bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polyphosphate-induced thrombosis in mice is factor XII dependent and is attenuated by histidine-rich glycoprotein
Authors: Malik Rida A. , Zhou Ji , Fredenburgh James C. , Truong Tammy K. , Crosby Jeff R. , Revenko Alexey S. , Weitz Jeffrey I. 
Published: September 2021

AbstractHistidine-rich glycoprotein (HRG) is an abundant plasma protein that binds factor XIIa (FXIIa) and inhibits factor XII (FXII) autoactivation and FXIIa-mediated activation of FXI. Polyphosphate (polyP), a potent procoagulant released from activated platelets, may serve as a physiological activator of the contact system. Previously, we showed that HRG binds DNA and neutralizes its procoagulant activity. Consequently, our goal was to determine whether the capacity of HRG to bind polyanions enables it to regulate polyP-induced thrombosis. In a plate-based assay, immobilized polyP bound HRG, FXII, and FXIIa in a zinc-dependent manner. Basal and polyP-induced thrombin generation was greater in plasma from HRG-deficient mice than in plasma from wild-type mice. Intraperitoneal injection of polyP shortened the activated partial thromboplastin time, enhanced thrombin generation, increased thrombin-antithrombin levels, reduced lung perfusion, and promoted pulmonary fibrin deposition to a greater extent in HRG-deficient mice than in wild-type mice, effects that were abrogated with FXII knockdown. HRG thus attenuates the procoagulant and prothrombotic effects of polyP in an FXII-dependent manner by modulating the contact system.
American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: May 2021 update on the use of intermediate-intensity anticoagulation in critically ill patients
Authors: Cuker Adam , Tseng Eric K. , Nieuwlaat Robby , Angchaisuksiri Pantep , Blair Clifton , Dane Kathryn , Davila Jennifer , DeSancho Maria T. , Diuguid David , Griffin Daniel O. , Kahn Susan R. , Klok Frederikus A. , Lee Alfred Ian , Neumann Ignacio , Pai Ashok , Righini Marc , Sanfilippo Kristen M. , Siegal Deborah , Skara Mike , Terrell Deirdra R. , Touri Kamshad , Akl Elie A. , Bou Akl Imad , Bognanni Antonio , Boulos Mary , Brignardello-Petersen Romina , Charide Rana , Chan Matthew , Dearness Karin , Darzi Andrea J. , Kolb Philipp , Colunga-Lozano Luis E. , Mansour Razan , Morgano Gian Paolo , Morsi Rami Z. , Muti-Schünemann Giovanna , Noori Atefeh , Philip Binu A. , Piggott Thomas , Qiu Yuan , Roldan Yetiani , Schünemann Finn , Stevens Adrienne , Solo Karla , Wiercioch Wojtek , Mustafa Reem A. , Schünemann Holger J. 
Published: September 2021

Abstract
Background: COVID-19–related critical illness is associated with an increased risk of venous thromboembolism (VTE).
Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19–related critical illness who do not have confirmed or suspected VTE.
Methods: ASH formed a multidisciplinary guideline panel that included 3 patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process by performing systematic evidence reviews (up to 5 March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update on guidelines published in February 2021.
Results: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation in favor of prophylactic-intensity over intermediate-intensity anticoagulation in patients with COVID-19–related critical illness who do not have confirmed or suspected VTE.
Conclusions: This recommendation was based on low certainty in the evidence, which underscores the need for additional high-quality, randomized, controlled trials comparing different intensities of anticoagulation in critically ill patients. Other key research priorities include better evidence regarding predictors of thrombosis and bleeding risk in critically ill patients with COVID-19 and the impact of nonanticoagulant therapies (eg, antiviral agents, corticosteroids) on thrombotic risk.
The effect of immunosuppressants on the prognosis of SARS-CoV-2 infection
Authors: Ward Daniel , Gørtz Sanne , Thomson Ernst Martin , Andersen Nynne Nyboe , Kjær Susanne K. , Hallas Jesper , Christensen Steffen , Fynbo Christiansen Christian , Bastrup Israelsen Simone , Benfield Thomas , Pottegård Anton , Jess Tine 
Published: September 2021

BackgroundImmunosuppression may worsen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a nationwide cohort study of the effect of exposure to immunosuppressants on the prognosis of SARS-CoV-2 infection in Denmark.MethodsWe identified all SARS-CoV-2 test-positive patients from February 2020 to October 2020 and linked healthcare data from nationwide registers, including prescriptions for the exposure (immunosuppressant drugs). We estimated relative risks of hospital admission, intensive care unit (ICU) admission and death (each studied independently up to 30 days from testing) with a log-linear binomial regression adjusted for confounders using a propensity score-based matching weights model.ResultsA composite immunosuppressant exposure was associated with a significantly increased risk of death (adjusted relative risk 1.56 (95% CI 1.10–2.22)). The increased risk of death was mainly driven by exposure to systemic glucocorticoids (adjusted relative risk 2.38 (95% CI 1.72–3.30)), which were also associated with an increased risk of hospital admission (adjusted relative risk 1.34 (95% CI 1.10–1.62)), but not of ICU admission (adjusted relative risk 1.76 (95% CI 0.93–3.35)); these risks were greater for high cumulative doses of glucocorticoids than for moderate doses. Exposure to selective immunosuppressants, tumour necrosis factor inhibitors or interleukin inhibitors was not associated with an increased risk of hospitalisation, ICU admission or death, nor was exposure to calcineurin inhibitors, other immunosuppressants, hydroxychloroquine or chloroquine.ConclusionsExposure to glucocorticoids was associated with increased risks of hospital admission and death. Further investigation is needed to determine the optimal management of coronavirus disease 2019 (COVID-19) in patients with pre-morbid glucocorticoid usage, specifically whether these patients require altered doses of glucocorticoids.
Current status of premature mortality from four non-communicable diseases and progress towards the Sustainable Development Goal target 3.4: a population-based study in northeast China, 2004–2017
Authors: Liu Li , Li Yanxia , Song Junmin , Chen Qian , Li Shuang , Mu Huijuan , Na Jun , Zhang Rui , Yu Liya , Sun Wei , Pan Guowei 
Published: September 2021

Abstract
Background and aim
According to the United Nations’ Sustainable Development Goal (SDG) target 3.4, premature mortality from four non-communicable diseases (cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes mellitus, collectively referred to as NCD4) should achieve a minimum decline of 33% in 2030 relative to 2015. This remains a challenge for China. This study aimed to evaluate the current status and progress towards this target in Liaoning Province, one of the three provinces in northeast China.

Methods
We calculated the premature mortality rates (PMRs) per year and average annual percentage changes (AAPCs) from NCD4 using mortality data between 2004 and 2017. The trend was analyzed in the whole population, as well as in subpopulations of gender (male/female) and inhabiting area (urban/rural). PMRs from NCD4 for 2030 were projected by fitting a linear regression based on the current trend, which was identified by a Joinpoint model.

Findings
In the whole population, only chronic respiratory diseases showed a significant decline (AAPC: − 6.5%, p < 0.05), while only cancer showed a significant increase (AAPC: + 1.3%, p < 0.05); taken together, NCD4 showed a significant increase (AAPC: + 0.6%, p < 0.05). In the subpopulations, while males showed a significant increase in NCD4 (AAPC: + 1.5%, p < 0.05), cardiovascular diseases (AAPC: + 1.7%, p < 0.05), cancer (AAPC: + 1.8%, p < 0.05), and diabetes mellitus (AAPC: + 4.2%, p < 0.05), females showed a significant decline in NCD4 (AAPC: − 1.2%, p < 0.05), cardiovascular diseases (AAPC: − 1.8%, p < 0.05), diabetes mellitus (AAPC: − 2.1%, p < 0.05), but showed a mild increase in cancer (AAPC: + 0.5%, p > 0.05). A comparative analysis of the projected PMRs for 2030 with the 2015 levels revealed that only chronic respiratory diseases are expected to achieve the SDG target 3.4, apart from in the urban male subpopulation.

Conclusion
Except for chronic respiratory diseases, NCD4 cannot be expected to achieve the SDG target 3.4 in the whole population of Liaoning Province. Under these circumstances, special attention should be paid to reducing the risks of cancer and providing preventative interventions for men.
Risk factors for depression during the COVID-19 pandemic: a longitudinal study in middle-aged and older adults
Authors: Rutland-Lawes Jamie , Wallinheimo Anna-Stiina , Evans Simon L. 
Published: September 2021

Background
The COVID-19 pandemic and resultant social restrictions have had widespread psychological ramifications, including a rise in depression prevalence. However, longitudinal studies on sociodemographic risk factors are lacking.

Aims
To quantify longitudinal changes in depression symptoms during the pandemic compared with a pre-pandemic baseline, in middle-aged and older adults, and identify the risk factors contributing to this.

Method
A total of 5331 participants aged ≥50 years were drawn from the English Longitudinal Study of Ageing. Self-reported depression symptoms in June/July 2020 were compared with baseline data from 2–3 years prior. Regression models investigated sociodemographic and lifestyle variables that could explain variance in change in depression.

Results
Within-participant depression scores increased significantly from pre-pandemic levels: 14% met the criteria for clinical depression at baseline, compared with 26% during the pandemic. Younger age, female gender, higher depression scores at baseline, living alone and having a long-standing illness were significant risk factors. Gender-stratified regression models indicated that older age was protective for women only, whereas urban living increased risk among women only. Being an alcohol consumer was a protective factor among men only.

Conclusions
Depression in UK adults aged ≥50 years increased significantly during the pandemic. Being female, living alone and having a long-standing illness were prominent risk factors. Younger women living in urban areas were at particularly high risk, suggesting such individuals should be prioritised for support. Findings are also informative for future risk stratification and intervention strategies, particularly if social restrictions are reimposed as the COVID-19 crisis continues to unfold.
Understanding the Link Between Obesity and Severe COVID-19 Outcomes: Causal Mediation by Systemic Inflammatory Response
Authors: Foulkes Andrea S , Selvaggi Caitlin , Shinnick Daniel , Lumish Heidi , Kim Eunyoung , Cao Tingyi , Thaweethai Tanayott , Qian Jing , Lu Frances , Yan Joyce , Cheng David , He Wei , Clerkin Kevin J , Madhavan Mahesh V , Meigs James B , Triant Virginia A , Lubitz Steven A , Gupta Aakriti , Bassett Ingrid V , Reilly Muredach P 
Published: September 2021

Abstract

Background
Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood.

Objective
To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes.

Methods
This hospital-based, observational study included 3828 SARS-CoV-2-infected patients who were hospitalized February to May 2020 at Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/New York Presbyterian Hospital (CUIMC/NYP). We use mediation analysis to evaluate whether peak inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], D-dimer, ferritin, white blood cell count and interleukin-6) are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care.

Results
In the MGH cohort (n = 1202), obesity was associated with greater likelihood of ventilation or death (OR = 1.73; 95% CI = [1.25, 2.41]; P = 0.001) and higher peak CRP (P &lt; 0.001) compared with nonobese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (P &lt; 0.001). Evidence of mediation was more pronounced in patients &lt; 65 years (proportion mediated = 0.52 [P &lt; 0.001] vs 0.44 [P = 0.180]). Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (n = 2626).

Conclusion
Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients &lt; 65 years, captured by CRP and ESR. Contextualized in clinical trial findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients.
The 3′UTR of the Drosophila CPEB translation factor gene orb2 plays a crucial role in spermatogenesis
Authors: Gilmutdinov Rudolf , Kozlov Eugene N. , Yakovlev Konstantin V. , Olenina Ludmila V. , Kotov Alexei A. , Barr Justinn , Zhukova Mariya , Schedl Paul , Shidlovskii Yulii V. 
Published: September 2021

ABSTRACT
CPEB proteins are conserved translation regulators involved in multiple biological processes. One of these proteins in Drosophila, Orb2, is a principal player in spermatogenesis. It is required for meiosis and spermatid differentiation. During the later process, orb2 mRNA and protein are localized within the developing spermatid. To evaluate the role of the orb2 mRNA 3′UTR in spermatogenesis, we used the CRISPR/Cas9 system to generate a deletion of the orb2 3′UTR, orb2R. This deletion disrupts the process of spermatid differentiation but has no apparent effect on meiosis. Differentiation abnormalities include defects in the initial polarization of the 64-cell spermatid cysts, mislocalization of mRNAs and proteins in the elongating spermatid tails, altered morphology of the elongating spermatid tails, and defects in the assembly of the individualization complex. These disruptions in differentiation appear to arise because orb2 mRNA and protein are not properly localized within the 64-cell spermatid cyst.
Flow cytometry allows rapid detection of protein aggregates in cellular and zebrafish models of spinocerebellar ataxia 3
Authors: Robinson Katherine J. , Tym Madelaine C. , Hogan Alison , Watchon Maxinne , Yuan Kristy C. , Plenderleith Stuart K. , Don Emily K. , Laird Angela S. 
Published: September 2021

ABSTRACT
Spinocerebellar ataxia 3 (SCA3, also known as Machado–Joseph disease) is a neurodegenerative disease caused by inheritance of a CAG repeat expansion within the ATXN3 gene, resulting in polyglutamine (polyQ) repeat expansion within the ataxin-3 protein. In this study, we have identified protein aggregates in both neuronal-like (SHSY5Y) cells and transgenic zebrafish expressing human ataxin-3 with expanded polyQ. We have adapted a previously reported flow cytometry methodology named flow cytometric analysis of inclusions and trafficking, allowing rapid quantification of detergent insoluble forms of ataxin-3 fused to a GFP in SHSY5Y cells and cells dissociated from the zebrafish larvae. Flow cytometric analysis revealed an increased number of detergent-insoluble ataxin-3 particles per nuclei in cells and in zebrafish expressing polyQ-expanded ataxin-3 compared to those expressing wild-type human ataxin-3. Treatment with compounds known to modulate autophagic activity altered the number of detergent-insoluble ataxin-3 particles in cells and zebrafish expressing mutant human ataxin-3. We conclude that flow cytometry can be harnessed to rapidly count ataxin-3 aggregates, both in vitro and in vivo, and can be used to compare potential therapies targeting protein aggregates.
This article has an associated First Person interview with the first author of the paper.
Prion protein and prion disease at a glance
Authors: Zhu Caihong , Aguzzi Adriano 
Published: September 2021

ABSTRACT
Prion diseases are neurodegenerative disorders caused by conformational conversion of the cellular prion protein (PrPC) into scrapie prion protein (PrPSc). As the main component of prion, PrPSc acts as an infectious template that recruits and converts normal cellular PrPC into its pathogenic, misfolded isoform. Intriguingly, the phenomenon of prionoid, or prion-like, spread has also been observed in many other disease-associated proteins, such as amyloid β (Aβ), tau and α-synuclein. This Cell Science at a Glance and the accompanying poster highlight recently described physiological roles of prion protein and the advanced understanding of pathogenesis of prion disease they have afforded. Importantly, prion protein may also be involved in the pathogenesis of other neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Therapeutic studies of prion disease have also exploited novel strategies to combat these devastating diseases. Future studies on prion protein and prion disease will deepen our understanding of the pathogenesis of a broad spectrum of neurodegenerative conditions.
Interplay between myofibers and pro-inflammatory macrophages controls muscle damage in mdx mice
Authors: Saclier Marielle , Ben Larbi Sabrina , My Ly Ha , Moulin Eugénie , Mounier Rémi , Chazaud Bénédicte , Juban Gaëtan 
Published: September 2021

ABSTRACT
Duchenne muscular dystrophy is a genetic muscle disease characterized by chronic inflammation and fibrosis mediated by a pro-fibrotic macrophage population expressing pro-inflammatory markers. Our aim was to characterize cellular events leading to the alteration of macrophage properties and to modulate macrophage inflammatory status using the gaseous mediator hydrogen sulfide (H2S). Using co-culture experiments, we first showed that myofibers derived from mdx mice strongly skewed the polarization of resting macrophages towards a pro-inflammatory phenotype. Treatment of mdx mice with NaHS, an H2S donor, reduced the number of pro-inflammatory macrophages in skeletal muscle, which was associated with a decreased number of nuclei per fiber, as well as reduced myofiber branching and fibrosis. Finally, we established the metabolic sensor AMP-activated protein kinase (AMPK) as a critical NaHS target in muscle macrophages. These results identify an interplay between myofibers and macrophages where dystrophic myofibers contribute to the maintenance of a highly inflammatory environment sustaining a pro-inflammatory macrophage status, which in turn favors myofiber damage, myofiber branching and establishment of fibrosis. Our results also highlight the use of H2S donors as a potential therapeutic strategy to improve the dystrophic muscle phenotype by dampening chronic inflammation.
This article has an associated First Person interview with the first author of the paper.
Design of financial incentive interventions to improve lifestyle behaviors and health outcomes: A systematic review
Authors: Miranda J. Jaime , Pesantes M. Amalia , Lazo-Porras María , Portocarrero Jill , Diez-Canseco Francisco , Carrillo-Larco Rodrigo M. , Bernabe-Ortiz Antonio , Trujillo Antonio J. , Aldridge Robert W. 
Published: September 2021

Background: Financial incentives may improve the initiation and engagement of behaviour change that reduce the negative outcomes associated with non-communicable diseases. There is still a paucity in guidelines or recommendations that help define key aspects of incentive-oriented interventions, including the type of incentive (e.g. cash rewards, vouchers), the frequency and magnitude of the incentive, and its mode of delivery. We aimed to systematically review the literature on financial incentives that promote healthy lifestyle behaviours or improve health profiles, and focused on the methodological approach to define the incentive intervention and its delivery. The protocol was registered at PROSPERO on 26 July 2018 (CRD42018102556). Methods: We sought studies in which a financial incentive was delivered to improve a health-related lifestyle behaviour (e.g., physical activity) or a health profile (e.g., HbA1c in people with diabetes). The search (which took place on March 3rd 2018) was conducted using OVID (MEDLINE and Embase), CINAHL and Scopus. Results: The search yielded 7,575 results and 37 were included for synthesis. Of the total, 83.8% (31/37) of the studies were conducted in the US, and 40.5% (15/37) were randomised controlled trials. Only one study reported the background and rationale followed to develop the incentive and conducted a focus group to understand what sort of incentives would be acceptable for their study population. There was a degree of consistency across the studies in terms of the direction, form, certainty, and recipient of the financial incentives used, but the magnitude and immediacy of the incentives were heterogeneous. Conclusions: The available literature on financial incentives to improve health-related lifestyles rarely reports on the rationale or background that defines the incentive approach, the magnitude of the incentive and other relevant details of the intervention, and the reporting of this information is essential to foster its use as potential effective interventions.
Quantification of fetal organ sparing in maternal low-protein dietary models
Authors: Serpente Patricia , Zhang Ying , Islimye Eva , Hart-Johnson Sarah , Gould Alex P. 
Published: September 2021

Background: Maternal malnutrition can lead to fetal growth restriction. This is often associated with organ sparing and long-lasting physiological dysfunctions during adulthood, although the underlying mechanisms are not yet well understood. Methods: Low protein (LP) dietary models in C57BL/6J mice were used to investigate the proximal effects of maternal malnutrition on fetal organ weights and organ sparing at embryonic day 18.5 (E18.5). Results: Maternal 8% LP diet induced strikingly different degrees of fetal growth restriction in different animal facilities, but adjustment of dietary protein content allowed similar fetal body masses to be obtained. A maternal LP diet that restricted fetal body mass by 40% did not decrease fetal brain mass to the same extent, reflecting positive growth sparing of this organ. Under these conditions, fetal pancreas and liver mass decreased by 60-70%, indicative of negative organ sparing. A series of dietary swaps between LP and standard diets showed that the liver is capable of efficient catch-up growth from as late as E14.5 whereas, after E10.5, the pancreas is not. Conclusions: This study highlights that the reproducibility of LP fetal growth restriction studies between laboratories can be improved by careful calibration of maternal dietary protein content. LP diets that induce 30-40% restriction of prenatal growth provide a good model for fetal organ sparing. For the liver, recovery of growth following protein restriction is efficient throughout fetal development but, for the pancreas, transient LP exposures spanning the progenitor expansion phase lead to an irreversible fetal growth deficit.