bluuebunny/crossref_metadata_2025_split huggingface dataset:
The spinal microglial IL-10/β-endorphin pathway accounts for cinobufagin-induced mechanical antiallodynia in bone cancer pain following activation of α7-nicotinic acetylcholine receptors
Authors: Apryani Evhy , Ali Usman , Wang Zi-Ying , Wu Hai-Yun , Mao Xiao-Fang , Ahmad Khalil Ali , Li Xin-Yan , Wang Yong-Xiang 
Published: February 2020

Abstract
Background
Cinobufagin is the major bufadienolide of Bufonis venenum (Chansu), which has been traditionally used for the treatment of chronic pain especially cancer pain. The current study aimed to evaluate its antinociceptive effects in bone cancer pain and explore the underlying mechanisms.

Methods
Rat bone cancer model was used in this study. The withdrawal threshold evoked by stimulation of the hindpaw was determined using a 2290 CE electrical von Frey hair. The β-endorphin and IL-10 levels were measured in the spinal cord and cultured primary microglia, astrocytes, and neurons.

Results
Cinobufagin, given intrathecally, dose-dependently attenuated mechanical allodynia in bone cancer pain rats, with the projected Emax of 90% MPE and ED50 of 6.4 μg. Intrathecal cinobufagin also stimulated the gene and protein expression of IL-10 and β-endorphin (but not dynorphin A) in the spinal cords of bone cancer pain rats. In addition, treatment with cinobufagin in cultured primary spinal microglia but not astrocytes or neurons stimulated the mRNA and protein expression of IL-10 and β-endorphin, which was prevented by the pretreatment with the IL-10 antibody but not β-endorphin antiserum. Furthermore, spinal cinobufagin-induced mechanical antiallodynia was inhibited by the pretreatment with intrathecal injection of the microglial inhibitor minocycline, IL-10 antibody, β-endorphin antiserum and specific μ-opioid receptor antagonist CTAP. Lastly, cinobufagin- and the specific α-7 nicotinic acetylcholine receptor (α7-nAChR) agonist PHA-543613-induced microglial gene expression of IL-10/β-endorphin and mechanical antiallodynia in bone cancer pain were blocked by the pretreatment with the specific α7-nAChR antagonist methyllycaconitine.

Conclusions
Our results illustrate that cinobufagin produces mechanical antiallodynia in bone cancer pain through spinal microglial expression of IL-10 and subsequent β-endorphin following activation of α7-nAChRs. Our results also highlight the broad significance of the recently uncovered spinal microglial IL-10/β-endorphin pathway in antinociception.
Abnormalities in spinal cord ultrastructure in a rat model of post-traumatic syringomyelia
Authors: Berliner Joel , Hemley Sarah , Najafi Elmira , Bilston Lynne , Stoodley Marcus , Lam Magdalena 
Published: February 2020

Abstract
Background
Syringomyelia is a serious complication of spinal cord trauma, occurring in approximately 28% of spinal cord injuries. Treatment options are limited and often produce unsatisfactory results. Post-traumatic syringomyelia (PTS) is presumably related to abnormalities of cerebrospinal fluid (CSF) and interstitial fluid hydrodynamics, but the exact mechanisms are unknown.

Methods
Transmission electron microscopy (TEM) was used to investigate in detail the interfaces between fluid and tissue in the spinal cords of healthy Sprague–Dawley rats (n = 3) and in a rat model of PTS (n = 3). PTS was induced by computer-controlled impact (75 kDyn) to the spinal cord between C6 and C8, followed by a subarachnoid injection of kaolin to produce focal arachnoiditis. Control animals received a laminectomy only to C6 and C7 vertebrae. Animals were sacrificed 12 weeks post-surgery, and spinal cords were prepared for TEM. Ultra-thin spinal cord sections at the level of the injury were counterstained for structural anatomy.

Results
Spinal cords from animals with PTS displayed several abnormalities including enlarged perivascular spaces, extracellular edema, cell death and loss of tissue integrity. Additionally, alterations to endothelial tight junctions and an abundance of pinocytotic vesicles, in tissue adjacent to syrinx, suggested perturbations to blood-spinal cord barrier (BSCB) function.

Conclusions
These findings support the hypothesis that perivascular spaces are important pathways for CSF flow into and out of the spinal cord, but also suggest that fluid may enter the cord through vesicular transport and an altered BSCB.
Safety and efficacy of a novel oral chewable combination tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against natural flea infestations in client-owned dogs in the USA
Authors: Kryda Kristina , Mahabir Sean P. , Inskeep Tammy , Rugg Jady 
Published: March 2020

Abstract
Background
One randomized, controlled clinical field study was conducted in 18 general veterinary practices throughout the USA to evaluate the safety and efficacy of a novel oral chewable combination tablet, Simparica Trio™, containing sarolaner, moxidectin and pyrantel for the treatment and prevention of fleas on dogs.

Methods
Client-owned dogs, from households of three or fewer dogs were eligible for enrollment. Four hundred and twenty-two dogs from 251 households were enrolled. Households were randomly assigned in a 2:1 ratio to treatment with either Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) or afoxolaner (NexGard®, Boehringer-Ingelheim) at the label dose. One dog per household was selected as the primary dog for efficacy evaluations. Treatments were dispensed and dogs were dosed in their home environment on Day 0 and on approximately Day 30. Flea counts and examination for clinical signs of flea allergy dermatitis (FAD) were performed at the initial visit the day before or on Day 0 prior to treatment and on Days 30 and 60. Additionally, all dogs were examined for general health at each visit and blood and urine were collected for clinical pathology at screening and Day 60.

Results
Simparica Trio™ reduced geometric mean live flea counts by 99.0% by Day 30 and by 99.7% by Day 60. As a result of the rapid reduction in flea infestations, clinical signs associated with FAD substantially improved following treatment. Simparica Trio™ was well-tolerated and a diverse range of concomitant medications were administered to dogs during the course of the study. Simparica Trio™ chewable tablets were well-accepted by dogs, with the majority of flavored chewable tablets (91.9%) voluntarily consumed by free choice without, or when offered in food.

Conclusions
Simparica Trio™ administered orally once monthly for two consecutive treatments was safe and effective against natural flea infestations and substantially improved clinical signs associated with FAD in client-owned dogs in a field study conducted in the USA.
Association between subthreshold depression and self-care behaviors in people with type 2 diabetes: a systematic review of observational studies
Authors: Shrestha Monika , Ng Ashley , Al-Ghareeb Amal , Alenazi Fatimah , Gray Richard 
Published: February 2020

Abstract
Background
Self-care behaviors in people living with type 2 diabetes are important to achieving optimal glycemic control. Major depression in type 2 diabetes is associated with decreased adherence to self-care behaviors. The association between subthreshold depression and self-care behaviors, however, has not previously been systematically reviewed. The objective of this review is to determine the association between subthreshold depression and self-care behaviors.

Methods
A systematic search was performed in five electronic databases that included MEDLINE, EMBASE, PsycINFO, Emcare, and CINAHL. Any observational studies in adults with type 2 diabetes, investigating the association between subthreshold depression and any self-care behaviors, were included in the review. Qualitative studies, review articles, and gray literature were excluded. Two reviewers independently completed the title and abstract and full-text screening, appraised the study quality, and extracted the data. A third reviewer resolved any discrepancies between the reviewers if needed. Included articles were critically appraised using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Meta-analyses were not conducted because criteria for conducting such analyses were not met.

Results
A total of 6408 articles were identified through the database searching. After the abstract and full-text review, two articles met the inclusion criteria. One of the included study was cross-sectional while the other was a longitudinal study. Both studies showed inconsistent findings in the association between subthreshold depression and self-care behaviors. Important risks of bias were identified in the included studies.

Discussion
The evidence from the two included studies on a possible association between subthreshold depression and self-care behaviors in adults with type 2 diabetes was not consistent and potentially biased. Our review established a gap in knowledge and suggests that further high-quality studies are needed to examine the association between subthreshold depression and self-care behaviors in people with type 2 diabetes.

Systematic review registration
PROSPERO CRD42018116373
PgCYP76B93 docks on phenylurea herbicides and its expression enhances chlorotoluron tolerance in Arabidopsis
Authors: Jang Jinhoon , Khanom Sanjida , Moon Youngkook , Shin Sooim , Lee Ok Ran 
Published: February 2020

AbstractThe phenylurea herbicides are used to control annual and perennial weeds on crop cultivating fields. The excessive usage of these agrochemicals increase many environmental problems. Thus, engineering transgenic plant for herbicide metabolism can provide efficient and eco-friendly means for enhanced phytoremediation capacity. Cytochrome P450 enzymes comprise one of the major plant enzyme families that mediate the oxidative degradation of xenobiotic chemicals, including herbicides. Considering these notions, phytoremediation properties of transgenic ginseng-derived PgCYP76B93 in Arabidopsis to phenylurea herbicides were assessed. Phylogenetic tree of PgCYP76B93 clustered in between close to the herbicide metabolism-related enzyme families and terpenoid biosynthesis-related. The expression of PgCYP76B93 was considerably upregulated upon treatment with phenylurea herbicide, chlorotoluron. Simulated docking using Autodoc program predicted possible interaction with chlorotoluron. Transgenic Arabidopsis plants overexpressing PgCYP76B93 were resulted in slightly reduced plant height with relatively small leaves. The lower plant height in the PgCYP76B93-overexpressing line than in the control revealed that it was linked to the expression of gibberellin oxidases (GAox). The bioassay of transgenic plants growing on herbicide-containing media revealed enhanced resistance against chlorotoluron.
Evening exercise is associated with lower odds of visual field progression in Chinese patients with primary open angle glaucoma
Authors: Pan Xiafei , Xu Kai , Wang Xin , Chen Guofu , Cheng Huanhuan , Liu Alice Jia , Hou Laurence Tang , Zhong Lin , Chen Jie , Liang Yuanbo 
Published: March 2020

Abstract
Background
Exercise is widely known to lower intraocular pressure and increase ocular blood flow, which may be beneficial for glaucoma management. However, there are few studies that have reported on the relationship between exercise and glaucoma progression. The aim of our study was to investigate the exercise habits of those with primary open angle glaucoma (POAG) and its association with the progression of visual field (VF) loss.

Methods
Daily physical activity (PA) was monitored by an accelerometer (ActiGraph wGT3x-BT) which patients wore for more than 10 h of being awake on their right wrists for 1 week.

Results
Seventy-one non-progressive and 27 progressive patients were enrolled in the study. 24-h moderate to vigorous physical activity (MVPA) exercise showed that POAG patients had similar variation trends consisting of 3 wave peaks and 2 wave hollows. Minutes spent in MVPA was 19.89 ± 15.81 and 21.62 ± 15.10 during 07:00–09:00 h (p = 0.204), 15.40 ± 14.49 and 15.67 ± 12.43 during 15:00–17:00 h (p = 0.822) and 17.26 ± 21.11 and 11.42 ± 11.58 during 18:00–20:00 h (p = 0.001) in the non-progressive and progressive group, respectively. Univariate analysis indicated that 10 min of MVPA (18:00–20:00 h) [odds ratio, OR (95% CI) = 0.82 (0.73, 0.92)], average mean arterial pressure [OR (95% CI) = 0.96 (0.94, 0.98)], age [OR (95% CI) = 1.06 (1.03, 1.08)], male [OR (95% CI) = 0.67 (0.48, 0.96)], spherical equivalent [OR (95% CI) = 1.14 (1.07, 1.22)] and IOP-lowering medications [OR (95% CI) = 1.54 (1.16, 2.05)] were significantly correlated with having progressive VF damage. Multivariable analysis showed that 10 min of MVPA (18:00–20:00 h) [OR (95% CI) = 0.85 (0.75, 0.97)] was associated with progressive VF loss even after adjusting for other risk factors.

Conclusions
Evening exercise may lower the odds of VF progression, suggesting that exercise habits possibly play an important role in glaucoma progression.
Does the preoperative platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio predict morbidity after gastrectomy for gastric cancer?
Authors: Mungan İbrahim , Dicle Çilem Bayındır , Bektaş Şerife , Sarı Sema , Yamanyar Serdar , Çavuş Mine , Turan Sema , Bostancı Erdal Birol 
Published: February 2020

Abstract
Background
Gastric cancer is the 2nd most common cause of cancer-related deaths, and the morbidity rate after surgery is reported to be as high as 46%. The estimation of possible complications, morbidity, and mortality and the ability to specify patients at high risk have become substantial for an intimate follow-up and for proper management in the intensive care unit. This study aimed to determine the prognostic value of the preoperative platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) and their relations with clinical outcomes and complications after gastrectomy for gastric cancer.

Methods
This single-center, retrospective cohort study evaluated the data of 292 patients who underwent gastrectomy with curative intent between January 2015 and June 2018 in a tertiary state hospital in Ankara, Turkey. A receiver operating characteristic curve was generated to evaluate the ability of laboratory values to predict clinically relevant postoperative complications. The area under the curve was computed to compare the predictive power of the NLR and PLR. Then, the cutoff points were selected as the stratifying values for the PLR and NLR.

Results
The area under the curve values of the PLR (0.60, 95% CI 0.542–0.657) and NLR (0.556, 95% CI 0.497–0.614) were larger than those of the other preoperative laboratory values. For the PLR, the diagnostic sensitivity and specificity were 50.00 and 72.22%, respectively, whereas for the NLR, the diagnostic sensitivity and specificity were 37.50 and 80.16%, respectively. The PLR was related to morbidity, whereas the relation of the NLR with mortality was more prominent. This study demonstrated that the PLR and NLR may predict mortality and morbidity via the Clavien-Dindo classification in gastric cancer patients. The variable was grade ≥ 3 in the Clavien-Dindo classification, including complications requiring surgical or endoscopic interventions, life-threatening complications, and death. Both the PLR and NLR differed significantly according to Clavien-Dindo grade ≥ 3. In this analysis, the PLR was related to morbidity, while the NLR relation with mortality was more intense.

Conclusion
Based on the results of the study, the PLR and NLR could be used as independent predictive factors for mortality and morbidity in patients with gastric cancer.
Opposite changes in blood pressure and pulse rate in two patients with distigmine and rivastigmine intoxication
Authors: Sedogawa Hiraku , Matsuo Mitsuhiro 
Published: February 2020

Abstract
Background
Cholinergic crisis caused by cholinesterase inhibitors is rare but life-threatening. Clinical manifestations are thought to be similar to those caused by organophosphates.

Case presentation
A 77-year-old woman on a standard dose of distigmine presented with impaired consciousness, blood pressure (BP) of 69/40 mmHg, a pulse rate (PR) of 60 beats/min, miosis, bronchorrhea, and serum cholinesterase (ChE) of 8 IU/L. After discontinuation of distigmine, altered mental status and pupil miosis were gradually resolved in 5 days with a concomitant increase of serum ChE. A 91-year-old woman presented with a headache, BP of 202/86 mmHg, PR of 83 beats/min, miosis, 9 rivastigmine patches on her knees, and ChE of 22 IU/L. The day after close observation without rivastigmine use, her symptoms were almost resolved with a concomitant increase of serum ChE.

Conclusion
Our cases and a literature review suggested that, in contrast to distigmine, rivastigmine-induced cholinergic crisis caused hypertension and tachycardia.
A leather coating with self-healing characteristics
Authors: Liang Feifei , Wang Tianyou , Fan Haojun , Xiang Jun , Chen Yi 
Published: February 2020

AbstractGenuine leather is often coated before making daily necessities such as shoes, clothing, bags, sofas, car seats, etc., so as to impart leather products various colours, higher wear resistance and water resistance and so on. However, the coating of these products is often damaged in daily use which will decrease its aesthetic effect and practicability. Therefore, how to improve the scratch resistance of leather coatings has been puzzling people all the time. It is a common knowledge that animals and plants can repair the injured biological tissues by himself. According to this principle, here, we prepared a type of self-healing water-borne polyurethane with disulfide bond in the main chain by using HEDS as chain extender, and the self-healing system was triggered by the disulfide bonds with the help of shape memory function of waterborne Polyurethane, self-healing experiments how that the damaged of leather coating can be repaired fully at 60 °C for 12 h.
Graphical abstract
Growth Hormone Therapy Does Not Increase the Risk of Craniopharyngioma and Nonfunctioning Pituitary Adenoma Recurrence
Authors: Losa Marco , Castellino Laura , Pagnano Angela , Rossini Alessandro , Mortini Pietro , Lanzi Roberto 
Published: February 2020

Abstract

Context
Recombinant human growth hormone (rhGH) replacement therapy is often prescribed in patients with nonfunctioning pituitary adenoma (NFPA) or craniopharyngioma,

Objective
To study whether rhGH therapy in patients with adult growth hormone deficiency (AGHD) increases the risk of pituitary tumor recurrence.

Design
Retrospective, observational study.

Setting
Tertiary care center.

Patients
We studied 283 consecutive patients with AGHD due to NFPA or craniopharyngioma between 1995 and 2018.

Intervention
rhGH treatment at standard doses was initiated in 123 patients (43.5%). The remaining 160 patients served as controls.

Main Outcome Measure
Risk of tumor recurrence in rhGH-treated and control patients.

Results
In univariate analysis, recurrence of the pituitary tumor was less frequent in rhGH-treated patients (19.5%) than in controls (29.7%; hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.32–0.86; P = .01). Multivariate Cox analysis demonstrated that the risk of tumor recurrence was associated with detection of residual disease at the baseline magnetic resonance imaging (HR 9.17; 95% CI, 4.88–17.22; P &lt; .001) and not having performed radiotherapy (HR 16.97; 95% CI, 7.55–38.16; P &lt; .001), while rhGH treatment was no longer associated with a lower risk of recurrence (HR 0.82; 95% CI, 0.47–1.44; P = .50).

Conclusions
We found no association between rhGH replacement and the risk of tumor recurrence in patients with AGHD caused by NFPA or craniopharyngioma. These data add to the mounting evidence that rhGH therapy has a neutral effect on the recurrence of pituitary tumors.

Précis
Replacement therapy with rhGH is prescribed to patients with adult growth hormone deficiency. Our study found no increased risk of pituitary tumor recurrence.
Circulating Follistatin and Activin A and Their Regulation by Insulin in Obesity and Type 2 Diabetes
Authors: Sylow Lykke , Vind Birgitte F , Kruse Rikke , Møller Pauline M , Wojtaszewski Jørgen F P , Richter Erik A , Højlund Kurt 
Published: February 2020

Abstract

Background
Circulating follistatin (Fst) binds activin A and thereby regulates biological functions such as muscle growth and β-cell survival. However, Fst and activin A’s implication in metabolic regulation is unclear.

Objective
To investigate circulating Fst and activin A in obesity and type 2 diabetes (T2D) and determine their association with metabolic parameters. Further, to examine regulation of Fst and activin A by insulin and the influence of obesity and T2D hereon.

Methods
Plasma Fst and activin A levels were analyzed in obese T2D patients (N = 10) closely matched to glucose-tolerant lean (N = 12) and obese (N = 10) individuals in the fasted state and following a 4-h hyperinsulinemic–euglycemic clamp (40 mU·m–2·min–1) combined with indirect calorimetry.

Results
Circulating Fst was ~30% higher in patients with T2D compared with both lean and obese nondiabetic individuals (P &lt; .001), while plasma activin A was unaltered. In the total cohort, fasting plasma Fst correlated positively with fasting plasma glucose, serum insulin and C-peptide levels, homeostasis model assessment of insulin resistance, and hepatic and adipose tissue insulin resistance after adjusting for age, gender and group (all r &gt; 0.47; P &lt; .05). However, in the individual groups these correlations only achieved significance in patients with T2D (not plasma glucose). Acute hyperinsulinemia at euglycemia reduced circulating Fst by ~30% (P &lt; .001) and this response was intact in patients with T2D. Insulin inhibited FST expression in human hepatocytes after 2 h and even further after 48 h.

Conclusions
Elevated circulating Fst, but not activin A, is strongly associated with measures of insulin resistance in patients with T2D. However, the ability of insulin to suppress circulating Fst is preserved in T2D.
Activating Antibodies to The Calcium-sensing Receptor in Immunotherapy-induced Hypoparathyroidism
Authors: Lupi Isabella , Brancatella Alessandro , Cetani Filomena , Latrofa Francesco , Kemp E Helen , Marcocci Claudio 
Published: February 2020

Abstract

Context
Immune checkpoint inhibitors (ICIs), such as programmed cell death protein-1 (PD-1), programmed cell death protein-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4) monoclonal antibodies, are approved for the treatment of some types of advanced cancer. Their main treatment-related side-effects are immune-related adverse events (irAEs), especially thyroid dysfunction and hypophysitis. Hypoparathyroidism, on the contrary, is an extremely rare irAE.

Objectives
The aim of the study was to investigate the etiology of autoimmune hypoparathyroidism in a lung cancer patient treated with pembrolizumab, an anti-PD-1.

Methods
Calcium-sensing receptor (CaSR) autoantibodies, their functional activity, immunoglobulin (Ig) subclasses and epitopes involved in the pathogenesis of autoimmune hypoparathyroidism were tested.

Results
The patient developed hypocalcemia after 15 cycles of pembrolizumab. Calcium levels normalized with oral calcium carbonate and calcitriol and no remission of hypocalcemia was demonstrated during a 9-month follow-up. The patient was found to be positive for CaSR-stimulating antibodies, of IgG1 and IgG3 subclasses, that were able to recognize functional epitopes on the receptor, thus causing hypocalcemia.

Conclusion
The finding confirms that ICI therapy can trigger, among other endocrinopathies, hypoparathyroidism, which can be caused by pathogenic autoantibodies.