bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency of deep vein thrombosis at admission for acute stroke and associated factors: a cross-sectional study
Authors: Mori Takahisa , Yoshioka Kazuhiro , Tanno Yuhei 
Published: September 2021

Abstract
Background
Intermittent pneumatic compression (IPC) is commonly used to prevent deep vein thrombosis (DVT) during hospitalization in patients with acute stroke. However, if DVT exists at admission, IPC of the legs with DVT may cause migration of the thrombi, resulting in pulmonary emboli. Whole-leg ultrasonography (wl-US) is a practical tool to detect DVT; however, wl-US is not always performed at admission in all stroke patients. This retrospective cross-sectional study aimed to investigate DVT frequency and identify significant factors indicating the presence of DVT at admission for acute stroke.

Methods
We included patients admitted within 24 h of stroke onset between 2017 and 2019. Patients who did not undergo blood tests for D-dimer or wl-US within 72 h of arrival were excluded. We collected patient data on age; sex; anthropometric variables; presence of DVT on wl-US; and biomarkers such as D-dimer, high-sensitivity C-reactive protein (hs-CRP), and lipids.

Results
Of 1129 acute stroke patients, 917 met our inclusion criteria. DVT was detected in 161 patients (17.6 %). Patients with DVT were older; were more likely to be female; had lower body weight; had higher D-dimer and hs-CRP levels; had lower albumin, hemoglobin, and triglyceride levels; and had higher National Institutes of Health Stroke Scale and pre-stroke modified Rankin scale scores than patients without DVT (n = 756). In addition, multiple logistic regression analysis showed that sex (female) and D-dimer levels (≥ 1.52 µg/mL) were independent significant factors for the presence of DVT. Among 161 patients with DVT, 78 (48.4 %) had both these significant factors. Among 756 patients without DVT, 602 (79.6 %) had no or one significant factor. The odds ratio of the presence of DVT in patients with both significant factors was 6.29, using patients without any significant factors as the group for comparison.

Conclusions
The frequency of DVT is high in acute stroke patients at admission. Female sex and a high D-dimer level were independent significant factors for the presence of DVT. Therefore, in patients with these two significant factors at admission, IPC should be avoided or wl-US should be performed before IPC.
Coevolution of COVID-19 research and China’s policies
Authors: Cheng Xi , Tang Li , Zhou Maotian , Wang Guoyan 
Published: September 2021

Abstract
Background
In the era of evidence-based policy-making (EBPM), scientific outputs and public policy should engage with each other in a more interactive and coherent way. Notably, this is becoming increasingly critical in preparing for public health emergencies.

Methods
To explore the coevolution dynamics between science and policy (SAP), this study explored the changes in, and development of, COVID-19 research in the early period of the COVID-19 outbreak in China, from 30 December 2019 to 26 June 2020. In this study, VOSviewer was adopted to calculate the link strength of items extracted from scientific publications, and machine learning clustering analysis of scientific publications was carried out to explore dynamic trends in scientific research. Trends in relevant policies that corresponded to changing trends in scientific research were then traced.

Results
The study observes a salient change in research content as follows: an earlier focus on “children and pregnant patients”, “common symptoms”, “nucleic acid test”, and “non-Chinese medicine” was gradually replaced with a focus on “aged patients”, “pregnant patients”, “severe symptoms and asymptomatic infection”, “antibody assay”, and “Chinese medicine”. “Mental health” is persistent throughout China’s COVID-19 research. Further, our research reveals a correlation between the evolution of COVID-19 policies and the dynamic development of COVID-19 research. The average issuance time of relevant COVID-19 policies in China is 8.36 days after the launching of related research.

Conclusions
In the early stage of the outbreak in China, the formulation of research-driven-COVID-19 policies and related scientific research followed a similar dynamic trend, which is clearly a manifestation of a coevolution model (CEM). The results of this study apply more broadly to the formulation of policies during public health emergencies, and provide the foundation for future EBPM research.
Innate immune responses after stimulation with Toll-like receptor agonists in ex vivo microglial cultures and an in vivo model using mice with reduced microglia
Authors: Carroll James A. , Race Brent , Williams Katie , Striebel James F. , Chesebro Bruce 
Published: September 2021

AbstractBackgroundPast experiments studying innate immunity in the central nervous system (CNS) utilized microglia obtained from neonatal mouse brain, which differ developmentally from adult microglia. These differences might impact our current understanding of the role of microglia in CNS development, function, and disease.MethodsCytokine protein secretion was compared in ex vivo P3 and adult microglial cultures after exposure to agonists for three different toll-like receptors (TLR4, lipopolysaccharide [LPS]; TLR7, imiquimod [IMQ]; and TLR9, CpG Oligodeoxynucleotide [CpG-ODN] 1585). In addition, changes in inflammatory gene expression in ex vivo adult microglia in response to the TLR agonists was assessed. Furthermore, in vivo experiments evaluated changes in gene expression associated with inflammation and TLR signaling in brains of mice with or without treatment with PLX5622 to reduce microglia.ResultsEx vivo adult and P3 microglia increased cytokine secretion when exposed to TLR4 agonist LPS and to TLR7 agonist IMQ. However, adult microglia decreased expression of numerous genes after exposure to TLR 9 agonist CpG-ODN 1585. In contrast, in vivo studies indicated a core group of inflammatory and TLR signaling genes increased when each of the TLR agonists was introduced into the CNS. Reducing microglia in the brain led to decreased expression of various inflammatory and TLR signaling genes. Mice with reduced microglia showed extreme impairment in upregulation of genes after exposure to TLR7 agonist IMQ.ConclusionsCultured adult microglia were more reactive than P3 microglia to LPS or IMQ exposure. In vivo results indicated microglial influences on neuroinflammation were agonist specific, with responses to TLR7 agonist IMQ more dysregulated in mice with reduced microglia. Thus, TLR7-mediated innate immune responses in the CNS appeared more dependent on the presence of microglia. Furthermore, partial responses to TLR4 and TLR9 agonists in mice with reduced microglia suggested other cell types in the CNS can compensate for their absence.
Acute myocardial infarction associated with abacavir and tenofovir based antiretroviral drug combinations in the United States
Authors: Dorjee Kunchok , Desai Manisha , Choden Tsering , Baxi Sanjiv M. , Hubbard Alan E. , Reingold Arthur L. 
Published: September 2021

Abstract
Introduction
Although individual antiretroviral drugs have been shown to be associated with elevated cardiovascular disease (CVD) risk, data are limited on the role of antiretroviral drug combinations. Therefore, we sought to investigate CVD risk associated with antiretroviral drug combinations.

Methods
Using an administrative health-plan dataset, risk of acute myocardial infarction (AMI) associated with current exposure to antiretroviral drug combinations was assessed among persons living with HIV receiving antiretroviral therapy (ART) across the U.S. from October 2009 through December 2014. To account for confounding-by-indication and for factors simultaneously acting as causal mediators and confounders, we applied inverse probability of treatment weighted marginal structural models to longitudinal data of patients.

Results
Over 114,417 person-years (n = 73,071 persons) of ART exposure, 602 cases of AMI occurred at an event rate of 5.26 (95% CI: 4.86, 5.70)/1000 person-years. Of the 14 antiretroviral drug combinations studied, persons taking abacavir-lamivudine-darunavir had the highest incidence rate (IR: 11/1000; 95% CI: 7.4–16.0) of AMI. Risk (HR; 95% CI) of AMI was elevated for current exposure to abacavir-lamivudine-darunavir (1.91; 1.27–2.88), abacavir-lamivudine-atazanavir (1.58; 1.08–2.31), and tenofovir-emtricitabine-raltegravir (1.35; 1.07–1.71). Tenofovir-emtricitabine-efavirenz was associated with reduced risk (0.65; 0.54–0.78). Abacavir-lamivudine-darunavir was associated with increased risk of AMI beyond that expected of abacavir alone, likely attributable to darunavir co-administration. We did not find an elevated risk of AMI when abacavir-lamivudine was combined with efavirenz or raltegravir.

Conclusion
The antiretroviral drug combinations abacavir-lamivudine-darunavir, abacavir-lamivudine-atazanavir and tenofovir-emtricitabine-raltegravir were found to be associated with elevated risk of AMI, while tenofovir-emtricitabine-efavirenz was associated with a lower risk. The AMI risk associated with abacavir-lamivudine-darunavir was greater than what was previously described for abacavir, which could suggest an added risk from darunavir. The results should be confirmed in additional studies.
Do international trade and investment agreements generate regulatory chill in public health policymaking? A case study of nutrition and alcohol policy in South Africa
Authors: Milsom Penelope , Smith Richard , Modisenyane Simon Moeketsi , Walls Helen 
Published: September 2021

AbstractBackgroundTrade and health scholars have raised concern that international trade and particularly investment disputes may be used by transnational health harmful commodity corporations (THCCs) to effectively generate public health regulatory chill. The purpose of this study was to contribute to the limited evidence base of trade or investment dispute-related regulatory chill using a case study of nutrition and alcohol policy in South Africa.MethodsWe conducted 35 semi-structured interviews with 36 key stakeholders involved in nutrition, alcohol and/or trade/investment policymaking in South Africa. Interview transcripts were analyzed using thematic analysis. We used Schram et al’s theory on three forms of regulatory chill (anticipatory, response and precedential) to guide the analysis. We report evidence on each form of regulatory chill as well as specific contextual factors that may influence the risk of regulatory chill.ResultsTrade obligations were found to generate a significantly greater anticipatory-type chilling effect on nutrition and alcohol regulation than South Africa’s investment treaty obligations. Response chill was reported to have occurred in relation to South Africa’s proposed tobacco plain packaging regulation while awaiting the outcome of both Australia’s investor-state and WTO state-state disputes. No cases were reported of THCCs threatening an investor-state dispute over nutrition or food regulations, but there were reported cases of THCCs using arguments related to South Africa’s trade obligations to oppose policy action in these areas. No evidence of nutrition or alcohol policy precedential chill were identified. Factors affecting the risk of policy chill include legitimacy and perceived bias of the dispute system, costs involved in pursuing a regulation/defending a dispute and capacity to pay, social acceptability of the industry, a product’s perceived risk to health and confidence in a successful dispute outcome e.g. through cross-border policy learning.ConclusionsOur findings indicate that currently, South Africa’s trade obligations have a more prominent role in inhibiting nutrition and alcohol action than investment treaty-related concerns. However, given the potential for wider use of the ISDS mechanism by THCCs in the future, strategies to protect public health policy space in the context of both international trade and investment treaty and dispute settlement contexts remain important.
A cross-sectional study of lactation room quality and Dutch working mothers’ satisfaction, perceived ease of, and perceived support for breast milk expression at work
Authors: van Dellen Sjoukje A. , Wisse Barbara , Mobach Mark P. , Albers Casper J. , Dijkstra Arie 
Published: September 2021

Abstract
Background
The challenge of combining professional work and breastfeeding is a key reason why women choose not to breastfeed or to stop breastfeeding early. We posited that having access to a high-quality lactation room at the workplace could influence working mothers’ satisfaction and perceptions related to expressing breast milk at work, which could have important longer term consequences for the duration of breastfeeding. Specifically, we aimed to (1) develop a checklist for assessing the quality of lactation rooms and (2) explore how lactation room quality affects lactating mothers’ satisfaction and perceptions. Drawing on social ecological insights, we hypothesized that the quality of lactation rooms (operationalized as any space used for expressing milk at work) would be positively related to mothers’ satisfaction with the room, perceived ease of, and perceived support for milk expression at work.

Methods
We conducted two studies. In Study 1 we developed a lactation room quality checklist (LRQC) and assessed its reliability twice, using samples of 33 lactation rooms (Study 1a) and 31 lactation rooms (Study 1b). Data were collected in the Northern part of the Netherlands (between December 2016 and April 2017). Study 2 comprised a cross-sectional survey of 511 lactating mothers, working in a variety of Dutch organizations. The mothers were recruited through the Facebook page of a popular Dutch breastfeeding website. They completed online questionnaires containing the LRQC and measures aimed at assessing their satisfaction and perceptions related to milk expression at work (in June and July 2017).

Results
The LRQC was deemed reliable and easy to apply in practice. As predicted, we found that objectively assessed higher-quality lactation rooms were associated with increased levels of satisfaction with the lactation rooms, perceived ease of milk expression at work, and perceived support from supervisors and co-workers for expressing milk in the workplace.

Conclusions
The availability of a high-quality lactation room could influence mothers’ decisions regarding breast milk expression at work and the commencement and/or continuation of breastfeeding. Future studies should explore whether and how lactation room quality affects breastfeeding choices, and which aspects are most important to include in lactation rooms.
Wild-type FUS corrects ALS-like disease induced by cytoplasmic mutant FUS through autoregulation
Authors: Sanjuan-Ruiz Inmaculada , Govea-Perez Noé , McAlonis-Downes Melissa , Dieterle Stéphane , Megat Salim , Dirrig-Grosch Sylvie , Picchiarelli Gina , Piol Diana , Zhu Qiang , Myers Brian , Lee Chao-Zong , Cleveland Don W , Lagier-Tourenne Clotilde , Da Cruz Sandrine , Dupuis Luc 
Published: September 2021

AbstractMutations in FUS, an RNA-binding protein involved in multiple steps of RNA metabolism, are associated with the most severe forms of amyotrophic lateral sclerosis (ALS). Accumulation of cytoplasmic FUS is likely to be a major culprit in the toxicity ofFUSmutations. Thus, preventing cytoplasmic mislocalization of the FUS protein may represent a valuable therapeutic strategy. FUS binds to its own pre-mRNA creating an autoregulatory loop efficiently buffering FUS excess through multiple proposed mechanisms including retention of introns 6 and/or 7. Here, we introduced a wild-typeFUSgene allele, retaining all intronic sequences, in mice whose heterozygous or homozygous expression of a cytoplasmically retained FUS protein (Fus∆NLS) was previously shown to provoke ALS-like disease or postnatal lethality, respectively. Wild-type FUS completely rescued the early lethality caused by the twoFus∆NLSalleles, and improved the age-dependent motor deficits and reduced lifespan caused by heterozygous expression of mutant FUS∆NLS. Mechanistically, wild-type FUS decreased the load of cytoplasmic FUS, increased retention of introns 6 and 7 in the endogenous mouseFusmRNA, and decreased expression of the mutant mRNA. Thus, the wild-typeFUSallele activates the homeostatic autoregulatory loop, maintaining constant FUS levels and decreasing the mutant protein in the cytoplasm. These results provide proof of concept that an autoregulatory competent wild-type FUS expression could protect against this devastating, currently intractable, neurodegenerative disease.
APOΕ4 lowers energy expenditure in females and impairs glucose oxidation by increasing flux through aerobic glycolysis
Authors: Farmer Brandon C. , Williams Holden C. , Devanney Nicholas A. , Piron Margaret A. , Nation Grant K. , Carter David J. , Walsh Adeline E. , Khanal Rebika , Young Lyndsay E. A. , Kluemper Jude C. , Hernandez Gabriela , Allenger Elizabeth J. , Mooney Rachel , Golden Lesley R. , Smith Cathryn T. , Brandon J. Anthony , Gupta Vedant A. , Kern Philip A. , Gentry Matthew S. , Morganti Josh M. , Sun Ramon C. , Johnson Lance A. 
Published: September 2021

Abstract
Background
Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer’s disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.

Methods
Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.

Results
Single-cell analysis of brain tissue from mice expressing human APOE revealed E4-associated decreases in genes related to oxidative phosphorylation, particularly in astrocytes. This shift was confirmed on a metabolic level with isotopic tracing of 13C-glucose in E4 mice and astrocytes, which showed decreased pyruvate entry into the TCA cycle and increased lactate synthesis. Metabolic phenotyping of E4 astrocytes showed elevated glycolytic activity, decreased oxygen consumption, blunted oxidative flexibility, and a lower rate of glucose oxidation in the presence of lactate. Together, these cellular findings suggest an E4-associated increase in aerobic glycolysis (i.e. the Warburg effect). To test whether this phenomenon translated to APOE4 humans, we analyzed the plasma metabolome of young and middle-aged human participants with and without the Ε4 allele, and used indirect calorimetry to measure whole body oxygen consumption and energy expenditure. In line with data from E4-expressing female mice, a subgroup analysis revealed that young female E4 carriers showed a striking decrease in energy expenditure compared to non-carriers. This decrease in energy expenditure was primarily driven by a lower rate of oxygen consumption, and was exaggerated following a dietary glucose challenge. Further, the stunted oxygen consumption was accompanied by markedly increased lactate in the plasma of E4 carriers, and a pathway analysis of the plasma metabolome suggested an increase in aerobic glycolysis.

Conclusions
Together, these results suggest astrocyte, brain and system-level metabolic reprogramming in the presence of APOE4, a ‘Warburg like’ endophenotype that is observable in young females decades prior to clinically manifest AD.
Protein degradation technology: a strategic paradigm shift in drug discovery
Authors: Li Haobin , Dong Jinyun , Cai Maohua , Xu Zhiyuan , Cheng Xiang-Dong , Qin Jiang-Jiang 
Published: September 2021

AbstractTargeting pathogenic proteins with small-molecule inhibitors (SMIs) has become a widely used strategy for treating malignant tumors. However, most intracellular proteins have been proven to be undruggable due to a lack of active sites, leading to a significant challenge in the design and development of SMIs. In recent years, the proteolysis-targeting chimeric technology and related emerging degradation technologies have provided additional approaches for targeting these undruggable proteins. These degradation technologies show a tendency of superiority over SMIs, including the rapid and continuous target consumption as well as the stronger pharmacological effects, being a hot topic in current research. This review mainly focuses on summarizing the development of protein degradation technologies in recent years. Their advantages, potential applications, and limitations are also discussed. We hope this review would shed light on the design, discovery, and clinical application of drugs associated with these degradation technologies.
Delayed pubarche
Authors: Baldo Francesco , Barbi Egidio , Tornese Gianluca 
Published: September 2021

AbstractIn healthy adolescents, delayed pubarche is generally a benign condition that is caused by a physiological discrepancy between gonadarche and adrenarche. In presence of other clinical signs and symptoms, delayed pubarche can be caused by single or multiple hormones deficiency (such as adrenal insufficiency, panhypopituitarism and hypothyroidism) and/or genetic conditions (Turner syndrome, androgen insensitivity syndrome). Exposition to endocrine disruptors has also been described as a possible cause of delay of pubic hair development. Basic blood tests, karyotype and first level imaging studies are helpful in the differential diagnosis.
Acupuncture for combat post-traumatic stress disorder: trial development and methodological approach for a randomized controlled clinical trial
Authors: Hollifield Michael , Hsiao An-Fu , Carrick Kala , Gory Munoz Andrea , Calloway Teresa , Cocozza Karen , Smith Besa , Smith Tyler , Jovanovic Tanja , Norrholm Seth , Sokhadze Estate , Reist Christopher 
Published: September 2021

Abstract
Background
Post-traumatic stress disorder (PTSD) is a significant public health problem, affecting approximately 7% of the general population and 13–18% of the combat Veteran population. The first study using acupuncture for PTSD in a civilian population showed large pre- to post-treatment effects for an empirically developed verum protocol, which was equivalent to group cognitive behavior therapy and superior to a wait-list control. The primary objective of this study is to determine both clinical and biological effects of verum acupuncture for combat-related PTSD in treatment-seeking US Veterans.

Methods
This is a two-arm, parallel-group, prospective randomized placebo-controlled clinical trial. The experimental condition is verum acupuncture and the placebo control is sham (minimal) acupuncture in 1-h sessions, twice a week for 12 weeks. Ninety subjects will provide adequate power and will be allocated to group by an adaptive randomization procedure. The primary outcome is change in PTSD symptom severity from pre- to post-treatment. The secondary biological outcome is change from pre- to post-treatment in psychophysiological response, startle by electromyographic (EMG) eyeblink. Assessments will be conducted at pre-, mid-, post-, and 1-month post-treatment, blind to group allocation. Intent-to-treat analyses will be conducted.

Discussion
The study results will be definitive because both clinical and biological outcomes will be assessed and correlated. Issues such as the number needed for recruitment and improvement, use of sham acupuncture, choice of biological measure, and future research need will be discussed.

Trial registration
ClinicalTrials.gov NCT02869646. Registered on 17 August 2016.