bluuebunny/crossref_metadata_2025 huggingface dataset:
Neighbourhood and path-based greenspace in three European countries: associations with objective physical activity
Authors: Mueller William , Wilkinson Paul , Milner James , Vardoulakis Sotiris , Steinle Susanne , Pärkkä Juha , Parmes Eija , Cluitmans Luc , Kuijpers Eelco , Pronk Anjoeka , Sarigiannis Denis , Karakitsios Spyros , Chapizanis Dimitris , Maggos Thomas , Stamatelopoulou Asimina , Loh Miranda
Published: February 2021

Background

Greenspace has been associated with health benefits in many contexts. An important pathway may be through outdoor physical activity. We use a novel approach to examine the link between greenspace microenvironments and outdoor physical activity levels in the HEALS study conducted in Edinburgh (UK), the Netherlands, and Athens and Thessaloniki (Greece).

Methods

Using physical activity tracker recordings, 118 HEALS participants with young children were classified with regard to daily minutes of moderate to vigorous physical activity (MVPA); 60 were classified with regard to the metabolic equivalent task (MET)-minutes for each of the 1014 active trips they made. Greenspace indicators were generated for Normalised Difference Vegetation Index (NDVI), tree cover density (TCD), and green land use (GLU). We employed linear mixed-effects models to analyse (1) daily MVPA in relation to greenspace within 300 m and 1000 m of residential addresses and (2) trip MET-minutes in relation to average greenspace within a 50 m buffer of walking/cycling routes. Models were adjusted for activity, walkability, bluespace, age, sex, car ownership, dog ownership, season, weekday/weekend day, and local meteorology.

Results

There was no clear association between MVPA-minutes and any residential greenspace measure. For example, in fully adjusted models, a 10 percentage point increase in NDVI within 300 m of home was associated with a daily increase of 1.14 (95% CI − 0.41 to 2.70) minutes of MVPA. However, we did find evidence to indicate greenspace markers were positively linked to intensity and duration of activity: in fully adjusted models, 10 percentage point increases in trip NDVI, TCD, and GLU were associated with increases of 10.4 (95% CI: 4.43 to 16.4), 10.6 (95% CI: 4.96 to 16.3), and 3.36 (95% CI: 0.00 to 6.72) MET-minutes, respectively. The magnitude of associations with greenspace tended to be greater for cycling.

Conclusions

More strenuous or longer walking and cycling trips occurred in environments with more greenspace, but levels of residential greenspace did not have a clear link with outdoor MVPA. To build on our research, we suggest future work examine larger, more diverse populations and investigate the influence of greenspace for trip purpose and route preference.
Temperature and current flow effects of different electrode placement in shoulder capacitive-resistive electric transfer applications: a cadaveric study
Authors: Rodríguez-Sanz Jacobo , López-de-Celis Carlos , Hidalgo-García César , Canet-Vintró Max , Fanlo-Mazas Pablo , Pérez-Bellmunt Albert
Published: February 2021

Background

Impingement syndrome is currently estimated to represent 60% of all shoulder pain disorders. Capacitive-Resistive electric transfer therapy is aimed to provoke temperature and current flow changes in superficial and deep tissues. This in vitro study has evaluated the variation of temperature and current flow in the shoulder tissues during two different areas of application of the movable capacitive-resistive electric transfer electrode.

Methods

A cross-sectional study designed, five fresh cryopreserved cadavers (10 shoulders) were included in this study. Four interventions (capacitive and resistive modes; low- and high-power) were performed for 5 min each by a diathermy “T-Plus” device in two shoulder regions: postero-superior and antero-lateral. Supraspinatus tendon, glenohumeral capsule and superficial temperatures were recorded at 1-min intervals and 5 min after treatment.

Results

A statistically significant difference was found only for the superficial area and time interaction, with high power-resistive application at the postero-superior shoulder area (P< 0.035). All the applications showed a 5 min after treatment temperature increase compared with the basal data, in all the application points. Superficial temperature in the high power-resistive application showed the greatest percent increase (42.93% ± 22.58), followed by the temperature in the tendon area with the same high power-resistive application (22.97% ± 14.70). The high power-resistive application showed the greatest percent of temperature increase in the applications, reaching 65.9% ± 22.96 at 5-min at the superficial level, and 32% ± 24.25 at 4-min at the level of the supraspinatus tendon. At the capsule level, high power-resistive was also the application that showed the greatest percent of increase, with 21.52% ± 16.16. The application with the lowest percent of temperature increase was the low power-capacitive, with a mean value of 4.86% at supraspinatus tendon level and 7.47% at capsular level.

Conclusion

The shoulder postero-superior or antero-lateral areas of application of capacitive-resistive electric transfer did not cause statistically significant differences in the temperature changes in either supraspinatus tendon or glenohumeral capsule tissues in cadaveric samples. The high power-resistive application in the postero-superior area significantly increased superficial temperature compared with the same application in the antero-lateral position area.
Associations of serum vitamins levels with bone mineral density in the different race-ethnicities US adults
Authors: Li Xiang , Liu Xun
Published: February 2021

Background

The conclusions on the associations of specific vitamin levels with bone mineral density (BMD) were controversial. Therefore, the aims of this study were to examine the associations of serum vitamins levels with BMD and the modified effect of race/ ethnicity on these associations in the US adults.

Methods

This study was from the third National Health and Nutrition Examination Survey. All participants aged ≥18 years with complete data were eligible. Serum vitamins A, B9, B12, C, and E levels were assayed using the Quantaphase II Radioassay Kit (Bio-Rad). Dual-energy X-ray absorptiometry was employed to measure BMD, including femur neck and the total hip.

Results

There were 6023 participants included in the final analysis. Serum folate, vitamins A and C levels were positively associated with BMD. No significant associations of serum vitamins B12 and E levels with BMD were observed. There were positive associations of serum folate level (β = 0.00027 and 0.00032; and 95% CI: 0.00002–0.00057 and 0.00002–0.00063, respectively), vitamin A level (β = 0.01132 and 0.01115; and 95% CI: 0.00478–0.01787 and 0.00430–0.01799, respectively), and vitamin C level (β = 0.00027 and 0.00029; and 95% CI: 0.00012–0.00042 and 0.00013–0.00045, respectively) with BMD at femur neck and the total hip only in the Not Hispanic participants.

Conclusion

Elevated serum folate, vitamins A and C levels were associated with a higher BMD. Furthermore, sex and race/ ethnicity modified the associations of serum vitamins levels with BMD.
Clinical efficacy of retrograde urethrography-assisted urethral catheterization after failed conventional urethral catheterization
Authors: Kim Si Hyun , Yang Hee Jo , Kim Doo Sang , Lee Chang Ho , Jeon Youn Soo , Kim Ki Hong
Published: February 2021

Background

Several approaches for urethral catheterization after the failure of initial urethral catheterization have been introduced. However, standard procedures regarding what should be done after failed conventional urethral catheterization have been not established. Therefore, we investigated the clinical efficacy of retrograde urethrography (RGU)-assisted urethral catheterization after failed conventional urethral catheterization.

Methods

Between July 2015 and July 2018, 136 patients who underwent RGU-assisted urethral catheterization after failed conventional urethral catheterization were included in this retrospective study. Patients’ clinical data, such as age, catheterization site, and previous history of urologic operations, were collected and assessed via chart review. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for the failure of this procedure.

Results

Of the 136 patients, 94 (69.1%) experienced successful RGU-assisted urethral catheterization. Having a previous history of urologic operations, such as urethrotomy and transurethral prostatectomy, was identified as an independent predictive factor for the failure of RGU-assisted urethral catheterization (odds ratio = 9.453, 95% confidence interval = 2.703–33.063, p < 0.001).

Conclusions

RGU-assisted urethral catheterization can be one of the modalities for providing successful catheterization after failed conventional urethral catheterization. We believe that RGU-assisted urethral catheterization can be an effective procedure if patients have no previous history of urologic operations, such as urethrotomy and transurethral prostatectomy. Trial registration Soonchunhyang university institutional review board approval (No. 2018-08-021).
Methanol (80%) leaf extract of Otostegia integrifolia Benth (Lamiaceae) lowers blood pressure in rats through interference with calcium conductance
Authors: Degu Abel , Abebe Abiy , Engidawork Ephrem
Published: February 2021

Background

Otostegia integrifolia Benth. (Lamiaceae) leaves are used to treat hypertension in Ethiopian folk medicine. However, the claim has so far not been investigated scientifically. Thus, the objective of this study was to evaluate the antihypertensive activity of 80% methanol leaf extract of O. integrifolia in animal model of hypertension and possible underlying mechanisms in isolated rat aorta.

Methods

Antihypertensive effect of various oral doses of the extract (250, 500 and 1000 mg/kg) was determined in fructose-induced hypertensive rats using the non-invasive tail-cuff method. Thoracic aortic strips of rats were isolated and suspended in organ bath, and the vasodepressor effect as well as the possible mechanism (s) of action were studied by means of isometric tension recording experiments ex vivo. Phytochemical analysis was also performed to suggest possible constituents related to the activity.

Results

Blood pressure was significantly lowered in a dose-dependent manner following extract administration, suggesting that the extract possesses antihypertensive activity. The extract also caused a dose-dependent relaxation of aortic strip precontracted with KCl at a concentration of 6.25–125 μg/L, with a maximum relaxation (100%) achieved at a cumulative concentration of 318.75 μg/ml. The relaxation mechanism was found to be independent of muscarinic receptors, prostanoids, histamine receptors, ATP dependent K+ channels, sarcoplasmic reticulum stored Ca2+ and the endothelium system. The extract shifted the Ca2+ concentration-response curve to the right similar to that caused by nifedipine, suggesting that vasorelaxation could possibly be mediated via calcium channel blockade. The extract was found to contain phenolic compounds (164.3 mg/g, expressed as gallic acid equivalents) and flavonoids (125.7 mg/g, expressed as quercetin equivalents).

Conclusion

The findings revealed that the plant is endowed with antihypertensive activity, providing evidence for its traditional use. The effect maybe, at least in part, due to dilation of blood vessels through blockade of Ca+ 2 channels mediated by phenolic and flavonoid constituents.
Impact of complementary and alternative medicines on antiepileptic medication adherence among epilepsy patients
Authors: Farrukh Muhammad Junaid , Makmor-Bakry Mohd , Hatah Ernieda , Jan Tan Hui
Published: February 2021

Background

The aim of this study was to assess the knowledge, attitude, and practice of complementary and alternative medicine (CAM) and its impact on antiepileptic drug (AED) adherence among patients with epilepsy.

Methods

A cross-sectional study was carried out on 100 epilepsy patients, aged 18 years or older that did not have any physical or psychiatric illness. A patient-administered questionnaire was used to assess their knowledge, attitude towards, practice, and perceived effectiveness (KAPP) of CAM. Established adherence assessment tools were used to determine patient medication adherence.

Results

The prevalence of CAM usage was found to be at 58%. CAM was used more frequently by males (n = 32, 60.4%) than by females (n = 26, 55.3%; p = 0.609). The most commonly used CAM included vitamins and minerals (36%), ginseng (16%), antioxidants (15%), and acupuncture (12%). A significant number of patients had low knowledge of (59%) and a positive attitude (54%) toward complementary and alternative medicine. Main reasons for using CAM were a lower price, better availability, and inadequate seizure control by AEDs. About 43% of the patients who used CAM informed their doctor. Prevalence of non-adherence to AED therapy was found to be 68%. A significant association was found between non-adherence and CAM usage (p < 0.01).

Conclusion

A high prevalence of CAM usage and non-adherence to AEDs among epilepsy patients was identified. CAM usage was associated with a non-adherence to AED therapy. This study highlights the need to explore CAM usage with patients before making clinical decisions to achieve the best outcomes from AED therapy.
Development of a novel mobile application, HBB Prompt, with human factors and user-centred design for Helping Babies Breathe skills retention in Uganda
Authors: Chan Natalie Hoi-Man , Merali Hasan S. , Mistry Niraj , Kealey Ryan , Campbell Douglas M. , Morris Shaun K. , Data Santorino
Published: February 2021

Background

Helping Babies Breathe (HBB) is a life-saving program that has helped reduce neonatal morbidity and mortality, but knowledge and skills retention after training remains a significant challenge for sustainability of impact. User-centred design (UCD) can be used to develop solutions to target knowledge and skills maintenance.

Methods

We applied a process of UCD beginning with understanding the facilitators of, and barriers to, learning and retaining HBB knowledge and skills. HBB Master Trainers and frontline HBB providers participated in a series of focus group discussions (FGDs) to uncover the processes of skills acquisition and maintenance to develop a mobile application called “HBB Prompt”. Themes derived from each FGD were identified and implications for development of the HBB Prompt app were explored, including feasibility of incorporating strategies into the format of an app. Data analysis took place after each iteration in Phase 1 to incorporate feedback and improve subsequent versions of HBB Prompt.

Results

Six HBB trainers and seven frontline HBB providers participated in a series of FGDs in Phase 1 of this study. Common themes included lack of motivation to practise, improving confidence in ventilation skills, ability to achieve the Golden Minute, fear of forgetting knowledge or skills, importance of feedback, and peer-to-peer learning. Themes identified that were not feasible to address pertained to health system challenges. Feedback about HBB Prompt was generally positive. Based on initial and iterative feedback, HBB Prompt was created with four primary functions: Training Mode, Simulation Mode, Quizzes, and Dashboard/Scoreboard.

Conclusions

Developing HBB Prompt with UCD to help improve knowledge and skills retention was feasible and revealed key concepts, including drivers for successes and challenges faced for learning and maintaining HBB skills. HBB Prompt will be piloted in Phase 2 of this study, where knowledge and skills retention after HBB training will be compared between an intervention group with HBB Prompt and a control group without the app.

Trial registration Clinicaltrials.gov (NCT03577054). Retrospectively registered July 5, 2018, https://clinicaltrials.gov/ct2/show/study/NCT03577054.
Discrepancies in decision making preferences between parents and surgeons in pediatric surgery
Authors: Carlisle Erica M. , Klipowicz Caleb J. , Shinkunas Laura A. , Scherer Aaron M. , Kaldjian Lauris C.
Published: February 2021

Background

Little data exists regarding decision-making preferences for parents and surgeons in pediatric surgery. Here we investigate whether parents and surgeons have similar decision-making preferences as well as which factors influence those preferences. Specifically, we compare parents’ and surgeons’ assessments of the urgency and complexity of pediatric surgical scenarios and the impact of their assessments on decision-making preferences.

Methods

A survey was emailed to parents of patients evaluated in a university-based pediatric surgery clinic and surgeons belonging to the American Pediatric Surgical Association. The survey asked respondents to rate 6 clinical vignettes for urgency, complexity, and desired level of surgeon guidance using the Controlled Preferences Scale (CPS).

Results

Regarding urgency, parents were more likely than surgeons to rate scenarios as emergent when cancer was involved (parents: 68.8% cancer vs. 29.5% non-cancer, p < .001; surgeons: 19.2% cancer vs. 25.4% non-cancer, p = .051). Parents and surgeons were more likely to rate a scenario as emergent when a baby was involved (parents: 45.2% baby vs. 36.2% child, p = .001; surgeons: 28.0% baby vs. 14.0% child, p < .001). Regarding decision-making preferences, parents and surgeons had similar CPS scores (2.56 vs. 2.72, respectively). Multivariable analysis showed parents preferred more surgeon guidance when scenarios involved a baby (OR 1.22; 95% CI 1.08–1.37; p < 0.01) or a cancer diagnosis (OR 1.29; 95% CI 1.11–1.49; p < 0.01), and that both parents and surgeons preferred more surgeon guidance when a scenario was considered emergent (parents: OR 1.81; 95% CI 1.37–2.38, p < 0.001; surgeons: OR 2.48 95% CI 1.76–3.49, p < 0.001).

Conclusions

When a pediatric patient is a baby or has cancer, parents are more likely then surgeons to perceive the clinical situation to be emergent, and both parents and surgeons prefer more surgeon guidance in decision-making when a clinical scenario is considered emergent. More research is needed to understand how parents’ decision-making preferences depend on clinical context.
Characterization of bariatric surgery and outcomes using administrative claims data in the research network of a nationwide commercial health plan
Authors: Ma Qinli , Mack Michael , Shambhu Sonali , McTigue Kathleen , Haynes Kevin
Published: February 2021

Background

The supplementation of electronic health records data with administrative claims data may be used to capture outcome events more comprehensively in longitudinal observational studies. This study investigated the utility of administrative claims data to identify outcomes across health systems using a comparative effectiveness study of different types of bariatric surgery as a model.

Methods

This observational cohort study identified patients who had bariatric surgery between 2007 and 2015 within the HealthCore Anthem Research Network (HCARN) database in the National Patient-Centered Clinical Research Network (PCORnet) common data model. Patients whose procedures were performed in a member facility affiliated with PCORnet Clinical Research Networks (CRNs) were selected. The outcomes included a 30-day composite adverse event (including venous thromboembolism, percutaneous/operative intervention, failure to discharge and death), and all-cause hospitalization, abdominal operation or intervention, and in-hospital death up to 5 years after the procedure. Outcomes were classified as occurring within or outside PCORnet CRN health systems using facility identifiers.

Results

We identified 4899 patients who had bariatric surgery in one of the PCORnet CRN health systems. For 30-day composite adverse event, the inclusion of HCARN multi-site claims data marginally increased the incidence rate based only on HCARN single-site claims data for PCORnet CRNs from 3.9 to 4.2%. During the 5-year follow-up period, 56.8% of all-cause hospitalizations, 31.2% abdominal operations or interventions, and 32.3% of in-hospital deaths occurred outside PCORnet CRNs. Incidence rates (events per 100 patient-years) were significantly lower when based on claims from a single PCORnet CRN only compared to using claims from all health systems in the HCARN: all-cause hospitalization, 11.0 (95% Confidence Internal [CI]: 10.4, 11.6) to 25.3 (95% CI: 24.4, 26.3); abdominal operations or interventions, 4.2 (95% CI: 3.9, 4.6) to 6.1 (95% CI: 5.7, 6.6); in-hospital death, 0.2 (95% CI: 0.11, 0.27) to 0.3 (95% CI: 0.19, 0.38).

Conclusions

Short-term inclusion of multi-site claims data only marginally increased the incidence rate computed from single-site claims data alone. Longer-term follow up captured a notable number of events outside of PCORnet CRNs. The findings suggest that supplementing claims data improves the outcome ascertainment in longitudinal observational comparative effectiveness studies.
Gene networks and transcriptional regulators associated with liver cancer development and progression
Authors: Meier Tatiana , Timm Max , Montani Matteo , Wilkens Ludwig
Published: February 2021

Background

Treatment options for hepatocellular carcinoma (HCC) are limited, and overall survival is poor. Despite the high frequency of this malignoma, its basic disease mechanisms are poorly understood. Therefore, the aim of this study was to use different methodological approaches and combine the results to improve our knowledge on the development and progression of HCC.

Methods

Twenty-three HCC samples were characterized by histological, morphometric and cytogenetic analyses, as well as comparative genomic hybridization (aCGH) and genome-wide gene expression followed by a bioinformatic search for potential transcriptional regulators and master regulatory molecules of gene networks.

Results

Histological evaluation revealed low, intermediate and high-grade HCCs, and gene expression analysis split them into two main sets: GE1-HCC and GE2-HCC, with a low and high proliferation gene expression signature, respectively. Array-based comparative genomic hybridization demonstrated a high level of chromosomal instability, with recurrent chromosomal gains of 1q, 6p, 7q, 8q, 11q, 17q, 19p/q and 20q in both HCC groups and losses of 1p, 4q, 6q, 13q and 18q characteristic for GE2-HCC. Gene expression and bioinformatics analyses revealed that different genes and gene regulatory networks underlie the distinct biological features observed in GE1-HCC and GE2-HCC. Besides previously reported dysregulated genes, the current study identified new candidate genes with a putative role in liver cancer, e.g. C1orf35, PAFAH1B3, ZNF219 and others.

Conclusion

Analysis of our findings, in accordance with the available published data, argues in favour of the notion that the activated E2F1 signalling pathway, which can be responsible for both inappropriate cell proliferation and initial chromosomal instability, plays a pivotal role in HCC development and progression. A dedifferentiation switch that manifests in exaggerated gene expression changes might be due to turning on transcriptional co-regulators with broad impact on gene expression, e.g. POU2F1 (OCT1) and NFY, as a response to accumulating cell stress during malignant development. Our findings point towards the necessity of different approaches for the treatment of HCC forms with low and high proliferation signatures and provide new candidates for developing appropriate HCC therapies.
COPD Clinical Control: predictors and long-term follow-up of the CHAIN cohort
Authors:   the CHAIN Study Investigators, Calle Rubio Myriam , Rodriguez Hermosa Juan Luis , de Torres Juan P. , Marín José María , Martínez-González Cristina , Fuster Antonia , Cosío Borja G. , Peces-Barba Germán , Solanes Ingrid , Feu-Collado Nuria , Lopez-Campos Jose Luis , Casanova Ciro
Published: February 2021

Background

Control in COPD is a dynamic concept that can reflect changes in patients’ clinical status that may have prognostic implications, but there is no information about changes in control status and its long-term consequences.

Methods

We classified 798 patients with COPD from the CHAIN cohort as controlled/uncontrolled at baseline and over 5 years. We describe the changes in control status in patients over long-term follow-up and analyze the factors that were associated with longitudinal control patterns and related survival using the Cox hazard analysis.

Results

134 patients (16.8%) were considered persistently controlled, 248 (31.1%) persistently uncontrolled and 416 (52.1%) changed control status during follow-up. The variables significantly associated with persistent control were not requiring triple therapy at baseline and having a better quality of life. Annual changes in outcomes (health status, psychological status, airflow limitation) did not differ in patients, regardless of clinical control status. All-cause mortality was lower in persistently controlled patients (5.5% versus 19.1%, p = 0.001). The hazard ratio for all-cause mortality was 2.274 (95% CI 1.394–3.708; p = 0.001). Regarding pharmacological treatment, triple inhaled therapy was the most common option in persistently uncontrolled patients (72.2%). Patients with persistent disease control more frequently used bronchodilators for monotherapy (53%) at recruitment, although by the end of the follow-up period, 20% had scaled up their treatment, with triple therapy being the most frequent therapeutic pattern.

Conclusions

The evaluation of COPD control status provides relevant prognostic information on survival. There is important variability in clinical control status and only a small proportion of the patients had persistently good control. Changes in the treatment pattern may be relevant in the longitudinal pattern of COPD clinical control. Further studies in other populations should validate our results.

Trial registration: Clinical Trials.gov: identifier NCT01122758.
Re-expression of miR-200s in claudin‐low mammary tumor cells alters cell shape and reduces proliferation and invasion potentially through modulating other miRNAs and SUZ12 regulated genes
Authors: Simpson K. , Conquer-van Heumen G. , Watson K. L. , Roth M. , Martin C. J. , Moorehead R. A.
Published: February 2021

Background

MicroRNAs are a class of non-coding RNAs that regulate gene expression through binding to mRNAs and preventing their translation. One family of microRNAs known as the miR-200 family is an important regulator of epithelial identity. The miR-200 family consists of five members expressed in two distinct clusters; the miR-200c/141 cluster and the miR-200b/200a/429 cluster. We have found that murine and human mammary tumor cells with claudin-low characteristics are associated with very low levels of all five miR-200s.

Methods

To determine the impact of miR-200s on claudin-low mammary tumor cells, the miR-200c/141 cluster and the miR-200b/200a/429 cluster were stably re-expressed in murine (RJ423) and human (MDA-MB-231) claudin-low mammary tumor cells. Cell proliferation and migration were assessed using BrdU incorporation and transwell migration across Matrigel coated inserts, respectively. miRNA sequencing and RNA sequencing were performed to explore miRNAs and mRNAs regulated by miR-200 re-expression while Enrichr-based pathway analysis was utilized to identify cellular functions modified by miR-200s.

Results

Re-expression of the miR-200s in murine and human claudin-low mammary tumor cells partially restored an epithelial cell morphology and significantly inhibited proliferation and cell invasion in vitro. miRNA sequencing and mRNA sequencing revealed that re-expression of miR-200s altered the expression of other microRNAs and genes regulated by SUZ12 providing insight into the complexity of miR-200 function. SUZ12 is a member of the polycomb repressor complex 2 that suppresses gene expression through methylating histone H3 at lysine 27. Flow cytometry confirmed that re-expression of miR-200s increased histone H3 methylation at lysine 27.

Conclusions

Re-expression of miR-200s in claudin-low mammary tumor cells alters cell morphology and reduces proliferation and invasion, an effect potentially mediated by SUZ12-regulated genes and other microRNAs.
Highly stable organic photothermal agent based on near-infrared-II fluorophores for tumor treatment
Authors: Xu Yunjian , Wang Shiqi , Chen Zhenjiang , Hu Rui , Li Shaoqiang , Zhao Yihua , Liu Liwei , Qu Junle
Published: February 2021

Background

The aim to develop a highly stable near-infrared (NIR) photoinduced tumor therapy agent stems from its considerable potential for biological application. Due to its long wavelength, biological imaging exhibits a high signal-to-background ratio, deep tissue penetration and maximum permissible light power, which can minimize damage to an organism during photoinduced tumor therapy.

Results

A class of stable NIR-II fluorophores (NIR998, NIR1028, NIR980, NIR1030, and NIR1028-S) based on aza–boron–dipyrromethene (aza-BODIPY) dyes with donor–acceptor-donor structures have been rationally designed and synthesized by harnessing the steric relaxation effect and intramolecular photoinduced electron transfer (IPET). These fluorophores exhibit an intense range of NIR-II emission, large Stokes shift (≥ 100 nm), excellent photothermal conversion performance, and superior stability against photobleaching. Among the NIR-II fluorophores, NIR998 possesses better NIR-II emission and photothermal conversion performance. NIR998 nanoparticles (NIR998 NPs) can be encapsulated by liposomes. NIR998 NPs show superior stability in the presence of light, heat, and reactive oxygen nitrogen species than that of indocyanine green NPs, as well as a higher photothermal conversion ability (η = 50.5%) compared to other photothermal agents. Finally, under the guidance of photothermal imaging, NIR998 NPs have been proven to effectively eliminate tumors via their excellent photothermal conversion performance while presenting negligible cytotoxicity.

Conclusions

Utilizing IPET and the steric relaxation effect can effectively induce NIR-II emission of aza-BODIPY dyes. Stable NIR998 NPs have excellent photothermal conversion performance and negligible dark cytotoxicity, so they have the potential to act as photothermal agents in biological applications.
Cost per DALY averted in low, middle- and high-income countries: evidence from the global burden of disease study to estimate the cost-effectiveness thresholds
Authors: Daroudi Rajabali , Akbari Sari Ali , Nahvijou Azin , Faramarzi Ahmad
Published: February 2021

Background

Determining the cost-effectiveness thresholds for healthcare interventions has been a severe challenge for policymakers, especially in low- and middle-income countries. This study aimed to estimate the cost per disability-adjusted life-year (DALY) averted for countries with different levels of Human Development Index (HDI) and Gross Domestic Product (GDP).

Methods

The data about DALYs, per capita health expenditure (HE), HDI, and GDP per capita were extracted for 176 countries during the years 2000 to 2016. Then we examined the trends on these variables. Panel regression analysis was performed to explore the correlation between DALY and HE per capita. The results of the regression models were used to calculate the cost per DALY averted for each country.

Results

Age-standardized rate (ASR) DALY (DALY per 100,000 population) had a nonlinear inverse correlation with HE per capita and a linear inverse correlation with HDI. One percent increase in HE per capita was associated with an average of 0.28, 0.24, 0.18, and 0.27% decrease on the ASR DALY in low HDI, medium HDI, high HDI, and very high HDI countries, respectively. The estimated cost per DALY averted was $998, $6522, $23,782, and $69,499 in low HDI, medium HDI, high HDI, and very high HDI countries. On average, the cost per DALY averted was 0.34 times the GDP per capita in low HDI countries. While in medium HDI, high HDI, and very high HDI countries, it was 0.67, 1.22, and 1.46 times the GDP per capita, respectively.

Conclusions

This study suggests that the cost-effectiveness thresholds might be less than a GDP per capita in low and medium HDI countries and between one and two GDP per capita in high and very high HDI countries.
Seasons, weather, and device-measured movement behaviors: a scoping review from 2006 to 2020
Authors: Turrisi Taylor B. , Bittel Kelsey M. , West Ashley B. , Hojjatinia Sarah , Hojjatinia Sahar , Mama Scherezade K. , Lagoa Constantino M. , Conroy David E.
Published: February 2021

Background

This scoping review summarized research on (a) seasonal differences in physical activity and sedentary behavior, and (b) specific weather indices associated with those behaviors.

Methods

PubMed, CINAHL, and SPORTDiscus were searched to identify relevant studies. After identifying and screening 1459 articles, data were extracted from 110 articles with 118,189 participants from 30 countries (almost exclusively high-income countries) on five continents.

Results

Both physical activity volume and moderate-to-vigorous physical activity (MVPA) were greater in summer than winter. Sedentary behavior was greater in winter than either spring or summer, and insufficient evidence existed to draw conclusions about seasonal differences in light physical activity. Physical activity volume and MVPA duration were positively associated with both the photoperiod and temperature, and negatively associated with precipitation. Sedentary behavior was negatively associated with photoperiod and positively associated with precipitation. Insufficient evidence existed to draw conclusions about light physical activity and specific weather indices. Many weather indices have been neglected in this literature (e.g., air quality, barometric pressure, cloud coverage, humidity, snow, visibility, windchill).

Conclusions

The natural environment can influence health by facilitating or inhibiting physical activity. Behavioral interventions should be sensitive to potential weather impacts. Extreme weather conditions brought about by climate change may compromise health-enhancing physical activity in the short term and, over longer periods of time, stimulate human migration in search of more suitable environmental niches.
Sirtuin 3 protects against anesthesia/surgery-induced cognitive decline in aged mice by suppressing hippocampal neuroinflammation
Authors: Liu Qiang , Sun Yi-Man , Huang Hui , Chen Chen , Wan Jie , Ma Lin-Hui , Sun Yin-Ying , Miao Hui-Hui , Wu Yu-Qing
Published: February 2021

Background

Postoperative cognitive dysfunction (POCD) is a very common complication that might increase the morbidity and mortality of elderly patients after surgery. However, the mechanism of POCD remains largely unknown. The NAD-dependent deacetylase protein Sirtuin 3 (SIRT3) is located in the mitochondria and regulates mitochondrial function. SIRT3 is the only sirtuin that specifically plays a role in extending lifespan in humans and is associated with neurodegenerative diseases. Therefore, the aim of this study was to evaluate the effect of SIRT3 on anesthesia/surgery-induced cognitive impairment in aged mice.

Methods

SIRT3 expression levels were decreased after surgery. For the interventional study, an adeno-associated virus (AAV)-SIRT3 vector or an empty vector was microinjected into hippocampal CA1 region before anesthesia/surgery. Western blotting, immunofluorescence staining, and enzyme-linked immune-sorbent assay (ELISA) were used to measure the oxidative stress response and downstream microglial activation and proinflammatory cytokines, and Golgi staining and long-term potentiation (LTP) recording were applied to evaluate synaptic plasticity.

Results

Overexpression of SIRT3 in the CA1 region attenuated anesthesia/surgery-induced learning and memory dysfunction as well as synaptic plasticity dysfunction and the oxidative stress response (superoxide dismutase [SOD] and malondialdehyde [MDA]) in aged mice with POCD. In addition, microglia activation (ionized calcium binding adapter molecule 1 [Iba1]) and neuroinflammatory cytokine levels (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-1β and IL-6) were regulated after anesthesia/surgery in a SIRT3-dependent manner.

Conclusion

The results of the current study demonstrate that SIRT3 has a critical effect in the mechanism of POCD in aged mice by suppressing hippocampal neuroinflammation and reveal that SIRT3 may be a promising therapeutic and diagnostic target for POCD.
The relationship between cerebral blood flow and venous sinus pressure: can hyperemia induce idiopathic intracranial hypertension?
Authors: Bateman Alexander Robert , Bateman Grant Alexander , Barber Tracie
Published: February 2021

Background

It has been shown that idiopathic intracranial hypertension (IIH) in children is associated with cerebral hyperemia, which induces an increase in cerebral venous pressure. The current literature suggests venous pressure scales with blood flow in a linear fashion, however, a linear relationship would not raise the pressure high enough to induce IIH. There is, however, some evidence to suggest that this relationship could be quadratic in nature. The purpose of this paper is to characterize the relationship between cerebral blood flow and the pressure drop across the cerebral venous system.

Methods

10 CT venogram data sets were collected for this study, with 5 useable geometries created. Computational fluid dynamics (CFD) models were generated using these geometries, with 10 simulations conducted per patient. The flow rates tested ranged from 200 mL/min to 2000 mL/min. 3D pressure and velocity streamline distributions were created and analyzed for each CFD model, with pressure drops across the cerebral venous system determined. The effective and hydraulic diameters were determined at the superior sagittal sinus, transverse sinus and both proximal and distal sigmoid sinuses.

Results

A quadratic relationship between blood flow and sinus pressure was found, with correlations of 0.99 or above in all five patients. The presence of vortical blood flow was found to explain this trend, with fluid curl and pressure drop correlations being above 0.97. This suggests that the presence of high blood flow should be considered in the diagnostic workup of IIH.

Conclusions

The cerebral venous sinus blood flow and pressure response relationship are quadratic in nature, with the major cause of this being the degree of rotation induced in the flow. The elevated blood flow found in children with IIH can explain the increased ICP that is found, secondary to the increase in venous pressure that develops.
Mismatch repair deficiency is associated with specific morphologic features and frequent loss of ARID1A expression in ovarian clear cell carcinoma
Authors: Ge Huijuan , Xiao Yaoxin , Qin Guangqi , Gu Yanzi , Cai Xu , Jiang Wenhua , Tu Xiaoyu , Yang Wentao , Bi Rui
Published: February 2021

Background

Ovarian clear cell carcinoma (OCCC) is the second subtype of ovarian epithelial carcinoma reported to be closely related to Lynch syndrome (LS). ARID1A mutation is an important pathogenetic mechanism in OCCC that leads to loss of ARID1A expression in approximately half of OCCCs. However, the correlation of MMR status and ARID1A deficiency is unclear. The current study aimed to identify the clinical and histopathological characteristics of OCCC associated with dMMR and to further explore the association between dMMR and ARID1A deficiency.

Methods

A cohort of 176 primary OCCC patients was enrolled and review included histological characteristics (nuclear atypia, necrosis, mitosis, stromal hyalinization, and background precursors) and host inflammatory response (tumor-infiltrating lymphocytes, peritumoral lymphocytes, intratumoral stromal inflammation and plasma cell infiltration). Immunohistochemical staining of MLH1, PMS2, MSH2, MSH6 and ARID1A was performed using tissue microarrays.

Results

dMMR was detected in 10/176 tumors (6 %), followed by MSH2/MSH6 (6/176), MLH1/PMS2 (3/176), and MSH6 (1/176). The average age of patients with dMMR was younger than that of patients with intact MMR (46 y vs. 53 y). Tumors with diffuse intratumoral stromal inflammation remained significantly associated after multivariate analysis. ARID1A expression was absent in 8 patients with dMMR (8/10), which is a significantly higher frequency than that observed in patients with intact MMR (80 % vs. 43.2 %).

Conclusions

Our study indicates that diffuse intratumoral stromal inflammation of OCCCs is associated with dMMR, with loss of MSH2/MSH6 expression being most frequent. dMMR is strongly associated with the loss of ARID1A expression in OCCC.
Dosimetric predictors of nephrotoxicity in patients receiving extended-field radiation therapy for gynecologic cancer
Authors: Kunogi Hiroaki , Yamaguchi Nanae , Terao Yasuhisa , Sasai Keisuke
Published: February 2021

Purpose

We sought dosimetric predictors of a decreasing estimated glomerular filtration rate (eGFR) in gynecological oncology patients receiving extended-field radiation therapy (EFRT).

Materials and methods

Between July 2012 and April 2020, 98 consecutive cervical or endometrial cancer patients underwent EFRT or whole-pelvis radiation therapy (WPRT) with concurrent cisplatin chemotherapy in our institution. To explore the effect of concurrent cisplatin chemotherapy on renal function, the renal function of the WPRT patients was examined. Of the 98 patients, 34 cervical or endometrial cancer patients underwent EFRT including extended-field intensity-modulated radiation therapy (EF-IMRT) and 64 cervical cancer patients underwent WPRT with cisplatin. Of the 34 EFRT patients, 32 underwent concurrent cisplatin chemotherapy. Excluding patients exhibiting recurrences within 6 months, 31 EFRT patients were analyzed in terms of the dose-volume kidney histograms (the percentages of kidney volumes receiving 12, 16, 20, and 24 Gy) and the post- to pre-treatment eGFR ratios. We calculated Pearson correlation coefficients between the renal dose volume and the percentage eGFR reductions of the 31 EFRT patients, and those treated via EF-IMRT. Renal dose constraint significance was evaluated using the Mann–Whitney U test.

Results

The eGFR value after WPRT with cisplatin remained largely unchanged for 12 months, unlike that after EFRT. In EFRT patients, a strong correlation was evident between the KV20Gy dose and the post- to pre-treatment eGFR ratio (correlation coefficients − 0.80 for all patients and − 0.74 for EF-IMRT patients). In EF-IMRT patients, the kidney volume receiving 20 Gy tended to correlate negatively with the eGFR reduction. The Mann–Whitney U test showed that patients with KV20Gy values < 10% retained significantly better renal function than did patients with KV20Gy values > 10% (P = 0.002).

Conclusions

Imposition of a severe kidney dose constraint during EF-IMRT may reduce nephrotic toxicity. Future prospective investigations of kidney-sparing EF-IMRT are required.
Implementation, adherence, and results of systematic SARS-CoV-2 testing for asymptomatic patients treated at a tertiary care regional radiation oncology network
Authors: Prabhu Roshan S. , Dhakal Reshika , Hicks Amy S. , McBride James , Patrick Alicia L. , Corso Christopher D. , Murphy Tomain , Thonen Melissa , Lipford Edward H. , Raghavan Derek , Burri Stuart H.
Published: February 2021

Background

Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus is a current pandemic. We initiated a program of systematic SARS-CoV-2 polymerase chain reaction (PCR) testing in all asymptomatic patients receiving radiotherapy (RT) at a large radiation oncology network in the Charlotte, NC metropolitan region and report adherence and results of the testing program.

Methods

Patients undergoing simulation for RT between May 18, 2020 and July 10, 2020 within the Levine Cancer Institute radiation oncology network who were asymptomatic for COVID-19 associated symptoms, without previous positive SARS-CoV-2 testing, and without recent high-risk contacts were included. PCR testing was performed on nasal cavity or nasopharyngeal swab samples. Testing was performed within 2 weeks of RT start (pre-RT) and at least every 4 weeks during RT for patients with prolonged RT courses (intra-RT). An automated task based process using the oncology electronic medical record (EMR) was developed specifically for this purpose.

Results

A total of 604 unique patients were included in the cohort. Details on testing workflow and implementation are described herein. Pre-RT PCR testing was performed in 573 (94.9%) patients, of which 4 (0.7%) were positive. The adherence rate to intra-RT testing overall was 91.6%. Four additional patients (0.7%) tested positive during their RT course, of whom 3 were tested due to symptom development and 1 was asymptomatic and identified via systematic testing. A total of 8 (1.3%) patients tested positive overall. There were no known cases of SARS-CoV-2 transmission from infected patients to clinic staff and/or other patients.

Conclusions

We detailed the workflows used to implement systematic SARS-CoV-2 for asymptomatic patients at a large radiation oncology network. Adherence rates for pre-RT and intra-RT testing were high using this process. This information allowed for appropriate delay in initiating RT, minimizing the occurrence of RT treatment interruptions, and no known cases of transmission from infected patients to clinic staff and/or other patients.
Tips and tricks to achieve osteotomy healing and prevent refracture after ulnar shortening osteotomy
Authors: Kang Jong Woo , Cha Soo Min , Kim Sang-gyun , Choi In Cheul , Suh Dong Hun , Park Jong Woong
Published: February 2021

Background

Parallel osteotomy is essential for favorable osteotomy reduction and healing and technically challenging during diaphyseal ulnar shortening osteotomy (USO). This study aimed to evaluate the advantages of guided osteotomy for parallel osteotomy and reduction osteotomies, healing over freehand osteotomy. It also aimed to identify surgical factors affecting healing after diaphyseal USO.

Methods

Between June 2005 and March 2016, 136 wrists that had undergone diaphyseal USO for ulnar impaction syndrome (UIS) were evaluated. The wrists were divided into two groups according to the osteotomy technique (group 1: freehand osteotomy, 74 wrists; group 2: guided osteotomy, 62 wrists). The osteotomy reduction gap and time to osteotomy healing (union and consolidation) were compared between the groups. A multiple regression test was performed to identify the surgical factors affecting healing. The cut-off length of the reduction gap to achieve osteotomy union on time and the cut-off period to decide the failure of complete consolidation were statistically calculated.

Results

The baseline characteristics did not differ between the two groups. The osteotomy reduction gap and time to osteotomy union, and complete consolidation were shorter in group 2 than in group 1 (p= 0.002, < 0.001, 0.002). The osteotomy reduction gap was a critical surgical factor affecting both time to osteotomy union and complete consolidation (p< 0.001, < 0.001). The use of a dynamic compression plate affected only the time to complete consolidation (p< 0.001). The cut-off length of the osteotomy reduction gap to achieve osteotomy union on time was 0.85 mm. The cut-off period to decide the failure of complete consolidation was 23.5 months after osteotomy.

Conclusions

The minimal osteotomy reduction gap was the most important for timely osteotomy healing in the healthy ulna, and guided osteotomy was beneficial for reducing the osteotomy reduction gap.