bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical efficacy and safety of pemetrexed with or without either Bevacizumab or Pembrolizumab in patients with metastatic nonsquamous non–small cell carcinoma
Authors: Kwok Wang Chun , Cheong Tan Fong , Chiang Ka Yan , Ho James Chung Man , Lam David Chi Leung , Ip Mary Sau Man , Tam Terence Chi Chun 
Published: April 2022

AbstractBackgroundPemetrexed was approved by United States Food and Drug Administration (US FDA) in combination with platinum for the treatment of advanced nonsquamous non–small cell lung carcinoma (NSCLC) and malignant mesothelioma. Bevacizumab and pembrolizumab can be added to chemotherapy for patients with nonsquamous NSCLC with benefits but there has not been any dedicated head‐to‐head comparison between pembrolizumab‐pemetrexed‐platinum (PAC) and bevacizumab‐pemetrexed‐platinum (BAC) on their efficacy and safety.MethodsThis was a retrospective single‐center cohort study conducted in Queen Mary Hospital in Hong Kong. The study included 451 patients with advanced stage nonsquamous NSCLC that received first‐line pemetrexed and platinum with or without bevacizumab or pembrolizumab. Patients who received pemetrexed‐platinum (AC) were compared with those who received PAC and BAC. The primary endpoint was the progression‐free survival (PFS).ResultsThe median PFS for patients that received PAC was significantly longer than those who received BAC and AC (9 months vs. 6.8 months vs. 4.8 months, p < 0.05 among all three groups), with OR of 0.578 (95% CI, 0.343–0.976; p = 0.040) and 0.430 (95% CI, 0.273–0.675; p < 0.001) when compared to BAC and AC, respectively. Patients who received PAC also had a higher disease control rate and higher likelihood to receive continuation maintenance therapy than those on AC. There is no statistically significant difference in the grade 3 to 4 toxicity among the three treatment groups.ConclusionsAlthough both regimens are superior to pemetrexed‐platinum alone, data from this retrospective single center study suggested a better PFS in advanced stage nonsquamous NSCLC patient treated with first‐line pembrolizumab‐pemetrexed‐platinum than bevacizumab‐pemetrexed‐platinum without an obvious increase in significant toxicity.
Bioavailability of acalabrutinib suspension delivered via nasogastric tube in the presence or absence of a proton pump inhibitor in healthy subjects
Authors: Sharma Shringi , Pepin Xavier , Cheung Jean , Zheng Lianqing , Wei Hua , Townsley Danielle , Han David , Majewski Michal , Ware Joseph A. , Mann James , Munugalavadla Veerendra , Sheridan Louise , Patel Priti , Gupta Ashok , Tomkinson Helen 
Published: April 2022

AimsAcalabrutinib, a selective Bruton tyrosine kinase inhibitor, is approved for the treatment of mantle cell lymphoma and chronic lymphocytic leukaemia. Many critically ill patients are unable to swallow and need oral medications to be delivered via a nasogastric (NG) tube. Furthermore, critically ill patients are typically administered proton‐pump inhibitors (PPIs) to prevent stress ulcers. Concomitant administration with PPIs reduces acalabrutinib exposure and is not currently recommended. To evaluate acalabrutinib in subjects co‐administered with PPIs who require NG delivery, a phase 1, open‐label, randomized, crossover, single‐dose study was conducted in healthy subjects.MethodsThe study assessed the relative bioavailability of an acalabrutinib suspension—in regular, degassed Coca‐Cola—administered via NG tube (Acala‐NG) versus the pharmacokinetics (PK) of an acalabrutinib capsule administered orally with water. In addition, the PPI effect was evaluated by comparing the PK following Acala‐NG in the presence or absence of rabeprazole.ResultsExposure of acalabrutinib and its active metabolite (ACP‐5862) were comparable following administration of Acala‐NG versus the oral capsule (Geo mean ratio, % ref [90% confidence interval, CI]: acalabrutinib AUCinf: 103 [93‐113]; Cmax: 144 [120‐173]). In addition, exposure was similar following administration of Acala‐NG with and without a PPI (Geo mean ratio, % ref [90% CI]: acalabrutinib AUCinf: 105 [79‐138]; Cmax: 95 [66‐137]). No safety or tolerability concerns were observed, and all adverse events were mild and resolved without treatment.ConclusionsAcala‐NG with or without a PPI is safe and well‐tolerated without impeding bioavailability.
Global sharing of COVID‐19 therapies during a “New Normal”
Authors: Jecker Nancy S. , Atuire Caesar A. 
Published: April 2022

AbstractThis paper argues for global sharing of COVID‐19 treatments during the COVID‐19 pandemic and beyond based on principles of global solidarity. It starts by distinguishing two types of COVID‐19 treatments and models sharing strategies for each in small‐group scenarios, contrasting groups that are solidaristic with those composed of self‐interest maximizers to show the appeal of solidaristic reasoning. It then extends the analysis, arguing that a similar logic should apply within and between nations. To further elaborate global solidarity, the paper distinguishes morally voluntary, sliding‐scale, and mandatory versions. It argues for an all‐hands‐on‐deck approach and gives examples to illustrate. The paper concludes that during the COVID‐19 crisis, global solidarity is a core value, and global sharing of COVID‐19 treatments should be considered a duty of justice, not of charity.
Ferroptosis is induced by lenvatinib through fibroblast growth factor receptor‐4 inhibition in hepatocellular carcinoma
Authors: Iseda Norifumi , Itoh Shinji , Toshida Katsuya , Tomiyama Takahiro , Morinaga Akinari , Shimokawa Masahiro , Shimagaki Tomonari , Wang Huanlin , Kurihara Takeshi , Toshima Takeo , Nagao Yoshihiro , Harada Noboru , Yoshizumi Tomoharu , Mori Masaki 
Published: April 2022

AbstractThe tyrosine kinase inhibitor lenvatinib is used to treat advanced hepatocellular carcinoma (HCC). Ferroptosis is a type of cell death characterized by the iron‐dependent accumulation of lethal lipid reactive oxygen species (ROS). Nuclear factor erythroid‐derived 2‐like 2 (Nrf2) protects HCC cells against ferroptosis. However, the mechanism of lenvatinib‐induced cytotoxicity and the relationships between lenvatinib resistance and Nrf2 are unclear. Thus, we investigated the relationship between lenvatinib and ferroptosis and clarified the involvement of Nrf2 in lenvatinib‐induced cytotoxicity. Cell viability, lipid ROS levels, and protein expression were measured using Hep3B and HuH7 cells treated with lenvatinib or erastin. We examined these variables after silencing fibroblast growth factor receptor‐4 (FGFR4) or Nrf2 and overexpressing‐Nrf2. We immunohistochemically evaluated FGFR4 expression in recurrent lesions after resection and clarified the relationship between FGFR4 expression and lenvatinib efficacy. Lenvatinib suppressed system Xc− (xCT) and glutathione peroxidase 4 (GPX4) expression. Inhibition of the cystine import activity of xCT and GPX4 resulted in the accumulation of lipid ROS. Silencing‐FGFR4 suppressed xCT and GPX4 expression and increased lipid ROS levels. Nrf2‐silenced HCC cells displayed sensitivity to lenvatinib and high lipid ROS levels. In contrast, Nrf2‐overexpressing HCC cells displayed resistance to lenvatinib and low lipid ROS levels. The efficacy of lenvatinib was significantly lower in recurrent HCC lesions with low‐FGFR4 expression than in those with high‐FGFR4 expression. Patients with FGFR4‐positive HCC displayed significantly longer progression‐free survival than those with FGFR4‐negative HCC. Lenvatinib induced ferroptosis by inhibiting FGFR4. Nrf2 is involved in the sensitivity of HCC to lenvatinib.
Association of Nrf2 expression and mutation with Weiss and Helsinki scores in adrenocortical carcinoma
Authors: Kamai Takao , Murakami Satoshi , Arai Kyoko , Ishida Kazuyuki , Kijima Toshiki 
Published: April 2022

AbstractAdrenocortical carcinoma (ACC) is a rare malignant tumor. Genetic abnormalities that may represent therapeutic targets and prognostic factors in ACC remain unclear. Besides being one of the main cellular defense mechanisms that regulates antioxidant pathways for detoxifying reactive oxygen species (ROS), the transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) promotes tumor proliferation by increasing metabolic activity. In surgical specimens from 12 cases of nonmetastatic ACCs and nine cases of benign adrenocortical adenoma (ACA), we investigated gene mutation and protein expressions for Nrf2 and the preoperative maximum standard glucose uptake (SUVmax) on [18F]fluorodeoxy‐glucose positron emission tomography. Three of five ACCs with a Weiss score of 7 to 9 were Nrf2 mutants; these ACCs had higher expression of Nrf2 and higher preoperative SUVmax. The other seven ACCs had a Weiss score of 3 to 6; these seven ACCs and all the ACAs were non‐Nrf2 gene mutants. Patients with a Weiss score of 7 to 9 and Nrf2 mutant ACC had shorter overall survival. Based on Helsinki scoring, three ACCs with a Helsinki score greater than 17 had Nrf2 mutants, higher expression of Nrf2, higher preoperative SUVmax, and shorter overall survival. Our findings indicate that Nrf2 activation and the associated increase in metabolism play roles in ACC, in particular in ACC with a Weiss score of 7 to 9 and a Helsinki score of greater than 17.
Soft tissue response to different abutment materials: A controlled and randomized human study using an experimental model
Authors: Enkling Norbert , Marder Michael , Bayer Stefan , Götz Werner , Stoilov Milan , Kraus Dominik 
Published: April 2022

AbstractObjectivesAim of this study was to compare the soft tissue response to implant abutments made of titanium, zirconia, zirconia veneered with feldspar ceramics and PEEK by various clinical, histological, microbiological, and molecular biological markers in an experimental model.Materials and MethodsA total of 40 experimental one‐piece healing abutments of four different materials were mounted on bone level implants in 20 volunteering patients (split‐mouth design). After a three‐month period of open healing, clinical parameters at the abutments were assessed and adjacent mucosa was sampled for inflammatory cytokine mRNA concentrations and histological analysis by a novel method. In addition, PISF samples were obtained for the analysis of periodonto‐pathogenic bacteria counts and active MMP‐8 levels. Marginal bone level change was measured by intra oral radiographs.ResultsAbutments of the different materials did not exhibit significant differences regarding clinical parameters, pathogenic bacteria counts or pro‐inflammatory cytokine concentrations. Likewise, no significant differences were detected regarding soft tissue morphology or bone level change. Compared to titanium abutments, significantly less mononuclear inflammatory cells were detected in the mucosa at abutments made of zirconia veneered with feldspar ceramics.ConclusionsAll examined abutment materials exhibited a similar soft tissue response compared to titanium and histological data did not reveal early signs of elevated inflammation caused by PEEK‐ and feldspar‐veneered zirconia abutments. Due to the short observation period and the small sample size, a final conclusion on the long‐term suitability of those abutment materials cannot be drawn. However, based on the presented data, we consider further studies on that subject as appropriate.
Epidemiologie von Hautkrankheiten in Deutschland: systematische Literaturanalyse des aktuellen Forschungsstands – Teil 2: nichtinfektiöse Hauterkrankungen
Authors: Hansen Inga , Augustin Matthias , Schäfer Ines , Mohr Nicole 
Published: April 2022

ZusammenfassungDas Ziel dieser Arbeit war die systematische Erfassung aller bisher publizierten bevölkerungsbezogenen epidemiologischen Daten zu Hauterkrankungen in Deutschland.Der vorliegende Teil 2 der Publikationsserie thematisiert die nichtinfektiösen Hauterkrankungen. Die Ergebnisse zu den Tumorerkrankungen der Haut (Teil 1) sowie zu den infektiösen Hauterkrankungen (Teil 3) bilden die weiteren Teile dieser Publikationsreihe.Es wurde eine systematische Literaturrecherche mit PubMed/MEDLINE für den Zeitraum der letzten 15 Jahre durchgeführt. Mit dem Ziel, alle dermatologischen Erkrankungen einzuschließen, wurde eine Diagnoseliste auf Basis des ICD‐11‐Katalogs erstellt. Diese Liste umfasste 1347 Hautkrankheiten und bildete die Basis für die Recherche.Die Literaturrecherche ergab 4650 Treffer, von denen 72 in die Synthese eingeschlossen wurden. Darunter waren 37 Publikationen zu nichtinfektiösen Hauterkrankungen. Hierunter waren die Psoriasis und das atopische Ekzem am häufigsten vertreten. Die höchste Lebenszeitprävalenz fand sich zur Akne.Diese Arbeit ist die erste systematische Literaturrecherche, die zum Ziel hatte, alle verfügbaren epidemiologischen Daten zu Hautkrankheiten in Deutschland zu berichten. Hierbei zeigte sich, dass zu vielen nichtinfektiösen Erkrankungen bisher keine repräsentativen Daten vorliegen. Unter den eingeschlossenen Arbeiten fand sich eine hohe Heterogenität hinsichtlich der Methodik. Dennoch ist der Nutzen dieser epidemiologischen Daten vielseitig und kann als Referenz verschiedenster epidemiologischer Fragestellungen dienen.
Novel echocardiographic score to predict duct‐dependency after percutaneous relief of critical pulmonary valve stenosis/atresia
Authors: Giordano Mario , Santoro Giuseppe , Gaio Gianpiero , Cappelli Bigazzi Maurizio , Esposito Raffaella , Marzullo Raffaella , Di Masi Antonio , Palladino Maria Teresa , Russo Maria Giovanna 
Published: April 2022

AbstractObjectivesThis study aimed to identify clinical, hemodynamic, or echocardiographic predictive features of persistent duct‐dependency of pulmonary circulation (PDDPC) after effective percutaneous relief of pulmonary atresia with the intact ventricular septum (PA‐IVS) or critical pulmonary stenosis (CPS).MethodsFrom 2010 to 2021, 55 neonates with PA‐IVS or CPS underwent percutaneous right ventricle (RV) decompression at our Institution. After successfully relief of critical obstruction, 27 patients (group I) showed PDDPC, whereas RV was able to support the pulmonary circulation in the remaining 28 patients (group II). Clinical, hemodynamic, and echocardiographic features of these two groups were compared.ResultsNo significant difference in clinical and hemodynamic data was found between the groups, although the group I had a lower oxygen saturation at hospital admission. However, tricuspid valve (TV) diameter <8.8 mm, TV z‐score ←2.12, tricuspid/mitral valve annular ratio <.78, pulmonary valve diameter <6.7 mm, pulmonary valve z‐score ←1.17, end‐diastolic RV area <1.35 cm2, end‐systolic right atrium area >2.45 cm2, percentage amount of interatrial right‐to‐left shunt >69.5%, moderate/severe tricuspid regurgitation, RV systolic pressure >42.5 mmHg, tricuspid E/E′ ratio >6.6 showed each significant predictive value of PDDPC. These parameters were used to build a composite echocardiographic score (PDDPC‐score), assigning one point each above the respective cut‐off value. A score ≥4.00 showed high sensitivity (100%) and specificity (86%) in predicting PDDPC.ConclusionClinical and hemodynamic features fail to predict the short‐term fate of the pulmonary circulation after successful treatment of PA‐IVS/CPS. However, a simple, composite echocardiographic score is useful to predict PDDPC and could be crucial in the management of this frail subset of patients.
Reduced genetic diversity of freshwater amphipods in rivers with increased levels of anthropogenic organic micropollutants
Authors: Švara Vid , Michalski Stefan G. , Krauss Martin , Schulze Tobias , Geuchen Stephan , Brack Werner , Luckenbach Till 
Published: April 2022

AbstractAnthropogenic chemicals in freshwater environments contribute majorly to ecosystem degradation and biodiversity decline. In particular anthropogenic organic micropollutants (AOM), a diverse group of compounds, including pesticides, pharmaceuticals, and industrial chemicals, can significantly impact freshwater organisms. AOM were found to impact genetic diversity of freshwater species; however, to which degree AOM cause changes in population genetic structure and allelic richness of freshwater macroinvertebrates remains poorly understood. Here, the impact of AOM on genetic diversity of the common amphipod Gammarus pulex (Linnaeus, 1758) (clade E) was investigated on a regional scale. The site‐specific AOM levels and their toxic potentials were determined in water and G. pulex tissue sample extracts for 34 sites along six rivers in central Germany impacted by wastewater effluents and agricultural run‐off. Population genetic parameters were determined for G. pulex from the sampling sites by genotyping 16 microsatellite loci. Genetic differentiation among G. pulex from the studied rivers was found to be associated with geographic distance between sites and to differences in site‐specific concentrations of AOM. The genetic diversity parameters of G. pulex were found to be related to the site‐specific AOM levels. Allelic richness was significantly negatively correlated with levels of AOM in G. pulex tissue (p < 0.003) and was reduced by up to 22% at sites with increased levels of AOM, despite a positive relationship of allelic richness and the presence of waste‐water effluent. In addition, the inbreeding coefficient of G. pulex from sites with toxic AOM levels was up to 2.5 times higher than that of G. pulex from more pristine sites. These results indicate that AOM levels commonly found in European rivers significantly contribute to changes in the genetic diversity of an ecologically relevant indicator species.
Impact of the 2018 Japan Floods on prescriptions for migraine: A longitudinal analysis using the National Database of Health Insurance Claims
Authors: Okazaki Yuji , Yoshida Shuhei , Kashima Saori , Koike Soichi , Matsumoto Masatoshi 
Published: April 2022

AbstractObjectiveTo determine the impact of the 2018 Japan Floods, one of the largest water disasters in Japan, on the number of prescriptions for triptans and ergotamine (acute treatment).BackgroundNatural disasters frequently occur worldwide and may cause psychological stress–related diseases. Acute migraine attacks can be triggered by psychological stress. Disaster victims are likely to experience tremendous psychological stress; however, the relationship between natural disasters and migraine attacks is not well investigated.MethodsA retrospective longitudinal cohort study was conducted using the National Database of Health Insurance Claims in the hardest‐hit areas of the disaster 1 year before and after the disaster. We included people between the ages of 15 and 64 years. Those who had a victim code that was certificated by a local government were assigned to the victim group, and others to the nonvictim group. For those who were not prescribed acute treatment before the disaster (i.e., group without previous acute treatment), the cumulative incidence of new prescriptions for acute treatment at 12 months of follow‐up was calculated and compared between victims and nonvictims with survival analysis.ResultsOf 3,475,515 people aged 15 to 64 years enrolled in the study, 16,103 (0.46%) were assigned to the victim group. In the group without previous acute treatment, 111 (0.70%) of 15,933 victims and 14,626 (0.43%) of 3,431,423 nonvictims were newly prescribed acute treatment after the disaster, and new prescriptions for acute treatment were significantly more likely to occur in victims than in nonvictims (adjusted hazard ratio, 1.68; 95% CI, 1.39–2.02).ConclusionsThe 2018 Japan Floods increased the number of prescriptions for acute migraine medications among victims, suggesting that acute migraine attacks occurred more frequently after a natural disaster.
Zircon U–Pb ages of the Higo plutonic complex: Implication for migration of Cretaceous igneous activity in Kyushu, southwest Japan
Authors: Tsutsumi Yukiyasu 
Published: April 2022

AbstractZircon U–Pb weighted mean ages of seven samples from the Higo plutonic complex (HPC) in Kyushu were determined as follows; Shiraishino granodiorite: 109.3 ± 0.9 Ma and 109.0 ± 1.1 Ma; Kugushima granodiorite: 109.1 ± 1.1 Ma; Miyanohara tonalite: 107.7 ± 1.3 Ma and 108.3 ± 0.9 Ma; Manzaka tonalite: 108.0 ± 0.9 Ma; Joyama tonalite: 112.7 ± 1.2 Ma. The plutonism of batholithic granitoids in the HPC occurred in 109–108 Ma, and granitic intrusions occurred in 113 Ma. The previously reported zircon U–Pb ages range from 107 to 98 Ma in northern Kyushu and concentrate around about 106 Ma in the Chikuhi area in the northern part of central Kyushu. The previously published age data and newly obtained data in this study demonstrate that Cretaceous igneous activity in Kyushu migrated northward from 114 to 98 Ma, accompanied by widespread igneous activity throughout central and northern Kyushu at 106–105 Ma. The HPC situated in the southernmost part of central Kyushu was the origin of this northward migration.
Land‐use change differentially affects endemic, forest and open‐land butterflies in Madagascar
Authors: Wurz Annemarie , Grass Ingo , Lees David C. , Rakotomalala Anjaharinony A. N. A. , Sáfián Szabolcs , Martin Dominic Andreas , Osen Kristina , Loos Jacqueline , Benasoavina Evrard , Alexis Theudy , Tscharntke Teja 
Published: April 2022

Abstract
The conversion of tropical forests into agriculture reduces biodiversity dramatically. However, species might differ in their responses, depending on their habitat specialisation and geographic origin. In this study, we assess how butterfly assemblages differ between old‐growth forests, forest fragments, forest‐derived vanilla agroforests, fallow‐derived vanilla agroforests, woody fallows, herbaceous fallows, and rice paddies in Madagascar.
We recorded 88 butterfly species, of which 65 species are endemic to Madagascar. Land‐use types with woody vegetation sustained many endemic (mean: 6.8 species) and forest butterfly species (mean: 4.8 species). Rice paddies and herbaceous fallows were richer in open‐land species (mean: 7.6 species) and poorer in forest species (mean: 1.7 species) compared to other land‐use types. Compared to herbaceous fallows, fallow‐derived vanilla agroforests hosted more endemic (+164%) and forest (+239%) species. Richness of open‐land species in forest‐derived vanilla agroforests was six times higher than in forest fragments.
Overall, 27% of species occurred exclusively in one land‐use type and 19% of all species when old‐growth forests were excluded. We found the highest number of exclusive species in forest‐derived vanilla agroforests.
We conclude that all studied land‐use types contribute to butterfly conservation in our study region. Especially the woody vegetation in forest fragments, vanilla agroforests, and woody fallows supports a high butterfly diversity and is pivotal for maintaining a broad diversity of forest butterflies in the agricultural matrix. Our study highlights the importance of preserving the diversity of small‐scale land‐use types, including agroforestry, forests and fallow land in this tropical biodiversity hotspot.