bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for rebleeding and long-term outcomes in patients with head and neck cancer bleeding: a multicenter study
Authors: Wang Chih-Kai , Ho Che-Fang , Niu Kuang-Yu , Wu Chia-Chien , Chang Yun-Chen , Hsiao Chien-Han , Yen Chieh-Ching
Published: August 2022

Background

Acute, catastrophic bleeding in patients with head and neck cancer (HNC) is challenging and also a burden for their families and frontline physicians. This study analyzed the risk factors for rebleeding and long-term outcomes in these patients with HNC.

Methods

Patients who presented to the emergency department (ED) with HNC bleeding were enrolled in this study (N = 231). Variables of patients with or without rebleeding were compared, and associated factors were investigated using Cox’s proportional hazard model.

Results

Of the 231 patients enrolled, 112 (48.5%) experienced a recurrent bleeding event. The cumulative rebleeding incidence rate was 23% at 30 days, 49% at 180 days, and 56% at 1 year. Multivariate Cox regression analyses demonstrated that overweight-to-obesity (HR = 0.52, 95% CI 0.28–0.98, p = 0.043), laryngeal cancer (hazard ratio [HR] = 2.13, 95% confidence interval [CI] 1.07–4.23, p = 0.031), chemoradiation (HR = 1.49, 95% CI 1.001–2.94, p = 0.049), and second primary cancer (HR = 1.75, 95% CI 1.13–2.70, p = 0.012) are significant independent predictors of rebleeding, and the prognostic factors for overall survival included underweight (HR = 1.89, 95% CI 1.22–2.93, p = 0.004), heart rate > 110 beats/min (HR = 1.58, 95% CI 1.04–2.39, p = 0.032), chemoradiation (HR = 2.31, 95% CI 1.18–4.52, p = 0.015), and local recurrence (HR = 1.74, 95% CI 1.14–2.67, p = 0.011).

Conclusions

Overweight-to-obesity is a protective factor, while laryngeal cancer, chemoradiation and a second primary cancer are risk factors for rebleeding in patients with HNC. Our results may assist physicians in risk stratification of patients with HNC bleeding.
Body Mass Index and risk for onset of mood and anxiety disorders in the general population: Results from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2)
Authors: de Wit Leonore , Have Margreet ten , Cuijpers Pim , de Graaf Ron
Published: August 2022

Background

Examine the onset of a clinical diagnosis of mood (major depression, dysthymia and bipolar disorder)- and anxiety disorders (panic disorder, agoraphobia without panic disorder, social phobia, specific phobia and generalized anxiety disorder) by Body Mass Index levels at baseline in the general adult population over three years.

Methods

Data are from NEMESIS-2, a representative psychiatric cohort study in the Netherlands. A total of 5303 subjects aged 18–64 were interviewed with the CIDI (3.0 based on DSM-IV) in two waves, with an interval of three years. The first wave was performed from November 2007 to July 2009, the second wave from November 2010 to June 2012.

Results

Persons with obesity at baseline had a significantly increased risk of the onset of any mood -or anxiety disorder adjusting for covariates compared to persons with a normal Body Mass Index (OR = 1.71; 95% CI: 1.11–2.62). The odds ratio of the underweight category was non-significant. A dose–response effect of the continuous BMI scores on the onset of any mood or anxiety disorder was found (OR = 1.06; 95% CI: 1.02 = 1.10; p < 0.01).

Conclusions

Obesity at baseline is a risk for the onset of mood -and anxiety disorders at three year follow up.
Prevalence of mental distress and associated factors among medical students of University of Gondar, Northwest Ethiopia: a cross-sectional study
Authors: Rtbey Gidey , Shumet Shegaye , Birhan Belete , Salelew Endalamaw
Published: August 2022

Background

Mental distress is the most common problem among medical students. This is associated with severe consequences of lack of empathy for their patients, committing medical errors, and suicidal ideations and attempts. However, there is limited data on this aspect where the study was conducted especially in this segment of the population. Considering its seriousness, this study will have pivotal input information to plan possible interventions for the future. So, this study is aimed at assessing the prevalence of mental distress and its associated factors among medical students of the University of Gondar, Northwest Ethiopia, 2021.

Methods

An institutional-based cross-sectional study was conducted using a stratified random sampling technique to get a total of 438 study subjects from April 15–30/2021. Mental distress data were collected using a self-administrated questionnaire of the 10-item Kessler Psychological Distress Scale. Data was entered to Epi-data version 4.6.02 and cleaned, coded, and analyzed using STATA version 14.

Results

The prevalence of mental distress among medical students was 193(45.95%) with 95% CI (41.2, 50.7). In multi-variable logistic regression being female sex (AOR = 4.5, 95% CI = 2.66, 8.12), lack of interest towards field of study (AOR = 4.4, 95%, CI = (2.18, 8.78), current alcohol use (AOR = 5.8, 95% CI = 3.03, 11.15), monthly pocket money < 735 Ethiopian birr (AOR = 3.1, 95% CI = 1.53, 6.04), extremely high test anxiety (AOR = 3.9, 95% CI = 1.27, 11.88), family history mental illness (AOR = 2.5 95% CI = 1.12, 5.53) and poor social support (AOR = 4.2, 95% CI = (1.94, 9.16) were significantly associated with mental distress.

Conclusion and recommendation

Prevalence of mental distress among medical students of University of Gondar was found to be higher when compared to previous studies among this population in Ethiopia. It is recommended that the school of medicine should give undue attention to address those identified factors by establishing counseling centers to minimize mental distress.
Exploring the opportunities and challenges of female health leaders in three regional states of Ethiopia: a phenomenological study
Authors: Muktar Sualiha Abdulkader , Desta Binyam Fekadu , Damte Heran Demissie , Heyi Wubishet Kebede , Gurmamo Elias Mamo , Abebe Melkamu Getu , Mesele Mestawot Getachew , Argaw Mesele Damte
Published: August 2022

Background

Gender equity involves fairness in all aspects of life for women and men and is usually determined by social, political, economic, and cultural contexts. The proportion of female leaders in healthcare within the health sector is low. The aim of this study was to explore and describe the experiences, opportunities, and challenges faced by women in their path towards becoming leaders within the health sector.

Methods

This study was conducted using the phenomenological method of qualitative inquiry. The approach was chosen for its merits to narratively explore and describe the lived stories and shared experiences of women leaders in the healthcare system. A purposive sampling technique was used to identify six women leaders. Semi-structured interviews were conducted through telephone by the investigators. The qualitative data analysis was conducted parallel with data collection, using steps of thematic analysis.

Results

This study identified individual, societal, and organizational level opportunities and challenges that had an influence on the career paths of female health leaders in Ethiopia. The leadership positions were an opportunity in the career development of women who had long-term goals, were known for their empathy, and exercised wise use of resources. In addition, women who had the support of close family members and their peers are more likely to compete and rise to leadership positions. Furthermore, women who received organizational support in the form of affirmative action, training, development, and recognition also tended to rise to leadership positions. However, women who assumed leadership positions but whose day-to-day decision-making was influenced by their supervisors, those who had experienced sexual harassment, and those under the influence of societal norms were less likely to attain leadership positions.

Conclusion

The opinions and experiences of female health leaders revealed that individual behaiour whileassumming a leadership positon, empathy, and wise resource management positivey influence their career development. In addition, female health workers who had support form close family members and peers strived for growth to leadership positions. Furthermore, the presence of organizational support, in the form of affirmative actions, and succession planning were another opportunity for females in their career paths. Conversely, some social norms were found to deter female health workers from advanicing to leadership positions. Therefore, enhancing the leadership capacity of women and improving social and organizational support is recommended. In addition, addressing the low level of self-image among women and patriarchal societal norms at the community level is recommended.
Obesity and health service utilization in Brazil: data from the National Health Survey
Authors: Rimes-Dias Karina Abibi , Costa Janaina Calu , Canella Daniela Silva
Published: August 2022

Background

Obesity, a complex public health problem, is generally associated with other chronic diseases. The association of obesity with health service utilization has been little investigated in low- and middle-income countries. This study aimed to analyze the association between obesity and health service utilization (considering those services related to hypertension and/or diabetes).

Methods

A cross-sectional, nationally-representative, study of Brazilians aged ≥18 years was conducted. Data from the National Health Survey (2013) for 59,402 individuals were analyzed, including measured weight and height. The association between body mass index (BMI) category (under/normal weight, overweight, and obesity) and health service utilization due to hypertension and/or diabetes was investigated using Poisson regression models (crude and adjusted). To analyze the health services utilization, the following variables were considered: 1) routine visits to a general doctor or health service; 2) referrals/consultations with a specialist; 3) prescribed exams done; and 4) hospital admission due to the disease or related complication. All analyses were stratified by sex.

Results

Compared with under/normal-weight individuals, subjects with obesity (both male and female) made roughly double the use of all health care services assessed. Men with hypertension that had obesity had a higher risk of hospital admission (adjusted PR = 2.55; 95%CI 1.81–3.61), than those with under/normal weight. Women with diabetes that had obesity had more referrals/consultations with specialists (adjusted PR = 2.56; 95%CI 1.94–3.38), than those with under/normal weight.

Conclusions

The presence of obesity was associated with increased use of health care services for hypertension and/or diabetes, indicating greater demand for human resources and materials, and a greater burden on the national health system.
Prevalence of complementary and alternative medicine use in Brazil: results of the National Health Survey, 2019
Authors: Boccolini Patricia de Moraes Mello , de Lima Sírio Boclin Karine , de Sousa Islândia Maria Carvalho , Boccolini Cristiano Siqueira
Published: August 2022

Background

In recent decades, it has been possible to observe an increase in Complementary and Alternative Medicine (CAM) usage globally for both disease prevention and health promotion purposes. we aim to estimate the prevalence of CAM use and analyze associated factors in Brazil.

Methods

Observational study with data from the 2019 National Health Survey that evaluated a sample of Brazilian adults. The outcome was CAM use, such as acupuncture, homeopathy, medicinal plants and herbal medicines, meditation, and yoga in the last 12 months. A logistic regression model with a 99% confidence interval was used to assess factors associated with CAM use.

Results

The prevalence of CAM use in 2019 was 5.2% (CI99% = 4.8–5.6%), the most used modalities: medicinal plants and herbal medicines, with a prevalence of 3.0% (CI99% = 2.7–3.33) followed by: acupuncture 1.4% (CI99% = 1.3–1.6) homeopathy 0.9% (CI99% = 0.7–1.0), meditation 0.7% (CI99% = 0.6–0.8) and yoga 0.4% (CI99% = 0.4–0.5). We observed important geographical differences in CAM use in Brazil, with a higher prevalence in the North Region, 3.7% (CI99% = 2.81–4.75), where herbal medicines were more frequent the in the other regions. After estimating an adjusted model, women, older people, and people with a higher level of education and per capita income were the ones who used all types of CAM the most. The practice of yoga stands out among women 3.6% (CI99% = 2.49–5.28) and among individuals with higher per capita income 7.5% (CI99% = 2.97–18.93); meditation among individuals with higher educational level 13.4% (CI99% = 6.41–28.33) and acupuncture for those who declared regular or poor health 1.9% (CI99% = 1.51–2.39).

Conclusions

We recommend that the Ministry of Health expand CAM access to Unified Health System users and promote health professionals’ conscious and guided use for the Brazilian population.
Utility of 3D printed models as adjunct in acetabular fracture teaching for Orthopaedic trainees
Authors: Goyal S , Chua CXK , Chen YS , Murphy D , O.’Neill GK
Published: August 2022

Objective

To evaluate the use of 3-D printed models as compared to didactic lectures in the teaching of acetabular fractures for Orthopaedic trainees.

Methods

This was a randomised prospective study conducted in a tertiary hospital setting which consisted of 16 Orthopaedic residents. Ten different cases of acetabular fracture patterns were identified and printed as 3-D models. The baseline knowledge of orthopaedic residents regarding acetabular fracture classification and surgical approach was determined by an x-ray based pre-test. Trainees were then randomly assigned into two groups. Group I received only lectures. Group II were additionally provided with 3-D printed models during the lecture. Participants were then assessed for comprehension and retention of teaching.

Results

Sixteen trainees participated in the trial. Both Group 1 and 2 improved post teaching with a mean score of 2.5 and 1.9 to 4.4 and 6 out of 10 respectively. The post test score for fracture classification and surgical approach were significantly higher for 3-D model group (p < 0.05). Trainees felt that the physical characteristics of the 3-D models were a good representation of acetabular fracture configuration, and should be used routinely for teaching and surgical planning.

Conclusion

3-D printed model of real clinical cases have significant educational impact compared to lecture-based learning towards improving young trainees’ understanding of complex acetabular fractures.
Exploring the nursing student experience at a remote Australian university campus: a qualitative study
Authors: Hays Catherine , Devine Susan , Glass Beverley D.
Published: August 2022

Background

Nurses constitute most of the rural and remote Australian health workforce, however staff shortages in these regions are common. Rural exposure, association, and undertaking rural clinical placements can influence health students’ decision to work rurally after graduation, however attending university in rural and remote regions has been shown to be a great contributor. An improved understanding of these nursing students’ experiences may inform changes to teaching and support strategies for these students, which in turn could improve their retention and completion rates, contributing to a more sustainable rural and remote Australian nursing workforce. This study aimed to explore and describe students’ experiences of studying nursing in the context of a satellite university campus located in a remote town, with a focus on education delivery methods, staff, support, student services, and barriers and enablers to successful study.

Methodology

Nine students participated in this qualitative descriptive study. Semi-structured interviews were undertaken, allowing participants to reflect on their experiences as nursing students in the context of a geographically remote satellite university campus. The resulting data were grouped into common themes and summarised.

Results

Students were generally positive regarding lectures delivered by videoconference or recorded lectures, as they allowed for greater flexibility which accommodated their busy personal lives. Face-to-face teaching was especially valuable, and students were particularly positive about their small cohort size, which enabled the creation of strong, supportive relationships between students, their cohort, and teaching and support staff. However, barriers related to student demographics and some difficulties with course engagement and campus staffing were experienced.

Conclusions

The experiences of nursing students at remote university campuses are different from those experienced by traditional, metropolitan university students. Although these nursing students face additional barriers unique to the remote campus context, they benefit from a range of enabling factors, including their close relationships with other students, staff, family, and their local community.
Readiness of health facilities to deliver non-communicable diseases services in Kenya: a national cross-sectional survey
Authors: Ammoun Rita , Wami Welcome Mkhululi , Otieno Peter , Schultsz Constance , Kyobutungi Catherine , Asiki Gershim
Published: August 2022

Background

Non-communicable diseases (NCDs) account for an estimated 71% of all global deaths annually and nearly 80% of these deaths occur in low- and middle-income countries. This study aimed to assess the readiness of existing healthcare systems at different levels of health care in delivering NCDs management and prevention services in Kenya.

Methods

A cross-sectional survey of 258 facilities was conducted between June 2019 and December 2020 using multistage sampling, examining facility readiness based on the availability of indicators such as equipment, diagnostic capacity, medicines and commodities, trained staff and guidelines for NCDs management. Readiness scores were calculated as the mean availability of tracer items expressed as a percentage and a cut-off threshold of ≥ 70% was used to classify facilities as “ready” to manage NCDs. Descriptive and bivariate analyses were performed to assess the readiness of facilities by type, level, and location settings. Logistic regressions were used to identify factors associated with the readiness of facilities to provide disease-specific services.

Results

Of the surveyed facilities, 93.8% offered chronic respiratory disease (CRD) diagnosis and/or management services, 82.2% diabetes mellitus, 65.1% cardiovascular disease (CVD), and only 24.4% cervical cancer screening services. The mean readiness scores for diabetes mellitus (71%; 95% CI: 67–74) and CVD (69%; 95% CI: 66–72) were relatively high. Although CRD services were reportedly the most widely available, its mean readiness score was low (48%; 95% CI: 45–50). The majority of facilities offering cervical cancer services had all the necessary tracer items available to provide these services. Modeling results revealed that private facilities were more likely to be “ready” to offer NCDs services than public facilities. Similarly, hospitals were more likely “ready” to provide NCDs services than primary health facilities. These disparities in service readiness extended to the regional and urban/rural divide.

Conclusions

Important gaps in the current readiness of facilities to manage NCDs in Kenya at different levels of health care were revealed, showing variations by disease and healthcare facility type. A collective approach is therefore needed to bridge the gap between resource availability and population healthcare needs.
Candidate genes for infertility: an in-silico study based on cytogenetic analysis
Authors: Sahota Jatinder Singh , Sharma Bhavna , Guleria Kamlesh , Sambyal Vasudha
Published: August 2022

Background

The cause of infertility remains unclear in a significant proportion of reproductive-age couples who fail to conceive naturally. Chromosomal aberrations have been identified as one of the main genetic causes of male and female infertility. Structural chromosomal aberrations may disrupt the functioning of various genes, some of which may be important for fertility. The present study aims to identify candidate genes and putative functional interaction networks involved in male and female infertility using cytogenetic data from cultured peripheral blood lymphocytes of infertile patients.

Methods

Karyotypic analyses was done in 201 infertile patients (100 males and 101 females) and 201 age and gender matched healthy controls (100 males and 101 females) after 72 h peripheral lymphocyte culturing and GTG banding, followed by bioinformatic analysis using Cytoscape v3.8.2 and Metascape.

Results

Several chromosomal regions with a significantly higher frequency of structural aberrations were identified in the infertile males (5q2, 10q2, and 17q2) and females (6q2, 16q2, and Xq2). Segregation of the patients based on type of infertility (primary v/s secondary infertility) led to the identification of chromosomal regions with a significantly higher frequency of structural aberrations exclusively within the infertile males (5q2, 17q2) and females (16q2) with primary infertility. Cytoscape identified two networks specific to these regions: a male specific network with 99 genes and a female specific network with 109 genes. The top enriched GO terms within the male and female infertility networks were “skeletal system morphogenesis” and “mRNA transport” respectively. PSME3, PSMD3, and CDC27 were the top 3 hub genes identified within the male infertility network. Similarly, UPF3B, IRF8, and PSMB1 were the top 3 hub genes identified with the female infertility network. Among the hub genes identified in the male- and female-specific networks, PSMB1, PSMD3, and PSME3 are functional components of the proteasome complex. These hub genes have a limited number of reports related to their respective roles in maintenance of fertility in mice model and humans and require validation in further studies.

Conclusion

The candidate genes predicted in the present study can serve as targets for future research on infertility.
Cluster analysis unveils a severe persistent respiratory impairment phenotype 3-months after severe COVID-19
Authors: Perotin Jeanne-Marie , Gierski Fabien , Bolko Lois , Dury Sandra , Barrière Sarah , Launois Claire , Dewolf Maxime , Chouabe Stéphane , Bongrain Eric , Picard Davy , Tran Eric , N’Guyen Yoann , Mourvillier Bruno , Servettaz Amélie , Rapin Amandine , Marcus Claude , Lebargy François , Kaladjian Arthur , Salmon Jean-Hugues , Deslee Gaetan
Published: August 2022

Background

The mid-term respiratory sequelae in survivors of severe COVID-19 appear highly heterogeneous. In addition, factors associated with respiratory sequelae are not known. In this monocentric prospective study, we performed a multidisciplinary assessment for respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. We analysed factors associated with severe persistent respiratory impairment, amongst demographic, COVID-19 severity, and 3-month assessment.

Methods

Patients with severe SARS-CoV-2 pneumonia requiring ≥ 4L/min were included for a systematic 3-month visit, including respiratory assessment (symptoms, lung function, CT scan), muscular evaluation (body composition, physical function and activity, disability), psychopathological evaluation (anxiety, depression, post-traumatic stress disorder-PTSD) and quality of life. A cluster analysis was performed to identify subgroups of patients based on objective functional measurements: DLCO, total lung capacity and 6-min walking distance (6MWD).

Results

Sixty-two patients were analysed, 39% had dyspnea on exercise (mMRC ≥ 2), 72% had DLCO < 80%, 90% had CT-scan abnormalities; 40% had sarcopenia/pre-sarcopenia and 31% had symptoms of PTSD. Cluster analysis identified a group of patients (n = 18, 30.5%) with a severe persistent (SP) respiratory impairment (DLCO48 ± 12%, 6MWD 299 ± 141 m). This SP cluster was characterized by older age, severe respiratory symptoms, but also sarcopenia/pre-sarcopenia, symptoms of PTSD and markedly impaired quality of life. It was not associated with initial COVID-19 severity or management.

Conclusions and clinical implication

We identified a phenotype of patients with severe persistent respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. Our results highlight the need for multidisciplinary assessment and management after severe SARS-CoV-2 pneumonia.

Trial registrationThe study was registered on ClinicalTrials.gov (May 6, 2020): NCT04376840
Association of lipid profile with obesity among breast cancer survivors: a cross-sectional study
Authors: Okekunle Akinkunmi Paul , Yie Ga-Eun , Song Sihan , Kim Zisun , Youn Hyun Jo , Cho Jihyoung , Min Jun Won , Kim Yoo Seok , Lee Jung Eun
Published: August 2022

Background

The role of lipid metabolism in obesity and cancer manifestations cannot be underestimated, but whether alterations in lipid metabolism can manipulate the vasculature to promote obesity among breast cancer (BC) survivors is yet to be clearly understood. This study quantified plasma lipid and particle sizes using high-throughput proton (1H) nuclear magnetic resonance (NMR) and tested their associations with obesity among breast cancer (BC) survivors.

Methods

A total of 348 (225 premenopausal and 123 postmenopausal) BC survivors enrolled from five hospitals in Korea were included. We assessed thirty-four plasma lipid biomarkers using 1H NMR, and obesity status was defined as a body mass index (BMI) of 25 kg/m2 or greater. Generalized linear and logistic regression models were applied to estimate the least-square means of BMI (kg/m2) and odds ratio (OR)s of obesity, respectively, and the corresponding 95% confidence interval (CI)s across plasma lipid levels.

Results

Mean (SD) values of BMI was 23.3 (3.2) kg/m2 and 90 (25.9%) had BMI of ≥ 25 kg/m2. BMI levels increased with increasing total triglycerides (TG), TG in lipoproteins and very-low-density lipoprotein (VLDL) subfractions. However, BMI levels decreased with increasing tertiles of high-density lipoprotein (HDL)-cholesterol (C) and HDL particle size (HDL-p). Similar associations were observed in the logistic regression models. The increasing and decreasing BMI trends with TG and HDL profiles respectively were predominantly limited to premenopausal BC survivors.

Conclusions

Increasing levels of plasma total TG and TG in lipoproteins were associated with increasing levels of BMI among premenopausal BC survivors. High HDL-C levels and large HDL-p were inversely associated with obesity among premenopausal BC survivors. Due to the cross-sectional design of this study, longitudinal studies are necessary to examine the association between obesity and lipid profile among BC survivors.
Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesis
Authors: He Xiaolie , Yang Li , Dong Kun , Zhang Feng , Liu Yuchen , Ma Bei , Chen Youwei , Hai Jian , Zhu Rongrong , Cheng Liming
Published: August 2022

Exosomes show potential for treating patients with spinal cord injury (SCI) in clinical practice, but the underlying repair mechanisms remain poorly understood, and biological scaffolds available for clinical transplantation of exosomes have yet to be explored. In the present study, we demonstrated the novel function of Gel-Exo (exosomes encapsulated in fibrin gel) in promoting behavioural and electrophysiological performance in mice with SCI, and the upregulated neural marker expression in the lesion site suggested enhanced neurogenesis by Gel-Exo. According to the RNA-seq results, Vgf (nerve growth factor inducible) was the key regulator through which Gel-Exo accelerated recovery from SCI. VGF is related to myelination and oligodendrocyte development according to previous reports. Furthermore, we found that VGF was abundant in exosomes, and Gel-Exo-treated mice with high VGF expression indeed showed increased oligodendrogenesis. VGF was also shown to promote oligodendrogenesis both in vitro and in vivo, and lentivirus-mediated VGF overexpression in the lesion site showed reparative effects equal to those of Gel-Exo treatment in vivo. These results suggest that Gel-Exo can thus be used as a biocompatible material for SCI repair, in which VGF-mediated oligodendrogenesis is the vital mechanism for functional recovery.
Laccase-mimicking Mn–Cu hybrid nanoflowers for paper-based visual detection of phenolic neurotransmitters and rapid degradation of dyes
Authors: Le Thao Nguyen , Le Xuan Ai , Tran Tai Duc , Lee Kang Jin , Kim Moon Il
Published: August 2022

Background

Laccase-based biosensors are efficient for detecting phenolic compounds. However, the instability and high cost of laccases have hindered their practical utilization.

Results

In this study, we developed hierarchical manganese dioxide–copper phosphate hybrid nanoflowers (H–Mn–Cu NFs) as excellent laccase-mimicking nanozymes. To synthesize the H–Mn–Cu NFs, manganese dioxide nanoflowers (MnO2 NFs) were first synthesized by rapidly reducing potassium permanganate using citric acid. The MnO2 NFs were then functionalized with amine groups, followed by incubation with copper sulfate for three days at room temperature to drive the coordination interaction between the amine moieties and copper ions and to induce anisotropic growth of the petals composed of copper phosphate crystals, consequently yielding H–Mn–Cu NFs. Compared with those of free laccase, at the same mass concentration, H–Mn–Cu NFs exhibited lower Km (~ 85%) and considerably higher Vmax (~ 400%), as well as significantly enhanced stability in the ranges of pH, temperature, ionic strength, and incubation periods evaluated. H–Mn–Cu NFs also catalyzed the decolorization of diverse dyes considerably faster than the free laccase. Based on these advantageous features, a paper microfluidic device incorporating H–Mn–Cu NFs was constructed for the convenient visual detection of phenolic neurotransmitters, including dopamine and epinephrine. The device enabled rapid and sensitive quantification of target neurotransmitters using an image acquired using a smartphone.

Conclusions

These results clearly show that H–Mn–Cu NFs could be potential candidates to replace natural laccases for a wide range of applications in biosensing, environmental protection, and biotechnology.

Graphical Abstract
Lactobacillus cell envelope-coated nanoparticles for antibiotic delivery against cariogenic biofilm and dental caries
Authors: Weng Luting , Wu Lang , Guo Rongjuan , Ye Jiajia , Liang Wen , Wu Wei , Chen Liang , Yang Deqin
Published: August 2022

Background

Due to their prevalence, dental caries ranks first among all diseases endangering human health. Therefore, the prevention of caries is of great significance, as caries have become a serious public health problem worldwide. Currently, using nanoscale drug delivery systems to prevent caries has received increased attention. However, the preventive efficacy of these systems is substantially limited due to the unique physiological structure of cariogenic biofilms. Thus, novel strategies aimed at combating cariogenic biofilms to improve preventive efficiency against caries are meaningful and very necessary. Herein, inspired by cell membrane coating technology and Lactobacillus strains, we coated triclosan (TCS)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TCS@PLGA-NPs) with an envelope of Lactobacillus (LA/TCS@PLGA-NPs) and investigated their potential as a nanoparticle delivery system against cariogenic biofilms and dental caries.

Results

LA/TCS@PLGA-NPs were successfully prepared with favorable properties, including a coated envelope, controllable size, negative charge, sustained drug-release kinetics and so on. The LA/TCS@PLGA-NPs inherited native properties from the source cell surface, thus the LA/TCS@PLGA-NPs adhered to S. mutans, integrated into the S. mutans biofilm, and interfered with the biofilm formation of S. mutans. The nanoparticles significantly inhibited the activity, biomass and virulence gene expression of S. mutans biofilms in vitro. Additionally, LA/TCS@PLGA-NPs exhibited a long-lasting inhibitory effect on the progression of caries in vivo. The safety performance of the nanoparticles is also favorable.

Conclusions

Our findings reveal that the antibiofilm effect of LA/TCS@PLGA-NPs relies not only on the inheritance of native properties from the Lactobacillus cell surface but also on the inhibitory effect on the activity, biomass and virulence of S. mutans biofilms. Thus, these nanoparticles could be considered feasible candidates for a new class of effective drug delivery systems for the prevention of caries. Furthermore, this work provides new insights into cell membrane coating technology and presents a novel strategy to combat bacterial biofilms and associated infections.

Graphical Abstract
Neutrophil membrane engineered HucMSC sEVs alleviate cisplatin-induced AKI by enhancing cellular uptake and targeting
Authors: Wu Peipei , Tang Yuting , Jin Can , Wang Min , Li Linli , Liu Zhong , Shi Hui , Sun Zixuan , Hou Xiaomei , Chen Wenya , Xu Wenrong , Qian Hui
Published: August 2022

Human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (hucMSC-sEVs) have been demonstrated as a therapeutic agent to prevent and treat cisplatin-induced acute kidney injury (AKI). However, hucMSC-sEVs still face many problems and challenges in the repair and treatment of tissue injury, including short circulation time, insufficient targeting, and low therapeutic efficacy. Therefore, we constructed engineered hybrid vesicles fused with nanovesicles derived from human neutrophil membranes and hucMSC-sEVs, named neutrophil membrane engineered hucMSC-sEVs (NEX). NEX significantly enhanced the targeting of hucMSC-sEVs to injured kidney tissues, improved the impaired renal function via reducing pro-inflammatory cytokines expression, promoted the proliferation of renal tissue cells, and inhibited renal cell apoptosis in vivo. In addition, NEX enhanced hucMSC-sEVs uptake by NRK52E cells, but inhibited its uptake by RAW264.7 cells. Moreover, administration of NEX reduced cellular oxidative stress and promoted proliferation of NRK52E cells treated with cisplatin in vitro. In summary, our findings indicate that this design of a universal approach enhances the targeting and therapeutic efficacy of hucMSC-sEVs in kidney tissue regeneration, and provides new evidence promoting its clinical application.
Impact of aspartate aminotransferase–to–platelet ratio index based score to assess posthepatectomy liver failure in patients with hepatocellular carcninoma
Authors: Yugawa Kyohei , Maeda Takashi , Nagata Shigeyuki , Shiraishi Jin , Sakai Akihiro , Yamaguchi Shohei , Konishi Kozo , Hashimoto Kenkichi
Published: August 2022

Background

Posthepatectomy liver failure (PHLF) is a life-threatening complication following hepatic resection. The aspartate aminotransferase-to-platelet ratio index (APRI) is a non-invasive model for assessing the liver functional reserve in patients with hepatocellular carcinoma (HCC). This study aimed to establish a scoring model to stratify patients with HCC at risk for PHLF.

Methods

This single-center retrospective study included 451 patients who underwent hepatic resection for HCC between 2004 and 2017. Preoperative factors, including non-invasive liver fibrosis markers and intraoperative factors, were evaluated. The predictive impact for PHLF was evaluated using receiver operating characteristic (ROC) curves of these factors.

Results

Of 451 patients, 30 (6.7%) developed severe PHLF (grade B/C). Multivariate logistic analysis indicated that APRI, model for end-stage liver disease (MELD) score, operating time, and intraoperative blood loss were significantly associated with severe PHLF. A scoring model (over 0–4 points) was calculated using these optimal cutoff values. The area under the ROC curve of the established score for severe PHLF was 0.88, which greatly improved the predictive accuracy compared with these factors alone (p < 0.05 for all).

Conclusions

The scoring model-based APRI, MELD score, operating time, and intraoperative blood loss can predict severe PHLF in patients with HCC.
Exosomes derived from myeloid-derived suppressor cells facilitate castration-resistant prostate cancer progression via S100A9/circMID1/miR-506-3p/MID1
Authors: Gao Feng , Xu Qiaoping , Tang Zhe , Zhang Nan , Huang Yasheng , Li Zhongyi , Dai Yuliang , Yu Qiqi , Zhu Jingyu
Published: August 2022

Background

Castration-resistant prostate cancer (CRPC) is a major cause of recurrence and mortality among prostate cancer (PCa) patients. Myeloid-derived suppressor cells (MDSCs) regulate castration resistance in PCa. Previously, it was shown that intercellular communication was efficiently mediated by exosomes (Exos), but the role and the mechanism of MDSC-derived Exos in CRPC progression was unclear.

Methods

In this study, the circRNA expression profiles in PC3 cells treated with MDSC-Exo and control cells were investigated using a circRNA microarray.

Results

The data showed that circMID1 (hsa_circ_0007718) expression was elevated in PC3 cells treated with MDSC-Exo. Moreover, high circMID1 expression was found in PCa compared with benign prostatic hyperplasia (BPH) tissues and in CRPC patients compared with hormone sensitive prostate cancer (HSPC) patients. Further studies showed that MDSC-Exo accelerated PCa cell proliferation, migration, and invasion, while circMID1 deficiency inhibited MDSC-Exo-regulated CRPC progression in vitro and in vivo. Mechanistically, MDSC-derived exosomal S100A9 increased circMID1 expression to sponge miR-506-3p, leading to increased MID1 expression and accelerated tumor progression.

Conclusion

Together, our results showed that a S100A9/circMID1/miR-506-3p/MID1 axis existed in MDSC-Exo-regulated CRPC progression, which provided novel insights into MDSC-Exo regulatory mechanisms in CRPC progression.
LINC00665 knockdown confers sensitivity in irradiated non-small cell lung cancer cells through the miR-582-5p/UCHL3/AhR axis
Authors: Xu Li-Ming , Yuan Ya-Jing , Yu Hao , Wang Shuai , Wang Ping
Published: August 2022

Background

The resistance to radiotherapy remains a major obstacle that limits the efficacy of radiotherapy in non-small cell lung cancer (NSCLC). This study aims to illustrate the molecular mechanism underlying the role of LINC00665 in the radiosensitivity of NSCLC, which involves ubiquitin C-terminal hydrolase L3 (UCHL3).

Methods and results

The expression of UCHL3 was determined in clinical tissue samples collected from NSCLC patients and NSCLC cell lines. We found that UCHL3 overexpression occurred in both NSCLC tissues and cells, associated with poor prognosis in NSCLC patients. Mechanistically, UCHL3 stabilized aryl hydrocarbon receptor (AhR) protein through deubiquitination, thereby promoting PD-L1 expression. UCHL3 reduced the radiosensitivity of NSCLC cells by stabilizing AhR protein. Upstream microRNAs (miRNAs) and lncRNAs of UCHL3 were predicted by microarray profiling and validated by functional experiments. LINC00665 functioned as a sponge of miR-582-5p and thus up-regulated the expression of the miR-582-5p target UCHL3. Gain- and loss- of function assays were performed to assess the effects of LINC00665, UCHL3 and miR-582-5p on the in vitro cell malignant behaviors and immune escape as well as on the in vivo tumor growth. Silencing LINC00665 or overexpressing miR-582-5p enhanced the sensitivity of NSCLC cells to radiotherapy. LINC00665 augmented the immune escape of NSCLC cells in vitro and in vivo through stabilizing AhR protein via the miR-582-5p/UCHL3 axis.

Conclusions

Overall, LINC00665 reduced the radiosensitivity of NSCLC cells via stabilization of AhR through the miR-582-5p/UCHL3 axis.
Non-coding RNAs in lung cancer: emerging regulators of angiogenesis
Authors: Liao Yajie , Wu Xudong , Wu Mengyu , Fang Yuan , Li Jie , Tang Weiqiang
Published: August 2022

Lung cancer is the second cancer and the leading cause of tumor-related mortality worldwide. Angiogenesis is a crucial hallmark of cancer development and a promising target in lung cancer. However, the anti-angiogenic drugs currently used in the clinic do not achieve long-term efficacy and are accompanied by severe adverse reactions. Therefore, the development of novel anti-angiogenic therapeutic approaches for lung cancer is urgently needed. Non-coding RNAs (ncRNAs) participate in multiple biological processes in cancers, including tumor angiogenesis. Many studies have demonstrated that ncRNAs play crucial roles in tumor angiogenesis. This review discusses the regulatory functions of different ncRNAs in lung cancer angiogenesis, focusing on the downstream targets and signaling pathways regulated by these ncRNAs. Additionally, given the recent trend towards utilizing ncRNAs as cancer therapeutics, we also discuss the tremendous potential applications of ncRNAs as biomarkers or novel anti-angiogenic tools in lung cancer.
A fetal fraction enrichment method reduces false negatives and increases test success rate of fetal chromosome aneuploidy detection in early pregnancy loss
Authors: Qiao Longwei , Zhang Bin , Wu Xiaojuan , Zhang Chunhua , Xue Ying , Tang Hui , Tang Haoyu , Shi Jingye , Liang Yuting , Yu Bin , Wang Ting
Published: August 2022

Objective

We and others have previously demonstrated that the size-selection enrichment method could remarkably improve fetal fraction (FF) in the early gestational age (GA, 12–13 weeks), suggesting that 9 or 10 weeks should not be used as a threshold for GA in size-selection noninvasive prenatal screening (NIPS). Here, we assessed whether this method was reliable for detecting fetal chromosomal aneuploidy at the earliest GA (6–8 weeks).

Methods

Size-selection NIPS for fetal chromosomal aneuploidy was applied to 208 pregnancy plasma samples (102 male and 106 female fetuses), while the 169 pregnancy samples with male fetuses also underwent standard NIPS. Multivariable linear regression models were used to evaluate the association between fold-change of FF and experimental factors.

Results

The sensitivity of the cell-free DNA (cfDNA) test in detecting aneuploidy was 100% when screened with FF enrichment, whereas the sensitivity of the same patients was only 62.5% (5/8) without FF enrichment. In the 102 pregnancy samples with male fetuses, FF increased from 6.1% to 15.7%, and the median increase in FF was 2.8-fold with enrichment. Moreover, there was a trend toward an increasing success rate of the cfDNA test from 6 to 13 weeks of gestation, especially when the test success rate reached 100% after 7 weeks with FF enrichment. Multivariate linear regression analysis demonstrated that a lower initial FF, shorter cfDNA size, increased body mass index (BMI), and later GA were all independent predictors of a higher fold-change of FF. Compared with ≤ 120 bp cfDNA fragments, the mean fold-change of FF differences was 0.820 for 121–125 bp, 0.229 for 126–130 bp, − 0.154 for 131–135 bp, − 0.525 for 136–140 bp and − 0.934 for > 140 bp (Ptrend < 0.0001), suggesting that fold-change of FF significantly decreased with cfDNA fragments > 125 bp. These results were statistically significant after adjusting for confounding factors in the models for fold-change of FF.

Conclusions

The FF enrichment method is a reasonable strategy to detect fetal chromosomal aneuploidy in early pregnancy loss with reduced false negatives and increased test success rate after 7 weeks of GA and should be recommended for patients with early pregnancy loss.
Associations between dietary fiber intake and mortality from all causes, cardiovascular disease and cancer: a prospective study
Authors: Xu Xin , Zhang Junmiao , Zhang Yanhui , Qi Honggang , Wang Ping
Published: August 2022

Objective

Several studies suggest that dietary fiber intake may reduce mortality risk, but this might depend on the fiber types and the evidence regarding the role of soluble fiber or insoluble fiber on death risk remain limited and inconsistent. Therefore, this study aimed to comprehensively evaluate multiple types of dietary fiber intake on mortality from all causes, cardiovascular disease and cancer in the large-scale Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial.

Methods

A multivariate Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

This study finally included 86,642 participants with 17,536 all-cause deaths, 4842 cardiovascular deaths and 5760 cancer deaths identified after a total of 1,444,068 follow-up years. After adjusting for potential confounders, dietary total fiber intake was statistically significantly inversely associated with all-cause death (Q5 vs Q1: HR 0.71, 95% CI 0.66–0.75; P for trend < 0.001), cardiovascular death (Q5 vs Q1: HR 0.73, 95% CI 0.65–0.83; P for trend < 0.001) and cancer mortality (Q5 vs Q1: HR 0.77, 95% CI 0.69–0.86; P for trend < 0.001). Similar results were observed for both insoluble and soluble fiber intake. Restricted cubic spline model analysis suggested that there was a nonlinear association of dietary fiber intake with mortality risk (all P for nonlinearity < 0.05).

Conclusions

In this large nationally representative sample of US adult population, intakes of total fiber, soluble fiber, and insoluble fiber were associated with lower risks of all-cause, cardiovascular and cancer mortality.
Breastfeeding, pregnancy, medicines, neurodevelopment, and population databases: the information desert
Authors: Jordan Sue , Bromley Rebecca , Damase-Michel Christine , Given Joanne , Komninou Sophia , Loane Maria , Marfell Naomi , Dolk Helen
Published: August 2022

Background

The pharmacoepidemiology of the long-term benefits and harms of medicines in pregnancy and breastfeeding has received little attention. The impact of maternal medicines on children is increasingly recognised as a source of avoidable harm. The focus of attention has expanded from congenital anomalies to include less visible, but equally important, outcomes, including cognition, neurodevelopmental disorders, educational performance, and childhood ill-health. Breastfeeding, whether as a source of medicine exposure, a mitigator of adverse effects or as an outcome, has been all but ignored in pharmacoepidemiology and pharmacovigilance: a significant ‘blind spot’.

Whole-population data on breastfeeding: why we need them

Optimal child development and maternal health necessitate breastfeeding, yet little information exists to guide families regarding the safety of medicine use during lactation. Breastfeeding initiation or success may be altered by medicine use, and breastfeeding may obscure the true relationship between medicine exposure during pregnancy and developmental outcomes. Absent or poorly standardised recording of breastfeeding in most population databases hampers analysis and understanding of the complex relationships between medicine, pregnancy, breastfeeding and infant and maternal health. The purpose of this paper is to present the arguments for breastfeeding to be included alongside medicine use and neurodevelopmental outcomes in whole-population database investigations of the harms and benefits of medicines during pregnancy, the puerperium and postnatal period. We review: 1) the current situation, 2) how these complexities might be accommodated in pharmacoepidemiological models, using antidepressants and antiepileptics as examples; 3) the challenges in obtaining comprehensive data.

Conclusions

The scarcity of whole-population data and the complexities of the inter-relationships between breastfeeding, medicines, co-exposures and infant outcomes are significant barriers to full characterisation of the benefits and harms of medicines during pregnancy and breastfeeding. This makes it difficult to answer the questions: ‘is it safe to breastfeed whilst taking this medicine’, and ‘will this medicine interfere with breastfeeding and/ or infants’ development’?