bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different patterns of cerebral perfusion in SLE patients with and without neuropsychiatric manifestations
Authors: Zhuo Zhizheng , Su Li , Duan Yunyun , Huang Jing , Qiu Xiaolu , Haller Sven , Li Haiyun , Zeng Xiaofeng , Liu Yaou 
Published: October 2019

AbstractTo investigate brain perfusion patterns in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric systemic lupus erythematosus (NPSLE and non‐NPSLE, respectively) and to identify biomarkers for the diagnosis of NPSLE using noninvasive three‐dimensional (3D) arterial spin labeling (ASL). Thirty‐one NPSLE and 24 non‐NPSLE patients and 32 age‐ and sex‐matched normal controls (NCs) were recruited. Three‐dimensional ASL‐MRI was applied to quantify cerebral perfusion. Whole brain, gray (GM) and white matter (WM), and voxel‐based analysis (VBA) were performed to explore perfusion characteristics. Correlation analysis was performed to find the relationship between the perfusion measures, lesion volumes, and clinical variables. Receiver operating characteristic (ROC) analysis and support vector machine (SVM) classification were applied to differentiate NPSLE patients from non‐NPSLE patients and healthy controls. Compared to NCs, NPSLE patients showed increased cerebral blood flow (CBF) within WM but decreased CBF within GM, while non‐NPSLE patients showed increased CBF within both GM and WM. Compared to non‐NPSLE patients, NPSLE patients showed significantly reduced CBF in the frontal gyrus, cerebellum, and corpus callosum. CBF within several brain regions such as cingulate and corpus callosum showed significant correlations with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics (SLICC) damage index scores. ROC analysis showed moderate performance in distinguishing NPSLE from non‐NPSLE patients with AUCs > 0.7, while SVM analysis demonstrated that CBF within the corpus callosum achieved an accuracy of 83.6% in distinguishing NPSLE from non‐NPSLE patients. Different brain perfusion patterns were observed between NPSLE and non‐NPSLE patients. CBF measured by noninvasive 3D ASL could be a useful biomarker for the diagnosis and disease monitoring of NPSLE and non‐NPSLE patients.
The relations of dosimetric parameters with long‐term outcomes and late toxicities in advanced T‐stage nasopharyngeal carcinoma with IMRT
Authors: Gou Xiaoxia , Duan Baofeng , Shi Huashan , Qin Lei , Xiao Jianghong , Chen Nianyong 
Published: October 2019

AbstractBackgroundBalancing the dose requirements between targets and normal tissue is a challenge in radiation of nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the dosimetric parameters and clinical outcomes in NPC.MethodsWe presented a retrospective review of patients with T3‐4 NPC treated by intensity‐modulated radiation therapy (IMRT). Patient characteristics, dosimetric parameters, and the follow‐up data for survival and late toxicities were analyzed.ResultsThe 5‐year overall survival, local relapse‐free survival, and distant metastasis‐free survival were 83.0%, 90.1%, and 82.4%, respectively. Multivariate analysis revealed that the volume of involved lymph node was an independent prognostic factor. The volume of primary tumor and the maximal dose were significant factors affecting temporal lobe injury.ConclusionsIMRT provided satisfactory local control for advanced T‐stage NPC, with acceptable late toxicities. The dose constraint criteria of selected critical structures can be appropriately loosen.
miR‐665 promotes the progression of gastric adenocarcinoma via elevating FAK activation through targeting SOCS3 and is negatively regulated by lncRNA MEG3
Authors: Tang Hailing , Long Qianfa , Zhuang Kun , Yan Yuan , Han Kun , Guo Hanqing , Lu Xiaolan 
Published: October 2019

AbstractStudies have found that miR‐665 acted as a tumor suppressor or an oncogene in different malignancies. miR‐665 expression was elevated in gastric adenocarcinoma tissues; however, its role and mechanism in this disease are not fully clarified. The expression of miR‐665 and its target gene was detected in human gastric adenocarcinoma tissues and cells. Moreover, we analyzed the effects of miR‐665 on the proliferation, migration, and epithelial–mesenchymal transition (EMT) of gastric adenocarcinoma cells as well as tumor growth in vivo. The mechanisms of miR‐665 in gastric adenocarcinoma were investigated by using molecular biology techniques. We found miR‐665 was upregulated and suppressor of cytokine signaling 3 (SOCS3) was downregulated in gastric adenocarcinoma tissues and cells. Elevated miR‐665 was positively correlated with tumor size, lymph node metastasis, invasion depth, TNM stage, and poor differentiation in gastric adenocarcinoma patients. Overexpression of miR‐665 promoted, whereas knockdown of miR‐665 suppressed the proliferation, migration, and EMT of gastric adenocarcinoma cells. Furthermore, we demonstrated that miR‐665 functioned through targeting SOCS3, followed by activation of the FAK/Src signaling pathway in gastric adenocarcinoma cells. miR‐665 antagomir inhibited tumor growth as well as the activation of the FAK/Src pathway but increased SOCS3 expression in nude mice. In addition, miR‐665 expression was negatively regulated by long noncoding RNA maternally expressed gene 3 (MEG3). In conclusion, miR‐665 acted as an oncogene in gastric adenocarcinoma by inhibiting SOCS3 followed by activation of the FAK/Src pathway and it was negatively modulated by MEG3. miR‐665 may be a promising therapeutic target for the treatment of gastric adenocarcinoma.
Reversals in complex traits uncovered as reticulation events: Lessons from the evolution of parity‐mode, chromosome morphology, and maternal resource transfer
Authors: Horreo Jose L. , Suarez Teresa , Fitze Patrick S. 
Published: October 2019

AbstractComplex traits include, among many others, the evolution of eyes, wings, body forms, reproductive modes, human intelligence, social behavior, diseases, and chromosome morphology. Dollo's law states that the evolution of complex traits is irreversible. However, potential exceptions have been proposed. Here, we investigated whether reticulation, a simple and elegant means by which complex characters may be reacquired, could account for suggested reversals in the evolution of complex characters using two datasets with sufficient genetic coverage and a total of five potential reversals. Our analyses uncovered a potential reversal in the evolution of parity mode and a potential reversal in the evolution of placentotrophy of fish (Cyprinodontiformes) as reticulation events. Moreover, in a reptile that exhibits a potential reversal from viviparity to oviparity (Zootoca vivipara), reticulation provided the most parsimonious explanation for sex chromosome evolution. Therefore, three of the five studied potential reversals were unraveled as reticulation events. This constitutes the first evidence that accounting for reticulation can fundamentally influence the interpretation of the evolution of complex traits, that testing for reticulation is crucial for obtaining robust phylogenies, and that complex ancestral characters may be reacquired through hybridization with a lineage that still exhibits the trait. Hybridization, rather than reappearance of ancestral traits by means of small evolutionary steps, may thus account for suggested exceptions to Dollo's law. Consequently, ruling out reticulation is required to claim the evolutionary reversal of complex characters and potential exceptions to Dollo's rule.
Challenges and facilitators of transition from adolescent to adult HIV care among young adults living with HIV in Moshi, Tanzania
Authors: Masese Rita V , Ramos Julia V , Rugalabamu Leonia , Luhanga Severa , Shayo Aisa M , Stewart Kearsley A , Cunningham Coleen K , Dow Dorothy E 
Published: October 2019

AbstractIntroductionScale up of anti‐retroviral therapy has enabled millions of children infected with HIV to survive into adulthood, requiring transition of care to the adult HIV clinic. This transition period is often met with anxiety and reluctance. Youth who fail to transition may create strain on capacity in the pediatric and adolescent clinics or result in individuals dropping out of care entirely. This study examined challenges and facilitators to the transition among young adults living with HIV in Moshi, Tanzania.MethodsFrom April to June 2017, in‐depth interviews were conducted with young adults aged 18 to 27 years living with HIV in order to capture the spectrum of experiences from pre‐transitioning youth to those who successfully transitioned to adult care. Young adults were purposively recruited based on prior study enrollees and recommendations from healthcare staff. Recruitment occurred in the adolescent, adult HIV and the prevention of mother to child transition clinics at Kilimanjaro Christian Medical Centre. Two separate in‐depth interviews were conducted with eligible participants. Medical records were reviewed retrospectively to collect information on HIV‐related outcomes.ResultsIn‐depth interviews were held with 19 young adults. Participants mean age was 23.8 years (interquartile range 22.2 to 26.3 years); 53% were female. Most (78.9%) participants had been receiving anti‐retroviral therapy for nearly a decade and 72.2% were virologically suppressed (HIV RNA <200 copies/mL). Barriers to transition included fear of losing peer networks formed in the adolescent clinic, the abrupt manner in which young adults were asked to transition, stigma, financial constraints and a lower quality of care in the adult clinic. Facilitators of transition included family and social support, positive perspectives on living with HIV and maintenance of good health. Recommendations for transition included transition preparation, transition as a group and adoption of desirable aspects of the adolescent clinic (peer networks and education) in the adult clinic.ConclusionsTransition is a complex process influenced by many factors. As the number of young adults living with HIV continues to grow, it is vital to develop a transition protocol that addresses these challenges and is feasible to implement in low‐resource settings.
Structural analysis of pathogenic mutations targeting Glu427 of ALDH7A1, the hot spot residue of pyridoxine‐dependent epilepsy
Authors: Laciak Adrian R. , Korasick David A. , Gates Kent S. , Tanner John J. 
Published: October 2019

AbstractCertain loss‐of‐function mutations in the gene encoding the lysine catabolic enzyme aldehyde dehydrogenase 7A1 (ALDH7A1) cause pyridoxine‐dependent epilepsy (PDE). Missense mutations of Glu427, especially Glu427Gln, account for ~30% of the mutated alleles in PDE patients, and thus Glu427 has been referred to as a mutation hot spot of PDE. Glu427 is invariant in the ALDH superfamily and forms ionic hydrogen bonds with the nicotinamide ribose of the NAD+ cofactor. Here we report the first crystal structures of ALDH7A1 containing pathogenic mutations targeting Glu427. The mutant enzymes E427Q, Glu427Asp, and Glu427Gly were expressed in Escherichia coli and purified. The recombinant enzymes displayed negligible catalytic activity compared to the wild‐type enzyme. The crystal structures of the mutant enzymes complexed with NAD+ were determined to understand how the mutations impact NAD+ binding. In the E427Q and E427G structures, the nicotinamide mononucleotide is highly flexible and lacks a defined binding pose. In E427D, the bound NAD+ adopts a “retracted” conformation in which the nicotinamide ring is too far from the catalytic Cys residue for hydride transfer. Thus, the structures revealed a shared mechanism for loss of function: none of the variants are able to stabilise the nicotinamide of NAD+ in the pose required for catalysis. We also show that these mutations reduce the amount of active tetrameric ALDH7A1 at the concentration of NAD+ tested. Altogether, our results provide the three‐dimensional molecular structural basis of the most common pathogenic variants of PDE and implicate strong (ionic) hydrogen bonds in the aetiology of a human disease.
Singlet oxygen‐induced protein aggregation: Lysozyme crosslink formation and nLC‐MS/MS characterization
Authors: Marques Emerson Finco , Medeiros Marisa H.G. , Di Mascio Paolo 
Published: October 2019

AbstractSinglet molecular oxygen (1O2) has been associated with a number of physiological processes. Despite the recognized importance of 1O2‐mediated protein modifications, little is known about the role of this oxidant in crosslink formation and protein aggregation. Thus, using lysozyme as a model, the present study sought to investigate the involvement of 1O2 in crosslink formation. Lysozyme was photochemically oxidized in the presence of rose bengal or chemically oxidized using [18O]‐labeled 1O2 released from thermolabile endoperoxides. It was concluded that both 1O2 generating systems induce lysozyme crosslinking and aggregation. Using SDS‐PAGE and nano‐scale liquid chromatography coupled to electrospray ionization mass spectrometry, the results clearly demonstrated that 1O2 is directly involved in the formation of covalent crosslinks involving the amino acids histidine, lysine, and tryptophan.
An ultra high performance liquid chromatography with tandem mass spectrometry method for simultaneous determination of thirteen components extracted from Radix Puerariae in rat plasma and tissues: Application to pharmacokinetic and tissue distribution study
Authors: Wei Liuting , Zhu Pingchuan , Chen Xiaoqing , Wang Yilin , Xu Yuanjin 
Published: October 2019

AbstractA rapid and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was established and validated for simultaneous determination of thirteen bioactive components (gallic acid, protocatechuic acid, puerarin, p‐hydroxycinnamic acid, daidzin, ononin, daidzein, naringenin, genistein, apigenin, formononetin, biochanin A, and β‐sitosterol) of Radix Puerariae extract in rat plasma and tissues. The plasma and tissues samples were pretreated by protein precipitation extraction, and umbelliferone and rutin were used as internal standards. Sample separation was performed on a ZORBAX RRHD Eclipse plus C18 column (2.1 mm × 50 mm, 1.8 µm, Agilent) with a mobile phase consisting of methanol–water (containing 0.1% formic acid). The mass spectrometry analysis was conducted in positive and negative ionization modes with multiple reaction monitoring. The lower limit of quantitation range for the 13 analytes was 0.2−35 ng/mL. The intra‐ and inter‐day precision of all the analytes were less than 10.92%, with an accuracy ranging from −13.10 to 11.96%. Both the recovery and matrix effect were within acceptable limits. This method was successfully applied to pharmacokinetic and tissue distribution study of the 13 bioactive components in rats after oral administration of R. Puerariae extract.
Comparison of total nitrogen data from direct and Kjeldahl‐based approaches in integrated data sets
Authors: Stanley Emily H. , Rojas‐Salazar Shirley , Lottig Noah R. , Schliep Erin M. , Filstrup Christopher T. , Collins Sarah M. 
Published: October 2019

AbstractThere are multiple protocols for determining total nitrogen (TN) in water, but most can be grouped into direct approaches (TN‐d) that convert N forms to nitrogen‐oxides (NOx) and combined approaches (TN‐c) that combine Kjeldahl N (organic N +NH3) and nitrite+nitrate (NO2+NO3‐N). TN concentrations from these two approaches are routinely treated as equal in studies that use data derived from multiple sources (i.e., integrated data sets) despite the distinct chemistries of the two methods. We used two integrated data sets to determine if TN‐c and TN‐d results were interchangeable. Accuracy, determined as the difference between reported concentrations and the most probable value (MPV) of reference samples, was high and similar in magnitude (within 3.5–4.5% of the MPV) for both methods, although the bias was significantly smaller at low concentrations for TN‐d. Detection limits and data flagged as below detection suggested greater sensitivity for TN‐d for one data set, while patterns from the other data set were ambiguous. TN‐c results were more variable (less precise) by many measures, although TN‐d data included a small fraction of notably inaccurate results. Precision of TN‐c was further compromised by propagated error, which may not be acknowledged or detectable in integrated data sets unless complete metadata are available and inspected. Finally, concurrent measures of TN‐c and TN‐d in lake samples were extremely similar. Overall, TN‐d tended to be slightly more accurate and precise, but similarities in accuracy and the near 1 : 1 relationship for concurrent TN‐d and TN‐c measurements support careful use of data interchangeably in analyses of heterogeneous, integrated data sets.
Cryptogenic small‐fiber neuropathies: Serum autoantibody binding to trisulfated heparan disaccharide and fibroblast growth factor receptor‐3
Authors: Levine Todd D. , Kafaie Jafar , Zeidman Lawrence A. , Saperstein David S. , Massaquoi Reyanna , Bland Ruth J. , Pestronk Alan 
Published: October 2019

AbstractIntroductionCauses of small‐fiber peripheral neuropathies (SFN) are often undefined. In this study we investigated associations of serum autoantibodies, immunoglobulin G (IgG) vs fibroblast growth factor receptor‐3 (FGFR‐3), and immunoglobulin M (IgM) vs trisulfated heparan disaccharide (TS‐HDS) in cryptogenic SFN.MethodsOne hundred fifty‐five patients with biopsy‐proven SFN and no identified cause for their neuropathy were blindly tested for serum IgM vs TS‐HDS and IgG vs FGFR‐3.ResultsForty‐eight percent of SFN patients had serum antibodies, 37% with IgM vs TS‐HDS and 15% with IgG vs FGFR‐3. TS‐HDS antibodies were more frequent in SFN patients than in controls (P = .0012). Both antibodies were more common in females, and with non–length‐dependent nerve pathology. Nintey‐two percent of patients with acute‐onset SFN had serum IgM vs TS‐HDS.DiscussionAutoantibodies directed against TS‐HDS and FGFR‐3 suggest an immune disorder in otherwise idiopathic SFN. Serum IgM vs TS‐HDS may be a marker for SFN with an acute onset.
Non‐masticatory dental wear patterns in individuals exhumed from the Middle Bronze Age rock‐cut tombs of Torre Velha 3 (Serpa, Portugal)
Authors: Fidalgo Daniel , Silva Ana Maria , Porfírio Eduardo 
Published: October 2019

AbstractDental examination of 21 individuals (11 females, nine males and one undetermined sex) exhumed from the rock‐cut tombs of Torre Velha 3 (Serpa, Portugal), dating from the 2nd millennium BC, revealed dental wear features and oral lesions that can be linked to non‐masticatory activities and/or dietary habits. A total of 471 teeth were macroscopically analyzed. One young‐adult female and a middle‐age adult of unknown sex display lingual surface attrition of the maxillary anterior teeth (LSAMAT). A middle‐age adult female has LSAMAT, anterior occlusal surface groove (AOSG) and chipping. Two other middle‐age adult females have oblique wear planes (OWP), one of them also with chipping. Overall variation and low frequencies of the observed alterations suggest that multiple activities and/or dietary habits could have caused these wear patterns. The hypothesis that atypical wear patterns are sex biased was tested using Fischer's exact test, and results were not statistically significant (p‐value = 0.09). Thus, it is possible to infer that these individuals had possible dietary or cultural idiosyncratic behaviors, besides repetitive non‐masticatory task related‐activities.
Polycaprolactone‐chitosan‐polypyrrole conductive biocomposite nanofibrous scaffold for biomedical applications
Authors: Talebi Alireza , Labbaf Sheyda , Karimzadeh Fathallah 
Published: October 2019

AbstractIn this study, polycaprolactone/chitosan/polypyrrole (PCL/chitosan/PPy) conductive composite nanofibrous scaffold is fabricated. For this purpose, initially, a polymer blend of PCL/chitosan (7:3) and (4:1) was selected and then 1, 2.5, 5 and 7.5 wt% of PPy was added to each solution. A range of techniques were applied to study the chemical, physical and biodegradability properties of the resultant fibrous mats. According to scanning electron microscope (SEM) images, with the addition of PPy to the PCL/chitosan blend, the size of the fiber diameter decrease. There was significant increase in the electrical conductivity of the mats such that the electrical conductivity of PCL/chitosan was around 0.1 S/cm but increased to 2 S/cm in biological environment with the addition of 7.5% PPy. Hydrophobicity was found to improve with the addition of PPy as water contact angle changed from 120 ± 10° for PCL/chitosan to 133 ± 18° at 7.5% PPy. The incorporation of PPy within the PCL/chitosan matrix was found to positively influence the overall properties of nanofibrous structure, making them suitable for biomedical applications.
Mass Spectrometry‐Based Analysis of Time‐Resolved Proteome Quantification
Authors: Valdés Alberto , Bergström Lind Sara 
Published: October 2019

AbstractThe aspect of time is essential in biological processes and thus it is important to be able to monitor signaling molecules through time. Proteins are key players in cellular signaling and they respond to many stimuli and change their expression in many time‐dependent processes. Mass spectrometry (MS) is an important tool for studying proteins, including their posttranslational modifications and their interaction partners—both in qualitative and quantitative ways. In order to distinguish the different trends over time, proteins, modification sites, and interacting proteins must be compared between different time points, and therefore relative quantification is preferred. In this review, the progress and challenges for MS‐based analysis of time‐resolved proteome dynamics are discussed. Further, aspects on model systems, technologies, sampling frequencies, and presentation of the dynamic data are discussed.
Consideration of a Credibility Assessment Framework in Model‐Informed Drug Development: Potential Application to Physiologically‐Based Pharmacokinetic Modeling and Simulation
Authors: Kuemmel Colleen , Yang Yuching , Zhang Xinyuan , Florian Jeffry , Zhu Hao , Tegenge Million , Huang Shiew‐Mei , Wang Yaning , Morrison Tina , Zineh Issam 
Published: October 2019

The use of computational models in drug development has grown during the past decade. These model‐informed drug development (MIDD) approaches can inform a variety of drug development and regulatory decisions. When used for regulatory decision making, it is important to establish that the model is credible for its intended use. Currently, there is no consensus on how to establish and assess model credibility, including the selection of appropriate verification and validation activities. In this article, we apply a risk‐informed credibility assessment framework to physiologically‐based pharmacokinetic modeling and simulation and hypothesize this evidentiary framework may also be useful for evaluating other MIDD approaches. We seek to stimulate a scientific discussion around this framework as a potential starting point for uniform assessment of model credibility across MIDD. Ultimately, an overarching framework may help to standardize regulatory evaluation across therapeutic products (i.e., drugs and medical devices).