bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of combined surgery and pembrolizumab for the treatment of pulmonary large cell carcinoma: a case report
Authors: Gu Linguo , Chen Hongzuo , Xia Zhenkun , Qing Bei , Yuan Yunchang
Published: December 2024

Pulmonary large cell carcinoma (LCC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC) with poor prognosis. Surgical resection remains the cornerstone of treatment for resectable LCC; however, its efficacy is limited in advanced stages, necessitating adjuvant therapies to reduce postoperative recurrence risk. Recent advances in immunotherapy have shown promising survival benefits. Here, we present a case of LCC successfully treated with a combination of surgery and pembrolizumab. A 56-year-old male smoker, diagnosed with LCC and staged as T2N1M0 postoperatively, developed recurrent disease one month after surgery, as evidenced by enlarged left hilar and mediastinal lymph nodes on chest CT. The patient received adjuvant chemotherapy and immunotherapy, guided by high PD-L1 expression. However, after three cycles, chemotherapy was discontinued due to severe side effects, and pembrolizumab monotherapy was initiated. After 21 cycles, there was substantial regression of the mediastinal and hilar lymph nodes. The patient remained progression-free after 24 cycles of treatment. This case underscores the potential of combining surgical resection with immunotherapy as an effective strategy not only for resectable LCC but also for other rare NSCLC subtypes with high PD-L1 expression.
Immune-related adverse events with renal colic as the main manifestation: a case report of sintilimab-induced ureteritis/cystitis treated by ureteral stent and review of the literature
Authors: Ji Jiaxiang , Lai Chin-Hui , Zhang Xiaowei , Hu Hao
Published: December 2024

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of systemic cancer therapy. During disinhibiting the antitumor responses of immune system, ICIs may also cause unique immune-related adverse events (irAEs) which could affect any organ. Here, we report a rare case of sintilimab-induced ureteritis/cystitis in a 55-year-old male undergoing neoadjuvant chemo-immunotherapy for gastric cancer. The patient presented with severe renal colic, hematuria, and hydronephrosis. Antibiotic antispasmodic and nonsteroidal anti-inflammatory drug treatment failed to alleviate symptoms. The application of corticosteroid was negated for recent extirpative surgery under plan. Bilateral ureteral stenting effectively resolved the pain and improved renal function. The patient later successfully underwent laparoscopic radical gastrectomy with significant tumor regression in postoperative pathology. This case highlights ureteral stenting as a potential corticosteroid-free treatment option for ICI-induced ureteritis/cystitis.
Epstein-Barr virus, vitamin D and the immune response: connections with consequences for multiple sclerosis
Authors: Rasheed Atia , Khan Gulfaraz
Published: December 2024

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with no definitive trigger. However, epidemiological studies indicate that environmental factors, such as infection with Epstein-Barr virus (EBV) and low vitamin D (Vit D) levels in genetically predisposed individuals, are important risk factors. One leading proposal is that EBV triggers MS via mechanisms such as molecular mimicry, where activated autoreactive B and T lymphocytes mistakenly target self-antigens. In line with other risk factors, low serum Vit D level, genetic polymorphism of Vit D receptor, and higher incidence of MS in countries in the northern hemisphere, suggest that Vit D also plays a role in MS pathology. Vitamin D, known for its neuroprotective and immunomodulatory effects, helps maintain a balance between pro-inflammatory and anti-inflammatory immune cells. Studies and ongoing clinical trials indicate that hypovitaminosis D is associated with an increased risk of MS, and Vit D supplement can help to reduce the disease severity. Moreover, hypovitaminosis D has also been associated with a dysregulated immune system and an increased risk of developing MS. This review explores how these three well-recognized risk factors - EBV infection, hypovitaminosis D, and dysregulated immune system - interact in the pathogenesis of MS. Understanding these interactions and their consequences could provide new insights into novel therapeutic approaches for treating this devastating disease.
Immunogenicity of the CoronaVac vaccine in children: a real-world study
Authors: Aguilar-Jimenez Wbeimar , Rodriguez-Perea Ana Lucia , Chvatal-Medina Mateo , Velilla Paula A. , Zapata-Builes Wildeman , Monsalve-Escudero Laura M. , Zapata-Cardona Maria I. , Tabares-Guevara Jorge Humberto , Rincón Daniel S. , Hernandez Juan C. , Tabares Yulied , Lopez-Carvajal Liliana , Rugeles Maria T.
Published: December 2024

Background

Despite its proven effectiveness and safety, there are limited real-world data on CoronaVac’s immunogenicity in children, especially in lower-income countries, particularly for SARS-CoV-2 variants. We present a real-world study evaluating CoronaVac’s immunogenicity in Colombian children stratified by previous exposure to this virus.

Methods

89 children aged 3-11 years were enrolled (50 Non-Exposed and 39 Exposed). Saliva samples were collected every 15 days to monitor potential SARS-CoV-2 infection, and blood samples were taken at two and six months after vaccination, to evaluate immunogenicity. Total IgG and IgA antibodies were measured by ELISA, and neutralizing titers against B.1, Delta, Mu, and Omicron variants were assessed by plaque reduction assay. T-cells were stimulated with wild-type and Omicron peptide pools to analyze activation-induced markers, memory phenotype, cytotoxic molecules, and cytokine production by flow cytometry.

Findings

CoronaVac was well tolerated, with only 7.8% infection incidence in both Exposed and Non-Exposed groups. It elicits a robust humoral response through IgG, IgA, and neutralizing antibodies against all variants. Despite waning, most participants maintained neutralizing titers ≥20 over time. CoronaVac also induced a polyfunctional cellular response against various strains, albeit reduced against Omicron, regardless of prior exposure. This response, characterized by IFN-γ/TNF-α and cytotoxic molecule production, was more pronounced in CD4+ than in CD8+ T-cells and remained detectable even after 6 months.

Interpretation

CoronaVac induces robust humoral and cellular immune responses against various variants in children, suggesting cross-recognition. However, these responses diminish over time, particularly in the context of variants, indicating the need for booster doses.
HLA-E/Mtb specific CD4+ and CD8+ T cells have a memory phenotype in individuals with TB infection
Authors: Voogd Linda , Riou Catherine , Scriba Thomas J. , van Wolfswinkel Marjolein , van Meijgaarden Krista E. , Franken Kees L. M. C. , Wilkinson Robert J. , Ottenhoff Tom H. M. , Joosten Simone A.
Published: December 2024

Introduction

Tuberculosis (TB) is the deadliest infectious disease worldwide and novel vaccines are urgently needed. HLA-E is a virtually monomorphic antigen presentation molecule and is not downregulated upon HIV co-infection. HLA-E restricted Mtb specific CD8+ T cells are present in the circulation of individuals with active TB (aTB) and Mtb infection (TBI) with or without HIV co-infection, making HLA-E restricted T cells interesting vaccination targets for TB.

Methods

Here, we performed in-depth phenotyping of HLA-E/Mtb specific and total T cell populations in individuals with TBI and in individuals with aTB or TBI and HIV using HLA-E/Mtb tetramers.

Results and Discussion

We show that HIV co-infection is the main driver in changing the memory distribution of HLA-E/Mtb specific CD4+ and CD8+ T cell subsets. HLA-E/Mtb specific CD4+ and CD8+ T cells were found to circulate with comparable frequencies in all individuals and displayed expression of KLRG1, PD-1 and 2B4 similar to that of total T cells. The presence of HLA-E/Mtb specific T cells in individuals with aTB and TBI highlights the potential of HLA-E as a vaccine target for TB.
Association between somatic microsatellite instability, hypermutation status, and specific T cell subsets in colorectal cancer tumors
Authors: Thomas Claire E. , Takashima Yasutoshi , Wesselink Evertine , Ugai Tomotaka , Steinfelder Robert S. , Buchanan Daniel D. , Qu Conghui , Hsu Li , Dias Costa Andressa , Gallinger Steven , Grant Robert C. , Huyghe Jeroen R. , Thomas Sushma S. , Ogino Shuji , Phipps Amanda I. , Nowak Jonathan A. , Peters Ulrike
Published: December 2024

Background

Microsatellite instability-high (MSI-high) tumors comprise ~15% of sporadic colorectal cancers (CRC) and are associated with elevated T cell infiltration. However, the universality of this response across T cell subtypes with distinct functions is unknown.

Methods

Including 1,236 CRC tumors from three observational studies, we conducted in-situ T cell profiling using a customized 9-plex (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, and DAPI) multispectral immunofluorescence assay. MSI status was assessed through polymerase chain reaction or immunohistochemical assays. We used multivariable ordinal logistic regression to estimate odds ratios (OR per increasing quantile) and 95% confidence intervals (CIs) for the association of MSI status with quantiles of T cell densities in either tumor epithelial or stromal tissue areas.

Results

Compared to microsatellite instability low or microsatellite stable (MSI-low/MSS) tumors, MSI-high status was associated with higher density for the majority of immune subsets (twelve out of eighteen) in both epithelial and stromal tissue areas. The strongest associations were for CD3+CD8+ T cells in epithelial areas [OR (95% CI) for naive, memory, and regulatory subsets = 3.49 (2.57, 4.75); 2.82 (2.10, 3.78); 3.04 (2.24, 4.13), respectively]. Conversely, stromal area CD3+CD4+ memory T cells were inversely associated [OR (95% CI) = 0.68 (0.51, 0.91)].

Discussion

MSI-high status was strongly associated with higher densities of most T cell subsets in both epithelial and stromal tissue areas. Our investigation supports efforts to identify patients who may be more likely to respond to current immunotherapy treatments.

Significance

This study helps us better understand how a clinically relevant tumor phenotype, microsatellite instability status, is related to different functioning T cell densities in colorectal tumors, which may impact future immunotherapy strategies.
New insights into roles of IL-7R gene as a diagnostic biomarker for post-stroke depression
Authors: Liu Mengyu , Sun Haochen , Yao Qun , Wang Duohao , Zhang Jihong , Ye Xing , Qi Xinyang
Published: December 2024

Background

Post-stroke depression (PSD) is the most prevalent neuropsychiatric complication following a stroke. The inflammatory theory suggests that PSD may be associated with an overactive inflammatory response. However, research findings regarding inflammation-related indicators in PSD remain inconsistent and elusive. This study aimed to screen the diagnostic markers that helps to distinguish between PSD and post-stroke non-depressed (PSND) patients.

Methods

Two GEO datasets, including patients with major depression disease (MDD) and controls (CON, GSE98793), ischemic stroke (IS) and CON (GSE16561), were used to analyzed differentially expressed genes (DEGs) and perform enrichment analysis. Protein-protein interaction (PPI) network and Random Forest analysis were used to screen the candidate hub genes. CIBERSORT was performed to analyze the immune infiltration. We analyzed the proteins that interact with the hub genes using string database, circRNA-miRNA-mRNA ceRNA network of the hub genes using RNAInter, miRWalk, miRDB and Starbase databases, and the drugs that regulate the hub genes by DSigDB database. We further verified the expression of the hub genes using Quantitative Real-Time PCR from the blood of patients and CON.

Results

From the screened 394 DEGs, the DEGs were found primarily related to activation of immune response. PPI network and random forest analysis obtained the hub genes: IL-7R. ROC analysis showed that IL-7R had a good diagnostic and predictive effect on MDD and IS patients. The proportions of macrophages M0 and monocytes in patients were significantly higher than those in CON. We constructed PPI network and ceRNA network that related to IL-7R. The perturbagen signatures and computational drug signatures were found that can target IL-7R. The expression of IL-7R in MDD, PSND and PSD patients was lower than that in CON, and the expression of IL-7R in PSD patients was lower than that in PSND patients.

Conclusion

These findings indicate that IL-7R may serve as a diagnostic marker to distinguish between PSD and PSND patients, and targeting IL-7R as a therapeutic target could potentially improve treatment outcomes for PSD.
Mechanisms of Keap1/Nrf2 modulation in bacterial infections: implications in persistence and clearance
Authors: Romero-Durán Marco Antonio , Silva-García Octavio , Perez-Aguilar Jose Manuel , Baizabal-Aguirre Víctor Manuel
Published: December 2024

Pathogenic bacteria trigger complex molecular interactions in hosts that are characterized mainly by an increase in reactive oxygen species (ROS) as well as an inflammation-associated response. To counteract oxidative damage, cells respond through protective mechanisms to promote resistance and avoid tissue damage and infection; among these cellular mechanisms the activation or inhibition of the nuclear factor E2-related factor 2 (Nrf2) is frequently observed. The transcription factor Nrf2 is considered the master regulator of several hundred cytoprotective and antioxidant genes. Under normal conditions, the Keap1/Nrf2 signaling protects the cellular environment by sensing deleterious oxygen radicals and inducing the expression of genes coding for proteins intended to neutralize the harmful effects of ROS. However, bacteria have developed strategies to harness Nrf2 activity to their own benefit, complicating the host response. This review is aimed to present the most recent information and probable mechanisms employed by a variety of bacteria to modulate the Keap1/Nrf2 activity in order to survive in the infected tissue. Particularly, those utilized by the Gram-positive bacteria Staphylococcus aureus, Streptococcus pneumoniae, Listeria monocytogenes, and Mycobacterium tuberculosis as well as by the Gram-negative bacteria Escherichia coli, Helicobacter pylori, Legionella pneumophila, Pseudomonas aeruginosa and Salmonella typhimurium. We also discuss and highlight the beneficial impact of the Keap1/Nrf2 antioxidant and anti-inflammatory role in bacterial clearance.
Effects of chemoradiotherapy on surface PD-L1 expression in esophageal cancer and its implications for immunotherapy
Authors: Hampe Lovis , Küffer Stefan , Niemeier Tim , Scheele Niklas Christian , Hampe Laetitia Zoe , Riedl Anna Luisa , Fischer Laura Anna , Ziegler David Alexander , Leu Martin , Dröge Leif Hendrik , König Alexander , Ghadimi Michael , Braulke Friederike , Rieken Stefan , Bohnenberger Hanibal , El Shafie Rami A.
Published: December 2024

Background

Esophageal cancer has a poor prognosis despite treatment advancements. Although the benefit of neoadjuvant chemoradiotherapy (CRT) followed by adjuvant immunotherapy is evident, the effects of CRT on PD-L1 expression in esophageal cancer are not well understood. This study examines the impact of neoadjuvant CRT on PD-L1 surface expression in esophageal cancer both in vitro and in vivo considering its implications for immunotherapy.

Methods

PD-L1 expression dynamics were assessed in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) cell lines (OE-33, FLO-1, KYSE-180) treated with Carboplatin, Paclitaxel, radiotherapy (RT), and CRT. PD-L1 expression was measured by flow cytometry at 48- and 72 hours post-treatment. Temporal changes of surface PD-L1 were further investigated in KYSE-180 cells following RT, up to 168h after treatment. Additionally, PD-L1 expression was analyzed via immunohistochemistry in histological samples from 19 patients (9 EAC, 10 ESCC) treated with neoadjuvant CRT according to the CROSS-scheme.

Results

PD-L1 expression was upregulated the most by Carboplatin, a combination of chemotherapy, or CRT in all cell lines. Higher irradiation doses were more effective in inducing PD-L1 expression, while Paclitaxel alone did not consistently increase PD-L1. The ESCC cell line KYSE-180 showed the highest relative PD-L1 increase. Measurement of PD-L1 kinetics revealed a transient upregulation of surface PD-L1, which peaked at 72 hours post-treatment and subsequently returned to baseline levels by 168 hours. In vivo, data demonstrated no significant PD-L1 expression changes when comparing pre- and post-treatment levels.

Conclusions

Chemotherapy, RT, and CRT can induce PD-L1 expression in various esophageal cancer cell lines. However, neoadjuvant CRT according to the CROSS protocol does not significantly induce PD-L1 in vivo. Considering the difference in time between pre- and post-therapeutic measurements, these findings suggest that PD-L1 upregulation due to neoadjuvant therapy may be transient in vivo as well. This highlights the potential benefit of administering immunotherapy in a neoadjuvant setting.
Epithelial immunotherapy for food allergy in children: a systematic review and meta-analysis
Authors: Chen Bin , Gao Hu , Li Xihong , Zou Zhuan , Wu Shanshan , Tang Fajuan
Published: December 2024

Objectives

Traditional methods of treating allergies primarily revolve around avoiding allergens and promptly using rescue medications when allergic symptoms occur. However, this approach is known for its inefficiency and limited success in achieving long-term relief. Our aim was to conduct a comprehensive analysis of previously published randomized controlled trials (RCTs) that explore the effectiveness and safety of epicutaneous immunotherapy (EPIT) as a means to manage food allergies in children.

Methods

We conducted a comprehensive search across multiple databases, including PubMed, Web of Science, Embase, and Cochrane Library, to identify RCTs comparing EPIT versus placebo for the management of allergen-triggered allergic reactions in children. Only RCTs published in English that evaluated the efficacy and safety of EPIT in pediatric patients with allergic diseases were considered eligible for inclusion. The quality assessment of the included studies was performed using the Cochrane risk-of-bias tool. The analysis comprised of seven RCTs involving a total of 1141 participants. The meta-analysis demonstrated that EPIT significantly facilitated desensitization in patients with food allergy (RR: 2.12, 95% CI: 1.74-2.59, P = 0.296, I² = 17.5%), particularly in individuals with peanut allergy (RR: 2.29, 95% CI: 1.83-2.86, P = 0.463, I² = 0%). However, it is important to note that EPIT was associated with an increased occurrence of treatment-related adverse events (TRAEs; RR: 1.24, 95% CI: 1.14-1.34, P < 0.01, I² = 99.2%). Notably, there were no notable disparities in the frequency of serious adverse events or utilization of rescue medications between the EPIT and placebo groups. EPIT may potentially induce desensitization of peanut allergy in children, but also carries an elevated risk of TRAEs.
Inflammatory discoveries two years after acute severe COVID-19: a longitudinal biomarker profile assessment in long COVID individuals in the Brazilian Amazon
Authors: Maciel Alex Bezerra Silva , Pinto Arlene Santos , Maia Silva Bernardo , Goulart Cassia Luz , Silva Luis Felipe Alho , Chaves Amanda Silva , Mouta Gabriel Santos , Sato Camila Miriam Suemi , Valente Jefferson , Mwangi Victor Irungu , de Melo Gisely Cardoso , Monteiro Wuelton , Lacerda Marcus , Arêas Guilherme Peixoto Tinoco , Sampaio Vanderson Souza , Costa Allyson Guimaraes , Almeida-Val Fernando
Published: December 2024

Background

In SARS-CoV-2 infection, cytokines and laboratory biomarkers play a key role in disease progression and their long-term levels have been associated with the outcome of long COVID-19.

Objectives

I) study the levels of cytokines, hematological and biochemical biomarkers in the acute and post-acute phases of COVID-19 disease; and II) assess the impact of COVID-19 vaccine doses on fatigue symptoms.

Methods

This study is an exploratory cohort nested within a clinical and laboratory follow-up of surviving participants after pre-vaccine acute COVID-19 infection with severe clinical manifestations. We analyzed the inflammatory biomarker profiles of fifty SARS-Cov-2 negative healthy controls from before the COVID-19 pandemic, and eighty patients in the acute phase (Day 1, Day 7 and Day 14), and during 4 months and 2 years after hospitalization.

Results

Four months after hospitalization, 91.3% (73/80) of patients exhibited onset of long COVID symptoms, which persisted in 63.7% (51/80) after 2 years. Comparing the baseline values of the cytokines in the controls versus the follow-up times, the cytokines IL-6, IL-8 and IL-10 were high in the acute phase, declining over time after the individual’s recovery, while IL-1β showed an inverse variation, remaining high after 2 years. IL-1β, IL-10, and TNF increased over time post-acute infection, indicating a long-term inflammatory response. Vaccination with four doses, compared to three doses, showed a slight protective effect against fatigue symptoms in the male population (IRR 0.48, 95% CI 0.22 - 1.02; p=0.054). Neutrophil and leukocyte counts showed a significant reduction 2 years after hospitalization. However, platelet count was the laboratory biomarker that best reflects the prediction of long COVID symptoms up for to 2 years.

Conclusion

Although the frequency of long COVID symptoms declines over time after the acute illness, symptoms continue to persist 2 years after hospital discharge. Vaccination with a fourth dose booster appears to significantly influence reduction of symptoms associated with long COVID fatigue among the males. We further identified important laboratory biomarkers for long COVID. Elevated levels of IL-1β, IL-10, and TNF, along with low levels of IL-6, IL-18, and IL-12p70, also offer new insights into the inflammatory state in long COVID.
Research on wave measurement and simulation experiments of binocular stereo vision based on intelligent feature matching
Authors: Wu Junjie , Chen Shizhe , Liu Shixuan , Song Miaomiao , Wang Bo , Zhang Qingyang , Wu Yushang , Lei Zhuo , Zhang Jiming , Yan Xingkui , Miao Bin
Published: December 2024

Waves are crucial in ocean observation and research. Stereo vision-based wave measurement, offering non-contact, low-cost, and intelligent processing, is an emerging method. However, improving accuracy remains a challenge due to wave complexity. This paper presents a novel approach to measure wave height, period, and direction by combining deep learning-based stereo matching with feature matching techniques. To improve the discontinuity and low accuracy in disparity maps from traditional wave image matching algorithms, this paper proposes the use of a high-precision stereo matching method based on Pyramid Stereo Matching Network (PSM-Net).A 3D reconstruction method integrating Scale-Invariant Feature Transform (SIFT) with stereo matching was also introduced to overcome the limitations of template matching and interleaved spectrum methods, which only provide 2D data and fail to capture the full 3D motion of waves. This approach enables accurate wave direction measurement. Additionally, a six-degree-of-freedom platform was proposed to simulate waves, addressing the high costs and attenuation issues of traditional wave tank simulations. Experimental results show the prototype system achieves a wave height accuracy within 5%, period accuracy within 4%, and direction accuracy of ±2°, proving the method’s effectiveness and offering a new approach to stereo vision-based wave measurement.
Novel approach to studying marine fauna: using long-life remote underwater video cameras to assess occurrence and behaviour of threatened and data-deficient elasmobranch species in southern Mozambique
Authors: Buschmann Jule , Roques Kim G. , Davies Jaime S. , Dissanayake Awantha , Keeping Jennifer A.
Published: December 2024

Understanding the behaviour and ecological role of elasmobranchs is essential for their conservation, particularly in regions harbouring threatened and data-deficient species like the Inhambane coastline in southern Mozambique, southwestern Indian Ocean. This study employed long-life remote underwater video cameras (LL-RUV) to observe elasmobranch occurrence and behaviour at a rocky reef near Praia do Tofo known for frequent elasmobranch sightings. Between 2021 and 2024, 524 hours of LL-RUV data were collected, revealing the presence of 14 threatened and data-deficient elasmobranch species. Reef manta rays (Mobula alfredi), small eye stingrays (Megatrygon microps), and oceanic manta rays (Mobula birostris) were identified as the primary elasmobranch users of the studied cleaning stations (n = 81, n = 72 and n = 61 respectively), engaging in mutualistic interactions with cleaner fish and spending significant amounts of time at the studied reef. In contrast, spotted eagle rays (Aetobatus narinari) and blacktip sharks (Carcharhinus limbatus) were solely observed cruising over the reef without engaging in cleaning interactions (n = 40 and n = 27 respectively). In addition, this study provides evidence of intra- and inter-specific interactions between reef and oceanic manta rays, small eye stingrays and bowmouth guitarfish (Rhina ancylostoma) and co-occurrences of both manta ray species and smalleye stingrays with “hitchhiker” species including cobia (Rachycentron canadum) and remoras (Echeneis spp.). The use of LL-RUV cameras represents a significant advancement in marine research. These cameras enable continuous, non-intrusive, long-term monitoring of marine environments, capturing natural behaviours, while minimising disturbances caused by divers. As a result, more accurate observations of elasmobranch behaviour and cleaning station dynamics can be recorded, which might be missed during short-term surveys. This research highlights the potential of LL-RUV cameras as powerful tools for advancing our understanding of elasmobranch occurrence and behaviour and underscores their value in informing targeted and effective conservation strategies. Beyond elasmobranch research, LL-RUVs hold tremendous potential for studying a wide range of marine species and habitats, offering a versatile tool for ecological monitoring and conservation efforts across diverse marine ecosystems.
Effects of microplastics pollution in sediments on physicochemical properties and microbial community distribution in coastal Spartina alterniflora-invaded wetlands
Authors: Li Guo , Ran Jiao , Dong Jing , Yang Kai , Hu Jingru , Shi Jing , Zhang Yumiao , Chen Jiabin , Zhao Yu , Zhu Ensheng , Huang Suzhen , Zheng Zheng
Published: December 2024

Introduction

Coastal wetlands play an important role in the global ecosystem, yet they are increasingly facing ecological degradation due to pollution and the spread of invasive Spartina alterniflora (S. alterniflora). Among the environmental challenges, microplastics (MPs) contamination in S. alterniflora-invaded coastal wetlands is of growing concern. However, the effects of MPs pollution in S. alterniflora-invaded coastal wetlands are not clear.

Methods

This study investigated the effects of S. altemiflora invasion on the distribution of MPs and the effects of MPs pollution on the physicochemical properties of sediments and the structure of microbial communities in the Tiaozini wetland of Jiangsu Province, China.

Results and discussion

The total MPs abundance of the S. altemiflora single-plant area was the highest (16.338 x103 items/kg d.w.). Polyurethane and Chlorinated polyisoprene are typical MPs types in the study area. Polyurethane exhibits high abundance at all sampling sites, while Chlorinated polyisoprene is one of the dominant MPs types in the single-plant and sub-mature area of S. alterniflora. The results showed that the invasion of S. alterniflora promoted the accumulation of MPs in the sediments of the coastal wetland. This accumulation increased the total organic carbon (TOC), available phosphorus (AP) and total nitrogen (TN) contents. Moreover, MPs pollution increased the ALP and SUC enzyme activities of sediment. In addition, MPs contamination increased the abundance of Proteobacteria and Bacteroidota in the sediments. This study highlights the complex interactions between MPs pollution and S. alterniflora invasion, providing the foundation for understanding the synergistic impacts of these stressors on coastal wetland ecosystems.
Socioeconomic predictors of preventive health check-ups by a general practitioner in the Czech Republic
Authors: Zimmermannova Jarmila , Vevoda Jiri , Schovankova Tereza , Holy Ondrej
Published: December 2024

Health is one of the Sustainable Development Goals. The importance of health promotion is growing in the context of an aging population and increasing life expectancy. Prevention is often underestimated and neglected by citizens. This article aims to identify the socioeconomic predictors of preventive health check-ups by general practitioners in the Czech Republic, focusing on selected age groups. An original dataset is prepared based on data for 2010–2019 provided by the largest health insurance company in the Czech Republic, the General Health Insurance Company. Correlation and regression analysis methods are used to achieve the objectives. Two models are built and tested: (1) preventive examinations model and (2) preventive examinations in age group 65+ model. Based on the results, preventive medical examinations in the pensioner group depended on economic indicators, such as the average wage, employment, and gross domestic product, in the analyzed period. For the total population, overall population size, the average age, urbanized area, and level of education play a key role. The results reveal a difference between the general population group and the 65+ population group. Government interventions and health policies promoting prevention should consider using appropriate incentive policy instruments targeting the 65+ population to prolong active life in senior age.
Fungal keratitis caused by Neurospora: a case report
Authors: Lu Yao , Mo Yijun , Weng Yuesong , Li Xiaohui
Published: December 2024

Background

We report a rare case of fungal keratitis caused by Neurospora, a filamentous fungus that is widely distributed in soil and graminaceous plants.

Case presentation

A 40-year-old Mongoloid male patient came to our outpatient clinic with painful swelling of the left eye and redness, after being cut by a tree branch 1 week prior. After examination, the patient was diagnosed with a corneal ulcer of the left eye, and was given levofloxacin eye drops and levofloxacin ophthalmic gel. However, the patient did not respond to the treatment. After admission to the hospital, fungal mycelium was found in the corneal smear. To further identify the pathogen, a corneal scraping culture was used to extract fungal DNA and PCR amplification was performed using ITS universal primers, which was later sequenced and identified as Neurospora. We used fluconazole injections (0.2 g/100 mL) as eye drops to treat the patient once every hour, and itraconazole (200 mg) was administered orally once a day. After a few days, the patient’s condition improved.

Conclusion

To the best of our knowledge, this is the first reported case of fungal keratitis caused by Neurospora in China. In this case, conventional topical and systemic treatment resulted in a favorable outcome. In patients with suspected fungal keratitis, medical treatment should be started urgently, and the treatment plan should be adjusted according to the subsequent experimental results and the patient’s condition.
Comparative analysis of gut microbiota in metabolic syndrome and obese children from Southeastern China
Authors: Wang Jingjing , Zhuang Peifeng , Lin Bin , Zheng Jinlu , Li Haiqing , Tang Wenlin , Ye Wenbin , Chen Xiangjian , Zheng Mingping
Published: December 2024

The prevalence of childhood obesity is rising globally, with some obese children progressing to develop metabolic syndrome (MS). However, the specific differences between these groups remain unclear. To investigate the differences in gut microbiota, we conducted physiological and biochemical assessments, alongside 16S rRNA sequencing, in a cohort of 32 children from Southeastern China, which included 4 normal-weight children, 5 with mild obesity, 9 with moderate obesity, 9 with severe obesity, and 5 with metabolic syndrome. Our results indicated that waist circumference, serum triglycerides, total cholesterol, non-HDL levels, and the prevalence of fatty liver were significantly elevated in both obese and MS children compared to their normal-weight peers, with the MS group exhibiting more pronounced abnormalities. Conversely, HDL levels showed a contrasting trend. Additionally, alpha diversity of gut microbiota increased with weight, while beta diversity analysis revealed significant compositional differences between children with MS and those who were normal weight or obese. At the class and genus levels, we found that the relative abundance of c_Gammaproteobacteria increased with weight, whereas c_Bacteroidia and g_Bacteroides decreased. Notably, g_Faecalibacterium was significantly less abundant in the MS group compared to the other cohorts. LEfSe and functional analyses identified distinct gut microbiota and functional differences between children with MS and those with normal weight or obesity. Furthermore, gavage experiments in mice showed that gut microbiota from obese and MS subjects significantly increased serum triglycerides and cholesterol levels, leading to hepatocellular damage. In contrast, fecal gavage from normal-weight individuals into obese model mice significantly reduced serum triglycerides and the number of degenerative liver cells, as well as the extent of fat accumulation. These findings provide critical insights into the understanding and management of obesity and metabolic syndrome in pediatric populations.
Evolution of community-associated MRSA: a 20-year genomic and epidemiological study in Region Örebro County, Sweden
Authors: Kekki Jan , Thegel Annethe , Stenmark Bianca , Söderquist Bo
Published: December 2024

Background

Methicillin-resistant Staphylococcus aureus (MRSA) has been an issue in healthcare since the 1960s. It was initially found only in healthcare facilities, but in the late 1990s it began to be seen with no healthcare connexion. The mechanisms of intercontinental and national spread are not fully understood, as sometimes novel outbreaks occur without any identifiable source or connexion to locally dominant clonal clusters.

Methods

This study investigated the epidemiology and genomics of community-associated MRSA in Region Örebro County, Sweden, through 330 isolates collected between 2000 and 2019.

Results

A shift in the dominant sequence type (ST) from ST80 to ST22 occurred in 2011–2019, along with an increase in the prevalence of STs belonging to clonal complexes CC5 and CC22. Both ST8 and ST80 isolates seemed to give way to emerging ST22 isolates, also indicated by the declining presence of the USA300 clone. The staphylococcal chromosomal cassette mec (SCCmec) type IV Remained dominant.

Conclusions

The SCCmec type IV characteristic appears to be relatively geographically stable, possibly due to its low fitness cost and transductal capabilities. This warrants further studies of SCCmec type IV variant's survival mechanics as well as the effects of migratory flow on local epidemiology, in preparation for future possible outbreaks.
Can there be calm during a cytokine storm? Immune checkpoint pathways affecting the severity of COVID-19 disease
Authors: Meggyes Matyas , Nagy David U. , Toth Ildiko , Feik Timoteus , Peterfalvi Agnes , Polgar Beata , Sipos David , Kemeny Agnes , Szereday Laszlo
Published: December 2024

Introduction

The COVID-19 pandemic has become a global health crisis, eliciting varying severity in infected individuals. This study aimed to explore the immune profiles between moderate and severe COVID-19 patients experiencing a cytokine storm and their association with mortality. This study highlights the role of PD-1/PD-L1 and the TIGIT/CD226/CD155/CD112 pathways in COVID-19 patients.

Methods

We performed a study using flow cytometry to compare the phenotypic and functional characteristics of peripheral blood mononuclear cells in patients with moderate or severe disease and healthy individuals. Soluble immune checkpoint molecule and ligand levels were measured by Luminex.

Results

Severe patients show reduced CD8+ T cell frequency, hyperactivation of CD8+ T, NK and NKT cells with concurrent upregulation of immune checkpoint ligands in monocytes. TIGIT expression by CD8+ T and NK cells and PD-1 by NKT cells suggest a spectrum of immune dysfunction, encompassing both hyperactivation and features of exhaustion. This dual phenomenon likely contributes to the impaired viral clearance and the exacerbation of inflammation characteristic of severe disease. Additionally, the study suggests that increased activation and cytotoxicity of NK cells may be associated with fatal outcomes in severe COVID-19 infection.

Conclusion

These findings shed light on the intricate immune response regulation in COVID-19, emphasizing the importance of immune checkpoint pathways and activation signatures in disease severity. A novel aspect of this study is that it includes only COVID-19 patients experiencing cytokine storms, allowing for a focused analysis of immune dysregulation during this critical phase of the disease.
dna2bit: high performance genomic distance estimation software for microbial genome analysis
Authors: Li Juzeng , Tian Yuxin , Wang Yi , Jin Li
Published: December 2024

dna2bit is an ultra-fast software specifically engineered for microbial genome analysis, particularly adept at calculating genome distances within metagenome and single amplified genome datasets. Distinguished from existing software such as Mash and Dashing, dna2bit employs feature hashing technique and Hamming distance to achieve enhanced speed and memory utilization, without sacrifice in the accuracy of average nucleotide identity calculations. dna2bit has promising applications in various domains such as average nucleotide identity approximation, metagenomic sequence clustering, and homology querying. dna2bit significantly boosts computational efficiency in handling large datasets including single amplified genomes, thereby facilitating a better understanding of the population heterogeneity and comparative genomics of microorganisms. dna2bit is available at https://github.com/lijuzeng/dna2bit.
Trauma and the default mode network: review and exploratory study
Authors: Chan Aldrich , Harvey Philip , Hernandez-Cardenache Rene , Alperin Noam , Lee Sang , Hunt Christopher , Petersen Nick , Northoff Georg , Robertson Nadine , Ouyang Jason , Karasik Ryan , Williams Kate
Published: December 2024

While PTSD continues to be researched in great depth, less attention has been given to the continuum of traumatic responses that resides outside this diagnosis. This investigation begins with a literature review examining the spectrum of responses through the lens of the default mode network (DMN). To build upon this literature, a systematic exploratory study was incorporated, examining DMN-related neuropsychological functioning of 27 participants (16 trauma-exposed, and 11 non-trauma-exposed), with a subset (15 participants) completing neuroimaging. This study revealed that in comparison to the control group, the trauma-exposed group had reductions in their capacity for self-referential processing, social cognition, autobiographical recall, prospection, and increased mind-wandering. While correlations were encountered between cognitive findings and brain volume, comparative volumetric findings between trauma-exposed and non-t rauma exposed were insignificant. This suggests that the conservation of DMN structural integrity may play a role in resilience, supporting the existing theory that reduced hippocampal volume may be a pre-existing vulnerability to PTSD rather than a consequence and that reductions in DMN related cognition are functionally mediated.
MGFusion: a multimodal large language model-guided information perception for infrared and visible image fusion
Authors: Yang Zengyi , Li Yunping , Tang Xin , Xie MingHong
Published: December 2024

Existing image fusion methods primarily focus on complex network structure designs while neglecting the limitations of simple fusion strategies in complex scenarios. To address this issue, this study proposes a new method for infrared and visible image fusion based on a multimodal large language model. The method proposed in this paper fully considers the high demand for semantic information in enhancing image quality as well as the fusion strategies in complex scenes. We supplement the features in the fusion network with information from the multimodal large language model and construct a new fusion strategy. To achieve this goal, we design CLIP-driven Information Injection (CII) approach and CLIP-guided Feature Fusion (CFF) strategy. CII utilizes CLIP to extract robust image features rich in semantic information, which serve to supplement the information of infrared and visible features, thereby enhancing their representation capabilities for the scene. CFF further utilizes the robust image features extracted by CLIP to select and fuse the infrared and visible features after the injection of semantic information, addressing the challenges of image fusion in complex scenes. Compared to existing methods, the main advantage of the proposed method lies in leveraging the powerful semantic understanding capabilities of the multimodal large language model to supplement information for infrared and visible features, thus avoiding the need for complex network structure designs. Experimental results on multiple public datasets validate the effectiveness and superiority of the proposed method.
Vascular injury in glomerulopathies: the role of the endothelium
Authors: Barbosa Géssica Sabrine Braga , Câmara Niels Olsen Saraiva , Ledesma Felipe Lourenço , Duarte Neto Amaro Nunes , Dias Cristiane Bitencourt
Published: December 2024

In glomerulopathies, endothelial dysfunction and the presence of histological vascular lesions such as thrombotic microangiopathy, arteriolar hyalinosis, and arteriosclerosis are related to a severe clinical course and worse renal prognosis. The endothelial cell, which naturally has anti-inflammatory and anti-thrombotic regulatory mechanisms, is particularly susceptible to damage caused by various etiologies and can become dysfunctional due to direct/indirect injury or a deficiency of protective factors. In addition, endothelial regulation and protection involve participation of the complement system, factors related to angiogenesis, the renin–angiotensin system (RAS), endothelin, the glycocalyx, the coagulation cascade, interaction between these pathways, interactions between glomerular structures (the endothelium, mesangium, podocyte, and basement membrane) and interstitial structures (tubules, arterioles and small vessels). Dysregulation of those components is also associated with the progression of renal fibrosis, since endothelial cell damage promotes endothelial-to-mesenchymal transition. Although the potential mechanisms of vascular injury have been widely described in diabetic kidney disease, hypertensive nephrosclerosis, and hemolytic uremic syndrome, they require further elucidation in other glomerulopathies. A better understanding of the pathogenesis of vascular injury in patients with glomerular diseases could contribute to the development of specific treatments for such injury.
The role and clinical implications of HIF-PHI daprodustat in dialysis-dependent and non-dialysis-dependent chronic kidney disease anemic patients: a general review
Authors: Waheed Yousuf Abdulkarim , Liu Jie , Almayahe Shifaa , Sun Dong
Published: December 2024

Chronic kidney disease (CKD) patients often suffer from complications such as anemia as the kidney function declines. More than 25% of CKD hemodialysis patients in China are complicated with renal anemia due to renal and hepatic impairment in the production of erythropoietin (EPO). In recent years, prolyl hydroxylase domain (PHD) inhibitors have been approved in China and Japan for the treatment of CKD patients complicated with anemia. Daprodustat is a novel orally administrated active hypoxia-induced factor-prolyl hydroxylase inhibitor (HIF-PHI) that may improve quality of life and ischemic conditions such as peripheral arterial disease (PAD), stimulate the synthesis of endogenous EPO, and can effectively induce the production of red blood cells. It has been shown to increase EPO levels, which can lead to an increase in hemoglobin (Hgb), hematocrit, and red blood cell counts. Clinical studies have shown its effectiveness in dialysis and non-dialysis CKD anemic patients. In this literature review, we will focus on the mechanism and metabolism of the drug as well as its clinical applications in dialysis and non-dialysis CKD patients and summarize the adverse reactions.
Commercial symptom monitoring devices in Parkinson’s disease: benefits, limitations, and trends
Authors: Rodríguez-Martín Daniel , Pérez-López Carlos
Published: December 2024

Parkinson’s disease (PD) is a neurodegenerative disorder that significantly impacts patients’ quality of life. Managing PD requires accurate assessment of motor and non-motor symptoms, often complicated by the subjectivity in symptom reporting and the limited availability of neurologists. To address these challenges, commercial wearable devices have emerged to continuously monitor PD symptoms outside the clinical setting. The main devices include PKG™, Kinesia 360™, Kinesia U™, PDMonitor™, and STAT-ON™. These devices utilize advanced technologies such as accelerometers, gyroscopes, and specific algorithms to provide objective data on motor symptoms like tremors, dyskinesia, and bradykinesia. Despite their potential, the adoption of these devices is limited due to concerns about their accuracy, complexity of use, and lack of independent validation. The correlation between these devices’ measurements and traditional clinical observations varies, and patient usability and adherence remain critical areas for improvement. To optimize their utility and improve patient outcomes, it is essential to conduct validation and usability studies with a sufficient number of patients, develop standardized protocols, and ensure integration with hospital information systems.