bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cyclic nano-reactor achieving enhanced photodynamic tumor therapy by reversing multiple resistances
Authors: Liu Peng , Zhou Yanbin , Shi Xinyi , Yuan Yu , Peng Ying , Hua Surong , Luo Qiange , Ding Jinsong , Li Yong , Zhou Wenhu 
Published: May 2021

AbstractBackgroundPhotodynamic therapy (PDT) is a clinically implemented modality to combat malignant tumor, while its efficacy is largely limited by several resistance factors from tumor microenvironment (TME), such as hypoxia, anti-oxidant systems, and ATP-dependent tumor adaptive resistances. The aim of this work is to construct a multifunctional nanoplatform to remodel multiple resistant TME for enhanced PDT.ResultsHere, a targeting nano-reactor was facilely constructed to reverse the multiple resistances of PDT by incorporating glucose oxidase (GOx) and chlorin e6 (Ce6) into poly (D, L-lactic-co-glycolic acid) (PLGA)/ metal–organic framework (MOF) core–shell nanoassembly, with surface deposition of hyaluronic acid (HA) stabilized MnO2. The nano-reactor could selectively target tumor cells by virtue of surface HA modification, and once internalization, a few reactions were initiated to modulate TME. Glucose was consumed by GOx to inhibit ATP generation, and the produced H2O2was catalyzed by MnO2to generate O2for tumor hypoxia alleviation and photodynamic sensitization, and glutathione (GSH) was also effectively depleted by MnO2to suppress the tumor antioxidant defense. Consequently, the nano-reactor achieved robust PDT with amplified tumor therapy via intravenous injection.ConclusionsThis nano-reactor offers a multifunctional nanoplatform to sensitize TME-limited tumor treatment means via reversing multiple resistances.Grpahic abstract
Calcitonin gene-related peptide regulates spinal microglial activation through the histone H3 lysine 27 trimethylation via enhancer of zeste homolog-2 in rats with neuropathic pain
Authors: An Qi , Sun Chenyan , Li Ruidi , Chen Shuhui , Gu Xinpei , An Shuhong , Wang Zhaojin 
Published: May 2021

Abstract
Background
Calcitonin gene-related peptide (CGRP) as a mediator of microglial activation at the transcriptional level may facilitate nociceptive signaling. Trimethylation of H3 lysine 27 (H3K27me3) by enhancer of zeste homolog 2 (EZH2) is an epigenetic mark that regulates inflammatory-related gene expression after peripheral nerve injury. In this study, we explored the relationship between CGRP and H3K27me3 in microglial activation after nerve injury, and elucidated the underlying mechanisms in the pathogenesis of chronic neuropathic pain.

Methods
Microglial cells (BV2) were treated with CGRP and differentially enrichments of H3K27me3 on gene promoters were examined using ChIP-seq. A chronic constriction injury (CCI) rat model was used to evaluate the role of CGRP on microglial activation and EZH2/H3K27me3 signaling in CCI-induced neuropathic pain.

Results
Overexpressions of EZH2 and H3K27me3 were confirmed in spinal microglia of CCI rats by immunofluorescence. CGRP treatment induced the increased of H3K27me3 expression in the spinal dorsal horn and cultured microglial cells (BV2) through EZH2. ChIP-seq data indicated that CGRP significantly altered H3K27me3 enrichments on gene promoters in microglia following CGRP treatment, including 173 gaining H3K27me3 and 75 losing this mark, which mostly enriched in regulation of cell growth, phagosome, and inflammation. qRT-PCR verified expressions of representative candidate genes (TRAF3IP2, BCL2L11, ITGAM, DAB2, NLRP12, WNT3, ADAM10) and real-time cell analysis (RTCA) verified microglial proliferation. Additionally, CGRP treatment and CCI increased expressions of ITGAM, ADAM10, MCP-1, and CX3CR1, key mediators of microglial activation in spinal dorsal horn and cultured microglial cells. Such increased effects induced by CCI were suppressed by CGRP antagonist and EZH2 inhibitor, which were concurrently associated with the attenuated mechanical and thermal hyperalgesia in CCI rats.

Conclusion
Our findings highly indicate that CGRP is implicated in the genesis of neuropathic pain through regulating microglial activation via EZH2-mediated H3K27me3 in the spinal dorsal horn.
Prediction of the risk of C5 palsy after posterior laminectomy and fusion with cervical myelopathy using a support vector machine: an analysis of 184 consecutive patients
Authors: Wang Haosheng , Tang Zhi-Ri , Li Wenle , Fan Tingting , Zhao Jianwu , Kang Mingyang , Dong Rongpeng , Qu Yang 
Published: May 2021

Abstract
Background
This study aimed to predict C5 palsy (C5P) after posterior laminectomy and fusion (PLF) with cervical myelopathy (CM) from routinely available variables using a support vector machine (SVM) method.

Methods
We conducted a retrospective investigation based on 184 consecutive patients with CM after PLF, and data were collected from March 2013 to December 2019. Clinical and imaging variables were obtained and imported into univariable and multivariable logistic regression analyses to identify risk factors for C5P. According to published reports and clinical experience, a series of variables was selected to develop an SVM machine learning model to predict C5P. The accuracy (ACC), area under the receiver operating characteristic curve (AUC), and confusion matrices were used to evaluate the performance of the prediction model.

Results
Among the 184 consecutive patients, C5P occurred in 26 patients (14.13%). Multivariate analyses demonstrated the following 4 independent factors associated with C5P: abnormal electromyogram (odds ratio [OR] = 7.861), JOA recovery rate (OR = 1.412), modified Pavlov ratio (OR = 0.009), and presence of C4–C5 foraminal stenosis (OR = 15.492). The SVM model achieved an area under the receiver operating characteristic curve (AUC) of 0.923 and an ACC of 0.918. Additionally, the confusion matrix showed the classification results of the discriminant analysis.

Conclusions
The designed SVM model presented satisfactory performance in predicting C5P from routinely available variables. However, future external validation is needed.
COVID-19 in Africa: an ovarian victory?
Authors: Dufailu Osman A. , Afriyie-Asante Afrakoma , Gyan Bernard , Kwabena David Adu , Yeboah Helena , Ntiakoh Frank , Asare-Werehene Meshach 
Published: May 2021

AbstractCoronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mainly attacks the respiratory system and is characterized by pneumonia, cytokine storm, coagulation disorders and severe immune downregulation. Although public health experts predicted worst outcomes in Africa, the incidence, hospitalization and mortality rates have been lower in Africa compared to other continents. Interestingly, lower incidence and mortality rates have been observed in women from Africa compared to their cohorts from other continents. Also, in the US non-Hispanic Black females have lower COVID-19 and death rates compared to their white counterparts. It’s unclear why this significant difference exists; however, the ovarian function, genetics and immunological statuses could play a major role. Women of African descent have elevated levels of estrogen compared with Caucasians hence we anticipate that estrogen might offer some protection against the SARS-CoV-2 infections. The racial differences in lifestyle, age and inaccessibility to contraceptive usage might also play a role. Here, we provide insight on how the high levels of estrogen in African women might contribute to the lower cases and fatalities in Africa. Specifically, estrogen might offer protection against COVID-19 by suppressing hyper-production of cytokines, promoting anti-inflammatory cytokines, stimulating antibody production and suppressing endoplasmic reticulum (ER) stress. This will as well provide useful information on how future pandemics could be managed using Africa as a case study.
Study on the reaction strategy of directional alkylation fulfilled by controlling the adsorption pose of benzene and methanol in space with Ru/HZSM-5
Authors: Wang Dongliang , Li Yanwei , Zhao Yu , Ji Dong , Dong Peng , Li Guixian 
Published: May 2021

Abstract
Background
The alkylation of benzene with methanol is an important synthetic method that is widely used in various chemical production processes. However, obtaining a high selectivity for xylene and annihilating the MTO side reaction remain challenges.

Results
In this work, a Ru/HZSM-5 catalyst was prepared using ZSM-5 as the precursor by a chemical precipitation method. Both XRD and TEM confirmed that Ru nanoparticles were evenly dispersed on the surface of the ZSM-5. The catalytic performance of benzene alkylation with methanol on the Ru/HZSM-5 catalyst was investigated. The results showed that the Ru/HZSM-5 catalyst could completely annihilate the MTO side reaction with a high conversion efficiency of benzene and selectivity for xylene, which resulted from the large gap between the transgression energy value of Ru and the ionization potential value of benzene, and the acidity of the catalyst changed greatly.

Conclusion
These findings may offer not only a new and efficient multifunctional catalyst for benzene alkylation but also fundamental insight into the catalytic mechanism of the Ru/HZSM-5 catalyst.
Lactate oxidative phosphorylation by annulus fibrosus cells: evidence for lactate-dependent metabolic symbiosis in intervertebral discs
Authors: Wang Dong , Hartman Robert , Han Chao , Zhou Chao-ming , Couch Brandon , Malkamaki Matias , Roginskaya Vera , Van Houten Bennett , Mullett Steven J. , Wendell Stacy G. , Jurczak Michael J. , Kang James , Lee Joon , Sowa Gwendolyn , Vo Nam 
Published: May 2021

Abstract
Background
Intervertebral disc degeneration contributes to low back pain. The avascular intervertebral disc consists of a central hypoxic nucleus pulpous (NP) surrounded by the more oxygenated annulus fibrosus (AF). Lactic acid, an abundant end-product of NP glycolysis, has long been viewed as a harmful waste that acidifies disc tissue and decreases cell viability and function. As lactic acid is readily converted into lactate in disc tissue, the objective of this study was to determine whether lactate could be used by AF cells as a carbon source rather than being removed from disc tissue as a waste byproduct.

Methods
Import and conversion of lactate to tricarboxylic acid (TCA) cycle intermediates and amino acids in rabbit AF cells were measured by heavy-isotope (13C-lactate) tracing experiments using mass spectrometry. Levels of protein expression of lactate converting enzymes, lactate importer and exporter in NP and AF tissues were quantified by Western blots. Effects of lactate on proteoglycan (35S-sulfate) and collagen (3H-proline) matrix protein synthesis and oxidative phosphorylation (Seahorse XFe96 Extracellular Flux Analyzer) in AF cells were assessed.

Results
Heavy-isotope tracing experiments revealed that AF cells imported and converted lactate into TCA cycle intermediates and amino acids using in vitro cell culture and in vivo models. Addition of exogenous lactate (4 mM) in culture media induced expression of the lactate importer MCT1 and increased oxygen consumption rate by 50%, mitochondrial ATP-linked respiration by 30%, and collagen synthesis by 50% in AF cell cultures grown under physiologic oxygen (2-5% O2) and glucose concentration (1-5 mM). AF tissue highly expresses MCT1, LDH-H, an enzyme that preferentially converts lactate to pyruvate, and PDH, an enzyme that converts pyruvate to acetyl-coA. In contrast, NP tissue highly expresses MCT4, a lactate exporter, and LDH-M, an enzyme that preferentially converts pyruvate to lactate.

Conclusions
These findings support disc lactate-dependent metabolic symbiosis in which lactate produced by the hypoxic, glycolytic NP cells is utilized by the more oxygenated AF cells via oxidative phosphorylation for energy and matrix production, thus shifting the current research paradigm of viewing disc lactate as a waste product to considering it as an important biofuel. These scientifically impactful results suggest novel therapeutic targets in disc metabolism and degeneration.
Repurposing beta-3 adrenergic receptor agonists for Alzheimer’s disease: beneficial effects in a mouse model
Authors: Tournissac Marine , Vu Tra-My , Vrabic Nika , Hozer Clara , Tremblay Cyntia , Mélançon Koralie , Planel Emmanuel , Pifferi Fabien , Calon Frédéric 
Published: May 2021

Abstract
Background
Old age, the most important risk factor for Alzheimer’s disease (AD), is associated with thermoregulatory deficits. Brown adipose tissue (BAT) is the main thermogenic driver in mammals and its stimulation, through β3 adrenergic receptor (β3AR) agonists or cold acclimation, counteracts metabolic deficits in rodents and humans. Studies in animal models show that AD neuropathology leads to thermoregulatory deficits, and cold-induced tau hyperphosphorylation is prevented by BAT stimulation through cold acclimation. Since metabolic disorders and AD share strong pathogenic links, we hypothesized that BAT stimulation through a β3AR agonist could exert benefits in AD as well.

Methods
CL-316,243, a specific β3AR agonist, was administered to the triple transgenic mouse model of AD (3xTg-AD) and non-transgenic controls from 15 to 16 months of age at a dose of 1 mg/kg/day i.p.

Results
Here, we show that β3AR agonist administration decreased body weight and improved peripheral glucose metabolism and BAT thermogenesis in both non-transgenic and 3xTg-AD mice. One-month treatment with a β3AR agonist increased recognition index by 19% in 16-month-old 3xTg-AD mice compared to pre-treatment (14-month-old). Locomotion, anxiety, and tau pathology were not modified. Finally, insoluble Aβ42/Aβ40 ratio was decreased by 27% in the hippocampus of CL-316,243-injected 3xTg-AD mice.

Conclusions
Overall, our results indicate that β3AR stimulation reverses memory deficits and shifts downward the insoluble Aβ42/Aβ40 ratio in 16-month-old 3xTg-AD mice. As β3AR agonists are being clinically developed for metabolic disorders, repurposing them in AD could be a valuable therapeutic strategy.
Recurrent noncirrhotic hyperammonemia causing acute metabolic encephalopathy in a patient with a continent ileocecal pouch: a case report
Authors: Skipina T. M. , Macbeth S. , Cummer E. L. , Wells O. L. , Kalathoor S. 
Published: May 2021

Abstract
Introduction
Acute encephalopathy, while a common presentation in the emergency department, is typically caused by a variety of metabolic, vascular, infectious, structural, or psychiatric etiologies. Among metabolic causes, hyperammonemia is relatively common and typically occurs in the setting of cirrhosis or liver dysfunction. However, noncirrhotic hyperammonemia is a rare occurrence and poses unique challenges for clinicians.

Case presentation
Here we report a rare case of a 50-year-old Caucasian female with history of bladder cancer status post chemotherapy, radical cystectomy, and ileocecal diversion who presented to the emergency department with severe altered mental status, combativeness, and a 3-day history of decreased urine output. Her laboratory tests were notable for hyperammonemia up to 289 μmol/L, hypokalemia, and hyperchloremic nonanion gap metabolic acidosis; her liver function tests were normal. Urine cultures were positive for Enterococcus faecium. Computed tomography imaging showed an intact ileoceal urinary diversion with chronic ileolithiasis. Upon administration of appropriate antibiotics, lactulose, and potassium citrate, she experienced rapid resolution of her encephalopathy and a significant reduction in hyperammonemia. Her hyperchloremic metabolic acidosis persisted, but her hypokalemia had resolved.

Conclusion
This case is an example of one of the unique consequences of urinary diversions. Urothelial tissue is typically impermeable to urinary solutes. However, when bowel segments are used, abnormal absorption of solutes occurs, including exchange of urinary chloride for serum bicarbonate, leading to a persistent hyperchloremic nonanion gap metabolic acidosis. In addition, overproduction of ammonia from urea-producing organisms can lead to abnormal absorption into the blood and subsequent oversaturation of hepatic metabolic capacity with consequent hyperammonemic encephalopathy. Although this is a rare case, prompt identification and treatment of these metabolic abnormalities is critical to prevent severe central nervous system complications such as altered mental status, coma, and even death in patients with urinary diversions.
Novel forward–backward algorithms for optimization and applications to compressive sensing and image inpainting
Authors: Suantai Suthep , Noor Muhammad Aslam , Kankam Kunrada , Cholamjiak Prasit 
Published: May 2021

AbstractThe forward–backward algorithm is a splitting method for solving convex minimization problems of the sum of two objective functions. It has a great attention in optimization due to its broad application to many disciplines, such as image and signal processing, optimal control, regression, and classification problems. In this work, we aim to introduce new forward–backward algorithms for solving both unconstrained and constrained convex minimization problems by using linesearch technique. We discuss the convergence under mild conditions that do not depend on the Lipschitz continuity assumption of the gradient. Finally, we provide some applications to solving compressive sensing and image inpainting problems. Numerical results show that the proposed algorithm is more efficient than some algorithms in the literature. We also discuss the optimal choice of parameters in algorithms via numerical experiments.
Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study
Authors: Zivanovic Oliver , Chi Dennis S. , Zhou Qin , Iasonos Alexia , Konner Jason A. , Makker Vicky , Grisham Rachel N. , Brown Amy K. , Nerenstone Stacy , Diaz John P. , Schroeder Eric D. , Langstraat Carrie L. , Paroder Viktoriya , Lakhman Yulia , Soldan Krysten , Su Katy , Gardner Ginger J. , Andikyan Vaagn , Guo Jianxia , Jewell Elizabeth L. , Long Roche Kara , Troso-Sandoval Tiffany , Lichtman Stuart M. , Moukarzel Lea A. , Dessources Kimberly , Abu-Rustum Nadeem R. , Aghajanian Carol , Tew William P. , Beumer Jan , Sonoda Yukio , O'Cearbhaill Roisin E. 
Published: May 2021

PURPOSEThe purpose of this phase II study was to evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin for recurrent ovarian cancer during secondary cytoreductive surgery.MATERIALS AND METHODSPatients were intraoperatively randomly assigned to carboplatin HIPEC (800 mg/m2for 90 minutes) or no HIPEC, followed by five or six cycles of postoperative IV carboplatin-based chemotherapy, respectively. Based on a binomial single-stage pick-the-winner design, an arm was considered winner if ≥ 17 of 49 patients were without disease progression at 24 months post-surgery. Secondary objectives included postoperative toxicity and HIPEC pharmacokinetics.RESULTSOf 98 patients, 49 (50%) received HIPEC. Complete gross resection was achieved in 82% of the HIPEC patients and 94% of the standard-arm patients. Bowel resection was performed in 37% of patients in the HIPEC arm compared with 65% in the standard ( P = .008). There was no perioperative mortality and no difference in use of ostomies, length of stay, or postoperative toxicity. At 24 months, eight patients (16.3%; 1-sided 90% CI, 9.7 to 100) were without progression or death in the HIPEC arm and 12 (24.5%; 1-sided 90% CI, 16.5 to 100) in the standard arm. With a medium follow-up of 39.5 months, 82 patients progressed and 37 died. The median progression-free survival in the HIPEC and standard arms were 12.3 and 15.7 months, respectively (hazard ratio, 1.54; 95% CI, 1 to 2.37; P = .05). There was no significant difference in median overall survival (52.5 v 59.7 months, respectively; hazard ratio, 1.39; 95% CI, 0.73 to 2.67; P = .31). These analyses were exploratory.CONCLUSIONHIPEC with carboplatin was well tolerated but did not result in superior clinical outcomes. This study does not support the use of HIPEC with carboplatin during secondary cytoreductive surgery for platinum-sensitive recurrent ovarian cancer.
Rare Variants in Triglycerides-Related Genes Increase Pancreatitis Risk in Multifactorial Chylomicronemia Syndrome
Authors: Paquette Martine , Amyot Julie , Fantino Manon , Baass Alexis , Bernard Sophie 
Published: May 2021

Abstract

Context
Severe hypertriglyceridemia (fasting triglycerides [TG] concentration ≥10 mmol/L) can be caused by multifactorial chylomicronemia syndrome (MCS) or familial chylomicronemia syndrome (FCS). Both conditions are associated with an increased risk of acute pancreatitis. The clinical differences between MCS patients with or without a rare variant in TG-related genes have never been studied.

Objective
To compare the clinical and biochemical characteristics of FCS, positive-MCS patients, and negative-MCS patients, as well as to investigate the predictors of acute pancreatitis in MCS patients.

Methods
All patients referred at the clinic for severe hypertriglyceridemia underwent genetic testing for the 5 canonical genes involved in TG metabolism (LPL, APOC2, GPIHBP1, APOA5, and LMF1) using next-generation sequencing.

Results
A total of 53 variant negative-MCS, 22 variant positive-MCS and 28 FCS subjects were included in this retrospective cross-sectional study. A significant difference was observed in the prevalence of pancreatitis (9%, 41%, and 61%) and multiple pancreatitis (6%, 23%, and 46%) in the negative-MCS, the positive-MCS, and the FCS groups, respectively (P &lt; 0.0001). Predictors of pancreatitis among MCS subjects included the presence of a rare variant, lower apolipoprotein B, as well as higher gamma-glutamyl transferase, maximal TG value, and fructose consumption.

Conclusion
We observed that the MCS individuals who carried a rare variant have an intermediate phenotype between FCS and negative-MCS subjects. Since novel molecules such as the antisense oligonucleotide against APOC3 mRNA showed high efficacy in reducing TG levels in patients with multifactorial chylomicronemia, identification of higher-risk MCS patients who would benefit from additional treatment is essential.
Tafazzin Deficiency Reduces Basal Insulin Secretion and Mitochondrial Function in Pancreatic Islets From Male Mice
Authors: Cole Laura K , Agarwal Prasoon , Doucette Christine A , Fonseca Mario , Xiang Bo , Sparagna Genevieve C , Seshadri Nivedita , Vandel Marilyne , Dolinsky Vernon W , Hatch Grant M 
Published: May 2021

Abstract
Tafazzin (TAZ) is a cardiolipin (CL) biosynthetic enzyme important for maintaining mitochondrial function. TAZ affects both the species and content of CL in the inner mitochondrial membrane, which are essential for normal cellular respiration. In pancreatic β cells, mitochondrial function is closely associated with insulin secretion. However, the role of TAZ and CL in the secretion of insulin from pancreatic islets remains unknown. Male 4-month-old doxycycline-inducible TAZ knock-down (KD) mice and wild-type littermate controls were used. Immunohistochemistry was used to assess β-cell morphology in whole pancreas sections, whereas ex vivo insulin secretion, CL content, RNA-sequencing analysis, and mitochondrial oxygen consumption were measured from isolated islet preparations. Ex vivo insulin secretion under nonstimulatory low-glucose concentrations was reduced ~52% from islets isolated from TAZ KD mice. Mitochondrial oxygen consumption under low-glucose conditions was also reduced ~58% in islets from TAZ KD animals. TAZ deficiency in pancreatic islets was associated with significant alteration in CL molecular species and elevated polyunsaturated fatty acid CL content. In addition, RNA-sequencing of isolated islets showed that TAZ KD increased expression of extracellular matrix genes, which are linked to pancreatic fibrosis, activated stellate cells, and impaired β-cell function. These data indicate a novel role for TAZ in regulating pancreatic islet function, particularly under low-glucose conditions.