bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing and amount of southern Cascadia earthquake subsidence over the past 1700 years at northern Humboldt Bay, California, USA
Authors: Padgett Jason S. , Engelhart Simon E. , Kelsey Harvey M. , Witter Robert C. , Cahill Niamh , Hemphill-Haley Eileen 
Published: February 2021

AbstractStratigraphic, lithologic, foraminiferal, and radiocarbon analyses indicate that at least four abrupt mud-over-peat contacts are recorded across three sites (Jacoby Creek, McDaniel Creek, and Mad River Slough) in northern Humboldt Bay, California, USA (∼44.8°N, −124.2°W). The stratigraphy records subsidence during past megathrust earthquakes at the southern Cascadia subduction zone ∼40 km north of the Mendocino Triple Junction. Maximum and minimum radiocarbon ages on plant macrofossils from above and below laterally extensive (&gt;6 km) contacts suggest regional synchroneity of subsidence. The shallowest contact has radiocarbon ages that are consistent with the most recent great earthquake at Cascadia, which occurred at 250 cal yr B.P. (1700 CE). Using Bchron and OxCal software, we model ages for the three older contacts of ca. 875 cal yr B.P., ca. 1120 cal yr B.P., and ca. 1620 cal yr B.P.For each of the four earthquakes, we analyze foraminifera across representative mud-over-peat contacts selected from McDaniel Creek. Changes in fossil foraminiferal assemblages across all four contacts reveal sudden relative sea-level (RSL) rise (land subsidence) with submergence lasting from decades to centuries. To estimate subsidence during each earthquake, we reconstructed RSL rise across the contacts using the fossil foraminiferal assemblages in a Bayesian transfer function. The coseismic subsidence estimates are 0.85 ± 0.46 m for the 1700 CE earthquake, 0.42 ± 0.37 m for the ca. 875 cal yr B.P. earthquake, 0.79 ± 0.47 m for the ca. 1120 cal yr B.P. earthquake, and ≥0.93 m for the ca. 1620 cal yr B.P. earthquake. The subsidence estimate for the ca. 1620 cal yr B.P. earthquake is a minimum because the pre-subsidence paleoenvironment likely was above the upper limit of foraminiferal habitation. The subsidence estimate for the ca. 875 cal yr B.P. earthquake is less than (&lt;50%) the subsidence estimates for other contacts and suggests that subsidence magnitude varied over the past four earthquake cycles in southern Cascadia.
Prehospital triage of patients with acute cardiac complaints: study protocol of HART-c, a multicentre prospective study
Authors: de Koning Enrico , Biersteker Tom E , Beeres Saskia , Bosch Jan , Backus Barbra E , Kirchhof Charles JHJ , Alizadeh Dehnavi Reza , Silvius Helen AM , Schalij Martin , Boogers Mark J 
Published: February 2021

IntroductionEmergency department (ED) overcrowding is a major healthcare problem associated with worse patient outcomes and increased costs. Attempts to reduce ED overcrowding of patients with cardiac complaints have so far focused on in-hospital triage and rapid risk stratification of patients with chest pain at the ED. The Hollands-Midden Acute Regional Triage—Cardiology (HART-c) study aimed to assess the amount of patients left at home in usual ambulance care as compared with the new prehospital triage method. This method combines paramedic assessment and expert cardiologist consultation using live monitoring, hospital data and real-time admission capacity.Methods and analysisPatients visited by the emergency medical services (EMS) for cardiac complaints are included. EMS consultation consists of medical history, physical examination and vital signs, and ECG measurements. All data are transferred to a newly developed platform for the triage cardiologist. Prehospital data, in-hospital medical records and real-time admission capacity are evaluated. Then a shared decision is made whether admission is necessary and, if so, which hospital is most appropriate. To evaluate safety, all patients left at home and their general practitioners (GPs) are contacted for 30-day adverse events.Ethics and disseminationThe study is approved by the LUMC’s Medical Ethics Committee. Patients are asked for consent for contacting their GPs. The main results of this trial will be disseminated in one paper.DiscussionThe HART-c study evaluates the efficacy and feasibility of a prehospital triage method that combines prehospital patient assessment and direct consultation of a cardiologist who has access to live-monitored data, hospital data and real-time hospital admission capacity. We expect this triage method to substantially reduce unnecessary ED visits.
Safety and feasibility of lung biopsy in diagnosis of acute respiratory distress syndrome: protocol for a systematic review and meta-analysis
Authors: Fukuda Yosuke , Sugimoto Hiroshi , Yamada Yoshie , Ito Hiroyuki , Tanaka Takeshi , Yoshida Takuo , Okamori Satoshi , Ando Koichi , Okada Yohei 
Published: February 2021

IntroductionAcute respiratory distress syndrome (ARDS) is a type of acute respiratory failure characterised by non-cardiac pulmonary oedema caused by various underlying conditions. ARDS is often pathologically characterised by diffuse alveolar damage, and its pathological findings have been reported to be associated with prognosis, although the adverse effects of lung biopsies to obtain pathological findings are still unclear. The purpose of this systematic review and meta-analysis is to reveal the safety and feasibility of lung biopsy in the diagnosis of ARDS.Methods and analysisWe will include studies that were published in MEDLINE and Cochrane Central Register of Controlled Trials until 1 June 2020. We will include the reports for critically ill patients in an intensive care unit or emergency department who undergo lung biopsy and require a mechanical ventilation. Two review authors will independently scan titles and abstracts of all identified studies. Furthermore, these two authors will read and assess the full text of study reports to identify trials that appeared broadly to address the subject of the review. We will perform a risk of bias assessment using the McMaster Quality Assessment Scale of Harms.Ethics and disseminationThis study will be based on the published data, therefore, it does not require ethical approval. The final results of the study will be published in a peer-reviewed journal.Trial registration numberUMIN000040650.
Evaluation of the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) in patients with suspected asthma: study protocol for a prospective diagnostic study
Authors: Kellerer Christina , Hapfelmeier Alexander , Jörres Rudolf A , Schultz Konrad , Brunn Benjamin , Schneider Antonius 
Published: February 2021

IntroductionThe measurement of fractional exhaled nitric oxide (FeNO) is promising for diagnosing asthma and might substitute for bronchial provocation (BP) tests. To evaluate the diagnostic accuracy of FeNO within a confirmatory study, the following hypotheses will be tested: (1) A FeNO cut-off >50 ppb (parts per billion) is suitable for diagnosing asthma (sensitivity 35%, specificity 95%); (2) If the clinical symptoms ‘allergic rhinitis’ and ‘wheezing’ are present, asthma can be diagnosed at FeNO >33 ppb with a positive predictive value (PPV)>70% and (3) A FeNO >33 ppb can predict responsiveness to inhaled corticosteroid (ICS) with a PPV>70%.Methods and analysisA prospective diagnostic study will be conducted in three practices of pneumologists in Germany. 300 patients suspected of suffering from asthma will be included. As an index test, patients perform FeNO measurement with the device NIOX VERO. As reference a test, patients are examined with whole bodyplethysmography and BP, if necessary. After 3 months, patients with an asthma diagnosis will be examined again to verify the diagnosis and evaluate ICS responsiveness. Patients who did not receive an asthma diagnosis at the initial examination will be phoned after 3 months and asked about persistent respiratory symptoms to exclude false negative findings. As a primary target, sensitivity and specificity of FeNO >50 ppb will be determined. As a secondary target the PPV for asthma at FeNO >33 ppb, when the symptoms ‘allergic rhinitis’ and ‘wheezing’ are present, will be calculated. Regarding ICS responsiveness, the PPV of FeNO >33 ppb will be determined.Ethics and disseminationThe study was approved by the Ethical Committee of the Technical University of Munich (Reference number 122/20 S). The major results will be published in peer-reviewed academic journals and disseminated through conferences.Trial registration numberDRKS00021125.
Antarctic palaeotopography
Authors: Paxman Guy J. G. 
Published: February 2021

Abstract
The development of a robust understanding of the response of the Antarctic Ice Sheet to present and projected future climatic change is a matter of key global societal importance. Numerical ice sheet models that simulate future ice sheet behaviour are typically evaluated with recourse to how well they reproduce past ice sheet behaviour, which is constrained by the geological record. However, subglacial topography, a key boundary condition in ice sheet models, has evolved significantly throughout Antarctica's glacial history. Since mantle processes play a fundamental role in the generation and modification of topography over geological timescales, an understanding of the interactions between the Antarctic mantle and palaeotopography is crucial for developing more accurate simulations of past ice sheet dynamics. This chapter provides a review of the influence of the Antarctic mantle on the long-term evolution of the subglacial landscape, through processes including structural inheritance, flexural isostatic adjustment, lithospheric cooling and thermal subsidence, volcanism and dynamic topography. The uncertainties associated with reconstructing these processes through time are discussed, as are important directions for future research and the implications of the evolving subglacial topography for the response of the Antarctic Ice Sheet to climatic and oceanographic change.
Crenolanib Regulates ERK and AKT/mTOR Signaling Pathways in RAS/BRAF-Mutated Colorectal Cancer Cells and Organoids
Authors: Fujino Shiki , Miyoshi Norikatsu , Ito Aya , Yasui Masayoshi , Ohue Masayuki , Ogino Takayuki , Takahashi Hidekazu , Uemura Mamoru , Matsuda Chu , Mizushima Tsunekazu , Doki Yuichiro , Eguchi Hidetoshi 
Published: February 2021

Abstract

Recently developed molecularly targeted therapies such as EGFR inhibitors have notably improved the prognosis of patients with cancer. However, patients with KRAS and BRAF mutations do not currently benefit from these therapies. Here, we aimed to examine potential effects of crenolanib as a new molecularly targeted therapy in colorectal cancer. We used multiple colorectal cancer cell lines to investigate the growth-inhibitory effect of crenolanib and its effect in combination with other cytotoxic agents. Primary cultures of patient-derived organoids (PDO), a model that reflects the heterogeneity of clinical colorectal cancer, were used to further validate the effects of crenolanib. Unlike cetuximab, crenolanib remarkably suppressed ERK and AKT/mTOR pathways in HT29 cells with BRAF mutation and in HCT116 cells with KRAS mutation with corresponding growth-suppressing effects. Additive or synergistic effects were observed in treatments with combination of crenolanib and other cytotoxic drugs. Moreover, crenolanib suppressed the expression of stem cell markers, such as OCT4, NANOG, and SOX2. These observations were substantiated in seven PDOs with KRAS mutation and two PDOs without KRAS/BRAF mutations, with crenolanib suppressing the growth of all PDOs regardless of their KRAS mutation status. Furthermore, crenolanib abrogated PDGF- and TGFβ-induced increase of OCT4-positive cells in PDOs. Together, these findings suggest that crenolanib may have clinical utility for patients with colorectal cancer, especially patients with KRAS/BRAF mutations.

Implications:
These findings indicate that crenolanib can be a useful target agent for patients with colorectal cancer, especially patients with KRAS/BRAF mutations.
Colorectal Cancer–Derived CAT1-Positive Extracellular Vesicles Alter Nitric Oxide Metabolism in Endothelial Cells and Promote Angiogenesis
Authors: Ikeda Atsushi , Nagayama Satoshi , Sumazaki Makoto , Konishi Makoto , Fujii Risa , Saichi Naomi , Muraoka Satoshi , Saigusa Daisuke , Shimada Hideaki , Sakai Yoshiharu , Ueda Koji 
Published: February 2021

AbstractAccumulating scientific evidences strongly support the importance of cancer-derived extracellular vesicles (EV) in organization of tumor microenvironment and metastatic niches, which are also considered as ideal tools for cancer liquid biopsy. To uncover the full scope of proteomic information packaged within EVs secreted directly from human colorectal cancer, we cultured surgically resected viable tissues and obtained tissue-exudative EVs (Te-EV). Our quantitative profiling of 6,307 Te-EV proteins and 8,565 tissue proteins from primary colorectal cancer and adjacent normal mucosa (n = 17) allowed identification of a specific cargo in colorectal cancer–derived Te-EVs, high-affinity cationic amino acid transporter 1 (CAT1, P = 5.0 × 10–3, fold change = 6.2), in addition to discovery of a new class of EV markers, VPS family proteins. The EV sandwich ELISA confirmed escalation of the EV-CAT1 level in plasma from patients with colorectal cancer compared with healthy donors (n = 119, P = 3.8 × 10–7). Further metabolomic analysis revealed that CAT1-overexpressed EVs drastically enhanced vascular endothelial cell growth and tubule formation via upregulation of arginine transport and downstream NO metabolic pathway. These findings demonstrate the potency of CAT1 as an EV-based biomarker for colorectal cancer and its functional significance on tumor angiogenesis.Implications:This study provides a proteome-wide compositional dataset for viable colorectal cancer tissue–derived EVs and especially emphasizes importance of EV-CAT1 as a key regulator of angiogenesis.
Identification and Therapeutic Targeting of GPR20, Selectively Expressed in Gastrointestinal Stromal Tumors, with DS-6157a, a First-in-Class Antibody–Drug Conjugate
Authors: Iida Kenji , Abdelhamid Ahmed Amr H. , Nagatsuma Akiko Kawano , Shibutani Tomoko , Yasuda Satoru , Kitamura Michiko , Hattori Chiharu , Abe Manabu , Hasegawa Jun , Iguchi Takuma , Karibe Tsuyoshi , Nakada Takashi , Inaki Koichiro , Kamei Reiko , Abe Yuki , Nomura Taisei , Andersen Jessica L. , Santagata Sandro , Hemming Matthew L. , George Suzanne , Doi Toshihiko , Ochiai Atsushi , Demetri George D. , Agatsuma Toshinori 
Published: February 2021

Abstract

Currently, the only approved treatments for gastrointestinal stromal tumor (GIST) are tyrosine kinase inhibitors (TKI), which eventually lead to the development of secondary resistance mutations in KIT or PDGFRA and disease progression. Herein, we identified G protein–coupled receptor 20 (GPR20) as a novel non–tyrosine kinase target in GIST, developed new GPR20 IHC, and assessed GPR20 expression in cell lines, patient-derived xenografts, and clinical samples from two institutes (United States and Japan). We studied GPR20 expression stratified by treatment line, KIT expression, GIST molecular subtype, and primary tumor location. We produced DS-6157a, an anti-GPR20 antibody–drug conjugate with a novel tetrapeptide-based linker and DNA topoisomerase I inhibitor exatecan derivative (DXd). DS-6157a exhibited GPR20 expression–dependent antitumor activity in GIST xenograft models including a GIST model resistant to imatinib, sunitinib, and regorafenib. Preclinical pharmacokinetics and safety profile of DS-6157a support its clinical development as a potential novel GIST therapy in patients who are refractory or have resistance or intolerance to approved TKIs.

Significance:
GPR20 is selectively expressed in GIST across all treatment lines, regardless of KIT/PDGFRA genotypes. We generated DS-6157a, a DXd-based antibody–drug conjugate that exhibited antitumor activity in GIST models by a different mode of action than currently approved TKIs, showing favorable pharmacokinetics and safety profiles.
This article is highlighted in the In This Issue feature, p. 1307
СИНТЕЗ ТА ВИВЧЕННЯ БІОЛОГІЧНОЇ АКТИВНОСТІ ПОЛІЦИКЛІЧНИХ 1-ТІОКСО-9,10a-ДИГІДРОПІРОЛО[3,4-b]КАРБАЗОЛ-3,10-ДІОНІВ
Authors: Kryshchyshyn-Dylevych A. P. 
Published: February 2021

Мета роботи. Дизайн та синтез нових конденсованих молекул на основі індольного та тіогідантоїнового (2-тіоксоімідазолідин-4-онового) циклів як потенційних «лікоподібних сполук». Дослідження їхньої протипухлинної активності.
Матеріали і методи. Органічний синтез, спектроскопія ЯМР, фармакологічний скринінг.
Результати й обговорення. Взаємодією 3-(4-оксо-2-тіоксотіазолідин-5-іліденметилен)-1H-індол-карбонових кислот із тіогідантоїном у середовищі ацетатної кислоти при нагріванні одержано конденсовані тетрациклічні 1-тіоксо-9,10a-дигідропіроло[3,4-b]карбазол-3,10-діони. У реакції метил-3-форміліндолін-2-карбоксилату із 2-тіогідантоїном утворюється метиловий естер 5-флюоро-3-(4-оксо-2-тіоксоімідазолідин-5-іліденметил)-1H-індол-2-карбонової кислоти. Антипроліферативну активність синтезованих сполук вивчали у концентрації 10-5 М на панелі ракових клітин.
Висновки. Опрацьовано ефективний метод синтезу 1-тіоксо-9,10a-дигідропіроло[3,4-b]карбазол-3,10-діонів. Встановлено помірний ефект синтезованих сполук щодо лінії раку нирок UO-31.
ОПИСОВЕ ПРОЄКТУВАННЯ УПРАВЛІННЯ ЯКІСТЮ МЕДИЧНОЇ ДОПОМОГИ ХВОРИМ З ГОСТРИМИ ПОРУШЕННЯМИ МОЗКОВОГО КРОВООБІГУ В ЧАСТИНІ ФАРМАКОТЕРАПІЇ
Authors: Levytska O. R. 
Published: February 2021

Мета роботи. Здійснити моделювання системи управління якістю медичної допомоги (МД) хворим з гострими порушеннями мозкового кровообігу (ГПМК), пов'язаною з використанням лікарських засобів (ЛЗ).
Матеріали і методи. Матеріалом дослідження були теоретичні питання управління якістю МД хворим з ГПМК в частині фармакотерапії. Використано концепцію управління якістю А. Фейгенбаума, методи системного підходу, інформаційного пошуку, узагальнення, моделювання.
Результати й обговорення. Опрацьовано модель управління якістю МД хворим з ГПМК, реалізація якої через інтеграцію 5 управлінських рівнів та 17 вертикальних функцій за концепцією управління якістю А. Фейгенбаума та скеровування основних зусиль на комплексний контроль якості МД уможливить доступ хворого з ГПМК до раціональної фармакотерапії (ФТ).
Висновок. На засадах концепції управління якістю А. Фейгенбаума опрацьована модель управління якістю МД хворим з ГПМК, реалізація якої закладами охорони здоров’я гіпотетично забезпечить отримання пацієнтами раціональної ФТ за комплексного контролю якості цього процесу, що в кінцевому результаті уможливить позитивний вплив на якість життя хворих з ГПМК.
Muslim Cultures beyond the Aperture: An East African Photo-Story Illuminated by First-Hand Accounts
Authors: Sheikh-Miller Nasira 
Published: February 2021

Abstract
This paper is an exploration of Indian Muslim culture in East Africa through pre- and post-independence eras via the medium of photography.
It examines the art and craft of photographic practice, the training of photographers, their social networks and those of their patrons, as well as the personal context of photographs. It also discusses the dispersal of archives and personal collections.
It is based upon first-hand accounts from professional photographers, their family members as well as patrons, whose ancestors travelled from India via Indian Ocean trade routes.
Fareh te chareh is a Gujarati proverb meaning ‘A person who roams advances.’
Performance Objects of Muḥarram in Iran: A Story through Steel
Authors: Collinet Annabelle 
Published: February 2021

Abstract
Some Muḥarram ceremonies in Iran today, such as taziyeh (ritual theatre) and dasteh (procession), often involve metal artifacts. They are commonly made of steel (mainly armor elements, arms, sculptures, and vessels). Many objects of similar types, generally without any historical data on their original contexts, are preserved in Islamic art collections. The present research proposes to identify these objects as Muḥarram performance objects. Based on two large collections (Paris, Musée du Louvre and Musée des Arts Décoratifs), this article aims to relocate them in their likely ritual contexts, especially those developed in the late Qajar period (from 1850 onward), and to look further into the past of their Safavid (1501–1722) models. Made of forged steel and inlaid with precious metals, these productions from the late Safavid period to the present day suggest the durability of some models with a strong visual identity and highlight the recurring use of this metal in Shiʿ⁠a devotional art in Iran.
High KIF11 expression is associated with poor outcome of NSCLC
Authors: Liu Junhui , Tian Yubin , Yi Lei , Gao Zhaojia , Lou Ming , Yuan Kai 
Published: February 2021

Purpose: To clarify the correlation between KIF11 (kinesin family member 11) and clinicopathologic characteristics of non-small cell lung cancer (NSCLC) and identify the prognostic value of KIF11 in patients with NSCLC. Methods: For investigating the expression of KIF11 in NSCLC, two tissue microarrays (TMAs: one contained 60 paired NSCLC tissues and paratumor tissues, the other contained 140 NSCLC tissues and 10 normal lung tissues) were constructed, stained, and scored. The Cancer Genome Atlas (TCGA) datasets were used to explore the differential expression level of KIF11 between NSCLC and paratumor. Kaplan-Meier survival curves were plotted and multivariate analysis were carried out. Results: The staining of KIF11 mainly distributed throughout the cytoplasm of tumor cells. Its expression was higher in NSCLC than paratumor cells, and similar results were obtained from TCGA datasets. We found that high expression of KIF11 had a significant correlation with lymph node metastases ( p = 0.024) and pathologic stage ( p = 0.018); that significant difference was not found in any other clinicopathologic characteristic. As univariate and multivariate analysis showed, KIF11 expression was significantly correlated with overall survival time of NSCLC ( p = 0.002, p = 0.025, respectively). High KIF11 expression was found to significantly associate with overall survival of stage II–III ( p = 0.001) and lung adenocarcinoma ( p = 0.036). Conclusion: High KIF11 expression predicts poor outcome in NSCLC. KIF11 is expected to be a viable prognostic biomarker for NSCLC.