bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient-centered outcomes and outcome measurements for people aged 65 years and older—a scoping review
Authors: Andersson Åsa G. , Dahlkvist Lisabet , Kurland Lisa
Published: June 2024

Introduction

The aging population is a challenge for the healthcare system that must identify strategies that meet their needs. Practicing patient-centered care has been shown beneficial for this patient-group. The effect of patient-centered care is called patient-centered outcomes and can be appraised using outcomes measurements.

Objectives

The main aim was to review and map existing knowledge related to patient-centered outcomes and patient-centered outcomes measurements for older people, as well as identify key-concepts and knowledge-gaps. The research questions were: How can patient-centered outcomes for older people be measured, and which patient-centered outcomes matters the most for the older people?

Study design

Scoping review.

Methods

Search for relevant publications in electronical databases, grey literature databases and websites from year 2000 to 2021. Two reviewers independently screened titles and abstracts, followed by full text review and extraction of data using a data extraction framework.

Results

Eighteen studies were included, of which six with involvement of patients and/or experts in the process on determine the outcomes. Outcomes that matter the most to older people was interpreted as: access to- and experience of care, autonomy and control, cognition, daily living, emotional health, falls, general health, medications, overall survival, pain, participation in decision making, physical function, physical health, place of death, social role function, symptom burden, and time spent in hospital. The most frequently mentioned/used outcomes measurements tools were the Adult Social Care Outcomes Toolkit (ASCOT), EQ-5D, Gait Speed, Katz- ADL index, Patient Health Questionnaire (PHQ9), SF/RAND-36 and 4-Item Screening Zarit Burden Interview.

Conclusions

Few studies have investigated the older people’s opinion of what matters the most to them, which forms a knowledge-gap in the field. Future research should focus on providing older people a stronger voice in what they think matters the most to them.
Experiences of family caregivers taking care getting lost of persons with dementia: a qualitative study
Authors: Li Shu-Hui , Wu Shu-Fang Vivienne , Liu Chieh-Yu , Lin Chiou-Fen , Lin Hung-Ru
Published: June 2024

Background

Getting lost with family members who have dementia is a significant source of stress for family caregivers. In Taiwan, family caregivers develop strategies to deal with dementia persons who may get lost. This study aimed to explore the experiences of family caregivers caring for persons with dementia who have been lost outside the home.

Methods

A descriptive phenomenological method was used. The COREQ checklist was used to ensure the explicit reporting of data. A total of 20 family caregivers caring for persons with dementia who were lost outside their homes were selected from hospital outpatient clinics and a day care center in northern Taiwan using purposive sampling. Data were analyzed using the Giorgi analysis method.

Results

Five main themes emerged: (i) surprised persons with dementia lost outside, (ii) using strategies to prevent persons with dementia from getting lost, (iii) using strategies to find lost persons with dementia, (iv) exhaustion in long-term care persons with dementia, and (v) coping with the care load. It was found that family caregivers were surprised, nervous, and worried about persons with dementia being lost outside. They used the first strategy to supervise persons with dementia to prevent external losses. In addition, long-term supervision of persons with dementia led to mental exhaustion in the family caregivers. Finally, the family caregivers learned about loss prevention strategies and obtained family support and care replacement workers to reduce the care burden.

Conclusions

It is essential to teach family caregivers early to prevent persons with dementia from losing external strategies. Nurses also provide long-term care services to reduce the care burden on family caregivers.
The longitudinal dispositions of people diagnosed with adjustment or severe stress disorders
Authors: Poremski Daniel , Hariram Jayaraman , Wong Wei Kang , EU Pui Wai , Lee Cheng
Published: June 2024

Background

Adjustment and stress-related disorders are prevalent among psychiatric service users. Despite their prevalence, little is known about their prognosis. To reduce that gap, the present article documents the service use and diagnostic outcomes of people with adjustment or stress-related disorders presenting at Singapore’s largest psychiatric emergency department.

Methods

Administrative data from 2014 to 2021 was retrieved to follow a group of 683 service users whose first-ever psychiatric presentation in 2014 warranted a diagnosis of adjustment or stress-related disorder. People were grouped a priori depending on whether different diagnoses were recorded within 7 days, 9 months, after 9 months or not at all. Survival curves characterized conversion to other diagnoses and engagement with healthcare services. Service use outcomes include the number of hospitalizations, outpatient appointments, emergency department visits, and prescriptions.

Results

Sixty-one percent (n = 417) never received another diagnosis over the 8-year period. This group used emergency services most and received the most pharmacotherapy shortly after their first visit. Of those who received another diagnosis, depression, personality disorders, and psychotic disorders were the most common. Those who received another diagnosis within 7 days (n = 70, 10%) received it on their first day of hospitalization (IQR 1–1), making the most use of inpatient services. The group who received another diagnosis within 9 months (n = 105, 15%) did so after 42 days (IQR 26–84) and had the highest relative number of deaths. Those who received another diagnosis after 9 months (n = 91, 13%) did so after 1,134 days (IQR 613–1,823) and had the longest period of engagement but made the least use of any psychiatric service, potentially suggesting a group whose early index diagnosis heralded vulnerability to future disorders.

Conclusions

A large group of service users with acute stress or adjustment disorders will likely never be given another psychiatric diagnosis and appear to disengage following an initial period of high-intensity service use. The group that received a different diagnosis after the 9-month mark had prolonged contact with services but low intensity of service use and may represent a target for preventative intervention to help them improve their stress-managing skills and avoid developing other disorders.
Do health literacy, physical health and past rehabilitation utilization explain educational differences in the subjective need for medical rehabilitation? Results of the lidA cohort study
Authors: Prel Jean-Baptist du , Rohrbacher Max , Schröder Chloé Charlotte , Breckenkamp Jürgen
Published: June 2024

Background

Medical rehabilitation can be helpful for maintaining workers’ health and work ability. Its contribution to longer working lives is of high economic relevance in aging populations. In Germany, individuals must apply for rehabilitative measures themselves. Therefore, the subjective need for rehabilitation (SNR) is a prerequisite for rehabilitation access. A low education level is associated with poor health, lower health literacy and more frequent utilization of health services. In the present study, we investigated whether lower educational levels are also associated with a greater SNR and whether health literacy, past rehabilitation utilization and physical health play a mediating role in this path in older employees.

Methods

3,130 socially insured older employees (born in 1959 or 1965) who participated in the German prospective lidA (leben in der Arbeit) cohort-study in 2011, 2014 and 2018 were included. A causal mediation analysis with an inverse odds weighting approach was performed with the SNR as the dependent variable; educational level as the independent variable; and health, health literacy and past rehabilitation utilization as the mediating variables. Sociodemographic variables were adjusted for.

Results

The SNR was significantly greater in subjects with a low education level, poor physical health, inadequate health literacy and those who had utilized rehabilitation in the past. For health literacy, past rehabilitation utilization and physical health, a significant partial mediating effect on the SNR was found for employees with low compared to those with high education levels. However, the combined mediating effect of all the mediators was lower than the sum of their individual effects. Among those with medium or high education levels, none of the variables constituted a significant mediator.

Conclusions

The path between a low education level and a high SNR is mediated by inadequate health literacy, past rehabilitation utilization and poor physical health; these factors do not act independently of each other. Promoting health education may lower the SNR by improving physical health and health literacy. While improving physical health is beneficial for individuals, improved health literacy can be economically advantageous for the health system by reducing inappropriate expectations of rehabilitation benefits and subsequent applications for rehabilitation.
The regulatory effect of zinc on the association between periodontitis and atherosclerotic cardiovascular disease: a cross-sectional study based on the National Health and Nutrition Examination Survey
Authors: Yang Xiuxiu , Luo Maoyu , Jiang Yao
Published: June 2024

Background

Zinc has been proven to be effective against periodontitis, and also reported to reduce the risk of cardiovascular diseases (CVD). This study aims to explore the regulatory effect of zinc intake on the association between periodontitis and atherosclerotic cardiovascular disease (ASCVD).

Methods

This was a cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). Logistic regression model was used to explore the association between zinc-RDA or periodontitis and 10-year ASCVD risk ≥ 20%, and results were shown as odds ratio (OR) and 95% confidence interval (95% CI). The regulatory effect of zinc intake on the association between periodontitis and 10-year ASCVD risk ≥ 20% was also assessed using logistic regression model. Subgroup analysis was performed based on age, gender, obesity, education level, lipid-lowering therapy, and dental floss.

Results

6,075 patients were finally included for analysis. Zinc intake reaching the recommended level (OR = 0.82, 95%CI: 0.69–0.98) and periodontitis (OR = 2.47, 95%CI: 2.04-3.00) were found to be associated with 0.82-fold and 2.47-fold odds of 10-year ASCVD risk ≥ 20%, respectively. In addition, we found that the odds of 10-year ASCVD risk ≥ 20% was lower in patients with zinc intake reaching the recommended level than those without [OR (95%CI): 2.25 (1.81–2.80) vs. 2.72 (2.05–3.62)]. The similar regulatory effect was found in patients with age ≥ 60 years and < 60 years, in male and female, with or without obesity, in different education levels, with or without lipid lowering therapy, and with or without use of dental floss (allP < 0.05).

Conclusions

This study found the regulatory effect of adequate zinc intake on the association between periodontitis and ASCVD, providing guidance for periodontitis patients to decrease the risk of ASCVD.
Psychological distress and uterine fibroids: a bidirectional two-sample mendelian randomization study
Authors: Han Xinyu , Wu Tian qiang , Bian Yuanyuan , Chen Lu , Feng Xiaoling
Published: June 2024

Background

Observational data indicates a connection between emotional discomfort, such as anxiety and depression, and uterine fibroids (UFs). However, additional investigation is required to establish the causal relationship between them. Hence, we assessed the reciprocal causality between four psychological disorders and UFs utilizing two-sample Mendelian randomization (MR).

Methods

To evaluate the causal relationship between four types of psychological distress (depressive symptoms, severe depression, anxiety or panic attacks, mood swings) and UFs, bidirectional two-sample MR was employed, utilizing single nucleotide polymorphisms (SNPs) associated with these conditions. Both univariate MR (UVMR) and multivariate MR (MVMR) primarily applied inverse variance weighted (IVW) as the method for estimating potential causal effects. Complementary approaches such as MR Egger, weighted median, simple mode, and weighted mode were utilized to validate the findings. To assess the robustness of our MR results, we conducted sensitivity analyses using Cochran’s Q-test and the MR Egger intercept test.

Results

The results of our UVMR analysis suggest that genetic predispositions to depressive symptoms (Odds Ratio [OR] = 1.563, 95% Confidence Interval [CI] = 1.209–2.021,P = 0.001) and major depressive disorder (MDD) (OR = 1.176, 95% CI = 1.044–1.324,P = 0.007) are associated with an increased risk of UFs. Moreover, the IVW model showed a nominally significant positive correlation between mood swings (OR: 1.578; 95% CI: 1.062–2.345;P = 0.024) and UFs risk. However, our analysis did not establish a causal relationship between UFs and the four types of psychological distress. Even after adjusting for confounders like body mass index (BMI), smoking, alcohol consumption, and number of live births in the MVMR, the causal link between MDD and UFs remained significant (OR = 1.217, 95% CI = 1.039–1.425,P = 0.015).

Conclusions

Our study presents evidence supporting the causal relationship between genetic susceptibility to MDD and the incidence of UFs. These findings highlight the significance of addressing psychological health issues, particularly depression, in both the prevention and treatment of UFs.
Cognitive load theory in workplace-based learning from the viewpoint of nursing students: application of a path analysis
Authors: Tabatabaee Shakiba Sadat , Jambarsang Sara , Keshmiri Fatemeh
Published: June 2024

Purpose

The present study aimed to test the relationship between the components of the Cognitive Load Theory (CLT) including memory, intrinsic and extraneous cognitive load in workplace-based learning in a clinical setting, and decision-making skills of nursing students.

Methods

This study was conducted at Shahid Sadoughi University of Medical Sciences in 2021–2023. The participants were 151 nursing students who studied their apprenticeship courses in the teaching hospitals. The three basic components of the cognitive load model, including working memory, cognitive load, and decision-making as the outcome of learning, were investigated in this study. Wechsler’s computerized working memory test was used to evaluate working memory. Cognitive Load Inventory for Handoffs including nine questions in three categories of intrinsic cognitive load, extraneous cognitive load, and germane cognitive load was used. The clinical decision-making skills of the participants were evaluated using a 24-question inventory by Lowry et al. based on a 5-point scale. The path analysis of AMOS 22 software was used to examine the relationships between components and test the model.

Findings

In this study, the goodness of fit of the model based on the cognitive load theory was reported (GIF = 0.99, CFI = 0.99, RMSEA = 0.03). The results of regression analysis showed that the scores of decision-making skills in nursing students were significantly related to extraneous cognitive load scores (p-value = 0.0001). Intrinsic cognitive load was significantly different from the point of view of nursing students in different academic years (p = 0.0001).

Conclusion

The present results showed that the CLT in workplace-based learning has a goodness of fit with the components of memory, intrinsic cognitive load, extraneous cognitive load, and clinical decision-making skill as the key learning outcomes in nursing education. The results showed that the relationship between nursing students’ decision-making skills and extraneous cognitive load is stronger than its relationship with intrinsic cognitive load and memory Workplace-based learning programs in nursing that aim to improve students’ decision-making skills are suggested to manage extraneous cognitive load by incorporating cognitive load principles into the instructional design of clinical education.
Concept analysis of conscience-based nursing care: a hybrid approach of Schwartz-Barcott and Kim’s hybrid model
Authors: Kalantari Soheyla , Modanloo Mahnaz , Ebadi Abbas , Khoddam Homeira
Published: June 2024

Background

The nursing profession considers conscience as the foundation and cornerstone of clinical practice, which significantly influences professional decision-making and elevates the level of patient care. However, a precise definition of conscience in the nursing field is lacking, making it challenging to measure. To address this issue, this study employed the hybrid approach of Schwartz Barcott and Kim to analyze the concept of conscience-based nursing care.

Methods

This approach involves a three-phase process; theoretical, fieldwork, and analytical. A systematic literature review was conducted using electronic databases during the first phase to find relevant papers. The content of 42 articles that met the inclusion criteria was extracted to determine the attributes, antecedents, and consequences of consciousness care using thematic analysis. Based on the working definition as a product of this phase, the plan of doing the fieldwork phase was designed. During this phase, data were collected through interviews with nurses all of whom were responsible for patient care in hospitals. In this phase, 5 participants were chosen for in-depth interviewing by purposeful sampling. Data were analyzed using directed content analysis. The findings of the theoretical and fieldwork phases were integrated and the final definition was derived.

Results

The integration of the theoretical and fieldwork phases resulted in identifying four key characteristics of conscience-based nursing care. Firstly, it involves providing professional care with a conscientious approach. Secondly, ethics is at the core of conscience-based care. Thirdly, external spirituality plays a significant role in shaping one's conscience in this context. Finally, conscience-based nursing care is both endogenous and exogenous, with professional commitment being the central focus of care.

Conclusion

Conscience-based nursing care is an essential component of ethical care, which elevates clinical practice to professional care. It requires the integration of individual and social values, influenced by personal beliefs and cultural backgrounds, and supported by professional competence, resources, and a conducive organizational atmosphere in the healthcare field. This approach leads to the provision of responsive care, moral integrity, and individual excellence, ultimately culminating in the development of professionalism in nursing.
Associations of neighborhood sociodemographic environment with mortality and circulating metabolites among low-income black and white adults living in the southeastern United States
Authors: Deng Kui , Xu Meng , Sahinoz Melis , Cai Qiuyin , Shrubsole Martha J. , Lipworth Loren , Gupta Deepak K. , Dixon Debra D. , Zheng Wei , Shah Ravi , Yu Danxia
Published: June 2024

Background

Residing in a disadvantaged neighborhood has been linked to increased mortality. However, the impact of residential segregation and social vulnerability on cause-specific mortality is understudied. Additionally, the circulating metabolic correlates of neighborhood sociodemographic environment remain unexplored. Therefore, we examined multiple neighborhood sociodemographic metrics, i.e., neighborhood deprivation index (NDI), residential segregation index (RSI), and social vulnerability index (SVI), with all-cause and cardiovascular disease (CVD) and cancer-specific mortality and circulating metabolites in the Southern Community Cohort Study (SCCS).

Methods

The SCCS is a prospective cohort of primarily low-income adults aged 40–79, enrolled from the southeastern United States during 2002–2009. This analysis included self-reported Black/African American or non-Hispanic White participants and excluded those who died or were lost to follow-up ≤ 1 year. Untargeted metabolite profiling was performed using baseline plasma samples in a subset of SCCS participants.

Results

Among 79,631 participants, 23,356 deaths (7214 from CVD and 5394 from cancer) were documented over a median 15-year follow-up. Higher NDI, RSI, and SVI were associated with increased all-cause, CVD, and cancer mortality, independent of standard clinical and sociodemographic risk factors and consistent between racial groups (standardized HRs among all participants were 1.07 to 1.20 in age/sex/race-adjusted model and 1.04 to 1.08 after comprehensive adjustment; all P < 0.05/3 except for cancer mortality after comprehensive adjustment). The standard risk factors explained < 40% of the variations in NDI/RSI/SVI and mediated < 70% of their associations with mortality. Among 1110 circulating metabolites measured in 1688 participants, 134 and 27 metabolites were associated with NDI and RSI (all FDR < 0.05) and mediated 61.7% and 21.2% of the NDI/RSI-mortality association, respectively. Adding those metabolites to standard risk factors increased the mediation proportion from 38.4 to 87.9% and 25.8 to 42.6% for the NDI/RSI-mortality association, respectively.

Conclusions

Among low-income Black/African American adults and non-Hispanic White adults living in the southeastern United States, a disadvantaged neighborhood sociodemographic environment was associated with increased all-cause and CVD and cancer-specific mortality beyond standard risk factors. Circulating metabolites may unveil biological pathways underlying the health effect of neighborhood sociodemographic environment. More public health efforts should be devoted to reducing neighborhood environment-related health disparities, especially for low-income individuals.
Bovine Digital Dermatitis: Treponema spp. on trimming equipment and chutes – effect of washing and disinfection
Authors: Ahlén Lina , Holmøy Ingrid Hunter , Sogstad Åse Margrethe , Jensen Tim Kåre , Frosth Sara , Rosander Anna , Fjeldaas Terje
Published: June 2024

Background

Digital dermatitis (DD) is a contagious bovine foot disease causing reduced animal welfare and negative economic consequences for the farmer.Treponemaspp. are the most important causative agents. Studies indicate that trimming equipment can transfer DD-associated treponemes between cows. The aim of this observational study in 22 DD-positive Norwegian dairy herds was to investigate the risk of transferringTreponemaspp. with trimming equipment and chutes after claw trimming, and after washing and disinfection. Swabs from the trimming equipment and chutes were collected from nine different locations, at five different time points. Bacterial DNA was extracted from 647 swabs and analysed by qPCR forTreponemaspp. In addition, 172 swabs taken immediately after trimming, were analysed by a multiplex qPCR targetingT. phagedenis,T. pedisandT. medium/vincentii.Biopsy sampling from DD lesions was performed on cows in the same herds during trimming. Altogether 109 biopsies were analysed by FISH for confirmation of the DD diagnosis and identification ofTreponemaphylotypes (PTs).

Results

High numbers ofTreponemaspp. were detected from all nine locations on the trimming equipment and chutes immediately after trimming, andT. phagedeniswas detected on two or more locations in all but two herds, 1 and 19. There was a decline in the amount ofTreponemaspp. after washing and disinfection. The belly belt, the cuff, and the footrest on the chute had the highest proportion of positive samples after disinfection. The belly belt had the highest copy numbers of all nine locations (median = 7.9, max = 545.1). NoTreponemaspp. was detected on the hoof knives after disinfection.Treponema phagedenis, T. pedis, andTreponemaphylotype 3 (T. refringens) were detected by FISH analysis of the biopsies.Treponema phagedeniswas detected in biopsies from all herds except 1 and 19.

Conclusion

This study shows that DD-associatedTreponemaspp. were present on the trimming equipment and chutes after trimming cows in DD-positive herds. Washing and disinfection reduced the load ofTreponemaspp. However, large differences inTreponemaspp. between different locations were documented. High copy numbers on the grinder and the chute after disinfection, indicates that sufficient cleaning and disinfection of these locations is difficult, and that passive transfer of DD-associated treponemes (viable or not) is possible.
An explainable machine learning-based model to predict intensive care unit admission among patients with community-acquired pneumonia and connective tissue disease
Authors: Huang Dong , Gong Linjing , Wei Chang , Wang Xinyu , Liang Zongan
Published: June 2024

Background

There is no individualized prediction model for intensive care unit (ICU) admission on patients with community-acquired pneumonia (CAP) and connective tissue disease (CTD) so far. In this study, we aimed to establish a machine learning-based model for predicting the need for ICU admission among those patients.

Methods

This was a retrospective study on patients admitted into a University Hospital in China between November 2008 and November 2021. Patients were included if they were diagnosed with CAP and CTD during admission and hospitalization. Data related to demographics, CTD types, comorbidities, vital signs and laboratory results during the first 24 h of hospitalization were collected. The baseline variables were screened to identify potential predictors via three methods, including univariate analysis, least absolute shrinkage and selection operator (Lasso) regression and Boruta algorithm. Nine supervised machine learning algorithms were used to build prediction models. We evaluated the performances of differentiation, calibration, and clinical utility of all models to determine the optimal model. The Shapley Additive Explanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) techniques were performed to interpret the optimal model.

Results

The included patients were randomly divided into the training set (1070 patients) and the testing set (459 patients) at a ratio of 70:30. The intersection results of three feature selection approaches yielded 16 predictors. The eXtreme gradient boosting (XGBoost) model achieved the highest area under the receiver operating characteristic curve (AUC) (0.941) and accuracy (0.913) among various models. The calibration curve and decision curve analysis (DCA) both suggested that the XGBoost model outperformed other models. The SHAP summary plots illustrated the top 6 features with the greatest importance, including higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP), lower level of CD4 + T cell, lymphocyte and serum sodium, and positive serum (1,3)-β-D-glucan test (G test).

Conclusion

We successfully developed, evaluated and explained a machine learning-based model for predicting ICU admission in patients with CAP and CTD. The XGBoost model could be clinical referenced after external validation and improvement.
Volatile communication in Actinobacteria: a language for secondary metabolism regulation
Authors: Cuervo Lorena , Méndez Carmen , Salas José A. , Olano Carlos , Malmierca Mónica G.
Published: June 2024

Background

Volatile compounds are key elements in the interaction and communication between organisms at both interspecific and intraspecific levels. In complex bacterial communities, the emission of these fast-acting chemical messengers allows an exchange of information even at a certain distance that can cause different types of responses in the receiving organisms. The changes in secondary metabolism as a consequence of this interaction arouse great interest in the field of searching for bioactive compounds since they can be used as a tool to activate silenced metabolic pathways. Regarding the great metabolic potential that the Actinobacteria group presents in the production of compounds with attractive properties, we evaluated the reply the emitted volatile compounds can generate in other individuals of the same group.

Results

We recently reported that volatile compounds released by different streptomycete species trigger the modulation of biosynthetic gene clusters in Streptomyces spp. which finally leads to the activation/repression of the production of secondary metabolites in the recipient strains. Here we present the application of this rationale in a broader bacterial community to evaluate volatiles as signaling effectors that drive the activation of biosynthesis of bioactive compounds in other members of the Actinobacteria group. Using cocultures of different actinobacteria (where only the volatile compounds reach the recipient strain) we were able to modify the bacterial secondary metabolism that drives overproduction (e.g., granaticins, actiphenol, chromomycins) and/or de novo production (e.g., collismycins, skyllamycins, cosmomycins) of compounds belonging to different chemical species that present important biological activities.

Conclusions

This work shows how the secondary metabolism of different Actinobacteria species can vary significantly when exposed in co-culture to the volatile compounds of other phylum-shared bacteria, these effects being variable depending on strains and culture media. This approach can be applied to the field of new drug discovery to increase the battery of bioactive compounds produced by bacteria that can potentially be used in treatments for humans and animals.
Advances in nanomaterial-targeted treatment of acute lung injury after burns
Authors: Zhang Shuo , Zhao Xinyu , Xue Yuhao , Wang Xianwen , Chen Xu-Lin
Published: June 2024

Acute lung injury(ALI)is a common complication in patients with severe burns and has a complex pathogenesis and high morbidity and mortality rates. A variety of drugs have been identified in the clinic for the treatment of ALI, but they have toxic side effects caused by easy degradation in the body and distribution throughout the body. In recent years, as the understanding of the mechanism underlying ALI has improved, scholars have developed a variety of new nanomaterials that can be safely and effectively targeted for the treatment of ALI. Most of these methods involve nanomaterials such as lipids, organic polymers, peptides, extracellular vesicles or cell membranes, inorganic nanoparticles and other nanomaterials, which are targeted to reach lung tissues to perform their functions through active targeting or passive targeting, a process that involves a variety of cells or organelles. In this review, first, the mechanisms and pathophysiological features of ALI occurrence after burn injury are reviewed, potential therapeutic targets for ALI are summarized, existing nanomaterials for the targeted treatment of ALI are classified, and possible problems and challenges of nanomaterials in the targeted treatment of ALI are discussed to provide a reference for the development of nanomaterials for the targeted treatment of ALI.
Programmed cell death disrupts inflammatory tumor microenvironment (TME) and promotes glioblastoma evolution
Authors: Liang Tingyu , Gu Lingui , Kang Xiaoman , Li Junlin , Song Yixuan , Wang Yu , Ma Wenbin
Published: June 2024

Glioblastoma (GBM) is the most common malignant brain tumor and has a dismal prognosis even under the current first-line treatment, with a 5-year survival rate less than 7%. Therefore, it is important to understand the mechanism of treatment resistance and develop new anti-tumor strategies. Induction of programmed cell death (PCD) has become a promising anti-tumor strategy, but its effectiveness in treating GBM remains controversial. On the one hand, PCD triggers tumor cell death and then release mediators to draw in immune cells, creating a pro-inflammatory tumor microenvironment (TME). One the other hand, mounting evidence suggests that PCD and inflammatory TME will force tumor cells to evolve under survival stress, leading to tumor recurrence. The purpose of this review is to summarize the role of PCD and inflammatory TME in the tumor evolution of GBM and promising methods to overcome tumor evolution.
Bimanual coordination and spinal cord neuromodulation: how neural substrates of bimanual movements are altered by transcutaneous spinal cord stimulation
Authors: Parhizi Behdad , Barss Trevor S. , Dineros Alphonso Martin , Sivadasan Gokul , Mann Darren , Mushahwar Vivian K.
Published: June 2024

Humans use their arms in complex ways that often demand two-handed coordination. Neurological conditions limit this impressive feature of the human motor system. Understanding how neuromodulatory techniques may alter neural mechanisms of bimanual coordination is a vital step towards designing efficient rehabilitation interventions. By non-invasively activating the spinal cord, transcutaneous spinal cord stimulation (tSCS) promotes recovery of motor function after spinal cord injury. A multitude of research studies have attempted to capture the underlying neural mechanisms of these effects using a variety of electrophysiological tools, but the influence of tSCS on cortical rhythms recorded via electroencephalography remains poorly understood, especially during bimanual actions. We recruited 12 neurologically intact participants to investigate the effect of cervical tSCS on sensorimotor cortical oscillations. We examined changes in the movement kinematics during the application of tSCS as well as the cortical activation level and interhemispheric connectivity during the execution of unimanual and bimanual arm reaching movements that represent activities of daily life. Behavioral assessment of the movements showed improvement of movement time and error during a bimanual common-goal movement when tSCS was delivered, but no difference was found in the performance of unimanual and bimanual dual-goal movements with the application of tSCS. In the alpha band, spectral power was modulated with tSCS in the direction of synchronization in the primary motor cortex during unimanual and bimanual dual-goal movements and in the somatosensory cortex during unimanual movements. In the beta band, tSCS significantly increased spectral power in the primary motor and somatosensory cortices during the performance of bimanual common-goal and unimanual movements. A significant increase in interhemispheric connectivity in the primary motor cortex in the alpha band was only observed during unimanual tasks in the presence of tSCS. Our observations provide, for the first time, information regarding the supra-spinal effects of tSCS as a neuromodulatory technique applied to the spinal cord during the execution of bi- and unimanual arm movements. They also corroborate the suppressive effect of tSCS at the cortical level reported in previous studies. These findings may guide the design of improved rehabilitation interventions using tSCS for the recovery of upper-limb function in the future.
Remodeling of anti-tumor immunity with antibodies targeting a p53 mutant
Authors: Chai Dafei , Wang Junhao , Fan Chunmei , Lim Jing-Ming , Wang Xu , Neeli Praveen , Yu Xinfang , Young Ken H. , Li Yong
Published: June 2024

Background

p53, the most frequently mutated gene in cancer, lacks effective targeted drugs.

Methods

We developed monoclonal antibodies (mAbs) that target a p53 hotspot mutation E285K without cross-reactivity with wild-type p53. They were delivered using lipid nanoparticles (LNPs) that encapsulate DNA plasmids. Western blot, BLI, flow cytometry, single-cell sequencing (scRNA-seq), and other methods were employed to assess the function of mAbs in vitro and in vivo.

Results

These LNP-pE285K-mAbs in the IgG1 format exhibited a robust anti-tumor effect, facilitating the infiltration of immune cells, including CD8+ T, B, and NK cells. scRNA-seq revealed that IgG1 reduces immune inhibitory signaling, increases MHC signaling from B cells to CD8+ T cells, and enriches anti-tumor T cell and B cell receptor profiles. The E285K-mAbs were also produced in the dimeric IgA (dIgA) format, whose anti-tumor activity depended on the polymeric immunoglobulin receptor (PIGR), a membrane Ig receptor, whereas that of IgG1 relied on TRIM21, an intracellular IgG receptor.

Conclusions

Targeting specific mutant epitopes using DNA-encoded and LNP-delivered mAbs represents a potential precision medicine strategy against p53 mutants in TRIM21- or PIGR-positive cancers.
Intravesical instillation-based mTOR-STAT3 dual targeting for bladder cancer treatment
Authors: Lee Dae Hoon , Yoo Jung Ki , Um Ki Hwan , Ha Wootae , Lee Soo Min , Park Junseong , Kye Min Jeong , Suh Jungyo , Choi Jin Woo
Published: June 2024

Background

Recent intravesical administration of adenoviral vectors, either as a single injection or in combination with immune checkpoint inhibitors, exemplified by cretostimogene grenadenorepvec and nadofaragene firadenovec, has demonstrated remarkable efficacy in clinical trials for non-muscle invasive bladder cancer. Despite their ability to induce an enhanced immune reaction within the lesion, the intracellular survival signaling of cancer cells has not been thoroughly addressed.

Methods

An analysis of the prognostic data revealed a high probability of therapeutic efficacy with simultaneous inhibition of mTOR and STAT3. Considering the challenges of limited pharmaco-accessibility to the bladder due to its pathophysiological structure and the partially undruggable nature of target molecules, we designed a dual siRNA system targeting both mRNAs. Subsequently, this dual siRNA system was encoded into the adenovirus 5/3 (Ad 5/3) to enhance in vivo delivery efficiency.

Results

Gene-targeting efficacy was assessed using cells isolated from xenografted tumors using a single-cell analysis system. Our strategy demonstrated a balanced downregulation of mTOR and STAT3 at the single-cell resolution, both in vitro and in vivo. This approach reduced tumor growth in bladder cancer xenograft and orthotopic animal experiments. In addition, increased infiltration of CD8+ T cells was observed in a humanized mouse model. We provided helpful and safe tissue distribution data for intravesical therapy of siRNAs coding adenoviruses.

Conclusions

The bi-specific siRNA strategy, encapsulated in an adenovirus, could be a promising tool to augment cancer treatment efficacy and overcome conventional therapy limitations associated with “undruggability.” Hence, we propose that dual targeting of mTOR and STAT3 is an advantageous strategy for intravesical therapy using adenoviruses.

Graphical Abstract

The current investigation introduces an innovative conceptualization of bispecific short hairpin RNA (bs_shRNA) tailored for the equilibrated modulation of dual genes within a singular cellular context. This novel bs_shRNA was loaded into the genome of an oncolytic adenovirus to augment the therapeutic efficacy of oncolytic viral interventions via the targeted inhibition of mTOR and STAT3 pathways. In addition, the administration of BSV significantly reduced the volume of bladder cancer tumors, concomitantly facilitating an enhanced recruitment of CD8+T lymphocytes in vivo.
Epidemiological survey and genetic diversity of Bartonella in fleas collected from rodents in Fujian Province, Southeast China
Authors: Zhou Shuheng , Nian Yuwei , Zeng Zhiwei , Han Tengwei , Liu Weijun , Zheng Kuicheng , Xiao Fangzhen
Published: June 2024

Background

Fleas, considered to be the main transmission vectors of Bartonella, are highly prevalent and show great diversity. To date, no investigations have focused on Bartonella vectors in Southeast China. The aim of this study was to investigate the epidemiological and molecular characteristics of Bartonella in fleas in Southeast China.

Methods

From 2016 to 2022, flea samples (n = 1119) were collected from 863 rodent individuals in seven inland and coastal cities in Southeast China. Flea species, region, gender, host species and habitat were recorded. The DNA samples from each individual flea were screened by real-time PCR for the Bartonella ssrA gene. All positive samples were confirmed by PCR based on the presence of the gltA gene and sequenced. The factors associated with Bartonella infection were analyzed by the Chi-square test and Fisher's exact test. ANOVA and the t-test were used to compare Bartonella DNA load.

Results

Bartonella DNA was detected in 26.2% (293/1119) of the flea samples, including in 27.1% (284/1047) of Xenopsylla cheopis samples, 13.2% (5/38) of Monopsyllus anisus samples, 8.3% (2/24) of Leptopsylla segnis samples and 20.0% (2/10) of other fleas (Nosopsyllus nicanus, Ctenocephalides felis, Stivalius klossi bispiniformis and Neopsylla dispar fukienensis). There was a significant difference in the prevalence of Bartonella among flea species, sex, hosts, regions and habitats. Five species of Bartonella fleas were identified based on sequencing and phylogenetic analyses targeting the gltA gene: B. tribocorum, B. queenslandensis, B. elizabethae, B. rochalimae and B. coopersplainsensis.

Conclusions

There is a high prevalence and diversity of Bartonella infection in the seven species of fleas collected in Southeast China. The detection of zoonotic Bartonella species in this study, including B. tribocorum, B. elizabethae and B. rochalimae, raises public health concerns.

Graphical Abstract
Fractal analysis of left ventricular trabeculae in heart failure with preserved ejection fraction patients with multivessel coronary artery disease
Authors: Gu Zi-Yi , Chen Bing-Hua , Zhao Lei , An Dong-Aolei , Wu Chong-Wen , Xue Song , Chen Wei-Bo , Huang Shan , Wang Yong-Yi , Wu Lian-Ming
Published: June 2024

Objectives

Endocardial trabeculae undergo varicose changes and hyperplasia in response to hemodynamic influences and are a variable phenotype reflecting changes in disease. Fractal analysis has been used to analyze the complexity of endocardial trabeculae in a variety of cardiomyopathies. The aim of this paper was to quantify the myocardial trabecular complexity through fractal analysis and to investigate its predictive value for the diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with multivessel coronary artery disease (CAD).

Methods

The retrospective study population consisted of 97 patients with multivessel CAD, 39 of them were diagnosed with HFpEF, while 46 healthy volunteers were recruited as controls. Fractal dimension (FD) was obtained through fractal analysis of endocardial trabeculae on LV short-axis cine images. Logistic regression analyses were used to confirm the predictors and compare different prediction models.

Results

Mean basal FD was significantly higher in patients with HFpEF than in patients without HFpEF or in the healthy group (median: 1.289; IQR: 0.078; p < 0.05). Mean basal FD was also a significant independent predictor in univariate and multivariate logistic regression (OR: 1.107 and 1.043, p < 0.05). Furthermore, adding FD to the prediction model improved the calibration and accuracy of the model (c-index: 0.806).

Conclusion

The left ventricular FD obtained with fractal analysis can reflect the complexity of myocardial trabeculae and has an independent predictive value for the diagnosis of HFpEF in patients with multivessel CAD. Including FD into the diagnostic model can help improve the diagnosis.

Critical relevance statement

Differences show in the complexity of endocardial trabeculae in multivessel coronary artery disease patients, and obtaining fractal dimensions (FD) by fractal analysis can help identify heart failure with preserved ejection fraction (HFpEF) patients.

Key Points

The complexity of myocardial trabeculae differs among patients with multivessel coronary artery disease.

Left ventricular fractal dimensions can reflect the complexity of the myocardial trabecular.

Fractal dimensions have predictive value for the diagnosis of heart failure with preserved ejection fraction.

Graphical Abstract
Insights into the role of mesenchymal stem cells in cutaneous medical aesthetics: from basics to clinics
Authors: Li Junyi , Liu Ye , Zhang Rui , Yang Qianyu , Xiong Wei , He Yan , Ye Qingsong
Published: June 2024

With the development of the economy and the increasing prevalence of skin problems, cutaneous medical aesthetics are gaining more and more attention. Skin disorders like poor wound healing, aging, and pigmentation have an impact not only on appearance but also on patients with physical and psychological issues, and even impose a significant financial burden on families and society. However, due to the complexities of its occurrence, present treatment options cannot produce optimal outcomes, indicating a dire need for new and effective treatments. Mesenchymal stem cells (MSCs) and their secretomics treatment is a new regenerative medicine therapy that promotes and regulates endogenous stem cell populations and/or replenishes cell pools to achieve tissue homeostasis and regeneration. It has demonstrated remarkable advantages in several skin-related in vivo and in vitro investigations, aiding in the improvement of skin conditions and the promotion of skin aesthetics. As a result, this review gives a complete description of recent scientific breakthroughs in MSCs for skin aesthetics and the limitations of their clinical applications, aiming to provide new ideas for future research and clinical transformation.
Stem cell-based therapy for fibrotic diseases: mechanisms and pathways
Authors: Taherian Marjan , Bayati Paria , Mojtabavi Nazanin
Published: June 2024

Fibrosis is a pathological process, that could result in permanent scarring and impairment of the physiological function of the affected organ; this condition which is categorized under the term organ failure could affect various organs in different situations. The involvement of the major organs, such as the lungs, liver, kidney, heart, and skin, is associated with a high rate of morbidity and mortality across the world. Fibrotic disorders encompass a broad range of complications and could be traced to various illnesses and impairments; these could range from simple skin scars with beauty issues to severe rheumatologic or inflammatory disorders such as systemic sclerosis as well as idiopathic pulmonary fibrosis. Besides, the overactivation of immune responses during any inflammatory condition causing tissue damage could contribute to the pathogenic fibrotic events accompanying the healing response; for instance, the inflammation resulting from tissue engraftment could cause the formation of fibrotic scars in the grafted tissue, even in cases where the immune system deals with hard to clear infections, fibrotic scars could follow and cause severe adverse effects. A good example of such a complication is post-Covid19 lung fibrosis which could impair the life of the affected individuals with extensive lung involvement. However, effective therapies that halt or slow down the progression of fibrosis are missing in the current clinical settings. Considering the immunomodulatory and regenerative potential of distinct stem cell types, their application as an anti-fibrotic agent, capable of attenuating tissue fibrosis has been investigated by many researchers. Although the majority of the studies addressing the anti-fibrotic effects of stem cells indicated their potent capabilities, the underlying mechanisms, and pathways by which these cells could impact fibrotic processes remain poorly understood. Here, we first, review the properties of various stem cell types utilized so far as anti-fibrotic treatments and discuss the challenges and limitations associated with their applications in clinical settings; then, we will summarize the general and organ-specific mechanisms and pathways contributing to tissue fibrosis; finally, we will describe the mechanisms and pathways considered to be employed by distinct stem cell types for exerting anti-fibrotic events.