bluuebunny/crossref_metadata_2025 huggingface dataset:
The synergistic effect of Levilactobacillus brevis IBRC-M10790 and vitamin D3 on Helicobacter pylori-induced inflammation
Authors: Nabavi-Rad Ali , Jamshidizadeh Shaghayegh , Azizi Mahsa , Yadegar Abbas , Robinson Karen , Monaghan Tanya M. , Zali Mohammad Reza
Published: May 2023

Background

Owing to the emergence and spread of multidrug resistance mechanisms in Helicobacter pylori, achieving a successful eradication has become exceedingly difficult. Thus, this study for the first time determines the effect of a combination of vitamin D3 and probiotic on the pathogenesis and treatment of H. pylori.

Methods

We established an in vitro experimental system using AGS human gastric carcinoma cells and explored the synergistic effect of Levilactobacillus brevis IBRC-M10790 and vitamin D3 on H. pylori. Live and pasteurized L. brevis, L. brevis-derived membrane vesicles (MVs), and L. brevis cell-free supernatant (CFS), as well as their combination with vitamin D3 were used during this study. We assessed the anti-inflammatory and anti-oxidative effects of these combinations using RT-qPCR and ELISA, respectively. We further performed an adhesion assay to evaluate the influence of L. brevis and vitamin D3 on the adherence rate of H. pylori to AGS cells.

Results

Our results demonstrated that L. brevis and vitamin D3 possess anti-inflammatory and anti-oxidative effects against H. pylori infection in AGS cells. The combination of vitamin D3 with the probiotic strain (particularly live L. brevis and its CFS) can more efficiently reduce the expression of pro-inflammatory cytokines IL-6, IL-8, IFN-γ, and TNF-α in the AGS cells. Moreover, vitamin D3 and L. brevis exhibited an additive impact preserving the integrity of the epithelial barrier by increasing the expression of the tight junction protein ZO-1. Furthermore, this combination can potentially reduce H. pylori adherence to AGS cells.

Conclusions

This study indicates the advantage of combining vitamin D3 and probiotic to attenuate H. pylori-induced inflammation and oxidative stress. Consequently, probiotic and vitamin D3 co-supplementation can be considered as a novel therapeutic approach to manage and prevent H. pylori infection.
The presentation of gut microbiome-based personalized nutrition on the internet: simple and accessible, complex and inaccessible
Authors: Lee Katharine , Davies Russell G. , Barnett Julie
Published: May 2023

The gut microbiome is related to health and wellbeing, although the precise nature of the relationship and the involvement of and interaction with other factors is not fully understood. In this context, private companies are providing gut microbiome-based personalized nutrition services on the internet. Framed by social representation theory, we conducted an analysis of the websites of 27 companies offering direct-to-consumer personalized nutrition based on the microbiome, to understand how they communicate to prospective consumers. We found that through imagery, metaphor, and personification, companies simultaneously position the gut microbiome, and gut microbiome-based personalized nutrition, as simple and accessible and complex and inaccessible. Highly medicalized content in the main web pages is negated in often peripheral disclaimer sections.
Intracardiac vs. transesophageal echocardiography for guiding transcatheter closure of interatrial communications: a systematic review and meta-analysis
Authors: Lan Qingsu , Wu Fengchao , Ye Xudong , Wang Shaohua , Zhong Jingquan
Published: May 2023

Background

Transcatheter closure of atrial septal defect (ASD) and patent foramen ovale (PFO) is an established practice, and it requires monitoring and guidance. Both transoesophageal echocardiography (TEE) and intracardiac echocardiography (ICE) can be used as guidance tools. However, the use of ICE and TEE in structural heart disease is controversial and the advantages and disadvantages of both for ASD and PFO closure need to be investigated. We did a systematic review and meta-analysis to compare the efficacy and safety of TEE and ICE for guiding transcatheter closure of ASD and PFO.

Methods

A systematic search of Embase, PubMed, Cochrane library, Web of Science was conducted from inception to May 2022. The outcomes of this study included average time for both fluoroscopy and the procedure, complete closure, length of stay at hospital and adverse events. This study was performed using mean difference (MD), relative risk (RR) and 95% confidence interval (CI).

Results

The meta-analysis was conducted with a total of 11 studies, involving 4,748 patients were included in meta-analysis, including 2,386 patients in the ICE group and 2,362 patients in the TEE group. The results of the meta-analysis showed that compared with TEE, ICE was shorter in time both fluoroscopy [MD: −3.72 (95%CI: −4.09 to −3.34) minutes, P < 0.00001] and the procedure [MD: −6.43 (95%CI: −7.65 to −5.21) minutes, P < 0.00001], shorter length of stay at hospital [MD = −0.95 (95% CI = −1.21 to −0.69) days, P < 0.00001], lower incidence of adverse events (RR = 0.72, 95%CI: 0.62 to 0.84, P < 0.0001), and the arrhythmia (RR = 0.50, 95% CI = 0.27 to 0.94, P = 0.03) and vascular complications (RR = 0.52, 95%CI = 0.29 to 0.92, P = 0.02) in ICE group were lower than those in TEE group. No significant difference in complete closure was found between ICE and TEE (RR = 1.00, 95% CI = 0.98 to 1.03, P = 0.74).

Conclusion

Under the premise of ensuring successful rate of complete closure, ICE can shorten time between fluoroscopy and procedure and length of stay at hospital, and there was no increase in adverse events. However, more high-quality studies are needed to confirm the benefits of using ICE in ASD and PFO closure.
Simulation of collapse failure process of rock slope based on the smoothed particle hydrodynamics method
Authors: Zhang Xiaoqiang , Song Xiong , Wu Shunchuan
Published: May 2023

The limit equilibrium method (LEM) or finite element method (FEM) for slope problems most frequently focusses on the stability analysis. There are, however, still some problems with the LEM or FEM when considering damage and failure evolution of a rock slope because of the distortion of mesh. In this work, a mesh-free particle approach, named the smoothed particle hydrodynamics (SPH) method, is presented and is improved to analyze the damage and failure process of a rock slope. In order to better describe the cause and mechanism of brittle failure for a rock slope, the plastic factor was suggested and introduced into the SPH algorithm, and the conservation equations of SPH for brittleness characteristics were obtained. Based on the variation of displacement and time, an effective criterion was proposed to define the factor of safety in SPH simulation. The Drucker-Prager Mohr-Coulomb strength criterion was implemented into the SPH algorithm to describe the elastic-plastic behavior. Then, three rock-slope models with different precast cracks were analyzed to illustrate the performance of the proposed method. It is shown that the proposed SPH algorithm can be effectively applied in the prediction of the deformation and failure process of rock slope.
Petroleum generation kinetics of unconventional Mississippian mudrocks in central Oklahoma, United States
Authors: Atwah Ibrahim , Sweet Stephen
Published: May 2023

The Mississippian mudrocks of central Oklahoma, USA, encompass hydrocarbon-rich unconventional reservoirs. Many factors control the success of hydrocarbon producibility from the Sooner Trend oilfield, Anadarko Basin, and Canadian and Kingfisher Counties (“STACK”) play in Oklahoma, including rock mineralogy, thermal maturity, and organic richness. Petroleum sourcing in these Mississippian reservoirs is complex, encompassing multiple hydrocarbon charges from different source rocks in addition to the Woodford Shale. Therefore, determining petroleum generation kinetic parameters for Mississippian mudrocks is crucial to understand the thermal maturation and associated hydrocarbon fluid types, which can ultimately aid in identifying the “sweet spot”. This investigation presents the first experimental evidence of petroleum generation kinetics for the Mississippian mudrocks in central Oklahoma. Here, core samples collected from Lincoln County, central Oklahoma, were examined for petroleum generation kinetics using a hydrous pyrolysis reactor. Generated pyrolysate products were then examined for key molecular parameters in comparison with produced crude oils. The results from the hydrous pyrolysis experiments and corresponding Arrhenius plots suggest slightly higher reaction rates for hydrocarbons generated from the Mississippian mudrocks compared to the Woodford Shale. These reaction rates result in lower activation energy and frequency factor values for the Mississippian mudrocks when compared to the Woodford Shale. Molecular signatures from pyrolysate oils match with Mississippian sourced crude oils with a predominance of lower and extended tricyclic terpane biomarkers. The geological implications of the determined kinetics suggest that Mississippian petroleum source rocks can generate oil and gas at lower temperatures compared to the Woodford Shale. The low kinetic parameters of Mississippian rocks are postulated due to organic-matter structure co-occurring as infused amorphinite and bituminite within the mineral matrix. The large surface area between the macerals and the mineral matrix could increase the reactivity, with clays acting as catalysts for petroleum generation.
Shakespeare as a vehicle for empathy and diagnostic skills training in undergraduate medical students in their psychiatry posting
Authors: Pang Nicholas Tze Ping , Thrichelvam Nathisha , Wider Walton
Published: May 2023

Psychiatry undergraduate training has been significantly curtailed by the advent of the COVID-19 pandemic. This article examines the use of Shakespeare’s Hamlet, especially via the characters of Hamlet and Ophelia, to impart two core skills in psychiatry, namely diagnostic abilities and empathy. Medical students undergoing the psychiatry posting watched Kenneth Branagh’s Hamlet online, focusing on identifying psychopathology, forming diagnoses, identifying countertransferences, and developing empathy through acting out close passages. Students were able to identify the features of bipolar disorder in Hamlet, correlating his behavior with separate depressive and manic episodes. They were also able to appreciate the unique quality of dissociation in Ophelia, especially in Act 4 of Hamlet, and recognize it as a manifestation of post-traumatic stress disorder. Through acting out closed passages, students were also able to feel empathy by putting themselves into the shoes of Hamlet and Ophelia. Such a pedagogical approach has additional unexpected utility in view of the COVID-19 pandemic, which has significantly curtailed face-to-face medical education, leading to alternative online methods such as movies and Shakespearean plays in psychiatry education. In conclusion, though online methods cannot fully supplant face-to-face patient contact, they can be crucial tools in times of necessity and allow students to engage in interdisciplinary education, marrying the arts and the humanities.
Mathematical prerequisites for non-STEM programs
Authors: Rohenroth Dunja , Neumann Irene , Heinze Aiso
Published: May 2023

Mathematics is applied in a broad range of academic disciplines and thus takes on a paramount role for college access. However, students often take for granted the necessity of mathematics for STEM subjects but are unaware of or insufficiently informed about the role of mathematics for subjects outside of STEM. In fact, there is no in-depth empirical investigation on which mathematical prerequisites are expected by university instructors from incoming non-STEM undergraduates. The present paper addresses this research gap. We conducted a three-round Delphi study with N = 19/547/337 university instructors in Germany teaching undergraduates in non-STEM programs. Our results show that many more subjects require mathematical knowledge than is commonly assumed. We present a comprehensive catalogue of mathematical prerequisites that students are expected to have at the beginning of their studies. The prerequisites include (1) mathematical content, (2) mathematical processes, (3) views about the nature of mathematics, and (4) personal characteristics. The expected mathematical prerequisites primarily address a basic understanding and do not require formalistic or abstract mathematical knowledge and skills. The Delphi study also revealed five subject groups in which similar mathematical prerequisites are expected. Although the study’s focus is on German instructors, it provides valuable insights for an international audience as well. For example, future research can use our results to adapt instruments to explore predictors of college success. In addition, our results inform stakeholders involved in the transition from high school to college and in college education, such as teachers preparing their students for future study, college instructors making their expectations transparent to incoming students, and policymakers involved in curriculum design.
Plant functional types and microtopography mediate climate change responses of fine roots in forested boreal peatlands
Authors: Bucher Melina , Ofiti Nicholas O. E. , Malhotra Avni
Published: May 2023

Peatlands store one-third of the world’s soil carbon, and their climate change response is a key unknown in the global carbon cycle-climate change feedback. In particular, peatland fine root responses to varied environmental changes are poorly constrained. Here, we synthesized fine root responses to warming and water level drawdown by performing a meta-analysis of existing data from boreal forested peatlands. We found seven studies and evaluated root responses from 65 observations. Overall, both warming (from 0 to 9.0°C) and water level drawdown (from 4.0 to 62.5 cm) increased fine root growth by over an order of magnitude, with plant functional type (PFT; graminoid, shrub, and tree) better predicting fine root biomass than treatment magnitude. We observed stronger responses for trees (+374.5% for warming and +868.6% for water level drawdown) than for shrubs (+44.0% for warming and +11.5% for water level drawdown) and graminoids (+59.5% for warming and −59.8% for water level drawdown). Among PFTs, tree fine roots increased significantly and non-linearly with increasing warming treatment, while graminoid fine roots responded significantly to lowering water level, decreasing 1.7% for every 1 cm decrease in water level. Fine roots in hollows, especially of shrubs, increased more strongly than those in hummocks, suggesting a possible flattening of peatland topography with sustained hollow growth from extended warming. Our synthesis highlights the important role of PFT’s in modulating fine root responses and the need for additional belowground data from these carbon-rich and globally relevant peatland soils. The altered fine root growth documented here, implies possible shifts in plant nutrient and water uptake as well as root inputs to soil carbon stocks, which in turn could strongly moderate and shape boreal peatland responses to future climate change.
Assessing the effects of aging on the renal endothelial cell landscape using single-cell RNA sequencing
Authors: Li Mengke , Wang Dongliang , Liu Zhong , Huang Yanjing , Zhang Qikai , Pan Caineng , Lin Yuheng , Sun Li , Zheng Yingfeng
Published: May 2023

Endothelial cells (ECs) with senescence-associated secretory phenotypes (SASP) have been identified as a key mechanism of aging that contributes to various age-related kidney diseases. In this study, we used single-cell RNA sequencing (scRNA-seq) to create a transcriptome atlas of murine renal ECs and identify transcriptomic changes that occur during aging. We identified seven different subtypes of renal ECs, with glomerular ECs and angiogenic ECs being the most affected by senescence. We confirmed our scRNA-seq findings by using double immunostaining for an EC marker (CD31) and markers of specialized EC phenotypes. Our analysis of the dynamics of capillary lineage development revealed a chronic state of inflammation and compromised glomerular function as prominent aging features. Additionally, we observed an elevated pro-inflammatory and pro-coagulant microenvironment in aged glomerular ECs, which may contribute to age-related glomerulosclerosis and renal fibrosis. Through intercellular communication analysis, we also identified changes in signaling involved in immune regulation that may contribute to a hostile microenvironment for renal homeostasis and function. Overall, our findings provide new insights into the mechanisms of aging in the renal endothelium and may pave the way for the discovery of diagnostic biomarkers and therapeutic interventions against age-related kidney diseases.
Gaps in obesity management in the UAE and the role of bariatric endoscopy
Authors: Alkhatry Maryam
Published: May 2023

The definitions of overweight and obesity include increased fat storage that might compromise one’s health. According to the World Health Organization (WHO), an adult is considered overweight if their Body Mass Index (BMI) is greater than or equal to 25, and obese if their BMI is greater than or equal to 30. Age must be taken into account when defining overweight and obesity in children. The prevalence of obesity and overweight was reported to be at 21% and 33%, respectively, in the Middle East region. As obesity incidence rises with ageing, those over 40 were found to have the highest prevalence of obesity and overweight. According to the Central Intelligence Agency’s World Factbook, the UAE has a prevalence rate of obesity of 31.7%, making it one of the top 20 nations in the world for high obesity rates in 2016. The prevalence of overweight and obesity in the UAE is estimated to have increased between 1989 and 2017 threefold.
Is TNF alpha a mediator in the co-existence of malaria and type 2 diabetes in a malaria endemic population?
Authors: Ademola Subulade A. , Bamikole Oluwayemi J. , Amodu Olukemi K.
Published: May 2023

Malaria remains a disease of public health importance globally, especially in sub-Saharan Africa. Malaria deaths reduced globally steadily between 2000-2019, however there was a 10% increase in 2020 due to disruptions in medical service during the COVID-19 pandemic. Globally, about 96% of malaria deaths occurred in 29 countries; out of which, four countries (Nigeria, the Democratic Republic of the Congo, the Niger, and the United Republic of Tanzania) accounted for just over half of the malaria deaths. Nigeria leads the four countries with the highest malaria deaths (accounting for 31% globally). Parallelly, sub-Saharan Africa is faced with a rise in the incidence of Type 2 diabetes (T2D). Until recently, T2D was a disease of adulthood and old age. However, this is changing as T2D in children and adolescents is becoming an increasingly important public health problem. Nigeria has been reported to have the highest burden of diabetes in Africa with a prevalence of 5.77% in the country. Several studies conducted in the last decade investigating the interaction between malaria and T2D in developing countries have led to the emergence of the intra-uterine hypothesis. The hypothesis has arisen as a possible explanation for the rise of T2D in malaria endemic areas; malaria in pregnancy could lead to intra-uterine stress which could contribute to low birth weight and may be a potential cause of T2D later in life. Hence, previous, and continuous exposure to malaria infection leads to a higher risk of T2D. Current and emerging evidence suggests that an inflammation-mediated link exists between malaria and eventual T2D emergence. The inflammatory process thus, is an important link for the co-existence of malaria and T2D because these two diseases are inflammatory-related. A key feature of T2D is systemic inflammation, characterized by the upregulation of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) which leads to impaired insulin signaling. Malaria infection is an inflammatory disease in which TNF-α also plays a major role. TNF-α plays an important role in the pathogenesis and development of malaria and T2D. We therefore hypothesize that TNF-α is an important link in the increasing co-existence of T2D.
Trans-population graph-based coverage optimization of allogeneic cellular therapy
Authors: Israeli Sapir , Krakow Elizabeth F. , Maiers Martin , Summers Corinne , Louzoun Yoram
Published: May 2023

Background

Pre-clinical development and in-human trials of ‘off-the-shelf’ immune effector cell therapy (IECT) are burgeoning. IECT offers many potential advantages over autologous products. The relevant HLA matching criteria vary from product to product and depend on the strategies employed to reduce the risk of GvHD or to improve allo-IEC persistence, as warranted by different clinical indications, disease kinetics, on-target/off-tumor effects, and therapeutic cell type (T cell subtype, NK, etc.).

Objective

The optimal choice of candidate donors to maximize target patient population coverage and minimize cost and redundant effort in creating off-the-shelf IECT product banks is still an open problem. We propose here a solution to this problem, and test whether it would be more expensive to recruit additional donors or to prevent class I or class II HLA expression through gene editing.

Study design

We developed an optimal coverage problem, combined with a graph-based algorithm to solve the donor selection problem under different, clinically plausible scenarios (having different HLA matching priorities). We then compared the efficiency of different optimization algorithms – a greedy solution, a linear programming (LP) solution, and integer linear programming (ILP) -- as well as random donor selection (average of 5 random trials) to show that an optimization can be performed at the entire population level.

Results

The average additional population coverage per donor decrease with the number of donors, and varies with the scenario. The Greedy, LP and ILP algorithms consistently achieve the optimal coverage with far fewer donors than the random choice. In all cases, the number of randomly-selected donors required to achieve a desired coverage increases with increasing population. However, when optimal donors are selected, the number of donors required may counter-intuitively decrease with increasing population size. When comparing recruiting more donors vs gene editing, the latter was generally more expensive. When choosing donors and patients from different populations, the number of random donors required drastically increases, while the number of optimal donors does not change. Random donors fail to cover populations different from their original populations, while a small number of optimal donors from one population can cover a different population.

Discussion

Graph-based coverage optimization algorithms can flexibly handle various HLA matching criteria and accommodate additional information such as KIR genotype, when such information becomes routinely available. These algorithms offer a more efficient way to develop off-the-shelf IECT product banks compared to random donor selection and offer some possibility of improved transparency and standardization in product design.
A novel immunogenic cell death–related subtype classification and risk signature for predicting prognosis and immunotherapy efficacy in gastric cancer
Authors: Dong Bingqi , Wu Yingchao , Zhang Junling , Gu Yanlun , Xie Ran , He Xu , Pang Xiaocong , Wang Xin , Cui Yimin
Published: May 2023

The majority of gastric cancer (GC) patients are in a progressive stage at the initial stage of treatment, and the overall response rate to immunotherapy remains unsatisfactory largely due to the lack of effective prognostic biomarkers. Immunogenic cell death (ICD) was identified as a new form of regulated cell death that can activate adaptive immune responses and further promote immunotherapy efficacy. Therefore, we attempted to characterize the ICD-associated signature to stratify patients who could benefit from immunotherapy. In our study, two subgroups of patients were identified based on the data of 34 ICD-related genes extracted from The Cancer Genome Atlas database via consensus clustering. The estimated scores, stromal scores, immune scores, tumor purity, and survival rate showed significant differences between the low and high ICD groups. Then, we constructed an ICD-related risk signature, including IFNB1, IL6, LY96, and NT5E, using least absolute shrinkage and selection operator Cox regression analysis; then, high- and low-risk groups could be clearly distinguished. Notably, the risk score is a reliable predictor of the prognosis and immunotherapy outcome in GC, which was further validated in an immunohistochemistry assay. These results suggest that ICD is closely associated with the prognosis and tumor immune microenvironment in GC. Taken together, this study first constructed and validated a prognostic ICD-related signature to predict the survival and effect of immunotherapy in GC, which provided new insight for potent individualized immunotherapy strategies.
Interleukin 36 receptor-inducible matrix metalloproteinase 13 mediates intestinal fibrosis
Authors: Koop Kristina , Enderle Karin , Hillmann Miriam , Ruspeckhofer Laura , Vieth Michael , Sturm Gregor , Trajanoski Zlatko , Kühl Anja A. , Atreya Raja , Leppkes Moritz , Baum Patrick , Roy Janine , Martin Andrea , Neurath Markus F. , Neufert Clemens
Published: May 2023

Background

Fibrostenotic disease is a common complication in Crohn’s disease (CD) patients hallmarked by transmural extracellular matrix (ECM) accumulation in the intestinal wall. The prevention and medical therapy of fibrostenotic CD is an unmet high clinical need. Although targeting IL36R signaling is a promising therapy option, downstream mediators of IL36 during inflammation and fibrosis have been incompletely understood. Candidate molecules include matrix metalloproteinases which mediate ECM turnover and are thereby potential targets for anti-fibrotic treatment. Here, we have focused on understanding the role of MMP13 during intestinal fibrosis.

Methods

We performed bulk RNA sequencing of paired colon biopsies taken from non-stenotic and stenotic areas of patients with CD. Corresponding tissue samples from healthy controls and CD patients with stenosis were used for immunofluorescent (IF) staining. MMP13 gene expression was analyzed in cDNA of intestinal biopsies from healthy controls and in subpopulations of patients with CD in the IBDome cohort. In addition, gene regulation on RNA and protein level was studied in colon tissue and primary intestinal fibroblasts from mice upon IL36R activation or blockade. Finally, in vivo studies were performed with MMP13 deficient mice and littermate controls in an experimental model of intestinal fibrosis. Ex vivo tissue analysis included Masson’s Trichrome and Sirius Red staining as well as evaluation of immune cells, fibroblasts and collagen VI by IF analysis.

Results

Bulk RNA sequencing revealed high upregulation of MMP13 in colon biopsies from stenotic areas, as compared to non-stenotic regions of patients with CD. IF analysis confirmed higher levels of MMP13 in stenotic tissue sections of CD patients and demonstrated αSMA+ and Pdpn+ fibroblasts as a major source. Mechanistic experiments demonstrated that MMP13 expression was regulated by IL36R signaling. Finally, MMP13 deficient mice, as compared to littermate controls, developed less fibrosis in the chronic DSS model and showed reduced numbers of αSMA+ fibroblasts. These findings are consistent with a model suggesting a molecular axis involving IL36R activation in gut resident fibroblasts and MMP13 expression during the pathogenesis of intestinal fibrosis.

Conclusion

Targeting IL36R-inducible MMP13 could evolve as a promising approach to interfere with the development and progression of intestinal fibrosis.
Omicron infection-associated T- and B-cell immunity in antigen-naive and triple-COVID-19-vaccinated individuals
Authors: Barros-Martins Joana , Hammerschmidt Swantje I. , Morillas Ramos Gema , Cossmann Anne , Hetzel Laura , Odak Ivan , Köhler Miriam , Stankov Metodi V. , Ritter Christiane , Friedrichsen Michaela , Ravens Inga , Schimrock Anja , Ristenpart Jasmin , Janssen Anika , Willenzon Stefanie , Bernhardt Günter , Lichtinghagen Ralf , Bošnjak Berislav , Behrens Georg M. N. , Förster Reinhold
Published: May 2023

Since early 2022, various Omicron variants have dominated the SARS-CoV-2 pandemic in most countries. All Omicron variants are B-cell immune escape variants, and antibodies induced by first-generation COVID-19 vaccines or by infection with earlier SARS-CoV-2 variants largely fail to protect individuals from Omicron infection. In the present study, we investigated the effect of Omicron infections in triple-vaccinated and in antigen-naive individuals. We show that Omicron breakthrough infections occurring 2–3.5 months after the third vaccination restore B-cell and T-cell immune responses to levels similar to or higher than those measured 14 days after the third vaccination, including the induction of Omicron-neutralizing antibodies. Antibody responses in breakthrough infection derived mostly from cross-reacting B cells, initially induced by vaccination, whereas Omicron infections in antigen-naive individuals primarily generated B cells binding to the Omicron but not the Wuhan spike protein. Although antigen-naive individuals mounted considerable T-cell responses after infection, B-cell responses were low, and neutralizing antibodies were frequently below the limit of detection. In summary, the detection of Omicron-associated B-cell responses in primed and in antigen-naive individuals supports the application of Omicron-adapted COVID-19 vaccines, but calls into question their suitability if they also contain/encode antigens of the original Wuhan virus.
Dysregulation of immune response in PCOS organ system
Authors: Wang Jingxuan , Yin Tailang , Liu Su
Published: May 2023

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder affecting women, which can lead to infertility. Infertility, obesity, hirsutism, acne, and irregular menstruation are just a few of the issues that PCOS can be linked to. PCOS has a complicated pathophysiology and a range of clinical symptoms. Chronic low-grade inflammation is one of the features of PCOS. The inflammatory environment involves immune and metabolic disturbances. Numerous organ systems across the body, in addition to the female reproductive system, have been affected by the pathogenic role of immunological dysregulation in PCOS in recent years. Insulin resistance and hyperandrogenism are associated with immune cell dysfunction and cytokine imbalance. More importantly, obesity is also involved in immune dysfunction in PCOS, leading to an inflammatory environment in women with PCOS. Hormone, obesity, and metabolic interactions contribute to the pathogenesis of PCOS. Hormone imbalance may also contribute to the development of autoimmune diseases. The aim of this review is to summarize the pathophysiological role of immune dysregulation in various organ systems of PCOS patients and provide new ideas for systemic treatment of PCOS in the future.
SIRT2 plays complex roles in neuroinflammation neuroimmunology-associated disorders
Authors: Lu Wenmei , Ji Haonan , Wu Danhong
Published: May 2023

Neuroinflammation and neuroimmunology-associated disorders, including ischemic stroke and neurodegenerative disease, commonly cause severe neurologic function deficits, including bradypragia, hemiplegia, aphasia, and cognitive impairment, and the pathological mechanism is not completely clear. SIRT2, an NAD+-dependent deacetylase predominantly localized in the cytoplasm, was proven to play an important and paradoxical role in regulating ischemic stroke and neurodegenerative disease. This review summarizes the comprehensive mechanism of the crucial pathological functions of SIRT2 in apoptosis, necroptosis, autophagy, neuroinflammation, and immune response. Elaborating on the mechanism by which SIRT2 participates in neuroinflammation and neuroimmunology-associated disorders is beneficial to discover novel effective drugs for diseases, varying from vascular disorders to neurodegenerative diseases.
Machine learning-based glycolysis-associated molecular classification reveals differences in prognosis, TME, and immunotherapy for colorectal cancer patients
Authors: Wang Zhenling , Shao Yu , Zhang Hongqiang , Lu Yunfei , Chen Yang , Shen Hengyang , Huang Changzhi , Wu Jingyu , Fu Zan
Published: May 2023

Background

Aerobic glycolysis is a process that metabolizes glucose under aerobic conditions, finally producing pyruvate, lactic acid, and ATP for tumor cells. Nevertheless, the overall significance of glycolysis-related genes in colorectal cancer and how they affect the immune microenvironment have not been investigated.

Methods

By combining the transcriptome and single-cell analysis, we summarize the various expression patterns of glycolysis-related genes in colorectal cancer. Three glycolysis-associated clusters (GAC) were identified with distinct clinical, genomic, and tumor microenvironment (TME). By mapping GAC to single-cell RNA sequencing analysis (scRNA-seq), we next discovered that the immune infiltration profile of GACs was similar to that of bulk RNA sequencing analysis (bulk RNA-seq). In order to determine the kind of GAC for each sample, we developed the GAC predictor using markers of single cells and GACs that were most pertinent to clinical prognostic indications. Additionally, potential drugs for each GAC were discovered using different algorithms.

Results

GAC1 was comparable to the immune-desert type, with a low mutation probability and a relatively general prognosis; GAC2 was more likely to be immune-inflamed/excluded, with more immunosuppressive cells and stromal components, which also carried the risk of the poorest prognosis; Similar to the immune-activated type, GAC3 had a high mutation rate, more active immune cells, and excellent therapeutic potential.

Conclusion

In conclusion, we combined transcriptome and single-cell data to identify new molecular subtypes using glycolysis-related genes in colorectal cancer based on machine-learning methods, which provided therapeutic direction for colorectal patients.
Electrical properties of a high-precision hexagonal spiral silicon drift detector
Authors: Li Xiaodan , Li Zheng , Sun Jiaxiong , Tan Zewen , Cai Xinyi , Li Xinqing , Liu Manwen , Wang Hongfei
Published: May 2023

With the deepening and expansion of semiconductor technology and research, in order to continuously optimize the structure and performance of semiconductor detectors, a high-precision hexagonal spiral silicon drift detector (SDD) is proposed in this paper. In order to obtain a more accurate spiral ring structure, this paper goes beyond the first-order formula in the Taylor expansion for calculating the radius of the spiral ring. Based on the first-order formula, the second-order formula for calculating the radius of the spiral ring is further developed and derived. The point coordinates are obtained by combining the radius, angle, and ring spacing change formula to obtain a more accurate spiral ring structure. The actual number of turns is more accurate than that obtained from first-order approximation, which better solves the problem of accurate calculation of the number of spiral rings and the structure of the spiral SDD in the existing technology, that is, the accurate calculation of the radius of the spiral ring. In order to verify the abovementioned theory, we model this new structure and use Technology Computer-Aided Design to system simulate and study its electrical properties, including potential distribution, electric field distribution, and electron concentration distribution. According to the simulation results, compared with the first-order formula, the second-order formula has better electrical properties; more uniform distribution of potential, electric field, and electron concentration; and a clearer electron drift channel.
One size does not fit all: an exploratory interview study on how translational researchers navigate the current academic reward system
Authors: Kools Farah R. W. , Fox Christine M. , Prakken Berent J. , van Rijen Harold V. M.
Published: May 2023

Introduction

Translational research is a subfield of the biomedical life sciences that focuses on clinically driven healthcare innovations. The workforce of this subfield, i.e., translational researchers, are diversely specialized and collaborate with a multitude of stakeholders from diverse disciplines in and outside academia in order to navigate the complex path of translating unmet clinical needs into research questions and ultimately into advancements for patient care. Translational researchers have varying responsibilities in the clinical, educational, and research domains requiring them to split their time two- or three-ways. Working between these domains and alongside peers who do not split their time as such, raises questions about the academic reward system used to recognize their performance, which mainly focuses on publication metrics within the research domain. What is unclear is how combining research tasks with tasks in the clinical and/or educational domains effects translational researchers and how they navigate the academic reward system.

Methods

In this exploratory interview study, semi-structured interviews were conducted to gain a deeper understanding of the current academic reward system for translational researchers. Stratified purposeful sampling was used to recruit 14 translational researchers from varying countries, subspecialties, and career stages. The interviews were coded after data collection was complete and arranged into three overarching result categories: intrinsic motivation, extrinsic factors, and ideal academic reward system and advice.

Results

We found that these 14 translational researchers were intrinsically motivated to achieve their translational goals while working in settings where clinical work was reported to take priority over teaching which in turn took priority over time for research. However, it is the latter that was explained to be essential in the academic reward system which currently measures scientific impact largely based on publications metrics.

Conclusion

In this study, translational researchers were asked about their thoughts regarding the current academic reward system. Participants shared possible structural improvements and ideas for specialized support on an individual, institutional, and also international level. Their recommendations focused on acknowledging all aspects of their work and led to the conclusion that traditional quantitative academic reward metrics do not fully align with their translational goals.
Skin infiltrating T-cell profile of drug reaction with eosinophilia and systemic symptoms (DRESS) reactions among HIV-infected patients
Authors: Chimbetete Tafadzwa , Choshi Phuti , Pedretti Sarah , Porter Mireille , Roberts Riyaadh , Lehloenya Rannakoe , Peter Jonathan
Published: May 2023

Introduction

Drug Reaction with Eosinophilia Systemic Symptoms (DRESS) is more common in persons living with HIV (PLHIV), and first-line anti-TB drugs (FLTDs) and cotrimoxazole are the commonest offending drugs. Limited data is available on the skin infiltrating T-cell profile among DRESS patients with systemic CD4 T-cell depletion associated with HIV.

Materials and methods

HIV cases with validated DRESS phenotypes (possible, probable, or definite) and confirmed reactions to either one or multiple FLTDs and/or cotrimoxazole were chosen (n = 14). These cases were matched against controls of HIV-negative patients who developed DRESS (n = 5). Immunohistochemistry assays were carried out with the following antibodies: CD3, CD4, CD8, CD45RO and FoxP3. Positive cells were normalized to the number of CD3+ cells present.

Results

Skin infiltrating T-cells were mainly found in the dermis. Dermal and epidermal CD4+ T-cells (and CD4+/CD8+ ratios) were lower in HIV-positive vs. negative DRESS; p < 0.001 and p = 0.004, respectively; without correlation to whole blood CD4 cell counts. In contrast, no difference in dermal CD4+FoxP3+ T-cells was found in HIV-positive vs. negative DRESS, median (IQR) CD4+FoxP3+ T-cells: [10 (0–30) cells/mm2 vs. 4 (3–8) cells/mm2, p = 0.325]. HIV-positive DRESS patients reacting to more than one drug had no difference in CD8+ T-cell infiltrates, but higher epidermal and dermal CD4+FoxP3+ T-cell infiltrates compared to single drug reactors.

Conclusion

DRESS, irrespective of HIV status, was associated with an increased skin infiltration of CD8+ T-cells, while CD4+ T-cells were lower in HIV-positive DRESS compared to HIV-negative DRESS skin. While inter-individual variation was high, the frequency of dermal CD4+FoxP3+ T-cells was higher in HIV-positive DRESS cases reacting to more than one drug. Further research is warranted to understand the clinical impact of these changes.
HAIC as a potential therapy for esophageal cancer patients with liver metastasis: a retrospective cohort study
Authors: Dong Fengxiao , Cao Guang , Lu Zhihao
Published: May 2023

Methods

This was a single-arm historical cohort study of ESCC patients with synchronous or heterochronous LM between December 2014 and July 2021 at the Department of Gastrointestinal Oncology. The patients were treated with HAIC for LM, and regular image assessments were performed according to the judgment of the interventional physician. Liver progression-free survival (PFS), liver objective response rate (ORR), liver disease control rate (DCR), overall survival (OS), adverse events (AEs), treatment information, and basic characteristics were observed retrospectively.

Results

Overall, a total of 33 patients were enrolled in this study. All included patients received catheterized HAIC therapy, with a median of three (ranging from 2 to 6) sessions. The treatment response of liver metastatic lesions included partial response (PR) in 16 (48.5%) patients, stable disease (SD) in 15 (45.5%) patients, and progressive disease (PD) in two (6.1%) patients, for an ORR of 48.5% and a DCR of 93.9%. The median liver PFS was 4.8 months (95% confidence interval (CI): 3.0–6.6 months), and the median OS was 6.4 months (95% CI: 6.1–6.6 months). Patients who achieved PR at the liver metastasis site after HAIC were more likely to have a longer OS than those who achieved SD or PD. Grade 3 AEs occurred in 12 patients. The most common grade 3 AE was nausea, occurring in 10 (30.0%) patients, followed by abdominal pain in three (9.1%) patients. Only one patient showed grade 3 elevation of alanine aminotransferase (ALT)/aspartate aminotransferase (AST), and one patient suffered from grade 3 embolism syndrome AEs. Grade 4 adverse events, followed by abdominal pain, occurred in one patient.

Conclusion

Hepatic arterial infusion chemotherapy might be an option as a regional therapy for ESCC patients with LM, as it is acceptable and tolerable.
Effect of ginsenosides on microbial community and enzyme activity in continuous cropping soil of ginseng
Authors: Miao Xinyue , Wang Ergang , Zhou Yi , Zhan Yu , Yan Ning , Chen Changbao , Li Qiong
Published: May 2023

Root exudates contain plant metabolites secreted by the roots into the soil, such as ginsenosides secreted by the ginseng root. However, little is known about ginseng root exudate and its impact on the chemical and microbial properties of soil. In this study, the effect of increasing concentrations of ginsenosides on the chemical and microbial properties of soil was tested. Chemical analysis and high-throughput sequencing techniques were used to evaluate the soil chemical properties and microbial characteristics following exogenous application of 0.1 mg·L−1, 1 mg·L−1, and 10 mg·L−1 ginsenosides. Ginsenosides application significantly altered soil enzyme activities; SOM-dominated physicochemical properties were significantly reduced which altered the composition and structure of the soil microbial community. In particular, treatment with 10 mg∙L−1 ginsenosides significantly increased the relative abundance of pathogenic fungi such as Fusarium, Gibberella and Neocosmospora. These findings indicate that ginsenosides in root exudates are important factors that may lead to increased deterioration of soil during ginseng cultivation and provided new research direction for the subsequent study on the mechanism of interaction between ginsenosides and soil microbial communities.
Biosensors for point-of-care testing and personalized monitoring of gastrointestinal microbiota
Authors: Ngashangva Lightson , Chattopadhyay Santanu
Published: May 2023

The gastrointestinal (GI) microbiota is essential in maintaining human health. Alteration of the GI microbiota or gut microbiota (GM) from homeostasis (i.e., dysbiosis) is associated with several communicable and non-communicable diseases. Thus, it is crucial to constantly monitor the GM composition and host–microbe interactions in the GI tract since they could provide vital health information and indicate possible predispositions to various diseases. Pathogens in the GI tract must be detected early to prevent dysbiosis and related diseases. Similarly, the consumed beneficial microbial strains (i.e., probiotics) also require real-time monitoring to quantify the actual number of their colony-forming units within the GI tract. Unfortunately, due to the inherent limitations associated with the conventional methods, routine monitoring of one’s GM health is not attainable till date. In this context, miniaturized diagnostic devices such as biosensors could provide alternative and rapid detection methods by offering robust, affordable, portable, convenient, and reliable technology. Though biosensors for GM are still at a relatively preliminary stage, they can potentially transform clinical diagnosis in the near future. In this mini-review, we have discussed the significance and recent advancements of biosensors in monitoring GM. Finally, the progresses on future biosensing techniques such as lab-on-chip, smart materials, ingestible capsules, wearable devices, and fusion of machine learning/artificial intelligence (ML/AI) have also been highlighted.
Genomic representation predicts an asymptotic host adaptation of bat coronaviruses using deep learning
Authors: Li Jing , Tian Fengjuan , Zhang Sen , Liu Shun-Shuai , Kang Xiao-Ping , Li Ya-Dan , Wei Jun-Qing , Lin Wei , Lei Zhongyi , Feng Ye , Jiang Jia-Fu , Jiang Tao , Tong Yigang
Published: May 2023

Introduction

Coronaviruses (CoVs) are naturally found in bats and can occasionally cause infection and transmission in humans and other mammals. Our study aimed to build a deep learning (DL) method to predict the adaptation of bat CoVs to other mammals.

Methods

The CoV genome was represented with a method of dinucleotide composition representation (DCR) for the two main viral genes, ORF1ab and Spike. DCR features were first analyzed for their distribution among adaptive hosts and then trained with a DL classifier of convolutional neural networks (CNN) to predict the adaptation of bat CoVs.

Results and discussion

The results demonstrated inter-host separation and intra-host clustering of DCR-represented CoVs for six host types: Artiodactyla, Carnivora, Chiroptera, Primates, Rodentia/Lagomorpha, and Suiformes. The DCR-based CNN with five host labels (without Chiroptera) predicted a dominant adaptation of bat CoVs to Artiodactyla hosts, then to Carnivora and Rodentia/Lagomorpha mammals, and later to primates. Moreover, a linear asymptotic adaptation of all CoVs (except Suiformes) from Artiodactyla to Carnivora and Rodentia/Lagomorpha and then to Primates indicates an asymptotic bats-other mammals-human adaptation.

Conclusion

Genomic dinucleotides represented as DCR indicate a host-specific separation, and clustering predicts a linear asymptotic adaptation shift of bat CoVs from other mammals to humans via deep learning.