bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progranulin deficiency exacerbates spinal cord injury by promoting neuroinflammation and cell apoptosis in mice
Authors: Wang Chao , Zhang Lu , Ndong Jean De La Croix , Hettinghouse Aubryanna , Sun Guodong , Chen Changhong , Zhang Chen , Liu Ronghan , Liu Chuan-ju 
Published: November 2019

AbstractPurposeSpinal cord injury (SCI) often results in significant and catastrophic dysfunction and disability and imposes a huge economic burden on society. This study aimed to determine whether progranulin (PGRN) plays a role in the progressive damage following SCI and evaluate the potential for development of a PGRN derivative as a new therapeutic target in SCI.MethodsPGRN-deficient (Gr−/−) and wild-type (WT) littermate mice were subjected to SCI using a weight-drop technique. Local PGRN expression following injury was evaluated by Western blotting and immunofluorescence. Basso Mouse Scale (BMS), inclined grid walking test, and inclined plane test were conducted at indicated time points to assess neurological recovery. Inflammation and apoptosis were examined by histology (Hematoxylin and Eosin (H&E) staining and Nissl staining, TUNEL assays, and immunofluorescence), Western blotting (from whole tissue protein for iNOS/p-p65/Bax/Bcl-2), and ex vivo ELISA (for TNFα/IL-1β/IL-6/IL-10). To identify the prophylactic and therapeutic potential of targeting PGRN, a PGRN derived small protein, Atsttrin, was conjugated to PLGA-PEG-PLGA thermosensitive hydrogel and injected into intrathecal space prior to SCI. BMS was recorded for neurological recovery and Western blotting was applied to detect the inflammatory and apoptotic proteins.ResultsAfter SCI, PGRN was highly expressed in activated macrophage/microglia and peaked at day 7 post-injury.Grn−/−mice showed a delayed neurological recovery after SCI at day 21, 28, 35, and 42 post-injury relative to WT controls. Histology, TUNEL assay, immunofluorescence, Western blotting, and ELISA all indicated thatGrn−/−mice manifested uncontrolled and expanded inflammation and apoptosis. Administration of control-released Atsttrin could improve the neurological recovery and the pro-inflammatory/pro-apoptotic effect of PGRN deficiency.ConclusionPGRN deficiency exacerbates SCI by promoting neuroinflammation and cellular apoptosis, which can be alleviated by Atsttrin. Collectively, our data provide novel evidence of using PGRN derivatives as a promising therapeutic approach to improve the functional recovery for patients with spinal cord injury.
Recombinant CC16 inhibits NLRP3/caspase-1-induced pyroptosis through p38 MAPK and ERK signaling pathways in the brain of a neonatal rat model with sepsis
Authors: Zhou Ruixi , Yang Xiaoyan , Li Xihong , Qu Yi , Huang Qun , Sun Xuemei , Mu Dezhi 
Published: November 2019

AbstractBackgroundSepsis is a critical disease associated with extremely high mortality. Some severe forms of sepsis can induce brain injury, thus causing behavioral and cognitive dysfunction. Pyroptosis is a type of cell death that differs from apoptosis and plays an important role in the occurrence and development of infectious diseases, nervous system-related diseases. A recent study has found that there is pyroptosis in the hippocampus of sepsis-induced brain injury, but its mechanism and treatment scheme have not been evaluated.MethodsWe established immediately a septic rat model by cecal ligation and perforation (CLP) after administration with recombinant club cell protein (rCC16) and/or U46619 in different groups. The clinical performance, survival percentage, vital signs, and neurobehavioral scores were monitored at different time points. Cortical pathological changes were also examined. The expression of cortical nucleotide-binding domain leucine-rich repeat-containing pyrin domain-containing 3 (NLRP3), caspase-1, (p)-p38 mitogen-activated protein kinase (MAPK), and (p)-extracellular signal-related kinase (ERK) was detected by western blotting and immunofluorescence analysis. The levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha in the cortical supernatant were detected by enzyme-linked immunosorbent assay.ResultsCompared with the sham group, the clinical performance, survival percentage, vital signs, and severe cortical pathological changes in the CLP group were worse; NLRP3, caspase-1, and inflammatory factor levels were increased; and phosphorylation of p38 MAPK and ERK was also increased. Meanwhile, multiple indicators were deteriorated further after administration of U46619 in CLP rats. The clinical performance of CLP rats, however, was better after rCC16 administration; cortical pathological changes were attenuated; and NLRP3, caspase-1, and inflammatory factor levels and the phosphorylation of signaling pathway proteins (p38 MAPK and ERK) were reduced. Interestingly, the CLP rats showed the opposite changes in all indicators after administration with both rCC16 and U46619 when compared with those administered rCC16 alone.ConclusionsIn sepsis, rCC16 inhibits cortical pyroptosis through p38 MAPK and ERK signaling pathways. Meanwhile, rCC16 has a protective effect on newborn rats with sepsis, but it is not clear whether its mechanism is directly related to pyroptosis.
HPV viral load in self-collected vaginal fluid samples as predictor for presence of cervical intraepithelial neoplasia
Authors: Berggrund Malin , Gustavsson Inger , Aarnio Riina , Hedlund-Lindberg Julia , Sanner Karin , Wikström Ingrid , Enroth Stefan , Olovsson Matts , Gyllensten Ulf 
Published: November 2019

Abstract
Objective
This study was performed to evaluate the use of high-risk HPV (hrHPV) viral load in screening tests for cervical cancer to predict persistent infection and presence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+).

Methods
We followed women between 30 and 60 years of age who performed self-sampling of vaginal fluid and subsequently a hrHPV test. Women who were hrHPV positive in their screening test repeated the hrHPV test 3–6 months later and were included in the present study.

Results
Our results show that women with a persistent HPV16 infection had higher HPV viral load in their primary screening test than women with transient infections (p = 5.33e-03). This was also true for sum of viral load for all hrHPV types in the primary screening test (p = 3.88e-07). 48% of women with persistent HPV16 infection and CIN2+ had an increase in HPV16 titer in the follow-up test, as compared to only 20% of women with persistent infection but without CIN2+ lesions. For the sum of all hrHPV types, 41% of women with persistent infection and CIN2+ had an increase in titer as compared to 26% of women without CIN2 + .

Conclusions
The results show that hrHPV viral load in the primary screening HPV test is associated with the presence of CIN2+ and could be used in triaging hrHPV positive women for different follow-up strategies or recall times. Serial testing of hrHPV viral load has the potential to distinguish women with CIN2+ lesions from women with persistent infection but without CIN2+ lesions.
Comparison of four nanoparticle monitoring instruments relevant for occupational hygiene applications
Authors: Jørgensen Rikke Bramming 
Published: November 2019

Abstract
Background
The aim of this study is to make a comparison of a new small sized nanoparticle monitoring instrument, Nanoscan SMPS, with more traditional large size instruments, known to be precise and accurate [Scanning Mobility Particle Sampler (SMPS) and Fast Mobility Particle Sizer (FMPS)], and with an older small size instrument with bulk measurements of 10–1000 nm particles (CPC3007). The comparisons are made during simulated exposure scenarios relevant to occupational hygiene studies.

Methods
Four scenarios were investigated: metal inert gas (MIG) welding, polyvinyl chloride (PVC) welding, cooking, and candle-burning. Ratios between results are compaed and Pearsson correlations analysis was performed.

Results
The highest correlation between the results is found between Nanoscan and SMPS, with Pearsson correlation coefficients above 0.9 for all scenarios. However, Nanoscan tended to overestimate the results from the SMPS; the ratio between the UFP concentrations vary between 1.44 and 2.01, and ratios of total concentrations between 1.18 and 2.33. CPC 3007 did not show comparable results with the remaining instruments.

Conclusion
Based on the results of this study, the choice of measurement equipment may be crucial when evaluating measurement results against a reference value or a limit value for nanoparticle exposure. This stresses the need for method development, standardisation, and harmonisation of particle sampling protocols before reference values are introduced. Until this is established, the SMPS instruments are the most reliable for quantification of the concentrations of UFP, but in a more practical occupational hygiene context, the Nanoscan SMPS should be further tested.
IARC 2019: “Night shift work” is probably carcinogenic: What about disturbed chronobiology in all walks of life?
Authors: Erren Thomas C. , Morfeld Peter , Groß J. Valérie , Wild Ursula , Lewis Philip 
Published: November 2019

AbstractIn June of 2019, a working group convened by the International Agency for Research on Cancer [IARC] concluded that “night shift work” is probably carcinogenic to humans (a Group 2A carcinogen). This was based on sufficient evidence of cancer and strong mechanistic evidence in experimental animals and limited evidence from human epidemiological studies. The biological basis from experimental work is clear and compelling: Disturbed chronobiology such as due to alterations in the light-dark schedule which shift-workers experience is associated with carcinogenicity. But is it correct to assume in epidemiological studies that “night shift work” provides the same dose of disturbed chronobiology to all night workers and that disturbed chronobiology from activities outside of work does not count? Both chronobiological theory and supporting evidence suggest that much-needed future epidemiology should address these questions and should consider disturbed chronobiology in all walks of life.
Can a multicomponent multidisciplinary implementation package change physicians’ and nurses’ perceptions and practices regarding thrombolysis for acute ischemic stroke? An exploratory analysis of a cluster-randomized trial
Authors: Hasnain Md Golam , Levi Christopher R. , Ryan Annika , Hubbard Isobel J. , Hall Alix , Oldmeadow Christopher , Grady Alice , Jayakody Amanda , Attia John R. , Paul Christine L. 
Published: November 2019

Abstract
Background
The Thrombolysis ImPlementation in Stroke (TIPS) trial tested the effect of a multicomponent, multidisciplinary, collaborative intervention designed to increase the rates of intravenous thrombolysis via a cluster randomized controlled trial at 20 Australian hospitals (ten intervention, ten control). This sub-study investigated changes in self-reported perceptions and practices of physicians and nurses working in acute stroke care at the participating hospitals.

Methods
A survey with 74 statements was administered during the pre- and post-intervention periods to staff at 19 of the 20 hospitals. An exploratory factor analysis identified the structure of the survey items and linear mixed modeling was applied to the final survey domain scores to explore the differences between groups over time.

Result
The response rate was 45% for both the pre- (503 out of 1127 eligible staff from 19 hospitals) and post-intervention (414 out of 919 eligible staff from 18 hospitals) period. Four survey domains were identified: (1) hospital performance indicators, feedback, and training; (2) personal perceptions about thrombolysis evidence and implementation; (3) personal stroke skills and hospital stroke care policies; and (4) emergency and ambulance procedures. There was a significant pre- to post-intervention mean increase (0.21 95% CI 0.09; 0.34; p < 0.01) in scores relating to hospital performance indicators, feedback, and training; for the intervention hospitals compared to control hospitals. There was a corresponding increase in mean scores regarding perceptions about the thrombolysis evidence and implementation (0.21, 95% CI 0.06; 0.36; p < 0.05). Sub-group analysis indicated that the improvements were restricted to nurses’ responses.

Conclusion
TIPS resulted in changes in some aspects of nurses’ perceptions relating to the evidence for intravenous thrombolysis and its implementation and hospital performance indicators, feedback, and training. However, there is a need to explore further strategies for influencing the views of physicians given limited statistical power in the physician sample.

Trial registration
ACTRN12613000939796, UTN: U1111–1145-6762.
Targeting adaptability to improve Medication Therapy Management (MTM) implementation in community pharmacy
Authors: Hohmeier Kenneth C. , Wheeler James S. , Turner Kea , Vick Jarrod S. , Marchetti Merrill L. , Crain Jeremy , Brookhart Andrea 
Published: November 2019

AbstractObjectives(1) To develop an adaptation framework for MTM delivery for pharmacists (the MTM Adaptability Framework), (2) to examine the impact of an educational intervention informed by the MTM Adaptability Framework on MTM completion rates over a 2-year period, and (3) to explore pharmacists’ perceptions regarding knowledge and beliefs about MTM and MTM implementation self-efficacy pre- and post-intervention.MethodsThis study is a prospective, mixed-methods research study including a quasi-experimental, one-group pretest-posttest quantitative study with a sequential explanatory qualitative study arm featuring semi-structured key informant interviews. US supermarket pharmacy chain setting included 93 community pharmacy sites located in Tennessee, Kentucky, and Alabama. MTM completion rates are reported as percentage of completed comprehensive medication reviews (CMRs) and targeted medication reviews (TMRs) and pharmacist perceptions.ResultsAn 11.4% absolute increase in MTM completion rates was seen after the educational intervention targeting adaptation of MTM in the community pharmacy setting. This was found to be significant (46.92% vs. 58.3%;p< 0.001). Responses to the semi-structured interviews were mapped against CFIR and included themes: “knowledge and beliefs about MTM (pre-intervention),” “self-efficacy for MTM implementation (pre-intervention),” “knowledge and beliefs about MTM (post-intervention),” and “self-efficacy for MTM implementation (post-intervention).” Data convergence was found across these methodologies and suggested that targeting adaptability of MTM delivery increases MTM completion rates (quantitative data) and positively changes perceptions of MTM feasibility and self-efficacy (interviews).ConclusionThe use of an educational intervention about adaptation of MTM to influence adaptation of MTM to a chain community pharmacy setting part of an implementation strategy improved MTM completion rates significantly. Future research should investigate combined implementation strategies and their impact on MTM implementation success.
Effect of sIL-13Rα2-Fc on the progression of rat tail intervertebral disc degeneration
Authors: Wang Xin , Sun Junhao , Tan Jianshi , Fang Pengzhong , Chen Jinlei , Yuan Wen , Chen Huajiang , Liu Yang 
Published: November 2019

Abstract
Background
The incidence of degenerative disc disease caused by intervertebral disc injury is increasing annually, seriously affecting the quality of life of patients and increasing the disease burden on society. The mechanisms of intervertebral disc degeneration include changes in extracellular matrix (ECM) deposition and tissue fibrosis. sIL-13Rα2-Fc potently inhibits interleukin (IL)-13, as well as blocks related cell signaling pathways and inhibits fibrosis in certain tissues. However, it is unknown whether sIL-13Rα2-Fc inhibits fibrosis in injured intervertebral discs and slows the process of degeneration. We hypothesized that sIL-13Rα2-Fc delays the progression of intervertebral disc degeneration by inhibiting intervertebral disc fibrosis and improving ECM deposition.

Methods
A rat tail intervertebral disc degeneration model was established. Pathological changes in rat intervertebral disc tissue were observed by hematoxylin and eosin staining and Masson staining. Glycosaminoglycan (GAG), chondroitin sulfate (CS), keratan sulfate (KS), and hyaluronic acid (HA) contents were quantitatively analyzed by enzyme-linked immunosorbent assay. Type I and type II collagen expression levels were analyzed by reverse transcription-PCR and western blotting.

Results
Hematoxylin and eosin staining and Masson staining revealed annulus fibrosus rupture, disordered arrangement, decreased nucleus pulposus tissue, and decreased collagen fiber in the rat intervertebral disc tissue. Following treatment with sIL-13Rα2-Fc, pathological changes in the rat intervertebral disc were reduced. Rat intervertebral disc tissue showed decreased GAG, CS-KS, and (HA) contents, increased type I collagen levels, and decreased type II collagen levels in degenerated intervertebral discs. sIL-13Rα2-Fc intervention increased the contents of GAG, CS, KS, and HA; inhibited the expression of type I collagen; and promoted the expression of type II collagen.

Conclusion
These results demonstrate that intervertebral disc degeneration is associated with tissue fibrosis. sIL-13Rα2-Fc can regulate type I and type II collagen expression levels by increasing GAG, CS, KS, and HA contents, thereby slowing the progression of intervertebral disc degeneration.
Comparison of ceramic-on-ceramic bearing vs ceramic-on-highly cross-linked polyethylene-bearing surfaces in total hip arthroplasty for avascular necrosis of femoral head: a prospective cohort study with a mid-term follow-up
Authors: Feng Bin , Ren Yi , Cao Shiliang , Lin Jin , Jin Jin , Qian Wenwei , Weng Xisheng 
Published: November 2019

Abstract
Background
The ideal bearing surface for patients of avascular necrosis (AVN) undergoing total hip arthroplasty (THA) remains controversial. The purpose of this study is to evaluate the clinical outcomes, health-related quality of life (HRQL), and wear of the bearing surface between ceramic-on-ceramic (CoC) and ceramic-on-highly cross-linked polyethylene (CoXPE) THA for patients of AVN after midterm follow-up.

Methods
We performed a retrospective case-control analysis of 93 CoC and 77 CoXPE consecutive THAs for patients of AVN. The cases were followed at a minimum 5 years follow-up (average 7 years). Harris hip score (HHS) score and bearing-related complications were assessed. The health-related quality of life (HRQL) was assessed with the Short Form 36 (SF-36). Plain radiographs and computed tomography (CT) were used for radiographic evaluation.

Results
Both the CoC group and CoXPE group showed statistically significant improvements in HHS scores with no difference between the two bearing surfaces. There was no significant difference as for SF-36 at the latest follow-up between two groups, except for significant higher scores in the dimensions of general health in the CoC group (75.7 vs 64.7, P = 0.032). No radiographic evidence of osteolysis and loosening was present at the final follow-up. The mean wear rate of the CoC was 0.0096 mm/year and the CoXPE was 0.047 mm/year after evaluation with reconstructed CT.

Conclusions
CoC THAs acts as well as CoXPE THAs for patients with femoral head avascular necrosis after midterm follow-up. CoC bearing can significantly decrease the wearing rate than CoXPE bearing.
Repair of a type B aortic dissection with a re-vascularization of the aberrant right subclavian artery in an adult patient
Authors: Abuharb Mahmoud Yousef Ibrahim , Ming Bian Xiao , Jian He 
Published: November 2019

Abstract
Background
An aberrant right subclavian artery which arises from the proximal descending aorta may result in aortic dissection. The dissection may occur at either the site of the primary intimal tear or from an aortic branch. These conditions may lead to blood flow limitation and possible aneurysmal degeneration in the future.

Case presentation
We described the clinical presentation and management of a 54-year old patient diagnosed with a rare case of an aberrant right subclavian artery with Stanford Type B aortic dissection. A hybrid surgical approach was successfully performed and the patient had an uneventful recovery.

Conclusion
Even though aortic dissection is often an incidental finding, this case highlighted that in rare situations, it can be associated with an aberrant right subclavian artery. It is important to disseminate this association as it has profound diagnostic and therapeutic implications in safeguarding the clinical outcomes of patients with such condition.
Autophagy protein NRBF2 has reduced expression in Alzheimer’s brains and modulates memory and amyloid-beta homeostasis in mice
Authors: Lachance Véronik , Wang Qian , Sweet Eric , Choi Insup , Cai Cui-Zan , Zhuang Xu-Xu , Zhang Yuanxi , Jiang Jessica Li , Blitzer Robert D. , Bozdagi-Gunal Ozlem , Zhang Bin , Lu Jia-Hong , Yue Zhenyu 
Published: November 2019

Abstract
Background
Dysfunctional autophagy is implicated in Alzheimer’s Disease (AD) pathogenesis. The alterations in the expression of many autophagy related genes (ATGs) have been reported in AD brains; however, the disparity of the changes confounds the role of autophagy in AD.

Methods
To further understand the autophagy alteration in AD brains, we analyzed transcriptomic (RNAseq) datasets of several brain regions (BA10, BA22, BA36 and BA44 in 223 patients compared to 59 healthy controls) and measured the expression of 130 ATGs. We used autophagy-deficient mouse models to assess the impact of the identified ATGs depletion on memory, autophagic activity and amyloid-β (Aβ) production.

Results
We observed significant downregulation of multiple components of two autophagy kinase complexes BECN1-PIK3C3 and ULK1/2-FIP200 specifically in the parahippocampal gyrus (BA36). Most importantly, we demonstrated that deletion of NRBF2, a component of the BECN1-PIK3C3 complex, which also associates with ULK1/2-FIP200 complex, impairs memory in mice, alters long-term potentiation (LTP), reduces autophagy in mouse hippocampus, and promotes Aβ accumulation. Furthermore, AAV-mediated NRBF2 overexpression in the hippocampus not only rescues the impaired autophagy and memory deficits in NRBF2-depleted mice, but also reduces β-amyloid levels and improves memory in an AD mouse model.

Conclusions
Our data not only implicates NRBF2 deficiency as a risk factor for cognitive impairment associated with AD, but also support the idea of NRBF2 as a potential therapeutic target for AD.
Directed evolution of the PcaV allosteric transcription factor to generate a biosensor for aromatic aldehydes
Authors: F. M. Machado Leopoldo , Currin Andrew , Dixon Neil 
Published: November 2019

AbstractBackgroundTranscription factor-based biosensors are useful tools for the detection of metabolites and industrially valuable molecules, and present many potential applications in biotechnology and biomedicine. However, the most common approach to develop biosensors relies on employing a limited set of naturally occurring allosteric transcription factors (aTFs). Therefore, altering the ligand specificity of aTFs towards the detection of new effectors is an important goal.ResultsHere, the PcaV repressor, a member of the MarR aTF family, was used to develop a biosensor for the detection of hydroxyl-substituted benzoic acids, including protocatechuic acid (PCA). The PCA biosensor was further subjected to directed evolution to alter its ligand specificity towards vanillin and other closely related aromatic aldehydes, to generate the Van2 biosensor. Ligand recognition of Van2 was explored in vitro using a range of biochemical and biophysical analyses, and extensive in vivo genetic-phenotypic analysis was performed to determine the role of each amino acid change upon biosensor performance.ConclusionsThis is the first study to report directed evolution of a member of the MarR aTF family, and demonstrates the plasticity of the PCA biosensor by altering its ligand specificity to generate a biosensor for aromatic aldehydes.