bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real‐world evidence of cisplatin versus carboplatin in patients with locally advanced nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: A multicenter analysis
Authors: Dechaphunkul Arunee , Danchaivijitr Pongwut , Jiratrachu Rungarun , Dechaphunkul Tanadech , Sookthon Chatsuda , Jiarpinitnun Chuleeporn , Paoin Chatchanok , Setakornnukul Jiraporn , Suktitipat Bhoom , Pattaranutaporn Poompis , Ngamphaiboon Nuttapong 
Published: April 2022

AbstractBackgroundThough concurrent chemoradiotherapy (CCRT) with cisplatin remains a standard of care for patients with locally advanced nasopharyngeal carcinoma (LA‐NPC), carboplatin has alternatively been used without sufficient supportive evidences. Thus, we evaluated an efficacy and tolerability of carboplatin CCRT compared with cisplatin in LA‐NPC patients.MethodsPatients with LA‐NPC treated with CCRT were identified through the Thai multicenter head and neck cancer database. Patient tolerability and survival were analyzed and compared between regimens. Survivals were calculated by using the Kaplan–Meier method, and compared by the log‐rank test. A p‐value of <0.05 was considered statistically significant.ResultsA total of 135 of 980 patients (13.8%) were treated with carboplatin. Patients treated with carboplatin were significantly associated with older age (p < 0.001), smoking (p = 0.003), more comorbidity (p = 0.014), kidney disease (p = 0.016), and lower baseline creatinine clearance (p < 0.001). Intensity‐modulated radiation therapy was used significantly more in the cisplatin group than carboplatin group (p < 0.001). Patients who received carboplatin were associated with delay (p = 0.049) and hospitalization (p = 0.006), whereas cisplatin CCRT had more dose reduction (p = 0.001). Patients treated with cisplatin had CCRT interruption from grade 3–4 mucositis (p = 0.019) more than carboplatin, whereas carboplatin had more grade 3–4 thrombocytopenia (p < 0.001). The 5‐year overall survival (OS) of patients treated with cisplatin and carboplatin was 59% and 49%, respectively (p = 0.128). Cisplatin or carboplatin CCRT was not a significant predictor for OS and locoregional recurrence‐free survival in multivariate analysis.ConclusionsCarboplatin CCRT provided acceptable efficacy and tolerability profiles in real‐world practice. Carboplatin should be considered as an alternative regimen, particularly in cisplatin‐ineligible patients with LA‐NPC treated with CCRT.
How can SMEs effectively embed environmental sustainability? Evidence on the relationships between cognitive frames, life cycle management and organizational learning process
Authors: Bianchi Guia , Testa Francesco 
Published: April 2022

AbstractCognitive frames help companies make sense of the intrinsic tensions of sustainability issues and influence how they respond to calls for sustainability over time. Yet, cognitive frames have been investigated as a static feature and previous studies have overlooked the evolutionary dynamics that can lead an organization to change its own frame. This study observes the evolution of life cycle management implementation through the theory of cognitive frames. We conducted a longitudinal multiple case study of 10 SMEs involved in a European‐funded project. Over a three‐year period we examined how cognitive approaches to sustainability issues changed according to different learning mindsets. A total of three cognitive frames and two learning mindsets were revealed from the analysis, thus providing two important contributions. First, cognitive frames are not static in time, but can change to give more importance to the environmental sustainability of a life cycle. Second, the type of learning mindsets that managers in SMEs share can trigger changes in organizational cognitive frames.
An Alternative Metric for Evaluating the Potential Patient Benefit of Response-Adaptive Randomization Procedures
Authors: Proper Jennifer , Murray Thomas A. 
Published: April 2022

Abstract
When planning a two-arm group sequential clinical trial with a binary primary outcome that has severe implications for quality of life (e.g., mortality), investigators may strive to find the design that maximizes in-trial patient benefit. In such cases, Bayesian response-adaptive randomization (BRAR) is often considered because it can alter the allocation ratio throughout the trial in favor of the treatment that is currently performing better. Although previous studies have recommended using fixed randomization over BRAR based on patient benefit metrics calculated from the realized trial sample size, these previous comparisons have been limited by failures to hold type I and II error rates constant across designs or consider the impacts on all individuals directly affected by the design choice. In this paper, we propose a metric for comparing designs with the same type I and II error rates that reflects expected outcomes among individuals who would participate in the trial if enrollment is open when they become eligible. We demonstrate how to use the proposed metric to guide the choice of design in the context of two recent trials in persons suffering out of hospital cardiac arrest. Using computer simulation, we demonstrate that various implementations of group sequential BRAR offer modest improvements with respect to the proposed metric relative to conventional group sequential monitoring alone.
Inflammatory Waldenström's macroglobulinaemia: A French monocentric retrospective study of 67 patients
Authors: Elessa Dikelele , Debureaux Pierre‐Edouard , Villesuzanne Camille , Davi Frederic , Bravetti Clotilde , Harel Stephanie , Talbot Alexis , Oksenhendler Eric , Malphettes Marion , Thieblemont Catherine , Moatti Hannah , Maarek Odile , Arnulf Bertrand , Royer Bruno 
Published: April 2022

SummaryWaldenström's macroglobulinaemia (WM) is a B‐cell neoplasm resulting from bone marrow lymphoplasmacytic infiltration and monoclonal IgM secretion. Some patients present concomitant inflammatory syndrome attributed to the disease activity; we named this syndrome inflammatory WM (IWM). We retrospectively analysed all WM patients seen in a single tertiary referral centre from January 2007 to May 2021, and after excluding aetiologies for the inflammatory syndrome using a pertinent blood workup, including C‐reactive protein (CRP), and imaging, we identified 67 (28%) IWM, 166 (68%) non‐IWM, and nine (4%) WM with inflammatory syndrome of unknown origin. At treatment initiation, IWM patients had more severe anaemia (median Hb 90 vs 99 g/l; p < 0.01), higher platelet count (median 245 vs 196 × 109/l; p < 0.01) and comparable serum IgM level (median 24.9 vs 23.0 g/l; p = 0.28). A positive correlation was found between inflammatory and haematological responses (minimal response or better) (odds ratio 32.08; 95% confidence interval 8.80–98.03; p < 0.001). Overall survivals (OS) were similar (median OS: 17 vs 20 years; p = 0.11) but time to next treatment (TNT) was significantly shorter for IWM (TNT1: 1.6 vs 4.8 years, p < 0.0001). IWM mostly shared the same presentation and outcome as WM without inflammatory syndrome.
Chronic liver diseases: From development to novel pharmacological therapies: IUPHAR Review 37
Authors: Borrello Maria Teresa , Mann Derek 
Published: April 2022

Chronic liver diseases comprise a broad spectrum of burdensome diseases that still lack effective pharmacological therapies. Our research group focuses on fibrosis, which is a major precursor of liver cirrhosis. Fibrosis consists in a progressive disturbance of liver sinusoidal architecture characterised by connective tissue deposition as a reparative response to tissue injury. Multifactorial events and several types of cells participate in fibrosis initiation and progression, and the process still needs to be completely understood. The development of experimental models of liver fibrosis alongside the identification of critical factors progressing fibrosis to cirrhosis will facilitate the development of more effective therapeutic approaches for such condition. This review provides an overlook of the main process leading to hepatic fibrosis and therapeutic approaches that have emerged from a deep knowledge of the molecular regulation of fibrogenesis in the liver.LINKED ARTICLESThis article is part of a themed issue on Translational Advances in Fibrosis as a Therapeutic Target. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc
Stocking in inland food fisheries of South and Southeast Asia: issues, risks, and rewards
Authors: Arthur Robert Ian , Valbo‐Jørgensen John , Lorenzen Kai , Kelkar Nachiket 
Published: April 2022

AbstractInland fisheries in South and Southeast Asia represent important sources of food, and many are extensively stocked. Stocking often catalyses wider changes in inland fisheries is considered in this context. Stocking can be beneficial, providing additional sources of food, incentives to manage, and income‐generating opportunities. However, there are also identifiable risks: stocking can be used to avoid or ignore addressing reasons underlying the degradation of inland fisheries and economic development, tenure arrangements, and culture technologies involved in stocking can combine to transform the very nature of inland fisheries. These transformations can degrade environments and alter the nature and distribution of benefits, potentially marginalising and impoverishing fishers. There is consequently a need to consider and assess more explicitly in advance the implications of stocking for the nature and distribution of social and environmental costs and benefits, and the risks related to access to, and availability of, food.
Labour market integration of FRY refugees in Sweden vs. Denmark
Authors: Andersson Joona Pernilla , Datta Gupta Nabanita 
Published: April 2022

AbstractWe compare the long‐run labour market integration of the Former Republic of Yugoslavia (FRY) refugees who arrived in the 1990s to the Scandinavian countries in the settings of Sweden and Denmark, respectively. These otherwise similar countries faced different economic conditions at the time of arrival and over the observation period. They also differed in terms of the restrictiveness of asylum policies and in attitudes towards immigration. Using register data from Statistics Sweden and Statistics Denmark, we show that FRY refugees, in both child and adult generations at arrival, are better integrated 12–15 years later in Sweden than in Denmark, even though Sweden experienced a higher level of unemployment than Denmark throughout the period. Our findings suggest that asylum policies promoting early labour market entry and early exposure to a host country's schooling system, as well as access to disability pension and social assistance, are important factors affecting refugee labour market integration.
The impact of using vacuum and isomaltulose as an osmotic agent on mass exchange during osmotic dehydration and their effects on qualitative parameters of strawberries
Authors: Macedo Leandro Levate , Corrêa Jefferson Luiz Gomes , Vimercati Wallaf Costa , da Silva Araújo Cintia 
Published: April 2022

AbstractThe impregnation of isomaltulose is an interesting strategy for the enrichment of strawberries since it is a carbohydrate with low glycemic and cariogenic indexes. The osmotic enrichment of strawberries with isomaltulose was performed considering the vacuum pulse in the first 0, 10, and 20 min in a total process time of 300 min, at 25°C. The tested solution concentrations were 25% and 35% (w w−1) of isomaltulose. The kinetics of solid gain, water loss, moisture content, and weight reduction were obtained. The fresh and final products had some physical and nutritional parameters evaluated. Osmotic processes resulted in a reduction of moisture content, water activity (aw), acidity, total anthocyanins and phenolic contents and antioxidant capacity, increased pH, influenced colorimetric parameters and caused shrinkage of the samples. The higher impregnation of isomaltulose was obtained with the vacuum pulse, which was 82% higher than the osmotic process without the vacuum pulse. The atmospheric process resulted in higher bioactive compounds levels and lower shrinkage and lower total color difference. Therefore, the 35% solution and use of vacuum were recommended when the objective was to maximize mass exchanges, while the 25% solution and without vacuum pulse were indicated for higher retention of strawberry bioactive compounds. The time of vacuum application at the beginning of the osmotic dehydration process and the use of osmotic solutions of different concentrations can result in different rates of dehydration and impregnation of isomaltulose in the strawberry and can influence important qualitative parameters. The evaluation of these factors helps in the optimization of the production of osmo‐dehydrated strawberries, increasing the process efficiency and the preservation of product quality.Practical ApplicationsThe time of vacuum application at the beginning of the osmotic dehydration process and the use of osmotic solutions of different concentrations can result in different rates of dehydration and impregnation of isomaltulose in the strawberry and can influence important qualitative parameters. The evaluation of these factors helps in the optimization of the production of osmo‐dehydrated strawberries, increasing the process efficiency and the preservation of product quality.
Hirayama disease: Nosological classification and neuroimaging clues for diagnosis
Authors: Iacono Salvatore , Di Stefano Vincenzo , Gagliardo Andrea , Cannella Roberto , Virzì Valentina , Pagano Sonia , Lupica Antonino , Romano Marcello , Brighina Filippo 
Published: April 2022

AbstractHirayama disease (HD) is a rare, benign, and nonprogressive motor neuron disease (MND) affecting the upper limbs. It usually presents with weakness and amyotrophy in a single upper extremity with an insidious onset between adolescence and the third decade of life. Since its description in 1959, HD has been known under several names and eponyms in Europe and in Asian countries probably due to its heterogeneous clinical features. Thus, the unclear nosological classification makes challenging the differential diagnosis between HD and other neuromuscular conditions, such as MNDs. However, apart from the nosological difficulties and the lack of evidence‐based guideline for diagnosis, the neuroimaging is the mainstay for the diagnosis of HD. Indeed, the specific findings on cervical flexion MRI usually lead to a prompt diagnosis. Here, we reviewed the nosological classifications of HD and its neuroimaging features. Also, we report a case of a 18‐year‐old boy who presented to our Clinic complaining of muscle weakness of the left distal upper limb without other neurological signs. The cervical MRI, in the neutral position, revealed a high T2 signal intensity in the C5‐C7 cervical myelomeres as well as the loss of cervical lordosis, whereas, during neck flexion, it showed the anterior displacement of the posterior dura ad the post‐gadolinium T1‐weighted imaging enhancement of the posterior epidural plexus. These findings are typical for HD allowing the diagnosis as well as the differential diagnosis from other neuromuscular diseases.
Reassessing North Eastern Atlantic‐Mediterranean species of Trapania (Mollusca, Nudibranchia)
Authors: Paz‐Sedano Sofía , Martín Álvarez José Francisco , Gosliner Terrence M. , Pola Marta 
Published: April 2022

AbstractTrapania is the second largest genus belonging to the family Goniodorididae, of which most of the species are reported from Indo‐Pacific waters. To date, there are nine species of Trapania distributed along the temperate coasts of the East Atlantic Ocean and Mediterranean Sea: Trapania fusca, Trapania graeffei, Trapania hispalensis, Trapania lineata, Trapania maculata, Trapania orteai, Trapania pallida, Trapania sanctipetrensis and Trapania tartanella. However, the validity of some of these species has been problematic due to uncertain taxonomic characteristics used for the differentiation of the species. The genus Trapania has a very uniformly external morphology and very similar internal anatomy. As a consequence, the features most commonly used to differentiate species have been the colour pattern of the body and the morphology of the radula. In the present study, we perform a morphological and molecular revision of the East Atlantic‐Mediterranean species of the genus Trapania. Morphological analyses include dissections and scanning electron microscope photographs of radulae, labial cuticles and penises. Molecular work includes phylogenetic, species delimitation and haplotype network analyses. Our results bring doubt on the taxonomic characteristics used so far, suggesting that the richness of the North Eastern Atlantic‐Mediterranean species has been overestimated. Trapania hispalensis, T. lineata and T. pallida are shown to belong to the same taxa, with Trapania lineata as senior synonym.
Resampling to address inequities in predictive modeling of suicide deaths
Authors: Reeves Majerle , Bhat Harish S , Goldman-Mellor Sidra 
Published: April 2022

ObjectiveImprove methodology for equitable suicide death prediction when using sensitive predictors, such as race/ethnicity, for machine learning and statistical methods.MethodsTrain predictive models, logistic regression, naive Bayes, gradient boosting (XGBoost) and random forests, using three resampling techniques (Blind, Separate, Equity) on emergency department (ED) administrative patient records. The Blind method resamples without considering racial/ethnic group. Comparatively, the Separate method trains disjoint models for each group and the Equity method builds a training set that is balanced both by racial/ethnic group and by class.ResultsUsing the Blind method, performance range of the models’ sensitivity for predicting suicide death between racial/ethnic groups (a measure of prediction inequity) was 0.47 for logistic regression, 0.37 for naive Bayes, 0.56 for XGBoost and 0.58 for random forest. By building separate models for different racial/ethnic groups or using the equity method on the training set, we decreased the range in performance to 0.16, 0.13, 0.19, 0.20 with Separate method, and 0.14, 0.12, 0.24, 0.13 for Equity method, respectively. XGBoost had the highest overall area under the curve (AUC), ranging from 0.69 to 0.79.DiscussionWe increased performance equity between different racial/ethnic groups and show that imbalanced training sets lead to models with poor predictive equity. These methods have comparable AUC scores to other work in the field, using only single ED administrative record data.ConclusionWe propose two methods to improve equity of suicide death prediction among different racial/ethnic groups. These methods may be applied to other sensitive characteristics to improve equity in machine learning with healthcare applications.
Developing a simulation-based learning model for acute medical education during COVID-19 pandemic with Simulation via Instant Messaging – Birmingham Advance (SIMBA)
Authors: Wallett Lucy , Chen Wentin , Thomas Lucretia , Blaggan Parisha , Ooi Emma , Zhou Dengyi , Hanania Thia , Ng Cai Ying , Evans Nia , Morgan Georgia , Allison Issy , Pan Carina Synn Cuen , Ponniah Gobeka , Radcliffe Eloise , Sheikh Jameela , Khashaba Alya , Hebbar Meghnaa , Delson Dwi , Reddy-Koanu Vinay , Ayuk John , Packer Gregory , Akufo-Tetteh Emily , Davitadze Meri , Melson Eka , Kempegowda Punith 
Published: April 2022

Simulation-based learning (SBL) is well-established in medical education and has gained popularity, particularly during the COVID-19 pandemic when in-person teaching is infeasible. SBL replicates real-life scenarios and provides a fully immersive yet safe learning environment to develop clinical competency. Simulation via Instant Messaging – Birmingham Advance (SIMBA) is an exemplar of SBL, which we previously showed to be effective in endocrinology and diabetes. Previous studies reported the efficacy of SBL in acute medicine. We studied SIMBA as a learning intervention for healthcare professionals interested in acute medicine and defined our aims using the Kirkpatrick model: (i) develop an SBL tool to improve case management; (ii) evaluate experiences and confidence before and after; and (iii) compare efficacy across training levels.Three sessions were conducted, each representing a PDSA cycle (Plan-Do-Study-Act), consisting of four cases and advertised to healthcare professionals at our hospital and social media. Moderators facilitated progression through 25 min simulations and adopted patient and clinical roles as appropriate. Consultants chaired discussion sessions using relevant guidelines. Presimulation and postsimulation questionnaires evaluated self-reported confidence, feedback and intended changes to clinical practice.Improvements were observed in self-reported confidence managing simulated cases across all sessions. Of participants, 93.3% found SIMBA applicable to clinical practice, while 89.3% and 88.0% felt SIMBA aided personal and professional development, respectively. Interestingly, 68.0% preferred SIMBA to traditional teaching methods. Following participant feedback, more challenging cases were included, and we extended the time for simulation and discussion. The transcripts were amended to facilitate more participant-moderator interaction representing clinical practice. In addition, we refined participant recruitment over the three sessions. In cycle 1, we advertised incentives: participation counted towards teaching requirements, certificates and feedback. To rectify the reduction in participants in cycle 2, we implemented new advertisement methods in cycle 3, including on-site posters, reminder emails and recruitment of the defence deanery cohort.
Functional Genomic Analysis ofCDK4andCDK6Gene Dependency across Human Cancer Cell Lines
Authors: Zhang Zhouwei , Golomb Lior , Meyerson Matthew 
Published: April 2022

AbstractCyclin-dependent kinase 4 (CDK4) and CDK6 are key cell-cycle regulators that are frequently dysregulated in human malignancies. CDK4/6 inhibitors are clinically approved for the treatment of hormone receptor–positive, HER2–negative (HR+/HER2−) breast cancer, but improved specificity and reduced toxicity might expand their use to other indications. Through analysis of publicly available genome-wide loss-of-function data combined with single and dual-targeting CRISPR assays, we found differential cell proliferation vulnerability of cell lines to either CDK4 deletion alone, CDK6 deletion alone, combined CDK4/CDK6 deletion, or neither. CDK6 expression was the best single predictor of CDK4 (negatively correlated) and CDK6 (positively correlated) dependencies in the cancer cell lines, with adenocarcinoma cell lines being more sensitive to CDK4 deletion and hematologic and squamous cancer cell lines being more sensitive to CDK6 deletion. RB–E2F signaling was confirmed as a main downstream node of CDK4/6 in these experiments as shown by the survival effects of RB1 deletion. Finally, we show in a subset of cancer cell lines not dependent on CDK4/6 that CDK2–CCNE1 is an important alternative dependency for cell proliferation. Together, our comprehensive data exploration and functional experiments delineate the landscape of pan-cancer CDK4/6 gene dependencies and define unique cancer cell populations that might be sensitive to CDK4-selective or CDK6-selective inhibitors.Significance:This study provides functional genomic insight toward understanding the scenarios in which cancer cells are differentially sensitive to CDK4 or CDK6 inhibition and their implications in current treatment strategies.
Dnmt3a-Mutant Hematopoietic Stem Cell Rewire IFNγ Signaling to Gain Clonal Advantage
Authors: De Dominici Marco , DeGregori James 
Published: April 2022

Summary:
Dnmt3a-mutant stem cells gain a competitive advantage via upregulation of a Txnip–p53–p21 axis and protection from IFNγ induced exhaustion.
See related article by Zhang et al., p. 220 (5).