bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of complicated all-α protein structures
Authors: Sakuma Koya , Kobayashi Naohiro , Sugiki Toshihiko , Nagashima Toshio , Fujiwara Toshimichi , Suzuki Kano , Kobayashi Naoya , Murata Takeshi , Kosugi Takahiro , Tatsumi-Koga Rie , Koga Nobuyasu 
Published: January 2024

AbstractA wide range of de novo protein structure designs have been achieved, but the complexity of naturally occurring protein structures is still far beyond these designs. Here, to expand the diversity and complexity of de novo designed protein structures, we sought to develop a method for designing ‘difficult-to-describe’ α-helical protein structures composed of irregularly aligned α-helices like globins. Backbone structure libraries consisting of a myriad of α-helical structures with five or six helices were generated by combining 18 helix–loop–helix motifs and canonical α-helices, and five distinct topologies were selected for de novo design. The designs were found to be monomeric with high thermal stability in solution and fold into the target topologies with atomic accuracy. This study demonstrated that complicated α-helical proteins are created using typical building blocks. The method we developed will enable us to explore the universe of protein structures for designing novel functional proteins.
Auto-detection of the coronavirus disease by using deep convolutional neural networks and X-ray photographs
Authors: Hussein Ahmad MohdAziz , Sharifai Abdulrauf Garba , Alia Osama Moh’d , Abualigah Laith , Almotairi Khaled H. , Abujayyab Sohaib K. M. , Gandomi Amir H. 
Published: January 2024

AbstractThe most widely used method for detecting Coronavirus Disease 2019 (COVID-19) is real-time polymerase chain reaction. However, this method has several drawbacks, including high cost, lengthy turnaround time for results, and the potential for false-negative results due to limited sensitivity. To address these issues, additional technologies such as computed tomography (CT) or X-rays have been employed for diagnosing the disease. Chest X-rays are more commonly used than CT scans due to the widespread availability of X-ray machines, lower ionizing radiation, and lower cost of equipment. COVID-19 presents certain radiological biomarkers that can be observed through chest X-rays, making it necessary for radiologists to manually search for these biomarkers. However, this process is time-consuming and prone to errors. Therefore, there is a critical need to develop an automated system for evaluating chest X-rays. Deep learning techniques can be employed to expedite this process. In this study, a deep learning-based method called Custom Convolutional Neural Network (Custom-CNN) is proposed for identifying COVID-19 infection in chest X-rays. The Custom-CNN model consists of eight weighted layers and utilizes strategies like dropout and batch normalization to enhance performance and reduce overfitting. The proposed approach achieved a classification accuracy of 98.19% and aims to accurately classify COVID-19, normal, and pneumonia samples.
Optimization, characterization, and cytotoxicity studies of novel anti-tubercular agent-loaded liposomal vesicles
Authors: Obiedallah Manar M. , Mironov Maxim A. , Belyaev Danila V. , Ene Antoaneta , Vakhrusheva Diana V. , Krasnoborova Svetlana Yu. , Bershitsky Sergey Y. , Shchepkin Daniil V. , Minin Artem S. , Ishmetova Rashida I. , Ignatenko Nina K. , Tolshchina Svetlana G. , Fedorova Olga V. , Rusinov Gennady L. 
Published: January 2024

AbstractThe treatment of tuberculosis is still a challenging process due to the widespread of pathogen strains resistant to antibacterial drugs, as well as the undesirable effects of anti-tuberculosis therapy. Hence, the development of safe and effective new anti-antitubercular agents, in addition to suitable nanocarrier systems, has become of utmost importance and necessity. Our research aims to develop liposomal vesicles that contain newly synthesized compounds with antimycobacterial action. The compound being studied is a derivative of imidazo-tetrazine named 3-(3,5-dimethylpyrazole-1-yl)-6-(isopropylthio) imidazo [1,2-b] [1,2,4,5] tetrazine compound. Several factors that affect liposomal characteristics were studied. The maximum encapsulation efficiency was 53.62 ± 0.09. The selected liposomal formulation T8* possessed a mean particle size of about 205.3 ± 3.94 nm with PDI 0.282, and zeta potential was + 36.37 ± 0.49 mv. The results of the in vitro release study indicated that the solubility of compound I was increased by its incorporation in liposomes. The free compound and liposomal preparation showed antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) at MIC value 0.94–1.88 μg/ml. We predict that the liposomes may be a good candidate for delivering new antitubercular drugs.
A pilot optical coherence tomography angiography classification of retinal neovascularization in retinopathy of prematurity
Authors: Chen Xi , Imperio Ryan , Viehland Christian , Patel Pujan R. , Tran-Viet Du , Mangalesh Shwetha , Prakalapakorn S. Grace , Freedman Sharon F. , Izatt Joseph A. , Toth Cynthia A. ,   BabySTEPS Group
Published: January 2024

AbstractExtraretinal neovascularization is a hallmark of treatment-requiring retinopathy of prematurity (ROP). Optical coherence tomography angiography (OCTA) offers vascular flow and depth information not available from indirect ophthalmoscopy and structural OCT, but OCTA is only commercially available as a tabletop device. In this study, we used an investigational handheld OCTA device to study the vascular flow in and around retinal neovascularization in seven preterm infants with treatment-requiring ROP and contrasted them to images of vascular flow in six infants of similar age without neovascular ROP. We showed stages of retinal neovascularization visible in preterm infants from 32 to 47 weeks postmenstrual age: Intraretinal neovascularization did not break through the internal limiting membrane; Subclinical neovascular buds arose from retinal vasculature with active flow through the internal limiting membrane; Flat neovascularization in aggressive ROP assumed a low-lying configuration compared to elevated extraretinal neovascular plaques; Regressed neovascularization following treatment exhibited decreased vascular flow within the preretinal tissue, but flow persisted in segments of retinal vessels elevated from their original intraretinal location. These findings enable a pilot classification of retinal neovascularization in eyes with ROP using OCTA, and may be helpful in detailed monitoring of disease progression, treatment response and predicting reactivation.
Copper-catalyzed synthesis of pyrazolo[1,5-a]pyrimidine based triazole-linked glycohybrids: mechanistic insights and bio-applications
Authors: Tiwari Ghanshyam , Khanna Ashish , Tyagi Rajdeep , Mishra Vinay Kumar , Narayana Chintam , Sagar Ram 
Published: January 2024

AbstractHybrid molecules maintain their stronghold in the drug market, with over 60% of drug candidates in pharmaceutical industries. The substantial expenses for developing and producing biologically privileged drugs are expected to create opportunities for producing hybrid molecule-based drugs. Therefore, we have developed a simple and efficient copper-catalyzed approach for synthesizing a wide range of triazole-linked glycohybrids derived from pyrazolo[1,5-a]pyrimidines. Employing a microwave-assisted copper-catalyzed approach, we developed a concise route using various 7-O-propargylated pyrazolo[1,5-a]pyrimidines and 1-azidoglycosides. This strategy afforded a series of twenty-seven glycohybrids up to 98% yield with diverse stereochemistry. All were achieved within a remarkably shortened time frame. Our investigation extends to evaluating the anticancer potential of these synthesized triazole-linked pyrazolo[1,5-a] pyrimidine-based glycohybrids. In-vitro assays against MCF-7, MDA-MB231, and MDA-MB453 cell lines reveal intriguing findings. (2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(4-(((5-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate emerges as a standout with better anticancer activity against MDA-MB231 cells (IC50 = 29.1 µM), while (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(4-(((5-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate demonstrates the best inhibitory effects against MCF-7 cells (IC50 = 15.3 µM) in all derived compounds. These results align with our docking analysis and structure–activity relationship (SAR) investigations, further validating the in-vitro outcomes. This work not only underscores the synthetic utility of our devised protocol but also highlights the promising potential of these glycohybrids as candidates for further anticancer therapeutic exploration.
The mitochondrial DNA common deletion as a potential biomarker of cancer-associated fibroblasts from skin basal and squamous cell carcinomas
Authors: Fontana Gabriele A. , MacArthur Michael R. , Rotankova Nadezhda , Di Filippo Michela , Beer Hans-Dietmar , Gahlon Hailey L. 
Published: January 2024

AbstractCancer-associated fibroblasts (CAFs) are components of the tumor microenvironment and represent appealing therapeutic targets for translational studies. Conventional protein-based biomarkers for CAFs have been reported to be limited in their specificity, rendering difficult the identification of CAFs from normal fibroblasts (NFs) in clinical samples and dampening the development of CAF-targeted therapies to treat cancer. In this study, we propose the mitochondrial RNA and the mitochondrial DNA (mtDNA) common deletion (CD) as novel indicators of CAF identity. We found that cancer-activation correlated with decreased levels of the mtDNA CD, a condition not due to altered mitochondria count or cellular redox state, but potentially linked to the generalized overexpression of mtDNA maintenance genes in CAFs. Decreased mtDNA CD content in CAFs was associated with moderate to strong overexpression of mtDNA-encoded genes and to slightly improved mitochondrial function. We identified similar patterns of upregulation of mtDNA-encoded genes in independent single-cell RNA seq data obtained from squamous cell carcinoma (SCC) patients. By using the identified nucleic acids-based indicators, identification of CAFs from NFs could be improved, leading to potential therapeutic benefits in advancing translational and clinical studies.
The nascent polypeptide-associated complex subunit Egd1 is required for efficient selective mitochondrial degradation in budding yeast
Authors: Tian Yuan , Okamoto Koji 
Published: January 2024

AbstractSelective degradation of dysfunctional or excess mitochondria is a fundamental process crucial for cell homeostasis in almost all eukaryotes. This process relies on autophagy, an intracellular self-eating system conserved from yeast to humans and is thus called mitophagy. Detailed mechanisms of mitophagy remain to be fully understood. Here we show that mitochondrial degradation in budding yeast, which requires the pro-mitophagic protein Atg32, is strongly reduced in cells lacking Egd1, a beta subunit of the nascent polypeptide-associated complex acting in cytosolic ribosome attachment and protein targeting to mitochondria. By contrast, loss of the sole alpha subunit Egd2 or the beta subunit paralogue Btt1 led to only a partial or slight reduction in mitophagy. We also found that phosphorylation of Atg32, a crucial step for priming mitophagy, is decreased in the absence of Egd1. Forced Atg32 hyperphosphorylation almost completely restored mitophagy in egd1-null cells. Together, we propose that Egd1 acts in Atg32 phosphorylation to facilitate mitophagy.
Deep learning-based optic disc classification is affected by optic-disc tilt
Authors: Nam Youngwoo , Kim Joonhyoung , Kim Kyunga , Park Kyung-Ah , Kang Mira , Cho Baek Hwan , Oh Sei Yeul , Kee Changwon , Han Jongchul , Lee Ga-In , Kang Min Chae , Lee Dongyoung , Choi Yeeun , Yun Hee Jee , Park Hansol , Kim Jiho , Cho Soo Jin , Chang Dong Kyung 
Published: January 2024

AbstractWe aimed to determine the effect of optic disc tilt on deep learning-based optic disc classification. A total of 2507 fundus photographs were acquired from 2236 eyes of 1809 subjects (mean age of 46 years; 53% men). Among all photographs, 1010 (40.3%) had tilted optic discs. Image annotation was performed to label pathologic changes of the optic disc (normal, glaucomatous optic disc changes, disc swelling, and disc pallor). Deep learning-based classification modeling was implemented to develop optic-disc appearance classification models with the photographs of all subjects and those with and without tilted optic discs. Regardless of deep learning algorithms, the classification models showed better overall performance when developed based on data from subjects with non-tilted discs (AUC, 0.988 ± 0.002, 0.991 ± 0.003, and 0.986 ± 0.003 for VGG16, VGG19, and DenseNet121, respectively) than when developed based on data with tilted discs (AUC, 0.924 ± 0.046, 0.928 ± 0.017, and 0.935 ± 0.008). In classification of each pathologic change, non-tilted disc models had better sensitivity and specificity than the tilted disc models. The optic disc appearance classification models developed based all-subject data demonstrated lower accuracy in patients with the appearance of tilted discs than in those with non-tilted discs. Our findings suggested the need to identify and adjust for the effect of optic disc tilt on the optic disc classification algorithm in future development.
Preparation and characterization of gelatin/chitosan nanocomposite reinforced by NiO nanoparticles as an active food packaging
Authors: Momtaz Mahdieh , Momtaz Elham , Mehrgardi Masoud A. , Momtaz Fatemeh , Narimani Tahmineh , Poursina Farkhondeh 
Published: January 2024

AbstractFood packaging with antibacterial properties has attracted much attention recently. In this study, nickel oxide nanoparticles (NiONPs) were synthesized by co-precipitation and then gelatin/chitosan polymer films (GEL/CS) with different percentages of NiONPs, bio-nanocomposites, were prepared by casting. Morphology, crystal microstructure, molecular interactions and thermal stabilities of the NPs and the composite films were characterized by FESEM, XRD, FTIR and TGA, respectively. The bio-nanocomposite films exhibited excellent barrier, thermal and mechanical properties by addition of an optimized content of NPs. For example, the tensile strength (TS) of the GEL/CS film without NPs was 23.83 MPa and increased to 30.13 MPa by incorporation of 1% NPs. The antibacterial properties and toxicity of the films were investigated. These films show good antibacterial behavior against Gram-positive (Staphylococcus aureus) bacteria compared to Gram-negative (Escherichia coli) bacteria. Furthermore, the films were found to be non-toxic to fibroblast cells that came into contact with the films, with a survival rate of more than 88%. Therefore, these films can be applied for food packaging due to their excellent mechanical, barrier, and antibacterial properties.
ITGB1 and DDR activation as novel mediators in acquired resistance to osimertinib and MEK inhibitors in EGFR-mutant NSCLC
Authors: De Rosa Caterina , De Rosa Viviana , Tuccillo Concetta , Tirino Virginia , Amato Luisa , Papaccio Federica , Ciardiello Davide , Napolitano Stefania , Martini Giulia , Ciardiello Fortunato , Morgillo Floriana , Iommelli Francesca , Della Corte Carminia Maria 
Published: January 2024

AbstractOsimertinib is a third-generation tyrosine kinase inhibitor clinically approved for first-line treatment of EGFR-mutant non-small cell lung cancer (NSCLC) patients. Although an impressive drug response is initially observed, in most of tumors, resistance occurs after different time and an alternative therapeutic strategy to induce regression disease is currently lacking. The hyperactivation of MEK/MAPKs, is one the most common event identified in osimertinib-resistant (OR) NSCLC cells. However, in response to selective drug pressure, the occurrence of multiple mechanisms of resistance may contribute to treatment failure. In particular, the epithelial-to-mesenchymal transition (EMT) and the impaired DNA damage repair (DDR) pathways are recognized as additional cause of resistance in NSCLC thus promoting tumor progression. Here we showed that concurrent upregulation of ITGB1 and DDR family proteins may be associated with an increase of EMT pathways and linked to both osimertinib and MEK inhibitor resistance to cell death. Furthermore, this study demonstrated the existence of an interplay between ITGB1 and DDR and highlighted, for the first time, that combined treatment of MEK inhibitor with DDRi may be relevant to downregulate ITGB1 levels and increase cell death in OR NSCLC cells.
Using optical emission spectroscopy in atmospheric conditions to track the inflight reduction of plasma sprayed TiO2−x feedstock for thermoelectric applications
Authors: Mauer Georg , Gildersleeve V Edward J. 
Published: January 2024

AbstractThermal spray deposition (specifically Atmospheric Plasma Spraying, APS) is a well-established surface coating technology with a broad scope of applications (i.e., insulative coatings, tribological coatings, anti-corrosion coatings, etc.). In addition, there is a constant drive to introduce the APS process into new and emerging fields. One such niche application for APS would be sub-stoichiometric TiO2−x coatings with enhanced thermoelectric performance (compared to the bulk material). The APS process in this context has a unique ability—given the use of hydrogen as a plasma gas—to reduce TiO2−x material during processing. However, to this point, there is neither a reliable nor self-consistent method to assess (nor control by parametric optimization) the inflight reduction of molten oxide particles during processing. This study shows that using Optical Emission Spectroscopy (OES), it can be possible—even in atmospheric conditions—to identify characteristic emission peaks associated with the inflight reduction of TiO2 during APS. Using this OES data, the input spray processing parameters and their influence on coating microstructure and the degree of inflight reduction of the material will be shown. Results suggest under equilibrium conditions only a minimal amount of hydrogen gas is needed in the plasma to fulfill the TiO2 reduction.
Diurnal retinal and choroidal gene expression patterns support a role for circadian biology in myopia pathogenesis
Authors: Stone Richard A. , Tobias John W. , Wei Wenjie , Schug Jonathan , Wang Xia , Zhang Lixin , Iuvone P. Michael , Nickla Debora L. 
Published: January 2024

AbstractThe prevalence of myopia (nearsightedness) is increasing to alarming levels, but its etiology remains poorly understood. Because both laboratory and clinical findings suggest an etiologic role for circadian rhythms in myopia development, we assayed gene expression by RNA-Seq in retina and choroid at the onset of unilateral experimental myopia in chick, isolating tissues every 4 h during a single 24-h period from myopic and contralateral control eyes. Occluded versus open eye gene expression differences varied considerably over the 24-h sampling period, with some occurring at multiple times of day but with others showing differences at only a single investigated timepoint. Some of the genes identified in retina or choroid of chick myopia were previously identified as candidate genes for common human myopia. Like differentially expressed genes, pathways identified by Gene Set Enrichment Analysis also varied dramatically by sampling time. Considered with other laboratory data, human genetic and epidemiology data, these findings further implicate circadian events in myopia pathogenesis. The present results emphasize a need to include time of day in mechanistic studies of myopia and to assess circadian biology directly in trying to understand better the origin of myopia and to develop more effective therapies.
Two-phase simulation of entropy optimized mixed convection flow of two different shear-thinning nanomaterials in thermal and mass diffusion systems with Lorentz forces
Authors: Suresha S. , Khan Umair , Soumya D. O. , Venkatesh P. , Gasmi Hatem , Sunitha M. , Zaib Aurang , Al-Naghi Ahmed , Karoui Hatem , Ishak Anuar , Ojok Walter 
Published: January 2024

AbstractThis research compares the momentum, thermal energy, mass diffusion and entropy generation of two shear thinning nanofluids in an angled micro-channel with mixed convection, nonlinear thermal radiation, temperature jump boundary condition and variable thermal conductivity effects. The $$RKF 45$$

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K
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approach was used to solve the Buongiorno nonlinear governing model. The effect of different parameters on the flow, energy, concentration, and entropy generating fields have been graphically illustrated and explained. The hyperbolic tangent nanoliquid has a better velocity than the Williamson nanofluid. The Williamson nanofluid has higher thermal energy and concentration than the hyperbolic tangent nanoliquid in the microchannel. The Grashof number, both thermal and solutal, increases the fluid flow rate throughout the flow system. The energy of the nanoliquid is reduced by the temperature jump condition, while the energy field of the nanoliquid is enhanced by the improving thermal conductivity value. The nanoliquids concentration rises as the Schmitt number rises. The irreversibility rate of the channel system is maximized by the variable thermal conductivity parameter.
Predictive model for a second hip fracture occurrence using natural language processing and machine learning on electronic health records
Authors: Larrainzar-Garijo Ricardo , Fernández-Tormos Esther , Collado-Escudero Carlos Alberto , Alcantud Ibáñez María , Oñorbe-San Francisco Fernando , Marin-Corral Judith , Casadevall David , Donaire-Gonzalez David , Martínez-Sanchez Luisa , Cabal-Hierro Lucia , Benavent Diego , Brañas Fátima 
Published: January 2024

AbstractHip fractures (HFx) are associated with a higher morbidity and mortality rates, leading to a significant reduction in life quality and in limitation of patient´s mobility. The present study aimed to obtain real-world evidence on the clinical characteristics of patients with an initial and a second hip fracture (HFx) and develop a predictive model for second HFx using artificial intelligence. Electronic health records from one hospital centre in Spain from January 2011 to December 2019 were analysed using EHRead® technology, based on natural language processing and machine learning. A total of 1,960 patients with HFx were finally included during the study period after meeting all inclusion and exclusion criteria. From this total, 1835 (93.6%) patients were included in the HFx subgroup, while 124 (6.4%) were admitted to the second HFx (2HFx) subgroup. The mean age of the participants was 84 years and 75.5% were female. Most of comorbidities were more frequently identified in the HFx group, including hypertension (72.0% vs. 67.2%), cognitive impairment (33.0% vs. 31.2%), diabetes mellitus (28.7% vs. 24.8%), heart failure (27.6% vs. 22.4%) and chronic kidney disease (26.9% vs. 16.0%). Based on clinical criteria, 26 features were selected as potential prediction factors. From there, 16 demographics and clinical characteristics such as comorbidities, medications, measures of disabilities for ambulation and type of refracture were selected for development of a competitive risk model. Specifically, those predictors with different associated risk ratios, sorted from higher to lower risk relevance were visual deficit, malnutrition, walking assistance, hypothyroidism, female sex, osteoporosis treatment, pertrochanteric fracture, dementia, age at index, osteoporosis, renal failure, stroke, COPD, heart disease, anaemia, and asthma. This model showed good performance (dependent AUC: 0.69; apparent performance: 0.75) and could help the identification of patients with higher risk of developing a second HFx, allowing preventive measures. This study expands the current available information of HFx patients in Spain and identifies factors that exhibit potential in predicting a second HFx among older patients.