bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and validation of an epigenetically regulated long noncoding RNA model for breast cancer metabolism and prognosis
Authors: Song Yu , Shen Songjie , Sun Qiang
Published: May 2022

Background

Breast cancer (BC) is the leading cause of death among women, and epigenetic alterations that can dysregulate long noncoding RNAs (lncRNAs) are thought to be associated with cancer metabolism, development, and progression. This study investigated the epigenetic regulation of lncRNAs and its relationship with clinical outcomes and treatment responses in BC in order to identify novel and effective targets for BC treatment.

Methods

We comprehensively analysed DNA methylation and transcriptome data for BC and identified epigenetically regulated lncRNAs as potential prognostic biomarkers using machine learning and multivariate Cox regression analysis. Additionally, we applied multivariate Cox regression analysis adjusted for clinical characteristics and treatment responses to identify a set of survival-predictive lncRNAs, which were subsequently used for functional analysis of protein-encoding genes to identify downstream biological pathways.

Results

We identified a set of 1350 potential epigenetically regulated lncRNAs and generated a methylated lncRNA dataset for BC, MylnBrna, comprising 14 lncRNAs from a list of 20 epigenetically regulated lncRNAs significantly associated with tumour survival. MylnBrna stratifies patients into high-risk and low-risk groups with significantly different survival rates. These lncRNAs were found to be closely related to the biological pathways of amino acid metabolism and tumour metabolism, revealing a potential tumour-regulation function.

Conclusion

This study established a potential prognostic biomarker model (MylnBrna) for BC survival and offered an insight into the epigenetic regulatory mechanisms of lncRNAs in BC in the context of tumour metabolism.
Unravelling the physiological roles of mazEF toxin–antitoxin system on clinical MRSA strain by CRISPR RNA-guided cytidine deaminase
Authors: Jain Sonia , Bhowmick Arghya , Jeong Bohyun , Bae Taeok , Ghosh Abhrajyoti
Published: May 2022

Background

Curiosity on toxin–antitoxin modules has increased intensely over recent years as it is ubiquitously present in many bacterial genomes, including pathogens like Methicillin-resistant Staphylococcus aureus (MRSA). Several cellular functions of TA systems have been proposed however, their exact role in cellular physiology remains unresolved.

Methods

This study aims to find out the impact of the mazEF toxin–antitoxin module on biofilm formation, pathogenesis, and antibiotic resistance in an isolated clinical ST239 MRSA strain, by constructing mazE and mazF mutants using CRISPR–cas9 base-editing plasmid (pnCasSA-BEC). Transcriptome analysis (RNA-seq) was performed for the mazE antitoxin mutant in order to identify the differentially regulated genes. The biofilm formation was also assessed for the mutant strains. Antibiogram profiling was carried out for both the generated mutants followed by murine experiment to determine the pathogenicity of the constructed strains.

Results

For the first time our work showed, that MazF promotes cidA mediated cell death and lysis for biofilm formation without playing any significant role in host virulence as suggested by the murine experiment. Interestingly, the susceptibility to oxacillin, daptomycin and vancomycin was reduced significantly by the activated MazF toxin in the mazE mutant strain.

Conclusions

Our study reveals that activated MazF toxin leads to resistance to antibiotics like oxacillin, daptomycin and vancomycin. Therefore, in the future, any potential antibacterial drug can be designed to target MazF toxin against the problematic multi-drug resistant bug.
Prognostic significance of metabolomic biomarkers in patients with diabetes mellitus and coronary artery disease
Authors: Karagiannidis Efstratios , Moysidis Dimitrios V. , Papazoglou Andreas S. , Panteris Eleftherios , Deda Olga , Stalikas Nikolaos , Sofidis Georgios , Kartas Anastasios , Bekiaridou Alexandra , Giannakoulas George , Gika Helen , Theodoridis George , Sianos Georgios
Published: May 2022

Background

Diabetes mellitus (DM) and coronary artery disease (CAD) constitute inter-related clinical entities. Biomarker profiling emerges as a promising tool for the early diagnosis and risk stratification of either DM or CAD. However, studies assessing the predictive capacity of novel metabolomics biomarkers in coexistent CAD and DM are scarce.

Methods

This post-hoc analysis of the CorLipid trial (NCT04580173) included 316 patients with CAD and comorbid DM who underwent emergency or elective coronary angiography due to acute or chronic coronary syndrome. Cox regression analyses were performed to identify metabolomic predictors of the primary outcome, which was defined as the composite of major adverse cardiovascular or cerebrovascular events (MACCE: cardiovascular death, myocardial infarction, stroke, major bleeding), repeat unplanned revascularizations and cardiovascular hospitalizations. Linear regression analyses were also performed to detect significant predictors of CAD complexity, as assessed by the SYNTAX score.

Results

After a median 2-year follow up period (IQR = 0.7 years), the primary outcome occurred in 69 (21.8%) of patients. Acylcarnitine ratio C4/C18:2, apolipoprotein (apo) B, history of heart failure (HF), age > 65 years and presence of acute coronary syndrome were independent predictors of the primary outcome in diabetic patients with CAD (aHR = 1.89 [1.09, 3.29]; 1.02 [1.01, 1.04]; 1.28 [1.01, 1.41]; 1.04 [1.01, 1.05]; and 1.12 [1.05–1.21], respectively). Higher levels of ceramide ratio C24:1/C24:0, acylcarnitine ratio C4/C18:2, age > 65 and peripheral artery disease were independent predictors of higher CAD complexity (adjusted β = 7.36 [5.74, 20.47]; 3.02 [0.09 to 6.06]; 3.02 [0.09, 6.06], respectively), while higher levels of apoA1 were independent predictors of lower complexity (adjusted β= − 0.65 [− 1.31, − 0.02]).

Conclusions

In patients with comorbid DM and CAD, novel metabolomic biomarkers and metabolomics-based prediction models could be recruited to predict clinical outcomes and assess the complexity of CAD, thereby enabling the integration of personalized medicine into routine clinical practice. These associations should be interpreted taking into account the observational nature of this study, and thus, larger trials are needed to confirm its results and validate them in different and larger diabetic populations.
Multifunctional thermo-sensitive hydrogel for modulating the microenvironment in Osteoarthritis by polarizing macrophages and scavenging RONS
Authors: Zhu Chunrong , Han Shangcong , Zeng Xianhu , Zhu Chunxiao , Pu Yuji , Sun Yong
Published: May 2022

Osteoarthritis (OA) is a common degenerative joint disease that can lead to disability. Blocking the complex malignant feedback loop system dominated by oxidative stress and pro-inflammatory factors is the key to treating OA. Here, we develop a multifunctional composite thermo-sensitive hydrogel (HPP@Cu gel), which is utilized by Poloxamer 407 (P407) and hyaluronic acid (HA) mixture as the gel matrix, then physically mixed with copper nanodots (Cu NDs) and platelet-rich plasma (PRP). Cu NDs is a novel nano-scavenger of reactive oxygen and nitrogen species (RONS) with efficient free radical scavenging activity. HPP@Cu gel is injected into the articular cavity, where it form an in situ gel that slowly released Cu NDs, HA, and PRP, prolonging the duration of drug action. Our results indicate that HPP@Cu gel could efficiently remove RONS from inflammatory sites and promote repolarization of macrophages to an anti-inflammatory phenotype. The HPP@Cu gel therapy dramatically reduces cartilage degradation and inflammatory factor production in OA rats. This study provides a reliable reference for the application of injectable hydrogels in inflammatory diseases associated with oxidative stress.

Graphical Abstract
Listening to families with a person with neurodegenerative disease talk about their quality of life: integrating quantitative and qualitative approaches
Authors: Aza Alba , Gómez-Vela María , Badia Marta , Begoña Orgaz M. , González-Ortega Eva , Vicario-Molina Isabel , Montes-López Estrella
Published: May 2022

Background

The diagnosis of a neurodegenerative disease (ND) produces profound changes in the quality of life of the affected families. Despite the vital importance of these processes, the scientific literature has addressed this topic almost exclusively relating to the main caregiver or using limited approaches. Thus, the main objective of this research is to achieve a deeper understanding of the quality of family life of people with a neurodegenerative disease, following a mixed-method approach that combines quantitative and qualitative methodology.

Methods

The quantitative instrument was the Spanish version of theFamily Quality of Life Survey-Neurodegenerative Disease(FQOLS-ND),which was completed by 300 participating families. The qualitative methodology was used in two focus groups with family caregivers, with a total of 21 participants.

Results

On the one hand, confirmation of the dimensional structure of the scale in the focus groups was obtained and, on the other hand, the results of family quality of life in attainment and satisfaction were shown to be high for Family Relations and Careers and Planning for Careers and low for Support from Services and Leisure and Recreation.

Conclusions

The results of this study, through the combination of quantitative and qualitative information, helps to identify key issues to optimize services that respond to the priority needs of families.
Because they’re worth it? A discussion paper on the value of 12-h shifts for hospital nursing
Authors: Dall’Ora Chiara , Ejebu Ourega-Zoé , Griffiths Peter
Published: May 2022

The organisation of the 24-h day for hospital nurses in two 12-h shifts has been introduced with value propositions of reduced staffing costs, better quality of care, more efficient work organisation, and increased nurse recruitment and retention. While existing reviews consider the impact of 12-h shifts on nurses’ wellbeing and performance, this discussion paper aims to specifically shed light on whether the current evidence supports the value propositions around 12-h shifts. We found little evidence of the value propositions being realised. Staffing costs are not reduced with 12-h shifts, and outcomes related to productivity and efficiency, including sickness absence and missed nursing care are negatively affected. Nurses working 12-h shifts do not perform more safely than their counterparts working shorter shifts, with evidence pointing to a likely negative effect on safe care due to increased fatigue and sleepiness. In addition, nurses working 12-h shifts may have access to fewer educational opportunities than nurses working shorter shifts. Despite some nurses preferring 12-h shifts, the literature does not indicate that this shift pattern leads to increased recruitment, with studies reporting that nurses working long shifts are more likely to express intention to leave their job. In conclusion, there is little if any support for the value propositions that were advanced when 12-h shifts were introduced. While 12-h shifts might be here to stay, it is important that the limitations, including reduced productivity and efficiency, are recognised and accepted by those in charge of implementing schedules for hospital nurses.
An overview of health workforce education and accreditation in Africa: implications for scaling-up capacity and quality
Authors: Okoroafor Sunny C. , Ahmat Adam , Asamani James Avoka , Millogo Jean Jacques Salvador , Nyoni Jennifer
Published: May 2022

Background

For countries to achieve universal health coverage, they need to have well-functioning and resilient health systems. Achieving this requires a sufficient number of qualified health workers and this necessitates the importance of investments in producing and regulating health workers. It is projected that by 2030, Africa would need additional 6.1 million doctors, nurses, and midwives. However, based on the current trajectory, only 3.1 million would be trained and ready for service delivery. To reduce current shortages of the health workforce, Africa needs to educate and train 3.0 million additional health workers by 2030. This study was conducted to describe the distribution and ownership of the health training institutions, production of health workers, and the availability of accreditation mechanisms for training programmes in the WHO African Region.

Methods

A cross-sectional study was conducted using a standardized questionnaire from January 2018 to April 2019. All the 47 countries in the Region were invited to complete a structured questionnaire based on available secondary information from health sector reports, annual HRH reports, country health workforce profiles, and HRH observatories and registries.

Results

Data from 43 countries in the World Health Organization African Region in 2018 show that there were 4001 health training institutions with 410, 1469 and 2122 being medical, health sciences, and nursing and midwifery schools, respectively, and 2221, 1359 and 421 institutions owned by the public, private for-profit and private not-for-profit sectors, respectively. A total of 148 357 health workers were produced in Region with 40% (59, 829) being nurses and midwives, 19% (28, 604) other health workers, and 14% (20 470) physicians. Overall, 31 countries (79%) in the Region have an accreditation framework for the health training institutions and seven countries do not have any accreditation mechanism.

Conclusion

To achieve universal health coverage, matching of competencies with population needs, as well as increasing capacities for health worker production to align with demand (numbers and skill-mix) for improved service delivery should be prioritized, as this would improve the availability of skilled health workforce in the Region.
Ultrasonic surgical and electrosurgical system (USES) with conventional ultrasonic scalpel (CUS) in gastrectomy: a retrospective cohort study
Authors: Jing Changqing , Chen Yuezhi , Shang Liang , Wang Jinshen , Lian Guodong , Tian Feng , Shao Yixue , Zhao Yingnan , Xuan Jianwei , Li Leping
Published: May 2022

Background

Harmonic ACE +7 Shears with Advanced Hemostasis is an upgraded ultrasonic device, an ultrasonic surgical and electrosurgical system (USES). The study aimed to evaluate the economic and clinical effectiveness of the USES compared with the conventional ultrasonic scalpel (CUS) in gastrectomy.

Methods

We conducted a single-center, retrospective cohort study using the electronic medical records in China. We collected intraoperative and postoperative data from gastric cancer patients who underwent the endoscope-assisted distal gastrectomy from 2018 to June 30, 2019. Procedure-related costs were estimated. We used linear regression by controlling a set of covariates to assess the effect of USES on outcomes.

Result

Out of 87 eligible patients, the USES group (40 patients) and CUS group (47 patients) were comparable in terms of age, medical history and stages of cancer. Compared with the CUS, the USES saved 4.27 hemoclips per person (95% CI 0.57–7.97, p < 0.05) and 34.18 ml intraoperative blood per person (95% CI 8.74–59.62 ml, p < 0.05), respectively. Postoperative length of stay (LOS) was shorter in the USES group (7.90 ± 1.95 vs. 9.26 ± 2.81 days) but the difference was not statistically significant (p = 0.05).

Conclusions

The USES group was associated with fewer hemoclips use and intraoperative blood loss in patients undergoing laparoscopic gastrectomy at comparable costs.
Evaluation of four gamma-based methods for calculating confidence intervals for age-adjusted mortality rates when data are sparse
Authors: Talih Makram , Anderson Robert N. , Parker Jennifer D.
Published: May 2022

Background

Equal-tailed confidence intervals that maintain nominal coverage (0.95 or greater probability that a 95% confidence interval covers the true value) are useful in interval-based statistical reliability standards, because they remain conservative. For age-adjusted death rates, while the Fay–Feuer gamma method remains the gold standard, modifications have been proposed to streamline implementation and/or obtain more efficient intervals (shorter intervals that retain nominal coverage).

Methods

This paper evaluates three such modifications for use in interval-based statistical reliability standards, the Anderson–Rosenberg, Tiwari, and Fay–Kim intervals, when data are sparse and sample size-based standards alone are overly coarse. Initial simulations were anchored around small populations (P = 2400 or 1200), the median crude all-cause US mortality rate in 2010–2019 (833.8 per 100,000), and the corresponding age-specific probabilities of death. To allow for greater variation in the age-adjustment weights and age-specific probabilities, a second set of simulations draws those at random, while holding the mean number of deaths at 20 or 10. Finally, county-level mortality data by race/ethnicity from four causes are selected to capture even greater variation: all causes, external causes, congenital malformations, and Alzheimer disease.

Results

The three modifications had comparable performance when the number of deaths was large relative to the denominator and the age distribution was as in the standard population. However, for sparse county-level data by race/ethnicity for rarer causes of death, and for which the age distribution differed sharply from the standard population, coverage probability in all but the Fay–Feuer method sometimes fell below 0.95. More efficient intervals than the Fay–Feuer interval were identified under specific circumstances. When the coefficient of variation of the age-adjustment weights was below 0.5, the Anderson–Rosenberg and Tiwari intervals appeared to be more efficient, whereas when it was above 0.5, the Fay–Kim interval appeared to be more efficient.

Conclusions

As national and international agencies reassess prevailing data presentation standards to release age-adjusted estimates for smaller areas or population subgroups than previously presented, the Fay–Feuer interval can be used to develop interval-based statistical reliability standards with appropriate thresholds that are generally applicable. For data that meet certain statistical conditions, more efficient intervals could be considered.
Patterns of contraceptive use among young Australian women with chronic disease: findings from a prospective cohort study
Authors: Harris Melissa L. , Egan Nicholas , Forder Peta M. , Bateson Deborah , Sverdlov Aaron L. , Murphy Vanessa E. , Loxton Deborah
Published: May 2022

Background

Given chronic disease is increasing among young women and unintended pregnancies among these women are associated with poor maternal and fetal outcomes, these women would benefit from effective preconception care. However, there is a lack of understanding of how these women use or don’t use contraception to inform such interventions. This study examined patterns of contraceptive use among an Australian cohort of young women and investigated the influence of chronic disease on contraceptive use over time.

Methods

Using data from 15,244 young women from the Australian Longitudinal Study on Women’s Health (born 1989–1995), latent transition analysis was performed to identify distinct contraceptive patterns among women who were at risk of an unintended pregnancy. Multinomial mixed-effect models were used to evaluate the relationship between contraceptive combinations and chronic disease.

Results

Contraceptive use for women with cardiac and autoinflammatory diseases differed to women without chronic disease over the observation period. Compared to women without chronic disease using the pill, women with cardiac disease had double the odds of using ‘other’ contraception and condoms (OR = 2.20, 95% CI 1.34, 3.59) and a modest increase in the odds of using the combined oral contraceptive pill and condoms (OR = 1.39, 95% CI 1.03, 1.89). Compared to women without chronic disease who used the pill, women with autoinflammatory disease had increased odds of using LARC and condoms (OR = 1.58, 95% CI 1.04, 2.41), using ‘other’ contraception and condoms (OR = 1.69, 95% CI 1.11, 2.57), and using the combined oral contraceptive pill and condoms (OR = 1.38, 95% CI 1.09, 1.75). No differences in contraceptive patterns over the observation period were found for women with asthma or diabetes when compared to women without chronic disease.

Conclusion

The findings identified a need for effective contraceptive counselling as part of routine chronic disease care and improved communication between health care providers and women with chronic disease to improve young women’s contraceptive knowledge and agency in contraceptive choice, particularly for those with cardiac or autoinflammatory conditions. This may be the key to reducing high-risk unintended pregnancies among this vulnerable population.
EMG-driven control in lower limb prostheses: a topic-based systematic review
Authors: Cimolato Andrea , Driessen Josephus J. M. , Mattos Leonardo S. , De Momi Elena , Laffranchi Matteo , De Michieli Lorenzo
Published: May 2022

Background

The inability of users to directly and intuitively control their state-of-the-art commercial prosthesis contributes to a low device acceptance rate. Since Electromyography (EMG)-based control has the potential to address those inabilities, research has flourished on investigating its incorporation in microprocessor-controlled lower limb prostheses (MLLPs). However, despite the proposed benefits of doing so, there is no clear explanation regarding the absence of a commercial product, in contrast to their upper limb counterparts.

Objective and methodologies

This manuscript aims to provide a comparative overview of EMG-driven control methods for MLLPs, to identify their prospects and limitations, and to formulate suggestions on future research and development. This is done by systematically reviewing academical studies on EMG MLLPs. In particular, this review is structured by considering four major topics: (1) type of neuro-control, which discusses methods that allow the nervous system to control prosthetic devices through the muscles; (2) type of EMG-driven controllers, which defines the different classes of EMG controllers proposed in the literature; (3) type of neural input and processing, which describes how EMG-driven controllers are implemented; (4) type of performance assessment, which reports the performance of the current state of the art controllers.

Results and conclusions

The obtained results show that the lack of quantitative and standardized measures hinders the possibility to analytically compare the performances of different EMG-driven controllers. In relation to this issue, the real efficacy of EMG-driven controllers for MLLPs have yet to be validated. Nevertheless, in anticipation of the development of a standardized approach for validating EMG MLLPs, the literature suggests that combining multiple neuro-controller types has the potential to develop a more seamless and reliable EMG-driven control. This solution has the promise to retain the high performance of the currently employed non-EMG-driven controllers for rhythmic activities such as walking, whilst improving the performance of volitional activities such as task switching or non-repetitive movements. Although EMG-driven controllers suffer from many drawbacks, such as high sensitivity to noise, recent progress in invasive neural interfaces for prosthetic control (bionics) will allow to build a more reliable connection between the user and the MLLPs. Therefore, advancements in powered MLLPs with integrated EMG-driven control have the potential to strongly reduce the effects of psychosomatic conditions and musculoskeletal degenerative pathologies that are currently affecting lower limb amputees.
Quantifying intra- and interlimb use during unimanual and bimanual tasks in persons with hemiparesis post-stroke
Authors: Duff Susan V. , Miller Aaron , Quinn Lori , Youdan Gregory , Bishop Lauri , Ruthrauff Heather , Wade Eric
Published: May 2022

Background

Individuals with hemiparesis post-stroke often have difficulty with tasks requiring upper extremity (UE) intra- and interlimb use, yet methods to quantify both are limited.

Objective

To develop a quantitative yet sensitive method to identify distinct features of UE intra- and interlimb use during task performance.

Methods

Twenty adults post-stroke and 20 controls wore five inertial sensors (wrists, upper arms, sternum) during 12 seated UE tasks. Three sensor modalities (acceleration, angular rate of change, orientation) were examined for three metrics (peak to peak amplitude, time, and frequency). To allow for comparison between sensor data, the resultant values were combined into one motion parameter, per sensor pair, using a novel algorithm. This motion parameter was compared in a group-by-task analysis of variance as a similarity score (0–1) between key sensor pairs: sternum to wrist, wrist to wrist, and wrist to upper arm. A use ratio (paretic/non-paretic arm) was calculated in persons post-stroke from wrist sensor data for each modality and compared to scores from the Adult Assisting Hand Assessment (Ad-AHA Stroke) and UE Fugl-Meyer (UEFM).

Results

A significant group × task interaction in the similarity score was found for all key sensor pairs. Post-hoc tests between task type revealed significant differences in similarity for sensor pairs in 8/9 comparisons for controls and 3/9 comparisons for persons post stroke. The use ratio was significantly predictive of the Ad-AHA Stroke and UEFM scores for each modality.

Conclusions

Our algorithm and sensor data analyses distinguished task type within and between groups and were predictive of clinical scores. Future work will assess reliability and validity of this novel metric to allow development of an easy-to-use app for clinicians.
Extracellular water to total body water ratio predicts survival in cancer patients with sarcopenia: a multi-center cohort study
Authors: Ge Yi-Zhong , Ruan Guo-Tian , Zhang Qi , Dong Wen-Jun , Zhang Xi , Song Meng-Meng , Zhang Xiao-Wei , Li Xiang-Rui , Zhang Kang-Ping , Tang Meng , Li Wei , Shen Xian , Shi Han-Ping ,   Investigation on the Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) Group
Published: May 2022

Background

Body water measured by bioelectrical impedance analysis (BIA) predicts the outcomes of many diseases. This study aimed to evaluate the relationship between body water and the prognosis of cancer patients with sarcopenia.

Methods

This study employed 287 cancer patients with sarcopenia underwent BIA from a prospective multicenter study of patients with cancer in China from 2013 to 2020. The primary outcome of interest was all-cause mortality presented as the longest time to follow-up available. Eight indicators of body water [total body water, extracellular water, intracellular water, free fat mass, active cell mass, extracellular water/intracellular water, extracellular water/total body water (ECW/TBW), and intracellular water/total body water] were included in the research. Neutrophil–lymphocyte ratio (NLR) = neutrophil (× 109)/lymphocyte (× 109). The discriminatory ability and prediction accuracy of each factor were assessed using the C-index. The hazard ratios (HR) and 95% confidence intervals (CI) were calculated using the Cox proportional hazard model.

Results

The median age was 65 years old, and 138 (48%) patients were men. During a mean follow-up of 46 months, 140 deaths were recorded, resulting in a rate of 204.6 events per 1000 patient-years. ECW/TBW showed the best predictive accuracy (C-index = 0.619) compared to the other indicators [p = 0.004, adjusted HR (95% CI) 1.70 (1.18,2.44)]. In the middle tertile (0.385–0.405), ECW/TBW had a strong independent negative association with patient survival [adjusted HR (95% CI) 2.88 (1.39–5.97), p = 0.004]. Patients who had a high ECW/TBW (ECW/TBW ≥ 0.395) combined with a high NLR had 3.84-fold risk of mortality (p < 0.001, 95% CI 1.99,7.38).

Conclusions

ECW/TBW was better than other indicators in predicting survival of cancer patients with sarcopenia. High ECW/TBW combined with high NLR would further increase the risk of mortality.

Trial registration: The Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) (Chinese Clinical Trial Registry: ChiCTR1800020329, URL of registration: http://www.chictr.org.cn/showprojen.aspx?proj=31813).
The application of existing genotoxicity methodologies for grouping of nanomaterials: towards an integrated approach to testing and assessment
Authors: Verdon Rachel , Stone Vicki , Murphy Fiona , Christopher Emily , Johnston Helinor , Doak Shareen , Vogel Ulla , Haase Andrea , Kermanizadeh Ali
Published: May 2022

The incorporation of nanomaterials (NMs) in consumer products has proven to be highly valuable in many sectors. Unfortunately, however, the same nano specific physicochemical properties, which make these material attractive, might also contribute to hazards for people exposed to these materials. The physicochemical properties of NMs will impact their interaction with biological surroundings and influence their fate and their potential adverse effects such as genotoxicity. Due to the large and expanding number of NMs produced, their availability in different nanoforms (NFs) and their utilization in various formats, it is impossible for risk assessment to be conducted on an individual NF basis. Alternative methods, such as grouping are needed for streamlining hazard assessment. The GRACIOUS Framework provides a logical and science evidenced approach to group similar NFs, allowing read-across of hazard information from source NFs (or non-NFs) with adequate hazard data to target NFs that lack such data. Here, we propose a simple three-tiered testing strategy to gather evidence to determine whether different NFs are sufficiently similar with respect to their potential to induce genotoxicity, in order to be grouped. The tiered testing strategy includes simple in vitro models as well as a number of alternative more complex multi-cellular in vitro models to allow for a better understanding of secondary NM-induced DNA damage, something that has been more appropriate in vivo until recently.
Becoming our young people’s case managers: caregivers’ experiences, needs, and ideas for improving opioid use treatments for young people using opioids
Authors: Marchand Kirsten , Turuba Roxanne , Katan Christina , Brasset Chantal , Fogarty Oonagh , Tallon Corinne , Fairbank Jill , Mathias Steve , Barbic Skye
Published: May 2022

Background

Evidence continues to show that young people, ages 15-24, remain at significant risk of harms from non-medical opioid use and opioid use disorder (OUD), with experts calling for widespread implementation of developmentally-appropriate interventions. These recommendations include the involvement of caregivers in the prevention, early intervention, and treatment of young people using opioids. However, little research has investigated caregivers’ experiences supporting young people, leaving critical gaps in understanding this role. The aim of this study is to explore caregivers’ experiences accessing opioid use treatments with young people and their needs and ideas for improving such treatments.

Methods

This study reports qualitative findings from Phase 1 of the Improving Treatment Together project, a multi-phase, multi-site community-based participatory study broadly aimed at co-designing opioid use treatments to improve the experiences and outcomes of young people using non-medical opioids. During Phase 1, a total of 27 caregivers (parents, guardians) participated in full-day workshops that were conducted in three communities in British Columbia, Canada. Following human-centred co-design methods, caregivers engaged in small and large group discussions of their experiences, needs, and ideas for improving opioid use treatments for young people. Discussions were audio-recorded, transcribed verbatim, and thematically analysed.

Results

Across communities, caregivers’ main experiences were defined as ‘becoming our young people’s case managers’ and ‘enduring a never-ending rollercoaster’. To improve these experiences, two needs themes were identified – expanding organizational and system-level capacity and wider-spread understanding of opioid use as a health issue. Caregivers brainstormed a total of 378 individual ideas to meet these needs, several of which spanned multiple needs themes.

Conclusions

Caregivers’ experiences, needs, and ideas reveal critical opportunities for improving the quality of interventions for opioid use among young people. This study represents a substantial contribution to the design and implementation of developmentally-appropriate and family-centred interventions for young people using opioids.
Developing an accurate model of spot-scanning treatment delivery time and sequence for a compact superconducting synchrocyclotron proton therapy system
Authors: Zhao Lewei , Liu Gang , Chen Shupeng , Shen Jiajian , Zheng Weili , Qin An , Yan Di , Li Xiaoqiang , Ding Xuanfeng
Published: May 2022

Background

A new compact superconducting synchrocyclotron single-room proton solution delivers pulsed proton beams to each spot through several irradiation bursts calculated by an iterative layer delivery algorithm. Such a mechanism results in a new beam parameter, burst switching time (BST) in the total beam delivery time (BDT) which has never been studied before. In this study, we propose an experimental approach to build an accurate BDT and sequence prediction model for this new proton solution.

Methods

Test fields and clinical treatment plans were used to investigate each beam delivery parameter that impacted BDT. The machine delivery log files were retrospectively analyzed to quantitatively model energy layer switching time (ELST), spot switching time (SSWT), spot spill time (SSPT), and BST. A total of 102 clinical IMPT treatment fields’ log files were processed to validate the accuracy of the BDT prediction model in comparison with the result from the current commercial system. Interplay effect is also investigated as a clinical application by comparing this new delivery system model with a conventional cyclotron accelerator model.

Results

The study finds that BST depends on the amount of data to be transmitted between two sequential radiation bursts, including a machine irradiation log file of the previous burst and a command file to instruct the proton system to deliver the next burst. The 102 clinical treatment fields showed that the accuracy of each component of the BDT matches well between machine log files and BDT prediction model. More specifically, the difference of ELST, SSWT, SSPT, and BST were (− 3.1 ± 5.7)%, (5.9 ± 3.9)%, (2.6 ± 8.7)%, and (− 2.3 ± 5.3)%, respectively. The average total BDT was about (2.1 ± 3.0)% difference compared to the treatment log files, which was significantly improved from the current commercial proton system prediction (58 ± 15)%. Compared to the conventional cyclotron system, the burst technique from synchrocyclotron effectively reduced the interplay effect in mobile tumor treatment.

Conclusion

An accurate BDT and sequence prediction model was established for this new clinical compact superconducting synchrocyclotron single-room proton solution. Its application could help users of similar facilities better assess the interplay effect and estimate daily patient treatment throughput.
Scanning methodology for contact lens-type ocular in vivo dosimeter (CLOD) dosimetry applying a silicone material
Authors: Son Jaeman , Cho Jin Dong , Jung Seongmoon , Choi Chang Heon , Park Jong Min , Kim Jung-in
Published: May 2022

Purpose

Contact lens-type ocular in vivo dosimeters (CLODs) were recently developed as the first in vivo dosimeter that can be worn directly on the eye to measure the dose delivered to the lens during radiotherapy. However, it has an inherent uncertainty because of its curved shape. Newton’s ring effect inevitably occurs because the spacing between the glass window and the active layer is not constant. Furthermore, it involves a large uncertainty because the objective of the CLOD with such morphological characteristics is to measure the dose delivered to an out-of-field lens. In this study, we aimed to investigate the effects of various compensating materials on the sensitivity, accuracy, and uniformity of analysis using a curved CLOD. We developed a new scanning methodology that involves applying a compensating material to reduce the uncertainty caused by the air gap.

Methods

Four compensating materials—Dragon Skin™ 10 (DS), a transparent silicon material, SORTA-Clear™ 40 (SC), optical grease (OG), and air (no compensating material)—were used in this study. The CLOD was scanned in the reflective mode and transmission mode using each compensating material. We then examined the sensitivity, accuracy, and scan uniformity to evaluate the scanning methodology using compensating materials.

Results

The increase in sensitivity was the highest for OG compared to that for air in the reflective mode. On average, the sensitivity in the reflective mode was higher than that in the transmission mode by a factor of 2.5 for each dose. Among the four compensating materials, OG had the smallest uncertainty. Therefore, the best scan uniformity was achieved when OG was used.

Conclusions

Scanning methodology was proposed in which a compensating material is applied for a curved lens-type dosimeter. Our results show that OG is the most suitable compensating material to obtain the best accuracy of dose analysis. Following this methodology, the scan uncertainty of curved dosimeters significantly decreased.
Possibilities and limits of using gyroscopic sensors in the diagnosis of progression of osteoarthritis and femoroacetabular impingement syndrome
Authors: Holeka Pavel , Studnička Filip , Bušovský Damián , Štěpán Jan , Matyska Jan , Šlégr Jan
Published: May 2022

Osteoarthritis is the most common type of degenerative joint disease and affects millions of people. In this paper, we propose a non-obtrusive and straightforward method to assess the progression of osteoarthritis. In standard medicine praxis, osteoarthritis is observed with X-rays. In this study, we use widely available wearable sensors with gyroscopes to make the observation. Two novel methods are proposed for gyroscope data processing. A small-scale study has shown that these methods can be used to monitor osteoarthritis’s progression, and to differentiate between healthy subjects and subjects with femoroacetabular impingement syndrome.
Accuracy of point-of-care coagulation testing during cardiopulmonary bypass in a patient post COVID-19 infection
Authors: Grewal Nimrat , Yousef David , Palmen Meindert , Klautz Robert , Eikenboom Jeroen , Wink Jeroen
Published: May 2022

Introduction

Extracorporeal circulation (ECC) in cardiac surgery is performed under systemic heparinization. Adequacy of heparin therapy and anticoagulation during ECC is assessed by activated clotting time (ACT), although there are concerns regarding the reliability of this measure. The ACT can be affected by factors other than heparin anticoagulation. A novel factor that should be considered is the influence of a COVID-19 infection. More than half of the hospitalized COVID-19 patients develop coagulation abnormalities with dysregulated coagulation test results. Patients recently recovered from COVID-19 may still demonstrate some forms of coagulation disorder affecting the ACT. This case describes an inaccurate point-of-care ACT testing in a patient with previous COVID-19 infection undergoing cardiac surgery with ECC and the alternative coagulation testing performed.

Case presentation

A 77-years-old Caucasian male presented with symptomatic severe mitral valve regurgitation for which he underwent surgery. Medical history revealed a COVID-19 infection one month before surgery. Pre-operative hematological lab results were normal and baseline ACT during surgery was 100 s. To achieve an adequate ACT of > 400 s, multiple doses of heparin were needed and after administration of a triple dose (75,000 IE heparin in total) this adequate ACT was achieved. In the meanwhile we measured anti-Xa level and APTT, which were at adequate levels when ACT was still < 400 s.

Discussion

This case emphasizes the need of alternative methods for monitoring heparin therapy in case ACT does not respond adequately. Another point to highlight in this case is the poorly correlated relation between ACT and APTT and anti-Xa in light of the recent COVID-19 infection. Although studies have shown that COVID-19 infection can cause coagulopathy and altered hemostatic parameters, ACT has never been investigated in COVID-19 patient. Understanding the correlation between ACT, APTT and anti-Xa in COVID-19 patients is mandatory.
Ascending aortic wall degeneration in patients with bicuspid versus tricuspid aortic valve
Authors: Mennander Ari , Kholova Ivana , Pelttari Saku , Paavonen Timo
Published: May 2022

Background

The magnitude of ascending aortic degeneration in patients with bicuspid aortic valves (BAV) is controversial.

Methods

The aim of this study was to investigate ascending aortic wall degeneration in patients with BAV as compared with tricuspid aortic valves (TAV). The ascending aortic wall of 67 consecutive patients was processed for histology and immunohistochemistry. The extent of surgery and wall degeneration were investigated. Unadjusted survival was evaluated by Kaplan–Meier analysis. Median follow-up for patients with BAV and TAV was 3.8 years (interquartile range [IQR] 3.5–4.1) and 3.7 years (IQR 3.4–3.9), respectively.

Results

There were 33 patients with BAV and 34 with TAV. Mid-ascending aorta diameter was 54 mm (IQR 50–60). Replacement of the aortic valve, together with an ascending aortic prosthesis, was more frequent in BAV vs TAV patients (24% vs. 3%, P = 0.013). However, medial fibrosis, elastic fiber thinning, incremental medial degeneration and smooth muscle cell nuclei loss were less prominent in BAV vs TAV patients (0.1 ± 0.4 vs. 0.8 ± 1.4, P = 0.016; 0.6 ± 1.4 vs. 1.6 ± 2.0, P = 0.027; 1.7 ± 0.7 vs. 2.2 ± 0.8, P = 0.045 and 2.3 ± 1.5 vs. 3.2 ± 1.3, P = 0.026, respectively).

Conclusions

Since degeneration of the ascending aortic wall was seldom prominent, histopathology alone may not support the need for surgery of the dilated ascending aorta in BAV patients as compared with TAV patients.
Mechanisms of hypoxia in the hippocampal CA3 region in postoperative cognitive dysfunction after cardiopulmonary bypass
Authors: Liu Ting , Deng Rui , Wang Xin , Liu Ping , Xiao Qiu-Xia , Liu Qing , Zhang Ying
Published: May 2022

Background

Postoperative cognitive dysfunction (POCD) is a complication with high morbidity and mortality, commonly observed in the elderly who underwent anesthesia and surgery. The incidence is much higher in cardiac surgery. However, the reason and the mechanism of POCD remains unclear, but cerebral hypoxia is a common neurological complication after cardiac surgery. This study aims to investigate what role cerebral hypoxia plays in the pathogenesis of POCD.

Methods

The POCD model was established using cardiopulmonary bypass (CPB) surgery. Cognitive function was detected using Y maze and Morris water maze. The hypoxia in central nervous system was assessed using HE staining, western blot, and immunofluorescence. Inflammatory factors in hippocampus and plasma were detected by enzyme-linked immunosorbent assay. Evans blue was used to detect destruction of the blood brain barrier (BBB).

Results

Cognitive impairment markedly occurred to rats underwent 2-h CPB operation. Cerebral thrombosis and hypoxia occurred in the hippocampal CA3 region of rats after surgery. In addition, microglia in hippocampal was activated and the expression of inflammatory factors such as IL-1β, IL-6 and TNF-α was upregulated. Moreover, the permeability of BBB increased in rats after CPB.

Conclusion

Hypoxia in hippocampal CA3 region was involved in the occurrence and the mechanism may be associated with neuroinflammation and the damage of BBB.
Beyond the clinical context: the process of losing oneself living with Huntington’s disease
Authors: Varela Luz-Estella , Arias María-Mercedes , Martorell-Poveda María-Antonia , Giraldo Clara V. , Estrada-Acuña Rosa A.
Published: May 2022

Background

People with Huntington's disease (HD) have increased functional and cognitive dependence. While numerous clinical, genetic, and therapeutic management studies have been carried out, few studies have investigated the disease from the personal experience and the context of people living with HD. To better serve these patients, our purpose is to understand, from the perspective of the patient and their families, how people with HD cope with their daily lives outside the clinical setting.

Methods

Thirty-three affected or at-risk people participated in this study. Participants were interviewed at their homes on distinct occasions during a family visit. We analyzed the data using Grounded Theory, which allowed us to understand how people live with the disease on their own terms.

Results

Living with HD is a process that begins with acceptance or denial that one is at risk for the disease or, growing awareness of the condition due to motor, behavioral, and cognitive changes, and, finally, loss of autonomy with physical dependence on another person, and loss of sense of self and family.

Conclusion

While the daily life of patients before disease onset was characterized by physical and mental/cognitive independence, with HD they become increasingly trapped in their bodies, and their complications are due to the lack of effective curable therapy.