bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association reveals host-specific genomic traits in Escherichia coli
Authors: Tiwari Sumeet K. , van der Putten Boas C. L. , Fuchs Thilo M. , Vinh Trung N. , Bootsma Martin , Oldenkamp Rik , La Ragione Roberto , Matamoros Sebastien , Hoa Ngo T. , Berens Christian , Leng Joy , Álvarez Julio , Ferrandis-Vila Marta , Ritchie Jenny M. , Fruth Angelika , Schwarz Stefan , Domínguez Lucas , Ugarte-Ruiz María , Bethe Astrid , Huber Charlotte , Johanns Vanessa , Stamm Ivonne , Wieler Lothar H. , Ewers Christa , Fivian-Hughes Amanda , Schmidt Herbert , Menge Christian , Semmler Torsten , Schultsz Constance
Published: April 2023

Background

Escherichia coli is an opportunistic pathogen which colonizes various host species. However, to what extent genetic lineages of E. coli are adapted or restricted to specific hosts and the genomic determinants of such adaptation or restriction is poorly understood.

Results

We randomly sampled E. coli isolates from four countries (Germany, UK, Spain, and Vietnam), obtained from five host species (human, pig, cattle, chicken, and wild boar) over 16 years, from both healthy and diseased hosts, to construct a collection of 1198 whole-genome sequenced E. coli isolates. We identified associations between specific E. coli lineages and the host from which they were isolated. A genome-wide association study (GWAS) identified several E. coli genes that were associated with human, cattle, or chicken hosts, whereas no genes associated with the pig host could be found. In silico characterization of nine contiguous genes (collectively designated as nan-9) associated with the human host indicated that these genes are involved in the metabolism of sialic acids (Sia). In contrast, the previously described sialic acid regulon known as sialoregulon (i.e. nanRATEK-yhcH, nanXY, and nanCMS) was not associated with any host species. In vitro growth experiments with a Δnan-9 E. coli mutant strain, using the sialic acids 5-N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) as sole carbon source, showed impaired growth behaviour compared to the wild-type.

Conclusions

This study provides an extensive analysis of genetic determinants which may contribute to host specificity in E. coli. Our findings should inform risk analysis and epidemiological monitoring of (antimicrobial resistant) E. coli.
Cost-effectiveness of pharmaceutical strategies to prevent respiratory syncytial virus disease in young children: a decision-support model for use in low-income and middle-income countries
Authors: Mahmud Sarwat , Baral Ranju , Sanderson Colin , Pecenka Clint , Jit Mark , Li You , Clark Andrew
Published: April 2023

Background

Respiratory syncytial virus (RSV) is a leading cause of respiratory disease in young children. A number of mathematical models have been used to assess the cost-effectiveness of RSV prevention strategies, but these have not been designed for ease of use by multidisciplinary teams working in low-income and middle-income countries (LMICs).

Methods

We describe the UNIVAC decision-support model (a proportionate outcomes static cohort model) and its approach to exploring the potential cost-effectiveness of two RSV prevention strategies: a single-dose maternal vaccine and a single-dose long-lasting monoclonal antibody (mAb) for infants. We identified model input parameters for 133 LMICs using evidence from the literature and selected national datasets. We calculated the potential cost-effectiveness of each RSV prevention strategy (compared to nothing and to each other) over the lifetimes of all children born in the year 2025 and compared our results to a separate model published by PATH. We ran sensitivity and scenario analyses to identify the inputs with the largest influence on the cost-effectiveness results.

Results

Our illustrative results assuming base case input assumptions for maternal vaccination ($3.50 per dose, 69% efficacy, 6 months protection) and infant mAb ($3.50 per dose, 77% efficacy, 5 months protection) showed that both interventions were cost-saving compared to status quo in around one-third of 133 LMICs, and had a cost per DALY averted below 0.5 times the national GDP per capita in the remaining LMICs. UNIVAC generated similar results to a separate model published by PATH. Cost-effectiveness results were most sensitive to changes in the price, efficacy and duration of protection of each strategy, and the rate (and cost) of RSV hospital admissions.

Conclusions

Forthcoming RSV interventions (maternal vaccines and infant mAbs) are worth serious consideration in LMICs, but there is a good deal of uncertainty around several influential inputs, including intervention price, efficacy, and duration of protection. The UNIVAC decision-support model provides a framework for country teams to build consensus on data inputs, explore scenarios, and strengthen the local ownership and policy-relevance of results.
The burden of RSV-associated illness in children aged < 5 years, South Africa, 2011 to 2016
Authors: Moyes Jocelyn , Tempia Stefano , Walaza Sibongile , McMorrow Meredith L. , Treurnicht Florette , Wolter Nicole , von Gottberg Anne , Kahn Kathleen , Cohen Adam L. , Dawood Halima , Variava Ebrahim , Cohen Cheryl
Published: April 2023

Background

Vaccines and monoclonal antibodies to protect the very young infant against the respiratory syncytial virus (RSV)-associated illness are effective for limited time periods. We aimed to estimate age-specific burden to guide implementation strategies and cost-effectiveness analyses.

Methods

We combined case-based surveillance and ecological data to generate a national estimate of the burden of RSV-associated acute respiratory illness (ARI) and severe acute respiratory illness (SARI) in South African children aged < 5 years (2011–2016), including adjustment for attributable fraction. We estimated the RSV burden by month of life in the < 1-year age group, by 3-month intervals until 2 years, and then 12 monthly intervals to < 5 years for medically and non-medically attended illness.

Results

We estimated a mean annual total (medically and non-medically attended) of 264,112 (95% confidence interval (CI) 134,357–437,187) cases of RSV-associated ARI and 96,220 (95% CI 66,470–132,844) cases of RSV-associated SARI (4.7% and 1.7% of the population aged < 5 years, respectively). RSV-associated ARI incidence was highest in 2-month-old infants (18,361/100,000 population, 95% CI 9336–28,466). The highest incidence of RSV-associated SARI was in the < 1-month age group 14,674/100,000 (95% CI 11,175–19,645). RSV-associated deaths were highest in the first and second month of life (110.8 (95% CI 74.8–144.5) and 111.3 (86.0–135.8), respectively).

Conclusions

Due to the high burden of RSV-associated illness, specifically SARI cases in young infants, maternal vaccination and monoclonal antibody products delivered at birth could prevent significant RSV-associated disease burden.
WFS1 autosomal dominant variants linked with hearing loss: update on structural analysis and cochlear implant outcome
Authors: Lim Hui Dong , Lee So Min , Yun Ye Jin , Lee Dae Hee , Lee Jun Ho , Oh Seung-Ha , Lee Sang-Yeon
Published: April 2023

Background

Wolfram syndrome type 1 gene (WFS1), which encodes a transmembrane structural protein (wolframin), is essential for several biological processes, including proper inner ear function. Unlike the recessively inherited Wolfram syndrome,WFS1heterozygous variants cause DFNA6/14/38 and wolfram-like syndrome, characterized by autosomal dominant nonsyndromic hearing loss, optic atrophy, and diabetes mellitus. Here, we identified twoWFS1heterozygous variants in three DFNA6/14/38 families using exome sequencing. We reveal the pathogenicity of theWFS1variants based on three-dimensional (3D) modeling and structural analysis. Furthermore, we present cochlear implantation (CI) outcomes inWFS1-associated DFNA6/14/38 and suggest a genotype-phenotype correlation based on our results and a systematic review.

Methods

We performed molecular genetic test and evaluated clinical phenotypes of threeWFS1-associated DFNA6/14/38 families. A putative WFS1–NCS1 interaction model was generated, and the impacts ofWFS1variants on stability were predicted by comparing intramolecular interactions. A total of 62WFS1variants associated with DFNA6/14/38 were included in a systematic review.

Results

One variant is a known mutational hotspot variant in the endoplasmic reticulum (ER)-luminal domain WFS1(NM_006005.3) (c.2051 C > T:p.Ala684Val), and the other is a novel frameshift variant in transmembrane domain 6 (c.1544_1545insA:p.Phe515LeufsTer28). The two variants were pathogenic, based on the ACMG/AMP guidelines. Three-dimensional modeling and structural analysis show that non-polar, hydrophobic substitution of Ala684 (p.Ala684Val) destabilizes the alpha helix and contributes to the loss of WFS1-NCS1 interaction. Also, the p.Phe515LeufsTer28 variant truncates transmembrane domain 7–9 and the ER-luminal domain, possibly impairing membrane localization and C-terminal signal transduction. The systematic review demonstrates favorable outcomes of CI. Remarkably, p.Ala684Val inWFS1is associated with early-onset severe-to-profound deafness, revealing a strong candidate variant for CI.

Conclusions

We expanded the genotypic spectrum ofWFS1heterozygous variants underlying DFNA6/14/38 and revealed the pathogenicity of mutant WFS1, providing a theoretical basis for WFS1-NCS1 interactions. We presented a range of phenotypic traits forWFS1heterozygous variants and demonstrated favorable functional CI outcomes, proposing p.Ala684Val a strong potential marker for CI candidates.
Cascade amplification of tumor chemodynamic therapy and starvation with re-educated TAMs via Fe-MOF based functional nanosystem
Authors: Zheng Xinmin , Li Xiang , Meng Siyu , Shi Guolin , Li Hui , Du Huiping , Dai Liangliang , Yang Hui
Published: April 2023

Tumor microenvironment is characterized by the high concentration of reactive oxygen species (ROS), which is an effective key used to open the Pandora’s Box against cancer. Herein, a tumor-targeted nanosystem HFNP@GOX@PFC composed of ROS-cleaved Fe-based metal–organic framework, hyaluronic acid (HA), glucose oxidase (GOX) and perfluorohexane (PFC) has been developed for tumor cascade amplified starvation and chemodynamic therapy (CDT). In response to the high concentration of hydrogen peroxide (H2O2) intratumorally, HFNP@GOX@PFC endocytosed by tumor cells can specially be disassembled and release GOX, PFC and Fe2+, which can collectively starve tumor and self-produce additional H2O2 via competitively glucose catalyzing, supply oxygen to continuous support GOX-mediated starvation therapy, initiate CDT and cascade amplify oxidative stress via Fe2+-mediated Fenton reaction, leading to the serious tumor damage with activated p53 signal pathway. Moreover, HFNP@GOX@PFC also significantly initiates antitumor immune response via re-educating tumor-associated macrophages (TAMs) by activating NF-κB and MAPK signal pathways. In vitro and in vivo results collectively demonstrate that nanosystem not only continuously initiates starvation therapy, but also pronouncedly cascade-amplify CDT and polarize TAMs, consequently efficiently inhibiting tumor growth with good biosafety. The functional nanosystem combined the cascade amplification of starvation and CDT provides a new nanoplatform for tumor therapy.
RA-RAR signaling promotes mouse vaginal opening through increasing β-catenin expression and vaginal epithelial cell apoptosis
Authors: Zheng Nana , Zhang Wenbo , Zhang Xiaodan , Li Biao , Wu Zhanying , Weng Yashuang , Wang Weiyong , Miao Jingjing , Yang Jing , Zhang Meijia , Xia Wei
Published: April 2023

Background

Retinoic acid (RA) plays important role in the maintenance and differentiation of the Müllerian ducts during the embryonic stage via RA receptors (RARs). However, the function and mechanism of RA-RAR signaling in the vaginal opening are unknown.

Method

We used the Rarα knockout mouse model and the wild-type ovariectomized mouse models with subcutaneous injection of RA (2.5 mg/kg) or E2 (0.1 µg/kg) to study the role and mechanism of RA-RAR signaling on the vaginal opening. The effects of Rarα deletion on Ctnnb1 mRNA levels and cell apoptosis in the vaginas were analyzed by real-time PCR and immunofluorescence, respectively. The effects of RA on the expression of β-catenin and apoptosis in the vaginas were analyzed by real-time PCR and western blotting. The effects of E2 on RA signaling molecules were analyzed by real-time PCR and western blotting.

Results

RA signaling molecules were expressed in vaginal epithelial cells, and the mRNA and/or protein levels of RALDH2, RALDH3, RARα and RARγ reached a peak at the time of vaginal opening. The deletion of Rarα resulted in 25.0% of females infertility due to vaginal closure, in which the mRNA (Ctnnb1, Bak and Bax) and protein (Cleaved Caspase-3) levels were significantly decreased, and Bcl2 mRNA levels were significantly increased in the vaginas. The percentage of vaginal epithelium with TUNEL- and Cleaved Caspase-3-positive signals were also significantly decreased in Rarα−/− females with vaginal closure. Furthermore, RA supplementation of ovariectomized wild-type (WT) females significantly increased the expression of β-catenin, active β-catenin, BAK and BAX, and significantly decreased BCL2 expression in the vaginas. Thus, the deletion of Rarα prevents vaginal opening by reducing the vaginal β-catenin expression and epithelial cell apoptosis. The deletion of Rarα also resulted in significant decreases in serum estradiol (E2) and vagina Raldh2/3 mRNA levels. E2 supplementation of ovariectomized WT females significantly increased the expression of RA signaling molecules in the vaginas, suggesting that the up-regulation of RA signaling molecules in the vaginas is dependent on E2 stimulation.

Conclusion

Taken together, we propose that RA-RAR signaling in the vaginas promotes vaginal opening through increasing β-catenin expression and vaginal epithelial cell apoptosis.
Intercellular adhesion molecule 4 and ischemic stroke: a two-sample Mendelian randomization study
Authors: Sun Lulu , Guo Daoxia , Jia Yiming , Shi Mengyao , Yang Pinni , Wang Yu , Liu Fanghua , Zhu Zhengbao , Zheng Jin
Published: April 2023

Background

Experimental studies suggested that intercellular adhesion molecule 4 (ICAM-4) might be implicated in ischemic stroke, but the population-based evidence on the relationship between ICAM-4 and ischemic stroke were limited. Herein, we performed a two-sample Mendelian randomization (MR) analysis to investigate the associations of genetically determined plasma ICAM-4 with the risks of ischemic stroke and its subtypes.

Methods

A total of 11 single-nucleotide polymorphisms associated with ICAM-4 were selected as instrumental variables based on the genome-wide association studies (GWAS) with 3,301 European individuals. Summary-level data about ischemic stroke and its subtypes were obtained from the Multi-ancestry GWAS launched by the International Stroke Genetics Consortium. We used the inverse-variance weighted method followed by a series of sensitivity analyses to evaluate the associations of genetically determined ICAM-4 with the risks of ischemic stroke and its subtypes.

Results

Genetically determined higher ICAM-4 levels were significantly associated with increased risks of ischemic stroke (in the IVW method fitted to multiplicative random effects model: odds ratio [OR] per standard deviation [SD] increase, 1.04; 95% confidence interval [CI], 1.01–1.07; P = 0.006; in the IVW analysis with fixed effects model: OR per SD increase, 1.04; 95% CI, 1.01–1.07; P = 0.003) and cardioembolic stroke (in multiplicative random effects model: OR per SD increase, 1.08; 95% CI, 1.02–1.14; P = 0.004; in fixed effects model: OR per SD increase, 1.08; 95% CI, 1.03–1.13; P = 0.003). There was no association of ICAM-4 with the risks of large artery stroke and small vessel stroke. MR-Egger regression showed no directional pleiotropy for all associations, and the sensitivity analyses with different MR methods further confirmed these findings.

Conclusions

We found positive associations of genetically determined plasma ICAM-4 with the risks of ischemic stroke and cardioembolic stroke. Future studies are needed to explore the detailed mechanism and investigate the targeting effect of ICAM-4 on ischemic stroke.
Antibiotic use in acute mesenteric ischemia: a review of the evidence and call to action
Authors: Tian Yuqian , Dhara Sanjeev , Barrett Christopher D. , Richman Aaron P. , Brahmbhatt Tejal S.
Published: April 2023

Acute mesenteric ischemia (AMI) is a life-threatening condition with a high mortality rate. The standard practice after making the diagnosis includes aggressive resuscitation, anticoagulation, followed by revascularization and resection of necrotic bowel. The role of empiric antibiotics in the management of AMI is not well defined in the literature. This review article aims to examine our current understanding on this matter, based on bench research and clinical studies. It is demonstrated in animal study model that the ischemia/reperfusion (I/R) injury damages intestinal epithelium, and subsequently lead to barrier dysfunction, a condition that can support bacterial translocation through a complex interplay between the intestinal epithelium, the intestinal immune system and the intestine’s endogenous bacterial population. Based on this mechanism, it is possible that the use of antibiotics may help mitigate the consequences of I/R injury, which is examined in few animal studies. In clinical practice, many guidelines support the use of prophylactic antibiotics, based on a meta-analysis of randomized control trials (RCTs) demonstrating the benefit of antibiotics in multi-organ dysfunction syndrome. However, there is no direct reference to AMI in this meta-analysis. Most clinical studies that focus on AMI and mentions the use of antibiotics are retrospective and single institution, and very few comments on the role of antibiotics in their discussions. We conclude that there is limited evidence in literature to support the use of prophylactic antibiotic in AMI to improve outcome. More clinical studies with high level of evidence and basic science research are needed to improve our understanding on this topic and ultimately help build a better clinical pathway for patients with AMI.
Insights into the impact of hepatitis B virus on hepatic stellate cell activation
Authors: You Hongjuan , Wang Xing , Ma Lihong , Zhang Fulong , Zhang Huanyang , Wang Yuxin , Pan Xiucheng , Zheng Kuiyang , Kong Fanyun , Tang Renxian
Published: April 2023

During chronic hepatitis B virus (HBV) infection, hepatic fibrosis is a serious pathological condition caused by virus-induced liver damage. The activation of hepatic stellate cells (HSCs) is a central event in the occurrence and progression of liver fibrosis. Although accumulating evidence has shown that HBV directly stimulates HSC activation, whether the virus infects and replicates in HSCs remains controversial. Inflammation is one of the obvious characteristics of chronic HBV infection, and it has been demonstrated that persistent inflammation has a predominant role in triggering and maintaining liver fibrosis. In particular, the regulation of HSC activation by HBV-related hepatocytes via various inflammatory modulators, including TGF-β and CTGF, in a paracrine manner has been reported. In addition to these inflammation-related molecules, several inflammatory cells are essential for the progression of HBV-associated liver fibrosis. Monocytes, macrophages, Th17 cells, NK cells, as well as NKT cells, participate in the modulation of HBV-related liver fibrosis by interacting with HSCs. This review summarizes current findings on the effects of HBV and the relevant molecular mechanisms involved in HSC activation. Because HSC activation is essential for liver fibrosis, targeting HSCs is an attractive therapeutic strategy to prevent and reverse hepatic fibrosis induced by HBV infection.
Generative adversarial networks in EEG analysis: an overview
Authors: Habashi Ahmed G. , Azab Ahmed M. , Eldawlatly Seif , Aly Gamal M.
Published: April 2023

Electroencephalogram (EEG) signals have been utilized in a variety of medical as well as engineering applications. However, one of the challenges associated with recording EEG data is the difficulty of recording large amounts of data. Consequently, data augmentation is a potential solution to overcome this challenge in which the objective is to increase the amount of data. Inspired by the success of Generative Adversarial Networks (GANs) in image processing applications, generating artificial EEG data from the limited recorded data using GANs has seen recent success. This article provides an overview of various techniques and approaches of GANs for augmenting EEG signals. We focus on the utility of GANs in different applications including Brain-Computer Interface (BCI) paradigms such as motor imagery and P300-based systems, in addition to emotion recognition, epileptic seizures detection and prediction, and various other applications. We address in this article how GANs have been used in each study, the impact of using GANs on the model performance, the limitations of each algorithm, and future possibilities for developing new algorithms. We emphasize the utility of GANs in augmenting the limited EEG data typically available in the studied applications.
SARS-CoV-2 infection aggravates cigarette smoke-exposed cell damage in primary human airway epithelia
Authors: Chen Rui , Hui Kenrie Pui-Yan , Liang Yingmin , Ng Ka-Chun , Nicholls John Malcolm , Ip Mary Sau-Man , Peiris Malik , Chan Michael Chi-Wai , Mak Judith Choi-Wo
Published: April 2023

Background

The coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic with over 627 million cases and over 6.5 million deaths. It was reported that smoking-related chronic obstructive pulmonary disease (COPD) might be a crucial risk for COVID-19 patients to develop severe condition. As cigarette smoke (CS) is the major risk factor for COPD, we hypothesize that barrier dysfunction and an altered cytokine response in CS-exposed airway epithelial cells may contribute to increased SARS-CoV-2-induced immune response that may result in increased susceptibility to severe disease. The aim of this study was to evaluate the role of CS on SARS-CoV-2-induced immune and inflammatory responses, and epithelial barrier integrity leading to airway epithelial damage.

Methods

Primary human airway epithelial cells were differentiated under air-liquid interface culture. Cells were then exposed to cigarette smoke medium (CSM) before infection with SARS-CoV-2 isolated from a local patient. The infection susceptibility, morphology, and the expression of genes related to host immune response, airway inflammation and damages were evaluated.

Results

Cells pre-treated with CSM significantly caused higher replication of SARS-CoV-2 and more severe SARS-CoV-2-induced cellular morphological alteration. CSM exposure caused significant upregulation of long form angiotensin converting enzyme (ACE)2, a functional receptor for SARS-CoV-2 viral entry, transmembrane serine protease (TMPRSS)2 and TMPRSS4, which cleave the spike protein of SARS-CoV-2 to allow viral entry, leading to an aggravated immune response via inhibition of type I interferon pathway. In addition, CSM worsened SARS-CoV-2-induced airway epithelial cell damage, resulting in severe motile ciliary disorder, junctional disruption and mucus hypersecretion.

Conclusion

Smoking led to dysregulation of host immune response and cell damage as seen in SARS-CoV-2-infected primary human airway epithelia. These findings may contribute to increased disease susceptibility with severe condition and provide a better understanding of the pathogenesis of SARS-CoV-2 infection in smokers.
Movement of cerebrospinal fluid tracer into brain parenchyma and outflow to nasal mucosa is reduced at 24 h but not 2 weeks post-stroke in mice
Authors: Warren K. E. , Coupland K. G. , Hood R. J. , Kang L. , Walker F. R. , Spratt N. J.
Published: April 2023

Background

Recent data indicates that cerebrospinal fluid (CSF) dynamics are disturbed after stroke. Our lab has previously shown that intracranial pressure rises dramatically 24 h after experimental stroke and that this reduces blood flow to ischaemic tissue. CSF outflow resistance is increased at this time point. We hypothesised that reduced transit of CSF through brain parenchyma and reduced outflow of CSF via the cribriform plate at 24 h after stroke may contribute to the previously identified post-stroke intracranial pressure elevation.

Methods

Using a photothrombotic permanent occlusion model of stroke in C57BL/6 adult male mice, we examined the movement of an intracisternally infused 0.5% Texas Red dextran throughout the brain and measured tracer efflux into the nasal mucosa via the cribriform plate at 24 h or two weeks after stroke. Brain tissue and nasal mucosa were collected ex vivo and imaged using fluorescent microscopy to determine the change in CSF tracer intensity in these tissues.

Results

At 24 h after stroke, we found that CSF tracer load was significantly reduced in brain tissue from stroke animals in both the ipsilateral and contralateral hemispheres when compared to sham. CSF tracer load was also reduced in the lateral region of the ipsilateral hemisphere when compared to the contralateral hemisphere in stroke brains. In addition, we identified an 81% reduction in CSF tracer load in the nasal mucosa in stroke animals compared to sham. These alterations to the movement of CSF-borne tracer were not present at two weeks after stroke.

Conclusions

Our data indicates that influx of CSF into the brain tissue and efflux via the cribriform plate are reduced 24 h after stroke. This may contribute to reported increases in intracranial pressure at 24 h after stroke and thus worsen stroke outcomes.
Biomechanical study of different fixation constructs for anterior column and posterior hemi-transverse acetabular fractures: a finite element analysis
Authors: Chen Kaifang , Huang Guixiong , Wan Yizhou , Yao Sheng , Su Yanlin , Li Lianxin , Guo Xiaodong
Published: April 2023

Background

To compare the biomechanical properties and stability, using a finite element model, of four fixation constructs used for the treatment of anterior column and posterior hemi-transverse (ACPHT) acetabular fractures under two physiological loading conditions (standing and sitting).

Methods

A finite element model simulating ACPHT acetabular fractures was created for four different scenarios: a suprapectineal plate combined with posterior column and infra-acetabular screws (SP-PS-IS); an infrapectineal plate combined with posterior column and infra-acetabular screws (IP-PS-IS); a special infrapectineal quadrilateral surface buttress plate (IQP); and a suprapectineal plate combined with a posterior column plate (SP-PP). Three-dimensional finite element stress analysis was performed on these models with a load of 700 N in standing and sitting positions. Biomechanical stress distributions and fracture displacements were analysed and compared between these fixation techniques.

Results

In models simulating the standing position, high displacements and stress distributions were observed at the infra-acetabulum regions. The degree of these fracture displacements was low in the IQP (0.078 mm), as compared to either the IP-PS-IS (0.079 mm) or the SP & PP (0.413 mm) fixation constructs. However, the IP-PS-IS fixation construct had the highest effective stiffness. In models simulating the sitting position, high fracture displacements and stress distributions were observed at the regions of the anterior and posterior columns. The degree of these fracture displacements was low in the SP-PS-IS (0.101 mm), as compared to the IP-PS-IS (0.109 mm) and the SP-PP (0.196 mm) fixation constructs.

Conclusion

In both standing and sitting positions, the stability and stiffness index were comparable between the IQP, SP-PS-IS, and IP-PS-IS. These 3 fixation constructs had smaller fracture displacements than the SP-PP construct. The stress concentrations at the regions of quadrilateral surface and infra-acetabulum suggest that the buttressing fixation of quadrilateral plate was required for ACPHT fractures.
Baicalein alleviates TNF-α-induced apoptosis of human nucleus pulposus cells through PI3K/AKT signaling pathway
Authors: Liu Yang , Liu Dao-kuo , Wang Zhi-wei , Zhao Chong , Miao Jun
Published: April 2023

Background

Nucleus pulposus (NP) cell apoptosis contributed to disc degeneration. Baicalein, a natural steroid saponin, has been demonstrated to have anti-inflammatory, antiapoptotic, and antioxidative effects in various diseases.However, little is known about the roles of baicalein in intervertebral disc degeneration.

Methods

To evaluate the roles of baicalein in disc degeneration and its specific mechanism, human NP cells were incubated with TNF-α and various concentrations of baicalein. Cell viability, extracellular matrix protein expression, catabolic factors, degree of apoptosis, inflammatory factors, and related signaling pathways were evaluated by western blotting, fluorescence immunostaining, TUNEL staining, and reverse transcription PCR.

Results

Baicalein inhibited TNF-α-activated apoptotic signaling and catabolic activity in NP cells. Baicalein promoted PI3K/Akt signaling and attenuated the level of apoptosis-related markers in TNF-α-stimulated human NP cells.

Conclusion

Our work provides that baicalein attenuates TNF-α-activated apoptosis in human NP cells through promoting the PI3K/Akt pathway, indicating that baicalein is a new potential candidate for clinical therapy to attenuate disc degeneration.
One-stage VATS surgery for synchronous bilateral lung lesion: a safe and feasible procedure
Authors: Wang Zhe , Zhang Xue , Sun Xusheng , Liu Junfeng
Published: April 2023

Background

Synchronous bilateral lung lesions are emerging as a common but tricky disease for surgical management. Whether one or two-stage surgery should be taken remains in debate. We retrospectively analysed 151 patients who underwent one and two-stage Video Assisted Thoracic Surgery (VATS) to investigate the safety and feasibility of the two surgical approaches.

Methods

A total of 151 patients were included in the study. Propensity score matching was performed to minimize the baseline characteristics difference between one and two-stage groups. Clinical factors including in-hospital days after surgery, chest tube drainage days, types and severity of post-operative complications were compared between the two groups. Logistic univariate and multivariate analyses were used to find the risk factors for post-operative complications. Nomogram was built to select the low risk candidates for the one-stage VATS.

Results

After propensity score matching, 36 one-stage and 23 two-stage patients were enrolled. The age (p = 0.669), gender (p = 0.3655), smoking status (p = 0.5555), pre-operative comorbidity (p = 0.8162), surgical resection (p = 0.798) and lymph node dissection (p = 9036) were balanced between the two groups. There was no difference in post-surgery hospital days (8.67 ± 2.68 versus 8.46 ± 2.92, p = 0.7711) and chest tube retaining days (5.47 ± 2.20 versus 5.46 ± 1.95, p = 0.9772). Moreover, post-operative complications also showed no difference between one-stage and two-stage groups (p = 0.3627). Univariate and multivariate analysis revealed that advanced age (p = 0.0495), pre-surgical low haemoglobin (p = 0.045) and blood loss (p = 0.002) were risk factors for post-operative complications. Nomogram built with the three risk factors showed reasonable predictive value.

Conclusions

One-stage VATS for synchronous bilateral lung lesion patients was proved to be a safety procedure. Advanced age, pre-surgical low haemoglobin and blood loss may predict complications after surgery.
Intravenous enoxaparin as alternative ECMO anticoagulation over a period of 94 days: a case report
Authors: Durila Miroslav , Berousek Jan , Vlasakova Vlasta , Vymazal Tomas
Published: April 2023

Background

Unfractionated heparin is used worldwide as a standard anticoagulation therapy for extracorporeal membrane oxygenation (ECMO) machines. However, its use brings about significant bleeding and thrombotic complications for critically ill patients. This case report shows that low molecular weight heparin together with ECMO-produced primary haemostasis pathology can be used as an alternative way of ECMO anticoagulation.

Case presentation

This paper presents the case of a patient with respiratory failure who subsequently suffered from cardiac failure and spent 94 days on combined V-V and V-A ECMO devices (two ECMO devices running simultaneously on one patient) with intravenous enoxaparin used instead of unfractionated heparin anticoagulation. No life-threatening bleeding/thrombotic events happened during this period, nor did any technical problems with ECMO occur.

Conclusions

In this case report, continuous intravenous low molecular weight heparin anticoagulation was used as a safe alternative to ECMO anticoagulation.
Efficacy of endovascular repair in the treatment of retrograde ascending aortic intramural haematoma
Authors: Chen Bailang , Zhang Rui , Liu Haibing , Chen Yao , Wang Zanxin , Wei Minxin
Published: April 2023

Background

The current treatment for retrograde ascending aortic intramural hematoma (RAIMH) remains challenging. This study aims to summarize the short-term results of endovascular repair in the treatment of retrograde ascending aortic intramural hematoma.

Methods

Between June 2019 and June 2021, 21 patients (16 males and 5 females) with a retrograde ascending aortic intramural hematoma, aged 53 ± 14years, received an endovascular repair in our hospital. All cases involved an ascending aortic or aortic arch intramural hematoma. 15 patients had an ulcer on the descending aorta combined with an intramural hematoma in the ascending aorta and 6 patients had typical dissection changes on the descending aorta combined with an intramural hematoma in the ascending aorta. All patients had a successful endovascular stent-graft repair, with 10 cases operated on in the acute phase (<14 days) and 11 cases in the chronic phase (14–35 days).

Results

A single-branched aortic stent graft system was implanted in 10 cases, a straight stent in 2 cases, and a fenestrated stent in 9 cases. All surgeries were technically successful. One of the patients developed a new rupture 2 weeks after surgery and was converted to a total arch replacement. No perioperative stroke, paraplegia, stent fracture or displacement, limb or abdominal organ ischemia occurred. The intramural hematomas started being absorbed on CT angiography images before discharge. There was no incidence of postoperative 30-day mortality, and the intramural hematomas in the ascending aorta and aortic arch were fully or partly absorbed.

Conclusion

Endovascular repair of retrograde ascending aortic intramural hematoma was shown to be safe and effective, and correlated with favorable short-term results.
Effectiveness of pharmacological cardioversion of new-onset atrial fibrillation during thoracic surgery operations: a single-centre experience
Authors: WU Dehua , LI Qiongzhen , XU Meiying , WU Jingxiang , Yang Jun
Published: April 2023

Objective

Prophylactic pharmacological conversion agents could reduce the incidence of postoperative atrial fibrillation (AF) in patients undergoing thoracic operations. The current study examined whether the use of pharmacological conversion agents could help to restore sinus rhythm in patients with AF newly developed during thoracic operations.

Methods

Medical records of 18,605 patients from January 1, 2015 to December 31, 2019, at the Shanghai Chest Hospital were reviewed. Patients with non-sinus rhythm prior to the surgery (n = 128) were excluded from data analysis. The final analysis included 18,477 patients (n = 16,292 undergoing lung operations; n = 2,185 undergoing esophageal operations).

Results

Intraoperative AF (defined as AF lasting for at least 5 min) occurred in 646 out of a total of 18,477 subjects (3.49%). Within the 646 subjects, 258 received pharmacological conversion agents during the surgery. sinus rhythm was restored in 20.15% (52/248) of patients treated with pharmacological cardioversion and in 20.87% (81/399) patients not receiving pharmacological intervention. In a subgroup analysis of the 258 patients receiving pharmacological conversion agents, recovery of sinus rhythm was highest in beta-blocker group (35.59%, 21/59 vs. 15.78%, 15/95 in amiodarone group, p = 0.008, 5.55%, and 1/18 in amiodarone plus beta-blockers group, p = 0.016). The incidence of hypotension was higher in pharmacological conversion (27.5% vs. 9.3% in patients not receiving pharmacological intervention, p < 0.001). In subjects not recovering to sinus rhythm during the surgery (n = 513), electrical cardioversion in post-anesthesia care unit (PACU) restored sinus rhythm in > 98% of the cases (155/158 vs. 63/355 in subjects not receiving cardioversion; p < 0.001).

Conclusions

Our experience shows that pharmacological conversion, in general, failed to show better treatment effectiveness on intraoperative new-onset AF within period of surgery except for beta-blockers. Patients with AF persisting beyond the surgery could be effectively managed with electrical cardioversion.
Reconstruction of the upper gastrointestinal tract using intra-thoracic Roux-en-Y technique after caustic agent ingestion: a case report from Aleppo, Syria
Authors: Alhames Samer , Alkhaled Mamdouh , Ghabally Mike
Published: April 2023

Background

Caustic substance ingestion is a high-risk medical emergency associated with high mortality and morbidity. To date, there are several treatment options with no standard method of care.

Case presentation

We report a case of a corrosive agent ingestion complicated with third-degree burns and severe stenosis of the esophagus and gastric outlet. After failure of conservative treatment, the patient underwent jejunostomy placement for nutritional support followed by transhiatal esophagectomy with gastric pull-up and intra-thoracic Roux-en-Y gastroenterostomy with good outcomes. The patient recovered from the procedure and has been tolerating oral intake very well with significant weight gain.

Conclusion

We put a new technique for treating severe gastrointestinal injuries caused by corrosive agent ingestion that resulted in both esophageal and gastric outlet strictures. These rare complex cases requires difficult treatment decisions. We believe that this technique provides many benefits for such cases and might be a feasible alternative for colon interposition.
The MANTRA study: a new umbrella concept prospectively applied to assess implantable medical devices for heart valve procedures
Authors: Meuris Bart , Günaydın Serdar , Lancellotti Patrizio , Badano Luigi , Aldea Gabriel , Herrenknecht Rita , Cerutti Elisa , Gaggianesi Sara , Dipinto Silvia , Morando Paola , Kempfert Jörg
Published: April 2023

Background

Clinical evidence is commonly obtained through individual trials that are time-, cost- and resource-consuming, and which often leave unanswered clinically relevant questions. Umbrella studies have been developed to address the need for more efficient and flexible trial structures, predominantly for cancer treatments. The umbrella concept foresees data collection within a unifying trial structure, to which one or more substudies may be added at any time to address product- or therapy-specific questions. To our knowledge, the umbrella concept has not yet been used in the medical device area, but it may offer similar advantages as in other settings, particularly in areas where multiple therapies are available within one large treatment area.

Methods

The MANTRA study (NCT05002543) is a prospective, global, post-marketing clinical follow-up study. The aim is to collect safety and device performance data covering the Corcym cardiac surgery portfolio for the treatment of aortic, mitral, and tricuspid valve diseases. The study uses a master protocol that outlines the main common parameters, and the specific questions are addressed in three substudies. The primary endpoints are device success at 30 days. Secondary endpoints include safety- and device performance-related data at 30 days, 1 year, and then annually through to 10 years. All endpoints are defined according to the more recent guidelines for heart valve procedures. Additionally, procedure and hospitalization information are collected, including Enhanced Recovery after Surgery in sites using such protocols, and patient outcome measures such as New York Heart Association classification and quality-of-life questionnaires.

Results

The study started in June 2021. Enrollment in all three substudies is ongoing.

Conclusions

The MANTRA study will provide contemporary information on the long-term outcomes of medical devices for the treatment of aortic, mitral, and tricuspid heart valve diseases in routine clinical practice. The umbrella approach adopted in the study has the potential of longitudinally assessing long-term efficacy of the devices and the flexibility to investigate new research questions as they arise.
Identifying responders to elamipretide in Barth syndrome: Hierarchical clustering for time series data
Authors: Van den Eynde Jef , Chinni Bhargava , Vernon Hilary , Thompson W. Reid , Hornby Brittany , Kutty Shelby , Manlhiot Cedric
Published: April 2023

Background

Barth syndrome (BTHS) is a rare genetic disease that is characterized by cardiomyopathy, skeletal myopathy, neutropenia, and growth abnormalities and often leads to death in childhood. Recently, elamipretide has been tested as a potential first disease-modifying drug. This study aimed to identify patients with BTHS who may respond to elamipretide, based on continuous physiological measurements acquired through wearable devices.

Results

Data from a randomized, double-blind, placebo-controlled crossover trial of 12 patients with BTHS were used, including physiological time series data measured using a wearable device (heart rate, respiratory rate, activity, and posture) and functional scores. The latter included the 6-minute walk test (6MWT), Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue score, SWAY Balance Mobile Application score (SWAY balance score), BTHS Symptom Assessment (BTHS-SA) Total Fatigue score, muscle strength by handheld dynamometry, 5 times sit-and-stand test (5XSST), and monolysocardiolipin to cardiolipin ratio (MLCL:CL). Groups were created through median split of the functional scores into “highest score” and “lowest score”, and “best response to elamipretide” and “worst response to elamipretide”. Agglomerative hierarchical clustering (AHC) models were implemented to assess whether physiological data could classify patients according to functional status and distinguish non-responders from responders to elamipretide. AHC models clustered patients according to their functional status with accuracies of 60–93%, with the greatest accuracies for 6MWT (93%), PROMIS (87%), and SWAY balance score (80%). Another set of AHC models clustered patients with respect to their response to treatment with elamipretide with perfect accuracy (all 100%).

Conclusions

In this proof-of-concept study, we demonstrated that continuously acquired physiological measurements from wearable devices can be used to predict functional status and response to treatment among patients with BTHS.
Shared decision-making and the caregiver experience in tuberous sclerosis complex: results from a UK survey
Authors: Skrobanski Hanna , Vyas Kishan , Bowditch Sally , Hubig Lena , Dziadulewicz Edward , Fish Louise , Takhar Pooja , Lo Siu Hing
Published: April 2023

Background

Tuberous sclerosis complex (TSC) is a rare genetic condition commonly accompanied by neurological and neuropsychological disorders, resulting in a high burden of illness for individuals and a substantial impact on their caregivers. Due to the diversity and complexity of clinical manifestations, patients with TSC need aligned multidisciplinary healthcare services starting in childhood through to adulthood. However, patients and caregivers are sometimes dissatisfied with the care provided, for which one of the most common reasons is a lack of involvement in clinical decision-making. Shared decision-making, whereby clinicians make clinical management decisions together with patients and their caregivers, is advocated for in the management of epilepsy, but evidence of its benefit in managing TSC is currently lacking. In this cross-sectional, UK-based analysis we used an online survey to capture the experiences of primary caregivers for individuals with TSC, including the impact on work productivity, clinical shared decision-making, satisfaction with care, and the impact of the coronavirus disease 2019 (COVID-19) pandemic.

Results

In total, 73 eligible caregivers provided consent (analysis set), with 14 completing the survey partially and 59 completing the full survey. Many caregivers (72%) reported receiving recommendations about new treatments from their doctor and discussing the treatment together, with a high proportion (89%) preferring that treatment was initiated at a low dose. Most caregivers (69%) were satisfied or extremely satisfied with pediatric TSC healthcare services, but only 25% were satisfied or extremely satisfied with the transition to adult TSC healthcare services. Several (n = 30) caregivers specified the impact of caring on their work productivity and career in optional open-ended survey responses. Finally, 80% of caregivers indicated that the COVID-19 pandemic had a “large” or “very large” impact on their caring activities, negatively affecting the emotional wellbeing and behavior of individuals with TSC, and caregivers’ ability to work and arrange medical appointments.

Conclusions

Caregivers largely feel involved in treatment decisions, and the majority were satisfied with healthcare services for children with TSC. However, many highlighted the need for an improved transition from pediatric to adult healthcare services. The survey also showed that COVID-19 has considerably affected caregivers and individuals with TSC.