bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trifecta and optimal perioperative outcomes of robotic and laparoscopic partial nephrectomy in surgical treatment of small renal masses: a multi‐institutional study
Authors: Zargar Homayoun , Allaf Mohamad E. , Bhayani Sam , Stifelman Michael , Rogers Craig , Ball Mark W. , Larson Jeffrey , Marshall Susan , Kumar Ramesh , Kaouk Jihad H. 
Published: September 2014

ObjectiveTo compare the perioperative outcomes of robotic partial nephrectomy (RPN) with laparoscopic PN (LPN) performed for small renal masses (SRMs), in a large multi‐institutional series and to define a new composite outcome measure, termed ‘optimal outcome’ for the RPN group.Patients and MethodsRetrospective review of 2392 consecutive cases of RPN and LPN performed in five high‐volume centres from 2004 to mid‐2013. We limited our study to SRMs and cases performed by surgeons with significant expertise with the technique. The Trifecta was defined as negative surgical margin, zero perioperative complications and a warm ischaemia time of ≤25 min. The ‘optimal outcome’ was defined as achievement of Trifecta with addition of 90% estimated glomerular filtration rate preservation and no chronic kidney disease stage upgrading. Univariable and multivariable analysis were used to identify factors predicting Trifecta and ‘optimal outcome’ achievement.ResultsIn all, 1185 RPN and 646 LPN met our inclusion criteria. Patients in the RPN group were older and had a higher median Charlson comorbidity index and higher R.E.N.A.L. nephrometry score. The RPN group had lower warm ischaemia time (18 vs 26 min), overall complication rate (16.2% vs 25.9%), and positive surgical margin rate (3.2% vs. 9.7%). There was a significantly higher Trifecta rate for RPN (70% vs 33%) and the rate of achievement of ‘optimal outcome’ for the RPN group was 38.5%.ConclusionsIn this large multi‐institutional series RPN was superior to LPN for perioperative surgical outcomes measured by Trifecta. Patients in the RPN group had better outcomes for all three components of Trifecta compared with their LPN counterparts. Our more strict definition for ‘optimal outcome’ might be a better tool for assessing perioperative and functional outcomes after minimally invasive PN. This tool needs to be externally validated.
YM155 down‐regulates survivin and XIAP, modulates autophagy and induces autophagy‐dependent DNA damage in breast cancer cells
Authors: Cheng S M , Chang Y C , Liu C Y , Lee J Y C , Chan H H , Kuo C W , Lin K Y , Tsai S L , Chen S H , Li C F , Leung E , Kanwar J R , Huang C C , Chang J Y , Cheung C H A 
Published: September 2014

Background and PurposeThe aim of this study was to determine the potency and molecular mechanism of action of YM155, a first‐in‐class survivin inhibitor that is currently under phase I/II clinical investigations, in various drug‐resistant breast cancers including the oestrogen receptor positive (ER+) tamoxifen‐resistant breast cancer and the caspase‐3‐deficient breast cancer.Experimental ApproachThe potency of YM155 in SK‐BR‐3, MDA‐MB‐231, MCF7 and its tamoxifen‐resistant sublines, TamR6, TamR7, TamR8, TamC3 and TamC6, were determined by MTT assay. Western blot analysis, flow cytometric analysis, reverse transcription‐PCR, fluorescent microscopy and comet assay were used to determine the molecular mechanism of action of YM155 in different breast cancer cell lines.Key ResultsYM155 was equally potent towards the parental ER+/caspase‐3‐deficient MCF7 breast cancer cells and its tamoxifen‐resistant sublines in vitro. The ER−/HER2+ SK‐BR‐3 breast cancer cells and the triple‐negative/caspase‐3‐expressing metastatic aggressive MDA‐MB‐231 breast cancer cells were also sensitive to YM155 with IC50 values in the low nanomolar range. Targeting survivin by YM155 modulated autophagy, induced autophagy‐dependent caspase‐7 activation and autophagy‐dependent DNA damage in breast cancer cells. Interestingly, YM155 also induced XIAP degradation and the degradation of XIAP might play an important role in YM155‐induced autophagy in breast cancer cells.Conclusions and ImplicationsYM155 is a potent survivin inhibitor that has potential for the management of various breast cancer subtypes regardless of the expression of ER, HER2 and caspase‐3. Importantly, this study provides new insights into YM155's molecular mechanism of action and therapeutic potential in the treatment of tamoxifen‐resistant breast cancer.
Biased allosteric modulation at the CaS receptor engendered by structurally diverse calcimimetics
Authors: Cook A E , Mistry S N , Gregory K J , Furness S G B , Sexton P M , Scammells P J , Conigrave A D , Christopoulos A , Leach K 
Published: September 2014

Background and PurposeClinical use of cinacalcet in hyperparathyroidism is complicated by its tendency to induce hypocalcaemia, arising partly from activation of calcium‐sensing receptors (CaS receptors) in the thyroid and stimulation of calcitonin release. CaS receptor allosteric modulators that selectively bias signalling towards pathways that mediate desired effects [e.g. parathyroid hormone (PTH) suppression] rather than those mediating undesirable effects (e.g. elevated serum calcitonin), may offer better therapies.Experimental ApproachWe characterized the ligand‐biased profile of novel calcimimetics in HEK293 cells stably expressing human CaS receptors, by monitoring intracellular calcium (Ca2+i) mobilization, inositol phosphate (IP)1 accumulation, ERK1/2 phosphorylation (pERK1/2) and receptor expression.Key ResultsPhenylalkylamine calcimimetics were biased towards allosteric modulation of Ca2+i mobilization and IP1 accumulation. S,R‐calcimimetic B was biased only towards IP1 accumulation. R,R‐calcimimetic B and AC‐265347 were biased towards IP1 accumulation and pERK1/2. Nor‐calcimimetic B was unbiased. In contrast to phenylalkylamines and calcimimetic B analogues, AC‐265347 did not promote trafficking of a loss‐of‐expression, naturally occurring, CaS receptor mutation (G670E).Conclusions and ImplicationsThe ability of R,R‐calcimimetic B and AC‐265347 to bias signalling towards pERK1/2 and IP1 accumulation may explain their suppression of PTH levels in vivo at concentrations that have no effect on serum calcitonin levels. The demonstration that AC‐265347 promotes CaS receptor receptor signalling, but not trafficking reveals a novel profile of ligand‐biased modulation at CaS receptors The identification of allosteric modulators that bias CaS receptor signalling towards distinct intracellular pathways provides an opportunity to develop desirable biased signalling profiles in vivo for mediating selective physiological responses.
Health and functioning in the everyday lives of young children with cancer: documenting with the International Classification of Functioning, Disability and Health – Children and Youth (ICF‐CY)
Authors: Darcy L. , Enskär K. , Granlund M. , Simeonsson R. J. , Peterson C. , Björk M. 
Published: September 2014

AbstractBackgroundHealth care focus is shifting for children from surviving childhood cancer to living with it on a daily basis. There is a need to document health and function in the everyday lives of young children with cancer using the multidimensional framework and language of the International Classification of Functioning, Disability and Health – Children and Youth (ICF‐CY).AimsThe aims of this study were (1) to document health and functioning in the everyday lives of young children with cancer using ICF‐CY codes and (2) to identify a comprehensive code set that can aid clinical assessment.MethodInterviews with children diagnosed with cancer and their parents, were transcribed, reviewed for content and coded to the ICF‐CY using linking procedures.ResultsA comprehensive code set (n = 70) for childhood cancer was identified. The majority of content identified to codes was related to activity and participation describing social relations with family, peers and professionals, preschool attendance and play, as well as issues related to support and independence.ConclusionsThe ICF‐CY can be used to document the nature and range of characteristics and consequences of cancer experienced by children. The identified comprehensive code set could be helpful to health care professionals, parents and teachers in assessing and supporting young children's health and everyday life through the cancer trajectory. The comprehensive code set could be developed as a clinical assessment tool for those caring for young children with cancer. The universal language of the ICF‐CY means that the utility of a clinical assessment tool based on identified codes can have wide reaching effects for the care of young children with cancer.
Early risk factors for pubertal asthma
Authors: Hovland V. , Riiser A. , Mowinckel P. , Carlsen K.‐H. , Lødrup Carlsen K. C. 
Published: September 2014

SummaryBackgroundEarly life risk factors are previously described for childhood asthma, but less is known related to asthma in adolescence. We aimed to investigate early risk factors (before 2 years) for pubertal asthma and secondarily for pubertal asthma phenotypes based upon allergic comorbidities.MethodsBased on data from 550 adolescents in the prospective birth cohort ‘Environment and Childhood Asthma’ study, subjects were categorized by recurrent bronchial obstruction (rBO) 0–2 years, asthma 2–10 years, and pubertal asthma from 10 to 16 years including incident asthma in puberty and asthma in remission from 10 to 16 years or as never rBO/asthma 0–16 years. Asthma in puberty was further classified based on the comorbidities atopic dermatitis and allergic rhinitis (AR) from 10 to 16 years. Twenty‐three common asthma risk factors identified by 2 years of age, including frequency and persistence of bronchial obstruction (severity score), were analysed by weighted logistic regression for each phenotype.ResultsIn adjusted models, the risk of pubertal asthma increased significantly with higher severity score, parental rhinitis, being the firstborn child, and familial stress around birth. Pubertal asthma in remission was significantly associated with severity score and number of lower respiratory tract infections and inversely associated with breastfeeding beyond 4 months. Pubertal incident asthma was more common among firstborn children. All asthma phenotypes with allergic diseases were significantly associated with severity score, whereas familial perinatal stress increased the risk of asthma only. Asthma combined with AR was associated with parental asthma and being firstborn, whereas the risk of asthma with both atopic dermatitis and AR increased with higher paternal education, atopic dermatitis, being firstborn, and familial perinatal stress.Conclusion and clinical relevanceImportant early risk factors for pubertal asthma were early airways obstruction, parental rhinitis, being the firstborn child, and perinatal familial stress.
T-bet regulates differentiation of forkhead box protein 3+ regulatory T cells in programmed cell death-1-deficient mice
Authors: Tahara M , Kondo Y , Yokosawa M , Tsuboi H , Takahashi S , Shibayama S , Matsumoto I , Sumida T 
Published: September 2014

SummaryProgrammed cell death-1 (PD-1) plays an important role in peripheral T cell tolerance, but whether or not it affects the differentiation of helper T cell subsets remains elusive. Here we describe the importance of PD-1 in the control of T helper type 1 (Th1) cell activation and development of forkhead box protein 3 (FoxP3+) regulatory T cells (Tregs). PD-1-deficient T cell-specific T-bet transgenic (P/T) mice showed growth retardation, and the majority died within 10 weeks. P/T mice showed T-bet over-expression, increased interferon (IFN)-γ production by CD4+T cells and significantly low FoxP3+Treg cell percentage. P/T mice developed systemic inflammation, which was probably induced by augmented Th1 response and low FoxP3+Treg count. The study identified a unique, previously undescribed role for PD-1 in Th1 and Treg differentiation, with potential implication in the development of Th1 cell-targeted therapy.
Accuracy of computer‐guided implantation in a human cadaver model
Authors: Yatzkair Gustavo , Cheng Alice , Brodie Stan , Raviv Eli , Boyan Barbara D. , Schwartz Zvi 
Published: September 2014

AbstractObjectivesTo examine the accuracy of computer‐guided implantation using a human cadaver model with reduced experimental variability.Materials and methodsTwenty‐eight (28) dental implants representing 12 clinical cases were placed in four cadaver heads using a static guided implantation template. All planning and surgeries were performed by one clinician. All radiographs and measurements were performed by two examiners. The distance of the implants from buccal and lingual bone and mesial implant or tooth was analyzed at the apical and coronal levels, and measurements were compared to the planned values.ResultsNo significant differences were seen between planned and implanted measurements. Average deviation of an implant from its planning radiograph was 0.8 mm, which is within the range of variability expected fromCTanalysis.ConclusionsGuided implantation can be used safely with a margin of error of 1 mm.
Influence of local administration of pamidronate on extraction socket healing – a histomorphometric proof‐of‐principle pre‐clinical in vivo evaluation
Authors: Fischer Kai R. , Stavropoulos Andreas , Calvo‐Guirado José‐Luis , Schneider David , Fickl Stefan 
Published: September 2014

AbstractObjectivesTo evaluate the influence of local administration of pamidronate histomorphometrically, adsorbed on a collagenated porcine bone substitute, on extraction socket healing.Material and methodsTwo American Fox‐hound dogs were used within this proof‐of‐principle study. Following endodontic treatment of the distal root of the three lower premolars, the teeth were hemisected, and the mesial roots were extracted flapless. The sockets were then loosely filled, in a split‐mouth fashion, with a collagenated porcine bone substitute (Osteobiol Gen‐Os; CPB), rehydrated either with 90 mg/ml pamidronate (Aredia®; test) or with sterile saline (control). Extraction sockets were sealed with connective tissue punches obtained from the palate and secured with sutures. After 4 months of healing, specimens containing the socket sites and remaining roots were retrieved and histomorphometrically examined.ResultsHistological evaluation of the sections revealed substantial differences in healing patterns. Control sites presented with various amounts of newly formed bone and no evidence of CPB inside the socket; in contrast, limited amounts of bone were observed at test sites, which were filled with CPB mainly embedded in connective tissue. Only minor differences were observed between test and control sites regarding vertical bone loss (buccal bone: −1.01 mm vs. −1.15 mm; lingual bone: −0.92 mm vs. −1.15 mm). Horizontal bone loss was nearly three times higher in control sites comparing to sites treated with pamidronate (−2.19 ± 1.81 mm vs. −0.80 ± 0.91 mm) at a level corresponding to 3 mm below the cemento‐enamel junction (CEJ).ConclusionLocal administration of pamidronate adsorbed on a collagenated porcine bone substitute in particulate form appeared to delay extraction socket healing, but may also reduce post‐extraction dimensional changes in terms of horizontal bone width. Additionally, pamidronate appears to obstruct resorption of the porcine bone substitute.
Narrative and the Stability of Intention
Authors: Hinchman Edward S. 
Published: September 2014

AbstractThis paper addresses a problem concerning the rational stability of intention. When you form an intention to φ at some future time t, you thereby make it subjectively rational for you to follow through and φ at t, even if—hypothetically—you would abandon the intention were you to redeliberate at t. It is hard to understand how this is possible. Shouldn't the perspective of your acting self be what determines what is then subjectively rational for you? I aim to solve this problem by highlighting a role for narrative in intention. I'll argue that committing yourself to a course of action by intending to pursue it crucially involves the expectation that your acting self will be ‘swept along’ by its participation in a distinctively narrative form of self‐understanding. I'll motivate my approach by criticizing Richard Holton's and Michael Bratman's recent treatments of the stability of intention, though my account also borrows from Bratman's work. I'll likewise criticize and borrow from David Velleman's work on narrative and self‐intelligibility. When the pieces fall into place, we'll see how intending is akin to telling your future self a kind of story. My thesis is not that you address your acting self but that your acting self figures as a ‘character’ in the ‘story’ that you address to a still later self. Unlike other appeals to narrative in agency, mine will explain how as narrator you address a specifically intrapersonal audience.
Cognitive and affective functions in diabetic patients associated with diabetes‐related factors, white matter abnormality and aging
Authors: Hishikawa N. , Yamashita T. , Deguchi K. , Wada J. , Shikata K. , Makino H. , Abe K. 
Published: September 2014

Background and purposeDiabetes mellitus (DM) is associated with a decline in cognitive and affective functions.MethodsIn all, 182 outpatients with DM were investigated for associations of cognitive and affective functions with diabetes‐related factors and cerebral white matter abnormalities. In addition, the difference in cognitive decline of age‐matched late elderly normal subjects and DM patients was investigated.ResultsThe present study revealed that cognitive and affective functions declined in some DM patients. Furthermore, the decline in these functions was unrelated to fasting blood sugar level but was related to glycosylated hemoglobin (HbA1c) and insulin resistance. Poor HbA1c control was associated with a significant decline in the ‘calculation’ subscale and insulin resistance for ‘naming’, ‘read list of letters’ and ‘delayed recall’ Montreal Cognitive Assessment (MoCA) subscale scores. Magnetic resonance imaging scans showed that both periventricular hyperintensity (PVH) and deep white matter hyperintensity were associated with Mini Mental State Examination (MMSE) and MoCA scores, but only PVH was related to homeostasis model assessment of insulin resistance scores. Compared with age‐matched late elderly normal subjects, ‘orientation to time’ and ‘registration’ MMSE subscales declined in late elderly DM patients.ConclusionsThese results suggest that cognitive and affective decline in DM patients was mostly related to glucose control and insulin resistance, whilst amongst late elderly subjects the impairment of ‘attention’ and ‘orientation’ were characteristic features of DM patients.
Effect of spontaneous seizures on GABAA receptor α4 subunit expression in an animal model of temporal lobe epilepsy
Authors: Grabenstatter Heidi L , Cogswell Meaghan , Cruz Del Angel Yasmin , Carlsen Jessica , Gonzalez Marco I. , Raol Yogendra H. , Russek Shelley J. , Brooks‐Kayal Amy R. 
Published: September 2014

SummaryObjectiveTemporal lobe epilepsy (TLE) is frequently medically intractable and often progressive. Compromised inhibitory neurotransmission due to altered γ‐aminobutyric acid (GABA)A receptor α4 subunit (GABAARα4) expression has been emphasized as a potential contributor to the initial development of epilepsy following a brain insult (primary epileptogenesis), but the regulation of GABAARα4 during chronic epilepsy, specifically, how expression is altered following spontaneous seizures, is less well understood.MethodsContinuous video–electroencephalography (EEG) recordings from rats with pilocarpine‐induced TLE were used to capture epileptic animals within 3 h of a spontaneous seizure (SS), or >24 h after the last SS, to determine whether recent occurrence of a seizure was associated with altered levels of GABAARα4 expression. We further evaluated whether this GABAARα4 plasticity is regulated by signaling mechanisms active in primary epileptogenesis, specifically, increases in brain‐derived neurotrophic factor (BDNF) and early growth response factor 3 (Egr3).ResultsElevated levels of GABAARα4 messenger RNA (mRNA) and protein were observed following spontaneous seizures, and were associated with higher levels of BDNF and Egr3 mRNA.SignificanceThese data suggest that spontaneous, recurrent seizures that define chronic epilepsy may influence changes in GABAARα4 expression, and that signaling pathways known to regulate GABAARα4 expression after status epilepticus may also be activated after spontaneous seizures in chronically epileptic animals.
Evaluation of serum calcium and serum parathyroid levels in post‐menopausal women with and without oral dryness
Authors: Singh Balwinder , Pallagatti Shambulingappa , Narang Ramandeep Singh , Kaur Kirandeep , Sheikh Soheyl , Manchanda Adesh , Arora Gagandeep 
Published: September 2014

ObjectiveThe primary objective of this study was to estimate and secondary objective was to compare the serum calcium levels and serum parathyroid hormone (PTH) levels in post‐menopausal women with and without oral dryness (OD).Materials and MethodsA case–control study was carried out on 80 selected post‐menopausal women. Salivary flow was assessed by flow rate; serum calcium concentrations were assessed through Semi Autoanalyzer by Arsenazo III reaction. The serum PTH concentration was measured by the enzyme‐linked immunosorbent assay. Severity of OD was assessed by a questionnaire through which the xerostomia inventory (XI) score could be measured. Statistical analysis of Student's t‐test, Mann–Whitney test and Pearson's correlation was used.ResultsThere was a significant difference in mean values of both serum PTH concentration and XI score in post‐menopausal women with/without OD (p < 0.001). No statistically significant difference (p = 0.354) was found in salivary flow rate and serum calcium levels in post‐menopausal women in both groups. A positive correlation was found between the serum PTH and XI score in both case and control groups (p < 0.05).ConclusionSeverity of oral dryness in post‐menopausal women is associated with the high levels of serum PTH. However, the correlation of severity of OD with serum calcium could not be established.
In vitro and in vivo removal of oral Candida from the denture base
Authors: Kawasaki Kiyotsugu , Kamikawa Yoshiaki , Sugihara Kazumasa 
Published: September 2014

ObjectivesTo clarify the effectiveness of ultrasonic cleaning for removing Candida lodged in the denture base.Materials and MethodsIn vitro – Specimens of acrylic resin for denture plates contaminated with Candida cells were ultrasonically cleaned for 30 min. Washings were sampled every 5 min and cultured to investigate residual contamination, measured as colony forming units/ml, and the surfaces of the specimens were subjected to low‐vacuum scanning electron microscopy (LV‐SEM). In vivo – A total of 24 maxillary denture bases were brushed for 2 min under running tap water, then ultrasonically cleaned for 30 min. The washings were sampled every 5 min and cultured to investigate residual contamination.ResultsIn vitro – Maximum removal was achieved during the first 5 min of cleaning, with the mean CFU/ml counts significantly declining over time. More than 85% of all Candida was removed within the first 15 min in specimens inoculated with phosphate‐buffered saline suspensions of Candida albicans and Candida glabrata. LV‐SEM revealed a decreased number of Candida on the surface of the specimens after 30 min of ultrasonic cleaning. In vivo – Maximum removal was achieved during the first 5 min of cleaning, then the mean CFU/ml count significantly declined during the first 10 min. Ultrasonic cleaning for 15 min removed 88.4% of Candida species from the denture base.ConclusionsUltrasonic cleaning is a reliable and simple method for removing Candida lodged in the denture base.