bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors affecting health insurance utilization among insured population: evidence from health insurance program of Bhaktapur district of Nepal
Authors: Ghimire Sushmita , Ghimire Sailaja , Khanal Pratik , Sagtani Reshu Agrawal , Paudel Sudarshan
Published: February 2023

Background

The Government of Nepal introduced the family-based health insurance program in 2016 to increase financial protection and improve access to health care services. The study aimed to assess factors associated with the utilization of health insurance among the insured population in an urban district of Nepal.

Methods

A cross-sectional survey using face-to-face interviews was conducted in 224 households in the Bhaktapur district of Nepal. Household heads were interviewed using a structured questionnaire. Logistic regression with weighted analysis was done to identify predictors of service utilization among the insured residents.

Results

The prevalence of health insurance service utilization at the household level in the Bhaktapur district was 77.2% (n = 173/224). The number of elder members in the family (AOR 2.7, 95% CI 1.09–7.07), having a family member with chronic illness (AOR 5.10, 95% CI 1.48–17.56), willingness to continue health insurance (AOR 2.18, 95% CI 1.47–3.25) and membership duration (AOR 1.14, 95% CI 1.05–1.24) were significantly associated with the utilization of the health insurance at the household level.

Conclusion

The study identified a particular group of the population who were more likely to utilize health insurance services, including the chronically ill and elderly. Health insurance program in Nepal would benefit from strategies to increase population coverage in health insurance, improve the quality of health services, and retain members in the program.
Implementation considerations for non-communicable disease-related integration in primary health care: a rapid review of qualitative evidence
Authors: Leon N. , Xu H.
Published: February 2023

Background

Integrated delivery of primary health care (PHC) services is a health reform recommended for achieving ambitious targets of the Sustainable Development Goals and Universal Health Coverage, responding to growing challenges of managing non-communicable and multimorbidity. However, more evidence is needed on effective implementation of PHC integration in different country settings.

Objective

This rapid review synthesized qualitative evidence on implementation factors affecting integration of non-communicable disease (NCD) into PHC, from the perspective of implementers. The review contributes evidence to inform the World Health Organizations’ guidance on integration of NCD control and prevention to strengthen health systems.

Method

The review was guided by standard methods for conducting rapid systematic reviews. Data analysis was guided by the SURE and WHO health system building blocks frameworks. We used Confidence in the Evidence of Reviews of Qualitative Research (GRADE-CERQual) to assess the confidence of the main findings.

Results

The review identified 81 records eligible for inclusion, from 595 records screened. We sampled 20 studies for analysis (including 3 from expert recommendations). Studies covered a wide range of countries (27 countries from 6 continents), the majority from low-and middle-income countries (LMICs), with a diverse set of NCD-related PHC integration combinations and implementation strategies. The main findings were categorised into three overarching themes and several sub-themes. These are, A: Policy alignment and governance, B: Health systems readiness, intervention compatibility and leadership, and C: Human resource management, development, and support. The three overarching findings were assessed as each having a moderate level of confidence.

Conclusion

The review findings present insights on how health workers responses may be shaped by the complex interaction of individual, social, and organizational factors that may be specific to the context of the intervention, the importance of cross-cutting influences such as policy alignment, supportive leadership and health systems constraints, knowledge that can inform the development of future implementation strategies and implementation research.
Performance of the 2019 ESC/EASD guideline strategy for the screening of silent coronary artery disease in patients with diabetes
Authors: Valensi Paul , Berkane Narimane , Pinto Sara , Sellier Nicolas , Soussan Michael , Nguyen Minh Tuan , Cosson Emmanuel
Published: February 2023

Background

The 2019 guidelines for cardiovascular risk stratification by the European Society of Cardiology and European Association for the Study of Diabetes (ESC-EASD) suggested screening for silent coronary disease in very high risk patients with severe target organ damage (TOD) (i.e. peripheral occlusive arterial disease or severe nephropathy) or high coronary artery calcium (CAC) score. This study aimed to test the validity of this strategy.

Methods

In this retrospective study, we included 385 asymptomatic patients with diabetes and no history of coronary disease but with TOD or ≥ 3 risk factors in addition to diabetes. CAC score was measured using computed tomography scan and a stress myocardial scintigraphy was performed to detect silent myocardial ischemia (SMI), with subsequent coronary angiography in those with SMI. Various strategies to select patients to be screened for SMI were tested.

Results

CAC score was ≥ 100 Agatston units (AU) in 175 patients (45.5%). SMI was present in 39 patients (10.1%) and among the 30 patients who underwent angiography, 15 had coronary stenoses and 12 had a revascularization procedure. The most effective strategy consisted in performing myocardial scintigraphy in the 146 patients with severe TOD and, among the 239 other patients without severe TOD, in those with CAC ≥ 100 AU: this strategy provided 82% sensitivity for SMI diagnosis, and identified all the patients with stenoses.

Conclusion

The ESC-EASD guidelines suggesting SMI screening in asymptomatic patients with very high risk assessed by severe TOD or high CAC score appears effective and could identify all the patients with stenoses eligible for revascularization.
Reported reasons for non-use of insecticide-treated nets in large national household surveys, 2009–2021
Authors: Koenker Hannah , Kumoji E. Kuor , Erskine Marcy , Opoku Robert , Sternberg Eleanore , Taylor Cameron
Published: February 2023

Background

Insecticide-treated nets (ITN) are the cornerstone of modern malaria vector control, with nearly 3 billion ITNs delivered to households in endemic areas since 2000. ITN access, i.e. availability within the household, based on the number of ITNs and number of household members, is a pre-requisite for ITN use. Factors determining ITN use are frequently examined in published literature, but to date, large household survey data on reasons given for non-use of nets have not been explored.

Methods

A total of 156 DHS, MIS, and MICS surveys conducted between 2003 and 2021 were reviewed for questions on reasons why nets were not used the previous night, identifying twenty-seven surveys. The percent of nets that were reported used the previous night was calculated for the 156 surveys, and frequencies and proportions of reasons for non-use were calculated within the twenty-seven surveys. Results were stratified by household supply of ITNs in three categories (not enough”, “enough”, and “more than enough”) and by residence (urban/rural).

Results

The proportion of nets used the previous night averaged over 70% between 2003 and 2021, with no discernible change over this period. Reported reasons for why a net goes unused fell largely into three categories—nets that are extra/being saved for future use; the perception that there is little risk of malaria (particularly in dry season); and “other” responses. Net attributes such as colour, size, shape, and texture, and concerns related to chemicals were the least frequent reasons given. Reasons for non-use of nets varied by household net supply, and in some surveys by residence. In Senegal’s continuous DHS, the proportion of nets used peaked during high transmission season, and the proportion of nets that went unused due to “no/few mosquitoes” peaked during the dry season.

Conclusions

Unused nets were primarily those being saved for later use, or were not used due to perceived low risk of malaria. Classifying reasons for non-use into broader categories facilitates the design of appropriate social and behaviour change interventions to address the major underlying reasons for non-use, where this is feasible.
Synthesizing multi-frame high-resolution fluorescein angiography images from retinal fundus images using generative adversarial networks
Authors: Li Ping , He Yi , Wang Pinghe , Wang Jing , Shi Guohua , Chen Yiwei
Published: February 2023

Background

Fundus fluorescein angiography (FA) can be used to diagnose fundus diseases by observing dynamic fluorescein changes that reflect vascular circulation in the fundus. As FA may pose a risk to patients, generative adversarial networks have been used to convert retinal fundus images into fluorescein angiography images. However, the available methods focus on generating FA images of a single phase, and the resolution of the generated FA images is low, being unsuitable for accurately diagnosing fundus diseases.

Methods

We propose a network that generates multi-frame high-resolution FA images. This network consists of a low-resolution GAN (LrGAN) and a high-resolution GAN (HrGAN), where LrGAN generates low-resolution and full-size FA images with global intensity information, HrGAN takes the FA images generated by LrGAN as input to generate multi-frame high-resolution FA patches. Finally, the FA patches are merged into full-size FA images.

Results

Our approach combines supervised and unsupervised learning methods and achieves better quantitative and qualitative results than using either method alone. Structural similarity (SSIM), normalized cross-correlation (NCC) and peak signal-to-noise ratio (PSNR) were used as quantitative metrics to evaluate the performance of the proposed method. The experimental results show that our method achieves better quantitative results with structural similarity of 0.7126, normalized cross-correlation of 0.6799, and peak signal-to-noise ratio of 15.77. In addition, ablation experiments also demonstrate that using a shared encoder and residual channel attention module in HrGAN is helpful for the generation of high-resolution images.

Conclusions

Overall, our method has higher performance for generating retinal vessel details and leaky structures in multiple critical phases, showing a promising clinical diagnostic value.
Too much equity – is there such a thing? The public discourse surrounding elective egg freezing subsidy in Israel
Authors: Birenbaum-Carmeli Daphna
Published: February 2023

Background

The preservation of human ova for future fertilization has been made available to healthy women in 2011–2012. This treatment, dubbed elective egg freezing (EEF), is undertaken primarily by highly educated unpartnered women without children, concerned of age-related fertility decline. In Israel, treatment is available to women aged 30–41. However, unlike many other fertility treatments, EEF is not state subsidized. The public discourse of EEF funding in Israel is the focus of the present study.

Method

The article analyzes three sources of data: press presentations of EEF; a Parliamentary Committee discussion dedicated to EEF funding; interviews with 36 Israeli women who have undertaken EEF.

Results

Numerous speakers raised the issue of equity, claiming that reproduction was a state interest and therefore, a state responsibility, including securing equitable treatment to Israeli women of all economic strata. Highlighting the generous funding of other fertility treatments, they claimed that EEF was inequitable, discriminating against poorer single women, who could not afford it. Few actors, however, rejected state funding as intervention in women’s reproductive lives and called for reconsideration of the local reproductive imperative.

Conclusion

The invocation of equity by Israeli users of EEF, clinicians and some policy makers as grounds for a call to fund a treatment that serves a well-established subpopulation seeking to relieve a social rather than a medical problem, illustrates the profound context-embeddedness of notions of health equity. More generally, it may suggest that using an inclusive language in a discourse of equity may potentially be invoked so as to promote the interests of a particular subpopulation.
Cost-effectiveness analysis of coronary arteries bypass grafting (CABG) and percutaneous coronary intervention (PCI) through drug stent in iran: a comparative study
Authors: Fakhrzad NourolHoda , Barouni Mohsen , Goudarzi Reza , Kojuri Javad , Jahani Yunes , Tasavon Gholamhoseini Mohammad
Published: February 2023

Background

Cost-effectiveness analysis plays a key role in evaluating health systems and services. Coronary artery disease is one of the primary health concerns worldwide. This study sought to compare the cost-effectiveness of Coronary Arteries Bypass Grafting (CABG) and Percutaneous Coronary Intervention (PCI) through drug stent using Quality-Adjusted Life Years (QALY) index.

Methods

This is a cohort study involving all patients undergoing CABG and PCI through drug stent in south of Iran. A total of 410 patients were randomly selected to be included in the study. Data were gathered using SF-36, SAQ and a form for cost data from the patients' perspective. The data were analyzed descriptively and inferentially. Considering the analysis of cost-effectiveness, Markov Model was initially developed using TreeAge Pro 2020. Both deterministic and probabilistic sensitivity analyses were performed.

Results

Compared with the group treated with PCI, the total cost of interventions was higher in the CABG group ($102,103.8 vs $71,401.22) and the cost of lost productivity ($20,228.68 vs $7632.11), while the cost of hospitalization was lower in CABG ($67,567.1 vs $49,660.97). The cost of hotel stay and travel ($6967.82 vs $2520.12) and the cost of medication ($7340.18 vs $11,588.01) was lower in CABG. From the patients' perspective and SAQ instrument, CABG was cost-saving, with a reduction of $16,581 for every increase in effectiveness. Based on patients’ perspective and SF-36 instrument, CABG was cost-saving, with a reduction of $34,543 for every increase in effectiveness.

Conclusion

In the same indications, CABG intervention leads to more resource savings.
Effectiveness of a Smartphone App (MINISTOP 2.0) integrated in primary child health care to promote healthy diet and physical activity behaviors and prevent obesity in preschool-aged children: randomized controlled trial
Authors: Alexandrou Christina , Henriksson Hanna , Henström Maria , Henriksson Pontus , Delisle Nyström Christine , Bendtsen Marcus , Löf Marie
Published: February 2023

Background

Childhood overweight and obesity is a public health priority. We have previously reported the efficacy of a parent-oriented mobile health (mHealth) app-based intervention (MINISTOP 1.0) which showed improvements in healthy lifestyle behaviors. However, the effectiveness of the MINISTOP app in real-world conditions needs to be established.

Objective

To evaluate the real-world effectiveness of a 6-month mHealth intervention (MINISTOP 2.0 app) on children’s intake of fruits, vegetables, sweet and savory treats, sweet drinks, moderate-to-vigorous physical activity, and screen time (primary outcomes), and on parental self-efficacy (PSE) for promoting healthy lifestyle behaviors, and children’s body mass index (BMI) (secondary outcomes).

Methods

A hybrid type 1 effectiveness-implementation design was utilized. For the effectiveness outcomes, a two-arm, individually randomized controlled trial was conducted. Parents (n = 552) of 2.5-to-3-year-old children were recruited from 19 child health care centers across Sweden, and, randomized to either a control (standard care) or intervention group (MINISTOP 2.0 app). The 2.0 version was adapted and translated into English, Somali and Arabic to increase reach. All recruitment and data collection were conducted by the nurses. Outcomes were assessed at baseline and after six months, using standardized measures (BMI) and a questionnaire (health behaviors, PSE).

Results

Among the participating parents (n = 552, age: 34.1 ± 5.0 years), 79% were mothers and 62% had a university degree. Twenty-four percent (n = 132) of children had two foreign-born parents. At follow-up, parents in the intervention group reported lower intakes of sweet and savory treats (-6.97 g/day; p = 0.001), sweet drinks (-31.52 g/day; p < 0.001), and screen time (-7.00 min/day; p = 0.012) in their children compared to the control group. The intervention group reported higher total PSE (0.91; p = 0.006), PSE for promoting healthy diet (0.34; p = 0.008) and PSE for promoting physical activity behaviors (0.31; p = 0.009) compared to controls. No statistically significant effect was observed for children’s BMI z-score. Overall, parents reported high satisfaction with the app, and 54% reported using the app at least once a week.

Conclusion

Children in the intervention group had lower intakes of sweet and savory treats, sweet drinks, less screen time (primary outcomes) and their parents reported higher PSE for promoting healthy lifestyle behaviors. Our results from this real-world effectiveness trial support the implementation of the MINISTOP 2.0 app within Swedish child health care.

Trial registration

Clinicaltrials.gov NCT04147039; https://clinicaltrials.gov/ct2/show/NCT04147039
Tumor-associated macrophages and Tregs influence and represent immune cell infiltration of muscle-invasive bladder cancer and predict prognosis
Authors: Koll Florestan J. , Banek Severine , Kluth Luis , Köllermann Jens , Bankov Katrin , Chun Felix K.-H. , Wild Peter J. , Weigert Andreas , Reis Henning
Published: February 2023

Introduction and objective

Muscle-invasive urothelial bladder cancer (MIBC) is associated with limited response rates to systemic therapy, risk of recurrence and death. Tumor infiltrating immune cells have been associated with outcome and response to chemo-and immunotherapy in MIBC. We aimed to profile the immune cells in the tumor microenvironment (TME) to predict prognosis in MIBC and responses to adjuvant chemotherapy.

Methods

We performed multiplex immunohistochemistry (IHC) profiling and quantification of immune and stromal cells (CD3, CD4, CD8, CD163, FoxP3, PD-1, and CD45, Vimentin, αSMA, PD-L1, Pan-Cytokeratin, Ki67) in 101 patients with MIBC receiving radical cystectomy. We used uni- and multivariate survival analyses to identify cell types predicting prognosis. Samples were subdivided using K-means clustering for Treg and macrophage infiltration resulting in 3 clusters, Cluster 1: Treg high, cluster 2: macrophage high, cluster 3: Treg and macrophage low. Routine CD68 and CD163 IHC were analyzed with QuPath in an extended cohort of 141 MIBC.

Results

High concentrations of macrophages were associated with increased risk of death (HR 10.9, 95% CI 2.8–40.5; p < 0.001) and high concentrations of Tregs were associated with decreased risk of death (HR 0.1, 95% CI 0.01–0.7; p = 0.03) in the multivariate Cox-regression model adjusting for adjuvant chemotherapy, tumor and lymph node stage. Patients in the macrophage rich cluster (2) showed the worst OS with and without adjuvant chemotherapy. The Treg rich cluster (1) showed high levels of effector and proliferating immune cells and had the best survival. Cluster 1 and 2 both were rich in PD-1 and PD-L1 expression on tumor and immune cells.

Conclusion

Treg and macrophage concentrations in MIBC are independent predictors of prognosis and are important players in the TME. Standard IHC with CD163 for macrophages is feasible to predict prognosis but validation to use immune-cell infiltration, especially to predict response to systemic therapies, is required.
Profiling the peripheral immune response to ex vivo TNF stimulation in untreated juvenile idiopathic arthritis using single cell RNA sequencing
Authors: Imbach Kathleen J. , Treadway Nicole J. , Prahalad Vaishali , Kosters Astrid , Arafat Dalia , Duan Meixue , Gergely Talia , Ponder Lori A. , Chandrakasan Shanmuganathan , Ghosn Eliver E. B. , Prahalad Sampath , Gibson Greg
Published: February 2023

Background

Juvenile Idiopathic Arthritis (JIA) is an autoimmune disease with a heterogenous clinical presentation and unpredictable response to available therapies. This personalized transcriptomics study sought proof-of-concept for single-cell RNA sequencing to characterize patient-specific immune profiles.

Methods

Whole blood samples from six untreated children, newly diagnosed with JIA, and two healthy controls were cultured for 24 h with or without ex vivo TNF stimulation and subjected to scRNAseq to examine cellular populations and transcript expression in PBMCs. A novel analytical pipeline, scPool, was developed wherein cells are first pooled into pseudocells prior to expression analysis, facilitating variance partitioning of the effects of TNF stimulus, JIA disease status, and individual donor.

Results

Seventeen robust immune cell-types were identified, the abundance of which was significantly affected by TNF stimulus, which resulted in notable elevation of memory CD8 + T-cells and NK56 cells, but down-regulation of naïve B-cell proportions. Memory CD8 + and CD4 + T-cells were also both reduced in the JIA cases relative to two controls. Significant differential expression responses to TNF stimulus were also characterized, with monocytes showing more transcriptional shifts than T-lymphocyte subsets, while the B-cell response was more limited. We also show that donor variability exceeds the small degree of possible intrinsic differentiation between JIA and control profiles. An incidental finding of interest was association of HLA-DQA2 and HLA-DRB5 expression with JIA status.

Conclusions

These results support the development of personalized immune-profiling combined with ex-vivo immune stimulation for evaluation of patient-specific modes of immune cell activity in autoimmune rheumatic disease.
Strategic use of levofolinic acid for methotrexate-induced side effects in juvenile idiopathic arthritis: a prospective observational study
Authors: Martini Giorgia , Meneghel Alessandra , Fastiggi Michele , Dell’Apa Filippo , Vittadello Fabio , Zulian Francesco
Published: February 2023

Objective

To evaluate the efficacy of levofolinic acid (LVF) administered 48 h before methotrexate (MTX) in reducing gastrointestinal side effects without interference with drug efficacy.

Methods

A prospective observational study was performed including patients with Juvenile Idiopathic Arthritis (JIA) reporting significant gastrointestinal discomfort after MTX despite taking a dose of LVF 48 h after MTX. Patients with anticipatory symptoms were excluded. A LVF supplemental dose was added 48 h before MTX and patients were followed every 3–4 months. At each visit data on gastrointestinal symptoms, disease activity (JADAS, ESR, CRP values) and treatment changes were collected. Friedman test for repeated measures analyzed differences between these variables over time.

Results

Twenty-one patients were recruited and followed for at least 12 months. All patients received MTX subcutaneously (mean 9.54 mg/m2) and LVF 48 h before and after MTX (mean 6.5 mg/dose), 7 received a biological agent too. Complete remission of gastrointestinal side effects was reported in 61.9% of study patients at first visit (T1) and increased over time (85.7%, 95.2%, 85.7% and 100% at T2, T3, T4, T5, respectively). MTX efficacy was maintained as showed by significant reduction of JADAS and CRP (p = 0.006 and 0.008) from T1 to T4 and it was withdrawn for remission in 7/21.

Conclusions

LVF given 48 h before MTX significantly reduced gastrointestinal side effects and did not reduce drug’s efficacy. Our results suggest that this strategy may improve compliance and quality of life in patients with JIA and other rheumatic diseases treated with MTX.
Juvenile idiopathic arthritis patients with positive family history of autoimmune thyroid disease might benefit from serological screening: analysis of the international Pharmachild registry
Authors: van Straalen Joeri W. , Baas Laurie , Giancane Gabriella , Grebenkina Lyudmila , Brunner Jurgen , Vega-Cornejo Gabriel , Chasnyk Vyacheslav G. , Harel Liora , Appenzeller Simone , Gervais Elisabeth , de Roock Sytze , Wulffraat Nico M. , Ruperto Nicolino , Swart Joost F. ,   for the Paediatric Rheumatology International Trials Organisation (PRINTO)
Published: February 2023

Background

Little is known about the association between juvenile idiopathic arthritis (JIA) and autoimmune thyroid disease (AITD) and therefore there are no indications for AITD screening in this population, which is possible using standard blood tests. The objective of this study is to determine the prevalence and predictors of symptomatic AITD in JIA patients from the international Pharmachild registry.

Methods

Occurrence of AITD was determined from adverse event forms and comorbidity reports. Associated factors and independent predictors for AITD were determined using univariable and multivariable logistic regression analyses.

Results

The prevalence of AITD after a median observation period of 5.5 years was 1.1% (96/8965 patients). Patients who developed AITD were more often female (83.3% vs. 68.0%), RF positive (10.0% vs. 4.3%) and ANA positive (55.7% vs. 41.5%) than patients who did not. AITD patients were furthermore older at JIA onset (median 7.8 years vs. 5.3 years) and had more often polyarthritis (40.6% vs. 30.4%) and a family history of AITD (27.5% vs. 4.8%) compared to non-AITD patients. A family history of AITD (OR = 6.8, 95% CI: 4.1 – 11.1), female sex (OR = 2.2, 95% CI: 1.3 – 4.3), ANA positivity (OR = 2.0, 95% CI: 1.3 – 3.2) and older age at JIA onset (OR = 1.1, 95% CI: 1.1 – 1.2) were independent predictors of AITD on multivariable analysis. Based on our data, 16 female ANA positive JIA patients with a family history of AITD would have to be screened during ±5.5 years using standard blood tests to detect one case of AITD.

Conclusions

This is the first study to report independent predictor variables for symptomatic AITD in JIA. Female ANA positive JIA patients with positive family history are at increased risk of developing AITD and thus might benefit from yearly serological screening.
Regulatory T cells alleviate myelin loss and cognitive dysfunction by regulating neuroinflammation and microglial pyroptosis via TLR4/MyD88/NF-κB pathway in LPC-induced demyelination
Authors: Wang Yao , Sadike Dilinuer , Huang Bo , Li Ping , Wu Qiao , Jiang Na , Fang Yongkang , Song Guini , Xu Li , Wang Wei , Xie Minjie
Published: February 2023

Demyelination occurs in multiple central nervous system (CNS) disorders and is tightly associated with neuroinflammation. Pyroptosis is a form of pro-inflammatory and lytic cell death which has been observed in CNS diseases recently. Regulatory T cells (Tregs) have exhibited immunoregulatory and protective effects in CNS diseases. However, the roles of Tregs in pyroptosis and their involvement in LPC-induced demyelination have not been explicated. In our study, Foxp3-diphtheria toxin receptor (DTR) mice treated with diphtheria toxin (DT) or PBS were subjected to two-site lysophosphatidylcholine (LPC) injection. Immunofluorescence, western blot, Luxol fast blue (LFB) staining, quantitative real-time PCR (qRT-PCR) and neurobehavior assessments were performed to evaluate the severity of demyelination, neuroinflammation and pyroptosis. Pyroptosis inhibitor was further used to investigate the role of pyroptosis in LPC-induced demyelination. RNA-sequencing was applied to explore the potential regulatory mechanism underlying the involvement of Tregs in LPC-induced demyelination and pyroptosis. Our results showed that depletion of Tregs aggravated microgliosis, inflammatory responses, immune cells infiltration and led to exacerbated myelin injury as well as cognitive defects in LPC-induced demyelination. Microglial pyroptosis was observed after LPC-induced demyelination, which was aggravated by Tregs depletion. Inhibition of pyroptosis by VX765 reversed myelin injury and cognitive function exacerbated by Tregs depletion. RNA-sequencing showed TLR4/myeloid differentiation marker 88 (MyD88) as the central molecules in Tregs-pyroptosis pathway, and refraining TLR4/MyD88/NF-κB pathway alleviated the aggravated pyroptosis induced by Tregs depletion. In conclusion, our findings for the first time indicate that Tregs alleviate myelin loss and improve cognitive function by inhibiting pyroptosis in microglia via TLR4/MyD88/NF-κB pathway in LPC-induced demyelination.
Literature review of stroke assessment for upper-extremity physical function via EEG, EMG, kinematic, and kinetic measurements and their reliability
Authors: Maura Rene M. , Rueda Parra Sebastian , Stevens Richard E. , Weeks Douglas L. , Wolbrecht Eric T. , Perry Joel C.
Published: February 2023

Background

Significant clinician training is required to mitigate the subjective nature and achieve useful reliability between measurement occasions and therapists. Previous research supports that robotic instruments can improve quantitative biomechanical assessments of the upper limb, offering reliable and more sensitive measures. Furthermore, combining kinematic and kinetic measurements with electrophysiological measurements offers new insights to unlock targeted impairment-specific therapy. This review presents common methods for analyzing biomechanical and neuromuscular data by describing their validity and reporting their reliability measures.

Methods

This paper reviews literature (2000–2021) on sensor-based measures and metrics for upper-limb biomechanical and electrophysiological (neurological) assessment, which have been shown to correlate with clinical test outcomes for motor assessment. The search terms targeted robotic and passive devices developed for movement therapy. Journal and conference papers on stroke assessment metrics were selected using PRISMA guidelines. Intra-class correlation values of some of the metrics are recorded, along with model, type of agreement, and confidence intervals, when reported.

Results

A total of 60 articles are identified. The sensor-based metrics assess various aspects of movement performance, such as smoothness, spasticity, efficiency, planning, efficacy, accuracy, coordination, range of motion, and strength. Additional metrics assess abnormal activation patterns of cortical activity and interconnections between brain regions and muscle groups; aiming to characterize differences between the population who had a stroke and the healthy population.

Conclusion

Range of motion, mean speed, mean distance, normal path length, spectral arc length, number of peaks, and task time metrics have all demonstrated good to excellent reliability, as well as provide a finer resolution compared to discrete clinical assessment tests. EEG power features for multiple frequency bands of interest, specifically the bands relating to slow and fast frequencies comparing affected and non-affected hemispheres, demonstrate good to excellent reliability for populations at various stages of stroke recovery. Further investigation is needed to evaluate the metrics missing reliability information. In the few studies combining biomechanical measures with neuroelectric signals, the multi-domain approaches demonstrated agreement with clinical assessments and provide further information during the relearning phase. Combining the reliable sensor-based metrics in the clinical assessment process will provide a more objective approach, relying less on therapist expertise. This paper suggests future work on analyzing the reliability of metrics to prevent biasedness and selecting the appropriate analysis.
Automated quantification of fluorescence and morphological changes in pretreated wood cells by fluorescence macroscopy
Authors: Audibert Edwige , Lebas Berangère , Spriet Corentin , Habrant Anouck , Chabbert Brigitte , Paës Gabriel
Published: February 2023

Background

Lignocellulosic biomass is a complex network of polysaccharides and lignin that requires a pretreatment step to overcome recalcitrance and optimize valorisation into biobased products. Pretreatment of biomass induces chemical and morphological changes. Quantification of these changes is critical to understand biomass recalcitrance and to predict lignocellulose reactivity. In this study, we propose an automated method for the quantification of chemical and morphological parameters through fluorescence macroscopy, which was applied on wood samples (spruce, beechwood) pretreated with steam explosion.

Results

Results in fluorescence macroscopy highlighted the impact of steam explosion on spruce and beechwood: fluorescence intensity of samples was highly altered, especially for the most severe conditions. Morphological changes were also revealed: shrinkage of cells and deformation of cell walls manifested as the loss of rectangularity or circular shape, for tracheids in spruce and vessels in beechwood respectively. Quantification of fluorescence intensity of cell walls and quantification of morphological parameters related to cell lumens were carried out accurately by applying the automated method onto the macroscopic images. The results showed that lumens area and circularity could be considered as complementary markers of cell deformation, and that fluorescence intensity of the cell walls could be related to morphological changes and to the conditions of pretreatment.

Conclusions

The developed procedure allows simultaneous and effective quantification of morphological parameters and fluorescence intensity of the cell walls. This approach can be applied to fluorescence macroscopy as well as other imaging techniques and provides encouraging results towards the understanding of biomass architecture.
Early fusion outcome after surgical treatment of single-level and multi-level pyogenic spondylodiscitis: experience at a level 1 center for spinal surgery—a single center cohort study
Authors: Hamed Motaz , Brandecker Simon , Lampmann Tim , Asoglu Harun , Salemdawod Abdallah , Güresir Erdem , Vatter Hartmut , Banat Mohammed
Published: February 2023

Study design

Retrospective single center cohort study.

Purpose

Spinal instrumentation in combination with antibiotic therapy is a treatment option for acute or chronic pyogenic spondylodiscitis (PSD). This study compares the early fusion outcome for multi-level and single-level PSD after urgent surgical treatment with interbody fusion in combination with fixation.

Methods

This is a retrospective cohort study. Over a 10 year period at a single institution, all surgically treated patients received surgical debridement, fusion und fixation of the spine to treat PSD. Multi-level cases were either adjacent to each other on the spine or distant. Fusion rates were assessed at 3 and 12 months after surgery. We analyzed demographic data, ASA status, duration of surgery, location and length of spine affected, Charlson comorbidity index (CCI), and early complications.

Results

A total of 172 patients were included. Of these, 114 patients suffered from single-level and 58 from multi-level PSD. The most frequent location was the lumbar spine (54.0%) followed by the thoracic spine (18.0%). The PSD was adjacent in 19.0% and distant in 81.0% of multi-level cases. Fusion rates at the 3 month follow-up did not differ among the multi-level group (p = 0.27 for both adjacent and distant sites). In the single-level group, sufficient fusion was achieved in 70.2% of cases. Pathogen identification was possible 58.5% of the time.

Conclusions

Surgical treatment of multi-level PSD is a safe option. Our study demonstrates that there was no significant difference in early fusion outcomes between single-level and multi-level PSD, whether adjacent or distant.
Icariin-conditioned serum combined with chitosan attenuates cartilage injury in rabbit knees with osteochondral defect
Authors: Zhang Juntao , Fan Fangyang , Zhang Chao , Liu Aifeng , Shang Man , Meng Lin
Published: February 2023

Background

Knee osteoarthritis (KOA) is one of the most common degenerative diseases. Its development is closely related to cartilage injury and subchondral bone remodeling homeostasis. In the present study, we combined icariin-conditioned serum (ICS) with thiolated chitosan (CSSH), a material widely used in tissue engineering for cartilage repair, to demonstrate its effect on the repair of cartilage damage and abnormal subchondral remodeling.

Methods

New Zealand rabbits were undergoing surgery for cartilage defect, and joint cavity injection was performed in each group with 0.5 mL normal saline (NS), ICS, CSSH and ICS-CSSH in the right joint every week for five times. Positioning performance was observed using VICON motion capture system. Glycosaminoglycans (GAG) secretion of articular fluid was assessed. Osteoarthritis Research Society International (OARSI) score and immunohistochemical (IHC) analysis including H&E, Safranin O and collagen II staining were employed to evaluate the morphologic repair of cartilage and subchondral bone. mRNA expression of COL2A1, MMP13 and ADAMTS5 was detected in chondrocytes from injury area.

Results

ICS combined with CSSH attenuated cartilage injury and abnormal subchondral remodeling in rabbits with KOA. ICS and CSSH groups showed slight improvement in positioning performance, while ICS-CSSH group exhibited better positioning performance. ICS-CSSH group showed increased GAG secretion of articular fluid and expression of COL2A1 in articular chondrocytes. Furthermore, both macroscopic observation and IHC analysis showed femoral condyle in ICS-CSSH rabbits were repaired with more native cartilage and subchondral bone regeneration.

Conclusions

ICS combined with CSSH could promote the repair of osteochondral defect and stabilize subchondral bone remodeling in rabbit knees.
A conceptual framework to develop a patient-reported experience questionnaire on the cystic fibrosis journey in France: the ExPaParM collaborative study
Authors: Pougheon Bertrand D. , Fanchini A. , Lombrail P. , Rault G. , Chansard A. , Le Breton N. , Frenod C. , Milon F. , Royer C. Heymes , Segretain D. , Silber M. , Therouanne S. , Haesebaert J. , Llerena C. , Michel P. , Reynaud Q.
Published: February 2023

Background

The objective of the study was to elaborate a conceptual framework related to the domains of patient experience along the cystic fibrosis (CF) journey from the patients and parents of children with CF to inform the design of a patient-reported experience questionnaire.

Method

A collaborative research group including patients and parents with clinicians and academic researchers was set up. They identified the situations along the CF care pathway from diagnosis to paediatric care, transition to adult care and adult follow-up, transfer to transplant centres and follow-up after transplantation. Participants were recruited by CF centres in metropolitan France and overseas departments. Semi-structured interviews were conducted, transcribed verbatim and subjected to an inductive analysis conducted in duos of researchers/co-researchers using NVivo®. The conceptual framework was discussed with the research group and presented to the CF centres during two video conferences. The protocol obtained a favourable opinion from the Ethics Evaluation Committee of INSERM (IRB00003888-no. 20-700).

Results

The analysis led to a conceptual framework composed of domains of the CF journey, each divided into several items. 1. CF care: Management of care by the CF centre team; in-hospital care; quality of care in the community; therapeutic education and self-management support; at-home care; new therapies and research; procreation; 2. Transplant care: management of transplant and CF care; coordination with other specialties; education and self-management support; at-home care; procreation; new therapies and research; 3. Turning points along the journey: diagnosis of CF, transition to adult care, transfer to transplantation; 4. Social life with CF: housing, employment and education, social relations, social welfare and family finances. The number of patients included and the diversity of situations made it possible to achieve a sufficient richness and saturation of codes by domain to develop patient experience questionnaires.

Conclusion

This conceptual framework, resulting from the participants’ experience, will inform the design of a patient-reported experience tool, whose construct will be tested during the next phase of the ExPaParM project to assess its fidelity, intelligibility, and ability to report patient experience of the CF journey.
Past and present: a bibliometric study on polycystic ovary syndrome
Authors: Cai Mengcheng , Ni Zhexin , Yuan Zike , Yu Jin , Zhang Danying , Yao Ruipin , Zhou Ling , Yu Chaoqin
Published: February 2023

Background

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease that has a great impact on women’s physical and mental health. It is a burden to social and patients’ economy. In recent years, researchers’ understanding of PCOS has reached a new level. However, many PCOS reports have different directions, and overlapping phenomena exist. Therefore, clarifying the research status of PCOS is important. This study aims to summarise the research status of PCOS and predict the hot spots of PCOS in the future by Bibliometricx.

Results

The keywords of PCOS research focused on PCOS, insulin resistance (IR), obesity and metformin. Keywords plus co-occurrence network showed that PCOS, IR and prevalence were hot spots in the recent 10 years. Moreover, we found that gut microbiota may be a carrier that can be used to study hormone levels, IR-related mechanisms, prevention and treatment in the future.

Conclusions

This study is helpful for researchers to quickly grasp the current situation of PCOS research and enlighten researchers to explore new problems in PCOS.
BOHEMIA: Broad One Health Endectocide-based Malaria Intervention in Africa—a phase III cluster-randomized, open-label, clinical trial to study the safety and efficacy of ivermectin mass drug administration to reduce malaria transmission in two African settings
Authors: Chaccour Carlos , Casellas Aina , Hammann Felix , Ruiz-Castillo Paula , Nicolas Patricia , Montaña Julia , Mael Mary , Selvaraj Prashant , Duthaler Urs , Mrema Sigilbert , Kakolwa Mwaka , Lyimo Issa , Okumu Fredros , Marathe Achla , Schürch Roger , Elobolobo Eldo , Sacoor Charfudin , Saute Francisco , Xia Kang , Jones Caroline , Rist Cassidy , Maia Marta , Rabinovich N. Regina
Published: February 2023

Background

Residual malaria transmission is the result of adaptive mosquito behavior that allows malaria vectors to thrive and sustain transmission in the presence of good access to bed nets or insecticide residual spraying. These behaviors include crepuscular and outdoor feeding as well as intermittent feeding upon livestock. Ivermectin is a broadly used antiparasitic drug that kills mosquitoes feeding on a treated subject for a dose-dependent period. Mass drug administration with ivermectin has been proposed as a complementary strategy to reduce malaria transmission.

Methods

A cluster randomized, parallel arm, superiority trial conducted in two settings with distinct eco-epidemiological conditions in East and Southern Africa. There will be three groups: human intervention, consisting of a dose of ivermectin (400 mcg/kg) administered monthly for 3 months to all the eligible population in the cluster (>15 kg, non-pregnant and no medical contraindication); human and livestock intervention, consisting human treatment as above plus treatment of livestock in the area with a single dose of injectable ivermectin (200 mcg/kg) monthly for 3 months; and controls, consisting of a dose of albendazole (400 mg) monthly for 3 months. The main outcome measure will be malaria incidence in a cohort of children under five living in the core of each cluster followed prospectively with monthly RDTs

Discussion

The second site for the implementation of this protocol has changed from Tanzania to Kenya. This summary presents the Mozambique-specific protocol while the updated master protocol and the adapted Kenya-specific protocol undergo national approval in Kenya. BOHEMIA will be the first large-scale trial evaluating the impact of ivermectin-only mass drug administration to humans or humans and cattle on local malaria transmission

Trial registration

ClinicalTrials.govNCT04966702. Registered on July 19, 2021.

Pan African Clinical Trials Registry PACTR202106695877303.
Design of the Building Research in CRC prevention (BRIDGE-CRC) trial: a 6-month, parallel group Mediterranean diet and weight loss randomized controlled lifestyle intervention targeting the bile acid-gut microbiome axis to reduce colorectal cancer risk among African American/Black adults with obesity
Authors: McLeod Andrew , Wolf Patricia , Chapkin Robert S. , Davidson Laurie A. , Ivanov Ivan , Berbaum Michael , Williams Lauren R. , Gaskins H. Rex , Ridlon Jason , Sanchez-Flack Jen , Blumstein Lara , Schiffer Linda , Hamm Alyshia , Cares Kate , Antonic Mirjana , Bernabe Beatriz Penalver , Fitzgibbon Marian , Tussing-Humphreys Lisa
Published: February 2023

Background

Among all racial/ethnic groups, people who identify as African American/Blacks have the second highest colorectal cancer (CRC) incidence in the USA. This disparity may exist because African American/Blacks, compared to other racial/ethnic groups, have a higher prevalence of risk factors for CRC, including obesity, low fiber consumption, and higher intakes of fat and animal protein. One unexplored, underlying mechanism of this relationship is the bile acid-gut microbiome axis. High saturated fat, low fiber diets, and obesity lead to increases in tumor promoting secondary bile acids. Diets high in fiber, such as a Mediterranean diet, and intentional weight loss may reduce CRC risk by modulating the bile acid-gut microbiome axis. The purpose of this study is to test the impact of a Mediterranean diet alone, weight loss alone, or both, compared to typical diet controls on the bile acid-gut microbiome axis and CRC risk factors among African American/Blacks with obesity. Because weight loss or a Mediterranean diet alone can reduce CRC risk, we hypothesize that weight loss plus a Mediterranean diet will reduce CRC risk the most.

Methods

This randomized controlled lifestyle intervention will randomize 192 African American/Blacks with obesity, aged 45–75 years to one of four arms: Mediterranean diet, weight loss, weight loss plus Mediterranean diet, or typical diet controls, for 6 months (48 per arm). Data will be collected at baseline, mid-study, and study end. Primary outcomes include total circulating and fecal bile acids, taurine-conjugated bile acids, and deoxycholic acid. Secondary outcomes include body weight, body composition, dietary change, physical activity, metabolic risk, circulating cytokines, gut microbial community structure and composition, fecal short-chain fatty acids, and expression levels of genes from exfoliated intestinal cells linked to carcinogenesis.

Discussion

This study will be the first randomized controlled trial to examine the effects of a Mediterranean diet, weight loss, or both on bile acid metabolism, the gut microbiome, and intestinal epithelial genes associated with carcinogenesis. This approach to CRC risk reduction may be especially important among African American/Blacks given their higher risk factor profile and increased CRC incidence.

Trial registration

ClinicalTrials.govNCT04753359. Registered on 15 February 2021.