bluuebunny/crossref_metadata_2025 huggingface dataset:
The application of artificial intelligence in health financing: a scoping review
Authors: Ramezani Maryam , Takian Amirhossein , Bakhtiari Ahad , Rabiee Hamid R. , Fazaeli Ali Akbar , Sazgarnejad Saharnaz
Published: November 2023

Introduction

Artificial Intelligence (AI) represents a significant advancement in technology, and it is crucial for policymakers to incorporate AI thinking into policies and to fully explore, analyze and utilize massive data and conduct AI-related policies. AI has the potential to optimize healthcare financing systems. This study provides an overview of the AI application domains in healthcare financing.

Method

We conducted a scoping review in six steps: formulating research questions, identifying relevant studies by conducting a comprehensive literature search using appropriate keywords, screening titles and abstracts for relevance, reviewing full texts of relevant articles, charting extracted data, and compiling and summarizing findings. Specifically, the research question sought to identify the applications of artificial intelligence in health financing supported by the published literature and explore potential future applications. PubMed, Scopus, and Web of Science databases were searched between 2000 and 2023.

Results

We discovered that AI has a significant impact on various aspects of health financing, such as governance, revenue raising, pooling, and strategic purchasing. We provide evidence-based recommendations for establishing and improving the health financing system based on AI.

Conclusions

To ensure that vulnerable groups face minimum challenges and benefit from improved health financing, we urge national and international institutions worldwide to use and adopt AI tools and applications.
Financial burden of prostate cancer in the Iranian population: a cost of illness and financial risk protection analysis
Authors: Alinezhad Farbod , Khalili Farhad , Zare Hossein , Lu Chunling , Mahmoudi Zahra , Yousefi Mahmood
Published: November 2023

Background

Prostate cancer is the second most common cancer in males worldwide and the third most common among Iran’s male population. However, there is a lack of evidence regarding its direct and indirect costs in low and middle-income countries. This study intends to bridge the gap using a cost of illness approach, assessing the costs of prostate cancer from the perspectives of patients, society, and the insurance system.

Methods

Two hundred ninety seven patients were included in the study. Data for a 2-month period were obtained from patients registered at two hospitals (Tabriz, Tehran) in Iran in 2017. We applied a prevalence-based, bottom-up approach to assess the costs of the illness. We used the World Health Organization methods to measure the prevalence and investigate the determinants of catastrophic and impoverishing health expenditures.

Results

We determined the total costs of the disease for the patients to be IRR 68 million (PPP $ 5,244.44). Total costs of the disease from the perspective of the society amounted to IRR 700,000 million (PPP $ 54 million). Insurance companies expended IRR 20 million (PPP $ 1,558.80) per patient. Our findings show that 31% of the patients incurred catastrophic health expenditure due to the disease. Five point forty-four percent (5.44%) of the patients were impoverished due to the costs of this cancer.

Conclusion

We found an alarmingly high prevalence of catastrophic health expenditures among prostate cancer patients. In addition, prostate cancer puts a substantial burden on both the patients and society.
Adjustable prosthetic sockets: a systematic review of industrial and research design characteristics and their justifications
Authors: Baldock Michael , Pickard Nicolaas , Prince Michael , Kirkwood Sarah , Chadwell Alix , Howard David , Dickinson Alex , Kenney Laurence , Gill Niamh , Curtin Sam
Published: November 2023

Background

The prosthetic socket is a key component that influences prosthesis satisfaction, with a poorly fitting prosthetic socket linked to prosthesis abandonment and reduced community participation. This paper reviews adjustable socket designs, as they have the potential to improve prosthetic fit and comfort through accommodating residual limb volume fluctuations and alleviating undue socket pressure.

Methods

Systematic literature and patent searches were conducted across multiple databases to identify articles and patents that discussed adjustable prosthetic sockets. The patents were used to find companies, organisations, and institutions who currently sell adjustable sockets or who are developing devices.

Results

50 literature articles and 63 patents were identified for inclusion, representing 35 different designs used in literature and 16 commercially available products. Adjustable sockets are becoming more prevalent with 73% of publications (literature, patents, and news) occurring within the last ten years. Two key design characteristics were identified: principle of adjustability (inflatable bladders, moveable panels, circumferential adjustment, variable length), and surface form (conformable, rigid multi-DOF, and rigid single DOF). Inflatable bladders contributed to 40% of literature used designs with only one identified commercially available design (n = 16) using this approach. Whereas circumferential adjustment designs covered 75% of identified industry designs compared to only 36% of literature devices. Clinical studies were generally small in size and only 17.6% of them assessed a commercially available socket.

Discussion

There are clear differences in the design focus taken by industry and researchers, with justification for choice of design and range of adjustment often being unclear. Whilst comfort is often reported as improved with an adjustable socket, the rationale behind this is not often discussed, and small study sizes reduce the outcome viability. Many adjustable sockets lack appropriate safety features to limit over or under tightening, which may present a risk of tissue damage or provide inadequate coupling, affecting function and satisfaction. Furthermore, the relationship between design and comfort or function are rarely investigated and remain a significant gap in the literature. Finally, this review highlights the need for improved collaboration between academia and industry, with a strong disconnect observed between commercial devices and published research studies.
A novel technique for treating simple transverse patellar fractures using cannulated screws: a cadaveric and clinical study
Authors: Han Feng , Zhong Zhenjia , Zhou Ming , Chen Qi , Liu Yinan , Rui Yongjun , Li Fengfeng
Published: November 2023

Background

Tension band wiring (TBW) has conventionally been used for the open reduction and internal fixation of the patella. However, it suffers from distinct disadvantages such as large incision, implant irritation, and need for subsequent implant removal. Here, we propose a novel technique using closed reduction and percutaneous fixation with three cannulated screws (TCS), which may be an alternative to this established conventional technique. Although some researchers have proposed alternative methods including closed reduction and cannulated screw fixation, with or without additional wires through the screws, and arthroscopic-assisted reduction and fixation, there are few studies that focus on the biomechanical stability of percutaneous fixation using only cannulated screws. Thus, the purpose of this study was to evaluate TCS versus TBW for simple transverse patellar fractures in cadaveric and patients' level, aiming to determine whether TCS show superiority over TBW in terms of biomechanical stability in a cadaveric study with benign clinical feasibility and outcomes in patients.

Methods

We conducted a cadaveric study with 15 knee specimens that had simple transverse patellar fractures. We used two fixation techniques: TBW (group A, n = 6) and TCS (group B, n = 9). We applied sinusoidal forces (25 N–125 N) at 1/5 Hz and 90° knee flexion to simulate knee movement. We compared the displacements at the fracture site between the two groups. We also used the same technique in a total of 23 patients and followed up them for at least 1 year.

Results

TCS demonstrated favourable biomechanical stability in the cadaveric study. The technique also performed excellently in terms of postoperative pain, knee function recovery, and complication rates during the follow-up period.

Conclusions

The technique provides a surgical treatment option with small incisions, minimal soft tissue irritation, and possibly lower removal rate of bothersome material.
Transcatheter closure in preterm infants with patent ductus arteriosus: feasibility, results, hemodynamic monitoring and future prospectives
Authors: Francescato Gaia , Doni Daniela , Annoni Giuseppe , Capolupo Irma , Ciarmoli Elena , Corsini Iuri , Gatelli Italo Francesco , Salvadori Sabrina , Testa Alberto , Butera Gianfranco
Published: November 2023

Ductal patency of preterm infants is potentially associated with long term morbidities related to either pulmonary overflow or systemic steal. When an interventional closure is needed, it can be achieved with either surgical ligation or a catheter-based approach.

Transcatheter PDA closure is among the safest of interventional cardiac procedures and it is the first choice for ductal closure in adults, children, and infants weighing more than 6 kg. In preterm and very low birth weight infants, it is increasingly becoming a valid and safe alternative to ligation, especially for the high success rate and the minor invasiveness and side effects. Nevertheless, being it performed at increasingly lower weights and gestational ages, hemodynamic complications are possible events to be foreseen.

Procedural steps, timing, results, possible complications and available monitoring systems, as well as future outlooks are here discussed.
Fluid balance control in critically ill patients: results from as-treated analyses of POINCARE-2 randomized trial
Authors: Mansouri Adil , Buzzi Marie , Gibot Sébastien , Charpentier Claire , Schneider Francis , Louis Guillaume , Outin Hervé , Monnier Alexandra , Quenot Jean-Pierre , Badie Julio , Argaud Laurent , Bruel Cédric , Soudant Marc , Agrinier Nelly ,   the POINCARE-2 group, Alleyrat Camille , Virion Jean-Marc , Bollaert Pierre-Edouard , Lemarie Jérémie , Alb Ionel , Welfringer Pascal , Gaci Rostane , Bemer Michel , Delaveuve Eric , Tahon Elsa , Andreu Pascal , Labruyere Marie , Roudaut Jean-Baptiste , Maire Bruno , Ziegler Laurent , Castelain Vincent , Philippart François , Tran Marc , Cour Martin , Simon Marie , Stevic Neven , Hayon Jann , Jamme Matthieu , Berdaguer Fernando , Slimani Hakim
Published: November 2023

Background

Intention-to-treat analyses of POINCARE-2 trial led to inconclusive results regarding the effect of a conservative fluid balance strategy on mortality in critically ill patients. The present as-treated analysis aimed to assess the effectiveness of actual exposure to POINCARE-2 strategy on 60-day mortality in critically ill patients.

Methods

POINCARE‑2 was a stepped wedge randomized controlled trial. Eligible patients were ≥ 18 years old, under mechanical ventilation and had an expected length of stay in ICU > 24 h. POINCARE-2 strategy consisted of daily weighing over 14 days, and subsequent restriction of fluid intake, administration of diuretics, and/or ultrafiltration. We computed a score of exposure to the strategy based on deviations from the strategy algorithm. We considered patients with a score ≥ 75 as exposed to the strategy. We used logistic regression adjusted for confounders (ALR) or for an instrumental variable (IVLR). We handled missing data using multiple imputations.

Results

A total of 1361 patients were included. Overall, 24.8% of patients in the control group and 69.4% of patients in the strategy group had a score of exposure ≥ 75. Exposure to the POINCARE-2 strategy was not associated with 60-day all-cause mortality (ALR: OR 1.2, 95% CI 0.85–1.55; IVLR: OR 1.0, 95% CI 0.76–1.33).

Conclusion

Actual exposure to POINCARE-2 conservative strategy was not associated with reduced mortality in critically ill patients.

Trial registration POINCARE-2 trial is registered at ClinicalTrials.gov (NCT02765009). Registered 29 April 2016.
Bruton’s tyrosine kinase is a possible therapeutic target in microscopic polyangiitis
Authors: Nakade Issei , Tamura Yuto , Hashimoto Fuyu , Ariza Yuko , Hotta Shingo , Fujigaya Hirofumi , Arai Suishin , Taniguchi Mai , Ogawa Hodaka , Nishibata Yuka , Masuda Sakiko , Nakazawa Daigo , Tomaru Utano , Ishizu Akihiro
Published: November 2023

Background

Bruton’s tyrosine kinase (Btk) is an enzyme expressed in leukocytes other than T lymphocytes and plasma cells and involved in B-cell receptor- and Fcγ receptor (FcγR)-mediated signal transduction. Btk inhibitors potentially suppress autoantibody production due to the expected inhibitory ability of B lymphocyte differentiation into antibody-producing plasma cells and reduce FcγR-mediated neutrophil activation, including the release of neutrophil extracellular traps (NETs). Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis characterized by the pathogenic autoantibody, antineutrophil cytoplasmic antibody (ANCA) that reacts with myeloperoxidase (MPO). MPO and MPO-ANCA immune complex (IC)-induced FcγR-mediated NETs are critically involved in MPA pathogenesis. This study aimed to demonstrate the therapeutic efficacy of the Btk inhibitor tirabrutinib on MPA.

Methods

Various doses of tirabrutinib or vehicle were orally administered to Sprague–Dawley rats daily. Four weeks later, the number of peripheral B lymphocytes was counted, and Btk phosphorylation in B lymphocytes was evaluated by flow cytometry. Human peripheral blood neutrophils were stimulated by MPO and anti-MPO antibody ICs (MPO and anti-MPO-ICs), and Btk and its downstream Vav phosphorylation were assessed by western blotting. The effects of tirabrutinib on MPO and anti-MPO-IC-induced NET formation were examined in vitro. Wistar Kyoto rats were immunized with human MPO to induce experimental MPA and given drug-free or tirabrutinib-containing feed (0.0037% or 0.012%) from day 0 or 28. All rats were euthanized on day 42 for serological and histological evaluation.

Results

Tirabrutinib inhibited Btk phosphorylation without decreasing B lymphocytes in vivo. Neutrophil Btk and Vav were phosphorylated when stimulated with MPO and anti-MPO-ICs. Tirabrutinib suppressed MPO and anti-MPO-IC-induced NET formation in vitro and ameliorated experimental MPA in a dose-dependent manner in vivo. Although MPO-ANCA production was not affected, NET-forming neutrophils in the blood were significantly reduced by tirabrutinib.

Conclusions

The Btk inhibitor tirabrutinib suppressed MPO and anti-MPO-IC-induced NET formation in vitro and ameliorated experimental MPA by reducing NET-forming neutrophils but not decreasing MPO-ANCA titer in vivo. This study suggests that Btk is a possible therapeutic target in MPA.
Impacts of different triathlon races on systemic cytokine profile and metabolic parameters in healthy individuals: a systematic review
Authors: de Sousa Fernandes Matheus Santos , Gomes Jefferson Mariano , Aidar Felipe J. , Thuany Mabliny , Filgueira Tayrine Ordonio , de Souza Raphael Fabrício , Badicu Georgian , Yagin Fatma Hilal , Greco Gianpiero , Cataldi Stefania , Castoldi Angela , Alghannam Abdullah F. , Souto Fabrício Oliveira
Published: November 2023

The present systematic review aimed to discuss the impacts of different triathlon protocols on the level of pro and anti-inflammatory cytokines, as well as biomarkers related to the performance of healthy individuals. Four databases [PubMed (28 articles), Scopus (24 articles), Science Direct (200 articles), and SPORT Discus (1101 articles) were assessed. The eligibility criteria were applied, and the selected articles were used in the peer review, independently, as they were identified by March 2022. Of the 1359 articles found, 10 were included in this systematic review. Despite the difference in triathlon protocols, it was observed an increase in pro and anti-inflammatory cytokines including IL-4 and IL-10, and chemokines, such as IL-8 and MCP-1. Moreover, the anti-inflammatory serum levels increase after triathlon. Overall, the studies also reported enhancement in the serum levels of cortisol, creatine kinase, C reactive protein, Endothelial Growth Factor, Vascular Endothelial Growth Factor, Myostatin, Lactate dehydrogenase, free fatty acids, and lactate dehydrogenase in triathlon athletes. This systematic review indicates that different triathlon race promotes an acute elevation of circulating cytokines and chemokines levels which return to standard levels after triathlon races. The findings of this systematic review demonstrate that the modulation of inflammatory parameters may be associated with an increase in metabolic indicators (CK, Cortisol, and LDH) after the end of different types of triathlon races.
The diagnostic performance of AFP and PIVKA-II models for non-B non-C hepatocellular carcinoma
Authors: Tran Vinh Thanh , Phan Thang Thanh , Nguyen Tran Bao , Le Thao Thi , Tran Thanh-Tram Thi , Nguyen Anh-Thu Thi , Nguyen Hang Thuy , Nguyen Ngoc-Diep Bui , Ho Toan Trong , Pho Suong Phuoc , Nguyen Thuy-An Thi , Nguyen Hue Thi , Mai Huyen Thi , Pham Bich-Tuyen Thi , Nguyen Khoa Dinh , Le Binh Thanh , Nguyen Thuc Tri , Nguyen Son Truong
Published: November 2023

Objective

This study aims to describe the diagnostic performance of alpha-fetoprotein (AFP), alpha-fetoprotein L3 isoform (AFP-L3), protein induced by vitamin K absence II (PIVKA-II), and combined biomarkers for non-B non-C hepatocellular carcinoma (NBNC-HCC).

Results

A total of 681 newly-diagnosed primary liver disease subjects (385 non-HCC, 296 HCC) who tested negativity for the hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) enrolled in this study. At the cut-off point of 3.8 ng/mL, AFP helps to discriminate HCC from non-HCC with an area under the curve (AUC) value of 0.817 (95% confidence interval [CI]: 0.785–0.849). These values of AFP-L3 (cut-off 0.9%) and PIVKA-II (cut-off 57.7 mAU/mL) were 0.758 (95%CI: 0.725–0.791) and 0.866 (95%CI: 0.836–0.896), respectively. The Bayesian Model Averaging (BMA) statistic identified the optimal model, including patients’ age, aspartate aminotransferase, AFP, and PIVKA-II combination, which helps to classify HCC with better performance (AUC = 0.896, 95%CI: 0.872–0.920, P < 0.001). The sensitivity and specificity of the optimal model reached 81.1% (95%CI: 76.1–85.4) and 83.2% (95%CI: 78.9–86.9), respectively. Further analyses indicated that AFP and PIVKA-II markers and combined models have good-to-excellent performance detecting curative resected HCC, separating HCC from chronic hepatitis, dysplastic, and hyperplasia nodules.
METTL3-mediated m6A methylation regulates ovarian cancer progression by recruiting myeloid-derived suppressor cells
Authors: Wang Jinyong , Ling Dakai , Shi Lulin , Li Huayun , Peng Minhua , Wen Huihong , Liu Tao , Liang Ruifang , Lin Yongjian , Wei Laiyou , Zhang Guangzhi , Chen Shanze
Published: November 2023

Background

Ovarian cancer (OC) typically develops an immunosuppressive microenvironment by funtional changes of host immune cells. Dysregulated m6A level is associated with cancer progression via the intrinsic oncogenic pathways. However, the role of m6A in regulating host immune cell function during anti-tumor immunity needs comprehensive analysis. This study aimed to investigate the role of METTL3, a catalytic subunit of the methyltransferase complex, in regulating host immune cell response against OC.

Methods

In this study, myeloid-specific Mettl3 gene knockout (Mettl3-cKO) mice were bred using the Cre-LoxP system. Intraperitoneally injection of ID8 cells was used as a syngeneic OC model. Furthermore, the compositions of immune cell populations were analyzed by flow cytometry and single-cell sequencing. Moreover, chemokines and cytokines secretion were assessed using ELISA. Lastly, the role of METTL3 in regulating IL-1β secretion and inflammasome activation in bone marrow-derived macrophages cocultured with ID8 cells was specified by ELISA and immunoblotting.

Results

It was revealed that OC cell growth was enhanced in Mettl3-cKO mice. Furthermore, a shift of decreased M1 to increased M2 macrophage polarization was observed during OC progression. Moreover, Mettl3 depletion in myeloid lineage cells increased secretion of CCL2 and CXCL2 in peritoneal lavage fluild. Interestingly, Mettl3 deficiency enhanced IL-1β secretion induced by viable ID8 cells independent of inflammasome activation and cell death. Therefore, OC cells in tumor-bearing mice trigger a slight inflammatory response with a low-to-moderate secretion of pro-inflammatory cytokines and chemokines.

Conclusion

This study provides new insights into METTL3-mediated m6A methylation, which regulates host immune response against OC.
Laboratory tests to understand tephra sliding behaviour on roofs
Authors: Osman Sara , Thomas Mark , Crummy Julia , Sharp Anna , Carver Steve
Published: November 2023

Following explosive eruptions, loading from tephra fall deposits can lead to roof collapse. However, the load may be reduced significantly by tephra sliding on pitched roofs. We present small-scale laboratory tests to investigate tephra sliding behaviour on metal, fibre cement sheet and tile roofing. We tested 10–30 cm thicknesses for dry and wet deposits of pumice, scoria and basaltic ash. We found that tephra did not slide on roof pitches ≤ 15° for coarse-grained deposits and ≤ 12° for dry ash. Thin deposits of wet ash were stable at pitches ≤ 30°. In addition, tephra was mainly shed on pitches ≥ 32° for metal roofs and ≥ 35° for fibre cement and tiles. Using these results, we have produced an initial set of sliding coefficients for tephra for simply pitched roofs that can be used to help prioritise roofs for clearing during an eruption and assist in designing roofs to withstand tephra fall.
Research of 5G HUDN network selection algorithm based on Dueling-DDQN
Authors: Xie Jianli , Zhu Binhan , Li Cuiran
Published: November 2023

Due to the dense deployment and the diversity of user service types in the 5G HUDN environment, a more flexible network selection algorithm is required to reduce the network blocking rate and improve the user’s quality of service (QoS). Considering the QoS requirements and preferences of the users, a network selection algorithm based on Dueling-DDQN is proposed by using deep reinforcement learning. Firstly, the state, action space and reward function of the user-selected network are designed. Then, by calculating the network selection benefits for different types of services initiated by users, the analytic hierarchy process is used to establish the weight relationship between the different user services and the network attributes. Finally, a deep Q neural network is used to solve and optimize the proposed target and obtain the user’s best network selection strategy and long-term network selection benefits. The simulation results show that compared with other algorithms, the proposed algorithm can effectively reduce the network blocking rate while reducing the switching times.
PPARG is a potential target of Tanshinone IIA in prostate cancer treatment: a combination study of molecular docking and dynamic simulation based on transcriptomic bioinformatics
Authors: Zhang Tongtong , Chen Xinglin , Ju Xiran , Yuan Jixiang , Zhou Jielong , Zhang Zhihang , Ju Guanqun , Xu Dongliang
Published: November 2023

Tanshinone IIA is a lipophilic organic compound from the root of Danshen (Salvia miltiorrhiza) and is one of the most well-known Tanshinone molecules by pharmacologists. In recent years, in addition to effects of anti-cardiovascular and neurological diseases, Tanshinone IIA has also shown some degrees of anti-prostate cancer potential. Although they do have some studies focusing on the molecular mechanism of Tanshinone IIA’s anti-prostate cancer effects, a further understanding on the transcriptomic and structural level is still lacking. In this study, transcriptomic sequencing technology and computer technology were employed to illustrate the effects of Tanshinone IIA on prostate cancer through bioinformatic analysis and molecular dynamics simulation, and PPARG was considered to be one of the targets for Tanshinone IIA according to docking scoring and dynamic calculation. Our study provides a novel direction to further understand the mechanism of the effects of Tanshinone IIA on prostate cancer, and further molecular biological studies need to be carried on to further investigate the molecular mechanism of Tanshinone IIA’s anti-prostate cancer effect through PPARG.
Chromatin condensation but not DNA integrity of pig sperm is greater in the sperm-rich fraction
Authors: Viñolas-Vergés Estel , Ribas-Maynou Jordi , Barranco Isabel , Peres Rubio Camila , Bonet Sergi , Roca Jordi , Yeste Marc
Published: November 2023

Background

Protamination and condensation of sperm chromatin as well as DNA integrity play an essential role during fertilization and embryo development. In some mammals, like pigs, ejaculates are emitted in three separate fractions: pre-sperm, sperm-rich (SRF) and post sperm-rich (PSRF). These fractions are known to vary in volume, sperm concentration and quality, as well as in the origin and composition of seminal plasma (SP), with differences being also observed within the SRF one. Yet, whether disparities in the DNA integrity and chromatin condensation and protamination of their sperm exist has not been interrogated.

Results

This study determined chromatin protamination (Chromomycin A3 test, CMA3), condensation (Dibromobimane test, DBB), and DNA integrity (Comet assay) in the pig sperm contained in the first 10 mL of the SRF (SRF-P1), the remaining portion of the sperm-rich fraction (SRF-P2), and the post sperm-rich fraction (PSRF). While chromatin protamination was found to be similar between the different ejaculate fractions (P > 0.05), chromatin condensation was seen to be greater in SRF-P1 and SRF-P2 than in the PSRF (P = 0.018 and P = 0.004, respectively). Regarding DNA integrity, no differences between fractions were observed (P > 0.05). As the SRF-P1 has the highest sperm concentration and ejaculate fractions are known to differ in antioxidant composition, the oxidative stress index (OSi) in SP, calculated as total oxidant activity divided by total antioxidant capacity, was tested and confirmed to be higher in the SRF-P1 than in SRF-P2 and PSRF (0.42 ± 0.06 vs. 0.23 ± 0.09 and 0.08 ± 0.00, respectively; P < 0.01); this index, in addition, was observed to be correlated to the sperm concentration of each fraction (Rs = 0.973; P < 0.001).

Conclusion

While sperm DNA integrity was not found to differ between ejaculate fractions, SRF-P1 and SRF-P2 were observed to exhibit greater chromatin condensation than the PSRF. This could be related to the OSi of each fraction.
Gut microbiota response to in vitro transit time variation is mediated by microbial growth rates, nutrient use efficiency and adaptation to in vivo transit time
Authors: Minnebo Yorick , Delbaere Karen , Goethals Valerie , Raes Jeroen , Van de Wiele Tom , De Paepe Kim
Published: November 2023

Background

Transit time is an important modulator of the human gut microbiome. The inability to modify transit time as the sole variable hampers mechanistic in vivo microbiome research. We singled out gut transit time in an unprecedented in vitro approach by subjecting faecal microbial communities from six individuals with either short, medium or long in vivo transit times, to three different colonic transit times of 21, 32 and 63 h in the validated human gut in vitro model, SHIME.

Results

Transit time was identified as the single most important driver of microbial cell concentrations (52%), metabolic activity (45%) and quantitative (24%) and proportional (22%) community composition. Deceleration of transit was characterised by a significant decrease of specific Bifidobacterium and Veillonella spp. and increase of specific fibre degrading bacteria and nutrient specialists, such as Bacteroides, Prevotella, Ruminococcus, Bilophila and Akkermansia spp. These microbial communities reached a higher population density and net carbohydrate fermentation, leading to an increased SCFA production at longer transit times. In contrast, the carbohydrate-to-biomass production efficiency was increased at shorter transits, particularly in well-adapted faecal microbiomes from donors with short in vivo transit. Said adaptation was also reflected in the carbohydrate-to-SCFA conversion efficiency which varied with donor, but also colon region and SCFA chain length. A long transit time promoted propionate production, whereas butyrate production and butyrate producers were selectively enriched in the proximal colon at medium transit time.

Conclusion

Microbial growth rates and nutrient utilisation efficiency mediate the species-specific gut microbiota response to in vitro transit time variation, which is the main driver of in vitro microbial load, metabolism and community composition. Given the in vivo transit time variation within and between individuals, the personalisation of in vitro transit time based on in vivo data is required to accurately study intra- and inter-individual differences in gut microbiome structure, functionality and interactions with host and environmental modulators.
ATM inhibition blocks glucose metabolism and amplifies the sensitivity of resistant lung cancer cell lines to oncogene driver inhibitors
Authors: Terlizzi Cristina , De Rosa Viviana , Iommelli Francesca , Pezone Antonio , Altobelli Giovanna G. , Maddalena Maurizio , Dimitrov Jelena , De Rosa Caterina , Della Corte Carminia Maria , Avvedimento Vittorio Enrico , Del Vecchio Silvana
Published: November 2023

Background

ATM is a multifunctional serine/threonine kinase that in addition to its well-established role in DNA repair mechanisms is involved in a number of signaling pathways including regulation of oxidative stress response and metabolic diversion of glucose through the pentose phosphate pathway. Oncogene-driven tumorigenesis often implies the metabolic switch from oxidative phosphorylation to glycolysis which provides metabolic intermediates to sustain cell proliferation. The aim of our study is to elucidate the role of ATM in the regulation of glucose metabolism in oncogene-driven cancer cells and to test whether ATM may be a suitable target for anticancer therapy.

Methods

Two oncogene-driven NSCLC cell lines, namely H1975 and H1993 cells, were treated with ATM inhibitor, KU55933, alone or in combination with oncogene driver inhibitors, WZ4002 or crizotinib. Key glycolytic enzymes, mitochondrial complex subunits (OXPHOS), cyclin D1, and apoptotic markers were analyzed by Western blotting. Drug-induced toxicity was assessed by MTS assay using stand-alone or combined treatment with KU55933 and driver inhibitors. Glucose consumption, pyruvate, citrate, and succinate levels were also analyzed in response to KU55933 treatment. Both cell lines were transfected with ATM-targeted siRNA or non-targeting siRNA and then exposed to treatment with driver inhibitors.

Results

ATM inhibition deregulates and inhibits glucose metabolism by reducing HKII, p-PKM2Tyr105, p-PKM2Ser37, E1α subunit of pyruvate dehydrogenase complex, and all subunits of mitochondrial complexes except ATP synthase. Accordingly, glucose uptake and pyruvate concentrations were reduced in response to ATM inhibition, whereas citrate and succinate levels were increased in both cell lines indicating the supply of alternative metabolic substrates. Silencing of ATM resulted in similar changes in glycolytic cascade and OXPHOS levels. Furthermore, the driver inhibitors amplified the effects of ATM downregulation on glucose metabolism, and the combined treatment with ATM inhibitors enhanced the cytotoxic effect of driver inhibitors alone by increasing the apoptotic response.

Conclusions

Inhibition of ATM reduced both glycolytic enzymes and OXPHOS levels in oncogene-driven cancer cells and enhanced apoptosis induced by driver inhibitors thus highlighting the possibility to use ATM and the driver inhibitors in combined regimens of anticancer therapy in vivo.
The effect of happiness-based education on women’s success of water pipe smoking cessation and happiness: a quasi-experimental study
Authors: Dehkami Samira , Rostami Khatereh , Khademian Zahra
Published: November 2023

Background

Water pipe smoking by women threatens their health. Therefore, it is necessary to take measures to reduce this unhealthy behavior. This study aimed to determine the effect of happiness-based education on women’s success of water pipe smoking cessation and happiness.

Methods

This quasi-experimental study was conducted on female water pipe smokers in Iran, from September to January 2021. The participants (n = 68) were selected using convenience sampling and assigned to the intervention and control groups (34 subjects per group) by blocked randomization. The intervention group received a happiness-based education for one month (eight sessions) based on the Fordyce happiness program. The control group did not receive any special education. Data were collected using the Water Pipe Dependence Scale and the Oxford Happiness Questionnaire before and two months after the intervention. Data were analyzed using descriptive statistics, Chi-square, Fisher’s exact test, Independent t-test, Mann-Whitney, and Wilcoxon tests by SPSS software version 22.

Results

Two months after the intervention, the mean change in the happiness score was significantly higher in the intervention group (2.32 ± 2.31) than that in the control group (-0.29 ± 1.81) (P < 0.001). Furthermore, the mean change in the score of water pipe dependence was significantly different between the intervention (-1.44 ± 1.4) and control (0.38 ± 0.85) groups (P < 0.001).

Conclusion

The results showed that education based on Fordyce happiness program can increase the success of water pipe smoking cessation and happiness in women. Therefore, it is recommended to use similar interventions in women’s health promotion programs.
Genomic characterization of IDH-mutant astrocytoma progression to grade 4 in the treatment setting
Authors: Rautajoki Kirsi J. , Jaatinen Serafiina , Hartewig Anja , Tiihonen Aliisa M. , Annala Matti , Salonen Iida , Valkonen Masi , Simola Vili , Vuorinen Elisa M. , Kivinen Anni , Rauhala Minna J. , Nurminen Riikka , Maass Kendra K. , Lahtela Sirpa-Liisa , Jukkola Arja , Yli-Harja Olli , Helén Pauli , Pajtler Kristian W. , Ruusuvuori Pekka , Haapasalo Joonas , Zhang Wei , Haapasalo Hannu , Nykter Matti
Published: November 2023

As the progression of low-grade diffuse astrocytomas into grade 4 tumors significantly impacts patient prognosis, a better understanding of this process is of paramount importance for improved patient care. In this project, we analyzed matched IDH-mutant astrocytomas before and after progression to grade 4 from six patients (discovery cohort) with genome-wide sequencing, 21 additional patients with targeted sequencing, and 33 patients from Glioma Longitudinal AnalySiS cohort for validation. The Cancer Genome Atlas data from 595 diffuse gliomas provided supportive information. All patients in our discovery cohort received radiation, all but one underwent chemotherapy, and no patient received temozolomide (TMZ) before progression to grade 4 disease. One case in the discovery cohort exhibited a hypermutation signature associated with the inactivation of the MSH2 and DNMT3A genes. In other patients, the number of chromosomal rearrangements and deletions increased in grade 4 tumors. The cell cycle checkpoint gene CDKN2A, or less frequently RB1, was most commonly inactivated after receiving both chemo- and radiotherapy when compared to other treatment groups. Concomitant activating PDGFRA/MET alterations were detected in tumors that acquired a homozygous CDKN2A deletion. NRG3 gene was significantly downregulated and recurrently altered in progressed tumors. Its decreased expression was associated with poorer overall survival in both univariate and multivariate analysis. We also detected progression-related alterations in RAD51B and other DNA repair pathway genes associated with the promotion of error-prone DNA repair, potentially facilitating tumor progression. In our retrospective analysis of patient treatment and survival timelines (n = 75), the combination of postoperative radiation and chemotherapy (mainly TMZ) outperformed radiation, especially in the grade 3 tumor cohort, in which it was typically given after primary surgery. Our results provide further insight into the contribution of treatment and genetic alterations in cell cycle, growth factor signaling, and DNA repair-related genes to tumor evolution and progression.
An investigating on the ritual elements influencing factor of decorative art: based on Guangdong's ancestral hall architectural murals text mining
Authors: Li Weicong , Lv Huabin , Liu Yueling , Chen Simin , Shi Wenwen
Published: November 2023

The gradual loss of certain good cultural genes in the traditional ritual system is, to some extent, driven by the value orientation of the art of ancestral hall decoration. This article uses wall paintings as a medium to uncover significant variables affecting the decorating of ancestral hall murals and to analyze the culturally formative relationships underlying their art from a ceremonial perspective. It depends on textual excavation. The analysis demonstrates that: (1) the 521 murals generally transmit positive content; (2) the shift in the painted figures’ seating and grooming from formal to casual represents the fading of ceremonial concepts; (3) The control of economic costs may be a possible explanation for the large number of figures in crouching, skirting, and side-lying postures in wall paintings; (4) The fact that the colors employed in the garments of the figures from the Ming and Qing dynasties don’t follow the folk color scheme demonstrates that the creative production at that time was not constrained by a lot of ritualistic considerations. The study concludes that the absence of an educational component in the arts is a contributing factor to the diluted nature of traditional rituals in modern China.
Chemogenetic inhibition of NTS astrocytes normalizes cardiac autonomic control and ameliorate hypertension during chronic intermittent hypoxia
Authors: Pereyra Katherin , Las Heras Alexandra , Toledo Camilo , Díaz-Jara Esteban , Iturriaga Rodrigo , Del Rio Rodrigo
Published: November 2023

Background

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of chronic intermittent hypoxia (CIH), which has been linked to the development of sympathoexcitation and hypertension. Furthermore, it has been shown that CIH induced inflammation and neuronal hyperactivation in the nucleus of the solitary tract (NTS), a key brainstem region involved in sympathetic and cardiovascular regulation. Since several studies have proposed that NTS astrocytes may mediate neuroinflammation, we aimed to determine the potential contribution of NTS-astrocytes on the pathogenesis of CIH-induced hypertension.

Results

Twenty-one days of CIH induced autonomic imbalance and hypertension in rats. Notably, acute chemogenetic inhibition (CNO) of medullary NTS astrocytes using Designer Receptors Exclusively Activated by Designers Drugs (DREADD) restored normal cardiac variability (LF/HF: 1.1 ± 0.2 vs. 2.4 ± 0.2 vs. 1.4 ± 0.3, Sham vs. CIH vs. CIH + CNO, respectively) and markedly reduced arterial blood pressure in rats exposed to CIH (MABP: 82.7 ± 1.2 vs. 104.8 ± 4.4 vs. 89.6 ± 0.9 mmHg, Sham vs. CIH vs. CIH + CNO, respectively). In addition, the potentiated sympathoexcitation elicit by acute hypoxic chemoreflex activation in rats exposed to CIH was also completely abolished by chemogenetic inhibition of NTS astrocytes using DREADDs.

Conclusion

Our results support a role for NTS astrocytes in the maintenance of heightened sympathetic drive and hypertension during chronic exposure to intermittent hypoxia mimicking OSA.
Association of dietary diversity of 6–23 months aged children with prenatal and postnatal obstetric care: evidence from a nationwide cross-sectional study
Authors: Ahmed Khandaker Tanveer , Karimuzzaman Md. , Pinky Guliva Nazneen , Dasgupta Dibbya Pravas , Rahman Labiba , Hossain Md Moyazzem , Rahman Azizur
Published: November 2023

Background

Dietary diversity is a key determinant of infant and young child eating patterns for a variety of food groups taken by children between the ages of 6–23 months. The study aimed to examine the association between prenatal and postnatal obstetric care factors of mother and child’s dietary diversity, and specific food practices in Bangladesh.

Methods

This study analyzed the data of 2497 children between the age of 6–23 extracted from the latest countrywide Bangladesh Demographic Health Survey 2017–2018 and explored relationships between prenatal and postnatal obstetric care received by mother and dietary diversity score (DDS), minimum dietary diversity (MDD), and introduction of solid, semi-solid, and soft foods (ISSSF) of their children.

Results

Findings revealed that ≥ 4 antenatal care (ANC) visits care visits increased the DDS (adjusted $$\beta$$
β
: 0.32, 95% CI [0.21, 0.43]), increased the likelihood of MDD (AOR 1.54, 95% CI [1.23, 1.93]), and ISSSF (AOR 1.24, 95% CI [1.08, 1.48]), consuming eggs (AOR 1.47, 95% CI [1.23, 1.76]), and vitamin A vegetables and fruits (AOR 1.38, 95% CI [1.15, 1.66]). Moreover, DDS (adjusted β: 0.05, 95% CI [0.00, 0.11]) and MDD (AOR 1.66, 95% CI [1.31, 2.11]) are linked to childbirth in a medical facility. The C-section delivery influences the DDS (adjusted $$\beta$$
β
: 0.05, 95% CI [0.00, 0.10]), MDD (AOR 1.39, 95% CI [1.10, 1.75]), and ISSSF (AOR 1.22, 95% CI [1.02, 1.48]). Besides, postnatal visits within 48 h of delivery linked to MDD (AOR 0.66, 95% CI [0.49, 0.89]) and ISSSF (AOR 0.76, 95% CI [0.59, 0.97]), and physicians or professionals providing postnatal checkups were significantly associated with DDS (adjusted $$\beta$$
β
: 0.09, 95% CI [0.02, 0.16]), MDD (AOR 1.69, 95% CI [1.26, 2.26]), and ISSSF (AOR 1.30, 95% CI [1.04, 1.62]).

Conclusion

Knowledge of child nutritional feeding should emphasize during prenatal and postnatal obstetric care of mother, particularly during antenatal and postnatal visits, C-section delivery, and birth in a healthcare facility to eradicate malnutrition and establish healthy child feeding practices.
The oral-gut axis: a missing piece in the IBD puzzle
Authors: Kitamoto Sho , Kamada Nobuhiko
Published: November 2023

Inflammatory bowel disease (IBD) is a multifactorial intractable intestinal disease. Focusing on only one facet of the pathogenesis of IBD is insufficient to fully capture the complexity of the disease, and results in limited advance in clinical management. Therefore, it is critical to dissect the interactions amongst the multifarious contributors to the pathogenesis to comprehensively understand its pathology and subsequently improve clinical outcomes. In this context, the systemic interactions between organs, particularly the oral-gut axis mediated by host immune cells and resident microorganisms, have garnered significant attention in IBD research. More specifically, periodontal disease such as periodontitis has been implicated in augmenting intestinal inflammation beyond the confines of the oral cavity. There is mounting evidence suggesting that potentially harmful oral resident bacteria, termed pathobionts, and pro-inflammatory immune cells from the oral mucosa can migrate to the gastrointestinal tract, thereby potentiating intestinal inflammation. This article aims to provide a holistic overview of the causal relationship between periodontal disease and intestinal inflammation. Furthermore, we will discuss potential determinants that facilitate the translocation of oral pathobionts into the gut, a key event underpinning the oral-gut axis. Unraveling the complex dynamics of microbiota and immunity in the oral-gut continuum will lead to a better understanding of the pathophysiology inherent in both oral and intestinal diseases and the development of prospective therapeutic strategies.
Prevalence of aortic aneurysmal sac expansion using CTA in type II endoleak: comparison between endoleak visualization in CTA phase and in delayed phase
Authors: Khantayanuwong Supawut , Wasinrat Jitladda , Patharateeranart Karnkawin
Published: November 2023

Background

To compare the prevalence of aneurysmal sac expansion in type II endoleak (T2E) presenting on CTA phase with T2E presenting on delayed phase.

Methods

A retrospective study at a single tertiary care center in Bangkok, Thailand. Serial measurement of aneurysmal sac diameters was obtained and the prevalence of aneurysmal sac expansion was compared.

Results

130 patients were enrolled from January 2005 to December 2019. The prevalence of aneurysmal sac expansion in T2E patients presenting in the CTA phase and delayed phase in this 2-year observational study were 16% and 0%, respectively (P = 0.065). Age > 80 years (25.8% vs. 8.8%; P = 0.028) and initial aneurysmal sac diameter (71.3 mm vs. 57.7 mm; P = 0.035) were associated with the aneurysmal sac expansion. Aneurysmal sac expansion occurred in 18.3% of patients with patent IMA and 6% of patients with occluded IMA (P = 0.053). The number and diameter of lumbar artery feeder, and the presence of intrastent thrombus were not associated with aneurysmal sac expansion. T2E presenting on CTA phase resolved in 9.2% of cases compared with 7.14% of delayed phase cases (P = 1.0).

Conclusions

The prevalence of aneurysmal sac expansion in T2E patients presenting on CTA phase was not statistically significantly higher than in patients on delayed phase. Age more than 80 years and initial aneurysmal sac diameter were significantly associated with aneurysmal sac expansion.
A modified model for laser-cornea interaction following the ablation effect in the laser eye-surgery
Authors: Abdelhalim Ibrahim , Hamdy Omnia , Hassan Aziza Ahmed , Abdelkawi Salwa , Elnaby Salah Hassab
Published: November 2023

Background

Laser corneal reshaping is a successful treatment of many refraction disorders. However, some physical demonstrations for the laser interaction with cornea are not fully explained. In the current paper, we present a modified model to precisely investigate the ablation threshold, the ablation rate and the physical/chemical mechanisms in that action.

Results

The model discusses the possible photochemical reaction between the incident photons and various components of the cornea. Such photochemical reaction may end by photo-ablation or just molecular electronic excitation. The ablation threshold is also produced by other chemical reaction. Finally another chemical reaction creates out-site fragments. Moreover, the effect of applying different laser wavelengths, namely the common excimer-laser (193-nm), and the solid-state lasers (213-nm & 266-nm) has been investigated.

Conclusion

Despite the success and ubiquity of the Argon Fluoride “ArF” laser, our results reveal that a carefully designed 213-nm laser gives the same outcomes with the potential of possible lower operational drawbacks related with heat generation and diffusion.