bluuebunny/crossref_metadata_2025_split huggingface dataset:
Models for predicting treatment efficacy of antiepileptic drugs and prognosis of treatment withdrawal in epilepsy patients
Authors: Yang Shijun , Wang Bin , Han Xiong 
Published: January 2021

AbstractAlthough antiepileptic drugs (AEDs) are the most effective treatment for epilepsy, 30–40% of patients with epilepsy would develop drug-refractory epilepsy. An accurate, preliminary prediction of the efficacy of AEDs has great clinical significance for patient treatment and prognosis. Some studies have developed statistical models and machine-learning algorithms (MLAs) to predict the efficacy of AEDs treatment and the progression of disease after treatment withdrawal, in order to provide assistance for making clinical decisions in the aim of precise, personalized treatment. The field of prediction models with statistical models and MLAs is attracting growing interest and is developing rapidly. What’s more, more and more studies focus on the external validation of the existing model. In this review, we will give a brief overview of recent developments in this discipline.
Atomically sculptured heart in oxide film using convergent electron beam
Authors: Lee Gwangyeob , Baek Seung-Hyub , Chang Hye Jung 
Published: January 2021

AbstractWe demonstrate a fabrication of an atomically controlled single-crystal heart-shaped nanostructure using a convergent electron beam in a scanning transmission electron microscope. The delicately controlled e-beam enable epitaxial crystallization of perovskite oxide LaAlO3 grown out of the relative conductive interface (i.e. 2 dimensional electron gas) between amorphous LaAlO3/crystalline SrTiO3.
Change of joint-line convergence angle should be considered for accurate alignment correction in high tibial osteotomy
Authors: Na Young Gon , Lee Beom Koo , Choi Ji Uk , Lee Byung Hoon , Sim Jae Ang 
Published: January 2021

AbstractBackgroundThe alignment correction after high tibial osteotomy (HTO) is made both by bony correction and soft-tissue correction around the knee. Change of the joint-line convergence angle (JLCA) represents the soft-tissue correction after HTO, which is the angle made by a tangential line between the femoral condyles and the tibial plateau. We described the patterns of JLCA change and related factors after HTO and investigated the appropriate preoperative planning method.MethodsEighty patients who underwent HTO between 2013 and 2016 were included for this retrospective study. Standing, whole-limb radiograph, supine knee anteroposterior (AP) and lateral were measured on the preoperative and postoperative radiographs. The patterns of JLCA changes and related factors were analyzed.ResultsJLCA decreased by a mean of 0.9° ± 1.2° (P < 0.001) after HTO. Sixteen patients (20%, group II) showed a greater JLCA decrease ≥ 2°, while 64 (80%, group I) patients remained in a narrow range of JLCA change < 2°. Group II showed more varus deformity (varus 8.1° vs. varus 4.7° in the mechanical femorotibial angle,P < 0.001), greater JLCA on standing (4.9° vs. 2.1°,P < 0.001), and the difference of JLCA in the standing and supine positions (2.8° vs. 0.7°,P < 0.001) preoperatively compared to group I. The risk of a greater JLCA decrease ≥ 2° was associated with greater preoperative JLCA in the standing position and the difference between the JLCA in the standing and supine positions. Postoperative JLCA correlated better with preoperative JLCA in the supine position than those in the standing position. A preoperative JLCA ≥ 4° or the difference of preoperative JLCA in the standing and supine positions ≥ 1.7° was the cut-off value to predict a large JLCA decrease ≥ 2° after HTO in the receiver operating characteristic (ROC) curve analysis.ConclusionsSurgeons should consider the effect of the JLCA change during the preoperative planning and intraoperative procedure to avoid unintended overcorrection.
Fractional anisotropy measurements of the left dorsolateral prefrontal cortex for therapeutic response assessment after repetitive transcranial magnetic stimulation (rTMS) in relapsing remitting multiple sclerosis patients suffering from depression
Authors: Hassan Talaat A. , Elkholy Shaima Fattouh , Shehata Hatem S. , Shalaby Nevin M. , Elmazny Alaa N. , Sadek Mohamed N. , Mahmoud Bahaa Eldin , Elsherbiny Mona M. 
Published: January 2021

AbstractBackgroundMultiple sclerosis (MS) is a major cause of neurological disability in adults. Depression is one of the most common psychiatric comorbidities in MS patients with negative impact on patients’ quality of life. The aim of the study is to evaluate the role of diffusion tensor imaging (DTI) in monitoring the therapeutic response after high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) versus selective serotonin reuptake inhibitor (SSRI) therapy for relapsing remitting multiple sclerosis (RRMS) patients presenting with depression by measuring the factional anisotropy of the dorsolateral prefrontal cortex (DLPFC) before and after treatment and also to assess the treatments’ impact on patients’ cognitive functions and depression.ResultsFractional anisotropy (FA) only increased in rTMS group (0.44 ± 0.03 pre-rTMS vs 0.53 ± 0.05 post-rTMS,P< 0.001), but there were no significant changes in the SSRI group (0.44 ± 0.04 pre-SSRIs vs 0.45 ± .37 post-SSRIs,P= 0.072). Both rTMS and SSRI groups showed significant clinical improvement in Beck Depression Inventory (BDI) and Paced Auditory Serial Addition Test (PASAT) after either intervention (17.6 ± 3.25 pre-rTMS vs 10.6 ± 1.89 post-rTMS and 23 ± 6.36 pre-rTMS vs 24.87 ± 6.6 post-rTMS, respectively,P< 0.001; 17.67 ± 3.15 pre-SSRIs vs 0.6 ± 1.84 post-SSRIs and 23.8 ± 6.45 pre-SSRIs vs 25.07 ± 7.02 post-SSRIs, respectively,P< 0.001).ConclusionDTI is an ideal non-invasive tool for examining white matter integrity and can detect microstructural changes in the dorsolateral prefrontal cortex after rTMS and SSRI therapies for patients with MS and depression. FA increased only with rTMS denoting positive alteration in white matter microstructure. Both rTMS and SSRIs were equally effective in improving depression and cognition.
Biomarker Discovery and Outcomes for Comprehensive Cell-Free Circulating Tumor DNA Versus Standard-of-Care Tissue Testing in Advanced Non–Small-Cell Lung Cancer
Authors: Palmero Ramon , Taus Alvaro , Viteri Santiago , Majem Margarita , Carcereny Enric , Garde-Noguera Javier , Felip Enriqueta , Nadal Ernest , Malfettone Andrea , Sampayo Miguel , Riva François , Nagy Rebecca J. , Lanman Richard B. , Faull Iris , Dix Daniel , Karachaliou Niki , Rosell Rafael 
Published: January 2021

Purpose Treatment guidelines for advanced non–small-cell lung cancer (aNSCLC) recommend broad molecular profiling for targeted therapy selection. This study prospectively assessed comprehensive next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) compared with standard-of-care (SOC) tissue-based testing to identify guideline-recommended alterations in aNSCLC. PATIENTS AND METHODS Patients with treatment-naïve aNSCLC were tested using a well-validated NGS cfDNA panel, and results were compared with SOC tissue testing. The primary objective was noninferiority of cfDNA vs. tissue analysis for the detection of two guideline-recommended biomarkers ( EGFR and ALK) and an additional six actionable biomarkers. Secondary analyses included tissue versus cfDNA biomarker discovery, overall response rate (ORR), progression-free survival (PFS) to targeted therapy, and positive predictive value (PPV) of cfDNA. RESULTS The primary objective was met with cfDNA identifying actionable mutations in 46 patients versus 48 by tissue ( P < .05). In total, 0/186 patients were genotyped for all eight biomarkers with tissue, compared with 90.8% using cfDNA. Targetable alterations or KRAS were identified in 80.7% when cfDNA was used first versus 57.1% when tissue was used first. PPV for cfDNA-detected EGFR was 100.0% (25/25). ORR and PFS in patients receiving targeted therapy based on tissue or cfDNA were similar to those previously reported. Conclusion This prospective study confirms a previous report that comprehensive cfDNA testing is noninferior to SOC tissue testing in detecting aNSCLC-recommended biomarkers. Furthermore, cfDNA-based first-line therapy produced outcomes similar to tissue-based testing, demonstrating the clinical utility of comprehensive cfDNA genotyping as the initial genotyping modality in patients with treatment-naïve aNSCLC when tissue is insufficient or when all actionable biomarkers cannot be rapidly assessed.
Erlotinib and Trametinib in Patients With EGFR-Mutant Lung Adenocarcinoma and Acquired Resistance to a Prior Tyrosine Kinase Inhibitor
Authors: Luo Jia , Makhnin Alex , Tobi Yosef , Ahn Linda , Hayes Sara A. , Iqbal Afsheen , Ng Kenneth , Arcila Maria E. , Riely Gregory J. , Kris Mark G. , Yu Helena A. 
Published: January 2021

PURPOSE Inhibition of the MEK/ERK pathway is critical for Bcl-2-like protein 11 (BIM)-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-induced apoptosis, and dysregulation of this pathway may be a mechanism of acquired resistance. Therefore, MEK inhibition with trametinib and an EGFR TKI may resensitize tumors with acquired resistance. Limited targeted therapies are available after progression on EGFR TKIs, and it is in this setting that we completed a phase I/II study of erlotinib and trametinib. METHODS Patients with metastatic EGFR-mutant lung adenocarcinoma and acquired resistance to an EGFR TKI received combination erlotinib 75 mg and trametinib 1.5 mg daily until progression or unacceptable side effects. The primary objective was objective response rate determined using RECIST version 1.1. RESULTS Twenty-three patients were accrued; patients had received a median of two lines of prior TKI therapy (61% prior osimertinib), and 48% had acquired EGFR T790M. We confirmed one partial response (1/23, 4%, 95% CI, 0 to 22). The median progression-free survival was 1.8 months, and the median overall survival was 21 months. Diarrhea (87%), acneiform rash (87%), and fatigue (52%) were the most common treatment-related adverse events. Two patients who had tumor shrinkage both harbored a BRAF fusion. CONCLUSION Addition of trametinib to erlotinib in the acquired resistance setting in an unselected population is not efficacious. Future studies should focus on targeted therapies in molecularly selected populations. Acquired BRAF fusions in patients with EGFR-sensitizing mutations may be a molecular subset where EGFR and MEK combination therapy could be studied further.
Bisphenol A promotes stress granule assembly and modulates the integrated stress response
Authors: Fay Marta M. , Columbo Daniella , Cotter Cecelia , Friend Chandler , Henry Shawna , Hoppe Megan , Karabelas Paulina , Lamy Corbyn , Lawell Miranda , Monteith Sarah , Noyes Christina , Salerno Paige , Wu Jingyi , Zhang Hedan Mindy , Anderson Paul J. , Kedersha Nancy , Ivanov Pavel , Farny Natalie G. 
Published: January 2021

ABSTRACT
Bisphenol-A (BPA) is a ubiquitous precursor of polycarbonate plastics that is found in the blood and serum of &gt;92% of Americans. While BPA has been well documented to act as a weak estrogen receptor (ER) agonist, its effects on cellular stress are unclear. Here, we demonstrate that high-dose BPA causes stress granules (SGs) in human cells. A common estrogen derivative, β-estradiol, does not trigger SGs, indicating the mechanism of SG induction is not via the ER pathway. We also tested other structurally related environmental contaminants including the common BPA substitutes BPS and BPF, the industrial chemical 4-nonylphenol (4-NP) and structurally related compounds 4-EP and 4-VP, as well as the pesticide 2,4-dichlorophenoxyacetic acid (2,4-D). The variable results from these related compounds suggest that structural homology is not a reliable predictor of the capacity of a compound to cause SGs. Also, we demonstrate that BPA acts primarily through the PERK pathway to generate canonical SGs. Finally, we show that chronic exposure to a low physiologically relevant dose of BPA suppresses SG assembly upon subsequent acute stress. Interestingly, this SG inhibition does not affect phosphorylation of eIF2α or translation inhibition, thus uncoupling the physical assembly of SGs from translational control. Our work identifies additional effects of BPA beyond endocrine disruption that may have consequences for human health.
What determines organ size during development and regeneration?
Authors: Boulan Laura , Léopold Pierre 
Published: January 2021

ABSTRACT
The sizes of living organisms span over 20 orders of magnitude or so. This daunting observation could intimidate researchers aiming to understand the general mechanisms controlling growth. However, recent progress suggests the existence of principles common to organisms as diverse as fruit flies, mice and humans. As we review here, these studies have provided insights into both autonomous and non-autonomous mechanisms controlling organ growth as well as some of the principles underlying growth coordination between organs and across bilaterally symmetrical organisms. This research tackles several aspects of developmental biology and integrates inputs from physics, mathematical modelling and evolutionary biology. Although many open questions remain, this work also helps to shed light on medically related conditions such as tissue and limb regeneration, as well as metabolic homeostasis and cancer.
High spatial resolution mapping of the mucosal proteome of the gills ofCrassostrea virginica: implication in particle processing
Authors: Pales Espinosa Emmanuelle , Allam Bassem 
Published: January 2021

ABSTRACTIn the oyster Crassostrea virginica, the organization of the gill allows bidirectional particle transport where a dorsal gill tract directs particles meant to be ingested while a ventral tract collects particles intended to be rejected as pseudofeces. Previous studies showed that the transport of particles in both tracts is mediated by mucus. Consequently, we hypothesized that the nature and/or the quantity of mucosal proteins present in each tract is likely to be different. Using endoscopy-aided micro-sampling of mucus from each tract followed by multidimensional protein identification technologies, and in situ hybridization, a high spatial resolution mapping of the oyster gill proteome was generated. Results showed the presence in gill mucus of a wide range of molecules involved in non-self recognition and interactions with microbes. Mucus composition was different between the two tracts, with mucus from the ventral tract shown to be rich in mucin-like proteins, providing an explanation of its high viscosity, while mucus from the dorsal tract was found to be enriched in mannose-binding proteins, known to be involved in food particle binding and selection. Overall, this study generated high-resolution proteomes for C. virginica gill mucus and demonstrated that the contrasting functions of the two pathways present on oyster gills are associated with significant differences in their protein makeup.
Transgenic expression of late embryogenesis abundant proteins improves tolerance to water stress in Drosophila melanogaster
Authors: Anderson John M. , Hand Steven C. 
Published: January 2021

ABSTRACT
Four lines of Drosophila melanogaster were created that expressed transgenes encoding selected late embryogenesis abundant (LEA) proteins originally identified in embryos of the anhydrobiote Artemia franciscana. The overall aim was to extend our understanding of the protective properties of LEA proteins documented with isolated cells to a desiccation-sensitive organism during exposure to drying and hyperosmotic stress. Embryos of D. melanogaster were dried at 57% relative humidity to promote a loss of 80% tissue water and then rehydrated. Embryos that expressed AfrLEA2 or AfrLEA3m eclosed 2 days earlier than wild-type embryos or embryos expressing green fluorescent protein (Gal4GFP control). For the third instar larval stage, all Afrlea lines and Gal4GFP controls experienced substantial drops in survivorship as desiccation proceeded. When results for all Afrlea lines were combined, Kaplan–Meier survival curves indicated a significant improvement in survivorship in fly lines expressing AfrLEA proteins compared with Gal4GFP controls. The percent water lost at the LT50 (lethal time for 50% mortality) for the AfrLEA lines was 78% versus 52% for Gal4GFP controls. Finally, offspring of fly lines that expressed AfrLEA2, AfrLEA3m or AfrLEA6 exhibited significantly greater success in reaching pupation, compared with wild-type flies, when adults were challenged with hyperosmotic stress (NaCl-fortified medium) and progeny forced to develop under these conditions. In conclusion, the gain of function studies reported here show that LEA proteins can improve tolerance to water stress in a desiccation-sensitive species that normally lacks these proteins, and, simultaneously, underscore the complexity of desiccation tolerance across multiple life stages in multicellular organisms.
Early-life effects of juvenile Western diet and exercise on adult gut microbiome composition in mice
Authors: McNamara Monica P. , Singleton Jennifer M. , Cadney Marcell D. , Ruegger Paul M. , Borneman James , Garland Theodore 
Published: January 2021

ABSTRACTAlterations to the gut microbiome caused by changes in diet, consumption of antibiotics, etc., can affect host function. Moreover, perturbation of the microbiome during critical developmental periods potentially has long-lasting impacts on hosts. Using four selectively bred high runner and four non-selected control lines of mice, we examined the effects of early-life diet and exercise manipulations on the adult microbiome by sequencing the hypervariable internal transcribed spacer region of the bacterial gut community. Mice from high runner lines run ∼3-fold more on wheels than do controls, and have several other phenotypic differences (e.g. higher food consumption and body temperature) that could alter the microbiome, either acutely or in terms of coevolution. Males from generation 76 were given wheels and/or a Western diet from weaning until sexual maturity at 6 weeks of age, then housed individually without wheels on standard diet until 14 weeks of age, when fecal samples were taken. Juvenile Western diet reduced bacterial richness and diversity after the 8-week washout period (equivalent to ∼6 human years). We also found interactive effects of genetic line type, juvenile diet and/or juvenile exercise on microbiome composition and diversity. Microbial community structure clustered significantly in relation to both line type and diet. Western diet also reduced the relative abundance of Muribaculum intestinale. These results constitute one of the first reports of juvenile diet having long-lasting effects on the adult microbiome after a substantial washout period. Moreover, we found interactive effects of diet with early-life exercise exposure, and a dependence of these effects on genetic background.
The effect of two clinical criteria in the assessment of caries lesions around restorations in children (CARDEC-03): study protocol for a diagnostic randomized clinical trial
Authors: Moro Bruna Lorena Pereira , Signori Cácia , Freitas Raiza Dias , Pontes Laura Regina Antunes , Lenzi Tathiane Larissa , Tedesco Tamara Kerber , Raggio Daniela Prócida , Braga Mariana Minatel , Ekstrand Kim Rud , Cenci Maximiliano Sérgio , Mendes Fausto Medeiros ,   CARDEC collaborative group,   CaCIA collaborative group
Published: January 2021

Introduction: The detection of caries lesions around restoration can be challenging. Therefore, the use of some criteria has been proposed in order to give more objectivity to the diagnosis process. Two of them are the International Dental Federation (FDI) and the Caries Associated with Restorations and Sealants (CARS) criteria. Both methods have a different approach to caries, and it is not possible to know which one of them is the best to use in clinical practice to assess restorations in children. Thus, the present protocol aims to evaluate the effect of the use of the FDI and CARS criteria in the assessment of caries lesions around restorations in primary teeth on outcomes related to oral health in children and costs resulting from the assessments. Methods and analysis: A total of 626 restorations of children from three to 10 years were randomly assessed and are being treated following the FDI criteria (FDI group) or CARS criteria (CARS group). Participants will be followed-up after six, 12, 18, and 24 months. The primary outcome will be the need for a new intervention in the evaluated restorations. This outcome consists of several components, and each of these events will be analyzed separately as secondary outcomes. The changes in children’s oral health-related quality of life and the cost of the restoration dental treatments will also be analyzed as secondary outcomes. The methods will be compared using the Cox regression model with shared frailty. A significance level of 5% will be adopted for all statistical analyses. Discussion: This will be the first randomized clinical study carried out regarding the detection of caries lesions around restorations in primary teeth. Trial registration: The study underwent registration in Clinicaltrials.gov (NCT03520309) on 9 May 2018.
A New Combinatorial Algorithm for Separable Convex Resource Allocation with Nested Bound Constraints
Authors: Wu Zeyang , Nip Kameng , He Qie 
Published: January 2021

The separable convex resource allocation problem with nested bound constraints aims to allocate B units of resources to n activities to minimize a separable convex cost function, with lower and upper bounds on the total amount of resources that can be consumed by nested subsets of activities. We develop a new combinatorial algorithm to solve this model exactly. Our algorithm is capable of solving instances with millions of activities in several minutes. The running time of our algorithm is at most 73% of the running time of the current best algorithm for benchmark instances with three classes of convex objectives. The efficiency of our algorithm derives from a combination of constraint relaxation and divide and conquer based on infeasibility information. In particular, nested bound constraints are relaxed first; if the solution obtained violates some bound constraints, we show that the problem can be divided into two subproblems of the same structure and smaller sizes according to the bound constraint with the largest violation. Summary of Contribution. The resource allocation problem is a collection of optimization models with a wide range of applications in production planning, logistics, portfolio management, telecommunications, statistical surveys, and machine learning. This paper studies the resource allocation model with prescribed lower and upper bounds on the total amount of resources consumed by nested subsets of activities. These nested bound constraints are motivated by storage limits, time-window requirements, and budget constraints in various applications. The model also appears as a subproblem in models for green logistics and machine learning, and it has to be solved repeatedly. The model belongs to the class of computationally challenging convex mixed-integer nonlinear programs. We develop a combinatorial algorithm to solve this model exactly. Our algorithm is faster than the algorithm that currently has the best theoretical complexity in the literature on an extensive set of test instances. The efficiency of our algorithm derives from the combination of an infeasibility-guided divide-and-conquer framework and a scaling-based greedy subroutine for resource allocation with submodular constraints. This paper also showcases the prevalent mismatch between the theoretical worst-case time complexity of an algorithm and its practical efficiency. We have offered some explanations of this mismatch through the perspectives of worst-case analysis, specially designed instances, and statistical metrics of numerical experiments. The implementation of our algorithm is available on an online repository.