bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a voided urine assay for detecting prostate cancer non‐invasively: a pilot study
Authors: Trabulsi Edouard J. , Tripathi Sushil K. , Gomella Leonard , Solomides Charalambos , Wickstrom Eric , Thakur Mathew L. 
Published: January 2017

ObjectiveTo validate a hypothesis that prostate cancer can be detected non‐invasively by a simple and reliable assay by targeting genomic VPAC receptors expressed on malignant prostate cancer cells shed in voided urine.Patients/Subjects and MethodsVPAC receptors were targeted with a specific biomolecule, TP4303, developed in our laboratory. With an Institutional Review Board exempt approval of use of de‐identified discarded samples, an aliquot of urine collected as a standard of care, from patients presenting to the urology clinic (207 patients, 176 men and 31 women, aged ≥21 years) was cytospun. The cells were fixed and treated with TP4303 and 4,6‐diamidino‐2‐phenylindole (DAPI). The cells were then observed under a microscope and cells with TP4303 orange fluorescence around the blue (DAPI) nucleus were considered ‘malignant’ and those only with a blue nucleus were regarded as ‘normal’. VPAC presence was validated using receptor blocking assay and cell malignancy was confirmed by prostate cancer gene profile examination.ResultsThe urine specimens were labelled only with gender and presenting diagnosis, with no personal health identifiers or other clinical data. The assay detected VPAC positive cells in 98.6% of the men with a prostate cancer diagnosis (141), and none of the 10 men with benign prostatic hyperplasia. Of the 56 ‘normal’ patients, 62.5% (35 patients, 10 men and 25 women) were negative for VPAC cells; 19.6% (11, 11 men and no women) had VPAC positive cells; and 17.8% (10, four men and six women) were uninterpretable due to excessive crystals in the urine. Although data are limited, the sensitivity of the assay was 99.3% with a confidence interval (CI) of 96.1–100% and the specificity was 100% with a CI of 69.2–100%. Receptor blocking assay and fluorescence‐activated cell sorting (FACS) analyses demonstrated the presence of VPAC receptors and gene profiling examinations confirmed that the cells expressing VPAC receptors were malignant prostate cancer cells.ConclusionThese preliminary data are highly encouraging and warrant further evaluation of the assay to serve as a simple and reliable tool to detect prostate cancer non‐invasively.
Cetuximab strongly enhances immune cell infiltration into liver metastatic sites in colorectal cancer
Authors: Inoue Yuka , Hazama Shoichi , Suzuki Nobuaki , Tokumitsu Yukio , Kanekiyo Shinsuke , Tomochika Shinobu , Tsunedomi Ryouichi , Tokuhisa Yoshihiro , Iida Michihisa , Sakamoto Kazuhiko , Takeda Shigeru , Ueno Tomio , Yoshino Shigefumi , Nagano Hiroaki 
Published: January 2017

Cetuximab has activity against colorectal cancers. Recent studies demonstrated that cetuximab induces antibody‐dependent cell‐mediated cytotoxicity via immune cells, and a new immune‐related mechanism of inducing immunogenic cell death. This study aimed to evaluate the immune responses induced by cetuximab in tumor microenvironments at liver metastasis sites of metastatic colorectal cancer patients. We assessed immune cell infiltration in the liver metastatic sites of 53 colorectal cancer patients. These patients were divided into three groups according to the treatment before operation: chemotherapy with cetuximab, chemotherapy without cetuximab, and no chemotherapy. The inflammatory cells in the liver metastatic sites were assessed by hematoxylin–eosin staining, focusing on the invasive margin. The overall inflammatory reaction and number of lymphoid cells were assessed with a four‐point scoring system. We then assessed immune cell infiltration (CD3, CD8 and CD56) in 15 liver metastatic sites. Hematoxylin–eosin staining demonstrated more inflammatory cells in the chemotherapy with cetuximab group than in the other groups (P < 0.001). Of note, inflammatory cells were found in intratumoral areas, and the destruction of cancer cell foci was observed in the chemotherapy with cetuximab group. Moreover, a higher infiltration of CD3+ (P = 0.003), CD8+ (P = 0.003) and CD56+ (P = 0.001) cells was observed in the chemotherapy with cetuximab group than in the other groups. These results suggest that cetuximab might have an immune‐enhancing effect. As such, the immune‐related mechanism of action of cetuximab may enhance the efficacy of combination therapy, such as chemotherapy and immunotherapy using therapeutic peptides.
Efficacy and safety of fixed‐dose combination therapy, alogliptin plus metformin, in Asian patients with type 2 diabetes: A phase 3 trial
Authors: Ji Linong , Li Ling , Kuang Jian , Yang Tao , Kim Dong‐Jun , Kadir Azidah A. , Huang Chien‐Ning , Lee Douglas 
Published: January 2017

This study evaluated the efficacy and safety of 26 weeks of twice‐daily (BID) alogliptin + metformin fixed‐dose combination (FDC) therapy in Asian patients with type 2 diabetes. Patients aged 18 to 75 years with hemoglobin A1c (HbA1c) of 7.5% to 10.0% after ≥2 months of diet and exercise and a 4‐week placebo run‐in were enrolled. Eligible patients were randomized (1:1:1:1) to placebo, alogliptin 12.5 mg BID, metformin 500 mg BID or alogliptin 12.5 mg plus metformin 500 mg FDC BID. The primary endpoint was change in HbA1c from baseline to end of treatment (Week 26). In total, 647 patients were randomized. The least‐squares mean change in HbA1c from baseline to Week 26 was −0.19% with placebo, −0.86% with alogliptin, −1.04% with metformin and −1.53% with alogliptin + metformin FDC. Alogliptin + metformin FDC was significantly more effective (
P
< .0001) in lowering HbA1c than either alogliptin or metformin alone. The safety profile of alogliptin + metformin FDC was similar to that of the individual components alogliptin and metformin. The study demonstrated that treatment with alogliptin + metformin FDC BID resulted in better glycaemic control than either monotherapy and was well tolerated in Asian patients with type 2 diabetes.
Soluble transferrin receptor and risk of type 2 diabetes in the obese and nonobese
Authors: Fernández‐Cao José C. , Arija Victoria , Aranda Núria , Basora Josep , Diez‐Espino Javier , Estruch Ramón , Fitó Montse , Corella Dolores , Salas‐Salvadó Jordi 
Published: January 2017

AbstractBackgroundStudies evaluating the relationship between soluble transferrin receptor (sTfR), a biomarker inversely related to body iron stores, and risk of type 2 diabetes mellitus (T2DM) are scarce and inconclusive. Furthermore, sTfR concentrations have been observed to be significantly higher in obese than in nonobese individuals. Therefore, the aim of this study was to assess the relationship between sTfR and the risk of T2DM in obese and nonobese subjects.DesignA nested case–control study of 153 cases of newly diagnosed diabetic subjects, 73 obese and 80 nonobese, and 306 individually matched controls, 138 obese and 166 nonobese, who did not develop T2DM for a median 6‐year follow‐up (interquartile range: 3·9–6·5) was conducted using data from the PREvention with MEDiterranean Diet (PREDIMED) cohort (http://www.controlled-trials.com/ISRCTN35739639). Cases and controls were matched for age (≤ 67 vs. > 67 years), gender, dietary intervention group and BMI (≤ 27 vs. > 27 kg/m2).ResultsWaist circumference is the main determinant of sTfR concentrations in the whole sample (β = 0·476, P < 0·001), in the obese (β = 0·802, P < 0·001) and the nonobese (β = 0·455, P = 0·003). Furthermore, sTfR is directly associated with the risk of T2DM in obese individuals (OR = 2·79; 95% CI: 1·35–5·77, P = 0·005) and inversely associated in nonobese individuals (OR = 0·40; 95% CI: 0·20–0·79, P = 0·015).ConclusionsThe association between sTfR levels and risk of T2DM in a population at high cardiovascular risk depend on the presence or absence of obesity. While in nonobese subjects elevated sTfR levels are associated with a decreased risk of developing T2DM, in obese subjects the risk increases. This suggests that obesity alters the relationship between sTfR and T2DM incidence.
Knowledge and its Objects: Revisiting the Bounds of Sense
Authors: Cassam Quassim 
Published: January 2017

AbstractThe Kantian project of investigating the necessary structure of experience presupposes answers to three questions: what is the purpose of such an investigation, what is the source of necessary features of experience, and by what means is it possible to establish the necessary structure of experience? This paper is a critical examination of Strawson's answers to these questions in The Bounds of Sense and his later work. The realism that is implicit in The Bounds of Sense is much more explicit in Strawson's later work but relies on problematic assumptions about the relationship between epistemology and metaphysics.
Binding and processing of β‐lactam antibiotics by the transpeptidase LdtMt2 from Mycobacterium tuberculosis
Authors: Steiner Eva Maria , Schneider Gunter , Schnell Robert 
Published: January 2017

β‐lactam antibiotics represent a novel direction in the chemotherapy of tuberculosis that brings the peptidoglycan layer of the complex mycobacterial cell wall in focus as a therapeutic target. Peptidoglycan stability in Mycobacterium tuberculosis, especially during infection, relies on the nonconventional peptide cross‐links formed by l,d‐transpeptidases. These enzymes are known to be inhibited by β‐lactams, primarily carbapenems, leading to a stable covalent modification at the enzyme active site. A panel of 16 β‐lactam antibiotics was characterized by inhibition kinetics, mass spectrometry, and x‐ray crystallography to identify efficient compounds and study their action on the essential transpeptidase, LdtMt2. Members of the carbapenem class displayed fast binding kinetics, but faropenem, a penem type compound showed a three to four time higher rate in the adduct formation. In three cases, mass spectrometry indicated that carbapenems may undergo decarboxylation, while faropenem decomposition following the acylation step results in a small 87 Da β‐OH‐butyryl adduct bound at the catalytic cysteine residue. The crystal structure of LdtMt2 at 1.54 Å resolution with this fragment bound revealed that the protein adopts a closed conformation that shields the thioester bond from the solvent, which is in line with the high stability of this dead‐end complex observed also in biochemical assays.DatabaseStructural data are available in Protein Data Bank under the accession numbers 5LB1 and 5LBG.
Large extents of intensive land use limit community reorganization during climate warming
Authors: Oliver Tom H. , Gillings Simon , Pearce‐Higgins James W. , Brereton Tom , Crick Humphrey Q. P. , Duffield Simon J. , Morecroft Michael D. , Roy David B. 
Published: January 2017

AbstractClimate change is increasingly altering the composition of ecological communities, in combination with other environmental pressures such as high‐intensity land use. Pressures are expected to interact in their effects, but the extent to which intensive human land use constrains community responses to climate change is currently unclear. A generic indicator of climate change impact, the community temperature index (CTI), has previously been used to suggest that both bird and butterflies are successfully ‘tracking’ climate change. Here, we assessed community changes at over 600 English bird or butterfly monitoring sites over three decades and tested how the surrounding land has influenced these changes. We partitioned community changes into warm‐ and cold‐associated assemblages and found that English bird communities have not reorganized successfully in response to climate change. CTI increases for birds are primarily attributable to the loss of cold‐associated species, whilst for butterflies, warm‐associated species have tended to increase. Importantly, the area of intensively managed land use around monitoring sites appears to influence these community changes, with large extents of intensively managed land limiting ‘adaptive’ community reorganization in response to climate change. Specifically, high‐intensity land use appears to exacerbate declines in cold‐adapted bird and butterfly species, and prevent increases in warm‐associated birds. This has broad implications for managing landscapes to promote climate change adaptation.
National implementation of a mental health service model: A survey of Crisis Resolution Teams in England
Authors: Lloyd‐Evans Brynmor , Paterson Bethan , Onyett Steve , Brown Ellie , Istead Hannah , Gray Richard , Henderson Claire , Johnson Sonia 
Published: January 2017

AbstractIn response to pressures on mental health inpatient beds and a perceived ‘crisis in acute care’, Crisis Resolution Teams (CRTs), acute home treatment services, were implemented nationally in England following the NHS Plan in the year 2000: an unprecedentedly prescriptive policy mandate for three new types of functional community mental health team. We examined the effects of this mandate on implementation of the CRT service model. Two hundred and eighteen CRTs were mapped in England, including services in all 65 mental health administrative regions. Eighty‐eight percent (n = 192) of CRT managers in England participated in an online survey. CRT service organization and delivery was highly variable. Nurses were the only professional group employed in all CRT staff teams. Almost no teams adhered fully to government implementation guidance. CRT managers identified several aspects of CRT service delivery as desirable but not routinely provided. A national policy mandate and government guidance and standards have proved insufficient to ensure CRT implementation as planned. Development and testing of resources to support implementation and monitoring of a complex mental health intervention is required.
A comparison of approaches for stratifying on the propensity score to reduce bias
Authors: Linden Ariel 
Published: January 2017

AbstractRationale, aims, and objectivesStratification is a popular propensity score (PS) adjustment technique. It has been shown that stratifying the PS into 5 quantiles can remove over 90% of the bias due to the covariates used to generate the PS. Because of this finding, many investigators partition their data into 5 quantiles of the PS without examining whether a more robust solution (one that increases covariate balance while potentially reducing bias in the outcome analysis) can be found for their data. Two approaches (referred to herein as PSCORE and PSTRATA) obtain the optimal stratification solution by repeatedly dividing the data into strata until balance is achieved between treatment and control groups on the PS. These algorithms differ in how they partition the data, and it is not known which is better, or if either is better than a 5‐quantile default approach, for reducing bias in treatment effect estimates.MethodMonte Carlo simulations and empirical data are used to assess whether PS strata defined by PSCORE, PSTRATA, or 5 quantiles is best at reducing bias in treatment effect estimates, when used within a marginal mean weighting framework (MMWS). These estimates are further compared to results derived using inverse probability of treatment weights (IPTW).ResultsPSTRATA was slightly better than PSCORE in balancing covariates and reducing bias, while both approaches outperformed the 5‐quantile approach. Overall MMWS using any stratification method outperformed IPTW.ConclusionsInvestigators should routinely use stratification approaches that obtain the optimal stratification solution, rather than simply partitioning the data into 5 quantiles of the PS. Moreover, MMWS (in conjunction with an optimal stratification approach) should be considered as an alternative to IPTW in studies that use PS weights.
Prevalence, geographic distribution and phenotypic differences of Piscirickettsia salmonis EM‐90‐like isolates
Authors: Saavedra J , Hernandez N , Osses A , Castillo A , Cancino A , Grothusen H , Navas E , Henriquez P , Bohle H , Bustamante F , Bustos P , Mancilla M 
Published: January 2017

AbstractEarly reports accounted for two main genotypes of Piscirickettsia salmonis, a fish pathogen and causative agent of piscirickettsiosis, placing the single isolate EM‐90 apart from the prototypic LF‐89 and related isolates. In this study, we provide evidence that, contrary to what has been supposed, the EM‐90‐like isolates are highly prevalent and disseminated across Chilean marine farms. Molecular analysis of 507 P. salmonis field isolates derived from main rearing areas, diverse hosts and collected over 6 years, revealed that nearly 50% of the entire collection were indeed typed as EM‐90‐like. Interestingly, these isolates showed a marked host preference, being recovered exclusively from Atlantic salmon (Salmo salar) samples. Although both strains produce undistinguishable pathological outcomes, differences regarding growth kinetics and susceptibility to the antibiotics and bactericidal action of serum could be identified. In sum, our results allow to conclude that the EM‐90‐like isolates represent an epidemiologically relevant group in the current situation of piscirickettsiosis. Based on the consistency between genotype and phenotype exhibited by this strain, we point out the need for genotypic studies that may be as important for the Chilean salmon industry as the continuous surveillance of antimicrobial susceptibility patterns.
Uncovering iron regulation with species‐specific transcriptome patterns in Atlantic and coho salmon during a Caligus rogercresseyi infestation
Authors: Valenzuela‐Muñoz V , Boltaña S , Gallardo‐Escárate C 
Published: January 2017

AbstractSalmon species cultured in Chile evidence different levels of susceptibility to the sea louse Caligus rogercresseyi. These differences have mainly been associated with specific immune responses. Moreover, iron regulation seems to be an important mechanism to confer immunity during the host infestation. This response called nutritional immunity has been described in bacterial infections, despite that no comprehensive studies involving in marine ectoparasites infestation have been reported. With this aim, we analysed the transcriptome profiles of Atlantic and coho salmon infected with C. rogercresseyi to evidence modulation of the iron metabolism as a proxy of nutritional immune responses. Whole transcriptome sequencing was performed in samples of skin and head kidney from Atlantic and coho salmon infected with sea lice. RNA‐seq analyses revealed significant upregulation of transcripts in both salmon species at 7 and 14 dpi in skin and head kidney, respectively. However, iron regulation transcripts were differentially modulated, evidencing species‐specific expression profiles. Genes related to heme degradation and iron transport such as hepcidin, transferrin and haptoglobin were primary upregulated in Atlantic salmon; meanwhile, in coho salmon, genes associated with heme biosynthesis were strongly transcribed. In summary, Atlantic salmon, which are more susceptible to infestation, presented molecular mechanisms to deplete cellular iron availability, suggesting putative mechanisms of nutritional immunity. In contrast, resistant coho salmon were less affected by sea lice, mainly activating pro‐inflammatory mechanisms to cope with infestation.
THE INNOVATION‐EMPLOYMENT NEXUS: A CRITICAL SURVEY OF THEORY AND EMPIRICS
Authors: Calvino Flavio , Virgillito Maria Enrica 
Published: January 2017

AbstractUnderstanding whether technical change is beneficial or detrimental for employment is at the center of the policy debate, especially in phases of economic recession. So far, the effects of innovation – in its manifold declinations and intrinsic complexity – on labor demand have proven to be not unequivocal. This essay critically reviews the role of technical change in shaping employment dynamics at different levels of aggregation. First, it disentangles theoretically the role of different compensation mechanisms through which employment adjusts after an innovation is introduced. Second, it critically presents the most recent empirical evidence on the topic, with a focus on methods and limitations. Finally, it provides an attempt to conceptualize a number of stylized facts and empirical regularities on the innovation‐employment nexus.
Oral tactile sensitivity and masticatory performance are impaired in stroke patients
Authors: Schimmel M. , Voegeli G. , Duvernay E. , Leemann B. , Müller F. 
Published: January 2017

SummaryOro‐facial impairment following stroke frequently involves reduced chewing performance, that is oral phase dysphagia. The aim was to investigate the sensitivity of oral tissues following stroke and its potential impact on masticatory function. Therefore, hospitalised post‐stroke patients were recruited and compared to healthy controls. Outcome measures comprised masticatory performance employing a colour‐mixing ability, that is a bolus‐kneading test, maximum lip‐ and bite force and the one‐point and two‐point tactile thresholds. Food hoarding and prevalence of dry mouth were evaluated with ordinal scales. Twenty‐seven stroke patients (age 64·3 ± 14·1 years) and 27 healthy controls (age 60·8 ± 14·3 years, P = 0·254) participated in this study. The groups had similar numbers of occluding units. Stroke patients reported more frequently dry mouth sensations and food hoarding. The intra‐oral tactile sensitivity on the contra‐lesional side was significantly lower in stroke patients compared to controls (0·0001 < P < 0·0002), and significant intra‐group side differences were found only in the stroke group (0·0001 < P < 0·0010). For the lip, both sides were less sensitive in the stroke group compared with controls. The experiments confirmed lower masticatory performance and lip force in the stroke group, but the bite force was similar compared to healthy controls. Oral sensitivity was correlated with masticatory performance when a global correlation model was applied. A stroke may affect the sensitivity of the intra‐oral tissues contra‐lesionally, thus potentially affecting chewing function. Rehabilitation should therefore not only focus on motor impairment, but equally stimulate the sensitivity of the oral tissues, employing dry ice application or similar specific treatments.
Efficacy of chlorhexidine for the prevention and treatment of oral mucositis in cancer patients: a systematic review with meta‐analyses
Authors: Cardona Alvin , Balouch Amir , Abdul Moiz Mohammed , Sedghizadeh Parish P. , Enciso Reyes 
Published: January 2017

BackgroundOral mucositis occurs in patients undergoing chemoradiation for cancer treatment. It is believed that colonization of ulcerated mucosa by bacteria, fungi, and virus results in secondary infections. The effect of chlorhexidine on the incidence and severity of oral mucositis in patients with cancer was evaluated in this review.MethodsStudies were limited to randomized placebo‐controlled trials. Three databases were searched: MEDLINE (via PubMed), Web of Science, and the Cochrane Library up to May 25, 2016.ResultsNinety‐eight abstracts were evaluated by three independent reviewers. Twelve studies met the criteria for inclusion. Four of these studies were assessed at unclear risk of bias and eight of them at high risk. Of the 12 studies, nine were included in two meta‐analyses. Pooled results showed that chlorhexidine did not significantly reduce incidence of mucositis compared to placebo (P = 0.129), nor chlorhexidine did significantly reduce the severity of mucositis (P = 0.127), although subgroup analysis in the chemotherapy group showed a trend toward significance (P = 0.054). Side effects reported in the included studies were teeth staining and altered taste perception.ConclusionsThis systematic review found that chlorhexidine is not significantly effective in reducing the severity of mucositis (moderate quality of evidence) nor in preventing the incidence of mucositis (low quality of evidence). However, more studies are needed in patients receiving chemotherapy only, as a positive trend toward significance was found (P = 0.054).