bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects on α‐ and β‐cell function of sequentially adding empagliflozin and linagliptin to therapy in people with type 2 diabetes previously receiving metformin: An exploratory mechanistic study
Authors: Forst Thomas , Falk Alexander , Andersen Grit , Fischer Annelie , Weber Matthias M. , Voswinkel Stephan , Heise Tim , Kapitza Christoph , Plum‐Mörschel Leona 
Published: December 2016

AimsTo investigate the effect of sequential treatment escalation with empagliflozin and linagliptin on laboratory markers of α‐ and β‐cell function in people with type 2 diabetes mellitus (T2DM) insufficiently controlled on metformin monotherapy.Research design and methodsA total of 44 people with T2DM received 25 mg empagliflozin for a duration of 1 month in an open‐label fashion (treatment period 1 [TP1]). Thereafter, they were randomized to a double‐blind add‐on therapy with linagliptin 5 mg or placebo (treatment period 2 [TP2]) for 1 additional month. α‐ and β‐cell function was assessed using a standardized liquid meal test and an intravenous (i.v.) glucose challenge. Efficacy measures comprised the areas under the curve for glucose, insulin, proinsulin and glucagon after the liquid meal test and the assessment of fast and late‐phase insulin release after an i.v. glucose load with a subsequent hyperglycaemic clamp.ResultsEmpagliflozin reduced fasting and postprandial plasma glucose levels, associated with a significant reduction in postprandial insulin levels and an improvement in the conversion rate of proinsulin (TP1). The addition of linagliptin during TP2 further improved postprandial glucose levels, probably as a result of a marked reduction in postprandial glucagon concentrations (TP2). The insulin response to an i.v. glucose load increased during treatment with empagliflozin (TP1), and further improved after the addition of linagliptin (TP2).ConclusionAfter metformin failure, sequential treatment escalation with empagliflozin and linagliptin is an attractive treatment option because of the additive effects on postprandial glucose control, probably mediated by complementary effects on α‐ and β‐cell function.
Modified CVAD and modified CBAD compared to high‐dose cyclophosphamide for peripheral blood stem cell mobilization in patients with multiple myeloma
Authors: Gettys Suzanne C. , Gulbis Alison , Wilhelm Kaci , Sasaki Koji , Dinh Yvonne , Rondon Gabriela , Qazilbash Muzaffar H. 
Published: December 2016

AbstractBackgroundThe optimal regimen for peripheral blood stem cell (PBSC) mobilization in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (auto‐HCT) has not been established. Experience at The University of Texas MD Anderson Cancer Center suggests in addition to single‐agent cyclophosphamide (Cy), modified cyclophosphamide, vincristine, doxorubicin, and dexamethasone (mCVAD), and modified cyclophosphamide, bortezomib, doxorubicin, and dexamethasone (mCBAD) may be successful chemomobilization regimens.MethodsThis retrospective review included 167 patients (66 with Cy, 74 with mCVAD, and 27 with mCBAD) with multiple myeloma undergoing mobilization for auto‐HCT between January 1, 2006 and September 30, 2013. The primary objective was to evaluate and compare the successful mobilization of CD34+ cells among high‐dose Cy, mCVAD or mCBAD.ResultsSuccessful mobilization (≥2×106 CD34+ cells/kg) was achieved in all patients, while 65 (98%), 72 (97%), and 27 (100%) patients achieved an optimal mobilization (≥4×106 CD34+ cells/kg) in the Cy, mCVAD, and mCBAD groups, respectively. There was no significant difference in the number of apheresis sessions (P=.63), incidence of febrile neutropenia (P=.57), or hospital admission rates (P=.55).ConclusionEither Cy, mCVAD, or mCBAD can yield successful PBSC mobilization in patients with multiple myeloma undergoing auto‐HCT.
Clinical implications of SCN1A missense and truncation variants in a large Japanese cohort with Dravet syndrome
Authors: Ishii Atsushi , Watkins Joseph C. , Chen Debbie , Hirose Shinichi , Hammer Michael F. 
Published: December 2016

SummaryObjectiveTwo major classes of SCN1A variants are associated with Dravet syndrome (DS): those that result in haploinsufficiency (truncating) and those that result in an amino acid substitution (missense). The aim of this retrospective study was to describe the first large cohort of Japanese patients with SCN1A mutation–positive DS (n = 285), and investigate the relationship between variant (type and position) and clinical expression and response to treatment.MethodsWe sequenced all exons and intron–exon boundaries of SCN1A in our cohort, investigated differences in the distribution of truncating and missense variants, tested for associations between variant type and phenotype, and compared these patterns with those of cohorts with milder epilepsy and healthy individuals.ResultsUnlike truncation variants, missense variants are found at higher density in the S4 voltage sensor and pore loops and at lower density in the domain I–II and II–III linkers and the first three segments of domain II. Relative to healthy individuals, there is an increased frequency of truncating (but not missense) variants in the noncoding C‐terminus. The rate of cognitive decline is more rapid for patients with truncation variants regardless of age at seizure onset, whereas age at onset is a predictor of the rate of cognitive decline for patients with missense variants.SignificanceWe found significant differences in the distribution of truncating and missense variants across the SCN1A sequence among healthy individuals, patients with DS, and those with milder forms of SCN1A‐variant positive epilepsy. Testing for associations with phenotype revealed that variant type can be predictive of rate of cognitive decline. Analysis of descriptive medication data suggests that in addition to conventional drug therapy in DS, bromide, clonazepam and topiramate may reduce seizure frequency.
Trophic plasticity, environmental gradients and food‐web structure of tropical pond communities
Authors: Schalk Christopher M. , Montaña Carmen G. , Winemiller Kirk O. , Fitzgerald Lee A. 
Published: December 2016

Summary

Freshwater pond communities exhibit strong patterns in species composition in response to environmental gradients such as ecosystem size, disturbance and productivity, serving as excellent systems for studies of food‐web structure.

We surveyed 13 ponds that varied along environmental gradients of canopy cover, pond size and hydroperiod at the beginning and end of the rainy season in the semi‐arid thorn forests of the Gran Chaco ecoregion of Bolivia. We collected basal resources and consumers (tadpoles, macroinvertebrates and fishes) from these ponds and used stable isotope ratios of carbon (13C/12C) and nitrogen (15N/14N), to quantify the spatiotemporal dynamics of the food webs in these tropical ponds.

There were no relationships between vertical structure of the food webs and the environmental gradients associated with the ponds. Consumers within these ponds exhibited high trophic variability, with multiple taxa occupying more than one trophic position across space or time.

Consumers from larger ponds had a greater degree of trophic redundancy. More shaded ponds supported food webs that had lower trophic diversity. More permanent ponds had significantly greater trophic diversity as well as a greater range of basal resource diversity.

The breeding ponds utilised by tadpoles and macroinvertebrates are patchily distributed across space and time. In these dynamic habitats, a feeding strategy of trophic generalism and plasticity enables consumers to exploit a broad range of resources and promote species coexistence. These results suggest that high diversity in tropical ponds does not necessarily translate into specialisation of trophic function.
Effects of plant architecture and drought stress level on lucerne forage quality
Authors: Pecetti L. , Annicchiarico P. , Scotti C. , Paolini M. , Nanni V. , Palmonari A. 
Published: December 2016

AbstractBreeding for enhanced quality in lucerne (Medicago sativa) frequently involves selection for higher leaf‐to‐stem ratio, multifoliolate leaves or short‐internode stems. Three populations selected for such alternative morphologies and a reference cultivar were evaluated for forage yield, leaf‐to‐stem ratio and protein and fibre concentrations in leaves, stems and whole plants. Four managed environments were obtained by combining two stress levels (moderate or nil) with two sowing times. The population selected for high leaf‐to‐stem ratio, as well as the short‐internode population, had highest leaf‐to‐stem ratio (1.27) across six harvests in two non‐stress environments. The latter population had higher stem protein (12.9%) and lower stem neutral‐detergent fibre (NDF) concentration (58.7%) than other populations. The multifoliolate population had intermediate quality, showing low expression of the multifoliolate trait (14.0% across four environments), particularly under stress (10.5%). The autumn‐sown, fully irrigated environment had, on average, highest dry‐matter yield (4.19 t ha−1) and lowest leaf‐to‐stem ratio (0.74). Drought‐stressed environments had lower plant NDF (−12.3% on average) and leaf protein (−9.7%), and higher stem protein (+8.6%) than fully irrigated environments. The results suggested that environmental effects might have greater impact on quality than genetic effects, even for a population set including material selected for quality‐driven morphology.
Anal verrucous carcinoma is not related to infection with human papillomaviruses and should be distinguished from giant condyloma (Buschke–Löwenstein tumour)
Authors: Zidar Nina , Langner Cord , Odar Katarina , Hošnjak Lea , Kamarádová Kateřina , Daum Ondrej , Pollheimer Marion J , Košorok Pavle , Poljak Mario 
Published: December 2016

AimsVerrucous carcinoma (VC) is a variant of well‐differentiated squamous cell carcinoma and in the anal region is regarded as synonymous with giant condyloma (Buschke–Löwenstein tumour) (BLT). Aetiology, diagnostic criteria and clinical behaviour of both lesions are controversial. Recent studies suggest that VC at other sites is not associated with human papillomaviruses (HPV). We hypothesized that anal VC is also not related to HPV, while BLT is a HPV‐induced lesion.Methods and resultsTen cases of VC and four cases of BLT were included. Several techniques were used for HPV detection: in‐situ hybridization for HPV6, 11, 16 and 18, six different polymerase chain reaction (PCR) protocols for detection of at least 89 HPV types from alpha‐, beta‐, gamma‐ and mu‐PV genera and in‐situ hybridization for high‐risk HPV E6/E7 mRNA; p16 immunohistochemistry and morphometric analysis were also performed. Alpha‐, gamma‐ and mu‐PVs were not found in any case of VC, while HPV6 was detected in all cases of BLT. p16 overexpression was not present in any of the lesions. Among microscopic features, only the absence of koilocytosis and enlarged spinous cells seem to be useful to distinguish VC from BLT.ConclusionsOur results suggest that anal VC, similarly to VC at other sites, is not associated with HPV infection, and must be distinguished from BLT, which is associated with low‐risk HPV. Only with well‐set diagnostic criteria will it be possible to ascertain clinical behaviour and optimal treatment for both lesions.
Sensory characterisation of gluten‐free bread with addition of quinoa, amaranth flour and sweeteners as an alternative for coeliac patients
Authors: Alencar Natália Manzatti Machado , de Morais Elisa Carvalho , Steel Caroline Joy , Bolini Helena Maria André 
Published: December 2016

SummaryThis study aimed to determine the acceptance of gluten‐ and sucrose‐free breads with addition of pseudocereals and sweeteners, characterise them using quantitative descriptive analysis (QDA®) and identify the drivers of liking using four different techniques of sensorial data evaluation. A consumer test with 118 people was performed, and a QDA® was carried out by 12 trained assessors to obtain the sensory profile. In addition, partial least squares (PLS) regression was used to identify the drivers of liking of gluten‐free breads, and principal component analysis (PCA) and external preference maps were provided to correlate the data obtained in the sensory studies. The attributes of amaranth aroma and taste contributed positively to consumer acceptance, whereas a brown crust colour and quinoa aroma and taste contributed negatively to consumer acceptance. The external preference map showed that samples containing amaranth and the sweeteners sucralose, stevia and sucralose–acesulfame‐K were the most accepted by consumers.
Tadalafil for male lower urinary tract symptoms improves endothelial function
Authors: Fukumoto Kazuhiko , Nagai Atsushi , Hara Ryoei , Fujii Tomohiro , Miyaji Yoshiyuki 
Published: December 2016

ObjectivesTo investigate the effects of tadalafil on vascular endothelial function and cardiovascular risk in patients with prostatic hyperplasia.MethodsTadalafil 5 mg was given to 20 patients with prostatic hyperplasia for whom an α1‐blocker was ineffective. Voiding symptoms and vascular endothelial function were investigated before and after 4 and 12 weeks of administration, using commercial tests for vascular function and vascular endothelial function.ResultsThe participants had a median age of 65 years, a mean body mass index of 24.2 and a mean prostate volume of 36.2 mL measured using transabdominal sonography. Voiding symptoms were significantly improved by tadalafil, based on the International Prostate Symptom Score, quality of life index and overactive bladder symptom score (P < 0.05). There were also significant improvements in vascular function (change of brachial‐ankle pulse wave velocity from 1701 [before] to 1657 [4 weeks tadalafil] and 1525 [10 weeks tadalafil] cm/s [P < 0.05]) and vascular endothelial function (change of reactive hyperemia index from 1.36 to 1.56 and 1.89 [P < 0.05]). The change in reactive hyperemia index was significantly correlated with International Prostate Symptom Score, quality of life index and brachial‐ankle pulse wave velocity.ConclusionsThe improvement in intrapelvic blood flow by tadalafil can result in improved vascular endothelial function, in addition to improvement of voiding symptoms. The change in reactive hyperemia index seems to correlate with the severity of voiding symptoms, with tadalafil being most effective in patients with mild voiding symptoms.
Chronic infections with viruses or parasites: breaking bad to make good
Authors: Godkin Andrew , Smith Katherine A. 
Published: December 2016

SummaryEukaryotic forms of life have been continually invaded by microbes and larger multicellular parasites, such as helminths. Over a billion years ago bacterial endosymbionts permanently colonized eukaryotic cells leading to recognized organelles with a distinct genetic lineage, such as mitochondria and chloroplasts. Colonization of our skin and mucosal surfaces with bacterial commensals is now known to be important for host health. However, the contribution of chronic virus and parasitic infections to immune homeostasis is being increasingly questioned. Persistent infection does not necessarily equate to exhibiting a chronic illness: healthy hosts (e.g. humans) have chronic viral and parasitic infections with no evidence of disease. Indeed, there are now examples of complex interactions between these microbes and hosts that seem to confer an advantage to the host at a particular time, suggesting that the relationship has progressed along an axis from parasitic to commensal to one of a mutualistic symbiosis. This concept is explored using examples from viruses and parasites, considering how the relationships may be not only detrimental but also beneficial to the human host.
Holistic Healing in Acts 3:1‐10
Authors: Kamba Micheline 
Published: December 2016

AbstractThe understanding of healing focuses on Acts 3:1‐10, where the rereading of this text with its picture of healing will lead to an understanding of inclusive healing, in the sense that the marginalized people are included in this healing. This means that the healing is holistic, rather than focusing on either physical or spiritual healing only. The research on which this paper is based sought to explore the issue of holistic healing for a transformative church. The paper brings into perspective the following questions: What is entailed in Jesus’ healing people with disabilities? And how can the issue of healing be opened to the possibility of building a community of love, justice, peace, and diversity? In an attempt to answer the preceding questions, this paper has two parts: in the first section, I focus on my personal rereading in view of my own disability experience and my experience with the participants of Bible study, whereby I use narrative interpretation of existing literature, and I interpret from a psycho‐spiritual perspective framed by a liberation theology of disability. In the second section, I engage a dialogue between biblical scholars and ordinary people on the different perspectives on healing. My overall objective in this paper is to offer a new biblical understanding on the text and, on the other hand, a theological reflection on healing to assist church leaders and Christians to understand that people with disabilities, like any human being, deserve to be in fellowship with God and with other people for the sake of social transformation.
Collective Resistance as Prophetic Witness
Authors: Longchar Wati 
Published: December 2016

AbstractAuthentic Christian witness today, marked by the mission from the margins, must engage communities of the marginalized at the structural level through collective solidarity resistance. This article first examines social structures themselves and their capacity to enhance or denigrate human dignity. Inherited structures of oppression can be identified and addressed. Christian witness has a particular exigence for and role in identifying and resisting oppressive structures for the sake of justice. Prophetic witness to kingdom values–saying no to unjust systems–involves joining with victims in active resistance through local and global mobilization for social change and celebration of life.
What to expect from reliability and validity claims? A pragmatic conception of psychiatric nosology
Authors: Lefere Sander , De Rouck Ruben , De Vreese Leen 
Published: December 2016

AbstractThe reliability and validity of psychiatric diagnoses have always been a major concern. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM‐5) reliability field trials yielded ambiguous results, with some diagnostic categories scoring well below par. We argue that the emphasis on the reliability of psychiatric diagnoses, which has dominated psychiatric nosology and guided the endeavor of improving the DSM in its consecutive editions, is misguided and lacks in structural validity.In this article, we defend a pragmatic view on psychiatric disease as the most fruitful approach to an understanding of what the categorical distinctions in the DSM (can) represent. Disorders in the DSM are descriptions of clinical pictures and do not necessarily correspond to an identified pathological substrate. Although this is a logical result of the nature of psychiatric disease, it bears important consequences. The various DSM disease categories are not uniform but should be regarded as representing different kinds of disorders, ranging from a separation from normal behavior based on practical grounds to the discrete kind of disorders envisioned by proponents of a strong realistic view. We argue that the explication of kinds of disorders outlined in this article provides interesting perspectives on the problems of reliability and validity that the DSM faces.
Use of computer‐assisted image analysis for semi‐quantitative histology of the hepatopancreas in whiteleg shrimp Penaeus vannamei (Boone)
Authors: Cervellione F , McGurk C , Berger Eriksen T , Van den Broeck W 
Published: December 2016

AbstractDespite the increasing use of novel molecular techniques in pathology, histology remains the standard method for monitoring tissue alterations and for assessing pathology. Histopathological evaluation is generally laborious and subjective with risk of discrepancies in semi‐quantitative scoring between pathologists. In contrast, computer‐assisted image analysis (CAIA) is potentially faster, more objective and thus suitable for routine screening. Limited research has been carried out on CAIA in crustacean histopathology, and the methods described were not fully automated. Therefore, the aim of this study was to develop CAIA in whiteleg shrimp (Penaeus vannamei) for the study of the hepatopancreas. Paraffin sections were immunohistochemically stained with monoclonal antibodies WSH8 against haemocytes and counterstained with Mayer′s haematoxylin for detection of haemocytes and B‐cell vacuoles, and modified toluidine blue protocol was used for detection of F‐cells; frozen sections were stained with Oil Red O for detection of lipid droplets within R‐cells. Visiopharm® software was used to develop and validated protocols for the quantification of morphological parameters (areas of haemocyte infiltration, F‐cells, B‐cell vacuoles, lipid droplets and their ratios to total tissue area and total lumen area). These protocols enable the future use of CAIA for determination of the nutritional and pathological condition of this organ.
Functional specialization of Nicotiana attenuata phytochromes in leaf development and flowering time
Authors: Fragoso Variluska , Oh Youngjoo , Kim Sang‐Gyu , Gase Klaus , Baldwin Ian Thomas 
Published: December 2016

AbstractPhytochromes mainly function in photoautotrophic organisms to adjust growth in response to fluctuating light signals. The different isoforms of plant phytochromes often display both conserved and divergent roles, presumably to fine‐tune plant responses to environmental signals and optimize fitness. Here we describe the distinct, yet partially redundant, roles of phytochromes NaPHYA, NaPHYB1 and NaPHYB2 in a wild tobacco species, Nicotiana attenuata using RNAi‐silenced phytochrome lines. Consistent with results reported from other species, silencing the expression of NaPHYA or NaPHYB2 in N. attenuata had mild or no influence on plant development as long as NaPHYB1 was functional; whereas silencing the expression of NaPHYB1 alone strongly altered flowering time and leaf morphology. The contribution of NaPHYB2 became significant only in the absence of NaPHYB1; plants silenced for both NaPHYB1 and NaPHYB2 largely skipped the rosette‐stage of growth to rapidly produce long, slender stalks that bore flowers early: hallmarks of the shade‐avoidance responses. The phenotyping of phytochrome‐silenced lines, combined with sequence and transcript accumulation analysis, suggest the independent functional diversification of the phytochromes, and a dominant role of NaPHYB1 and NaPHYB2 in N. attenuata's vegetative and reproductive development.