bluuebunny/crossref_metadata_2025 huggingface dataset:
Student well-being during dedicated preparation for USMLE Step 1 and COMLEX Level 1 exams
Authors: Tackett Sean , Jeyaraju Maniraj , Moore Jesse , Hudder Alice , Yingling Sandra , Park Yoon Soo , Grichanik Mark
Published: January 2022

Background

Nearly all U.S. medical students engage in a 4–8 week period of intense preparation for their first-level licensure exams, termed a “dedicated preparation period” (DPP). It is widely assumed that student well-being is harmed during DPPs, but evidence is limited. This study characterized students’ physical, intellectual, emotional, and social well-being during DPPs.

Methods

This was a cross-sectional survey sent electronically to all second-year students at four U.S. medical schools after each school’s respective DPP for USMLE Step 1 or COMLEX Level 1 in 2019. Survey items assessed DPP characteristics, cost of resources, and perceived financial strain as predictors for 18 outcomes measured by items with Likert-type response options. Open-ended responses on DPPs’ influence underwent thematic analysis.

Results

A total of 314/750 (42%) students completed surveys. DPPs lasted a median of 7 weeks (IQR 6–8 weeks), and students spent 70 h/week (IQR 56–80 h/week) studying. A total of 62 (20%) reported experiencing a significant life event that impacted their ability to study during their DPPs. Most reported 2 outcomes improved: medical knowledge base (95%) and confidence in ability to care for patients (56%). Most reported 9 outcomes worsened, including overall quality of life (72%), feeling burned out (77%), and personal anxiety (81%). A total of 25% reported paying for preparation materials strained their finances. Greater perceived financial strain was associated with worsening 11 outcomes, with reported amount spent associated with worsening 2 outcomes. Themes from student descriptions of how DPPs for first-level exams influenced them included (1) opportunity for synthesis of medical knowledge, (2) exercise of endurance and self-discipline required for professional practice, (3) dissonance among exam preparation resource content, formal curriculum, and professional values, (4) isolation, deprivation, and anguish from competing for the highest possible score, and (5) effects on well-being after DPPs.

Conclusions

DPPs are currently experienced by many students as a period of personal and social deprivation, which may be worsened by perceived financial stress more than the amount of money they spend on preparation materials. DPPs should be considered as a target for reform as medical educators attempt to prevent student suffering and enhance their well-being.
Deep Q-networks with web-based survey data for simulating lung cancer intervention prediction and assessment in the elderly: a quantitative study
Authors: Chen Songjing , Wu Sizhu
Published: January 2022

Background

Lung cancer screening and intervention might be important to help detect lung cancer early and reduce the mortality, but little was known about lung cancer intervention strategy associated with intervention effect for preventing lung cancer. We employed Deep Q-Networks (DQN) to respond to this gap. The aim was to quantitatively predict lung cancer optimal intervention strategy and assess intervention effect in aged 65 years and older (the elderly).

Methods

We screened lung cancer high risk with web-based survey data and conducted simulative intervention. DQN models were developed to predict optimal intervention strategies to prevent lung cancer in elderly men and elderly women separately. We assessed the intervention effects to evaluate the optimal intervention strategy.

Results

Proposed DQN models quantitatively predicted and assessed lung cancer intervention. DQN models performed well in five stratified groups (elderly men, elderly women, men, women and the whole population). Stopping smoking and extending quitting smoking time were optimal intervention strategies in elderly men. Extending quitting time and reducing smoked cigarettes number were optimal intervention strategies in elderly women. In elderly men and women, the maximal reductions of lung cancer incidence were 31.81% and 24.62% separately. Lung cancer incidence trend was deduced from the year of 1984 to 2050, which predicted that the difference of lung cancer incidence between elderly men and women might be significantly decreased after thirty years quitting time.

Conclusions

We quantitatively predicted optimal intervention strategy and assessed lung cancer intervention effect in the elderly through DQN models. Those might improve intervention effects and reasonably prevent lung cancer.
Comparing machine learning algorithms for predicting COVID-19 mortality
Authors: Moulaei Khadijeh , Shanbehzadeh Mostafa , Mohammadi-Taghiabad Zahra , Kazemi-Arpanahi Hadi
Published: January 2022

Background

The coronavirus disease (COVID-19) hospitalized patients are always at risk of death. Machine learning (ML) algorithms can be used as a potential solution for predicting mortality in COVID-19 hospitalized patients. So, our study aimed to compare several ML algorithms to predict the COVID-19 mortality using the patient’s data at the first time of admission and choose the best performing algorithm as a predictive tool for decision-making.

Methods

In this study, after feature selection, based on the confirmed predictors, information about 1500 eligible patients (1386 survivors and 144 deaths) obtained from the registry of Ayatollah Taleghani Hospital, Abadan city, Iran, was extracted. Afterwards, several ML algorithms were trained to predict COVID-19 mortality. Finally, to assess the models’ performance, the metrics derived from the confusion matrix were calculated.

Results

The study participants were 1500 patients; the number of men was found to be higher than that of women (836 vs. 664) and the median age was 57.25 years old (interquartile 18–100). After performing the feature selection, out of 38 features, dyspnea, ICU admission, and oxygen therapy were found as the top three predictors. Smoking, alanine aminotransferase, and platelet count were found to be the three lowest predictors of COVID-19 mortality. Experimental results demonstrated that random forest (RF) had better performance than other ML algorithms with accuracy, sensitivity, precision, specificity, and receiver operating characteristic (ROC) of 95.03%, 90.70%, 94.23%, 95.10%, and 99.02%, respectively.

Conclusion

It was found that ML enables a reasonable level of accuracy in predicting the COVID-19 mortality. Therefore, ML-based predictive models, particularly the RF algorithm, potentially facilitate identifying the patients who are at high risk of mortality and inform proper interventions by the clinicians.
Demand for community-based Case Management in Austria - a qualitative analysis
Authors: Gessl Alessandra Schirin , Flörl Angela , Schulc Eva
Published: January 2022

Background

The number of people with complex nursing and care needs living in their own homes is increasing. The implementation of Case and Care Management has shown to have a positive effect on unmet care needs. Research on and implementation of Case and Care Management in the community setting in Austria is limited. This study aimed to understand the changes and challenges of changing care needs by mobile nurses and to evaluate the need for Case Management in mobile care organizations by investigating the evolution of mobile care nurses‘task profiles and the challenges in working in a dynamic field with changing target groups and complexifying care needs.

Methods

A qualitative study with reductive-interpretative data analysis consisting of semi-structured focus groups was conducted. Community care nurses, head nurses, and managers of community mobile care units as well as discharge managers of a community hospital (n = 24) participated in nine qualitative, semi-structured focus groups. The recorded focus groups were transcribed and analyzed using qualitative content analysis.

Results

The analysis revealed three main categories: the complexity of the case, innerinstitutional frameworks, and interinstitutional collaboration, which influence the perception of need for further development in the direction of Case and Care Management. Feelings of overwhelmedness among nurses were predominantly tied to cases that presented with issues beyond healthcare such as legal, financial, or social that necessitated communication and collaboration across multiple care providers.

Conclusions

Care institutions need to adapt to changing and increasingly complex care needs that necessitate cooperation between organizations within and across the health and social sectors. A key facilitator for care coordination and the adequate service provision for complex care needs are multidisciplinary institutional networks, which often remain informal, leaving nurses in the role of petitioner without equal footing. Embedding Case and Care Management in the community has the potential to fill this gap and facilitate flexible, timely, and coordinated care across multiple care providers.
Translation and psychometric properties of the MISSCARE survey-Persian version
Authors: Hosseini Zeinab , Raisi Leila , Maghari Amirhossein , Karimollahi Mansoureh
Published: January 2022

Background

Providing safe and high-quality nursing care is an essential task of nursing. Nurses may be unable to provide patients with all of the necessary care for numerous reasons, such as an increase in the number of patients and a low number of nursing staff. Moreover, they may have to omit, postpone, or incompletely perform a series of care, referred to as missed nursing care. The purpose of this study was to translate and conduct psychometric testing of the MISSCARE Survey.

Method

In this study, we accurately translated the MISSCARE Survey. Its acceptability, construct validity, and internal consistency were analyzed. This cross-sectional study was conducted in the summer of 2020 in educational hospitals in Ardabil, Iran. The participants were 300 nurses who worked in educational hospitals and were randomly selected.

Results

Participants in this study included 300 nurses from five units, including general medicine (13.3%), COVID-19 (45.0%), surgery (18.7%), critical care unit (6.3%), and intensive care unit (16.7%), who worked various shifts, of whom 84.7% were female. The total content validity in Part A was 0.944, and that in Part B was 0.969. Part A was divided into three domains (necessary care, secondary care, and supportive care), and Part B was divided into five domains (communication, labor resources, material resources, responsibility, and unpredictable situations). In both parts, the chi-square index was < 3, and the RMSEA index was < 0.08. The internal consistency measured by Cronbach’s alpha was 0.933 for Part A and 0.910 for Part B for the Persian version of the MISSCARE Survey.

Conclusion

Based on the outcomes of this research, it can be concluded that the Persian version of the MISSCARE Survey is valid for use in Iranian hospitals and can be used to identify missed care and the reasons behind it. Nursing managers can also use it to improve the situation and provide the highest-quality care.
Capitated versus fee-for-service reimbursement and quality of care for chronic disease: a US cross-sectional analysis
Authors: Tummalapalli Sri Lekha , Estrella Michelle M. , Jannat-Khah Deanna P. , Keyhani Salomeh , Ibrahim Said
Published: January 2022

Background

Upcoming alternative payment models Primary Care First (PCF) and Kidney Care Choices (KCC) incorporate capitated payments for chronic disease management. Prior research on the effect of capitated payments on chronic disease management has shown mixed results. We assessed the patient, physician, and practice characteristics of practices with capitation as the majority of revenue, and evaluated the association of capitated reimbursement with quality of chronic disease care.

Methods

We performed a cross-sectional analysis of visits in the United States’ National Ambulatory Medical Care Survey (NAMCS) for patients with hypertension, diabetes, or chronic kidney disease (CKD). Our predictor was practice reimbursement type, classified as 1) majority capitation, 2) majority FFS, or 3) other reimbursement mix. Outcomes were quality indicators of hypertension control, diabetes control, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEi/ARB) use, and statin use.

Results

About 9% of visits were to practices with majority capitation revenue. Capitated practices, compared with FFS and other practices, had lower visit frequency (3.7 vs. 5.2 vs. 5.2, p = 0.006), were more likely to be located in the West Census Region (55% vs. 18% vs. 17%, p < 0.001), less likely to be solo practice (21% vs. 37% vs. 35%, p = 0.005), more likely to be owned by an insurance company, health plan or HMO (24% vs. 13% vs. 13%, p = 0.033), and more likely to have private insurance (43% vs. 25% vs. 19%, p = 0.004) and managed care payments (69% vs. 23% vs. 26%, p < 0.001) as the majority of revenue. The prevalence of controlled hypertension, controlled diabetes, ACEi/ARB use, and statin use was suboptimal across practice reimbursement types. Capitated reimbursement was not associated with differences in hypertension, diabetes, or CKD quality indicators, in multivariable models adjusting for patient, physician, and practice characteristics.

Conclusions

Practices with majority capitation revenue differed substantially from FFS and other practices in patient, physician, and practice characteristics, but were not associated with consistent quality differences. Our findings establish baseline estimates of chronic disease quality of care performance by practice reimbursement composition, informing chronic disease care delivery within upcoming payment models.
A practical approach for geographic prioritization and targeting of insecticide-treated net distribution campaigns during public health emergencies and in resource-limited settings
Authors: Young Alyssa J. , Eaton Will , Worges Matt , Hiruy Honelgn , Maxwell Kolawole , Audu Bala Mohammed , Marasciulo Madeleine , Nelson Charles , Tibenderana James , Abeku Tarekegn A.
Published: January 2022

Background

The use of data in targeting malaria control efforts is essential for optimal use of resources. This work provides a practical mechanism for prioritizing geographic areas for insecticide-treated net (ITN) distribution campaigns in settings with limited resources.

Methods

A GIS-based weighted approach was adopted to categorize and rank administrative units based on data that can be applied in various country contexts wherePlasmodium falciparumtransmission is reported. Malaria intervention and risk factors were used to rank local government areas (LGAs) in Nigeria for prioritization during mass ITN distribution campaigns. Each factor was assigned a unique weight that was obtained through application of the analytic hierarchy process (AHP). The weight was then multiplied by a value based on natural groupings inherent in the data, or the presence or absence of a given intervention. Risk scores for each factor were then summated to generate a composite unique risk score for each LGA. This risk score was translated into a prioritization map which ranks each LGA from low to high priority in terms of timing of ITN distributions.

Results

A case study using data from Nigeria showed that a major component that influenced the prioritization scheme was ITN access. Sensitivity analysis results indicate that changes to the methodology used to quantify ITN access did not modify outputs substantially. Some 120 LGAs were categorized as ‘extremely high’ or ‘high’ priority when a spatially interpolated ITN access layer was used. When prioritization scores were calculated using DHS-reported state level ITN access, 108 (90.0%) of the 120 LGAs were also categorized as being extremely high or high priority. The geospatial heterogeneity found among input risk factors suggests that a range of variables and covariates should be considered when using data to inform ITN distributions.

Conclusion

The authors provide a tool for prioritizing regions in terms of timing of ITN distributions. It serves as a base upon which a wider range of vector control interventions could be targeted. Its value added can be found in its potential for application in multiple country contexts, expediated timeframe for producing outputs, and its use of systematically collected malaria indicators in informing prioritization.
Development of a bowel sound detector adapted to demonstrate the effect of food intake
Authors: Wang Ning , Testa Alison , Marshall Barry J.
Published: January 2022

Objective

Bowel sounds (BS) carry useful information about gastrointestinal condition and feeding status. Interest in computerized bowel sound-based analysis has grown recently and techniques have evolved rapidly. An important first step for these analyses is to extract BS segments, whilst neglecting silent periods. The purpose of this study was to develop a convolutional neural network-based BS detector able to detect all types of BS with accurate time stamps, and to investigate the effect of food consumption on some acoustic features of BS with the proposed detector.

Results

Audio recordings from 40 volunteers were collected and a BS dataset consisting of 6700 manually labelled segments was generated for training and testing the proposed BS detector. The detector attained 91.06% and 90.78% accuracy for the validation dataset and across-subject test dataset, respectively, with a well-balanced sensitivity and specificity. The detection rates evaluated on different BS types were also satisfactory. Four acoustic features were evaluated to investigate the food effect. The total duration and spectral bandwidth of BS showed significant differences before and after food consumption, while no significant difference was observed in mean-crossing rate values.

Conclusion

We demonstrated that the proposed BS detector is effective in detecting all types of BS, and providing an accurate time stamp for each BS. The characteristics of BS types and the effect on detection accuracy is discussed. The proposed detector could have clinical application for post-operative ileus prognosis, and monitoring of food intake.
What is the carbon footprint of primary care practices? A retrospective life-cycle analysis in Switzerland
Authors: Nicolet John , Mueller Yolanda , Paruta Paola , Boucher Julien , Senn Nicolas
Published: January 2022

Background

The medical field causes significant environmental impact. Reduction of the primary care practice carbon footprint could contribute to decreasing global carbon emissions. This study aims to quantify the average carbon footprint of a primary care consultation, describe differences between primary care practices (best, worst and average performing) in western Switzerland and identify opportunities for mitigation.

Methods

We conducted a retrospective carbon footprint analysis of ten private practices over the year 2018. We used life-cycle analysis to estimate carbon emissions of each sector, from manufacture to disposal, expressing results as CO2 equivalents per average consultation and practice. We then modelled an average and theoretical best- case and worst-case practices. Collected data included invoices, medical and furniture inventories, heating and power supply, staff and patient transport, laboratory analyses (in/out-house) waste quantities and management costs.

Results

An average medical consultation generated 4.8 kg of CO2eq and overall, an average practice produced 30 tons of CO2eq per year, with 45.7% for staff and patient transport and 29.8% for heating. Medical consumables produced 5.5% of CO2eq emissions, while in-house laboratory and X-rays contributed less than 1% each. Emergency analyses requiring courier transport caused 5.8% of all emissions. Support activities generated 82.6% of the total CO2eq. Simulation of best- and worst-case scenarios resulted in a ten-fold variation in CO2eq emissions.

Conclusion

Optimizing structural and organisational aspects of practice work could have a major impact on the carbon footprint of primary care practices without large-scale changes in medical activities.
The risk of perchlorate and iodine on the incidence of thyroid tumors and nodular goiter: a case-control study in southeastern China
Authors: Wang Huirong , Jiang Yousheng , Song Jiayi , Liang Huiwen , Liu Yuan , Huang Jiewu , Yin Pengliang , Wu Dongting , Zhang Hang , Liu Xinjie , Zhou Dongxian , Wei Wei , Lei Lin , Peng Ji , Zhang Jianqing
Published: January 2022

Background

The incidence rates of thyroid tumors and nodular goiter show an upward trend worldwide. There are limited reports on the risk of perchlorate and iodine on thyroid tumors, but evidence from population studies is scarce, and their impact on thyroid function is still uncertain. Therefore, the objective of this study was to investigate the association of perchlorate and iodine with the risk of nodular goiter (NG), papillary thyroid microcarcinoma (PTMC), and papillary thyroid carcinoma (PTC) and to assess the correlation between perchlorate and iodine with thyroid function indicators.

Methods

A case–control population consisting of 184 pairs of thyroid tumors and nodular goiter matched by gender and age (±2 years) was recruited in this study. Serum and urine samples were collected from each participant. Thyroid function indicators in serum were tested by automatic chemical immunofluorescence, and perchlorate and iodine levels in urine were determined by ultra-high performance liquid chromatography tandem-mass spectrometry and inductively coupled plasma-mass spectrometry, respectively. Conditional logistic regressions and multiple linear regressions were used to analyze the associations.

Results

Urinary perchlorate concentration was significantly higher in total cases, NG and PTC than in the corresponding controls (P < 0.05). Perchlorate was positively associated with PTC (OR = 1.058, 95% CI: 1.009, 1.110) in a non-linear dose–response relationship, but there was no association between perchlorate and NG or PTMC. Iodine was not associated with the risk of thyroid tumors and NG and did not correlate with the thyroid function indicators. Furthermore, perchlorate showed a positive correlation with thyroid stimulating hormone (TSH) at iodine adequate levels (P < 0.05), and a negative correlation with free triiodothyronine (FT3) and a positive correlation with thyroglobulin antibody (TgAb) at iodine more than adequate or excess levels (P < 0.05).

Conclusions

Perchlorate can increase the risk of PTC in a non-linear dose–response relationship and disturb the thyroid hormone homeostasis and thyroid autoantibody levels.
Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis
Authors: Wang Mengling , Zeng Feng , Ning Fengling , Wang Yinhang , Zhou Shilin , He Jiaqi , Li Cong , Wang Cong , Sun Xiaolin , Zhang Dongliang , Xiao Jisheng , Hu Ping , Reilly Svetlana , Xin Hong , Xu Xudong , Zhang Xuemei
Published: January 2022

Background and aims

Renal fibrosis is the common outcome in all progressive forms of chronic kidney disease. Unfortunately, the pathogenesis of renal fibrosis remains largely unexplored, among which metabolic reprogramming plays an extremely crucial role in the evolution of renal fibrosis. Ceria nanoparticles (CeNP-PEG) with strong ROS scavenging and anti-inflammatory activities have been applied for mitochondrial oxidative stress and inflammatory diseases. The present study aims to determine whether CeNP-PEG has therapeutic value for renal fibrosis.

Methods

The unilateral ureteral obstructive fibrosis model was used to assess the therapeutic effects in vivo. Transforming growth factor beta1-induced epithelial-to-mesenchymal transition in HK-2 cells was used as the in vitro cell model. The seahorse bioscience X96 extracellular flux analyzer was used to measure the oxygen consumption rate and extracellular acidification rate.

Results

In the present study, CeNP-PEG treatment significantly ameliorated renal fibrosis by increased E-cadherin protein expression, and decreased α-SMA, Vimentin and Fibronectin expression both in vitro and in vivo. Additionally, CeNP-PEG significantly reduced the ROS formation and improved the levels of mitochondrial ATP. The seahorse analyzer assay demonstrated that the extracellular acidification rate markedly decreased, whereas the oxygen consumption rate markedly increased, in the presence of CeNP-PEG. Furthermore, the mitochondrial membrane potential markedly enhanced, hexokinase 1 and hexokinase 2 expression significantly decreased after treatment with CeNP-PEG.

Conclusions

CeNP-PEG can block the dysregulated metabolic status and exert protective function on renal fibrosis. This may provide another therapeutic option for renal fibrosis.

Graphical Abstract
Nanomedicine-enabled chemotherapy-based synergetic cancer treatments
Authors: Wu Wencheng , Pu Yinying , Shi Jianlin
Published: January 2022

Chemotherapy remains one of the most prevailing regimens hitherto in the fight against cancer, but its development has been being suffering from various fatal side effects associated with the non-specific toxicity of common chemical drugs. Advances in biomedical application of nanomedicine have been providing alternative but promising approaches for cancer therapy, by leveraging its excellent intrinsic physicochemical properties to address these critical concerns. In particular, nanomedicine-enabled chemotherapy has been established as a safer and promising therapeutic modality, especially the recently proposed nanocatalytic medicine featuring the capabilities to generate toxic substances by initiating diverse catalytic reactions within the tumor without directly relying on highly toxic but non-selective chemotherapeutic agents. Of special note, under exogenous/endogenous stimulations, nanomedicine can serve as a versatile platform that allows additional therapeutic modalities (photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), etc.) to be seamlessly integrated with chemotherapy for efficacious synergistic treatments of tumors. Here, we comprehensively review and summarize the representative studies of multimodal synergistic cancer treatments derived from nanomedicine and nanocatalytic medicine-enabled chemotherapy in recent years, and their underlying mechanisms are also presented in detail. A number of existing challenges and further perspectives for nanomedicine-synergized chemotherapy for malignant solid tumor treatments are also highlighted for understanding this booming research area as comprehensively as possible.

Graphical Abstract
Conjugation of VEGFR1/R2-targeting peptide with gold nanoparticles to enhance antiangiogenic and antitumoral activity
Authors: Zanjanchi Pegah , Asghari S. Mohsen , Mohabatkar Hassan , Shourian Mostafa , Shafiee Ardestani Mehdi
Published: January 2022

Background

Inhibition of tumor angiogenesis through simultaneous targeting of vascular endothelial growth factor receptor (VEGFR)-1 and -2 is highly efficacious. An antagonist peptide of VEGFA/VEGFB, referred to as VGB3, can recognize and neutralize both VEGFR1 and VEGFR2 on the endothelial and tumoral cells, thereby inhibits angiogenesis and tumor growth. However, improved efficacy and extending injection intervals is required for its clinical translation. Given that gold nanoparticles (GNPs) can enhance the efficacy of biotherapeutics, we conjugated VGB3 to GNPs to enhance its efficacy and extends the intervals between treatments without adverse effects.

Results

GNP–VGB3 bound to VEGFR1 and VEGFR2 in human umbilical vein endothelial (HUVE) and 4T1 mammary carcinoma cells. GNP–VGB3 induced cell cycle arrest, ROS overproduction and apoptosis and inhibited proliferation and migration of endothelial and tumor cells more effectively than unconjugated VGB3 or GNP. In a murine 4T1 mammary carcinoma tumor model, GNP–VGB3 more strongly than VGB3 and GNP inhibited tumor growth and metastasis, and increased animal survival without causing weight loss. The superior antitumor effects were associated with durable targeting of VEGFR1 and VEGFR2, thereby inhibiting signaling pathways of proliferation, migration, differentiation, epithelial-to-mesenchymal transition, and survival in tumor tissues. MicroCT imaging and inductively coupled plasma mass spectrometry showed that GNP–VGB3 specifically target tumors and exhibit greater accumulation within tumors than the free GNPs.

Conclusion

Conjugation to GNPs not only improved the efficacy of VGB3 peptide but also extended the intervals between treatments without adverse effects. These results suggest that GNP–VGB3 is a promising candidate for clinical translation.

Graphical Abstract
pH-switchable nanozyme cascade catalysis: a strategy for spatial–temporal modulation of pathological wound microenvironment to rescue stalled healing in diabetic ulcer
Authors: Du Xuancheng , Jia Bingqing , Wang Weijie , Zhang Chengmei , Liu Xiangdong , Qu Yuanyuan , Zhao Mingwen , Li Weifeng , Yang Yanmei , Li Yong-Qiang
Published: January 2022

The management of diabetic ulcer (DU) to rescue stalled wound healing remains a paramount clinical challenge due to the spatially and temporally coupled pathological wound microenvironment that features hyperglycemia, biofilm infection, hypoxia and excessive oxidative stress. Here we present a pH-switchable nanozyme cascade catalysis (PNCC) strategy for spatial–temporal modulation of pathological wound microenvironment to rescue stalled healing in DU. The PNCC is demonstrated by employing the nanozyme of clinically approved iron oxide nanoparticles coated with a shell of glucose oxidase (Fe3O4-GOx). The Fe3O4-GOx possesses intrinsic glucose oxidase (GOx), catalase (CAT) and peroxidase (POD)-like activities, and can catalyze pH-switchable glucose-initiated GOx/POD and GOx/CAT cascade reaction in acidic and neutral environment, respectively. Specifically, the GOx/POD cascade reaction generating consecutive fluxes of toxic hydroxyl radical spatially targets the acidic biofilm (pH ~ 5.5), and eradicates biofilm to shorten the inflammatory phase and initiate normal wound healing processes. Furthermore, the GOx/CAT cascade reaction producing consecutive fluxes of oxygen spatially targets the neutral wound tissue, and accelerates the proliferation and remodeling phases of wound healing by addressing the issues of hyperglycemia, hypoxia, and excessive oxidative stress. The shortened inflammatory phase temporally coupled with accelerated proliferation and remodeling phases significantly speed up the normal orchestrated wound-healing cascades. Remarkably, this Fe3O4-GOx-instructed spatial–temporal remodeling of DU microenvironment enables complete re-epithelialization of biofilm-infected wound in diabetic mice within 15 days while minimizing toxicity to normal tissues, exerting great transformation potential in clinical DU management. The proposed PNCC concept offers a new perspective for complex pathological microenvironment remodeling, and may provide a powerful modality for the treatment of microenvironment-associated diseases.

Graphical Abstract
A novel therapeutic strategy of multimodal nanoconjugates for state-of-the-art brain tumor phototherapy
Authors: Kim Hyung Shik , Seo Minwook , Park Tae-Eun , Lee Dong Yun
Published: January 2022

Background

The outcome of phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT) for glioblastoma multiforme (GBM), is disappointing due to insufficient photoconversion efficiency and low targeting rate. The development of phototherapeutic agents that target GBM and generate high heat and potent ROS is important to overcome the weak anti-tumor effect.

Results

In this study, nanoconjugates composed of gold nanoparticles (AuNPs) and photosensitizers (PSs) were prepared by disulfide conjugation between Chlorin e6 (Ce6) and glutathione coated-AuNP. The maximum heat dissipation of the nanoconjugate was 64.5 ± 4.5 °C. Moreover, the proximate conjugation of Ce6 on the AuNP surface resulted in plasmonic crossover between Ce6 and AuNP. This improves the intrinsic ROS generating capability of Ce6 by 1.6-fold compared to that of unmodified-Ce6. This process is called generation of metal-enhanced reactive oxygen species (MERos). PEGylated-lactoferrin (Lf-PEG) was incorporated onto the AuNP surface for both oral absorption and GBM targeting of the nanoconjugate (denoted as Ce6-AuNP-Lf). In this study, we explored the mechanism by which Ce6-AuNP-Lf interacts with LfR at the intestinal and blood brain barrier (BBB) and penetrates these barriers with high efficiency. In the orthotopic GBM mice model, the oral bioavailability and GBM targeting amount of Ce6-AuNP-Lf significantly improved to 7.3 ± 1.2% and 11.8 ± 2.1 μg/kg, respectively. The order of laser irradiation, such as applying PDT first and then PTT, was significant for the treatment outcome due to the plasmonic advantages provided by AuNPs to enhance ROS generation capability. As a result, GBM-phototherapy after oral administration of Ce6-AuNP-Lf exhibited an outstanding anti-tumor effect due to GBM targeting and enhanced photoconversion efficiency.

Conclusions

The designed nanoconjugates greatly improved ROS generation by plasmonic crossover between AuNPs and Ce6, enabling sufficient PDT for GBM as well as PTT. In addition, efficient GBM targeting through oral administration was possible by conjugating Lf to the nanoconjugate. These results suggest that Ce6-AuNP-Lf is a potent GBM phototherapeutic nanoconjugate that can be orally administered.

Graphical Abstract
Quaternary ammonium iminofullerenes improve root growth of oxidative-stress maize through ASA-GSH cycle modulating redox homeostasis of roots and ROS-mediated root-hair elongation
Authors: Tai Fuju , Wang Shuai , Liang Benshuai , Li Yue , Wu Jiakai , Fan Chenjie , Hu Xiuli , Wang Hezhong , He Rui , Wang Wei
Published: January 2022

Background

Various environmental factors are capable of oxidative stress to result in limiting plant development and agricultural production. Fullerene-based carbon nanomaterials can enable radical scavenging and positively regulate plant growth. Even so, to date, our knowledge about the mechanism of fullerene-based carbon nanomaterials on plant growth and response to oxidative stress is still unclear.

Results

20 or 50 mg/L quaternary ammonium iminofullerenes (IFQA) rescued the reduction in root lengths and root-hair densities and lengths of Arabidopsis and maize induced by accumulation of endogenous hydrogen peroxide (H2O2) under 3-amino-1,2,4-triazole or exogenous H2O2 treatment, as well as the root active absorption area and root activity under exogenous H2O2 treatment. Meanwhile, the downregulated contents of ascorbate acid (ASA) and glutathione (GSH) and the upregulated contents of dehydroascorbic acid (DHA), oxidized glutathione (GSSG), malondialdehyde (MDA), and H2O2 indicated that the exogenous H2O2 treatment induced oxidative stress of maize. Nonetheless, application of IFQA can increase the ratios of ASA/DHA and GSH/GSSG, as well as the activities of glutathione reductase, and ascorbate peroxidase, and decrease the contents of H2O2 and MDA. Moreover, the root lengths were inhibited by buthionine sulfoximine, a specific inhibitor of GSH biosynthesis, and subsequently rescued after addition of IFQA. The results suggested that IFQA could alleviate exogenous-H2O2-induced oxidative stress on maize by regulating the ASA-GSH cycle. Furthermore, IFQA reduced the excess accumulation of ROS in root hairs, as well as the NADPH oxidase activity under H2O2 treatment. The transcript levels of genes affecting ROS-mediated root-hair development, such as RBOH B, RBOH C, PFT1, and PRX59, were significantly induced by H2O2 treatment and then decreased after addition of IFQA.

Conclusion

The positive effect of fullerene-based carbon nanomaterials on maize-root-hair growth under the induced oxidative stress was discovered. Application IFQA can ameliorate oxidative stress to promote maize-root growth through decreasing NADPH-oxidase activity, improving the scavenging of ROS by ASA-GSH cycle, and regulating the expressions of genes affecting maize-root-hair development. It will enrich more understanding the actual mechanism of fullerene-based nanoelicitors responsible for plant growth promotion and protection from oxidative stress.

Graphical Abstract
Mn doped Prussian blue nanoparticles for T1/T2 MR imaging, PA imaging and Fenton reaction enhanced mild temperature photothermal therapy of tumor
Authors: Tao Quan , He Genghan , Ye Sheng , Zhang Di , Zhang Zhide , Qi Li , Liu Ruiyuan
Published: January 2022

Background

Combining the multimodal imaging and synergistic treatment in one platform can enhance the therapeutic efficacy and diagnosis accuracy.

Results

In this contribution, innovative Mn-doped Prussian blue nanoparticles (MnPB NPs) were prepared via microemulsion method. MnPB NPs demonstrated excellent T1 and T2 weighted magnetic resonance imaging (MRI) enhancement in vitro and in vivo. The robust absorbance in the near infrared range of MnPB NPs provides high antitumor efficacy for photothermal therapy (PTT) and photoacoustics imaging property. Moreover, with the doping of Mn, MnPB NPs exhibited excellent Fenton reaction activity for chemodynamic therapy (CDT). The favorable trimodal imaging and Fenton reaction enhanced mild temperature photothermal therapy in vitro and in vivo were further confirmed that MnPB NPs have significant positive effectiveness for integration of diagnosis and treatment tumor.

Conclusions

Overall, this Mn doped Prussian blue nanoplatform with multimodal imaging and chemodynamic/mild temperature photothermal co-therapy provides a reliable tool for tumor treatment.

Graphical Abstract
Screening and analysis of RNAs associated with activated memory CD4 and CD8 T cells in liver cancer
Authors: Yan Zhang , Lijuan Yin , Yinhang Wu , Yin Jin , Jiamin Xu , Wei Wu , Yuefen Pan , Shuwen Han
Published: January 2022

Background

Liver cancer is one of the most common malignant tumors in the world. T cell-mediated antitumor immune response is the basis of liver cancer immunotherapy.

Objective

To screen and analyze the RNAs associated with activated memory CD4 T cells and CD8 T cells in liver cancer.

Methods

ESTIMATE was used to calculate the stromal and immune scores of tumor samples, which were downloaded from The Cancer Genome Atlas (TCGA). The differentially expressed genes (DEGs) in high and low stromal and immune scores were screened, followed by functional enrichment of overlapped DEGs. We then conducted a survival analysis to identify immune-related prognostic indicators and constructed protein-protein interaction (PPI) networks and ceRNA networks. Finally, chemical small-molecule–target interaction pairs associated with liver cancer were screened.

Results

A total of 55,955 stromal-related DEGs and 1811 immune-related DEGs were obtained. The 1238 overlapped DEGs were enriched in 1457 biological process terms and 74 KEGG pathways. In addition, a total of 120 activated memory CD4 T cell-related genes and 309 CD8 T cell-related genes were identified. The survival analysis revealed that upregulated expression of T cell-related genes including EOMES, CST7, and CD5L indicated the favorable prognosis of liver cancer. EOMES was regulated by has-miR-23b-3p and has-miR-23b-3p was regulated by lncRNA AC104820.2 in the ceRNA network of activated memory CD4 T cell-related genes. In addition, EOMES was regulated by has-miR-23a-3p and has-miR-23a-3p was regulated by lncRNA AC000476.1 in the ceRNA network of CD8 T cells.

Conclusion

T cell-related RNAs EOMES, CST7, CD5L, has-miR-23b-3p, and has-miR-23a-3p may be associated with the prognosis of liver cancer. And the molecular characteristics of these T cell-related genes were plotted.
Association between obstructive sleep apnea and venous thromboembolism recurrence: results from a French cohort
Authors: Nepveu Olivier , Orione Charles , Tromeur Cécile , Fauché Alexandre , L’heveder Cecile , Guegan Marie , Lemarié Catherine , Jimenez David , Leroyer Christophe , Lacut Karine , Couturaud Francis , Le Mao Raphael
Published: January 2022

Background

Growing evidence suggests the relationship between obstructive sleep apnea (OSA) and venous thromboembolism (VTE). Few studies focused on VTE recurrence risk associated with OSA after anticoagulation cessation.

Methods

In a prospective cohort study, patients with documented VTE, were followed for an indefinite length of time and VTE recurrence were documented and adjudicated. The primary outcome was recurrent VTE after anticoagulation discontinuation. Secondary outcomes included all-cause mortality and the clinical presentation of VTE. Univariable and multivariable analyses were performed to identify risk factors for recurrence and mortality.

Results

Among the 2109 patients with documented VTE included, 74 patients had moderate to severe OSA diagnosis confirmed by home sleep test or polysomnography. During a median follow-up of 4.8 (interquartile range 2.5–8.0) years recurrent VTE occurred in 252 patients (9 with OSA and 243 without OSA). The recurrence risk in the univariable and multivariable analysis was not increased in patients with OSA, regardless of the time of diagnosis (before or after index VTE or pooled). VTE phenotype was significantly more often PE with or without associated deep vein thrombosis in the first event and recurrence for OSA patients compared to non-OSA patients. The risk of death was not increased in the OSA population compared to non-OSA patients in multivariable analysis.

Conclusions

In patients with OSA and VTE, the risk of all-cause mortality and VTE recurrence after anticoagulation discontinuation was not increased compared to non-OSA patients.
On the measurement of healthy lifespan inequality
Authors: Permanyer Iñaki , Spijker Jeroen , Blanes Amand
Published: January 2022

Background

Current measures to monitor population health include indicators of (i) average length-of-life (life expectancy), (ii) average length-of-life spent in good health (health expectancy), and (iii) variability in length-of-life (lifespan inequality). What is lacking is an indicator measuring the extent to which healthy lifespans are unequally distributed across individuals (the so-called ‘healthy lifespan inequality’ indicators).

Methods

We combine information on age-specific survival with the prevalence of functional limitation or disability in Spain (2014–2017) by sex and level of education to estimate age-at-disability onset distributions. Age-, sex- and education-specific prevalence rates of adult individuals’ daily activities limitations were based on the GALI index derived from Spanish National Health Surveys held in 2014 and 2017. We measured inequality using the Gini index.

Results

In contemporary Spain, education differences in health expectancy are substantial and greatly exceed differences in life expectancy. The female advantage in life expectancy disappears when considering health expectancy indicators, both overall and across education groups. The highly educated exhibit lower levels of lifespan inequality, and lifespan inequality is systematically higher among men. Our new healthy lifespan inequality indicators suggest that the variability in the ages at which physical daily activity limitations start are substantially larger than the variability in the ages at which individuals die. Healthy lifespan inequality tends to decrease with increasing educational attainment, both for women and for men. The variability in ages at which physical limitations start is slightly higher for women than for men.

Conclusions

The suggested indicators uncover new layers of health inequality that are not traceable with currently existing approaches. Low-educated individuals tend to not only die earlier and spend a shorter portion of their lives in good health than their highly educated counterparts, but also face greater variation in the eventual time of death and in the age at which they cease enjoying good health—a multiple burden of inequality that should be taken into consideration when evaluating the performance of public health systems and in the elaboration of realistic working-life extension plans and the design of equitable pension reforms.
Neuroinflammation as an etiological trigger for depression comorbid with inflammatory bowel disease
Authors: Craig Colin F. , Filippone Rhiannon T. , Stavely Rhian , Bornstein Joel C. , Apostolopoulos Vasso , Nurgali Kulmira
Published: January 2022

Patients with inflammatory bowel disease (IBD) suffer from depression at higher rates than the general population. An etiological trigger of depressive symptoms is theorised to be inflammation within the central nervous system. It is believed that heightened intestinal inflammation and dysfunction of the enteric nervous system (ENS) contribute to impaired intestinal permeability, which facilitates the translocation of intestinal enterotoxins into the blood circulation. Consequently, these may compromise the immunological and physiological functioning of distant non-intestinal tissues such as the brain. In vivo models of colitis provide evidence of increased blood–brain barrier permeability and enhanced central nervous system (CNS) immune activity triggered by intestinal enterotoxins and blood-borne inflammatory mediators. Understanding the immunological, physiological, and structural changes associated with IBD and neuroinflammation may aid in the development of more tailored and suitable pharmaceutical treatment for IBD-associated depression.
Perceptions of cervical cancer care among Ethiopian women and their providers: a qualitative study
Authors: Burrowes Sahai , Holcombe Sarah Jane , Leshargie Cheru Tesema , Hernandez Alexandra , Ho Anthony , Galivan Molly , Youb Fatuma , Mahmoud Eiman
Published: January 2022

Background

Cervical cancer is the second most commonly diagnosed cancer among Ethiopian women, killing an estimated 4700 women each year. As the government rolls out the country’s first national cancer control strategy, information on patient and provider experiences in receiving and providing cervical cancer screening, diagnosis, and treatment is critical.

Methods

This qualitative study aimed to assess the availability of cervical cancer care; explore care barriers and sources of delay; and describe women’s and providers’ perceptions and experiences of care. We analyzed data from 45 informants collected at 16 health centers, district hospitals and referral hospitals in East Gojjam Zone and a support center in Addis Ababa. Thirty providers and ten women receiving care were interviewed, and five women in treatment or post-treatment participated in a focus group discussion. Deductive and inductive codes were used to thematically analyze data.

Results

Providers lacked equipment and space to screen and treat patients and only 16% had received in-service cervical cancer training. Consequently, few facilities provided screening or preventative treatment. Patients reported low perceptions of risk, high stigma, a lack of knowledge about cervical cancer, and delayed care initiation. All but one patient sought care only when she became symptomatic, and, pre-diagnosis, only half of the patients knew about cervical cancer. Even among those aware of cervical cancer, many assumed they were not at risk because they were not sexually active. Misdiagnosis was another common source of delay experienced by half of the patients. Once diagnosed, women faced multiple-month waits for referrals, and, once in treatment, broken equipment and shortages of hospital beds resulted in additional delays. Barriers to therapeutic treatment included a lack of housing and travel funds. Patient-provider communication of cancer diagnosis was often lacking.

Conclusions

In-service provider training should be intensified and should include discussions of cervical cancer symptoms. Better distribution of screening and diagnostic supplies to lower-level facilities and better maintenance of treatment equipment at tertiary facilities are also a priority. Expanded cervical cancer health education should focus on stigma reduction and emphasize a broad, wide-spread risk of cervical cancer.