bluuebunny/crossref_metadata_2025_split huggingface dataset:
Life Expectancy Loss among Native Americans During the COVID-19 Pandemic
Authors: Goldman Noreen , Andrasfay Theresa 
Published: March 2022

AbstractBackgroundThere has been little systematic research on the mortality impact of COVID-19 in the Native American population.ObjectiveWe provide estimates of loss of life expectancy in 2020 and 2021 for the Native American population.MethodsWe use data on age-specific all-cause mortality rates from CDC WONDER and the 2019 life table recently released by the National Vital Statistics System for Native Americans to calculate life tables for the Native American population in 2020 and 2021 and obtain estimates of life expectancy reductions during the COVID-19 pandemic.ResultsThe pandemic has set Native Americans further behind other major racial/ethnic groups in terms of life expectancy: the estimated loss in life expectancy at birth for Native Americans is 4.5 years in 2020 and 6.4 years in 2021.ConclusionsThese results underscore the disproportionate share of deaths experienced by Native Americans: a loss in life expectancy at birth in 2020 that is more than three years larger than that for Whites and about 1.5 years greater than the losses for the Black and Latino populations. Despite a successful vaccination campaign among Native Americans, the estimated loss in life expectancy at birth in 2021 unexpectedly exceeds that in 2020.ContributionThe increased loss in life expectancy in 2021, despite higher vaccination rates than in other racial/ethnic groups, highlights the huge challenges faced by Native Americans in their efforts to control the deleterious consequences of the pandemic.
Generation and proof-of-concept for allogeneic CD123 CAR-Delta One T (DOT) cells in Acute Myeloid Leukemia
Authors: Sánchez-Martínez Diego , Tirado Néstor , Mensurado Sofia , Martínez-Moreno Alba , Romecin Paola , Gutiérrez-Agüera Francisco , Correia Daniel V , Silva-Santos Bruno , Menéndez Pablo 
Published: March 2022

ABSTRACTChimeric Antigen Receptor (CAR)-T cells have emerged as a breakthrough treatment for relapse/refractory (r/r) hematological tumors, showing impressive complete remission rates in B-cell malignancies. However, around 50% of the patients relapse before 1-year post-treatment. T-cell “fitness” is critical to prolong the persistence and activity of the adoptively transferred product. Allogeneic T cells from healthy donors are less dysfunctional or exhausted than autologous patient-derived T cells, enabling a very attractive and cost-effective “off-the-shelf” therapy option. In this context, Delta One T cells (DOTs), a recently described cellular product based on MHC/HLA-independent Vδ1+ γδ T cells generated from the peripheral blood of healthy donors, represent a robust platform of allogeneic effector T cells. Here we generated and pre-clinically validated 4-1BB-based CAR-DOTs directed against the IL-3α chain receptor (CD123), a target antigen widely expressed on acute myeloid leukemia (AML) blasts. CD123CAR-DOTs showed vigorous, superior to control DOTs, cytotoxicity against AML cell lines and primary samples both in vitro and in vivo. Continuous administration of IL-15 supported the long-term persistence of a single-dose CD123CAR-DOTs in patient-derived xenograft models, sustaining their anti-leukemic efficacy as demonstrated in a re-challenge assay in vivo. Our results provide proof-of-concept for an allogeneic next-generation therapy based on CD123CAR-DOTs for r/r AML patients.KEY POINTS- CD123CAR-DOTs exert specific and robust cytotoxicity in vitro and anti-leukemic activity in vivo against AML cell lines and primary cells.- CD123CAR-DOTs show IL-15-dependent long-term persistence in vivo and vigorous anti-leukemic activity upon re-challenge.
Differential expression of Nanog 3UTR and coding region mRNA components defines an embryonic stem cell niche
Authors: Yang Ze , Ji Shaoyi , Gozali Leonardi , Ullah Mujib , Parsa Sophie , Behr Barry , Hynes Mary A. 
Published: March 2022

SummaryThe known molecular heterogeneity among pluripotent embryonic stem cells (ESCs) in culture may be maladaptive or a beneficial determinant of normal biology. In other systems such as hair and intestine, normal and dynamic heterogeneity among stem cells is necessary for balancing stem cell division and quiescence in order to maintain the stem cell pool. In ESCs, Sox2, Oct4 and Nanog (the SON genes) critically regulate pluripotency but their role in stem cell heterogeneity or pool maintenance is not clear. We previously reported an additional level of gene expression, the unexpected differential expression of mRNA coding region (CDS) and cognate 3′untranslated region (3UTR) components, often revealing novel developmental patterns. Here we show dramatic, patterned, concentric, differential expression of pluripotent gene 3UTR and CDS mRNA components in both undifferentiated ESCs in culture and in developing human and mouse embryos. This differential expression reveals robust pluripotent ESC heterogeneity that provides the underpinnings of a previously unrecognized ESC cell niche structure. A hallmark of the niche is the presence of cells expressing high levels of Nanog 3UTR but only low or no Nanog CDS at structure perimeters, We used a novel bioinformatic approach combining the 3UTR to CDS ratio and gene expression, and identified unique ESC clusters. High Nanog 3UTR cells have lower cell cycle activity and higher quiescence than other ESCs and express a distinct complement of cellular histone marks. These quiescent perimeter cells exchange with interior domains, opening the possibility that they act as cell replenishment reservoirs in the niche or the embryo. Functionally, the Nanog 3UTR, independent of its CDS, is critical, as its selective deletion decreases ESC cell division while increasing trophectoderm markers. Lastly, self-organization of ESCs according to pluripotent gene differential 3UTR and CDS expression is modified by activin signaling, indicating extrinsic modulation of the niche structure. Pluripotent embryonic stem cells, actively display regulated, dynamic differential expression of SON gene mRNA components, allowing the formation of a heterogenous, ordered, stem cell niche bordered by quiescent hub stem cells, thus illuminating the role of SON genes in pluripotent embryonic stem cell pool maintenance. More generally this suggests that differential mRNA component expression may widely define cell types that exist in non-permanent, different states in either development or disease.
Beyond the average: An updated framework for understanding the relationship between cell growth, DNA replication, and division in a bacterial system
Authors: Sanders Sara , Joshi Kunaal , Levin Petra Anne , Iyer-Biswas Srividya 
Published: March 2022

AbstractOur current understanding of the bacterial cell cycle is framed largely by population-based experiments that focus on the behavior of idealized average cells. Most famously, the contributions of Cooper and Helmstetter help to contextualize the phenomenon of overlapping replication cycles observed in rapidly growing bacteria. Despite the undeniable value of these approaches, their necessary reliance on the behavior of idealized average cells washes out the stochasticity inherent in single cell growth and physiology limiting their mechanistic value. To bridge this gap, we propose an updated and agnostic framework, informed by extant single-cell data, that quantitatively accounts for stochastic variations in single-cell dynamics and the impact of medium composition on cell growth and cell cycle progression. In this framework, stochastic timers sensitive to medium composition impact the relationship between cell cycle events, accounting for observed differences in the relationship between cell cycle events in slow and fast growing cells. We conclude with a roadmap for potential application of this framework to longstanding open questions in the bacterial cell cycle field.
Minimal SARS-CoV-2 classroom transmission at a large urban university experiencing repeated into campus introduction
Authors: Kuhfeldt Kayla , Turcinovic Jacquelyn , Sullivan Madison , Landaverde Lena , Doucette-Stamm Lynn , Hamer Davidson H. , Platt Judy , Klapperich Catherine , Landsberg Hannah E. , Connor John H. 
Published: March 2022

AbstractSARS-CoV-2, the causative agent of COVID-19, has displayed person to person transmission in a variety of indoor situations. This potential for robust transmission has posed significant challenges to day-to-day activities of colleges and universities where indoor learning is a focus. Concerns about transmission in the classroom setting have been of concern for students, faculty and staff. With the simultaneous implementation of both non-pharmaceutical and pharmaceutical control measures meant to curb the spread of the disease, defining whether in-class instruction without any physical distancing is a risk for driving transmission is important. We examined the evidence for SARS-CoV-2 transmission on a large urban university campus that mandated vaccination and masking but was otherwise fully open without physical distancing during a time of ongoing transmission of SARS-CoV-2 both at the university and in the surrounding counties. Using weekly surveillance testing of all on-campus individuals and rapid contact tracing of individuals testing positive for the virus we found little evidence of in-class transmission. Of more than 140,000 in-person class events, only nine instances of potential in-class transmission were identified. When each of these events were further interrogated by whole-genome sequencing of all positive cases significant genetic distance was identified between all potential in-class transmission pairings, providing evidence that all individuals were infected outside of the classroom. These data suggest that under robust transmission abatement strategies, in-class instruction is not an appreciable source of disease transmission.
Determinants and causes of early neonatal mortality: Hospital based retrospective cohort study in Somali region of Ethiopia
Authors: Tahir Ahmed Ahmed , Elmi Farah Abdifatah , Ali Hussein Nooh , Ibrahim Muse Obsiye 
Published: March 2022

AbstractBackgroundEarly neonatal mortality occurs when a newborn dies within the first seven days of life. Despite interventions, newborn mortality in Ethiopia has grown over time (33 death per 1000 live births). Determinants varies on level of neonatal mortality. The study’s goal was to determine magnitude of early newborn death, as well as its causes and drivers, in Newborn Intensive Care Unit of Referral hospital in Ethiopia’s Somali region.MethodsHealth facility based retrospective study review was conducted between May 2019 to May 2021 in Shiek Hassan Yabare Referral Hospital of Jigjiga University of Ethiopia. All neonates between 0 to 7 days admitted at NICU and get registered using the new NICU registration book from May 2019 to May 2021 with complete data were included. Kobo toolkit was used for data collection and analyzed in SPSS 20. Logistic regression model was used to estimate determinants.ResultThe magnitude of early neonatal mortality rate (defined as death between 0-7 days) of Ethiopia’s Somali region is estimated to be 130 per 1000 live births—That is say 130 newborn couldn’t celebrate their seventh day in every 1000 live births. Hypothermia, prematurity, maternal death at birth and shorter length of stay in NICU were increasing the chance of neonatal mortality at early stage while neonatal resuscitation had shown protective effect against neonatal mortality. Similarly birth asphyxia, preterm, sepsis, and congenital abnormalities were major causes of admission and death in the NICU.ConclusionThe magnitude of early neonatal mortality is considerable and causes are preventable. Enhancing quality of care including infection prevention and hypothermia through mentorship and encouraging the Kangaroo Mother Care practice is necessary at childbirth and NICU of the Hospital.
Phase separated ribosome nascent chain complexes paused in translation are capable to continue expression of proteins playing role in genotoxic stress response upon DNA damage
Authors: Németh-Szatmári Orsolya , Györkei Ádám , Varga Dániel , Kovács Bálint Barna H. , Igaz Nóra , Német Kristóf , Bagi Nikolett , Nagy-Mikó Bence , Balogh Dóra , Rázga Zsolt , Erdélyi Miklós , Papp Balázs , Kiricsi Mónika , Blastyák András , Collart Martine A. , Boros Imre M. , Villányi Zoltán 
Published: March 2022

AbstractEDTA- and RNase-resistant ribonucleoprotein complexes of arrested ribosomes with protruding nascent polypeptide chains have recently been described in yeast and human cells. These complexes have been termed assemblysomes, a type of soluble condensates distinct from other known granules. Here, we use bioinformatics to identify additional proteins that likely form assemblysomes during translation. We characterize soluble condensates of the DNA helicase Sgs1, one such identified protein and a key player in the repair of DNA double-strand breaks in yeast. We show that paused ribosome-associated nascent chains of Sgs1 in condensates are able to resume translation upon UV irradiation, consistent with the return of mRNA to the ribosome pool. By extending our studies to human cell lines, we found that EDTA-resistant pellets of ribosomes from the human prostate cancer cell line DU145 are sensitive to treatment with 1,6-hexanediol, which is known to dissolve liquid-liquid phase-separated condensates. In addition, transmission electron microscopy shows that 1,6-hexanediol dissolves ring ribosomal structures from the cytoplasm of radioresistant A549 cells while making the cells more sensitive to X-rays. These results suggest that the stress response is based on a conserved mechanism involving the regulated return of phase-separated paused ribosome-nascent chain complexes to translating ribosomes.
Investigating the determinants of happiness index in EU-27 countries: a quantile regression approach
Authors: Akgun Ali İhsan , Türkoğlu Serap Pelin , Erikli Süheyla 
Published: March 2022

PurposeThis paper examines the determinants of happiness index ratings in European countries over 8 time points using unique data from the Eurostat, World Bank and World Happiness Reports.Design/methodology/approachTo examine the determinants of happiness index ratings for EU-27 countries over the period 2012–2019, panel ordinary least square and quantile regression model are used to data obtained from all sample.FindingsEvidence from European data on happiness index generate some important key outcomes; economic outcomes levels with both current taxes and inflation rate have a positively relationship on happiness index ratings (HIR), while total employment rate has a significant negativity on HIR. Additionally, in a quantile panel regression of 27 countries, the impact of financial inclusion on happiness index looks to change with a country's level of income. On the macroeconomic level, gross domestic product (GDP) improves the happiness index for the individual under certain conditions. Thus, GDP on 0.25th quantile levels positively and significantly impacts the HIR for leader countries.Social implicationsEmpirical evidence suggests that macro-economic variables and the labor market proxies of the countries play a key role in determining HIR as well.Originality/valueThe study extends the literature on developed countries and suggestions a particular perspective on the relationship between economic outcomes and happiness index. This study offers two main originalities: it simultaneously examines the “happiness-macroeconomic level” and “happiness-employment status dimension”, and it uses a quantile regression approach, including financial inclusion variation.
Exploring design discourses and liminality as features of professional learning in an elementary makerspace
Authors: Becker Sandra , Jacobsen Michele 
Published: March 2022

Purpose
Using Johansson-Sköldberg et al.’s (2013) descriptions of design discourses, this study aims to analyze teacher interviews, research notes and teacher and student artifacts to determine if engagement in design practices led to changes in the teacher’s thinking.

Design/methodology/approach
This article presents results from a year-long study that explored how a teacher enacted design discourses to engage in curriculum learning within an elementary school makerspace. The design-based study involved a collaborative partnership where a teacher and researcher co-designed, co-enacted and co-reflected on three cycles of making featuring curriculum studies in science, mathematics and social studies.

Findings
The authors determined that engagement in all four design discourses led to transformative changes in the teacher’s thinking about herself as a teacher and her students as learners. The evidence suggests the school makerspace can serve as a liminal design space for professional learning, given that implicit in the makerspace is the embodiment of design practices such as problem finding, iteration and reflection.

Research limitations/implications
Engaging in design discourses in the makerspace can lead teachers to question the frames they hold about teaching and learning. However, teachers need ongoing support in developing discipline knowledge and prioritizing the time required for designing, iterating and reflecting on learning in the makerspace.

Practical implications
The makerspace provides a liminal space for teachers’ professional learning in that implicit in the makerspace is the embodiment of design practices such as problem finding, iteration and reflection.

Originality/value
This study is unique, in that it places the importance of teacher learning in the elementary school makerspace on equal footing with student learning, thereby creating a culture of inquiry for all.
A study of the implementation of patient safety policies in the NHS in England since 2000: what can we learn?
Authors: Wood David Phillip , Robinson Catherine A. , Nathan Rajan , McPhillips Rebecca 
Published: March 2022

PurposeDespite repeated policy initiatives, progress in improving patient safety in the National Health Service (NHS) in England over the past two decades has been slow. The NHS Patient Safety Strategy (NHS England and NHS Improvement, 2019), which is being implemented currently, aims to address this problem. The purpose of this study is to identify learning from the implementation of past patient safety policies and thereby suggest means of supporting the NHS in delivering the current policy initiative successfully.Design/methodology/approachThe authors identified key health policies in the domain of patient safety, published since 2000, by searching the United Kingdom (UK) government website. Discussion papers from the research literature concerning these policies were collated and reviewed. The authors then used a thematic analysis approach to identify themes discussed within these papers. These themes represent factors that support the effective delivery of patient safety policy initiatives.FindingsWithin the discussion papers the authors collated, concerning 11 patient safety policies implemented between 2000 and 2017, five inter-related core themes of capability, culture, systems, candour and leadership were identified. By evaluating these themes and identifying composite sub-themes, a conceptual framework is presented that can be used to support the delivery of patient safety policy initiatives to maximise their impact.Originality/valueThe conceptual framework the authors illustrate, arising from this new contribution to the body of knowledge, can be translated into a novel self-assessment for individual NHS trusts to understand organisational development areas in the domain of patient safety improvement.
Does Multilateralism still Matter? ASEAN and the Arctic Council in Comparative Perspective
Authors: Beeson Mark , Hewitt Jolanta 
Published: March 2022

AbstractAt a time when the world faces a number of complex problems that transcend national borders and which individual states appear unable to address on their own, multilateralism ought to matter more than ever. All too often, however, attempts to encourage collaborative and effective responses to transnational problems are unable to overcome national interests, or lack the capacity to address novel challenges that defy easy resolution. Despite the urgent need for international cooperation, it is often conspicuous by its absence and it is not unreasonable to ask, does multilateralism really matter anymore? We argue that it does, if only because, there is no alternative. To illustrate multilateralism's weaknesses and potential strengths we provide a novel comparison of the Association of Southeast Asian Nations (ASEAN) and the Arctic Council, which reveals the importance of history, diplomatic styles, the significance of issue areas, and the motivations of members. The two bodies literally and metaphorically illustrate developments in the North and South, and provide a novel and revealing benchmark for measuring the success of multilateral bodies at different moments in history.
Circ_0003340 downregulation mitigates esophageal squamous cell carcinoma progression by targeting miR‐940/PRKAA1 axis
Authors: Guan Xingzhuo , Guan Xiaohui , Wang Yuanshi , Lan Tingzhu , Cheng Tongshuang , Cui Yan , Xu Hongjun 
Published: March 2022

AbstractBackgroundEsophageal squamous cell carcinoma (ESCC) is a highly prevalent type of esophageal cancer (EC), usually found at an advanced stage with a high mortality rate, and it is now crucial to find new ways to diagnose and treat ESCC. This study analyzed the function of circular RNA_0003340 (circ_0003340)/microRNA‐940 (miR‐940)/protein kinase AMP‐activated alpha 1 catalytic subunit (PRKAA1) axis in ESCC.MethodsCirc_0003340, miR‐940 and PRKAA1 contents were measured with the application of real‐time quantitative polymerase chain reaction (RT‐qPCR) and western blot. Cell proliferation, cell cycle, apoptosis, migration, invasion and angiogenesis were assessed with a cell counting kit‐8 (CCK8), 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, wound healing, transwell and tube formation assays. We used both the luciferase reporter system and RNA immunoprecipitation (RIP) to analyze the relationship between miR‐940 and circ_0003340 or PRKAA1. Finally, xenograft models were applied to analyze the effect of circ_0003340 on tumor growth in vivo.ResultsUpregulated circ_0003340 and PRKAA1, and downregulated miR‐940 levels were detected in ESCC. Meanwhile, ESCC progression was apparently restrained by circ_0003340 knockdown in vitro. Circ_0003340 acted as a ceRNA for miR‐940 in regulating ESCC progression and miR‐940 was proved to target PRKAA1 to arrest ESCC progression in vitro. Finally, in vivo experiments established that silencing of circ_0003340 slowed tumor growth in vivo.ConclusionCirc_0003340 downregulation mitigated esophageal squamous cell carcinoma progression by targeting miR‐940/PRKAA1 axis.