bluuebunny/crossref_metadata_2025 huggingface dataset:
Life Expectancy Loss among Native Americans During the COVID-19 Pandemic
Authors: Goldman Noreen , Andrasfay Theresa
Published: March 2022

Background

There has been little systematic research on the mortality impact of COVID-19 in the Native American population.

Objective

We provide estimates of loss of life expectancy in 2020 and 2021 for the Native American population.

Methods

We 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.

Results

The 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.

Conclusions

These 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.

Contribution

The 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

Chimeric 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

The 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

Our 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

SARS-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

Background

Early 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.

Methods

Health 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.

Result

The 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.

Conclusion

The 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

EDTA- 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.
The role of free space in photochemical reactions in crystals at high pressure – the case of 9-methylanthracene
Authors: Bąkowicz Julia , Turowska-Tyrk Ilona
Published: March 2022

The influence of pressure on the course of [4+4] photodimerization in crystals of 9-methylanthracene is presented. The studies were performed at 0.1 and 0.4 GPa. As a result of the reaction at high pressure, crystals of the pure product were obtained, which allowed for monitoring of the reaction until its completion. The initial increase in the unit-cell volume caused by the reaction under ambient conditions was reduced at high pressure due to the decrease in the void volume. Despite the smaller size of the void volume at high pressure, dimer molecules formed during the reaction changed the orientation of the monomer molecules in the crystal structure. The size of the voids above the terminal rings of the monomers correlates with the position of the terminal rings in the dimer. The reaction rate increased at high pressure, indicating that the decrease in the distance between adjacent monomers caused by pressure dominates over the decrease in the void volume. This distance is statistically constant as the reaction progresses, contrary to the reaction at ambient pressure.
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

Purpose

This 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/approach

To 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.

Findings

Evidence 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 implications

Empirical evidence suggests that macro-economic variables and the labor market proxies of the countries play a key role in determining HIR as well.

Originality/value

The 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

Purpose

Despite 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/approach

The 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.

Findings

Within 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/value

The 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

At 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

Background

Esophageal 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.

Methods

Circ_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.

Results

Upregulated 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.

Conclusion

Circ_0003340 downregulation mitigated esophageal squamous cell carcinoma progression by targeting miR‐940/PRKAA1 axis.
Refractive error, accommodation and lens opacification in adults born preterm and full‐term: Results from the Gutenberg Prematurity Eye Study (GPES)
Authors: Fieß Achim , Fauer Agnes , Mildenberger Eva , Urschitz Michael S. , Elflein Heike M. , Zepp Fred , Stoffelns Bernhard , Pfeiffer Norbert , Schuster Alexander K.
Published: March 2022

Purpose

To evaluate the long‐term effects of different degrees of prematurity, retinopathy of prematurity (ROP) and associated perinatal factors on refractive error, accommodation and lens opacification development in adults born preterm aged 18–52 years.

Methods

The Gutenberg Prematurity Eye Study (GPES) investigated adults born preterm and full‐term at 18–52 years in Germany to assess refractive error, accommodation amplitude and lens opacification. The participants were grouped into normal gestational age (GA) ≥37 weeks (control group), preterm participants without ROP and GA 33–36 weeks (group 2), GA 29–32 weeks (group 3), GA ≤28 weeks (group 4) and those with ROP without (group 5) or with treatment (group 6). Main outcome measures were refractive error, anisometropia, accommodation amplitude and lens opacification.

Results

In total, 856 eyes of 433 preterm and full‐term individuals (aged 28.4 +/− 8.6 years, 242 females) were included. A myopic refractive error of >6 diopter was observed in 4% (11/278), 2.7% (7/264), 1.2% (2/174), 5.6% (2/36), 10.5% (8/78) and 26.9% (7/26) of eyes and anisometropia ≥2 diopter in 2.9% (4/139), 2.3% (3/132), 3.5% (3/87), 11.1% (2/18), 9.5% (4/44) and 38.5% (5/13) of participants in the respective groups. Spherical equivalent did not differ between participants without postnatal ROP born moderately, very and extremely preterm compared to the full‐term control group. ROP treatment was associated with lower accommodation and more lens opacifications.

Conclusion

Retinopathy of prematurity treatment using cryocoagulation and laser coagulation increases refractive error associated with increased lens opacifications and reduced accommodation. Preterm delivery has little effect on absolute refractive error but is associated with anisometropia in adulthood.
Melatonin inhibits EMT and PD‐L1 expression through the ERK1/2/FOSL1 pathway and regulates anti‐tumor immunity in HNSCC
Authors: Luo Xinyue , Chen Yang , Tang Hokeung , Wang Hui , Jiang Erhui , Shao Zhe , Liu Ke , Zhou Xiaocheng , Shang Zhengjun
Published: March 2022

Melatonin is an endogenous hormone with various biological functions and possesses anti‐tumor properties in multiple malignancies. Immune evasion is one of the most important hallmarks of head and neck squamous cell carcinoma (HNSCC) and is closely related to tumor progression. However, as an immune modulator under physiological conditions, the roles of melatonin in tumor immunity in HNSCC remains unclear. In this study, we found that the endogenous melatonin levels in patients with HNSCC were lower than those in patients with benign tumors in head and neck. Importantly, lower melatonin levels were related to lymph node metastasis among patients with HNSCC. Moreover, melatonin significantly suppressed programmed death‐ligand 1 (PD‐L1) expression and inhibited epithelial–mesenchymal transition (EMT) of HNSCC through the ERK1/2/FOSL1 pathway in vitro and in vivo. In SCC7/C3H syngeneic mouse models, anti‐programmed death‐1 (PD‐1) antibody combined with melatonin significantly inhibited tumor growth and modulated anti‐tumor immunity by increasing CD8+ T cell infiltration and decreasing the regulatory T cell (Treg) proportion in the tumor microenvironment. Taken together, melatonin inhibited EMT and downregulated PD‐L1 expression in HNSCC through the ERK1/2/FOSL1 pathway and exerted synergistic effects with anti‐PD‐1 antibody in vivo, which could provide promising strategies for HNSCC treatment.
Characterization of intravascular papillary endothelial hyperplasia: a multicentre cohort
Authors: Yang Kevin , Pan Catherina X. , Russell-Goldman Eleanor E. , Nambudiri Vinod E.
Published: March 2022

Intravascular papillary endothelial hyperplasia (IPEH) is an uncommon benign malformation of the skin and subcutaneous tissue. In this retrospective multicentre study, we aimed to investigate the clinical and pathological features of 261 patients with IPEH. IPEH is classified into three categories; in our study, the proportions were pure (50%), mixed (46%) and extravascular (4%). IPEH frequently stained positive for immunohistochemical markers such as CD31, CD34, smooth muscle actin and erythroblast transformation-specific-related gene. Clinicians' initial impression of the lesion often included ambiguous terms such as ‘soft tissue mass’. There is an opportunity for increased awareness of this lesion and its consideration within a differential diagnosis.
Reforming Canada's dairy supply management scheme and the consequences for international trade
Authors: McLachlan Brennan A. , van Kooten G. Cornelis
Published: March 2022

Following Carter and Mérel (2016), we explore the export benefits of reforming supply management (SM) in Canada's dairy sector. A trade model with ten regions and five dairy product categories is developed and used to examine the potential benefits of opening international markets to Canadian dairy products. In addition to a baseline, three scenarios are compared—one with SM in place but with Canada able to export freely. Two other scenarios assume SM is eliminated and there is complete free trade, but with high‐ and low‐cost structures. Findings indicate that, in the high‐cost scenario, domestic consumers gain from lower prices as the domestic supply and exports fall compared to the status quo, but producers are less well off. However, under a low domestic cost structure, Canada becomes a major exporter of milk, with both producers and consumers gaining from free trade. This scenario assumes that domestic producers take advantage of economies of scale, enabling them to compete in international markets. Appropriate policies will be required to reform the quota regime, while minimizing the harm done to dairy farmers.
An Analogical Model of Pretense
Authors: Rabkina Irina , Forbus Kenneth D.
Published: March 2022

We argue that pretense can be viewed as analogical projection: a structural comparison between the pretend scenario and its real‐world counterpart that leads to inferences about the pretend scenario. For example, in pretending to make a phone call with a banana, a number pad might be projected on the banana's surface. We model two empirical studies of early childhood pretense, and show how successful pretense requires making and accepting such inferences, while failed pretense can be traced to failure of such projection. Other models of pretense, both theoretical and computational, and their relationships to our model, are discussed.
A single‐step pad‐steam cationisation and dyeing process for improving dyeing properties of cotton fabrics
Authors: Wang Lei , Xie Guangyuan , Mi Xiang , Kang Xiaohu , Zhu Qiuyu , Yu Zhicheng
Published: March 2022

The cationic modification technology for cotton could greatly enhance colour strength and fixation of reactive dyes. However, it is a two‐step method when cationic modification is applied to salt‐free dyeing. Cotton fabric is initially treated with a cationic compound through exhaust or pad‐cure, acid washing and drying process, then the cationic modified cotton is dyed with reactive dye. In this study, a single‐step pad‐steam cationisation and dyeing process was proposed to shorten the process and improve dye fixation. The fixation reaction between reactive dye and cotton fabrics was conducted at the temperature range 100–140°C and relative humidity range 40–90%. The effects of quaternary ammonium salt and inorganic salt as well as alkaline agent on K/S value and dye fixation were also studied. Furthermore, the drying kinetic of the wet cotton fabric was studied in this article. The result showed that the drying process fitted well to the Page model. The effective moisture diffusivity of wet cotton under different steaming conditions were calculated. An activation energy value of 32.25 kJ/mol was determined. Compared with the conventional process, a single‐step pad‐steam cationisation and dyeing process not only shortened the process but also increased K/S value and dye fixation.
Heterozygous loss of Zbtb38 leads to early embryonic lethality via the suppression of Nanog and Sox2 expression
Authors: Nishio Miki , Matsuura Takuya , Hibi Shunya , Ohta Shiomi , Oka Chio , Sasai Noriaki , Ishida Yasumasa , Matsuda Eishou
Published: March 2022

Objectives

Mammalian DNA methyltransferases are essential to re‐establish global DNA methylation patterns during implantation, which is critical for transmitting epigenetic information to the next generation. In contrast, the significance of methyl‐CpG binding proteins (MBPs) that bind methylated CpG remains almost unknown at this stage. We previously demonstrated that Zbtb38 (also known as CIBZ)—a zinc finger type of MBP—is required for mouse embryonic stem (ES) cell proliferation by positively regulating Nanog expression. However, the physiological function of Zbtb38 in vivo remains unclear.

Materials and Methods

This study used the Cre‐loxP system to generate conditional Zbtb38 knockout mice. Cell proliferation and apoptosis were studied by immunofluorescence staining. Quantitative real‐time PCR, immunoblotting and immunofluorescence were performed to investigate the molecular mechanisms.

Results

Germline loss of the Zbtb38 single allele resulted in decreased epiblast cell proliferation and increased apoptosis shortly after implantation, leading to early embryonic lethality. Heterozygous loss of Zbtb38 reduced the expression of Nanog, Sox2, and the genes responsible for epiblast proliferation, differentiation, and cell viability. Although this early lethal phenotype, Zbtb38 is dispensable for ES cell establishment and identity.

Conclusions

These findings indicate that Zbtb38 is essential for early embryonic development via the suppression of Nanog and Sox2 expression.
Long noncoding RNAs regulated spermatogenesis in varicocele‐induced spermatogenic dysfunction
Authors: Wang Shangren , Kang Jiaqi , Song Yuxuan , Zhang Aiqiao , Pan Yang , Zhang Zhexin , Li Yuezheng , Niu Shuai , Liu Li , Liu Xiaoqiang
Published: March 2022

Objectives

To evaluate the expression, potential functions and mechanisms of long noncoding RNAs (lncRNAs) in the pathogenesis of varicocele (VC)‐induced spermatogenic dysfunction.

Materials and Methods

We established a rat model with left experimental VC and divided rats into the sham group, the VC group, and the surgical treatment group (each group, n = 10). Haematoxylin and eosin (HE) staining and sperm quality were analysed to evaluate spermatogenesis function. LncRNA expression profiles were analysed using lncRNA‐Seq (each group n = 3) and validated using quantitative real‐time polymerase chain reaction (each group n = 10). Correlation analysis and gene target miRNA prediction were used to construct competing endogenous RNA network. The regulated signalling pathway and spermatogenic dysfunction of differentially expressed lncRNAs (DE lncRNAs) were validated by Western blot.

Results

HE detection and sperm quality analysis showed that VC could induce spermatogenic dysfunction. Eight lncRNAs were upregulated and three lncRNAs were downregulated in the VC group compared with the sham group and surgical treatment group. The lncRNA of NONRATG002949.2, NONRATG001060.2, NONRATG013271.2, NONRATG022879.2, NONRATG023424.2, NONRATG005667.2 and NONRATG010686.2 were significantly negatively related to sperm quality, while NONRATG027523.1, NONRATG017183.2 and NONRATG023747.2 were positively related to sperm quality. The lncRNAs promote spermatogenic cell apoptosis and inhibit spermatogonia and spermatocyte proliferation and meiotic spermatocytes by regulating the PI3K–Akt signalling pathway.

Conclusion

DE lncRNAs may be potential biomarkers for predicting the risk of spermatogenic dysfunction in VC and the effect of surgical repair. These DE lncRNAs promote spermatogenic dysfunction by regulating the PI3K–Akt signalling pathway.
Extrusion of pilosebaceous units into blisters of patients affected by a new variant of endemic pemphigus in El Bagre, Colombia, South America
Authors: Abreu‐Velez Ana Maria , Upegui‐Zapata Yulieth Alexandra , Valencia‐Yepes Carlos Andres , Upegui‐Quiceño Eduardo , Howard Michael S.
Published: March 2022

Background

A new variant of endemic pemphigus foliaceus is present in El Bagre, Colombia, and surrounding municipalities (El Bagre‐EPF) that affects the skin and in some presentations affects other organs with autoantibodies directed against cell junctions.

Methods

We studied 200 El Bagre‐EPF patient perilesional skin biopsies, as well as 200 skin biopsies from normal controls in the endemic area.

Results

We observed blister extrusions of sebaceous glands or entire pilosebaceous units via the isthmus in 23% of the patients and not in the controls.

Conclusions

The extrusion of hair follicular unit contents is consistent with our previous pathologic findings of autoreactivity to these units, and their observed clinical decrease in patients affected by El Bagre‐EPF.
Long‐term cost‐effectiveness of Dexcom G6 real‐time continuous glucose monitoring system in people with type 1 diabetes in Australia
Authors: Isitt J. J. , Roze S. , Tilden D. , Arora N. , Palmer A. J. , Jones T. , Rentoul D. , Lynch P.
Published: March 2022

Introduction

Real‐time continuous glucose monitoring (rt‐CGM) allows patients with diabetes to adjust insulin dosing, potentially improving glucose control. This study aimed to compare the long‐term cost‐effectiveness of the Dexcom G6 rt‐CGM device versus self‐monitoring of blood glucose (SMBG) and flash glucose monitoring (FGM) in Australia in people with type 1 diabetes (T1D).

Methods

Long‐term costs and clinical outcomes were estimated using the CORE Diabetes Model. Clinical input data for the analysis of rt‐CGM versus SMBG and FGM were sourced from the DIAMOND study and a network meta‐analysis, respectively. Rt‐CGM and FGM were associated with quality of life (QoL) benefits due to reduced fear of hypoglycaemia (FoH) and fingerstick testing. Analyses were performed over a lifetime time horizon from an Australian healthcare payer perspective, including direct costs from published data. Future costs and clinical outcomes were discounted at 5% per annum.

Results

Rt‐CGM was associated with an increased quality‐adjusted life expectancy of 1.199 quality‐adjusted life years (QALYs), increased mean total lifetime costs of AUD 21,596 and an incremental cost‐effectiveness ratio (ICER) of AUD 18,020 per QALY gained compared with SMBG.

Compared with FGM, rt‐CGM was associated with an increased quality‐adjusted life expectancy of 0.569 QALYs, increased mean total lifetime costs of AUD 11,064 and an ICER of AUD 19,455 per QALY gained. Key drivers of outcomes included HbA1c benefits and QoL benefits associated with reduced FoH and fingerstick testing.

Conclusions

Due to improved clinical outcomes and QoL gains rt‐CGM is highly cost‐effective compared with SMBG and FGM in people with T1D in Australia.
Surgical strategy of lumbopelvic instrumentation in the treatment of lumbosacral tuberculosis: S2‐alar‐iliac screws vs iliac screws
Authors: Yu Long , Li Litao , Li Dawei , Luo Zhanpeng , Liu Ning , Wu Yunfeng , Bao Da , Cui Xu
Published: March 2022

The objective of this study was to evaluate the feasibility and clinical outcomes of S2‐alar‐iliac (S2AI) and iliac screw (IS) techniques in the lumbopelvic reconstruction of lumbosacral tuberculosis patients. From January 2014 to August 2016, 26 patients with lumbosacral tuberculosis attending the 8th Medical Centre of Chinese PLA General Hospital were included in this retrospective study. The subjects were divided into two groups based on the lumbopelvic fixation type (16 patients in the S2AI group, 10 patients in the IS group). The operation time, blood loss, length of hospitalisation, erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP) level, visual analogue scale (VAS), Oswestry Disability Index (ODI), ambulatory status, and 36‐Item Short‐Form Health Survey (SF‐36) scores of the patients in two groups were recorded and compared. In addition, surgical complications were collected and analysed. The operation time and intraoperative blood loss were significantly lower in the S2AI group than that in the IS group (P < .05). Compared with preoperative data, postoperative data showed significant improvement in ESR, CRP level, ODI scores, VAS scores, ambulatory status, and SF‐36 (P < .05), but there was no significant difference in remission degree between the two groups. Compared with IS group, The S2AI group had significantly lower rates of symptomatic screw prominence (P < .05). Both the IS and S2AI fixation techniques can achieve satisfactory outcomes for the restoration of lumbosacral stability of lumbosacral tuberculosis. Furthermore, compared to the traditional IS fixation technique, the S2AI fixation technique can shorten operation time and reduce surgical trauma for the treatment of lumbosacral tuberculosis.
Evaluation of the association between admission systolic blood pressure and the choice of initial antiplatelet therapy for minor ischemic stroke in real‐world
Authors: Liu Tingting , Wang Yongle , Niu Xiaoyuan , Li Yanan , Zhang Kaili , Fan Haimei , Ren Jing , Li Juan , Ma Liansheng , Li Xinyi , Wu Xuemei
Published: March 2022

To evaluate whether admission systolic blood pressure (SBP) is associated with the choice of initial antiplatelet therapy for minor stroke. Eligible patients retrospectively gathered from 2010 to 2018. Finally, 1312 of 1494 patients were divided into three groups: aspirin monotherapy (AM, n = 538, 41.0%), dual antiplatelet therapy with aspirin and load‐clopidogrel (clopidogrel loading dose of 300 mg on the first day, DAPT‐ALC, n = 474, 35.6%), and dual antiplatelet therapy with aspirin and unload‐clopidogrel (clopidogrel 75 mg daily with no loading dose, DAPT‐AUC, n = 300, 22.9%). The mean ± SD age of final patients was 62.0 ± 12.7 years old; 903 (70.9%) participants were male. Patients in the DAPT‐ALC group were more likely to be younger, to arrive earlier, and to have a lower proportion of intracerebral hemorrhage than those in the AM group. DAPT‐AUC group patients were more like to have a history of acute myocardial infarction and less likely to have a history of ICH than the AM group (4.7% vs. 1.7% and .3% vs. 2.6%, p < .05). Overall, there was a likely “S‐shaped” association between the selection of the DAPT‐ALC or DAPT‐AUC scheme and admission systolic blood pressure (P for nonlinearity = .012). Compared with the SBP < 140 mmHg group, the SBP ≥ 180 mmHg group was more likely to be given DAPT‐AUC (OR = 2.92 [1.62–5.26], p < .001) than DAPT‐ALC. Our findings support that admission SBP is associated with the choice of initial antiplatelet, especially when the SBP was greater than or equal to 180 mmHg.
Impact of fixed‐dose combination Cal/BD foam on the work productivity of patients with psoriasis: results from the 52‐week randomized, double‐blind, PSO‐LONG trial
Authors: Guenther L. , Takhar A. , Megna M. , Sebastian M. , Nyholm N. , Thoning H. , Levin L.‐Å.
Published: March 2022

Background

Psoriasis contributes to unemployment, work impairment, missed workdays and substantial indirect costs due to lost productivity. Combination Cal/BD foam is the only topical that is approved for long‐term maintenance treatment of plaque psoriasis for 52 weeks. This is the first known investigation of the effect of topical psoriasis therapy on productivity.

Objective

To examine the change in work productivity and activity impairment after 4 weeks of treatment with fixed‐dose combination calcipotriol 50 µg/g/betamethasone dipropionate 0.5 mg/g (Cal/BD) foam and observe long‐term changes after 52 weeks of long‐term management (proactive or reactive treatment).

Methods

This is a post‐hoc analysis of the PSO‐LONG trial – a phase 3, randomized, double‐blind, vehicle‐controlled, parallel group, international multi‐centre trial of treatment with combination Cal/BD foam. Work and activity impairment due to psoriasis were assessed by the Dermatology Life Quality Index (DLQI) and the Work Productivity and Activity Impairment Psoriasis (WPAI:PSO) questionnaire at baseline, week 4, week 28 and week 56. The improvement in hours of work productivity was translated into monthly and annual indirect cost savings estimates for patients in Italy, Sweden, United Kingdom, Canada and Germany.

Results

Using fixed‐dose combination Cal/BD foam for four weeks significantly reduced psoriasis‐related work presenteeism, total work productivity impairment (TWPI) and total activity impairment (TAI) over 56 weeks, with significant improvements observed as early as 4 weeks after the baseline visit. The proportion of patients reporting impact on work productivity (as measured by presenteeism and TWPI) and activity impairment (as measured by both DLQI‐Q7b and TAI) also decreased.

Conclusion

Fixed‐dose combination Cal/BD foam used for long‐term management of psoriasis significantly reduces psoriasis‐related work productivity and activity impairment which may result in substantial indirect cost savings.

Clinical Trial Registration NCT02899962, EudraCT number: 2016‐000556‐95
The Regional‐Supremacy Trap: Disorder in the Middle East
Authors: Mousavi Shafaee Seyed Masoud , Golmohammadi Vali
Published: March 2022

This article analyzes the logic of recent instability and disorder in the Middle East. It offers two interrelated arguments. First, the region has turned into a battle zone in the aftermath of US retrenchment. The United States and other external powers refrained from direct engagement in shaping Middle Eastern order and, therefore, aspirant regional powers were prompted to redesign that order. Second, what makes instability and disorder a geopolitical feature of the Middle East is the “regional‐supremacy trap,” the seduction of a power vacuum and a desire for regional hegemony, a trap that draws all influential actors into a series of endless and cumulative conflicts. According to our findings, there is a meaningful relationship between the instability and the regional power struggle for supremacy in the post‐American Middle East. As there is no sign of cooperative mechanisms for shaping the regional order by the major Middle Eastern actors, the syndrome of disorder will continue for the foreseeable future.
Periostin regulates LPS‐induced apoptosis via Nrf2/HO‐1 pathway in periodontal ligament fibroblasts
Authors: Jiang Yujun , Yang Panpan , Li Congshan , Lu Yupu , Kou Yuying , Liu Hongrui , Guo Jie , Li Minqi
Published: March 2022

Objective

Periostin is important for the maintenance of periodontal tissue, but its role in periodontitis is controversial. This research investigated the effect of periostin in periodontitis and the underlying mechanism.

Design

Mouse periodontitis models in vivo and inflammation model in vitro which were induced by Porphyromonas gingivalis lipopolysaccharide were established to evaluate periostin expression. Human periodontal ligament fibroblasts (PDLFs) were treated with lipopolysaccharide and N‐acetylcysteine, fluorescence staining, flow cytometry, Western blot, and qRT‐PCR were used to detect reactive oxygen species (ROS), periostin expression, and apoptosis‐related makers. The periostin gene was successfully transfected into PDLFs to verify the effect of periostin on apoptosis. Then, the Nrf2 inhibitor was added to clarify the mechanism.

Results

Periostin expression decreased in the periodontal ligaments of mouse periodontitis models and lipopolysaccharide‐induced PDLFs. Lipopolysaccharide promoted the activation of ROS and apoptosis in PDLFs, whereas N‐acetylcysteine reversed this condition. Overexpression of periostin suppressed apoptosis of PDLFs and reversed the inhibitory effect of lipopolysaccharide on nuclear Nrf2 expression. Moreover, the Nrf2 inhibitor attenuated the protective effect of periostin on lipopolysaccharide‐induced apoptosis.

Conclusions

Lipopolysaccharide induced apoptosis in PDLFs by inhibiting periostin expression and thus Nrf2/HO‐1 pathway, indicating that periostin could be a potential therapeutic target for periodontitis.