bluuebunny/crossref_metadata_2025 huggingface dataset:
Topological alterations in white matter anatomical networks in cervical dystonia
Authors: Zhang Jiana , Luo Yuhan , Zhong Linchang , Liu Huiming , Yang Zhengkun , Weng Ai , Zhang Yue , Zhang Weixi , Yan Zhicong , Xu Jinping , Liu Gang , Peng Kangqiang , Ou Zilin
Published: May 2024

Background

Accumulating neuroimaging evidence indicates that patients with cervical dystonia (CD) have changes in the cortico-subcortical white matter (WM) bundle. However, whether these patients’ WM structural networks undergo reorganization remains largely unclear. We aimed to investigate topological changes in large-scale WM structural networks in patients with CD compared to healthy controls (HCs), and explore the network changes associated with clinical manifestations.

Methods

Diffusion tensor imaging (DTI) was conducted in 30 patients with CD and 30 HCs, and WM network construction was based on the BNA-246 atlas and deterministic tractography. Based on the graph theoretical analysis, global and local topological properties were calculated and compared between patients with CD and HCs. Then, the AAL-90 atlas was used for the reproducibility analyses. In addition, the relationship between abnormal topological properties and clinical characteristics was analyzed.

Results

Compared with HCs, patients with CD showed changes in network segregation and resilience, characterized by increased local efficiency and assortativity, respectively. In addition, a significant decrease of network strength was also found in patients with CD relative to HCs. Validation analyses using the AAL-90 atlas similarly showed increased assortativity and network strength in patients with CD. No significant correlations were found between altered network properties and clinical characteristics in patients with CD.

Conclusion

Our findings show that reorganization of the large-scale WM structural network exists in patients with CD. However, this reorganization is attributed to dystonia-specific abnormalities or hyperkinetic movements that need further identification.
Association between gut microbiota and anxiety disorders: a bidirectional two-sample mendelian randomization study
Authors: Li Jianbing , Fan Changhe , Wang Jiaqi , Tang Bulang , Cao Jiafan , Hu Xianzhe , Zhao Xuan , Feng Caiqin
Published: May 2024

Background

There are many articles reporting that the component of intestinal microbiota implies a link to anxiety disorders (AD), and the brain-gut axis is also a hot topic in current research. However, the specific relevance between gut microbiota and AD is uncertain. We aimed to investigate causal relationship between gut microbiota and AD by using bidirectional Mendelian randomization (MR).

Methods

Genetic instrumental variable (IV) for the gut microbiota were obtained from a genome-wide association study (GWAS) involving 18,340 participants. Summary data for AD were derived from the GWAS and included 158,565 cases and 300,995 controls. We applied the inverse variance weighted (IVW) method as the main analysis. Cochran’s Q values was computed to evaluate the heterogeneity among IVs. Sensitivity analyses including intercept of MR-Egger method and MR-PRESSO analysis were used to test the horizontal pleiotropy.

Result

We discovered 9 potential connections between bacterial traits on genus level and AD. Utilizing the IVW method, we identified 5 bacterial genera that exhibited a direct correlation with the risk of AD: genus Eubacteriumbrachygroup, genus Coprococcus3, genus Enterorhabdus, genus Oxalobacter, genus Ruminiclostridium6. Additionally, we found 4 bacterial genera that exhibited a negative association with AD: genus Blautia, genus Butyricicoccus, genus Erysipelotrichaceae-UCG003 and genus Parasutterella. The associations were confirmed by the sensitivity analyses.

Conclusion

Our study found a causal relation between parts of the gut microbiota and AD. Further randomized controlled trials are crucial to elucidate the positive effects of probiotics on AD and their particular protection systems.
Gendered differences in the prevalence and associated factors of dementia in Ghana: a cross-sectional survey
Authors: Duodu Precious Adade , Dey Nutifafa Eugene Yaw , Okyere Joshua , Simkhada Bibha , Barker Caroline , Gillibrand Warren , Simkhada Padam
Published: May 2024

Background

Dementia as a global phenomenon has received significant attention in research due to the adverse effects it has on the daily functioning of its victims. Despite studies conducted in relation to the prevalence and associated factors of dementia in Ghana, not much attention has been paid to the influence of gender. The study, therefore, focused on estimating gender differences in the prevalence and associated factors of dementia in the Ashanti Region of Ghana.

Methods

This study adopted a cross-sectional design with surveys to recruit 800 participants who were 45 years or older. The data was obtained using the standardized Rowland Universal Dementia Assessment Scale (RUDAS) together with information on the various associated factors. A series of logistic models comprising of the total sample model, male sample model, and female sample model were estimated to analyse the data. All data analyses were completed in Stata version 14.

Results

The overall prevalence of dementia was 23.38% [95% CI:20.44, 26.31]. More females 24.56% [95% CI:20.81, 28.31] compared to males 21.31% [95% CI:16.57, 26.04] were at risk of dementia. Younger age, attaining formal education, and belonging to richer households were negatively associated with the risk of dementia. In the total sample model, younger age and attaining formal education were negatively associated with dementia risk. In the male-female stratified models, education and household wealth index were negatively associated with dementia risk in the male sample while age and education were negatively related to dementia risk in the female sample.

Conclusion

The study concludes that there are gendered differences in the prevalence and factors associated with the risk of dementia in Ghana. As such, interventions and programmes to identify dementia cases must be gender sensitive. Specifically, when addressing dementia risk in males, interventions should be directed towards those with lower wealth status. Likewise, when developing programmes to mitigate dementia risk in women, particular attention should be given to women in the oldest age category.
The effects of cognitive leisure activities on frailty transitions in older adults in China: a CHARLS-Based longitudinal study
Authors: Sheng Kai , Chen Hao , Qu Xianguo
Published: May 2024

Background

In an effort to identify factors associated with frailty transitions that trigger a significant difference in preventing and postponing the progression of frailty, questions regarding the role of cognitive leisure activities on various aspects of older adults’ health were raised. However, the relationship between cognitive leisure activities and frailty transitions has rarely been studied.

Methods

A total of 5367 older Chinese adults aged over 60 years from the China Health and Retirement Longitudinal Study (CHARLS) were selected as participants. The 2nd wave of the CHARLS in 2013 was selected as the baseline, and sociodemographic and health-related status baseline data were collected. The FRAIL Scale was used to measure frailty, while cognitive leisure activities were measured by the Cognitive Leisure Activity Index (CLAI) scores, which consisted of playing mahjong or cards, stock investment, and using the internet. After two years of follow-up, frailty transition from baseline was assessed at the 3rd wave of the CHARLS in 2015. Ordinal logistic regression analysis was used to examine the relationship between cognitive leisure activities and frailty transitions.

Results

During the two-year follow-up of 5367 participants, the prevalence of frailty that improved, remained the same and worsened was 17.8% (957/5367), 57.5% (3084/5367) and 24.7% (1326/5367), respectively. Among all participants, 79.7% (4276/5367), 19.6% (1054/5367), and 0.7% (37/5367) had CLAI scores of 0, 1, and 2 to 3, respectively. In the univariate analysis, there was a statistically significant association between a score of 2 to 3 on the Cognitive Leisure Activity Index and frailty transitions (odds ratio [OR] = 1.93, 95% CI 0.03 to 1.29, p = .04), while all other covariates were not significantly different across the three groups. After adjusting for covariates, participants with more cognitive leisure activities had a higher risk of frailty improvement than those without cognitive leisure activities (odds ratio [OR] = 1.99, 95% CI 1.05 to 3.76, p = .04).

Conclusions

Cognitive leisure activities were positively associated with the risk of frailty improvement in older adults, mainly when participating in multiple such activities. Older adults may be encouraged to participate in a wide variety of cognitive leisure activities to promote healthy aging.
Predicting higher child BMI z-score and obesity incidence in Malaysia: a longitudinal analysis of a dynamic cohort study
Authors: Salway Ruth , Armstrong Miranda , Mariapun Jeevitha , Reidpath Daniel D , Brady Sophia , Yasin Mohamed Shajahan , Su Tin Tin , Johnson Laura
Published: May 2024

Background

To target public health obesity prevention, we need to predict who might become obese i.e. predictors of increasing Body Mass Index (BMI) or obesity incidence. Predictors of incidence may be distinct from more well-studied predictors of prevalence, therefore we explored parent, child and sociodemographic predictors of child/adolescent BMI z-score and obesity incidence over 5 years in Malaysia.

Methods

The South East Asia Community Observatory in Segamat, Malaysia, provided longitudinal data on children and their parents (n = 1767). Children were aged 6–14 years at baseline (2013-14) and followed up 5 years later. Linear multilevel models estimated associations with child BMI z-score at follow-up, adjusting for baseline BMI z-score and potential confounders. Predictors included parent cardiometabolic health (overweight/obesity, central obesity, hypertension, hyperglycaemia), and socio-demographics (ethnicity, employment, education). Logistic multilevel models explored predictors of obesity incidence.

Results

Higher baseline BMI z-score predicted higher follow-up BMI z-score both in childhood to late adolescence (0.60; 95% CI: 0.55, 0.65) and early to late adolescence (0.76; 95% CI: 0.70, 0.82). There was inconsistent evidence of association between child BMI z-score at follow-up with parent cardiometabolic risk factors independent of baseline child BMI z-score. For example, maternal obesity, but not overweight, predicted a higher BMI z-score in childhood to early adolescence (overweight: 0.16; 95% CI: -0.03, 0.36, obesity: 0.41; 95% CI: 0.20, 0.61), and paternal overweight, but not obesity, predicted a higher BMI z-score in early to late adolescence (overweight: 0.22; 95% CI: 0.01, 0.43, obesity: 0.16; 95% CI: -0.10, 0.41). Parental obesity consistently predicted five-year obesity incidence in early to late adolescence, but not childhood to early adolescence. An adolescent without obesity at baseline with parents with obesity, had 3–4 times greater odds of developing obesity during follow-up (incidence OR = 3.38 (95% CI: 1.14–9.98, mother) and OR = 4.37 (95% CI 1.34–14.27, father) respectively).

Conclusions

Having a higher BMI z-score at baseline was a stronger predictor of a higher BMI z-score at follow-up than any parental or sociodemographic factor. Targeting prevention efforts based on parent or sociodemographic factors is unwarranted but early childhood remains a key period for universal obesity prevention.
How well do participants in clinical trials represent the U.S. population with chronic neck or back pain?
Authors: Leininger Brent D. , Johnson Pamela Jo , Bronfort Gert , Kuntz Karen M. , Enns Eva , Hodges James S. , Evans Roni
Published: May 2024

Background

Randomized clinical trials (RCTs) are the gold standard for assessing treatment effectiveness; however, they have been criticized for generalizability issues such as how well trial participants represent those who receive the treatments in clinical practice. We assessed the representativeness of participants from eight RCTs for chronic spine pain in the U.S., which were used for an individual participant data meta-analysis on the cost-effectiveness of spinal manipulation for spine pain. In these clinical trials, spinal manipulation was performed by chiropractors.

Methods

We conducted a retrospective secondary analysis of RCT data to compare trial participants’ socio-demographic characteristics, clinical features, and health outcomes to a representative sample of (a) U.S. adults with chronic spine pain and (b) U.S. adults with chronic spine pain receiving chiropractic care, using secondary data from the National Health Interview Survey (NHIS) and Medical Expenditure Panel Survey (MEPS). We assessed differences between trial and U.S. spine populations using independent t-tests for means and z-tests for proportions, accounting for the complex multi-stage survey design of the NHIS and MEPS.

Results

We found the clinical trials had an under-representation of individuals from health disparity populations with lower percentages of racial and ethnic minority groups (Black/African American 7% lower, Hispanic 8% lower), less educated (No high school degree 19% lower, high school degree 11% lower), and unemployed adults (25% lower) with worse health outcomes (physical health scores 2.5 lower and mental health scores 5.3 lower using the SF-12/36) relative to the U.S. population with spine pain. While the odds of chiropractic use in the U.S. are lower for individuals from health disparity populations, the trials also under-represented these populations relative to U.S. adults with chronic spine pain who visit a chiropractor.

Conclusions

Health disparity populations are not well represented in spine pain clinical trials. Embracing key community-based approaches, which have shown promise for increasing participation of underserved communities, is needed.
Laser debonding of ultrathin occlusal veneers fabricated from different CAD/CAM ceramic materials
Authors: El-Sheikh Nourhan Ali , Wahsh Marwa Mohamad , Hussein Ghada Abdelfattah
Published: May 2024

Background

Erbium lasers safely offer the possibility of reuse for debonded restorations. Since these lasers have a high affinity for water molecules, they are absorbed by resin cement causing explosive ablation of the cement and thus, the restoration debonds. The efficiency of this process depends on many factors, including the ceramic type, its chemical composition and thickness. Therefore, this study was designed to test the time taken to debond ultrathin occlusal veneers made of three types of milled ceramic materials and evaluate the integrity of these restorations after debonding.

Methods

Three ceramic types were evaluated in this study: lithium disilicate (IPS Emax CAD), highly condensed lithium disilicate (GC initial®LiSi), and translucent zirconia (Katana zirconia STML). Each group consisted of 8 occlusal veneers of 0.5 mm thickness. The samples were cemented to the occlusal surfaces of the upper molar teeth. An Er; Cr: YSGG laser was applied to the occlusal veneers using the scanning method, and time until debonding was calculated. The debonded samples were then inspected under a stereomicroscope for possible damage. Numerical data are presented as the mean with 95% confidence interval (CI), standard deviation (SD), minimum (min.) and maximum (max.) values. Normality and variance homogeneity assumptions were confirmed using Shapiro-Wilk’s and Levene’s tests, respectively. Data were normally distributed and were analyzed using one-way ANOVA followed by Tukey’s post hoc test. The significance level was set at p < 0.05 for all tests. Statistical analysis was performed with R statistical analysis software version 4.3.2 for Windows (R Core Team (2023). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/).

Results

There was no significant difference in debonding time between the different materials (p = 0.995). The longest debonding time was found for Katana STML (87.52 ± 20.45) (seconds), followed by Emax (86.94 ± 20.63) (seconds), while the lowest value was found for LiSi initial (86.14 ± 25.16) (seconds). In terms of damage to the debonded veneers, The Emax and zirconia samples showed no damage. However, 40% of the LiSi samples fractured during debonding, and 20% exhibited cracks. Only 40% of the LiSi samples were sound after debonding.

Conclusion

Er; Cr: YSGG laser can be used efficiently to remove ceramic occlusal veneers. However, its effect on LiSi restorations needs further research.
Determination of safety margin of nasal septum osteotomy for sphenoid sinus in cleft lip and palate patients
Authors: Ozturk Ergin , Tekin Gorkem , Saruhan Kose Nesrin , Ugurlu Mehmet , Bilgir Elif , Dereci Omur
Published: May 2024

Background

Nasal septum osteotomy is used for separating the nasal septum and maxilla during a Le Fort I osteotomy. If this osteotomy is applied too high or is tilted into the nasal cavity, the sphenoid sinus and various adjacent vital structures may be damaged, and serious bleeding, neurological complications, blindness or even death may occur. The aim of this study is to determine the safety margin of the nasal septum osteotomy for sphenoid sinus during the Le Fort I surgery in cleft lip and palate (CLP) patients.

Methods

Twenty cleft lip and palate (the CLP group) and 20 healthy individuals (the control group) were included in this study. Three values (two lines and an angle) were measured by cone beam computed tomography (CBCT). The first line is the line passing through the junction of the spina nasalis anterior point and the lower point of the perpendicular lamina of the palatine bone. The undersired line is the line passing through the junction of the spina nasalis anterior point and the lower anterior border of the base of the sphenoid sinus. The osteotomy angle is the angle between these two lines.

Results

In the control group; a surgical line of 44.11–61.14 mm (mean 51.91 ± 4.32), an undesired line of 52.48–69.58 mm (mean 59.14 ± 5.08) and an angle of 18.22–27.270 (mean 22.66 ± 2.55) were found, while in the CLP group, a surgical line of 34.53–51.16 mm (mean 43.38 ± 4.79), an undesired line of 46.86–61.35 mm (mean 55.02 ± 3.24) and an angle of 17.60–28.810 (mean 22.60 ± 2.81) were found.

Conclusions

Although the angle to the sphenoid sinus was not significantly affected by CLP, careful planning and consideration of these anatomical differences are crucial to prevent complications and ensure the safety of Le Fort I surgery in CLP patients. Further research with larger sample sizes and subgroup analysis of unilateral and bilateral CLP cases is needed to improve our understanding of these anatomical variations and improve surgical approaches to individuals with CLP undergoing orthognathic procedures.
Using the technology acceptance model to assess clinician perceptions and experiences with a rheumatoid arthritis outcomes dashboard: qualitative study
Authors: Nasrallah Catherine , Wilson Cherish , Hamblin Alicia , Young Cammie , Jacobsohn Lindsay , Nakamura Mary C. , Gross Andrew , Matloubian Mehrdad , Ashouri Judith , Yazdany Jinoos , Schmajuk Gabriela
Published: May 2024

Background

Improving shared decision-making using a treat-to-target approach, including the use of clinical outcome measures, is important to providing high quality care for rheumatoid arthritis (RA). We developed an Electronic Health Record (EHR) integrated, patient-facing sidecar dashboard application that displays RA outcomes, medications, and lab results for use during clinical visits (“RA PRO dashboard”). The purpose of this study was to assess clinician perceptions and experiences using the dashboard in a university rheumatology clinic.

Methods

We conducted focus group (FG) discussions with clinicians who had access to the dashboard as part of a randomized, stepped-wedge pragmatic trial. FGs explored clinician perceptions towards the usability, acceptability, and usefulness of the dashboard. FG data were analyzed thematically using deductive and inductive techniques; generated themes were categorized into the domains of the Technology Acceptance Model (TAM).

Results

3 FG discussions were conducted with a total of 13 clinicians. Overall, clinicians were enthusiastic about the dashboard and expressed the usefulness of visualizing RA outcome trajectories in a graphical format for motivating patients, enhancing patient understanding of their RA outcomes, and improving communication about medications. Major themes that emerged from the FG analysis as barriers to using the dashboard included inconsistent collection of RA outcomes leading to sparse data in the dashboard and concerns about explaining RA outcomes, especially to patients with fibromyalgia. Other challenges included time constraints and technical difficulties refreshing the dashboard to display real-time data. Methods for integrating the dashboard into the visit varied: some clinicians used the dashboard at the beginning of the visit as they documented RA outcomes; others used it at the end to justify changes to therapy; and a few shared it only with stable patients.

Conclusions

The study provides valuable insights into clinicians’ perceptions and experiences with the RA PRO dashboard. The dashboard showed promise in enhancing patient-clinician communication, shared decision-making, and overall acceptance among clinicians. Addressing challenges related to data collection, education, and tailoring dashboard use to specific patient populations will be crucial for maximizing its potential impact on RA care. Further research and ongoing improvements in dashboard design and implementation are warranted to ensure its successful integration into routine clinical practice.
Usage and limitations of medical consultation with patients’ families using online video calls: a prospective cohort study
Authors: Hayashi Tetsuro , Bito Seiji
Published: May 2024

Background

Few studies have been conducted on the usage of telehealth focusing on consultations between patients’ families and physicians. This study aimed to identify the usage and limitations of online medical consultations with patients’ families compared to the traditional in-person consultations.

Methods

We conducted a prospective cohort study from April 1, 2020, to September 30, 2021, at an educational acute-care hospital in Japan. The study included hospitalized patients aged 20 years or older and their family members for whom an online or in-person medical consultation between the family member and physician was conducted during the hospitalization period. The primary endpoints assessed were three topics pertaining to medical consultation: medical conditions and treatment plans, policies for life-threatening events, and post-discharge support. The secondary endpoint was the number of consultations required.

Results

Online consultations and traditional in-person consultations were provided to 58 and 53 patients’ families, respectively. Of the patients in the online consultation group who underwent multiple consultations, 46 (79%) also underwent in-person consultations. Regarding the topics, all the patients’ families in both consultation groups had consultations on medical conditions and treatment plans; regarding the policy for life-threatening events, 47% of patient families in the online consultation group were consulted compared to 53% of those in the in-person group. Regarding post-discharge support, 59% of patient families in the online group were consulted compared to 40% in the in-person group. In the online consultation group of 58 patients’ families, 188 consultations were conducted, including 95 online and 93 in-person consultations. Consultations on policy for life-threatening events were significantly more frequent in in-person consultations than in online consultations (p < 0.05). Regarding post-discharge support, online consultations were significantly more frequent than in-person consultations (p < 0.05). The number of family members who attended online consultations was significantly higher than those who attended in-person consultations (p < 0.05).

Conclusions

Online consultation between the physician and patient’s family may be an alternative to in-person consultation for explaining medical conditions and treatment plans. However, in-person consultation still plays an important role in sensitive topics, such as policy consultation for life-threatening events.
Establishment of disulfidptosis-related LncRNA signature as biomarkers in colon adenocarcinoma
Authors: Yao Hongfei , Liu Peng , Yao Linli , Li Xiao
Published: May 2024

Purpose

Metabolic reprogramming is a hallmark of cancer and plays a key role in precision oncology treatment. Long non-coding RNAs (lncRNAs) regulate cancer cell behavior, including metabolism. Disulfidptosis, a newly identified form of regulated cell death triggered by glucose starvation, has yet to be fully understood in colon adenocarcinoma (COAD). This study aimed to confirm the existence and role of disulfidptosis in COAD and identify disulfidptosis-related lncRNAs that may be targeted to induce disulfidptosis in COAD.

Methods

PI and F-actin staining were used to observe disulfidptosis in COAD cell lines. Disulfidptosis-related lncRNAs were identified based on the expression of disulfidptosis-associated genes in the TCGA-COAD database. A four-lncRNA signature for disulfidptosis was established. Subsequently, loss-of-function assays explored the roles of AC013652.1 and MCM3AP-AS1 in disulfidptosis.

Results

Disulfidptosis was observed in COAD cells under glucose starvation and could be reversed by agents that prevent disulfide stress, such as dithiothreitol (DTT) and tris-(2-carboxyethyl)-phosphine (TCEP). The prognostic value of disulfidptosis-associated genes in COAD patients was confirmed, with higher expression indicating longer survival. A disulfidptosis-related lncRNA signature comprising four lncRNAs was established based on the expression of these genes. Among these, AC013652.1 and MCM3AP-AS1 predicted worse prognoses. Furthermore, inhibiting AC013652.1 or MCM3AP-AS1 increased disulfidptosis-associated gene expression and cellular death, which could be reversed by DTT and TCEP.

Conclusions

This study provides hitherto undocumented evidence of the existence of disulfidptosis and the prognostic value of disulfidptosis-associated genes in COAD. Importantly, we identified lncRNAs AC013652.1 and MCM3AP-AS1, which suppress disulfidptosis and may serve as potential therapeutic targets for COAD.
A cross-sectional analysis of the relationship between the non-high density to high density lipoprotein cholesterol ratio (NHHR) and kidney stone risk in American adults
Authors: Du Yuan-Zhuo , Dong Qian-Xi , Hu Hong-Ji , Guo Biao , Li Yi-He , Zhang Ji , Li Fu-Chun , Guo Ju
Published: May 2024

Background

Recent interest in the Non-High Density to High Density Lipoprotein Cholesterol ratio (NHHR) has emerged due to its potential role in metabolic disorders. However, the connection between NHHR and the development of kidney stones still lacks clarity. The primary goal of this research is to explore how NHHR correlates with kidney stone incidence.

Methods

An analysis was conducted on the data collected by the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018, focusing on adults over 20 years diagnosed with kidney stones and those with available NHHR values. Employing weighted logistic regression and Restricted Cubic Spline (RCS) models, NHHR levels’ correlation with kidney stone risk was examined. Extensive subgroup analyses were conducted for enhanced reliability of the findings.

Results

The findings indicate a heightened kidney stone risk for those at the highest NHHR levels relative to those at the lowest (reference group). A notable non-linear correlation of NHHR with kidney stone incidence has been observed, with a significant P-value (< 0.001), consistent across various subgroups.

Conclusion

A clear link exists between high NHHR levels and increased kidney stone risk in the American adult population. This study highlights NHHR’s significance as a potential indicator in kidney stone formation.
A SU6668 pure nanoparticle-based eyedrops: toward its high drug Accumulation and Long-time treatment for corneal neovascularization
Authors: Wu Han , Ye Jinfa , Zhang Minjie , Zhang Lingyu , Lin Sijie , Li Qingjian , Liu Yanbo , Han Yun , Huang Caihong , Wu Yiming , Cheng Yuhang , Cai Shundong , Ke Lang , Liu Gang , Li Wei , Chu Chengchao
Published: May 2024

Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.
Multifunctional elastin-like polypeptide nanocarriers for efficient miRNA delivery in cancer therapy
Authors: Hong Jisan , Sim Dahye , Lee Byung-Heon , Sarangthem Vijaya , Park Rang-Woon
Published: May 2024

Background

The exogenous delivery of miRNA to mimic and restore miRNA-34a activity in various cancer models holds significant promise in cancer treatment. Nevertheless, its effectiveness is often impeded by challenges, including a short half-life, propensity for off-target accumulation, susceptibility to inactivation by blood-based enzymes, concerns regarding patient safety, and the substantial cost associated with scaling up. As a means of overcoming these barriers, we propose the development of miRNA-loaded Tat-A86 nanoparticles by virtue of Tat-A86's ability to shield the loaded agent from external environmental factors, reducing degradation and inactivation, while enhancing circulation time and targeted accumulation.

Results

Genetically engineered Tat-A86, featuring 16 copies of the interleukin-4 receptor (IL-4R)-binding peptide (AP1), Tat for tumor penetration, and an elastin-like polypeptide (ELP) for presenting target ligands and ensuring stability, served as the basis for this delivery system. Comparative groups, including Tat-E60 and A86, were employed to discern differences in binding and penetration. The designed ELP-based nanoparticle Tat-A86 effectively condensed miRNA, forming stable nanocomplexes under physiological conditions. The miRNA/Tat-A86 formulation bound specifically to tumor cells and facilitated stable miRNA delivery into them, effectively inhibiting tumor growth. The efficacy of miRNA/Tat-A86 was further evaluated using three-dimensional spheroids of lewis lung carcinoma (LLC) as in vitro model and LLC tumor-bearing mice as an in vivo model. It was found that miRNA/Tat-A86 facilitates effective cell killing by markedly improving miRNA penetration, leading to a substantial reduction in the size of LLC spheroids. Compared to other controls, Tat-A86 demonstrated superior efficacy in suppressing the growth of 3D cellular aggregates. Moreover, at equivalent doses, miRNA-34a delivered by Tat-A86 inhibited the growth of LLC cells in allograft mice.

Conclusions

Overall, these studies demonstrate that Tat-A86 nanoparticles can deliver miRNA systemically, overcoming the basic hurdles impeding miRNA delivery by facilitating both miRNA uptake and stability, ultimately leading to improved therapeutic effects.

Graphical Abstract
Human and financial resource needs for universal access to WHO-PEN interventions for diabetes and hypertension care in Eswatini: results from a time-and-motion and bottom-up costing study
Authors: Harkare Harsh Vivek , Osetinsky Brianna , Ginindza Ntombifuthi , Cindzi Bongekile Thobekile , Mncina Nomfundo , Akomolafe Babatunde , Marowa Lisa-Rufaro , Ntshalintshali Nyasatu , Tediosi Fabrizio
Published: May 2024

Background

Eswatini faces persistent challenges in providing care for diabetes and hypertension, exacerbated by a shortage of healthcare workers. The implementation of WHO-PEN interventions aimed to address these issues, yet their effects on healthcare worker time requirements and associated costs remain unclear.

Methods

This study employed a time-and-motion analysis and a bottom-up cost assessment to quantify the human and financial resources required for scaling up WHO-PEN interventions nationally in Eswatini for all estimated diabetic and hypertensive patients.

Results

Findings reveal that healthcare workers in intervention-arm clinics reported longer workday durations compared to those in control-arm clinics, yet spent less time per patient while seeing more patients. The implementation of WHO-PEN interventions increased the workload on healthcare workers but also led to a notable increase in patient care utilization. Furthermore, a morning peak in patient visits was identified, suggesting potential opportunities for optimizing patient flow. Notably, scaling up care provision nationally with WHO-PEN interventions proved to be more cost saving than expanding standard-of-care treatment.

Conclusion

WHO-PEN interventions hold promise in improving access to diabetes and hypertension care in Eswatini while offering an efficient solution. However, addressing challenges in healthcare workforce creation and retention is crucial for sustained effectiveness. Policy makers must consider all aspects of the WHO-PEN intervention for informed decision-making.

Trial registration US Clinical Trials Registry. NCT04183413. Trial registration date: December 3, 2019. https://ichgcp.net/clinical-trials-registry/NCT04183413
Trends in the geographic inequality of advanced practice nursing workforce in cancer care in Japan from 1996 to 2022: a panel data analysis
Authors: Tamaki Tomoko , Morioka Noriko , Machida Ako , Kashiwagi Masayo
Published: May 2024

Background

Cancer was ranked as the second leading cause of global mortality in 2019, with an increasing incidence. An adequate workforce of healthcare professionals with special skills and knowledge in cancer care is vital for addressing the disparities in cancer prognosis. This study aimed to elucidate the trends in the advanced practice nursing workforce (APNW) in cancer care, which included certified nurse specialists (CNSs) and certified nurses (CNs) in each prefecture of Japan from the system's inception to the present. Further, it sought to analyze the regional disparities and compare these trends with other healthcare resources to identify contributing factors associated with the APNW in cancer care in each prefecture.

Methods

We performed a panel data analysis using publicly available data on the APNW in cancer care in each prefecture of Japan from 1996 to 2022. Gini coefficients were calculated to examine the trends in geographic equality. Univariate and multivariable fixed effect panel data regression models were used to examine regional factors associated with an APNW in cancer care.

Results

From 1996 to 2012, the APNW in cancer care increased from four to 6982 staff, while their Gini coefficients decreased from 0.79 to 0.43. However, from 2012 to 2022, the Gini coefficients decreased slightly from 0.43 to 0.41. The coefficient value was comparable to that for the disparity between hospital doctors (0.43) but more pronounced compared to those for other medical resources, such as hospitals (0.34), hospital nurses (0.37), and designated cancer care hospitals (0.29). The APNW in cancer care in each prefecture was significantly associated with a higher number of designed cancer care hospitals in the previous year (see first quartile, the coefficient for second quartile: 0.31, 95% confidence interval (CI) 0.21–0.40), and a fewer number of hospital doctors (− 1.89, 95%CI − 2.70 to − 1.09).

Conclusions

The size of the APNW in cancer care has increased since the system was established in 1996 up till 2022. With the increase in numbers, geographic inequality narrowed until 2012 and has since then remained stagnant.
Decentralization of the health system – experiences from Pakistan, Portugal and Brazil
Authors: Mahmood Shafaq , Sequeira Rita , Siddiqui Muhammad Muneeb Ullah , Herkenhoff Marcos Batista Araujo , Ferreira Patrícia Pita , Fernandes Adalberto Campos , Sousa Paulo
Published: May 2024

Background

Decentralization of a health system is a complex and multidimensional phenomenon that demands thorough investigation of its process logistics, predisposing factors and implementation mechanisms, within the broader socio-political environment of each nation. Despite its wide adoption across both high-income countries (HICs) and low-and-middle-income countries (LMICs), empirical evidence of whether decentralization actually translates into improved health system performance remains inconclusive and controversial. This paper aims to provide a comprehensive description of the decentralization processes in three countries at different stages of their decentralization strategies – Pakistan, Brazil and Portugal.

Main body

This study employed a systematic analysis of peer-reviewed academic journals, official government reports, policy documents and publications from international organizations related to health system decentralization. A comprehensive search was conducted using reputable databases such as PubMed, Google Scholar, the WHO repository and other relevant databases, covering the period up to the knowledge cutoff date in June 2023. Information was systematically extracted and organized into the determinants, process mechanics and challenges encountered during the planning, implementation and post-decentralization phases. Although decentralization reforms have achieved some success, challenges persist in their implementation. Comparing all three countries, it was evident that all three have prioritized health in their decentralization reforms and aimed to enhance local decision-making power. Brazil has made significant progress in implementing decentralization reforms, while Portugal and Pakistan are still in the process. Pakistan has faced significant implementation challenges, including capacity-building, resource allocation, resistance to change and inequity in access to care. Brazil and Portugal have also faced challenges, but to a lesser extent. The extent, progress and challenges in the decentralization processes vary among the three countries, each requiring ongoing evaluation and improvement to achieve the desired outcomes.

Conclusion

Notable differences exist in the extent of decentralization, the challenges faced during implementation and inequality in access to care between the three countries. It is important for Portugal, Brazil and Pakistan to address these through reinforcing implementation strategies, tackling inequalities in access to care and enhancing monitoring and evaluation mechanism. Additionally, fostering knowledge sharing among these different countries will be instrumental in facilitating mutual learning.
Enhancing the delivery of comprehensive care for people living with HIV in Canada: insights from citizen panels and a national stakeholder dialogue
Authors: Wilson Michael G. , Mattison Cristina , Waddell Kerry , Bacon Jean , Becker Marissa , Bibeau Christine , Lavis John N. , Rosenes Ron , Kendall Claire E.
Published: May 2024

Background

People living with human immunodeficiency virus (HIV) are living longer with health-related disability associated with ageing, including complex conditions. However, health systems in Canada have not adapted to meet these comprehensive care needs.

Methods

We convened three citizen panels and a national stakeholder dialogue. The panels were informed by a plain-language citizen brief that outlined data and evidence about the challenge/problem, elements of an approach for addressing it and implementation considerations. The national dialogue was informed by a more detailed version of the same brief that included a thematic analysis of the findings from the panels.

Results

The 31 citizen panel participants emphasized the need for more prevention, testing and social supports, increased public education to address stigma and access to more timely data to inform system changes. The 21 system leaders emphasized the need to enhance person-centred care and for implementing learning and improvement across provinces, territories and Indigenous communities. Citizens and system leaders highlighted that policy actions need to acknowledge that HIV remains unique among conditions faced by Canadians.

Conclusions

Action will require a national learning collaborative to support spread and scale of successful prevention, care and support initiatives. Such a collaborative should be grounded in a rapid-learning and improvement approach that is anchored on the needs, perspectives and aspirations of people living with HIV; driven by timely data and evidence; supported by appropriate decision supports and aligned governance, financial and delivery arrangements; and enabled with a culture of and competencies for rapid learning and improvement.
Estimation and probabilistic projection of age- and sex-specific mortality rates across Brazilian municipalities between 2010 and 2030
Authors: Gonzaga Marcos R. , Queiroz Bernardo L. , Freire Flávio H.M.A. , Monteiro-da-Silva José H.C. , Lima Everton E.C. , Silva-Júnior Walter P. , Diógenes Victor H. D. , Flores-Ortiz Renzo , da Costa Lilia C. C. , Pinto-Junior Elzo P. , Ichihara Maria Yury , Teixeira Camila S. S. , Alves Flávia J. O. , Rocha Aline S. , Ferreira Andrêa J. F. , Barreto Maurício L. , Katikireddi Srinivasa Vittal , Dundas Ruth , Leyland Alastair H.
Published: May 2024

Background

Mortality rate estimation in small areas can be difficult due the low number of events/exposure (i.e. stochastic error). If the death records are not completed, it adds a systematic uncertainty on the mortality estimates. Previous studies in Brazil have combined demographic and statistical methods to partially overcome these issues. We estimated age- and sex-specific mortality rates for all 5,565 Brazilian municipalities in 2010 and forecasted probabilistic mortality rates and life expectancy between 2010 and 2030.

Methods

We used a combination of the Tool for Projecting Age-Specific Rates Using Linear Splines (TOPALS), Bayesian Model, Spatial Smoothing Model and an ad-hoc procedure to estimate age- and sex-specific mortality rates for all Brazilian municipalities for 2010. Then we adapted the Lee-Carter model to forecast mortality rates by age and sex in all municipalities between 2010 and 2030.

Results

The adjusted sex- and age-specific mortality rates for all Brazilian municipalities in 2010 reveal a distinct regional pattern, showcasing a decrease in life expectancy in less socioeconomically developed municipalities when compared to estimates without adjustments. The forecasted mortality rates indicate varying regional improvements, leading to a convergence in life expectancy at birth among small areas in Brazil. Consequently, a reduction in the variability of age at death across Brazil’s municipalities was observed, with a persistent sex differential.

Conclusion

Mortality rates at a small-area level were successfully estimated and forecasted, with associated uncertainty estimates also generated for future life tables. Our approach could be applied across countries with data quality issues to improve public policy planning.
Influence of intersignaling crosstalk on the intracellular localization of YAP/TAZ in lung cells
Authors: Govorova I. A. , Nikitochkina S. Y. , Vorotelyak E. A.
Published: May 2024

A cell is a dynamic system in which various processes occur simultaneously. In particular, intra- and intercellular signaling pathway crosstalk has a significant impact on a cell’s life cycle, differentiation, proliferation, growth, regeneration, and, consequently, on the normal functioning of an entire organ. Hippo signaling and YAP/TAZ nucleocytoplasmic shuttling play a pivotal role in normal development, homeostasis, and tissue regeneration, particularly in lung cells. Intersignaling communication has a significant impact on the core components of the Hippo pathway and on YAP/TAZ localization. This review describes the crosstalk between Hippo signaling and key lung signaling pathways (WNT, SHH, TGFβ, Notch, Rho, and mTOR) using lung cells as an example and highlights the remaining unanswered questions.
Extracellular vesicles containing MFGE8 from colorectal cancer facilitate macrophage efferocytosis
Authors: Ma Zhixin , Sun Yu , Yu Yang , Xiao Wenjun , Xiao Zhijie , Zhong Tianyu , Xiang Xi , Li Zhigang
Published: May 2024

Background

Colorectal cancer (CRC) commonly exhibits tolerance to cisplatin treatment, but the underlying mechanisms remain unclear. Within the tumor microenvironment, macrophages play a role in resisting the cytotoxic effects of chemotherapy by engaging in efferocytosis to clear apoptotic cells induced by chemotherapeutic agents. The involvement of extracellular vesicles (EVs), an intercellular communicator within the tumor microenvironment, in regulating the efferocytosis for the promotion of drug resistance has not been thoroughly investigated.

Methods

We constructed GFP fluorescent-expressing CRC cell lines (including GFP-CT26 and GFP-MC38) to detect macrophage efferocytosis through flow cytometric analysis. We isolated and purified CRC-secreted EVs using a multi-step ultracentrifugation method and identified them through electron microscopy and nanoflow cytometry. Proteomic analysis was conducted to identify the protein molecules carried by CRC-EVs. MFGE8 knockout CRC cell lines were constructed using CRISPR-Cas9, and their effects were validated through in vitro and in vivo experiments using Western blotting, immunofluorescence, and flow cytometric analysis, confirming that these EVs activate the macrophage αvβ3-Src-FAK-STAT3 signaling pathway, thereby promoting efferocytosis.

Results

In this study, we found that CRC-derived EVs (CRC-EVs) enhanced macrophage efferocytosis of cisplatin-induced apoptotic CRC cells. Analysis of The Cancer Genome Atlas (TCGA) database revealed a high expression of the efferocytosis-associated gene MFGE8 in CRC patients, suggesting a poorer prognosis. Additionally, mass spectrometry-based proteomic analysis identified a high abundance of MFGE8 protein in CRC-EVs. Utilizing CRISPR-Cas9 gene edition system, we generated MFGE8-knockout CRC cells, demonstrating that their EVs fail to upregulate macrophage efferocytosis in vitro and in vivo. Furthermore, we demonstrated that MFGE8 in CRC-EVs stimulated macrophage efferocytosis by increasing the expression of αvβ3 on the cell surface, thereby activating the intracellular Src-FAK-STAT3 signaling pathway.

Conclusions

Therefore, this study highlighted a mechanism in CRC-EVs carrying MFGE8 activated the macrophage efferocytosis. This activation promoted the clearance of cisplatin-induced apoptotic CRC cells, contributing to CRC resistance against cisplatin. These findings provide novel insights into the potential synergistic application of chemotherapy drugs, EVs inhibitors, and efferocytosis antagonists for CRC treatment.