bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication techniques of polymeric nanocomposites: A comprehensive review
Authors: Kamal Abdallah , Ashmawy Mayar , S Shanmugan , Algazzar Almoataz M , Elsheikh Ammar H
Published: December 2021

Nanotechnology is the key solution for many human problems such as energy conversion, water treatment, and material science. In composite materials, nanoparticles are dispersed in a matrix material such as metals, ceramics, or polymers to enhance their mechanical and thermophysical properties. Polymer nanocomposite materials found their applications in vital fields such as the automotive and aircraft industries. There are many techniques adopted to produce polymer nanocomposites, and they are summarized and discussed according to our best known in this paper. All techniques aim to produce nanocomposite materials with uniform dispersion and without aggregations. Melt-mixing, mixing, in-situ polymerization, electrospinning, and selective laser sintering techniques are the most commonly used techniques to produce polymer nanocomposite. The utilization of water, atomic layer deposition, and plasma-assisted mechanochemistry are found to eradicate the issue of nanoparticles aggregation for melt-mixing technique. Also, sonication with high frequencies plays the same role for mixing techniques. In-situ polymerization provides fabrication of nanocomposites that are thermodynamically stable. Electrospinning represents an effective method which is suitable for producing porous structures. In addition, fabrication of nanocomposites via selective laser sintering has obvious benefits to overcome the problem of aggregation. The working principles of each technique, including the advantages and disadvantages, are discussed.
Numerical simulation of the influence of tool geometry on energy consumption during micro turning of titanium alloy
Authors: Nijin JR , Jagadesh T
Published: December 2021

Fabrication of an axisymmetric biomedical implant with good dimensions, form and surface integrity features are a challenging task in the micro-manufacturing industry. This is due to workpiece deflection, vibrations, tool wear and adhesion of the chip on the cutting inset during the micromachining process. So experimental evaluation on the variation of tool geometry is expensive and difficult as stated in prior literature. So, in this work, a finite-element method simulation is developed to comprehend the physics of the process and predict the energy consumption by incorporating the effect of material strengthening caused by shearing of material across the grain, shear band pattern upon strain rate and tool geometry such as edge radius, nose radius and rake angle. The modified Johnson-Cook material model is used to state the flow stress and an adaptive remeshing technique is utilized to model the plastic deformation at a higher strain rate during the simulation process. Initially, the model is developed in a transient state and then modified to a steady-state to obtain the output process parameters. The proposed model is calibrated and validated with experimental results reported in the literature. It is inferred that the cutting force, thrust force and feed force acquired from finite-element method simulation have been confirmed experimentally with prediction accuracy of 94%, 82.66% and 87.02%, respectively. It is also inferred that energy consumption during machining reduces with an increase in rake angle because of the sharpness of the cutting edge and less friction between tool and chip. An increase of nose radius and edge radius produces high thrust force and energy consumption and impedes high radial depth of cut. For the same machining parameters with the increase of edge radius and decrease of rake angle the mechanism of material removal changes from shearing to ploughing.
Processing Intensive Care Unit Treatment Experiences: A Thematic Analysis of a Diary Intervention
Authors: Zisopoulos George , Triliva Sofia , Roussi Pagona
Published: December 2021

Survivors of the intensive care unit (ICU) report an aggregate of burdensome memories. ICU diaries have been proposed to address the psychological impact of ICU treatment. Twenty-six participants wrote about their ICU experiences in three successive sessions, while in the second session, they were presented with a dairy derived from their medical records. Using inductive thematic analysis in the first and third narratives, we explore how participants initially describe their ICU experience and how they process it after the intervention. Participants described a martyrdom experience, including being emotionally distressed, disorientated, and physically trapped that provoked a quest for any available interpersonal support. A vacuum-like state permeated their existence, impacted their sense-making ability, and the proximity to death uniquely characterized this experience. After intervention, participants made small but significant changes in their written narratives. They appeared to reorganize their recollections, reestablish self-continuity by integrating their ICU experiences, and authored restitution narratives.
High dose valacyclovir for cytomegalovirus prophylaxis following allogeneic hematopoietic cell transplantation
Authors: Hawks Kelly G , Fegley Amanda , Sabo Roy T , Roberts Catherine H , Toor Amir A
Published: December 2021

Introduction

Cytomegalovirus (CMV) is one of the most common and clinically significant viral infections following allogeneic hematopoietic cell transplantation (HCT). Currently available options for CMV prophylaxis and treatment present challenges related to side effects and cost.

Methods

In this retrospective medical record review, the incidence of clinically significant CMV infection (CMV disease or reactivation requiring preemptive treatment) following allogeneic HCT was compared in patients receiving valacyclovir 1 g three times daily versus acyclovir 400 mg every 12 h for viral prophylaxis.

Results

Forty-five patients who received valacyclovir were matched based on propensity scoring to 35 patients who received acyclovir. All patients received reduced-intensity conditioning regimens containing anti-thymocyte globulin. Clinically significant CMV infection by day + 180 was lower in the valacyclovir group compared to the acyclovir group (18% vs. 57%, p = 0.0004). Patients receiving valacyclovir prophylaxis also had less severe infection evidenced by a reduction in CMV disease, lower peak CMV titers, delayed CMV reactivation, and less secondary neutropenia.

Conclusion

Prospective evaluation of valacyclovir 1 g three times daily for viral prophylaxis following allogeneic HCT is warranted. Due to valacyclovir's favorable toxicity profile and affordable cost, it has the potential to benefit patients on a broad scale as an option for CMV prophylaxis.
Does Financial Development Raise Tourism Demand? A Cross-Country Panel Evidence
Authors: Khanna Rupika , Sharma Chandan
Published: December 2021

This study examines the effects of bank and stock market development on three tourism demand indicators: number of tourist arrivals, expenditure to gross domestic product ratio, and expenditure per arrival. We analyze annual data spanning the period 1995-2018 for a sample of 207 countries. The theoretical contribution of this study is threefold: first, we assess a variety of financial development indicators; second, we employ cross-sectionally augmented distributed lags estimator that produces estimates robust to the dependence structure in the data; third, using data on a wide assortment of countries, we generalize the findings of several country-specific case studies. We observe that financial development affects both tourist arrivals and tourism expenditure positively. However, the gains in tourist arrivals are more significant relative to those in tourism expenditure. Furthermore, we find the responsiveness of tourism demand to financial development to vary with the income level.
Validation of a novel ultrasound Doppler monitoring device (earlybird) for measurements of volume flow rate in arteriovenous fistulas for hemodialysis
Authors: Pettersen Erik Mulder , Avdal Jørgen , Fiorentini Stefano , Salvesen Øyvind , Hisdal Jonny , Torp Hans , Seternes Arne
Published: December 2021

Background:

Controversy exists regarding surveillance of arteriovenous fistulas for hemodialysis to increase patency. A significant reduction in volume flow rate (VFR) should lead to diagnostic evaluation and eventually intervention. Several methods are available for VFR measurements, but all of them are associated with low reproducibility. VFR trend analysis is suggested as an improved solution. It is therefore a need to find user-friendly, cost and time-effective modalities. We present a novel Doppler ultrasound device (earlybird) which could bridge this gap. It includes an easy-to-use and light-weight single element transducer.

Methods:

In an experimental and clinical setting, we compared earlybird to duplex ultrasound to assess VFR. In a closed circuit of blood-mimicking fluid, 36 paired calculations of calibrated, duplex ultrasound and earlybird VFR was measured. In addition, 23 paired recordings of duplex ultrasound and earlybird VFR was measured in 16 patients with underarm arteriovenous fistulas. Pearson correlation, intraclass correlation coefficient, root-mean-square and Bland-Altman plots were analyzed.

Results:

Strong correlation ( r = 0.991, p < 0.001), and excellent level of agreement (ICC = 0.970 (95% CI 0.932 - 0.985), p < 0.001) between earlybird and the calibrated VFR was found in the experimental setup. This was confirmed in the clinical setting, with a strong correlation ( r = 0.781, p < 0.001) and moderate to good level of agreement (ICC = 0.750 (95% CI 0.502–0.885), p < 0.001) between earlybird and duplex ultrasound VFR measured at the arteriovenous fistulas outflow veins. In the Bland-Altman plot-analysis for the experimental setup, we found smaller limits of agreement, a smaller consistent and proportional bias, as well as greater accuracy of earlybird than DUS when compared to the calibrated VFR.

Conclusion:

Earlybird is a feasible tool for VFR measurements and could be a future promising device for easy assessment and surveillance of AVF for hemodialysis.
Innovative solutions for an age-old issue: How transparency and data analytic tools can improve diversity in international arbitration
Authors: Brodlija Fahira
Published: December 2021

International arbitration is an inherently diverse field. The disputing parties and their counsel come from all over the world, but the arbitrators selected by these same parties and their counsel rarely reflect their diverse backgrounds. Although the arbitration community largely supports diversity initiatives and the goal of making arbitral tribunals more reflective of the parties and the global community, the available studies that parties and their counsel continue to appoint a small number of repeat players to the tribunals. This paper traces the diversity deficiency to its roots in the lack of available information about diverse arbitrators and the cognitive biases that perpetuate the vicious cycle of repeat appointments. The paper then turns to potential solutions in the form of data analytic tools, that would collect, analyze and provide information on the case management and decision making of arbitrators.
Are we prepared to educate the next generation of bachelor nursing students? A discussion paper
Authors: Gjevjon Edith Roth , Rolland Espan Gade , Olsson Cecilia
Published: December 2021

This paper answers a call from Nordic colleagues for new strategies in education to meet the needs of a new generation of bachelor nursing students regarding the development of clinical skills. We, as they, believe that educational models targeting the development of clinical skills must be customised to meet the learning style of the current and future generations of bachelor nursing students. In this paper we put forward that using a comprehensive, collaborative, student-centred approach will assist younger generations’ learning processes. We describe a pedagogical model of peer learning that combines collaboration, reflection and assessment aligned with learning outcomes. Such an approach, we believe, is likely to be in line with expectations, needs and preconditions of the current and future generations of nursing students.
COVID-19 Infection and Myocarditis: A State-of-the-Art Systematic Review
Authors: Jaiswal Vikash , Sarfraz Zouina , Sarfraz Azza , Mukherjee Dattatreya , Batra Nitya , Hitawala Gazala , Yaqoob Sadia , Patel Abhinav , Agarwala Preeti , Ruchika  , Sarfraz Muzna , Bano Shehar , Azeem Nishwa , Naz Sidra , Jaiswal Akash , Sharma Prachi , Chaudhary Gaurav
Published: December 2021

Background:

COVID-19 was initially considered to be a respiratory illness, but current findings suggest that SARS-CoV-2 is increasingly expressed in cardiac myocytes as well. COVID-19 may lead to cardiovascular injuries, resulting in myocarditis, with inflammation of the heart muscle.

Objective:

This systematic review collates current evidence about demographics, symptomatology, diagnostic, and clinical outcomes of COVID-19 infected patients with myocarditis.

Methods:

In accordance with PRISMA 2020 guidelines, a systematic search was conducted using PubMed, Cochrane Central, Web of Science and Google Scholar until August, 2021. A combination of the following keywords was used: SARS-CoV-2, COVID-19, myocarditis. Cohorts and case reports that comprised of patients with confirmed myocarditis due to COVID-19 infection, aged >18 years were included. The findings were tabulated and subsequently synthesized.

Results:

In total, 54 case reports and 5 cohorts were identified comprising 215 patients. Hypertension (51.7%), diabetes mellitus type 2 (46.4%), cardiac comorbidities (14.6%) were the 3 most reported comorbidities. Majority of the patients presented with cough (61.9%), fever (60.4%), shortness of breath (53.2%), and chest pain (43.9%). Inflammatory markers were raised in 97.8% patients, whereas cardiac markers were elevated in 94.8% of the included patients. On noting radiographic findings, cardiomegaly (32.5%) was the most common finding. Electrocardiography testing obtained ST segment elevation among 44.8% patients and T wave inversion in 7.3% of the sample. Cardiovascular magnetic resonance imaging yielded 83.3% patients with myocardial edema, with late gadolinium enhancement in 63.9% patients. In hospital management consisted of azithromycin (25.5%), methylprednisolone/steroids (8.5%), and other standard care treatments for COVID-19. The most common in-hospital complication included acute respiratory distress syndrome (66.4%) and cardiogenic shock (14%). On last follow up, 64.7% of the patients survived, whereas 31.8% patients did not survive, and 3.5% were in the critical care unit.

Conclusion:

It is essential to demarcate COVID-19 infection and myocarditis presentations due to the heightened risk of death among patients contracting both myocardial inflammation and ARDS. With a multitude of diagnostic and treatment options available for COVID-19 and myocarditis, patients that are under high risk of suspicion for COVID-19 induced myocarditis must be appropriately diagnosed and treated to curb co-infections.
Understanding Medical Distrust Among African American/Black and Latino Persons Living With HIV With Sub-Optimal Engagement Along the HIV Care Continuum: A Machine Learning Approach
Authors: He Ning , Cleland Charles M. , Gwadz Marya , Sherpa Dawa , Ritchie Amanda S. , Martinez Belkis Y. , Collins Linda M.
Published: December 2021

Medical distrust is a potent barrier to participation in HIV care and medication use among African American/Black and Latino (AABL) persons living with HIV (PLWH). However, little is known about sociodemographic and risk factors associated with distrust. We recruited adult AABL PLWH from low socio-economic status backgrounds with insufficient engagement in HIV care ( N = 512). Participants completed structured assessments on three types of distrust (of health care providers, health care systems, and counter-narratives), HIV history, and mental health. We used a type of machine learning called random forest to explore predictors of trust. On average, participants were 47 years old ( SD = 11 years), diagnosed with HIV 18 years prior ( SD = 9 years), and mainly male (64%) and African American/Black (69%). Depression and age were the most important predictors of trust. Among those with elevated depressive symptoms, younger participants had less trust than older, while among those without depression, trust was greater across all ages. The present study adds nuance to the literature on medical distrust among AABL PLWH and identifies junctures where interventions to build trust are needed most.
Exploring Primary-School EFL Teacher Expertise in Scaffolding: A Comparative Study
Authors: Li Weiying , Zou Weicheng
Published: December 2021

While much attention has been focused—in the field of teacher expertise—on expert teachers’ cognitive and behavioral characteristics, little attention has been devoted to how expert teachers reciprocally interact with the learning process. To bridge this gap in knowledge, this study seeks to explore primary-school EFL (English as a Foreign Language)—teacher expertise in the area of scaffolding. A comparison has been made among 2 expert EFL teachers, 20 experienced non-expert teachers, and 2 novice teachers in Chinese primary-school settings. By adopting a qualitative method of inquiry using interviews, classroom observations, and stimulated recalls, (yet with a quantitative aspect incorporating data analysis), the study demonstrates that expert teachers show a tendency to use scaffolding strategies more frequently and appropriately. These findings suggest that more open-ended activities be conducted to allow for scaffolding in EFL classrooms and that ESL/EFL teacher education raise scaffolding awareness in pre-service and in-service teachers.
In-line Pullout Strength of 2 Acetabular Fixation Methods for Ligamentum Teres Reconstruction of the Hip: A Cadaveric Study
Authors: Lall Ajay C. , Ankem Hari K. , Ryan Michael K. , Beason David P. , Diulus Samantha C. , Roach Ryan P. , Rosinsky Philip J. , Maldonado David R. , Emblom Benton A. , Domb Benjamin G.
Published: December 2021

Background:

Ligamentum teres (LT) reconstruction is an appropriate alternative in select cases of LT full-thickness tears, resulting in hip micro- or macroinstability. Graft fixation at the acetabular fossa is critical to achieving the best functional results.

Purpose:

The purpose of this study is to compare the pullout strength of 2 graft fixation methods used for LT reconstruction of the hip.

Study Design:

Controlled laboratory study.

Methods:

In 7 cadaveric specimens, the acetabular socket was prepared after the native LT was transected and the femoral head was removed. Seven separate tibialis anterior grafts were then prepared by suturing a running-locking No. 2 suture on each tail of the graft. Three specimens had fixation of the graft to the acetabulum using an adjustable cortical suspension suture button; the remaining 4 were fixed to the acetabulum using a knotless suture anchor. Specimens were then mounted onto a custom jig within a mechanical test frame to allow for the in-line pull of the graft fixation construct. After a preload of 5 N, each specimen was loaded to failure at 0.5 mm/s. Stiffness and load to failure were measured for each specimen construct.

Results:

Suture button fixation had a higher mean load to failure when compared with the knotless anchor fixation method (mean ± SD, 438.1 ± 114.3 vs 195.9 ± 50.0 N; P = .01). There was no significant difference in mean stiffness between the methods of fixation (24.5 ± 1.4 vs 26.5 ± 5.8 N/mm; P = .6).

Conclusion:

In this cadaveric study, the suture button fixation demonstrated greater load to failure than the knotless anchor fixation.

Clinical Relevance:

Results of this study can guide surgical decision making when selecting an acetabular fixation method for LT reconstruction.
Pilot randomized controlled trial Protocol: Life context-informed pre-visit planning to improve care plans for primary care patients with multiple chronic conditions including diabetes
Authors: Magnan Elizabeth , Gosdin Melissa , Tancredi Daniel , Jerant Anthony
Published: December 2021

Background

Multimorbidity is common, and care is impacted by patient life context. Effective, efficient interventions to improve patient-centered outcomes such as perceived treatment burden are limited. There is a need for interventions that integrate patient contextual information into primary care encounters to improve such outcomes. Patient life context is a multitude of factors that influence a patient’s life and healthcare, including social determinants of health and broader elements such as family and work demands.

Methods

This pilot randomized controlled trial (RCT) protocol will compare standard pre-visit planning to context-informed pre-visit planning that incorporates the patient’s life context, for patients with diabetes plus other chronic comorbid conditions. Primary outcomes include measures of trial protocol and intervention feasibility and acceptability: physician study and visit perceived burden, patient satisfaction, and patient, physician and staff experience with the trial. Additional measurements of intervention impact include: initial estimates of effect size on patient treatment burden and other patient-oriented outcomes, change in glycemic control, and other intermediate medical outcomes.

Discussion

This intervention is novel as it collects patient life context information using a direct person-to-person approach, allows physicians to review the information prior to patient arrival at the clinic and, where appropriate, incorporate it when negotiating treatment plans, and is longitudinal, summarizing evolving contextual information over time. This pilot RCT has the potential to demonstrate trial protocol and intervention feasibility and acceptability, and estimate effect size on patient and provider outcomes, to inform for a future, definitive RCT. Trial Registration: This trial was registered at ClinicalTrials.gov prior to patient enrollment: NCT04568382
The effect of the 2018 Japan Floods on cognitive decline among long-term care insurance users in Japan: a retrospective cohort study
Authors: Yoshida Shuhei , Kashima Saori , Matsumoto Masatoshi
Published: December 2021

Background

The July 2018 Japan Floods caused enormous damage to western Japan. Such disasters can especially impact elderly persons. Research has shown that natural disasters exacerbated a decline in cognitive function, but to date, there have been no studies examining the effects of this disaster on the elderly. The object of this study was to reveal the effect of this disaster in terms of cognitive decline among the elderly.

Methods

Study participants were certified users of the long-term care insurance (LTCI) system in Hiroshima, Okayama, and Ehime prefectures from May 2018 to June 2018. The observation period was from July 2018 to December 2018. Our primary outcome was cognitive decline after the disaster using a dementia symptomatology assessment. In addition to a crude model, a multivariate Cox proportional hazards model was used to assess the cognitive decline of victims, adjusting for age classification, gender, the level of dementia scale before the disaster occurred, residential environment, whether a participant used facilities shut down after the disaster, and population density. After we confirmed that the interaction term between victims and residential environment was statistically significant, we stratified them for the analysis.

Results

The total number of participants was 264,614. Victims accounted for 1.10% of the total participants (n = 2,908). For the Cox proportional hazards model, the hazard ratio of the victims was 1.18 (95% confidential interval (CI): 1.05–1.32) in the crude model and 1.12 (95% CI: 1.00–1.26) in the adjusted model. After being stratified by residential environment, the hazard ratio of home victims was 1.20 (95% CI: 1.06–1.36) and the hazard ratio of facility victims was 0.89 (95% CI: 0.67–1.17).

Conclusions

This study showed that elderly living at home during the 2018 Japan Floods were at risk for cognitive decline. Medical providers, care providers, and local governments should establish a system to check on the cognitive function of elderly victims and provide necessary care support.
Exploring cell-specific miRNA regulation with single-cell miRNA-mRNA co-sequencing data
Authors: Zhang Junpeng , Liu Lin , Xu Taosheng , Zhang Wu , Zhao Chunwen , Li Sijing , Li Jiuyong , Rao Nini , Le Thuc Duy
Published: December 2021

Background

Existing computational methods for studying miRNA regulation are mostly based on bulk miRNA and mRNA expression data. However, bulk data only allows the analysis of miRNA regulation regarding a group of cells, rather than the miRNA regulation unique to individual cells. Recent advance in single-cell miRNA-mRNA co-sequencing technology has opened a way for investigating miRNA regulation at single-cell level. However, as currently single-cell miRNA-mRNA co-sequencing data is just emerging and only available at small-scale, there is a strong need of novel methods to exploit existing single-cell data for the study of cell-specific miRNA regulation.

Results

In this work, we propose a new method, CSmiR (Cell-Specific miRNA regulation) to combine single-cell miRNA-mRNA co-sequencing data and putative miRNA-mRNA binding information to identify miRNA regulatory networks at the resolution of individual cells. We apply CSmiR to the miRNA-mRNA co-sequencing data in 19 K562 single-cells to identify cell-specific miRNA-mRNA regulatory networks for understanding miRNA regulation in each K562 single-cell. By analyzing the obtained cell-specific miRNA-mRNA regulatory networks, we observe that the miRNA regulation in each K562 single-cell is unique. Moreover, we conduct detailed analysis on the cell-specific miRNA regulation associated with the miR-17/92 family as a case study. The comparison results indicate that CSmiR is effective in predicting cell-specific miRNA targets. Finally, through exploring cell–cell similarity matrix characterized by cell-specific miRNA regulation, CSmiR provides a novel strategy for clustering single-cells and helps to understand cell–cell crosstalk.

Conclusions

To the best of our knowledge, CSmiR is the first method to explore miRNA regulation at a single-cell resolution level, and we believe that it can be a useful method to enhance the understanding of cell-specific miRNA regulation.
Gene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence
Authors: Ohori Momoko , Nakayama Yusuke , Ogasawara-Shimizu Mari , Toyoshiba Hiroyoshi , Nakanishi Atsushi , Aparicio Samuel , Araki Shinsuke
Published: December 2021

Background

Endothelial cell senescence is the state of permanent cell cycle arrest and plays a critical role in the pathogenesis of age-related diseases. However, a comprehensive understanding of the gene regulatory network, including genome-wide alternative splicing machinery, involved in endothelial cell senescence is lacking.

Results

We thoroughly described the transcriptome landscape of replicative senescent human umbilical vein endothelial cells. Genes with high connectivity showing a monotonic expression increase or decrease with the culture period were defined as hub genes in the co-expression network. Computational network analysis of these genes led to the identification of canonical and non-canonical senescence pathways, such as E2F and SIRT2 signaling, which were down-regulated in lipid metabolism, and chromosome organization processes pathways. Additionally, we showed that endothelial cell senescence involves alternative splicing. Importantly, the first and last exon types of splicing, as observed in FLT1 and ACACA, were preferentially altered among the alternatively spliced genes during endothelial senescence. We further identified novel microexons in PRUNE2 and PSAP, each containing 9 nt, which were altered within the specific domain during endothelial senescence.

Conclusions

These findings unveil the comprehensive transcriptome pathway and novel signaling regulated by RNA processing, including gene expression and splicing, in replicative endothelial senescence.
Prevalence and burden of multiple sclerosis-related fatigue: a systematic literature review
Authors: Oliva Ramirez Abril , Keenan Alexander , Kalau Olivia , Worthington Evelyn , Cohen Lucas , Singh Sumeet
Published: December 2021

Background

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system that results in progressive and irreversible disability. Fatigue is one of the most common MS-related symptoms and is characterized by a persistent lack of energy that impairs daily functioning. The burden of MS-related fatigue is complex and multidimensional, and to our knowledge, no systematic literature review has been conducted on this subject. The purpose of this study was to conduct a systematic literature review on the epidemiology and burden of fatigue in people with multiple sclerosis (pwMS).

Methods

Systematic searches were conducted in MEDLINE, Embase, and Evidence-Based Medicine Reviews to identify relevant studies of fatigue in pwMS. English-language records published from 2010 to January 2020 that met predefined eligibility criteria were included. We initially selected studies that reported quality of life (QoL) and economic outcomes according to categories of fatigue (e.g., fatigued vs non-fatigued). Studies assessing associations between economic outcomes and fatigue as a continuous measure were later included to supplement the available data.

Results

The search identified 8147 unique records, 54 of which met the inclusion criteria. Of these, 39 reported epidemiological outcomes, 11 reported QoL, and 9 reported economic outcomes. The supplementary screen for economic studies with fatigue as a continuous measure included an additional 20 records.

Fatigue prevalence in pwMS ranged from 36.5 to 78.0%. MS-related fatigue was consistently associated with significantly lower QoL. Results on the economic impact of fatigue were heterogeneous, but most studies reported a significant association between presence or severity of fatigue and employment status, capacity to work, and sick leave. There was a gap in evidence regarding the direct costs of MS-related fatigue and the burden experienced by caregivers of pwMS.

Conclusion

Fatigue is a prevalent symptom in pwMS and is associated with considerable QoL and economic burden. There are gaps in the evidence related to the direct costs of MS-related fatigue and the burden of fatigue on caregivers. Addressing fatigue over the clinical course of the disease may improve health and economic outcomes for patients with MS.
Distance matters: barriers to antenatal care and safe childbirth in a migrant population on the Thailand-Myanmar border from 2007 to 2015, a pregnancy cohort study
Authors: Steinbrook Eric , Min Myo Chit , Kajeechiwa Ladda , Wiladphaingern Jacher , Paw Moo Kho , Pimanpanarak Mu Paw Jay , Hiranloetthanyakit Woranit , Min Aung Myat , Tun Nay Win , Gilder Mary Ellen , Nosten François , McGready Rose , Parker Daniel M.
Published: December 2021

Background

Antenatal care and skilled childbirth services are important interventions to improve maternal health and lower the risk of poor pregnancy outcomes and mortality. A growing body of literature has shown that geographic distance to clinics can be a disincentive towards seeking care during pregnancy. On the Thailand-Myanmar border antenatal clinics serving migrant populations have found high rates of loss to follow-up of 17.4%, but decades of civil conflict have made the underlying factors difficult to investigate. Here we perform a comprehensive study examining the geographic, demographic, and health-related factors contributing to loss to follow-up.

Methods

Using patient records we conducted a spatial and epidemiological analysis looking for predictors of loss to follow-up and pregnancy outcomes between 2007 and 2015. We used multivariable negative binomial regressions to assess for associations between distance travelled to the clinic and birth outcomes (loss to follow-up, pregnancy complications, and time of first presentation for antenatal care.)

Results

We found distance travelled to clinic strongly predicts loss to follow-up, miscarriage, malaria infections in pregnancy, and presentation for antenatal care after the first trimester. People lost to follow-up travelled 50% farther than people who had a normal singleton childbirth (a ratio of distances (DR) 1.5; 95% confidence interval (CI): 1.4 – 1.5). People with pregnancies complicated by miscarriage travelled 20% farther than those who did not have miscarriages (DR: 1.2; CI 1.1–1.3), and those with Plasmodium falciparum malaria in pregnancy travelled 60% farther than those without P. falciparum (DR: 1.6; CI: 1.6 – 1.8). People who delayed antenatal care until the third trimester travelled 50% farther compared to people who attended in the first trimester (DR: 1.5; CI: 1.4 – 1.5).

Conclusions

This analysis provides the first evidence of the complex impact of geography on access to antenatal services and pregnancy outcomes in the rural, remote, and politically complex Thailand-Myanmar border region. These findings can be used to help guide evidence-based interventions to increase uptake of maternal healthcare both in the Thailand-Myanmar region and in other rural, remote, and politically complicated environments.
Cement augmentation of the proximal femoral nail antirotation for the treatment of two intertrochanteric fractures - a comparative finite element study
Authors: Zheng Liqin , Chen Xinmin , Zheng Yongze , He Xingpeng , Wu Jingxiong , Lin Ziling
Published: December 2021

Background

There are concerns regarding initial stability and cutout effect in proximal femoral nail antirotation (PFNA) treating intertrochanteric fractures. No study have used finite element analysis (FEA) to investigate the biomechanics. This study aimed to compare the cutout effect, stress and displacement between stable (AO31-A1.3) and unstable (AO31-A2.2) intertrochanteric fractures treated by cement augmented PFNA.

Methods

Four femoral finite element models (FEMs) were constructed and tested under the maximum loading during walking. Non-augmented and augmented PFNA in two different intertrochanteric fractures were respectively simulated, assuming Tip Apex Distance (TAD) < 25 mm within each FEM. The cutout effect, stress and displacement between femur and PFNA were compared in each condition.

Results

Cutout effect was observed in both non-augmented femoral head and was more apparently in unstable intertrochanteric fracture model. After reinforced by bone cement, no cutout effect occurred in two models. Stress concentration were observed on medial part of intertrochanteric region and the proximal part of helical blade before augmented while were observed on femoral shaft and the conjunction between blade and nail after augmented in both FEMs. Displacement mainly appeared on femoral head and the helical blade tip before augmented while distributed moderately on intertrochanteric region and the upper part of nail after augmented in both FEMs. The maximum stress and displacement value of femur decreased both in stable and unstable model after augmented but was more significantly in the unstable one. The maximum stress and displacement value of PFNA increased both in stable and unstable model after augmented but was more significantly in the unstable one.

Conclusion

Our FEA study indicated that the cement augmentation of the PFNA biomechanically enhances the cutout resistance in intertrochanteric fracture, this procedure is especially efficient for the unstable intertrochanteric fracture.
Chikungunya virus infection: molecular biology, clinical characteristics, and epidemiology in Asian countries
Authors: Khongwichit Sarawut , Chansaenroj Jira , Chirathaworn Chintana , Poovorawan Yong
Published: December 2021

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne human pathogen that causes chikungunya fever, which is typically accompanied by severe joint pain. In Asia, serological evidence indicated that CHIKV first emerged in 1954. From the 1950’s to 2005, sporadic CHIKV infections were attributed to the Asian genotype. However, the massive outbreak of CHIKV in India and the Southwest Indian Ocean Islands in 2005 has since raised chikungunya as a worldwide public health concern. The virus is spreading globally, but mostly in tropical and subtropical regions, particularly in South and Southeast Asia. The emergence of the CHIKV East/Central/South African genotype-Indian Ocean lineage (ECSA-IOL) has caused large outbreaks in South and Southeast Asia affected more than a million people over a decade. Notably, the massive CHIKV outbreaks before 2016 and the more recent outbreak in Asia were driven by distinct ECSA lineages. The first significant CHIKV ECSA strains harbored the Aedes albopictus-adaptive mutation E1: A226V. More recently, another mass CHIKV ECSA outbreak in Asia started in India and spread beyond South and Southeast Asia to Kenya and Italy. This virus lacked the E1: A226V mutation but instead harbored two novel mutations (E1: K211E and E2: V264A) in an E1: 226A background, which enhanced its fitness in Aedes aegypti. The emergence of a novel ECSA strain may lead to a more widespread geographical distribution of CHIKV in the future. This review summarizes the current CHIKV situation in Asian countries and provides a general overview of the molecular virology, disease manifestation, diagnosis, prevalence, genotype distribution, evolutionary relationships, and epidemiology of CHIKV infection in Asian countries over the past 65 years. This knowledge is essential in guiding the epidemiological study, control, prevention of future CHIKV outbreaks, and the development of new vaccines and antivirals targeting CHIKV.
Prevalence of potential mediators of artemisinin resistance in African isolates of Plasmodium falciparum
Authors: Owoloye Afolabi , Olufemi Michael , Idowu Emmanuel T. , Oyebola Kolapo M.
Published: December 2021

Background

The devastating public health impact of malaria has prompted the need for effective interventions. Malaria control gained traction after the introduction of artemisinin-based combination therapy (ACT). However, the emergence of artemisinin (ART) partial resistance in Southeast Asia and emerging reports of delayed parasite sensitivity to ACT in African parasites signal a gradual trend towards treatment failure. Monitoring the prevalence of mutations associated with artemisinin resistance in African populations is necessary to stop resistance in its tracks. Mutations in Plasmodium falciparum genes pfk13, pfcoronin and pfatpase6 have been linked with ART partial resistance.

Methods

Findings from published research articles on the prevalence of pfk13, pfcoronin and pfatpase6 polymorphisms in Africa were collated. PubMed, Embase and Google Scholar were searched for relevant articles reporting polymorphisms in these genes across Africa from 2014 to August 2021, for pfk13 and pfcoronin. For pfatpase6, relevant articles between 2003 and August 2021 were retrieved.

Results

Eighty-seven studies passed the inclusion criteria for this analysis and reported 742 single nucleotide polymorphisms in 37,864 P. falciparum isolates from 29 African countries. Five validated-pfk13 partial resistance markers were identified in Africa: R561H in Rwanda and Tanzania, M476I in Tanzania, F446I in Mali, C580Y in Ghana, and P553L in an Angolan isolate. In Tanzania, three (L263E, E431K, S769N) of the four mutations (L263E, E431K, A623E, S769N) in pfatpase6 gene associated with high in vitro IC50 were reported. pfcoronin polymorphisms were reported in Senegal, Gabon, Ghana, Kenya, and Congo, with P76S being the most prevalent mutation.

Conclusions

This meta-analysis provides an overview of the prevalence and widespread distribution of pfk13, pfcoronin and pfatpase6 mutations in Africa. Understanding the phenotypic consequences of these mutations can provide information on the efficacy status of artemisinin-based treatment of malaria across the continent.

Graphical Abstract
Global health diplomacy in Mexico: insights from key actors in the field
Authors: Guerra German , Orozco Emanuel , Jiménez Paulina , Ruckert Arne , Labonté Ronald , Snyder Nelly Salgado de
Published: December 2021

Background

Global health diplomacy (GHD) focuses on the actions taken by diverse stakeholders from different nations –governments, multilateral agents, and civil society– to phenomena that can affect population health and its determinants beyond national borders. Although the literature on conceptual advancements of GHD exists, empirical studies about how health becomes an issue of relevance for foreign policy are scarce. We present an analysis of the entry processes of health into the foreign policy and diplomatic domains in Mexico from the perspective of key informants of three different sectors.

Methods

A purposive sample of high-rank representatives of three sectors involved in GHD was designed: Two from Health Sector (HS), four from Foreign Affairs Sector (FAS), and three from Non-governmental organizations (NGOs). Nine semi-structured interviews were conducted exploring the topics of: (1) Health concerns entering diplomatic and foreign policy; (2) Processes that allow actors to influence foreign policy and negotiation and; (3) Impact of multilateral negotiations on decision-making at the national level.

Results

Our analysis suggests that GHD in Mexico is hierarchically driven by the FAS and health concerns only enter foreign policy when they are relevant to national priorities (such as trade or security). HS possesses a lesser degree of influence in GHD, serving as an instance of consultation for the FAS when deciding on health-related issues at global meetings (i.e., World Health Assembly). NGOs resort to lobbying, advocacy, networking, and coalition-working practices with other sectors (academy, think-tanks) to prevent harmful impacts on local health from multilateral decisions and as a mean to compensate its power asymmetry for influencing GHD processes in relation to the government.

Conclusions

GHD in Mexico occurs in a context of asymmetric power relationships where government actors have the strongest influence. However, NGOs’ experience in raising awareness of health risks needs to be weighted by government decision-makers. This situation calls for capacity building on intersectoral communication and coordination to create formal mechanisms of GHD practices, including the professionalization and training on GHD among government agencies.
Circ-ATAD1 is overexpressed in osteosarcoma (OS) and suppresses the maturation of miR-154-5p to increase cell invasion and migration
Authors: Zhou Jihui , Xu Li , Yang Peng , Lin Shibang , Huang Haizhou
Published: December 2021

Background

Circ-ATAD1 plays an oncogenic role in gastric cancer. However, its roles in other cancers are unclear. We aimed to analyze the role of circ-ATAD1 in osteosarcoma (OS).

Methods

The expression levels of circ-ATAD1, mature miR-154-5p, and premature miR-154-5p in paired OS and non-tumor tissues from 56 OS patients were determined using RT-qPCR. Nuclear fractionation assay was performed to analyze the subcellular location of circ-ATAD1. The interaction between circ-ATAD1 and premature miR-154-5p was analyzed using RNA pull-down assay. The role of circ-ATAD1 in regulating miR-154-5p maturation was analyzed using RT-qPCR in cells with overexpression. Transwell assays were performed to analyze the roles of circ-ATAD1 and miR-154-5p in regulating OS cell invasion and migration.

Results

Circ-ATAD1 was overexpressed in OS compared to non-tumor tissues and was detected in the nuclei of OS cells. Mature miR-154-5p, but not premature miR-154-5p, was downregulated in OS tissues compared to non-tumor tissues and was inversely correlated with circ-ATAD1. In OS cells, circ-ATAD1 overexpression decreased the expression of mature miR-154-5p, but not premature miR-154-5p. Transwell assay analysis showed that circ-ATAD1 overexpression increased cell invasion and migration, and mature miR-154-5p overexpression suppressed these cell behaviors. In addition, circ-ATAD1 overexpression reduced the effects of mature miR-154-5p overexpression on cell behaviors.

Conclusions

Circ-ATAD1 is overexpressed in OS and suppresses miR-154-5p maturation to increase cell invasion and migration.
GSK3-beta as a candidate therapeutic target in soft tissue sarcomas
Authors: Verbeke S. , Perret R. , Chaire V. , Richard E. , Velasco V. , Giles F. , Cavalcante L. , Italiano A.
Published: December 2021

Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy.
Estimating the risk of malignancy of adnexal masses: validation of the ADNEX model in the hands of nonexpert ultrasonographers in a gynaecological oncology centre in China
Authors: He Ping , Wang Jing-jing , Duan Wei , Song Chao , Yang Yu , Wu Qing-qing
Published: December 2021

Background

This study aims to validate the diagnostic accuracy of the International Ovarian Tumor Analysis (IOTA) the Assessment of Different NEoplasias in the adneXa (ADNEX) model in the preoperative diagnosis of adnexal masses in the hands of nonexpert ultrasonographers in a gynaecological oncology centre in China.

Methods

This was a single oncology centre, retrospective diagnostic accuracy study of 620 patients. All patients underwent surgery, and the histopathological diagnosis was used as a reference standard. The masses were divided into five types according to the ADNEX model: benign ovarian tumours, borderline ovarian tumours (BOTs), stage I ovarian cancer (OC), stage II-IV OC and ovarian metastasis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of the ADNEX model to classify tumours into different histological types with and without cancer antigen 125 (CA 125) results.

Results

Of the 620 women, 402 (64.8%) had a benign ovarian tumour and 218 (35.2%) had a malignant ovarian tumour, including 86 (13.9%) with BOT, 75 (12.1%) with stage I OC, 53 (8.5%) with stage II-IV OC and 4 (0.6%) with ovarian metastasis. The AUC of the model to differentiate benign and malignant adnexal masses was 0.97 (95% CI, 0.96–0.98). Performance was excellent for the discrimination between benign and stage II-IV OC and between benign and ovarian metastasis, with AUCs of 0.99 (95% CI, 0.99–1.00) and 0.99 (95% CI, 0.98–1.00), respectively. The model was less effective at distinguishing between BOT and stage I OC and between BOT and ovarian metastasis, with AUCs of 0.54 (95% CI, 0.45–0.64) and 0.66 (95% CI, 0.56–0.77), respectively. When including CA125 in the model, the performance in discriminating between stage II–IV OC and stage I OC and between stage II–IV OC ovarian metastasis was improved (AUC increased from 0.88 to 0.94, P = 0.01, and from 0.86 to 0.97, p = 0.01).

Conclusions

The IOTA ADNEX model has excellent performance in differentiating benign and malignant adnexal masses in the hands of nonexpert ultrasonographers with limited experience in China. In classifying different subtypes of ovarian cancers, the model has difficulty differentiating BOTs from stage I OC and BOTs from ovarian metastases.