bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orally Administered DHA‐Enriched Phospholipids and DHA‐Enriched Triglyceride Relieve Oxidative Stress, Improve Intestinal Barrier, Modulate Inflammatory Cytokine and Gut Microbiota, and Meliorate Inflammatory Responses in the Brain in Dextran Sodium Sulfate Induced Colitis in Mice
Authors: Che Hongxia , Li Hongyan , Song Lin , Dong Xiufang , Yang Xihong , Zhang Tiantian , Wang Yuming , Xie Wancui 
Published: May 2021

ScopeStudies based on DHA/EPA supplementation in animal models of inflammatory bowel disease (IBD) reveal controversial results. It is speculated that different forms of DHA may explain the controversial results. Therefore, the effects of DHA‐enriched phospholipids (DHA‐PL) and DHA‐enriched triglyceride (DHA‐TG) on IBD are compared.Methods and resultsMale C57BL6/J mice are given DHA‐PL and DHA‐TG for 14 consecutive days, and receive ad libitum a 3.0% dextran sodium sulfate solution on the eighth day to establish IBD model. The results show that both DHA‐PL and DHA‐TG can reverse the colitis pathological process by decreasing the disease activity indexes (DAI), raising the colon length, suppressing the intestinal permeability, suppressing the oxidative stress, down‐regulating pro‐inflammatory factors, up‐regulating anti‐inflammatory factor in colon tissues. DHA‐PL and DHA‐TG also regulate the composition of gut microbiota via decreasing of the abundance Bacteroidetes and Firmicutes, and DHA‐TG increases the abundance of Odoribacter. Importantly, DHA‐PL and DHA‐TG obviously attenuate the activation of microglia.ConclusionsDHA‐PL shows outstanding advantages in regulating oxidative stress, inflammatory responses, and intestinal barrier permeability. The current research indicates that the existence of DHA affects the improvement, DHA in phospholipid form could be a more effective choice for nutritional intervention to prevent and treat colitis.
Generation and analysis of Prss28 and Prss29 deficient mice using CRISPR‐Cas9 genome‐editing
Authors: Dhakal Pramod , Spencer Thomas E. 
Published: May 2021

AbstractGlands of the uterus are essential for the establishment of pregnancy in mice and their products regulate embryo implantation and stromal cell decidualization critical for pregnancy establishment. Forkhead box A2 (FOXA2) is expressed specifically in the glands and a critical regulator of their differentiation, development and function. Progesterone and FOXA2 regulate members of a serine proteinase gene family (Prss28 and Prss29). Here, CRISPR‐Cas9 genome‐editing was used to create mice with a heterozygous or homozygous deletion of Prss28 or/and Prss29 to determine their biological roles in uterine function. Female mice lacking Prss28 and Prss29 or both developed normally and were fertile without alterations in uterine histoarchitecture, uterine gland number, or and gene expression. Thus, Prss28 and Prss29 are dispensable for female fertility and do not impact endometrial gland development or uterine function mice.
Voluntary and magnetically evoked muscle contraction protocol in males with Duchenne muscular dystrophy: Safety, feasibility, reliability, and validity
Authors: Trost Joyceann P. , Chen Mo , Stark Molly M. , Hodges James S. , Richter Sara , Lindsay Angus , Warren Gordon L. , Lowe Dawn A. , Kimberley Teresa J. 
Published: May 2021

AbstractIntroduction/AimsClinical trials addressing treatments for Duchenne muscular dystrophy (DMD) require reliable and valid measurement of muscle contractile function across all disease severity levels. In this work we aimed to evaluate a protocol combining voluntary and evoked contractions to measure strength and excitability of wrist extensor muscles for safety, feasibility, reliability, and discriminant validity between males with DMD and controls.MethodsWrist extensor muscle strength and excitability were assessed in males with DMD (N = 10; mean ± standard deviation: 15.4 ± 5.9 years of age), using the Brooke Upper Extremity Rating Scale (scored 1‐6), and age‐matched healthy male controls (N = 15; 15.5 ± 5.0 years of age). Torque and electromyographic (EMG) measurements were analyzed under maximum voluntary and stimulated conditions at two visits.ResultsA protocol of multiple maximal voluntary contractions (MVCs) and evoked twitch contractions was feasible and safe, with 96% of the participants completing the protocol and having a less than 7% strength decrement on either measure for both DMD patients and controls (P ≥ .074). Reliability was excellent for voluntary and evoked measurements of torque and EMG (intraclass correlation coefficient [ICC] over 0.90 and over 0.85 within and between visits, respectively). Torque, EMG, and timing of twitch‐onset measurements discriminated between DMD and controls (P < .001). Twitch contraction time did not differ significantly between groups (P = .10).DiscussionFindings from this study show that the protocol is a safe, feasible, reliable, and a valid method to measure strength and excitability of wrist extensors in males with DMD.
First-in-Human Phase I Study of Envafolimab, a Novel Subcutaneous Single-Domain Anti-PD-L1 Antibody, in Patients with Advanced Solid Tumors
Authors: Papadopoulos Kyriakos P. , Harb Wael , Peer Cody J. , Hua Qiong , Xu Siying , Lu Haolan , Lu Ni , He Yue , Xu Ting , Dong Ruiping , Gong John , Liu David 
Published: May 2021

Abstract

Lessons Learned
Subcutaneous injection was an effective route of administration for envafolimab with a favorable pharmacokinetic profile in patients with previously treated advanced solid tumors. Subcutaneous envafolimab was well tolerated and had durable antitumor activity at a wide range of doses and schedules. Envafolimab has the potential to be a more convenient option than currently approved intravenous PD-1/PD-L1 inhibitors.

Background
Envafolimab is a novel fusion of a humanized single-domain PD-L1 antibody and human IgG1 Fc fragment formulated for subcutaneous injection. This study explored the safety and feasibility of subcutaneous administration of envafolimab as an alternative to intravenous administration of PD-1/PD-L1 inhibitors in the treatment of advanced, refractory solid tumors.

Methods
This was a first-in-human, open-label phase I trial. In a dose-escalation phase, patients received subcutaneous envafolimab 0.01–10 mg/kg once weekly following a modified 3+3 design. In a dose-exploration phase, patients received subcutaneous envafolimab 300 mg once every 4 weeks.

Results
Twenty-eight patients were enrolled (dose escalation n = 18, dose exploration n = 10, median age 66 years; 71% male; ECOG performance score = 0 [21%] or 1 [79%]). No dose-limiting toxicities or injection-site reactions were reported. Envafolimab demonstrated dose-proportional increases in area under the time-concentration curve and maximum plasma concentration. Median time to maximum plasma concentration was 4–7 days. In the dose-exploration phase, terminal half-life was 14 days after dose 1 in cycle 1 and 23 days at steady state. Three patients experienced a confirmed partial response.

Conclusion
Subcutaneous envafolimab had a favorable safety and pharmacokinetic profile, with promising preliminary antitumor activity in patients with advanced solid tumors.
Overview and recent developments in cell‐based noninvasive prenatal testing
Authors: Vossaert Liesbeth , Chakchouk Imen , Zemet Roni , Van den Veyver Ignatia B. 
Published: May 2021

AbstractInvestigators have long been interested in the natural phenomenon of fetal and placental cell trafficking into the maternal circulation. The scarcity of these circulating cells makes their detection and isolation technically challenging. However, as a DNA source of fetal origin not mixed with maternal DNA, they have the potential of considerable benefit over circulating cell‐free DNA‐based noninvasive prenatal genetic testing (NIPT). Endocervical trophoblasts, which are less rare but more challenging to recover are also being investigated as an approach for cell‐based NIPT. We review published studies from around the world describing both forms of cell‐based NIPT and highlight the different approaches’ advantages and drawbacks. We also offer guidance for developing a sound cell‐based NIPT protocol.
Modelling picosecond and nanosecond laser ablation for prediction of induced damage on textured SiNx/Si surfaces of Si solar cells
Authors: Shen Xiaowei , Hsiao Pei‐Chieh , Wang Zhimeng , Liu Mengdi , Phua Benjamin , Song Ning , Stokes Alex , Lennon Alison 
Published: May 2021

AbstractThis study investigated the laser‐induced damage arising from 266 and 532 nm laser ablation of SiNx films on alkaline textured Si surfaces with nanosecond and picosecond pulse durations using a combination of optical‐thermal simulations and measurements of carrier recombination current density. Simulations predict that the melting depth is limited to within 150 nm of the SiNx/Si surface after 266 nm ps laser irradiation due to the greater absorption in both the SiNx and Si resulting in more direct ablation, while temperatures exceeding the melting temperature of Si are predicted to extend up to 1000 nm into the Si substrate with 532 nm ps pulses leading primarily to spallation. Ablation of the SiNx by 266 nm ps irradiation is predicted to be more homogeneous on smaller sized pyramids due to the increased absorption of double‐bounce reflected light on the pyramid faces. This finding has implications for applications requiring uniform ablation of dielectrics on textured Si surfaces. Ablation of SiNx by the longer wavelength 532 nm ps pulses also increases carrier recombination compared to that incurred with 266 nm ps pulses due to the increased melting depth. Longer ns pulses result in less steep temperature gradients and, for 266 nm pulses, an increased melting depth compared to ps pulses. Consequently, shorter ps UV pulses are preferred for SiNx ablation on Si surfaces due to their reduced laser damage penetration, whereas the less steep temperature gradients resulting from ns 532 nm pulses are beneficial for laser doping to form selective emitters.
Sleep in children with cystic fibrosis: More under the covers
Authors: Reiter Joel , Breuer Oded , Cohen‐Cymberknoh Malena , Forno Erick , Gileles‐Hillel Alex 
Published: May 2021

AbstractCystic fibrosis (CF) is a chronic multisystem disease with manifestations from birth. It involves the entire respiratory system, with increased cough, and recurrent pulmonary infections, and it also leads to intestinal malabsorption, all of which can have an impact on sleep. In this review, we summarize the available literature on the various sleep disturbances in children with CF. Sleep quality and sleep efficiency are often impaired in children with CF. They may be accompanied by symptoms associated with sleep‐disordered breathing (SDB), and objective findings, such as nocturnal hypoxemia. Importantly, a strong association has been shown between SDB and the severity of lung disease, and some studies have reported a similar association for sleep quality. Further research is needed to better characterize the association of sleep disturbances with respiratory outcomes and the impact of treatment of sleep disorders on pulmonary status in children with CF.
Design of a foundational sciences curriculum: Applying the ICAP framework to pharmacology education in integrated medical curricula
Authors: Quesnelle Kelly M. , Zaveri Naunihal T. , Schneid Stephen D. , Blumer Joe B. , Szarek John L. , Kruidering Marieke , Lee Michael W. 
Published: May 2021

AbstractExpectations for physicians are rapidly changing, as is the environment in which they will practice. In response, preclerkship medical education curricula are adapting to meet these demands, often by reducing the time for foundational sciences. This descriptive study compares preclerkship pharmacology education curricular practices from seven allopathic medical schools across the United States. We compare factors and practices that affect how pharmacology is integrated into the undergraduate medical education curriculum, including teaching techniques, resources, time allocated to pharmacology teaching, and assessment strategies. We use data from seven medical schools in the United States, along with results from a literature survey, to inform the strengths and weaknesses of various approaches and to raise important questions that can guide future research regarding integration of foundational sciences in medical school and health professions’ curricula. In this comparative study, we found that there is significant heterogeneity in the number of hours dedicated to pharmacology in the preclerkship curriculum, whereas there was concordance in the use of active learning pedagogies for content delivery. Applying the ICAP (Interactive, Constructive, Active, Passive) Framework for cognitive engagement, our data showed that pharmacology was presented using more highly engaging pedagogies during sessions that are integrated with other foundational sciences. These findings can serve as a model that can be applied beyond pharmacology to other foundational sciences such as genetics, pathology, microbiology, biochemistry, etc.
Prescribed‐time control of uncertain strict‐feedback‐like systems
Authors: Ye Hefu , Song Yongduan 
Published: May 2021

AbstractIn this paper, we present a control method for achieving prescribed‐time regulation of strict‐feedback‐like systems in the presence of unknown yet time‐varying control gains and mismatched uncertainties. The developed control algorithms are capable of full‐state regulation within pre‐set time independent of initial condition and any other design parameter. The corresponding control action is continuous and bounded during the entire control process, which, for vanishing uncertainties/disturbances, reduces to zero as the states approach the equilibrium and remains zero thereafter, allowing for nonstop running of the system beyond the settling time. The efficiency of the proposed method is verified through numerical examples.
G2 and S phase‐expressed‐1 acts as a putative tumor promoter in cervical cancer by enhancing Wnt/β‐catenin signaling via modulation of GSK‐3β
Authors: Guo Wenting , Zhu Jing , Zhu Yuan , Wang Kai 
Published: May 2021

AbstractG2 and S phase‐expressed‐1 (GTSE1) is currently identified as a key regulator of carcinogenesis. However, the involvement of GTSE1 in cervical cancer is unclear. The aims of this work were to explore the relationship between GTSE1 and cervical cancer. Our data elucidated high GTSE1 expression in cervical cancer tissue, which predicted a poor prognosis in cervical cancer patients. GTSE1 knockdown had tumor‐suppressive effects in cervical cancer cells by inhibiting cell proliferative and invasive abilities. GTSE1 knockdown decreased the level of phosphorylated glycogen synthase kinase‐3β (GSK‐3β) and active β‐catenin, resulted in inactivation of Wnt/β‐catenin signaling. Suppression of GSK‐3β remarkably abolished the GTSE1‐knockdown‐induced inhibitory effects on Wnt/β‐catenin signaling. Suppression of Wnt/β‐catenin signaling abolished the GTSE1‐overexpression‐induced oncogenic effects. Notably, GTSE1 knockdown impeded the in vivo tumorigenicity of cervical cancer cells. In short, this work demonstrates that GTSE1 is overexpressed in cervical cancer and GTSE1 suppression exerts a tumor‐inhibiting role in cervical cancer by down‐regulating Wnt/β‐catenin signaling. Our work underlines a crucial relevance between GTSE1 and cervical cancer progression and suggests GTSE1 as a promising therapeutic target for cervical cancer.
HBCD, TBECH, and BTBPE exhibit cytotoxic effects in human vascular endothelial cells by regulating mitochondria function and ROS production
Authors: Shi Jun , Wang Xueting , Chen Lulu , Deng Huiping , Zhang Min 
Published: May 2021

AbstractBrominated flame retardants (BFRs), such as, 1,2,5,6‐tetrabromocyclooctane (HBCD), 1,2‐dibromo‐4‐(1,2‐dibromopropyl)cyclohexane (TBECH), and 1 1,2‐bis‐(2,4,6‐tribromophenoxy)ethane (BTBPE), have garnered increasing attention due to their potent biological effects. In the present study, the toxicity of HBCD, TBECH, and BTBPE in human vascular endothelial cells (ECs) was explored. The data showed that HBCD, TBECH, and BTBPE induced cytotoxicity, namely dose–dependent cell viability reduction, cell membrane permeability and apoptosis increase, migration, and lumen formation inhibition. Moreover, HBCD was found to be more toxic than BTBPE or TBECH. Exposure to HBCD, TBECH, and BTBPE led to the production of reactive oxygen species, mitochondrial superoxide generation, and mitochondrial membrane potential collapse, implying that reactive stress caused the cytotoxicity. The ATP content, glutathione content, superoxide dismutase, and MDA activities were reduced, indicating that mitochondrial dysfunction may be the key mechanisms responsible for apoptosis. The present study suggested that mitochondria are a new target of BFRs in ECs and further deepened our understanding of the developmental toxicity of BFRs.
Engineering heterogeneity of precision nanoparticles for biomedical delivery and therapy
Authors: Zheng Di , Yang Kuikun , Nie Zhihong 
Published: May 2021

AbstractNanoparticle (NP)‐based vehicles are attractive for biomedical delivery and therapy, owing to improved therapeutic efficiency and reduced adverse effects compared to free drugs. Uncontrolled NP heterogeneity at the suspension level or single particle level poses grand challenges in the effective use of NPs for biology and medicines. Precision nanoparticles (PNPs) are a class of discrete nanostructures exhibiting elaborately tailored surface or structural heterogeneity, but minimal variations between nanostructures in one solution. Benefiting from their precisely controlled NP heterogeneity, PNPs have emerged as promising platforms for modulating various biological processes to improve the biomedical performance of NP‐based vehicles. This review summarizes recent advances in the development of precisely tailored PNPs for biomedical applications, with an emphasis on the nano‐bio interactions, and drug delivery and therapy. We start with a brief overview of the major categories of PNPs and their fabrication strategies (section 2). We then focus on reviewing the use of PNPs for enhancing biomolecular recognition or detection, regulating the NP‐protein interactions, modulating the NP‐biomembrane interactions, and improving the biological delivery and therapy (section 3). Finally, we discuss the challenges and perspectives on the design and use of PNPs for biomedical applications (section 4).
A Web-Based Co-Creation and User Engagement Method and Platform
Authors: Tocchetti Andrea , Corti Lorenzo , Brambilla Marco , Marco Diletta Di 
Published: May 2021

AbstractIn recent years, new methods to engage citizens in deliberative processes of governments and institutions have been studied. Such methodologies have become a necessity to assure the efficacy and longevity of policies. Several tools and solutions have been proposed while trying to achieve such a goal. The dual problem to citizen engagement is how to provide policy-makers with useful and actionable insights stemming from those processes. In this paper, we propose a research featuring a method and implementation of a crowdsourcing and co-creation technique that can provide value to both citizens and policy-makers engaged in the policy-making process. Thanks to our methodology, policy-makers can design challenges for citizens to partake, cooperate and provide their input. We also propose a web-based tool that allow citizens to participate and produce content to support the policy-making processes through a gamified interface that focuses on emotional and vision-oriented content.
Probing Hawking radiation through capacity of entanglement
Authors: Kawabata Kohki , Nishioka Tatsuma , Okuyama Yoshitaka , Watanabe Kento 
Published: May 2021

Abstract
We consider the capacity of entanglement in models related with the gravitational phase transitions. The capacity is labeled by the replica parameter which plays a similar role to the inverse temperature in thermodynamics. In the end of the world brane model of a radiating black hole the capacity has a peak around the Page time indicating the phase transition between replica wormhole geometries of different types of topology. Similarly, in a moving mirror model describing Hawking radiation the capacity typically shows a discontinuity when the dominant saddle switches between two phases, which can be seen as a formation of island regions. In either case we find the capacity can be an invaluable diagnostic for a black hole evaporation process.
Spillway preheating
Authors: Fan JiJi , Lozanov Kaloian D. , Lu Qianshu 
Published: May 2021

Abstract
In traditional models only an order one fraction of energy is transferred from the inflaton to radiation through nonperturbative resonance production in preheating immediately after inflation, due to backreaction effects. We propose a particle production mechanism that could improve the depletion of the inflaton energy density by up to four orders of magnitude. The improvement comes from the fast perturbative decays of resonantly produced daughter particles. They act as a “spillway” to drain these daughter particles, reducing their backreaction on the inflaton and keeping the resonant production effective for a longer period. Thus we dub the scenario “spillway preheating”. We also show that the fraction of energy density remaining in the inflaton has a simple inverse power-law scaling in the scenario. In general, spillway preheating is a much more efficient energy dissipation mechanism, which may have other applications in model building for particle physics.
Metaplectic flavor symmetries from magnetized tori
Authors: Almumin Yahya , Chen Mu-Chun , Knapp-Pérez Víctor , Ramos-Sánchez Saúl , Ratz Michael , Shukla Shreya 
Published: May 2021

Abstract
We revisit the flavor symmetries arising from compactifications on tori with magnetic background fluxes. Using Euler’s Theorem, we derive closed form analytic expressions for the Yukawa couplings that are valid for arbitrary flux parameters. We discuss the modular transformations for even and odd units of magnetic flux, M, and show that they give rise to finite metaplectic groups the order of which is determined by the least common multiple of the number of zero-mode flavors involved. Unlike in models in which modular flavor symmetries are postulated, in this approach they derive from an underlying torus. This allows us to retain control over parameters, such as those governing the kinetic terms, that are free in the bottom-up approach, thus leading to an increased predictivity. In addition, the geometric picture allows us to understand the relative suppression of Yukawa couplings from their localization properties in the compact space. We also comment on the role supersymmetry plays in these constructions, and outline a path towards non-supersymmetric models with modular flavor symmetries.
Nonlinear evolution problems with singular coefficients in the lower order terms
Authors: Farroni Fernando , Greco Luigi , Moscariello Gioconda , Zecca Gabriella 
Published: May 2021

AbstractWe consider a Cauchy–Dirichlet problem for a quasilinear second order parabolic equation with lower order term driven by a singular coefficient. We establish an existence result to such a problem and we describe the time behavior of the solution in the case of the infinite–time horizon.