bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social Relationship Quality Among Patients With Chronic Pain: A Population-Based Sample
Authors: Philpot Lindsey M , Schumann Matthew E , Ebbert Jon O 
Published: August 2019

Objective: Chronic daily pain is experienced by 11.2% of United States adults and psychosocial factors have significant impact on self-reported pain. Most research in this area has focused on pain-related conditions, not the general population. This study sought to understand the associations between clinically significant chronic pain and multiple dimensions of social relationship quality in a general population. Methods: A cross-sectional survey was deployed and adjusted logistic regression models were constructed for chronic pain against independent social support domains. The moderating effect of self-rated health on social support quality was explored. Results: Of all, 26.1% of surveys were completed (3920/15 000) and 18.8% reported clinically significant chronic pain. Patients with chronic pain had lower friendship quality (aOR = 0.78; 0.64-0.94) and higher perceived rejection (aOR = 1.26; 1.04-1.53) and perceived hostility (aOR = 1.26; 1.05-1.52). Within our moderation analysis, chronic pain patients with low self-rated health had higher odds of low friendship quality, high loneliness, and high perceived rejection. Conclusions: Chronic pain patients experience social relationships differently than those without, and self-rated health differentially impacts these perceptions.
The multi-peak adaptive landscape of crocodylomorph body size evolution
Authors: Godoy Pedro L. , Benson Roger B. J. , Bronzati Mario , Butler Richard J. 
Published: August 2019

AbstractBackgroundLittle is known about the long-term patterns of body size evolution in Crocodylomorpha, the > 200-million-year-old group that includes living crocodylians and their extinct relatives. Extant crocodylians are mostly large-bodied (3–7 m) predators. However, extinct crocodylomorphs exhibit a wider range of phenotypes, and many of the earliest taxa were much smaller (< 1.2 m). This suggests a pattern of size increase through time that could be caused by multi-lineage evolutionary trends of size increase or by selective extinction of small-bodied species. Here, we characterise patterns of crocodylomorph body size evolution using a model fitting-approach (with cranial measurements serving as proxies). We also estimate body size disparity through time and quantitatively test hypotheses of biotic and abiotic factors as potential drivers of crocodylomorph body size evolution.ResultsCrocodylomorphs reached an early peak in body size disparity during the Late Jurassic, and underwent an essentially continual decline since then. A multi-peak Ornstein-Uhlenbeck model outperforms all other evolutionary models fitted to our data (including both uniform and non-uniform), indicating that the macroevolutionary dynamics of crocodylomorph body size are better described within the concept of an adaptive landscape, with most body size variation emerging after shifts to new macroevolutionary regimes (analogous to adaptive zones). We did not find support for a consistent evolutionary trend towards larger sizes among lineages (i.e., Cope’s rule), or strong correlations of body size with climate. Instead, the intermediate to large body sizes of some crocodylomorphs are better explained by group-specific adaptations. In particular, the evolution of a more aquatic lifestyle (especially marine) correlates with increases in average body size, though not without exceptions.ConclusionsShifts between macroevolutionary regimes provide a better explanation of crocodylomorph body size evolution on large phylogenetic and temporal scales, suggesting a central role for lineage-specific adaptations rather than climatic forcing. Shifts leading to larger body sizes occurred in most aquatic and semi-aquatic groups. This, combined with extinctions of groups occupying smaller body size regimes (particularly during the Late Cretaceous and Cenozoic), gave rise to the upward-shifted body size distribution of extant crocodylomorphs compared to their smaller-bodied terrestrial ancestors.
RETRACTED ARTICLE: Long non-coding RNA MACC1-AS1 promoted pancreatic carcinoma progression through activation of PAX8/NOTCH1 signaling pathway
Authors: Qi Chen , Xiaofeng Chen , Dongen Li , Liang Yang , Liping Xu , Yue Hu , Jianshuai Jiang 
Published: August 2019

Abstract
Background
Accumulated evidences have demonstrated that long non-coding RNAs (lncRNAs) are dysregulated and correlate with the pathophysiological basis of malignant tumors. The objective of this research is to uncover the possible molecular mechanism of MACC1-AS1 regarding the regulation of pancreatic carcinoma (PC) metastasis.

Methods
lncRNA microarray and qRT-PCR were applied to identify differentially expressed lncRNA profile in PC. The function and role of MACC1-AS1 in PC were assessed via in vitro as well as in vivo assays. Luciferase analyses, RNA immunoprecipitation, and RNA pull-down were performed to determined the underlying MACC1-AS1 mechanisms.

Results
Numbers of differentially expressed lncRNAs in PC were identified via lncRNA microarrays, among which MACC1-AS1 was revealed as the most abundant lncRNA. The upregulation of MACC1-AS1 in PC was further confirmed in two expanded PC cohorts, which showed that MACC1-AS1 expression was upregulated in those PC patients with poor survival. Functionally, knockdown of MACC1-AS1 inhibited the proliferation as well as metastasis of PC cells. Meanwhile, MACC1-AS1 upregulated the expression of PAX8 protein, which promoted aerobic glycolysis and activated NOTCH1 signaling. Additionally, PAX8 was upregulated in PC tissues, which was correlated with the expression of MACC1-AS1 and the overall survival of PC patients.

Conclusions
Together, our findings indicate a critical role of MACC1-AS1/PAX8/NOTCH1 signaling, which may be an alternative treatment target in PC therapy.
The progression rate of peripheral arterial disease in patients with intermittent claudication: a systematic review
Authors: Mizzi A. , Cassar K. , Bowen C. , Formosa C. 
Published: August 2019

AbstractBackgroundIntermittent claudication (IC) is the most common symptom of peripheral arterial disease and is generally treated conservatively due to limited prognostic evidence to support early revascularisation in the individual patient. This approach may lead to the possible loss of opportunity of early revascularisation in patients who are more likely to deteriorate to critical limb ischaemia. The aim of this review is to evaluate the available literature related to the progression rate of symptomatic peripheral arterial disease.MethodsWe conducted a systematic review of the literature in PubMed and MEDLINE, Cochrane library, Elsevier, Web of Science, CINAHL and Opengrey using relevant search terms to identify the progression rate of peripheral arterial disease in patients with claudication. Outcomes of interest were progression rate in terms of haemodynamic measurement and time to development of adverse outcomes. Two independent reviewers determined study eligibility and extracted descriptive, methodologic, and outcome data. Quality of evidence was evaluated using the Cochrane recommendations for assessing risk of bias and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines.ResultsSeven prospective cohort studies and one retrospective cohort study were identified and included in this review with the number of participants in each study ranging from 38 to 1244. Progression rate reports varied from a yearly decrease of 0.01 in ankle‐brachial pressure index (ABPI) to a yearly decrease ABPI of 0.014 in 21% of participants. Quality of evidence ranged from low to moderate mostly due to limited allocation concealment at recruitment and survival selection bias.ConclusionsProgression of PAD in IC patients is probably underestimated in the literature due to study design issues. Predicting which patients with claudication are likely to deteriorate to critical limb ischaemia is difficult since there is a lack of evidence related to lower limb prognosis. Further research is required to enable early identification of patients at high risk of progressing to critical ischaemia and appropriate early revascularisation to reduce lower limb morbidity.
Stratigraphic architecture and petrophysical characterization of formations for deep disposal in the Fort Worth Basin, Texas
Authors: Smye Katie M. , Lemons Casee R. , Eastwood Ray , McDaid Guinevere , Hennings Peter H. 
Published: August 2019

Disposal of hydraulic fracturing flowback and produced water into Ordovician and Cambrian formations of the Fort Worth Basin (FWB), coupled with an increase in observed seismicity in the Dallas-Fort Worth area, necessitates an understanding of the geologic character of these disposal targets. More than 2 billion barrels (Bbbls) of wastewater have been disposed into the Ordovician Ellenburger Group of the FWB over the past 35 years. Since the implementation of the TexNet Earthquake Catalog (1 January 2017), more than 20 earthquakes of local magnitude ML2.0 or greater have been detected in the area, with depths ranging from 2 to 10 km (approximately 6500–33,000 ft). The cited mechanism for inducement of these earthquakes is reactivation of basement faults due to pore pressure changes, either directly related to proximal disposal or due to disposal volume buildup over time. Here, we present a stratigraphic and petrophysical analysis of FWB disposal targets and their relation to basement rocks. The Ellenburger consists of alternating layers of limestone and dolomite, with minor siliciclastics above the basement toward the Llano Uplift. Matrix porosity averages <5 porosity units (p.u.), with higher porosity in dolomitic layers than in limestone. Dolomite dominates at the top of the Ellenburger, which was exposed at the end of both the Lower and Upper Ordovician. Where crystalline basement rocks are penetrated, the composition ranges from granitic to chlorite-bearing metamorphosed lithology. The basement-sediment interface is frequently marked by increased porosity. An updated map of structure on top of basement indicates elevations ranging from outcrop at the Llano Uplift to more than [Formula: see text] ([Formula: see text]) subsea toward the northeast. The disposal zone pore volume is estimated from thickness and porosity maps and ranges from [Formula: see text] to [Formula: see text] billion barrels per square mile ([Formula: see text]).
Characterization of the Role of NKA in the Control of Puberty Onset and Gonadotropin Release in the Female Mouse
Authors: León Silvia , Fergani Chrysanthi , Talbi Rajae , Simavli Serap , Maguire Caroline A , Gerutshang Achi , Navarro Víctor M 
Published: August 2019

Abstract
The tachykinin neurokinin B (NKB, Tac2) is critical for proper GnRH release in mammals, however, the role of the other tachykinins, such as substance P (SP) and neurokinin A (NKA) in reproduction, is still not well understood. In this study, we demonstrate that NKA controls the timing of puberty onset (similar to NKB and SP) and stimulates LH release in adulthood through NKB-independent (but kisspeptin-dependent) mechanisms in the presence of sex steroids. Furthermore, this is achieved, at least in part, through the autosynaptic activation of Tac1 neurons, which express NK2R (Tacr2), the receptor for NKA. Conversely, in the absence of sex steroids, as observed in ovariectomy, NKA inhibits LH through a mechanism that requires the presence of functional receptors for NKB and dynorphin (NK3R and KOR, respectively). Moreover, the ability of NKA to modulate LH secretion is absent in Kiss1KO mice, suggesting that its action occurs upstream of Kiss1 neurons. Overall, we demonstrate that NKA signaling is a critical component in the central control of reproduction, by contributing to the indirect regulation of kisspeptin release.
PKCδ Mediates Mineralocorticoid Receptor Activation by Angiotensin II to Modulate Smooth Muscle Cell Function
Authors: Lu Qing , Davel Ana P , McGraw Adam P , Rao Sitara P , Newfell Brenna G , Jaffe Iris Z 
Published: August 2019

AbstractAngiotensin II (AngII) and the mineralocorticoid receptor (MR) ligand aldosterone both contribute to cardiovascular disorders, including hypertension and adverse vascular remodeling. We previously demonstrated that AngII activates MR-mediated gene transcription in human vascular smooth muscle cells (SMCs), yet the mechanism and the impact on SMC function are unknown. Using an MR-responsive element-driven transcriptional reporter assay, we confirm that AngII induces MR transcriptional activity in vascular SMCs and endothelial cells, but not in Cos1 or human embryonic kidney-293 cells. AngII activation of MR was blocked by the MR antagonist spironolactone or eplerenone and the protein kinase C-δ (PKCδ) inhibitor rottlerin, implicating both in the mechanism. Similarly, small interfering RNA knockdown of PKCδ in SMCs prevented AngII-mediated MR activation, whereas knocking down of MR blocked both aldosterone- and AngII-induced MR function. Coimmunoprecipitation studies reveal that endogenous MR and PKCδ form a complex in SMCs that is enhanced by AngII treatment in association with increased serine phosphorylation of the MR N terminus. AngII increased mRNA expression of the SMC-MR target gene, FKBP51, via an MR-responsive element in intron 5 of the FKBP51 gene. The impact of AngII on FKBP51 reporter activity and gene expression in SMCs was inhibited by spironolactone and rottlerin. Finally, the AngII-induced increase in SMC number was also blocked by the MR antagonist spironolactone and the PKCδ inhibitor rottlerin. These data demonstrate that AngII activates MR transcriptional regulatory activity, target gene regulation, and SMC proliferation in a PKCδ-dependent manner. This new mechanism may contribute to synergy between MR and AngII in driving SMC dysfunction and to the cardiovascular benefits of MR and AngII receptor blockade in humans.
Imaging and Manipulating Pituitary Function in the Awake Mouse
Authors: Hoa Ombeline , Lafont Chrystel , Fontanaud Pierre , Guillou Anne , Kemkem Yasmine , Kineman Rhonda D , Luque Raul M , Fiordelisio Coll Tatiana , Le Tissier Paul , Mollard Patrice 
Published: August 2019

Abstract
Extensive efforts have been made to explore how the activities of multiple brain cells combine to alter physiology through imaging and cell-specific manipulation in different animal models. However, the temporal regulation of peripheral organs by the neuroendocrine factors released by the brain is poorly understood. We have established a suite of adaptable methodologies to interrogate in vivo the relationship of hypothalamic regulation with the secretory output of the pituitary gland, which has complex functional networks of multiple cell types intermingled with the vasculature. These allow imaging and optogenetic manipulation of cell activities in the pituitary gland in awake mouse models, in which both neuronal regulatory activity and hormonal output are preserved. These methodologies are now readily applicable for longitudinal studies of short-lived events (e.g., calcium signals controlling hormone exocytosis) and slowly evolving processes such as tissue remodeling in health and disease over a period of days to weeks.
Acute Deletion of METTL14 in β-Cells of Adult Mice Results in Glucose Intolerance
Authors: Men Lili , Sun Juan , Luo Guanzheng , Ren Decheng 
Published: August 2019

Abstract
N6-Methyladenosine (m6A) is the most common and abundant mRNA modification that involves regulating the RNA metabolism. However, the role of m6A in regulating the β-cell function is unclear. Methyltransferase-like 14 (METTL14) is a key component of the m6A methyltransferase complex. To define the role of m6A in regulating the β-cell function, we generated β-cell METTL14-specific knockout (βKO) mice by tamoxifen administration. Acute deletion of Mettl14 in β-cells results in glucose intolerance as a result of a reduction in insulin secretion in β-cells even though β-cell mass is increased, which is related to increased β-cell proliferation. To define the molecular mechanism, we performed RNA sequencing to detect the gene expression in βKO islets. The genes responsible for endoplasmic reticulum stress, such as Ire1α, were among the top upregulated genes. Both mRNA and protein levels of IRE1α and spliced X-box protein binding 1 (sXBP-1) were increased in βKO islets. The protein levels of proinsulin and insulin were decreased in βKO islets. These results suggest that acute METTL14 deficiency in β-cells induces glucose intolerance by increasing the IRE1α/sXBP-1 pathway.
Targeted Therapy for Advanced Thyroid Cancer: Kinase Inhibitors and Beyond
Authors: Cabanillas Maria E , Ryder Mabel , Jimenez Camilo 
Published: August 2019

AbstractThe treatment of advanced thyroid cancer has undergone rapid evolution in the last decade, with multiple kinase inhibitor drug approvals for each subtype of thyroid cancer and a number of other commercially available drugs that have been studied for this indication. Although most of the US Food and Drug Administration (FDA)–approved drugs are antiangiogenic multikinase inhibitors—vandetanib, cabozantinib, sorafenib, lenvatinib—there are two FDA indications that are mutation specific—dabrafenib/trametinib for BRAF-mutated anaplastic thyroid cancer and larotrectinib for NTRK-fusion thyroid cancer. Furthermore, other mutation-specific drugs, immunotherapies, and novel strategies for advanced thyroid cancer are under investigation. Understanding the molecular basis of thyroid cancer, the drugs of interest for treatment of advanced thyroid cancer, and how these drugs can be administered safely and in the appropriate clinical scenario are the topics of this review.
Measurement of Salivary Adrenal-Specific Androgens as Biomarkers of Therapy Control in 21-Hydroxylase Deficiency
Authors: Bacila Irina , Adaway Jo , Hawley James , Mahdi Sundus , Krone Ruth , Patel Leena , Alvi Sabah , Randell Tabitha , Gevers Evelien , Dattani Mehul , Cheetham Timothy , Kyriakou Andreas , Schiffer Lina , Ryan Fiona , Crowne Elizabeth , Davies Justin H , Ahmed Syed Faisal , Keevil Brian , Krone Nils 
Published: August 2019

AbstractBackgroundMonitoring of hormonal control represents a key part of the management of congenital adrenal hyperplasia (CAH). Monitoring strategies remain suboptimal because they rely on frequent blood tests and are not specific for adrenal-derived hormones. Recent evidence suggests the crucial role of adrenal-specific 11-oxygenated-C19 androgens in the pathogenesis of CAH.ObjectiveTo establish a correlation between plasma and salivary adrenal-specific androgens in CAH as a noninvasive monitoring strategy.DesignThis prospective cross-sectional study recruited patients between 2015 and 2018.SettingMulticenter study including 13 tertiary centers in the United Kingdom.ParticipantsSeventy-eight children with CAH and 62 matched healthy controls.MethodsUsing liquid chromatography–tandem mass spectrometry, plasma and salivary concentrations of five steroids were measured: 17-hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11-hydroxyandrostenedione (11OHA4), and 11-ketotestosterone (11KT). The correlation between plasma and salivary steroids was analyzed to assess their use in clinical practice.ResultsStrong correlations between plasma and salivary steroid concentrations in patients with CAH were detected: 17OHP (rs = 0.871; P < 0.001), A4 (rs = 0.931; P < 0.001), T (rs = 0.867; P < 0.001), 11OH4A (rs = 0.876; P < 0.001), and 11KT (rs = 0.944; P < 0.001). These results were consistent for patient subgroups based on sex and age. Analysis of patient subgroups based on 17OHP concentrations established clear correlations between plasma and salivary concentrations of the adrenal-specific androgen 11KT.ConclusionsThe current study identified tight correlations between plasma and saliva for the adrenal-derived 11-oxygenated C19 androgen 11KT, as well as 17OHP and A4, which are widely used for monitoring treatment in CAH. This combination of steroid hormones will serve as an improved noninvasive salivary test for disease monitoring in patients with CAH.
Exercise Mitigates Bone Loss in Women With Severe Obesity After Roux-en-Y Gastric Bypass: A Randomized Controlled Trial
Authors: Murai Igor H , Roschel Hamilton , Dantas Wagner S , Gil Saulo , Merege-Filho Carlos , de Cleva Roberto , de Sá-Pinto Ana L , Lima Fernanda , Santo Marco A , Benatti Fabiana B , Kirwan John P , Pereira Rosa M , Gualano Bruno 
Published: August 2019

AbstractContextBone loss after bariatric surgery potentially could be mitigated by exercise.ObjectiveTo investigate the role of exercise training (ET) in attenuating bariatric surgery–induced bone loss.DesignRandomized, controlled trial.SettingReferral center for bariatric surgery.PatientsSeventy women with severe obesity, aged 25 to 55 years, who underwent Roux-en-Y gastric bypass (RYGB).InterventionSupervised, 6-month, ET program after RYGB vs. standard of care (RYGB only).OutcomesAreal bone mineral density (aBMD) was the primary outcome. Bone microarchitecture, bone turnover, and biochemical markers were secondary outcomes.ResultsSurgery significantly decreased femoral neck, total hip, distal radius, and whole body aBMD (P < 0.001); and increased bone turnover markers, including collagen type I C-telopeptide (CTX), procollagen type I N-propeptide (P1NP), sclerostin, and osteopontin (P < 0.05). Compared with RYGB only, exercise mitigated the percent loss of aBMD at femoral neck [estimated mean difference (EMD), −2.91%; P = 0.007;], total hip (EMD, −2.26%; P = 0.009), distal radius (EMD, −1.87%; P = 0.038), and cortical volumetric bone mineral density at distal radius (EMD, −2.09%; P = 0.024). Exercise also attenuated CTX (EMD, −0.20 ng/mL; P = 0.002), P1NP (EMD, −17.59 ng/mL; P = 0.024), and sclerostin levels (EMD, −610 pg/mL; P = 0.046) in comparison with RYGB. Exercise did not affect biochemical markers (e.g., 25(OH)D, calcium, intact PTH, phosphorus, and magnesium).ConclusionExercise mitigated bariatric surgery–induced bone loss, possibly through mechanisms involving suppression in bone turnover and sclerostin. Exercise should be incorporated in postsurgery care to preserve bone mass.
Continuous Free Cortisol Profiles—Circadian Rhythms in Healthy Men
Authors: Bhake R C , Kluckner V , Stassen H , Russell G M , Leendertz J , Stevens K , Linthorst A C E , Lightman S L 
Published: August 2019

AbstractContextThe pituitary–adrenal axis had historically been considered a representative model for circadian rhythms. A recently developed portable collection device has provided the opportunity to evaluate free cortisol profiles using the microdialysis approach in individuals free to conduct their day-to-day activities in their own surroundings.MethodsTwo separate experiments were conducted in healthy male volunteers. The total and subcutaneous (SC) free cortisol levels were measured at 10-minute intervals for a 24-hour period in one experiment, and the SC free cortisol levels were measured at 20-minute interval for 72 consecutive hours in free-living individuals in the second experiment.ResultsThe characteristic circadian rhythm was evident in both serum total and SC free cortisol, with the lowest levels achieved and maintained in the hours surrounding sleep onset and the peak levels occurring in every individual around waking. In all free-living individuals, the circadian rhythm was consistent across the 72-hour period, despite a wide range of activities. All the participants also showed increased cortisol after the consumption of lunch. The lowest levels during all 24-hour periods were observed during the hours after lights off, at the onset of sleep.ConclusionsTo the best of our knowledge, the present study is the first to report up to three consecutive 24-hour measurements of SC free cortisol in healthy individuals. We believe our study is a landmark study that paves the way for ambulatory monitoring of free cortisol profiles continuously for a period of 72 hours in free-living individuals performing their day-to-day activities whether healthy or with diseases involving the hypothalamic–pituitary–adrenal axis.