bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visual displays in a nocturnal rhacophorid frog (Buergeria japonica)
Authors: Anderson Nigel K. , Legett Henry D. , Aihara Ikkyu , Bernal Ximena E. 
Published: September 2021

Abstract
We report a visual display, leg-stretching, in the nocturnal Ryukyu Kajika frog (Buergeria japonica) on Iriomote Island in southern Okinawa, Japan. This visual display is produced by males before, during, or after a vocalization and involves the extension of one or both hindlimbs outwards at substrate level. Leg-stretches in this species are performed during male-male agonistic interactions in choruses, and almost exclusively in concert with aggressive vocalizations. These observations are one of the first reports of visual displays for the Rhacophoridae family and provide insights into why visual displays evolve in frogs, especially in nocturnal species. We discuss our observations in the context of underlying mechanisms and selective pressures driving the evolution of anuran visual displays.
Variations of Tropical Lapse Rates in Climate Models and their Implications for Upper Tropospheric Warming
Authors: Keil P. , Schmidt H. , Stevens B. , Bao J. 
Published: September 2021

AbstractThe vertical temperature structure in the tropics is primarily set by convection and therefore follows a moist adiabat to first order. However, tropical upper tropospheric temperatures differ among climate models and observations, as atmospheric convection remains poorly understood. Here, we quantify the variations in tropical lapse rates in CMIP6 models and explore reasons for these variations. We find that differences in surface temperatures weighted by the regions of strongest convection cannot explain these variations and therefore we hypothesise that the representation of convection itself and associated small scale processes are responsible. We reproduce these variations in perturbed physics experiments with the global atmospheric model ICON-A, in which we vary autoconversion and entrainment parameters. For smaller autoconversion values, additional freezing enthalpy from the cloud water that is not precipitated warms the upper troposphere. Smaller entrainment rates also lead to a warmer upper troposphere, as convection and thus latent heating reaches higher. Furthermore, we show that according to most radiosonde datasets all CMIP6 AMIP simulations overestimate recent upper tropospheric warming. Additionally, all radiosonde datasets agree that climate models on average overestimate the amount of upper tropospheric warming for a given lower tropospheric warming. We demonstrate that increased entrainment rates reduce this overestimation, likely because of the reduction of latent heat release in the upper troposphere. Our results suggest that imperfect convection parameterisations are responsible for a considerable part of the variations in tropical lapse rates and also part of the overestimation of warming compared to the observations.
An Assessment of Climate Feedbacks in Observations and Climate Models Using Different Energy Balance Frameworks
Authors: Chao Li-Wei , Dessler Andrew E. 
Published: September 2021

AbstractThis study evaluates the performance of Coupled Model Intercomparison Project (CMIP) phase 5 and phase 6 models by comparing feedbacks in models to those inferred from observations. Overall, we find no systematic disagreements between the feedbacks in the model ensembles and feedbacks inferred from observations, although there is a wide range in the ability of individual models to reproduce the observations. In particular, 40 of 52 models have best estimates that fall within the uncertainty of the observed total feedback. We quantify two sources of uncertainty in the model ensembles: (1) the structural difference, due to the differences in model parameterizations, and (2) the unforced pattern effect, due to unforced variability, and find that both are important when comparing to an 18-year observational data set. We perform the comparison using two energy balance frameworks: the traditional energy balance framework, in which it is assumed that changes in energy balance are controlled by changes in global average surface temperatures, and an alternative framework that assumes the changes in energy balance are controlled by tropical atmospheric temperatures. We find that the alternative framework provides a more robust way of comparing the models to observations, with both smaller structural differences and smaller unforced pattern effect. However, when considering the relation of feedbacks in response to interannual variability and long-term warming, the traditional framework has advantages. There are no great differences between the CMIP5 and CMIP6 ensembles’ ability to reproduce the observed feedbacks.
The impact of del Nido cardioplegia solution on blood morphology parameters
Authors: Sanetra Krzysztof , Domaradzki Wojciech , Cisowski Marek , Shrestha Rajesh , Białek Krzysztof , Bochenek Andrzej , Jankowska-Sanetra Justyna , Paweł Buszman Piotr , Gerber Witold 
Published: September 2021

Background: Crystalloid cardioplegic solutions are believed to reduce hemoglobin significantly and increase the transfusion rate. However, recent reports indicate that the del Nido cardioplegia may preserve blood morphology parameters. Methods: In “The del Nido versus cold blood cardioplegia in aortic valve Replacement” trial patients undergoing aortic valve replacement were randomized into the del Nido (DN) or cold blood cardioplegia (CB) group. For the subanalysis, patients who underwent blood transfusions were excluded from the study. Red blood cell (RBC) count, hemoglobin, white blood cell (WBC) count and platelet (PLT) count were measured before the surgery, 24-, 48-, and 96 hours postoperatively. Furthermore, percental variation in first-last measure was compared in groups. In addition, indexed normalized ratio (INR) and activated partial thromboplastin time (aPTT) were compared preoperatively and 24 hours after the surgery. Results: Eighteen (24%) patients from the del Nido group and 22 (29.3%) patients from the CB group received blood product transfusions (p = 0.560) and were excluded from further analysis. As such, 57 patients remained in DN group and 53 patients remained in CB group. No difference was found in RBC, hemoglobin, WBC, and platelet count in time intervals. Percental variation in first-last measure revealed higher fall in RBC (p = 0.0024) and hemoglobin (p = 0.0028) in the CB group. No difference was shown in preoperative and 24-hour postoperative INR and aPTT. Conclusions: The del Nido cardioplegia does not decrease blood morphology parameters when compared to cold blood cardioplegia and may be used alternatively regardless of bleeding and coagulopathy risk.
Establishment of a prognostic model for patients with sepsis based on SOFA: a retrospective cohort study
Authors: Liu Hui , Zhang Luming , Xu Fengshuo , Li Shaojin , Wang Zichen , Han Didi , Zhang Feng , Lyu Jun , Yin Haiyan 
Published: September 2021

Objective To construct a nomogram based on the Sequential Organ Failure Assessment (SOFA) that is more accurate in predicting 30-, 60-, and 90-day mortality risk in patients with sepsis. Methods Data from patients with sepsis were retrospectively collected from the Medical Information Mart for Intensive Care (MIMIC) database. Included patients were randomly divided into training and validation cohorts. Variables were selected using a backward stepwise selection method with Cox regression, then used to construct a prognostic nomogram. The nomogram was compared with the SOFA model using the concordance index (C-index), area under the time-dependent receiver operating characteristics curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA). Results A total of 5240 patients were included in the study. Patient’s age, SOFA score, metastatic cancer, SpO2, lactate, body temperature, albumin, and red blood cell distribution width were included in the nomogram. The C-index, AUC, NRI, IDI, and DCA of the nomogram showed that it performs better than the SOFA alone. Conclusion A nomogram was established that performed better than the SOFA in predicting 30-, 60-, and 90-day mortality risk in patients with sepsis.
Is there a role for tapered topical dose steroidal treatment for dry eye disease? A randomized, pilot study
Authors: Barabino Stefano , Montaldo Elisa , Mingari Maria Cristina , Mazzotta Cosimo , Giuffrida Sebastiano , Rolando Maurizio 
Published: September 2021

Purpose: To evaluate the effect of tapered doses of loteprednol-etabonate in dry eye disease patients. Materials and methods: Dry eye and treatment outcomes were assessed by Schirmer I test, tear BUT, lissamine green conjunctival staining, fluorescein corneal staining, and HLA-DR expression on conjunctival cells. Patients received either loteprednol-etabonate 0.5% twice daily for 14 days tapered to once daily for 14 days, and then twice weekly for 28 days ( n = 10), or NaCl 0.9%. Results: A significant decrease of ocular surface inflammation and improvement of symptoms was recorded in the study group compared with controls at days 14 and 56. Change from baseline in HLA-DR expression in CD45+ conjunctival cells was significantly higher in treated patients at day 14. Intraocular pressure and best corrected visual acuity were preserved in all treated eyes. Conclusions: Tapered doses of loteprednol etabonate 0.5% suspension controlled ocular surface inflammation, improving dry eye symptoms.
Evaluation of optimal medical therapy in acute myocardial infarction patients with prior stroke
Authors: Zhang Dongfeng , Song Xiantao , Raposeiras-Roubín Sergio , Abu-Assi Emad , Simao Henriques Jose Paulo , D’Ascenzo Fabrizio , Saucedo Jorge , González-Juanatey José Ramón , Wilton Stephen B. , Kikkert Wouter J. , Nuñez-Gil Iván , Ariza-Sole Albert , Alexopoulos Dimitrios , Liebetrau Christoph , Kawaji Tetsuma , Moretti Claudio , Huczek Zenon , Nie Shaoping , Fujii Toshiharu , Correia Luis , Kawashiri Masa-aki , Southern Danielle , Kalpak Oliver 
Published: September 2021

Background: Treatment of acute myocardial infarction (AMI) patients with prior stroke is a common clinical dilemma. Currently, the application of optimal medical therapy (OMT) and its impact on clinical outcomes are not clear in this patient population. Methods: We retrieved 765 AMI patients with prior stroke who underwent percutaneous coronary intervention (PCI) during the index hospitalization from the international multicenter BleeMACS registry. All of the subjects were divided into two groups based on the prescription they were given prior to discharge. Baseline characteristics and procedural variables were compared between the OMT and non-OMT groups. Mortality, re-AMI, major adverse cardiovascular events (MACE), and bleeding were followed-up for 1 year. Results: Approximately 5% of all patients presenting with AMI were admitted to the hospital for ischemic stroke. Although the prescription rate of each OMT medication was reasonably high (73.3%–97.3%), 47.7% lacked at least one OMT medication. Patients receiving OMT showed a significantly decreased occurrence of mortality (4.5% vs 15.1%, p < 0.001), re-AMI (4.2% vs 9.3%, p = 0.004), and the composite endpoint of death/re-AMI (8.6% vs 20.5%, p < 0.001) compared to those without OMT. No significant difference was observed between the groups regarding bleeding. After adjusting for confounding factors, OMT was the independent protective factor of 1-year mortality, while age was the independent risk factors. Conclusions: OMT at discharge was associated with a significantly lower 1-year mortality of patients with AMI and prior stroke in clinical practice. However, OMT was provided to just half of the eligible patients, leaving room for substantial improvement. Clinical Trial Registration: NCT02466854
Pro-protein convertase subtilisin/kexin type 9 promotes intestinal tumor development by activating Janus kinase 2/signal transducer and activator of transcription 3/SOCS3 signaling in ApcMin/+ mice
Authors: Yang Kai , Zhu Jie , Luo Huan-hua , Yu Shu-wen , Wang Lu 
Published: September 2021

Introduction Pro-protein convertase subtilisin/kexin type 9 (PCSK9) regulates lipoprotein homeostasis in humans. Evolocumab is a selective PCSK9 inhibitor that can reduce low-density lipoprotein cholesterol (LDLC) level and decrease hypercholesterolemia. The current study aimed to explore whether PCSK9 increases the risk of colorectal cancer. Methods First, we utilized the classic intestinal tumor ApcMin/+ mouse model and PCSK9 knock-in (KI) mice to establish ApcMin/+PCSK9(KI) mice. Then, we investigated the effect of PCSK9 overexpression in ApcMin/+PCSK9(KI) mice and PCSK9 inhibition using evolocumab on the progression of intestinal tumors in vivo by hematoxylin and eosin (HE) staining, Western blot, and immunohistochemistry (IHC) assay. Results ApcMin/+PCSK9(KI) mice had higher numbers and larger sizes of adenomas, with 83.3% of these mice developing adenocarcinoma (vs. 16.7% of ApcMin/+ mice). However, treatment with evolocumab reduced the number and size of adenomas and prevented the development of adenocarcinomas in ApcMin/+ mice. PCSK9 overexpression reduced tumor cell apoptosis, the Bax/bcl-2 ratio, and the levels of cytokine signaling 3 protein (SOCS3) suppressors, but activated Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling in intestinal tumors. In contrast, evolocumab treatment had the opposite effect on ApcMin/+mice. Conclusion PCSK9 might act as an oncogene or have an oncogenic role in the development and progression of colorectal cancer in vivo via activation of JAK2/STAT3/SOCS3 signaling.
Efficient production of human neutrophils from iPSCs that prevent murine lethal infection with immune cell recruitment
Authors: Miyauchi Masashi , Ito Yusuke , Nakahara Fumio , Hino Toshiya , Nakamura Fumi , Iwasaki Yuki , Kawagoshi Taiki , Koya Junji , Yoshimi Akihide , Arai Shunya , Kagoya Yuki , Kurokawa Mineo 
Published: September 2021

AbstractNeutrophils play an essential role in innate immune responses to bacterial and fungal infections, and loss of neutrophil function can increase the risk of acquiring lethal infections in clinical settings. Here, we show that engineered neutrophil-primed progenitors derived from human induced pluripotent stem cells can produce functional neutrophil-like cells at a clinically applicable scale that can act rapidly in vivo against lethal bacterial infections. Using 5 different mouse models, we systematically demonstrated that these neutrophil-like cells migrate to sites of inflammation and infection and increase survival against bacterial infection. In addition, we found that these human neutrophil-like cells can recruit murine immune cells. This system potentially provides a straight-forward solution for patients with neutrophil deficiency: an off-the-shelf neutrophil transfusion. This platform should facilitate the administration of human neutrophils for a broad spectrum of physiological and pathological conditions.
The bone marrow niche from the inside out: how megakaryocytes are shaped by and shape hematopoiesis
Authors: Stone Andrew P. , Nascimento Thais F. , Barrachina Maria N. 
Published: September 2021

Abstract
Megakaryocytes (MKs), the largest of the hematopoietic cells, are responsible for producing platelets by extending and depositing long proplatelet extensions into the bloodstream. The traditional view of megakaryopoiesis describes the cellular journey from hematopoietic stem cells (HSCs) along the myeloid branch of hematopoiesis. However, recent studies suggest that MKs can be generated from multiple pathways, some of which do not require transit through multipotent or bipotent MK-erythroid progenitor stages in steady-state and emergency conditions. Growing evidence suggests that these emergency conditions are due to stress-induced molecular changes in the bone marrow (BM) microenvironment, also called the BM niche. These changes can result from insults that affect the BM cellular composition, microenvironment, architecture, or a combination of these factors. In this review, we explore MK development, focusing on recent studies showing that MKs can be generated from multiple divergent pathways. We highlight how the BM niche may encourage and alter these processes using different mechanisms of communication, such as direct cell-to-cell contact, secreted molecules (autocrine and paracrine signaling), and the release of cellular components (eg, extracellular vesicles). We also explore how MKs can actively build and shape the surrounding BM niche.
Insights in ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopenia
Authors: Greinacher Andreas , Selleng Kathleen , Palankar Raghavendra , Wesche Jan , Handtke Stefan , Wolff Martina , Aurich Konstanze , Lalk Michael , Methling Karen , Völker Uwe , Hentschker Christian , Michalik Stephan , Steil Leif , Reder Alexander , Schönborn Linda , Beer Martin , Franzke Kati , Büttner Andreas , Fehse Boris , Stavrou Evi X. , Rangaswamy Chandini , Mailer Reiner K. , Englert Hanna , Frye Maike , Thiele Thomas , Kochanek Stefan , Krutzke Lea , Siegerist Florian , Endlich Nicole , Warkentin Theodore E. , Renné Thomas 
Published: September 2021

AbstractSARS-CoV-2 vaccine ChAdOx1 nCoV-19 (AstraZeneca) causes a thromboembolic complication termed vaccine-induced immune thrombotic thrombocytopenia (VITT). Using biophysical techniques, mouse models, and analysis of VITT patient samples, we identified determinants of this vaccine-induced adverse reaction. Super-resolution microscopy visualized vaccine components forming antigenic complexes with platelet factor 4 (PF4) on platelet surfaces to which anti-PF4 antibodies obtained from VITT patients bound. PF4/vaccine complex formation was charge-driven and increased by addition of DNA. Proteomics identified substantial amounts of virus production-derived T-REx HEK293 proteins in the ethylenediaminetetraacetic acid (EDTA)-containing vaccine. Injected vaccine increased vascular leakage in mice, leading to systemic dissemination of vaccine components known to stimulate immune responses. Together, PF4/vaccine complex formation and the vaccine-stimulated proinflammatory milieu trigger a pronounced B-cell response that results in the formation of high-avidity anti-PF4 antibodies in VITT patients. The resulting high-titer anti-PF4 antibodies potently activated platelets in the presence of PF4 or DNA and polyphosphate polyanions. Anti-PF4 VITT patient antibodies also stimulated neutrophils to release neutrophil extracellular traps (NETs) in a platelet PF4-dependent manner. Biomarkers of procoagulant NETs were elevated in VITT patient serum, and NETs were visualized in abundance by immunohistochemistry in cerebral vein thrombi obtained from VITT patients. Together, vaccine-induced PF4/adenovirus aggregates and proinflammatory reactions stimulate pathologic anti-PF4 antibody production that drives thrombosis in VITT. The data support a 2-step mechanism underlying VITT that resembles the pathogenesis of (autoimmune) heparin-induced thrombocytopenia.
SARS-CoV-2 vaccination and ITP in patients with de novo or preexisting ITP
Authors: Lee Eun-Ju , Beltrami-Moreira Marina , Al-Samkari Hanny , Cuker Adam , DiRaimo Jennifer , Gernsheimer Terry , Kruse Alexandra , Kessler Craig , Kruse Caroline , Leavitt Andrew D. , Lee Alfred I. , Liebman Howard A. , Newland Adrian C. , Ray Ashley E. , Tarantino Michael D. , Thachil Jecko , Kuter David J. , Cines Douglas B. , Bussel James B. 
Published: September 2021

Abstract
Cases of de novo immune thrombocytopenia (ITP), including a fatality, following SARS-CoV-2 vaccination in previously healthy recipients led to studying its impact in preexisting ITP. In this study, 4 data sources were analyzed: the Vaccine Adverse Events Reporting System (VAERS) for cases of de novo ITP; a 10-center retrospective study of adults with preexisting ITP receiving SARS-CoV-2 vaccination; and surveys distributed by the Platelet Disorder Support Association (PDSA) and the United Kingdom (UK) ITP Support Association. Seventy-seven de novo ITP cases were identified in VAERS, presenting with median platelet count of 3 [1-9] ×109/L approximately 1 week postvaccination. Of 28 patients with available data, 26 responded to treatment with corticosteroids and/or intravenous immunoglobulin (IVIG), and/or platelet transfusions. Among 117 patients with preexisting ITP who received a SARS-CoV-2 vaccine, 19 experienced an ITP exacerbation (any of: ≥50% decline in platelet count, nadir platelet count &lt;30 × 109/L with &gt;20% decrease from baseline, and/or use of rescue therapy) following the first dose and 14 of 70 after a second dose. Splenectomized persons and those who received 5 or more prior lines of therapy were at highest risk of ITP exacerbation. Fifteen patients received and responded to rescue treatment. In surveys of both 57 PDSA and 43 UK patients with ITP, prior splenectomy was associated with worsened thrombocytopenia. ITP may worsen in preexisting ITP or be identified de novo post–SARS-CoV2 vaccination; both situations responded well to treatment. Proactive monitoring of patients with known ITP, especially those postsplenectomy and with more refractory disease, is indicated.
Clinical presentation and outcomes of non-typhoidal Salmonella infections in patients with cancer
Authors: Mori Nobuyoshi , Szvalb Ariel D. , Adachi Javier A. , Tarrand Jeffrey J. , Mulanovich Victor E. 
Published: September 2021

Abstract
Background
Non-typhoidal Salmonella (NTS) infection is thought to be more severe in cancer patients, but this has not been studied since the development of new cancer therapies, increasing antibiotic resistance and the introduction of new antibiotics. We sought to describe the demographic characteristics, microbiological findings, clinical manifestations, and outcomes of NTS infections in cancer patients at our institution.

Methods
We reviewed microbiology laboratory records and identified patients who had cancer and from whom NTS organisms were recovered between January 1, 2000 and December 31, 2013, at a comprehensive cancer center in Houston, Texas. Descriptive statistics were used to summarize patient characteristics, clinical presentation and outcomes.

Results
We identified 110 isolates from 82 patients with 88 episodes of NTS infection (including five relapses [6%] in four patients, and two consecutive episodes in one patient). Fifty-five patients (67%) had hematologic malignancies. Most NTS isolates were susceptible to the commonly prescribed antimicrobials. Sixty-nine percent of patients had sepsis and one-third had severe sepsis or septic shock. Gastroenteritis, bacteremia, or both were present in 69% of patients, and the rest had focal infection. Mortality at 30 days was low (8%). Relapses occurred only in patients receiving ≤ 10 days of antibiotic therapy.

Conclusions
NTS affects predominantly patients with hematologic malignancies, followed by gastrointestinal and genitourinary cancers. Invasive disease, sepsis, and septic shock are common presentations among admitted patients. Antimicrobial prophylaxis may not prevent NTS infection. Thirty-day mortality and attributable mortality rates were low in our series compared to older case series. Early appropriate antibiotic therapy may have had a role in decreasing mortality. Relapses occurred in patients receiving ≤ 10 days of therapy, suggesting the need for longer duration of antibiotic therapy in cancer patients with uncomplicated NTS infections.