bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory cytokines as potential biomarkers for early diagnosis of severe malaria in children in Ghana
Authors: Obeng-Aboagye Elizabeth , Frimpong Augustina , Amponsah Jones Amo , Danso Samuel E. , Owusu Ewurama D. A. , Ofori Michael Fokuo
Published: July 2023

Background

Severe malaria (SM) is a fatal multi-system disease which accounted for an estimated 619,000 deaths in 2021. Less than 30% of children presenting with SM are diagnosed and treated promptly, resulting in increased mortality and neurologic impairments in survivors. Studies have identified cytokine profiles that differentiate the various clinical manifestations of malaria (severe and uncomplicated). However, the diagnostic capability of these cytokines in differentiating between the disease states in terms of cut-off values has not yet been determined.

Methods

The plasma levels of 22 pro-inflammatory cytokines (Eotaxin/CCL 11, interferon-gamma (IFN-γ), interleukin (IL)- 2, IL-6, IL-1β, IL-12p40/p70, IL-17A, RANTES, MCP-1, IL-15, IL-5, IL-1RA, IL-2R, IFN-α, IP-10, TNF, MIG, MIP-1α, MIP-1β, IL-7, IL-8 and Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), and 3 anti-inflammatory cytokines-(IL-4, IL-13 and IL-10) in patients with SM, uncomplicated malaria (UM) and other febrile conditions, were measured and compared using the Human Cytokine Magnetic 25-Plex Panel. The receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of these cytokines.

Results

The level of the pro-inflammatory cytokine, IL-17A, was significantly higher in the SM group as compared to the UM group. Levels of the anti-inflammatory cytokines however did not differ significantly among the SM and UM groups. Only IL-1β and IL-17A showed good diagnostic potential after ROC curve analysis.

Conclusion

The data show that levels of pro-inflammatory cytokines correlate with malaria disease severity. IL-1β and IL-17A showed good diagnostic potentials and can be considered for use in clinical practice to target treatment.
Risk factors of early bacterial infection and analysis of bacterial composition, distribution and drug susceptibility after cadaveric liver transplantation
Authors: Liu Min , Li Cuiying , Liu Jing , Wan Qiquan
Published: July 2023

Background

This study provided a theoretical basis for the clinical diagnosis and treatment of bacterial infection after liver transplantation through analyzing the pathogenic distribution, drug sensitivity and risk factors of bacterial infection after liver transplantation.

Methods

We collected clinical data from 207 recipients undergoing liver transplantation of graft from donation after citizens’ death donors in the Third Xiangya Hospital of Central South University from January 2019 to December 2021 and analyzed the composition and distribution of bacterial pathogens, drug resistance and risk factors of infection.

Results

A total of 90 bacterial infections occurred in 55 recipients within two months after liver transplantation, and the incidence of bacterial infection was 26.6% (55/207). The gram-negative bacteria (46/90, 51.1%) were more prevalent than gram-positive bacteria (44/90, 48.9%). Common sites of infection were the abdominal/biliary tract (26/90, 28.9%), lung (22/90, 22.4%) and urinary tract (22/90, 22.4%). Fourteen cases (6.8%) died after liver transplantation. Klebsiella pneumoniae (17/90, 18.9%) was the most frequent gram-negative bacteria causing infection in liver transplant recipients and 58.7%, 50%, 80.4% and 89.1% of gram-negative bacteria were sensitive to amikacin, minocycline, tigecycline and polymyxin B, respectively. The most common gram-positive bacteria was Enterococcus faecium (30/90, 33.3%) and 97.7%, 100%, 86.4%, 100% and 100% of gram-positive bacteria were sensitive to vancomycin, teicoplanin, daptomycin, tigecycline and linezolid, respectively. Univariate analysis revealed that bacterial infection was associated with female, age (≥ 50 years old), preoperative albumin (≤ 30 g/L), operation duration (≥ 400 min), intraoperative blood loss (≥ 3000 ml) and postoperative ventilator support. Binary Logistic regression analysis showed that female (OR = 3.149, 95% CI: 1.418–6.993, P = 0.005), operation duration (≥ 400 min) (OR = 2.393, 95% CI: 1.202–4.765, P = 0.013) and intraoperative blood loss (≥ 3000 ml) (OR = 2.052, 95% CI: 1.007–4.183, P = 0.048) were independent risk factors for bacterial infection after liver transplantation.

Conclusion

The incidence of early bacterial infection after liver transplantation was high, and the infection sites were mainly abdominal/biliary tract, respiratory tract and urinary tract. The most common pathogenic bacterium was gram-negative bacterium. Our study also identified several independent risk factors for bacterial infection after liver transplantation, including female gender, operation duration of 400 min or more, and intraoperative blood loss of 3000 ml or more. By addressing these risk factors, such as implementing strategies to optimize surgical procedures and minimize blood loss, healthcare professionals can work towards reducing the incidence of bacterial infections following liver transplantation.
Impacts of seasonal flooding on geographical access to maternal healthcare in the Barotse Floodplain, Zambia
Authors: Mroz Elizabeth Jade , Willis Thomas , Thomas Chris , Janes Craig , Singini Douglas , Njungu Mwimanenwa , Smith Mark
Published: July 2023

Background

Seasonal floods pose a commonly-recognised barrier to women’s access to maternal services, resulting in increased morbidity and mortality. Despite their importance, previous GIS models of healthcare access have not adequately accounted for floods. This study developed new methodologies for incorporating flood depths, velocities, and extents produced with a flood model into network- and raster-based health access models. The methodologies were applied to the Barotse Floodplain to assess flood impact on women’s walking access to maternal services and vehicular emergency referrals for a monthly basis between October 2017 and October 2018.

Methods

Information on health facilities were acquired from the Ministry of Health. Population density data on women of reproductive age were obtained from the High Resolution Settlement Layer. Roads were a fusion of OpenStreetMap and data manually delineated from satellite imagery. Monthly information on floodwater depth and velocity were obtained from a flood model for 13-months. Referral driving times between delivery sites and EmOC were calculated with network analysis. Walking times to the nearest maternal services were calculated using a cost-distance algorithm.

Results

The changing distribution of floodwaters impacted the ability of women to reach maternal services. At the peak of the dry season (October 2017), 55%, 19%, and 24% of women had walking access within 2-hrs to their nearest delivery site, EmOC location, and maternity waiting shelter (MWS) respectively. By the flood peak, this dropped to 29%, 14%, and 16%. Complete inaccessibility became stark with 65%, 76%, and 74% unable to access any delivery site, EmOC, and MWS respectively. The percentage of women that could be referred by vehicle to EmOC from a delivery site within an hour also declined from 65% in October 2017 to 23% in March 2018.

Conclusions

Flooding greatly impacted health access, with impacts varying monthly as the floodwave progressed. Additional validation and application to other regions is still needed, however our first results suggest the use of a hydrodynamic model permits a more detailed representation of floodwater impact and there is great potential for generating predictive models which will be necessary to consider climate change impacts on future health access.
A potential correlation between adipokines, skeletal muscle function and bone mineral density in middle-aged and elderly individuals
Authors: Wang Wenhao , Gu Xuchao , Cao Ziyi , Wang Xiaojun , Lei Yiming , Xu Xiaoli , Wang Shiwen , Wu Tao , Bao Zhijun
Published: July 2023

Background

Evidence exists of a strong association between inflammation and a decrease in skeletal muscle function and bone mineral density (BMD); however, the specific mechanisms of these associations remain unclear. Adipokines, as key regulators of the inflammatory response, may be implicated in these processes. The objective of this study was to explore the potential correlation between adipokines, skeletal muscle function and BMD in middle-aged and elderly individuals.

Methods

A comparative cross-sectional study was carried out at the Huadong Hospital Affiliated with Fudan University (Shanghai, China). A total of 460 middle-aged and elderly individuals were recruited, and 125 were enrolled in the analysis. Their biochemical indices, body composition, skeletal muscle function and BMD were measured. Bioinformatic analysis was also employed to identify potential adipokine targets linked to skeletal muscle function and BMD. To validate these targets, plasma and peripheral blood mononuclear cells (PBMCs) were harvested from these individuals and subjected to western blotting (WB) and enzyme-linked immunosorbent assay (ELISA).

Results

Individuals in this cross-sectional study were categorized into 2 groups according to their median skeletal muscle mass (SMM) (28.8 kg for males and 20.6 kg for females). Individuals with lower SMM exhibited poorer grip strength (P = 0.017), longer 5-Times-Sit-to-Stand Test (FTSST) duration (P = 0.029), lower total hip BMD (P = 0.043), lower femoral neck BMD (P = 0.011) and higher levels of inflammatory markers in comparison with individuals with higher SMM. Bioinformatics analysis identified LEP, ADIPOQ, RBP4, and DPP4 as potential adipokine targets associated with skeletal muscle function and BMD. In vitro experiments demonstrated that individuals with decreased skeletal muscle function and BMD expressed higher levels of these adipokines.

Conclusions

Skeletal muscle function is positively correlated with BMD and negatively correlated with levels of inflammatory markers among middle-aged and elderly individuals. Those with lower skeletal muscle function and BMD tend to have a higher expression of LEP, ADIPOQ, RBP4 and DPP4.
Differentiating the role of alcohol in young men’s use of substances with sex: A qualitative study
Authors: Goodyear Trevor , Oliffe John L. , Parent Natasha , Mniszak Caroline , Jenkins Emily , Knight Rod
Published: July 2023

Background

Alcohol consumption is common among young men and occurs in many contexts. The sexualized substance use literature has generated some insight into the role of alcohol alongside other substances in the context of sex, though there remain opportunities for targeted and context-sensitive studies to examine the sexual practices and outcomes associated with alcohol, specifically.

Methods

This interpretive description study explores how experiences and contexts of alcohol use feature in the sexual lives of young men who use substances with sex. Data collection involved in-depth interviews conducted between 2018 and 2021 in Vancouver, Canada, with N = 76 young men (ages 18–30; mean = 23.9 years) who use substances with sex, including men with diverse sexual identities. Data were analyzed in an iterative manner through a social constructivist lens and an interpretive description framework, leveraging constant comparison techniques.

Findings

This analysis yielded three interconnected themes: (1) using alcohol for sexual(ity) freedoms; (2) backgrounding alcohol within a sexualized polysubstance milieu; and (3) navigating the risks and consequences of using alcohol with sex. Alcohol use was found to reduce inhibitions and support experimentation, including by facilitating the transgression of conservative or restrictive social and sexual norms. Alcohol was seldom explicitly classified as a sexualized substance, though it was evidently a widespread and normative social practice. This practice was associated with important risk and consequences, including with respect to consent, pregnancy and sexually transmitted and bloodborne infection risk, and sexual dysfunction.

Conclusions

Findings from this study position alcohol as a backgrounded yet significantly influential substance that young men use with sex. The sexualized use of substances must be understood, and responded to, in a manner that is grounded in harm reduction and that considers the full spectrum of substances—inclusive of but not limited to alcohol—and associated benefits and risks that feature in young men’s sexual lives. Specifically, sexual health and primary care providers working with young men should invite and open up meaningful conversation about how they may be using substances (including alcohol) with sex, while offering de-stigmatizing, sex-positive, and affirming education and supports to promote safer sex and substance use.
Association between Chinese visceral adiposity index and risk of stroke incidence in middle-aged and elderly Chinese population: evidence from a large national cohort study
Authors: Zhang Zenglei , Zhao Lin , Lu Yiting , Meng Xu , Zhou Xianliang
Published: July 2023

Background

Abdominal obesity has long been considered as a crucial risk factor of stroke. Chinese visceral adiposity index (CVAI), a novel surrogate indicator of abdominal obesity, has been confirmed as a better predictor for coronary heart disease than other indicators in Asian population. However, the data on the relationship of CVAI with stroke is limited. The objective of our study is evaluating the relationship between CVAI and stroke incidence.

Methods

In the present study, we enrolled 7242 middle-aged and elderly residents from the China Health and Retirement Longitudinal Study (CHARLS) and placed them into groups according to quartile of CVAI. The outcome of interest was stroke. Kaplan–Meier curves were used to estimate the cumulative incidences of stroke. Cox regression analyses and multivariable-adjusted restricted cubic spline (RCS) curves were performed to evaluate the relationship between CVAI and incident stroke. Multiple sensitivity analyses and subgroups analyses were performed to test the robustness of the findings.

Results

During a median 84 months of follow-up, 612 (8.45%) participants experienced incident stroke, and the incidences of stroke for participants in quartiles (Q) 1–4 of CVAI were 4.42%, 7.29%, 9.06% and 13.04%, respectively. In the fully adjusted model, per 1.0-SD increment in CVAI has a significant increased risk of incident stroke: hazard ratio (HR) [95% confidence interval (CI)] was 1.17 (1.07–1.28); compared with participants in Q1 of CVAI, the HRs (95% CI) of incident stroke among those in Q2–4 were 1.47 (1.10–1.95), 1.62 (1.22–2.15), and 1.70 (1.28–2.27), respectively. Subgroups analyses suggested the positive association was significant in male participants, without diabetes, hypertension and heart disease. The findings were robust in all the sensitivity analyses. Additional, RCS curves showed a significant dose-response relationship of CVAI with risk of incident stroke (P for non-linear trend = 0.319).

Conclusion

Increased CVAI is significantly associated with higher risk of stroke incidence, especially in male individuals, without hypertension, diabetes and heart disease. The findings suggest that baseline CVAI is a reliable and effective biomarker for risk stratification of stroke, which has far-reaching significance for primary prevention of stroke and public health.
Clinical outcomes and safety of anakinra in the treatment of multisystem inflammatory syndrome in children: a single center observational study
Authors: Dizon Brian L.P. , Redmond Christopher , Gotschlich Emily C. , Sule Sangeeta , Ronis Tova , Vazzana Kathleen M. , Sherman Matthew A. , Connor Rachael , Bosk Abigail , Dham Niti , Harahsheh Ashraf S. , Wells Elizabeth , DeBiasi Roberta , Srinivasalu Hemalatha
Published: July 2023

Background and objective

Evidence for the treatment of multisystem inflammatory syndrome in children (MIS-C) is lacking. Anakinra, which targets IL-1-mediated inflammation, is reserved for refractory cases of MIS-C; however, its use in the treatment of MIS-C is not clearly established.

Patients and methods

To examine a role for anakinra in MIS-C, we performed a single center observational cohort study of all MIS-C patients diagnosed at our children’s hospital from May 15 to November 15, 2020. Demographics, clinical features, diagnostic testing, and cardiac function parameters were compared between MIS-C patients treated with intravenous immunoglobulin (IVIG) monotherapy and IVIG with anakinra (IVIG + anakinra).

Results

Among 46 patients with confirmed MIS-C, 32 (70%) were in the IVIG + anakinra group, of which 9 (28%) were also given corticosteroids (CS). No patients were treated with anakinra alone. MIS-C patients in the IVIG + anakinra group were enriched in a CV shock phenotype (p = 0.02), and those with CV shock were treated with higher doses of anakinra for a longer duration. Furthermore, MIS-C patients in the IVIG + anakinra group exhibited improvements in fever and cardiac function with or without CS. No significant adverse events were observed, and no differences in IL-1β levels were found among MIS-C patients in the IVIG + anakinra group.

Conclusions

Anakinra treatment, which was co-administered with IVIG primarily in patients with severe MIS-C, was associated with improvements in fever and cardiac function, and demonstrated a favorable side-effect profile. These findings suggest a role for adjunctive anakinra in the treatment of severe MIS-C.
The one-week prevalence of neck pain and low back pain in post-secondary students at two Canadian institutions
Authors: Campbell Alexandra , Wang Dan , Martin Krystle , Côté Pierre
Published: July 2023

Background

Low back and neck pain are common in the general population, but the prevalence among Canadian post-secondary students is not well known. We aimed to determine the one-week prevalence of neck pain (NP) and low back pain (LBP) among postsecondary students in Canada.

Methods

We conducted a cross-sectional study of students enrolled in the Faculty of Health Sciences and Faculty of Education at Ontario Tech University, and the Canadian Memorial Chiropractic College (CMCC) in the Fall of 2017. Neck and low back pain intensity in the past week were measured with the 11-point numerical rating scale. We report the cumulative, gender- and institution-specific one-week prevalence (95% CI) of any pain (1–10/10) and moderate to severe pain (≥ 3/10).

Results

The one-week prevalence of any neck pain ranged from 45.4% (95% CI: 38.4, 52.4) in the Faculty of Education to 76.9% (95% CI: 72.9, 80.4) at CMCC. The one-week prevalence of neck pain ≥3/10 ranged from 44.4% (95% CI: 37.5, 51.4) in the Faculty of Education to 58.4% (95% CI: 54.0, 62.7) at CMCC. The one-week prevalence of any low back pain ranged from 60.9% (95% CI: 53.8, 67.5) in the Faculty of Education to 69.0% (95% CI: 64.8, 73.0) at CMCC, and the one-week prevalence of low back pain ≥ 3/10 ranged from 47.8% (95% CI: 43.4, 52.2) at CMCC to 55.1% (95% CI: 51.2, 58.9) in the Faculty of Health Sciences. The prevalence of any back or neck pain and pain ≥ 3/10 was consistently higher in females than males, with the largest difference seen for neck pain at CMCC.

Conclusion

Most post-secondary students in our samples experienced LBP and NP in the past week. Overall, the one-week prevalence of NP and LBP was higher among chiropractic students and among females. This study should draw attention to school administrators about the burden of NP and LBP in post-secondary students.
Down-regulation of long noncoding RNA HULC inhibits the inflammatory response in ankylosing spondylitis by reducing miR-556-5p-mediated YAP1 expression
Authors: Yi LuLu , Song ChangJun , Liu YuanYuan , Li DongSheng , Xiao TianTian , Guo XuQin , Wu YiCai
Published: July 2023

Objective

Ankylosing spondylitis (AS) is a progressive systemic disease characterized by a chronic inflammatory response in the sacroiliac joints and spine. Long noncoding RNAs suggest significant actions in the progression of AS. Therefore, a specific lncRNA, highly upregulated in liver cancer (HULC), was studied here regarding its functions and related mechanisms in AS.

Methods

Measurements of miR-556-5p, HULC, and YAP1 expression were performed on AS cartilage tissues and chondrocytes. The interaction between miR-556-5p and HULC or YAP1 was verified. CCK-8, flow cytometry and enzyme-linked immunosorbent assay were used to evaluate the effects of HULC, miR-556-5p, and YAP1 on the proliferation, apoptosis, and inflammatory response of AS chondrocytes. Furthermore, the action of HULC/miR-556-5p/YAP1 was experimentally observed in AS mice.

Results

HULC and YAP1 levels were augmented, while miR-556-5p levels were suppressed in AS cartilage tissues and chondrocytes. Downregulating HULC or upregulating miR-556-5p stimulated chondrocyte proliferation and inhibited apoptosis and inflammation in AS. miR-556-5p was a downstream factor of HULC, and YAP1 was a potential target of miR-556-5p. The improvement effect of downregulated HULC on AS chondrocytes was saved when YAP1 expression was forced. In addition, silence of HULC improved the pathological injury of spinal cartilage in AS mice by enhancing miR-556-5p-related regulation of YAP1.

Conclusion

HULC inhibition relieves the inflammatory response in AS by reducing miR-556-5p-mediated YAP1 expression.
High EVI1 and PARP1 expression as favourable prognostic markers in high-grade serous ovarian carcinoma
Authors: Jank Paul , Leichsenring Jonas , Kolb Svenja , Hoffmann Inga , Bischoff Philip , Kunze Catarina Alisa , Dragomir Mihnea P. , Gleitsmann Moritz , Jesinghaus Moritz , Schmitt Wolfgang D. , Kulbe Hagen , Sers Christine , Stenzinger Albrecht , Sehouli Jalid , Braicu Ioana Elena , Westhoff Christina , Horst David , Denkert Carsten , Gröschel Stefan , Taube Eliane T.
Published: July 2023

Background

Mechanisms of development and progression of high-grade serous ovarian cancer (HGSOC) are poorly understood. EVI1 and PARP1, part of TGF-ß pathway, are upregulated in cancers with DNA repair deficiencies with DNA repair deficiencies and may influce disease progression and survival. Therefore we questioned the prognostic significance of protein expression of EVI1 alone and in combination with PARP1 and analyzed them in a cohort of patients with HGSOC.

Methods

For 562 HGSOC patients, we evaluated EVI1 and PARP1 expression by immunohistochemical staining on tissue microarrays with QuPath digital semi-automatic positive cell detection.

Results

High EVI1 expressing (> 30% positive tumor cells) HGSOC were associated with improved progression-free survival (PFS) (HR = 0.66, 95% CI: 0.504–0.852, p = 0.002) and overall survival (OS) (HR = 0.45, 95% CI: 0.352–0.563, p < 0.001), including multivariate analysis. Most interestingly, mutual high expression of both proteins identifies a group with particularly good prognosis. Our findings were proven technically and clinically using bioinformatical data sets for single-cell sequencing, copy number variation and gene as well as protein expression.

Conclusions

EVI1 and PARP1 are robust prognostic biomarkers for favorable prognosis in HGSOC and imply further research with respect to their reciprocity.
Guideline on multimodal rehabilitation for patients with post-intensive care syndrome
Authors: Renner Caroline , Jeitziner Marie-Madlen , Albert Monika , Brinkmann Sabine , Diserens Karin , Dzialowski Imanuel , Heidler Maria-Dorothea , Lück Martina , Nusser-Müller-Busch Ricki , Sandor Peter S. , Schäfer Andreas , Scheffler Bettina , Wallesch Claus , Zimmermann Gudrun , Nydahl Peter
Published: July 2023

Background

Intensive Care Unit (ICU) survivors often experience several impairments in their physical, cognitive, and psychological health status, which are labeled as post-intensive care syndrome (PICS). The aim of this work is to develop a multidisciplinary and -professional guideline for the rehabilitative therapy of PICS.

Methods

A multidisciplinary/-professional task force of 15 healthcare professionals applied a structured, evidence-based approach to address 10 scientific questions. For each PICO-question (Population, Intervention, Comparison, and Outcome), best available evidence was identified. Recommendations were rated as “strong recommendation”, “recommendation” or “therapy option”, based on Grading of Recommendations, Assessment, Development and Evaluation principles. In addition, evidence gaps were identified.

Results

The evidence resulted in 12 recommendations, 4 therapy options, and one statement for the prevention or treatment of PICS. Recommendations: early mobilization, motor training, and nutrition/dysphagia management should be performed. Delirium prophylaxis focuses on behavioral interventions. ICU diaries can prevent/treat psychological health issues like anxiety and post-traumatic stress disorders. Early rehabilitation approaches as well as long-term access to specialized rehabilitation centers are recommended. Therapy options include additional physical rehabilitation interventions. Statement: A prerequisite for the treatment of PICS are the regular and repeated assessments of the physical, cognitive and psychological health in patients at risk for or having PICS.

Conclusions

PICS is a variable and complex syndrome that requires an individual multidisciplinary, and multiprofessional approach. Rehabilitation of PICS should include an assessment and therapy of motor-, cognitive-, and psychological health impairments.
Long-term longitudinal study on swine VML model
Authors: De Paolis Francesca , Testa Stefano , Guarnaccia Gabriele , Reggio Alessio , Fornetti Ersilia , Cicciarelli Felice , Deodati Rebecca , Bernardini Sergio , Peluso Daniele , Baldi Jacopo , Biagini Roberto , Bellisari Flavia Cobianchi , Izzo Antonio , Sgalambro Ferruccio , Arrigoni Francesco , Rizzo Francesco , Cannata Stefano , Sciarra Tommaso , Fuoco Claudia , Gargioli Cesare
Published: July 2023

Background

Volumetric Muscle Loss (VML), resulting from severe trauma or surgical ablation, is a pathological condition preventing myofibers regeneration, since skeletal muscle owns the remarkable ability to restore tissue damage, but only when limited in size. The current surgical therapies employed in the treatment of this pathology, which particularly affects military personnel, do not yet provide satisfactory results. For this reason, more innovative approaches must be sought, specifically skeletal muscle tissue engineering seems to highlight promising results obtained from preclinical studies in VML mouse model. Despite the great results obtained in rodents, translation into human needs a comparable animal model in terms of size, in order to validate the efficacy of the tissue engineering approach reconstructing larger muscle mass (human-like). In this work we aim to demonstrate the validity of a porcine model, that has underwent a surgical ablation of a large muscle area, as a VML damage model.

Results

For this purpose, morphological, ultrasound, histological and fluorescence analyses were carried out on the scar tissue formed following the surgical ablation of the peroneus tertius muscle of Sus scrofa domesticus commonly called mini-pig. In particular, the replenishment of the damaged area, the macrophage infiltration and the vascularization at different time-points were evaluated up to the harvesting of the scar upon six months.

Conclusion

Here we demonstrated that following VML damage, there is an extremely poor regenerative process in the swine muscle tissue, while the formation of fibrotic, scar tissue occurs. The analyses performed up to 180 days after the injury revealed the development of a stable, structured and cellularized tissue, provided with vessels and extracellular matrix acquiring the status of granulation tissue like in human.
Leukocyte- and platelet-rich fibrin in endoscopic endonasal skull base reconstruction: study protocol for a multicenter prospective, parallel-group, single-blinded randomized controlled non-inferiority trial
Authors: Coucke Birgit , Van Hoylandt Anaïs , Jorissen Mark , Meulemans Jeroen , Decramer Thomas , van Loon Johannes , Vander Poorten Vincent , Theys Tom , Van Gerven Laura
Published: July 2023

Background

Recent advances in endoscopic endonasal transsphenoidal approaches (EETA) for skull base lesions have resulted in a significant increase in extent and complexity of skull base defects, demanding more elaborate and novel reconstruction techniques to prevent cerebrospinal fluid (CSF) leakage and to improve healing. Currently, commercially available fibrin sealants are often used to reinforce the skull base reconstruction. However, problems have been reported regarding hypersensitivity reactions, efficacy, and costs. This trial aims to investigate autologous leukocyte- and platelet-rich fibrin (L-PRF) membranes as an alternative for commercially available fibrin glues in EETA-related skull base reconstruction reinforcement.

Methods/design

This multicenter, prospective randomized controlled trial aims to demonstrate non-inferiority of L-PRF membranes compared to commercially available fibrin sealants in EETA cases (1) without intra-operative CSF-leak as dural or sellar floor closure reinforcement and (2) in EETA cases with intra-operative CSF-leak (or very large defects) in which a classic multilayer reconstruction has been made, as an additional sealing. The trial includes patients undergoing EETA in three different centers in Belgium. Patients are randomized in a 1:1 fashion comparing L-PRF with commercially available fibrin sealants. The primary endpoint is postoperative CSF leakage. Secondary endpoints are identification of risk factors for reconstruction failure, assessment of rhinological symptoms, and interference with postoperative imaging. Additionally, a cost-effectiveness analysis is performed.

Discussion

With this trial, we will evaluate the safety and efficacy of L-PRF compared to commercially available fibrin sealants.

Trial registration

ClinicalTrials.gov NCT03910374. Registered on 10 April 2019.
Metagenomic analysis reveals the relationship between intestinal protozoan parasites and the intestinal microecological balance in calves
Authors: Fu Yin , Zhang Kaihui , Yang Mengyao , Li Xiaoying , Chen Yuancai , Li Junqiang , Xu Huiyan , Dhakal Pitambar , Zhang Longxian
Published: July 2023

Background

A close connection between a protozoan parasite and the balance of the other gut microbes of the host has been demonstrated. The calves may be naturally co-infected with many parasites, and the co-effects of parasites on other intestinal microbes of calves remain unclear. This study aims to preliminarily reveal the relationship between intestinal parasites and other intestinal microbes in calves.

Methods

Fecal samples were collected from four calves with bloody diarrhea, four calves with watery diarrhea, and seven normal calves, and the microbial flora of the samples were analyzed by whole-genome sequencing. Protozoal parasites were detected in the metagenome sequences and identified using polymerase chain reaction (PCR).

Results

Cryptosporidium, Eimeria, Giardia, Blastocystis, and Entamoeba were detected by metagenomic analysis, and the identified species were Giardia duodenalis assemblage E, Cryptosporidium bovis, Cryptosporidium ryanae, Eimeria bovis, Eimeria subspherica, Entamoeba bovis, and Blastocystis ST2 and ST10. Metagenomic analysis showed that the intestinal microbes of calves with diarrhea were disordered, especially in calves with bloody diarrhea. Furthermore, different parasites show distinct relationships with the intestinal microecology. Cryptosporidium, Eimeria, and Giardia were negatively correlated with various intestinal bacteria but positively correlated with some fungi. However, Blastocystis and Entamoeba were positively associated with other gut microbes. Twenty-seven biomarkers not only were significantly enriched in bloody diarrhea, watery diarrhea, and normal calves but were also associated with Eimeria, Cryptosporidium, and Giardia. Only Eimeria showed a distinct relationship with seven genera of bacteria, which were significantly enriched in the healthy calves. All 18 genera of fungi were positively correlated with Cryptosporidium, Eimeria, and Giardia, which were also significantly enriched in calves with bloody diarrhea. Functional genes related to parasites and diseases were found mainly in fungi.

Conclusions

This study revealed the relationship between intestinal protozoan parasites and the other calf gut microbiome. Different intestinal protozoan parasites have diametrically opposite effects on other gut microecology, which not only affects bacteria in the gut, but also is significantly related to fungi and archaea.

Graphical Abstract
Neurofeedback training and motor learning: the enhanced sensorimotor rhythm protocol is better or the suppressed alpha or the suppressed mu?
Authors: Afrash Sana , Saemi Esmaeel , Gong Anmin , Doustan Mohammadreza
Published: July 2023

A large number of previous studies have examined how different neurofeedback-based techniques may influence motor learning. However, only a few studies attempted to compare the effects of these different techniques on motor learning. Therefore, the present study attempts to examine the effects of neurofeedback training on motor learning in novice golfers, using three protocols, namely enhanced sensorimotor rhythm (SMR) at Cz, suppressed alpha waves at Fz, and suppressed mu waves at Cz. The participants were 64 adults (32 females; mean age = 22.31 ± 2.25 years). The study consisted of a pretest stage (day 1), intervention (6 sessions, over two weeks, 3 sessions per week), short-term retention (one day after intervention), and long-term retention (two weeks after intervention); in the pretest and short-term and long-term retention, motor performance for golf putting (12 trials) as well as amplitudes of SMR wave at Cz, alpha at Fz, and Mu at Cz were recorded. During each intervention session, the participants in three neurofeedback groups and a sham group first performed neurofeedback training (enhanced SMR at Cz, suppressed alpha at Fz, and suppressed Mu at Cz) for 20 min. Then, the participants in all groups performed three blocks of 12 trials consisting of golf putting training. The results indicated no difference between the sham and the experimental groups in the acquisition stage, as individuals in all groups experienced similar improvement in putting accuracy. However, in the short-term retention, all the three neurofeedback groups outperformed the sham group, although in the long-term retention, only the SMR group and the Alpha group showed a better performance than the sham group while the Mu group did not exhibit a notably better performance than the sham group. Our results also showed significant variations in the amplitudes of the SMR, alpha, and mu waves depending on the neurofeedback intervention provided, while no significant variation was observed in the sham group. Based on these results, it is recommended that coaches should make further use of enhanced SMR at Cz or suppressed alpha at Fz as their neurofeedback interventions to facilitate longer-term motor learning in golfers.
Bronchodilator-responsive bronchiolar obstruction in term neonates: a case series
Authors: Ezenwa Beatrice N. , Gai Abdou , Kujabi Ellen , Garba Abdoulie , Suso Yarreh , Sallah Abdulwahab , Obidike Egbuna O.
Published: July 2023

Background

Bronchiolar obstruction, which causes airway obstruction in hyperresponsive airways, often results from the contraction of the airway's smooth muscles, increased viscid mucous secretions, and mucosal oedema consequent upon a reduced cyclic 3,5-adenosine monophosphate (c-AMP). These processes respond to bronchodilators. The six cases presented to us, in Edward Francis Small Teaching Hospital (EFSTH), Banjul, The Gambia, in the newborn period with clinical features suggesting obstruction with airway reactivity with response to bronchodilator treatment are presented here. Our capacity-limited literature search did not show any such report in neonates. This report highlights the need for this condition to be sought in neonates, medically managed in resource-poor countries without resorting to high-cost equipment use, and for its possible future classification.

Case presentation

We report six cases of Gambian neonates consisting of four males and two females ages 2–27 days who presented to us with histories of fast breathing of a few hours duration and expiratory respiratory distress. All were term babies with rhonchi and demonstrable prolonged expiration with terminal effort. They all had a diagnosis of hyperreactive airway disease with bronchiolar obstruction. Five cases were first-time wheezers, while one was a recurrence. All were eventually treated with bronchodilators and steroids with good results. The median duration for resolution of most symptoms with treatment was two days, with a range of 1–5 days.

Conclusion

Clinically determined bronchiolar obstructions in term neonates can be relieved with bronchodilators and steroids, and this treatment modality, if employed where the pathological process can be established, can reduce the demand on scarce resources in resource-poor countries.
Determinants of agro-pastoralists’ willingness to pay for improved contagious caprine pleuropneumonia vaccine in Kenya
Authors: Ouya Fredrick Ochieng , Bett Eric , Nguhiu Purity , Makokha Stella , Lutta Harrison , Abwao Willis Adero , Mwirigi Martin
Published: July 2023

Animal health care is critical for livestock production especially in arid and semi-arid areas where majority are agro-pastoralists. Contagious caprine pleuropneumonia (CCPP) is a highly contagious and fatal disease which commonly affects goats in arid and semi-arid areas. The government has been the major provider of CCPP vaccine and few large-scale farmers who are licensed and able to purchase directly from the vaccine producer. Although the vaccine is sold to farmers at a subsidized price by the government, its distribution has been characterized by scarcity, irregular and late administration by the authority concerned. It is envisioned that if the willingness to pay for the CCPP vaccine among the agro-pastoralists was high, the sustainability for the vaccine availability and accessibility to everyone will be assured. This study was conducted in Kajiado and Taita Taveta counties where 323 households were sampled; thus, 276 households who were aware of the CCPP were considered for the analysis. Double-bounded dichotomous choice contingent valuation model was used to elicit agro-pastoralists’ willingness to pay for the improved CCPP vaccine with new attributes. The model revealed that off-farm income, membership to a group, previous experience on CCPP attack on goats and access to extension services positively influenced households’ willingness to pay for the improved CCPP vaccine. The results implied that provision of extension services by the government through promotion of public awareness on CCPP and on the benefit of vaccination will motivate farmers to willingly pay for vaccination services. This can be done through enhanced trainings, seminars and demonstrations to the village level, encouraging formation of groups which facilitates information sharing between agro-pastoralists as awareness and knowledge can drive the demand for the improved CCPP vaccine.
Exploring the cellular and molecular differences between ovarian clear cell carcinoma and high-grade serous carcinoma using single-cell RNA sequencing and GEO gene expression signatures
Authors: Guo Dan , Zhang Sumei , Gao Yike , Shi Jinghua , Wang Xiaoxi , Zhang Zixin , Zhang Yaran , Wang Yuming , Zhao Kun , Li Mei , Wang Anqi , Wang Pan , Gou Yanqin , Zhang Miao , Liu Meiyu , Zhang Yuhan , Chen Rui , Sun Jian , Wang Shu , Wu Xunyao , Liang Zhiyong , Chen Jie , Lang Jinghe
Published: July 2023

The two most prevalent subtypes of epithelial ovarian carcinoma (EOC) are ovarian clear cell carcinoma (OCCC) and high-grade serous ovarian carcinoma (HGSC). Patients with OCCC have a poor prognosis than those with HGSC due to chemoresistance, implying the need for novel treatment target. In this study, we applied single-cell RNA sequencing (scRNA-seq) together with bulk RNA-seq data from the GEO (Gene Expression Omnibus) database (the GSE189553 dataset) to characterize and compare tumor heterogeneity and cell-level evolution between OCCC and HGSC samples. To begin, we found that the smaller proportion of an epithelial OCCC cell subset in the G2/M phase might explain OCCC chemoresistance. Second, we identified a possible pathogenic OCCC epithelial cell subcluster that overexpresses LEFTY1. Third, novel biomarkers separating OCCC from HGSC were discovered and subsequently validated on a wide scale using immunohistochemistry. Amine oxidase copper containing 1 (AOC1) was preferentially expressed in OCCC over HGSC, while S100 calcium-binding protein A2 (S100A2) was detected less frequently in OCCC than in HGSC. In addition, we discovered that metabolic pathways were enriched in the epithelial compartment of the OCCC samples. In vitro experiments verified that inhibition of oxidative phosphorylation or glycolysis pathways exerted direct antitumor effects on both OCCC and HGSC cells, while targeting glutamine metabolism or ferroptosis greatly attenuated chemosensitivity only in OCCC cells. Finally, to determine whether there were any variations in immune cell subsets between OCCC and HGSC, data from scRNA-seq and mass cytometry were pooled for analysis. In summary, our work provides the first holistic insights into the cellular and molecular distinctions between OCCC and HGSC and is a valuable source for discovering new targets to leverage in clinical treatments to improve the poor prognosis of patients with OCCC.
Experimental and Numerical Analysis of the Ribbed Reinforced Concrete Fracture Behavior Based on the Mesoscale FE Model
Authors: Wang Zhanliang , Zhang Wei , Huang Yiqun
Published: July 2023

This study presented a meso-model for the fracture analysis of the reinforced concrete (RC) structure. A modeling method of RC meso-structure was proposed, and the rebars were allowed to separate from the concrete. The model was built using the cohesive zone model (CZM). The zero-thickness cohesive elements were adopted to characterize the mechanical behavior of potential fracture surfaces and rebar–concrete interfaces. The constitutive model for concrete was developed by considering the damage relation and friction effect, and the corresponding constitutive for the rebar–concrete interface (especially ribbed rebar) was developed by considering the influence of normal separation on the tangential bond–slip relation. To validate the proposed meso-model, a series of ribbed RC beams with an initial notch was designed and tested by four-point bending loading to obtain different fracture patterns. Through comparison, the developed RC meso-model was validated to simulate the RC structure's fracture behavior appropriately. The influence of the rebar–concrete interface constitutive model on the simulation results was investigated. The investigation results indicate that neglecting normal separation would result in an overestimation of the structure's stiffness and bearing capacity (the peak load was overestimated by more than 10%). Finally, an analysis was conducted on the energy consumption during the failure process of the RC beams. It was found that the proportion of energy consumption during tensile failure of the beam decreased from approximately 86% to 89% in the early stage to approximately 43% to 52% in the later stage, indicating a transition in the beam's failure mode from tensile failure to shear failure.
Transcriptome and proteome analysis reveals the anti-cancer properties of Hypnea musciformis marine macroalga extract in liver and intestinal cancer cells
Authors: Begolli Rodiola , Chatziangelou Myrto , Samiotaki Martina , Goutas Andreas , Barda Sofia , Goutzourelas Nikolaos , Kevrekidis Dimitrios Phaedon , Malea Paraskevi , Trachana Varvara , Liu Ming , Lin Xiukun , Kollatos Nikolaos , Stagos Dimitrios , Giakountis Antonis
Published: July 2023

Background

Marine seaweeds are considered as a rich source of health-promoting compounds by the food and pharmaceutical industry. Hypnea musciformis is a marine red macroalga (seaweed) that is widely distributed throughout the world, including the Mediterranean Sea. It is known to contain various bioactive compounds, including sulfated polysaccharides, flavonoids, and phlorotannins. Recent studies have investigated the potential anticancer effects of extracts from H. musciformis demonstrating their cytotoxic effects on various cancer cell lines. The anticancer effects of these extracts are thought to be due to the presence of bioactive compounds, particularly sulfated polysaccharides, which have been shown to have anticancer and immunomodulatory effects. However, further studies are needed to fully understand the molecular mechanisms that underlie their anticancer effects and to determine their potential as therapeutic agents for cancer treatment.

Methods

H. musciformis was collected from the Aegean Sea (Greece) and used for extract preparation. Transcriptome and proteome analysis was performed in liver and colon cancer human cell lines following treatment with H. musciformis seaweed extracts to characterize its anticancer effect in detail at the molecular level and to link transcriptome and proteome responses to the observed phenotypes in cancer cells.

Results

We have identified that treatment with the seaweed extract triggers a p53-mediated response at the transcriptional and protein level in liver cancer cells, in contrast to colon cancer cells in which the effects are more associated with metabolic changes. Furthermore, we show that in treated HepG2 liver cancer cells, p53 interacts with the chromatin of several target genes and facilitates their upregulation possibly through the recruitment of the p300 co-activator.

Conclusions

Overall, the available evidence suggests that extracts from H. musciformis have the potential to serve as a source of anticancer agents in liver cancer cells mainly through activation of a p53-mediated anti-tumor response that is linked to inhibition of cellular proliferation and induction of cell death.