bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiphysics Modeling and Experiments of Grayscale Photopolymerization With Application to Microlens Fabrication
Authors: Emami M. M. , Jamshidian M. , Rosen D. W. 
Published: March 2021

Abstract
A phenomenological model of a single-shot grayscale photopolymerization process is developed and used within a virtual process planning framework for microlens fabrication. Along with previous research, the kinetic relations describing the solidification of UV-curable resin are derived based on the underlying chemical reactions involved in free radical photopolymerization. As enhancements to the state-of-the-art, our multiphysics model includes a recently proposed super-Gaussian description of the light field, as well as the photobleaching effect due to the live reduction in photoinitiator concentration during UV illumination. In addition, heat generation and thermal strains due to the exothermic chemical reactions, and chemical shrinkage due to polymerization and cross-linking of monomers are considered. The model is numerically implemented via finite element method in comsol multiphysics software. Using a simulation-based virtual process planning framework, customized microlenses are fabricated with an in-house grayscale lithography experimental setup for digital micromirror device (DMD)-based volumetric additive manufacturing. Simulation and experimental results show that after the end of exposure, the temperature quickly rises by the advancement of exothermic chemical reactions and reaches a maximum rise of 100 K in a few seconds, followed by a slow cooling and recovery of thermal strains. It is observed that chemical and thermal shrinkages can compromise the dimensional accuracy of the final part near the resin–substrate interface due to the strong adhesion of the solidified part to the rigid substrate that prevents material shrinkage in the vicinity of the rigid substrate.
Genetic Optimization for the Design of a Machine Tool Slide Table for Reduced Energy Consumption
Authors: Triebe Matthew J. , Zhao Fu , Sutherland John W. 
Published: March 2021

Abstract
Reducing the energy consumption of machine tools is important from a sustainable manufacturing perspective. Much of a machine tool’s environmental impact comes from the energy it consumes during its use phase. To move elements of a machine tool requires energy, and if the mass of those elements can be reduced, then the required energy would be reduced. Therefore, this paper proposes a genetic algorithm to design lightweight machine tools to reduce their energy consumption. This is specifically applied to optimize the structure of a machine tool slide table, which moves throughout the use of the machine tool, with the goal of reducing its mass without sacrificing its stiffness. The table is envisioned as a sandwich panel, and the proposed genetic algorithm optimizes the core of the sandwich structure while considering both mass and stiffness. A finite element model is used to assess the strength of the proposed designs. Finite element results indicate that the strength of the lightweight tables is comparable with a traditional table design.
Hospital chaplains as ethical consultants in making difficult medical decisions
Authors: Głusiec Waldemar 
Published: March 2021

Background and aimsFew Polish hospitals have Hospital Ethics Committee (HECs) and the services are not always adequate. In this situation, the role of HECs, in providing, among others, ethical advice on the discontinuation of persistent therapies, may be taken over by other entities. The aim of our research was to investigate, how often and on what issues hospital chaplains are asked for ethical advice in reaching difficult medical decisions.MethodsA survey of 100 Roman Catholic chaplains was conducted, that is, at least 10% of all chaplains currently working in Polish hospitals.ResultsOf the participants, 29% confirmed receiving requests for advice in making a morally difficult medical decision. Receiving this type of request was not conditional on the place of their service, duration of their pastoral mission or HEC membership. The largest group of chaplains (21%) encounter questions concerning the ethical dilemmas associated with discontinuing persistent therapy. Patients and their families most often raise issues related to the methods of birth control, and the medical staff raise the issue of termination of pregnancy—as reported by 9% and 15% of chaplains, respectively. Most of the chaplains asked for help (79%) experience a deficit of specialist knowledge in the area of medicine or ethics.ConclusionsIn order to improve the quality of ethical consultations in Polish hospitals, in addition to further development of HECs, it is postulated to develop a system for bioethical education of chaplains.
Importance of axial stretch on the determination of Young’s modulus of electrospun poly(ε-caprolactone) nanofibres by atomic force microscopy
Authors: Makaremi Sara , Wan Wankei , Hutter Jeffrey L. 
Published: March 2021

With increasing interest in the use of polymeric nanofibres for biomedical applications such as composite materials and tissue scaffolding, accurate determination of their mechanical properties is essential. Fibre orientation and the stiffness of individual fibres determine the overall elastic modulus of nanofibrous materials. However, accurate measurements of the elastic properties of single fibres are challenging at the nanoscale, and distinguishing between results arising from competing models can be difficult. We report here on investigations of the Young’s modulus of single poly(ε-caprolactone) (PCL) electrospun nanofibres by measuring the deflection of fibres due to a loading force applied by an atomic force microscope (AFM). Although such testing is often performed with the tacit assumption that bending resistance alone is responsible for the fibre response, we found that consistent results could only be obtained if the overall fibre stretch is taken into account. The Young’s modulus we measured for electrospun PCL fibres with diameters ranging from 100 to 400 nm was 0.48 ± 0.03 GPa, which is similar to the modulus of bulk PCL, with no apparent dependence on diameter. Our findings highlight the importance of the assumptions used in the analysis of bending data, as discounting the effects of axial stretch and pre-existing tension typically lead to an overestimate of the Young’s modulus.
Generating solutions for charged stellar models in general relativity
Authors: Ivanov B. V. 
Published: March 2021

AbstractIt is shown that the expressions for the tangential pressure, the anisotropy factor and the radial pressure in the Einstein–Maxwell equations may serve as generating functions for charged stellar models. The latter can incorporate an equation of state when the expression for the energy density is also used. Other generating functions are based on the condition for the existence of conformal motion (conformal flatness in particular) and the Karmarkar condition for embedding class one metrics, which do not depend on charge. In all these cases the equations are linear first order differential equations for one of the metric components and Riccati equations for the other. The latter may be always transformed into second order homogenous linear differential equations. These conclusions are illustrated by numerous particular examples from the study of charged stellar models.
Traditional Chinese Medicine in the United States: Current state, regulations, challenges, and the way forward
Authors: Jin Louis Lei , Zheng Jin , Honarvar Niyaz M. , Chen Xiqun 
Published: March 2021

In the United States, there has been a steady presence and growth of Traditional Medicine (interchangeable in this paper with Complementary or Alternative Medicine) over the past few decades. The costs for such practices are relatively low along with minimal-to-no obvious side effects. Amongst a variety of traditional medical systems, Traditional Chinese Medicine is one of the most popular alternatives to help manage chronic health conditions or to improve the overall quality of life. While not exhaustive, this paper provides a snapshot of Traditional Chinese Medicine in the United States with insights into its current state, regulations, challenges, and the way forward.
The KRASG12C Inhibitor MRTX849 Reconditions the Tumor Immune Microenvironment and Sensitizes Tumors to Checkpoint Inhibitor Therapy
Authors: Briere David M. , Li Shuai , Calinisan Andrew , Sudhakar Niranjan , Aranda Ruth , Hargis Lauren , Peng David H. , Deng Jiehui , Engstrom Lars D. , Hallin Jill , Gatto Sole , Fernandez-Banet Julio , Pavlicek Adam , Wong Kwok-Kin , Christensen James G. , Olson Peter 
Published: March 2021

Abstract
KRASG12C inhibitors, including MRTX849, are promising treatment options for KRAS-mutant non–small cell lung cancer (NSCLC). PD-1 inhibitors are approved in NSCLC; however, strategies to enhance checkpoint inhibitor therapy (CIT) are needed. KRASG12C mutations are smoking-associated transversion mutations associated with high tumor mutation burden, PD-L1 positivity, and an immunosuppressive tumor microenvironment. To evaluate the potential of MRTX849 to augment CIT, its impact on immune signaling and response to CIT was evaluated. In human tumor xenograft models, MRTX849 increased MHC class I protein expression and decreased RNA and/or plasma protein levels of immunosuppressive factors. In a KrasG12C-mutant CT26 syngeneic mouse model, MRTX849 decreased intratumoral myeloid-derived suppressor cells and increased M1-polarized macrophages, dendritic cells, CD4+, and CD8+ T cells. Similar results were observed in lung KrasG12C-mutant syngeneic and a genetically engineered mouse (GEM) model. In the CT26 KrasG12C model, MRTX849 demonstrated marked tumor regression when tumors were established in immune-competent BALB/c mice; however, the effect was diminished when tumors were grown in T-cell–deficient nu/nu mice. Tumors progressed following anti–PD-1 or MRTX849 single-agent treatment in immune-competent mice; however, combination treatment demonstrated durable, complete responses (CRs). Tumors did not reestablish in the same mice that exhibited durable CRs when rechallenged with tumor cell inoculum, demonstrating these mice developed adaptive antitumor immunity. In a GEM model, treatment with MRTX849 plus anti–PD-1 led to increased progression-free survival compared with either single agent alone. These data demonstrate KRAS inhibition reverses an immunosuppressive tumor microenvironment and sensitizes tumors to CIT through multiple mechanisms.
Preclinical Studies of OBI-999: A Novel Globo H–Targeting Antibody–Drug Conjugate
Authors: Yang Ming-Chen , Shia Chi-Sheng , Li Wan-Fen , Wang Chun-Chung , Chen I-Ju , Huang Teng-Yi , Chen Yu-Jung , Chang Hui-Wen , Lu Chi-Huan , Wu Yueh-Chin , Wang Nan-Hsuan , Lai Jiann-Shiun , Yu Cheng-Der , Lai Ming-Tain 
Published: March 2021

Abstract
Globo H (GH), a hexasaccharide, is expressed at low levels in normal tissues but is highly expressed in multiple cancer types, rendering it a promising target for cancer immunotherapy. OBI-999, a novel antibody–drug conjugate, is derived from a conjugation of a GH-specific mAb with a monomethyl auristatin E (MMAE) payload through a site-specific ThioBridge and a cleavable linker. OBI-999 high homogeneity with a drug-to-antibody ratio of 4 (&gt;95%) was achieved using ThioBridge. OBI-999 displayed GH-dependent cellular internalization and trafficked to endosome and lysosome within 1 and 5 hours, respectively. Furthermore, OBI-999 showed low nanomolar cytotoxicity in the assay with high GH expression on tumor cells and exhibited a bystander killing effect on tumor cells with minimal GH expression. Tissue distribution indicated that OBI-999 and free MMAE gradually accumulated in the tumor, reaching maximum level at 168 hours after treatment, whereas OBI-999 and free MMAE decreased quickly at 4 hours after treatment in normal organs. Maximum MMAE level in the tumor was 16-fold higher than in serum, suggesting that OBI-999 is stable during circulation and MMAE is selectively released in the tumor. Excellent tumor growth inhibition of OBI-999 was demonstrated in breast, gastric, and pancreatic cancer xenograft or lung patient–derived xenograft models in a dose-dependent manner. The highest nonseverely toxic dose in cynomolgus monkeys is 10 mg/kg determined by a 3-week repeated-dose toxicology study demonstrating an acceptable safety margin. Taken together, these results support further clinical development of OBI-999, which is currently in a phase I/II clinical study in multiple solid tumors (NCT04084366). OBI-999, the first GH-targeting ADC, displayed excellent tumor inhibition in animal models across multiple cancer types, including breast, gastric, pancreatic, and lung cancers, warranting further investigation in the treatment of solid tumors.
Use of a Clinical Electrocardiographic Database to Enhance Atrial Fibrillation/Atrial Flutter Identification Algorithms Based on Administrative Data
Authors: Liu Hongwei , Collins Reid , Miller Robert J. H. , Southern Danielle A. , Arena Ross , Aggarwal Sandeep , Sajobi Tolulope , James Matthew T. , Wilton Stephen B. 
Published: March 2021

Background
Administrative data have limited sensitivity for case finding of atrial fibrillation/atrial flutter (AF/AFL). Linkage with clinical repositories of interpreted ECGs may enhance diagnostic yield of AF/AFL.

Methods and Results
We retrieved 369 ECGs from the institutional Marquette Universal System for Electrocardiography (MUSE) repository as validation samples, with rhythm coded as AF (n=49), AFL (n=50), or other competing rhythm diagnoses (n=270). With blinded, duplicate review of ECGs as the reference comparison, we compared multiple MUSE coding definitions for identifying AF/AFL. We tested the agreement between MUSE diagnosis and reference comparison, and calculated the sensitivity and specificity. Using a data set linking clinical registries, administrative data, and the MUSE repository (n=11 662), we assessed the incremental diagnostic yield of AF/AFL by incorporating ECG data to administrative data‐based algorithms. The agreement between MUSE diagnosis and reference comparison depended on the coding definitions applied, with the Cohen κ ranging from 0.57 to 0.75. Sensitivity ranged from 60.6% to 79.1%, and specificity ranged from 93.2% to 98.0%. A coding definition with AF/AFL appearing in the first 3 ECG statements had the highest sensitivity (79.1%), with little loss of specificity (94.5%). Compared with the algorithms with only administrative data, incorporating ECG data increased the diagnostic yield of preexisting AF/AFL by 14.5% and incident AF/AFL by 7.5% to 16.1%.

Conclusions
Routine ECG interpretation using MUSE coding is highly specific and moderately sensitive for AF/AFL detection. Inclusion of MUSE ECG data in AF/AFL case identification algorithms can identify cases missed using administrative data‐based algorithms alone.
Effects of Influenza Vaccine on Mortality and Cardiovascular Outcomes in Patients With Cardiovascular Disease: A Systematic Review and Meta‐Analysis
Authors: Yedlapati Siva H. , Khan Safi U. , Talluri Swapna , Lone Ahmed N. , Khan Muhammad Zia , Khan Muhammad Shahzeb , Navar Ann M. , Gulati Martha , Johnson Heather , Baum Seth , Michos Erin D. 
Published: March 2021

Background
Influenza infection causes considerable morbidity and mortality in patients with cardiovascular disease. We assessed the effects of the influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease.

Methods and Results

We searched PubMed, Embase, and the Cochrane Library through January 2020 for randomized controlled trials and observational studies assessing the effects of influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease. Estimates were reported as random effects risk ratios (RRs) with 95% CIs. Analyses were stratified by study design into randomized controlled trials and observational studies. A total of 16 studies (n=237 058), including 4 randomized controlled trials (n=1667) and 12 observational studies (n=235 391), were identified. Participants' mean age was 69.2±7.01 years, 36.6% were women, 65.1% had hypertension, 31.1% had diabetes mellitus, and 23.4% were smokers. At a median follow‐up duration of 19.5 months, influenza vaccine was associated with a lower risk of all‐cause mortality (RR, 0.75; 95% CI, 0.60–0.93 [
P
=0.01]), cardiovascular mortality (RR, 0.82; 95% CI, 0.80–0.84 [
P
<0.001]), and major adverse cardiovascular events (RR, 0.87; 95% CI, 0.80–0.94 [
P
<0.001]) compared with control. The use of the influenza vaccine was not associated with a statistically significant reduction of myocardial infarction (RR, 0.73; 95% CI, 0.49–1.09 [
P
=0.12]) compared with control.

Conclusions
Data from both randomized controlled trials and observational studies support the use of the influenza vaccine in adults with cardiovascular disease to reduce mortality and cardiovascular events, as currently supported by clinical guidelines. Clinicians and health systems should continue to promote the influenza vaccine as part of comprehensive secondary prevention.
Extreme Rainfall in Taiwan: Seasonal Statistics and Trends
Authors: Henny Lexi , Thorncroft Chris D. , Hsu Huang-Hsiung , Bosart Lance F. 
Published: March 2021

AbstractTaiwan regularly experiences precipitation extremes of hundreds of millimeters per day, especially between May and September. In this study, Taiwan’s extreme rainfall (ER) is analyzed over a 56-yr time period in different seasons and geographic regions, using a recently released, high-resolution gridded rainfall dataset. ER is defined using a seasonally and geographically varying 99th-percentile threshold to better resolve the characteristics of the most intense rainfall seen in different locations and times of year. The resulting monthly ER rates are largest in typhoon season and smallest in fall, winter, and spring. ER is spatially homogeneous in the mei-yu and typhoon seasons and concentrated in northern Taiwan during the rest of the year. A trend analysis revealed a positive trend in island-mean ER for the winter, spring, and typhoon seasons. In winter and spring, these trends are most pronounced in the north. In the mei-yu season, ER has increased most over the southwestern mountain slopes; in typhoon season, ER has increased consistently over much of Taiwan. These changes often exceed 1% yr−1. In many areas, typhoon season accounts for the largest fraction of the observed annual ER trend. TCs produce most of the observed typhoon season ER and ER trend, with nearly half of the typhoon season ER trend being associated with increases in TC frequency and duration around central and northern Taiwan. Certain regional changes in ER characteristics, particularly in areas with low sample size or complex seasonal contributions, merit further investigation in future work.
The Relationship between Temperature Changes and Peacemaking Events between Farming and Nomadic Groups in Northern China over the Past 2000 Years
Authors: Su Yun , Kang Yuan , Zhai Xianshuai , Fang Xiuqi 
Published: March 2021

AbstractClimate change affects relationships between regions. The sequence of peacemaking events between farming and nomadic groups in northern China from the Western Han to the Qing dynasty was constructed based on historical documents. We analyzed the impacts of climate change on ethnic relationships using war and temperature sequence data from previous studies. The main results are as follows: 1) There were 504 peacemaking events between farming and nomadic groups, with an average frequency of 2.4 times per decade. Paying tribute (68.9%) occurred significantly more frequently than intermarriage for pacification (31.1%). The sequences showed different stages. 2) There were more peacemaking events during cold periods and fewer during warm periods. Intermarriage for pacification played a greater role in peacemaking during warm periods, while paying tribute was more important during cold periods. 3) High-incidence stages of war and of peacemaking events alternated. Peacemaking events occurred more frequently during cold periods and wars occurred more frequently during warm periods. 4) During warm periods, farming and nomadic groups had enough power to contend with each other, wars occurred frequently, and intermarriage was often used for peacemaking. During cold periods, agriculture and animal husbandry declined, both sides weakened, and the power difference between them usually increased. Wars rarely occurred, and paying tribute was often used for peacemaking. Ethnic relationships are affected by many factors. As a background factor influencing land productivity, climate indirectly affected conflict-resolution measures between farming and nomadic groups. We can hereby consider ways to manage interregional ethnic relationships under global climate change today.
Does the Weather Contribute to Admissions of Neck of Femur Fractures?
Authors: Koizia Louis J. , Dani Melanie , Brown Hannah , Lee Malcolm , Reilly Peter , Fertleman Michael B. 
Published: March 2021

Background: The effects of weather on overall mortality are well documented. Anecdotally, icy conditions are perceived to result in more falls and admissions for neck of femur (NOF) fractures. The aim of this pilot study was to determine whether relationships could be extracted or at least not ruled out by analysing a small dataset, and so give impetus to a larger project. Methods: Seven trauma units across North West London were identified and NOF fracture data extracted for 5 years. Visual inspection of the time series, consideration of the weather on specific days and correlation analysis were used to assess associations between fracture numbers and a variety of weather parameters (temperature, rainfall, wind and ice risk). Results: Overall, 10929 individuals with hip fractures were admitted over the 5-year period. The highest number of admissions in a day was 14. No clear association was found between a weather parameter and daily admissions. However, when accumulated to a weekly timescale, a negative relationship with maximum temperature was found. No seasonal cycle was detected. Conclusion: The lack of a daily relationship and presence of a weekly relationship points to a possible delayed response to weather or insufficient daily data to extract a signal. The inconclusive results also indicate a larger data sample is required in future studies. In addition, even in cold weather an urban environment may not create icy conditions, being ameliorated by the heat island effect and gritting.
Very long chain fatty acid metabolism is required in acute myeloid leukemia
Authors: Tcheng Matthew , Roma Alessia , Ahmed Nawaz , Smith Richard W. , Jayanth Preethi , Minden Mark D. , Schimmer Aaron D. , Hess David A. , Hope Kristin , Rea Kevin A. , Akhtar Tariq A. , Bohrnsen Eric , D’Alessandro Angelo , Mohsen Al-Walid , Vockley Jerry , Spagnuolo Paul A. 
Published: March 2021

Abstract
Acute myeloid leukemia (AML) cells have an atypical metabolic phenotype characterized by increased mitochondrial mass, as well as a greater reliance on oxidative phosphorylation and fatty acid oxidation (FAO) for survival. To exploit this altered metabolism, we assessed publicly available databases to identify FAO enzyme overexpression. Very long chain acyl-CoA dehydrogenase (VLCAD; ACADVL) was found to be overexpressed and critical to leukemia cell mitochondrial metabolism. Genetic attenuation or pharmacological inhibition of VLCAD hindered mitochondrial respiration and FAO contribution to the tricarboxylic acid cycle, resulting in decreased viability, proliferation, clonogenic growth, and AML cell engraftment. Suppression of FAO at VLCAD triggered an increase in pyruvate dehydrogenase activity that was insufficient to increase glycolysis but resulted in adenosine triphosphate depletion and AML cell death, with no effect on normal hematopoietic cells. Together, these results demonstrate the importance of VLCAD in AML cell biology and highlight a novel metabolic vulnerability for this devastating disease.