bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis and Evaluation of the Effects of Melatonin on Oral Keratinocytes: A Pilot Study
Authors: Tufteland Megan , Lenon Allison Jae , Carlile Spencer , Kingsley Karl 
Published: June 2022

Objective: Twenty to 30 percent of children in cross-sectional studies have significant bedtime problems or night waking. Melatonin, a synthetic form of the hormone produced by the pineal gland as a biomarker of the circadian system, is a commonly used nonprescription pharmacologic treatment for sleep disorders in children. Many studies have demonstrated the effect of melatonin supplementation on sleep duration and sleep quality, which can improve overall systemic health and disease prevention. However, despite the growing number of studies demonstrating the effects of melatonin to improve disordered sleep, no available studies have evaluated the effects of melatonin on normal oral tissues. Based upon this lack of knowledge, the primary objective of this study is to evaluate any potential effects of melatonin on normal oral cells and tissues within the physiologically relevant (supplementation) range.
Methods: Normal oral keratinocytes (OKF4) and human gingival fibroblasts (HGF-1) were obtained and cultured for this study. Melatonin was administered in 96-well growth assays at supplement-equivalent physiologic concentrations at the low, mid and high range (1, 5 and 10 ug/uL) to determine any effects on cellular growth and proliferation. Changes in cellular viability and expression of cell cycle and apoptosis-related pathways were also evaluated.
Results: Curvilinear U-shaped dose responses were observed in OKF cells under melatonin administration, ranging from -11.4% (low), to a maximum of -13.6% (mid) and -5.0% (high) compared with non-treated controls, p=0.029. Dose-responses among HGF-1 cells ranged from +12.1% (low), +17.4% (mid), and +5.0% (high), p=0.021. No changes in cellular viability were observed between control and experimental cells. However, qPCR screening of total RNA revealed significant changes in cell cycle related pathways, including c-myc, GAPDH and P53 but no changes in any apoptosis-related pathways, including Bcl-2, Bax, caspase-3, caspase-8 and caspase-9.
Conclusions: This study demonstrated that melatonin does affect growth but not viability among these cell lines, which was found to be dose-dependent. These results suggest that melatonin may have some limited effects on oral tissues that may influence wound healing and repair but may not affect normal physiologic function or other cellular pathways. In agreement with other pediatric literature supporting the safety of melatonin use, this pilot study does not reveal any deleterious effects that would caution against its use in children or adults.
Extraction of Lepidium sativum Seed Mucilage: Optimization of Extraction Process with Maximum Yield by using Full Factorial Design
Authors: Mahapatra Abikesh Prasada Kumar , Murthy P. N. , Panda Niranjan , Gupta Amit , Paul Basudev , Malla Suryanaryan , Panigrahy Subodhkant 
Published: June 2022

Objective: The present investigation helps to isolate the seed mucilage of Lepidium sativum by using an economic extraction process with utmost yield. Diligence effort was given to get the maximum yield of the mucilage with good flow properties without affecting the intrinsic properties of the extracted mucilage. The yield of the seed mucilage of Lepidium sativum was optimized by using a quality by design approach. The full factorial design was used using three variables (pH of extract, water to seed ratio, and drying temperature) at two levels (high and low). Overall, ten formulation trials were generated through statistical software Minitab placing 2 center points, 1 replicate, and 1 block. All trials were executed to evaluate the percentage yield.
Results: The extraction process was evaluated with different solvents (such as ethanol and acetone) and different techniques to monitor the yield of the process. The maximum yield was achieved by soaking Lepidium sativum seeds in water (1:30 ratio), maintaining an alkaline pH, blending by hand blender, and using acetone as a solvent. A factorial design was used to observe the responses like the yield of the isolated mucilage for different levels of all the independent variables. A polynomial equation was developed and model plots (contour plot and Pareto chart) were generated to study the impact of the critical variables on the response yield. ANOVA analysis of the model suggested that the independent variables had significantly affected (p < 0.05) in predicting the response (% yield) and the coefficient terms with a p-value less than 0.05 had a significant effect on the prediction efficacy of the model. Finally, the optimized parameter was established based on statistical evaluation obtained from the polynomial equation as well as the recommendation obtained from the response optimizer. The study indicates that the obtained linear regression equation has a linear relation with a regression coefficient of 0.9869 % for response % yield.
Conclusion: A cost-effective extraction and isolation process was established to extract the seed mucilage of Lepidium sativum with maximum yield. The isolated mucilage was evaluated for flow properties and demonstrated that it is having good flow properties and can be used as an excipient or adjuvant in different pharmaceuticals and food industries. The applicability of factorial design was well demonstrated to optimize the yield by optimizing the critical factors.
Outcomes and Predictors of Non-Responsiveness in Treatment of Naïve and Non-Cirrhotic Patients with HCV Genotype 3 Infection – A Third World Perspective
Authors: Mehboob Saima , Mohammad Noor , Abbas Amer , Danish Syed Hassan 
Published: June 2022

Objective: To assess the clinical outcome in treatment naïve and non-cirrhotic patients with HCV genotype 3 infection after treatment with Sofosbuvir with declastasvir and valpatasvir (in case of non-responsiveness).
Methods: Study included 263 participants. The inclusion criteria were HCV genotype 3 infection confirmed through PCR, age above 18 years, treatment naïve and non-cirrhotic. HCV PCR below the threshold of quantification at 12th week of treatment was defined as SVR12 (sustained virological response). The patients were started on a fixed dose generic combination of declastasvir 60 mg and Sofosbuvir 400 mg and PCR was performed at 12, 24 and 48 weeks. PCR positive patients at 24 weeks were given valpatasvir with Sofosbuvir.
Results: There were 162 males and 101 females. PCR performed at 12 weeks showed that 251 patients (95.4%) became PCR negative and 12 (4.56%) remained positive. Repeat PCR of these 12 patients started on valpatasvir and Sofosbuvir at 48 weekswas negative. The treatment was well tolerated by all.Probability of positive HCV PCR at 12 weeks decreases by 0.73 with one unit increase in the hemoglobin, whereas one unit increase in TLC reduces the probability of HCV PCR at 12 weeks, positive by 0.001.
Conclusion: The combination of Sofosbuvir and declastasvir is a cheap and effective treatment strategy for treatment naïve and non-cirrhotic HCV genotype 3 infections. Those not responding will achieve PCR negativity with a 6 month therapy of Sofosbuvir and valpatasvir combination. A high hemoglobin level and high total leucocyte count are predictors of good treatment response.
Combining dense elements with attention mechanisms for 3D radiotherapy dose prediction on head and neck cancers
Authors: Cros Samuel , Bouttier Hugo , Nguyen‐Tan Phuc Felix , Vorontsov Eugene , Kadoury Samuel 
Published: June 2022

AbstractPurposeExternal radiation therapy planning is a highly complex and tedious process as it involves treating large target volumes, prescribing several levels of doses, as well as avoiding irradiating critical structures such as organs at risk close to the tumor target. This requires highly trained dosimetrists and physicists to generate a personalized plan and adapt it as treatment evolves, thus affecting the overall tumor control and patient outcomes. Our aim is to achieve accurate dose predictions for head and neck (H&N) cancer patients on a challenging in‐house dataset that reflects realistic variability and to further compare and validate the method on a public dataset.MethodsWe propose a three‐dimensional (3D) deep neural network that combines a hierarchically dense architecture with an attention U‐net (HDA U‐net). We investigate a domain knowledge objective, incorporating a weighted mean squared error (MSE) with a dose‐volume histogram (DVH) loss function. The proposed HDA U‐net using the MSE‐DVH loss function is compared with two state‐of‐the‐art U‐net variants on two radiotherapy datasets of H&N cases. These include reference dose plans, computed tomography (CT) information, organs at risk (OARs), and planning target volume (PTV) delineations. All models were evaluated using coverage, homogeneity, and conformity metrics as well as mean dose error and DVH curves.ResultsOverall, the proposed architecture outperformed the comparative state‐of‐the‐art methods, reaching 0.95 (0.98) on D95 coverage, 1.06 (1.07) on the maximum dose value, 0.10 (0.08) on homogeneity, 0.53 (0.79) on conformity index, and attaining the lowest mean dose error on PTVs of 1.7% (1.4%) for the in‐house (public) dataset. The improvements are statistically significant () for the homogeneity and maximum dose value compared with the closest baseline. All models offer a near real‐time prediction, measured between 0.43 and 0.88 s per volume.ConclusionThe proposed method achieved similar performance on both realistic in‐house data and public data compared to the attention U‐net with a DVH loss, and outperformed other methods such as HD U‐net and HDA U‐net with standard MSE losses. The use of the DVH objective for training showed consistent improvements to the baselines on most metrics, supporting its added benefit in H&N cancer cases. The quick prediction time of the proposed method allows for real‐time applications, providing physicians a method to generate an objective end goal for the dosimetrist to use as reference for planning. This could considerably reduce the number of iterations between the two expert physicians thus reducing the overall treatment planning time.
Adaptive estimation of external fields in reproducing kernel Hilbert spaces
Authors: Guo Jia , Kepler Michael E. , Tej Paruchuri Sai , Wang Hoaran , Kurdila Andrew J. , Stilwell Daniel J. 
Published: June 2022

SummaryThis article studies the distributed parameter system that governs adaptive estimation by mobile sensor networks of external fields in a reproducing kernel Hilbert space (RKHS). The article begins with the derivation of conditions that guarantee the well‐posedness of the ideal, infinite dimensional governing equations of evolution for the centralized estimation scheme. Subsequently, convergence of finite dimensional approximations is studied. Rates of convergence in all formulations are established using history‐dependent bases defined from translates of the RKHS kernel that are centered at sample points along the agent trajectories. Sufficient conditions are derived that ensure that the finite dimensional approximations of the ideal estimator equations converge at a rate that is bounded by the fill distance of samples in the agents' assigned subdomains. The article concludes with examples of simulations and experiments that illustrate the qualitative performance of the introduced algorithms.
Deregulation of ceRNA Networks in Frontal Cortex and Choroid Plexus of Brain during SARS‐CoV‐2 Infection Aggravates Neurological Manifestations: An Insight from Bulk and Single‐Cell Transcriptomic Analyses
Authors: Das Deepyaman , Podder Soumita 
Published: June 2022

AbstractAlthough transcriptomic studies of SARS‐CoV‐2‐infected brains have depicted variability in gene expression, the landscape of deregulated cell‐specific regulatory circuits has not been elucidated yet. Hence, bulk and single‐cell RNA‐seq data are analyzed to gain detailed insights. Initially, two ceRNA networks with 19 and 3 differentially expressed (DE) hub lncRNAs are reconstructed in SARS‐CoV‐2 infected Frontal Cortex (FC) and Choroid Plexus (CP), respectively. Functional and pathway enrichment analyses of downstream mRNAs of deregulated ceRNA axes demonstrate impairment of neurological processes. Mapping of hub lncRNA‐mRNA pairs from bulk RNA‐seq with snRNA‐seq data has indicated that NORAD, NEAT1, and STXBP5‐AS1 are downregulated across 4, 4, and 2 FC cell types, respectively. At the same time, MIRLET7BHG and MALAT1 are upregulated in excitatory neurons of FC and neurons of CP, respectively. Here, it is hypothesized that downregulation of NORAD, NEAT1, and STXBP5‐AS1, and upregulation of MIRLET7BHG and MALAT1 might deregulate respectively 51, 6, and 37, and 31 and 19 mRNAs in cell types of FC and CP. Afterward, 13 therapeutic miRNAs are traced that might safeguard against deregulated lncRNA‐mRNA pairs of NORAD, NEAT1, and MIRLET7BHG in FC. This study helps to explain the plausible mechanism of post‐COVID neurological manifestation and also to devise therapeutics against it.
Stem Cell‐Based Models for Studying the Effects of Cancer and Cancer Therapies on the Peripheral Nervous System
Authors: Richter Mikayla N. , Fattahi Faranak 
Published: June 2022

AbstractIn recent years, the complexity of cancer and cancer therapies and their interactions with the peripheral nervous system have come into focus, but limitations in experimental models have remained a significant challenge in the field. As evidence, there are currently no therapies approved that target cancer–peripheral nervous system or cancer therapy–peripheral nervous system interactions as an anti‐neoplastic or anti‐neurotoxic agent, respectively. Human pluripotent stem cells offer an appealing model system that, unlike rodent models, is compatible with high throughput, high content applications; techniques that reflect modern drug discovery methodologies. Thus, utilizing the key advantages of stem cell‐based models in tandem with the strengths of traditional animal models offers a complementary and interdisciplinary strategy to advance cancer and cancer therapy‐peripheral nervous system research and drug discovery. In this review, the current status of the cancer‐peripheral nervous system and cancer therapy‐peripheral nervous system research is discussed, examples where stem cell‐based models have been implemented are described, and avenues where stem cell‐based models may further advance the field are proposed.
Photo‐Crosslinked Antimicrobial Hydrogel Exhibiting Wound Healing Ability and Curing Infections In Vivo
Authors: Dey Rajib , Mukherjee Riya , Haldar Jayanta 
Published: June 2022

AbstractWith the increasing focus on healthcare research in the current times, therapeutic and biomaterial interventions for healing of wounds and mitigation of wound‐associated infections have seen expedited progress. Conventional approaches consist of release‐active gels, which demonstrate leaching of antimicrobials, such as antibiotics, metal ions, etc. However, these systems suffer from the disadvantages of burst release, reservoir exhaustion, and associated toxicity. In this report, intrinsically antimicrobial hydrogel (HyDex) is developed by one‐pot UV crosslinking of methacrylated dextran, polyethylene glycol diacrylate, and cationic lipophilic methacrylate with varied hydrophobic chain, which displays broad‐spectrum antimicrobial activity, hemostatic ability, and rapid wound closure efficacy. The optimized hydrogel exhibits potent antimicrobial efficacy against multidrug‐resistant Gram‐positive and Gram‐negative bacteria as well as against pathogenic fungus Candida albicans. The HyDex hydrogel shows rapid arrest of bleeding in mice liver puncture model. The hydrogel kills carbapenem‐resistant Acinetobacter baumannii in a murine model of burn wound infection with >99% reduction in bacterial burden. Furthermore, this hydrogel displays significant reduction in inflammatory responses, with accelerated wound healing in rat deep wound model. Collectively, these results imply the excellent promise held by lead hydrogel to be developed for tackling deep tissue wounds, notorious infections, and resulting inflammatory responses.
Liquid Metal/Wood Anisotropic Conductors for Flexible and Recyclable Electronics
Authors: Wang Tiansheng , Liu Sanhu , Hu Yuanyuan , Xu Zhiwu , Hu Shunyou , Li Guoqiang , Xu Jie , Wang Mi , Zhang Jiaheng , Yu Wen , Ma Xing 
Published: June 2022

AbstractNext‐generation electronics requiring high performance, recyclability, and low environmental impact are still in its infancy because of limited design strategies and materials. Herein, a facile approach for constructing liquid metal/wood anisotropic (LMWA) conductors via integration of gallium based LMs and delignified flexible wood (DF‐wood) is reported. Using a delignification treatment and a subsequent LM transfer process with patterns, a rigid and electrically insulating wood slice is converted into a flexible wood‐based LM conductor while retaining its original hierarchical porous structure. The LMWA conductor demonstrates a remarkable anisotropic electrical conductivity (σz/σx) on the order of 108. Subsequently, the LMWA conductors are successfully applied as flexible four‐channel tactile sensor, which exhibits excellent tactile sensitivity. Moreover, by immersing in a deep eutectic solvent (DES) composed of choline chloride with oxalic acid to dissolve the LM circuit, recycling of the LM is achieved with efficiency up to 96%. This is the first time that a DES is used to recycle LM, leading to increased economic and environmental viability of these sustainable electronics. The present LMWA conductors, which have the potential for a scalable and feasible fabrication process, substantially extend the scope of next‐generation electronics toward flexible and recyclable systems.
Dynamic Interference Colors in Electrospun Microfibrous Mats
Authors: Thum Matthew D. , Kołacz Jakub , Ratchford Daniel C. , Camarella Gerald , Maza William , Lundin Jeffrey G. 
Published: June 2022

AbstractThe design of soft materials that change their optical properties in response to a variety of external stimuli is one step toward mimicking the dynamic color changing systems that are observed in nature. A simple, multiresponsive system is presented where the colors of core/sheath microfibers and microfibrous mats can be tuned by confinement (i.e., fiber diameter), temperature, and UV–vis irradiation. Microfibers are fabricated using coaxial electrospinning with a nematic liquid crystal core and a polymer sheath. This results in soft, flexible mats of material that display uniform color when viewed between crossed‐polarizers both under a microscope and by the naked eye. The observed interference color is dictated by the inner fiber diameter and the birefringence of the liquid crystal core. While the fiber diameter is set during mat fabrication, continuous in situ color change by tuning the birefringence of the liquid crystal is demonstrated using temperature or photochemical control of azobenzene‐based surfactants embedded in the polymer sheath. The expected colors are calculated and easy‐to‐use color charts are generated to accurately predict fiber behavior.
Synthesis of (Hetero)Aroyl Fluorides via a Mild Amides C−N Bond Cleavage
Authors: Aliyu Idris Muhammad , Song Kwang Ho , Lee Sunwoo 
Published: June 2022

AbstractAmides, such as N‐benzoylsaccharin, N,N‐diBocbenzamide, and N‐phenyl‐N‐tosylbenzamides reacted with Et3N⋅3HF to provide the corresponding acyl fluorides in good yields. The reaction was conducted under environmentally friendly conditions using i‐PrOAc as the solvent. Moreover, the reaction was performed at room temperature and did not require a transition‐metal catalyst or additives. The methodology showed functional group tolerance toward amines, alkoxy, halides, ketones, esters, and aldehydes.magnified image
Conscription of Immune Cells by Light‐Activatable Silencing NK‐Derived Exosome (LASNEO) for Synergetic Tumor Eradication
Authors: Zhang Mengjie , Shao Wanxuan , Yang Tongren , Liu Houli , Guo Shuai , Zhao Deyao , Weng Yuhua , Liang Xing‐Jie , Huang Yuanyu 
Published: June 2022

AbstractExosomes derived from natural killer (NK) cells (NEO) constitute promising antineoplastic nano‐biologics because of their versatile functions in immune regulation. However, a significant augment of their immunomodulatory capability is an essential need to achieve clinically meaningful treatment outcomes. Light‐activatable silencing NK‐derived exosomes (LASNEO) are orchestrated by engineering the NEO with hydrophilic small interfering RNA (siRNA) and hydrophobic photosensitizer Ce6. Profiling of genes involved in apoptosis pathway with Western blot and RNA‐seq in cells receiving NEO treatment reveals that NEO elicits effective NK cell‐like cytotoxicity toward tumor cells. Meanwhile, reactive oxygen species (ROS) generation upon laser irradiation not only triggers substantial photodynamic therapy effect but also boosts M1 tumor‐associated macrophages polarization and DC maturation in the tumor microenvironment (TME). In addition, ROS also accelerates the cellular entry and endosomal escape of siRNA in TME. Finally, siRNAs targeting PLK1 or PD‐L1 induce robust gene silencing in cancer cells, and downregulation of PD‐L1 restores the immunological surveillance of T cells in TME. Therefore, the proposed LASNEO exhibit excellent antitumor effects by conscripting multiple types of immune cells. Considering that its manufacture is quite simple and controllable, LASNEO show compelling potential for clinical translational application.
Spin‐Decoupled Transflective Spatial Light Modulations Enabled by a Piecewise‐Twisted Anisotropic Monolayer
Authors: Yuan Rui , Xu Chun‐Ting , Cao Han , Zhang Yi‐Heng , Wang Guang‐Yao , Chen Peng , Lu Yan‐Qing , Hu Wei 
Published: June 2022

AbstractWavefront control lies at the heart of modern optics. Metasurfaces with specifically tailored resonators can encode different phases to two orthogonal polarization components, but suffer from wavelength‐dependent efficiency, sophisticated fabrication, and limited size. Liquid crystals, another excellent candidate for planar optics, are restricted to spin‐coupled conjugated phase modulations. Planar optics with spin‐decoupled functions is expected to release the multifunctionality of modern optics. Here, a spin‐decoupled transflective spatial light modulator is presented with a piecewise‐twisted anisotropic monolayer. The phases of reflected and transmitted light can be independently customized by preprogramming the initial orientations of the periodic helix and mirror‐symmetric dual‐twist configuration, respectively. A transflective orbital angular momentum encoder and decoder is demonstrated, which is simultaneously compatible with different multiplexing techniques. This work releases the multifunctionality of advanced planar optics and may upgrade existing devices in optical informatics.