bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimated public health impact of concurrent mask mandate and vaccinate-or-test requirement in Illinois, October to December 2021
Authors: Castonguay François M. , Barnes Arti , Jeon Seonghye , Fornoff Jane , Adhikari Bishwa B. , Fischer Leah S. , Greening Bradford , Hassan Adebola O. , Kahn Emily B. , Kang Gloria J. , Kauerauf Judy , Patrick Sarah , Vohra Sameer , Meltzer Martin I.
Published: April 2024

Background

Facing a surge of COVID-19 cases in late August 2021, the U.S. state of Illinois re-enacted its COVID-19 mask mandate for the general public and issued a requirement for workers in certain professions to be vaccinated against COVID-19 or undergo weekly testing. The mask mandate required any individual, regardless of their vaccination status, to wear a well-fitting mask in an indoor setting.

Methods

We used Illinois Department of Public Health’s COVID-19 confirmed case and vaccination data and investigated scenarios where masking and vaccination would have been reduced to mimic what would have happened had the mask mandate or vaccine requirement not been put in place. The study examined a range of potential reductions in masking and vaccination mimicking potential scenarios had the mask mandate or vaccine requirement not been enacted. We estimated COVID-19 cases and hospitalizations averted by changes in masking and vaccination during the period covering October 20 to December 20, 2021.

Results

We find that the announcement and implementation of a mask mandate are likely to correlate with a strong protective effect at reducing COVID-19 burden and the announcement of a vaccinate-or-test requirement among frontline professionals is likely to correlate with a more modest protective effect at reducing COVID-19 burden. In our most conservative scenario, we estimated that from the period of October 20 to December 20, 2021, the mask mandate likely prevented approximately 58,000 cases and 1,175 hospitalizations, while the vaccinate-or-test requirement may have prevented at most approximately 24,000 cases and 475 hospitalizations.

Conclusion

Our results indicate that mask mandates and vaccine-or-test requirements are vital in mitigating the burden of COVID-19 during surges of the virus.
Prevalence and predictors of iron deficiency anaemia among children with sickle cell disease in Dodoma, Tanzania: a cross-sectional study
Authors: Bossy Asha O. , Yahaya James J. , Jumanne Shakilu
Published: April 2024

Background

Patients with sickle cell disease (SCD) are prone to iron profile derangements. This study aimed to determine the prevalence of iron deficiency anaemia (IDA) and their predictors among children with SCD aged between 6 months and 14 years. Assessment of the prevalence of IDA and its predictors helps to understand ways of alleviating the magnitude of the problem so as to prevent possible complications such as shortness of breath and chest pain.

Methods

This was a cross-sectional analytical hospital-based study which included 174 patients with SCD attending SCD clinics at St. Gema hospital and Dodoma regional referral hospital in Dodoma city from October 2020 to March 2021. The cut-off points for detection of IDA was serum ferritin level < 30 µg/L and low mean corpuscular volume (MCV) for age. Data were analyzed using SPSS software version 25.0. Multivariate logistic regression analysis was used to determine the predictors of IDA. P-value less than 0.05 was considered significant.

Results

The prevalence of IDA in this study was (16.1%, n = 28). Family income of less than 70,000/= TZS/month (AOR = 2.2, 95% CI = 1.07–2.49, p = 0.023), being transfused with blood less than 3 times from the time of being diagnosed with SCD (AOR = 5.5, 95% CI = 1.03–8.91, p = 0.046), and eating red meat at least once per month (AOR = 3.60, 95% CI = 1.37–9.46, p = 0.010) remained the independent predictors of IDA in multivariate regression analysis.

Conclusion

The findings of this study have shown that, support of families with children suffering from SCD in terms of financial support for improving medical services including optimal blood transfusion and affordability of diet which is rich in iron such as red meat is imperative.
The global burden and risk factors of cardiovascular diseases in adolescent and young adults, 1990–2019
Authors: Tong Zhuang , Xie Yingying , Li Kaixiang , Yuan Ruixia , Zhang Liang
Published: April 2024

Background

To provide details of the burden and the trend of the cardiovascular disease (CVD) and its risk factors in adolescent and young adults.

Methods

Age-standardized rates (ASRs) of incidence, mortality and Disability-Adjusted Life Years (DALYs) were used to describe the burden of CVD in adolescents and young adults. Estimated Annual Percentage Changes (EAPCs) of ASRs were used to describe the trend from 1990 to 2019. Risk factors were calculated by Population Attributable Fractions (PAFs).

Results

In 2019, the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) of CVD were 129.85 per 100 000 (95% Confidence interval (CI): 102.60, 160.31), 15.12 per 100 000 (95% CI: 13.89, 16.48) and 990.64 per 100 000 (95% CI: 911.06, 1076.46). The highest ASRs were seen in low sociodemographic index (SDI) and low-middle SDI regions. The burden was heavier in male and individuals aged 35–39. From 1990 to 2019, 72 (35.29%) countries showed an increasing trend of ASIR and more than 80% countries showed a downward trend in ASMR and ASDR. Rheumatic heart disease had the highest ASIR and Ischemic Heart Disease was the highest in both ASMR and ASDR. The main attributable risk factor for death and DALYs were high systolic blood pressure, high body-mass index and high LDL cholesterol.

Conclusions

The burden of CVD in adolescent and young adults is a significant global health challenge. It is crucial to take into account the disparities in SDI levels among countries, gender and age characteristics of the population, primary types of CVD, and the attributable risk factors when formulating and implementing prevention strategies.
Dose-response relationship between 15 weeks of running and aerobic fitness: a retrospective analysis based on the fun running program
Authors: Tao Zhixuan , Sun Xugui , Sun Jun , Zhu Ergang
Published: April 2024

Background

Students’ physical fitness, particularly aerobic fitness, has seriously declined during the COVID-19 epidemic. However, in the post-epidemic era, there are few studies on the methods of improving aerobic fitness. Understanding the dose-response relationship between physical activity and aerobic fitness is crucial for developing effective exercise prescriptions.

Method

This retrospective study reviewed the Fun Running program at Wannan Medical College in China. We conducted a pre-post study design to analyze the impact of 15 weeks of Fun Running training on aerobic fitness. Middle and long-distance running pace (MLDR-P) was used as the primary indicator of aerobic fitness. A paired sample T-test was used to analyze the differences between the two MLDR-Ps. Pearson’s correlation was used to examine the correlation between variables. Multiple linear regression was used to determine the extent to which Fun Running components explain the variance in MLDR-P.

Results

A total of 3244 college students participated in this study. 15 weeks of Fun Running training can significantly improve the MLDR-P in both females (P < 0.001, ES = 0.68) and males (P < 0.001, ES = 0.72). The MLDR-P was significantly correlated with Fun Running (R2 = 0.95, p < 0.05, for females; R2 = 0.96, p < 0.05, for males). The component that had the greatest impact on MLDR-P was pace (β = 1.39, for females; β = 1.09, for males), followed by distance (β = 0.49, for females; β = 0.15, for males), and last frequency (β = -0.03, for all).

Conclusion

This study fills the gap in research on the dose-response relationship between running and aerobic fitness among college students in the post-epidemic era. The results show that 15 weeks of Fun Running training can significantly improve aerobic fitness. Examination of the dose-response relationship between Fun Running and MLDR-P provides practitioners with valuable insights into prescribing aerobic fitness training, allowing them to develop more effective training programs. Future research should focus on how to implement a hierarchical Fun Running program effectively.
The association between device-measured sitting time and cardiometabolic health risk factors in children
Authors: Contardo Ayala Ana María , Ridgers Nicola D. , Timperio Anna , Arundell Lauren , Dunstan David W. , Hesketh Kylie D. , Daly Robin M. , Salmon Jo
Published: April 2024

Background

There is limited evidence of the associations between postural-derived sitting time, waist-worn derived sedentary time and children’s health and the moderation effect of physical activity (PA). This study examined associations of children’s device-measured sitting time with cardiometabolic health risk factors, including moderation by physical activity.

Methods

Cross-sectional baseline data from children (mean-age 8.2 ± 0.5 years) in Melbourne, Australia (2010) participating in the TransformUs program were used. Children simultaneously wore an activPAL to assess sitting time and an ActiGraph GT3X to assess sedentary time and physical activity intensity. Cardiometabolic health risk factors included: adiposity (body mass index [BMI], waist circumference [WC]), systolic and diastolic blood pressure (SBP, DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), cholesterol, triglycerides, fasting plasma glucose (FPG), serum insulin, and 25-hydroxyvitaminD (25[OH]D). Linear regression models (n = 71–113) assessed associations between sitting time with each health risk factor, adjusted for different PA intensities (i.e. light [LIPA], moderate-vigorous intensities [MVPA], separately on each model), age, sex, adiposity, and clustering by school. Interaction terms examined moderation. The analyses were repeated using device-measured sedentary time (i.e. ActiGraph GT3X) for comparison.

Results

Sitting time was positively associated with SBP (b = 0.015; 95%CI: 0.004, 0.026), DBP (b = 0.012; 95%CI:0.004, 0.020), and FPG (b = 0.001; 95%CI: 0.000, 0.000), after adjusting for higher PA intensities. The association between sitting time and insulin (b = 0.003; 95%CI: 0.000, 0.006) was attenuated after adjusting for higher PA intensities. When the models were adjusted for LIPA and MVPA, there was a negative association with LDL (b=-0.001; 95%CI: -0.002, -0.000 and b=-0.001; 95%CI: -0.003, -0.000, respectively). There was a negative association of sedentary time with WCz (b=-0.003; 95%CI: -0.005, 0.000) and BMIz (b=-0.003; 95%CI: -0.006, -0.000) when the models were adjusted by MVPA. Sedentary time was positively associated with triglycerides (b = 0.001; 95%CI: 0.000, 0.001) but attenuated after adjusting for MVPA. No evidence of moderation effects was found.

Conclusions

Higher volumes of sitting and sedentary time were associated with some adverse associations on some cardiometabolic health risk factors in children. These associations were more evident when sitting time was the predictor. This suggests that reducing time spent sitting may benefit some cardiometabolic health outcomes, but future experimental research is needed to confirm causal relationships and identify the biological mechanisms that might be involved.

Trial registration

Australian New Zealand Clinical Trials Registry: ACTRN12609000715279.
Treatment of tibial bone defects caused by infection: a retrospective comparative study of bone transport using a combined technique of unilateral external fixation over an intramedullary nail versus circular external fixation over an intramedullary nail
Authors: Maimaiti Xiayimaierdan , Liu Kai , Yusufu Aihemaitijiang , Xie Zengru
Published: April 2024

Background

The purpose of the study was to assess and compare the clinical efficacy of bone transport with either circular or unilateral external fixators over an intramedullary nail in the treatment of tibial bone defects caused by infection.

Methods

Between May 2010 and January 2019, clinical and radiographic data were collected and analyzed for patients with bone defects caused by infection. Thirteen patients underwent bone transport using a unilateral external fixator over an intramedullary nail (Group A), while 12 patients were treated with a circular external fixator over an intramedullary nail (Group B). The bone and functional outcomes of both groups were assessed and compared using the Association for the Study and Application of the Method of the Ilizarov criteria, and postoperative complications were evaluated according to the Paley classification.

Results

A total of 25 patients were successfully treated with bone transport using external fixators over an intramedullary nail, with a mean follow-up time of 31.63 ± 5.88 months. There were no significant statistical differences in age, gender, previous surgery per patient, duration of infection, defect size, and follow-up time between Group A and Group B (P > 0.05). However, statistically significant differences were observed in operation time (187.13 ± 21.88 min vs. 255.76 ± 36.42 min, P = 0.002), intraoperative blood loss (39.26 ± 7.33 mL vs. 53.74 ± 10.69 mL, P < 0.001), external fixation time (2.02 ± 0.31 month vs. 2.57 ± 0.38 month, P = 0.045), external fixation index (0.27 ± 0.08 month/cm vs. 0.44 ± 0.09 month/cm, P = 0.042), and bone union time (8.37 ± 2.30 month vs. 9.07 ± 3.12, P = 0.032) between Group A and Group B. The excellent and good rate of bone and functional results were higher in Group A compared to Group B (76.9% vs. 75% and 84.6% vs. 58.3%). Statistically significant differences were observed in functional results (excellent/good/fair/poor, 5/6/2/0 vs. 2/5/4/1, P = 0.013) and complication per patient (0.38 vs. 1.16, P = 0.012) between Group A and Group B.

Conclusions

Bone transport using a combined technique of external fixators over an intramedullary nail proved to be an effective method in treating tibial bone defects caused by infection. In comparison to circular external fixators, bone transport utilizing a unilateral external fixator over an intramedullary nail resulted in less external fixation time, fewer complications, and better functional outcomes.
Survivorship of the fixed-bearing medial unicompartmental knee arthroplasty: mean 14-year follow-up in a single medical center
Authors: Hung Kung-Tseng , Chen Chun‑Chieh , Lin Yu-Chih , Lee Sheng-Hsun , Hu Chih-Chien , Chang Yu-Han , Hsieh Pang-Hsin , Shih Hsin-Nung , Chang Chih-Hsiang
Published: April 2024

Background

This study aimed to report the long-term survival of fixed-bearing medial unicompartmental knee arthroplasty (UKA) with a mean of 14-year follow-up, and to determine possible risk factors of failure.

Methods

We retrospectively evaluated 337 fixed-bearing medial UKAs implanted between 2003 and 2014. Demographic and radiographic parameters were measured, including pre-operative and post-operative anatomical femorotibial angle (aFTA), posterior tibial slope (PTS), and anatomical medial proximal tibial angle (aMPTA). Multivariate logistic regression analysis was applied to figure out risk factors.

Results

The mean follow-up time was 14.0 years. There were 32 failures categorized into implant loosening (n = 11), osteoarthritis progression (n = 7), insert wear (n = 7), infection (n = 4), and periprosthetic fracture (n = 3). Cumulative survival was 91.6% at 10 years and 90.0% at 15 years. No statistically significant parameters were found between the overall survival and failure groups. Age and hypertension were significant factors of implant loosening with odds ratio (OR) 0.909 (p = 0.02) and 0.179 (p = 0.04) respectively. In the insert wear group, post-operative aFTA and correction of PTS showed significance with OR 0.363 (p = 0.02) and 0.415 (p = 0.03) respectively. Post-operative aMPTA was a significant factor of periprosthetic fracture with OR 0.680 (p < 0.05).

Conclusions

The fixed-bearing medial UKA provides successful long-term survivorship. Tibial component loosening is the major cause of failure. Older age and hypertension were factors with decreased risk of implant loosening.
Reliability of thoracolumbar burst fracture classification in the Swedish Fracture Register
Authors: Blixt Simon , Burmeister Fabian , Mukka Sebastian , Bobinski Lukas , Försth Peter , Westin Olof , Gerdhem Paul
Published: April 2024

Background

The Swedish Fracture Register (SFR) is a national quality register for all types of fractures in Sweden. Spine fractures have been included since 2015 and are classified using a modified AOSpine classification. The aim of this study was to determine the accuracy of the classification of thoracolumbar burst fractures in the SFR.

Methods

Assessments of medical images were conducted in 277 consecutive patients with a thoracolumbar burst fracture (T10-L3) identified in the SFR. Two independent reviewers classified the fractures according to the AOSpine classification, with a third reviewer resolving disagreement. The combined results of the reviewers were considered the gold standard. The intra- and inter-rater reliability of the reviewers was determined with Cohen’s kappa and percent agreement. The SFR classification was compared with the gold standard using positive predictive values (PPV), Cohen’s kappa and percent agreement.

Results

The reliability between reviewers was  high (Cohen’s kappa 0.70–0.97). The PPV for correctly classifying burst fractures in the SFR was high irrespective of physician experience (76–89%), treatment (82% non-operative, 95% operative) and hospital type (83% county, 95% university). The inter-rater reliability of B-type injuries and the overall SFR classification compared with the gold standard was low (Cohen’s kappa 0.16 and 0.17 respectively).

Conclusions

The SFR demonstrates a high PPV for accurately classifying burst fractures, regardless of physician experience, treatment and hospital type. However, the reliability of B-type injuries and overall classification in the SFR was found to be low. Future studies on burst fractures using SFR data where classification is important should include a review of medical images to verify the diagnosis.
Transcriptomic and targeted metabolomic analyses provide insights into the flavonoids biosynthesis in the flowers of Lonicera macranthoides
Authors: Lv Ling Ling , Li Li Yun , Xiao Long Qian , Pi Jian Hui
Published: April 2024

Background

Flavonoids are one of the bioactive ingredients of Lonicera macranthoides (L. macranthoides), however, their biosynthesis in the flower is still unclear. In this study, combined transcriptomic and targeted metabolomic analyses were performed to clarify the flavonoids biosynthesis during flowering of L. macranthoides.

Results

In the three sample groups, GB_vs_WB, GB_vs_WF and GB_vs_GF, there were 25, 22 and 18 differentially expressed genes (DEGs) in flavonoids biosynthetic pathway respectively. A total of 339 flavonoids were detected and quantified at four developmental stages of flower in L. macranthoides. In the three sample groups, 113, 155 and 163 differentially accumulated flavonoids (DAFs) were detected respectively. Among the DAFs, most apigenin derivatives in flavones and most kaempferol derivatives in flavonols were up-regulated. Correlation analysis between DEGs and DAFs showed that the down-regulated expressions of the CHS, DFR, C4H, F3’H, CCoAOMT_32 and the up-regulated expressions of the two HCTs resulted in down-regulated levels of dihydroquercetin, epigallocatechin and up-regulated level of kaempferol-3-O-(6’’-O-acetyl)-glucoside, cosmosiin and apigenin-4’-O-glucoside. The down-regulated expressions of F3H and FLS decreased the contents of 7 metabolites, including naringenin chalcone, proanthocyanidin B2, B3, B4, C1, limocitrin-3,7-di-O-glucoside and limocitrin-3-O-sophoroside.

Conclusion

The findings are helpful for genetic improvement of varieties in L.macranthoides.
Participatory methods used in the evaluation of medical devices: a comparison of focus groups, interviews, and a survey
Authors: Woudstra Kas , Tummers Marcia , Klijn Catharina J. M. , Sondag Lotte , Schreuder Floris , Reuzel Rob , Rovers Maroeska
Published: April 2024

Background

Stakeholder engagement in evaluation of medical devices is crucial for aligning devices with stakeholders’ views, needs, and values. Methods for these engagements have however not been compared to analyse their relative merits for medical device evaluation. Therefore, we systematically compared these three methods in terms of themes, interaction, and time-investment.

Methods

We compared focus groups, interviews, and an online survey in a case-study on minimally invasive endoscopy-guided surgery for patients with intracerebral haemorrhage. The focus groups and interviews featured two rounds, one explorative focussing on individual perspectives, and one interactive focussing on the exchange of perspectives between participants. The comparison between methods was made in terms of number and content of themes, how participants interact, and hours invested by all researchers.

Results

The focus groups generated 34 themes, the interviews 58, and the survey 42. Various improvements for the assessment of the surgical procedure were only discussed in the interviews. In focus groups, participants were inclined to emphasise agreement and support, whereas the interviews consisted of questions and answers. The total time investment for researchers of focus groups was 95 h, of interviews 315 h, and survey 81 h.

Conclusions

Within the context of medical device evaluation, interviews appeared to be the most appropriate method for understanding stakeholder views since they provide a scope and depth of information that is not generated by other methods. Focus groups were useful to rapidly bring views together. Surveys enabled a quick exploration. Researchers should account for these methodological differences and select the method that is suitable for their research aim.
Stakeholder opinions on perceived sub-standard emergency obstetric and newborn care in Ghana
Authors: Ayawine Alice , Asaarik Mathias J. A. , Atinga Roger A.
Published: April 2024

Background

Sub-Saharan Africa is unlikely to achieve sustainable development goal (SDG) 3 on maternal and neonatal health due to perceived sub-standard maternal and newborn care in the region. This paper sought to explore the opinions of stakeholders on intricacies dictating sub-standard emergency obstetric and newborn care (EmONC) in health facilities in Northern Ghana.

Methods

Drawing from a qualitative study design, data were obtained from six focus group discussions (FGDs) among 42 health care providers and 27 in-depth interviews with management members, clients and care takers duly guided by the principle of data saturation. Participants were purposively selected from basic and comprehensive level facilities. Data analysis followed Braun and Clarke’s qualitative thematic analysis procedure.

Results

Four themes and 13 sub-themes emerged as root drivers to sub-standard care. Specfically, the findings highlight centralisation of EmONC, inadequate funding, insufficient experiential training, delay in recruitment of newly trained essential staff and provider disinterest in profession.

Conclusion

Setbacks in the training and recruitment systems in Ghana, inadequate investment in rural health coupled with extent of health provider inherent disposition to practice may be partly responsible for sub-standard obstetric care in the study area. Interventions targeting the afore-mentioned areas may reduce events of sub-standard care.
Identification and support of autistic individuals within the UK Criminal Justice System: a practical approach based upon professional consensus with input from lived experience
Authors: Woodhouse Emma , Hollingdale Jack , Davies Lisa , Al-Attar Zainab , Young Susan , Vinter Luke P. , Agyemang Kwaku , Bartlett Carla , Berryessa Colleen , Chaplin Eddie , Deeley Quinton , Freckelton Ian , Gerry Felicity , Gudjonsson Gisli , Maras Katie , Mattison Michelle , McCarthy Jane , Mills Richard , Misch Peter , Murphy David , Allely Clare
Published: April 2024

Background

Autism spectrum disorder (hereafter referred to as autism) is characterised by difficulties with (i) social communication, social interaction, and (ii) restricted and repetitive interests and behaviours. Estimates of autism prevalence within the criminal justice system (CJS) vary considerably, but there is evidence to suggest that the condition can be missed or misidentified within this population. Autism has implications for an individual’s journey through the CJS, from police questioning and engagement in court proceedings through to risk assessment, formulation, therapeutic approaches, engagement with support services, and long-term social and legal outcomes.

Methods

This consensus based on professional opinion with input from lived experience aims to provide general principles for consideration by United Kingdom (UK) CJS personnel when working with autistic individuals, focusing on autistic offenders and those suspected of offences. Principles may be transferable to countries beyond the UK. Multidisciplinary professionals and two service users were approached for their input to address the effective identification and support strategies for autistic individuals within the CJS.

Results

The authors provide a consensus statement including recommendations on the general principles of effective identification, and support strategies for autistic individuals across different levels of the CJS.

Conclusion

Greater attention needs to be given to this population as they navigate the CJS.
Nanobiotechnology augmented cancer stem cell guided management of cancer: liquid-biopsy, imaging, and treatment
Authors: Sun Si , Yang Qiang , Jiang Dawei , Zhang Yuan
Published: April 2024

Cancer stem cells (CSCs) represent both a key driving force and therapeutic target of tumoral carcinogenesis, tumor evolution, progression, and recurrence. CSC-guided tumor diagnosis, treatment, and surveillance are strategically significant in improving cancer patients’ overall survival. Due to the heterogeneity and plasticity of CSCs, high sensitivity, specificity, and outstanding targeting are demanded for CSC detection and targeting. Nanobiotechnologies, including biosensors, nano-probes, contrast enhancers, and drug delivery systems, share identical features required. Implementing these techniques may facilitate the overall performance of CSC detection and targeting. In this review, we focus on some of the most recent advances in how nanobiotechnologies leverage the characteristics of CSC to optimize cancer diagnosis and treatment in liquid biopsy, clinical imaging, and CSC-guided nano-treatment. Specifically, how nanobiotechnologies leverage the attributes of CSC to maximize the detection of circulating tumor DNA, circulating tumor cells, and exosomes, to improve positron emission computed tomography and magnetic resonance imaging, and to enhance the therapeutic effects of cytotoxic therapy, photodynamic therapy, immunotherapy therapy, and radioimmunotherapy are reviewed.
Macrophage membrane-camouflaged pH-sensitive nanoparticles for targeted therapy of oral squamous cell carcinoma
Authors: Yang Lin , Li Hongjiao , Luo Aihua , Zhang Yao , Chen Hong , Zhu Li , Yang Deqin
Published: April 2024

Background

Oral cancer is the most common malignant tumor of the head and neck, and 90% of cases are oral squamous cell carcinoma (OSCC). Chemotherapy is an important component of comprehensive treatment for OSCC. However, the clinical treatment effect of chemotherapy drugs, such as doxorubicin (DOX), is limited due to the lack of tumor targeting and rapid clearance by the immune system. Thus, based on the tumor-targeting and immune evasion abilities of macrophages, macrophage membrane-encapsulated poly(methyl vinyl ether alt maleic anhydride)-phenylboronic acid-doxorubicin nanoparticles (MM@PMVEMA-PBA-DOX NPs), briefly as MM@DOX NPs, were designed to target OSCC. The boronate ester bonds between PBA and DOX responded to the low pH value in the tumor microenvironment, selectively releasing the loaded DOX.

Results

The results showed that MM@DOX NPs exhibited uniform particle size and typical core-shell structure. As the pH decreased from 7.4 to 5.5, drug release increased from 14 to 21%. The in vitro targeting ability, immune evasion ability, and cytotoxicity of MM@DOX NPs were verified in HN6 and SCC15 cell lines. Compared to free DOX, flow cytometry and fluorescence images demonstrated higher uptake of MM@DOX NPs by tumor cells and lower uptake by macrophages. Cell toxicity and live/dead staining experiments showed that MM@DOX NPs exhibited stronger in vitro antitumor effects than free DOX. The targeting and therapeutic effects were further confirmed in vivo. Based on in vivo biodistribution of the nanoparticles, the accumulation of MM@DOX NPs at the tumor site was increased. The pharmacokinetic results demonstrated a longer half-life of 9.26 h for MM@DOX NPs compared to 1.94 h for free DOX. Moreover, MM@DOX NPs exhibited stronger tumor suppression effects in HN6 tumor-bearing mice and good biocompatibility.

Conclusions

Therefore, MM@DOX NPs is a safe and efficient therapeutic platform for OSCC.
Attenuation of inflammatory bowel disease by oral administration of mucoadhesive polydopamine-coated yeast β-glucan via ROS scavenging and gut microbiota regulation
Authors: Yang Fan , Su Yuting , Yan Chi , Chen Tianfeng , Cheung Peter Chi Keung
Published: April 2024

Treatment for inflammatory bowel disease (IBD) is challenging since current anti-inflammatory and immunosuppressive therapies do not address the underlying causes of the illness, which include increased levels of reactive oxygen species (ROS) and dysbiosis of the gut commensal microbiota. Additionally, these treatments often have systemic off-target effects and adverse side effects. In this study, we have developed a prebiotic yeast β-glucan nanocomplex coated with bio-adhesive polydopamine (YBNs@PDA) to effectively prolong their retention time in the gastrointestinal (GI) tract. The oral administration of YBNs@PDA restored the epithelium barriers, reduced ROS levels, and minimized systemic drug exposure while improved therapeutic efficacy in an acute colitis mouse model. Furthermore, 16S ribosomal RNA genes sequencing demonstrated a higher richness and diversity in gut microflora composition following the treatments. In particular, YBNs@PDA markedly augmented the abundance of Lachnospiraceae NK4A136 and Bifidobacterium, both of which are probiotics with crucial roles in relieving colitis via retaining gut homeostasis. Cumulatively, these results demonstrate that the potential of YBNs@PDA as a novel drug-free, ROS-scavenging and gut microbiota regulation nanoplatform for the treatment of GI disorders.
Development of nanoparticles incorporated with quercetin and ACE2-membrane as a novel therapy for COVID-19
Authors: Fang Jia-You , Huang Kuo-Yen , Wang Tong-Hong , Lin Zih-Chan , Chen Chin-Chuan , Chang Sui-Yuan , Chen En-Li , Chao Tai-Ling , Yang Shuenn-Chen , Yang Pan-Chyr , Chen Chi-Yuan
Published: April 2024

Introduction

Angiotensin-converting enzyme 2 (ACE2) and AXL tyrosine kinase receptor are known to be involved in the SARS-CoV-2 entry of the host cell. Therefore, targeting ACE2 and AXL should be an effective strategy to inhibit virus entry into cells. However, developing agents that can simultaneously target ACE2 and AXL remains a formidable task. The natural compound quercetin has been shown to inhibit AXL expression.

Materials and methods

In this study, we employed PLGA nanoparticles to prepare nanoparticles encapsulated with quercetin, coated with ACE2-containing cell membranes, or encapsulated with quercetin and then coated with ACE-2-containing cell membranes. These nanoparticles were tested for their abilities to neutralize or inhibit viral infection.

Results

Our data showed that nanoparticles encapsulated with quercetin and then coated with ACE2-containing cell membrane inhibited the expression of AXL without causing cytotoxic activity. Nanoparticles incorporated with both quercetin and ACE2-containing cell membrane were found to be able to neutralize pseudo virus infection and were more effective than free quercetin and nanoparticles encapsulated with quercetin at inhibition of pseudo virus and SARS-CoV-2 infection.

Conclusions

We have shown that the biomimetic nanoparticles incorporated with both ACE-2 membrane and quercetin showed the most antiviral activity and may be further explored for clinical application.
HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfractures
Authors: Chen Zhian , Zhou Tianhua , Luo Huan , Wang Zhen , Wang Qiang , Shi Rongmao , Li Zian , Pang Rongqing , Tan Hongbo
Published: April 2024

The current first-line treatment for repairing cartilage defects in clinical practice is the creation of microfractures (MF) to stimulate the release of mesenchymal stem cells (MSCs); however, this method has many limitations. Recent studies have found that MSC-derived extracellular vesicles (MSC-EVs) play an important role in tissue regeneration. This study aimed to verify whether MSC-EVs promote cartilage damage repair mediated by MFs and to explore the repair mechanisms. In vitro experiments showed that human umbilical cord Wharton’s jelly MSC-EVs (hWJMSC-EVs) promoted the vitality of chondrocytes and the proliferation and differentiation ability of bone marrow-derived MSCs. This was mainly because hWJMSC-EVs carry integrin beta-1 (ITGB1), and cartilage and bone marrow-derived MSCs overexpress ITGB1 after absorbing EVs, thereby activating the transforming growth factor-β/Smad2/3 axis. In a rabbit knee joint model of osteochondral defect repair, the injection of different concentrations of hWJMSC-EVs into the joint cavity showed that a concentration of 50 µg/ml significantly improved the formation of transparent cartilage after MF surgery. Extraction of regenerated cartilage revealed that the changes in ITGB1, transforming growth factor-β, and Smad2/3 were directly proportional to the repair of regenerated cartilage. In summary, this study showed that hWJMSC-EVs promoted cartilage repair after MF surgery.

Graphical abstract
Nicotine restores olfactory function by activation of prok2R/Akt/FoxO3a axis in Parkinson’s disease
Authors: Guo Qinglong , Wang Yi , Yu Liangchen , Guan Liao , Ji Xuefei , Li Xiaohui , Pang Gang , Ren Zhenhua , Ye Lei , Cheng Hongwei
Published: April 2024

Background

Olfactory dysfunction occurs frequently in Parkinson’s disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice.

Methods

MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Next, prok2R overexpression (prok2R+) and knockdown (prok2R−) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP+ were evaluated in prok2R overexpression (prok2R+) HEK293T cell lines.

Results

Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R+ and prok2R− HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R+ HEK293T cells were resistant to MPP+-induced apoptosis.

Conclusions

This study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients.
Lactation duration and development of type 2 diabetes and metabolic syndrome in postpartum women with recent gestational diabetes mellitus
Authors: Suthasmalee Sasiwan , Phaloprakarn Chadakarn
Published: April 2024

Background

The World Health Organization and United Nations Children’s Fund recommend exclusive breastfeeding (EBF) for the first six months of an infant’s life. Although evidence suggests that maintaining breastfeeding has positive impacts on glucose and lipid metabolism in postpartum women with a history of gestational diabetes mellitus (GDM), no study has investigated whether such effects differ between breastfeeding intensities. This study aimed to evaluate the impact of maintaining breastfeeding on prediabetes, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS) six months postpartum in women with GDM. This study also examined the potential variations in glucometabolic outcomes between EBF at six months and partial breastfeeding at six months.

Methods

This prospective cohort study included 130 women with recent GDM who experienced live births between 7 September 2020 and 31 January 2023 at a university hospital in Bangkok, Thailand. All the women were free of T2DM and MetS at baseline (six weeks postpartum). We followed up these women six months postpartum to assess their breastfeeding practices (EBF at six months, partial breastfeeding at six months, or not maintaining breastfeeding) and evaluate their progression to prediabetes, T2DM, and MetS. Maintaining breastfeeding was defined as breastfeeding for six months. EBF was determined using the “recall since birth” method.

Results

Of the 130 participants included, the rates of prediabetes, T2DM, and MetS six months postpartum were 33% (n = 43), 2% (n = 3), and 17% (n = 22), respectively. In the unadjusted model, maintaining breastfeeding was associated with a reduction in the risks of prediabetes and MetS but not T2DM. After adjusting for potential confounders, maintaining breastfeeding was a significant protective factor only for prediabetes. The adjusted risk ratios and 95% confidence intervals were 0.54 (0.29, 0.99) for prediabetes and 0.47 (0.19, 1.06) for MetS. When EBF at six months and partial breastfeeding at six months were separately analyzed, the risks of prediabetes and MetS differed between the two groups. In the EBF at six months-to-partial breastfeeding at six months comparison, the adjusted risk ratios (95% confidence intervals) of prediabetes and MetS were 0.46 (0.22, 0.97) vs. 0.79 (0.25, 2.49) and 0.34 (0.11, 0.99) vs. 0.69 (0.22, 2.07), respectively.

Conclusions

Maintaining breastfeeding reduced the risk of prediabetes and MetS, but not of T2DM, six months postpartum; these effects were significant only with EBF. These findings indicate that supporting maternal efforts to practice EBF for six months may improve women’s health after GDM.

Trial registration

Thai Clinical Trials Registry Registration No. TCTR20200902003. Date of registration: September 2, 2020. Date of initial participant enrollment: September 7, 2020.
Non-traumatic osteonecrosis of the femoral head induced by steroid and alcohol exposure is associated with intestinal flora alterations and metabolomic profiles
Authors: Zheng Qing-Yuan , Tao Ye , Geng Lei , Ren Peng , Ni Ming , Zhang Guo-Qiang
Published: April 2024

Objective

Osteonecrosis of the femoral head (ONFH) is a severe disease that primarily affects the middle-aged population, imposing a significant economic and social burden. Recent research has linked the progression of non-traumatic osteonecrosis of the femoral head (NONFH) to the composition of the gut microbiota. Steroids and alcohol are considered major contributing factors. However, the relationship between NONFH caused by two etiologies and the microbiota remains unclear. In this study, we examined the gut microbiota and fecal metabolic phenotypes of two groups of patients, and analyzed potential differences in the pathogenic mechanisms from both the microbial and metabolic perspectives.

Methods

Utilizing fecal samples from 68 NONFH patients (32 steroid-induced, 36 alcohol-induced), high-throughput 16 S rDNA sequencing and liquid chromatography with tandem mass spectrometry (LC-MS/MS) metabolomics analyses were conducted. Univariate and multivariate analyses were applied to the omics data, employing linear discriminant analysis effect size to identify potential biomarkers. Additionally, functional annotation of differential metabolites and associated pathways was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Subsequently, Spearman correlation analysis was employed to assess the potential correlations between differential gut microbiota and metabolites.

Results

High-throughput 16 S rDNA sequencing revealed significant gut microbial differences. At the genus level, the alcohol group had higher Lactobacillus and Roseburia, while the steroid group had more Megasphaera and Akkermansia. LC-MS/MS metabolomic analysis indicates significant differences in fecal metabolites between steroid- and alcohol-induced ONFH patients. Alcohol-induced ONFH (AONFH) showed elevated levels of L-Lysine and Oxoglutaric acid, while steroid-induced ONFH(SONFH) had increased Gluconic acid and Phosphoric acid. KEGG annotation revealed 10 pathways with metabolite differences between AONFH and SONFH patients. Correlation analysis revealed the association between differential gut flora and differential metabolites.

Conclusions

Our results suggest that hormones and alcohol can induce changes in the gut microbiota, leading to alterations in fecal metabolites. These changes, driven by different pathways, contribute to the progression of the disease. The study opens new research directions for understanding the pathogenic mechanisms of hormone- or alcohol-induced NONFH, suggesting that differentiated preventive and therapeutic approaches may be needed for NONFH caused by different triggers.
Impact of delayed mobile medical team dispatch for respiratory distress calls: a propensity score matched study from a French emergency communication center
Authors: Charrin Léo , Romain-Scelle Nicolas , Di-Filippo Christian , Mercier Eric , Balen Frederic , Tazarourte Karim , Benhamed Axel
Published: April 2024

Background

Shortness of breath is a common complaint among individuals contacting emergency communication center (EMCCs). In some prehospital system, emergency medical services include an advanced life support (ALS)-capable team. Whether such team should be dispatched during the phone call or delayed until the BLS-capable paramedic team reports from the scene is unclear. We aimed to evaluate the impact of delayed MMT dispatch until receiving the paramedic review compared to immediate dispatch at the time of the call on patient outcomes.

Methods

A cross-sectional study conducted in Lyon, France, using data obtained from the departmental EMCC during the period from January to December 2019. We included consecutive calls related to adult patients experiencing acute respiratory distress. Patients from the two groups (immediate mobile medical team (MMT) dispatch or delayed MMT dispatch) were matched on a propensity score, and a conditional weighted logistic regression assessed the adjusted odds ratios (ORs) for each outcome (mortality on days 0, 7 and 30).

Results

A total of 870 calls (median age 72 [57–84], male 466 53.6%) were sought for analysis [614 (70.6%) “immediate MMT dispatch” and 256 (29.4%) “delayed MMT” groups]. The median time before MMT dispatch was 25.1 min longer in the delayed MMT group (30.7 [26.4–36.1] vs. 5.6 [3.9–8.8] min, p < 0.001). Patients subjected to a delayed MMT intervention were older (median age 78 [66–87] vs. 69 [53–83], p < 0.001) and more frequently highly dependent (16.3% vs. 8.6%, p < 0.001). A higher proportion of patients in the delayed MMT group required bag valve mask ventilation (47.3% vs. 39.1%, p = 0.03), noninvasive ventilation (24.6% vs. 20.0%, p = 0.13), endotracheal intubation (7.0% vs. 4.1%, p = 0.07) and catecholamine infusion (3.9% vs. 1.3%, p = 0.01). After propensity score matching, mortality at day 0 was higher in the delayed MMT group (9.8% vs. 4.2%, p = 0.002). Immediate MMT dispatch at the call was associated with a lower risk of mortality on day 0 (0.60 [0.38;0.82], p < 0.001) day 7 (0.50 [0.27;0.72], p < 0.001) and day 30 (0.56 [0.35;0.78], p < 0.001)

Conclusions

This study suggests that the deployment of an MMT at call in patients in acute respiratory distress may result in decreased short to medium-term mortality compared to a delayed MMT following initial first aid assessment.
Risk of conversion to mild cognitive impairment or dementia among subjects with amyloid and tau pathology: a systematic review and meta-analysis
Authors: Huszár Zsolt , Engh Marie Anne , Pavlekovics Márk , Sato Tomoya , Steenkamp Yalea , Hanseeuw Bernard , Terebessy Tamás , Molnár Zsolt , Hegyi Péter , Csukly Gábor
Published: April 2024

Background

Measurement of beta-amyloid (Aβ) and phosphorylated tau (p-tau) levels offers the potential for early detection of neurocognitive impairment. Still, the probability of developing a clinical syndrome in the presence of these protein changes (A+ and T+) remains unclear. By performing a systematic review and meta-analysis, we investigated the risk of mild cognitive impairment (MCI) or dementia in the non-demented population with A+ and A- alone and in combination with T+ and T- as confirmed by PET or cerebrospinal fluid examination.

Methods

A systematic search of prospective and retrospective studies investigating the association of Aβ and p-tau with cognitive decline was performed in three databases (MEDLINE via PubMed, EMBASE, and CENTRAL) on January 9, 2024. The risk of bias was assessed using the Cochrane QUIPS tool. Odds ratios (OR) and Hazard Ratios (HR) were pooled using a random-effects model. The effect of neurodegeneration was not studied due to its non-specific nature.

Results

A total of 18,162 records were found, and at the end of the selection process, data from 36 cohorts were pooled (n= 7,793). Compared to the unexposed group, the odds ratio (OR) for conversion to dementia in A+ MCI patients was 5.18 [95% CI 3.93; 6.81]. In A+ CU subjects, the OR for conversion to MCI or dementia was 5.79 [95% CI 2.88; 11.64]. Cerebrospinal fluid Aβ42 or Aβ42/40 analysis and amyloid PET imaging showed consistent results. The OR for conversion in A+T+ MCI subjects (11.60 [95% CI 7.96; 16.91]) was significantly higher than in A+T- subjects (2.73 [95% CI 1.65; 4.52]). The OR for A-T+ MCI subjects was non-significant (1.47 [95% CI 0.55; 3.92]). CU subjects with A+T+ status had a significantly higher OR for conversion (13.46 [95% CI 3.69; 49.11]) than A+T- subjects (2.04 [95% CI 0.70; 5.97]). Meta-regression showed that the ORs for Aβ exposure decreased with age in MCI. (beta = -0.04 [95% CI -0.03 to -0.083]).

Conclusions

Identifying Aβ-positive individuals, irrespective of the measurement technique employed (CSF or PET), enables the detection of the most at-risk population before disease onset, or at least at a mild stage. The inclusion of tau status in addition to Aβ, especially in A+T+ cases, further refines the risk assessment. Notably, the higher odds ratio associated with Aβ decreases with age.

Trial registration

The study was registered in PROSPERO (ID: CRD42021288100).