bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety, pharmacokinetics and pharmacodynamics of BI 705564, a highly selective, covalent inhibitor of Bruton's tyrosine kinase, in Phase I clinical trials in healthy volunteers
Authors: Litzenburger Tobias , Steffgen Jürgen , Benediktus Ewald , Müller Fabian , Schultz Armin , Klein Elliott , Ramanujam Meera , Harcken Christian , Gupta Alpana , Wu Jing , Wiebe Sabrina , Li Xiujiang , Flack Mary , Padula Steven J. , Visvanathan Sudha , Hünnemeyer Andreas , Hui Jianan 
Published: September 2020

AimsTo evaluate the safety, pharmacokinetics and pharmacodynamics of single‐ and multiple‐rising doses (MRDs) of BI 705564 and establish proof of mechanism.MethodsBI 705564 was studied in 2 placebo‐controlled, Phase I clinical trials testing single‐rising doses (1–160 mg) and MRDs (1–80 mg) of BI 705564 over 14 days in healthy male volunteers. Blood samples were analysed for BI 705564 plasma concentration, Bruton's tyrosine kinase (BTK) target occupancy (TO) and CD69 expression in B cells stimulated ex vivo. A substudy was conducted in allergic, otherwise healthy, MRD participants. Safety was assessed in both studies.ResultsAll doses of BI 705564 were well tolerated. Geometric mean BI 705564 plasma terminal half‐life ranged from 10.1 to 16.9 hours across tested doses, with no relevant accumulation after multiple dosing. Doses ≥20 mg resulted in ≥85% average TO that was maintained for ≥48 hours after single‐dose administration. Functional effects of BTK signalling were demonstrated by dose‐dependent inhibition of CD69 expression. In allergic participants, BI 705564 treatment showed a trend in wheal size reduction in a skin prick test and complete inhibition of basophil activation. Mild bleeding‐related adverse events were observed with BI 705564; bleeding time increased in 1/12 participants (8.3%) who received placebo vs 26/48 (54.2%) treated with BI 705564.ConclusionBI 705564 showed efficient target engagement through durable TO and inhibition of ex vivo B‐cell activation, and proof of mechanism through effects on allergic skin responses. Mild bleeding‐related adverse events were probably related to inhibition of platelet aggregation by BTK inhibition.
Current status and future outlook for patient‐derived cancer models from a rare cancer research perspective
Authors: Kondo Tadashi 
Published: September 2020

AbstractRare cancers are a group of approximately 200 malignancies with extremely low incidences and with a wide variety of genotypes and phenotypes. Collectively, they are more common than any single malignancy. However, given the small numbers of individuals diagnosed with rare cancers, it is difficult to design clinical trials with sufficient patient numbers. Therefore, few effective anticancer drugs have been developed, and evidence‐based medicine is not always feasible for rare cancers. Consequently, their clinical outcomes are generally poorer. Cancer research requires adequate models that faithfully recapitulate molecular features and reproduce treatment responses of the original tumors. Such models allow us to focus on more efficacious drugs in the clinical studies. For rare cancers, patient‐derived cancer models are particularly important because the enrollment of sufficient patients is rarely attainable within a reasonable period of time. However, extremely few models are available for rare cancers. For example, cell lines and xenografts are available for only a limited number of histological subtypes of sarcomas; therefore, most sarcoma research is performed without such models, and a lack of adequate cancer models causes a lag in therapeutic development. The establishment of novel rare cancer models will dramatically facilitate rare cancer research and treatment development in the near future. This review focuses on the status of patient‐derived rare cancer models and discusses their pivotal problems and possibilities, using sarcomas as a representative rare cancer type. Multi‐institutional collaboration will help address the scarcity of patient‐derived rare cancer models.
A randomized, placebo‐controlled trial evaluating effects of lebrikizumab on airway eosinophilic inflammation and remodelling in uncontrolled asthma (CLAVIER)
Authors: Austin Cary D. , Gonzalez Edick Melissa , Ferrando Ronald E. , Solon Margaret , Baca Miriam , Mesh Kathryn , Bradding Peter , Gauvreau Gail M. , Sumino Kaharu , FitzGerald J. Mark , Israel Elliot , Bjermer Lief , Bourdin Arnaud , Arron Joseph R. , Choy David F. , Olsson Julie K. , Abreu Francis , Howard Monet , Wong Kit , Cai Fang , Peng Kun , Putnam Wendy S. , Holweg Cécile T.J. , Matthews John G. , Kraft Monica , Woodruff Prescott G. ,   the CLAVIER Investigators
Published: September 2020

AbstractBackgroundThe anti‐interleukin 13 (IL‐13) monoclonal antibody lebrikizumab improves lung function in patients with moderate‐to‐severe uncontrolled asthma, but its effects on airway inflammation and remodelling are unknown. CLAVIER was designed to assess lebrikizumab's effect on eosinophilic inflammation and remodelling.ObjectiveTo report safety and efficacy results from enrolled participants with available data from CLAVIER.MethodsWe performed bronchoscopy on patients with uncontrolled asthma before and after 12 weeks of randomized double‐blinded treatment with lebrikizumab (n = 31) or placebo (n = 33). The pre‐specified primary end‐point was relative change in airway subepithelial eosinophils per mm2 of basement membrane (cells/mm2). Pre‐specified secondary and exploratory outcomes included change in IL‐13‐associated biomarkers and measures of airway remodelling.ResultsThere was a baseline imbalance in tissue eosinophils and high variability between treatment groups. There was no discernible change in adjusted mean subepithelial eosinophils/mm2 in response to lebrikizumab (95% CI, −82.5%, 97.5%). As previously observed, FEV1 increased after lebrikizumab treatment. Moreover, subepithelial collagen thickness decreased 21.5% after lebrikizumab treatment (95% CI, −32.9%, −10.2%), and fractional exhaled nitric oxide, CCL26 and SERPINB2 mRNA expression in bronchial tissues also reduced. Lebrikizumab was well tolerated, with a safety profile consistent with other lebrikizumab asthma studies.Conclusions & Clinical RelevanceWe did not observe reduced tissue eosinophil numbers in association with lebrikizumab treatment. However, in pre‐specified exploratory analyses, lebrikizumab treatment was associated with reduced degree of subepithelial fibrosis, a feature of airway remodelling, as well as improved lung function and reduced key pharmacodynamic biomarkers in bronchial tissues. These results reinforce the importance of IL‐13 in airway pathobiology and suggest that neutralization of IL‐13 may reduce asthmatic airway remodelling.Clinical Trial Registration: NCT02099656.
Gamma Knife radiosurgery for acromegaly: Evaluating the role of the biological effective dose associated with endocrine remission in a series of 42 consecutive cases
Authors: Balossier Anne , Tuleasca Constantin , Cortet‐Rudelli Christine , Soto‐Ares Gustavo , Levivier Marc , Assaker Richard , Reyns Nicolas 
Published: September 2020

AbstractIntroductionStereotactic radiosurgery (SRS) is a valuable treatment option for persistent and/or recurrent acromegaly secondary to growth hormone (GH) secreting pituitary adenoma (PA). Here, we assess the role of biological effective dose (BED) received by PA treated with SRS in relation with endocrine remission.MethodsForty‐two patients (minimum 6 months follow‐up) were included. Mean marginal dose was 27.7 (median 28, 20–35), and mean BED received by tumour was 193.1 Gy2.47 (median 199.7, 64.1–237.1). Based on the median values, we divided the patients in high tumour BED group (H‐BEDtm, 199.7–237.1 Gy2.47, n = 12) and low BED one (L‐ BEDtm, 64.1–199.7 Gy2.47, n = 10). The two groups did not differ by pretherapeutic IGF‐1 levels (p = .1) or by the prescribed dose (p = .6).ResultsMean follow‐up period was 62.5 months (median 60.5, 9–127). Probability of IGF‐1 normalization was 65% at 3 years and 72.4% at 4 years, remaining stable until last follow‐up. Twenty‐two (52.4%) patients had complete endocrine remission in absence of any Somatostatin analogues. Actuarial rates were 33% at 3 years and 57.4% at 7 years, further remaining stable during follow‐up course. In univariate analysis, only statistically significant parameter was pretherapeutic serum IGF‐1 and IGF‐1 index (p = .01). Five patients (5/26, 19.3%) without previous hypopituitarism developed new pituitary insufficiency. H‐BEDtm was associated with higher rates of endocrine remission compared with L‐BEDtm, with actuarial probability of 70.2% versus 48.2% at 9 years, although this did not reach statistical significance (p > .05).ConclusionOur study confirms that SRS by Gamma Knife is safe and effective for GH‐secreting PA. Pretherapeutic serum levels of IGF‐1 were only statistically significant parameter for endocrine remission.
Flags and Shields: Muslim Socialities and Informal Livelihoods in Dar es Salaam
Authors: Kirby Benjamin 
Published: September 2020

AbstractIn this article, I explore entanglements of Muslim sociality and informal livelihoods in Dar es Salaam. I propose that Muslim practices of affiliation deserve to be counted among the ordinary strategies that urban majorities employ to navigate the city amidst conditions of uncertainty. Building on Stephan Lanz and Martijn Oosterbaan’s (2016) work on “entrepreneurial religion,” I draw on fifteen months of ethnographic research in Kariakoo, a super‐dense market district at the center of the city. The first part of my analysis explores associational life in Dar es Salaam, combining a historical overview with ethnographic description. I explore how urban actors use affiliations to football teams and political parties to generate livelihood opportunities and to secure protection. The second part of my analysis uses emic notions of “flags” (bendera) and “shields” (ngao) to demonstrate that Muslim modes of association operate in strikingly similar ways to those pertaining to football and politics. Engaging with the conceptual vocabularies of AbdouMaliq Simone and Erving Goffman, as well as recent debates about “everyday” and “lived Islam,” this article foregrounds the interplay between religious forms and neoliberal processes of informalization as they are unfolding in African cities and beyond.[Tanzania; Dar es Salaam; Urban Religion; Muslim Urbanism; Informal Economy; Associational Life.]
Physicians certified by the American Board of Obesity Medicine provide evidence‐based care
Authors: Gudzune Kimberly A. , Wickham Edmond P. , Schmidt Stacy L. , Stanford Fatima Cody 
Published: September 2020

SummaryOur objective was to determine the clinical services offered by American Board of Obesity Medicine (ABOM) Diplomates and whether guideline concordant services varied by clinical practice attributes. We conducted a cross‐sectional analysis of the 2019 ABOM Diplomate survey (response rate 19.2%). Respondents (n = 494) self‐reported services offered: nutrition, exercise, mental health, minimally invasive bariatric procedures, perioperative bariatric surgical care and FDA‐approved anti‐obesity medications. We graded concordance of services offered with three evidence‐based obesity guidelines, and then conducted bivariate analyses comparing concordance by practice attributes. Most responding ABOM Diplomates offered nutrition (90.1%), exercise (67.8%) and mental health (76.7%). Few offered minimally invasive procedures (24.3%), and most provided perioperative surgical care (63.0%). Most (83.4%) prescribed FDA‐approved medications—typically both short‐ and long‐term agents (70.9%). Few Diplomates had low concordance with the American Heart Association/American College of Cardiology/The Obesity Society (AHA/ACC/TOS) guidelines (24.7%). Those who managed more obesity‐related conditions and endorsed AHA/ACC/TOS guideline use had higher concordance with these recommendations. No differences in guideline concordance existed by population, clinical effort or location. We found similar findings regarding concordance with ) American Association of Clinical Endocrinologists/American College of Endocrinology and Obesity Medicine Association guidelines. In conclusion, most responding ABOM Diplomates offer evidence‐based obesity medicine services. Clinicians may therefore have increased confidence in patient receipt of evidence‐based care when referring to an ABOM Diplomate.
More than a “monstrous obesity”! Time to overcome the “anti‐fat” bias
Authors: Palmese Francesco , Reggidori Nicola , Pappas Georgios , Gramenzi Annagiulia 
Published: September 2020

SummaryA 54‐years‐old woman complained of unintentional important body weight gain associated with abdominal bloating. For this reason, she had consulted many different diet and nutritional professionals, general practitioners and a gastroenterology specialist, but no one went beyond a simple diagnosis of “monstrous obesity”. At our hospital division, based on physical examination, a computed tomography (CT) of the abdomen and pelvis was performed. It showed a voluminous intraperitoneal mass occupying the most part of the abdomen. The patient underwent laparotomy with resection of the abdomino‐pelvic mass, originating from the left ovary, measuring 60 x 45 cm and weighing 46 kg. Histopathology examination revealed a tumor composed of three different areas, including a well‐differentiated adenocarcinoma of intestinal‐type. It is emblematic of a grotesque misdiagnosis generated by a non‐comprehensive patient assessment and consequently by a too quick judgement related to the "anti‐fat bias".
Exotic animal cafes are increasingly home to threatened biodiversity
Authors: McMillan Sharne E. , Dingle Caroline , Allcock John A. , Bonebrake Timothy C. 
Published: September 2020

AbstractExploitation of species for wildlife trade, including the demand for exotic pets (likely sourced from the wild or recent generations of captivity) is a major threat to biodiversity. Although not traditionally considered “pet keeping” countries, pet ownership is growing in Asia. Exotic animals are also appearing in cafes, which are growing in popularity and have the potential to impact wild populations by stimulating exotic pet trade. We identified 406 animal cafes across Asia, of which 27% housed exotic species, including mammals (e.g., otter, slow loris, meerkat), birds (e.g., owls, hawks, parrots), and reptiles (e.g., geckos, pythons, turtles). Of the 252 exotic species recorded, 46% were threatened either as classified by the IUCN Red List, having a decreasing population trend, and/or threatened by the pet trade. These results, alongside the alignment of cafe traits with recognized factors influencing exotic pet trade, demonstrate as yet unclear (but potentially dramatic) implications for conservation.
Machine colour constancy: a work in progress
Authors: Lecca Michela 
Published: September 2020

AbstractThe term “colour constancy” denotes the human capability to recognise an object as the same entity even if its colours change due to illumination. Implementing such a human capability is highly desirable in computer vision to retrieve, detect, recognise and track objects regardless of the illumination. Many efforts have been made in this direction, leading to several “machine colour constancy” (MCC) algorithms, that is, routines inspired by human colour constancy (HCC) that are aiming to achieve an image representation independent of the light and thus invariant against light changes. Different to HCC, which is subject to illusions and only partially removes illuminant effects, MCC pursues the implementation of a perfect, total removal of light effects from images. Such an implementation represents a major challenge and is therefore a focus of ongoing research. In fact, the currently available MCC algorithms only work under constrained domains. Therefore, a priori knowledge about the image content is needed to choose the most appropriate MCC procedure and to properly set its parameters. Here, we present the main common assumptions underlying most of MCC algorithms. Our work shows that two main issues should be addressed in the future to ensure MCC is more efficacious and useable: first, the lack of a reliable MCC algorithm operating without supervision in multiple scenarios; and second, the difficulty which any user encounters when choosing the MCC procedure most appropriate for a particular application.
COMACO, from snares to plowshares: A conservation and human wellbeing success story
Authors: Lewis Dale , Wilkie David S. 
Published: September 2020

AbstractCommunity Markets for Conservation is a private sector, not‐for‐profit social enterprise in Zambia. It was established in 2003 to halt wildlife poaching and illegal tree cutting for charcoal by helping poor rural families to increase their food and income security through improved farming practices and marketing of value‐added agricultural commodities. COMACO supports 178,891 farmers in the Luangwa Valley, providing them with improved farming skills, seed loans, a premium price for their crop surplus, and a dividend if they comply with sustainable farming and wildlife, and forest conservation best practices. Maize yields using COMACO methods increased by 63% and net income was 37% higher than for farmers who purchased inorganic fertilizers. Between 2012 and 2018 the number of food secure families increased from 67–84%. Elephant poaching has declined in all but one COMACO district, poaching is now primarily conducted by nonlocal hunters, and leg‐hold snare detections by community game scouts have decreased significantly in COMACO areas. Increasing food and income security while reducing deforestation and unsustainable hunting for ~$US10 per farmer per year is cheap and can be replicated in Zambia and other nations in Africa.
Dyskeratosis congenita: ein Literaturüberblick
Authors: AlSabbagh Manahel Mahmood 
Published: September 2020

ZusammenfassungDie Dyskeratosis congenita ist eine seltene Erbkrankheit, die hauptsächlich Männer betrifft und klinisch durch die klassische Trias retikuläre Hyperpigmentierung, Onychodystrophie und Leukoplakie gekennzeichnet ist. Sie erhöht das Risiko für maligne Erkrankungen und andere potenziell zum Tod führende Komplikationen wie Knochenmarksversagen, Lungen‐ und Lebererkrankungen. Mutationen in 19 Genen wurden mit der Dyskeratosis congenita assoziiert. Circa ein Fünftel der pathogenen Mutationen finden sich in DKC1, dem für Dyskerin kodierenden Gen. Die vorliegende Übersicht soll die klinischen und genetischen Aspekte der Erkrankung aufzeigen.
Evaluation of right ventricular dyssynchrony in patients with acute inferior myocardial infarction and its relation with mortality
Authors: Kanar Batur Gonenc , Tigen Mustafa Kursat , Sunbul Murat , Cincin Ahmet Altug , Gurel Emre , Sayar Nurten , Kepez Alper , Sadıc Beste Ozben 
Published: September 2020

AbstractPurposeThe aim of this study was to evaluate right ventricle (RV) dyssynchrony and its relation with mortality using speckle‐tracking echocardiography (STE) in patients with acute inferior myocardial infarction (IMI).MethodsOne hundred and fifty‐eight consecutive patients with acute IMI treated with primary percutaneous coronary intervention, and 44 healthy subjects were included. RV myocardial involvement (RVMI) was defined as an elevation >1 mm in V1 or V4R and/or the presence of a culprit lesion at the proximal portion of the first RV marginal branch after reviewing coronary angiography. Patients were followed for 3 years to determine the cardiovascular mortality.ResultsOverall, 70 patients with IMI had RVMI. IMI patients had significantly higher RV peak systolic longitudinal strain dyssynchrony (PLSSD) index, lower peak longitudinal systolic strain (PLSS), longer time to PLSS, and time to PLSS differences compared to healthy controls while the patients with RVMI had significantly worse values compared to patients without RVMI and healthy controls. Twenty‐seven patients (17.1%) died within 2 years. RVMI was more prevalent in mortality group, and they had significantly higher RV PSSD index, whereas they had lower RV free wall PLSS and longer time to PLSS differences. Receiver operating characteristics (ROC) analysis revealed that a RV PLSSD index > 65 ms predicted mortality with a sensitivity of 88.9% and specificity of 71.8% in IMI patients.ConclusionsIntra‐ and inter‐ventricular dyssynhcrony may develop in patients with acute IMI, especially in those with RV involvement, which might have a negative effect on the prognosis of these patients.
Structural change and misallocation: Firm‐level evidence from Poland*
Authors: Hagemejer Jan , Tyrowicz Joanna 
Published: September 2020

AbstractEarly transition literature linked a large number of firm failures with the inability to overcome the pre‐transition misallocation of resources, that is, the inadequate capital–labour ratio. We look at the link between misallocation and firm survival using a rich firm‐level dataset of over 1,600 manufacturing plants established in a centrally planned economy after 1945. Our duration models include the standard Olley–Pakes misallocation measures as well as a firm‐level measure of the counterfactual level of capital that takes into account the present‐day market allocation and productivity. We show that while privatization is positively related to firm survival, misallocation (a) was more of a firm‐level than sector‐level phenomenon and, more importantly, (b) it, in general, did not have a sizeable effect on the actual firm survival nor it had an impact on the outcome of privatization.
Assessing self‐reported clinical high risk symptoms: The psychometric properties of the polish version of the prodromal questionnaire‐brief and a proposal for an alternative approach to scoring
Authors: Starkowska Anna , Tyburski Ernest , Kucharska‐Mazur Jolanta , Mak Monika , Samochowiec Jerzy 
Published: September 2020

AbstractBackgroundPsychotic‐like experiences (PLEs) might occur in the general population as low‐risk individual differences or prodromal features, requiring quick detection and early intervention. The aims of this study were to conduct a mini‐systematic review of the prognostic abilities of the Prodromal Questionnaire‐Brief (PQ‐B), describe the PLEs distribution for the first time in a Polish population, assess PQ‐B reliability and propose an innovative scoring approach based on cluster analysis.MethodsFive hundred and twenty eight (334 female) adult volunteers underwent screening with the PQ‐B, 49% also underwent the early psychosis screening test PRIME, to verify the tests' psychometric properties, to compare the prognostic accuracy of the PQ‐B to the more restrictive PRIME, and to the detected types of possible diagnosis in the general population.ResultsAlmost 70% of respondents met the prognostic criteria of the PQ‐B while only 30.6% met the PRIME criteria. Both tests proved reliable (α > .835) and valid (rho >.710; P < .001). A cluster analysis identified three different sub‐groups detected with the PQ‐B: healthy individuals without PLE; healthy with low‐distressing PLEs; and possibly prodromal subjects reporting less frequent but more distressing PLEs and no worries about their own mental state. Also in systematic reviews, authors of different adaptations have observed that the PQ‐B has too low specificity and postulated the need for higher cut‐offs.ConclusionStudy provides evidence of good reliability and sensitivity of the PQ‐B in assessing PLEs among the general population, but emphasizes that straightforward quantitative scoring criteria are still unclear. A more qualitative approach might be useful for differentiating true prodromal subjects from clinically low‐risk individual differences.