bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of the triglyceride glucose index with all-cause and cardiovascular mortality in a general population of Iranian adults
Authors: Alavi Tabatabaei Ghazaal , Mohammadifard Noushin , Rafiee Hamed , Nouri Fatemeh , Maghami mehr Asieh , Najafian Jamshid , Sadeghi Masoumeh , Boshtam Maryam , Roohafza Hamidreza , Haghighatdoost Fahimeh , Taheri Marzieh , Sarrafzadegan Nizal 
Published: February 2024

Abstract
Background
The triglyceride glucose (TyG) index is a new and low-cost marker to determine insulin resistant which may be a predictor of cardiovascular disease (CVD). Although available evidence showed that its association with CVD mortality (CVM) and all-cause mortality (ACM) may differ in different populations, scarce data are available in this regard specially in low and middle-income countries.

Purpose
To examine the association between TyG index and risk of CVM and ACM in Iranians.

Methods
This prospective cohort study included 5432 adults (age ≥ 35 years) with no history of CVD events. Fasting glucose and triglyceride were measured at baseline in all participants and TyG index was calculated. Cox frailty model was used to calculate hazard ratios (HRs) for CVM and ACM across the tertiles of TyG index.

Results
After a median follow-up of 11.25 years, a total number of 191 cardiovascular deaths, and 487 all-cause mortality was recorded. The risk of both CVM and ACM increased across the tertiles of TyG index. In the adjusted model for lifestyle and metabolic variables, the risks of ACM and CVM increased by 41% (95% CI 1.11, 1.81; P for trend = 0.005) and 64% (95% CI 1.07, 2.50; P for trend = 0.024), respectively. However, adjustment for diabetes mellitus disappeared the significance for both ACM and CVM. These associations may vary by sex. TyG was not related to the risk of non-CVD mortality.

Conclusion
The predicting value of TyG index for ACM and CVM might be mediated by diabetes status. Further studies are required to confirm these findings.
Scalable production of recombinant three-finger proteins: from inclusion bodies to high quality molecular probes
Authors: Xu Jiang , Lei Xiao , Li Ao , Li Jun , Li Shuxing , Chen Lin 
Published: February 2024

Abstract
Background
The three-finger proteins are a collection of disulfide bond rich proteins of great biomedical interests. Scalable recombinant expression and purification of bioactive three-finger proteins is quite difficult.

Results
We introduce a working pipeline for expression, purification and validation of disulfide-bond rich three-finger proteins using E. coli as the expression host. With this pipeline, we have successfully obtained highly purified and bioactive recombinant α-Βungarotoxin, k-Bungarotoxin, Hannalgesin, Mambalgin-1, α-Cobratoxin, MTα, Slurp1, Pate B etc. Milligrams to hundreds of milligrams of recombinant three finger proteins were obtained within weeks in the lab. The recombinant proteins showed specificity in binding assay and six of them were crystallized and structurally validated using X-ray diffraction protein crystallography.

Conclusions
Our pipeline allows refolding and purifying recombinant three finger proteins under optimized conditions and can be scaled up for massive production of three finger proteins. As many three finger proteins have attractive therapeutic or research interests and due to the extremely high quality of the recombinant three finger proteins we obtained, our method provides a competitive alternative to either their native counterparts or chemically synthetic ones and should facilitate related research and applications.
Evaluation of the malaria elimination programme in Muara Enim Regency: a qualitative study from Indonesia
Authors: Hasyim Hamzah , Marini Heni , Misnaniarti Misnaniarti , Flora Rostika , Liberty Iche Andriyani , Elagali Ahmed , Hartoni Hartoni , Maharani Fadhilah Eka 
Published: February 2024

Abstract
Background
Malaria remains an enduring public health concern in Indonesia, exacerbated by its equatorial climate that fosters the proliferation of Anopheles mosquitoes. This study seeks to assess the performance of the malaria elimination programme comprehensively.

Methods
Between May and August 2022, a qualitative study was conducted in Muara Enim Regency, South Sumatra Province, involving 22 healthcare professionals from diverse backgrounds. These informants were strategically chosen for their pivotal roles in providing profound insights into various facets of the malaria elimination programme. This encompasses inputs such as human resources, budgetary allocation, and infrastructural support; processes like case identification and management, capacity enhancement, epidemiological surveillance, prevention measures, outbreak control, and enhanced communication and educational initiatives; and, notably, the programme’s outcomes. Data were collected through 3-h Focus Group Discussions (FGDs) divided into two groups, each with 12 participants: healthcare professionals and programme managers. Additionally, in-depth interviews (IDIs) were conducted with ten informants. Employing the Input-Process-Output (IPO) model, this study meticulously analysed the healthcare system dynamics and the interventions’ efficacy.

Results
The study unveiled many challenges during the input phase, including the absence of entomologists and a shortage of diagnostic tools. Despite these obstacles, it documented remarkable accomplishments in the output domain, marked by significant advancements in the distribution of mosquito nets and the successful implementation of the Early Warning System (EWS). Despite the adversities, the programme has made substantial strides towards malaria elimination.

Conclusions
Urgent action is imperative to bolster the effectiveness of the malaria elimination programme. Key measures encompass augmenting the entomologist workforce, optimizing resource allocation, and ensuring stringent adherence to regional regulations. Addressing these concerns will enhance programme efficacy, yielding enduring public health benefits. This research substantially contributes to Indonesia’s ongoing malaria elimination endeavours, furnishing actionable insights for programme enhancement. Consequently, this research holds significant importance for the malaria elimination drive.
Two promising candidates for paratransgenesis, Elizabethkingia and Asaia, increase in both sexes of Anopheles gambiae mosquitoes after feeding
Authors: Egyirifa Richardson K. , Akorli Jewelna 
Published: February 2024

Abstract
Background
The male mosquito microbiome may be important for identifying ideal candidates for disease control. Among other criteria, mosquito-associated symbionts that have high localization in both male and female mosquitoes and are transmissible through both vertical and sexual routes are desirable. However, mosquito microbiome studies have mainly been female-focused. In this study, the microbiota of male and female Anopheles gambiae sensu lato (s.l.) were compared to identify shared or unique bacteria.

Methods
Late larval instars of Anopheles mosquitoes were collected from the field and raised to adults. Equal numbers of males and females of 1-day-old non-sugar-fed, 4–5-day-old sugar-fed and post-blood-fed females were randomly selected for whole-body analyses of bacteria 16S rRNA.

Results
Results revealed that male and female mosquitoes generally share similar microbiota except when females were blood-fed. Compared to newly emerged unfed mosquitoes, feeding on sugar and/or blood increased variability in microbial composition (⍺-diversity), with a higher disparity among females (39% P = 0.01) than in males (29% P = 0.03). Elizabethkingia meningoseptica and Asaia siamensis were common discriminants between feeding statuses in both males and females. While E. meningoseptica was particularly associated with sugar-fed mosquitoes of both sexes and sustained after blood feeding in females, A. siamensis was also increased in sugar-fed mosquitoes but decreased significantly in blood-fed females (LDA score > 4.0, P < 0.05). Among males, A. siamensis did not differ significantly after sugar meals.

Conclusions
Results indicate the opportunities for stable infection in mosquitoes should these species be used in bacteria-mediated disease control. Further studies are recommended to investigate possible host-specific tissue tropism of bacteria species which will inform selection of the most appropriate microbes for effective transmission-blocking strategies.
Mesenchymal stem cell-derived extracellular vesicles exert pro-angiogenic and pro-lymphangiogenic effects in ischemic tissues by transferring various microRNAs and proteins including ITGa5 and NRP1
Authors: Łabędź-Masłowska Anna , Vergori Luisa , Kędracka-Krok Sylwia , Karnas Elżbieta , Bobis-Wozowicz Sylwia , Sekuła-Stryjewska Małgorzata , Sarna Michał , Andriantsitohaina Ramaroson , Zuba-Surma Ewa K. 
Published: February 2024

AbstractMesenchymal stem cells/stromal cells (MSCs)-derived extracellular vesicles (EVs) mediate pro-regenerative effects in damaged ischemic tissues by regulating angiogenesis. MSCs-EVs modulate functions of cells including endogenous mature cells, progenitors and stem cells, resulting in restoration of blood flow. However, the mechanisms underlying such MSC-EV activity still remain poorly understood. The present study analyzes biological effects of bone marrow (BM) MSC-EVs on endothelial cells (ECs) in ischemic tissues both in in vitro and in vivo conditions and elucidates the molecular mechanisms underlying the tissue repair. MSC-EVs were isolated from murine BM-derived MSCs and their morphological, antigenic and molecular composition regarding protein and microRNA levels were evaluated to examine their properties. Global proteomic analysis demonstrated the presence in MSC-EVs of proteins regulating pro-regenerative pathways, including integrin α5 (Itgα5) and neuropilin-1 (NRP1) involved in lymphangiogenesis. MSC-EVs were also enriched in microRNAs regulating angiogenesis, TGF-β signaling and processes guiding cellular adhesion and interactions with extracellular matrix. The functional effects of MSC-EVs on capillary ECs in vitro included the increase of capillary-like tube formation and cytoprotection under normal and inflammatory conditions by inhibiting apoptosis. Notably, MSC-EVs enhanced also capillary-like tube formation of lymphatic ECs, which may be regulated by Itgα5 and NRP1. Moreover, in a mouse model of critical hind limb ischemia, MSC-EVs increased the recovery of blood flow in ischemic muscle tissue, which was accompanied with increased vascular density in vivo. This pro-angiogenic effect was associated with an increase in nitric oxide (NO) production via endothelial NO-synthase activation in ischemic muscles. Interestingly, MSC-EVs enhanced lymphangiogenesis, which has never been reported before. The study provides evidence on pro-angiogenic and novel pro-lymphangiogenic role of MSC-EVs on ECs in ischemic tissue mediated by their protein and miRNA molecular cargos. The results highlight Itgα5 and NRP1 carried by MSC-EVs as potential therapeutic targets to boost lymphangiogenesis.
Graphical Abstract
Cost-utility analysis of treating mild stage normal tension glaucoma by surgery in China: a decision-analytic Markov model
Authors: Song Di , Wang Liwen 
Published: February 2024

Abstract
Background
Many individuals suffer from normal tension glaucoma (NTG) in China. This study utilized Markov models to evaluate the cost-utility of applying many medications and surgery for mild-stage NTG when disease progression occurred at a mild stage.

Methods
A 10-year decision-analytic Markov model was developed for the cost-utility analysis of treating mild-stage NTG with surgery and increased application of medication. We hypothesized that all 100,000 samples with a mean age of 64 were in mild stages of NTG. Transitional probabilities from the mild to moderate to severe stages and the basic parameters acquired from the CNTGS were calculated. Incremental cost-utility ratios (ICUR) were calculated for treating all patients with NTG by probabilistic sensitivity analysis (PSA) and Monte Carlo simulation. One-way sensitivity analysis were conducted by adjusting the progression rate, cost of medications or trabeculectomy, cost of follow-up, and surgical acceptance rate.

Results
The ICUR of treating mild stage NTG with medication over 10 years was $12743.93 per quality-adjusted life years (QALYs). The ICUR for treating mild stage NTG patients with a 25% and 50% surgery rate with medication were $8798.93 and $4851.93 per QALYs, respectively. In this model, the cost-utility of treating NTG was sensitive to disease progression rate, surgical treatment rate, and medication costs.

Conclusions
According to the results of the cost-utility analysis, it was a reasonable and advantageous strategy to administer a lot of medication and surgery for NTG in the mild stages of the disease. In the model, the greater the probability of patients undergoing surgery, the strategy becomes more valuable.
Characterization of two distinct immortalized endothelial cell lines, EA.hy926 and HMEC-1, for in vitro studies: exploring the impact of calcium electroporation, Ca2+ signaling and transcriptomic profiles
Authors: Lisec Barbara , Bozic Tim , Santek Iva , Markelc Bostjan , Vrecl Milka , Frangez Robert , Cemazar Maja 
Published: February 2024

Abstract
Background
Disruption of Ca2+ homeostasis after calcium electroporation (CaEP) in tumors has been shown to elicit an enhanced antitumor effect with varying impacts on healthy tissue, such as endothelium. Therefore, our study aimed to determine differences in Ca2+ kinetics and gene expression involved in the regulation of Ca2+ signaling and homeostasis, as well as effects of CaEP on cytoskeleton and adherens junctions of the established endothelial cell lines EA.hy926 and HMEC-1.

Methods
CaEP was performed on EA.hy926 and HMEC-1 cells with increasing Ca2+ concentrations. Viability after CaEP was assessed using Presto Blue, while the effect on cytoskeleton and adherens junctions was evaluated via immunofluorescence staining (F-actin, α-tubulin, VE-cadherin). Differences in intracellular Ca2+ regulation ([Ca2+]i) were determined with spectrofluorometric measurements using Fura-2-AM, exposing cells to DPBS, ionomycin, thapsigargin, ATP, bradykinin, angiotensin II, acetylcholine, LaCl3, and GdCl3. Molecular distinctions were identified by analyzing differentially expressed genes and pathways related to the cytoskeleton and Ca2+ signaling through RNA sequencing.

Results
EA.hy926 cells, at increasing Ca2+ concentrations, displayed higher CaEP susceptibility and lower survival than HMEC-1. Immunofluorescence confirmed CaEP-induced, time- and Ca2+-dependent morphological changes in EA.hy926’s actin filaments, microtubules, and cell–cell junctions. Spectrofluorometric Ca2+ kinetics showed higher amplitudes in Ca2+ responses in EA.hy926 exposed to buffer, G protein coupled receptor agonists, bradykinin, and angiotensin II compared to HMEC-1. HMEC-1 exhibited significantly higher [Ca2+]i changes after ionomycin exposure, while responses to thapsigargin, ATP, and acetylcholine were similar in both cell lines. ATP without extracellular Ca2+ ions induced a significantly higher [Ca2+]i rise in EA.hy926, suggesting purinergic ionotropic P2X and metabotropic P2Y receptor activation. RNA-sequencing analysis showed significant differences in cytoskeleton- and Ca2+-related gene expression, highlighting upregulation of ORAI2, TRPC1, TRPM2, CNGA3, TRPM6, and downregulation of TRPV4 and TRPC4 in EA.hy926 versus HMEC-1. Moreover, KEGG analysis showed upregulated Ca2+ import and downregulated export genes in EA.hy926.

Conclusions
Our finding show that significant differences in CaEP response and [Ca2+]i regulation exist between EA.hy926 and HMEC-1, which may be attributed to distinct transcriptomic profiles. EA.hy926, compared to HMEC-1, displayed higher susceptibility and sensitivity to [Ca2+]i changes, which may be linked to overexpression of Ca2+-related genes and an inability to mitigate changes in [Ca2+]i. The study offers a bioinformatic basis for selecting EC models based on research objectives.
Human Parathyroid Hormone (1–34) accelerates skin wound healing through inducing cell migration via up-regulating the expression of Rac1
Authors: Sun Qingpeng , Zhou Liya , Yu Zhiyong , Zhang Jun , Zhang Chao , Pi Honglin 
Published: February 2024

AbstractDelayed wound healing is a public issue that imposes a significant burden on both society and the patients themselves. To date, although numerous methods have been developed to accelerate the speed of wound closure, the therapeutic effects are partially limited due to the complex procedures, high costs, potential side effects, and ethical concerns. While some studies have reported that the in-vivo application of Human Parathyroid Hormone (1–34) (hPTH(1–34)) promotes the wound-healing process, the definitive role and underlying mechanisms through which it regulates the behavior of fibroblasts and keratinocytes remains unclear. Herein, hPTH(1–34)’s role in cell migration is evaluated with a series of in-vitro and in-vivo studies, whereby hPTH(1–34)’s underlying mechanism in activating the two types of cells was detected. The in-vitro study revealed that hPTH(1–34) enhanced the migration of both fibroblasts and HaCaT cells. Ras-associated C3 botulinum toxin subunit 1 (Rac1), a classical member of the Rho family, was upregulated in hPTH(1–34)-treated fibroblasts and HaCaT cells. Further study by silencing the expression of Rac1 with siRNA reversed the hPTH(1–34)-enhanced cell migration, thus confirming that Rac1 was involved in hPTH(1–34)-induced cell behavior. In-vivo study on rat wound models confirmed the effects of hPTH(1–34) on fibroblasts and keratinocytes, with increased collagen deposition, fibroblasts accumulation, and Rac1 expression in the hPTH(1–34)-treated wounds. In summary, the present study demonstrated that hPTH(1–34) accelerated wound healing through enhancing the migration of cells through the up-regulation of Rac1 expression.
Impact of sustentaculum tali screw positioning on radiographic and functional outcomes in calcaneal fractures
Authors: Li Zihua , Xiao Fajiao , Huang Hui , Xia Jiang , Zhou Haichao , Li Bing , Yang Yunfeng 
Published: February 2024

Abstract
Background
To investigate whether accurate placement of sustentaculum tali screws have the impacts on the clinical efficacy of calcaneal fractures.

Methods
A retrospective analysis of 72 cases (73 feet) of calcaneal fractures from September 2015 to September 2019 treated with open reduction and internal fixation with sustentaculum tali screws was conducted. Patients were divided into the sustentaculum tali fixation group (ST group) and the sustentaculum fragment fixation group (STF group) according to the location of the sustentaculum tali screw placement. The functional outcomes at preoperative, 7 days and 1 year postoperative were collected and analyzed.

Results
In the ST group (40 feet), the Gissane's angle altered from (109.89 ± 12.13)° to (121.23 ± 9.34)° and (119.08 ± 8.31)° at 7 days and 1 year postoperative, respectively. For Böhler’s angles altered from (11.44 ± 5.94)°, to (31.39 ± 7.54)°, and (30.61 ± 7.94)° at 7 days and 1 year postoperative, respectively. In the STF group (33 feet), Gissane’s angle altered from (110.47 ± 14.45)°, to (122.08 ± 8.84)°, and (120.67 ± 9.07)° and Böhler’s angle altered from (11.32 ± 6.77)°, to (28.82 ± 8.52)°, and (28.25 ± 9.13)° (P < 0.001). However, there was no statistically significant difference in functional outcomes at 1 week after surgery and 1 year after surgery (P > 0.05). The AOFAS scores at the final follow-up of the two groups: ST group (88.95 ± 6.16) and STF group (89.78 ± 8.76); VAS scores, ST group (0.83 ± 0.98) and STF group (1.03 ± 1.59), all differences were not statistically significant (P > 0.05).

Conclusion
The position of sustentaculum tali screws has no significant difference on the short-term clinical outcome in patients with calcaneal fractures, while reliable fixation of screws to sustentaculum tali fragment can achieve similar clinical outcome.
Level of evidence V.
The negative pressure wound therapy for prevention of sternal wound infection: Can we reduce infection rate after the use of bilateral internal thoracic arteries? A systematic literature review and meta-analysis
Authors: Elhassan Hind , Amjad Ridha , Palaniappan Unna , Loubani Mahmoud , Rose David 
Published: February 2024

Abstract
Background
Negative pressure wound therapy (NPWT) is traditionally used to treat postoperative wound infections. However, its use in closed wound sternotomy post cardiac surgery in high-risk patients has become increasingly popular. The potential preventive benefit of reducing sternal wound infections has been recently acknowledged. Bilateral internal mammary artery (BIMA) grafts are used in coronary artery bypass grafting but have been associated with an increased risk of sternal wound infections (SWIs).

Objectives
This systematic analysis examines whether NPWT can reduce the incidence of SWI following BIMA grafts, leading to more patients benefiting from the better survival outcome associated with BIMA grafting.

Method
A comprehensive systematic search and meta-analysis were performed to identify studies on the use of NPWT in closed wound sternotomy. Ovid MEDLINE (in-process and other nonindexed citations and Ovid MEDLINE 1990 to present), Ovid EMBASE (1990 to present), and The Cochrane Library (Wiley), PubMed, and Google Scholar databases were searched from their inception to May 2022 using keywords and MeSH terms. Thirty-four articles from 1991 to May 2022 were selected.

Result
Three studies reported on the outcome of NPWT following BIMA grafting. The pooled analysis did not show any significant difference in the incidence of sternal wound infection between NPWT and standard dressing (RR 0.48 95% CI 0.17–1.37; P = 0.17) with substantial heterogeneity (I2 65%). Another seven studies were found comparing the outcome of SWI incidence of negative pressure closed wound therapy with conventional wound therapy in patients undergoing adult cardiac surgery. The pooled analysis showed that NPWT was associated with a low risk of SWIs compared to conventional dressing (RR 0.47 95% CI 0.36–0.59; P < 0.00001), with low heterogeneity (I2 1%).

Conclusion
The literature identified that NPWT significantly decreased the incidence of sternal wound complications when applied to sutured sternotomy incisions in high-risk patients, and in some cases, it eliminated the risk. However, the inadequate number of randomized controlled trials assessing the effectiveness of NPWT in BIMA grafting emphasizes the need for further, robust studies.