bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperprogressive disease in patients with non‐small cell lung cancer treated with nivolumab: A case series
Authors: Kanazu Masaki , Edahiro Ryuya , Krebe Hiroyuki , Nishida Kohei , Ishijima Mikako , Uenami Takeshi , Akazawa Yuki , Yano Yukihiro , Yamaguchi Toshihiko , Mori Masahide 
Published: October 2018

BackgroundNivolumab is an anti‐PD‐1 blocking monoclonal antibody approved for the treatment of non‐small cell lung cancer (NSCLC). However, some patients on immunotherapy may experience rapid progression and worsening clinical status, known as hyperprogressive disease. We retrospectively reviewed the clinical records of patients with NSCLC administered nivolumab therapy at Toneyama National Hospital, Japan, from January 2016 to January 2018. Of the 87 patients administered nivolumab therapy, five experienced rapid progression during one cycle of nivolumab therapy. Four patients were treated with corticosteroids to overcome their symptomatic events. Nivolumab exhibited efficacy after temporal progression, so‐called “pseudoprogression”, in three patients, and their symptoms and laboratory results improved. In the other patient, pleural and pericardial effusions increased after nivolumab therapy, and drainage was required, with no subsequent recurrence. The clinical courses of our case series indicate that alternative treatment, namely high‐dose corticosteroids, antibiotics, and drainage, effectively treated the symptoms of rapid tumor progression. Of note, corticosteroids suppressed the temporary inflammatory reaction to nivolumab. Although hyperprogressive disease is thought to be associated with poor quality of life and survival, these treatment strategies may be useful in patients with expected responses to immunotherapy.
Patterns of cerebral tissue oxygen tension and cytoplasmic redox state in bacterial meningitis
Authors: Larsen Lykke , Nielsen Troels H. , Nordström Carl‐Henrik , Andersen Aase B. , Schierbeck Jens , Schulz Mette K. , Poulsen Frantz R. 
Published: October 2018

BackgroundCompromised cerebral energy metabolism is common in patients with bacterial meningitis. In this study, simultaneous measurements of cerebral oxygen tension and lactate/pyruvate ratio were compared to explore whether disturbed energy metabolism was usually caused by insufficient tissue oxygenation or compromised oxidative metabolism of pyruvate indicating mitochondrial dysfunction.Subject and MethodsTen consecutive patients with severe streptococcus meningitis were included in this prospective cohort study. Intracranial pressure, brain tissue oxygen tension (PbtO2), and energy metabolism (intracerebral microdialysis) were continuously monitored in nine patients. A cerebral lactate/pyruvate (LP) ratio <30 was considered indicating normal oxidative metabolism, LP ratio >30 simultaneously with pyruvate below lower normal level (70 µmol/L) was interpreted as biochemical indication of ischemia, and LP ratio >30 simultaneously with a normal or increased level of pyruvate was interpreted as mitochondrial dysfunction. The biochemical variables were compared with PbtO2 simultaneously monitored within the same cerebral region.ResultsIn two cases, the LP ratio was normal during the whole study period and the simultaneously monitored PbtO2 was 18 ± 6 mm Hg. In six cases, interpreted as mitochondrial dysfunction, the simultaneously monitored PbtO2 was 20 ± 6 mm Hg and without correlation with the LP ratio. In one patient, exhibiting a pattern interpreted as ischemia, PbtO2 decreased below 10 mm Hg and a correlation between LP and PbtO2 was observed.ConclusionThis study demonstrated that compromised cerebral energy metabolism, evidenced by increased LP ratio, was common in patients with severe bacterial meningitis while not related to insufficient tissue oxygenation.
Editorial: Global mental health: challenges & opportunities
Authors: Joshi Paramjit T. 
Published: October 2018

There are few human tragedies that stir sympathy and concern more deeply than to see the suffering of children from around the world, often giving rise to spontaneous feelings and impulses of wanting to help. However, such impulses need to be harnessed in a productive manner. Knowledge and training in the psychopathology and phenomenology of mental illness is not enough. New, innovative, evidence‐based treatments and interventions are equally important if we are to adequately address the needs of our youth who carry the burden of a psychiatric and/or behavioral condition.This edition of CAMH includes papers that address both the challenges and opportunities in terms of the way in which interventions underpinned by research can work to improve global mental health and how we can better understand the environmental, familial, cultural and societal underpinnings of global child mental health problems.
Static computer‐aided implant surgery (s‐CAIS) analysing patient‐reported outcome measures (PROMs), economics and surgical complications: A systematic review
Authors: Joda Tim , Derksen Wiebe , Wittneben Julia Gabriela , Kuehl Sebastian 
Published: October 2018

AbstractObjectiveTo systematically evaluate the scientific literature for patient‐reported outcome measures (PROMs) in static computer‐aided implant surgery (s‐CAIS).MethodsA PICO strategy was executed using an electronic (MEDLINE, EMBASE, CENTRAL), plus manual search up to 15‐06‐2017 focusing on clinical studies investigating s‐CAIS with regard to patients’ pain & discomfort, economics and/or intra‐operative complications. Search strategy was assembled from multiple conjunctions of MeSH Terms and unspecific free‐text words. Assessment of risk of bias in selected studies was made at a “trial level” applying the Cochrane Collaboration Tool and the Newcastle–Ottawa Assessment Scale, respectively.ResultsThe systematic search identified 112 titles. Seventy abstracts were screened, and 14 full texts were included for analysis. A total of 484 patients were treated with s‐CAIS for placement of 2,510 implants. Due to the heterogeneity of the included studies, meta‐analyses could not be performed.ConclusionsThe number of identified studies investigating s‐CAIS for PROMs was low. Scientifically proven recommendations for clinical routine cannot be given at this time; however, the number of clinical complications with s‐CAIS seems to be negligible and comparable to conventional implant surgery. s‐CAIS may offer a beneficial treatment option in edentulous cases if a flapless approach is applicable. Nevertheless, the economic effects in terms of time efficiency and treatment costs are unclear. Clinical investigations with well‐designed RCTs investigating PROMs with standardized parameters are compellingly necessary for the field of s‐CAIS.
A systematic review of the survival and complication rates of zirconia‐ceramic and metal‐ceramic multiple‐unit fixed dental prostheses
Authors: Sailer Irena , Strasding Malin , Valente Nicola Alberto , Zwahlen Marcel , Liu Shiming , Pjetursson Bjarni Elvar 
Published: October 2018

AbstractObjectivesThe aim of the present review was to compare the outcomes, that is, survival and complication rates of zirconia‐ceramic and/or monolithic zirconia implant‐supported fixed dental prostheses (FDPs) with metal‐ceramic FDPs.Materials and MethodsAn electronic MEDLINE search complemented by manual searching was conducted to identify randomized controlled clinical trials, prospective cohort studies and retrospective case series on implant‐supported FDPs with a mean follow‐up of at least 3 years. Patients had to have been examined clinically at the follow‐up visit. Assessment of the identified studies and data extraction was performed independently by two reviewers. Failure and complication rates were analyzed using robust Poisson regression models to obtain summary estimates of 5‐year proportions.ResultsThe search provided 5,263 titles and 455 abstracts. Full‐text analysis was performed for 240 articles resulting in 19 studies on implant FDPs that met the inclusion criteria. The studies reported on 932 metal‐ceramic and 175 zirconia‐ceramic FDPs. Meta‐analysis revealed an estimated 5‐year survival rate of 98.7% (95% CI: 96.8%–99.5%) for metal‐ceramic implant‐supported FDPs, and of 93.0% (95% CI: 90.6%–94.8%) for zirconia‐ceramic implant‐supported FDPs (p < 0.001). Thirteen studies including 781 metal‐ceramic implant‐supported FDPs estimated a 5‐year rate of ceramic fractures and chippings to be 11.6% compared with a significantly higher (p < 0.001) complication rate for zirconia implant‐supported FDPs of 50%, reported in a small study with 13 zirconia implant‐supported FDPs. Significantly (p = 0.001) more, that is, 4.1%, of the zirconia‐ceramic implant‐supported FDPs were lost due to ceramic fractures compared to only 0.2% of the metal‐ceramic implant‐supported FDPs. Detailed analysis of factors like number of units of the FDPs or location in the jaws was not possible due to heterogeneity of reporting. No studies on monolithic zirconia implant‐supported FDPs fulfilled the inclusion criteria of the present review. Furthermore, no conclusive results were found for the aesthetic outcomes of both FDP‐types.ConclusionFor implant‐supported FDPs, conventionally veneered zirconia should not be considered as material selection of first priority, as pronounced risk for framework fractures and chipping of the zirconia veneering ceramic was observed. Monolithic zirconia may be an interesting alternative, but its clinical medium‐ to long‐term outcomes have not been evaluated yet. Hence, metal ceramics seems to stay the golden standard for implant‐supported multiple‐unit FDPs.
Immediate loading vs. early/conventional loading of immediately placed implants in partially edentulous patients from the patients’ perspective: A systematic review
Authors: Huynh‐Ba Guy , Oates Thomas W. , Williams Mary Ann H. 
Published: October 2018

AbstractObjectivesThis systematic review aimed at answering the followingPICOquestion: In patients receiving immediate (Type 1) implant placement, how does immediate compare to early or conventional loading in terms of Patient‐Reported Outcome Measures (PROMs)?Material and MethodsFollowing search strategy development, theOVID, PubMed,EMBASE, and Cochrane Database of Systematic Reviews databases were search for the relevant literature. All levels of evidence including randomized controlled trials, prospective and retrospective cohort studies, and case series of at least five patients were considered for possible inclusion. An additional manual search was performed by screening the reference lists of relevant studies and systematic reviews published up to May 2017. The intervention considered was the placement of immediate implant.Study selection and data extraction were performed independently by two reviewers.ResultsThe search yielded a list of 1,102 references, of which nine were included in this systematic review. The limited number of studies included and the heterogeneity of the data identified prevented the performance of a meta‐analysis. Three studies, one of which was a randomized controlled trial, allowed the extraction of comparative data specific to the aim of the present systematic review. The remaining studies allowed only data extraction for one single treatment modality and were viewed as single cohort studies. Overall, irrespective of thePROMs chosen, patients’ satisfaction was overall high with little difference between the two loading protocols. Moreover, studies indicated a positive impact on oral health‐related quality of life following immediate implant placement and loading.ConclusionsWithin the limitations of the present systematic review, immediate implant placement and loading in single tooth edentulous space seems to be a well‐accepted treatment modality from the patients’ perspective and is worthy of consideration in clinical practice. However, the paucity of comparative data limits any definitive conclusions as to which loading protocol; immediate or early/conventional, should be given preference based onPROMs.
Number of implants placed for complete‐arch fixed prostheses: A systematic review and meta‐analysis
Authors: Daudt Polido Waldemar , Aghaloo Tara , Emmett Thomas W. , Taylor Thomas D. , Morton Dean 
Published: October 2018

AbstractObjectivesThe main purpose of this systematic review was to evaluate outcomes related to the number of implants utilized to support complete‐arch fixed prostheses, both for the maxilla and the mandible.Materials and methodsThis review followed the reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA). A focused question using the PICO format was developed, questioning whether “In patients with an implant supported fixed complete dental prosthesis, do implant and prosthetic survival outcomes differ between five or more compared to fewer than five supporting implants?”. A comprehensive search of the literature was formulated and performed electronically and by hand search. Two independent reviewers selected the papers and tabulated results. Primary outcomes analyzed were implant and prosthesis survival. Implant distribution, loading, and type of retention were observed as secondary outcomes, as they relate to the number of implants. A meta‐analysis was performed to compare results for studies by number of implants.ResultsThe search strategy identified 1,579 abstracts for initial review. Based on evaluation of the abstracts, 359 articles were identified for full‐text evaluation. From these, 93 were selected and included in this review, being nine RCTs, 42 prospective and 42 retrospective. Of the 93 selected studies, 28 reported number of implants for the maxilla, 46 for the mandible, and 19 for both maxilla and mandible. The most reported number of implants for the “fewer than five” group is 4 for the maxilla, and 3 and 4 for the mandible, whereas for the “five or more” implants group, the most reported number of implants was 6 for the maxilla and 5 for the mandible. No significant differences in the primary outcomes analyzed were identified when fewer than five implants per arch were compared with five or more implants per arch (p > 0.05), in a follow‐up time ranging from 1 to 15 years (median of 8 years).ConclusionsEvidence from this systematic review and meta‐analysis suggests that the use of fewer than five implants per arch, when compared to five or more implants per arch, to support a fixed prosthesis of the completely edentulous maxilla or mandible, present similar survival rates, with no statistical significant difference at a p < 0.05 and a confidence interval of 95%.
Effects of a toothpaste containing 0.3% triclosan in the maintenance phase of peri‐implantitis treatment: 2‐Year randomized clinical trial
Authors: Stewart Bernal , Shibli Jamil Awad , Araujo Mauricio , Figueiredo Luciene Cristina , Panagakos Fotinos , Matarazzo Flavia , Mairink Renata , Onuma Tatiana , Faveri Marcelo , Retamal‐Valdes Belén , Feres Magda 
Published: October 2018

AbstractObjectiveTo evaluate the effects of a toothpaste containing 0.3% triclosan in volunteers that have been treated for peri‐implantitis and were enrolled in a maintenance program.Material and methodsSubjects presenting at least one implant with peri‐implantitis were selected. They received anti‐infective surgical therapy, and sixty days post‐surgery (baseline) were randomized into two groups, brushing twice/day for 2 years (a) with a toothpaste containing 0.3% triclosan+2.0% PVM/MA copolymer (GantrezTM)+1,450 ppm fluoride (test) or (b) with a toothpaste containing 1,450 ppm fluoride (control). They received clinical and microbiological monitoring at baseline, 3, 6, 12, 18, and 24 months, and professional maintenance every 3 months.ResultsA total of 102 subjects were enrolled (test: 48; control: 54). The control group showed loss of clinical attachment (CA) around treated implants over the course of the study (p < 0.05), while the test group was stable for this parameter. The difference between groups (0.55 mm) for CA change between baseline and 24 months (primary outcome variable) was statistically significant (p < 0.05). Red complex pathogens were only reduced in the test group at 24 months. The implants with no history of peri‐implantitis in the test group had a significant reduction in the percentage of sites with bleeding on probing and in mean probing depth, throughout the study (p < 0.05). This improvement was not observed in the control group.ConclusionA toothpaste containing 0.3% triclosan was more effective than a toothpaste without triclosan in maintaining a healthy peri‐implant environment around treated implants and implants with no history of peri‐implantitis during a 2‐year maintenance program (ClinicalTrials.govNCT03191721).
Polarity protein Canoe mediates overproliferation via modulation of JNK, Ras‐MAPK and Hippo signalling
Authors: Ma Zhiwei , Li Ping , Hu Xingjie , Song Haiyun 
Published: October 2018

AbstractObjectivesOver the past decade an intriguing connection between cell polarity and tumorigenesis has emerged. Multiple core components of the junction complexes that help to form and maintain cell polarity display both pro‐ and anti‐tumorigenic functions in a context‐dependent manner, with the underlying mechanisms poorly understood.Materials and MethodsWith transgenic fly lines that overexpress or knock down specific signalling components, we perform genetic analysis to investigate the precise role of the polarity protein Canoe (Cno) in tumorigenesis and the downstream pathways.ResultsWe show that overexpression of cno simultaneously activates JNK and Ras‐MEK‐ERK signalling, resulting in mixed phenotypes of both overproliferation and cell death in the Drosophila wing disc. Moderate alleviation of JNK activation eliminates the effect of Cno on cell death, leading to organ overgrowth and cell migration that mimic the formation and invasion of tumours. In addition, we find that the Hippo pathway acts downstream of JNK and Ras signalling to mediate the effect of Cno on cell proliferation.ConclusionsOur work reveals an oncogenic role of Cno and creates a new type of Drosophila tumour model for cancer research.
Learning about Type 1 diabetes and learning to live with it when diagnosed in adulthood: two distinct but inter‐related psychological processes of adaptation A qualitative longitudinal study
Authors: Due‐Christensen M. , Willaing I. , Ismail K. , Forbes A. 
Published: October 2018

AbstractAimTo explore the experiences of adults with newly diagnosed Type 1 diabetes in order to understand the adaptive processes that occur in the early phase of the condition.MethodsWe conducted longitudinal semi‐structured interviews with 30 adults newly diagnosed with Type 1 diabetes (age range 20–67 years; 16 men; median diabetes duration 23.5 months), recruited from hospitals in Denmark and the UK. The data were analysed using a narrative approach.ResultsThe narratives could be grouped into three thematic areas: the diagnosis; learning about diabetes; and learning to live with diabetes. Diabetes was characterized as a major disruptor to the established and future life plans of participants, causing significant emotional distress. The narratives showed how early experiences triggered the development of ongoing psychological problems (fear of complications or hypoglycaemia) and diabetes distress, and that navigating different social scenarios (relationships and employment) could be challenging, leading to suboptimal self‐management behaviours. The narratives also showed that health professionals often did not attend effectively to participants’ emotional needs after diagnosis, and that the language used frequently triggered negative feelings, such as fear or a sense of failure.ConclusionsMany of the common psychosocial problems associated with Type 1 diabetes seem to gestate in the early phase of life with the condition. There appear to be opportunities to enhance the support provided in this phase to minimize these problems.
GlucoTab‐guided insulin therapy using insulin glargine U300 enables glycaemic control with low risk of hypoglycaemia in hospitalized patients with type 2 diabetes
Authors: Aberer Felix , Lichtenegger Katharina M. , Smajic Edin , Donsa Klaus , Malle Oliver , Samonigg Judith , Höll Bernhard , Beck Peter , Pieber Thomas R. , Plank Johannes , Mader Julia K. 
Published: October 2018

AimsTo investigate efficacy, safety and usability of the GlucoTab system for glycaemic management using insulin glargine U300 in non‐critically ill hospitalized patients with type 2 diabetes (T2D).Materials and MethodsIn this open, non‐controlled single‐arm pilot study, glycaemic control at the general ward of a tertiary care hospital was guided by a mobile decision support system (GlucoTab) for basal‐bolus insulin dosing using the novel basal insulin analogue insulin glargine U300 for the first time. Glycaemic control was surveilled with capillary glucose measurements and continuous glucose monitoring (CGM). The primary endpoint was efficacy of glycaemic management, defined as the percentage of blood glucose measurements within the target range of 3.9 to 7.8 mmol/L.ResultsA total of 30 patients with T2D (12 female; age, 67 ± 11 years; HbA1c, 70 ± 26 mmol/mol; BMI, 31.8 ± 5.6 kg/m2; length of study, 8.5 ± 4.5 days) were included. In total, 894 capillary glucose values and 49 846 data points of CGM were available, of which 56.1% of all measured capillary glucose values and 54.3% of CGM values were within the target area (3.9‐7.8 mmol/L). Overall capillary mean glucose was 8.5 ± 1.2 and 8.4 ± 1.2 mmol/L assessed by CGM. Time within glucose target improved continuously during the course of treatment, while time within hypoglycaemia (<3.9 mmol/L) decreased substantially. The GlucoTab‐suggested total daily dose was accepted by staff in 97.3% of situations.ConclusionsTreatment with GlucoTab using insulin glargine U300 in hospitalized patients with T2D is effective and safe.
FGF21 decreases food intake and body weight in obese Göttingen minipigs
Authors: Christoffersen Berit , Straarup Ellen M. , Lykkegaard Kirsten , Fels Johannes J. , Sass‐Ørum Kristian , Zhang Xujia , Raun Kirsten , Andersen Birgitte 
Published: October 2018

AimsThe aim of this study was to assess the effect of FGF21 on food intake, body weight, body composition, glucose homeostasis, bone mineral density (BMD), cortisol and growth hormone (GH) in obese minipigs. The pig is a unique model for studying FGF21 pharmacology as it does not express UCP1, unlike mice and humans.MethodsTwelve obese Göttingen minipigs with a mean body weight of 91.6 ± 6.7 kg (mean ± SD) received subcutaneously either vehicle (n = 6) or recombinant human FGF21 (n = 6) once daily for 14 weeks (0.1 mg/kg for 9.5 weeks and 0.3 mg/kg for 4.5 weeks).ResultsTreatment of obese minipigs with FGF21 led to a 50% reduction in food intake and a body weight loss of, on average, 18 kg compared to the vehicle group after 14 weeks of dosing. Glucose tolerance and insulin sensitivity, evaluated by intravenous glucose tolerance test, were significantly improved in the FGF21 group compared to the vehicle group at the end of the study. The plasma cortisol profile was unaffected by FGF21, whereas a small decrease in peak GH values was observed in the FGF21‐treated animals after 7 to 9.5 weeks of treatment compared to the vehicle group. Whole‐body BMD was not affected by 13 weeks of FGF21 dosing.ConclusionDespite a lack of UCP‐1 in obese minipigs, FGF21 treatment induced a significant weight loss, primarily a result of reduction in food intake, with no adverse effect on BMD or plasma cortisol.