bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parental exposure of Eastern oysters (Crassostrea virginica) to elevated pCO2 mitigates its negative effects on early larval shell growth and morphology
Authors: McNally Elise M. , Downey‐Wall Alan M. , Titmuss F. Dylan , Cortina Camila , Lotterhos Kathleen , Ries Justin B. 
Published: June 2022

AbstractLarvae of marine calcifying organisms are particularly vulnerable to the adverse effects of elevated pCO2 on shell formation because of their rapid calcification rates, reduced capacity to isolate calcifying fluid from seawater, and use of more soluble polymorphs of calcium carbonate. However, parental exposure to elevated pCO2 could benefit larval shell formation through transgenerational plastic responses. We examined the capacity of intergenerational exposure to mitigate the adverse effects of elevated pCO2 on Eastern oyster (Crassostrea virginica) early larval shell growth, shell morphology, and survival. Adult oysters were exposed to control (572 ppm pCO2) or elevated pCO2 (2827 ppm pCO2) conditions for 30 d during reproductive conditioning. Offspring from each parental treatment were produced using a partial North Carolina II cross design and grown under control and elevated pCO2 conditions for 3 d. We found evidence of transgenerational plasticity in early larval shell growth and morphology, but not in survival, in response to the parental pCO2 exposure. Larvae from parents exposed to elevated pCO2 exhibited faster shell growth rates than larvae from control parents, with this effect being significantly larger when larvae were grown under elevated pCO2 compared to control conditions. Parental exposure to elevated pCO2, however, was insufficient to completely counteract the adverse effects of the prescribed elevated pCO2 on early larval shell formation and survival. Nevertheless, these results suggest that oysters have some capacity to acclimate intergenerationally to ocean acidification.
Isotopic signatures of biotic and abiotic N2O production and consumption in the water column of meromictic, ferruginous Lake La Cruz (Spain)
Authors: Tischer Jana , Zopfi Jakob , Frey Claudia , Magyar Paul M. , Brand Andreas , Oswald Kirsten , Jegge Corinne , Frame Caitlin H. , Miracle María R. , Sòria‐Perpinyà Xavier , Vicente Eduardo , Lehmann Moritz F. 
Published: June 2022

AbstractLakes can be important sources of the potent greenhouse gas nitrous oxide (N2O) to the atmosphere, but to what extent abiotic processes may contribute to lacustrine N2O production remains uncertain. We assessed pathways of N2O production and reduction in the water column of meromictic and iron‐rich Lake La Cruz, Spain, including chemodenitrification‐induced N2O formation via the reaction of reactive nitrogen (N) (e.g., ) with ferrous iron (Fe[II]). In the oxic waters (~8–10 m), N2O concentrations above atmospheric equilibrium were associated with comparatively low δ15N‐N2O, high , and high N2O 15N‐site‐preference (SP) values (up to ~29‰), suggesting N2O production by nitrification. N2O concentrations were highest (23–33 nM) near the depth of oxygen depletion (~11–14.5 m), likely due to production by nitrifier denitrification and/or denitrification, as indicated by decreasing SP values (as low as 12‰). Further below (~14.5–17 m), N2O consumption was indicated by increasing SP values and a δ18O‐vs.‐δ15N relationship (1.8–2.9) typical for stand‐alone N2O reduction. The coupled N‐vs.‐O isotope signatures thus highlight the spatial, redox‐dependent separation of incomplete and complete denitrification. In incubations with sterile‐filtered lake water and 15N‐labeled or unlabeled substrate, was reduced by Fe2+ to N2O, even at low nitrite concentrations (5 μM ). In the water column, the spatial separation of and Fe(II) during our samplings appears to preclude elevated rates of chemodenitrification, but during periods of overlapping and Fe(II) in Lake La Cruz, and potentially in other lakes, its distinct N2O δ18O‐vs.‐δ15N relationship of ~1 : 1, as experimentally determined, could help to detect it.
Antimicrobial Polymers of Linear and Bottlebrush Architecture: Probing the Membrane Interaction and Physicochemical Properties
Authors: Bapolisi Alain Murhimalika , Kielb Patrycja , Bekir Marek , Lehnen Anne‐Catherine , Radon Christin , Laroque Sophie , Wendler Petra , Müller‐Werkmeister Henrike M. , Hartlieb Matthias 
Published: June 2022

AbstractPolymeric antimicrobial peptide mimics are a promising alternative for the future management of the daunting problems associated with antimicrobial resistance. However, the development of successful antimicrobial polymers (APs) requires careful control of factors such as amphiphilic balance, molecular weight, dispersity, sequence, and architecture. While most of the earlier developed APs focus on random linear copolymers, the development of APs with advanced architectures proves to be more potent. It is recently developed multivalent bottlebrush APs with improved antibacterial and hemocompatibility profiles, outperforming their linear counterparts. Understanding the rationale behind the outstanding biological activity of these newly developed antimicrobials is vital to further improving their performance. This work investigates the physicochemical properties governing the differences in activity between linear and bottlebrush architectures using various spectroscopic and microscopic techniques. Linear copolymers are more solvated, thermo‐responsive, and possess facial amphiphilicity resulting in random aggregations when interacting with liposomes mimicking Escheria coli membranes. The bottlebrush copolymers adopt a more stable secondary conformation in aqueous solution in comparison to linear copolymers, conferring rapid and more specific binding mechanism to membranes. The advantageous physicochemical properties of the bottlebrush topology seem to be a determinant factor in the activity of these promising APs.
“On Chorea”: 150 Years of the Beginning of Hope
Authors: Franklin Gustavo L. , Teive Hélio A.G. , Meira Alex T. , Nepomuceno Adriana M.T. , Tabrizi Sarah J. 
Published: June 2022

Abstract“On Chorea” by George Huntington was published on April 13, 1872, in The Medical and Surgical Reporter of Philadelphia. Despite being a milestone in the recognition of the disease that later would bear his name, some myths and curiosities continue to surround the history of this publication and its author. In this History, the authors pay tribute to the 150th anniversary of the publication of this iconic article. © 2022 International Parkinson and Movement Disorder Society.
Effect of KRAS mutations and p53 expression on the postoperative prognosis of patients with colorectal cancer
Authors: Wang Lingfeng , Lin Shengtao , Yang Changshun , Cai Shaoxin , Li Weihua 
Published: June 2022

AbstractBackgroundIn the occurrence and development of colorectal cancer, p53 is an important regulator downstream of the MAPK signaling pathway and plays an important role in inhibiting abnormal proliferation signals generated by KRAS mutations. The purpose of this study is to explore the correlation between KRAS mutations and p53 expression and evaluate their prognosis values in colorectal cancer.MethodsPCR technology and immunohistochemical (IHC) staining were used to detect KRAS mutation status and p53 expression level in 266 specimens of colorectal adenocarcinoma. Based on p53 expression level, these were divided into high expression and normal groups. Patients with KRAS mutations were divided into mutant and wild‐type groups. The two were combined with each other to analyze the relationship between patients' clinical data and their impact on the prognosis.ResultsKRAS mutations were found in 38.6% of the patients and 40.8% had a high p53 expression. There was no significant difference in the overall survival rate of patients, with or without KRAS gene mutations, and p53 expression level. In the group of patients with KRAS mutations, the survival time of patients with a high p53 expression was significantly lower than that of patients with a normal p53 expression (p = 0.020, log‐rank test). Multivariate analysis showed that p53 high expression is an independent risk factor for the overall survival time of patients with KRAS mutations (HR = 2.330, 95% CI = 1.041–5.216, p < 0.05).ConclusionColorectal cancer patients with KRAS mutations with a high p53 expression have a poor prognosis.
Time‐varying piecewise nonlinear dynamic model of the vibrating machinery with elliptical trajectory consider the interactions between its frame and particles
Authors: Li Lingxuan , Zhang Haonan , Zhong Hao 
Published: June 2022

AbstractVibrating machinery with an elliptical trajectory widely exists. The bulk particles show a regular sliding motion and throwing motion under the periodic vibration of the frame. It is essential for the theoretical design and engineering application of such machinery to study the particle's motion theory based on considering the interactions between particles and frame in detail. In the first, a time‐varying piecewise nonlinear dynamic model of the system is established based on the force analysis of the particles in the state of sliding and throwing motion. The dimensionless equations of systems with nonlinear terms are deduced. After that, the feasibility of using a single particle to study the particle flow's movement is verified by the discrete element method. Then, the system's approximate steady‐state analytical solution is obtained by the incremental harmonic balance method. Its numerical solutions are solved by the Newmark‐β method, and the solutions obtained by the three methods are verified mutually. In addition, the Sommerfeld effect in vibration system and the system's related parameters are analyzed. Finally, an experimental platform of particles' movement is built. The feasibility of the theoretical analysis in this article was verified by particle's movement experiments.
Molecular deciphering of primary liver neuroendocrine neoplasms confirms their distinct existence with foregut‐like profile
Authors: de Mestier Louis , Nicolle Rémy , Poté Nicolas , Rebours Vinciane , Cauchy François , Hentic Olivia , Maire Frédérique , Ronot Maxime , Lebtahi Rachida , Sauvanet Alain , Paradis Valérie , Ruszniewski Philippe , Couvelard Anne , Cros Jérôme 
Published: June 2022

AbstractIsolated hepatic localizations of neuroendocrine tumors (NETs) are generally considered as metastatic NETs of unknown primary but could correspond to primary hepatic NETs (PHNETs), a poorly explored entity. We aimed to describe the clinicopathological and molecular features of PHNETs and compare them with other primary NETs. We assembled a retrospective cohort of patients managed for hepatic localization of NET without extra‐hepatic primary tumor after exhaustive clinical, imaging, and immunohistochemical characterization. We performed whole‐exome sequencing with mutational and copy number analysis. Transcriptomic profiles were compared with pancreatic (n = 31), small‐bowel (n = 22), and lung (n = 15) NETs using principal component analysis, unsupervised clustering, and gene set enrichment analysis. Among 27 screened patients, 16 had PHNET (solitary tumor in 63%, median size 11 cm, G2 NETs in 81%) following clinical and pathological review. DNA analyses showed ‘foregut‐like’ genomic profiles with frequent alterations in pathways of Fanconi DNA repair (75%), histone modifiers (58%), adherens junctions (58%), and cell cycle control (50%). The most frequently involved genes were KMT2A (58%), ATM (42%), CDH1, CDKN2C, FANCF, and MEN1 (33% each). Transcriptomic analyses showed that PHNETs clustered closer to foregut (pancreatic, lung) NETs than to midgut (small‐bowel) NETs, while remaining a distinct entity with a specific profile. Assessment of potentially predictive biomarkers suggested efficacy of treatments usually active in foregut NETs. In conclusion, PHNETs display a foregut‐like molecular profile distinct from other types of NETs, with recurrent molecular alterations. Upon exhaustive work‐up to exclude an unrecognized primary tumor, PHNETs should not be considered metastatic NETs from an unknown primary. © 2022 The Pathological Society of Great Britain and Ireland.
Peak density of immature nerve cells occurs with high‐grade dysplasia in intraductal papillary mucinous neoplasms of the pancreas
Authors: Trinh Vincent Quoc‐Huy , Roland Joseph Thomas , Wong Jahg , Revetta Frank , Patel Krutika , Shi Chanjuan , DelGiorno Kathleen E , Carter Bruce D , Tan Marcus Chuan Beng 
Published: June 2022

AbstractThe development of neural structures within tumors is now considered vital for carcinogenesis. However, the time course of this development in human pre‐invasive neoplasia has been incompletely described. Therefore, we performed a detailed analysis of nerves across the neoplastic spectrum in resected intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Histology and multiplexed immunochemistry demonstrated that nerve density increased from low‐grade (LG) to high‐grade dysplasia (HG) but did not further increase once invasive IPMN (INV IPMN) was present. Higher nerve density correlated with increasing expression of nerve growth factor (NGF) by the tumor cells. Intra‐tumoral nerves were immature and lacked markers of sympathetic, parasympathetic, and sensory lineages. Here, we show for the first time the presence of neural precursor cells (NPCs) within the stroma of pancreatic tumors. The density of these doublecortin (DCX)‐positive NPCs increased from LG to HG, but not from HG to INV IPMN. We conclude that peak neural density of tumors is reached in high‐grade dysplasia (often termed carcinoma in situ) rather than after invasion. These findings suggest that nerve–tumor interactions are important in IPMN progression and may serve as the basis for future mechanistic studies and novel therapeutic modalities. © 2022 The Pathological Society of Great Britain and Ireland.
End‐of‐life care quality for children with cancer who receive palliative care
Authors: Ananth Prasanna , Lindsay Meghan , Nye Russell , Mun Sophia , Feudtner Chris , Wolfe Joanne 
Published: June 2022

AbstractBackground: We previously developed stakeholder‐informed quality measures to assess end‐of‐life care quality for children with cancer. We sought to implement a subset of these quality measures in the multi‐center pediatric palliative care (PPC) database.Procedures: We utilized the Shared Data and Research database to evaluate the proportion of childhood cancer decedents from 2017–2021 who, in the last 30 days of life, avoided chemotherapy, mechanical ventilation, intensive care unit admissions, and > 1 hospital admission; were enrolled in hospice services, and reported ≤ 2 highly distressing symptoms. We then explored patient factors associated with the attainment of quality benchmarks.Results: Across 79 decedents, 82% met ≥ 4 quality benchmarks. Most (76%) reported > 2 highly distressing symptoms; 17% were enrolled in hospice. In univariable analyses, patients with an annual household income ≤$50,000 had lower odds of hospice enrollment and avoidance of mechanical ventilation or intensive care unit admissions near end of life (odds ratio [OR] 0.10 [95% confidence interval (C.I.) 0.01, 0.86], p = 0.04; OR 0.13 [0.02, 0.64], p = 0.01; OR 0.36 [0.13, 0.98], p = 0.04, respectively). In multivariable analyses, patients with an income ≤$50,000 remained less likely to enroll in hospice, after adjusting for cancer type (OR 0.10 [0.01, 0.87]; p = 0.04).Conclusions: Childhood cancer decedents who received PPC met a large proportion of quality measures near the end of their life. Yet, many reported highly distressing symptoms. Moreover, patients with lower household incomes appeared less likely to enroll in hospice and more likely to receive intensive hospital services near the end of life. This study identifies opportunities for palliative oncology quality improvement.
Adherence to dietary prescriptions in patients with acute food protein‐induced enterocolitis syndrome
Authors: Miceli Sopo Stefano , Sinatti Dario , Sodero Giorgio , Gelsomino Mariannita , Mastellone Francesco 
Published: June 2022

ABSTRACTFood protein‐induced enterocolitis syndrome (FPIES) is a non‐Immunoglobulin (non‐IgE)‐mediated food allergy. The elimination diet is the only therapy, the culprit food will be reintroduced if tolerance is acquired. However, it is possible that patients do not follow the recommendations given by the healthcare professional. We investigated if our advice to avoid the trigger food in patients with active FPIES and to reintroduce it in the diet in patients who achieved tolerance had been implemented. We interviewed by telephone the parents of children who were diagnosed with acute FPIES. About 23.2% of our patients disregarded our dietary recommendations: 6/42 (14.3%) of patients who passed a tolerance oral food challenge (OFC) did not eat the trigger food, 4/22 (18.2%) of patients who failed OFC ate the trigger food, and 9/18 (50.0%) of patients who did not perform a tolerance OFC ate the trigger food. We have analyzed some possible influencing factors and no difference was found to be statistically significant. Our results are in line with those reported for IgE‐mediated food allergies. As has already been proposed by others, we suggest reassessing food consumption in all patients after a food challenge.
Calibration and validation of the rabbit model of electrolytic‐mediated arterial thrombosis against the standard‐of‐care anticoagulant apixaban
Authors: Wong Pancras C. , Crain Earl 
Published: June 2022

AbstractApixaban is a factor Xa (FXa) inhibitor and standard‐of‐care anticoagulant with FXa Ki and plasma protein binding (free fraction) averages 0.08 nM and 0.13 in humans and 0.16 nM and 0.37 in rabbits, respectively. Apixaban at the approved dose of 5 mg BID achieved maximum and minimum plasma concentration of 373 nM (95% CI: 198 – 699 nM) and 224 nM (95% CI 89–501 nM), respectively, in patients with nonvalvular atrial fibrillation (AF). We calibrated the rabbit model of electrolytic‐mediated arterial thrombosis (ECAT) against apixaban and correlated the potencies derived from the rabbit ECAT to in vivo efficacious exposure levels in AF patients. Vehicle and apixaban at multiple doses were infused IV in ECAT rabbits and their effects on thrombus weight were measured. Apixaban exhibited dose‐related efficacy in preventing thrombosis in ECAT rabbits with EC20, EC50, EC60, EC70 and EC80 of 18, 101, 169, 296, and 585 nM, respectively. After correcting for the human‐to‐rabbit potency based on FXa Ki and plasma protein binding, we estimated a rabbit‐equally‐effective plasma concentration of 157 and 259 nM to the trough and peak plasma concentration in AF patients treated with 5 mg BID of apixaban. These rabbit‐equally‐effective plasma concentrations matched well with the rabbit ECAT EC60 and EC70. This study supports the potential of the rabbit ECAT to predict in vivo therapeutic drug exposure of FXa inhibitors. Achieving human‐equally‐effective plasma concentrations to the rabbit ECAT EC60 and EC70 may produce clinical efficacy in patient populations like AF.
Oridonin relieves depressive‐like behaviors by inhibiting neuroinflammation and autophagy impairment in rats subjected to chronic unpredictable mild stress
Authors: Liang Liang , Wang Hui , Hu Ying , Bian Hetao , Xiao Ling , Wang Gaohua 
Published: June 2022

AbstractMajor depressive disorder (MDD) is a severe life‐threatening disorder with increasing prevalence. However, the mechanistic interplay between depression, neuroinflammation, and autophagy is yet to be demonstrated. This study investigated the effect of Oridonin on CUMS‐induced depression, neuroinflammation, and autophagy impairment. Male 4‐week‐old Sprague–Dawley rats were subjected to chronic unpredictable mild stress (CUMS), some of which were injected with Oridonin, fluoxetine (FLX), or their combination at different durations of CUMS. CUMS significantly increased the levels of cytokines (IL‐1β, IL‐18, and caspase‐1), reduced autophagy‐related protein levels (Beclin‐1, p62, Atg5, and LC3B), and caused microglia cells activation. Oridonin prevented and reversed the depressive‐like behavior. Furthermore, it has a stronger and longer‐lasting antidepressant effect than FLX. And the antidepressant effect of Oridonin in combination with fluoxetine was greater than that of high‐dose fluoxetine alone. In addition, Oridonin significantly normalized autophagy‐related protein levels, and reduced levels of cytokines by blocking the interaction between NLRP3 and NEK7. Similarly, Oridonin abolished levels of cytokines and reversed autophagy impairment in LPS‐activated BV2 cells. All these results supported our hypothesis that Oridonin possesses potent anti‐depressive action, which might be mediated via inhibition of neuroinflammation and autophagy impairment by blocking the interaction between NLRP3 and NEK7.
Isobavachalcone: A comprehensive review of its plant sources, pharmacokinetics, toxicity, pharmacological activities and related molecular mechanisms
Authors: Xing Nan , Meng Xianli , Wang Shaohui 
Published: June 2022

AbstractIsobavachalcone (IBC), also known as isobapsoralcone, is a natural flavonoid widely derived from many medicinal plants, including Fabaceae, Moraceae, and so forth. IBC has been paid more and more attention by researchers in recent years due to its pharmacological activity in many diseases. This review aims to describe in detail the plant sources, pharmacokinetics, toxicity, pharmacological activities, and molecular mechanisms of IBC on various diseases. We found that IBC can be obtained not only by extraction but also by chemical synthesis. Pharmacokinetic studies have shown that IBC has low bioavailability, but can penetrate the blood–brain barrier and is widely distributed in the brain. Its pharmacological activities mainly include anticancer, antibacterial, anti‐inflammatory, antiviral, neuroprotective, bone protection, and other activities. In particular, IBC shows strong anti‐tumor and anti‐inflammatory therapeutic potential due to its anti‐cancer and anti‐inflammatory activities. However, due to its hepatotoxicity, there may be more drug interactions. Therefore, more and more in‐depth studies are needed for its clinical application. Mechanically, IBC can induce the production of reactive oxygen species (ROS), inhibit AKT, ERK, and Wnt pathways, and promote apoptosis of cancer cells through mitochondrial or endoplasmic reticulum pathways. IBC can inhibit the NF‐κB pathway and the production of multiple inflammatory mediators by activating NRF2/HO‐1 pathway, thus producing anti‐inflammatory effects. Moreover, we discussed the limitations of current research on IBC and put forward some new perspectives and challenges, which provide a strong basis for clinical application and new drug development of IBC in the future.
Controllable fast light in quantum dot molecules assisted hybrid optomechanical system
Authors: Ghaffar Ammal Abdul , Khan Muhammad Aslam , Niaz Shanawer , Khan Farooq , Jamil Muhammad Ashfaq , Ramay Shahid M. 
Published: June 2022

AbstractWe investigate the superluminal effect of transmitted probe field in three‐level quantum dot molecules (QDMs) assisted optomechanical system which consist of mechanical resonator. We show that the superluminal behavior of transmitted probe field can be controlled by changing the tunneling strength and number of QDMs inside the cavity. Furthermore, it is shown that in the absence of tunneling strength, the transmitted probe field shows the fast light effect and by increasing the number of QDMs, the enhancement in superluminal behavior is decreased and converts into slow light. While, in the presence of the tunneling strength, with the increase of the number of QDMs the superluminal behavior of transmitted field is obtained at smaller detuning frequency. The influence of tunneling strength and number of QDMs on superluminal part of the transmitted probe field is quite useful in optical memory, optical buffers, and quantum information processing.