bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model‐based meta‐analysis of individual International Prostate Symptom Score trajectories in patients with benign prostatic hyperplasia with moderate or severe symptoms
Authors: D'Agate Salvatore , Wilson Timothy , Adalig Burkay , Manyak Michael , Palacios‐Moreno Juan Manuel , Chavan Chandrashekhar , Oelke Matthias , Roehrborn Claus , Della Pasqua Oscar 
Published: March 2020

AimsInternational Prostate Symptom Score (IPSS) is a marker of lower urinary tract symptoms (LUTS) deterioration or improvement in benign prostate hyperplasia (BPH). Whereas changes in IPSS relative to baseline have been used as endpoints in clinical trials, little attention has been given to the time course of symptoms. The current investigation aimed to develop a drug‐disease model to describe individual IPSS trajectories in moderate and severe BPH patients.MethodsA model‐based meta‐analytical approach was used including data from 10 238 patients enrolled into Phase III and IV studies receiving placebo, tamsulosin, dutasteride or combination therapy over a period of up to 4 years. Model predictive performance was assessed using statistical and graphical criteria. Subsequently, simulations were performed to illustrate the implications of treatment with drugs showing symptomatic and disease‐modifying properties in patients with varying disease progression rates.ResultsImprovement and worsening of IPSS could be characterized by a model including a sigmoid function which disentangles drug effects from placebo and varying disease progression rates on IPSS. Mean estimate (95% confidence intervals) for the disease progression rate was 0.319 (0.271–0.411) month−1. Treatment effect on IPSS (DELTA) was found to be 0.0605, 0.0139 and 0.0310 month−1 for placebo, tamsulosin and combination therapy, respectively. In addition, it appears that individual trajectories can be clustered together into different phenotypes describing the underlying disease progression rate (i.e. slow, moderate and fast progressors).ConclusionsThe availability of a drug‐disease model enables the evaluation of interindividual differences in disease progression rate, deterioration of symptoms and treatment effects on LUTS/BPH.
Dose‐dependent naloxone‐induced morphine withdrawal symptoms in opioid‐dependent males—a double‐blinded, randomized study
Authors: Weisshaar Stefan , Brandt Laura , Litschauer Brigitte , Sheik‐Rezaei Safoura , Moser Laura , Nirnberger Günther , Kühberger Elisabeth , Bauer Ulrike , Firbas Christa , Gouya Ghazaleh , Wolzt Michael , Fischer Gabriele 
Published: March 2020

AimsOral opioid preparations combined with naloxone are intended to induce a transient acute withdrawal syndrome to avoid intravenous misuse. This trial aimed to establish an appropriate morphine–naloxone dose ratio for an abuse‐deterrent oral opioid formulation.MethodsIn a randomized, double‐blinded, 2 × 2 cross‐over trial, 43 patients with opioid use disorder were challenged with intravenous morphine HCl Ph.Eur. (75 mg; [morphine mono]) or morphine HCl Ph.Eur. and naloxone HCl Ph.Eur. at ratios of 100:1 (75 mg: 0.75 mg; [morphine–naloxone 100:1]) or 200:1 (75 mg: 0.375 mg; [morphine–naloxone 200:1]). Acute naloxone‐induced opioid withdrawal was evaluated using subjective (Short Opiate Withdrawal Scale–German [SOWS‐G]) and observer‐rated (Objective Opiate Withdrawal Scale [OOWS], Wang scale) questionnaires, and physiological parameters. For statistical analysis, the area under the curve between baseline and 20 minutes after drug administration of the outcome variables was calculated.ResultsIntravenous morphine–naloxone caused rapid withdrawal symptoms. Coadministration of naloxone dose‐dependently (morphine–naloxone 100:1 > morphine–naloxone 200:1) increased SOWS‐G, OOWS and Wang Scale area under the curve when compared to morphine mono, respectively (all P < .0001). A similar response was detectable for changes of pupil diameter. Blood pressure and respiratory rate changed heterogeneously, and heart rate was unaltered by morphine without or with naloxone.ConclusionMorphine–naloxone 100:1 effectively suppresses the pleasurable effects of intravenous morphine and results in an aversive withdrawal reaction. A lower naloxone concentration as used in morphine–naloxone 200:1 does not appear to be appropriate to prevent intravenous morphine misuse.
Bridging learning sciences, machine learning and affective computing for understanding cognition and affect in collaborative learning
Authors: Järvelä Sanna , Gašević Dragan , Seppänen Tapio , Pechenizkiy Mykola , Kirschner Paul A. 
Published: March 2020

AbstractCollaborative learning (CL) can be a powerful method for sharing understanding between learners. To this end, strategic regulation of processes, such as cognition and affect (including metacognition, emotion and motivation) is key. Decades of research on self‐regulated learning has advanced our understanding about the need for and complexity of those mediating processes in learning. Recent research has shown that it is not only the individual's but also the group's shared processes that matter and, thus, that regulation at the group level is critical for learning success. A problem here is that the “shared” processes in CL are invisible, which makes it almost impossible for researchers to study and understand them, for learners to recognize them and for teachers to support them. Traditionally, research has not been able to make these processes visible nor has it been able to collect data about them. With the aid of advanced technologies, signal processing and machine learning, we are on the verge of “seeing” these complex phenomena and understanding how they interact. We posit that technological solutions and digital tools available today and in the future will help advance the theory underlying the cognitive, metacognitive, emotional and social components of individual, peer and group learning when seen through a multidisciplinary lens. The aim of this paper is to discuss and demonstrate how multidisciplinary collaboration among the learning sciences, affective computing and machine learning is applied for understanding and facilitating CL.Practitioner NotesWhat is already known about this topicCollaborative learning occurs when team members systematically activate, sustain and regulate their cognition, motivation, emotions and behaviors towards the attainment of their goals.Socially shared regulation in learning contributes to success in collaborative learning.What this paper adds“Shared” processes in collaborative learning are hard for researchers to study and understand them, for learners to recognize them and for teachers to support them.Multimodal data collection provides opportunities to study multiple aspects of student behaviors and regulation processes.With the aid of advanced technologies multidisciplinary collaboration between the learning sciences, affective computing and machine learning can help to study these complex phenomena.Implications for practice and/or policyThe case examples demonstrate how multidisciplinary collaboration can meet the challenges in understanding and facilitating collaborative learning.Multidisciplinary efforts with multimodal data will contribute to collaborative learning practice by providing theoretically informed feedback and personalized support.
Inhibition of erythropoietin‐producing hepatoma receptor B4 (EphB4) signalling suppresses the vascularisation and growth of endometriotic lesions
Authors: Rudzitis‐Auth Jeannette , Fuß Sophia A. , Becker Vivien , Menger Michael D. , Laschke Matthias W. 
Published: March 2020

Background and PurposeThe development of endometriotic lesions is crucially dependent on the formation of new blood vessels. In the present study, we analysed whether this process is regulated by erythropoietin‐producing hepatoma receptor B4 (EphB4) signalling.Experimental ApproachWe first assessed the anti‐angiogenic action of the EphB4 inhibitor NVP‐BHG712 in different in vitro angiogenesis assays. Then, endometriotic lesions were surgically induced in the dorsal skinfold chamber and peritoneal cavity of NVP‐BHG712‐ or vehicle‐treated BALB/c mice. This allowed to study the effect of EphB4 inhibition on their vascularisation and growth by means of intravital fluorescence microscopy, high‐resolution ultrasound imaging, histology and immunohistochemistry.Key ResultsNon‐cytotoxic doses of NVP‐BHG712 suppressed the migration, tube formation and sprouting activity of both human dermal microvascular endothelial cells (HDMEC) and mouse aortic rings. Accordingly, we also detected a lower blood vessel density in NVP‐BHG712‐treated endometriotic lesions. This was associated with a reduced lesion growth due to a significantly lower number of proliferating stromal cells when compared to vehicle‐treated controls.Conclusions and ImplicationsInhibition of EphB4 signalling suppresses the vascularisation and growth of endometriotic lesions. Hence, EphB4 represents a promising pharmacological target for the treatment of endometriosis.
Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF‐1α‐independent VEGF expression and angiogenesis in hepatocellular carcinoma
Authors: Zhang Cheng , Wang Ning , Tan Hor‐Yue , Guo Wei , Chen Feiyu , Zhong Zhangfeng , Man Kwan , Tsao Sai Wah , Lao Lixing , Feng Yibin 
Published: March 2020

Background and PurposeAs a typical hypervascular tumour, hepatocellular carcinoma (HCC) is predominantly grown through angiogenesis. Geniposide is a promising anti‐inflammatory compound found in Gardenia jasminoides, but its effects on the progression of HCC remain untested.Experimental ApproachThe anti‐HCC effects of geniposide was investigated in cellular models and orthotopic HCC mice. Transcriptional regulation of the VEGF promoter was measured by dual‐luciferase reporter assay. The anti‐angiogenic action of geniposide was measured by tube formation assay. Both surface plasmon resonance techniques and human phospho‐kinase array analysis were utilized to validate the relationship between targets of geniposide and hepatocarcinogenesis.Key ResultsGeniposide exhibited significant disruption of HCC proliferation, invasion, angiogenesis and lung metastasis in orthotopic HCC mice. Geniposide inhibited secretion of VEGF by HCC and suppressed the migration of endothelial cells and the formation of intra‐tumour blood vessels, without cytotoxicity and independently of the transcription factor HIF‐1α. Direct inhibition of TLR4 by geniposide led to the shutdown of the TLR4/MyD88 pathway and STAT3/Sp1‐dependent VEGF production. However, LPS, an agonist of TLR4, restored STAT3/Sp1‐related VEGF production in geniposide‐inhibited HCC angiogenesis.Conclusion and ImplicationsThe direct inhibitory effect of geniposide on TLR4/MyD88 activation contributes to the suppression of STAT3/Sp1‐dependent VEGF overexpression in HCC angiogenesis and pulmonary metastasis. This action of geniposide was not affected by stabilization of HIF‐1α. Our study offers a novel anti‐VEGF mechanism for the inhibition of HCC.
Updates in antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis for the ENT surgeon
Authors: Coates Matthew L. , Martinez Del Pero Marcos 
Published: March 2020

AbstractENT involvement is common in ANCA‐associated vasculitis (AAV), particularly in GPA and EGPA. Early recognition and treatment is important for good outcomes, yet evidence suggests that UK ENT surgeons may not consistently recognise the early features of AAV, despite a similar incidence to vestibular schwannoma. AAV is a rapidly advancing field, with significant developments in the understanding of its pathogenesis, classification and treatment over the past decade. Relevant vasculitis mimics are also discussed with a particular focus on the increasing prevalence of vasculitis mimics driven by an increase in recreational cocaine use, as well as the emergence and reclassification of several other vasculitis mimics in the head and neck. This article reviews key recent updates in the vasculitis literature, with a particular focus on those relevant to recognition and diagnosis of AAV for the ENT surgeon. Strengths and limitations of relevant diagnostic testing are discussed, and a method of evaluation of patients with features of AAV presenting to ENT services is outlined.
Recognizing animal personhood in compassionate conservation
Authors: Wallach Arian D. , Batavia Chelsea , Bekoff Marc , Alexander Shelley , Baker Liv , Ben‐Ami Dror , Boronyak Louise , Cardilin Adam P. A. , Carmel Yohay , Celermajer Danielle , Coghlan Simon , Dahdal Yara , Gomez Jonatan J. , Kaplan Gisela , Keynan Oded , Khalilieh Anton , Kopnina Helen , Lynn William S. , Narayanan Yamini , Riley Sophie , Santiago‐Ávila Francisco J. , Yanco Esty , Zemanova Miriam A. , Ramp Daniel 
Published: March 2020

AbstractCompassionate conservation is based on the ethical position that actions taken to protect biodiversity should be guided by compassion for all sentient beings. Critics argue that there are 3 core reasons harming animals is acceptable in conservation programs: the primary purpose of conservation is biodiversity protection; conservation is already compassionate to animals; and conservation should prioritize compassion to humans. We used argument analysis to clarify the values and logics underlying the debate around compassionate conservation. We found that objections to compassionate conservation are expressions of human exceptionalism, the view that humans are of a categorically separate and higher moral status than all other species. In contrast, compassionate conservationists believe that conservation should expand its moral community by recognizing all sentient beings as persons. Personhood, in an ethical sense, implies the individual is owed respect and should not be treated merely as a means to other ends. On scientific and ethical grounds, there are good reasons to extend personhood to sentient animals, particularly in conservation. The moral exclusion or subordination of members of other species legitimates the ongoing manipulation and exploitation of the living worlds, the very reason conservation was needed in the first place. Embracing compassion can help dismantle human exceptionalism, recognize nonhuman personhood, and navigate a more expansive moral space.
12‐year data on skin diseases in the Finnish Register of Occupational Diseases II: Risk occupations with special reference to allergic contact dermatitis
Authors: Aalto‐Korte Kristiina , Koskela Kirsi , Pesonen Maria 
Published: March 2020

AbstractBackgroundDetailed epidemiological studies on occupational skin diseases (OSDs) are scarce.ObjectivesTo analyze risk occupations for OSDs in the Finnish Register of Occupational Diseases (FROD).MethodsWe retrieved numbers of OSD cases (excluding skin infections) for different occupations from the FROD in 2005‐2016. In the FROD, Finnish ISCO‐08–based classification of occupations was used since 2011, and the preceding ISCO‐88–based version until 2010. We combined cases from the earlier and the later period using conversion tables provided by Statistics Finland. We included occupations with at least five cases and analyzed them in detail. We calculated incidence rates for OSDs and separately for allergic contact dermatitis (ACD) in different risk occupations using national labor force statistics. We also studied causes of ACD in these occupations.ResultsRisk occupations with the largest number of OSD cases included farmers, hairdressers, assistant nurses, cooks, cleaners, machinists, and nurses. Occupations with the highest incidences of OSDs comprised spray painters (23.8/10 000 person years), bakers (20.4), and dental technicians (19.0). Epoxy compounds and acrylates were prominent causes of ACD in occupations with the highest incidences of ACD.ConclusionsUniform use of International Standard Classification of Occupations (ISCO) would facilitate comparisons of OSD figures in different countries.
Occupational contact dermatitis in Triveneto: Analysis of patch test data of the North Eastern Italian Database from 1996 to 2016
Authors: Santarossa Monica , Mauro Marcella , Belloni Fortina Anna , Corradin Maria T. , Larese Filon Francesca 
Published: March 2020

ABSTRACTBackgroundOccupational contact dermatitis (OCD) is frequent in the workplace.ObjectivesTo provide recent data on the epidemiology of OCD in Italy.MethodsThis multicenter retrospective study, conducted from 1996 to 2016, included patients with suspected allergic contact dermatitis (ACD) patch tested in the departments comprising the North‐East Italy Contact Dermatitis Group.ResultsWe studied 18 859 workers with a diagnosis of contact dermatitis (CD), of which 10.4% were recognized as being of professional origin. OCD declined from 1996 to 2011–2013 and increased in 2014–2016. The overall prevalence of both CD and OCD was higher in women compared to men, but the share of OCD of the total CD was greater for men compared to women. A history of atopic dermatitis was less frequent in workers with OCD than in non‐OCD patients (5.8% vs 8.6%). Hairdressers were the youngest profession (27.1 ± 11.7 years). Hands were the primary site of involvement in patients with OCD (76.6%). The five highest risk occupations for OCD were hairdressers, cooks, metalworkers, chemical industry workers, and construction workers.ConclusionsOCDs have a relevant impact in our region, mainly for five job categories, and the increase in the last 3 years suggests the need to improve preventive measures.
Marine spatial planning on the Caribbean island of Montserrat: Lessons for data‐limited small islands
Authors: Flower Jason , Ramdeen Robin , Estep Andy , Thomas Lennon R. , Francis Sarita , Goldberg Grace , Johnson Ayana E. , McClintock Will , Mendes Stephen R. , Mengerink Kathryn , O'Garro Melissa , Rogers Lavern , Zischka Ute , Lester Sarah E. 
Published: March 2020

AbstractAs human use of the oceans increases, marine spatial planning (MSP) is being more widely adopted to achieve improved environmental, economic, and social outcomes. However, there is a lack of practical guidance for stakeholder driven, scientifically informed MSP processes in small island and data‐limited contexts. Here, we present an overview of MSP on the Caribbean island of Montserrat, with a focus on the scientific and technical input that helped inform the process. Montserrat presents an interesting case study of MSP in the small island context as it has ocean uses that are common to many islands, namely small‐scale fisheries and tourism, but the marine environment has been heavily impacted due to volcanic activity. We detail the methods for data collection and analysis and the decision‐making process that contributed to a marine spatial plan. We highlight aspects of the process that may be useful for other small islands embarking on MSP, and lessons learned regarding scientific support, including the need for on‐site scientific support and guidance throughout MSP, the importance of setting clear objectives, working within data limitations and making data accessible, and choosing and using appropriate decision support tools.
Is seabird light‐induced mortality explained by the visual system development?
Authors: Atchoi Elizabeth , Mitkus Mindaugas , Rodríguez Airam 
Published: March 2020

AbstractSeabirds are impacted by coastal light pollution, leading to massive mortality events. Juveniles comprise the majority of affected individuals, while adults are only seldom grounded and reported in rescue programs. We propose a connection between visual system development of burrow nesting seabirds and the observed higher vulnerability to light pollution by a specific age group. We illustrate the need for multidisciplinary research to better understand and further mitigate light‐induced mortality.
No QTc Prolongation With Zanubrutinib: Results of Concentration‐QTc Analysis From a Thorough QT Study in Healthy Subjects
Authors: Mu Song , Darpo Borje , Tang Zhiyu , Novotny William , Tawashi Manal , Xue Hongqi , Willett Michael , Lin Leo , Sahasranaman Sri , Ou Ying C. 
Published: March 2020

This thorough QT (TQT) study evaluated the effect of zanubrutinib on electrocardiogram (ECG) parameters by using concentration‐QTc (C‐QTc) analysis as the primary analysis for this study. Part A of the study determined the safety and tolerability of a single supratherapeutic dose of zanubrutinib (480 mg) in healthy volunteers. Part B was a randomized, blinded, placebo‐controlled and positive‐controlled, four‐way crossover, TQT study of single therapeutic (160 mg) and supratherapeutic (480 mg) doses of zanubrutinib, placebo, and open‐label moxifloxacin 400 mg. Thirty‐two participants received at least 1 dose of zanubrutinib, and 26 participants completed all 4 periods. Zanubrutinib did not have any effect on heart rate or cardiac conduction (pulse rate, QRS interval, or T‐wave morphology) and was generally well‐tolerated. Using C‐QTc analysis, the predicted placebo‐corrected change‐from‐baseline QT interval using Fridericia’s formula (ΔΔQTcF) was −3.4 msec (90% confidence interval: −4.9 to −1.9 msec) at peak concentrations of the 480 mg dose. A QT effect (ΔΔQTcF) exceeding 10 msec could be excluded within the observed concentration range at 160 and 480 mg doses. Assay sensitivity was established by moxifloxacin with 90% lower bound exceeding 5 msec. Implementing a C‐QTc analysis prospectively in this TQT study resulted in a substantially smaller sample size to maintain a similar study power as shown in the traditional time‐point analysis. A single 160‐mg or 480‐mg zanubrutinib dose did not prolong the QTc interval or have any other clinically relevant effects on ECG parameters.
One language or two? Navigating cross‐language conflict in statistical word segmentation
Authors: Antovich Dylan M. , Graf Estes Katharine 
Published: March 2020

AbstractBilingual infants must navigate the similarities and differences between their languages to achieve native proficiency in childhood. Bilinguals learning to find individual words in fluent speech face the possibility of conflicting cues to word boundaries across their languages. Despite this challenge, bilingual infants typically begin to segment and learn words in both languages around the same time as monolinguals. It is possible that early bilingual experience may support infants’ abilities to track regularities relevant for word segmentation separately across their languages. In a dual speech stream statistical word segmentation task, we assessed whether 16‐month‐old infants could track syllable co‐occurrence regularities in two artificial languages despite conflicting information across the languages. We found that bilingual, but not monolingual, infants were able to segment the dual speech streams using statistical regularities. Although the two language groups did not differ on secondary measures of cognitive and linguistic development, bilingual infants’ real‐world experience with bilingual speakers was predictive of their performance in the dual language statistical segmentation task.