bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normalization of magnesium deficiency attenuated mechanical allodynia, depressive-like behaviors, and memory deficits associated with cyclophosphamide-induced cystitis by inhibiting TNF-α/NF-κB signaling in female rats
Authors: Chen Jia-Liang , Zhou Xin , Liu Bo-Long , Wei Xu-Hong , Ding Hong-Lu , Lin Zhi-Jun , Zhan Hai-Lun , Yang Fei , Li Wen-Biao , Xie Jun-Cong , Su Min-Zhi , Liu Xian-Guo , Zhou Xiang-Fu 
Published: April 2020

Abstract
Background
Bladder-related pain symptoms in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) are often accompanied by depression and memory deficits. Magnesium deficiency contributes to neuroinflammation and is associated with pain, depression, and memory deficits. Neuroinflammation is involved in the mechanical allodynia of cyclophosphamide (CYP)-induced cystitis. Magnesium-L-Threonate (L-TAMS) supplementation can attenuate neuroinflammation. This study aimed to determine whether and how L-TAMS influences mechanical allodynia and accompanying depressive symptoms and memory deficits in CYP-induced cystitis.

Methods
Injection of CYP (50 mg/kg, intraperitoneally, every 3 days for 3 doses) was used to establish a rat model of BPS/IC. L-TAMS was administered in drinking water (604 mg·kg−1·day−1). Mechanical allodynia in the lower abdomen was assessed with von Frey filaments using the up-down method. Forced swim test (FST) and sucrose preference test (SPT) were used to measure depressive-like behaviors. Novel object recognition test (NORT) was used to detect short-term memory function. Concentrations of Mg2+ in serum and cerebrospinal fluid (CSF) were measured by calmagite chronometry. Western blot and immunofluorescence staining measured the expression of tumor necrosis factor-α/nuclear factor-κB (TNF-α/NF-κB), interleukin-1β (IL-1β), and N-methyl-d-aspartate receptor type 2B subunit (NR2B) of the N-methyl-d-aspartate receptor in the L6–S1 spinal dorsal horn (SDH) and hippocampus.

Results
Free Mg2+ was reduced in the serum and CSF of the CYP-induced cystitis rats on days 8, 12, and 20 after the first CYP injection. Magnesium deficiency in the serum and CSF correlated with the mechanical withdrawal threshold, depressive-like behaviors, and short-term memory deficits (STMD). Oral application of L-TAMS prevented magnesium deficiency and attenuated mechanical allodynia (n = 14) and normalized depressive-like behaviors (n = 10) and STMD (n = 10). The upregulation of TNF-α/NF-κB signaling and IL-1β in the L6–S1 SDH or hippocampus was reversed by L-TAMS. The change in NR2B expression in the SDH and hippocampus in the cystitis model was normalized by L-TAMS.

Conclusions
Normalization of magnesium deficiency by L-TAMS attenuated mechanical allodynia, depressive-like behaviors, and STMD in the CYP-induced cystitis model via inhibition of TNF-α/NF-κВ signaling and normalization of NR2B expression. Our study provides evidence that L-TAMS may have therapeutic value for treating pain and comorbid depression or memory deficits in BPS/IC patients.
LipoDDx: a mobile application for identification of rare lipodystrophy syndromes
Authors: Araújo-Vilar David , Fernández-Pombo Antía , Rodríguez-Carnero Gemma , Martínez-Olmos Miguel Ángel , Cantón Ana , Villar-Taibo Rocío , Hermida-Ameijeiras Álvaro , Santamaría-Nieto Alicia , Díaz-Ortega Carmen , Martínez-Rey Carmen , Antela Antonio , Losada Elena , Muy-Pérez Andrés E. , González-Méndez Blanca , Sánchez-Iglesias Sofía 
Published: April 2020

Abstract
Background
Lipodystrophy syndromes are a group of disorders characterized by a loss of adipose tissue once other situations of nutritional deprivation or exacerbated catabolism have been ruled out. With the exception of the HIV-associated lipodystrophy, they have a very low prevalence, which together with their large phenotypic heterogeneity makes their identification difficult, even for endocrinologists and pediatricians. This leads to significant delays in diagnosis or even to misdiagnosis.
Our group has developed an algorithm that identifies the more than 40 rare lipodystrophy subtypes described to date. This algorithm has been implemented in a free mobile application, LipoDDx®. Our aim was to establish the effectiveness of LipoDDx®.
Forty clinical records of patients with a diagnosis of certainty of most lipodystrophy subtypes were analyzed, including subjects without lipodystrophy. The medical records, blinded for diagnosis, were evaluated by 13 physicians, 1 biochemist and 1 dentist. Each evaluator first gave his/her results based on his/her own criteria. Then, a second diagnosis was given using LipoDDx®. The results were analysed based on a score table according to the complexity of each case and the prevalence of the disease.

Results
LipoDDx® provides a user-friendly environment, based on usually dichotomous questions or choice of clinical signs from drop-down menus. The final result provided by this app for a particular case can be a low/high probability of suffering a particular lipodystrophy subtype. Without using LipoDDx® the success rate was 17 ± 20%, while with LipoDDx® the success rate was 79 ± 20% (p < 0.01).

Conclusions
LipoDDx® is a free app that enables the identification of subtypes of rare lipodystrophies, which in this small cohort has around 80% effectiveness, which will be of help to doctors who are not experts in this field. However, it will be necessary to analyze more cases in order to obtain a more accurate efficiency value.
Design, synthesis, in silico studies and biological evaluation of 5-((E)-4-((E)-(substituted aryl/alkyl)methyl)benzylidene)thiazolidine-2,4-dione derivatives
Authors: Kumar Harsh , Deep Aakash , Marwaha Rakesh Kumar 
Published: April 2020

Abstract
Background
Looking at the extensive biological potential of thiazolidine-2,4-dione (TZD) moiety, a new series of thiazolidine-2,4-dione analogues was synthesized. Different spectral techniques (1H-NMR, IR, MS etc.) were used to confirm the chemical structures of the synthesized analogues. These synthesized compounds were screened for their antioxidant and antimicrobial potential.

Results and discussion
The antimicrobial screening was carried out against selected strains of fungi and bacteria using serial tube dilution method. The antioxidant potential was assessed using stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. Further, the interaction between synthesized thiazolidine-2,4-dione compounds and DNA gyrase was explored using molecular docking studies. Various ADME parameters were also studied to evaluate the drug likeness of the synthesized compounds.

Conclusion
In antimicrobial evaluation, the compounds 4, 9, 11, 12, 13, 15 and 16 displayed promising activity against selected strains of microbes. Antioxidant evaluation found compound 6 having IC50 = 9.18 μg/mL to be the most potent compound in the series. The molecular docking study revealed compounds 4 (dock score = − 4.73) and 7 (dock score = − 4.61) with decent docking score, possess good interaction inside the ATP binding pocket of DNA gyrase and therefore can be used as lead structure for further optimizing into potent antimicrobial molecule.
Biotransformation of keratin waste to amino acids and active peptides based on cell-free catalysis
Authors: Peng Zheng , Mao Xinzhe , Zhang Juan , Du Guocheng , Chen Jian 
Published: April 2020

Abstract
Background
Keratin is the primary constituent of the vertebrate epidermis and epidermal appendages, as well as the main waste product generated during poultry processing from feathers, hair, scales, nails, etc. Keratin is generally hard, stubborn and difficult to hydrolyze; however, it is also inexpensive and contains more than 85% protein. Currently, tens of millions of tons of keratin waste are produced each year worldwide; however, no effective methods for the recovery of keratin waste have been reported thus far, making such research urgent. Keratinase has been reported to be useful for keratin waste recovery; however, nearly all keratinases are unable to hydrolyze keratin after they are detached from living cell systems. This may be due to low keratinase activity and lack of synergistic factors.

Results
Herein, the keratinase gene from Bacillus licheniformis BBE11-1 was successfully expressed in Bacillus subtilis WB600, allowing for improved activity of the recombinant keratinase KerZ1 to 45.14 KU/mL via promoter substitution and screening of the ribosome-binding sites. Further, real-time control of temperature, pH, dissolved oxygen, and feed strategy allowed the activity of KerZ1 to reach 426.60 KU/mL in a 15-L fermenter, accounting for a 3552-fold increase compared to the wild-type keratinase (120.1 U/mL). Most importantly, we proposed a method based on the synergistic action of keratinase KerZ1 and sodium sulfite, to hydrolyze feathers into amino acids. In specific, 100 g/L of feather waste can be successfully converted into 56.6% amino acids within 12 h, while supporting the production of dozens of bioactive peptides.

Conclusions
The activity of recombinant keratinase can be greatly enhanced via transcription and translational regulation in Bacillus subtilis. The synergistic action of keratinase and sulfite can rapidly degrade feather waste and produce amino acids and polypeptides.
B cells induced by Schistosoma japonicum infection display diverse regulatory phenotypes and modulate CD4+ T cell response
Authors: Xiao Junli , Guan Fei , Sun Li , Zhang Yijie , Zhang Xiaoyan , Lu Shengjun , Liu Wenqi 
Published: April 2020

AbstractBackgroundThe increased activity of regulatory B cells (Breg) is known to be involved in immunosuppression during helminth infection, which is characterized by inducing IL-10-producing Breg cells. However, the current knowledge of B cell subsets differentiation and IL-10-independent immunoregulatory mechanisms of B cells in schistosomiasis is insufficient.MethodsBALB/c mice were percutaneously infected with cercariae for investigating the profile of B cell subsets duringSchistosoma japonicuminfection. B cells isolated from the spleen or peritoneal cavity were analyzed for the regulatory phenotype after stimulation with soluble egg antigens (SEA)in vitro. CD4+T cells were then cocultured with B cells pretreated with or without anti-PD-L1 antibody for investigating the role of B cells from infected mice on regulating CD4+T cells. Furthermore, thein vivoadministration of anti-PD-L1 antibody was conducted to investigate the role of PD-L1 in regulating host immunity during infection.ResultsThe percentages of peritoneal and splenic B-1a cells, as well as marginal zone B (MZB) cells were decreased at eight and twelve weeks after infection compared to those from uninfected mice. In splenic B cells, TGF-β expression was increased at eight weeks but declined at twelve weeks of infection, and PD-L1 expression was elevated at both eight and twelve weeks of infection. In addition, SEA stimulationin vitrosignificantly promoted the expression of IL-10 in peritoneal B cells and CD5 in splenic B cells, and the SEA-stimulated splenic and peritoneal B cells preferentially expressed PD-L1 and TGF-β. The splenic B cells from infected mice were able to suppress the function of Th1 and Th2 cellsin vitrobut to expand the expression of Tfh transcription factor Bcl6, which was further enhanced by blocking PD-L1 of B cells before co-cultivation. Moreover, Th2 response and Bcl6 expression in CD4+T cells were also increasedin vivoby blocking PD-L1 after infection, although the hepatic pathology was slightly influenced.ConclusionsOur findings revealed thatS. japonicuminfection modulates the differentiation of B cell subsets that have the capability to affect the CD4+T cell response. This study contributes to a better understanding of B cells immune response during schistosomiasis.
Air ambulance outcome measures using Institutes of Medicine and Donabedian quality frameworks: protocol for a systematic scoping review
Authors: Edwards Kristin H. , FitzGerald Gerard , Franklin Richard C. , Edwards Mark Terrell 
Published: April 2020

AbstractBackgroundDedicated air ambulance services provide a vital link for critically ill and injured patients to higher levels of care. The recent developments of pre-hospital and retrieval medicine create an opportunity for air ambulance providers and policy-makers to utilize a dashboard of quality performance measures to assess service performance. The objective of this scoping systematic review will be to identify and evaluate the range of air ambulance outcome measures reported in the literature and help to construct a quality dashboard based on a healthcare quality framework.MethodsWe will search PubMed, MEDLINE, CINAHL, Scopus, and Cochrane Database of Systematic Reviews (from January 2001 onwards). Complementary searches will be conducted in selected relevant journals. We will include systematic reviews and observational studies (cohort, cross-sectional, interrupted time series) in critically ill or injured patients published in English and focusing on air ambulance delivery and quality measures. Two reviewers will independently screen all citations, full-text articles, and abstract data. The study methodological quality (or bias) will be appraised using appropriate tools. Analysis of the characteristics associated with outcome measure will be mapped and described according to the proposed healthcare quality framework.DiscussionThis review will contribute to the development of an air ambulance quality dashboard designed to combine multiple quality frameworks. Our findings will provide a basis for helping decision-making in health planning and policy.Systematic review registrationPROSPEROCRD42019144652
On the Hurwitz zeta function with an application to the beta-exponential distribution
Authors: Arbel Julyan , Marchal Olivier , Nipoti Bernardo 
Published: April 2020

AbstractWe prove a monotonicity property of the Hurwitz zeta function which, in turn, translates into a chain of inequalities for polygamma functions of different orders. We provide a probabilistic interpretation of our result by exploiting a connection between Hurwitz zeta function and the cumulants of the beta-exponential distribution.
Global and blow-up solutions for a nonlinear reaction diffusion equation with Robin boundary conditions
Authors: Tian Huimin , Zhang Lingling 
Published: April 2020

AbstractIn the paper, we investigate global and blow-up solutions for a class of nonlinear reaction diffusion equations with Robin boundary conditions. By using auxiliary functions and a first-order differential inequality technique, we establish conditions on the data to prove the existence of global solution. Moreover, based on maximum principles, we obtain a criterion that guarantees the occurrence of the blow-up. When blow-up occurs, we discuss an upper bound and a lower bound on blow-up time. At last, we apply two examples to illustrate our main results.
Calpain proteolytic systems counteract endothelial cell adaptation to inflammatory environments
Authors: Miyazaki Takuro , Akasu Risako , Miyazaki Akira 
Published: April 2020

AbstractVascular endothelial cells (ECs) make up the innermost surface of arteries, veins, and capillaries, separating the remaining layers of the vessel wall from circulating blood. Under non-inflammatory conditions, ECs are quiescent and form a robust barrier structure; however, exposure to inflammatory stimuli induces changes in the expression of EC proteins that control transcellular permeability and facilitate angiogenic tube formation. Increasing evidence suggests that dysfunction in intracellular proteolytic systems disturbs EC adaptation to the inflammatory environment, leading to vascular disorders such as atherosclerosis and pathological angiogenesis. Recent work has highlighted the contribution of the calpain–calpastatin stress-responsive intracellular proteolytic system to adaptation failure in ECs. In this review, we summarize our current knowledge of calpain–calpastatin-mediated physiologic and pathogenic regulation in ECs and discuss the molecular basis by which disruption of this system perturbs EC adaptation to the inflammatory environment.
State of the art in selection of variables and functional forms in multivariable analysis—outstanding issues
Authors:   for TG2 of the STRATOS initiative, Sauerbrei Willi , Perperoglou Aris , Schmid Matthias , Abrahamowicz Michal , Becher Heiko , Binder Harald , Dunkler Daniela , Harrell Frank E. , Royston Patrick , Heinze Georg 
Published: April 2020

AbstractBackgroundHow to select variables and identify functional forms for continuous variables is a key concern when creating a multivariable model. Ad hoc ‘traditional’ approaches to variable selection have been in use for at least 50 years. Similarly, methods for determining functional forms for continuous variables were first suggested many years ago. More recently, many alternative approaches to address these two challenges have been proposed, but knowledge of their properties and meaningful comparisons between them are scarce. To define a state of the art and to provide evidence-supported guidance to researchers who have only a basic level of statistical knowledge, many outstanding issues in multivariable modelling remain. Our main aims are to identify and illustrate such gaps in the literature and present them at a moderate technical level to the wide community of practitioners, researchers and students of statistics.MethodsWe briefly discuss general issues in building descriptive regression models, strategies for variable selection, different ways of choosing functional forms for continuous variables and methods for combining the selection of variables and functions. We discuss two examples, taken from the medical literature, to illustrate problems in the practice of modelling.ResultsOur overview revealed that there is not yet enough evidence on which to base recommendations for the selection of variables and functional forms in multivariable analysis. Such evidence may come from comparisons between alternative methods. In particular, we highlight seven important topics that require further investigation and make suggestions for the direction of further research.ConclusionsSelection of variables and of functional forms are important topics in multivariable analysis. To define a state of the art and to provide evidence-supported guidance to researchers who have only a basic level of statistical knowledge, further comparative research is required.
Different strategies in the management of thalamic space-occupying lesions
Authors: Fayed Ahmed Abdel Aziz , Abdel Aziz Osama , Eshra Mohamed 
Published: April 2020

Abstract
Introduction
Thalamic space-occupying lesions (SOL) are considered challenging for microsurgical removal. Unfortunately, the pathological features of lesions occurring in the thalamic region are different with a wide variation in clinical behavior and outcome. Although microsurgery is still the gold standard in the management of these lesions through different approaches, questions remain whether surgery is feasible and safe in these patients and what are the alternatives? It is well known that stereotactic techniques may be favorable especially in cystic, small, multiple lesions and in combination with adjuvant therapy. Transventricular endoscopic approach is also an alternative technique to combine tumor biopsy and treatment of hydrocephalus.

Aim of the study
The identification of the different procedures for the management of thalamic SOL in respect to the age of the patient, the clinical condition, and the site of the lesion as well as its extent and pathology.

Patients and methods
This prospective study included 35 patients having thalamic lesions with a mean age of 27 years old who were treated with different approaches including microsurgical, stereotactic, and endoscopic approaches. The clinical outcome was assessed as the same, improved, deteriorated, or died in comparison to the initial clinical status, while the radiological control was measured as no gross residual, residual < 10% and residual > 10%. Chi-square test was used to test the association between two categorical variables.

Results
Thirty-five patients were included in this study, 20 were males and 15 were females. Eight cases were children, and 27 cases were adults. The most common clinical presentation was contralateral hemiparesis. The most common pathology was pilocytic astrocytoma. Radiological studies showed that the total thalamic type was the most common topographic variant and that 10 cases had hydrocephalus treated with CSF diversion procedures. For the definitive lesion, 2 cases underwent endoscopic biopsy and cystoventriculostomy and 18 cases had stereotactic technique in the form of biopsy, aspiration, and ommaya reservoir application, while 15 cases had microsurgery through different approaches with stereotactic technique preceding surgery in 2 of them.

Conclusion
The main factors involved in choosing the appropriate approach included nature of the lesion (solid or cystic, multiplicity), suspected pathological type, and diffusion tensor imaging. Abscesses are best treated with stereotaxy, while non-neoplastic cystic lesions (other than abscesses) related to the ventricles are best treated with endoscopy. For the remaining pathologies, maximum surgical removal is the best management. Best lesion control was provided by microsurgery.

Trial registration
ISRCTN 1380 registered 6/11/2018
Gamma Gap: A Point-of-Care Test That Correlates With Disease Burden and Treatment Response in Multiple Myeloma
Authors: Dupuis Megan M. , Paul Barry , Loitsch Gavin , Mathews Parker , Feinberg Daniel , Barak Ian , Li Zhiguo , Tuchman Sascha A. , Kang Yubin 
Published: April 2020

PURPOSE: We performed a retrospective chart review on 393 patients with multiple myeloma (MM) to determine the utility of the gamma gap (GG). METHODS: We calculated the difference between a patient’s total serum protein and albumin as a point-of-care test for assessing disease status in MM. RESULTS: GG is highly correlated with the level of M-spike, and the change in GG correlates with myeloma treatment response. In addition, fitted linear models were established that allow for the calculation of M-protein level from the GG within hours from blood draw. CONCLUSION: Our study has important implications in the care of MM, particularly in countries/areas with limited resources.
Composting treatment of fur waste originating from tannery
Authors: Puente César , Jara-Samaniego Janneth , Guapulema Alexander , Burbano-Salas Diego 
Published: April 2020

The tanning industry generates effluents with a high contaminant load represented in a considerable amount of liquid, solid, and gaseous waste. Solid waste, such as residual hair, fat, and meat, are dumped directly in landfills, triggering serious environmental problems. The objective of this research was to compost this waste, previously desulfurized, in a mixture with remnants from pruning as a bulking agent. This low-cost strategy may reduce the total amount of waste. A composting pile was created using residual hair and pruning remnants in a proportion of 3:1 (w/w) and then an inoculum was added. The waste degrading process ran for 141 days, followed by a maturation period of 64 days. Throughout the process, the temperature, moisture, pH, and electrical conductivity (EC) were monitored. The highest temperature reached was 69.7°C, which secured good disinfection. The EC was 0.27 dS/cm, having lower values than Spanish regulations, possibly due to the salt removal over the irrigation periods. The organic matter content decreased continuously, to reach an endpoint of 42%; this result agrees with the high organic matter content of the tannery waste and the pruning remnants. Germination index was 43.55%, which indicates the presence of phytotoxic substances. As compared to the initial value (10.73%) there was partial degrading of these substances. The challenge is to improve this parameter by identifying new mixtures and adding efficient microorganisms that help to degrade phytotoxic substances.