bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between biomarkers of inflammation and dyslipidemia in drug resistant tuberculosis in Uganda
Authors: Baluku Joseph Baruch , Nalwanga Robinah , Kazibwe Andrew , Olum Ronald , Nuwagira Edwin , Mugenyi Nathan , Mulindwa Frank , Bongomin Felix 
Published: March 2024

Abstract
Background
Active tuberculosis (TB) significantly increases the risk of cardiovascular disease, but the underlying mechanisms remain unclear. This study aimed to investigate the association between inflammation biomarkers and dyslipidemia in patients with drug-resistant TB (DR-TB).

Methods
This was a secondary analysis of data from a cross-sectional multi-center study in Uganda conducted 2021. Participants underwent anthropometric measurements and laboratory tests included a lipid profile, full haemogram and serology for HIV infection. Dyslipidemia was defined as total cholesterol > 5.0 mmol/l and/or low-density lipoprotein cholesterol > 4.14 mmol/l, and/or triglycerides (TG) ≥ 1.7 mmol/l, and/or high density lipoprotein cholesterol (HDL-c) < 1.03 mmol/l for men and < 1.29 mmol/l for women. Biomarkers of inflammation were leukocyte, neutrophil, lymphocyte, monocyte, and platelet counts, as well as neutrophil/lymphocyte (NLR), platelet/lymphocyte, and lymphocyte/monocyte (LMR) ratios, mean corpuscular volume (MCV), and the systemic immune inflammation index (SII) (neutrophil × platelet/lymphocyte). Modified Poisson Regression analysis was used for determining the association of the biomarkers and dyslipidemia.

Results
Of 171 participants, 118 (69.0%) were co-infected with HIV. The prevalence of dyslipidemia was 70.2% (120/171) with low HDL-c (40.4%, 69/171) and hypertriglyceridemia (22.5%, 38/169) being the most common components. Patients with dyslipidemia had significantly higher lymphocyte (P = 0.008), monocyte (P < 0.001), and platelet counts (P = 0.014) in addition to a lower MCV (P < 0.001) than those without dyslipidemia. Further, patients with dyslipidemia had lower leucocyte (P < 0.001) and neutrophil (P = 0.001) counts, NLR (P = 0.008), LMR (P = 0.006), and SII (P = 0.049). The MCV was inversely associated with low HDL-C (adjusted prevalence ratio (aPR) = 0.97, 95% CI 0.94–0.99, P = 0.023) but was positively associated with hypertriglyceridemia (aPR = 1.04, 95% CI 1.00-1.08, P = 0.052).

Conclusions
Individuals with dyslipidemia exhibited elevated lymphocyte, monocyte, and platelet counts compared to those without. However, only MCV demonstrated an independent association with specific components of dyslipidemia. There is need for further scientific inquiry into the potential impact of dyslipidemia on red cell morphology and a pro-thrombotic state among patients with TB.
Development of an action programme tackling obesity-related behaviours in adolescents: a participatory system dynamics approach
Authors: Luna Pinzon Angie , Waterlander Wilma , de Pooter Naomi , Altenburg Teatske , Dijkstra Coosje , Emke Helga , van den Eynde Emma , Overman Meredith L. , Busch Vincent , Renders Carry M. , Halberstadt Jutka , Nusselder Wilma , den Hertog Karen , Chinapaw Mai , Verhoeff Arnoud , Stronks Karien 
Published: March 2024

AbstractSystem dynamics approaches are increasingly addressing the complexity of public health problems such as childhood overweight and obesity. These approaches often use system mapping methods, such as the construction of causal loop diagrams, to gain an understanding of the system of interest. However, there is limited practical guidance on how such a system understanding can inform the development of an action programme that can facilitate systems changes. The Lifestyle Innovations Based on Youth Knowledge and Experience (LIKE) programme combines system dynamics and participatory action research to improve obesity-related behaviours, including diet, physical activity, sleep and sedentary behaviour, in 10–14-year-old adolescents in Amsterdam, the Netherlands. This paper illustrates how we used a previously obtained understanding of the system of obesity-related behaviours in adolescents to develop an action programme to facilitate systems changes. A team of evaluation researchers guided interdisciplinary action-groups throughout the process of identifying mechanisms, applying the Intervention Level Framework to identify leverage points and arriving at action ideas with aligning theories of change. The LIKE action programme consisted of 8 mechanisms, 9 leverage points and 14 action ideas which targeted the system’s structure and function within multiple subsystems. This illustrates the feasibility of developing actions targeting higher system levels within the confines of a research project timeframe when sufficient and dedicated effort in this process is invested. Furthermore, the system dynamics action programme presented in this study contributes towards the development and implementation of public health programmes that aim to facilitate systems changes in practice.
A cost-effectiveness evaluation of a dietitian-delivered telephone coaching program during pregnancy for preventing gestational diabetes mellitus
Authors: de Jersey Susan , Keramat Syed Afroz , Chang Angela , Meloncelli Nina , Guthrie Taylor , Eakin Elizabeth , Comans Tracy 
Published: March 2024

Abstract
Background
This study aimed to evaluate the cost-effectiveness of a telehealth coaching intervention to prevent gestational diabetes mellitus (GDM) and to calculate the breakeven point of preventing GDM.

Methods
Data to inform the economic evaluation model was sourced directly from the large quaternary hospital in Brisbane, where the Living Well during Pregnancy (LWdP) program was implemented, and further supplemented with literature-based estimates where data had not been directly collected in the trial. A cost-effectiveness model was developed using a decision tree framework to estimate the potential for cost savings and quality of life improvement. A total of 1,315 pregnant women (49% with a BMI 25-29.9, and 51% with a BMI ≥ 30) were included in the analyses.

Results
The costs of providing routine care and routine care plus LWdP coaching intervention to pregnant women were calculated to be AUD 20,933 and AUD 20,828, respectively. The effectiveness of the LWdP coaching program (0.894 utility) was slightly higher compared to routine care (0.893). Therefore, the value of the incremental cost-effectiveness ratio (ICER) was negative, and it indicates that the LWdP coaching program is a dominant strategy to prevent GDM in pregnant women. We also performed a probabilistic sensitivity analysis using Monte Carlo simulation through 1,000 simulations. The ICE scatter plot showed that the LWdP coaching intervention was dominant over routine care in 93.60% of the trials using a willingness to pay threshold of AUD 50,000.

Conclusion
Findings support consideration by healthcare policy and decision makers of telehealth and broad-reach delivery of structured lifestyle interventions during pregnancy to lower short-term costs associated with GDM to the health system.
Exosomes derived from programmed cell death: mechanism and biological significance
Authors: Xiong Min , Chen Zhen , Tian Jiaqi , Peng Yanjie , Song Dandan , Zhang Lin , Jin Yulan 
Published: March 2024

AbstractExosomes are nanoscale extracellular vesicles present in bodily fluids that mediate intercellular communication by transferring bioactive molecules, thereby regulating a range of physiological and pathological processes. Exosomes can be secreted from nearly all cell types, and the biological function of exosomes is heterogeneous and depends on the donor cell type and state. Recent research has revealed that the levels of exosomes released from the endosomal system increase in cells undergoing programmed cell death. These exosomes play crucial roles in diseases, such as inflammation, tumors, and autoimmune diseases. However, there is currently a lack of systematic research on the differences in the biogenesis, secretion mechanisms, and composition of exosomes under different programmed cell death modalities. This review underscores the potential of exosomes as vital mediators of programmed cell death processes, highlighting the interconnection between exosome biosynthesis and the regulatory mechanisms governing cell death processes. Furthermore, we accentuate the prospect of leveraging exosomes for the development of innovative biomarkers and therapeutic strategies across various diseases.
O-GlcNAc of STING mediates antiviral innate immunity
Authors: Li Yujia , An Wang , Lu Liyuan , Yuan Jiali , Wu Danhui , Yang Qi , Guo Jinrong , Yang Jingyu , Liu Mengjie , He Kaiyue , Lei Xinyuan , Xu Zhi-Xiang 
Published: March 2024

Abstract
Background
O-GlcNAcylation modification affects multiple physiological and pathophysiolocal functions of cells. Altered O-GlcNAcylation was reported to participate in antivirus response. Stimulator of interferon genes (STING) is an adaptor mediating DNA virus-induced innate immune response. Whether STING is able to be modified by O-GlcNAcylation and how O-GlcNAcylation affects STING-mediated anti-DNA virus response remain unknown.

Methods
Metabolomics analysis was used for detecting metabolic alterations in HSV-1 infection cells. Succinylated wheat germ agglutinin (sWGA), co-immunoprecipitation, and pull-down assay were employed for determining O-GlcNAcylation. Mutagenesis PCR was applied for the generation of STING mutants. WT and Sting1−/− C57BL/6 mice (KOCMP-72512-Sting1-B6NVA) were infected with HSV-1 and treated with O-GlcNAcylation inhibitor for validating the role of STING O-GlcNAcylation in antiviral response.

Results
STING was functionally activated by O-GlcNAcylation in host cells challenged with HSV-1. We demonstrated that this signaling event was initiated by virus infection-enhanced hexosamine biosynthesis pathway (HBP). HSV-1 (or viral DNA mimics) promotes glucose metabolism of host cells with a marked increase in HBP, which provides donor glucosamine for O-GlcNAcylation. STING was O-GlcNAcylated on threonine 229, which led to lysine 63-linked ubiquitination of STING and activation of antiviral immune responses. Mutation of STING T229 to alanine abrogated STING activation and reduced HSV-1 stimulated production of interferon (IFN). Application of 6-diazo-5-oxonorleucine (DON), an agent that blocks the production of UDP-GlcNAc and inhibits O-GlcNAcylation, markedly attenuated the removal of HSV-1 in wild type C57BL/6 mice, leading to an increased viral retention, elevated infiltration of inflammatory cells, and worsened tissue damages to those displayed in STING gene knockout mice. Together, our data suggest that STING is O-GlcNAcylated in HSV-1, which is crucial for an effective antiviral innate immune response.

Conclusion
HSV-1 infection activates the generation of UDP-Glc-NAc by upregulating the HBP metabolism. Elevated UDP-Glc-NAc promotes the O-GlcNAcylation of STING, which mediates the anti-viral function of STING. Targeting O-GlcNAcylation of STING could be a useful strategy for antiviral innate immunity.
The clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver disease: a meta-analysis and systematic review
Authors: Nie Qilong , Li Mingyang , Huang Caiyang , Yuan Yongwei , Liang Qiuyan , Ma Xiaojun , Qiu Tengyu , Li Jianhong 
Published: March 2024

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, emerging as a significant health issue on a global scale. Berberine exhibits potential for treating NAFLD, but clinical evidence remains inconclusive. This meta-analysis was conducted to assess the efficacy and safety of berberine for treating NAFLD.

Methods
This study was registered with PROSPERO (No. CRD42023462338). Identification of randomized controlled trials (RCTs) involved searching 6 databases covering the period from their initiation to 9 September 2023. The primary outcomes comprised liver function markers such as glutamyl transpeptidase (GGT), alanine transaminase (ALT), aspartate transaminase (AST), lipid indices including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), homeostasis model assessment for insulin resistance (HOMA-IR) and body mass index (BMI). Review Manager 5.4 and STATA 17.0 were applied for analysis.

Results
Among 10 RCTs involving 811 patients, berberine demonstrated significant reductions in various parameters: ALT (standardized mean difference (SMD) = − 0.72), 95% confidence interval (Cl) [− 1.01, − 0.44], P < 0.00001), AST (SMD = − 0.79, 95% CI [− 1.17, − 0.40], P < 0.0001), GGT (SMD = − 0.62, 95% CI [− 0.95, − 0.29], P = 0.0002), TG (SMD = − 0.59, 95% CI [− 0.86, − 0.31], P < 0.0001), TC(SMD = − 0.74, 95% CI [− 1.00, − 0.49], P < 0.00001), LDL-C (SMD = − 0.53, 95% CI [− 0.88, − 0.18], P = 0.003), HDL-C (SMD = − 0.51, 95% CI [− 0.12, 1.15], P = 0.11), HOMA-IR (SMD = − 1.56, 95% CI [− 2.54, − 0.58], P = 0.002), and BMI (SMD = − 0.58, 95% CI [− 0.77, − 0.38], P < 0.00001). Importantly, Berberine exhibited a favorable safety profile, with only mild gastrointestinal adverse events reported.

Conclusion
This meta-analysis demonstrates berberine's efficacy in improving liver enzymes, lipid profile, and insulin sensitivity in NAFLD patients. These results indicate that berberine shows promise as an adjunct therapy for NAFLD.
Trial registration The protocol was registered with PROSPERO (No. CRD42023462338). Registered on September 27, 2023

Graphical Abstract
Single-cell RNA sequencing reveals peripheral blood leukocyte responses to spinal cord injury in mice with humanised immune systems
Authors: Gillespie Ellen R. , Grice Laura F. , Courtney Isabel G. , Lao Hong Wa , Jung Woncheol , Ramkomuth Sonny , Xie Jacky , Brown David A. , Walsham James , Radford Kristen J. , Nguyen Quan H. , Ruitenberg Marc J. 
Published: March 2024

AbstractNext-generation humanised mouse models and single-cell RNA sequencing (scRNAseq) approaches enable in-depth studies into human immune cell biology. Here we used NSG-SGM3 mice engrafted with human umbilical cord haematopoietic stem cells to investigate how human immune cells respond to and/or are changed by traumatic spinal cord injury (SCI). We hypothesised that the use of such mice could help advance our understanding of spinal cord injury-induced immune depression syndrome (SCI-IDS), and also how human leukocytes change as they migrate from the circulation into the lesion site. Our scRNAseq experiments, supplemented by flow cytometry, demonstrate the existence of up to 11 human immune cell (sub-) types and/or states across the blood and injured spinal cord (7 days post-SCI) of humanised NSG-SGM3 mice. Further comparisons of human immune cell transcriptomes between naïve, sham-operated and SCI mice identified a total of 579 differentially expressed genes, 190 of which were ‘SCI-specific’ (that is, genes regulated only in response to SCI but not sham surgery). Gene ontology analysis showed a prominent downregulation of immune cell function under SCI conditions, including for T cell receptor signalling and antigen presentation, confirming the presence of SCI-IDS and the transcriptional signature of human leukocytes in association with this phenomenon. We also highlight the activating influence of the local spinal cord lesion microenvironment by comparing the transcriptomes of circulating versus infiltrated human immune cells; those isolated from the lesion site were enriched for genes relating to both immune cell activity and function (e.g., oxidative phosphorylation, T cell proliferation and antigen presentation). We lastly applied an integrated bioinformatics approach to determine where immune responses in humanised NSG-SGM3 mice appear congruent to the native responses of human SCI patients, and where they diverge. Collectively, our study provides a valuable resource and methodological framework for the use of these mice in translational research.
Brief communication: body composition and hidden obesity in people living with HIV on antiretroviral therapy
Authors: Konishi K. , Nakagawa H. , Asaoka T. , Kasamatsu Y. , Goto T. , Shirano M. 
Published: March 2024

Abstract
Background
Increased incidence of lifestyle diseases as side-effects of antiretroviral therapy (ART) have been reported in people living with HIV (PLWH). Few studies have evaluated obesity and hidden obesity in Japanese PLWH and their association with ART. In order to provide more appropriate drug selection and lifestyle guidance, we investigated the relationship between the effects of HIV infection and ART on the body composition of Japanese PLWH.

Methods
PLWH who visited the outpatient clinic and had body composition measured using the body composition analyzer InBody 570 were included in this study. Medications, comorbidities, and blood test data were obtained. Body mass index (BMI), body fat percentage, and skeletal muscle mass index (SMI) were measured.

Results
In this study, 543 patients were included. Based on body shape, patients were classified into a thin group (13), normal weight group (14), hidden obesity group (158), apparent obesity group (14), and obesity group (218). Compared with the normal weight group, the hidden obesity group had a higher prevalence of comorbidities and a lower SMI.

Conclusions
PLWH are more likely to have obesity than the general population, indicating that hidden obesity is common even among those with a normal BMI. It is important to measure body fat percentage along with body weight, as hidden obesity can be missed. Further investigation of the effects of ART on body composition is needed.
Bupivacaine–fentanyl isobaric spinal anesthesia reduces the risk of ICU admission in elderly patients undergoing lower limb orthopedic surgery
Authors: Liu Wenxun , Bao Shuzhen , Chen Jiaxin , Li Yan , Gu Yinghua , Ye Qingshan , Hai Kerong 
Published: March 2024

Abstract

Background
To evaluate if bupivacaine–fentanyl isobaric spinal anesthesia could reduce the risk of ICU admission compared with general anesthesia in elderly patients undergoing lower limb orthopedic surgery.

Methods
This study comprised a retrospective review of all lower limb orthopedic surgeries performed at our hospital between January 2013 and December 2019. According to anesthesia methods, patients were divided into the spinal anesthesia group (n = 1,728) and the general anesthesia group (n = 188). The primary outcome evaluated was the occurrence of ICU admission. Secondary outcomes included hemodynamic changes, postoperative complications, and mortality.

Results
Repeated measure analysis of variance indicated that the difference between the two groups in the systolic blood pressure (SBP) was not significant before anesthesia (T0), immediately after anesthesia (T1), and before leaving the operation room (T8) (P > 0.05), but significant (P < 0.01) from 5 min after anesthesia (T2) to after operation (T7). The proportions of ICU admission (6.4% vs. 23.8%, P < 0.01) and unplanned intubation (0.1% vs. 3.8%, P < 0.01) were significantly lower in the spinal anesthesia group compared with those in the general anesthesia group. Multivariate logistic regression revealed that after controlling for potential confounding factors, the odds of ICU admission for patients in the spinal anesthesia group was 0.240 times (95% CI 0.115–0.498; P < 0.01) than those in the general anesthesia group.

Conclusions
Bupivacaine–fentanyl isobaric spinal anesthesia significantly reduced the risk of ICU admission and unplanned intubation, and provided better intraoperative hemodynamics in elderly patients undergoing lower limb orthopedic surgery.

Trial registration: This study has been registered in the Chinese Clinical Trial Registry (ChiCTR2000033411).
Comparative analysis of bone turnover markers in bone marrow and peripheral blood: implications for osteoporosis
Authors: Jiang Chuan , Zhu Sibo , Zhan Wanda , Lou Linbing , Li Aoying , Cai Jun 
Published: March 2024

Abstract
Introduction
This study examines bone turnover marker (BTM) variations between bone marrow and peripheral blood in osteoporotic and non-osteoporotic patients. BTMs offer insights into bone remodeling, crucial for understanding osteoporosis.

Methods
A total of 133 patients were categorized into osteoporotic and non-osteoporotic cohorts. BTMs—C-telopeptide cross-linked type 1 collagen (β-CTX), serum osteocalcin (OC), Procollagen type I N-propeptide (P1NP), 25(OH)D—were measured in bone marrow and peripheral blood. Lumbar spine bone mineral density (BMD) was assessed.

Results
Osteoporotic patients exhibited elevated β-CTX and OC levels in peripheral blood, indicating heightened bone resorption and turnover. β-CTX levels in osteoporotic bone marrow were significantly higher. Negative correlations were found between peripheral blood β-CTX and OC levels and lumbar spine BMD, suggesting their potential as osteoporosis severity indicators. No such correlations were observed with bone marrow markers. When analyzing postmenopausal women separately, we obtained consistent results.

Conclusions
Elevated β-CTX and OC levels in osteoporotic peripheral blood highlight their diagnostic significance. Negative β-CTX and OC-BMD correlations underscore their potential for assessing osteoporosis severity. Discrepancies between peripheral blood and bone marrow markers emphasize the need for further exploration. This research advances our understanding of BTM clinical applications in osteoporosis diagnosis and treatment.
Lever sign test for anterior cruciate ligament injuries: a diagnostic meta-analysis
Authors: Hu Shiqiang , Wang Xiaoping , Wang Qiyue , Feng Weili 
Published: March 2024

AbstractBackgroundSports-related ACL (anterior cruciate ligament) injuries are frequent. Successful management requires early diagnosis and treatment. One of the clinical tests used to identify ACL damage is the lever sign test. This meta-analysis aimed to assess the lever sign test's diagnostic efficacy for ACL injuries.MethodsAn extensive investigation of the Cochrane Library, Embase, and PubMed databases was conducted until April 2023. Studies assessing the lever sign test's diagnostic efficacy for ACL injuries were also included. A bivariate random-effects model was employed to acquire the pooled estimates of diagnostic odds ratios, specificity, positive and negative likelihood ratios, sensitivity, and curves of the summary receiver operating characteristic (SROC).ResultsThe meta-analysis comprised twelve investigations with a total of 1365 individuals. The lever sign test's combined sensitivity and specificity for the purpose of diagnosing injuries to the ACL were 0.810 (95% confidence interval [CI] 0.686–0.893) and 0.784 (95% CI 0.583–0.904), respectively. The positive and negative likelihood ratios were 3.148 (95% CI 1.784–5.553) and 0.210 (95% CI 0.084–0.528), respectively. The study revealed a diagnostic odds ratio of 17.656, with a 95% CI ranging from 4.800 to 64.951. The SROC curve's area was determined to be 0.912 (95% CI 0.857–0.967).ConclusionWith high specificity and sensitivity, the lever sign test is a reliable diagnostic modality for ACL injuries. However, the test should be used in combination with other diagnostic tests to increase the accuracy of the diagnosis. Further investigations are warranted to assess the clinical practicability of the lever sign test in various populations and settings.