bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosing and characterizing inflammatory myopathies at an Australian tertiary public hospital: Resource utilization and direct healthcare costs
Authors: Huang Victoria , Ciciriello Sabina , Nikpour Mandana , Oon Shereen , Day Jessica 
Published: April 2024

AbstractAimTo determine the direct health service costs and resource utilization associated with diagnosing and characterizing idiopathic inflammatory myopathies (IIMs), and to assess for limitations and diagnostic delay in current practice.MethodsA retrospective, single‐center cohort analysis of all patients diagnosed with IIMs between January 2012 and December 2021 in a large tertiary public hospital was conducted. Demographics, resource utilization and costs associated with diagnosing IIM and characterizing disease manifestations were identified using the hospital's electronic medical record and Health Intelligence Unit, and the Medicare Benefits Schedule.ResultsThirty‐eight IIM patients were identified. IIM subtypes included dermatomyositis (34.2%), inclusion body myositis (18.4%), immune‐mediated necrotizing myopathy (18.4%), polymyositis (15.8%), and anti‐synthetase syndrome (13.2%). The median time from symptom onset to diagnosis was 212 days (IQR: 118–722), while the median time from hospital presentation to diagnosis was 30 days (8–120). Seventy‐six percent of patients required emergent hospitalization during their diagnosis, with a median length of stay of 8 days (4–15).The average total cost of diagnosing IIM was $15 618 AUD (STD: 11331) per patient. Fifty percent of patients underwent both MRI and EMG to identify affected muscles, 10% underwent both pan‐CT and PET‐CT for malignancy detection, and 5% underwent both open surgical and percutaneous muscle biopsies. Autoimmune serology was unnecessarily repeated in 37% of patients.ConclusionThe diagnosis of IIMs requires substantial and costly resource use; however, our study has identified potential limitations in current practice and highlighted the need for streamlined diagnostic algorithms to improve patient outcomes and reduce healthcare‐related economic burden.
Denmark: Political Developments and Data in 2023
Authors: KOSIARA‐PEDERSEN KARINA 
Published: April 2024

AbstractThe government of Mette Frederiksen II took office on 15 December 2022, six weeks after the 1 November 2022 elections. Hence, expectations were high for this new type of government, a ‘cross‐the‐aisle’ majority, to get down to business. However, the government only used the majority to abolish a public holiday and has since then progressed only slowly on its agenda. It has been fairly unpopular with the electorate, losing up to a third of its support. The exits and defections in the Danish Parliament, Folketinget, continue to be higher than before 2019.
Leukopenia, neutropenia, and procalcitonin levels in young febrile infants with invasive bacterial infections
Authors: Krack Andrew T. , Eckerle Michelle , Mahajan Prashant , Ramilo Octavio , VanBuren John M. , Banks Russell K. , Casper T. Charles , Schnadower David , Kuppermann Nathan ,   for the Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN)
Published: April 2024

AbstractBackground and objectiveSerum procalcitonin (PCT) is a highly accurate biomarker for stratifying the risk of invasive bacterial infections (IBIs) in febrile infants ≤60 days old. However, PCT is unavailable in some settings. We explored the association of leukopenia and neutropenia with IBIs in non–critically ill febrile infants ≤60 days old, with and without PCT.MethodsWe conducted a secondary analysis of a prospective observational cohort consisting of 7407 non–critically ill infants ≤60 days old with temperatures ≥38°C. We focused on the risk of IBIs in patients with leukopenia (white blood cell [WBC] count <5000 cells/μL) or neutropenia (absolute neutrophil count [ANC] <1000 cells/μL), categorized to extremes of lower values, and the impact of PCT on these associations. Multiple logistic regression was used to identify independent predictors of IBIs.ResultsFinal analysis included 6865 infants with complete data; 45% (3098) had PCT data available. Of the 6865, a total of 111 (1.6%) had bacteremia without bacterial meningitis, 18 (0.3%) had bacterial meningitis without bacteremia, and 19 (0.3%) had both bacteremia and bacterial meningitis. IBI was present in four of 20 (20%) infants with WBC counts ≤2500 cells/μL and four of 311 (1.3%) with ANC ≤1000 cells/μL. In multivariable logistic regression analysis not including PCT, a WBC count ≤2500 cells/μL was significantly associated with IBI (OR 13.48, 95% CI 2.92–45.35). However, no patients with leukopenia or neutropenia and PCT ≤0.5 ng/mL had IBIs.ConclusionsLeukopenia ≤2500 cells/μL in febrile infants ≤60 days old is associated with IBIs. However, in the presence of normal PCT levels, no patients with leukopenia had IBIs. While this suggests leukopenia ≤2500 cells/μL is a risk factor for IBIs in non–critically ill young febrile infants only when PCT is unavailable or elevated, the overall low frequency of leukopenia in this cohort warrants caution in interpretation, with future validation required.
First‐line immunotherapy of metastatic renal cell carcinoma: an updated network meta‐analysis including triplet therapy
Authors: Yanagisawa Takafumi , Kawada Tatsushi , Bekku Kensuke , Laukhtina Ekaterina , Rajwa Pawel , von Deimling Markus , Chlosta Marcin , Quhal Fahad , Pradere Benjamin , Karakiewicz Pierre I. , Mori Keiichiro , Kimura Takahiro , Shariat Shahrokh F. , Schmidinger Manuela 
Published: April 2024

ObjectiveTo compare the differential efficacy of first‐line immune checkpoint inhibitor (ICI)‐based combined therapies among patients with intermediate‐ and poor‐risk metastatic renal cell carcinoma (mRCC), as recently, the efficacy of triplet therapy comprising nivolumab plus ipilimumab plus cabozantinib has been published.Patients and MethodsThree databases were searched in December 2022 for randomised controlled trials (RCTs) analysing oncological outcomes in patients with mRCC treated with first‐line ICI‐based combined therapies. We performed network meta‐analysis (NMA) to compare the outcomes, including progression‐free survival (PFS) and objective response rates (ORRs), in patients with intermediate‐ and poor‐risk mRCC; we also assessed treatment‐related adverse events.ResultsOverall, seven RCTs were included in the meta‐analyses and NMAs. Treatment ranking analysis revealed that pembrolizumab + lenvatinib (99%) had the highest likelihood of improved PFS, followed by nivolumab + cabozantinib (79%), and nivolumab + ipilimumab + cabozantinib (77%). Notably, compared to nivolumab + cabozantinib, adding ipilimumab to nivolumab + cabozantinib did not improve PFS (hazard ratio 1.02, 95% confidence interval 0.72–1.43). Regarding ORRs, treatment ranking analysis also revealed that pembrolizumab + lenvatinib had the highest likelihood of providing better ORRs (99.7%). The likelihoods of improved PFS and ORRs of pembrolizumab + lenvatinib were true in both International Metastatic RCC Database Consortium (IMDC) risk groups.ConclusionsOur analyses confirmed the robust efficacy of pembrolizumab + lenvatinib as first‐line treatment for patients with intermediate or poor IMDC risk mRCC. Triplet therapy did not result in superior efficacy. Considering both toxicity and the lack of mature overall survival data, triplet therapy should only be considered in selected patients.
Non‐linear blood–brain barrier transport and dosing strategies influence receptor occupancy ratios of morphine and its metabolites in pain matrix
Authors: Budda Divakar , Gülave Berfin , van Hasselt J. G. Coen , de Lange Elizabeth C. M. 
Published: April 2024

AbstractBackground and PurposeMorphine is important for treatment of acute and chronic pain. However, there is high interpatient variability and often inadequate pain relief and adverse effects. To better understand variability in the dose‐effect relationships of morphine, we investigated the effects of its non‐linear blood–brain barrier (BBB) transport on μ‐receptor occupancy in different CNS locations, in conjunction with its main metabolites that bind to the same receptor.Experimental ApproachCNS exposure profiles for morphine, M3G and M6G for clinically relevant dosing regimens based on intravenous, oral immediate‐ and extended‐release formulations were generated using a physiology‐based pharmacokinetic model of the CNS, with non‐linear BBB transport of morphine. The simulated CNS exposure profiles were then used to derive corresponding μ‐receptor occupancies at multiple CNS pain matrix locations.Key ResultsSimulated CNS exposure profiles for morphine, M3G and M6G, associated with non‐linear BBB transport of morphine resulted in varying μ‐receptor occupancies between different dose regimens, formulations and CNS locations. At lower doses, the μ‐receptor occupancy of morphine was relatively higher than at higher doses of morphine, due to the relative contribution of M3G and M6G. At such higher doses, M6G showed higher occupancy than morphine, whereas M3G occupancy was low throughout the dose ranges.Conclusion and ImplicationsNon‐linear BBB transport of morphine affects the μ‐receptor occupancy ratios of morphine with its metabolites, depending on dose and route of administration, and CNS location. These predictions need validation in animal or clinical experiments, to understand the clinical implications.
High N6‐methyladenosine‐activated TCEAL8 mRNA is a novel pancreatic cancer marker
Authors: Hara Tomoaki , Meng Sikun , Sato Hiromichi , Tatekawa Shotaro , Sasaki Kazuki , Takeda Yu , Tsuji Yoshiko , Arao Yasuko , Ofusa Ken , Kitagawa Toru , Yamada Daisaku , Takahashi Hidenori , Kobayashi Shogo , Motooka Daisuke , Suzuki Yutaka , Rennie Sarah , Uchida Shizuka , Mori Masaki , Ogawa Kazuhiko , Doki Yuichiro , Eguchi Hidetoshi , Ishii Hideshi 
Published: April 2024

AbstractN6‐methyladenosine (m6A) is an RNA modification involved in RNA processing and widely found in transcripts. In cancer cells, m6A is upregulated, contributing to their malignant transformation. In this study, we analyzed gene expression and m6A modification in cancer tissues, ducts, and acinar cells derived from pancreatic cancer patients using MeRIP‐seq. We found that dozens of RNAs highly modified by m6A were detected in cancer tissues compared with ducts and acinar cells. Among them, the m6A‐activated mRNA TCEAL8 was observed, for the first time, as a potential marker gene in pancreatic cancer. Spatially resolved transcriptomic analysis showed that TCEAL8 was highly expressed in specific cells, and activation of cancer‐related signaling pathways was observed relative to TCEAL8‐negative cells. Furthermore, among TCEAL8‐positive cells, the cells expressing the m6A‐modifying enzyme gene METTL3 showed co‐activation of Notch and mTOR signaling, also known to be involved in cancer metastasis. Overall, these results suggest that m6A‐activated TCEAL8 is a novel marker gene involved in the malignant transformation of pancreatic cancer.
Rhinoconjunctivitis severity induced by cat exposure influences early and late asthmatic responses: Evidence from an environmental exposure chamber
Authors: Piotin Anays , Godet Julien , Domis Nathalie , de Blay Frédéric 
Published: April 2024

AbstractBackgroundThe impact of allergic rhinoconjunctivitis on the early (EAR) and late asthmatic response (LAR) has yet to be assessed during optimal allergen exposure conditions.ObjectiveWe aimed to assess predictive factors of the EAR and LAR and to evaluate the relation between rhinitis, conjunctivitis and asthma induced by cat allergen exposure in an environmental exposure chamber (EEC).MethodsData from two cohort studies involving asthmatic patients with cat allergy who performed a cat allergen exposure challenge in ALYATEC EEC were analysed. Spirometry, visual analogue scale (VAS) for asthma, VAS for rhinitis, Total Nasal Symptoms Score, Total Ocular Symptoms Score (TOSS), Rhinoconjunctivitis Total Symptoms Score and Abelson score were used to assess asthma, rhinitis and conjunctivitis during and after exposure.ResultsAn EAR occurred in 65.1% of patients, 32.1% of whom had a LAR. The diameter of the prick test to cat allergens and non‐specific bronchial hypersensitivity level were independent risk factors for EAR (p < .05). No independent risk factors for LAR were identified. Rhinoconjunctivitis severity during exposure correlated with the asthma VAS during EAR and LAR (p < .05). Allergen exposure time needed to trigger an EAR correlated with the Abelson score during exposure (p < .05). The asthma VAS and TOSS during exposure correlated with faster LAR occurrence (p < .05).ConclusionPrick test size and non‐specific bronchial hypersensitivity level were confirmed as independent predictive factors of EAR during allergen exposure in an EEC. This study demonstrated the relation between the severity of rhinitis, conjunctivitis and asthma induced by allergen exposure for both EAR and LAR.
Multimodal approach utilising a weight management programme prior to bariatric surgery in patients with BMI ≥50 kg/m2: A propensity score matching retrospective cohort study
Authors: Sari Cetin , Santana Connie , Seip Richard L. , Bond Dale , Benbrahim Aziz , Hannoush Edward , McLaughlin Tara , Li Ya‐Huei , Staff Ilene , Wu Yin , Papasavas Pavlos , Tishler Darren , Umashanker Devika 
Published: April 2024

SummaryWe evaluated preoperative weight loss and days from initial consult to surgery in patients with BMI ≥50 kg/m2 who were and were not enrolled in medical weight management (MWM) prior to laparoscopic sleeve gastrectomy. We retrospectively identified patients with BMI ≥50 kg/m2 who had primary sleeve gastrectomy between 2014 and 2019 at two bariatric surgery centres in our healthcare system. Patients presenting after 2017 that received preoperative MWM (n = 28) were compared to a historical cohort of non‐MWM patients (n = 118) presenting prior to programme initiation in 2017 on preoperative percent total body weight loss (%TBWL) and days from initial consult to surgery. A total of 151 patients (MWM, 33; non‐MWM, 118) met inclusion criteria. BMI was significantly greater in MWM versus non‐MWM (p = .018). After propensity score matching, median BMI at initial consult in non‐MWM versus MWM no longer differed (p = .922) neither were differences observed on the basis of weight, age, sex, race or ethnicity. After PSM, MWM had significantly lower BMI at surgery (p = .018), lost significantly more weight from consult to surgery (p < .001) and achieved significantly greater median %TBWL from consult to surgery (p < .001). We noted no difference between groups on 6‐month weight loss (p = .533). Days from initial consult to surgery did not differ between groups (p < .863). A preoperative MWM programme integrated into multimodal treatment for obesity in patients with a BMI ≥50 kg/m2 resulted in clinically significant weight loss without prolonging time to surgery.
Baseline assessment and early effects of a network of marine protected areas
Authors: Brun Victor , de Ville d'Avray Laure Thierry , Saludsod Ma. May , Dolorosa Roger G. , Mecha Niño Jess Mar F. , Sorgon Kent Elson S. , Claudet Joachim 
Published: April 2024

AbstractMarine protected areas (MPAs) can be a useful tool to manage coastal ecosystems, delivering both social and ecological outcomes. However, in many instances, relevant data is missing to conduct proper impact assessments, which is key to identifying ecological and social synergies and potential trade‐offs, and to adapting management according to local objectives. The ecological effects of an MPA established in Palawan, Philippines, in 2016, were assessed. The most common species targeted by fisheries were identified by local fishers. Species size and number were collected through underwater visual census with n = 288 belt transects assigned in different sites and locations to ensure to provide both protected and control (fished) sites for the MPA assessment, and baseline data for three new MPAs that were created in 2022. 91 coral‐reef fish species belonging to 12 families were recorded. Mixed effect linear regression was used to compare target fish populations in protected and control sites. Compared to control locations, 5 years after its implementation, the MPA showed significantly higher species richness, abundance, mean size, and biomass while no significant difference was found on the average trophic level between MPA and control sites. Monitoring the early effects of an MPA and collecting baseline data prior the implementation of an MPA network is key for adaptive management.
The Jordan Compact, Refugee Labour and the Limits of Indicator‐oriented Formalization
Authors: Lenner Katharina , Turner Lewis 
Published: April 2024

ABSTRACTThis article explores the significance of initiatives to formalize the labour market participation of refugees. Many practitioners believe that formalization is a panacea for improving the lives of marginalized workers, including refugees. This article argues, however, that in practice it easily becomes an indicator‐oriented exercise, where readily quantifiable targets are prioritized over substantive improvements. To this end, the article analyses the trajectory of the Jordan Compact, a flagship initiative that brought together humanitarian, development and labour actors to create ‘win‐win’ solutions for Syrians and Jordanians. Drawing on years of qualitative fieldwork in Jordan, the article traces how the Jordan Compact has made formalization an end in itself, with little regard for how much it actually benefits workers. It examines three central areas of programming: work permits, home‐based businesses and working conditions. In each area, the article demonstrates how the chosen indicators have shaped initiatives while undermining meaningful reform. Bringing together insights from humanitarianism, development and critical labour studies, the analysis shows that indicator‐oriented formalization, a form of measurement‐driven governance, ostensibly produces impressive results, yet it can simultaneously undermine longer‐term, multidimensional processes that would benefit workers more. The article advocates shifting the focus onto the individual and collective power of workers so that they can better realize the potential benefits of formalization.
Gamma‐aminobutyric acid supplementation improves olanzapine‐induced insulin resistance by inhibiting macrophage infiltration in mice subcutaneous adipose tissue
Authors: Ren Lulu , Xuan Lingling , Li Anning , Yang Yaqi , Zhang Wen , Zhang Jie , Zhang Yi , An Zhuoling 
Published: April 2024

AbstractAimsTo investigate whether gamma‐aminobutyric acid (GABA) supplementation improves insulin resistance during olanzapine treatment in mice and to explore the underlying mechanisms.Materials and MethodsInsulin resistance and body weight gain were induced in mice by 10 weeks of olanzapine treatment. Simultaneously, the mice were administered GABA after 4 weeks of olanzapine administration.ResultsWe found that mice treated with olanzapine had lower GABA levels in serum and subcutaneous white adipose tissue (sWAT). GABA supplementation restored GABA levels and improved olanzapine‐induced lipid metabolism disorders and insulin resistance. Chronic inflammation in adipose tissue is one of the main contributors to insulin resistance. We found that GABA supplementation inhibited olanzapine‐induced adipose tissue macrophage infiltration and M1‐like polarization, especially in sWAT. In vitro studies showed that stromal vascular cells, rather than adipocytes, were sensitive to GABA. Furthermore, the results suggested that GABA improves olanzapine‐induced insulin resistance at least in part through a GABAB receptor‐dependent pathway.ConclusionsThese findings suggest that targeting GABA may be a potential therapeutic approach for olanzapine‐induced metabolic disorders.
Towards complete development finance data: Quantifying China's international education co‐operation and presence in the Global South
Authors: Doi Kenichi , Ikeda Ami , Murakami Yuki , Kuroda Kazuo 
Published: April 2024

AbstractMotivationChina does not participate in the development co‐operation reporting mechanism of the Organisation for Economic Co‐operation and Development's (OECD) development co‐operation reporting mechanism, nor does it voluntarily publish overseas development finance data. Despite recent quantitative research on China's foreign aid to other sectors, such as health, no precedent exists for quantifying China's international education co‐operation (IEC).PurposeThis article will use AidData's Chinese Official Finance Dataset (AidData 2.0) to estimate the IEC using the OECD's internationally standardized definitions of development finance and frameworks for classifying IEC projects.Approach and methodsWe thoroughly examined all types of IEC projects, including official finance projects other than those that meet the definition of official development assistance (ODA). In our comparative analysis of educational aid between China and traditional donors, we focused on ODA‐like projects and examined the number of projects and funding amounts to determine China's IEC priorities.FindingsThe result shows that, between 2000 and 2017, China's IEC commitments totalled 1,524 education‐related international projects, representing 12% of the total international finance project portfolio, most of which are in Africa. Compared to the OECD framework, China prioritized higher education (n = 784, 51%) and education facilities and training (n = 244, 16%). An estimate of cumulative funding between 2000 to 2017 showed that China was the 10th largest donor of education aid to African countries, behind France, the World Bank, Germany, the United States, the EU, the United Kingdom, Canada, Japan, and the Netherlands.Policy implicationsThe findings of this study help our understanding of China's IEC finance. With China's involvement in education development aid growing in recent years and donors looking for solutions to developing countries' debt crises, this will allow for more effective collaboration, co‐ordination, and resource mobilization for both donor and recipient countries.