bluuebunny/crossref_metadata_2025 huggingface dataset:
Application value of multi-gene mutation detection in the clinical management of pediatric papillary thyroid carcinoma: a preliminary exploration
Authors: Wang Yuguo , Wang Hui , Tan Gongxun , Wu Xinping , Wang Bin , Tan Zhihan , Du Jing , Li Xiuying , Xu Ying , Yan Na , Qian Xiaoqin
Published: June 2024

Objectives

Thyroid cancer rarely occurs in children and adolescents. Molecular markers such as BRAF, RAS, and RET/PTC have been widely used in adult PTC. It is currently unclear whether these molecular markers have equivalent potential for application in pediatric patients. This study aims to explore the potential utility of a multi-gene conjoint analysis based on next-generation targeted sequencing for pediatric papillary thyroid carcinoma (PTC).

Materials and methods

The patients diagnosed with PTC (aged 18 years or younger) in the pediatrics department of Lishui District Hospital of Traditional Chinese Medicine were retrospectively screened. A targeted enrichment and sequencing analysis of 116 genes associated with thyroid cancer was performed on paraffin-embedded tumor tissues and paired paracancerous tissue of fifteen children (average age 14.60) and nine adults (average age 49.33) PTC patients. Demographic information, clinical indicators, ultrasonic imaging information and pathological data were collected. The Kendall correlation test was used to establish a correlation between molecular variations and clinical characteristics in pediatric patients.

Results

A sample of 15 pediatric PTCs revealed a detection rate of 73.33% (11/15) for driver gene mutations BRAF V600E and RET fusion. Compared to adult PTCs, the genetic mutation landscape of pediatric PTCs was more complex. Six mutant genes overlap between the two groups, and an additional seventeen unique mutant genes were identified only in pediatric PTCs. There was only one unique mutant gene in adult PTCs. The tumor diameter of pediatric PTCs tended to be less than 4cm (p<0.001), and the number of lymph node metastases was more than five (p<0.001). Mutations in specific genes unique to pediatric PTCs may contribute to the onset and progression of the disease by adversely affecting hormone synthesis, secretion, and action mechanisms, as well as the functioning of thyroid hormone signaling pathways. But, additional experiments are required to validate this hypothesis.

Conclusion

BRAF V600E mutation and RET fusion are involved in the occurrence and development of adolescent PTC. For pediatric thyroid nodules that cannot be determined as benign or malignant by fine needle aspiration biopsy, multiple gene combination testing can provide a reference for personalized diagnosis and treatment by clinical physicians.
PV grid-connected information interaction methods based on public information modeling
Authors: Wu Peng , Yu Lei , Zhang Ruifeng , Liu Yinliang , Lin Xinhao , Chen Hang , Liu Tong
Published: June 2024

The grid integration of large-scale photovoltaic and other distributed energy sources is an effective solution for addressing power supply shortages and environmental pollution. However, the widespread adoption of photovoltaics and grid integration presents various technological and management challenges. To fulfill the demands of grid management and ensure safe operations, the exchange of information between different terminals is continuously escalating. Use of diverse communication standards creates the problem of “information islands” among terminals. Hence, a standardized information model is crucial for describing the photovoltaic grid integration business and enhancing the efficiency of related software platform research and development. This study extends the IEC 61970/61968 standards and presents a common information model for the integration of photovoltaic systems into the grid. Initially, the operational procedures for integrating photovoltaic systems into the grid are analyzed, and UML modeling tools are employed for business modeling purposes. Subsequently, leveraging the outcomes of the business modeling and the content of the IEC 61970/61968 standards, the development of the common information model is executed. Lastly, causal analysis is conducted along with the modeling of communication standard extensions specifically targeted for the integration of photovoltaic systems into the grid, culminating in the finalization of the construction of the common information model for photovoltaic grid connection.
Technoeconomic analysis: the potential and opportunities of transforming Saudi Arabian scrap tires into synthetic fuel via vacuum pyrolysis
Authors: Yahya Sulaiman Al , Omar Muhammad Mubashar
Published: June 2024

Environmental hazards linked with scrap tires have been a great concern for the Saudi government. The Kingdom of Saudi Arabia has a Vision 2030 project with an aim to produce 50% of its energy through renewable energy resources. The tire market in the country reached 22.2 million units in 2022 and is expected to increase up to 24.9 million in 2028 with a growth rate of 2.11%. This study used a vacuum pyrolyzer for transforming scrap tires into tire-derived oil (TDO), along with other products such as synthesis gas (syngas) and carbon black. It provides a feasible way of transforming scrap tires into synthetic fuel via vacuum pyrolysis (a thermochemical approach). Vacuum pyrolysis of scrap tires at temperature 350–400oC yields 45%–55% derived oil, 10%–15% steel wires, 30%–35% carbon black, and 10%–15% non-condensable gases. The heating value of the obtained tire-derived oil is 32–37 MJ/kg, which is somehow less than that of diesel, which has an energy value of 44–46 MJ/kg. Such products are expected to be obtained after the successful adaptation of advanced techniques such as thermochemical approaches and can successfully be used as an alternative to fossil fuels. Based on the scrap tire produced in the country, if Saudi Arabia can process 22.2 million units of tires (trucks and passenger cars) annually through vacuum pyrolysis, it can earn approximately $47.40 million annually (or $2.14 per tire) through tire pyrolysis. Utilization of carbon black (recovered from scrap tire pyrolysis) in manufacturing tires can save approximately 2.5 tons of CO2 production compared to per ton production of new (virgin) carbon black. This study suggested pyrolysis to be a viable recycling and waste tire management technique, and it can be an independent profitable operation in Saudi Arabia and helps in meeting the Saudi Vision 2030.
A comparative assessment of the capabilities and success of the wood construction industry in Slovakia and Ukraine based on life cycle assessment certification standards
Authors: Delehan Svitlana , Vilčeková Silvia , Melehanych Hanna , Krídlová Burdová Eva , Khorolskyi Andrii
Published: June 2024

This study assessed the possibility of using wood as a building material for the construction of houses. A comprehensive method was used, which consisted of analysing environmental management regulations, applying the life cycle assessment method to minimise the carbon footprint; using software to calculate the carbon footprint of a wooden house at different stages of the life cycle. The object of study is the carbon footprint of a house built of wood. The Life Cycle Assessment method was used as a methodology for assessing the life cycle. Using the One Click Life Cycle Assessment and Life Cycle Cost software, the carbon footprint of a log house was calculated for the product life cycle stage mentioned above (A1-A3). When calculating the carbon footprint of wood-based building materials, carbon emissions were taken into account not only from the finished products, but also from all other products obtained as a result of logging. When calculating the carbon footprint, greenhouse gas emissions from all activities are estimated. We have obtained data on the life cycle cost of a wooden house in terms of electricity use. Accordingly, we obtained a value of global warming potential (A1-A3) of 0.51 kg CO2 e/kWh. We also obtained data on the life cycle cost of a wooden house in terms of diesel consumption. According to the results of the LCA, the value of the global warming potential due to meeting the water supply/sewage needs is (A1-A3) 0.69 kg CO2 e/m3. The value of the global warming potential due to meeting the heat supply needs of production needs is (A1- A3) 0.13 kg CO2 e/kWh. Based on the information obtained, we can conclude that it is advisable to use a wooden log house as a building material, as the carbon footprint is smaller than that of a brick building. The final section presents the results of calculating the life cycle cost of a wooden house by discount factor and inflation, the results of the life cycle cost of a wooden house by percentage of energy costs, and the results of assessing the life cycle cost of a wooden house (displaying parameters according to the European energy certification scale). Based on the carbon footprint assessment (using the Life Cycle Assessment methodology), economic comparison (Life Cycle Cost and total construction costs), and expert assessment (based on technical and ergonomic parameters) of the two construction technologies, the feasibility and possibility of using wood as a building material was established. The study proves the feasibility of applying the LCA method in the construction industry.
Flexibility evaluation of psammophytes using Young’s modulus based on 3D numerical simulation
Authors: Xiang Hongxu , Wu Xiaoxu , Wang Rende , Shi Chunming , Fang Hui , Zou Xueyong , Guo Zhiyi , Yin Jie , Liu Xingchen , Yang Xiaofan
Published: June 2024

Flexible psammophytes play an important role in controlling soil wind erosion and desertification, owing to their characteristics. Although flexibility of psammophytes has been considered in previous studies, the interaction between flexible psammophytes and the surrounding airflow field still remained unclear. In this study, we used the Young’s modulus to describe plant flexibility and conducted a 3D computational fluid dynamics simulation using a standard k-ε model and a fluid–structure interaction model. Taking Caragana korshinskii (Caragana), a typical psammophyte, as the research object, we constructed 3D geometric models with different diameters to simulate the airflow field around the flexible psammophytes. By comparing with the simulation results of rigid plants and simulation results of flexible plants at different wind speeds, we could verify the rationality of the simulation method. Based on the simulation results, the maximum swing amplitude of the model and the Young’s modulus were found to have a negative correlation, presenting an exponential functional relationship with good fitting. The relationship between the actual Young’s modulus of the plant branches and that of different diameter models in the numerical simulation was also established. This study is expected to improve our basic understanding of the interaction between flexible psammophytes and the surrounding airflow field, and provide some qualitative reference for the numerical simulation of the airflow field around flexible psammophytes.
Evidence to support phytosanitary policies–the minimum effective heat treatment parameters for pathogens associated with forest products
Authors: Noseworthy Meghan K. , Allen Eric A. , Dale Angela L. , Leal Isabel , John Esme P. , Souque Tyranna J. , Tanney Joey B. , Uzunovic Adnan
Published: June 2024

Research on reducing the movement of pests on wood products has led to several options for safer trade including heat treatment of wood to mitigate pests. In this study, pathogenic organisms commonly regulated in the trade of forest products were tested to determine the minimum heat dose (temperature and time) required to cause mortality. The mycelial stage of tree pathogens, Heterobasidion occidentale, Grosmannia clavigera, Bretziella fagacearum, Phytophthora cinnamomi, P. lateralis, P. ramorum and P. xmultiformis, which may be found in untreated wood products, were tested in vitro using the Humble water bath with parameters simulating the rate of heat applied to wood in a commercial kiln. RNA detection using reverse transcription real-time PCR was used to validate pathogen mortality following treatment for: P. ramorum, P. lateralis, P. cinnamomi, P. xmultiformis and G. clavigera. The lethal temperature for all pathogens ranged from 44 to 50°C for a 30-min treatment duration. Using this method to evaluate heat treatment for other forest product pests is recommended to accurately identify the minimum dose required to support phytosanitary trade. With more data potentially lower heat treatment applications may be recommended under specific conditions to produce more efficient and economical heat treatment schedules and reduce environmental impacts.
The causal effect of Alzheimer’s disease and family history of Alzheimer’s disease on non-ischemic cardiomyopathy and left ventricular structure and function: a Mendelian randomization study
Authors: Li Zhenjie , Chen Xiandong , He Wangping , Chen Huazeng , Chen Dehai
Published: June 2024

Background

Previous studies have shown that Alzheimer’s disease (AD) can cause myocardial damage. However, whether there is a causal association between AD and non-ischemic cardiomyopathy (NICM) remains unclear. Using a comprehensive two-sample Mendelian randomization (MR) method, we aimed to determine whether AD and family history of AD (FHAD) affect left ventricular (LV) structure and function and lead to NICM, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM).

Methods

The summary statistics for exposures [AD, paternal history of AD (PH-AD), and maternal history of AD (MH-AD)] and outcomes (NICM, HCM, DCM, and LV traits) were obtained from the large European genome-wide association studies. The causal effects were estimated using inverse variance weighted, MR-Egger, and weighted median methods. Sensitivity analyses were conducted, including Cochran’s Q test, MR-Egger intercept test, MR pleiotropy residual sum and outlier, MR Steiger test, leave-one-out analysis, and the funnel plot.

Results

Genetically predicted AD was associated with a lower risk of NICM [odds ratio (OR) 0.9306, 95% confidence interval (CI) 0.8825–0.9813, p = 0.0078], DCM (OR 0.8666, 95% CI 0.7752–0.9689, p = 0.0119), and LV remodeling index (OR 0.9969, 95% CI 0.9940–0.9998, p = 0.0337). Moreover, genetically predicted PH-AD was associated with a decreased risk of NICM (OR 0.8924, 95% CI 0.8332–0.9557, p = 0.0011). MH-AD was also strongly associated with a decreased risk of NICM (OR 0.8958, 95% CI 0.8449–0.9498, p = 0.0002). Different methods of sensitivity analysis demonstrated the robustness of the results.

Conclusion

Our study revealed that AD and FHAD were associated with a decreased risk of NICM, providing a new genetic perspective on the pathogenesis of NICM.
Delivery of a national prenatal exome sequencing service in England: a mixed methods study exploring healthcare professionals’ views and experiences
Authors: Peter Michelle , Mellis Rhiannon , McInnes-Dean Hannah , Daniel Morgan , Walton Holly , Fisher Jane , Leeson-Beevers Kerry , Allen Stephanie , Baple Emma L. , Beleza-Meireles Ana , Bertoli Marta , Campbell Jennifer , Canham Natalie , Cilliers Deirdre , Cobben Jan , Eason Jacqueline , Harrison Victoria , Holder-Espinasse Muriel , Male Alison , Mansour Sahar , McEwan Alec , Park Soo-Mi , Smith Audrey , Stewart Alison , Tapon Dagmar , Vasudevan Pradeep , Williams Denise , Wu Wing Han , Chitty Lyn S. , Hill Melissa
Published: June 2024

Introduction

In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England, requiring the coordination of care from specialist genetics, fetal medicine (FM) and laboratory services. This mixed methods study explored the experiences of professionals involved in delivering the pES service during the first 2 years of its delivery in the NHS.

Methods

A survey (n = 159) and semi-structured interviews (n = 63) with healthcare professionals, including clinical geneticists, FM specialists, and clinical scientists (interviews only) were used to address: 1) Views on the pES service; 2) Capacity and resources involved in offering pES; 3) Awareness, knowledge, and educational needs; and 4) Ambitions and goals for the future.

Results

Overall, professionals were positive about the pES service with 77% rating it as Good or Excellent. A number of benefits were reported, including the increased opportunity for receiving actionable results for parental decision-making, improving equity of access to genomic tests and fostering close relationships between FM and genetics departments. Nonetheless, there was evidence that the shift to offering pES in a clinical setting had brought some challenges, such as additional clinic time, administrative processes, perceived lack of autonomy in decision-making regarding pES eligibility and difficulty engaging with peripheral maternity units. Concerns were also raised about the lack of confidence and gaps in genomics knowledge amongst non-genetics professionals - especially midwives. However, the findings also highlighted value in both FM, obstetric and genetics professionals benefiting from further training with a focus on recognising and managing prenatally diagnosed genetic conditions.

Conclusion

Healthcare professionals are enthusiastic about the benefits of pES, and through multi-collaborative working, have developed relationships that have contributed to effective communication across specialisms. Although limitations on resources and variation in knowledge about pES have impacted service delivery, professionals were hopeful that improvements to infrastructure and the upskilling of all professionals involved in the pathway would optimise the benefits of pES for both parents and professionals.
Immune cell populations and induced immune responses at admission in patients hospitalized with vaccine breakthrough SARS-CoV-2 infections
Authors: Sejdic Adin , Hartling Hans Jakob , Holler Jon Gitz , Klingen Gjærde Lars , Lindegaard Birgitte , Dungu Arnold Matovu , Gnesin Filip , Møller Maria Elizabeth Engel , Teglgaard Rebecca Svanberg , Niemann Carsten Utoft , Brooks Patrick Terrence , Jørgensen Charlotte Sværke , Franck Kristina Træholt , Fischer Thea K. , Marquart Hanne Vibeke , Harboe Zitta Barrella , Ostrowski Sisse Rye
Published: June 2024

Background

Vaccine breakthrough SARS-CoV-2 infections are common and of clinical and public health concern. However, little is known about the immunological characteristics of patients hospitalized due to these infections. We aimed to investigate and compare immune cell subpopulations and induced immune responses in vaccinated and non-vaccinated patients hospitalized with severe COVID-19.

Methods

A nested case-control study on adults (≥ 18 years) who received at least two doses of a mRNA-COVID-19 vaccine and were hospitalized with SARS-CoV-2 breakthrough infections and severe COVID-19 between January 7, 2021, and February 1, 2022, were eligible for inclusion. Age- and sex-matched non-vaccinated controls were identified. Immunophenotyping was performed using a custom-designed 10-color flow cytometry prefabricated freeze-dried antibody panel (DuraClone, Beckman Coulter (BC), Brea, Calif). TruCulture (Myriad RBM, Austin, USA) was used to assess induced immune response in whole blood, revealing different critical signaling pathways as a proxy for immune function. All samples were obtained within 48 hours of admission.

Results

In total, 20 hospitalized patients with severe COVID-19 and a breakthrough SARS-CoV-2 infection were included, ten vaccinated and ten non-vaccinated patients. Vaccinated patients had lower concentrations of CD19 B cells (p = 0.035), naïve CD4 T cells (p = 0.015), a higher proportion of γδ1 T cells (p = 0.019), and higher unstimulated immune cell release of IL-10 (p = 0.015).

Conclusion

We observed immunological differences between vaccinated and non-vaccinated patients hospitalized due to severe COVID-19 that indicate that vaccinated patients had lower B cell concentrations, lower concentrations of CD4 naïve T cells, a skewed gamma-delta V1/V2 ratio, and an exaggerated IL-10 response at admission. These results could indicate a suboptimal immune response involved in SARS-CoV-2 breakthrough infections that cause severe COVID-19 in vaccinated adults. However, the sample size was small, and further research is needed to confirm these results.
Evaluating the link between immune characteristics and attention deficit hyperactivity disorder through a bi-directional Mendelian randomization study
Authors: Jue Hu , Dan-fei Chen , Fang-fang Li , Ke-pin Yu , Jia-ye Xu , Hui-ting Zhang , Xiao-bo Xuan , Jian Chen
Published: June 2024

Context

Despite the recognition of attention deficit hyperactivity disorder (ADHD) as a multifaceted neurodevelopmental disorder, its core causes are still ambiguous. The objective of this study was to explore if the traits of circulating immune cells contribute causally to susceptibility to ADHD.

Methods

By employing a unified GWAS summary data covering 731 immune traits from the GWAS Catalog (accession numbers from GCST0001391 to GCST0002121), our analysis focused on the flow cytometry of lymphocyte clusters, encompassing 3,757 Sardinians, to identify genetically expected immune cells. Furthermore, we obtained summarized GWAS statistics from the Psychiatric Genomics Consortium to evaluate the genetic forecasting of ADHD. The studies employed ADHD2019 (20,183 cases and 35,191 controls from the 2019 GWAS ADHD dataset) and ADHD2022 (38,691 cases and 275,986 controls from the 2022 GWAS ADHD dataset). Through the examination of genome-wide association signals, we identified shared genetic variances between circulating immune cells and ADHD, employing the comprehensive ADHD2022 dataset. We primarily utilized inverse variance weighted (IVW) and weighted median methods in our Mendelian randomization research and sensitivity assessments to evaluate diversity and pleiotropy.

Results

After adjusting for false discovery rate (FDR), three distinct immunophenotypes were identified as associated with the risk of ADHD: CD33 in Im MDSC (OR=1.03, CI: 1.01~1.04, P=3.04×10−5, PFDR=0.015), CD8br NKT %T cell (OR=1.08, 95%CI: 1.04~1.12, P=9.33×10−5, PFDR=0.023), and CD8br NKT %lymphocyte (OR=1.08, 95%CI: 1.03~1.12, P=3.59×10−4, PFDR=0.066). Furthermore, ADHD showed no statistical effects on immunophenotypes. It’s worth noting that 20 phenotypes exist where ADHD’s appearance could diminish 85% of immune cells, including FSC-A in myeloid DC (β= -0.278, 95% CI: 0.616~0.931, P=0.008), CD3 in CD45RA- CD4+ (β= -0.233, 95% CI: 0.654~0.960, P=0.017), CD62L- monocyte AC (β=0.227, 95% CI: 0.038~1.518, P=0.019), CD33 in CD33br HLA DR+ CD14dim (β= -0.331, 95% CI: 0.543~0.950, P=0.020), and CD25 in CD39+ resting Treg (β=0.226, 95% CI: 1.522, P=0.022), and FSC-A in monocytes (β= -0.255, 95% CI: 0.621~0.967, P=0.234), among others.

Conclusion

Studies indicate that the immune system’s response influences the emergence of ADHD. The findings greatly improve our understanding of the interplay between immune responses and ADHD risk, aiding in the development of treatment strategies from an immunological perspective.
Bevacizumab-induced immune thrombocytopenia in an ovarian cancer patient with mixed connective tissue disease: case report and literature review
Authors: Zhang Yunting , Yang Fanchun , Wang Jining , Fu Hui , Shen Fuming , Liu Jie , Li Dongjie
Published: June 2024

Drug-induced immune thrombocytopenia is an adverse reaction marked by accelerated destruction of blood platelets. In cancer therapy, thrombocytopenia has many other causes including bone marrow suppression induced by chemotherapeutic agents, infection, and progression of cancer; drug-induced thrombocytopenia can easily be misdiagnosed or overlooked. Here, we present a case of an ovarian cancer patient with a history of mixed connective tissue disease who underwent surgery followed by treatment with paclitaxel, cisplatin, and bevacizumab. The patient developed acute isolated thrombocytopenia after the sixth cycle. Serum antiplatelet antibody testing revealed antibodies against glycoprotein IIb. After we analyzed the whole therapeutic process of this patient, drug-induced immune thrombocytopenia was assumed, and bevacizumab was conjectured as the most probable drug. Thrombocytopenia was ultimately successfully managed using recombinant human thrombopoietin, prednisone, and recombinant human interleukin-11. We provide a summary of existing literature on immune thrombocytopenia induced by bevacizumab and discuss related mechanisms and triggers for drug-induced immune thrombocytopenia. The present case underscores the potential of bevacizumab to induce immune-mediated thrombocytopenia, emphasizing the need for heightened vigilance towards autoimmune diseases or an autoimmune-activated state as plausible triggers for rare drug-induced immune thrombocytopenia in cancer therapy.
Clinical and genetic characteristics of BAP1-mutated non-uveal and uveal melanoma
Authors: Matull Johanna , Placke Jan-Malte , Lodde Georg , Zaremba Anne , Utikal Jochen , Terheyden Patrick , Pföhler Claudia , Herbst Rudolf , Kreuter Alexander , Welzel Julia , Kretz Julia , Möller Inga , Sucker Antje , Paschen Annette , Livingstone Elisabeth , Zimmer Lisa , Hadaschik Eva , Ugurel Selma , Schadendorf Dirk , Thielmann Carl Maximilian , Griewank Klaus Georg
Published: June 2024

Background

Screening for gene mutations has become routine clinical practice across numerous tumor entities, including melanoma. BAP1 gene mutations have been identified in various tumor types and acknowledged as a critical event in metastatic uveal melanoma, but their role in non-uveal melanoma remains inadequately characterized.

Methods

A retrospective analysis of all melanomas sequenced in our department from 2014–2022 (n=2650) was conducted to identify BAP1 mutated samples. Assessment of clinical and genetic characteristics was performed as well as correlations with treatment outcome.

Results

BAP1 mutations were identified in 129 cases and distributed across the entire gene without any apparent hot spots. Inactivating BAP1 mutations were more prevalent in uveal (55%) compared to non-uveal (17%) melanomas. Non-uveal BAP1 mutated melanomas frequently exhibited UV-signature mutations and had a significantly higher mutation load than uveal melanomas. GNAQ and GNA11 mutations were common in uveal melanomas, while MAP-Kinase mutations were frequent in non-uveal melanomas with NF1, BRAF V600 and NRAS Q61 mutations occurring in decreasing frequency, consistent with a strong UV association. Survival outcomes did not differ among non-uveal melanoma patients based on whether they received targeted or immune checkpoint therapy, or if their tumors harbored inactivating BAP1 mutations.

Conclusion

In contrast to uveal melanomas, where BAP1 mutations serve as a significant prognostic indicator of an unfavorable outcome, BAP1 mutations in non-uveal melanomas are primarily considered passenger mutations and do not appear to be relevant from a prognostic or therapeutic perspective.
Case report: “Fur stole and turtleneck” and “halter-back” signs: an expanded wardrobe for dermatomyositis
Authors: Ho Jonathan D. , Burton Andrew T. M. , McKenzie Trimane , Best Ciara , Clare-Lyn Shue Andrea , Smith-Matthews Stephanie , Fraser Kimone , Anderson Asana
Published: June 2024

A diagnosis of dermatomyositis requires recognition of distinct patterns of skin disease in combination with, and sometimes without, muscle weakness. Often, a striking contrast between involved and uninvolved areas is observed. Familiar patterns include eyelid and midfacial eruptions, Gottron papules/sign, and upper back (shawl sign), central chest (V/open collar sign), and lateral thigh (holster sign) involvement. More recently, new specific antibody/phenotype-associated patterns have been reported. We describe a case series of two distinct patterns of skin involvement in six adult patients with both classical and amyopathic dermatomyositis. Three had paraneoplastic disease. All had intermediate to richly pigmented skin; five were of Afro-Caribbean and one was of Asian-Caribbean descent. Four were men, and two were women. Ages ranged from 41 to 89 years. All patients had concomitant hallmark signs (facial, hand, and/or trunk signs). Three were amyopathic. The first pattern involved a sharply demarcated, horizontally oriented hyperpigmented patch/thin plaque across the shoulders and upper chest, extending up the anterior neck. The second was the combination of the classical upper back shawl distribution with distinct mid-back sparing and diffuse involvement of the lower back. Named patterns help with the recognition of skin rashes in dermatomyositis. Based on the current lexicon describing items of apparel, we liken the first pattern to a “fur stole and turtleneck” sign and the latter to a “halter-back” or “reflected-shawl” sign. Biopsies revealed hyperkeratosis and interface dermatitis, often with epidermal atrophy, compatible with dermatomyositis. These patterns perhaps represent the coalescence of already well-described signs, photo-exacerbation, koebnerization, mechanical stretch, and other currently unclear factors contributing to patterning in dermatomyositis. Pattern distribution recognition is particularly valuable in individuals with richly pigmented skin who may lack typical violaceous erythema. The distinct demarcation led to the initial misdiagnosis of allergic contact dermatitis or other exogenous dermatitis in most of our patients. Further work involves evaluation of antibody phenotype and internal involvement associations. Limitations include lack of specific antibody panels and longitudinal follow-up data.
Proliferating macrophages in human tumours show characteristics of monocytes responding to myelopoietic growth factors
Authors: Park Saem Mul , Chen Chun-Jen J. , Verdon Daniel J. , Ooi Marcus P. Y. , Brooks Anna E. S. , Martin Richard C. W. , Mathy Jon A. , Emanuel Patrick O. , Dunbar P. Rod
Published: June 2024

Macrophages play essential roles in maintaining tissue homeostasis and immune defence. However, their extensive infiltration into tumours has been linked to adverse outcomes in multiple human cancers. Within the tumour microenvironment (TME), tumour-associated macrophages (TAMs) promote tumour growth and metastasis, making them prime targets for cancer immunotherapy. Recent single-cell analysis suggest that proliferating TAMs accumulate in human cancers, yet their origins and differentiation pathways remain uncertain. Here, we show that a subpopulation of CD163+ TAMs proliferates in situ within the TME of melanoma, lung cancer, and breast cancer. Consistent with their potential role in suppressing anti-tumour activities of T cells, CD163+ TAMs express a range of potent immunosuppressive molecules, including PD-L1, PD-L2, IL-10, and TGF-β. Other phenotypic markers strongly suggested that these cells originate from CD14+ CCR2+ monocytes, a cell population believed to have minimal capacity for proliferation. However, we demonstrate in vitro that certain myelopoietic cytokines commonly available within the TME induce robust proliferation of human monocytes, especially the combination of interleukin 3 (IL-3) and Macrophage Colony-Stimulating Factor 1 (M-CSF). Monocytic cells cultured with these cytokines efficiently modulate T cell proliferation, and their molecular phenotype recapitulates that of CD163+ TAMs. IL-3-driven proliferation of monocytic cells can be completely blocked by IL-4, associated with the induction of CDKN1A, alongside the upregulation of transcription factors linked to dendritic cell function, such as BATF3 and IRF4. Taken together, our work suggests several novel therapeutic routes to reducing immunosuppressive TAMs in human tumours, from blocking chemokine-mediated recruitment of monocytes to blocking their proliferation.
Recent advances in understanding the immune microenvironment in ovarian cancer
Authors: Chen Jinxin , Yang Lu , Ma Yiming , Zhang Ye
Published: June 2024

The occurrence of ovarian cancer (OC) is a major factor in women’s mortality rates. Despite progress in medical treatments, like new drugs targeting homologous recombination deficiency, survival rates for OC patients are still not ideal. The tumor microenvironment (TME) includes cancer cells, fibroblasts linked to cancer (CAFs), immune-inflammatory cells, and the substances these cells secrete, along with non-cellular components in the extracellular matrix (ECM). First, the TME mainly plays a role in inhibiting tumor growth and protecting normal cell survival. As tumors progress, the TME gradually becomes a place to promote tumor cell progression. Immune cells in the TME have attracted much attention as targets for immunotherapy. Immune checkpoint inhibitor (ICI) therapy has the potential to regulate the TME, suppressing factors that facilitate tumor advancement, reactivating immune cells, managing tumor growth, and extending the survival of patients with advanced cancer. This review presents an outline of current studies on the distinct cellular elements within the OC TME, detailing their main functions and possible signaling pathways. Additionally, we examine immunotherapy rechallenge in OC, with a specific emphasis on the biological reasons behind resistance to ICIs.
Can government subsidy promote the light-blue fishery upgrade to deep-blue fishery?
Authors: Zheng Shan , Zhang Ying
Published: June 2024

Introduction

The expansion of fishery development from offshore to deep-sea areas has become essential for countries to address environmental constraints and ensure food security. This study aims to establish a cooperative development model for deep-blue fishery involving the government, fishery enterprises, and consumers.

Methods

We constructed an evolutionary game and simulation model to analyze the government's deep-blue fishery subsidy strategy. The model considers the interactions between the government, fishery enterprises, and consumers, evaluating how different subsidy strategies influence the development of deep-blue fishery.

Results

Our results demonstrate that government subsidies can stimulate the growth of deep-blue fishery from both the demand and supply sides. Specifically, the likelihood of government subsidies positively affects fishery enterprises' engagement in deep-blue fishery development and consumers' willingness to purchase deep-blue fishery products. The evolutionary game system reaches different steady states based on the cost-benefit changes for the government, fishery enterprises, and consumers, leading to various optimal subsidy strategies.

Discussion

The findings indicate that the amount of government subsidy should be optimized rather than maximized, as excessive subsidies may not yield proportionate benefits. Additionally, subsidizing fishery enterprises proves to be more effective in promoting the development of deep-blue fishery compared to subsidizing consumers. These insights can guide policymakers in designing efficient subsidy strategies to foster sustainable deep-sea fishery development.
Elucidating the multifaceted roles of GPR146 in non-specific orbital inflammation: a concerted analytical approach through the prisms of bioinformatics and machine learning
Authors: Wu Zixuan , Li Ling , Xu Tingting , Hu Yi , Peng Xin , Zhang Zheyuan , Yao Xiaolei , Peng Qinghua
Published: June 2024

Background

Non-specific Orbital Inflammation (NSOI) is a chronic idiopathic condition marked by extensive polymorphic lymphoid infiltration in the orbital area. The integration of metabolic and immune pathways suggests potential therapeutic roles for C-peptide and G protein-coupled receptor 146 (GPR146) in diabetes and its sequelae. However, the specific mechanisms through which GPR146 modulates immune responses remain poorly understood. Furthermore, the utility of GPR146 as a diagnostic or prognostic marker for NSOI has not been conclusively demonstrated.

Methods

We adopted a comprehensive analytical strategy, merging differentially expressed genes (DEGs) from the Gene Expression Omnibus (GEO) datasets GSE58331 and GSE105149 with immune-related genes from the ImmPort database. Our methodology combined LASSO regression and support vector machine-recursive feature elimination (SVM-RFE) for feature selection, followed by Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) to explore gene sets co-expressed with GPR146, identifying a significant enrichment in immune-related pathways. The tumor microenvironment’s immune composition was quantified using the CIBERSORT algorithm and the ESTIMATE method, which confirmed a positive correlation between GPR146 expression and immune cell infiltration. Validation of GPR146 expression was performed using the GSE58331 dataset.

Results

Analysis identified 113 DEGs associated with GPR146, with a significant subset showing distinct expression patterns. Using LASSO and SVM-RFE, we pinpointed 15 key hub genes. Functionally, these genes and GPR146 were predominantly linked to receptor ligand activity, immune receptor activity, and cytokine-mediated signaling. Specific immune cells, such as memory B cells, M2 macrophages, resting mast cells, monocytes, activated NK cells, plasma cells, and CD8+ T cells, were positively associated with GPR146 expression. In contrast, M0 macrophages, naive B cells, M1 macrophages, activated mast cells, activated memory CD4+ T cells, naive CD4+ T cells, and gamma delta T cells showed inverse correlations. Notably, our findings underscore the potential diagnostic relevance of GPR146 in distinguishing NSOI.

Conclusion

Our study elucidates the immunological signatures associated with GPR146 in the context of NSOI, highlighting its prognostic and diagnostic potential. These insights pave the way for GPR146 to be a novel biomarker for monitoring the progression of NSOI, providing a foundation for future therapeutic strategies targeting immune-metabolic pathways.
Prediction of prolonged length of stay on the intensive care unit in severely injured patients—a registry-based multivariable analysis
Authors: Lefering Rolf , Waydhas Christian ,   TraumaRegister DGU
Published: June 2024

Purpose

Mortality is the primary outcome measure in severely injured trauma victims. However, quality indicators for survivors are rare. We aimed to develop and validate an outcome measure based on length of stay on the intensive care unit (ICU).

Methods

The TraumaRegister DGU of the German Trauma Society (DGU) was used to identify 108,178 surviving patients with serious injuries who required treatment on ICU (2014–2018). In a first step, need for prolonged ICU stay, defined as 8 or more days, was predicted. In a second step, length of stay was estimated in patients with a prolonged stay. Data from the same trauma registry (2019–2022, n = 72,062) were used to validate the models derived with logistic and linear regression analysis.

Results

The mean age was 50 years, 70% were males, and the average Injury Severity Score was 16.2 points. Average/median length of stay on ICU was 6.3/2 days, where 78% were discharged from ICU within the first 7 days. Prediction of need for a prolonged ICU stay revealed 15 predictors among which injury severity (worst Abbreviated Injury Scale severity level), need for intubation, and pre-trauma condition were the most important ones. The area under the receiver operating characteristic curve was 0.903 (95% confidence interval 0.900–0.905). Length of stay prediction in those with a prolonged ICU stay identified the need for ventilation and the number of injuries as the most important factors. Pearson’s correlation of observed and predicted length of stay was 0.613. Validation results were satisfactory for both estimates.

Conclusion

Length of stay on ICU is a suitable outcome measure in surviving patients after severe trauma if adjusted for severity. The risk of needing prolonged ICU care could be calculated in all patients, and observed vs. predicted rates could be used in quality assessment similar to mortality prediction. Length of stay prediction in those who require a prolonged stay is feasible and allows for further benchmarking.
Clinical characteristics and the risk factors for the exacerbation of symptoms in patients with inflammatory bowel disease during the COVID-19 pandemic
Authors: Wu Juan , Fang Yuanyuan , Bai Bingqing , Wu Yumei , Liu Qiuyuan , Hu Jing , Hu Naizhong , Mei Qiao , Han Wei
Published: June 2024

Background

In 2023, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant caused a large-scale outbreak of coronavirus disease 2019 (COVID-19) in China. It is not clear the risk factors that lead to the exacerbation of symptoms in patients with inflammatory bowel disease (IBD) after COVID-19 infection. Our study aims to find out the risk factors for the exacerbation of IBD-related symptoms in IBD patients with COVID-19 infection and to provide guidance for the clinical management of IBD.

Methods

This is a retrospective, observational study. The online questionnaire was distributed to conduct a survey to collect demographic, clinical, and IBD related characteristics in IBD patients. Univariate and multivariate regression analyses were conducted to assess the independent effects.

Results

In total, 534 cases of IBD patients were analyzed in our study. Among them, 466 (87.3%) cases diagnosed with COVID-19, 160 (34.3%) cases experienced exacerbation of IBD symptoms, and 84 (18.0%) patients opted for medication discontinuation. Male sex (OR 2.04, 95% CI 1.34–3.49, p = 0.001), and the decrease in body mass index (BMI) (OR 0.93, 95% CI 0.87–1.00, p = 0.035) were positively correlated with the exacerbation of IBD symptoms. Furthermore, the medication discontinuation (OR 2.60, 95% CI 1.58–4.30, p < 0.001) was strongly positively correlated with the exacerbation of IBD symptoms. No significant association was seen between age, comorbidities, smoking, disease activity, vaccination, therapy for COVID-19 and the worsening of IBD symptoms.

Conclusion

This study confirms that the infection rate of COVID-19 in China IBD patients was comparable to the general population. Male sex, the decrease in BMI and medication discontinuation are significant risk factors for the exacerbation of IBD-related symptoms in IBD patients with COVID-19 infection.
Investigating the effects of radiation, T cell depletion, and bone marrow transplantation on murine gut microbiota
Authors: Kreisinger Jakub , Dooley James , Singh Kailash , Čížková Dagmar , Schmiedová Lucie , Bendová Barbora , Liston Adrian , Moudra Alena
Published: June 2024

Microbiome research has gained much attention in recent years as the importance of gut microbiota in regulating host health becomes increasingly evident. However, the impact of radiation on the microbiota in the murine bone marrow transplantation model is still poorly understood. In this paper, we present key findings from our study on how radiation, followed by bone marrow transplantation with or without T cell depletion, impacts the microbiota in the ileum and caecum. Our findings show that radiation has different effects on the microbiota of the two intestinal regions, with the caecum showing increased interindividual variation, suggesting an impaired ability of the host to regulate microbial symbionts, consistent with the Anna Karenina principle. Additionally, we observed changes in the ileum composition, including an increase in bacterial taxa that are important modulators of host health, such as Akkermansia and Faecalibaculum. In contrast, radiation in the caecum was associated with an increased abundance of several common commensal taxa in the gut, including Lachnospiraceae and Bacteroides. Finally, we found that high doses of radiation had more substantial effects on the caecal microbiota of the T-cell-depleted group than that of the non-T-cell-depleted group. Overall, our results contribute to a better understanding of the complex relationship between radiation and the gut microbiota in the context of bone marrow transplantation and highlight the importance of considering different intestinal regions when studying microbiome responses to environmental stressors.
Wolbachia endosymbionts in Drosophila regulate the resistance to Zika virus infection in a sex dependent manner
Authors: Tafesh-Edwards Ghada , Kyza Karavioti Margarita , Markollari Klea , Bunnell Dean , Chtarbanova Stanislava , Eleftherianos Ioannis
Published: June 2024

Drosophila melanogaster has been used extensively for dissecting the genetic and functional bases of host innate antiviral immunity and virus-induced pathology. Previous studies have shown that the presence of Wolbachia endosymbionts in D. melanogaster confers resistance to infection by certain viral pathogens. Zika virus is an important vector-borne pathogen that has recently expanded its range due to the wide geographical distribution of the mosquito vector. Here, we describe the effect of Wolbachia on the immune response of D. melanogaster adult flies following Zika virus infection. First, we show that the presence of Wolbachia endosymbionts promotes the longevity of uninfected D. melanogaster wild type adults and increases the survival response of flies following Zika virus injection. We find that the latter effect is more pronounced in females rather than in males. Then, we show that the presence of Wolbachia regulates Zika virus replication during Zika virus infection of female flies. In addition, we demonstrate that the antimicrobial peptide-encoding gene Drosocin and the sole Jun N-terminal kinase-specific MAPK phosphatase Puckered are upregulated in female adult flies, whereas the immune and stress response gene TotM is upregulated in male individuals. Finally, we find that the activity of RNA interference and Toll signaling remain unaffected in Zika virus-infected female and male adults containing Wolbachia compared to flies lacking the endosymbionts. Our results reveal that Wolbachia endosymbionts in D. melanogaster affect innate immune signaling activity in a sex-specific manner, which in turn influences host resistance to Zika virus infection. This information contributes to a better understanding of the complex interrelationship between insects, their endosymbiotic bacteria, and viral infection. Interpreting these processes will help us design more effective approaches for controlling insect vectors of infectious disease.
Cas-OPRAD: a one-pot RPA/PCR CRISPR/Cas12 assay for on-site Phytophthora root rot detection
Authors: Li Zhiting , Feng Wanzhen , Zhu Zaobing , Lu Shengdan , Lin Mingze , Dong Jiali , Wang Zhixin , Liu Fuxiu , Chen Qinghe
Published: June 2024

Phytophthora sojae is a devastating plant pathogen that causes soybean Phytophthora root rot worldwide. Early on-site and accurate detection of the causal pathogen is critical for successful management. In this study, we have developed a novel and specific one-pot RPA/PCR-CRISPR/Cas12 assay for on-site detection (Cas-OPRAD) of Phytophthora root rot (P. sojae). Compared to the traditional RPA/PCR detection methods, the Cas-OPRAD assay has significant detection performance. The Cas-OPRAD platform has excellent specificity to distinguish 33 P. sojae from closely related oomycetes or fungal species. The PCR-Cas12a assay had a consistent detection limit of 100 pg. μL−1, while the RPA-Cas12a assay achieved a detection limit of 10 pg. μL−1. Furthermore, the Cas-OPRAD assay was equipped with a lateral flow assay for on-site diagnosis and enabled the visual detection of P. sojae on the infected field soybean samples. This assay provides a simple, efficient, rapid (<1 h), and visual detection platform for diagnosing Phytophthora root rot based on the one-pot CRISPR/Cas12a assay. Our work provides important methods for early and accurate on-site detection of Phytophthora root rot in the field or customs fields.