bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reciprocal perspective as a super learner improves drug-target interaction prediction (MUSDTI)
Authors: Dick Kevin , Kyrollos Daniel G. , Cosoreanu Eric D. , Dooley Joseph , Fryer Joshua S. , Gordon Shaun M. , Kharbanda Nikhil , Klamrowski Martin , LaCasse Patrick N. L. , Leung Thomas F. , Nasir Muneeb A. , Qiu Chang , Robinson Aisha S. , Shao Derek , Siromahov Boyan R. , Starlight Evening , Tran Christophe , Wang Christopher , Yang Yu-Kai , Green James R. 
Published: August 2022

AbstractThe identification of novel drug-target interactions (DTI) is critical to drug discovery and drug repurposing to address contemporary medical and public health challenges presented by emergent diseases. Historically, computational methods have framed DTI prediction as a binary classification problem (indicating whether or not a drug physically interacts with a given protein target); however, framing the problem instead as a regression-based prediction of the physiochemical binding affinity is more meaningful. With growing databases of experimentally derived drug-target interactions (e.g. Davis, Binding-DB, and Kiba), deep learning-based DTI predictors can be effectively leveraged to achieve state-of-the-art (SOTA) performance. In this work, we formulated a DTI competition as part of the coursework for a senior undergraduate machine learning course and challenged students to generate component DTI models that might surpass SOTA models and effectively combine these component models as part of a meta-model using the Reciprocal Perspective (RP) multi-view learning framework. Following 6 weeks of concerted effort, 28 student-produced component deep-learning DTI models were leveraged in this work to produce a new SOTA RP-DTI model, denoted the Meta Undergraduate Student DTI (MUSDTI) model. Through a series of experiments we demonstrate that (1) RP can considerably improve SOTA DTI prediction, (2) our new double-cold experimental design is more appropriate for emergent DTI challenges, (3) that our novel MUSDTI meta-model outperforms SOTA models, (4) that RP can improve upon individual models as an ensembling method, and finally, (5) RP can be utilized for low computation transfer learning. This work introduces a number of important revelations for the field of DTI prediction and sequence-based, pairwise prediction in general.
Exploring synthetic lethal network for the precision treatment of clear cell renal cell carcinoma
Authors: Liu Zhicheng , Lin Dongxu , Zhou Yi , Zhang Linmeng , Yang Chen , Guo Bin , Xia Feng , Li Yan , Chen Danyang , Wang Cun , Chen Zhong , Leng Chao , Xiao Zhenyu 
Published: August 2022

AbstractThe emerging targeted therapies have revolutionized the treatment of advanced clear cell renal cell carcinoma (ccRCC) over the past 15 years. Nevertheless, lack of personalized treatment limits the development of effective clinical guidelines and improvement of patient prognosis. In this study, large-scale genomic profiles from ccRCC cohorts were explored for integrative analysis. A credible method was developed to identify synthetic lethality (SL) pairs and a list of 72 candidate pairs was determined, which might be utilized to selectively eliminate tumors with genetic aberrations using SL partners of specific mutations. Further analysis identified BRD4 and PRKDC as novel medical targets for patients with BAP1 mutations. After mapping these target genes to the comprehensive drug datasets, two agents (BI-2536 and PI-103) were found to have considerable therapeutic potentials in the BAP1 mutant tumors. Overall, our findings provided insight into the overview of ccRCC mutation patterns and offered novel opportunities for improving individualized cancer treatment.
Mitochondrial dysfunction and epithelial to mesenchymal transition in head neck cancer cell lines
Authors: Greier Maria Carmo , Runge Annette , Dudas Jozsef , Pider Viktoria , Skvortsova Ira-Ida , Savic Dragana , Riechelmann Herbert 
Published: August 2022

AbstractMitochondrial dysfunction promotes cancer aggressiveness, metastasis, and resistance to therapy. Similar traits are associated with epithelial mesenchymal transition (EMT). We questioned whether mitochondrial dysfunction induces EMT in head and neck cancer (HNC) cell lines. We induced mitochondrial dysfunction in four HNC cell lines with carbonyl cyanide-4(trifluoromethoxy)phenylhydrazone (FCCP), a mitochondrial electron transport chain uncoupling agent, and oligomycin, a mitochondrial ATP synthase inhibitor. Extracellular flux analyses and expression of the cystine/glutamate antiporter system xc (xCT) served to confirm mitochondrial dysfunction. Expression of the EMT-related transcription factor SNAI2, the mesenchymal marker vimentin and vimentin/cytokeratin double positivity served to detect EMT. In addition, holotomographic microscopy was used to search for morphological features of EMT. Extracellular flux analysis and xCT expression confirmed that FCCP/oligomycin induced mitochondrial dysfunction in all cell lines. Across the four cell lines, mitochondrial dysfunction resulted in an increase in relative SNAI2 expression from 8.5 ± 0.8 to 12.0 ± 1.1 (mean ± SEM; p = 0.007). This effect was predominantly caused by the CAL 27 cell line (increase from 2.2 ± 0.4 to 5.5 ± 1.0; p < 0.001). Similarly, only in CAL 27 cells vimentin expression increased from 2.2 ± 0.5 × 10–3to 33.2 ± 10.2 × 10–3(p = 0.002) and vimentin/cytokeratin double positive cells increased from 34.7 ± 5.1 to 67.5 ± 9.8% (p = 0.003), while the other 3 cell lines did not respond with EMT (all p > 0.1). Across all cell lines, FCCP/oligomycin had no effect on EMT characteristics in holotomographic microscopy. Mitochondrial dysfunction induced EMT in 1 of 4 HNC cell lines. Given the heterogeneity of HNC, mitochondrial dysfunction may be sporadically induced by EMT, but EMT does not explain the tumor promoting effects of mitochondrial dysfunction in general.
Prediction of anatomically and biomechanically feasible precision grip posture of the human hand based on minimization of muscle effort
Authors: Nakajima Takayuki , Asami Yuki , Endo Yui , Tada Mitsunori , Ogihara Naomichi 
Published: August 2022

AbstractWe developed a method to estimate a biomechanically feasible precision grip posture of the human hand for a given object based on a minimization of the muscle effort. The hand musculoskeletal model was constructed as a chain of 21 rigid links with 37 intrinsic and extrinsic muscles. To grasp an object, the static force and moment equilibrium condition of the object, force balance between the muscle and fingertip forces, and static frictional conditions must be satisfied. We calculated the hand posture, fingertip forces, and muscle activation signals for a given object to minimize the square sum of the muscle activations while satisfying the above kinetic constraints using an evolutionary optimization technique. To evaluate the estimated hand posture and fingertip forces, a wireless fingertip force-sensing device with two six-axis load cells was developed. When grasping the object, the fingertip forces and hand posture were experimentally measured to compare with the corresponding estimated values. The estimated hand postures and fingertip forces were in reasonable agreement to the corresponding measured data, indicating that the proposed hand posture estimation method based on the minimization of muscle effort is effective for the virtual ergonomic assessment of a handheld product.
PILRA polymorphism modifies the effect of APOE4 and GM17 on Alzheimer’s disease risk
Authors: Lopatko Lindman Karin , Jonsson Caroline , Weidung Bodil , Olsson Jan , Pandey Janardan P. , Prokopenko Dmitry , Tanzi Rudolph E. , Hallmans Göran , Eriksson Sture , Elgh Fredrik , Lövheim Hugo 
Published: August 2022

AbstractPILRA (rs1859788 A > G) has been suggested to be a protective variant for Alzheimer’s disease (AD) and is an entry co-receptor for herpes simplex virus-1. We conducted a nested case–control study of 360 1:1-matched AD subjects. Interactions between the PILRA-A allele, APOE risk variants (ε3/ε4 or ε4/ε4) and GM17 for AD risk were modelled. The associations were cross-validated using two independent whole-genome sequencing datasets. We found negative interactions between PILRA-A and GM17 (OR 0.72, 95% CI 0.52–1.00) and between PILRA-A and APOE risk variants (OR 0.56, 95% CI 0.32–0.98) in the discovery dataset. In the replication cohort, a joint effect of PILRA and PILRA × GM 17/17 was observed for the risk of developing AD (p .02). Here, we report a negative effect modification by PILRA on APOE and GM17 high-risk variants for future AD risk in two independent datasets. This highlights the complex genetics of AD.
miRNA expression patterns in blood leukocytes and milk somatic cells of goats infected with small ruminant lentivirus (SRLV)
Authors: Urbańska Daria M. , Jarczak Justyna , Czopowicz Michał , Kaba Jarosław , Horbańczuk Karina , Bagnicka Emilia 
Published: August 2022

AbstractThe study aims to determine the selected miRNAs expression in milk somatic cells (MSC) and blood leukocytes (BL) of SRLV-seronegative (SRLV-SN) and SRLV-seropositive (SRLV-SP) goats. A functional in silico analysis of their target genes was also conducted. MiR-93-5p and miR-30e-5p were expressed only in BL, while miR-144 was expressed only in MSC, regardless of SRLV infection. In the SRLV-SP goats, higher miR-214-3p and miR-221-5p levels were found in the MSC than in the BL. Only miR-30e-5p was influenced by the lactation stage in BL in both groups, while only miR-93-5p was altered in BL of SRLV-SN goats. The target gene protein products exhibited contradictory functions, protecting the host from virus on the one hand and assisting viruses in their life cycle on the other. The differential expression of the miRNAs observed between the MSC and BL of SRLV-SP goats may suggest that the local immune response to the infection in the udder differs from the systemic response, and acts independently. Some miRNAs demonstrated different expression between lactation stages. It may be influenced by the metabolic burden occurring in early lactation and its peak. Some of the studied miRNAs may influence viral infection by regulating the expression of their target genes.
Experimental research and analysis on the resistance characteristics of simulated ore bin in water
Authors: Xiao Linjing , Liu Qiang , Huang Weimin 
Published: August 2022

AbstractIn order to research the variation law of the longitudinal resistance coefficient of the ore bin in the marine mining system under different length–diameter ratio, external shape, additional weight and Reynolds number, a set of experimental system for testing the resistance coefficient was designed and built independently. By analyzing the experimental results, it can be seen that under the same conditions, the resistance coefficient decreases gradually with the increase of Reynolds number and finally fluctuates around a certain value. Increasing the excitation displacement will reduce the overall resistance coefficient of the ore bin. The smaller the length-diameter ratio is, the larger the corresponding force value when the vibration acceleration of the ore bin is 0, and the larger the overall resistance coefficient is. The resistance coefficient of the cylindrical section is greater than that of the rectangular shape. In order to reduce the longitudinal vibration and the transverse towing offset, the shape of the ore bin should be cylindrical in actual design and production. At low Reynolds number, the increase of added weight will increase the resistance coefficient, while at high Reynolds number, the change of added weight will not cause the change of resistance coefficient.
PCL insufficient patients with increased translational and rotational passive knee joint laxity have no increased range of anterior–posterior and rotational tibiofemoral motion during level walking
Authors: Oehme Stephan , Moewis Philippe , Boeth Heide , Bartek Benjamin , Lippert Annika , von Tycowicz Christoph , Ehrig Rainald , Duda Georg N. , Jung Tobias 
Published: August 2022

AbstractPassive translational tibiofemoral laxity has been extensively examined in posterior cruciate ligament (PCL) insufficient patients and belongs to the standard clinical assessment. However, objective measurements of passive rotational knee laxity, as well as range of tibiofemoral motion during active movements, are both not well understood. None of these are currently quantified in clinical evaluations of patients with PCL insufficiency. The objective of this study was to quantify passive translational and rotational knee laxity as well as range of anterior–posterior and rotational tibiofemoral motion during level walking in a PCL insufficient patient cohort as a basis for any later clinical evaluation and therapy. The laxity of 9 patient knees with isolated PCL insufficiency or additionally posterolateral corner (PLC) insufficiency (8 males, 1 female, age 36.78 ± 7.46 years) were analysed and compared to the contralateral (CL) knees. A rotometer device with a C-arm fluoroscope was used to assess the passive tibiofemoral rotational laxity while stress radiography was used to evaluate passive translational tibiofemoral laxity. Functional gait analysis was used to examine the range of anterior–posterior and rotational tibiofemoral motion during level walking. Passive translational laxity was significantly increased in PCL insufficient knees in comparison to the CL sides (15.5 ± 5.9 mm vs. 3.7 ± 1.9 mm, p < 0.01). Also, passive rotational laxity was significantly higher compared to the CL knees (26.1 ± 8.2° vs. 20.6 ± 5.6° at 90° knee flexion, p < 0.01; 19.0 ± 6.9° vs. 15.5 ± 5.9° at 60° knee flexion, p = 0.04). No significant differences were observed for the rotational (16.3 ± 3.7° vs. 15.2 ± 3.6°, p = 0.43) and translational (17.0 ± 5.4 mm vs. 16.1 ± 2.8 mm, p = 0.55) range of anterior–posterior and rotational tibiofemoral motion during level walking conditions for PCL insufficient knees compared to CL knees respectively. The present study illustrates that patients with PCL insufficiency show a substantial increased passive tibiofemoral laxity, not only in tibiofemoral translation but also in tibiofemoral rotation. Our data indicate that this increased passive multiplanar knee joint laxity can be widely compensated during level walking. Further studies should investigate progressive changes in knee joint laxity and kinematics post PCL injury and reconstruction to judge the individual need for therapy and effects of physiotherapy such as quadriceps force training on gait patterns in PCL insufficient patients.
Simultaneous assessment of lung morphology and respiratory motion in retrospectively gated in-vivo microCT of free breathing anesthetized mice
Authors: Dullin Christian , Svetlove Angelika , Zschüntzsch Jana , Alves Frauke 
Published: August 2022

AbstractRetrospective gating (RG) is a well established technique in preclinical computed tomography (CT) to assess 3D morphology of the lung. In RG additional angular projections are recorded typically by performing multiple rotations. Consequently, the projections are sorted according to the expansion state of the chest and those sets are then reconstructed separately. Thus, the breathing motion artefacts are suppressed at a cost of strongly elevated X-ray dose levels. Here we propose to use the entire raw data to assess respiratory motion in addition to retrospectively gated 3D reconstruction that visualize anatomical structures of the lung. Using this RG based X-ray respiratory motion measurement approach, which will be referred to as RG based X-ray lung function measurement (rgXLF) on the example of the mdx mouse model of Duchenne muscle dystrophy (mdx) we accurately obtained both the 3D anatomical morphology of the lung and the thoracic bones as well as functional temporal parameters of the lung. Thus, rgXLF will remove the necessity for separate acquisition procedures by being able to reproduce comparable results to the previously established planar X-ray based lung function measurement approach in a single low dose CT scan.
Synergistic use of gradient flipping and phase prediction for inline electron holography
Authors: Ozsoy-Keskinbora Cigdem , Van den Broek Wouter , Boothroyd Chris B. , Dunin-Borkowski Rafal E. , van Aken Peter A. , Koch Christoph T. 
Published: August 2022

AbstractInline holography in the transmission electron microscope is a versatile technique which provides real-space phase information that can be used for the correction of imaging aberrations, as well as for measuring electric and magnetic fields and strain distributions. It is able to recover high-spatial-frequency contributions of the phase effectively but suffers from the weak transfer of low-spatial-frequency information, as well as from incoherent scattering. Here, we combine gradient flipping and phase prediction in an iterative flux-preserving focal series reconstruction algorithm with incoherent background subtraction that gives extensive access to the missing low spatial frequencies. A procedure for optimizing the reconstruction parameters is presented, and results from Fe-filled C nanospheres, and MgO cubes are compared with phase images obtained using off-axis holography.
The lithological characteristics of natural gas hydrates in permafrost on the Qinghai of China
Authors: Lei Da , Fu Changmin , Zhen Qihui , Wang Zhongxing , Wang Ruo 
Published: August 2022

AbstractThe environment is seriously threatened by the methane emitted as permafrost melts. Studying deposits of natural gas hydrates that include methane is therefore important. This study presents a novel approach based on the rock Archie formula to discover the porosity and saturation of gas hydrates. The relationship between resistivity and porosity and the porosity of hydrates was studied, and the results showed that the resistivity of hydrate reservoirs was closely related to porosity and hydrate saturation, and the polarization rate was only related to the concentration of natural gas hydrates and had nothing to do with porosity. Using the multi-channel time domain induced polarization (MTIP) method, the profile with five boreholes in the Muli area of the permafrost area of the Qinghai-Tibet Plateau was observed, and the thickness of the shallow permafrost distribution and the underground structure were inferred based on the resistivity of the MTIP data. The polarization rate and hydrate saturation of the inversion assessed the presence of hydrates in the Muli region. The results show that the MTIP method can be used to detect the thickness of permafrost distribution, determine fault boundaries, reveal the distribution of natural gas transport paths, and evaluate the presence of natural gas hydrates.
Further slowing down of hydrolysis of amylose heated with black soybean extract by treating with nitrite under gastric conditions
Authors: Takahama Umeo , Hirota Sachiko 
Published: August 2022

AbstractBlack soybean (BSB), which contains cyanidin-3-O-glucoside (C3G) and procyanidins, is cooked with rice in Japan. The color of the cooked rice is purplish red due to the binding of C3G and reddish oxidation products of procyanidins. These components can slowdown pancreatin-induced hydrolysis of amylose more significantly than the hydrolysis of amylopectin, and can react with nitrous acid in the stomach. This manuscript deals with the effects of nitrous acid on pancreatin-induced hydrolysis of amylose heated with BSB extract. The hydrolysis of amylose heated with BSB extract was slow, and the slowdown was due to the binding of C3G/its degradation products and degradation products of procyanidins. The amylose hydrolysis was slowed down further by treating with nitrite under gastric conditions. The further slowdown was discussed to be due to the binding of the products, which were formed by the reaction of procyanidins with nitrous acid, to amylose. In the products, dinitroprocyanidins were included. In this way, the digestibility of amylose heated with BSB extract can be slowed down further by reacting with nitrous acid in the stomach.
Development of smart cold forging die life cycle management system based on real-time forging load monitoring
Authors: Seo Young Ho 
Published: August 2022

AbstractCold forging dies are manufactured through the shrink fit process to withstand high pressure loads, but fatigue failure eventually occurs due to repeated compressive stresses. The life cycle until fatigue failure was defined as the limit life, and attempts were made to predict the die life based on finite element method. However, accurate prediction was impossible owing to uncontrollable environmental variables. Consequently, it is impossible to clearly determine the die replacement cycle, resulting in negative consequences such as poor quality, production delay, and cost increase. Various environmental factors affecting the prediction of die life cycle result in the increase or decrease of the forming load, which is an important variable that determines the die life cycle. In this study, a system for monitoring load data generated from forging facilities was developed based on a piezo sensor. In addition, the die life cycle was more accurately predicted by using the forming load data measured in real time, and a die life management system that can determine the die replacement cycle was applied to the automobile steering parts production line.
Inequality of public facilities between urban and rural areas and its driving factors in ten cities of China
Authors: Xu Ronghua , Yue Wenze , Wei Feiyang , Yang Guofu , Chen Yi , Pan Kaixuan 
Published: August 2022

AbstractUrban development continues to face the dilemma of spatial inequality of public facilities, particularly educational and medical facilities. Identifying inequalities in various types of public facilities and their driving mechanisms is crucial in reducing social inequality. However, information on this topic is limited. This study took 10 typical cities in China as cases. We used the methods of the Gini coefficient and hedonic price model as bases in evaluating the equality of nine types of education and medical facilities, focusing on the differences between urban and rural areas. Moreover, we further analyzed the driving factors of facility equality. Results showed that equality of public facilities in urban areas was significantly higher than that in rural areas. Primary schools, middle schools, and health service centers were relatively equal, and kindergartens and pharmacies were unequal only in rural areas. However, the equality of facilities with large-size or commercial attributes was not optimistic. Furthermore, there remained a significant gap among counties (or districts), which was mainly driven by population, economy, and building density in the form of logarithm and logarithmic linear models. Our research contributes to an in-depth understanding of the inequality of public facilities and further supports decision-making to improve social equality.