bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment withIL‐19improves locomotor functional recovery after contusion trauma to the spinal cord
Authors: Guo Jidong , Wang Huadong , Li Li , Yuan Yanli , Shi Xiuxiu , Hou Shuxun 
Published: March 2018

Background and PurposeIL‐19 skews the immune response towards a Th2 type and appears to stimulate angiogenesis. In the current study, we tested if IL‐19 treatment could reduce secondary injury and improve functional recovery after contusion spinal cord injury (SCI).Experimental ApproachFirstly, mice were given a moderate–severe thoracic SCI at the T9–10level and expression of IL‐19 and its receptor was measured in the injured spinal cord. Then SCI mice were treated with mouse recombinant IL‐19 and its blocking antibody to investigate the therapeutic effect of IL‐19.Key ResultsProtein expression of IL‐19 and its receptor IL‐20R1 and IL‐20R2 was up‐regulated in the injured spinal cord of mice. IL‐19 treatment promoted the recovery of locomotor function dose‐dependently and reduced loss of motor neurons and microglial and glial activation following SCI. Treatment of SCI mice with IL‐19 attenuated macrophage accumulation, reduced protein levels of TNF‐α and CCL2 and promoted Th2 response and M2 macrophage activation in the injured region. Treatment of SCI mice with IL‐19 promoted angiogenesis through up‐regulating VEGF in the injured region. Treatment of SCI mice with IL‐19 up‐regulated HO‐1 expression and decreased oxidative stress in the injured region. The beneficial effect of IL‐19 was abolished by coadministration of the blocking antibody. Additionally, IL‐19 deficiency in mice delayed the recovery of locomotor function following SCI.Conclusions and ImplicationsIL‐19 treatment reduced secondary injuries and improved locomotor functional recovery after contusion SCI, through diverse mechanisms including immune cell polarization, angiogenesis and anti‐oxidative responses.
Phase I study of taselisib in Japanese patients with advanced solid tumors or hormone receptor‐positive advanced breast cancer
Authors: Tamura Kenji , Kodaira Makoto , Shimizu Chikako , Yonemori Kan , Yunokawa Mayu , Shimomura Akihiko , Kobayashi Takayuki , Nakano Kenji , Tomomatsu Junichi , Ito Yoshinori , Tanaka Jun , Kuriki Hiroshi , Gu Zhaodi , Takahashi Shunji 
Published: March 2018

Taselisib is a potent and selective phosphatidylinositide 3‐kinase (PI3K) inhibitor. The present article reports the first study of taselisib administration in Japanese patients. The aim of this 2‐stage, phase I, multicenter, open‐label, dose‐escalation study was to evaluate the safety, pharmacokinetics, and preliminary efficacy of taselisib as monotherapy in Japanese patients with advanced solid tumors (stage 1), and as part of combination therapy in Japanese patients with hormone receptor (HR)‐positive locally advanced or recurrent breast cancer (stage 2). In stage 1, oral taselisib tablets 2, 4, and 6 mg/d were given in 28‐day cycles. In stage 2, successive cohorts of patients received oral taselisib tablets (2 or 4 mg/d) with i.m. fulvestrant 500 mg. Nine and 6 patients were enrolled in stage 1 and stage 2, respectively. Taselisib was well tolerated. No dose‐limiting toxicities were experienced in any cohort of patients and no deaths were observed. The most common treatment‐related adverse events in stage 1 and stage 2, respectively, were rash (55.6%, 66.7%), diarrhea (44.4%, 66.7%), and stomatitis (44.4%, 66.7%). Taselisib was rapidly absorbed after dosage; its half‐life was 12.9‐32.0 hours in stage 1 and 16.1‐26.5 hours in stage 2. Two patients achieved partial response (PR), 5 patients had stable disease (SD) and 2 patients had progressive disease (PD) in stage 1, and 1 patient had PR and 3 patients had SD in stage 2. All patients with PR were positive for PIK3CA gene mutations. These preliminary data suggest that taselisib may be effective in patients with PIK3CA‐mutated solid tumors or HR‐positive advanced breast cancer.
Identification of inhibitors of Tartrate‐resistant acid phosphatase (TRAP/ACP5) activity by small‐molecule screening
Authors: Reithmeier Anja , Lundbäck Thomas , Haraldsson Martin , Frank Martin , Ek‐Rylander Barbro , Nyholm Per‐Georg , Gustavsson Anna‐Lena , Andersson Göran 
Published: March 2018

Tartrate‐resistant acid phosphatase (TRAP/ACP5) occurs as two isoforms—TRAP 5a with low enzymatic activity due to a loop interacting with the active site and the more active TRAP isoform 5b generated upon proteolytic cleavage of this loop. TRAP has been implicated in several diseases, including cancer. Thus, this study set out to identify small‐molecule inhibitors of TRAP activity. A microplate‐based enzymatic assay for TRAP 5b was applied in a screen of 30,315 compounds, resulting in the identification of 90 primary hits. After removal of promiscuous compounds, unwanted groups, and false positives by orthogonal assays and three‐concentration validation, the properties of 52 compounds were further investigated to better understand their mechanism of action. Full‐concentration–response curves for these compounds were established under different enzyme concentrations and (pre)incubation times to remove compounds with inconsistent results and low potencies. Full‐concentration–response curves were also performed for both isoforms, to examine isoform prevalence. Filtering led to six prioritized compounds, representing different clusters. One of these, CBK289001 or (6S)‐6‐[3‐(2H‐1,3‐benzodioxol‐5‐yl)‐1,2,4‐oxadiazol‐5‐yl]‐N‐(propan‐2‐yl)‐1H,4H,5H,6H,7H‐imidazo[4,5‐c]pyridine‐5‐carboxamide, demonstrated efficacy in a migration assay and IC50 values from 4 to 125 μm. Molecular docking studies and analog testing were performed around CBK289001 to provide openings for further improvement toward more potent blockers of TRAP activity.
Inhibition of phosphodiesterases as a strategy to achieve neuroprotection in Huntington's disease
Authors: Cardinale Antonella , Fusco Francesca R. 
Published: March 2018

SummaryHuntington's disease (HD) is a fatal neurodegenerative condition, due to a mutation in the IT15 gene encoding for huntingtin. Currently, disease‐modifying therapy is not available for HD, and only symptomatic drugs are administered for the management of symptoms. In the last few years, preclinical and clinical studies have indicated that pharmacological strategies aimed at inhibiting cyclic nucleotide phosphodiesterase (PDEs) may develop into a novel therapeutic approach in neurodegenerative disorders. PDEs are a family of enzymes that hydrolyze cyclic nucleotides into monophosphate isoforms. Cyclic nucleotides are second messengers that transduce the signal of hormones and neurotransmitters in many physiological processes, such as protein kinase cascades and synaptic transmission. An alteration in their balance results in the dysregulation of different biological mechanisms (transcriptional dysregulation, immune cell activation, inflammatory mechanisms, and regeneration) that are involved in neurological diseases. In this review, we discuss the action of phosphodiesterase inhibitors and their role as therapeutic agents in HD.
Abnormal resting‐state functional connectivity in posterior cingulate cortex of Parkinson's disease with mild cognitive impairment and dementia
Authors: Zhan Zhou‐Wei , Lin Li‐Zhen , Yu Er‐Han , Xin Jia‐Wei , Lin Lin , Lin Hai‐Long , Ye Qin‐Yong , Chen Xiao‐Chun , Pan Xiao‐Dong 
Published: March 2018

SummaryObjectiveTo investigate changes in the functional connectivity (FC) pattern in the posterior cingulate cortex (PCC) of Parkinson's disease (PD) patients with mild cognitive impairment and dementia by employing resting‐state functional magnetic resonance imaging (RS‐fMRI).MethodsTwenty‐seven PD patients with different cognitive status and 9 healthy control subjects (control group) were enrolled for RS‐fMRI. The RS‐fMRI data were analyzed with DPARSF and REST software. Regions with changed functional connectivity were determined by the seed‐based voxelwise method and compared between groups. Correlation between the intensity of FC and the MoCA scores of PD group was analyzed.ResultsParametric maps showed statistical increases in PCC functional connectivity in PD‐MCI patients and decreases in PCC connectivity in PDD patients. The latter group of patients also showed evidence for increased connectivity between prefrontal cortices and posterior cerebellum. A significant positive correlation was found between the MoCA scores and the strength of PCC connectivity in the angular gyrus and posterior cerebellum and a negative correlation between MoCA scores and PCC connectivity in all other brain regions.ConclusionWhen patients transition from PD‐NCI to PD‐MCI, there appears to be an increase in functional connectivity in the PCC, suggesting an expansion of the cortical network. Another new network (a compensatory prefrontal cortical‐cerebellar loop) later develops during the transition from PD‐MCI to PDD.
Efficacy of a new nail brace for the treatment of ingrown toenails
Authors: Liu Che‐Wei , Huang Yu‐Chen 
Published: March 2018

SummaryBackground and objectivesSurgery is the mainstay of treatment for complicated ingrown toenails. However, alternative treatments using nail braces have been reported to show good efficacy. The objective of the present study was to investigate the efficacy of a new nail brace for the treatment of ingrown toenails.Patients and methodsWe conducted a retrospective study on patients with ingrown toenails treated at Wan Fang Hospital between June 1, 2015 and May 30, 2016. Ingrown toenails were classified into acute inflamed/infected (AI) and chronic dystrophic (CD) types. Using physician global assessment scores, the efficacy of nail braces for the two types of ingrown toenails was compared 1, 2, 3, and 6 months after treatment initiation and during the final visit.ResultsTwenty‐one patients (42 sites) had CD‐type ingrown toenails; 25 patients (36 sites) had ingrown toenails of the AI type. Of the affected sites, 81 %, 94 %, and 100 % showed an excellent or fair outcome at 1, 3, and 6 months, respectively. Recurrence rates were 10.3 %; complication rates, 7.7 %. While, in the first three months, AI‐type ingrown toenails tended to achieve excellent results more rapidly than CD‐type nails, outcomes were similar at six months.ConclusionsNail braces are an effective therapeutic option, particularly for CD‐type ingrown toenails.
Survival of Ralstonia solanacearum and Ralstonia pseudosolanacearum in drain water
Authors: Stevens L. H. , van der Zouwen P. S. , van Tongeren C. A. M. , Kastelein P. , van der Wolf J. M. 
Published: March 2018

The survival in drain water of two strains of Ralstonia solanacearum and three strains of Ralstonia pseudosolanacearum, including two strains able to cause wilt in roses, was determined. Water draining from drip‐irrigated rock wool mats on which roses were grown was supplemented with the pathogen and survival was monitored at 4, 12, 20 and 28°C for up to 112 days. All strains were able to survive for at least 112 days in drain water at 12 and 20°C, but at 4°C maximum survival was 56 days. At 28°C, the survival period was strain dependent, but was at least 56 days. Populations declined gradually in non‐sterile drain water to a low level (maximum 100 cfu mL−1 after 112 days). In sterile drain water (autoclaved prior to addition of populations), no or only a limited decline in populations was found at 112 days, dependent on strain and temperature. Drain water that tested negative for Ralstonia in the dilution plating assay was tested for the presence of cells in a viable but non‐culturable state (VBNCs). Tomato plants were inoculated, but no symptoms developed, and plants sampled 22 days post‐inoculation were negative in a plating assay. Therefore, no indications were found that VBNCs were present.
Head and neck abscessation and thrombophlebitis following cheek tooth extraction in a pony
Authors: Horbal A. A. , Reardon R. J. M. , Froydenlund T. , Jago R. C. , Dixon P. M. 
Published: March 2018

SummaryDue to their long hypsodont reserve crowns, extraction of equid cheek teeth can be difficult and result in more complications than the extraction of their shorter brachydont counterparts although the more recent resumption of oral extraction has greatly reduced such complications. The more common post‐extraction sequelae in equids include non‐healing alveoli due to retained dental or alveolar sequestrae which may lead to oromaxillary or oronasal fistula formation, chronic external sinus tract formation or osteomyelitis of the supporting bones. Collateral damage to adjacent teeth has also occasionally been reported during dental repulsion. Systemic complications following equine cheek tooth extraction have been infrequently described, including a small number of cases of exodontia‐related bacterial meningioencephalitis. This is surprising, as dental manipulation can lead to bacteraemia in many species, including horses. Infections at distant sites related to the spread of dental pathogens have been well described in humans and in small animals. This report describes deep abscessation of the masseter muscles followed by extensive thrombophlebitis of the jugular, facial and rostral cervical veins following oral cheek tooth extraction in a pony affected by pituitary pars intermedia dysfunction (PPID) that was successfully treated by abscess drainage and thrombectomy of the affected veins.
Role of CD81 and CD58 in minimal residual disease detection in pediatric B lymphoblastic leukemia
Authors: Tsitsikov E. , Harris M. H. , Silverman L. B. , Sallan S. E. , Weinberg O. K. 
Published: March 2018

AbstractIntroductionMinimal residual disease (MRD) in B lymphoblastic leukemia has been demonstrated to be a powerful predictor of clinical outcome in numerous studies in both children and adults. In this study, we evaluated 86 pediatric patients with both diagnostic and remission flow cytometry studies and compared expression of CD81, CD58, CD19, CD34, CD20, and CD38 in the detection of MRD.MethodsWe evaluated 86 patients with B lymphoblastic leukemia who had both diagnostic studies and remission studies for the presence of MRD using multicolor flow cytometry. We established our detection limit for identifying abnormal lymphoblasts using serial dilutions. We also compared flow cytometry findings with molecular MRD detection in a subset of patients.ResultsWe found that we can resolve differences between hematogones and lymphoblasts in 85 of 86 cases using a combination of CD45, CD19, CD34, CD10, CD20, CD38, CD58, and CD81. Our detection limit using flow cytometry is 0.002% for detecting a population of abnormal B lymphoblasts. Comparison with MRD assessment by molecular methods showed a high concordance rate with flow cytometry findings.ConclusionsOur study highlights importance of using multiple markers to detect MRD in B lymphoblastic leukemia. Our findings indicate that including both CD58 and CD81 markers in addition to CD19, CD34, CD20, CD38, and CD10 are helpful in MRD detection by flow cytometry.
Green tea prevents vascular disturbs and attenuates periodontal breakdown in long‐term hyperglycaemia in T1D rats
Authors: Catanzaro Daniela Pereira , Mena Laura Ever Elias , Cestari Tania Mary , Arantes Ricardo Vinicius Nunes , Garlet Gustavo Pompermaier , Taga Rumio , Assis Gerson Francisco 
Published: March 2018

AbstractAimThe effects of green tea on the modulation of vascularization during the progression of spontaneous periodontitis in long‐term hyperglycaemia in streptozotocin‐induced type 1 diabetic (T1D) rats were evaluated.Materials and MethodsWistar rats normoglycaemic (NG) and T1D were divided into two control groups, which received water (NG‐W and T1D‐W) and two experimental groups that received green tea (NG‐GT and T1D‐GT). Periodontal structures were evaluated by microtomographic and histological analyses. Number of immunostained cells for VEGF (NcVEGF+/mm2) and CD31 (NcCD31+/mm2), as well microvessel density (MVD) in the periodontal ligament (PDL) were evaluated.ResultsLong‐term hyperglycaemia in T1D‐W rats induced vascular alterations in PDL with a reduction of 36% in MVD, a decrease of 33% in NcCD31+/mm2 and an increase of 53% in NcVEGF+/mm2. Concomitantly, a severe degree of periodontitis with higher reduction in bone volume and periodontal bone level was observed. In T1D‐GT, green tea maintained the MVD, NcCD31+/mm2 and NcVEGF+/mm2 in the PDL similar to normoglycaemic groups. Clinically, in T1D‐GT rats, green tea reduced dental plaque accumulation and the degree of periodontitis when compared to T1D‐W.ConclusionDaily green tea consumption has a therapeutic effect on the diabetic vascular disorder in PDL and the progression of periodontitis in long‐term hyperglycaemia in T1D rats.
The effect of decellularized tissue engineered constructs on periodontal regeneration
Authors: Farag Amro , Hashimi Saeed M. , Vaquette Cedryck , Bartold Peter M. , Hutmacher Dietmar W. , Ivanovski Saso 
Published: March 2018

AbstractAimTo evaluate the effect of decellularized tissue engineered constructs on cell differentiation in vitro and periodontal regeneration in vivo.Materials and MethodsPeriodontal ligament cell (PDLC) sheets were loaded on polycaprolactone (PCL) scaffolds and then decellularized. Constructs were assessed for their effect on allogenic PDLC and mesenchymal stem cell (MSC) differentiation in vitro, as evaluated by gene expression of bone and periodontal ligament tissue markers post‐seeding. Expression of MSC marker STRO‐1 was assessed by immunostaining. Decellularized constructs were evaluated in a rat periodontal defect model to assess their biocompatibility and tissue integration. Microcomputed topography (μCT) and histological assessment were performed to assess the regenerative potential of the constructs at 2 and 4 weeks postoperatively.ResultsThere was upregulation of bone marker gene expression by PDLCs especially on the 14th day. MSCs lacked bone markers expression, but showed increased collagen I marker expression on day 14. STRO‐1 expression by the MSCs decreased over the three timepoints when seeded on decellularized sheets. Histological assessment demonstrated the biocompatibility of the decellularized constructs in vivo. More new attachment formation was observed on the decellularized constructs compared to scaffold only controls.ConclusionDecellularized tissue engineered constructs are capable of inducing cell differentiation in vitro and have the potential to facilitate periodontal regeneration in vivo.
Minimum Data Set Changes in Health, End‐Stage Disease and Symptoms and Signs Scale: A Revised Measure to Predict Mortality in Nursing Home Residents
Authors: Ogarek Jessica A. , McCreedy Ellen M. , Thomas Kali S. , Teno Joan M. , Gozalo Pedro L. 
Published: March 2018

ObjectivesTo revise the Minimum Data Set (MDS) Changes in Health, End‐stage disease and Symptoms and Signs (CHESS) scale, an MDS 2.0‐based measure widely used to predict mortality in institutional settings, in response to the release of MDS 3.0.DesignDevelopment of a predictive scale using observational data from the MDS and Medicare Master Beneficiary Summary File.SettingAll Centers for Medicare and Medicaid Services (CMS)‐certified nursing homes in the United States.ParticipantsDevelopment cohort of 1.3 million Medicare beneficiaries newly admitted to a CMS‐certified nursing home during 2012. Primary validation cohort of 1.2 million Medicare recipients who were newly admitted to a CMS‐certified nursing home during 2013.MeasurementsItems from the MDS 3.0 assessments identified as likely to predict mortality. Death information was obtained from the Medicare Master Beneficiary Summary File.ResultsMDS‐CHESS 3.0 scores ranges from 0 (most stable) to 5 (least stable). Ninety‐two percent of the primary validation sample with a CHESS scale score of 5 and 15% with a CHESS scale of 0 died within 1 year. The risk of dying was 1.63 times as great (95% CI=1.628–1.638) for each unit increase in CHESS scale score. The MDS‐CHESS 3.0 is also strongly related to hospitalization within 30 days and successful discharge to the community. The scale predicted death in long‐stay residents at 30 days (C=0.759, 95% confidence interval (CI)=0.756–0.761), 60 days (C=0.716, 95% CI=0.714–0.718) and 1 year (C=0.655, 95% CI=0.654–0.657).ConclusionThe MDS‐CHESS 3.0 predicts mortality in newly admitted and long‐stay nursing home populations. The additional relationship to hospitalizations and successful discharges to community increases the utility of this scale as a potential risk adjustment tool.
Predicting Potential Adverse Events During a Skilled Nursing Facility Stay: A Skilled Nursing Facility Prognosis Score
Authors: Burke Robert E. , Hess Edward , Barón Anna E. , Levy Cari , Donzé Jacques D. 
Published: March 2018

ObjectivesTo derive a risk prediction score for potential adverse outcomes in older adults transitioning to a skilled nursing facility (SNF) from the hospital.DesignRetrospective analysis.SettingMedicare Current Beneficiary Survey (2003–11).ParticipantsPreviously community‐dwelling Medicare beneficiaries who were hospitalized and discharged to SNF for postacute care (N=2,043).MeasurementsRisk factors included demographic characteristics, comorbidities, health status, hospital length of stay, prior SNF stays, SNF size and ownership, treatments received, physical function, and active signs or symptoms at time of SNF admission. The primary outcome was a composite of undesirable outcomes from the patient perspective, including hospital readmission during the SNF stay, long SNF stay (≥100 days), and death during the SNF stay.ResultsOf the 2,043 previously community‐dwelling beneficiaries hospitalized and discharged to a SNF for post‐acute care, 589 (28.8%) experienced one of the three outcomes, with readmission (19.4%) most common, followed by mortality (10.5%) and long SNF stay (3.5%). A risk score including 5 factors (Barthel Index, Charlson‐Deyo comorbidity score, hospital length of stay, heart failure diagnosis, presence of an indwelling catheter) demonstrated very good discrimination (C‐statistic=0.75), accuracy (Brier score=0.17), and calibration for observed and expected events.ConclusionOlder adults frequently experience potentially adverse outcomes in transitions to a SNF from the hospital; this novel score could be used to better match resources with patient risk.
Hemopexin increases the neurotoxicity of hemoglobin when haptoglobin is absent
Authors: Chen‐Roetling Jing , Ma Sheng‐Kai , Cao Yang , Shah Aishwarya , Regan Raymond F. 
Published: March 2018

AbstractHemopexin (Hpx) binds heme with extraordinary affinity, and after haptoglobin may provide a second line of defense against the toxicity of extracellular hemoglobin (Hb). In this series of experiments, the hypothesis that Hpx protects neurons from Hb neurotoxicity was evaluated in murine primary cultures containing neurons and glial cells. Contrary to hypothesis, Hpx increased neuronal loss due to micromolar concentrations of Hb by 4‐ to 12‐fold, as measured by LDH release assay; conversely, the neurotoxicity of hemin was completely prevented. The endogenous fluorescence of Hpx was quenched by Hb, consistent with transfer of Hb‐bound heme to Hpx. This was associated with precipitation of globin chains, as detected by immunostaining and fluorescent Hb labeling. A portion of this precipitate attached firmly to cells and could not be removed by multiple washes. Concomitant treatment with haptoglobin (Hp) prevented globin precipitation and most of the increase in neuronal loss. Hpx weakly attenuated the increase in culture non‐heme iron produced by Hb treatment, quantified by ferrozine assay. However, Hb‐Hpx toxicity was iron‐dependent, and was blocked by deferoxamine and ferrostatin‐1. Up‐regulation of cell ferritin expression, a primary cell defense against Hb toxicity, was not observed on western blots of culture lysates that had been concomitantly treated with Hpx. These results suggest that Hpx destabilizes Hb in the absence of haptoglobin, leading to globin precipitation and exacerbation of iron‐dependent oxidative cell injury. Combined therapy with hemopexin plus haptoglobin may be preferable to hemopexin alone after CNS hemorrhage.
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