bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of epigenetic modification-related signals for the diagnosis and prognosis of colorectal cancer
Authors: Li Xia , Li Jingjing , Li Jie , Liu Nannan , Zhuang Liwei
Published: January 2024

Background

Colorectal cancer (CRC) is one of the world's most common malignancies. Epigenetics is the study of heritable changes in characteristics beyond the DNA sequence. Epigenetic information is essential for maintaining specific expression patterns of genes and the normal development of individuals, and disorders of epigenetic modifications may alter the expression of oncogenes and tumor suppressor genes and affect the development of cancer. This study elucidates the relationship between epigenetics and the prognosis of CRC patients by developing a predictive model to explore the potential value of epigenetics in the treatment of CRC.

Methods

Gene expression data of CRC patients’ tumor tissue and controls were downloaded from GEO database. Combined with the 720 epigenetic-related genes (ERGs) downloaded from EpiFactors database, prognosis-related epigenetic genes were selected by univariate cox and LASSO analyses. The Kaplan–Meier and ROC curve were used to analyze the accuracy of the model. Data of 238 CRC samples with survival data downloaded from the GSE17538 were used for validation. Finally, the risk model is combined with the clinical characteristics of CRC patients to perform univariate and multivariate cox regression analysis to obtain independent risk factors and draw nomogram. Then we evaluated the accuracy of its prediction by calibration curves.

Results

A total of 2906 differentially expressed genes (DEGs) were identified between CRC and control samples. After overlapping DEGs with 720 ERGs, 56 epigenetic-related DEGs (DEERGs) were identified. Combining univariate and LASSO regression analysis, the 8 epigenetic-related genes-based risk score model of CRC was established. The ROC curves and survival difference of high and low risk groups revealed the good performance of the risk score model based on prognostic biomarkers in both training and validation sets. A nomogram with good performance to predict the survival of CRC patients were established based on age, NM stage and risk score. The calibration curves showed that the prognostic model had good predictive performance.

Conclusion

In this study, an epigenetically relevant 8-gene signature was constructed that can effectively predict the prognosis of CRC patients and provide potential directions for targeted therapies for CRC.
The pan-plastome of Hemerocallis citrina reveals new insights into the genetic diversity and cultivation history of an economically important food plant
Authors: Jia Minlong , Wang Jie , Cao Dongmei , Jiang Congrong , Li Wei , Tembrock Luke R. , Xing Guoming , Li Sen , Wu Zhiqiang
Published: January 2024

Background

Hemerocallis citrina Baroni (Huang hua cai in Chinese) is a perennial herbaceous plant grown for its flower buds that are eaten fresh or dried and is known as the vegetarian three treasures. The nuclear genome of H. citrina has been reported, but the intraspecific variation of the plastome (plastid genome) has not yet been studied. Therefore, the panplastome of this species collected from diverse locations is reported here for the first time.

Results

In this study, 65 H. citrina samples were resequenced, de novo assembled, and aligned with the published plastome of H. citrina to resolve the H. citrina panplastome. The sizes of the 65 newly assembled complete plastomes of H. citrina ranged from 156,048 bp to 156,263 bp, and the total GC content ranged from 37.31 to 37.34%. The structure of the complete plastomes showed a typical tetrameric structure, including a large single copy (LSC), a small single copy (SSC), and a pair of inverted repeat regions (IRA and IRB). Many nucleotide variants were identified between plastomes, among which the variants in the intergenic spacer region were the most abundant, with the highest number of variants concentrated in the LSC region. Based on the phylogenetic tree constructed using the ML method, population structure analysis, and principal component analysis (PCA), the panplastome data were subdivided into five genetic clusters. The C5 genetic cluster was mostly represented by samples from Qidong, Hunan Province, while samples from Shanxi and Shaanxi Provinces were classified into the C4 genetic cluster. The greatest genetic diversity was found in the C1 genetic cluster, and the greatest genetic distance between any two clusters was found between the C4 and C5 clusters.

Conclusion

The resolution of the panplastome and the analysis of the population structure of H. citrina plastomes provide important data for future breeding projects and germplasm preservation.
Gastroparesis might not be uncommon in patients with diabetes mellitus in a real-world clinical setting: a cohort study
Authors: Lee Jeongmin , Park Hye Lim , Park Su Young , Lim Chul-Hyun , Kim Min-Hee , Lee Jung Min , Chang Sang-Ah , Oh Jung-Hwan
Published: January 2024

Background

This study investigated the frequency of diabetic gastroparesis and associated risk factors in a real-world clinical setting.

Methods

This retrospective cross-sectional study included patients who underwent assessments of solid gastric emptying time (GET) by technetium-99 m scintigraphy between May 2019 and December 2020. We categorized patients into three groups according to gastric retention of technetium-99 m: rapid (< 65% at 1 h or < 20% at 2 h), normal (≤60% at 2 h and/or ≤ 10% at 4 h), and delayed (> 60% at 2 h and/or > 10% at 4 h).

Results

Patients with diabetes mellitus (DM) were more likely to show abnormal GET than those without DM (119 [70.8%] vs. 16 [44.4%]). The mean glycated A1c was 10.3% in DM patients. DM patients with normal GET were significantly younger (57.2 years, P = 0.044) than those with delayed (65.0 years) or rapid GET (60.2 years). Fasting glucose levels were the lowest in the normal GET group and the highest in the rapid GET group (delayed: 176.3 mg/dL, normal: 151.2 mg/dL, rapid: 181.0 mg/dL, P = 0.030). However, glycated A1c was not significantly different among the delayed, normal, and rapid GET groups in patients with DM. Patients with delayed and rapid GET showed a higher frequency of retinopathy (6.0 vs. 15.5%, P = 0.001) and peripheral neuropathy (11.3 vs. 24.4%, P = 0.001) than those with normal GET. In the multinomial logistic regression analysis, retinopathy demonstrated a positive association with delayed GET, while nephropathy showed a significant negative correlation.

Conclusion

DM gastroparesis in the clinical setting was not uncommon. Abnormal GET, including delayed and rapid GET, was associated with DM retinopathy or peripheral neuropathy.
Introducing a pharmacist-led transmural care program to reduce drug-related problems in orthogeriatric patients: a prospective interventional study
Authors: Bailly Rachel , Wuyts Stephanie , Toelen Loic , Mets Tony , Van Hauwermeiren Carmen , Scheerlinck Thierry , Cortoos Pieter-Jan , Lieten Siddhartha
Published: January 2024

Background

Orthogeriatric patients have an increased risk for complications due to underlying comorbidities, chronic drug therapy and frequent treatment changes during hospitalization. The clinical pharmacist (CP) plays a key role in transmural communication concerning polypharmacy to improve continuity of care by the general practitioner (GP) after discharge. In this study, a pharmacist-led transmural care program, tailored to orthogeriatric patients, was evaluated to reduce drug related problems (DRPs) after discharge.

Methods

An interventional study was performed (pre-period: 1/10/2021-31/12/2021; post-period: 1/01/2022-31/03/2022). Patients (≥ 65 years) from the orthopedic department were included. The pre-group received usual care, the post-group received the pharmacist-led transmural care program. The DRP reduction rate one month after discharge was calculated. Associated factors for the DRP reduction rate were determined in a multiple linear regression analysis. The GP acceptance rate was determined for the proposed interventions, as well as their clinical impact using the Clinical, Economic and Organizational (CLEO) tool. Readmissions one month after discharge were evaluated.

Results

Overall, 127 patients were included (control n = 61, intervention n = 66). The DRP reduction rate was statistically significantly higher in the intervention group compared to the control group (p < 0.001). The pharmacist’s intervention was associated with an increased DRP reduction rate (+ 1.750, 95% confidence interval 1.222–2.278). In total, 141 interventions were suggested by the CP, of which 71% were accepted one month after discharge. In both periods, four patients were readmitted one month after discharge. 58% of the interventions had a clinical impact (≥ 2 C level using the CLEO-tool) according to the geriatrician and for the CP it was 45%, indicating that they had the potential to avoid patient harm.

Conclusions

The pharmacist-led transmural care program significantly reduced DRPs in geriatric patients from the orthopedic department one month after discharge. The transmural communication with GPs resulted in a high acceptance rate of the proposed interventions.
Psychometric properties of the COVID-19 Yorkshire Rehabilitation Scale: Post-Covid-19 syndrome in Iranian elderly population
Authors: Tamadoni Negar , Bakhtiari Afsaneh , Nikbakht Hossein-Ali
Published: January 2024

Background

This study aimed to assess the construct validity and reliability of the Iranian version of the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) among the elderly population.

Method

A cohort of 230 elderly individuals who tested positive for Covid-19 via PCR were administered a health and demographic information questionnaire along with the C19-YRS. Both exploratory and confirmatory factor analyses were conducted, and Cronbach’s alpha was calculated.

Results

Findings from the exploratory and confirmatory factor analyses of the C19-YRS revealed alterations compared to the original version, resulting in an adapted version with three factors achieved by redistributing the questions. These factors accounted for 57.46% of the total variance. Despite a relatively lower factor loading in the 6th question, it was retained due to its significance among the elderly. The Cronbach’s alpha for the C19-YRS subscales ranged from 0.730 to 0.890, indicating acceptable reliability.

Conclusion

The validation results indicated a well-adjusted factor structure and internal consistency, affirming the utility of this tool among the elderly population. Consequently, the C19-YRS in Iran can serve as a valuable resource in healthcare settings, aiding in the assessment of chronic complications arising from Covid-19 in the elderly. It can be utilized as an initial screening or triage test and to evaluate the effectiveness of interventions.
SEA-NET: medical image segmentation network based on spiral squeeze-and-excitation and attention modules
Authors: Xiong Liangli , Yi Chen , Xiong Qiliang , Jiang Shaofeng
Published: January 2024

Background

Medical image segmentation is an important processing step in most of medical image analysis. Thus, high accuracy and robustness are required for them. The current deep neural network based medical segmentation methods have good effect on image with balanced foreground and background, but it will loss the characteristics of small targets on image with imbalanced foreground and background after multiple convolutions.

Methods

In order to retain the features of small targets in the deep network, we proposed a new medical image segmentation model based on the U-Net with squeeze-and-excitation and attention modules which form a spiral closed path,callled as Spiral Squeeze-and-Excitation and Attention NET (SEA-NET) in this paper. The segmentation model used squeeze-and-extraction modules to adjust the channel information to enhance the useful information and used attention modules to adjust the spatial information of the feature map to highlight the target area for small target segmentation when up-sampling. The deep semantic information is integrated into the shallow feature map by the attention model. Therefore, the deep semantic information cannot be scattered by continuous up-sampling. We used cross entropy loss + Tversky loss function for fast convergence and well processing the imbalanced data sets. Our proposed SEA-NET was tested on the brain MRI dataset LPBA40 and peripheral blood smear images.

Conclusions

On brain MRI data, the average value of the Dice coefficient we obtained reached 98.1$$\%$$
%
. On the peripheral blood smear dataset, our proposed model has a good segmentation effect on adhesion cells.

Results

The experimental results proved that the proposed SEA-Net performed better than U-Net, U-Net++, etc. in medical image segmentation.
The effects of lockdown during the COVID-19 pandemic on fetal movement profiles
Authors: Reissland N. , Ustun B , Einbeck J.
Published: January 2024

Purpose

The current study investigated the direct impact of the COVID-19 lockdown on fetal movements, addressing a critical research gap. While previous research has predominantly examined the effects of lockdown on maternal health and postnatal outcomes, little attention has been paid to the direct consequences on fetal well-being as indicated by their movement profile.

Methods

We conducted analysis of movement profiles in 20 healthy fetuses during the COVID-19 pandemic lockdown (third national UK lockdown period between January and March 2021) and compared them with 20 healthy fetuses from pre-covid pregnancies, all at 32 weeks gestation. We controlled for maternal stress, depression, and anxiety.

Results

Pregnant mothers during pre-covid compared with those during the COVID-19 lockdown reported similar levels of stress (p = 0.47), depression (p = 0.15), and anxiety (p = 0.07). Their fetuses, however, differed in their movement profiles with mouth movement frequencies significantly higher during COVID-19 lockdown (COVID-19 lockdown: mean of 5.909) compared to pre-Covid pregnancies (mean of 3.308; p = 0.029). Furthermore, controlling for maternal anxiety a regression analysis indicated that frequency of fetal mouth movements (p = 0.017), upper face movements (p = 0.008), and touch movements (p = 0.031) were all significantly higher in fetuses observed during lockdown compared to fetuses before the Covid period.

Conclusion

Fetuses show an effect of lockdown independent of maternal anxiety, stress, or depression. These findings contribute to our understanding of fetal development during extraordinary circumstances, raising questions about the potential effects of having to stay indoors during lockdowns.
Relationship between DXA measured systemic bone mineral density and subchondral bone cysts in postmenopausal female patients with knee osteoarthritis: a cross-sectional study
Authors: Tönük Şükrü Burak , Yorgancıoğlu Zeynep Rezan , Ramadan Selma Uysal , Kocaoğlu Seher
Published: January 2024

Background

Individuals with high systemic bone mineral density (BMD) may have an increased risk of incident knee osteoarthritis (OA). Besides that, radiographic osteophytes are strongly associated with BMD. Because of these reasons, the aim of the study was to investigate the possible association between radiological subchondral bone cyst (SBC) grade and systemic BMD and vitamin D status in the postmenopausal female patients with knee OA in a crosss-sectional study.

Methods

This study included of 48 osteoporosis treatment-free postmenopausal patients diagnosed with symptomatic medial compartment knee OA. BMD analysis was performed using dual-energy X-ray absorptiometry (DXA) and serum vitamin D levels were measured after recording patients’ findings. Each knee was scanned using computed tomography (CT), and categorical SBC scores were graded for the medial and lateral tibiofemoral (TF) and patellofemoral (PF) compartments and further calculated as compartmental total, total TF and grand total of both TF compartments. SBC scores were analysed with correlation analysis.

Results

The patient population was characterized by radiographic joint space narrowing, obesity and low vitamin D status. Median medial total and grand total TF SBC scores were significantly different between the patient groups according to the Kellgren-Lawrence (KL) radiographic grading (p = 0.006 and p = 0.007, respectively). There were no correlations between femoral BMD values and SBC scores. However, positive correlations were detected significantly between L1 − 4 DXA values and TF SBC scores, but not with PF SBC scores (p = 0.005 for the correlation between L1 − 4 BMD and medial compartments total TF SBC score, p = 0.021 for the correlation between L1 − 4 BMD and grand total TF SBC score). No significant correlations were found with Vitamin D levels.

Conclusions

Development of TF OA high-grade SBCs may be linked to systemic bone mass as represented by trabecular bone-rich lumbar vertebrae. The relationship might point to the importance of bone stiffness as an acting factor in knee OA possibly with mechanical energy transfer to the joint.
Prediabetes remission after bariatric surgery: a 4-years follow-up study
Authors: Borges-Canha Marta , Neves João Sérgio , Silva Maria Manuel , Mendonça Fernando , Moreno Telma , Ribeiro Sara , Vale Catarina , Gonçalves Juliana , Ferreira Helena Urbano , Gil-Santos Sara , Calheiros Raquel , Meira Inês , Menino João , Guerreiro Vanessa , Pedro Jorge , Sande Ana , Souto Selma B. , da Costa Eduardo Lima , Carvalho Davide , Freitas Paula ,   CRIO group, Preto John Rodrigues , Sousa Hugo Miguel Santos , Pinho André Manuel Costa , Galego Carla Cristina Oliveira Rodrigues T , Correia Maria Flora Ferreira Sampaio Carval , Gil Cidália Fátima Castro , Melim Diva Bizarro Figueiredo , Pinto Eduardo Gil Ferreira Rodrigues , Silva Marco António Costa , Martins Cristina Sarmento Pontes , Pereira Luís Miguel Gonçalves , Magalhães Inês Vasconcelos Sousa , Brandão Isabel Maria Boavista Vieira Marque , Andrade Sertório Manuel Freitas , Nunes Patrícia Maria Lopes
Published: January 2024

Background

Bariatric surgery leads to weight loss and to cardiometabolic risk improvement. Although prediabetes remission after bariatric surgery is biologically plausible, data on this topic is scarce. We aimed to assess prediabetes remission rate and clinical predictors of remission in a 4 year follow up period.

Methods

Observational longitudinal study including patients with obesity and prediabetes who had undergone bariatric surgery in our centre. Prediabetes was defined as having a baseline glycated haemoglobin (A1c) between 5.7% and 6.4% and absence of anti-diabetic drug treatment. We used logistic regression models to evaluate the association between the predictors and prediabetes remission rate.

Results

A total of 669 patients were included, 84% being female. The population had a mean age of 45.4 ± 10.1 years-old, body mass index of 43.8 ± 5.7 kg/m2, and median A1c of 5.9 [5.8, 6.1]%. After bariatric surgery, prediabetes remission rate was 82%, 73%, 66%, and 58%, respectively in the 1st, 2nd, 3rd, and 4th years of follow-up. Gastric sleeve (GS) surgery was associated with higher prediabetes remission rate than Roux-en-Y gastric bypass surgery in the 3rd year of follow-up. Men had a higher remission rate than women, in the 1st and 3nd years of follow-up in the unadjusted analysis. Younger patients presented a higher remission rate comparing to older patients in the 3rd year of follow-up.

Conclusion

We showed a high prediabetes remission rate after bariatric surgery. The remission rate decreases over the follow-up period, although most of the patients maintain the normoglycemia. Prediabetes remission seems to be more significant in patients who had undergone GS, in male and in younger patients.
Comparison of the prevalence of malocclusion and oral habits between children with cerebral palsy and healthy children
Authors: Almotareb Fuad Lutf , Al-Shamahy Hassan Abdulwahab
Published: January 2024

Background

Cerebral palsy (CP) represents for children an important problem of health and affects roughly 2 per 1000 live births and is the most common pediatric developmental motor disability. Therefore, the purpose of this study was to determine the prevalence, type and severity of malocclusion and oral habits in children with Cerebral Palsy (CP) and to compare them with a control group of healthy children in Sana’a city.

Materials and methods

A prospective, case–control study was made of two groups, a cerebral palsy and a control group. The study population consisted of 60 children who had CP, and a control group of 60 matched children with no physical or mental disabilities. Data were collected using a questionnaire and assessment for malocclusion was done clinically. The patients were compared with equal number of age-matched controls. The inclusion criteria were individuals aged over 6 years; absence of previous orthodontic treatment; no missing permanent first molars.

Results

Results showed an increased prevalence of malocclusion in children with cerebral palsy. Molar class II relationship was statistically higher in cerebral palsy children than healthy control (P = 0.001). Cerebral palsied children are likely to have a significantly increased protrusion of the anterior teeth (P < 0.001) when compared with normal children. Mouth breathing and Tongue thrust. Habits were significantly higher in the CP group (p = 0.0001) when compared with normal children.

Conclusion

The prevalence of malocclusion was higher in children with Cerebral palsy than in normal children, and the present study concludes that in children with Cerebral Palsy, more oral Habits problems due to oral motor dysfunctions are common and problems of mouth breathing and Tongue thrust produce different malocclusion and poor oral hygiene complications in these children.
Characterization of patients with brain metastases referred to palliative care
Authors: Harrison Rebecca A. , Tang Michael , Shih Kaoswi Karina , Khan Maria , Pham Lily , De Moraes Aline Rozman , O’Brien Barbara J. , Bassett Roland , Bruera Eduardo
Published: January 2024

Purpose

In this study, we aimed to assess the clinical characteristics, reasons for referral, and outcomes of patients with brain metastases (BM) referred to the supportive care center.

Methods

Equal numbers of patients with melanoma, breast cancer, and lung cancer with (N = 90) and without (N = 90) BM were retrospectively identified from the supportive care database for study. Descriptive statistics were used to analyze demographic, disease, and clinical data. Kaplan Meier method was used to evaluate survival outcomes.

Results

While physical symptom management was the most common reason for referral to supportive care for both patients with and without BM, patients with BM had significantly lower pain scores on ESAS at time of referral (p = 0.002). They had greater interaction with acute care in the last weeks of life, with higher rates of ICU admission, emergency room visits, and hospitalizations after initial supportive care (SC) visit. The median survival time from referral to Supportive Care Center (SCC) was 0.90 years (95% CI 0.73, 1.40) for the brain metastasis group and 1.29 years (95% CI 0.91, 2.29) for the group without BM.

Conclusions

Patients with BM have shorter survival and greater interaction with acute care in the last weeks of life. This population also has distinct symptom burdens from patients without BM. Strategies to optimize integration of SC for patients with BM warrant ongoing study.
Reflexology in oncological treatment – a systematic review
Authors: Klaus Moritz , Kutschan Sabine , Männle Heidrun , Hübner Jutta , Dörfler Jennifer
Published: January 2024

Background

As cancer and its therapy comes with a wide range of negative effects, people look for options to mitigate these effects. Reflexology is among the options of complementary medicine.

Method

In March 2022 a systematic search was conducted searching five electronic databases (Embase, Cochrane, PsychInfo, CINAHL and Medline) to find studies concerning the use, effectiveness and potential harm of reflexology on cancer patients.

Results

From all 821 search results, 29 publications concerning 26 studies with 2465 patients were included in this systematic review. The patients treated with reflexology were mainly diagnosed with breast, lung, gastrointestinal and hematological cancer. Outcomes were mainly pain, quality of life, anxiety, depression, fatigue. The studies had moderate to low quality and reported heterogeneous results: Some studies reported significant improvements in above mentioned outcomes while other studies did not find any changes concerning these endpoints.

Conclusion

Due to the very heterogeneous results and methodical limitations of the included studies, a clear statement regarding the effectiveness of reflexology on cancer patients is not possible. The current evidence indicates that reflexology is superior to passive control groups for pain, quality of life and fatigue, however, more studies with comparable active control groups are needed.
Utilizing decision tree machine learning model to map dental students’ preferred learning styles with suitable instructional strategies
Authors: Shoaib Lily Azura , Safii Syarida Hasnur , Idris Norisma , Hussin Ruhaya , Sazali Muhamad Amin Hakim
Published: January 2024

Background

Growing demand for student-centered learning (SCL) has been observed in higher education settings including dentistry. However, application of SCL in dental education is limited. Hence, this study aimed to facilitate SCL application in dentistry utilising a decision tree machine learning (ML) technique to map dental students’ preferred learning styles (LS) with suitable instructional strategies (IS) as a promising approach to develop an IS recommender tool for dental students.

Methods

A total of 255 dental students in Universiti Malaya completed the modified Index of Learning Styles (m-ILS) questionnaire containing 44 items which classified them into their respective LS. The collected data, referred to as dataset, was used in a decision tree supervised learning to automate the mapping of students' learning styles with the most suitable IS. The accuracy of the ML-empowered IS recommender tool was then evaluated.

Results

The application of a decision tree model in the automation process of the mapping between LS (input) and IS (target output) was able to instantly generate the list of suitable instructional strategies for each dental student. The IS recommender tool demonstrated perfect precision and recall for overall model accuracy, suggesting a good sensitivity and specificity in mapping LS with IS.

Conclusion

The decision tree ML empowered IS recommender tool was proven to be accurate at matching dental students’ learning styles with the relevant instructional strategies. This tool provides a workable path to planning student-centered lessons or modules that potentially will enhance the learning experience of the students.
A closer look at the international health regulations capacities in Lebanon: a mixed method study
Authors: Hassan Maya , Jamal Diana , El-Jardali Fadi
Published: January 2024

Background

Lebanon ratified the International Health Regulations (IHR) (2005) in 2007, and since then, it has been facing complex political deadlocks, financial deterioration, and infectious disease emergencies. We aimed to understand the IHR capacities’ scores of Lebanon in comparison to other countries, the IHR milestones and activities in Lebanon, the challenges of maintaining the IHR capacities, the refugee crisis's impact on the development of these capacities; and the possible recommendations to support the IHR performance in Lebanon.

Methods

We used a mixed-method design. The study combined the use of secondary data analysis of the 2020 State Party Self-Assessment Annual Report (SPAR) submissions and qualitative design using semi-structured interviews with key informants. Semi-structured interviews were conducted with nine key informants. The analysis of the data generated was based on inductive thematic analysis.

Results

According to SPAR, Lebanon had levels of 4 out of 5 (≤ 80%) in 2020 in the prevention, detection, response, enabling functions, and operational readiness capacities, pertaining that the country was functionally capable of dealing with various events at the national and subnational levels. Lebanon scored more than its neighboring countries, Syria, and Jordan, which have similar contexts of economic crises, emergencies, and refugee waves. Despite this high level of commitment to meeting IHR capacities, the qualitative findings demonstrated several gaps in IHR performance as resource shortage, governance, and political challenges. The study also showed contradictory results regarding the impact of refugees on IHR capacities. Some key informants agreed that the Syrian crisis had a positive impact, while others suggested the opposite. Whether refugees interfere with IHR development is still an area that needs further investigation.

Conclusion

The study shows that urgent interventions are needed to strengthen the implementation of the IHR capacities in Lebanon. The study recommends 1) reconsidering the weight given to IHR capacities; 2) promoting governance to strengthen IHR compliance; 3) strengthening the multisectoral coordination mechanisms; 4) reinforcing risk communication strategies constantly; 5) mobilizing and advancing human resources at the central and sub-national levels; 6) ensuring sustainable financing; 7) integrating refugees and displaced persons in IHR framework and its assessment tools; 8) acknowledging risk mapping as a pre-requisite to a successful response; and 9) strengthening research on IHR capacities in Lebanon.
Inpatient healthcare utilization among people with disabilities in Iran: determinants and inequality patterns
Authors: Karami Badriyeh , Rezaei Satar , Gillan Hadi Darvishi , Akbari Shahram , Maleki Raheleh , Moradi Fardin , Jalili Faramarz , Karami Mohammad , Soltani Shahin
Published: January 2024

Background

People with disabilities (PWD) have different health service needs and different factors affect the utilization of these services. Therefore, the aim of this present study was to identify determinants of inpatient healthcare utilization among PWDs in Iran.

Methods

This research was a secondary data analysis of a cross-sectional study. The present study used data gathered for 766 PWDs (aged 18 years and older) within the Iranian Society with Disabilities (ISD) between September and December 2020. Multiple logistic regression models calculated adjusted odds ratios (aOR) and 95% confidence intervals in order to identify determinants of inpatient healthcare utilization among PWDs.

Results

Data for 766 people with disabilities were analyzed. A large number of participants were over 28 years of age (70.94%), male (64.36%), and single (54.02%). In the present study, more than 71% of participants had no history of hospitalization during the last year. In this study, males [aOR 2.11(1.14–3.91), participants with Civil Servants health insurance coverage [aOR 3.44 (1.16 − 10.17)] and individuals in the 3th quartile of disability severity [aOR 2.13 (1.01 − 4.51)] had greater odds of inpatient healthcare utilization compared to the other groups. The value of the concentration index (C) for inpatient healthcare utilization was − 0.084 (P.value = 0.046). The decomposition analysis indicated that gender was the greatest contributor (21.92%) to the observed inequality in inpatient healthcare utilization among participants.

Conclusion

Our findings suggested that the likelihood of hospitalization among the study participants could be significantly influenced by factors such as gender, the health insurance scheme, and the degree of disability severity. These results underscore the imperative for enhanced access to outpatient services, affordable insurance coverage, and reduced healthcare expenditures for this vulnerable population. Addressing these issues has the potential to mitigate the burden of hospitalization and promote better health outcomes for disadvantaged individuals.
Exploring community insights on antimicrobial resistance in Nepal: a formative qualitative study
Authors: Parajuli Ayuska , Garbovan Lidis , Bhattarai Basudev , Arjyal Abriti , Baral Sushil , Cooke Paul , Latham Sophia , Barrington Dani J. , Mitchell Jessica , King Rebecca
Published: January 2024

Background

Antimicrobial resistance (AMR) is the process by which microbes evolve mechanisms to survive the medicines designed to destroy them i.e. antimicrobials (AMs). Despite being a natural process, AMR is being hastened by the abuse of AMs. In context of Nepal, there is limited information on drivers of AMR and barriers in addressing it from a community perspective. This study explores the local language and terminology used around AMs in the community, commonly used AMs and reasons for their usage, how these AMs are sourced, and the perceived barriers to addressing AMR via One Health approach.

Methods

A phenomenological study design was utilized with applied qualitative research theoretically framed as pragmatism. Twelve in-depth interviews and informal discussions with a One Health focus, were purposively conducted with wide range of stakeholders and community resident of Kapilvastu municipality of Nepal during April 2022. The acquired data was analyzed manually via a thematic framework approach. The study obtained ethical approval from ethical review board of Nepal Health Research Council and University of Leeds.

Results

Nepali and Awadhi languages does not have specific words for AMs or AMR, which is understandable by the community people. Rather, community use full explanatory sentences. People use AMs but have incomplete knowledge about them and they have their own local words for these medicines. The knowledge and usage of AMs across human and animal health is impacted by socio-structural factors, limited Government regulation, inadequate supply of AMs in local government health facilities and the presence of various unregulated health providers that co-exist within the health system. Novel ideas such as the use of visual and smart technology, for instance mobile phones and social media exposure, can enable access to information about AMs and AMR.

Conclusion

This study shows that terminology that is understandable by the community referring to AMs and AMR in Nepali and Awadhi languages does not exist, but full explanatory sentences and colloquial names are used. Despite regular utilisation, communities have incomplete knowledge regarding AMs. Since, knowledge alone cannot improve behaviour, behavioural interventions are required to address AMR via community engagement to co-produce their own solutions.

Trial registration

Not applicable.
Impact of baseline and trajectory of the atherogenic index of plasma on incident diabetic kidney disease and retinopathy in participants with type 2 diabetes: a longitudinal cohort study
Authors: Zhang Jia , Liu Cong , Peng Ying , Fang Qianhua , Wei Xing , Zhang Cui , Sun Lin , Hu Zhuomeng , Hong Jie , Gu Weiqiong , Wang Weiqing , Shi Juan , Zhang Yifei
Published: January 2024

Background

Some studies have assessed the predictive role of the atherogenic index of plasma (AIP) for macrovascular diseases. This prospective investigation aimed to elucidate whether AIP is associated with diabetic kidney disease (DKD) and diabetic retinopathy (DR) incidence.

Methods

The data were extracted from 4831 participants, of whom 2943 and 3360 participants with type 2 diabetes (T2D) were included in the DKD and DR follow-up analyses, respectively. Cox regression models were performed to test the relationships of AIP value at baseline with the risk of incident DKD and DR. Group-based trajectory modelling was utilized to discern AIP trajectories during the follow-up period. Subsequently, logistic regressions were applied to ascertain the influence of AIP trajectories on the incidence of DKD and DR.

Results

During the follow-up period, 709 (24.1%) and 193 (5.7%) participants developed DKD and DR, respectively. The median (interquartile range) follow-up time was 24.2 (26.3) months for DKD and 25.7 (27.0) months for DR. According to the multivariate Cox regression models, baseline AIP was positively and linearly related to the occurrence of DKD, with a hazard ratio of 1.75 (95% confidence interval [CI] 1.36–2.26). Three distinct trajectories of AIP were identified throughout the follow-up time: Low (31.4%), Median (50.2%), and High (18.3%). Compared to participants with the Low AIP trajectory, those with High and Median AIP trajectories presented 117% (95% CI: 1.62–2.91) and 84% (95% CI 1.46–2.32) greater odds of developing DKD, respectively. However, neither baseline levels nor trajectories of AIP were shown to be related to DR after adjusting for confounding factors.

Conclusions

Baseline levels and trajectories of AIP were independently related to elevated DKD risk, indicating that AIP could be used as a predictor for identifying T2D participants at higher risk of DKD. No association between AIP and DR was detected.
Interleukin-6-elicited chronic neuroinflammation may decrease survival but is not sufficient to drive disease progression in a mouse model of Leigh syndrome
Authors: Aguilar Kevin , Canal Carla , Comes Gemma , Díaz-Clavero Sandra , Llanos Maria Angeles , Quintana Albert , Sanz Elisenda , Hidalgo Juan
Published: January 2024

Background

Mitochondrial diseases (MDs) are genetic disorders characterized by dysfunctions in mitochondria. Clinical data suggest that additional factors, beyond genetics, contribute to the onset and progression of this group of diseases, but these influencing factors remain largely unknown. Mounting evidence indicates that immune dysregulation or distress could play a role. Clinical observations have described the co-incidence of infection and the onset of the disease as well as the worsening of symptoms following infection. These findings highlight the complex interactions between MDs and immunity and underscore the need to better understand their underlying relationships.

Results

We used Ndufs4 KO mice, a well-established mouse model of Leigh syndrome (one of the most relevant MDs), to test whether chronic induction of a neuroinflammatory state in the central nervous system before the development of neurological symptoms would affect both the onset and progression of the disease in Ndufs4 KO mice. To this aim, we took advantage of the GFAP-IL6 mouse, which overexpresses interleukin-6 (IL-6) in astrocytes and produces chronic glial reactivity, by generating a mouse line with IL-6 overexpression and NDUFS4 deficiency. IL-6 overexpression aggravated the mortality of female Ndufs4 KO mice but did not alter the main motor and respiratory phenotypes measured in any sex. Interestingly, an abnormal region-dependent microglial response to IL-6 overexpression was observed in Ndufs4 KO mice compared to controls.

Conclusion

Overall, our data indicate that chronic neuroinflammation may worsen the disease in Ndufs4 KO female mice, but not in males, and uncovers an abnormal microglial response due to OXPHOS dysfunction, which may have implications for our understanding of the effect of OXPHOS dysfunction in microglia.
Administration of an AAV vector coding for a P2X7-blocking nanobody-based biologic ameliorates colitis in mice
Authors: Abad Catalina , Demeules Mélanie , Guillou Charlotte , Gondé Henri , Zoubairi Rachid , Tan Yossan-Var , Pinto-Espinoza Carolina , Schäfer Waldemar , Mann Anna Marei , Vouret-Craviari Valérie , Koch-Nolte Friedrich , Adriouch Sahil
Published: January 2024

Background

The pro-inflammatory ATP-gated P2X7 receptor is widely expressed by immune and non-immune cells. Nanobodies targeting P2X7, with potentiating or antagonistic effects, have been developed. Adeno-associated virus (AAV)-mediated gene transfer represents an efficient approach to achieve long-term in vivo expression of selected nanobody-based biologics. This approach (AAVnano) was used to validate the relevance of P2X7 as a target in dextran sodium sulfate (DSS)-induced colitis in mice.

Results

Mice received an intramuscular injection of AAV vectors coding for potentiating (14D5-dimHLE) or antagonistic (13A7-Fc) nanobody-based biologics targeting P2X7. Long-term modulation of P2X7 activity was evaluated ex vivo from blood samples. Colitis was induced with DSS in mice injected with AAV vectors coding for nanobody-based biologics. Severity of colitis, colon histopathology and expression of chemokines and cytokines were determined to evaluate the impact of P2X7 modulation. A single injection of an AAV vector coding for 13A7-Fc or 14D5-dimHLE efficiently modulated P2X7 function in vivo from day 15 up to day 120 post-injection in a dose-dependent manner. An AAV vector coding for 13A7-Fc significantly ameliorated DSS-induced colitis and significantly reduced immune cell infiltration and expression of chemokines and proinflammatory cytokines in colonic tissue.

Conclusions

We have demonstrated the validity of AAVnano methodology to modulate P2X7 functions in vivo. Applying this methodological approach to a DSS-induced colitis model, we have shown that P2X7 blockade reduces inflammation and disease severity. Hence, this study confirms the importance of P2X7 as a pharmacological target and suggests the use of nanobody-based biologics as potential therapeutics in inflammatory bowel disease.

Graphical Abstract
Predictive value of HTS grade in patients with intrahepatic cholangiocarcinoma undergoing radical resection: a multicenter study from China
Authors: Huang Guan , Zhang Haofeng , Yang Zhenwei , Li Qingshan , Yuan Hao , Chen Pengyu , Xie Chenxi , Meng Bo , Zhang Xianzhou , Chen Kunlun , Yu Haibo
Published: January 2024

Background

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant tumor with a poor prognosis. This study aimed to investigate whether Hemoglobin, Albumin, Lymphocytes, and Platelets (HALP) score and Tumor Burden Score (TBS) serves as independent influencing factors following radical resection in patients with ICC. Furthermore, we sought to evaluate the predictive capacity of the combined HALP and TBS grade, referred to as HTS grade, and to develop a prognostic prediction model.

Methods

Clinical data for ICC patients who underwent radical resection were retrospectively analyzed. Univariate and multivariate Cox regression analyses were first used to find influencing factors of prognosis for ICC. Receiver operating characteristic (ROC) curves were then used to find the optimal cut-off values for HALP score and TBS and to compare the predictive ability of HALP, TBS, and HTS grade using the area under these curves (AUC). Nomogram prediction models were constructed and validated based on the results of the multivariate analysis.

Results

Among 423 patients, 234 (55.3%) were male and 202 (47.8) were aged ≥ 60 years. The cut-off value of HALP was found to be 37.1 and for TBS to be 6.3. Our univariate results showed that HALP, TBS, and HTS grade were prognostic factors of ICC patients (all P < 0.05), and ROC results showed that HTS had the best predictive value. The Kaplan–Meier curve showed that the prognosis of ICC patients was worse with increasing HTS grade. Additionally, multivariate regression analysis showed that HTS grade, carbohydrate antigen 19–9 (CA19-9), tumor differentiation, and vascular invasion were independent influencing factors for Overall survival (OS) and that HTS grade, CA19-9, CEA, vascular invasion and lymph node invasion were independent influencing factors for recurrence-free survival (RFS) (all P < 0.05). In the first, second, and third years of the training group, the AUCs for OS were 0.867, 0.902, and 0.881, and the AUCs for RFS were 0.849, 0.841, and 0.899, respectively. In the first, second, and third years of the validation group, the AUCs for OS were 0.727, 0.771, and 0.763, and the AUCs for RFS were 0.733, 0.746, and 0.801, respectively. Through the examination of calibration curves and using decision curve analysis (DCA), nomograms based on HTS grade showed excellent predictive performance.

Conclusions

Our nomograms based on HTS grade had excellent predictive effects and may thus be able to help clinicians provide individualized clinical decision for ICC patients.
Taming microglia: the promise of engineered microglia in treating neurological diseases
Authors: Luo Echo Yongqi , Sugimura Rio Ryohichi
Published: January 2024

Microglia, the CNS-resident immune cells, are implicated in many neurological diseases. Nearly one in six of the world’s population suffers from neurological disorders, encompassing neurodegenerative and neuroautoimmune diseases, most with dysregulated neuroinflammation involved. Activated microglia become phagocytotic and secret various immune molecules, which are mediators of the brain immune microenvironment. Given their ability to penetrate through the blood–brain barrier in the neuroinflammatory context and their close interaction with neurons and other glial cells, microglia are potential therapeutic delivery vehicles and modulators of neuronal activity. Re-engineering microglia to treat neurological diseases is, thus, increasingly gaining attention. By altering gene expression, re-programmed microglia can be utilized to deliver therapeutics to targeted sites and control neuroinflammation in various neuroinflammatory diseases. This review addresses the current development in microglial engineering, including genetic targeting and therapeutic modulation. Furthermore, we discuss limitations to the genetic engineering techniques and models used to test the functionality of re-engineered microglia, including cell culture and animal models. Finally, we will discuss future directions for the application of engineered microglia in treating neurological diseases.

Graphical Abstract