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Background: AV malformations are aberrations in the development of vessels with varied presentations that may lead to aesthetic, limb and life-threatening complications. Identification and treatment of the vascular malformations is a challenging task for surgeons. Aims & Objectives: To study clinical presentation/ diagnostic modalities/ treatment strategies, complications and recurrence rates of surgical and other interventional strategies. Material and Methods: A retrospective study of 150 patients who were treated over a period of 3 years from a tertiary centre with regular follow-ups was done to study the best diagnostic and treatment plans for initial and recurrent lesions. Results: The study showed an age group of

Abstract Background Despite advances in managing secondary health complications after spinal cord injury (SCI), challenges remain in developing targeted community health strategies. In response, the SCI Health Maintenance Tool (SCI-HMT) was developed between 2018 and 2023 in NSW, Australia to support people with SCI and their general practitioners (GPs) to promote better community self-management. Successful implementation of innovations such as the SCI-HMT are determined by a range of contextual factors, including the perspectives of the innovation recipients for whom the innovation is intended to benefit, who are rarely included in the implementation process. During the digitizing of the booklet version of the SCI-HMT into a website and App, we used the Consolidated Framework for Implementation Research (CFIR) as a tool to guide collection and analysis of qualitative data from a range of innovation recipients to promote equity and to inform actionable findings designed to improve the implementation of the SCI-HMT. Methods Data from twenty-three innovation recipients in the development phase of the SCI-HMT were coded to the five CFIR domains to inform a semi-structured interview guide. This interview guide was used to prospectively explore the barriers and facilitators to planned implementation of the digital SCI-HMT with six health professionals and four people with SCI. A team including researchers and innovation recipients then interpreted these data to produce a reflective statement matched to each domain. Each reflective statement prefaced an actionable finding, defined as alterations that can be made to a program to improve its adoption into practice. Results Five reflective statements synthesizing all participant data and linked to an actionable finding to improve the implementation plan were created. Using the CFIR to guide our research emphasized how partnership is the key theme connecting all implementation facilitators, for example ensuring that the tone, scope, content and presentation of the SCI-HMT balanced the needs of innovation recipients alongside the provision of evidence-based clinical information. Conclusions Understanding recipient perspectives is an essential contextual factor to consider when developing implementation strategies for healthcare innovations. The revised CFIR provided an effective, systematic method to understand, integrate and value recipient perspectives in the development of an implementation strategy for the SCI-HMT. Trial registration N/A.

ObjectivesAdults with spinal cord injury (SCI) are often sedentary, increasing their risk of cardiometabolic diseases. Leisure-time Physical Activity (LTPA) is physical activity completed during recreation time for enjoyment. We aimed to quantify LTPA in people ≥45 years with SCI and to explore its relationship with participants’ characteristics.MethodsThis is a secondary analysis on a subset of the Australian International SCI Survey in participants ≥45 years, at least 12 months post-injury. We described levels of LTPA and used multivariable regressions to estimate the associations between participant characteristics and LTPA.ResultsOf 1,281 participants (mean age: 62.7 years, mean time since injury: 18.7 years; 74% males) 44% reported no participation in LTPA. The average LTPA participation was 197 (SD 352) minutes per week (median: 50). Females (β = −62.3, 95% CI [−112.9, −11.7]), and participants with non-traumatic injuries (β = −105.2, 95% CI [−165.9, −44.6]) performed less LTPA. Time since injury was not associated with moderate-to-heavy LTPA (LR: Probability > F = 0.785).ConclusionLTPA promotion in the SCI population ≥45 years focusing on females and non-traumatic injuries is warranted.

Moving from participatory approaches incorporating co-design to co-production in health research involves a commitment to full engagement and partnership with people with lived experience through all stages of the research process—start to finish. However, despite the increased enthusiasm and proliferation of research that involves co-production, practice remains challenging, due in part to the lack of consensus on what constitutes co-production, a lack of guidance about the practical steps of applying this approach in respect to diverse research methods from multiple paradigms, and structural barriers within academia research landscape. To navigate the challenges in conducting co-produced research, it has been recommended that attention be paid to focusing and operationalising the underpinning principles and aspirations of co-production research, to aid translation into practice. In this article, we describe some fundamental principles essential to conducting co-production research (sharing power, relational resilience, and adopting a learning mindset) and provide tangible, practical strategies, and processes to engage these values. In doing so, we hope to support rehabilitation researchers who wish to engage in co-production to foster a more equitable, ethical, and impactful collaboration with people with lived experience and those involved in their circle of care.

Cognitive impairment is common in persons with spinal cord injury (SCI), impacting their daily functioning and rehabilitation. This study assesses the extent of self-reported cognitive failures in everyday life in persons with SCI and its relationships with objective neurocognitive measures and psychosocial factors, including depressive mood, anxiety, perceived control, and fatigue. The differences between forty-one adults with a chronic SCI and forty-one able-bodied controls were examined. The participants completed the Cognitive Failures Questionnaire (CFQ) to assess cognitive failure and neurocognitive tests assessing attention and executive functions, as well as a psychosocial assessment. The SCI group reported higher cognitive failure rates than the able-bodied group (31.7% versus 19%, p > 0.05). Objective neurocognitive tests did not significantly correlate with the CFQ scores in either group. However, the CFQ scores were positively associated with most psychosocial factors, even after controlling for covariates. The CFQ scores were significantly associated with depressive mood in persons with SCI. These findings highlight the importance of incorporating self-reported cognitive measures into neurocognitive assessments and rehabilitation planning for adults with SCI. Self-reports capture everyday cognitive challenges that objective tests may miss. Additionally, this study highlights the strong connections between cognitive failures and psychosocial issues, particularly mood disorders, emphasizing the need for comprehensive rehabilitation and psychosocial support post-SCI, addressing both cognitive and emotional wellbeing.

Siglecs belong to a family of immune regulatory receptors predominantly found on hematopoietic cells. They interact with Sia, resulting in the activation or inhibition of the immune response. Previous reports have suggested that the SIGLEC12 gene, which encodes the Siglec-XII protein, is expressed in the epithelial tissues and upregulated in carcinomas. However, studies deciphering the role of Siglec-XII in renal cancer (RC) are still unavailable, and here we provide insights on this question. We conducted expression analysis using the Human Protein Atlas and UALCAN databases. The impact of SIGLEC12 on RC prognosis was determined using the KM plotter, and an assessment of immune infiltration with SIGLEC12 was performed using the TIMER database. GSEA was conducted to identify the pathways affected by SIGLEC12. Finally, using GeneMania, we identified Siglec-XII interacting proteins. Our findings indicated that macrophages express SIGLEC12 in the kidney. Furthermore, we hypothesize that Siglec-XII expression might be involved in the increase of primary RC, but this effect may not be dependent on the age of the patient. In the tumour microenvironment, oncogenic pathways appeared to be upregulated by SIGLEC12. Similarly, our analysis suggested that SIGLEC12-related kidney renal papillary cell carcinomas may be more suitable for targeted immunotherapy, such as CTLA-4 and PD-1/PD-L1 inhibitors. These preliminary results suggested that high expression of SIGLEC12 is associated with poor prognosis for RC. Future studies to assess its clinical utility are necessitated.

Abstract Background Inequality in health is a prevalent and growing concern among countries where people with disabilities are disproportionately affected. Unmet healthcare needs explain a large part of the observed inequalities between and within countries; however, there are other causes, many non-modifiable, that also play a role. Aim This article explores the difference in health across income levels in populations with spinal cord injury (SCI). SCI is of special interest in the study of health systems, as it is an irreversible, long-term health condition that combines a high level of impairment with subsequent comorbidities. Methods We estimated the importance of modifiable and non-modifiable factors that explain health inequalities through a direct regression approach. We used two health outcomes: years living with the injury and a comorbidity index. Data come from the International Spinal Cord Injury Survey (InSCI), which has individual data on people with SCI in 22 countries around the world. Due to the heterogeneity of the data, the results were estimated country by country. Results On average, the results exhibit a prevalence of pro-rich inequalities, i.e., better health outcomes are more likely observed among high-income groups. For the years living with the injury, the inequality is mostly explained by non-modifiable factors, like the age at the time of the injury. In contrast, for the comorbidity index, inequality is mostly explained by unmet healthcare needs and the cause of the injury, which are modifiable factors. Conclusions A significant portion of health inequalities is explained by modifiable factors like unmet healthcare needs or the type of accident. This result is prevalent in low, middle, and high-income countries, with pervasive effects for vulnerable populations like people with SCI, who, at the same time are highly dependent on the health system. To reduce inequity, it is important not only to address problems from public health but from inequalities of opportunities, risks, and income in the population. Highlights • Better health status is evident among high-income groups, which is reflected in pro-rich inequalities. • Age at the time of the injury is the most important factor to explain inequalities in years living with the injury. • Unmet health care needs are the most important factor to explain inequalities in comorbidities. • The inequality in health varies by country dependent upon socioeconomic factors.

A study was conducted to investigate the effects of chemical treatment in characterizing the tensile strength, durability, and application of untreated/treated coir geotextile in low-volume roads. Two woven and two nonwoven coir geotextiles were used in this study. Sodium hydroxide and potassium permanganate were the chemicals used to treat the coir geotextiles. The results show that the tensile strength of both the woven coir geotextiles treated with potassium permanganate was lower as compared to both the untreated woven coir geotextiles. The tensile strength of both the nonwoven coir geotextiles treated with sodium hydroxide was higher as compared to both the untreated nonwoven coir geotextiles. Further, the tensile strength of both the woven as well as nonwoven coir geotextiles treated with potassium permanganate was higher in comparison to the one treated with sodium hydroxide. The tensile strength of both the woven as well as nonwoven coir geotextiles first treated with sodium hydroxide followed by potassium permanganate was higher as compared to both the woven as well as nonwoven coir geotextiles treated with sodium hydroxide and potassium permanganate individually. The percentage reduction in tensile strength due to deterioration in the cross-machine direction for both the woven and nonwoven coir geotextiles was higher as compared to the direction of the machine. The results of monotonic load tests show that the models reinforced with untreated/treated woven and nonwoven coir geotextiles show an increase in the bearing pressure at greater deformation. Untreated woven/treated nonwoven coir geotextiles placed at the interface of the sand layer overlying silty sand can be useful in the low-volume roads.

Abstract Software effort estimation is a significant part of software development and project management. The accuracy of effort estimation and scheduling results determines whether a project succeeds or fails. Many studies have focused on improving the accuracy of predicted results, yet accurate estimation of effort has proven to be a challenging task for researchers and practitioners, particularly when it comes to projects that use agile approaches. This work investigates the application of the adaptive neuro-fuzzy inference system (ANFIS) along with the novel Energy-Efficient BAT (EEBAT) technique for effort prediction in the Scrum environment. The proposed ANFIS-EEBAT approach is evaluated using real agile datasets. It provides the best results in all the evaluation criteria used. The proposed approach is also statistically validated using nonparametric tests, and it is found that ANFIS-EEBAT worked best as compared to various state-of-the-art meta-heuristic and machine learning (ML) algorithms such as fireworks, ant lion optimizer (ALO), bat, particle swarm optimization (PSO), and genetic algorithm (GA).

Summary: Background: Cauda equina syndrome (CES) results from nerve root compression in the lumbosacral spine, usually due to a prolapsed intervertebral disc. Evidence for management of CES is limited by its infrequent occurrence and lack of standardised clinical definitions and outcome measures. Methods: This is a prospective multi-centre observational cohort study of adults with CES in the UK. We assessed presentation, investigation, management, and all Core Outcome Set domains up to one year post-operatively using clinician and participant reporting. Univariable and multivariable associations with the Oswestry Disability Index (ODI) and urinary outcomes were investigated. Findings: In 621 participants with CES, catheterisation for urinary retention was required pre-operatively in 31% (191/615). At discharge, only 13% (78/616) required a catheter. Median time to surgery from symptom onset was 3 days (IQR:1–8) with 32% (175/545) undergoing surgery within 48 h. Earlier surgery was associated with catheterisation (OR:2.2, 95%CI:1.5–3.3) but not with admission ODI or radiological compression. In multivariable analyses catheter requirement at discharge was associated with pre-operative catheterisation (OR:10.6, 95%CI:5.8–20.4) and one-year ODI was associated with presentation ODI (r = 0.3, 95%CI:0.2–0.4), but neither outcome was associated with time to surgery or radiological compression. Additional healthcare services were required by 65% (320/490) during one year follow up. Interpretation: Post-operative functional improvement occurred even in those presenting with urinary retention. There was no association between outcomes and time to surgery in this observational study. Significant healthcare needs remained post-operatively. Funding: DCN Endowment Fund funded study administration. Castor EDC provided database use. No other study funding was received.

Objectives: This study described leisure-time physical activity (LTPA) for people in Australia with spinal cord injury (SCI) and whether certain sociodemographic and psychosocial variables might be associated with LTPA uptake and guidelines adherence.Methods: The Physical Activity Scale for Individuals with a Physical Disability was used to measure the intensity and volume of LTPA of 1,579 individuals with SCI. Summary statistics were calculated for LTPA guidelines adherence. Analyses included regression modelling.Results: Of the 1,579 participants, 58% performed LTPA and 13% adhered to recommended guidelines for weekly LTPA. There was an association with being an “exerciser” based on the time since injury (OR = 1.02 [95% 1.01–1.03]), a traumatic injury (OR = 1.53 [95% CI 1.13–2.08]) and a higher self-rating of health (OR = 1.10 [95% CI 0.95–1.27]). Where LTPA guidelines were met, adherence was most related to a traumatic injury (OR = 1.75 [95% CI 1.02–3.02]) and being unemployed (OR = 1.53 [95% CI 1.03–2.25]).Conclusion: Of those who performed LTPA with SCI, one in four met population-specific LTPA guidelines. Sociodemographic variables were moderately associated with being an “exerciser” or LTPA “guideline-adherent.”

Abstract Background Spinal cord injury (SCI) is associated with autonomic imbalance and significant secondary conditions, including cardiac and brain dysfunction that adversely impact health and wellbeing. This study will investigate the effectiveness (intention-to-treat) of a neuro-cardiac self-regulation therapy to improve autonomic and neural/brain activity in adults with SCI living in the community. Methods A two-arm parallel, randomised controlled trial in which adults with SCI living in the community post-rehabilitation will be randomly assigned to a treatment or control group. The treatment group (N = 60) aged 18–70 years with a chronic traumatic or non-traumatic SCI, will receive intervention sessions once per week for 10 weeks, designed to regulate autonomic activity using computer-based feedback of heart rate variability and controlled breathing (called HRV-F). Comprehensive neurophysiological and psychological assessment will occur at baseline, immediate post-treatment, and 6 and 12-months post-treatment. Primary outcome measures include electrocardiography/heart rate variability (to assess autonomic nervous system function) and transcranial doppler sonography (to assess cerebral blood circulation in basal cerebral arteries). Secondary outcomes measures include continuous blood pressure, electroencephalography, functional near-infrared spectroscopy, respiration/breath rate, electrooculography, cognitive capacity, psychological status, pain, fatigue, sleep and quality of life. Controls (N = 60) will receive usual community care, reading material and a brief telephone call once per week for 10 weeks and be similarly assessed over the same time period as the HRV-F group. Linear mixed model analysis with repeated measures will determine effectiveness of HRV-F and latent class mixture modelling used to determine trajectories for primary and selected secondary outcomes of interest. Discussion Treatments for improving autonomic function after SCI are limited. It is therefore important to establish whether a neuro-cardiac self-regulation therapy can result in improved autonomic functioning post-SCI, as well as whether HRV-F is associated with better outcomes for secondary conditions such as cardiovascular health, cognitive capacity and mental health. Trial registration The study has been prospectively registered with the Australian and New Zealand Clinical Trial Registry ( ACTRN12621000870853 .aspx). Date of Registration: 6th July 2021. Trial Sponsor: The University of Sydney, NSW 2006. Protocol version: 22/07/2021.

The paper presents the bearing ratio behavior of sand overlying silty sandy with two woven and two non-woven treated coir geotextiles at the interface under unsoaked and soaked condition. The chemicals such as sodium hydroxide and potassium permanganate were used to treat the coir geotextiles. The coir geotextiles were placed at two different locations (Designated as Series A and Series B). The results indicated that the bearing ratio of the sand overlying silty sand with untreated/ treated woven/non-woven coir geotextiles at the interface was higher in the unsoaked condition in comparison to soaked condition for the Series A and Series B. The improvement in the bearing ratio of the sand overlying silty sand with untreated/ treated woven/non-woven coir geotextiles at the interface in the unsoaked/soaked condition was higher for the Series A in comparison to the Series B. The bearing ratio of the sand overlying silty sand increased when the woven/non-woven coir geotextiles at the interface were treated with sodium hydroxide. The improvement in the bearing ratio of the sand overlying silty sand with potassium permanganate treated woven/non-woven coir geotextiles at the interface was higher in comparison to the sodium hydroxide treated woven/non-woven coir geotextiles. The highest improvement in the bearing ratio was achieved when both the woven/non-woven coir geotextiles were treated with sodium hydroxide followed by potassium permanganate.

Objectives: To describe the 3-month prevalence and correlates of self-reported physical health conditions in persons with spinal cord injury (SCI) worldwide. Study design: Multinational cross-sectional survey. Subjects: Community-living persons with traumatic or non-traumatic SCI aged >18 years from 21 countries representing all the 6 World Health Organization regions. Methods: The study used data from 11,058 participants in the International SCI Community Survey (InSCI). The survey, based on the International Classification of Functioning, Disability and Health (ICF) Core Sets for SCI, was conducted in 2017–19 simultaneously in the participating countries. The health conditions were reported on a modified version of the SCI Secondary Conditions Scale. Results: Overall, 95.8% of the participants reported having experienced 1 or more health problems secondary to SCI. Having pain was the most prevalent problem (77.3%), followed by spasticity/muscle spasms (73.5%) and sexual dysfunction (71.3%), and the least prevalent was respiratory problems (28.8%). The participants reported a mean of 7.4 concurrent health conditions. Unmet healthcare needs, being a smoker, being a female, having a complete lesion, and a traumatic injury exhibited significant associations with comorbidity. Conclusion: Physical health problems secondary to SCI are extremely common worldwide and demand investment in appropriate management, medical care and preventative measures. LAY ABSTRACT More than 500,000 people experience a spinal cord injury (SCI) every year. Because of the impairments of having SCI, many experience co-occurrence of additional health conditions, called comorbidity. This study describes the 3-month prevalence, and associated factors of self-reported physical health conditions secondary to SCI across 21 countries worldwide. The study uses data from 11,058 adults with SCI participating in the International SCI Community Survey in 2017–19. The results showed that physical health problems secondary to SCI are extremely common worldwide. Having pain, muscle spasms/spasticity, sexual dysfunction and bowel dysfunction were the most common, all with rates above 70%. The participants experienced a mean of 7 concurrent health conditions in addition to their SCI. Those reporting unmet healthcare needs, being a smoker, female, and having a complete lesion were most at risk for having comorbidity. These findings demand investment in appropriate management, medical care and preventative measures.

Cysteine cathepsins are lysosomal proteases that require Cys-His ion pair in their catalytic site for enzymatic activity. While their aberrant expression and oncogenic functions have been widely reported in solid tumors, recent findings suggest that these proteases also play an important role in the pathogenesis of hematological malignancies. In this review, we summarize the potential clinical implications of cysteine cathepsins as diagnostic and prognostic markers in leukemia, and present evidences which supports the utility of these proteases as potential therapeutic targets in hematological malignancies. We also highlight the available information on the expression patterns, regulation, and potential functions of cysteine cathepsins in normal hematopoiesis and hematological malignancies. In hematopoiesis, cysteine cathepsins play a variety of physiological roles including regulation of hematopoietic stem cell adhesion in the bone marrow, trafficking, and maturation. They are also involved in several functions of immune cells which include the selection of lymphocytes in the thymus, antigen processing, and presentation. However, the expression of cysteine cathepsins is dysregulated in hematological malignancies where they have been shown to play diverse functions. Interestingly, several pieces of evidence over the past few years have demonstrated overexpression of cathepsins in leukemia and their association with worst survival outcomes in patients. Strategies aimed at altering the expression, activity, and subcellular localization of these cathepsins are emerging as potential therapeutic modalaties in the management of hematological malignancies. Recent findings also suggest the involvement of these proteases in modulating the immune response in leukemia and lymphomas.

Abstract Background Studies report rates of mild cognitive impairment (MCI) in spinal cord injury (SCI) range between 10 and 60%. This broad estimate of MCI in SCI is most likely a result of: (i) inconsistent operationalization of MCI; (ii) heterogeneity among individuals with SCI; (iii) failure to account for MCI subtypes, thereby adding to the heterogeneity of samples; and, (iv) poor control for traumatic brain injury (TBI) that obscures differentiation of MCI attributable to TBI versus other factors. There is a paucity of longitudinal studies following the course of MCI in SCI, and none that account for multiple predictors of MCI, including interactions among predictors. Methods An inception cohort longitudinal study will assess approximately 100 individuals aged 17–80 years with acute SCI, with measures taken at three timepoints (baseline, 3 months post-baseline, and 12 months post-injury). Data relevant to medical care received within the first 24–48 h of presentation to the emergency department will be analysed, as will measures of cognition, injury characteristics, medical history, personal factors, psychological status, psychosocial functioning, and quality of life. Latent class mixture modelling will determine trajectories for the primary outcome of interest, cognitive functioning and its subtypes, and secondary outcomes of interest such as depression. Multiple regression analyses will identify predictors of MCI and its subtypes. Discussion The prospective design will reveal change in cognitive functioning across time and unveil different outcome trajectories; thus addressing the lack of knowledge on trajectories of MCI and MCI subtypes in SCI. Through subtyping MCI, we hope to yield groups of cognitively impaired individuals with SCI that are potentially more homogenous and thereby stable and predictable. This is the first study to capture emergency department and acute care diagnostic evidence of mild TBI, which has been poorly controlled in previous studies. Our study will also be the first to distinguish the contribution of TBI from other factors to the development of MCI in individuals with SCI. Trial registration The study was prospectively registered with the Australian and New Zealand Clinical Trial Registry ( ACTRN12619001702101 ) on 3rd December 2019.

The COVID-19 pandemic has caused an unprecedented crisis for the air transportation industry, affecting millions of aviation users and stakeholders. As the aviation sector has faced disease outbreaks and extreme events before—albeit not at the same scale—and will, in all likelihood, face them again, we provide an assessment in this study that a) gives an overview of the effects of the pandemic, b) categorizes the response mechanisms that were observed, and c) proposes a framework for a coordinated global response to future disease outbreaks. We highlight that of the many lessons, recommendations, and suggestions that emerged during previous outbreaks, few were introduced effectively into civil aviation practices and operations. Based on multiple data sources for passengers, cargo, and flight schedules, we assess the impact of COVID-19 on the global aviation industry and compare the data of some prominent airports to highlight the need for a coordinated response to effectively deal with future disruptions. As global aviation navigates its ongoing recovery, we discuss different responses during the pandemic including guidelines issued by bodies such as the International Civil Aviation Organization (ICAO), operational decisions such as closing terminals, increased cleaning frequencies, and mask mandates etc. We emphasize the need for resilience to accommodate disease outbreaks in future planning, design, and preparedness strategies for airports and airlines. We further argue that the existing civil aviation system needs a coordinated global response mechanism to combat future outbreaks and propose a framework with a threat response matrix to keep aviation safe and operational during future pandemics and mitigate socioeconomic fallout.

Wetlands play a vital role in sustainable ecological development. They hold balanced environment conditions, filter the surface and sub-surface water, and moderate the local weather condition. The current study is mainly focused on assessment and monitoring of optically active water quality parameters on wetland ecosystems over the Harike and Keshopur wetlands in Punjab region, India. Sentinel-2 multispectral imager (MSI) product have been analyzed in two phases: Pre-monsoon and Post-monsoon during period from 2018 to 2021 to extract spatial and temporal variations of water quality parameters. A normalized difference water index (NDWI) has been utilized to extract the water and non-water pixels, and the semi-analytical inversion model is used to retrieve the optically water quality parameters. The images of derived chlorophyll concentrations and total suspended matter have been found ranging from 0 to 36 mg/m3 and 0 to 156 mg/m3. This study revealed that the semi-analytical model is very helpful to identify the small scale changes in optically active constituents through using multispectral imagery. Water quality parameters monitoring is an important indicator to measure the productivity and eutrophication of the river water system. This research will help in understanding the water cycle and water conditions, and is paramount to researchers, scientists, and policy makers for sustainable management. The current study also concluded that the significant reduction of highly biodiversity wetland area is required to conserve.

Hepatocellular carcinoma (HCC) is an aggressive gastrointestinal malignancy with a high rate of mortality. Multiple studies have individually recognized members of RAP gene family as critical regulators of tumor progression in several cancers, including hepatocellular carcinoma. These studies suffer numerous limitations including a small sample size and lack of analysis of various clinicopathological and molecular features. In the current study, we utilized authoritative multi-omics databases to determine the association of RAP gene family expression and detailed molecular and clinicopathological features in hepatocellular carcinoma (HCC). All five RAP genes were observed to harbor dysregulated expression in HCC compared to normal liver tissues. RAP2A exhibited strongest ability to differentiate tumors from the normal tissues. RAP2A expression was associated with progressive tumor grade, TP53 and CTNNB1 mutation status. Additionally, RAP2A expression was associated with the alteration of its copy numbers and DNA methylation. RAP2A also emerged as an independent marker for patient prognosis. Further, pathway analysis revealed that RAP2A expression is correlated with tumor-infiltrating immune cell composition and oncogenic molecular pathways, such as cell cycle and cellular metabolism.

Abstract Background Studies aimed at improving the provision of evidence-based care (EBC) for the management of acute whiplash injuries have been largely successful. However, whether EBC is broadly provided and whether delivery of EBC varies based on risk of non-recovery, is uncertain. Receiving EBC should improve recovery, though this relationship has yet to be established. Further, mitigating the effect of EBC is the relationship with the practitioner, a phenomenon poorly understood in WAD. This study aimed to determine the proportion of individuals with whiplash, at differing baseline risk levels, receiving EBC. This study also aimed to determine whether receiving EBC and the therapeutic relationship were associated with recovery at 3 months post injury. Methods Participants with acute whiplash were recruited from public hospital emergency departments, private physiotherapy practices, and State Insurance Regulatory Authority (SIRA) databases. Participants completed questionnaires at baseline (demographics, risk of non-recovery) and 3-months (treatment received, risk identification, therapeutic relationship) post injury. Primary health care providers (HCPs) treating these participants also completed questionnaires at 3-months. Recovery was defined as neck disability index ≤4/50 and global perceived effect of ≥4/5. Results Two-hundred and twenty-eight people with acute whiplash, and 53 primary care practitioners were recruited. The majority of the cohort reported receiving EBC, with correct application of the Canadian C-spine rule (74%), and provision of active treatments (e.g. 89% receiving advice) high. Non-recommended (passive) treatments were also received by a large proportion of the cohort (e.g. 50% receiving massage). The therapeutic relationship was associated with higher odds of recovery, which was potentially clinically significant (OR 1.34, 95% CI 1.18–1.62). EBC was not significantly associated with recovery. Conclusions Guideline-based knowledge and practice has largely been retained from previous implementation strategies. However, recommendations for routine risk identification and tailored management, and reduction in the provision of passive treatment have not. The therapeutic relationship was identified as one of several important predictors of recovery, suggesting that clinicians must develop rapport and understanding with their patients to improve the likelihood of recovery.

China is in a critical stage of ambient air quality management after global attention on pollution in its cities. Industrial development and urbanization have led to alarming levels of air pollution with serious health hazards in densely populated cities. The quantification of cause-specific PM2.5-related health impacts and corresponding economic loss estimation is crucial for control policies on ambient PM2.5 levels. Based on ground-level direct measurements of PM2.5 concentrations in 338 Chinese cities for the year 2016, this study estimates cause-specific mortality using integrated exposure-response (IER) model, non-linear power law (NLP) model and log-linear (LL) model followed by morbidity assessment using log-linear model. The willingness to pay (WTP) and cost of illness (COI) methods have been used for PM2.5-attributed economic loss assessment. In 2016 in China, the annual PM2.5 concentration ranged between 10 and 157 μg/m3 and 78.79% of the total population was exposed to >35 μg/m3 PM2.5 concentration. Subsequently, the national PM2.5-attributable mortality was 0.964 (95% CI: 0.447, 1.355) million (LL: 1.258 million and NPL: 0.770 million), about 9.98% of total reported deaths in China. Additionally, the total respiratory disease and cardiovascular disease-specific hospital admission morbidity were 0.605 million and 0.364 million. Estimated chronic bronchitis, asthma and emergency hospital admission morbidity were 0.986, 1.0 and 0.117 million respectively. Simultaneously, the PM2.5 exposure caused the economic loss of 101.39 billion US$, which is 0.91% of the national GDP in 2016. This study, for the first time, highlights the discrepancies associated with the three commonly used methodologies applied for cause-specific mortality assessment. Mortality and morbidity results of this study would provide a measurable assessment of 338 cities to the provincial and national policymakers of China for intensifying their efforts on air quality improvement. Keywords: China, Spatial distributions of PM2.5, Long-term mortality, Morbidity, Economic loss

Objectives: As advancing evidence on modifiable resources to support mental health in persons experiencing physical disabilities is of particular importance, we investigate whether structural and functional social relationships relate to mental health in people with spinal cord injury (SCI).Methods: Data from 12,330 participants of the International SCI community survey (InSCI) from 22 countries were analyzed. Structural (partnership status, living situation) and functional aspects of social relationships (belongingness, relationship satisfaction, problems with social interactions) were regressed on the SF-36 mental health index (MHI-5), stratified by countries and for the total sample using multilevel models.Results: Functional aspects of social relationships were consistently related to clinically relevant higher MHI-5 scores and lower risk of mental health disorders (MHI-5 >56). Structural social relationships were inconsistently associated with mental health in our sample.Conclusion: This study provides evidence that functional aspects of social relationships are important resources for mental health. Interventions to establish and maintain high quality relationships should be considered in public health interventions and rehabilitation programs to reduce long-term mental health problems in persons experiencing physical disabilities.

Glucocorticoid (GC), such as prednisolone, is an essential component of multidrug chemotherapy regimen for pediatric acute lymphoblastic leukemia (ALL). Resistance to GC in leukemia cells is associated with disease progression and poor prognosis. Despite the extensive use of GC for many years, molecular mechanisms underlying its resistance in ALL have not been fully uncovered. Recent studies have shown a potential role of EMP1, CASP1, and NLRP3 genes in prednisolone response. In this study on 148 pediatric B-ALL patients, we studied these three genes to assess their association with prednisolone response measured by day 8 blast count after 7 days of induction therapy with prednisolone. Intriguingly, ALL samples exhibited higher expression of EMP1 along with a low expression of CASP1 and NLRP3 compared to disease free normal bone marrow collected from patients with solid tumors. Among the three analyzed genes, only EMP1 was found to be overexpressed in prednisolone poor responders (p=0.015). Further, a comparison of gene expression between cytogenetic subtypes revealed higher expression of EMP1 in BCR-ABL subtype. Expression of EMP1 in multiple gene expression datasets was used for gene set enrichment analysis, which revealed TNF-α, IL-2-STAT5 signaling, inflammatory responses and hypoxia as the major positively associated pathways and E2F targets as negatively associated pathways. Interestingly, the clinical remission rate was higher in CASP1 high patients (p=0.048). In univariate survival analysis, higher EMP1 expression was associated with poor prognostic measures while higher expression of NLRP3 and CASP1 was associated with better prognostic measures in our data. Further, multivariate analysis revealed an independent association of high CASP1 and NLRP3 with a better prognosis. This study strengthens the available evidence that mRNA expression of EMP1, CASP1, and NLRP3 may serve as potential biomarkers for risk stratification of pediatric B-ALL patients.

BackgroundSocial relationships are powerful determinants of health and inequalities in social relationships across socioeconomic status (SES) groups may contribute to social inequalities in health. This study investigates inequalities in social relationships in an international sample of persons with spinal cord injury and explores whether social gradients in relationships are moderated by the countries' socioeconomic development (SED).MethodsData from 12,330 participants of the International SCI Community Survey (InSCI) performed in 22 countries were used. We regressed social relationships (belongingness, relationship satisfaction, social interactions) on individual SES (education, income, employment, financial hardship, subjective status) and countries' SED (Human Development Index) using multi-level models (main effects). To test potential moderation of the SED, interaction terms between individual SES and countries' SED were entered into multi-level models.ResultsPaid work, absence of financial hardship and higher subjective status were related to higher belongingness (OR, 95% CI: 1.50, 1.34-1.67; 1.76, 1.53-2.03; 1.16, 1.12-1.19, respectively), higher relationship satisfaction (OR, 95% CI: 1.28, 1.15-1.42; 1.97, 1.72-2.27; 1.20, 1.17-1.24, respectively) and fewer problems with social interactions (Coeff, 95% CI: 0.96, 0.82-1.10; 1.93, 1.74-2.12; 0.26, 0.22-0.29, respectively), whereas associations with education and income were less consistent. Main effects for countries' SED showed that persons from lower SED countries reported somewhat higher relationship satisfaction (OR, 95% CI: 0.97, 0.94-0.99) and less problems with social interactions (Coeff, 95% CI: -0.04, -0.09- -0.003). Results from moderation analysis revealed that having paid work was more important for relationships in lower SED countries, while education and subjective status were more important for relationships in higher SED countries (interaction terms pConclusionSocial relationships in persons with spinal cord injury are patterned according to individual SES and the countries' SED and larger socioeconomic structures partly moderate associations between individual SES and social relationships.

Melanoma associated antigen (MAGE) is an extensively studied family of tumor-associated genes that share a common MAGE homology domain (MHD). Based upon their expression pattern, MAGE genes have been broadly classified into type 1 MAGEs (T1Ms) and type 2 MAGEs (T2Ms) categories. Interestingly, several T2Ms are highly expressed in the brain and involved in the regulation of neuronal development, differentiation, and survival. Available literature suggests possible tumor suppressor functions of a few T2Ms, while information available about their expression, regulation, and clinical significance in glioma is scanty. This prompted us to perform a comprehensive analysis of T2M expression in glioma. Gene expression data from glioma datasets: Oncomine, TCGA, and REMBRANDT study, were used to assess the mRNA expression of T2M genes (MAGED1, MAGED2, MAGED3, MAGED4, MAGED4B, MAGEE1, MAGEE2, MAGEF1, MAGEH1, MAGEL2, NSMCE3, and NDN), and their association with clinical characteristics and composition of the tumor microenvironment. Further, mutation, copy number alteration, and DNA methylation data from TCGA were assessed for determining potential mechanisms of T2Ms expression in glioma. Expression analysis revealed overexpression of MAGED subfamily genes in glioma, while other genes of this family exhibited reduced expression in advanced grades of this malignancy. Further, the expression of T2Ms exhibited varying extent of positive correlations with each other. Amongst downregulated T2Ms, MAGEH1 expression exhibited negative correlations with DNA methylation. Additionally, genes associated with MAGEH1 were enriched in Myc and Hedgehog signaling. Furthermore, T2Ms downregulation was associated with immune infiltration in glioma tissues and poor overall survival of glioma patients. In multivariate Cox regression analysis, MAGEH1 emerged as an independent prognosticator in lower grade glioma. Conclusively, these results suggest that expression of T2Ms is associated with important clinical and molecular features in glioma. Mechanistic studies may further provide novel insights into their role in glioma progression.

Classical Non-homologous End Joining (NHEJ) pathway is the mainstay of cellular response to DNA double strand breaks. While aberrant expression of genes involved in this pathway has been linked with genomic instability and drug resistance in several cancers, limited information is available about its clinical significance in colon cancer. We performed a comprehensive analysis of seven essential genes, including XRCC5, XRCC6, PRKDC, LIG4, XRCC4, NHEJ1, and PAXX of this pathway, in colon cancer using multi-omics datasets, and studied their associations with molecular and clinicopathological features, including age, gender, stage, KRAS mutation, BRAF mutation, microsatellite instability status and promoter DNA methylation in TCGA colon cancer dataset. This analysis revealed upregulation of XRCC5, PRKDC, and PAXX in colon cancer compared to normal colon tissues, while LIG4 and NHEJ1 (XLF) displayed downregulation. The expression of these genes was independent of age and KRAS status, while XRCC5, PRKDC, and LIG4 exhibited reduced expression in BRAF mutant tumors. Interestingly, we observed a strong association between XRCC6, XRCC5, PRKDC and LIG4 overexpression and microsatellite instability status of the tumors. In multivariate analysis, high PAXX expression emerged as an independent prognostic marker for poor overall and disease specific survival. We also observed hypomethylation of PAXX promoter in tumors, which exhibited a strong correlation with its overexpression. Furthermore, PAXX overexpression was also associated with several oncogenic pathways as well as a reduction in numbers of tumor-infiltrating lymphocytes.

Malignant glioma is characterised by a rapid growth rate and high capacity for invasive infiltration to surrounding brain tissue; hence, diagnosis and treatment is difficult and patient survival is poor. Aptamers contribute a promising and unique technology for the in vitro imaging of live cells and tissues, with a potentially bright future in clinical diagnostics and therapeutics for malignant glioma. The binding selectivity, uptake capacity and binding target of two DNA aptamers, SA43 and SA44, were investigated in glioma cells and patient tissues. The binding assay showed that SA43 and SA44 bound with strong affinity (Kd, 21.56 ± 4.60 nM and Kd, 21.11 ± 3.30 nM respectively) to the target U87MG cells. Quantitative analysis by flow cytometry showed that the aptamers were able to actively internalise in U87MG and 1321N1 glioma cells compared to the non-cancerous and non-glioma cell types. Confocal microscopy confirmed staining in the cytoplasm, and co-localisation studies with endoplasmic reticulum, Golgi apparatus and lysosomal markers suggested internalisation and compartmentalisation within the endomembrane system. Both aptamers selectively bound to Ku 70 and Ku 80 DNA repair proteins as determined by aptoprecipitation (AP) followed by mass spectrometry analysis and confirmation by Western blot. In addition, aptohistochemical (AHC) staining on paraffin embedded, formalin fixed patient tissues revealed that the binding selectivity was significantly higher for SA43 aptamer in glioma tissues (grade I, II, III and IV) compared to the non-cancerous tissues, whereas SA44 did not show selectivity towards glioma tissues. The results indicate that SA43 aptamer can differentiate between glioma and non-cancerous cells and tissues and therefore, shows promise for histological diagnosis of glioma.

The goals of this project were: (1) development of an interactive multimedia medical education tool (CO-ED) utilizing modern features of handheld computing (PDA) and major constructs of adult learning theories, and (2) pilot testing of the computer-assisted education in residents and clinicians. Comparison of the knowledge scores using paired t-test demonstrated statistically significant increase in subject knowledge (p

The aim of this project was construction of a universal platform for rapid development and implementation of interactive computer-based collection of clinical data. A TabletPC was used to pilot-test the platform and to implement two self-administered questionnaires: SF-12 Health Survey (SF-12) and Health Utilities Index (HUI). Qualitative analysis of the system acceptance in 12 patients showed that computer-assisted data collection in elderly patients with no previous computer experience can be successfully implemented using a TabletPC.

Purpose. To evaluate the outcome of single screw-rod anterior instrumentation for thoracolumbar burst fractures with incomplete neurological deficit. Methods. 16 men and 5 women aged 22 to 55 (mean, 34) years underwent single screw-rod anterior instrumentation for thoracolumbar burst fractures with incomplete neurological deficit. The vertebrae involved were T10 (n=2), T11 (n=2), T12 (n=7), L1 (n=8), and L2 (n=2). No patient had disruption of the posterior ligament complex. Postoperatively, a thoracolumbar sacral orthosis was used until solid fusion. Outcome measures included neurological recovery, degree of kyphosis, complications, and pain and functional status of the patients. Results. The mean follow-up duration was 36 (range, 13–50) months. All patients recovered neurologically by at least one grade. Of the 21 patients, 6 improved from grade B to grade C (n=4) or grade D (n=2), 13 from grade C to grade D, and 2 from grade D to grade E. The mean degree of kyphosis improved from 23°±5° to 7°±3°. Seven patients had complications including ipsilateral basal atelectasis (n=3), urinary tract infection (n=1), haematuria (n=1), postoperative ileus (n=1), and superficial wound infection (n=1). None had iatrogenic visceral or vascular injury, pseudoarthrosis or hardware-related complications. Only one patient had severe back pain persistently. Conclusion. Single screw-rod anterior instrumentation supplemented with an orthosis can be an alternative for double screw-rod anterior instrumentation for thoracolumbar burst fractures in patients with smaller vertebral bodies.