bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pembrolizumab monotherapy versus pembrolizumab plus chemotherapy in patients with non‐small‐cell lung cancer: A multicenter retrospective trial
Authors: Matsumoto Hiromi , Kobayashi Nobuaki , Somekawa Kohei , Fukuda Nobuhiko , Kaneko Ayami , Kamimaki Chisato , Kubo Sousuke , Tanaka Katsushi , Tagami Yoichi , Teranishi Shuhei , Watanabe Keisuke , Horita Nobuyuki , Hara Yu , Yamamoto Masaki , Kudo Makoto , Koizumi Harumi , Miura Kenji , Miyazawa Naoki , Kaneko Takeshi 
Published: December 2021

AbstractBackgroundPembrolizumab alone or in combination with chemotherapy is a standard treatment for patients with non‐small‐cell lung cancer (NSCLC) with high programmed death‐ligand 1 (PD‐L1) expression. However, no study has compared the efficacies of these two regimens. Therefore, we aimed to compare the efficacy of pembrolizumab alone and in combination with chemotherapy in NSCLC patients with high PD‐L1 expression.MethodsWe conducted a multicenter retrospective trial involving patients with diagnosed unresectable or recurrent NSCLCs who had received pembrolizumab with or without chemotherapy in the first‐line setting. Patients were divided into monotherapy and combination therapy groups. The progression‐free survival (PFS), overall survival (OS), and response rate (RR) were analyzed and compared between the groups. Clinical characteristics of patients were analyzed to assess their possible relationship with treatment outcomes.ResultsWe enrolled 96 patients from five hospitals. Of these, 47 and 49 patients received monotherapy and combination therapy, respectively. The median PFS was 343 and 328 days in the monotherapy and combination therapy groups, respectively (hazard ratio 1.003, p = 0.99). No statistically significant differences were observed in the OS and RR between the two groups. However, in patients with metastases to the liver, lung, adrenal glands, bone, or lymph nodes, the PFS was longer in the monotherapy group than in the combination therapy group.ConclusionAlthough the PFS, OS, and RR were not significantly different between patients treated with pembrolizumab alone and or with pembrolizumab in combination with chemotherapy, patients with NSCLC having metastases to specific sites may benefit more from monotherapy.
Risk factors for in‐hospital mortality in patients with advanced lung cancer with interstitial pneumonia undergoing systemic chemotherapy: A retrospective and observational study using a nationwide administrative database in Japan
Authors: Shiraishi Tomoko , Oda Keishi , Yamasaki Kei , Kido Takashi , Sennari Konomi , Mukae Hiroshi , Ohtani Makoto , Fujino Yoshihisa , Matsuda Shinya , Fushimi Kiyohide , Yatera Kazuhiro 
Published: December 2021

AbstractBackgroundThe safety profile of systemic chemotherapy for lung cancer patients with interstitial pneumonia (IP) in clinical practice remains unclear. Using Diagnostic Procedure Combination (DPC) data from the Japanese administrative database, we investigated the mortality of hospitalized lung cancer patients with IP as they underwent a course of systemic chemotherapy nationwide.MethodsThe DPC data of patients with stage IIIB or IV lung cancer as defined by the Union for International Cancer Control Tumor‐Nodes‐Metastases 6th and 7th editions from April 2014 to March 2016 were obtained. Among those patients, only patients with concomitant IP and receiving systemic chemotherapy without radiotherapy were included.ResultsAmong 1524 included patients, 70 (4.6%) died in the hospital. Multivariate analysis revealed that low activities of daily living (ADL) scores on admission (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.24–4.12, p = 0.008) and high‐dose corticosteroid therapy following chemotherapy (HR 2.62, 95% CI 1.44–4.77, p = 0.002) were strongly associated with in‐hospital mortality. It was determined that patients possibly received high‐dose corticosteroids for IP exacerbations; these patients had a higher in‐hospital mortality rate of 67.7% (21/31 patients) and a significantly shorter median survival time of 55 days (95% CI 31–69 days, p < 0.001) than those who did not receive high‐dose corticosteroids.ConclusionAcute exacerbation of IP treated with systemic high‐dose corticosteroids is significantly associated with in‐hospital mortality, and a low ADL score on admission is a risk factor for in‐hospital mortality in lung cancer patients with IP who undergo systemic chemotherapy.
Management of acute atrial fibrillation in the intensive care unit: An international survey
Authors: Wetterslev Mik , Møller Morten Hylander , Granholm Anders , Hassager Christian , Haase Nicolai , Aslam Tayyba Naz , Shen Jiawei , Young Paul J. , Aneman Anders , Hästbacka Johanna , Siegemund Martin , Cronhjort Maria , Lindqvist Elin , Myatra Sheila N. , Kalvit Kushal , Arabi Yaseen M. , Szczeklik Wojciech , Sigurdsson Martin I. , Balik Martin , Keus Frederik , Perner Anders ,   the AFIB‐ICU collaborators
Published: December 2021

AbstractBackgroundAtrial fibrillation (AF) is common in intensive care unit (ICU) patients and is associated with poor outcomes. Different management strategies exist, but the evidence is limited and derived from non‐ICU patients. This international survey of ICU doctors evaluated the preferred management of acute AF in ICU patients.MethodWe conducted an international online survey of ICU doctors with 27 questions about the preferred management of acute AF in the ICU, including antiarrhythmic therapy in hemodynamically stable and unstable patients and use of anticoagulant therapy.ResultsA total of 910 respondents from 70 ICUs in 14 countries participated in the survey with 24%–100% of doctors from sites responding. Most ICUs (80%) did not have a local guideline for the management of acute AF. The preferred first‐line strategy for the management of hemodynamically stable patients with acute AF was observation (95% of respondents), rhythm control (3%), or rate control (2%). For hemodynamically unstable patients, the preferred strategy was observation (48%), rhythm control (48%), or rate control (4%). Overall, preferred antiarrhythmic interventions included amiodarone, direct current cardioversion, beta‐blockers other than sotalol, and magnesium in that order. A total of 67% preferred using anticoagulant therapy in ICU patients with AF, among whom 61% preferred therapeutic dose anticoagulants and 39% prophylactic dose anticoagulants.ConclusionThis international survey indicated considerable practice variation among ICU doctors in the clinical management of acute AF, including the overall management strategies and the use of antiarrhythmic interventions and anticoagulants.
Isoflurane promotes early spontaneous breathing in ventilated intensive care patients: A post hoc subgroup analysis of a randomized trial
Authors: Müller‐Wirtz Lukas M. , Behne Florian , Kermad Azzeddine , Wagenpfeil Gudrun , Schroeder Matthias , Sessler Daniel I. , Volk Thomas , Meiser Andreas 
Published: December 2021

AbstractBackgroundSpontaneous breathing is desirable in most ventilated patients. We therefore studied the influence of isoflurane versus propofol sedation on early spontaneous breathing in ventilated surgical intensive care patients and evaluated potential mediation by opioids and arterial carbon dioxide during the first 20 h of study sedation.MethodsWe included a single‐center subgroup of 66 patients, who participated in a large multi‐center trial assessing efficacy and safety of isoflurane sedation, with 33 patients each randomized to isoflurane or propofol sedation. Both sedatives were titrated to a sedation depth of −4 to −1 on the Richmond Agitation Sedation Scale. The primary outcome was the fraction of time during which patients breathed spontaneously.ResultsBaseline characteristics of isoflurane and propofol‐sedated patients were well balanced. There were no substantive differences in management or treatment aside from sedation, and isoflurane and propofol provided nearly identical sedation depths. The mean fraction of time spent spontaneously breathing was 82% [95% CI: 69, 90] in patients sedated with isoflurane compared to 35% [95% CI: 22, 51] in those assigned to propofol: median difference: 61% [95% CI: 14, 89], p < .001. After adjustments for sufentanil dose and arterial carbon dioxide partial pressure, patients sedated with isoflurane were twice as likely to breathe spontaneously than those sedated with propofol: adjusted risk ratio: 2.2 [95%CI: 1.4, 3.3], p < .001.ConclusionsIsoflurane compared to propofol sedation promotes early spontaneous breathing in deeply sedated ventilated intensive care patients. The benefit appears to be a direct effect isoflurane rather than being mediated by opioids or arterial carbon dioxide.
A local general‐equilibrium emergency response modeling approach for sub‐Saharan Africa
Authors: Filipski Mateusz , Gupta Anubhab , Kagin Justin , Husain Arif , Grinspun Alejandro , Caccavale Oscar Maria , Daidone Silvio , Giuffrida Valerio , Greb Friederike , Hooker Joseph , Sandström Susanna , Fletcher‐Taylor Julian , Taylor J. Edward 
Published: December 2021

AbstractSwift response models are vital tools for emergency assistance agencies. The COVID‐19 pandemic revealed the lack of economic models for short‐run policy relevant research to anticipate local impacts and design effective policy responses. The most direct effects of the pandemic and lockdown tended to be concentrated in urban areas; however, markets quickly transmitted impacts to rural areas as well as among poor and non‐poor households. General equilibrium modeling is a tool of choice to capture indirect, spillover effects of exogenous shocks. This article describes an unusual micro general‐equilibrium (GE) modeling approach that we developed to quickly simulate impacts of the pandemic and lockdowns on poor and non‐poor rural and urban households across sub‐Saharan Africa. Monte Carlo bootstrapping was used to construct four stylized regional GE models from 34 existing local economy‐wide impact evaluation (LEWIE) models. Simulations revealed that the pandemic and policy responses to curtail its spread were likely to affect rural households at least as severely as urban households. Simulated income losses are greater in poor households in both urban and rural settings. These findings are relatively consistent across models spanning sub‐Saharan Africa. Because COVID‐19 impacts are so far‐reaching, all types of economies experience downturns. Our research underlines the importance of modeling assumptions. We find total annualized impacts of around a 6‐percent loss of GDP, smaller than estimates from single‐country models that ignore price effects, such as SAM‐multiplier models, but in line with The World Bank's baseline forecast of a 5.2% contraction in global GDP in 2020. The largest negative impacts are on poor rural households.
Gross anatomy of the craniolateral antebrachial muscles in kinkajou (Potos flavus, Carnivora): Intra‐ and interspecific variants within the family Procyonidae
Authors: Vélez‐García Juan Fernando , Chunganá‐Caicedo Daniela , Saavedra‐Montealegre Sebastián 
Published: December 2021

AbstractThe kinkajou (Potos flavus) is a carnivoran that has special morphological adaptations in its thoracic limbs to climb threes and handling food. This study aimed to describe the craniolateral muscles of the antebrachium in P. flavus. Five specimens were used. The extensor carpi radialis longus and brevis were seen as two separate muscles. The extensor carpi ulnaris muscle can present two bellies with different insertions. An extensor digit III muscle was found. The P. flavus has anatomical variants on the craniolateral antebrachial muscles that were previously reported in other procyonids. Thus, those variants are phylogenetically related within the family Procyonidae, except the doubled bellies of the extensor carpi ulnaris muscle which is exclusive of P. flavus.
Party Elite Engagement and Coordination in House Primary Elections: A Test of Theories of Parties
Authors: Hassell Hans J.G. 
Published: December 2021

AbstractThe support of party elites in the primary has a strong influence on who runs in a primary and how well they do. Yet party elites do not always engage or coordinate their efforts. Moreover, theories of parties disagree about whether and where party elites should engage and coordinate in primaries, depending on their view of the relative importance of electoral and policy goals. This article examines party elites’ engagement and coordination in primary elections in the U.S. House between 2004 and 2018. Consistent with theories of parties as networks of policy demanders, party elites are engaged in primaries in both competitive and safe districts. But, while party elites coordinate their efforts in competitive districts, they are less likely to coordinate in safe districts. Their disparate coordination efforts reflect different electoral priorities in these districts.
Retinol binding protein 1‐dependent activation of NF‐ κB signaling enhances the malignancy of non‐glioblastomatous diffuse gliomas
Authors: Wu Wei , Wang Yichang , Niu Chen , Wahafu Alafate , Huo Longwei , Guo Xiaoye , Xiang Jianyang , Li Xiaodong , Xie Wanfu , Bai Xiaobin , Wang Maode , Wang Jia 
Published: December 2021

AbstractNonglioblastomatous diffuse glioma (non‐GDG) is a heterogeneous neuroepithelial tumor that exhibits a varied survival range from 4 to 13 years based on the diverse subtypes. Recent studies demonstrated novel molecular markers can predict prognosis for non‐GDG patients; however, these findings as well as pathological classification strategies show obvious limitations on malignant transition due to the heterogeneity among non‐GDGs. Therefore, developing reliable prognostic biomarkers and therapeutic targets have become an urgent need for precisely distinguishing non‐GDG subtypes, illuminating the underlying mechanism. Nuclear factor κβ (NF‐κB) has been proved to be a significant nuclear transcriptional regulator with specific DNA‐binding sequences to participate in multiple pathophysiological processes. However, the underlying mechanism of NF‐κB activation still needs to be further investigated. Herein, our results indicated retinol‐binding protein 1 (RBP1) was significantly upregulated in the IDHWT and 1p19qNon co‐del non‐GDG subtypes and enriched RBP1 expression was markedly correlated with more severe outcomes. Additionally, malignant signatures of the non‐GDG cells including proliferation, migration, invasion, and self‐renewal were significantly suppressed by lentiviral knockdown of RBP1. To further explore the underlying molecular mechanism, bioinformatics analysis was performed using databases, and the results demonstrated RBP1 was strongly correlated with tumor necrosis factor α (TNFα)–NF‐κB signaling. Moreover, exogenous silencing of RBP1 reduced phosphorylation of IkB‐kinase α (IKKα) and thus decreased NF‐κB expression via decreasing the degradation of the IκBα protein. Altogether, these data suggested RBP1‐dependent activation of NF‐κB signaling promoted malignancy of non‐GDG, indicating that RBP1 could be a reliable prognostic biomarker and potential therapeutic target for non‐GDG.
Neurodevelopmental phenotype in 36 new patients with 8p inverted duplication–deletion: Genotype–phenotype correlation for anomalies of the corpus callosum
Authors: Vibert Roseline , Mignot Cyril , Keren Boris , Chantot‐Bastaraud Sandra , Portnoï Marie‐France , Nouguès Marie‐Christine , Moutard Marie‐Laure , Faudet Anne , Whalen Sandra , Haye Damien , Garel Catherine , Chatron Nicolas , Rossi Massimiliano , Vincent‐Delorme Catherine , Boute Odile , Delobel Bruno , Andrieux Joris , Devillard Françoise , Coutton Charles , Puechberty Jacques , Pebrel‐Richard Céline , Colson Cindy , Gerard Marion , Missirian Chantal , Sigaudy Sabine , Busa Tiffany , Doco‐Fenzy Martine , Malan Valérie , Rio Marlène , Doray Bérénice , Sanlaville Damien , Siffroi Jean‐Pierre , Héron Delphine , Heide Solveig 
Published: December 2021

AbstractInverted duplication deletion 8p [invdupdel(8p)] is a complex and rare chromosomal rearrangement that combines a distal deletion and an inverted interstitial duplication of the short arm of chromosome 8. Carrier patients usually have developmental delay and intellectual disability (ID), associated with various cerebral and extra‐cerebral malformations. Invdupdel(8p) is the most common recurrent chromosomal rearrangement in ID patients with anomalies of the corpus callosum (AnCC). Only a minority of invdupdel(8p) cases reported in the literature to date had both brain cerebral imaging and chromosomal microarray (CMA) with precise breakpoints of the rearrangements, making genotype–phenotype correlation studies for AnCC difficult. In this study, we report the clinical, radiological, and molecular data from 36 new invdupdel(8p) cases including three fetuses and five individuals from the same family, with breakpoints characterized by CMA. Among those, 97% (n = 32/33) of patients presented with mild to severe developmental delay/ID and 34% had seizures with mean age of onset of 3.9 years (2 months–9 years). Moreover, out of the 24 patients with brain MRI and 3 fetuses with neuropathology analysis, 63% (n = 17/27) had AnCC. We review additional data from 99 previously published patients with invdupdel(8p) and compare data of 17 patients from the literature with both CMA analysis and brain imaging to refine genotype–phenotype correlations for AnCC. This led us to refine a region of 5.1 Mb common to duplications of patients with AnCC and discuss potential candidate genes within this region.
Dynamic Diffuse Global Illumination Resampling
Authors: Majercik Zander , Müller Thomas , Keller Alexander , Nowrouzezahrai Derek , McGuire Morgan 
Published: December 2021

AbstractInteractive global illumination remains a challenge in radiometrically and geometrically complex scenes. Specialized sampling strategies are effective for specular and near‐specular transport because the scattering has relatively low directional variance per scattering event. In contrast, the high variance from transport paths comprising multiple rough glossy or diffuse scattering events remains notoriously difficult to resolve with a small number of samples. We extend unidirectional path tracing to address this by combining screen‐space reservoir resampling and sparse world‐space probes, significantly improving sample efficiency for transport contributions that terminate on diffuse scattering events. Our experiments demonstrate a clear improvement—at equal time and equal quality—over purely path traced and purely probe‐based baselines. Moreover, when combined with commodity denoisers, we are able to interactively render global illumination in complex scenes.
Antimicrobial effects of a new brushing solution concept on a multispecies in vitro biofilm model growing on titanium surfaces
Authors: Virto Leire , Simões‐Martins David , Sánchez María Carmen , Encinas Ana , Sanz Mariano , Herrera David 
Published: December 2021

AbstractObjectivesTo evaluate the antibiofilm and antibacterial effects of a new brushing solution concept, in a validated peri‐implant biofilm model.Materials and MethodsA multispecies in vitro biofilm model, including Streptococcus oralis, Actinomyces naeslundii, Veillonella parvula, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum, was used. To evaluate the antibiofilm capacity, titanium discs (Ti‐SLA) were immersed in 1 ml of the tested solution (one tablet dissolved in warm water) for 2 min, prior and every 24 h during a 3‐day biofilm development. Negative (water) and positive (0.12% chlorhexidine/0.05% cetylpyridinium chloride mouth rinse) controls treated discs were run in parallel. To evaluate the antibacterial effects, planktonic cells and 72‐h biofilms on sterile Ti‐SLA discs were exposed (2 min) to the mentioned treatments. Biofilm structure was analysed by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Bacterial load was measured by quantitative polymerase chain reaction and by culture in planktonic cells.ResultsThe tested product showed antibiofilm effects, impacting on the 48‐h and 72‐h biofilm thickness and significantly reducing viability of all bacterial species, except A. actinomycetemcomitans. Antibacterial effects were observed against the six bacterial species in planktonic state and in 72‐h biofilms, especially for F. nucleatum and A. actinomycetemcomitans.ConclusionThe tested brushing solution demonstrated antibacterial and antibiofilm properties, mainly against the peri‐implant pathogens included in the validated in vitro biofilm model used.
Spatiotemporal patterns of vegetation conversion under the Grain for Green Program in southwest China
Authors: Zhao Haiwei , Wu Ruidong , Yang Feiling , Hu Jinming , Wang Junjun , Guo Yang , Feng Zhixue , Zhang Chen , Wang Yiting , Zhou Jian 
Published: December 2021

AbstractChina's Grain for Green Program (GGP) is the largest reforestation program in the world. Previous studies lacked targeted assessments regarding its effectiveness in vegetation conversion. Using the time series of Vegetation Continuous Fields in southwest China, we derived the spatiotemporal variations in total vegetation cover, short vegetation (SV) cover and tree canopy (TC) cover during the period from 2000 to 2016. By conducting residual trend analyses independently on the SV and TC cover time series, the trends in human‐induced SV cover (SVH) and TC cover (TCH) were detected. Then, we performed overlay analyses to derive the human‐induced SV–TC conversion in cropland. The study found that the SV in southwest China showed a net browning trend whereas the TC presented a net greening trend. Approximately 69.5% of the pixels with a significant browning trend in SVH showed a significant greening trend in TCH. Furthermore, 50.6% of the human‐induced SV–TC conversion in southwest China occurred in cropland, and the proportion was even larger for the eastern provinces. Our study provides a targeted evaluation of the performance of the GGP and highlights that the implementation of the GGP has caused widespread SV–TC conversion that potentially mitigates global climate change.
LEARN: Essential Elements of Museum Education Programs for Young Children
Authors: Young Sarah , Eadie Tricia , Suda Liz , Church Amelia 
Published: December 2021

AbstractMuseums provide rich multimodal learning opportunities and long‐lasting memories for children and teachers who participate in museum excursions and outreach programs. Museum programs for preschool children embed hands‐on opportunities to engage children with new and diverse artefacts. Interactions in museum settings provide opportunities for adults and children to collaborate in learning. Our aim in this project was to explore the elements of museum programs that prove essential in engaging young children in museum education programs. Five museum presenters and 14 early childhood groups (14 teachers and 296 children) participated in the research project. Data collection included audio recordings of museum presentations, observations of child‐teacher interactions, multiliteracy observations, teacher interviews, and written reflections from the museum presenters. Coding across all datasets contributed to the five main themes in the findings, which we detail using the acronym LEARN: Learning artefacts; Embodied teaching and learning; Asking questions; Repetition: and Narrative. Multiple elements of museum education programs influence learning opportunities for young children. Both structural elements (e.g. designing a core narrative around concepts, or time for children’s individual queries during the program and hands‐on explorations with museum artefacts) and learning interactions (e.g. conversations where children and adults collaborate) contribute to engaging museum education programs for young children.