bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epsilon aminocaproic acid is associated with acute kidney injury after life‐threatening hemorrhage in children
Authors: Kolodziej Julia H. , Leeper Christine M. , Leonard Julie C. , Josephson Cassandra D. , Zenati Mazen S. , Spinella Philip C. 
Published: April 2023

AbstractBackgroundAntifibrinolytic medications have been associated with reduced mortality in pediatric hemorrhage but may contribute to adverse events such as acute kidney injury (AKI).Study Design and MethodsWe conducted a secondary analysis of the MAssive Transfusion in Children (MATIC), a prospectively collected database of children with life‐threatening hemorrhage (LTH), and evaluated for risk of adverse events with either antifibrinolytic treatment, epsilon aminocaproic acid (EACA) or tranexamic acid (TXA). The primary outcome was AKI and secondary outcomes were acute respiratory distress syndrome (ARDS) and sepsis.ResultsOf 448 children included, median (interquartile range) age was 7 (2–15) years, 55% were male, and LTH etiology was 46% trauma, 34% operative, and 20% medical. Three hundred and ninety‐three patients did not receive an antifibrinolytic (88%); 37 (8%) received TXA and 18 (4%) received EACA. Sixty‐seven (17.1%) patients in the no antifibrinolytic group developed AKI, 6 (16.2%) patients in the TXA group, and 9 (50%) patients in the EACA group (p = .002). After adjusting for cardiothoracic surgery, cyanotic heart disease, preexisting renal disease, lowest hemoglobin pre‐LTH, and total weight‐adjusted transfusion volume during the LTH, the EACA group had increased risk of AKI (adjusted odds ratio 3.3 [95% CI: 1.0–10.3]) compared to no antifibrinolytic. TXA was not associated with AKI. Neither antifibrinolytic treatment was associated with ARDS or sepsis.ConclusionAdministration of EACA during LTH may increase the risk of AKI. Additional studies are needed to compare the risk of AKI between EACA and TXA in pediatric patients.
Adaptive closed‐loop resuscitation controllers for hemorrhagic shock resuscitation
Authors: Vega Saul J. , Berard David , Avital Guy , Ross Evan , Snider Eric J. 
Published: April 2023

AbstractBackgroundAfter hemorrhage control, fluid resuscitation is the most important intervention for hemorrhage. Even skilled providers can find resuscitation challenging to manage, especially when multiple patients require care. In the future, attention‐demanding medical tasks like fluid resuscitation for hemorrhage patients may be reassigned to autonomous medical systems when availability of skilled human providers is limited, such as in austere military settings and mass casualty incidents. Central to this endeavor is the development and optimization of control architectures for physiological closed‐loop control systems (PCLCs). PCLCs can take many forms, from simple table look‐up methods to widely used proportional–integral–derivative or fuzzy‐logic control theory. Here, we describe the design and optimization of multiple adaptive resuscitation controllers (ARCs) that we have purpose‐built for the resuscitation of hemorrhaging patients.Study Design and MethodsThree ARC designs were evaluated that measured pressure–volume responsiveness using different methodologies during resuscitation from which adapted infusion rates were calculated. These controllers were adaptive in that they estimated required infusion flow rates based on measured volume responsiveness. A previously developed hardware‐in‐loop test platform was used to evaluate the ARCs implementations across several hemorrhage scenarios.ResultsAfter optimization, we found that our purpose‐built controllers outperformed traditional control system architecture as embodied in our previously developed dual‐input fuzzy‐logic controller.DiscussionFuture efforts will focus on engineering our purpose‐built control systems to be robust to noise in the physiological signal coming to the controller from the patient as well as testing controller performance across a range of test scenarios and in vivo.
Thermal, Dynamic Mechanical, Mechanical and Flammability Properties of Halloysite Nanotubes Filled Polyamide 11 Nanocomposites
Authors: Azahari Nur Najma Athirah , Anuar Hazleen , Hassan Azman , Jawaid Mohammed , Halim Zahurin , Samsudin Sani Amril 
Published: April 2023

The effects of various filler contents on the thermal, dynamic mechanical, mechanical, as well as flammability properties of halloysite nanotubes (HNTs) filler and polyamide 11 (PA 11) matrixes are investigated in this research. The nanocomposites were made out of 100 phr of PA 11 and three distinct HNTs loadings of 2, 4, and 6 phr each. PA 11 nanocomposites without HNTs filler was used as the reference sample. To melt-compound the nanocomposites, a twin-screw extruder was used, and the specimen for testing was then injected using an injection mold. SEM, TGA, DSC, FTIR, DMA, tensile, flexural, impact, and UL-94 flammability tests were conducted on the nanocomposites. Incorporation of 4 phr HNTs into the nanocomposites resulted in the highest tensile and flexural strength. Maximum improvement in the DMA, Young’s and flexural modulus was achieved at 6 phr HNTs content. The elongation at break and TGA resulted the highest increase at 2 phr HNTs content. However, the impact strength decreased with increasing HNTs content. Scanning electron microscopy revealed the ductility of the nanocomposites with increased HNTs content up to 4 phr. The DSC showed a steady increase in melting temperature (Tm) as HNTs content increased up to 4 phr, while the crystallization temperature (Tc) remained unchanged. TGA of PA 11/HNTs nanocomposites showed high thermal stability at 2 phr HNTs content. However, on further addition of HNTs up to 6 phr, thermal stability of the nanocomposites decreased due to the excess amount of HNTs. All the nanocomposites passed the horizontal and vertical UL-94 test with HB and V-2 grade. PA 11/4HNTs nanocomposite has the highest tensile strength, flexural strength compared to other PA 11/HNTs nanocomposites. PA 11/4HNTs nanocomposite can be suggested as an optimum formulation with balanced mechanical properties in terms of toughness.
Optimization of CTLA-4 and PD-1 proteins in EMT6 Mouse Mammary Cancer Cells by Western Blot
Authors: Sham Nur Fatihah Ronny , Hasani Narimah Abdul Hamid , Idorus Mohd Yusri , Karim Muhammad Khalis Abdul , Syed Ahmad Fuad Syed Baharom , Hasbullah Harissa Husainy , Ibahim Mohammad Johari 
Published: April 2023

Targeting the activation of immune checkpoints is recognized as an effective strategy for triggering anti-tumour immune responses in cancer cells. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) were identified as potential crucial targets for cancer treatment. Overexpression of CTLA-4 and PD-1 proteins in primary tumour and human cell lines is well documented. In contrary, lack of data was available using animal cell lines. The presence study aims to optimize the expression of CTLA-4 and PD-1 proteins in EMT6 mouse mammary cancer cells using Western blot, and provide basic understanding of their association with breast cancer cell progression. Proteins extracted from EMT6 parental cells were adjusted to 30ng for gel electrophoresis. Afterwards, the protein was transferred to a nitrocellulose membrane for blotting. The membrane was then subjected to chemiluminescent for band detection. Results obtained using beta-actin as a housekeeping gene show that both CTLA-4 (32 kDa) and PD-1 (34 kDa) proteins were expressed by using a 1:1000 dilution for each antibody from the lysate of EMT6 mouse mammary cancer cells. The relative expression of PD-1 (4.0 ± 0.26) is higher compared to CTLA-4 (1.2 ± 1.8). As a conclusion, both CTLA-4 and PD-1 proteins were indeed expressed in EMT6 mouse mammary cancer cells and this outcome provide the platform for extensive in vivo research on the link of both proteins with breast cancer using animal model.
Estado de la investigación contable en Perú: Una revisión desde la academia y el gremio profesional
Authors: Díaz Becerra Oscar Alfredo , Choy Zevallos Elsa Esther 
Published: April 2023

La investigación contable en Perú tiene un desarrollo incipiente y con poca producción, en particular, en revistas científicas locales, situación que ha mejorado en los últimos años con las estrategias implementadas. Este artículo tiene como propósito determinar el estado actual de la investigación contable desarrollada en las universidades y en los colegios de contadores públicos departamentales, a través del órgano de investigación de la Junta de Decanos de Colegios de Contadores Públicos del Perú (JDCCPP), para ello se revisó bibliografía pública como también privada, utilizando el método analítico, con una visión descriptiva y la técnica de revisión documental. Los resultados evidencian baja producción en investigación contable en la academia y poco desarrollo de competencias en el proceso formativo del contador, como observación, reflexión, análisis y predicción. En el caso del gremio profesional contable, también existe baja producción intelectual, lo que genera espacios laborales para otras disciplinas o las nuevas que aparezcan en esta era de transformación digital, por lo que se concluye que la investigación contable será el fundamento de soporte de las nuevas competencias profesionales que necesita el contador para solucionar problemas complejos que presenta el quehacer profesional.
Mobility and Dual Tasking in the Everyday Lives of Adults with Multiple Sclerosis: A Qualitative Exploration
Authors: VanNostrand Michael , Emberley Katie , Cairns Erin , Shanahan Kristina , Kasser Susan L. 
Published: April 2023

Objective: The purpose of the study was to understand how people with multiple sclerosis experience dual-tasking situations in their everyday lives. Methods: Focus groups involving a total of 11 individuals with multiple sclerosis (eight females and three males) participated in this qualitative inquiry. Participants were asked open-ended questions focused on the nature of and consequences around dual tasking when standing or walking. Reflexive thematic analysis was employed to examine the data. Results: Three themes were generated from the data: (a) Life Is a Dual Task, (b) The Social Divide, and (c) Sacrifices for Stability. Conclusions: This study highlights the significance and impact of dual tasking on the lived experience of adults with multiple sclerosis, furthering the need to more fully examine this phenomenon and potentially improve fall-prevention interventions and facilitate community participation.
Denosumab and incidence of type 2 diabetes among adults with osteoporosis: population based cohort study
Authors: Lyu Houchen , Zhao Sizheng Steven , Zhang Licheng , Wei Jie , Li Xiaoxiao , Li Hui , Liu Yi , Yin Pengbin , Norvang Vibeke , Yoshida Kazuki , Tedeschi Sara K , Zeng Chao , Lei Guanghua , Tang Peifu , Solomon Daniel H 
Published: April 2023

Abstract

Objective
To estimate the effect of denosumab compared with oral bisphosphonates on reducing the risk of type 2 diabetes in adults with osteoporosis.

Design
Population based study involving emulation of a randomized target trial using electronic health records.

Setting
IQVIA Medical Research Data primary care database in the United Kingdom, 1995-2021.

Participants
Adults aged 45 years or older who used denosumab or an oral bisphosphonate for osteoporosis.

Main outcome measures
The primary outcome was incident type 2 diabetes, as defined by diagnostic codes. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals, comparing denosumab with oral bisphosphonates using an as treated approach.

Results
4301 new users of denosumab were matched on propensity score to 21 038 users of an oral bisphosphonate and followed for a mean of 2.2 years. The incidence rate of type 2 diabetes in denosumab users was 5.7 (95% confidence interval 4.3 to 7.3) per 1000 person years and in oral bisphosphonate users was 8.3 (7.4 to 9.2) per 1000 person years. Initiation of denosumab was associated with a reduced risk of type 2 diabetes (hazard ratio 0.68, 95% confidence interval 0.52 to 0.89). Participants with prediabetes appeared to benefit more from denosumab compared with an oral bisphosphonate (hazard ratio 0.54, 0.35 to 0.82), as did those with a body mass index ≥30 (0.65, 0.40 to 1.06).

Conclusions
In this population based study, denosumab use was associated with a lower risk of incident type 2 diabetes compared with oral bisphosphonate use in adults with osteoporosis. This study provides evidence at a population level that denosumab may have added benefits for glucose metabolism compared with oral bisphosphonates.
Optimized density and locations of stroke centers for improved cost effectiveness of mechanical thrombectomy in patients with acute ischemic stroke
Authors: Ennab Vogel Nicklas , Wester Per , Andersson Granberg Tobias , Levin Lars-Åke 
Published: April 2023

BackgroundDespite the proven cost effectiveness of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion, treatment within 6 hours from symptom onset remains inaccessible for many patients. We aimed to find the optimal number and location of treatment facilities with respect to the cost effectiveness of MT in patients with AIS, first by the most cost effective implementation of comprehensive stroke centers (CSCs), and second by the most cost effective addition of complementary thrombectomy capable stroke centers (TSCs).MethodsThis study was based on nationwide observational data comprising 18 793 patients with suspected AIS potentially eligible for treatment with MT. The most cost effective solutions were attained by solving the p median facility location–allocation problem with the objective function of maximizing the incremental net monetary benefit (INMB) of MT compared with no MT in patients with AIS. Deterministic sensitivity analysis (DSA) was used as the basis of the results analysis.ResultsThe implementation strategy with seven CSCs produced the highest annual INMB per patient of all possible solutions in the base case scenario. The most cost effective implementation strategy of the extended scenario comprised seven CSCs and four TSCs. DSA revealed sensitivity to variability in MT rate and the maximum willingness to pay per quality adjusted life year gained.ConclusionThe combination of optimization modeling and cost effectiveness analysis provides a powerful tool for configuring the extent and locations of CSCs (and TSCs). The most cost effective implementation of CSCs in Sweden entails 24/7 MT services at all seven university hospitals.
On full subdirect products of a bi-semilattice and a (zero-symmetric) near-ring
Authors: Mukherjee Rajlaxmi , Chakraborty Kamalika , Sardar Sujit Kumar 
Published: April 2023

In order to find an analogue of the structure theorem,“a semigroup is a full subdirect product of a semilattice and a group if and only if it is an [Formula: see text]-inversive sturdy semilattice of cancellative monoids (Theorem 14 of [H. Mitsch, Subdirect products of E-inversive semigroups, J. Austral. Math. Soc. 48 (1990) 66–78])”, in the setting of seminearrings we have characterized the seminearrings which are full subdirect products of a bi-semilattice and a (zero-symmetric) near-ring and which are subdirect products of a distributive lattice and a (zero-symmetric) near-ring.
Data from Multicenter Phase I Trial of Ivosidenib as Maintenance Treatment Following Allogeneic Hematopoietic Cell Transplantation for <i>IDH1</i>-Mutated Acute Myeloid Leukemia
Authors: Fathi Amir T. , Kim Haesook T. , Soiffer Robert J. , Levis Mark J. , Li Shuli , Kim Annette S. , DeFilipp Zachariah , El-Jawahri Areej , McAfee Steve L. , Brunner Andrew M. , Amrein Philip C. , Mims Alice S. , Knight Laura W. , Kelley Devon , Bottoms AJ S. , Perry Lindsey H. , Wahl Jonathan L. , Brock Jennifer , Breton Elayne , Marchione Dylan M. , Ho Vincent T. , Chen Yi-Bin 
Published: April 2023

<div>AbstractPurpose:<p>Isocitrate dehydrogenase 1 (<i>IDH1</i>) mutations occur in 5% to 10% of patients with acute myeloid leukemia (AML). Ivosidenib is an IDH1 inhibitor, approved for use in patients with <i>IDH1</i>-mutated AML.</p>Methods:<p>We conducted a multicenter, phase I trial of maintenance ivosidenib following allogeneic hematopoietic cell transplantation (HCT) in patients with <i>IDH1</i>-mutated AML. Ivosidenib was initiated between days 30 and 90 following HCT and continued for up to 12 28-day cycles. The first dose level was 500 mg daily, with level reduction to 250 mg daily, if needed, in a 3 × 3 de-escalation design. Ten additional patients would then receive the MTD or recommended phase 2 dose (RP2D). The primary endpoint was establishing the MTD or RP2D of ivosidenib.</p>Results:<p>Eighteen patients were enrolled, of whom 16 initiated post-HCT ivosidenib. One dose-limiting toxicity, grade(g) 3 QTc prolongation, was observed. The RP2D was established at 500 mg daily. Attributable g≥3 adverse events were uncommon, with the most common being QTc prolongation in 2 patients. Eight patients discontinued maintenance, with only one due to adverse event. Six-month cumulative incidence (CI) of gII-IV aGVHD was 6.3%, and 2-year CI of all cGVHD was 63%. Two-year CI of relapse and nonrelapse mortality (NRM) were 19% and 0%, respectively. Two-year progression-free (PFS) was 81%, and 2-year overall survival (OS) was 88%.</p>Conclusions:<p>Ivosidenib is safe and well-tolerated as maintenance therapy following HCT. Cumulative incidence of relapse and NRM, as well as estimations of PFS and OS, were promising in this phase I study.</p></div>
MDM2 Inhibition Enhances Immune Checkpoint Inhibitor Efficacy by Increasing IL15 and MHC Class II Production
Authors: Langenbach Marlene , Giesler Sophie , Richtsfeld Stefan , Costa-Pereira Sara , Rindlisbacher Lukas , Wertheimer Tobias , Braun Lukas M. , Andrieux Geoffroy , Duquesne Sandra , Pfeifer Dietmar , Woessner Nadine M. , Menssen Hans D. , Taromi Sanaz , Duyster Justus , Börries Melanie , Brummer Tilman , Blazar Bruce R. , Minguet Susana , Turko Patrick , Levesque Mitchell P. , Becher Burkhard , Zeiser Robert 
Published: April 2023

Abstract

The treatment of patients with metastatic melanoma with immune checkpoint inhibitors (ICI) leads to impressive response rates but primary and secondary resistance to ICI reduces progression-free survival. Novel strategies that interfere with resistance mechanisms are key to further improve patient outcome during ICI therapy. P53 is often inactivated by mouse-double-minute-2 (MDM2), which may decrease immunogenicity of melanoma cells. We analyzed primary patient-derived melanoma cell lines, performed bulk sequencing analysis of patient-derived melanoma samples, and used melanoma mouse models to investigate the role of MDM2-inhibition for enhanced ICI therapy. We found increased expression of IL15 and MHC-II in murine melanoma cells upon p53 induction by MDM2-inhibition. MDM2-inhibitor induced MHC-II and IL15-production, which was p53 dependent as Tp53 knockdown blocked the effect. Lack of IL15-receptor in hematopoietic cells or IL15 neutralization reduced the MDM2-inhibition/p53-induction–mediated antitumor immunity. P53 induction by MDM2-inhibition caused anti-melanoma immune memory as T cells isolated from MDM2-inhibitor–treated melanoma-bearing mice exhibited anti-melanoma activity in secondary melanoma-bearing mice. In patient-derived melanoma cells p53 induction by MDM2-inhibition increased IL15 and MHC-II. IL15 and CIITA expressions were associated with a more favorable prognosis in patients bearing WT but not TP53-mutated melanoma.

Implications:
MDM2-inhibition represents a novel strategy to enhance IL15 and MHC-II–production, which disrupts the immunosuppressive tumor microenvironment. On the basis of our findings, a clinical trial combining MDM2-inhibition with anti–PD-1 immunotherapy for metastatic melanoma is planned.
Data from Patterns of Oncogene Coexpression at Single-Cell Resolution Influence Survival in Lymphoma
Authors: Hoppe Michal Marek , Jaynes Patrick , Shuangyi Fan , Peng Yanfen , Sridhar Shruti , Hoang Phuong Mai , Liu Clementine Xin , De Mel Sanjay , Poon Limei , Chan Esther Hian Li , Lee Joanne , Ong Choon Kiat , Tang Tiffany , Lim Soon Thye , Nagarajan Chandramouli , Grigoropoulos Nicholas F. , Tan Soo-Yong , Hue Susan Swee-Shan , Chang Sheng-Tsung , Chuang Shih-Sung , Li Shaoying , Khoury Joseph D. , Choi Hyungwon , III Carl Harris , Bottos Alessia , Gay Laura J. , Runge Hendrik F.P. , Moutsopoulos Ilias , Mohorianu Irina , Hodson Daniel J. , Farinha Pedro , Mottok Anja , Scott David W. , Pitt Jason J. , Chen Jinmiao , Kumar Gayatri , Kannan Kasthuri , Chng Wee Joo , Chee Yen Lin , Ng Siok-Bian , Tripodo Claudio , Jeyasekharan Anand D. 
Published: April 2023

<div>Abstract<p>Cancers often overexpress multiple clinically relevant oncogenes, but it is not known if combinations of oncogenes in cellular subpopulations within a cancer influence clinical outcomes. Using quantitative multispectral imaging of the prognostically relevant oncogenes <i>MYC</i>, <i>BCL2</i>, and <i>BCL6</i> in diffuse large B-cell lymphoma (DLBCL), we show that the percentage of cells with a unique combination <i>MYC</i>+<i>BCL2</i>+<i>BCL6</i>− (M+2+6−) consistently predicts survival across four independent cohorts (<i>n</i> = 449), an effect not observed with other combinations including M+2+6+. We show that the M+2+6− percentage can be mathematically derived from quantitative measurements of the individual oncogenes and correlates with survival in IHC (<i>n</i> = 316) and gene expression (<i>n</i> = 2,521) datasets. Comparative bulk/single-cell transcriptomic analyses of DLBCL samples and <i>MYC</i>/<i>BCL2</i>/<i>BCL6</i>-transformed primary B cells identify molecular features, including cyclin D2 and PI3K/AKT as candidate regulators of M+2+6− unfavorable biology. Similar analyses evaluating oncogenic combinations at single-cell resolution in other cancers may facilitate an understanding of cancer evolution and therapy resistance.</p>Significance:<p>Using single-cell–resolved multiplexed imaging, we show that selected subpopulations of cells expressing specific combinations of oncogenes influence clinical outcomes in lymphoma. We describe a probabilistic metric for the estimation of cellular oncogenic coexpression from IHC or bulk transcriptomes, with possible implications for prognostication and therapeutic target discovery in cancer.</p></div>
O igualitarianismo de Mary Wollstonecraft em A Vindication of the Rights of Men
Authors: Ostrensky Eunice 
Published: April 2023

Em A Vindication of the Rights of Men, Mary Wollstonecraft elabora uma resposta a Reflections on the Revolution in France, de Edmund Burke, com base na oposição irredutível entre justiça e o estatuto da propriedade fundiária aristocrática. Entre os vários efeitos perniciosos da dominação dos proprietários sobre os não-proprietários, está a opressão das mulheres, legitimada pelo emprego da linguagem da sensibilidade. O artigo visa discutir a análise de Wollstonecraft sobre os fundamentos da sociedade aristocrática, lançando luz sobre seus valores morais.
Naming and Free Will
Authors: Merlussi Pedro , Lampert Fabio 
Published: April 2023

Abstract
Rigidity does interesting philosophical work, with important consequences felt throughout metaphysics, epistemology, philosophy of mind, and so on. The authors’ aim in this article is to show that rigidity has yet another role to play, with surprising consequences for the problem of free will and determinism, for the phenomenon of rigidity has the upshot that some metaphysically necessary truths are up to us. The significance of this claim is shown in the context of influential arguments against free will. The authors show that some virtually indisputable inference rules employed in formulations of the Consequence Argument, as well as in fatalistic arguments, fail with a variety of counter-examples. Along the way, the authors compare the present arguments to other, similar arguments made in recent years.