases is not known. We found increased numbers of β3+ tumor cells in murine bone metastases after docetaxel chemotherapy. β3+ tumor cells were present in 97% of post-neoadjuvant chemotherapy triple-negative breast cancer patient samples (n = 38). High tumoral β3 expression was associated with worse outcomes in both pre- and postchemotherapy triple-negative breast cancer groups. Genetic deletion of tumoral β3 had minimal effect in vitro, but significantly enhanced in vivo docetaxel activity, particularly in the bone. Rescue experiments confirmed that this effect required intact β3 signaling. Ultrastructural, transcriptomic, and functional analyses revealed an alternative metabolic response to chemotherapy in β3-expressing cells characterized by enhanced oxygen consumption, reactive oxygen species generation, and protein production. We identified mTORC1 as a candidate for therapeutic targeting of this β3-mediated, chemotherapy-induced metabolic response. mTORC1 inhibition in combination with docetaxel synergistically attenuated murine bone metastases. Furthermore, micelle nanoparticle delivery of mTORC1 inhibitor to cells expressing activated αvβ3 integrins enhanced docetaxel efficacy in bone metastases. Taken together, we show that β3 integrin induction by the bone microenvironment promotes resistance to chemotherapy through an altered metabolic response that can be defused by combination with αvβ3-targeted mTORC1 inhibitor nanotherapy. Our work demonstrates the importance of the metastatic microenvironment when designing treatments and presents new, bone-specific strategies for enhancing chemotherapeutic efficacy.
Dutch Outcome in Implantable Cardioverter‐Defibrillator Therapy: Implantable Cardioverter‐Defibrillator–Related Complications in a Contemporary Primary Prevention Cohort
Authors: van Barreveld Marit , Verstraelen Tom E. , van Dessel Pascal F. H. M. , Boersma Lucas V. A. , Delnoy Peter Paul H. M. , Tuinenburg Anton E. , Theuns Dominic A. M. J. , van der Voort Pepijn H. , Kimman Geert‐Jan , Buskens Erik , Zwinderman Aeilko H. , Wilde Arthur A. M. , Dijkgraaf Marcel G. W. ,   the DO‐IT Registry Investigators
Published: March 2021

Background
One third of primary prevention implantable cardioverter‐defibrillator patients receive appropriate therapy, but all remain at risk of defibrillator complications. Information on these complications in contemporary cohorts is limited. This study assessed complications and their risk factors after defibrillator implantation in a Dutch nationwide prospective registry cohort and forecasts the potential reduction in complications under distinct scenarios of updated indication criteria.

Methods and Results
Complications in a prospective multicenter registry cohort of 1442 primary implantable cardioverter‐defibrillator implant patients were classified as major or minor. The potential for reducing complications was derived from a newly developed prediction model of appropriate therapy to identify patients with a low probability of benefitting from the implantable cardioverter‐defibrillator. During a follow‐up of 2.2 years (interquartile range, 2.0–2.6 years), 228 complications occurred in 195 patients (13.6%), with 113 patients (7.8%) experiencing at least one major complication. Most common ones were lead related (n=93) and infection (n=18). Minor complications occurred in 6.8% of patients, with lead‐related (n=47) and pocket‐related (n=40) complications as the most prevailing ones. A surgical reintervention or additional hospitalization was required in 53% or 61% of complications, respectively. Complications were strongly associated with device type. Application of stricter implant indication results in a comparable proportional reduction of (major) complications.

Conclusions
One in 13 patients experiences at least one major implantable cardioverter‐defibrillator–related complication, and many patients undergo a surgical reintervention. Complications are related to defibrillator implantations, and these should be discussed with the patient. Stricter implant indication criteria and careful selection of device type implanted may have significant clinical and financial benefits.
Conjoint Associations of Adherence to Physical Activity and Dietary Guidelines With Cardiometabolic Health: The Framingham Heart Study
Authors: Lee Joowon , Walker Maura E. , Bourdillon Maximillian T. , Spartano Nicole L. , Rogers Gail T. , Jacques Paul F. , Vasan Ramachandran S. , Xanthakis Vanessa 
Published: March 2021

Background
The conjoint associations of adherence to the recent physical activity and dietary guidelines with the metabolic syndrome (MetS) are incompletely understood.

Methods and Results
We evaluated 2379 FHS (Framingham Heart Study) Third Generation participants (mean age, 47 years; 54.4% women) attending examination cycle 2. We examined the cross‐sectional relations of adherence to the 2018 Physical Activity Guidelines for Americans (binary; moderate‐to‐vigorous physical activity ≥150 versus <150 min/wk) and 2015 Dietary Guidelines for Americans (binary; 2015 Dietary Guidelines for Americans Adherence Index ≥median versus <median [score, 62.1/100]) with prevalence of the MetS using generalized linear models. We also related adherence to guidelines with the incidence of MetS prospectively, using Cox proportional hazards regression with discrete time intervals. Adherence rates to the 2018 Physical Activity Guidelines for Americans (odds ratio [OR], 0.49; 95% CI, 0.40–0.60) and 2015 Dietary Guidelines for Americans (OR, 0.67; 95% CI, 0.51–0.90) were individually associated with lower odds of prevalent MetS, whereas conjoint adherence to both guidelines was associated with the lowest odds of MetS (OR, 0.35; 95% CI, 0.26–0.47) compared with the referent group (nonadherence to both guidelines). Adherence rates to the 2018 Physical Activity Guidelines for Americans (hazard ratio [HR], 0.66; 95% CI, 0.50–0.88) and 2015 Dietary Guidelines for Americans (HR, 0.68; 95% CI, 0.51–0.90) were associated with lower risk of MetS, prospectively. In addition, we observed a 52% lower risk of MetS in individuals who adhered to both guidelines compared with the referent group.

Conclusions
Maintaining both regular physical activity and a healthy diet in midlife may be required for optimal cardiometabolic health in later life.
Comparing Modern and Classical Perspectives on Spider Silks and Webs
Authors: Greco Gabriele , Mastellari Virginia , Holland Chris , Pugno Nicola M. 
Published: March 2021

Abstract
Spiders have always fascinated humankind as whilst they are often reviled, their product, the web and its silk, are commonly viewed in awe. As such, silks’ material properties and the fear and fascination surrounding the animals that spin it are seen to play an important role in the development of many cultures and societies. More recently this is even more so with the formalization of this inspiration in scientific and technical communities through biomimetics. The aim of this work is to reflect on the beginnings of our relationship with silk and discuss concepts associated with spider silks and webs in ancient Greek and Roman times whilst comparing this with our current understanding of the field. In this way, ancient texts, namely Greek and Latin ones, are found to intersect with modern advanced disciplines, ranging from architecture to medicine to physics. This allows us not only to understand how natural observation has evolved from antiquity to today, but also how such a highly interdisciplinary research network has been spun by some shared conceptual threads.
Shaping Education Policy of Home-School Cooperation in China’s Preschool Education: Trends and Strategies
Authors: Li Jian 
Published: March 2021

Abstract
Preschool education is the beginning of individual development, which directly affects the subsequent primary education, secondary education, higher education and even the lifelong development of individuals. This study explores the education policy development of China’s home-school cooperation in the field of preschool education. The trends and strategies of home-school cooperation in China’s preschool education are also investigated in this study.
A Scale-Adaptive Turbulence Model for the Dry Convective Boundary Layer
Authors: Zhou Bowen , Li Yuhuan , Miao Shiguang 
Published: March 2021

AbstractA scale-adaptive model is developed for the representation of dry convective boundary layer (CBL) turbulence in numerical models operating at O(100) m to O(1) km horizontal resolution, also known as the model gray zone of the CBL. The new model is constructed based on a planetary boundary layer (PBL) scheme and a large-eddy simulation (LES) closure that are both turbulence kinetic energy–based parameterizations. Scale adaptivity is achieved by “blending” the PBL scheme with the LES closure through an inverse averaging procedure that naturally accounts for vertical variations of the dominant turbulent length scales, hence the gray zone range. High-resolution wide-domain LES benchmark cases covering a broad range of CBL bulk stability are filtered to gray zone resolutions, and analyzed to determine the averaging coefficients. Stability dependence of the dominant length scales is revealed by the analysis and accounted for in the new model. The turbulence model is implemented into a community atmospheric model, and tested for idealized cases. Compared to two established gray zone models, the new model performs equally well under strongly convective conditions, and is more advantageous for the weakly unstable and near neutral CBL.
Reply to “Comments on ‘Global and Regional Entropy Production by Radiation Estimated from Satellite Observations’”
Authors: Kato Seiji , Rose Fred G. 
Published: March 2021

AbstractThis reply addresses a comment on the study by Kato and Rose (herein referred to as KR2020). The comment raises four points of criticism. These are 1) on notations used, 2) on a steady-state assumption made, 3) on the result of entropy production change with Earth’s albedo, and 4) disputing the statement that a simple energy balance model cannot produce absorption temperature change with Earth’s albedo. We concur on points 2 and 3 raised by the comment and recognize the significance of entropy storage due to ocean heating in the analysis of how entropy production changes with the shortwave absorptivity of Earth. Once entropy storage is considered, the results of KR2020 indicate that the increase of entropy production rate by irreversible processes, including by radiative processes, is smaller than the increase of entropy storage when absorptivity is increased. This is a manifestation of the primary contribution of positive top-of-atmosphere net irradiances (i.e., energy input to Earth) to heating the ocean and is consistent with an energy budget perspective. Once entropy storage is separated, the entropy production by irreversible processes increases with the shortwave absorptivity.
Effect of Boundary Conditions on Adjoint-Based Forecast Sensitivity Observation Impact in a Regional Model
Authors: Kim Hyun Mee , Kim Dae-Hui 
Published: March 2021

AbstractIn this study, the effect of boundary-condition configurations in the regional Weather Research and Forecasting (WRF) Model on the adjoint-based forecast sensitivity observation impact (FSOI) for 24 h forecast error reduction was evaluated. The FSOI has been used to diagnose the impact of observations on the forecast performance in several global and regional models. Different from the global model, in the regional model, the lateral boundaries affect forecasts and FSOI results. Several experiments with different lateral boundary conditions were conducted. The experimental period was from 1 to 14 June 2015. With or without data assimilation, the larger the buffer size in lateral boundary conditions, the smaller the forecast error. The nonlinear and linear forecast error reduction (i.e., observation impact) decreased as the buffer size increased, implying larger impact of lateral boundaries and smaller observation impact on the forecast error. In most experiments, in terms of observation types (variables), upper-air radiosonde observations (brightness temperature) exhibited the greatest observation impact. The ranking of observation impacts was consistent for observation types and variables among experiments with a constraint in the response function at the upper boundary. The fractions of beneficial observations were approximately 60%, and did not considerably vary depending on the boundary conditions specified when calculating the FSOI in the regional modeling framework.
Impact of the Novel Coronavirus 2019 (COVID‐19) Pandemic on Head and Neck Cancer Care
Authors: Thompson Joshua Adam , Lubek Joshua E. , Amin Neha , Joy Reju , Dyalram Donita , Ord Robert A. , Taylor Rodney J. , Wolf Jeffrey S. , Mehra Ranee , Cullen Kevin J. , Molitoris Jason K. , Witek Matthew , Papadimitriou John C. , Morales Robert E. , Hatten Kyle M. 
Published: March 2021

ObjectiveThe study aimed to assess the impact of the coronavirus disease 2019 (COVID‐19) pandemic on head and neck oncologic care at a tertiary care facility.Study DesignThis was a cross‐sectional study conducted between March 18, 2020, and May 20, 2020. The primary planned outcome was the rate of treatment modifications during the study period. Secondary outcome measures were tumor conference volume, operative volume, and outpatient patient procedure and clinic volumes.SettingThis single‐center study was conducted at a tertiary care academic hospital in a large metropolitan area.MethodsThe study included a consecutive sample of adult subjects who were presented at a head and neck interdepartmental tumor conference during the study period. Patients were compared to historical controls based on review of operative data, outpatient procedures, and clinic volumes.ResultsIn total, 117 patients were presented during the review period in 2020, compared to 69 in 2019. There was an 8.4% treatment modification rate among cases presented at the tumor conference. There was a 61.3% (347 from 898) reduction in outpatient clinic visits and a 63.4% (84 from 230) reduction in procedural volume compared to the prior year. Similarly, the operative volume decreased by 27.0% (224 from 307) compared to the previous year.ConclusionRestrictions related to the COVID‐19 pandemic resulted in limited treatment modifications. Transition to virtual tumor board format observed an increase in case presentations. While there were reductions in operative volume, there was a larger proportion of surgical cases for malignancy, reflecting the prioritization of oncologic care during the pandemic.
Comparison of Percutaneous Transluminal Angiography With or Without Catheter-Directed Thrombolysis for Chronic Femoropopliteal Occlusive Disease
Authors: Yi Mengfei , Guo Jianjun , Gao Yanxia , Ren Jianzhuang , Bi Yonghua , Han Xinwei 
Published: March 2021

Background: Catheter-directed thrombolysis (CDT) is seldom used for chronic femoropopliteal occlusive disease. Methods: Patients with chronic femoropopliteal occlusive disease enrolled between January, 2011 and April, 2017. Hospitalization expense, limb salvage rate and survival rate were calculated. Results: Twenty-nine patients were treated with CDT (CDT group) and 31 patients without CDT (Non-CDT group).The mean hospitalization expense (5.2 ± 0.5), balloon catheter (1.0 ± 0.2) and stents number (0.8 ± 0.2) in CDT group were significantly less compared to Non-CDT group ( P < 0.05). The short-term and long-term effect scales showed similar in both groups. The incidences of perioperative complications (10.3% vs. 19.4%), primary patency and second patency rate, limb salvage rate (14.8% vs. 16.1%) and survival rate were also similar ( P > 0.05). Six patients died in each group and only 2 disease related deaths were found in Non-CDT group. Conclusion: CDT is a safe and economic strategy for patients with chronic femoropopliteal occlusive disease, and should be served as blanket treatment for every patient without thrombolytic contradictions or a remedy for failure PTA to achieve a comparable clinical effect.
Parenting Mediates Associations Between Intimate Partner Violence at Different Life Stages and Toddler Social–Emotional Problems
Authors: Riggs Jessica L. , Janisse Heather , Huth-Bocks Alissa 
Published: March 2021

Background: Researchers have linked parent experiences of intimate partner violence (IPV) to engagement in more negative and less positive parenting behaviors with their own children. This parenting behavior is associated with more negative child social-emotional outcomes. There is little research examining the impact of exposure to IPV during childhood on subsequent parenting and child outcomes in the next generation. This study aimed to better understand the complex relationship between IPV, parenting, and child social-emotional development among mothers of toddler-aged children, using both mothers’ self-reported and observed parenting. Method: This study utilized longitudinal data from an economically disadvantaged, racially diverse sample of 120 women who participated in data collection across the perinatal period, until children were 2 years of age. Measures included self-reported and observed parenting, mother-reported IPV history, and mother-report of toddler social-emotional difficulties. Results: Childhood exposure to IPV predicted observed parenting problems, which in turn predicted greater toddler social-emotional problems. Conversely, adult experiences of IPV predicted self-reported parenting difficulties, which predicted greater toddler social-emotional problems. Summary: Findings suggest that exposure to IPV at different time points may influence parenting in different ways, representing unique pathways between maternal IPV experiences and child social-emotional difficulties
Patterns of Orbital Fractures Needing Surgical Reconstruction in a Large Tertiary Hospital in Northern India
Authors: Gupta Sneha , Singh Praveen Kumar , Mehrotra Divya , Mohammad Shadab , Singh Vibha , Kaur Apjit , Ojha Bal Krishna 
Published: March 2021

Study Design: This is a prospective study for 3 year duration. Objective: The aim of this study was to observe the incidence and patterns of orbital fractures and discuss their treatment options. Methods: A total 29604 trauma patients visited our emergency department within May 2017 to Oct 2019, where 1230 (4.15%) patients presented with orbital fractures, of which only 44 (3.6% of orbital fracture) patients required surgical reconstruction, and were enrolled in our study and evaluated for their fracture patterns, size of bone defect, clinical presentation, timing of surgery, reconstruction, and complications. Results: The incidence of orbital fracture was 4.15%, of which only 20.5% were pure blow out. Associated fractures included 72.7% zygomatic complex, 50% LeFort, 31.8% mandible and 20.5% pan facial fractures. The most common pattern was the 1 wall orbital defect in 38.6%, 2 wall in 27.3%, 3 wall in 29.5% and 4 wall in 4.5%. The orbital floor fracture was seen in 100%, medial wall in 27.3%, lateral wall in 61.4%, roof in 15.9%. Different reconstruction options used included calvarial bone (2.3%), ear cartilage (2.3%), medpore (36.4%), polycaprolactone sheet (6.8%), titanium mesh (52.3%), patient specific implant (6.8%) and navigation (4.5%). Conclusion: Orbital fractures are mostly impure fractures, associated with zygomatic complex fractures, hence lateral wall fractures are seen more commonly. Patient specific implants, navigation guided reconstruction, autologous calvarial bone graft and preformed titanium mesh show better results, and fulfill the objectives of orbital reconstruction by restoring the normal anatomy and volume of the orbit.
Targeting AXL kinase sensitizes leukemic stem and progenitor cells to venetoclax treatment in acute myeloid leukemia
Authors: Niu Xiaojia , Rothe Katharina , Chen Min , Grasedieck Sarah , Li Rick , Nam Sung-Eun , Zhang Xiuyan , Novakovskiy German E. , Ahn Ye-Hyeon , Maksakova Irina , Lai Shenshen , Zhang Hong , Yan Jun , Liu Hong , Zhao Yun , Wu Depei , Ge Yubin , Wasserman Wyeth W. , Rouhi Arefeh , Kuchenbauer Florian , Yip Calvin K. , Zhang Zaihui , Jiang Xiaoyan 
Published: March 2021

Abstract
The abundance of genetic abnormalities and phenotypic heterogeneities in acute myeloid leukemia (AML) poses significant challenges to the development of improved treatments. Here, we demonstrated that a key growth arrest-specific gene 6/AXL axis is highly activated in cells from patients with AML, particularly in stem/progenitor cells. We developed a potent selective AXL inhibitor that has favorable pharmaceutical properties and efficacy against preclinical patient-derived xenotransplantation (PDX) models of AML. Importantly, inhibition of AXL sensitized AML stem/progenitor cells to venetoclax treatment, with strong synergistic effects in vitro and in PDX models. Mechanistically, single-cell RNA-sequencing and functional validation studies uncovered that AXL inhibition, alone or in combination with venetoclax, potentially targets intrinsic metabolic vulnerabilities of AML stem/progenitor cells and shows a distinct transcriptomic profile and inhibits mitochondrial oxidative phosphorylation. Inhibition of AXL or BCL-2 also differentially targets key signaling proteins to synergize in leukemic cell killing. These findings have a direct translational impact on the treatment of AML and other cancers with high AXL activity.