bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molidustat for anemia correction in Japanese patients undergoing hemodialysis: a single‐arm, phase 3 study
Authors: Akizawa Tadao , Nobori Kiyoshi , Matsuda Yoshimi , Hayashi Yasuhiro , Hayasaki Takanori , Yamamoto Hiroyasu 
Published: January 2021

AbstractMolidustat, an orally administered hypoxia‐inducible factor prolyl‐hydroxylase inhibitor, is under development for the treatment of anemia of CKD. This 24‐week, phase 3, single‐arm, multicenter study evaluated the efficacy and safety of molidustat in Japanese patients with renal anemia who were undergoing hemodialysis and who were not receiving an erythropoiesis‐stimulating agent. Twenty‐five patients received molidustat at a starting dose of 75 mg once daily, which was adjusted to maintain a Hb target of ≥10.0 to <12.0 g/dL. The mean rates of Hb increase from baseline and week 0 to the first dose change up to week 8 were −0.030 and 0.080 g/dL/week, respectively. By week 24, 89% of patients had a Hb level within target range. No adverse events of special interest were reported. Treatment with dose‐titrated molidustat for 24 weeks was well tolerated in Japanese patients undergoing hemodialysis, and no new safety signal was observed. Clinicaltrials.gov identifier: NCT03351166.
Social media in interventional radiology
Authors: Wang Michael T. , Foo Michelle , Maingard Julian , Kok Hong Kuan , Lamanna Anthony , Jhamb Ashu , Brooks Mark , Asadi Hamed 
Published: January 2021

AbstractIntroductionSocial media provides opportunities for Interventional Radiologists to share research, communicate with colleagues, provide health information and advertise their clinical practice. This study aims to examine the online and social media presence of currently practicing Australian Interventional Radiologists.MethodsSystematic Google searches were undertaken in May 2019 and updated in May 2020 to identify practicing Interventional Radiologists in Australia. Comprehensive searches of practice websites and social media platforms (Facebook, LinkedIn, Twitter, ResearchGate, YouTube) were undertaken for each Interventional Radiologist.ResultsThere were 265 Interventional Radiologists identified as currently practising in Australia, including 209 Interventional Radiologists (excluding Interventional Neuroradiologists), 49 Interventional Neuroradiologists and 7 that practise across both Interventional Radiology and Interventional Neuroradiology. 72% of Interventional Radiologists had at least one social media account, with LinkedIn the most widely used social media platform (60%). There was a significant negative correlation between the total number of social media accounts and years in practice (P = 0.04). Across the states, a higher population per IR was positively correlated with a higher average number of social media accounts per IR (P = 0.04). Interventional Neuroradiologists had a significantly higher average number of social media accounts compared to Interventional Radiologists (1.94 vs 1.29, P < 0.01).ConclusionsMost Australian Interventional Radiologists have a readily identifiable social media presence. There is potential for further utilisation of social media for academic, educational and business purposes.
Pharmacokinetics and safety of pegylated recombinant human granulocyte colony‐stimulating factor in children with acute leukaemia
Authors: Liu Xi‐Ting , Zhao Yan‐Xia , Jia Guang‐Wei , Yang Fan , Zhang Chuan‐Zhou , Han Bing , Dai Jian‐Hua , Han Yue‐Qin , Tang Bo‐Hao , Yang Xin‐Mei , Shi Hai‐Yan , Zhou Yue , Sui Zhong‐Guo , Chen Jian‐Zhong , van den Anker Johannes N. , Zhao Wei 
Published: January 2021

AimsThis open‐label, phase I study evaluated the pharmacokinetics and safety of pegylated recombinant human granulocyte colony‐stimulating factor (PEG‐rhG‐CSF) for the treatment of chemotherapy‐induced neutropenia in children with acute leukaemia.MethodsPEG‐rhG‐CSF was administered as a single 100 mcg/kg (3 mg maximum dose) subcutaneous injection at the end of each chemotherapy period when neutropenia occurred. Blood samples were obtained from patients treated with PEG‐rhG‐CSF. PEG‐rhG‐CSF serum concentrations were determined by an enzyme‐linked immunosorbent assay. Population pharmacokinetic (PPK) analysis was implemented using the nonlinear mixed‐effects model. Short‐term safety was evaluated through adverse events collection (registered at clinicaltrials.gov identifier: 03844360).ResultsA total of 16 acute leukaemia patients (1.8–13.6 years) were included, of whom two (12.5%) had grade 3 neutropenia, six (37.5%) had grade 4 neutropenia, and eight (50.0%) had severe neutropenia. For PPK modelling, 64 PEG‐rhG‐CSF serum concentrations were obtainable. A one‐compartment model with first‐order elimination was used for pharmacokinetic data modelling. The current weight was a significant covariate. The median (range) of clearance (CL) and area under the serum concentration–time curve (AUC) were 5.65 (1.49–14.45) mL/h/kg and 16514.75 (6632.45–54423.30) ng·h/mL, respectively. Bone pain, pyrexia, anaphylaxis and nephrotoxicity were not observed. One patient died 13 days after administration, and the objective assessment of causality was that an association with PEG‐rhG‐CSF was “possible”.ConclusionsThe AUC of PEG‐rhG‐CSF (100 mcg/kg, 3 mg maximum dose) in paediatric patients with acute leukaemia were similar to those of PEG‐rhG‐CSF (100 mcg/kg) in children with sarcoma. PEG‐rhG‐CSF is safe, representing an important therapeutic option for chemotherapy‐induced neutropenia in paediatric patients with acute leukaemia.
Change in the regulatory framework for zolpidem: What is the impact on the landscape of the prescription of sedative medications? The French national ZORRO study
Authors: Istvan Marion , Caillet Pascal , Rousselet Morgane , Guerlais Marylène , Laforgue Edouard‐Jules , Gérardin Marie , Jolliet Pascale , Feuillet Fanny , Victorri‐Vigneau Caroline 
Published: January 2021

AimsIn recent years, zolpidem has been the subject of numerous reports of misuse, abuse and dependence. In view of these risks, the French drug agency (ANSM) decreed in April 2017 the implementation of secure prescription pads. The objective of this study was to evaluate the impact of this regulatory measure on the prescription of zolpidem and other sedative medications (zopiclone, benzodiazepines and antihistamines) in long‐term users of zolpidem and associated factors.MethodsWe performed a historical cohort study using data from the Generalist Sample of Beneficiaries (EGB). All patients aged over 18 years old who were long‐term users (at least 3 months) before the measure were enacted. We analysed the reimbursement trajectories of zolpidem, zopiclone, benzodiazepines and antihistamines (hydroxyzine and alimemazine) up to 2 years after the measure using a state sequence analysis.ResultsOverall, 2502 patients were analysed. A four‐cluster typology was identified: continuation of zolpidem (n = 1044, 42%), discontinuation of sedative medications (n = 766, 31%), change to zopiclone (n = 537, 21%) and change to hypnotic benzodiazepines (n = 155, 6%). The most frequently prescribed hypnotic benzodiazepine was lormetazepam. We identified age, sex, treatment for psychiatric or addictive disorder and volume of zolpidem use before the measure as factors associated with different reimbursement trajectories after the regulatory change.ConclusionThe regulatory change for zolpidem prescriptions reduced exposure to zolpidem among long‐term users and also had a broad impact on prescriptions of other sedative medications. Switching to other medications that also present a potential risk of abuse or dependence should be carefully monitored.
Capmatinib in Japanese patients with MET exon 14 skipping–mutated or MET‐amplified advanced NSCLC: GEOMETRY mono‐1 study
Authors: Seto Takashi , Ohashi Kadoaki , Sugawara Shunichi , Nishio Makoto , Takeda Masayuki , Aoe Keisuke , Moizumi Sanae , Nomura Satoshi , Tajima Takeshi , Hida Toyoaki 
Published: January 2021

AbstractMET mutations leading to exon 14 skipping (METΔex14) are strong molecular drivers for non–small‐cell lung cancer (NSCLC). Capmatinib is a highly potent, selective oral MET inhibitor that showed clinically meaningful efficacy and a manageable safety profile in a global phase II study (GEOMETRY mono‐1, NCT02414139) in patients with advanced METΔex14‐mutated/MET‐amplified NSCLC. We report results of preplanned analyses of 45 Japanese patients according to MET status (METΔex14‐mutated or MET‐amplified) and line of therapy (first‐ [1L] or second‐/third‐line [2/3L]). The starting dose was 400 mg twice daily. The primary endpoint was the objective response rate (ORR) assessed by a blinded independent review committee. A key secondary endpoint was duration of response (DOR). Among METΔex14‐mutated patients, in the 1L group, one patient achieved partial response (DOR of 4.24 months) and the other had stable disease. In the 2/3L group, the ORR was 36.4% (95% confidence interval [CI] 10.9%‐69.2%), median DOR was not evaluable, and progression‐free survival was 4.70 months. One patient (2/3L group) showed partial resolution of brain lesions per independent neuroradiologist review. In MET‐amplified patients with a MET gene copy number of ≥10, the ORR was 100% (2/2 patients) in the 1L group and 45.5% (5/11 patients) in the 2/3L group, with DOR of 8.2 and 8.3 months, respectively. Common treatment‐related adverse events among the 45 Japanese patients were blood creatinine increased (53.3%), nausea (35.6%), and oedema peripheral (31.1%); most were grade 1/2 severity. In conclusion, capmatinib was effective and well tolerated by Japanese patients with METΔex14/MET‐amplified NSCLC, consistent with the overall population.
NAFLD exacerbates cholangitis and promotes cholangiocellular carcinoma in mice
Authors: Maeda Shin , Hikiba Yohko , Fujiwara Hiroaki , Ikenoue Tsuneo , Sue Soichiro , Sugimori Makoto , Matsubayashi Mao , Kaneko Hiroaki , Irie Kuniyasu , Sasaki Tomohiko , Chuma Makoto 
Published: January 2021

AbstractNonalcoholic fatty liver disease (NAFLD) is an increasingly common condition, affecting up to 25% of the population worldwide. NAFLD has been linked to several conditions, including hepatic inflammation, fibrosis, and hepatocellular carcinoma (HCC), however the role of NAFLD in cholangitis and the development of cholangiocellular carcinoma (CCC) remains poorly understood. This study investigated whether a high‐fat diet (HFD) promotes cholangitis and the development of CCC in mice. We used liver‐specific E‐cadherin gene (CDH1) knockout mice, CDH1∆Liv, which develop spontaneous inflammation in the portal areas along with periductal onion skin‐like fibrosis, similar to that of primary sclerosing cholangitis (PSC). An HFD or normal diet (ND) was fed to CDH1∆Liv mice for 7 mo. In addition, CDH1∆Liv mice were crossed with LSL‐KrasG12D mice, fed an HFD, and assessed in terms of liver tumor development. The extent of cholangitis and number of bile ductules significantly increased in mice fed an HFD compared with ND‐administered CDH1∆Liv mice. The numbers of Sox9 and CD44‐positive stem cell‐like cells were significantly increased in HFD mice. LSL‐KrasG12D /CDH1∆Liv HFD mice exhibited increased aggressiveness along with the development of numerous HCC and CCC, whereas LSL‐KrasG12D/CDH1∆Liv ND mice showed several macroscopic tumors with both HCC and CCC components. In conclusion, NAFLD exacerbates cholangitis and promotes the development of both HCC and CCC in mice.
Skraban‐Deardorff syndrome: Six new cases of WDR26‐related disease and expansion of the clinical phenotype
Authors: Cospain Auriane , Schaefer Elise , Faoucher Marie , Dubourg Christèle , Carré Wilfrid , Bizaoui Varoona , Assoumani Jessica , Van Maldergem Lionel , Piton Amélie , Gérard Bénédicte , Tran Mau‐Them Frédéric , Bruel Ange‐Line , Faivre Laurence , Demurger Florence , Pasquier Laurent , Odent Sylvie , Fradin Mélanie , Lavillaureix Alinoë 
Published: January 2021

AbstractSkraban‐Deardorff syndrome (a disease related to variations in the WDR26 gene; OMIM #617616) was first described in a cohort of 15 individuals in 2017. The syndrome comprises intellectual deficiency, severe speech impairment, ataxic gait, seizures, mild hypotonia with feeding difficulties during infancy, and dysmorphic features. Here, we report on six novel heterozygous de novo pathogenic variants in WDR26 in six probands. The patients' phenotypes were consistent with original publication. One patient displayed marked hypotonia with an abnormal muscle biopsy; this finding warrants further investigation. Gait must be closely monitored, in order to highlight any musculoskeletal or neurological abnormalities and prompt further examinations. Speech therapy and alternative communication methods should be initiated early in the clinical follow‐up, in order to improve language and oral eating and drinking.
Child protection policy: Understanding drivers of violence affecting children in Côte d’Ivoire
Authors: Ballet Jérôme , Konaté Francis , Kouamé Séverin Yao , Maternowska Catherine , Olié Louis 
Published: January 2021

AbstractMotivationSince the campaign launched by UNICEF in 2013, the momentum for measuring violence has grown significantly. Such studies generally measure risk and protective factors at the individual and interpersonal levels, but often overlook the critical institutional and structural drivers of violence.PurposeThis article demonstrates how socioeconomic transformations, including “modern” forms of violence fuelled by social fragmentation, armed conflict and urbanization, are important conditions favouring violence against children.Approach and methodsThe article offers a systematic literature review following protocols in the original Multi‐Country Study on the Drivers of Violence Affecting Children, an approach first proposed by the UNICEF Office of Research ‐ Innocenti.FindingsWe underline two main changes among the drivers of violence in Côte d’Ivoire: economic crisis and urbanization, which combine to foster a climate of violence; and politico‐military crisis, which also creates a fertile ground for violence and its acceptance.Policy implicationsChild protection policy in Côte d’Ivoire is out of step with the evolution of the social context. It is mainly oriented towards “traditional” practices, which contrast with newer forms of violence developed over the past 30 years. The article shows that the country’s child protection policy does not take these changes sufficiently into account, and argues for policy change.
Predicting socio‐economic and biodiversity impacts of invasive species: Red Imported Fire Ant in the developing western Pacific
Authors: Gruber Monica A. M. , Janssen‐May Sharon , Santoro Davide , Cooling Meghan , Wylie Ross 
Published: January 2021

SummaryEffective biosecurity and pest management are fundamental to sustainable development. Invasive ants pose significant risks to the environment and economy, which are well‐managed by biosecurity agencies in developed countries. However, a comprehensive view of the potential impacts of invasive ants in developing Pacific Island Countries and Territories (PICTs) is lacking. We quantified the potential costs of the Red Imported Fire Ant (Solenopsis invicta Buren) across multiple sectors using an extrapolation analysis. Overall, we estimated that the impacts of Red Imported Fire Ant on developing PICTs could amount to over USD 329 million annually, corresponding to approximately 0.7% of combined GDP. Over half of the costs were predicted to result from impacts on the agriculture sector, a major source of employment and subsistence. We found that over 350 highly threatened species could be at risk from Red Imported Fire Ant. We would expect countries with Least Developed Country status and relatively low GDP to be least able to respond to an incursion of these ants, and as a result the costs could be higher than we have extrapolated. Red Imported Fire Ant could therefore potentially have considerable impact on the on‐going development of the region.
Association between external female genital mutilation and securing paternity in a spider
Authors: Nakata Kensuke 
Published: January 2021

AbstractMales sometimes injure their partner physically or physiologically during mating. While harmful mating is assumed to incur fitness costs, it is thought to confer increased paternity for males; this advantage may have driven the evolution of harmful mating. To date, two spider species are known to exhibit external female genital mutilation (EFGM), in which males remove a scape, a small projection on female's external genitalia, to secure their paternity. This study investigated whether a similar phenomenon occurs in Cyclosa ginnaga to assess whether EFGM is commonly associated with paternity securing in spiders. Two consecutive staged mating using a unmated female and two males was conducted and female genitalia was inspected after mating. Results showed that while EFGM occurred among C. ginnaga, the mutilation rate was less than half that of the two previously studied species. Mated females, irrespective of whether they experienced mutilation, attacked the second males that courted them. Consequently, most mating trials ended without successful copulation due to the retreat of the second male, and EFGM was seldom responsible for the failure of the second mating. These results do not support the hypothesis that EFGM evolved because it secured paternity for mutilator males.
Evolution of a public sector audit office: Evidence from the Republic of Fiji
Authors: Nath Nirmala , Van Peursem Karen A. , Lowe Alan 
Published: January 2021

AbstractThe Office of the Auditor General, Republic of Fiji was founded in 1970 on audit principles and national laws inspired by its former British colonial power. The Fijian Office operates in a challenging national context of coup‐determined regimes, military authority and ethnically‐dividing social practices. The purpose of this study is to uncover the processes and dynamics that explain how this Office remains a stable institution despite its challenging environment. We seek to understand how members of Fiji's Office of the Auditor General comprehend their role, find meaning in their actions and negotiate their authority in the context of powerful others. Our approach is qualitative and employs data from 28 interviews conducted over 12 years and historical documents. Our findings take into account wider social processes and reveal that through shared commitment and international associationism the Office of the Auditor General comes to absorb the norms and values of its westernised professional organizations. The contribution of the study is in revealing how external professional bodies and an empowered internal rationale can construct an institutional discourse that offers the potential for social stability even where local resistance is strong.
Social capital and the business models of financial cooperatives: Evidence from Japanese Shinkin banks
Authors: Chronopoulos Dimitris K. , Sobiech Anna L. , Wilson John O. S. 
Published: January 2021

AbstractWe investigate the link between social capital and business model choice of financial cooperatives (Shinkin banks) in Japan. We identify two forms of business model, which concentrate on the issuance of loans funded by deposits (traditional) and the investment and management of large investment portfolios (new).Traditionalbusiness models are more likely to emerge in geographic areas with higher levels of social capital. These findings are robust after controlling for bank‐ and prefecture‐level characteristics (such as unemployment, population and income) that may influence bank business model choice. We repeat our analysis for a sample of shareholder‐oriented (regional) banks, but fail to establish any relationship between social capital and this organisational form. Overall, our findings suggest that financial cooperatives in high‐social‐capital areas are more likely to adhere to a traditional model of financial intermediation focused on lending which promotes community and economic development.
Non‐profit theatre managers as multi‐stakeholder managers: The plate‐spinning of accountability
Authors: FitzGibbon Ali 
Published: January 2021

AbstractThis exploratory study identifies that more can be understood about how accountability operates within an increasingly complex non‐profit environment by applying stakeholder theory to managers and their decision‐making in non‐profit theatre organisations (NPTOs). On the surface, this may appear to be ground already covered. Previous research has explored the challenges of achieving more holistic accountability in the face of dominant stakeholders. Approaches have been proposed to increase efficiency, effectiveness and transparency. Less is known about how individual managers respond to competing accountabilities in decision‐making and what factors influence their attention to stakeholder interests. NPTOs operate in both the non‐profit and cultural industries sectors and, as such, are an interesting site to investigate accountability complexity in managerial decision‐making. However, NPTOs (and arts organisations generally) feature little in non‐profit and social accountability research. Particular features of NPTOs amplify the challenges of a multi‐stakeholder environment in discharging accountability. These include artistic mission beyond production/distribution; blended business models; policy‐driven leadership rhetoric; the prevalence of interorganisational collaboration; and a significantly freelance workforce. This study argues that NPTOs are the vanguard of changes in contemporary non‐profit management and their study offers new insights to problems associated with practising accountability within such multi‐stakeholder complexity. By drawing on creative non‐profit organisations, for example NPTOs, this study introduces new knowledge to existing non‐profit and social accountability literatures. Based on transdisciplinary research into perceived inter‐relationships between NPTO managers and stakeholder groups, this study proposes NPTO managers are engaged in a balancing or ‘plate‐spinning’ act of accountability, influenced by dominant stakeholders, and an interdependent triple logic in their operations. They negotiate ambiguous competing expectations by deploying self‐interest and ambiguity, with high potential for managerial paralysis and trade‐off. Recommendations arising include de‐emphasis of efficiency/effectiveness and increased attention to complex multi‐stakeholder accountability beyond current approaches. In addition, it suggests further research into NPTOs and arts organisations could yield additional knowledge in the study of non‐profit accountability.