bluuebunny/crossref_metadata_2025_split huggingface dataset:
The evolution of clot strength in critically-ill COVID-19 patients: a prospective observational thromboelastography study
Authors: Neethling Colette , Calligaro Gregory , Miller Malcolm , Opie Jessica J. S. 
Published: November 2021

Abstract
Background
Few studies detail the evolution of COVID-19 associated coagulopathy. We performed serial thromboelastography (TEG) and laboratory coagulation studies in 40 critically-ill, mechanically ventilated COVID-19 patients over a 14-day period and analysed differences between 30-day survivors and non-survivors.

Methods
Single-center prospective, observational study including 40 patients with severe COVID-19 pneumonia admitted to the intensive care unit (ICU) for mechanical ventilation. TEG analysis was performed on days 1, 7 and 14 of ICU admission and laboratory coagulation studies were performed on days 1 and 14. Coagulation variables were evaluated for change over the 14-day observation period. Differences between survivors and non-survivors at 30-days were analysed and compared.

Results
On admission, TEG maximum amplitude (MA) with heparinase correction was above the upper limit of the reference range in 32 (80%) patients while 33 (82.5%) presented with absent clot lysis at 30 min. The functional fibrinogen MA was also elevated above the upper limit of the reference range in 37 (92.5%) patients. All patients had elevated D-dimer and fibrinogen levels, mildly prolonged prothrombin times (PT), normal platelet counts and normal activated partial thromboplastin times (aPTT). The heparinase MA decreased significantly with time and normalised after 14 days (p = < 0.001) while the increased fibrin contribution to clot strength persisted with time (p = 0.113). No significant differences in TEG analysis were noted between 30-day survivors and non-survivors at all time points. No patients developed disseminated intravascular coagulopathy (DIC) after 14-days, however thrombosis and bleeding were each reported in 3 (7.5%) patients.

Conclusion
Critically-ill patients with COVID-19 present in a hypercoagulable state characterised by an increased clot strength. This state normalises after 14 days despite a persistently increased fibrin contribution to clot strength. We were unable to demonstrate any significant differences in TEG parameters between 30-day survivors and non-survivors at all time points.
24-hour movement behaviour profiles and their transition in children aged 5.5 and 8 years – findings from a prospective cohort study
Authors: Padmapriya Natarajan , Chen Bozhi , Goh Claire Marie Jie Lin , Shek Lynette Pei Chi , Chong Yap Seng , Tan Kok Hian , Chan Shiao-Yng , Yap Fabian , Godfrey Keith M. , Lee Yung Seng , Eriksson Johan G. , Bernard Jonathan Y. , Müller-Riemenschneider Falk 
Published: November 2021

Abstract
Background
Time spent in movement behaviours, including physical activity (PA), sedentary behaviour (SB) and sleep, across the 24-h day may have distinct health consequences. We aimed to describe 24-h movement behaviour (24 h-MB) profiles in children and how profile membership changed from age 5.5 to 8 years.

Methods
Children in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort were asked to wear an accelerometer (ActiGraph-GT3X+) on their wrist for seven consecutive days at ages 5.5 and 8 years to measure 24 h-MB patterns. Time spent in night sleep, inactivity (proxy for SB), light PA, moderate PA (MPA), and vigorous PA (VPA) per day were calculated using the R-package GGIR 2.0. Using latent profile analyses (n = 442) we identified 24 h-MB profiles, which were given animal names to convey key characteristics. Latent transition analyses were used to describe the profile membership transition from ages 5.5 to 8 years. Associations with sex and ethnicity were examined.

Results
We identified four profiles, “Rabbits” (very high-MPA/VPA, low-inactivity and average-night-sleep), “Chimpanzees” (high-MPA, low-inactivity and average-night-sleep), “Pandas” (low-PA, high-inactivity and high-night-sleep) and “Owls” (low-PA, high-inactivity and low-night-sleep), among children at both time points. At ages 5.5 and 8 years, the majority of children were classified into profiles of “Chimpanzees” (51 and 39%, respectively) and “Pandas” (24 and 37%). Half of the sample (49%), particularly “Rabbits”, remained in the same profile at ages 5.5 and 8 years: among children who changed profile the predominant transitions occurred from “Chimpanzees” (27%) and “Owls” (56%) profiles to “Pandas”. Sex, but not ethnicity, was associated with profile membership: compared to girls, boys were more likely to be in the “Rabbits” profile (adjusted OR [95% CI]: 3.6 [1.4, 9.7] and 4.5 [1.8, 10.9] at ages 5.5 and 8 years, respectively) and less likely to be in the “Pandas” profile (0.5 [0.3, 0.9] and 0.4 [0.2, 0.6]) at both ages.

Conclusions
With increasing age about half the children stayed in the same of four 24 h-MB profiles, while the predominant transition for the remaining children was towards lower PA, higher inactivity and longer sleep duration. These findings can aid development and implementation of public health strategies to promote better health.

Study registration
This study was registered on 4th August 2010 and is available online at ClinicalTrials.gov: NCT01174875.
The semantics of microglia activation: neuroinflammation, homeostasis, and stress
Authors: Woodburn Samuel C. , Bollinger Justin L. , Wohleb Eric S. 
Published: November 2021

AbstractMicroglia are emerging as critical regulators of neuronal function and behavior in nearly every area of neuroscience. Initial reports focused on classical immune functions of microglia in pathological contexts, however, immunological concepts from these studies have been applied to describe neuro-immune interactions in the absence of disease, injury, or infection. Indeed, terms such as ‘microglia activation’ or ‘neuroinflammation’ are used ubiquitously to describe changes in neuro-immune function in disparate contexts; particularly in stress research, where these terms prompt undue comparisons to pathological conditions. This creates a barrier for investigators new to neuro-immunology and ultimately hinders our understanding of stress effects on microglia. As more studies seek to understand the role of microglia in neurobiology and behavior, it is increasingly important to develop standard methods to study and define microglial phenotype and function. In this review, we summarize primary research on the role of microglia in pathological and physiological contexts. Further, we propose a framework to better describe changes in microglia1 phenotype and function in chronic stress. This approach will enable more precise characterization of microglia in different contexts, which should facilitate development of microglia-directed therapeutics in psychiatric and neurological disease.
Continuum of maternity care among rural women in Ethiopia: does place and frequency of antenatal care visit matter?
Authors: Dadi Tegene Legese , Medhin Girmay , Kasaye Habtamu Kebebe , Kassie Getnet Mitike , Jebena Mulusew Gerbaba , Gobezie Wasihun Adualem , Alemayehu Yibeltal Kiflie , Teklu Alula Meresa 
Published: November 2021

AbstractIntroductionThe ministry of health (MOH) of Ethiopia recommends 4 or more focused antenatal care (ANC) visits at health centre (HC) or at a higher level of health facility (HF). In Ethiopia, few studies investigated time dimension of maternal health continuum of care but lack data regarding place dimension and its effect on continuum of care. The aim of this study is to estimate effect of place of ANC-1 visit and adherence to MOH’s recommendations of MOH for ANC visits on continuum of care rural in Ethiopia.MethodsWe used data collected from 1431 eligible women included in the National Health Extension Program (HEP) assessment survey that covered 6324 households from 62 woredas in nine regions. The main outcome variable is continuum of care (CoC), which is the uptake of all recommended ANC visits, institutional delivery and postnatal care services. Following descriptive analysis, Propensity Score Matching was used to estimate the effect of place of ANC-1 visit on completion of CoC. Zero inflated Poisson regression was used to model the effect of adherence to MOH recommendation of ANC visits on intensity of maternal health continuum of care.ResultOnly 13.9% of eligible women completed the continuum of care, and place of first antenatal care (ANC) visit was not significantly associated with the completion of continuum of care (β = 0.04, 95% CI = -0.02, 0.09). Adherence of ANC visit to the MOH recommendation (at least 4 ANC visits at higher HFs than health posts (HPs)) increased the likelihood of higher intensity of continuum of care (aIRR = 1.29, 95% CI: 1.26, 1.33). Moreover, the intensity of continuum of care was positively associated with being in agrarian areas (aIRR = 1.17, 95% CI: 1.06, 1.29), exposed to HEP (IRR = 1.22, 95% CI: 1.16, 1.28), being informed about danger signs (aIRR = 1.14, 95% CI: 1.11, 1.18) and delivery of second youngest child at HF (IRR = 1.16, 95% CI: 1.13, 1.20). Increasing age of women was negatively associated with use of services (IRR = 0.90, 95% CI: 0.87, 0.94).ConclusionCompletion of maternal health continuum of care is very low in Ethiopia, however most of the women use at least one of the services. Completion of continuum of care was not affected by place of first ANC visit. Adherence to MOH recommendation of ANC visit increased the intensity of continuum of care. Intensity of continuum of care was positively associated with residing in agrarian areas, HEP exposure, danger sign told, delivery of second youngest child at health facility. To boost the uptake of all maternal health services, it is crucial to work on quality of health facilities, upgrading the infrastructures of HPs and promoting adherence to MOH recommendations of ANC visit.
A pandemic treaty, revised international health regulations, or both?
Authors: Labonté Ronald , Wiktorowicz Mary , Packer Corinne , Ruckert Arne , Wilson Kumanan , Halabi Sam 
Published: November 2021

Abstract
Background
A special session of the World Health Assembly (WHA) will be convened in late 2021 to consider developing a WHO convention, agreement or other international instrument on pandemic preparedness and response – a so-called ‘Pandemic Treaty’. Consideration is given to this treaty as well as to reform of the International Health Regulations (IHR) as our principal governing instrument to prevent and mitigate future pandemics.

Main body
Reasons exist to continue to work with the IHR as our principal governing instrument to prevent and mitigate future pandemics. All WHO member states are party to it. It gives the WHO the authority to oversee the collection of surveillance data and to issue recommendations on trade and travel advisories to control the spread of infectious diseases, among other things. However, the limitations of the IHR in addressing the deep prevention of future pandemics also must be recognized. These include a lack of a regulatory framework to prevent zoonotic spillovers. More advanced multi-sectoral measures are also needed. At the same time, a pandemic treaty would have potential benefits and drawbacks as well. It would be a means of addressing the gross inequity in global vaccine distribution and other gaps in the IHR, but it would also need more involvement at the negotiation table of countries in the Global South, significant funding, and likely many years to adopt.

Conclusions
Reform of the IHR should be undertaken while engaging with WHO member states (and notably those from the Global South) in discussions on the possible benefits, drawbacks and scope of a new pandemic treaty. Both options are not mutually exclusive.
Efficacy of concurrent chemoradiotherapy in subgroups of stage III nasopharyngeal carcinoma: an analysis based on 10-year follow-up
Authors: Wang Lei , Wu Zheng , Cheng Wanqin , Xie Dehuan , Lin Feifei , Xia Liangping , Su Yong 
Published: November 2021

Abstract
Purpose
To evaluate the efficacy of concurrent chemoradiotherapy (CCRT) in subgroups of stage III nasopharyngeal carcinoma (NPC) in the context of intensity-modulated radiotherapy (IMRT).

Methods
A total of 272 patients with stage III NPC who underwent IMRT with or without concurrent chemotherapy were retrospectively reviewed. Clinicopathological features were evaluated by a Cox regression model to identify independent prognostic factors. Survival outcomes were assessed using the Kaplan–Meier method and log-rank test.

Results
The median follow-up time was 108 months. The 10-year locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 87.8%, 80.7%, 68.8%, and 74.9%, respectively. Multivariate analysis showed that the N classification was significantly associated with DMFS (hazard ratio [HR] 3.616, 95% confidence interval [CI] 1.387–9.428, P = 0.009), DFS (HR 2.417, 95% CI 1.291–4.423, P = 0.006), and OS (HR 3.024, 95% CI 1.385–6.602, P = 0.005). In patients with T1-3N2 disease, CCRT was associated with improved 10-year LRFS (89.6% vs. 65.4%, P = 0.005), DFS (71.9% vs. 39.4% P = 0.001) and OS (80.0% vs. 50.5%, P = 0.004) compared with IMRT alone. However, in patients with T3N0-1 disease, no significant survival differences were observed between patients treated with IMRT alone and CCRT (P > 0.05).

Conclusions
CCRT is an effective therapy in stage III NPC, especially for patients with N2 disease, but IMRT alone may be adequate for N0-1 disease. Individualized treatment strategies are essential for patients with varying disease risks.
What is the effectiveness of radiofrequency ablation in the management of patients with spinal metastases? A systematic review and meta-analysis
Authors: Murali Navanith , Turmezei Thomas , Bhatti Sumbal , Patel Puja , Marshall Thomas , Smith Toby 
Published: November 2021

Abstract
Purpose
Spinal metastases are indicative of progressive cancer which can lead to vertebral body fractures and spinal cord compression. Radiofrequency ablation (RFA) treatment is infrequently used in patients with refractory pain. The aim of this systematic review is to determine the clinical efficacy of RFA, with the scope of using it as front-line management of spinal metastases.

Methods
Electronic databases were searched (to July 2020) for studies evaluating RFA treatment for spinal metastases in adults. Measured outcomes were pain (primary), disability, health-related quality of life (HRQOL), complications, tumour control and mortality. Study inclusion, data extraction and risk of bias using the ROBIN-I tool were assessed. Meta-analysis was conducted for pooled results with homogeneity, and narrative synthesis was conducted otherwise.

Results
15 studies were included. RFA reduces pain scores at 3–5 weeks [standardised mean difference (SMD 2.24, 95% confidence intervals (CI) 1.55–2.93], 3–4 months (SMD 3.00, 95% CI 1.11–4.90) and 5–6 months (SMD 3.54, 95% CI 1.96–5.11). RFA is effective in reducing disability/improving HRQOL in the short-term but longer-term efficacy remains unclear. 13.2% cases reported local tumour control failure (2.5 months–5 year follow-up) whereas mortality was 23.6% (follow-up of up to 1 year).

Conclusion
Low quality evidence has proven RFA to be safe and effective in reducing pain and disability, especially in the short-term. RFA may be routinely implemented in all cases involving refractory pain or radiotherapy-resistant tumours but controlled trials are required to compare the efficacy of RFA to current frontline treatments.
PROSPERO protocol registration number: CRD42020202377.
Fixation failure in patients with traumatic diastasis of pubic symphysis: impact of loss of reduction on early functional outcomes
Authors: Rojas Claudio , Ewertz Ernesto , Hormazábal Jose Miguel 
Published: November 2021

Abstract
Background
Failure of fixation (FF) in pubic symphysis diastasis (SD) ranges between 12 and 75%, though whether it influences functional outcomes is still debated. The objective of this study is to evaluate the impact of anterior pelvic plate failure and loss of reduction on Majeed’s functional scores.

Methods
Single center retrospective review of consecutive patients with acute SD treated by means of anterior pubic plating. Thirty-seven patients with a mean age 45.7 ± 14.4 years were included. Demographics, AO classification, pelvic fixation and secondary procedures were recorded. Majeed’s functional scores at minimum 6 months follow-up were compared according to the presence of FF and loss of reduction.

Results
Fifteen patients presented FF. Eight presented an additional loss of symphyseal reduction. Mean Majeed´s score (MMS) in patients with and without FF was 64.4 ± 13.04 and 81.8 ± 15.65, respectively (p = 0.0012). Differences in MMS in patients without FF and those with FF and maintained or loss of anterior reduction were 11.3 [70.5 vs 81.8] (p = 0.092) and 22.7 [59.1 vs 81.8] (p = 0.001), respectively. Significant association of FF with AO classification was noted. (OR 12.6; p = 0.002).

Conclusions
Differences in MMS in the analyzed groups suggest that loss of reduction might be more relevant than failure of the anterior osteosynthesis in functional outcomes.
“It was with my consent since he was providing me with money”: a mixed methods study of adolescent perspectives on peacekeeper-perpetrated sexual exploitation and abuse in the Democratic Republic of Congo
Authors: Fraulin Georgia , Lee Sabine , Lusamba Sandrine , Bartels Susan A. 
Published: November 2021

Abstract
Background
The United Nations Organization Stabilization Mission in the Democratic Republic of Congo (MONUSCO) has been marred by widespread allegations of sexual exploitation and abuse (SEA) of women and girls by UN peacekeepers. There is minimal research conducted on the perceptions of communities most affected by the SEA themselves, and even less about those below the age of 18.

Methods
Using mixed-methods data, we examined the perceptions of adolescents aged 13–17 on how the lives of women and girls have been affected by the presence of UN peacekeepers within the DRC. SenseMaker, a mixed-methods narrative capture tool, was used to survey participants around six United Nations bases across eastern DRC. Each participant shared a story about the experiences of Congolese women and girls in relation to MONUSCO personnel and interpreted their own stories by answering a series of questions. Patterns of adolescent perspectives (aged 13–17) were analyzed in comparison to all other age groups and emerging qualitative themes were mapped onto quantitative variables.

Results
Quantitative data showed that adolescents were more likely, in comparison to all other age groups, to perceive interactions between peacekeepers and women/girls as being initiated by the woman/girl, that the MONUSCO personnel was perceived to be able to offer protection, and that the interactions between local women/girls and peacekeepers were sexual in nature. Three qualitative themes emerged: poverty bringing peacekeepers and women/girls together, material/financial gain through transactional sex and sex work, and support-seeking actions of affected women/girls.

Conclusions
Our mixed methods data illustrate the problematic finding that adolescents facing poverty may perceive SEA as protective through the monetary and material support gained. These findings contribute to the growing body of literature on peacekeeping economies and have implications for the prevention of, and response to, peacekeeper-perpetrated SEA.
Synaptic potentiation of anterior cingulate cortex contributes to chronic pain of Parkinson’s disease
Authors: Zhou Zhaoxiang , Ye Penghai , Li Xu-Hui , Zhang Yuxiang , Li Muhang , Chen Qi-Yu , Lu Jing-Shan , Xue Man , Li Yanan , Liu Weiqi , Lu Lin , Shi Wantong , Xu Ping-Yi , Zhuo Min 
Published: November 2021

AbstractParkinson’s disease (PD) is a multi-system neurodegenerative disorder. Patients with PD often suffer chronic pain. In the present study, we investigated motor, sensory and emotional changes in three different PD mice models. We found that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treatment caused significant changes in all measurements. Mechanical hypersensitivity of PD model induced by MPTP peaked at 3 days and persisted for at least 14 days. Using Fos transgenic mice, we found that neurons in the anterior cingulate cortex (ACC) were activated after MPTP treatment. Inhibiting ACC by bilateral microinjection of muscimol significantly reduced mechanical hypersensitivity and anxiety-like responses. By contrast, MPTP induced motor deficit was not affected, indicating ACC activity is mostly responsible for sensory and emotional changes. We also investigated excitatory synaptic transmission and plasticity using brain slices of MPTP treated animals. While L-LTP was blocked or significantly reduced. E-LTP was not significantly affected in slices of MPTP treated animals. LTD induced by repetitive stimulation was not affected. Furthermore, we found that paired-pulse facilitation and spontaneous release of glutamate were also altered in MPTP treated animals, suggesting presynaptic enhancement of excitatory transmission in PD. Our results suggest that ACC synaptic transmission is enhanced in the animal model of PD, and cortical excitation may play important roles in PD related pain and anxiety.
VEGF pathway inhibition potentiates PARP inhibitor efficacy in ovarian cancer independent of BRCA status
Authors: Bizzaro Francesca , Fuso Nerini Ilaria , Taylor Molly A. , Anastasia Alessia , Russo Massimo , Damia Giovanna , Guffanti Federica , Guana Francesca , Ostano Paola , Minoli Lucia , Hattersley Maureen M. , Arnold Stephanie , Ramos-Montoya Antonio , Williamson Stuart C. , Galbiati Alessandro , Urosevic Jelena , Leo Elisabetta , Cavallaro Ugo , Ghilardi Carmen , Barry Simon T. , Bani Maria Rosa , Giavazzi Raffaella 
Published: November 2021

AbstractPoly ADP-ribose polymerase inhibitors (PARPi) have transformed ovarian cancer (OC) treatment, primarily for tumours deficient in homologous recombination repair. Combining VEGF-signalling inhibitors with PARPi has enhanced clinical benefit in OC. To study drivers of efficacy when combining PARP inhibition and VEGF-signalling, a cohort of patient-derived ovarian cancer xenografts (OC-PDXs), representative of the molecular characteristics and drug sensitivity of patient tumours, were treated with the PARPi olaparib and the VEGFR inhibitor cediranib at clinically relevant doses. The combination showed broad anti-tumour activity, reducing growth of all OC-PDXs, regardless of the homologous recombination repair (HRR) mutational status, with greater additive combination benefit in tumours poorly sensitive to platinum and olaparib. In orthotopic models, the combined treatment reduced tumour dissemination in the peritoneal cavity and prolonged survival. Enhanced combination benefit was independent of tumour cell expression of receptor tyrosine kinases targeted by cediranib, and not associated with change in expression of genes associated with DNA repair machinery. However, the combination of cediranib with olaparib was effective in reducing tumour vasculature in all the OC-PDXs. Collectively our data suggest that olaparib and cediranib act through complementary mechanisms affecting tumour cells and tumour microenvironment, respectively. This detailed analysis of the combined effect of VEGF-signalling and PARP inhibitors in OC-PDXs suggest that despite broad activity, there is no dominant common mechanistic inter-dependency driving therapeutic benefit.