bluuebunny/crossref_metadata_2025 huggingface dataset:
RVFScan predicts virulence factor genes and hypervirulence of the clinical metagenome
Authors: Jiang Yue , Hu Xuejiao , Fan Shu , Liu Weijiang , Chen Jingjing , Wang Liang , Deng Qianyun , Yang Jing , Yang Aimei , Lou Zheng , Guan Yuanlin , Xia Han , Gu Bing
Published: November 2023

Bacterial infections often involve virulence factors that play a crucial role in the pathogenicity of bacteria. Accurate detection of virulence factor genes (VFGs) is essential for precise treatment and prognostic management of hypervirulent bacterial infections. However, there is a lack of rapid and accurate methods for VFG identification from the metagenomic data of clinical samples. Here, we developed a Reads-based Virulence Factors Scanner (RVFScan), an innovative user-friendly online tool that integrates a comprehensive VFG database with similarity matrix-based criteria for VFG prediction and annotation using metagenomic data without the need for assembly. RVFScan demonstrated superior performance compared to previous assembly-based and read-based VFG predictors, achieving a sensitivity of 97%, specificity of 98% and accuracy of 98%. We also conducted a large-scale analysis of 2425 clinical metagenomic datasets to investigate the utility of RVFScan, the species-specific VFG profiles and associations between VFGs and virulence phenotypes for 24 important pathogens were analyzed. By combining genomic comparisons and network analysis, we identified 53 VFGs with significantly higher abundances in hypervirulent Klebsiella pneumoniae (hvKp) than in classical K. pneumoniae. Furthermore, a cohort of 1256 samples suspected of K. pneumoniae infection demonstrated that RVFScan could identify hvKp with a sensitivity of 90%, specificity of 100% and accuracy of 98.73%, with 90% of hvKp samples consistent with clinical diagnosis (Cohen’s kappa, 0.94). RVFScan has the potential to detect VFGs in low-biomass and high-complexity clinical samples using metagenomic reads without assembly. This capability facilitates the rapid identification and targeted treatment of hvKp infections and holds promise for application to other hypervirulent pathogens.
Enhanced annotation of CD45RA to distinguish T cell subsets in single-cell RNA-seq via machine learning
Authors: Ran Ran , Brubaker Douglas K
Published: November 2023

Motivation

T cell heterogeneity presents a challenge for accurate cell identification, understanding their inherent plasticity, and characterizing their critical role in adaptive immunity. Immunologists have traditionally employed techniques such as flow cytometry to identify T cell subtypes based on a well-established set of surface protein markers. With the advent of single-cell RNA sequencing (scRNA-seq), researchers can now investigate the gene expression profiles of these surface proteins at the single-cell level. The insights gleaned from these profiles offer valuable clues and a deeper understanding of cell identity. However, CD45RA, the isoform of CD45 which distinguishes between naive/central memory T cells and effector memory/effector memory cells re-expressing CD45RA T cells, cannot be well profiled by scRNA-seq due to the difficulty in mapping short reads to genes.

Results

In order to facilitate cell-type annotation in T cell scRNA-seq analysis, we employed machine learning and trained a CD45RA+/− classifier on single-cell mRNA count data annotated with known CD45RA antibody levels provided by cellular indexing of transcriptomes and epitopes sequencing data. Among all the algorithms we tested, the trained support vector machine with a radial basis function kernel with optimized hyperparameters achieved a 99.96% accuracy on an unseen dataset. The multilayer perceptron classifier, the second most predictive method overall, also achieved a decent accuracy of 99.74%. Our simple yet robust machine learning approach provides a valid inference on the CD45RA level, assisting the cell identity annotation and further exploring the heterogeneity within human T cells. Based on the overall performance, we chose the support vector machine with a radial basis function kernel as the model implemented in our Python package scCD45RA.

Availability and implementation

The resultant package scCD45RA can be found at https://github.com/BrubakerLab/ScCD45RA and can be installed from the Python Package Index (PyPI) using the command “pip install sccd45ra.”
aaHash: recursive amino acid sequence hashing
Authors: Wong Johnathan , Kazemi Parham , Coombe Lauren , Warren René L , Birol Inanç
Published: November 2023

Motivation

K-mer hashing is a common operation in many foundational bioinformatics problems. However, generic string hashing algorithms are not optimized for this application. Strings in bioinformatics use specific alphabets, a trait leveraged for nucleic acid sequences in earlier work. We note that amino acid sequences, with complexities and context that cannot be captured by generic hashing algorithms, can also benefit from a domain-specific hashing algorithm. Such a hashing algorithm can accelerate and improve the sensitivity of bioinformatics applications developed for protein sequences.

Results

Here, we present aaHash, a recursive hashing algorithm tailored for amino acid sequences. This algorithm utilizes multiple hash levels to represent biochemical similarities between amino acids. aaHash performs ∼10× faster than generic string hashing algorithms in hashing adjacent k-mers.

Availability and implementation

aaHash is available online at https://github.com/bcgsc/btllib and is free for academic use.
Phylogeography of an insect inhabiting ‘Sky Islands’: the relationships among genetic structures and geographical characteristics, geohistorical characteristics, and cyclical climate changes
Authors: Suzuki Hirohisa , Takenaka Masaki , Tojo Koji
Published: November 2023

When gene flow has been restricted between populations, the genetic structure of such species often reflects geohistory and climate changes. Populations of species inhabiting high-altitude regions, known as ‘Sky Islands’, are isolated and exhibit restricted gene flow, so they often have habitat-specific genetic structures that correspond to their surrounding geographical structures. Here we focus on a limnephilid caddisfly, Rivulophilus sakaii, which inhabits the alpine zone of Japan. Phylogenetic analyses were conducted based on the mtDNA COI and 16S rRNA regions, and the nDNA 18S rRNA, 28S rRNA, CAD, EF1-α, and POL-II regions; the results indicated three phylogeographically differentiated intraspecific lineages. Haplotype network and demographic analyses based on the mtDNA COI region suggested the size of the respective isolated populations has stabilized. This suggests that mountain formation in the Japanese Archipelago due to volcanic activity has resulted in barriers to migration and dispersal between high-altitude aquatic insect populations. This was inferred to be an effect of Quaternary climate changes that caused vertical distributional shifts following mountain formation, resulting in repeated connection and fragmentation of the populations. This is important supporting information with regard to discussing the effects and functions of geohistory and climatic changes on the phylogenetic evolution of organisms presently inhabiting interglacial ‘Sky Islands’.
CK1α deficiency impairs mouse uterine adenogenesis by inducing epithelial cell apoptosis through GSK3β pathway and inhibiting Foxa2 expression through p53 pathway
Authors: Zhang Di , Lu Chenyang , Zhou Yewen , Luo Xuan , Guo Hongzhou , Zhang Jinglin , Gao Qiao , Liu Hui , Shang Chongxing , Cui Sheng
Published: November 2023

Uterine glands and their secretions are crucial for conceptus survival and implantation in rodents and humans. In mice, the development of uterine gland known as adenogenesis occurs after birth, whereas the adenogenesis in humans initiates from fetal life and completed at puberty. Uterine adenogenesis involves dynamic epithelial cell proliferation, differentiation, and apoptosis. However, it is largely unexplored about the mechanisms governing adenogenesis. CK1α plays important roles in regulating cell division, differentiation, and death, but it is unknown whether CK1α affects adenogenesis. In the current study, uterus-specific CK1α knockout female mice (Csnk1a1d/d) were infertile resulted from lack of uterine glands. Subsequent analysis revealed that CK1α deletion induced massive apoptosis in uterine epithelium by activating GSK3β, which was confirmed by injections of GSK3β inhibitor SB216763 to Csnk1a1d/d females, and the co-treatment of SB216763 and CK1 inhibitor d4476 on cultured epithelial cells. Another important finding was that our results revealed CK1α deficiency activated p53, which then blocked the expression of Foxa2, an important factor for glandular epithelium development and function. This was confirmed by that Foxa2 expression level was elevated in p53 inhibitor pifithrin-α injected Csnk1a1d/d mouse uterus and in vitro dual-luciferase reporter assay between p53 and Foxa2. Collectively, these studies reveal that CK1α is a novel factor regulating uterine adenogenesis by inhibiting epithelial cell apoptosis through GSK3β pathway and regulating Foxa2 expression through p53 pathway. Uncovering the mechanisms of uterine adenogenesis is expected to improve pregnancy success in humans and other mammals.
Reversible female contraceptives: historical, current, and future perspectives
Authors: Barton Brooke E , Erickson Jeffery A , Allred Stephanie I , Jeffries Jenna M , Stephens Kalli K , Hunter Mark I , Woodall Kirby A , Winuthayanon Wipawee
Published: November 2023

Contraception is a practice with extensive and complicated social and scientific histories. From cycle tracking, to the very first prescription contraceptive pill, to now having over-the-counter contraceptives on demand, family planning is an aspect of healthcare that has undergone and will continue to undergo several transformations through time. This review provides a comprehensive overview of current reversible hormonal and non-hormonal birth control methods as well as their mechanism of action, safety, and effectiveness specifically for individuals who can become pregnant. Additionally, we discuss the latest Food and Drug Administration (FDA)-approved hormonal method containing estetrol and drospirenone that has not yet been used worldwide as well as the first FDA-approved hormonal over-the-counter progestin-only pills. We also review available data on novel hormonal delivery through microchip, microneedle, and the latest FDA-approved non-hormonal methods such as vaginal pH regulators. Finally, this review will assist in advancing female contraceptive method development by underlining constructive directions for future pursuits. Information was gathered from the NCBI and Google Scholars databases using English and included publications from 1900 to present. Search terms included contraceptive names as well as efficacy, safety, and mechanism of action. In summary, we suggest that investigators consider the side effects and acceptability together with the efficacy of contraceptive candidate towards their development.
Working Through Desistance: Employment in Women’s Identity and Relational Desistance
Authors: Low Grace
Published: November 2023

Desistance and re-entry literature has traditionally explored particular types of women’s relationships and social roles (such as maternal identities and familial relationships), while neglecting the potential for employment and work-related roles to support change. Through interviews with 15 (predominantly Indigenous) women with histories of imprisonment in Aotearoa New Zealand, this article contributes to feminist literature on women’s desistance by exploring the role of employment in their change. The article explores how women (particularly Indigenous women) face significant barriers to employment, based on multiple sites of inequality. It also explores how employment (and employers) can support women’s identity and relational desistance. It is argued that policy and practice should recognize and attempt to leverage the beneficial effects of employment on women’s desistance.
Prevention of incisional hernia with retrorectus synthetic mesh versus biological mesh following loop ileostomy closure (Preloop trial)
Authors: Mäkäräinen Elisa J , Wiik Heikki T , Kössi Jyrki A O , Pinta Tarja M , Mäntymäki Leena-Mari J , Mattila Anne K , Nikki Marko J , Järvinen Jyri E , Ohtonen Pasi P , Rautio Tero T
Published: November 2023

Background

The rate of incisional hernia after closure of a temporary loop ileostomy is significant. Synthetic meshes are still commonly avoided in contaminated wounds. The Preloop trial was a multicentre RCT designed to evaluate the benefits of synthetic mesh in incisional hernia prevention, and its safety for use in a contaminated surgical site compared with biological mesh.

Methods

Study patients who underwent closure of a loop ileostomy after anterior resection for rectal cancer were assigned to receive either retrorectus synthetic or biological mesh to prevent incisional hernia. The primary outcomes were surgical-site infections within 30 days, and clinical or radiological incisional hernia incidence at 10 months. Secondary outcomes were reoperation rate, operating time, duration of hospital stay, other complications within 30 days of surgery, 5-year quality of life measured by RAND-36, and incisional hernia incidence within 5 years of follow-up.

Results

Between November 2018 and September 2021, 102 patients were randomised, of whom 97 received the intended allocation. At 10-month follow-up, 90 patients had undergone clinical evaluation and 88 radiological evaluation. One patient in each group (2 per cent) had a clinical diagnosis of incisional hernia (P = 0.950) and one further patient in each group had a CT-confirmed incisional hernia (P = 0.949). The number of other complications, reoperation rate, operating time, and duration of hospital stay did not differ between the study groups.

Conclusion

Synthetic mesh appeared comparable to biological mesh in efficacy and safety for incisional hernia prevention at the time of loop ileostomy closure.

Registration number

NCT03445936 (http://www.clinicaltrials.gov).
Multi-omics analysis revealed the regulation mode of intratumor microorganisms and microbial signatures in gastrointestinal cancer
Authors: Wang Siqi , Liu Pei , Yu Jie , Liu Tongxiang
Published: November 2023

Objective

Gastrointestinal cancer is one of the most common malignant tumors in the world, and its incidence rate is always high. In recent years, research has shown that microorganisms may play a broad role in the diagnosis, pathogenesis, and treatment of cancer.

Methods

In this study, samples were first classified according to the microbial expression data of Gastrointestinal cancer, followed by functional enrichment and Immunoassay. In order to better understand the role of intratumor microorganisms in the prognosis, we screened gene signatures and constructed risk model through univariate cox and lasso regression and multivariable cox, then screened microbial signatures using zero-inflated model regression model and constructed risk index (RI), and finally predicted the immunotherapeutic effect of the risk model.

Results

The results indicate that the composition of tumor microorganisms in the C3 subtype is closely related to tumor angiogenesis, and there is a significant difference in the proportion of innate and acquired immune cells between the C2 and C1 subtypes, as well as differences in the physiological functions of immune cells. There are significant differences in the expression of microbial signatures between high and low risk subtypes, with 9 microbial signatures upregulated in high risk subtypes and 15 microbial signatures upregulated in low risk subtypes. These microbial signatures were significantly correlated with the prognosis of patients. The results of immunotherapy indicate that immunotherapy for high-risk subtypes is more effective.

Conclusion

Overall, we analyze from the perspective of microorganisms within tumors, pointing out new directions for the diagnosis and treatment of cancer.
Dermoscopic characteristics of cutaneous larva migrans in dark skin: a study from Banjul, The Gambia
Authors: Enechukwu Nkechi A , Ogun Gabriel O , Malachy Divinefavour Echezona , Errichetti Enzo , Rudnicka Lidia
Published: November 2023

Cutaneous larva migrans (CLM) results from hookworm larvae infestation, mainly Ancylostoma braziliense or Ancylostoma caninum. It is common in Sub-Saharan Africa, often acquired through soil contact, especially in sandy beaches, manifesting as serpiginous, erythematous and intensely pruritic tracts within the epidermis, and presenting with diverse clinical appearances. Diagnosis is mostly clinical; however, dermoscopy can enhance diagnostic accuracy and distinction from mimics. The current body of literature is deficient in its representation of dermoscopic data for CLM in Black patients. This study explores dermoscopy in nine dark-skinned patients with 16 CLM lesions. Distinctive serpiginous structureless areas displaying a range of colours, peripheral scales surrounding brown areas and brown dots were predominant features, whereas vascular characteristics were less evident. This article highlights the presence of distinct reaction patterns, including brown dots, scales, and accentuated, often disrupted brown reticular lines in addition to the characteristic winding tracts in darker skin.
Xenograft: a suitable treatment of eyelid complications in long-standing necrobiotic xanthogranuloma
Authors: Majtanova Nora , Kolar Petr , Takacova Adriana , Kurilova Veronika , Majtan Juraj , Szep Zoltan
Published: November 2023

A porcine xenograft was successfully used as a temporary biological cover for severe xanthogranulomatous defects of the eyelid. Xenografts were successfully used in both upper and lower eyelid reconstructions. Other surgical techniques or the use of full-thickness skin grafts were not possible.
Hidradenitis suppurativa disease control associated with type of hormonal contraceptive use
Authors: Huang Charles Y , Shah Saloni A , Cochrane Mikayla , Douglas Annyella , Yang Sherry
Published: November 2023

Hidradenitis suppurativa (HS) is a painful chronic skin condition of apocrine gland regions. This retrospective cohort study aimed to assess the impact of hormonal contraception type on HS disease control in adult women. In total, 160 patients were included, with the majority identifying as Black or African American (73.1%). Multivariate logistic regression showed that oestrogen–progesterone users were 3.14 times more likely to experience stable or improved HS than progesterone-only users (adjusted odds ratio 3.14, 95% CI 1.18–8.35; P = 0.02). Further investigation is needed to elucidate the antiandrogenic mechanisms affecting HS symptom response to hormonal contraceptives.
Unlocking the link: how hippocampal glutathione–glutamate coupling predicts cognitive impairment in multiple sclerosis patients
Authors: Li Fuyan , Zong Wei , Xin Chenxi , Ren Fuxin , Li Ning , Li Honghao , Li Xiao , Wu Lili , Dai Zongrui , Chen Weibo , Li Muwei , Gao Fei , Wang Guangbin
Published: November 2023

Cognitive impairment is a common symptom of multiple sclerosis and profoundly impacts quality of life. Glutathione (GSH) and glutamate (Glu) are tightly linked in the brain, participating in cognitive function. However, GSH–Glu couplings in cognitive brain regions and their relationship with cognitive impairment in relapsing–remitting multiple sclerosis (RRMS) remains unclear. Forty-one RRMS patients and 43 healthy controls underwent magnetic resonance spectroscopy to measure GSH and Glu levels in the posterior cingulate cortex, medial prefrontal cortex and left hippocampus. Neuropsychological tests were used to evaluate the cognitive function. The Glu/GSH ratio was used to indicate the coupling between GSH and Glu and was tested as a predictor of cognitive performance. The results show that RRMS patients exhibited reduced hippocampal GSH and Glu levels, which were found to be significant predictors of worse verbal and visuospatial memory, respectively. Moreover, GSH levels were dissociated from Glu levels in the left hippocampus of RRMS patients. Hippocampal Glu/GSH ratio is significantly correlated with processing speed and has a greater predictive effect. Here we show the hippocampal Glu/GSH ratio could serve as a new potential marker for characterizing cognitive impairment in RRMS, providing a new direction for clinical detection of cognitive impairment.
White matter fiber integrity and structural brain network topology: implications for balance function in postischemic stroke patients
Authors: Li Ling-Ling , Wu Jia-Jia , Ma Jie , Li Yu-Lin , Xue Xin , Li Kun-Peng , Jin Jing , Hua Xu-Yun , Zheng Mou-Xiong , Xu Jian-Guang
Published: November 2023

Previous studies have suggested that ischemic stroke can result in white matter fiber injury and modifications in the structural brain network. However, the relationship with balance function scores remains insufficiently explored. Therefore, this study aims to explore the alterations in the microstructural properties of brain white matter and the topological characteristics of the structural brain network in postischemic stroke patients and their potential correlations with balance function. We enrolled 21 postischemic stroke patients and 21 age, sex, and education-matched healthy controls (HC). All participants underwent balance function assessment and brain diffusion tensor imaging. Tract-based spatial statistics (TBSS) were used to compare the fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity of white matter fibers between the two groups. The white matter structural brain network was constructed based on the automated anatomical labeling atlas, and we conducted a graph theory-based analysis of its topological properties, including global network properties and local node properties. Additionally, the correlation between the significant structural differences and balance function score was analyzed. The TBSS results showed that in comparison to the HC, postischemic stroke patients exhibited extensive damage to their whole-brain white matter fiber tracts (P < 0.05). Graph theory analysis showed that in comparison to the HC, postischemic stroke patients exhibited statistically significant reductions in the values of global efficiency, local efficiency, and clustering coefficient, as well as an increase in characteristic path length (P < 0.05). In addition, the degree centrality and nodal efficiency of some nodes in postischemic stroke patients were significantly reduced (P < 0.05). The white matter fibers of the entire brain in postischemic stroke patients are extensively damaged, and the topological properties of the structural brain network are altered, which are closely related to balance function. This study is helpful in further understanding the neural mechanism of balance function after ischemic stroke from the white matter fiber and structural brain network topological properties.
Metagenomic Thermometer
Authors: Kurokawa Masaomi , Higashi Koichi , Yoshida Keisuke , Sato Tomohiko , Maruyama Shigenori , Mori Hiroshi , Kurokawa Ken
Published: November 2023

Various microorganisms exist in environments, and each of them has its optimal growth temperature (OGT). The relationship between genomic information and OGT of each species has long been studied, and one such study revealed that OGT of prokaryotes can be accurately predicted based on the fraction of seven amino acids (IVYWREL) among all encoded amino-acid sequences in its genome. Extending this discovery, we developed a ‘Metagenomic Thermometer’ as a means of predicting environmental temperature based on metagenomic sequences. Temperature prediction of diverse environments using publicly available metagenomic data revealed that the Metagenomic Thermometer can predict environmental temperatures with small temperature changes and little influx of microorganisms from other environments. The accuracy of the Metagenomic Thermometer was also confirmed by a demonstration experiment using an artificial hot water canal. The Metagenomic Thermometer was also applied to human gut metagenomic samples, yielding a reasonably accurate value for human body temperature. The result further suggests that deep body temperature determines the dominant lineage of the gut community. Metagenomic Thermometer provides a new insight into temperature-driven community assembly based on amino-acid composition rather than microbial taxa.
Antibody Responses to Influenza Vaccination are Diminished in Patients With Inflammatory Bowel Disease on Infliximab or Tofacitinib
Authors: Liu Zhigang , Alexander James L , Yee Eng Kai , Ibraheim Hajir , Anandabaskaran Sulak , Saifuddin Aamir , Constable Laura , Castro Seoane Rocio , Bewshea Claire , Nice Rachel , D’Mello Andrea , Jones Gareth R , Balarajah Sharmili , Fiorentino Francesca , Sebastian Shaji , Irving Peter M , Hicks Lucy C , Williams Horace R T , Kent Alexandra J , Linger Rachel , Parkes Miles , Kok Klaartje , Patel Kamal V , Teare Julian P , Altmann Daniel M , Boyton Rosemary J , Hart Ailsa L , Lees Charlie W , Goodhand James R , Kennedy Nicholas A , Pollock Katrina M , Ahmad Tariq , Powell Nick
Published: November 2023

Background and Aims

We sought to determine whether six commonly used immunosuppressive regimens were associated with lower antibody responses after seasonal influenza vaccination in patients with inflammatory bowel disease [IBD].

Methods

We conducted a prospective study including 213 IBD patients and 53 healthy controls: 165 who had received seasonal influenza vaccine and 101 who had not. IBD medications included infliximab, thiopurines, infliximab and thiopurine combination therapy, ustekinumab, vedolizumab, or tofacitinib. The primary outcome was antibody responses against influenza/A H3N2 and A/H1N1, compared to controls, adjusting for age, prior vaccination, and interval between vaccination and sampling.

Results

Lower antibody responses against influenza A/H3N2 were observed in patients on infliximab (geometric mean ratio 0.35 [95% confidence interval 0.20–0.60], p = 0.0002), combination of infliximab and thiopurine therapy (0.46 [0.27–0.79], p = 0.0050), and tofacitinib (0.28 [0.14–0.57], p = 0.0005) compared to controls. Lower antibody responses against A/H1N1 were observed in patients on infliximab (0.29 [0.15–0.56], p = 0.0003), combination of infliximab and thiopurine therapy (0.34 [0.17–0.66], p = 0.0016), thiopurine monotherapy (0.46 [0.24–0.87], p = 0.017), and tofacitinib (0.23 [0.10–0.56], p = 0.0013). Ustekinumab and vedolizumab were not associated with reduced antibody responses against A/H3N2 or A/H1N1. Vaccination in the previous year was associated with higher antibody responses to A/H3N2. Vaccine-induced anti-SARS-CoV-2 antibody concentration weakly correlated with antibodies against H3N2 [r = 0.27; p = 0.0004] and H1N1 [r = 0.33; p < 0.0001].

Conclusions

Vaccination in both the 2020–2021 and 2021–2022 seasons was associated with significantly higher antibody responses to influenza/A than no vaccination or vaccination in 2021–2022 alone. Infliximab and tofacitinib are associated with lower binding antibody responses to influenza/A, similar to COVID-19 vaccine-induced antibody responses.
Cancer Biology or Ineffective Surveillance? A Multicentre Retrospective Analysis of Colitis-Associated Post-Colonoscopy Colorectal Cancers
Authors: Kabir Misha , Thomas-Gibson Siwan , Ahmad Ahmir , Kader Rawen , Al-Hillawi Lulia , Mcguire Joshua , David Lewis , Shah Krishna , Rao Rohit , Vega Roser , East James E , Faiz Omar D , Hart Ailsa L , Wilson Ana
Published: November 2023

Background and Aims

Inflammatory bowel disease [IBD] is associated with high rates of post-colonoscopy colorectal cancer [PCCRC], but further in-depth qualitative analyses are required to determine whether they result from inadequate surveillance or aggressive IBD cancer evolution.

Methods

All IBD patients who had a colorectal cancer [CRC] diagnosed between January 2015 and July 2019 and a recent [<4 years] surveillance colonoscopy at one of four English hospital trusts underwent root cause analyses as recommended by the World Endoscopy Organisation to identify plausible PCCRC causative factors.

Results

In total, 61% [n = 22/36] of the included IBD CRCs were PCCRCs. They developed in patients with high cancer risk factors [77.8%; n = 28/36] requiring annual surveillance, yet 57.1% [n = 20/35] had inappropriately delayed surveillance. Most PCCRCs developed in situations where [i] an endoscopically unresectable lesion was detected [40.9%; n = 9/22], [ii] there was a deviation from the planned management pathway [40.9%; n = 9/22], such as service-, clinician- or patient-related delays in acting on a detected lesion, or [iii] lesions were potentially missed as they were typically located within areas of active inflammation or post-inflammatory change [36.4%; n = 8/22].

Conclusions

IBD PCCRC prevention will require more proactive strategies to reduce endoscopic inflammatory burden, and to improve lesion optical characterization, adherence to recommended surveillance intervals, and patient acceptance of prophylactic colectomy. However, the significant proportion appearing to originate from non-adenomatous-looking mucosa which fail to yield neoplasia on biopsy yet display aggressive cancer evolution highlights the limitations of current surveillance. Emerging molecular biomarkers may play a role in enhancing cancer risk stratification in future clinical practice.
A case report on intravascular lithotripsy to facilitate retrograde wire passage from the subintimal to the luminal space in a calcified chronic total occlusion
Authors: Werner Gerald S , Yaginuma Kenji
Published: November 2023

Background

Severe calcifications are a major reason for failures in chronic total coronary occlusions, as they can obstruct the wire passage both in the antegrade and retrograde technique.

Case summary

The proximal occlusion of the left anterior descending artery in a 75-year-old man presented with a completely concentric calcified ring all along the segment proximal to the occlusion. The antegrade wire could not pass the calcified occlusion, and in a retrograde approach via the right posterior descending artery the retrograde wire was not able to enter the lumen from a subintimal position outside of the calcified ring. Intravascular lithoplasty in the proximal segment led to a crack in this ring to enable the same retrograde wire now to pass into the true lumen with then successful conclusion of the case. Intravascular ultrasound demonstrated the modification of the calcified ring and the passage of the wire with only a very short subintimal pathway.

Discussion

Intravascular lithoplasty is a new option to modify severely calcified vessel segments to facilitate the reverse controlled antegrade and retrograde tracking approach. In the present case, this helped to avoid a long subintimal pathway and preserved the vessel anatomy.
Repeated thrombus occlusion in superficial femoral artery at the gap between two stents: a case report
Authors: Matsumoto Yuki , Shimada Ryutaro , Morioka Hidemi , Morino Yoshihiro
Published: November 2023

Background

In recent years, endovascular treatment has emerged as a preferred option for treating long lesions in the superficial femoral artery (SFA), including those classified as Trans-Atlantic Inter-Society Consensus IIC and D. This approach may involve the use of multiple stents to ensure adequate coverage of the entire lesion, as maintaining primary patency is a key consideration in the treatment strategy.

Case summary

An 82-year-old woman underwent endovascular treatment with two stents for a chronic total occlusion lesion in the left SFA. Six months later, she was admitted to our hospital with acute limb ischaemia (ALI). Angiography revealed significant thrombus within the stents and a gap between the stents, while intravascular ultrasounds showed neointimal hyperplasia at the gap. Initially, the patient was treated with a cutting balloon for the gap, but experienced another episode of ALI the following day. Subsequently, a stent was placed to cover the gap, resulting in the resolution of ALI without further recurrence.

Discussion

Superficial femoral arteries expose the stent to high stresses due to the unique external forces. When multiple stents are implanted, there must be sufficient overlap. If a stent gap occurs, stent deployment is unavoidable due to the neointimal hyperplasia as well as the coronary stent gap. Further research and clinical expertise are needed to optimize stent placement strategies and minimize stent-related complications in SFA lesions.
Case series: cardiac sarcoma
Authors: Killian Michael , Barry Timothy , Larsen Carolyn , Alsidawi Said
Published: November 2023

Background

Cardiac masses encompass a wide differential including primary and secondary malignancies and can present with a variety of symptoms, many of which are non-specific. Early identification and classification are important, particularly for cardiac malignancies such as sarcomas as these are aggressive tumours with exceptionally poor prognoses when metastases are present at diagnosis.

Case summary

We report two cases of patients who presented with dyspnoea and were diagnosed with cardiac sarcomas; the former a primary sarcoma (undifferentiated pleomorphic subtype) and the latter a secondary sarcoma (round cell myxoid liposarcoma) that serve as comparisons for presentation and management of different types of this disease. Computed Tomography (CT) and echocardiography imaging findings are demonstrated showing the typical location and morphology of each subtype.

Discussion

Cardiac sarcomas are the most common primary cardiac malignancy, of which undifferentiated pleomorphic sarcoma is a common subtype. Undifferentiated pleomorphic sarcomas are aggressive, have a tendency to arise in the left atrium, and can appear similar to benign cardiac masses. Round cell myxoid liposarcomas by contrast are rare causes of secondary cardiac malignancies, metastasizing to the heart from soft tissues. Both diagnoses carry poor prognoses and although rare, are important to recognize as timely intervention with surgery, radiotherapy, and consideration of chemotherapy is key to maximizing survival.
Vertebral osteomyelitis secondary to infective endocarditis detected by repeated magnetic resonance imaging: a case report
Authors: Hashimoto Masaki , Ueda Kazutaka , Nakao Tomoko , Tanaka Takahiro , Komuro Issei
Published: November 2023

Background

Patients with infective endocarditis (IE) experience various symptoms, a major one being back pain, which is occasionally caused by concomitant vertebral osteomyelitis (VO). Magnetic resonance imaging (MRI) is generally used to detect VO; however, the sensitivity of detection using MRI is very low in the early stages of VO.

Case summary

A 60-year-old man visited our hospital with complaints of fever and persistent back pain over the past 7 days. A holosystolic heart murmur was auscultated, and an echocardiography revealed a vegetation on the posterior mitral leaflet. Blood cultures were positive for Streptococcus sanguinis. He was diagnosed with IE and treated with antimicrobials. A lumbar spine MRI on Day 1 showed no clear signs of vertebral infection, but the back pain continued and gradually worsened. Magnetic resonance imaging retest on Day 8 showed high signal intensity within the lumbar vertebral bodies and the disk on T2-weighted sequences, indicating VO. Intravenous antimicrobial therapy was extended, followed by oral antimicrobials, and a corset was put on to protect the lumbar spine to prevent bone degradation.

Discussion

For persistent back pain in IE patients, repeat MRIs at regular intervals of time can detect possible vertebral infection even if signs of vertebral infection were absent on the initial MRI.
Risk of hyperkalaemia in patients with type 2 diabetes mellitus prescribed with SGLT2 versus DPP-4 inhibitors
Authors: Wu Mei-zhen , Teng Tiew-Hwa Katherine , Tsang Christopher Tze-Wei , Chan Yap-Hang , Lee Chi-Ho , Ren Qing-wen , Huang Jia-Yi , Cheang Iok-fai , Tse Yi-Kei , Li Xin-li , Xu Xin , Tse Hung-Fat , Lam Carolyn S P , Yiu Kai-Hang
Published: November 2023

Aims

To investigate the risk of hyperkalaemia in new users of sodium–glucose cotransporter 2 (SGLT2) inhibitors vs. dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes mellitus (T2DM).

Methods and results

Patients with T2DM who commenced treatment with an SGLT2 or a DPP-4 inhibitor between 2015 and 2019 were collected. A multivariable Cox proportional hazards analysis was applied to compare the risk of central laboratory-determined severe hyperkalaemia, hyperkalaemia, hypokalaemia (serum potassium ≥6.0, ≥5.5, and <3.5 mmol/L, respectively), and initiation of a potassium binder in patients newly prescribed an SGLT2 or a DPP-4 inhibitor. A total of 28 599 patients (mean age 60 ± 11 years, 60.9% male) were included after 1:2 propensity score matching, of whom 10 586 were new users of SGLT2 inhibitors and 18 013 of DPP-4 inhibitors. During a 2-year follow-up, severe hyperkalaemia developed in 122 SGLT2 inhibitor users and 325 DPP-4 inhibitor users. Use of SGLT2 inhibitors was associated with a 29% reduction in incident severe hyperkalaemia [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58–0.88] compared with DPP-4 inhibitors. Risk of hyperkalaemia (HR 0.81, 95% CI 0.71–0.92) and prescription of a potassium binder (HR 0.74, 95% CI 0.67–0.82) were likewise decreased with SGLT2 inhibitors compared with DPP-4 inhibitors. Occurrence of incident hypokalaemia was nonetheless similar between those prescribed an SGLT2 inhibitor and those prescribed a DPP-4 inhibitor (HR 0.90, 95% CI 0.81–1.01).

Conclusion

Our study provides real-world evidence that compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with lower risk of hyperkalaemia and did not increase the incidence of hypokalaemia in patients with T2DM.
4-Hydroxynonenal impairs miRNA maturation in heart failure via Dicer post-translational modification
Authors: Kiyuna Ligia A , Candido Darlan S , Bechara Luiz R G , Jesus Itamar C G , Ramalho Lisley S , Krum Barbara , Albuquerque Ruda P , Campos Juliane C , Bozi Luiz H M , Zambelli Vanessa O , Alves Ariane N , Campolo Nicolás , Mastrogiovanni Mauricio , Bartesaghi Silvina , Leyva Alejandro , Durán Rosario , Radi Rafael , Arantes Guilherme M , Cunha-Neto Edécio , Mori Marcelo A , Chen Che-Hong , Yang Wenjin , Mochly-Rosen Daria , MacRae Ian J , Ferreira Ludmila R P , Ferreira Julio C B
Published: November 2023

Background and Aims

Developing novel therapies to battle the global public health burden of heart failure remains challenging. This study investigates the underlying mechanisms and potential treatment for 4-hydroxynonenal (4-HNE) deleterious effects in heart failure.

Methods

Biochemical, functional, and histochemical measurements were applied to identify 4-HNE adducts in rat and human failing hearts. In vitro studies were performed to validate 4-HNE targets.

Results

4-HNE, a reactive aldehyde by-product of mitochondrial dysfunction in heart failure, covalently inhibits Dicer, an RNase III endonuclease essential for microRNA (miRNA) biogenesis. 4-HNE inhibition of Dicer impairs miRNA processing. Mechanistically, 4-HNE binds to recombinant human Dicer through an intermolecular interaction that disrupts both activity and stability of Dicer in a concentration- and time-dependent manner. Dithiothreitol neutralization of 4-HNE or replacing 4-HNE-targeted residues in Dicer prevents 4-HNE inhibition of Dicer in vitro. Interestingly, end-stage human failing hearts from three different heart failure aetiologies display defective 4-HNE clearance, decreased Dicer activity, and miRNA biogenesis impairment. Notably, boosting 4-HNE clearance through pharmacological re-activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) using Alda-1 or its improved orally bioavailable derivative AD-9308 restores Dicer activity. ALDH2 is a major enzyme responsible for 4-HNE removal. Importantly, this response is accompanied by improved miRNA maturation and cardiac function/remodelling in a pre-clinical model of heart failure.

Conclusions

4-HNE inhibition of Dicer directly impairs miRNA biogenesis in heart failure. Strikingly, decreasing cardiac 4-HNE levels through pharmacological ALDH2 activation is sufficient to re-establish Dicer activity and miRNA biogenesis; thereby representing potential treatment for patients with heart failure.
Cardiovascular hospitalizations and mortality among adults aged 25–64 years in the USA
Authors: Henry Chantal M , Oseran Andrew S , Zheng ZhaoNian , Dong Huaying , Wadhera Rishi K
Published: November 2023

Background and Aims

Declines in cardiovascular mortality have stagnated in the USA since 2011. There is growing concern that these patterns reflect worsening cardiovascular health in younger adults. However, little is known about how the burden of acute cardiovascular hospitalizations and mortality has changed in this population. Changes in cardiovascular hospitalizations and mortality among adults aged 25–64 years were evaluated, overall and by community-level income.

Methods

Using the National Inpatient Sample, age-standardized annual hospitalization and in-hospital mortality rates for acute myocardial infarction (AMI), heart failure, and ischaemic stroke were determined among adults aged 25–64 years. Quasi-Poisson and quasi-binominal regression models were fitted to compare outcomes between individuals residing in low- and higher-income communities.

Results

Between 2008 and 2019, age-standardized hospitalization rates for AMI increased among younger adults from 155.0 (95% confidence interval: 154.6, 155.4) per 100 000 to 160.7 (160.3, 161.1) per 100 000 (absolute change +5.7 [5.0, 6.3], P < .001). Heart failure hospitalizations also increased (165.3 [164.8, 165.7] to 225.3 [224.8, 225.8], absolute change +60.0 (59.3, 60.6), P < .001), as ischaemic stroke hospitalizations (76.3 [76.1, 76.7] to 108.1 [107.8, 108.5], absolute change +31.7 (31.2, 32.2), P < .001). Across all conditions, hospitalizations rates were significantly higher among younger adults residing in low-income compared with higher-income communities, and disparities did not narrow between groups. In-hospital mortality decreased for all conditions over the study period.

Conclusions

There was an alarming increase in cardiovascular hospitalizations among younger adults in the USA from 2008 to 2019, and disparities between those residing in low- and higher-income communities did not narrow.
Identification of Brugada syndrome based on P-wave features: an artificial intelligence-based approach
Authors: Zanchi Beatrice , Faraci Francesca Dalia , Gharaviri Ali , Bergonti Marco , Monga Tomas , Auricchio Angelo , Conte Giulio
Published: November 2023

Aims

Brugada syndrome (BrS) is an inherited disease associated with an increased risk of ventricular arrhythmias. Recent studies have reported the presence of an altered atrial phenotype characterized by abnormal P-wave parameters. The aim of this study was to identify BrS based exclusively on P-wave features through an artificial intelligence (AI)-based model.

Methods and results

Continuous 5 min 12-lead ECG recordings were obtained in sinus rhythm from (i) patients with spontaneous or ajmaline-induced BrS and no history of AF and (ii) subjects with suspected BrS and negative ajmaline challenge. The recorded ECG signals were processed and divided into epochs of 15 s each. Within these epochs, P-waves were first identified and then averaged. From the averaged P-waves, a total of 67 different features considered relevant to the classification task were extracted. These features were then used to train nine different AI-based supervised classifiers. A total of 2228 averaged P-wave observations, resulting from the analysis of 33 420 P-waves, were obtained from 123 patients (79 BrS+ and 44 BrS−). Averaged P-waves were divided using a patient-wise split, allocating 80% for training and 20% for testing, ensuring data integrity and reducing biases in AI-based model training. The BrS+ patients presented with longer P-wave duration (136 ms vs. 124 ms, P < 0.001) and higher terminal force in lead V1 (2.5 au vs. 1.7 au, P < 0.01) compared with BrS− subjects. Among classifiers, AdaBoost model had the highest values of performance for all the considered metrics, reaching an accuracy of over 81% (sensitivity 86%, specificity 73%).

Conclusion

An AI machine-learning model is able to identify patients with BrS based only on P-wave characteristics. These findings confirm the presence of an atrial hallmark and open new horizons for AI-guided BrS diagnosis.
Optimizing the balance between heterologous acetate- and CO2-reduction pathways in anaerobic cultures of Saccharomyces cerevisiae strains engineered for low-glycerol production
Authors: van Aalst Aafke C A , Geraats Ellen H , Jansen Mickel L A , Mans Robert , Pronk Jack T
Published: November 2023

In anaerobic Saccharomyces cerevisiae cultures, NADH (reduced form of nicotinamide adenine dinucleotide)-cofactor balancing by glycerol formation constrains ethanol yields. Introduction of an acetate-to-ethanol reduction pathway based on heterologous acetylating acetaldehyde dehydrogenase (A-ALD) can replace glycerol formation as ‘redox-sink’ and improve ethanol yields in acetate-containing media. Acetate concentrations in feedstock for first-generation bioethanol production are, however, insufficient to completely replace glycerol formation. An alternative glycerol-reduction strategy bypasses the oxidative reaction in glycolysis by introducing phosphoribulokinase (PRK) and ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). For optimal performance in industrial settings, yeast strains should ideally first fully convert acetate and, subsequently, continue low-glycerol fermentation via the PRK-RuBisCO pathway. However, anaerobic batch cultures of a strain carrying both pathways showed inferior acetate reduction relative to a strain expressing only the A-ALD pathway. Complete A-ALD-mediated acetate reduction by a dual-pathway strain, grown anaerobically on 50 g L−1 glucose and 5 mmol L−1 acetate, was achieved upon reducing PRK abundance by a C-terminal extension of its amino acid sequence. Yields of glycerol and ethanol on glucose were 55% lower and 6% higher, respectively, than those of a nonengineered reference strain. The negative impact of the PRK-RuBisCO pathway on acetate reduction was attributed to sensitivity of the reversible A-ALD reaction to intracellular acetaldehyde concentrations.