bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Picture-based health education and counselling on knowledge and adherence to preconception Iron-folic acid supplementation among women planning to be pregnant in Eastern Ethiopia: a randomized controlled trial
Authors: Berhane Anteneh , Belachew Tefera
Published: July 2022

The present study examined the effect of picture-based nutrition education on knowledge and adherence to pre-conception iron–folic acid supplement (IFAS) in Ethiopia, a country where there is a high burden of neural tube defects (NTDs) and anaemia. In eastern Ethiopia, a parallel randomised controlled trial design was employed among women planning to get pregnant. The interventional arm (n 122) received a preconception picture-based nutrition education and counselling along with an IFAS and the control arm (n 122) received only a preconception IFAS. The effects of the intervention between-group differences were assessed using a χ2 and independent sample t-test. Bivariate and multivariable linear regression model was fitted to detect independent variables affecting the outcome. The outcome measures regarding the knowledge and adherence to the IFAS intake during the three months of the intervention period were deteremined. It was observed that large proportion of women in the intervention group (42⋅6 %) had an adherence to IFAS compared to the control group (3⋅3 %); (P < 0⋅0001). Based on bivariate and multivariable linear regression analyses, among NTDs affecting pregnancy, the history of spontaneous abortion and knowledge were independently associated with adherence to the IFAS (P < 0⋅05). Preconception nutrition education with regular follow-ups could be effective in improving knowledge and adherence to the IFAS intake. This intervention is very short, simple, cost-effective and has the potential for adaptation development to a large-scale implementation in the existing healthcare system in Ethiopia to prevent NTDs and adverse birth outcomes among women who plan to get pregnant. This clinical trial was registered on 6 April 2021 under the ClinicalTrials.gov with an identifier number PACTR202104543567379.
Collaboration, Survival, and Flight: Fulbe Narratives of Guinea-Bissau's War for Independence, 1961–74
Authors: Glovsky David N.
Published: July 2022

Throughout the 1960s and early 1970s, Bissau-Guineans fought a bloody war for independence. Typical narratives of the war emphasize the ethnic dimension of the liberation struggle, with Balanta freedom fighters opposing Portuguese-allied Fulbe. This dominant narrative is open to question, as it ignores the war as a ‘social condition’, and the role that local circumstances played in determining collaboration with the Portuguese, fighting in liberation militaries, or fleeing to neighboring states for personal safety. Oral and archival evidence suggests a more nuanced perspective that blurs the binary nature of this dominant narrative along ethnic fault lines, viewed as either resistance or collaboration. The argument presented in this article allows us to move past defining the war along ethnic or regional lines, and instead urges a view of the conflict as a complex, fractured experience for all Bissau-Guineans, shaped by the particularities of local circumstances.
Performing the New Order: The Tripartite Pact, 1940–1945
Authors: Goeschel Christian
Published: July 2022

The tripartite pact, concluded by Germany, Italy, and Japan in 1940, sought to create a new global order. This article is part of a broader shift in scholarship, inspired by global and cultural history. Instead of revisiting the decision-making that led to the pact's conclusion, this article explores the pact through the dialectics of culture and power. Through an archive-based interpretation of the pact's signing and the celebrations of its anniversaries from 1941 until 1945 that involved ordinary people in Axis-dominated territories around the world, the central mechanisms of this global fascist alliance become clear. A performative diplomacy of power and unity held the alliance together. Style and substance were not mutually exclusive categories of tripartite politics; instead, ‘real’ and representational politics shaped each other. The pact was a concerted attempt by the three signatories to transform global political structures and supersede the purported global hegemony of the liberal democracies.
COVID-19 accelerated mortality shocks and the impact on life insurance: the Italian situation
Authors: Carannante Maria , D’Amato Valeria , Haberman Steven
Published: July 2022

The Covid-19 pandemic caused an alarming mortality stress. The evidence shows that a significant proportion of people who die from Covid-19 are in a frail state. According to this consideration, we assume that the mortality shocks are related to a group of the individuals with some co-morbidities at Covid-19 diagnosis. In other words, the mortality shocks present a specific characterisation, which consists of a causal connection with pre-existing conditions, and the phenomenon could be described as a mortality acceleration. In this paper, an Accelerated Mortality Model is proposed in order to capture the different effects on mortality that depend on the evolution of the pandemic and the presence of co-morbidities at diagnosis. Furthermore, we assess the impact of Covid-19 mortality acceleration on a set of traditional life insurance contracts. We observe that, although mortality acceleration by Covid-19 affects more markedly the elderly and unhealthy sub-populations, it could be considered as a temporary shock with a limited impact on the life insurance market.
All Rights Reserved: Behind the Strategic Copyright of “We Shall Overcome”
Authors: Davis Lizzy Cooper
Published: July 2022

In 2015, musician and non-profit director Isaías Gamboa and filmmaker Lee Butler sued The Richmond Organization (TRO) and its offshoot Ludlow Music over their copyright to the anthem of the civil rights movement, “We Shall Overcome.” The copyright had initially been registered in 1960 and named four white folksingers: Guy Carawan, Frank Hamilton, Zilphia Horton, and Pete Seeger. Suspicious of the white names on the copyright, Gamboa wanted to liberate the song from what appeared to be corporate control. The suit was ultimately successful and the song was placed in the public domain. However, while Gamboa and Butler celebrated their win in a Manhattan court, activists across the South took it as a loss. Although overseen by TRO and Ludlow, the copyright's royalties had long gone to the Highlander Research and Education Center (formerly The Highlander Folk School), a pre-eminent and decades-old grassroots organizing hub best known for its work with such icons as Rosa Parks, Septima Clark, and Dr. Martin Luther King. The money was housed there in the We Shall Overcome Fund, which had been created by cultural workers of the civil rights movement in collaboration with those named on the copyright to facilitate the redistribution of royalties to Black artist-activists across the South. Far from facilitating theft, the copyright had strategically scaffolded Black-led community organizing for nearly 60 years. This article traces the history and work of this remarkable effort to turn the civil rights movement's anthem into its most lasting cultural tool.
The Public Law Paradoxes of Climate Emergency Declarations
Authors: Stacey Jocelyn
Published: July 2022

Climate emergency declarations occupy a legally ambiguous space between emergency measure and political rhetoric. Their uncertain status in public law provides a unique opportunity to illuminate latent assumptions about emergencies and how they are regulated in law. This article analyzes climate emergency declarations in Canada, the United Kingdom, Australia, and Aotearoa/New Zealand. It argues that these climate emergency declarations reflect back a set of paradoxes about the legal regulation of emergencies – paradoxes about defining the emergency, how time regulates and contains emergency power, and who gets to respond to the emergency and how. These paradoxes challenge long-held and over-simplified assumptions about emergencies and allow us to see the complex ways in which public law regulates emergencies – a necessity in a climate-disrupted world.
Global Characteristics of Cold Protons Around Midnight in the Magnetotail: Implication for Efficient Heating and Origin
Authors: Keika K. , Asami R. , Hoshino M. , Fuselier S. A.
Published: July 2022

We investigate plasma transport to and plasma heating in the plasma sheet in the noon‐midnight meridian, characterizing protons with temperature colder than the core plasma sheet protons (<700 eV). We extract the density and temperature of the cold protons from velocity distribution functions measured by the Hot Plasma Composition Analyzer instrument on board the Magnetospheric Multiscale spacecraft in the radial distance (r) of 6–25 Re, performing two‐component Maxwellian fits. We selected time intervals with no fast flow observed, to examine the characteristics of magnetotail plasma not directly affected by magnetic reconnection and associated phenomena. In the region of r > ∼10 Re, the two‐component populations are identified more frequently near the plasma sheet boundary than the central plasma sheet. The cold component density peaks near the boundary, in contrast to the hot components which display high density near the central plasma sheet. These characteristics suggest that cold protons are convected from the lobe by the open field lines and then heated and mixed with the plasma sheet hot plasma near the lobe‐plasma sheet boundary. The statistical features of the extracted cold components indicate that, in the tailward regions (r > ∼20 Re), temperature increases with decreasing vertical distance from the plasma sheet (represented by plasma β) in a similar trend to the hot components. In the near‐Earth plasma sheet (r < ∼15 Re), cold proton temperature is lower at higher‐β regions; the density decreases as increasing r. These features suggest that cold protons in the near‐Earth plasma sheet are of ionospheric origin, transported to the plasma sheet in the closed magnetic field configuration.
Contrasting Responses of Hailstorms to Anthropogenic Climate Change in Different Synoptic Weather Systems
Authors: Fan Jiwen , Zhang Yuwei , Wang Jingyu , Jeong Jong‐Hoon , Chen Xiaodong , Zhang Shixuan , Lin Yun , Feng Zhe , Adams‐Selin Rebecca
Published: July 2022

Hailstones and extreme precipitation generate substantial economic losses across the United States (US) and the globe. Their strong association with short‐lived, intense convective storms poses a great challenge in predicting their future changes. Here, we conducted model simulations at 1.2 km grid spacing for severe convective storms with large hail and heavy precipitation that occurred in two typical types of synoptic‐scale environments in spring seasons over the central US under both current and future climate conditions. We find that the responses of large hail (diameters >2.5 cm) to anthropogenic climate change (ACC) are markedly different between the hailstorms developed in the two types of synoptic‐scale environments, with over 110% increase in large hail occurrences for the frontal systems, whereas less than 30% increase for the Great Plains low‐level jet (GPLLJ) systems. This is explained by the larger increase in convective intensity and updraft width and a smaller increase in warm cloud depth in the frontal storms compared with the GPLLJ storms. Interestingly, the occurrences and intensity of heavy precipitation (rain rate >20 mm hr−1) in both types of systems are similarly sensitive to ACC (e.g., 40% and 33% increases in the occurrences for the frontal and GPLLJ systems, respectively). These results advance our knowledge of hail projection and have important implications for managing risks for future hail.
Proteinaceous Matter and Liquid Water in Fine Aerosols in Nanchang, Eastern China: Seasonal Variations, Sources, and Potential Connections
Authors: Xu Yu , Dong Xin‐Ni , Xiao Hua‐Yun , Zhou Jin‐Xiu , Wu Dai‐She
Published: July 2022

The transformation of aerosol proteinaceous matter (PrM) has potentially adverse environmental and health effects. The origins and atmospheric processes of PrM have obtained an increasing interest, but there are still large uncertainties. Although aerosol liquid water (ALW) has been found to be vital in numerous atmospheric processes, its impact on atmospheric degradation of PrM remains poorly understood. ALW, proteins, and low molecular weight PrM (LMW PrM, <10 kDa) were investigated in fine aerosols (PM2.5) collected in urban and suburban Nanchang (Eastern China) over a 1‐year period. The average concentrations of proteins and LMW PrM in the urban center were higher than those in the suburban area. Urban PrM tended to increase from cool season to warm season, which was opposite to the case of suburban PrM. These differences could be attributed to varied sources and atmospheric processes of PrM. Increase in ALW was prominent from the suburban site to the urban site, which was attributable to increased anthropogenic nitrate and sulfate. LMW PrM can be degraded from higher molecular weight PrM by ozone. Furthermore, correlation analysis between LMW PrM and ozone and ALW suggested that the enhanced ALW in the urban center facilitated the ozone‐induced LMW PrM release. The ALW‐related protein degradation was further supported by ozone exposure experiments with bovine serum albumin and PM2.5 samples under dry condition. Our findings suggest that ALW is a crucial promoter during PrM degradation by ozone, providing new insights into atmospheric transformation of proteins.
RacGAP1 promotes the malignant progression of cervical cancer by regulating AP-1 via miR-192 and p-JNK
Authors: Zhang Tianli , Wang Chunyan , Wang Kun , Liang Ying , Liu Ting , Feng Liping , Yang Xingsheng
Published: July 2022

Cervical cancer (CC) is the most frequently diagnosed genital tract cancer in females worldwide. Rac GTPase-activating protein 1 (RacGAP1) is one of the specific GTPase-activating proteins. As a novel tumor protooncogene, overexpression of RacGAP1 was related to the occurrence of various tumors, but its function in CC is still unclear. In this study, bioinformatics analyses showed that RacGAP1 might be a key candidate gene in the progression of CC. RacGAP1 was significantly overexpressed in CC tissues. High RacGAP1 expression was positively associated with poor prognosis. Downregulating RacGAP1 significantly inhibited the proliferation, migration, and invasion of CC cells, while overexpressing RacGAP1 had the opposite effects. Further research showed that miR-192, which plays as a tumor suppressor in CC, was identified as a downstream target of RacGAP1 in CC cells. miR-192 inhibition could partially rescue the decrease in cell proliferation, migration, and invasion caused by RacGAP1 downregulation. In opposite, miR-192 overexpression could decrease the promotion of malignant progression caused by RacGAP1 upregulation. Mechanism studies revealed that RacGAP1 could regulate the expression and phosphorylation of c-Jun, which was the component of AP-1, via miR-192 and p-JNK separately. These findings suggested that RacGAP1 promoted tumorigenicity, migration, and invasion of CC. Therefore, it represented a potential novel prognostic marker in CC and may probably be a therapeutic target.
Single cell sequencing identifies clonally expanded synovial CD4+ TPH cells expressing GPR56 in rheumatoid arthritis
Authors: Argyriou Alexandra , Wadsworth Marc H. , Lendvai Adrian , Christensen Stephen M. , Hensvold Aase H. , Gerstner Christina , van Vollenhoven Annika , Kravarik Kellie , Winkler Aaron , Malmström Vivianne , Chemin Karine
Published: July 2022

Rheumatoid arthritis (RA) is an autoimmune disease affecting synovial joints where different CD4+ T cell subsets may contribute to pathology. Here, we perform single cell sequencing on synovial CD4+ T cells from anti-citrullinated protein antibodies (ACPA)+ and ACPA- RA patients and identify two peripheral helper T cell (TPH) states and a cytotoxic CD4+ T cell subset. We show that the adhesion G-protein coupled receptor 56 (GPR56) delineates synovial CXCL13high TPH CD4+ T cells expressing LAG-3 and the tissue-resident memory receptors CXCR6 and CD69. In ACPA- SF, TPH cells display lower levels of GPR56 and LAG-3. Further, most expanded T cell clones in the joint are within CXCL13high TPH CD4+ T cells. Finally, RNA-velocity analyses suggest a common differentiation pathway between the two TPH clusters and effector CD4+ T cells. Our study provides comprehensive immunoprofiling of the synovial CD4+ T cell subsets in ACPA+ and ACPA- RA.
Scalable multiplex co-fractionation/mass spectrometry platform for accelerated protein interactome discovery
Authors: Havugimana Pierre C. , Goel Raghuveera Kumar , Phanse Sadhna , Youssef Ahmed , Padhorny Dzmitry , Kotelnikov Sergei , Kozakov Dima , Emili Andrew
Published: July 2022

Co-fractionation/mass spectrometry (CF/MS) enables the mapping of endogenous macromolecular networks on a proteome scale, but current methods are experimentally laborious, resource intensive and afford lesser quantitative accuracy. Here, we present a technically efficient, cost-effective and reproducible multiplex CF/MS (mCF/MS) platform for measuring and comparing, simultaneously, multi-protein assemblies across different experimental samples at a rate that is up to an order of magnitude faster than previous approaches. We apply mCF/MS to map the protein interaction landscape of non-transformed mammary epithelia versus breast cancer cells in parallel, revealing large-scale differences in protein-protein interactions and the relative abundance of associated macromolecules connected with cancer-related pathways and altered cellular processes. The integration of multiplexing capability within an optimized workflow renders mCF/MS as a powerful tool for systematically exploring physical interaction networks in a comparative manner.
Reconstitution of a telomeric replicon organized by CST
Authors: Zaug Arthur J. , Goodrich Karen J. , Song Jessica J. , Sullivan Ashley E. , Cech Thomas R.
Published: July 2022

Telomeres, the natural ends of linear chromosomes, comprise repeat-sequence DNA and associated proteins1. Replication of telomeres allows continued proliferation of human stem cells and immortality of cancer cells2. This replication requires telomerase3 extension of the single-stranded DNA (ssDNA) of the telomeric G-strand ((TTAGGG)n); the synthesis of the complementary C-strand ((CCCTAA)n) is much less well characterized. The CST (CTC1–STN1–TEN1) protein complex, a DNA polymerase α-primase accessory factor4,5, is known to be required for telomere replication in vivo6–9, and the molecular analysis presented here reveals key features of its mechanism. We find that human CST uses its ssDNA-binding activity to specify the origins for telomeric C-strand synthesis by bound Polα-primase. CST-organized DNA polymerization can copy a telomeric DNA template that folds into G-quadruplex structures, but the challenges presented by this template probably contribute to telomere replication problems observed in vivo. Combining telomerase, a short telomeric ssDNA primer and CST–Polα–primase gives complete telomeric DNA replication, resulting in the same sort of ssDNA 3′ overhang found naturally on human telomeres. We conclude that the CST complex not only terminates telomerase extension10,11 and recruits Polα–primase to telomeric ssDNA4,12,13 but also orchestrates C-strand synthesis. Because replication of the telomere has features distinct from replication of the rest of the genome, targeting telomere-replication components including CST holds promise for cancer therapeutics.
European primary datasets of alien bacteria and viruses
Authors: Magliozzi Chiara , Artois Marc , Bertaccini Assunta , Candresse Thierry , Tsiamis Konstantinos , D’Amico Fabio , Deriu Ivan , Gervasini Eugenio , Cardoso Ana Cristina
Published: July 2022

Bacteria and viruses are a natural component of Earth biodiversity and play an essential role in biochemical and geological cycles. They may also pose problems outside their native range, where they can negatively impact on natural resources, wildlife, and human health. To address these challenges and develop sustainable conservation strategies, a thorough understanding of their invasion related- factors is needed: origin, country and year of introduction, and pathways dynamics. Yet, alien bacteria and viruses are underrepresented in invasion ecology studies, which limits our ability to quantify their impacts and address future introductions. This study provides primary datasets of alien bacteria and viruses of plants and animals present in the European environment. The datasets contain expert-revised data on 446 taxa and their invasion related- factors across terrestrial and aquatic environments. Taxa information are complemented with spatial occurrences. The datasets provide a basis for collaborative initiatives to improve the collection of alien bacteria and viruses’ data, and a starting point for data-driven conservation practices.
Experimental study on the influence of mental fatigue on risk decision-making of miners
Authors: Jia Aifang , Guo Xinyue , Tian Shuicheng
Published: July 2022

Mental fatigue increases risk-taking behavior. Using data collected between June 15 and August 6, 2020, this study investigates the impact of miners’ mental fatigue on risk decision-making to improve risk prevention and prediction abilities, and to reduce the occurrence of coal mine safety accidents. A total of 273 and 33 people participated in the preliminary and formal experiments, respectively. The participants, coal miners, visited a lab thrice to complete the pre-experiment, Balloon Analog Risk Task (BART), and Iowa Gambling Task (IGT). On the BART, mental fatigue displayed a significantly positive association with risk preference. On the IGT, as mental fatigue increased, net scores continuously decreased, while the frequency of making unfavorable decisions and the probability of taking risks increased. The BART value had no or weak correlations with the net score. Results suggest that mental fatigue leads to an increasing propensity to take risks. Therefore, regarding coal mine safety management, further attention is necessary concerning miners’ mental health, addressing mental fatigue, increasing rest time, and reducing night work. Furthermore, reasonable diet, improved working environments, and a positive attitude toward work should be promoted to reduce or eliminate mental fatigue and avoid decision-making errors that could cause accidents.
Maternal childbirth experience and time in labor: a population-based cohort study
Authors: Carlhäll Sara , Nelson Marie , Svenvik Maria , Axelsson Daniel , Blomberg Marie
Published: July 2022

A negative childbirth experience may have long term negative effects on maternal health. New international guidelines allow a slower progress of labor in the early active phase. However, a longer time in labor may influence the childbirth experience. In this population-based cohort study including 26,429 women, who gave birth from January 2016 to March 2020, the association between duration of different phases of active labor and childbirth experience was studied. The women assessed their childbirth experience by visual analogue scale (VAS) score. Data was obtained from electronic medical records. The prevalence of negative childbirth experience (VAS 1–3) was 4.9%. A significant association between longer duration of all labor phases and a negative childbirth experience was found for primi- and multipara. The adjusted odds ratio (aOR (95%CI)) of negative childbirth experience and longer time in active labor (above the 90th percentile) in primipara was 2.39 (1.98–2.90) and in multipara 2.23 (1.78–2.79). In primi-and multipara with duration of labor ≥ 12 h or ≥ 6 h the aOR (95%CI) of negative childbirth experience were 2.22 (1.91–2.58) and 1.91 (1.59–2.26) respectively. It is of great importance to identify and optimize the clinical care of women with longer time in labor to reduce the risk of negative childbirth experience and associated adverse long-term effects.
Responsiveness of the Italian version of the Pediatric Quality of Life Multidimensional Fatigue Scale in adult inpatients with obesity
Authors: Smout Matthew F. , Manzoni Gian Mauro , Guerrini-Usubini Anna , Caroli Diana , De Col Alessandra , Castelnuovo Gianluca , Pietrabissa Giada , Molinari Enrico , Sartorio Alessandro
Published: July 2022

This study aimed to evaluate the responsiveness of the Italian version of the Paediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL-MFS) to changes in BMI, fatigue and depressive symptoms in adult inpatients with obesity. 198 adults (81% female, mean age = 44.7 years) with obesity completed the PedsQL-MFS, the Fatigue Severity Scale (FFS) and the Centre for Epidemiologic Studies Depression Scale (CESD) before and after completing a 3-week body weight reduction program. Internal responsiveness was measured via paired t-tests, standardized mean response (SMR) and Glass’s delta (d). Changes in FFS, CESD and BMI were used as anchors to categorize participants as “improved”, “unchanged” or “deteriorated”. External Responsiveness was assessed by comparing mean post-intervention PedsQL-MFS scores across change groups, adjusting for pre-intervention PedsQL-MFS scores and in area-under-curve (AUC) analysis. PedsQL-MFS Total, Sleep/Rest Fatigue and Cognitive Fatigue scores demonstrated significant reductions in response to an established body weight reduction program. Post-intervention PedsQL-MFS scale scores were lower among those who had improved on the CESD and FSS than among those whose CESD and FSS scores had not significantly changed. There was no difference in PedsQL-MFS scale scores according to whether participants had reduced their BMI by at least 5%. AUC analyses indicated that change in PedsQL-MFS scores was somewhat more predictive of improvement in CESD than FSS scores. The Italian version of the PedsQL-MFS demonstrated both internal and external responsiveness. It appeared more sensitive to improvement than deterioration in fatigue symptoms and its sensitivity to deterioration in depressive symptoms and weight loss could not be evaluated in the present study as there was no reliable deterioration in CESD scores and weight loss was modest. Future studies should include a control group to assess the sensitivity of the PedsQL-MFS more thoroughly.
Multi-objective optimization can balance trade-offs among boreal caribou, biodiversity, and climate change objectives when conservation hotspots do not overlap
Authors: Martin Amanda E. , Neave Erin , Kirby Patrick , Drever C. Ronnie , Johnson Cheryl A.
Published: July 2022

The biodiversity and climate change crises have led countries—including Canada—to commit to protect more land and inland waters and to stabilize greenhouse gas concentrations. Canada is also obligated to recover populations of at-risk species, including boreal caribou. Canada has the opportunity to expand its protected areas network to protect hotspots of high value for biodiversity and climate mitigation. However, co-occurrence of hotspots is rare. Here we ask: is it possible to expand the network to simultaneously protect areas important for boreal caribou, other species at risk, climate refugia, and carbon stores? We used linear programming to prioritize areas for protection based on these conservation objectives, and assessed how prioritization for multiple, competing objectives affected the outcome for each individual objective. Our multi-objective approach produced reasonably strong representation of value across objectives. Although trade-offs were required, the multi-objective outcome was almost always better than when we ignored one objective to maximize value for another, highlighting the risk of assuming that a plan based on one objective will also result in strong outcomes for others. Multi-objective optimization approaches could be used to plan for protected areas networks that address biodiversity and climate change objectives, even when hotspots do not co-occur.
Short-sighted decision-making by those not vaccinated against COVID-19
Authors: Halilova Julia G. , Fynes-Clinton Samuel , Green Leonard , Myerson Joel , Wu Jianhong , Ruggeri Kai , Addis Donna Rose , Rosenbaum R. Shayna
Published: July 2022

Widespread vaccination is necessary to minimize or halt the effects of many infectious diseases, including COVID-19. Stagnating vaccine uptake can prolong pandemics, raising the question of how we might predict, prevent, and correct vaccine hesitancy and unwillingness. In a multinational sample (N = 4,452) recruited from 13 countries that varied in pandemic severity and vaccine uptake (July 2021), we examined whether short-sighted decision-making as exemplified by steep delay discounting—choosing smaller immediate rewards over larger delayed rewards—predicts COVID-19 vaccination status. Delay discounting was steeper in unvaccinated individuals and predicted vaccination status over and above demographics or mental health. The results suggest that delay discounting, a personal characteristic known to be modifiable through cognitive interventions, is a contributing cause of differences in vaccine compliance.
Predictive factors for massive hemorrhage in women with retained products of conception: a prospective study
Authors: Sonehara Reina , Nakamura Tomoko , Iwase Akira , Nishida Kazuki , Takikawa Sachiko , Murakami Mayuko , Yoshita Sayako , Muraoka Ayako , Miyake Natsuki , Nakanishi Natsuki , Osuka Satoko , Goto Maki , Kajiyama Hiroaki
Published: July 2022

Retained products of conception (RPOC) is a common cause of postpartum bleeding, which may be life-threatening; however, no evidence-based guidelines exist to assist in evaluating the risk of massive hemorrhage in women with RPOC. In this prospective study, we aimed to evaluate the predictive factors for massive hemorrhage in women with RPOC. The primary and secondary endpoints were to validate the usefulness of power Doppler color scoring (PDCS) in evaluating hypervascularity and to identify other predictive factors (such as maximum RPOC diameter and serum βhCG and Hb level at first visit), respectively. Among the 51 women with RPOC included in this study, 16 (31.5%) experienced massive hemorrhage during follow-up. None of the women with PDCS 1 or 2 (18) experienced massive hemorrhage, whereas 16 (48.5%) women with PDCS 3 or 4 (33) did. Multiple logistic regression analysis showed that the odds ratio [95% confidence interval] (P value) for PDCS, assisted reproductive technology (ART), and low serum hemoglobin (Hb) levels were 22.39 [2.25 − 3087.92] (P = 0.004), 5.72 [1.28 − 33.29] (P = 0.022), and 4.24 [0.97 − 22.99] (P = 0.056), respectively. Further, the decision tree method identified PDCS, ART, and low serum Hb levels as potential predictive factors for massive hemorrhage. This study identified PDCS as useful predictor of massive hemorrhage in women with RPOC. With additional inclusion of factors such as ART and low serum Hb levels, the risk of massive hemorrhage may be effectively evaluated, leading to better management of women of reproductive age.
The lack of association between PADI4_94 or PADI4_104 polymorphisms and RF, ACPA and anti-PAD4 in patients with rheumatoid arthritis
Authors: Ciesla Marek , Kolarz Bogdan , Darmochwal-Kolarz Dorota
Published: July 2022

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to chronic inflammation of synovial tissue, ultimately causing joint damage, disability, and premature mortality. The peptidylarginine deiminase (PAD) family of proteins is involved in the production of anticitrullinated peptide antibodies (ACPA), which are clinically relevant markers of RA. ACPA recognizes citrullinated proteins generated mainly by PAD4. Polymorphisms of the PADI4 gene have been associated with RA in Asian populations, but in Europeans these associations are still difficult to estimate. A total of 147 subjects, 122 patients with RA, 52 ± 12.3 aged, 84.4% women and 25 healthy controls, 53 ± 8.4 aged, 72% women were enrolled in the study. Two single nucleotide polymorphisms (SNPs) of the PADI4 gene (PADI4_94, rs2240340 and PADI4_104, rs1748033) were genotyped using a real-time polymerase chain reaction. Genetic models (co-dominant-1 and 2, dominant, over-dominant, and recessive) were applied to find the associations between genotypes and ACPA as well as PAD4 antibodies (anti-PAD4) levels. We found no relationship between the distribution of genotypes in different genetic models and the levels of anti-PAD4, ACPA and RF antibodies. There were also no differences with respect to the haplotypes. Genetic variants PADI4_94 and PADI4_104 may not be clinically relevant as prognostic factors in patients with established RA.
Efficacy of auranofin as an inhibitor of desmoid progression
Authors: Ito Kan , Nishida Yoshihiro , Hamada Shunsuke , Shimizu Koki , Sakai Tomohisa , Ohkawara Bisei , Alman Benjamin A. , Enomoto Atsushi , Ikuta Kunihiro , Koike Hiroshi , Zhang Jiarui , Ohno Kinji , Imagama Shiro
Published: July 2022

Anticancer drugs and molecular targeted therapies are used for refractory desmoid-type fibromatosis (DF), but occasionally cause severe side effects. The purpose of this study was to identify an effective drug with fewer side effects against DF by drug repositioning, and evaluate its efficacy. FDA-approved drugs that inhibit the proliferation of DF cells harboring S45F mutations of CTNNB1 were screened. An identified drug was subjected to the investigation of apoptotic effects on DF cells with analysis of Caspase 3/7 activity. Expression of β-catenin was evaluated with western blot analysis, and immunofluorescence staining. Effects of the identified drug on in vivo DF were analyzed using Apc1638N mice. Auranofin was identified as a drug that effectively inhibits the proliferation of DF cells. Auranofin did not affect Caspase 3/7 activity compared to control. The expression level of β-catenin protein was not changed regardless of auranofin concentration. Auranofin effectively inhibited the development of tumorous tissues by both oral and intraperitoneal administration, particularly in male mice. Auranofin, an anti-rheumatic drug, was identified to have repositioning effects on DF. Since auranofin has been used for many years as an FDA-approved drug, it could be a promising drug with fewer side effects for DF.
Varus stress MRI in the refined assessment of the posterolateral corner of the knee joint
Authors: Ciba Malin , Winkelmeyer Eva-Maria , Schock Justus , Westfechtel Simon , Nolte Teresa , Knobe Matthias , Prescher Andreas , Kuhl Christiane , Truhn Daniel , Nebelung Sven
Published: July 2022

Magnetic resonance imaging (MRI) is commonly used to assess traumatic and non-traumatic conditions of the knee. Due to its complex and variable anatomy, the posterolateral corner (PLC)—often referred to as the joint’s dark side—remains diagnostically challenging. We aimed to render the diagnostic evaluation of the PLC more functional by combining MRI, varus loading, and image post-processing in a model of graded PLC injury that used sequential transections of the lateral collateral ligament, popliteus tendon, popliteofibular ligament, and anterior cruciate ligament. Ten human cadaveric knee joint specimens underwent imaging in each condition as above, and both unloaded and loaded using an MR-compatible device that standardized loading (of 147 N) and position (at 30° flexion). Following manual segmentation, 3D joint models were used to computationally measure lateral joint space opening for each specimen, configuration, and condition, while manual measurements provided the reference standard. With more extensive ligament deficiency and loading, lateral joint spaces increased significantly. In conclusion, varus stress MRI allows comprehensive PLC evaluation concerning structural integrity and associated functional capacity. Beyond providing normative values of lateral compartment opening, this study has potential implications for diagnostic and surgical decision-making and treatment monitoring in PLC injuries.
Association between time in range of relative normoglycemia and in-hospital mortality in critically ill patients: a single-center retrospective study
Authors: Okazaki Tomoya , Inoue Akihiko , Taira Takuya , Nakagawa Shun , Kawakita Kenya , Kuroda Yasuhiro
Published: July 2022

The aim of this single-center retrospective study was to investigate the association between the time in range (TIR) of relative normoglycemia (RN) and in-hospital mortality. We defined RN as measured blood glucose in the range of 70–140% of A1C-derived average glucose and absolute normoglycemia (AN) as 70–140 mg/dL. We conducted multivariate logistic regression analyses to examine the association between TIR of RN > 80% or TIR of AN > 80% up to 72 h after ICU admission and in-hospital mortality (Model 1 and Model 2, respectively). The discrimination of the models was assessed using the area under the receiver operating characteristic curve (AUROC). Among 328 patients, 35 died in hospital (11%). Model 1 showed that TIR of RN > 80% was associated with reduced in-hospital mortality (adjusted OR 0.16; 95% CI 0.06–0.43; P < 0. 001); however, Model 2 showed that the TIR of AN > 80% was not. The AUROC of Model 1 was significantly higher than that of Model 2 (0.84 [95% CI 0.77–0.90] vs. 0.79 [0.70–0.87], P = 0.008).Our findings provide a foundation for further studies exploring individualized glycemic management in ICUs.
Genetic variations in methotrexate metabolic pathway genes influence methotrexate responses in rheumatoid arthritis patients in Malaysia
Authors: Sha Hong Xi , Veerapen Kumar , Chow Sook Khuan , Gun Suk Chyn , Lau Ing Soo , Lim Renee Lay Hong , Zulkifli Zaliha , Yow Yoon-Yen , Peh Suat Cheng , Hwang Jung Shan
Published: July 2022

Methotrexate (MTX) is the most widely used disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA). Many studies have attempted to understand the genetic risk factors that affect the therapeutic outcomes in RA patients treated with MTX. Unlike other studies that focus on the populations of Caucasians, Indian and east Asian countries, this study investigated the impacts of six single nucleotide polymorphisms (SNPs) that are hypothesized to affect the outcomes of MTX treatment in Malaysian RA patients. A total of 647 RA patients from three ethnicities (NMalay = 153; NChinese = 326; NIndian = 168) who received MTX monotherapy (minimum 15 mg per week) were sampled from three hospitals in Malaysia. SNPs were genotyped in patients using TaqMan real-time PCR assay. Data obtained were statistically analysed for the association between SNPs and MTX efficacy and toxicity. Analysis of all 647 RA patients indicated that none of the SNPs has influence on either MTX efficacy or MTX toxicity according to the Chi-square test and binary logistic regression. However, stratification by self-identified ancestries revealed that two out of six SNPs, ATIC C347G (rs2372536) (OR 0.5478, 95% CI 0.3396–0.8835, p = 0.01321) and ATIC T675C (rs4673993) (OR 0.5247, 95% CI 0.3248–0.8478, p = 0.008111), were significantly associated with MTX adequate response in RA patients with Malay ancestry (p < 0.05). As for the MTX toxicity, no significant association was identified for any SNPs selected in this study. Taken all together, ATIC C347G and ATIC T675C can be further evaluated on their impact in MTX efficacy using larger ancestry-specific cohort, and also incorporating high-order gene–gene and gene–environment interactions.
A first-principles-based high fidelity, high throughput approach for the design of high entropy alloys
Authors: Sorkin V. , Yu Z. G. , Chen S. , Tan Teck L. , Aitken Z. H. , Zhang Y. W.
Published: July 2022

Here, we present a preselected small set of ordered structures (PSSOS) method, a first principles-based high fidelity (HF), high throughput (HT) approach, for fast screening of the large composition space of high entropy alloys (HEAs) to select the most energetically stable, single-phase HEAs. Taking quinary AlCoCrFeNi HEA as an example system, we performed PSSOS calculations on the formation energies and mass densities of 8801 compositions in both FCC and BCC lattices and selected five most stable FCC and BCC HEAs for detailed analysis. The calculation results from the PSSOS approach were compared with existing experimental and first-principles data, and the good agreement was achieved. We also compared the PSSOS with the special quasi-random structures (SQS) method, and found that with a comparable accuracy, the PSSOS significantly outperforms the SQS in efficiency, making it ideal for HF, HT calculations of HEAs.
Deficiency of protocadherin 9 leads to reduction in positive emotional behaviour
Authors: Uemura Masato , Furuse Tamio , Yamada Ikuko , Kushida Tomoko , Abe Takaya , Imai Keiko , Nagao Soichi , Kudoh Moeko , Yoshizawa Katsuhiko , Tamura Masaru , Kiyonari Hiroshi , Wakana Shigeharu , Hirano Shinji
Published: July 2022

Protocadherin 9 (Pcdh9) is a member of the cadherin superfamily and is uniquely expressed in the vestibular and limbic systems; however, its physiological role remains unclear. Here, we studied the expression of Pcdh9 in the limbic system and phenotypes of Pcdh9-knock-out mice (Pcdh9 KO mice). Pcdh9 mRNA was expressed in the fear extinction neurons that express protein phosphatase 1 regulatory subunit 1 B (Ppp1r1b) in the posterior part of the basolateral amygdala (pBLA), as well as in the Cornu Ammonis (CA) and Dentate Gyrus (DG) neurons of the hippocampus. We show that the Pcdh9 protein was often localised at synapses. Phenotypic analysis of Pcdh9 KO mice revealed no apparent morphological abnormalities in the pBLA but a decrease in the spine number of CA neurons. Further, the Pcdh9 KO mice were related to features such as the abnormal optokinetic response, less approach to novel objects, and reduced fear extinction during recovery from the fear. These results suggest that Pcdh9 is involved in eliciting positive emotional behaviours, possibly via fear extinction neurons in the pBLA and/or synaptic activity in the hippocampal neurons, and normal optokinetic eye movement in brainstem optokinetic system-related neurons.
An integrated analysis and comparison of serum, saliva and sebum for COVID-19 metabolomics
Authors: Spick Matt , Lewis Holly-May , Frampas Cecile F. , Longman Katie , Costa Catia , Stewart Alexander , Dunn-Walters Deborah , Greener Danni , Evetts George , Wilde Michael J. , Sinclair Eleanor , Barran Perdita E. , Skene Debra J. , Bailey Melanie J.
Published: July 2022

The majority of metabolomics studies to date have utilised blood serum or plasma, biofluids that do not necessarily address the full range of patient pathologies. Here, correlations between serum metabolites, salivary metabolites and sebum lipids are studied for the first time. 83 COVID-19 positive and negative hospitalised participants provided blood serum alongside saliva and sebum samples for analysis by liquid chromatography mass spectrometry. Widespread alterations to serum-sebum lipid relationships were observed in COVID-19 positive participants versus negative controls. There was also a marked correlation between sebum lipids and the immunostimulatory hormone dehydroepiandrosterone sulphate in the COVID-19 positive cohort. The biofluids analysed herein were also compared in terms of their ability to differentiate COVID-19 positive participants from controls; serum performed best by multivariate analysis (sensitivity and specificity of 0.97), with the dominant changes in triglyceride and bile acid levels, concordant with other studies identifying dyslipidemia as a hallmark of COVID-19 infection. Sebum performed well (sensitivity 0.92; specificity 0.84), with saliva performing worst (sensitivity 0.78; specificity 0.83). These findings show that alterations to skin lipid profiles coincide with dyslipidaemia in serum. The work also signposts the potential for integrated biofluid analyses to provide insight into the whole-body atlas of pathophysiological conditions.
Transgenic overexpression of microRNA-30d in pancreatic beta-cells progressively regulates beta-cell function and identity
Authors: Mao Yiping , Schoenborn Jacob , Wang Zhihong , Chen Xinqian , Matson Katy , Mohan Ramkumar , Zhang Shungang , Tang Xiaohu , Arunagiri Anoop , Arvan Peter , Tang Xiaoqing
Published: July 2022

Abnormal microRNA functions are closely associated with pancreatic β-cell loss and dysfunction in type 2 diabetes. Dysregulation of miR-30d has been reported in the individuals with diabetes. To study how miR-30d affects pancreatic β-cell functions, we generated two transgenic mouse lines that specifically overexpressed miR-30d in β-cells at distinct low and high levels. Transgenic overexpressed miR-30d systemically affected β-cell function. Elevated miR-30d at low-level (TgL, 2-fold) had mild effects on signaling pathways and displayed no significant changes to metabolic homeostasis. In contrast, transgenic mice with high-level of miR-30d expression (TgH, 12-fold) exhibited significant diet-induced hyperglycemia and β-cell dysfunction. In addition, loss of β-cell identity was invariably accompanied with increased insulin/glucagon-double positive bihormonal cells and excess plasma glucagon levels. The transcriptomic analysis revealed that miR-30d overexpression inhibited β-cell-enriched gene expression and induced α-cell-enriched gene expression. These findings implicate that an appropriate miR-30d level is essential in maintaining normal β-cell identity and function.
Integrated transcriptomic and regulatory network analyses uncovers the role of let-7b-5p, SPIB, and HLA-DPB1 in sepsis
Authors: Mohsin Mohd , Singh Prithvi , Khan Salman , Verma Amit Kumar , Jha Rishabh , Alsahli Mohammed A. , Rahmani Arshad Husain , Almatroodi Saleh A. , Alrumaihi Faris , Kaprwan Nisha , Dev Kapil , Dohare Ravins , Syed Mansoor Ali
Published: July 2022

Sepsis has affected millions of populations of all age groups, locations, and sexes worldwide. Immune systems, either innate or adaptive are dysregulated due to the infection. Various biomarkers are present to date, still sepsis is a primary cause of mortality. Globally, post-operative body infections can cause sepsis and septic shock in ICU. Abnormal antigen presentation to T-cells leads to a dysregulated immune system. miRNAs are sparkly evolved as biomarkers due to their high sensitivity and efficiency. In this work, we analyzed high-throughput mRNA data collected from Gene Expression Omnibus (GEO) and linked it to significant miRNAs and TFs using a network-based approach. Protein–protein interaction (PPI) network was constructed using sepsis-specific differentially expressed genes (DEGs) followed by enrichment analyses and hub module detection. Sepsis-linked decrease transcription of the classical HLA gene such as HLA-DPB1 and its interplay with miR-let-7b-5p and transcription factor SPIB was observed. This study helped to provide innovative targets for sepsis.
Improved inpatient deterioration detection in general wards by using time-series vital signs
Authors: Su Chang-Fu , Chiu Shu-I , Jang Jyh-Shing Roger , Lai Feipei
Published: July 2022

Although in-hospital cardiac arrest is uncommon, it has a high mortality rate. Risk identification of at-risk patients is critical for post-cardiac arrest survival rates. Early warning scoring systems are generally used to identify hospitalized patients at risk of deterioration. However, these systems often require clinical data that are not always regularly measured. We developed a more accurate, machine learning-based model to predict clinical deterioration. The time series early warning score (TEWS) used only heart rate, systolic blood pressure, and respiratory data, which are regularly measured in general wards. We tested the performance of the TEWS in two tasks performed with data from the electronic medical records of 16,865 adult admissions and compared the results with those of other classifications. The TEWS detected more deteriorations with the same level of specificity as the different algorithms did when inputting vital signs data from 48 h before an event. Our framework improved in-hospital cardiac arrest prediction and demonstrated that previously obtained vital signs data can be used to identify at-risk patients in real-time. This model may be an alternative method for detecting patient deterioration.