bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical evidence for pioglitazone and bexarotene combination in oral cancer chemoprevention
Authors: Rosas Rolando R. , Nachbor Kristine M. , Handley Nathan , Mathison Grant , Wuertz Beverly R. , Ba'th Fadlullah , Ondrey Frank G. 
Published: December 2021

AbstractBackgroundHead and neck squamous cell carcinoma (HNSCC) requires new treatments and targeted approaches to improve survival. The peroxisome proliferator‐activated receptor γ (PPARγ) and retinoic X receptor alpha (RXRα) nuclear receptor pathways may be targetable with repurposed Food and Drug Administration (FDA)‐approved agents for prevention and treatment.MethodsOral cancer and leukoplakia cell lines were treated with the PPARγ agonist (pioglitazone) and RXRα activator (bexarotene). PPARγ activation, cellular proliferation, apoptosis activity and phenotype, including the pharmacodynamic marker, involucrin (IVL), were subsequently analyzed using a reporter gene assay, genomic data, MTT assay and western blot.ResultsMicroarray analysis of HNSCC tumor versus normal tissue shows IVL expression is significantly increased in normal tissue compared to HNSCC tumors (p < 0.0001). In MSK Leuk1 and CA 9‐22 cell lines, pioglitazone increases PPARγ DNA binding activity and IVL promoter activity in a dose dependent manner (p < 0.01 and p < 0.0001). Combination treatment with pioglitazone and bexarotene increases PPARγ DNA binding activity and IVL promoter activity (p < 0.01 and p < 0.0001). MTT analysis shows decreases in cell proliferation when cells are treated with pioglitazone and bexarotene. Decreases in cell proliferation are significant to at least p < 0.05 for all combination versus single agent treatments. Western blot on whole‐cell lysate from cells treated with pioglitazone and bexarotene alone or in combination for IVL showed increased protein levels with combination treatment.ConclusionsTargeting the PPARγ/RXRα heterodimer with pioglitazone and bexarotene was effective in this preclinical project. This was functional in both preneoplastic and oral cancer cell lines. A better understanding of the molecular mechanism on downstream effects on cellular proliferation could potentially have implications clinically, both in oral preneoplasia and possibly head and neck cancer; however, more research needs to be done to explore the potential these medications have in chemoprevention.
Nanofluid influenced convective heat transfer and nanoparticles dispersion in porous media with a two‐phase lattice Boltzmann analysis
Authors: Aliu Oluwaseyi , Sakidin Hamzah , Foroozesh Jalal 
Published: December 2021

AbstractIn this study, a two‐phase lattice Boltzmann model (LBM) is developed and verified to study natural convective heat transfer in a porous medium that is fully saturated with Zn–H2O nanofluid (NF). Zinc, being an environmentally friendly material, is selected as the nanoparticle (NP) here. We aim to analyze NP heat enhancement augmentation and dispersion during NF transport at different Rayleigh number (Ra) values, various porosity (), and varying nanoparticle volume fraction (NVF). The equations of flow (velocity), temperature (energy), and NVF fields in porous media are solved numerically. Physical parameters of Rayleigh number, NVF, and Darcy number (Da) are varied to examine their effects on flow patterns (streamlines), temperature distribution (Isotherms), and NP spread (dispersion). Nusselt number is calculated to elucidate its relationship with Ra, Da, and NVF. Results show that Nusselt number increases upon Ra and Da numbers increment thereby accounting for convective heat transfer augmentation. However, it is noted that at Ra = 105; , the effects of varying NVF are almost the same, thereby suggesting an optimum for positive NP effect. An improved NP dispersion leading to good suspension stability for optimum Zn NP performance is observed with a higher temperature gradient at , compared to , where NP sedimentation is noticed. Likewise, an increase of NVF suggests an increase in Nusselt number until a certain optimum. This study provides deeper insight into NP dynamics and their heat transfer behavior in porous media using LBM.
Angiogenic efficacy of ASC spheroids filtrated on porous nanosheets for the treatment of a diabetic skin ulcer
Authors: Suematsu Yoshitaka , Nagano Hisato , Kiyosawa Tomoharu , Takeoka Shinji , Fujie Toshinori 
Published: December 2021

AbstractStem cell transplantation is expected to be an effective treatment for intractable skin ulcers by promoting angiogenesis; however, it is challenging to quickly realize a sufficient bloodstream for the ulcers. For this treatment, sheet‐like materials with monolayer cells such as cell sheets have been investigated. However, they have a limitation of cell number that can be transplanted at one time due to the two‐dimensional, monolayer cell structure, and sufficient secretion of growth factors cannot be expected. In this regard, cellular aggregates, such as spheroids, can reproduce three‐dimensional cell‐cell interactions that cause biological functions of living tissues more representative than monolayer cells, which is important to achieving efficient secretion of growth factors. In this study, we focused on free‐standing porous polymer ultrathin films (“porous nanosheets”) comprising poly(d,l‐lactic acid) (PDLLA) and succeeded in developing a spheroid‐covered nanosheet, on which more than 1000 spheroids from adipose‐tissue derived stem cells (ASCs) were loaded. The porous structure with an average pore diameter of 4 μm allowed for facile filtration and carrying spheroids on the nanosheet, as well as sufficient oxygen and nutrients inflow to the cells. The spheroid‐covered nanosheet achieved homogeneous transference of spheroids to a whole skin defect in diabetic model mice. Given the continuous release of vascular endothelial growth factor (VEGF) from the spheroids, the transplanted spheroids promoted healing with more accelerated angiogenesis than a nanosheet with a monolayer of cells. The spheroid‐covered nanosheet may be a new regenerative material for promoting intractable skin ulcer healing.
Protein acetylation effects on enzyme activity and metabolic pathway fluxes
Authors: Marín‐Hernández Álvaro , Rodríguez‐Zavala José S. , Jasso‐Chávez Ricardo , Saavedra Emma , Moreno‐Sánchez Rafael 
Published: December 2021

AbstractAcetylation of proteins seems a widespread process found in the three domains of life. Several studies have shown that besides histones, acetylation of lysine residues also occurs in non‐nuclear proteins. Hence, it has been suggested that this covalent modification is a mechanism that might regulate diverse metabolic pathways by modulating enzyme activity, stability, and/or subcellular localization or interaction with other proteins. However, protein acetylation levels seem to have low correlation with modification of enzyme activity and pathway fluxes. In addition, the results obtained with mutant enzymes that presumably mimic acetylation have frequently been over‐interpreted. Moreover, there is a generalized lack of rigorous enzyme kinetic analysis in parallel to acetylation level determinations. The purpose of this review is to analyze the current findings on the impact of acetylation on metabolic enzymes and its repercussion on metabolic pathways function/regulation.
Conditional relative survival among patients with chronic lymphocytic leukaemia: A population‐based study in the Netherlands
Authors: van der Straten Lina , Levin Mark‐David , Visser Otto , Posthuma Eduardus F.M. , Doorduijn Jeanette K. , Kater Arnon P. , Dinmohamed Avinash G. 
Published: December 2021

AbstractStudies on conditional relative survival (CRS) in chronic lymphocytic leukaemia (CLL) have hitherto been lacking in the literature. We predicted up‐to‐date estimates of 5‐year RS at diagnosis and for each additional year survived (i.e., CRS) up to 15 years post‐diagnosis among CLL patients diagnosed during 2007–2020. We showed that 5‐year CRS continues to decline gradually with each additional year survived in a contemporary era with access to novel‐based agents, irrespective of age. This finding indicates that CLL patients continue to experience substantial excess mortality compared to an age‐ and sex‐matched group from the general population.
Follow‐up CT of “reversed halo sign” in SARS‐CoV‐2 delta VOC pneumonia: A report of two cases
Authors: Wu Jing , Tang Jie , Zhang Tao , Chen Yu‐Chen , Du Chao 
Published: December 2021

AbstractIn December 2019, a new type of virus, coronavirus disease 2019 broke out globally and caused great harm. The virus mutates rapidly, and more research reports are urgently needed to increase our understanding of the disease. We found the reversed halo sign (RHS) occurred in the imaging manifestations of severe acute respiratory syndrome coronavirus 2 delta variant of concern pneumonia. In the absence of pathology, the mechanism is unknown. Therefore, we reported two cases of RHS and tried to speculate the pathological mechanism through multiple computed tomography follow‐up comparisons to judge the prognosis of the disease.
Interplay between microbial community composition and chemodiversity of dissolved organic matter throughout the Black Sea water column redox gradient
Authors: Suominen Saara , Gomez‐Saez Gonzalo V. , Dittmar Thorsten , Sinninghe Damsté Jaap S. , Villanueva Laura 
Published: December 2021

AbstractLarge quantities of carbon are stored in marine dissolved organic matter (DOM), and its recycling has a major effect on the carbon cycle. Microbes are responsible for turnover of DOM. Little is known about how the complex pool of DOM shapes microbial communities and vice versa, especially in anoxic systems. In this study, we characterized the DOM pool with high‐resolution Fourier transform ion cyclotron resonance mass spectrometry and analyzed the microbial community composition with 16S rRNA gene amplicon sequencing across a redox gradient in the Black Sea. The chemical stratification of the water column was clearly reflected in the microbial community, with different putative autotrophic taxa abundant across redox zones. The nitrate maximum was characterized by a high abundance of Thaumarchaeota, the suboxic zone by Gammaproteobacteria Chromatiales, while Epsilonbacteraeota Campylobacterales were abundant at the onset of the sulfidic zone. Compared to the variance in the microbial community, the molecular composition of DOM was relatively uniform across the sampled depths. However, underlying differences in the oxidation state of the DOM molecular formulas showed distinct changes that were linked to the redox zones, possibly connecting autotrophic metabolisms to changes in the DOM composition. In addition, known heterotrophs like Planctomycetes Phycisphaerae and Chloroflexi Anaerolineales were linked to more oxidized molecular forms of DOM, and not to the identified redox zones, suggesting that these fermentative organisms are reliant on newly formed carbon molecules. Our study suggests that the metabolism of autotrophic microbes influences the composition of DOM across the Black Sea water column.
Shape‐Memory Semicrystalline Polymeric Materials Based on Various Rubbers
Authors: Akca Ozge , Okay Oguz 
Published: December 2021

AbstractA simple strategy is presented for the fabrication of shape‐memory materials containing commercial rubbers including natural rubber, cis‐polybutadiene, and styrene‐butadiene rubber. Dissolution of the rubbers in n‐octadecyl acrylate (C18A) monomer followed by UV polymerization at 30 °C leads to the formation of interconnected interpenetrating polymer networks (c‐IPNs) possessing crystalline domains. They exhibit melting (Tm) and crystallization temperatures (Tcry) between 45–50 and 35–40 °C, respectively, that can be tuned by the amount and the type of the rubbers. All c‐IPNs exhibit a significant temperature sensitivity in their viscoelastic and mechanical properties when the temperature is changed between below and above Tm and Tcry. The morphology of c‐IPNs consists of amorphous nanoparticles of around 64 nm diameter composed of interconnected noncrystalline poly(C18A) (PC18A) and rubber networks, surrounded by crystalline PC18A segments. c‐IPNs exhibit tunable mechanical properties, for example, their Young's modulus and toughness can be varied between 8.3–73 MPa, and 1.9–23 MJ·m−3, respectively, by changing the amount and type of the rubber. Because of the coexistence of chemical cross‐links and crystalline domains acting as the netpoints and switching segments, respectively, c‐IPNs exhibit an efficient shape‐memory function as demonstrated by their potential application as a robotic gripper.
Semi‐Crystalline Polyetherimide Microparticles via Liquid‐Liquid Phase Separation and Precipitation
Authors: Unger Laura , Dechet Maximilian A. , Fischer Sybille , Schmidt Jochen , Bück Andreas 
Published: December 2021

AbstractA novel approach for production of polyetherimide (PEI) microparticles by liquid–liquid phase separation (LLPS) and precipitation is demonstrated and the effect of the used solvents acetophenone and dimethyl phthalate on the obtained powders is outlined. Interestingly, the method allows one to produce semi‐crystalline particles, while PEI is known to be hard to crystallize and typically obtained in amorphous form. To get a deeper understanding of the phase behavior of the polymer‐solvent systems, cloud point curves in dependence on system composition are determined. The obtained particles are thoroughly characterized. They are highly semi‐crystalline, as proven by DSC and X‐ray diffraction and are an ideal novel feedstock for powder bed fusion of polymers with laser beam (PBF‐LB/P). Polymorphism and, thus, thermal characteristics like the melting point, can be tuned by the used solvent. After heating the precipitated powder samples above their melting temperature and subsequent cooling fully amorphous polymer is obtained, which is assessed to be advantageous with respect to mechanical properties (toughness) of the PBF‐LB/P‐produced component from this novel feedstock.
Evaluation of MR‐neurography in diagnosis and treatment in peripheral nerve surgery of the upper extremity: A matched cohort study
Authors: Boecker Arne Hendrik , Lukhaup Lara , Aman Martin , Bergmeister Konstantin , Schwarz Daniel , Bendszus Martin , Kneser Ulrich , Harhaus Leila 
Published: December 2021

AbstractIntroduction“Watch and wait”‐strategies from 3 to 6 months for peripheral nerve injuries are standard of care in specialized centers. However, this contradiction between delayed decision‐making and the demand for fast reinnervation, especially of the motoric endplate, has not yet been overcome. Therefore, this study aimed to investigate the time‐sparing effects by accelerated decision‐making due to the complementary MR‐neurography application combined with established diagnostics like electroneurography and neurosonography from the first admission to the determination of the treatment plan.Patients and MethodsA retrospective matched‐pair chart review analysis with Supplementary MR‐neurography in the period between 2014 and 2017 was designed. Matching was performed by the parameters of nerve type, localization of the nerve injury, patient age, and treatment of the injury. Twenty‐nine patients were included and matched in the study. MR‐neurography imaging was performed by a 3T magnetic resonance imaging with a sampling perfection with application optimized contrasts using different flip angle evolution short tau inversion recovery sequence for the brachial plexus and gradient echo accurate fast imaging with steady‐state free precession sequence for the upper extremity. Time to decision‐making was investigated for or against a surgical intervention for patients with or without a Supplementary MR‐neurography.ResultsIn general, MR‐neurography accelerated decision‐making for 28 days, with results of 37.5 + 5.4 days with Supplementary MR‐neurography and 65.3 + 9.7 days without Supplementary MR‐neurography (p = .05). Within the first 90 days following trauma, patients with MR‐neurography (38.2 ± 7.7 days) benefit under a significant faster decision‐making (p = .05) than patients without MR‐neurography (79.0 + 14.2 days). After 90 days, no evidence of accelerated decision‐making was found with the addition of MR‐neurography (p = .6). In 10 of the 29 patients, despite additional electroneurography and neurosonography, no decision could be made and the MR‐neurography has been used primarily as a diagnostic tool.ConclusionMR‐neurography has significant time‐sparing effects on the decision‐making for approximately 4 weeks within the first 90 days after the trauma. This may help overcome the paradigm of “watch and wait”‐strategies during the first 3–6 months after the peripheral nerve injury.
Dose kernel decomposition for spot‐based radiotherapy treatment planning
Authors: Chen Mingli , Yang Zi , Wardak Zabi , Stojadinovic Strahinja , Gu Xuejun , Lu Weiguo 
Published: December 2021

AbstractPurposePre‐calculation of accurate dose deposition kernels for treatment planning of spot‐based radiotherapies, such as Gamma Knife (GK) and Gamma Pod (GP), can be very time‐consuming and may require large data storage with an enormous number of possible spots. We proposed a novel kernel decomposition (KD) model to address accurate and fast (real‐time) dose calculation with reduced data storage requirements for spot‐based treatment planning. The application of the KD model was demonstrated for clinical GK and GP radiotherapy platforms.MethodsThe dose deposition kernel at each spot (shot position) is modeled as the product of a shift‐invariant kernel based on a reference kernel and spatially variant scale factor. The reference kernel, one for each collimator, is defined at the center of the commissioning phantom for GK and at the center of the treatment target for GP and calculated using the Monte Carlo (MC) method. The spatially variant scale factor is defined as the ratio of the mean tissue maximum ratio (TMR) at the candidate shot position to that at the reference kernel position, and the mean TMR map is calculated within the entire volume through parallel beam ray tracing on the density image followed by averaging over all source directions. The proposed KD dose calculations were compared with the MC method and with the GK and GP treatment planning system (TPS) computations for various shot positions and collimator sizes utilizing a phantom and 14 and 12 clinical plans for GK and GP, respectively.ResultsFor the phantom study, the KD Gamma index (3%/1 mm) passing rates were greater than 99% (median 100%) relative to the MC doses, except for the shots close to the boundary. The passing rates dropped below 90% for 8 mm (16 mm) shots positioned within ∼1 cm (∼2 cm) of the boundary. For the clinical GK plans, the KD Gamma passing rates were greater than 99% (median 100%) compared to the MC and greater than 92% (median 99%) compared to the TPS. For the clinical GP plans, the KD Gamma passing rates were greater than 95% (median 98%) compared to the MC and greater than 91% (median 97%) compared to the TPS. The scale factors were calculated in sub‐seconds with GPU implementation and only need to be calculated once before treatment plan optimization. The calculation of the dose kernel was also within sub‐seconds without requiring beam‐by‐beam calculation commonly done in the TPS.ConclusionThe proposed model can provide an accurate dose and enables real‐time dose and derivative calculations by kernel shifting and scaling without pre‐calculating or requiring large data storage for GK and GP dose deposition kernels during treatment planning. This model could be useful for spot‐based radiotherapy treatment planning by allowing an efficient global fine search for optimal spots.
Body composition and cardiometabolic health across the menopause transition
Authors: Marlatt Kara L. , Pitynski‐Miller Dori R. , Gavin Kathleen M. , Moreau Kerrie L. , Melanson Edward L. , Santoro Nanette , Kohrt Wendy M. 
Published: December 2021

AbstractEvery year, 2 million women reach menopause in the United States, and they may spend 40% or more of their life in a postmenopausal state. In the years immediately preceding menopause—known as the menopause transition (or perimenopause)—changes in hormones and body composition increase a woman’s overall cardiometabolic risk. In this narrative review, we summarize the changes in weight, body composition, and body fat distribution, as well as the changes in energy intake, energy expenditure, and other cardiometabolic risk factors (lipid profile, glucose metabolism, sleep health, and vascular function), that occur during the menopause transition. We also discuss the benefits of lifestyle interventions in women in the earlier stages of menopause before these detrimental changes occur. Finally, we discuss how to include perimenopausal women in research studies so that women across the life‐span are adequately represented.image
Randomized controlled trial of financial incentives during weight‐loss induction and maintenance in online group weight control
Authors: West Delia S. , Krukowski Rebecca A. , Monroe Courtney M. , Stansbury Melissa L. , Carpenter Chelsea A. , Finkelstein Eric A. , Naud Shelly , Ogden Doris , Harvey Jean R. 
Published: December 2021

AbstractObjectiveThis study examined the impact of a financial incentive scheme integrating process and outcome incentives across weight‐loss induction and weight maintenance on 18‐month weight outcomes.MethodsThis was a randomized controlled trial. Participants with overweight or obesity (n = 418; 91% female; 28% racial/ethnic minority) were randomized to an 18‐month, online, group‐based behavioral weight‐control program (Internet‐Only) or the same program with financial incentives provided for 12 months, contingent on self‐regulatory weight‐control behaviors (self‐weighing, dietary self‐monitoring, and physical activity) and weight‐outcome benchmarks (Internet+Incentives). No financial incentives were provided from Months 13 to 18 to examine the durability of weight‐control behaviors and outcomes without incentives.ResultsWeight‐loss induction at Month 6 was significantly greater for Internet+Incentives than Internet‐Only (6.8% vs. 4.9%, respectively, p = 0.01). Individuals receiving incentives were significantly more likely to maintain weight loss ≥ 5% at Month 12 (45% in Internet+Incentives vs. 32% in Internet‐Only, p < 0.02) and remain weight stable (39% vs. 27%, respectively, p < 0.01). Internet+Incentives participants also reported significantly greater behavioral engagement through Month 12. However, once incentives ceased, there were no differences in sustained weight outcomes (Month 18), and engagement declined dramatically.ConclusionsDespite promoting greater treatment engagement and initial weight loss, financial incentives as offered in this study did not promote better extended weight control.