bluuebunny/crossref_metadata_2025_split huggingface dataset:
The epidemiology of bacille Calmette–Guérin infections after bladder instillation from 2002 through 2017: a nationwide retrospective cohort study
Authors: Larsen Emilie S. , Nordholm Anne C. , Lillebaek Troels , Holden Inge K. , Johansen Isik S. 
Published: May 2019

ObjectiveTo describe incidence and clinical characteristics of bacille Calmette–Guérin (BCG) infections after BCG bladder instillation amongst patients with non‐muscle‐invasive bladder cancer in Denmark.Patients and methodsWe conducted a nationwide register‐based cohort study in Denmark between 2002 through 2017. Patients with BCG infection were identified by cross‐linking data from the Danish National Hospital Registry on patients treated with BCG instillations and patients diagnosed with tuberculosis according to the International Classification of Diseases 10, and data obtained from International Reference Laboratory of Mycobacteriology. Hospital records were reviewed for clinical information.ResultsDuring the study period, 6753 patients (5281 men; mean [SD] age 71.1 (0.1) years) received BCG instillations, of which 66 patients (1%) developed BCG infections. There were no differences in age or Charlson Comorbidity Index between the patients in the study population stratified by BCG infection. The median (interquartile range) time from first BCG instillation until symptoms of BCG infection was 169.5 (38–585) days. Extrapulmonary localisation of BCG infections (37 patients, 56.1%) was significantly more frequent than pulmonary BCG infections (20 patients, 30.3%; P < 0.001). The most common extrapulmonary localisation was the genitourinary tract (29 patients, 78.4%).ConclusionBCG infections after bladder instillation are rare, mainly affect male patients, and are most frequently extrapulmonary. BCG infections should be suspected despite a long time span between occurrence of symptoms and prior bladder instillation.
Genomic classifiers for treatment selection in newly diagnosed prostate cancer
Authors: Fine Noam David , LaPolla Fred , Epstein Matthew , Loeb Stacy , Dani Hasan 
Published: May 2019

ObjectivesTo review systematically the literature on genomic tests for prostate cancer (PCa) and to evaluate the current state of the evidence on their use in patients with newly diagnosed PCa.MethodsWe conducted a systematic review by searching PubMed, Embase, Cochrane Central and conference abstracts from the American Urological Association, published between 2010 and 2018. Studies evaluating Prolaris, Oncotype Dx and Decipher assays were assessed for inclusion by two authors. Studies were excluded if the results were derived from surgical specimens rather than biopsy specimens. A meta‐analysis was not performed owing to significant variations in methodologies, definitions and outcome measures.ResultsA total of 729 articles were retrieved in our initial search. After removing duplicates (270) and excluding articles deemed not relevant (432), 21 full‐text articles were deemed suitable for inclusion in the present analysis. The full‐text articles comprised eight studies on Prolaris, eight studies on Oncotype Dx and five studies on Decipher. For each genomic test we extracted data regarding the risks of adverse pathology, biochemical recurrence, metastasis and PCa‐specific mortality.ConclusionThe results of genomic tests that use biomarkers derived from prostate biopsy can be used in conjunction with clinicopathological variables to improve our ability to risk‐stratify patients with newly diagnosed PCa. Additional data are needed on the impact of using these tests on long‐term patient outcomes and their cost‐effectiveness.
Design, synthesis, and antimicrobial activities of novel functional peptides against Gram‐positive and Gram‐negative bacteria
Authors: Lee Ping‐Chien , Chu Chia‐Chun , Tsai Yi‐Je , Chuang Ya‐Chu , Lung Feng‐Di 
Published: May 2019

AbstractThe extensive use of antibiotics in medicine results in the multidrug resistance of bacteria, making the development of new antimicrobial agents an urgent need. Antimicrobial peptides (AMPs) are considered as a new class of antibiotic with characteristics including an ability to kill target cells rapidly and a broad spectrum of activity. We have developed a potent antimicrobial peptide MAP‐0403 (MIC = 5 μM), but it exhibited a high hemolytic side‐effect (70.7%). To reduce its hemolytic effect and increase antimicrobial activity, three peptides derivatives of MAP‐0403 (J‐1, J‐2, and J‐3) were designed, synthesized by solid phase synthesis, purified by RP‐HPLC, and characterized by MALDI‐TOF MS. Structure–activity relationships of these peptides were studied by using circular dichroism and antimicrobial assays. The percentage of helical structure in J‐1, J‐2, and J‐3 was lower than that of MAP‐0403. The antimicrobial activity of J‐1 was the same as that of MAP‐0403 (MIC = 5 μM), J‐2 exhibited the highest activity (MIC = 2.5 μM), while J‐3 showed decreased activity (MIC = 10 μM). Compared to MAP‐0403, J‐2 showed significantly reduced hemolytic effect (3.4%), while J‐1 and J‐3 showed slightly decreased hemolytic effect (46.2%, 55.6%, respectively). Peptide J‐2 was discovered as a novel and potent antimicrobial agents.
Labial soft tissue contour dynamics following immediate implants and immediate provisionalization of single maxillary incisors: A 1‐year prospective study
Authors: Tian Jiehua , Wei Donghao , Zhao Yijiao , Di Ping , Jiang Xi , Lin Ye 
Published: May 2019

AbstractBackgroundSoft tissue dynamics in the esthetic zone are gaining increasing attention in recent years. Emerging intraoral scanning technology allows easier capture of soft tissue contours.PurposeTo quantitatively assess the time‐dependent contour alterations of labial soft tissue following single immediate implants and immediate provisionalization (IIPP) in maxillary incisors via intraoral scanning.Materials and MethodsThis was a prospective cohort study. Thirty eligible consecutive patients were included and received immediate replacement of a failure maxillary single incisor. A screw‐retained immediate restoration was delivered for each patient. Subsequently, the anterior maxillary region was scanned by an intraoral scanning system at four time points: preoperation (baseline, BL), 3 months (3 m), 6 months (6 m), and 12 months (12 m). The Standard Tessellation Language files were exported to a dedicated software and superimposed for visual analysis. At 3, 6, and 12 months, the mid‐facial mucosa level (ML) was assessed, and the precise three‐dimensional (3D) configuration of the altered volume was calculated and reconstructed for visual analysis. Furthermore, quantitative analysis of the reconstructed morphology was performed using the following parameters: mean change in thickness (△d), mesio‐distal width (w), coronal‐apical height (h), and horizontal and vertical position of the thickest point represented by coordinates (x, z).ResultTwenty‐seven of thirty enrolled patients were finally available for analysis at the 1‐year follow‐up. In general, the frontal view of the reconstructed volume exhibited a crescent shape. The mid‐facial ML change at 3, 6, and 12 months was −0.05 ± 0.36 mm, −0.03 ± 0.32 mm, and −0.24 ± 0.37 mm, respectively (P = .012). The mean change in thickness at 3 months (△d3m), 6 months (△d6m), and 12 months (△d12m) was 0.50 ± 0.19 mm, 0.59 ± 0.21 mm, and 0.62 ± 0.22 mm, respectively (P <.001). At 12 months, nine patients had a △d less than 0.5 mm. The mean △d3 m/△d12 m and △d6 m/△d12 m was 0.81 ± 0.17 and 0.96 ± 0.13. The w, h, x, and z results showed no significant differences during the 1‐year observation (P = .126, P = .324, P = .635, P = .263). At 12 months, w, h, x, and z were 11.57 ± 1.77 mm, 6.46 ± 2.01 mm, 0.03 ± 1.43 mm, and 2.16 ± 0.65 mm, respectively.ConclusionDuring the 1‐year observation following single IIPP treatment in maxillary incisors, the labial soft tissue contour showed a continuous alteration resulting in a mean change in thickness of 0.62 mm that occurred mainly in the first 3 months and tended to be relatively stable after 6 months, while the crescent‐like shape, width, height, and thickest point position of the alteration volume remained stable after 3 months. No advanced mid‐facial recession was observed.
Crop research, biotech canola, and innovation policy in Canada: Challenges, opportunities, and evolution
Authors: Malla Stavroula , Brewin Derek G. 
Published: May 2019

AbstractIncreased investment in agricultural research could contribute to sustainable development goals and benefit farmers, consumers, the environment, and the economy. This paper provides recent evidence and a critical assessment of the evolving Canadian canola crop development and innovation policy and compares it to the wheat and pulse sectors that differ in degree of biotechnology adoption, seeded acreage, intellectual property rights, and private sector involvement. This study also assesses how crop characteristics and technological changes affect future optimal public policy. A number of innovation policies are discussed that could stimulate further growth within the crop sector.
The accuracy of static vs. dynamic computer‐assisted implant surgery in single tooth space: A randomized controlled trial
Authors: Kaewsiri Dechawat , Panmekiate Soontra , Subbalekha Keskanya , Mattheos Nikos , Pimkhaokham Atiphan 
Published: May 2019

AbstractObjectivesThe aim of this RCT was to compare the accuracy of implant placement between static and dynamic computer‐assisted implant surgery (CAIS) systems in single tooth space.Materials and methodsA total of 60 patients in need of a single implant were randomly assigned to two CAIS groups (Static n = 30, Dynamic n = 30) and implants were placed by one surgeon. Preoperative CBCT was transferred to implant planning software to plan the optimal implant position. Implants were placed using either stereolithographic guide template (Static CAIS) or implant navigation system (Dynamic CAIS). Postoperative CBCT was imported to implant planning software, and deviation analysis with the planned position was performed. Primary outcomes were the deviation measurements at implant platform, apex, and angle of placement. Secondary outcome was the distribution of the implant deviation into each 3D direction.ResultsThe mean deviation at implant platform and implant apex in the static CAIS group was 0.97 ± 0.44 mm and 1.28 ± 0.46 mm, while that in the dynamic CAIS group was 1.05 ± 0.44 mm and 1.29 ± 0.50 mm, respectively. The angular deviation in static and dynamic CAIS group was 2.84 ± 1.71 degrees and 3.06 ± 1.37 degrees. None of the above differences between the two groups reached statistical significance. The deviation of implants toward the mesial direction in dynamic CAIS group was significantly higher than that of the static CAIS (p = 0.032).ConclusionsImplant placement accuracy in single tooth space using dynamic CAIS appear to be the same to that of static CAIS. (Thai Clinical Trials Registry TCTR20180826001).
Neural activity in the periaqueductal gray and other specific subcortical structures is enhanced when a selective serotonin reuptake inhibitor selectively prevents seizure‐induced sudden death in the DBA/1 mouse model of sudden unexpected death in epilepsy
Authors: Kommajosyula Srinivasa P. , Faingold Carl L. 
Published: May 2019

AbstractObjectiveSudden unexpected death in epilepsy (SUDEP) is a critical issue in epilepsy, and DBA/1 mice are a useful animal model of this devastating epilepsy sequela. The serotonin hypothesis for SUDEP proposes that modifying serotonergic function significantly alters susceptibility to seizure‐induced respiratory arrest (S‐IRA). Agents that enhance serotonergic function, including a selective serotonin reuptake inhibitor, fluoxetine, selectively prevent S‐IRA in DBA/1 mice. This study examined fluoxetine‐induced changes in brain activity using manganese‐enhanced magnetic resonance imaging (MEMRI) to reveal sites in the DBA/1 mouse brain where fluoxetine acts to prevent S‐IRA.MethodsDBA/1 mice were subjected to audiogenic seizures (Sz) after saline or fluoxetine (45 mg/kg, intraperitoneal) administration. Control DBA/1 mice received fluoxetine or saline, but Sz were not evoked. A previous MEMRI study established the regions of interest (ROIs) for Sz in the DBA/1 mouse brain, and the present study examined MEMRI differences in the ROIs of these mouse groups.ResultsThe neural activity in several ROIs was significantly increased in fluoxetine‐treated DBA/1 mice that exhibited Sz but not S‐IRA when compared to the saline‐treated mice that exhibited both Sz and respiratory arrest. These structures included the periaqueductal gray (PAG), amygdala, reticular formation (sensorimotor‐limbic network), Kölliker‐Fuse nucleus, facial‐parafacial group (respiratory network), and pontine raphe. Of these ROIs, only the PAG showed significantly decreased neural activity with saline pretreatment when seizure‐induced respiratory arrest occurred as compared to saline treatment without seizure.SignificanceThe PAG is known to play an important compensatory role for respiratory distress caused by numerous exigent situations in normal animals. The pattern of fluoxetine‐induced activity changes in the present study suggests that PAG may be the most critical target for fluoxetine's action to prevent seizure‐induced sudden death. These findings have potential clinical importance, because there is evidence of anomalous serotonergic function and PAG imaging abnormalities in human SUDEP.
Consistency of females’ stridulatory behaviour during inter‐sexual interactions in spiders
Authors: Calbacho‐Rosa Lucía , Cargnelutti Franco , Córdoba‐Aguilar Alex , Peretti Alfredo V. 
Published: May 2019

AbstractIn a sexual context, it is expected that females base their choice of mate on the behaviours that males perform during courtship, as such behaviours are associated with the male's mate quality. Stridulation is one form of female communication in arthropods, for example, spiders. In spiders, stridulation during sexual interactions is relatively common in some groups but mainly restricted to males. In the pholcid spider Holocnemus pluchei (Pholcidae), both sexes have stridulatory organs. The aims of the present work were to: (a) determine possible differences in the frequency of occurrence of stridulation between females during inter‐sexual interactions, (b) establish female consistency in stridulation along repeated interactions and (c) analyse if female stridulation is associated with certain male behaviours during pre‐copulatory courtship and with male size. Female H. pluchei showed highly repeatable differences in their frequency of stridulation across consecutive encounters with males (ICC = 0.64). However, only a modest level of repeatability was detected in total time females spent stridulating across trials (ICC = 0.19). Females’ mean stridulatory behaviour did not change across ten consecutive trials spread across 20 days, and their behaviour was apparently unaffected by male persistence of copulatory attempted and/or size. These results imply that the frequency of female stridulatory behaviour is a trait that is highly characteristic of each individual. Finally, our work opens the door to determine whether behavioural consistency manifests in other ecological contexts and their functional implications.
Simvastatin enhances chemotherapy in cervical cancer via inhibition of multiple prenylation‐dependentGTPases‐regulated pathways
Authors: Pan Qin , Xu Jiazhen , Ma Liang 
Published: May 2019

AbstractAberrant activation ofGTPases is common in cervical cancer, and their proper biological functions largely depend on a post‐translational modification termed prenylation. Simvastatin is a cholesterol‐lowering drug via inhibitingHMG‐CoA reductase, thereby inhibiting protein prenylation. In this study, we show that simvastatin selectively inhibits proliferation and induces apoptosis in cervical cancer cells while sparing normal cervical epithelial cells. This is achieved by depleting geranylgeranyl pyrophosphate, inhibiting prenylation, decreasingGTPases activities and suppressing the activation of downstream Ras and RhoA signaling. The combination of simvastatin and paclitaxel remarkably augments in vitro as well as in vivo efficacy of either drug alone in cellular system and xenograft mouse model. Importantly, we show that cervical cancer cells have higher level ofHMG‐CoA reductase and elevated activities ofGTPases, suggesting that cervical cancer cells may be more dependent on prenylation than normal cervical epithelial cells. This might explain the selective inhibitory effects of simvastatin in cervical cancer. Since simvastatin is already available for clinic use, these results suggest that simvastatin is a promising drug candidate in combination with chemotherapy for the treatment of cervical cancer. Our findings also emphasize the therapeutic value of prenylation inhibition and provide preclinical evidence to evaluate prenylation‐targeted drugs in cervical cancer.
Company matters: The presence of other genotypes alters traits and intraspecific selection in an Arctic diatom under climate change
Authors: Wolf Klara K. E. , Romanelli Elisa , Rost Björn , John Uwe , Collins Sinead , Weigand Hannah , Hoppe Clara J. M. 
Published: May 2019

AbstractArctic phytoplankton and their response to future conditions shape one of the most rapidly changing ecosystems on the planet. We tested how much the phenotypic responses of strains from the same Arctic diatom population diverge and whether the physiology and intraspecific composition of multistrain populations differs from expectations based on single strain traits. To this end, we conducted incubation experiments with the diatom Thalassiosira hyalina under present‐day and future temperature and pCO2 treatments. Six fresh isolates from the same Svalbard population were incubated as mono‐ and multistrain cultures. For the first time, we were able to closely follow intraspecific selection within an artificial population using microsatellites and allele‐specific quantitative PCR. Our results showed not only that there is substantial variation in how strains of the same species cope with the tested environments but also that changes in genotype composition, production rates, and cellular quotas in the multistrain cultures are not predictable from monoculture performance. Nevertheless, the physiological responses as well as strain composition of the artificial populations were highly reproducible within each environment. Interestingly, we only detected significant strain sorting in those populations exposed to the future treatment. This study illustrates that the genetic composition of populations can change on very short timescales through selection from the intraspecific standing stock, indicating the potential for rapid population level adaptation to climate change. We further show that individuals adjust their phenotype not only in response to their physicochemical but also to their biological surroundings. Such intraspecific interactions need to be understood in order to realistically predict ecosystem responses to global change.
UK vs US physician decision‐making in the treatment of haemophilia
Authors: Lamb Christopher C. , Wolfberg Adrian , Lyytinen Kalle 
Published: May 2019

AbstractIntroductionPatient–physician shared decision‐making (SDM) has become increasingly seen as having a positive effect on management of chronic diseases. However, little is known of the factors that encourage SDM or how effective it may be at improving health outcomes or how cost‐effective it is.AimTo investigate the uses and applications of patient physician–SDM in the management of haemophilia and the influence of healthcare systems in the United States and the United Kingdom.MethodsThis was a qualitative study based on interviews with treatment experts in the United States and United Kingdom. A grounded theory approach was used to analyse the data from the transcribed interviews and themes that emerged as related to the decision influencers. Twelve physicians from each country were interviewed by the author.ResultsTreatment guidelines were viewed as having only limited applicability because of the lack of universal best options in haemophilia. The US physicians in the sample appeared to be more influenced by patient preferences than physicians in the UK, who instead tended to follow policies and standards of care more closely. Physicians in both countries commented that many of their patents had become highly knowledgeable of their bleeding disorder. US physicians were sometimes limited by insurance company policies but also reported that they were often successful in appealing insurance decisions.ConclusionThe research suggests that there are different influences on decision‐making between healthcare systems; patients and overarching healthcare systems play a major role in how physicians treat haemophilia.
Designing a co‐productive study to overcome known methodological challenges in organ donation research with bereaved family members
Authors: Noyes Jane , Mclaughlin Leah , Morgan Karen , Roberts Abigail , Stephens Michael , Bourne Janette , Houlston Michael , Houlston Jessica , Thomas Sarah , Rhys Revd Gethin , Moss Bethan , Duncalf Sue , Lee Dawn , Curtis Rebecca , Madden Susanna , Walton Phillip 
Published: May 2019

AbstractBackgroundCo‐production of research into public health services has yet to demonstrate tangible benefits. Few studies have reported the impact of co‐production on research outcomes. The previous studies of organ donation have identified challenges in engaging with public organizations responsible, gaining ethical approval for sensitive studies with the recently bereaved and difficulty in recruiting bereaved family members who were approached about organ donation.ObjectiveTo address these challenges, we designed the first large co‐productive observational study to evaluate implementation of a new system of organ donation in Wales. This paper outlines the co‐productive strategies that were designed to overcome known methodological challenges and reports what impact they had on resolving these challenges.DesignTwo‐year co‐produced study with multiple stakeholders with the specific intention of maximizing engagement with the National Health Service arm in Wales responsible for organ donation, and recruitment of bereaved family members whose perspectives are essential but commonly absent from studies.Setting and participantsNHS Blood and Transplant, Welsh Government and multiple patient and public representatives who served as co‐productive partners with the research team.ResultsCo‐productive strategies enabled a smooth passage through four different ethics processes within the 10‐week time frame, family member recruitment targets to be surpassed, sharing of routinely collected data on 100% of potential organ donor cases and development of further research capacity and capability in a critically under researched area.Discussion and conclusionAlthough expensive and time consuming, co‐production was effective and added value to research processes and study outcomes.