bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bolusing frequency and amount impacts glucose control during hybrid closed‐loop
Authors: Bally L. , Thabit H. , Ruan Y. , Mader J. K. , Kojzar H. , Dellweg S. , Benesch C. , Hartnell S. , Leelarathna L. , Wilinska M. E. , Evans M. L. , Arnolds S. , Pieber T. R. , Hovorka R. 
Published: July 2017

AbstractAimTo compare bolus insulin delivery patterns during closed‐loop home studies in adults with suboptimally [HbA1c 58–86 mmol/mol (7.5%–10%)] and well‐controlled [58 mmol/mol (< 7.5%)] Type 1 diabetes.MethodsRetrospective analysis of daytime and night‐time insulin delivery during home use of closed‐loop over 4 weeks. Daytime and night‐time controller effort, defined as amount of insulin delivered by closed‐loop relative to usual basal insulin delivery, and daytime bolus effort, defined as total bolus insulin delivery relative to total daytime insulin delivery were compared between both cohorts. Correlation analysis was performed between individual bolus behaviour (bolus effort and frequency) and daytime controller efforts, and proportion of time spent within and below sensor glucose target range.ResultsIndividuals with suboptimally controlled Type 1 diabetes had significantly lower bolus effort (P = 0.038) and daily bolus frequency (P < 0.001) compared with those with well‐controlled diabetes. Controller effort during both daytime (P = 0.007) and night‐time (P = 0.005) were significantly higher for those with suboptimally controlled Type 1 diabetes. Time when glucose was within the target range (3.9–10.0 mmol/L) during daytime correlated positively with bolus effort (r = 0.37, P = 0.016) and bolus frequency (r = 0.33, P = 0.037). Time when glucose was below the target range during daytime was comparable in both groups (P = 0.36), and did not correlate significantly with bolus effort (r = 0.28, P = 0.066) or bolus frequency (r = –0.21, P = 0.19).ConclusionMore frequent bolusing and higher proportion of insulin delivered as bolus during hybrid closed‐loop use correlated positively with time glucose was in target range. This emphasises the need for user input and educational support to benefit from this novel therapeutic modality.
No calcitonin change in a person taking dulaglutide diagnosed with pre‐existing medullary thyroid cancer
Authors: Sherman S. I. , Kloos R. T. , Tuttle R. M. , Pontecorvi A. , Völzke H. , Harper K. , Vance C. , Alston J. T. , Usborne A. L. , Sloop K. W. , Lakshmanan M. 
Published: July 2017

AbstractBackgroundGlucagon‐like peptide‐1 receptor agonists, such as dulaglutide, exenatide and liraglutide, are approved to treat Type 2 diabetes mellitus. Although these drugs provide substantial glycaemic control, studies in rodents have prompted concerns about the development of medullary thyroid carcinoma. These data are reflected in the US package insert, with boxed warnings and product labelling noting the occurrence of these tumours after clinically relevant exposures in rodents, and contraindicating glucagon‐like peptide‐1 receptor agonist use in people with a personal or family history of medullary thyroid carcinoma, or in people with multiple endocrine neoplasia type 2. However, there are substantial differences between rodent and human responses to glucagon‐like peptide‐1 receptor agonists. This report presents the case of a woman with pre‐existing medullary thyroid carcinoma who exhibited no significant changes in serum calcitonin levels despite treatment with dulaglutide 2.0 mg for 6 months in the Assessment of Weekly AdministRation of LY2189265 [dulaglutide] in Diabetes‐5 clinical study (NCT00734474).Case reportElevated serum calcitonin was noted in a 56‐year‐old woman with Type 2 diabetes mellitus at the 6‐month discontinuation visit in a study of long‐term dulaglutide therapy. Retroactive assessment of serum collected before study treatment yielded an elevated calcitonin level. At 3 months post‐study, calcitonin level remained elevated; ultrasonography revealed multiple bilateral thyroid nodules. Eventually, medullary thyroid carcinoma was diagnosed; the woman was heterozygous positive for a germline RET proto‐oncogene mutation.ConclusionThe tumour was not considered stimulated by dulaglutide therapy because calcitonin remained stable throughout.
A first‐in‐human pharmacodynamic and pharmacokinetic study of a fully human anti‐glucagon receptor monoclonal antibody in normal healthy volunteers
Authors: Kostic Ana , King Thomas Alexander , Yang Feng , Chan Kuo‐Chen , Yancopoulos George D. , Gromada Jesper , Harp Joyce B. 
Published: July 2017

AimsGlucagon receptor (GCGR) blockers are being investigated as potential therapeutics for type 1 and type 2 diabetes. Here we report the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of REGN1193, a fully human glucagon receptor blocking monoclonal antibody from a first‐in‐human healthy volunteer randomized double‐blinded trial.MethodsHealthy men and women received single ascending doses of REGN1193 ranging from 0.05 to 0.6 mg/kg (n = 42) or placebo (n = 14) intravenously. Safety, tolerability and PK were assessed over 106 days. The glucose‐lowering effect of REGN1193 was assessed after induction of hyperglycaemia by serial glucagon challenges.ResultsREGN1193 was generally well tolerated. There were small (<3× the upper limit of normal) and transient dose‐dependent increases in hepatic aminotransferases. No increase in LDL‐C was observed. Hypoglycaemia, assessed as laboratory blood glucose ≤70 mg/dL, occurred in 6/14 (43%) subjects on placebo and 27/42 (57%) on REGN1193 across all dose groups. All episodes of hypoglycaemia were asymptomatic, >50 mg/dL, and did not require treatment or medical assistance. Concentration‐time profiles suggest a 2‐compartment disposition and marked nonlinearity, consistent with target‐mediated clearance. REGN1193 inhibited the glucagon‐stimulated glucose increase in a dose‐dependent manner. The 0.6 mg/kg dose inhibited the glucagon‐induced glucose area under the curve for 0 to 90 minutes (AUC0‐90 minutes) by 80% to 90% on days 3 and 15, while blunting the increase in C‐peptide. REGN1193 dose‐dependently increased total GLP‐1, GLP‐2 and glucagon, with plasma levels returning to baseline by day 29 in all dose groups.ConclusionREGN1193, a GCGR‐blocking monoclonal antibody, produced a safety, tolerability and PK/PD profile suitable for further clinical development. The occurrence of transient elevations in serum hepatic aminotransferases observed here and reported with several small molecule glucagon receptor antagonists suggests an on‐target effect of glucagon receptor blockade. The underlying mechanism is unknown.
Love thy neighbour: Social identity and public support for humanitarian aid
Authors: Alvarez Linda , Boussalis Constantine , Merolla Jennifer L. , Peiffer Caryn A. 
Published: July 2017

AbstractHumanitarian aid can be contentious. Should finite national resources be sacrificed to serve the needy abroad? Social identity theorists argue that identification with a superordinate group, in this case the larger world community, should increase individual support for policies such as international humanitarian assistance. However, individuals can simultaneously associate with multiple identities. How does the combination of world and national identities affect support for humanitarian assistance? Using cross‐national survey data, we find evidence that support for international humanitarian aid is highest among those with a strong world identity and weak national identity relative to other identity combinations, though even those with a strong world identity and strong national identity can be supportive of aid.
Molecular characterization of a phytoplasma associated with Euonymus bungeanus witches’ broom in China
Authors: Ren Z. G. , Zhao X. Y. , Dong Y. R. , Wang J. Z. , Yang R. , Wang S. J. , Tian G. Z. , Wei Y. M. 
Published: July 2017

SummaryEuonymus bungeanus plants exhibiting symptoms of abnormal branches, small leaves and phyllody, which is indicative of E. bungeanus witches’ broom (EbWB) disease, have recently been found in Beijing, China. A phytoplasma from symptomatic E. bungeanus plants was identified by 16S rRNA polymerase chain reaction (PCR) using the phytoplasma‐specific universal primer pair R16mF2/R16mR1. Inoculation of healthy E. bungeanus plants by grafting with diseased scions was also performed. The rp and secY genes of the EbWB phytoplasma were cloned and sequenced as was the 16S rRNA gene. Sequence and phylogenetic analyses of 16S rRNA, rp and secY genes indicated that the phytoplasma associated with E. bungeanus belongs to the 16SrV‐B, rpV‐C and secY‐C subgroup, the same subgroup as the jujube witches’ broom (JWB) phytoplasma that is widely distributed among jujube trees in China. Comparative analyses based on virtual restriction fragment length polymorphism (RFLP) showed that the EbWB phytoplasma is more closely related to another 16SrV‐B subgroup strain: RPWB (Robinia pseudoacacia witches’ broom). To the best of our knowledge, this is the first report of a witches’ broom phytoplasma in E. bungeanus in China, and the findings add a new cultivated plant species to the already broad natural host range of 16SrV‐B subgroup phytoplasmas.
Optimal metabolic regulation along resource stoichiometry gradients
Authors: Manzoni Stefano , Čapek Petr , Mooshammer Maria , Lindahl Björn D. , Richter Andreas , Šantrůčková Hana 
Published: July 2017

AbstractMost heterotrophic organisms feed on substrates that are poor in nutrients compared to their demand, leading to elemental imbalances that may constrain their growth and function. Flexible carbon (C)‐use efficiency (CUE, C used for growth over C taken up) can represent a strategy to reduce elemental imbalances. Here, we argue that metabolic regulation has evolved to maximise the organism growth rate along gradients of nutrient availability and translated this assumption into an optimality model that links CUE to substrate and organism stoichiometry. The optimal CUE is predicted to decrease with increasing substrate C‐to‐nutrient ratio, and increase with nutrient amendment. These predictions are generally confirmed by empirical evidence from a new database of c. 2200 CUE estimates, lending support to the hypothesis that CUE is optimised across levels of organisation (microorganisms and animals), in aquatic and terrestrial systems, and when considering nitrogen or phosphorus as limiting nutrients.
Variable silicon accumulation in plants affects terrestrial carbon cycling by controlling lignin synthesis
Authors: Klotzbücher Thimo , Klotzbücher Anika , Kaiser Klaus , Vetterlein Doris , Jahn Reinhold , Mikutta Robert 
Published: July 2017

AbstractCurrent climate and land‐use changes affect regional and global cycles of silicon (Si), with yet uncertain consequences for ecosystems. The key role of Si in marine ecology by controlling algae growth is well recognized but research on terrestrial ecosystems neglected Si since not considered an essential plant nutrient. However, grasses and various other plants accumulate large amounts of Si, and recently it has been hypothesized that incorporation of Si as a structural plant component may substitute for the energetically more expensive biosynthesis of lignin. Herein, we provide evidence supporting this hypothesis. We demonstrate that in straw of rice (Oryza sativa) deriving from a large geographic gradient across South‐East Asia, the Si concentrations (ranging from 1.6% to 10.7%) are negatively related to the concentrations of carbon (31.3% to 42.5%) and lignin‐derived phenols (32 to 102 mg/g carbon). Less lignin may explain results of previous studies that Si‐rich straw decomposes faster. Hence, Si seems a significant but hardly recognized factor in organic carbon cycling through grasslands and other ecosystems dominated by Si‐accumulating plants.
Prostate carcinoma with amphicrine features: further refining the spectrum of neuroendocrine differentiation in tumours of primary prostatic origin?
Authors: Prendeville Susan , Al‐Bozom Issam , Compérat Eva , Sweet Joan , Evans Andrew J , Ben‐Gashir Mohamed , Mete Ozgur , van der Kwast Theodorus H , Downes Michelle R 
Published: July 2017

AimsThe current World Health Organization classification categorises high‐grade neuroendocrine (NE) carcinomas of the prostate into small‐cell and large‐cell types. A distinct form of carcinoma showing synchronous dual exocrine and NE differentiation, termed amphicrine carcinoma, has been described at various other sites, primarily within the gastrointestinal tract. The aim of this study was to investigate the clinicopathological features of a series of metastatic prostate carcinoma (PCa) cases with amphicrine features.Methods and resultsFive cases of high‐grade PCa showing an amphicrine immunohistochemical phenotype were prospectively collected. The serum prostate‐specific antigen (PSA) level at diagnosis ranged from 38 ng/ml to 992 ng/ml (median 200 ng/ml). All five patients had metastatic disease, four at initial presentation. Microscopically, the tumours showed a solid/nested growth pattern composed of cells with amphophilic cytoplasm, vesicular nuclei, and macronucleoli. Morphological features of small‐cell or large‐cell NE carcinoma were absent. As compared with conventional high‐grade PCa, the tumour cells showed a higher level of nuclear pleomorphism, brisk mitotic activity, and a high Ki67 proliferation index (median 50%). All cases showed immunohistochemical positivity for PSA, androgen receptor, and prostate‐specific acid phosphatase, combined with diffuse or confluent/non‐focal positivity for chromogranin‐A and synaptophysin. Two hormone‐naive cases showed a clinical response to androgen deprivation therapy.ConclusionThis series highlights a previously undefined, clinically aggressive variant of PCa showing dual exocrine and NE differentiation, for which we are proposing the term PCa with amphicrine features. Increased recognition of these tumours may lead to a better understanding of their biology, and ultimately improve their clinical management.
Killer‐cell immunoglobulin‐like receptors on the cusp of modern immunogenetics
Authors: Colucci Francesco , Traherne James 
Published: July 2017

SummaryKiller‐cell immunoglobulin‐like receptors (KIR) and their human leukocyte antigen (HLA) ligands play a central role in immunity and human health. These molecules are encoded by gene families with copy number variation, extreme levels of sequence diversity and complex expression patterns. The rapid evolution of KIR and HLA genes and their associations with infectious diseases, pregnancy disorders, immunopathologies and outcome of cell transplantation have generated considerable interest from immunologists, geneticists and clinicians. Until recently, however, analyses have been stuck at low‐level resolution, focusing primarily on presence or absence of KIR genes. This is changing with the advent of modern high throughput sequencing, cell phenotyping and bioinformatics. These developments allow high‐resolution analysis and much deeper understanding of KIR evolution and KIR function. The impending deluge of high dimensional data brings inevitably new challenges in analysis, interpretation and communication of results, but the benefits are already tangible. The diversity of KIR across worldwide human populations is being catalogued at the allele level. Structures of KIR molecules and their interactions with HLA–peptide complexes are being determined. How KIR modulate natural killer cell education is being defined. Ligands for activating KIR, elusive for many years, are being discovered. KIR gene complexes and their related receptor gene families are being characterized in animal models and livestock breeds. These advances are helping to generate a more complete picture of the impact of KIR variation in health and disease and offer new opportunities for immunotherapy, as highlighted in a recent meeting (The Tenth KIR Workshop, April 2017 Cambridge, UK).
RNomic identification and evaluation of npcTB_6715, a non‐protein‐coding RNA gene as a potential biomarker for the detection of Mycobacterium tuberculosis
Authors: Kanniappan Priyatharisni , Ahmed Siti Aminah , Rajasekaram Ganeswrie , Marimuthu Citartan , Ch'ng Ewe Seng , Lee Li Pin , Raabe Carsten A. , Rozhdestvensky Timofey S. , Tang Thean Hock 
Published: July 2017

AbstractTechnological advances in RNA biology greatly improved transcriptome profiling during the last two decades. Besides the discovery of many small RNAs (sRNA) that are involved in the physiological and pathophysiological regulation of various cellular circuits, it becomes evident that the corresponding RNA genes might also serve as potential biomarkers to monitor the progression of disease and treatment. sRNA gene candidate npcTB_6715 was previously identified via experimental RNomic (unpublished data), and we report its application as potential biomarker for the detection of Mycobacterium tuberculosis (MTB) in patient samples. For proof of principle, we developed a multiplex PCR assay and report its validation with 500 clinical cultures, positive for Mycobacteria. The analysis revealed 98.9% sensitivity, 96.1% specificity, positive and negative predictive values of 98.6% and 96.8%, respectively. These results underscore the diagnostic value of the sRNA gene as diagnostic marker for the specific detection of MTB in clinical samples. Its successful application and the general ease of PCR‐based detection compared to standard bacterial culture techniques might be the first step towards ‘point‐of‐care’ diagnostics of Mycobacteria. To the best of our knowledge, this is the first time for the design of diagnostic applications based on sRNA genes, in Mycobacteria.
Frailty as a Risk Factor for Falls Among Community Dwelling People: Evidence From a Meta‐Analysis
Authors: Cheng Mei‐Hsun , Chang Shu‐Fang 
Published: July 2017

AbstractPurposeThis study was conducted to investigate the relationships between different frailty stages and the fall incidence rates of community‐dwelling older adults. The differences between various frailty indicators regarding assessment accuracy of the fall incidence rates of community‐dwelling elders were also analyzed. Finally, the relationship between frailty and recurrent falls was explored.MethodsThis study comprised a systematic literature review and meta‐analysis. Two researchers independently examined and extracted the related literature. The key search terms included frailty, frail, fall, older people, older, geriatric, and senior. The literature sampling period was from January 2001 to December 2016. The quality of each paper was assessed according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA). The databases of the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, and MEDLINE were used to conduct a systematic literature search by using the random effect mode to analyze the compiled papers.FindingsA total of 102,130 community‐dwelling older adults ≥65 years of age and 33,503 older adults who had experienced a fall were compiled to investigate the relationship between frailty and falls. The meta‐analysis results revealed that compared with robust older adults, frail older adults demonstrated the greatest risk for falls, followed by prefrail older adults. Furthermore, the use of different frailty indicators to predict the fall incidence rates of older adults yielded nonsignificantly different outcomes. In short, studies of either cardiovascular health or osteoporotic fracture indicators are effective for predicting the risk for falls in older people. Finally, this study confirmed that compared with robust older adults, frail older adults were more likely to experience recurrent falls.ConclusionsFrailty is a crucial healthcare topic of people with geriatric syndromes. Frail older adults are likely to experience recurrent falls. In addition, the evidence‐based study indicated that once older people enter the prefrail stage, they are likely to experience falls. Therefore, older adults should be evaluated for the possibility of geriatric syndromes such as frailty, which may be addressed to reduce the risk for bone fractures and death.Clinical RelevanceProfessional nurses should use frailty assessment indicators as early as possible to evaluate the possibility of frailty in community‐dwelling older people. Meanwhile, effective frailty prevention strategies should be applied to prevent frailty, thereby reducing the incidence of falls and enhancing older persons’ quality of life.
Association between Gallbladder Ultrasound Findings and Bacterial Culture of Bile in 70 Cats and 202 Dogs
Authors: Policelli Smith R. , Gookin J.L. , Smolski W. , Di Cicco M.F. , Correa M. , Seiler G.S. 
Published: July 2017

BackgroundBacterial cholecystitis often is diagnosed by combination of gallbladder ultrasound (US) findings and positive results of bile culture. The value of gallbladderUSin determining the likelihood of bile bacterial infection in cats and dogs with suspected biliary disease is unknown.Hypothesis/ObjectivesTo determine the value of gallbladderUSin predicting bile bacterial culture results, identify most common bacterial isolates from bile, and describe complications after cholecystocentesis in cats and dogs with suspected hepatobiliary disease.AnimalsCats (70) and dogs (202) that underwent an abdominalUSand submission of bile for culture were included in the study.MethodsA cross‐sectional study design was used to determine the association of gallbladderUSabnormalities and the results of bile cultures, and complications of cholecystocentesis.ResultsAbnormal gallbladderUShad high sensitivity (96%) but low specificity (49%) in cats with positive and negative results of bile bacterial culture, respectively. Cats with normal gallbladderUSfindings were unlikely to have positive bile bacterial culture (negative predictive value of 96%). GallbladderUShad lower sensitivity (81%), specificity (31%), positive predictive value (20%), and negative predictive value (88%) in dogs. The most common bacterial isolates were of enteric origin, the prevalence being higher in cats. Incidence of complications after cholecystocentesis was 3.4%.Conclusions and clinical importanceGallbladderUShas a high negative predictive value for bile culture results in cats. This modality is less predictive of infection in dogs. PercutaneousUS‐guided cholecystocentesis has a low complication rate.