bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune regulatory genes impact the hot/cold tumor microenvironment, affecting cancer treatment and patient outcomes
Authors: Sang Mengmeng , Ge Jia , Ge Juan , Tang Gu , Wang Qiwen , Wu Jiarun , Mao Liming , Ding Xiaoling , Zhou Xiaorong 
Published: January 2025

Background and aimsImmunologically hot tumors, characterized by an inflamed tumor microenvironment (TME), contrast significantly with immunologically cold tumors. The identification of these tumor immune subtypes holds clinical significance, as hot tumors may exhibit improved prognoses and heightened responsiveness to checkpoint blockade therapy. Nevertheless, as yet there is no consensus regarding the clinically relevant definition of hot/cold tumors, and the influence of immune genes on the formation of hot/cold tumors remains poorly understood.MethodsData for 33 different types of cancer were obtained from The Cancer Genome Atlas database, and their immune composition was assessed using the CIBERSORT algorithm. Tumors were categorized as either hot or cold based on their distinct immune composition, ongoing immune response, and overall survival. A customized immunogram was created to identify important immunological characteristics. Kyoto Encyclopedia of Genes and Genomes and Hallmark pathway enrichment were evaluated through gene set variation analysis. Additionally, hub genes that regulate the tumor microenvironment were identified, and their expression patterns were analyzed using single-cell RNA sequencing. Furthermore, drug sensitivity and molecular docking analyses were performed to identify potential drug candidates capable of transforming cold tumors into hot tumors. For validation, a clinical cohort of patients diagnosed with pancreatic adenocarcinoma was examined using multiplex immunohistochemistry.ResultsWe were able to differentiate between hot and cold tumors in various types of cancer (bladder urothelial carcinoma, pancreatic adenocarcinoma, and cervical squamous cell carcinoma) by analyzing the presence of CD8+ T cells, activated natural killer cells, and M2-type macrophages, as well as the cytolytic activity and T cell proliferation. Hub genes that regulate the TME, including PDCD1, CD276, and NT5E, were discovered. The increased expression of NT5E and its prognostic significance were confirmed through multiplex immunohistochemistry in pancreatic adenocarcinoma. Finally, dasatinib and tozasertib were identified as drug candidates capable of converting cold pancreatic adenocarcinoma tumors into hot tumors.ConclusionIn this study, we developed a framework for discerning clinically significant immune subtypes across various cancer types, further identifying several potential targets for converting cold tumors into hot tumors to enhance anticancer treatment efficacy.
Discordance between humoral and cellular immune responses to cytomegalovirus infection in CMV seropositive patients awaiting lung transplantation
Authors: Boada-Pérez Meritxell , Berastegui Cristina , Erro Marta , Ussetti Piedad , Crespo Elena , Donadeu Laura , Bestard Oriol , Anguera Gabriel , Solé Amparo , Ponz Mir Ricardo , Molloy Brian , Revilla-López Eva , Monforte Víctor , Gómez-Ollés Susana 
Published: January 2025

IntroductionRisk stratification for CMV infection in lung transplantation (LT) currently relies on determining donor and recipient CMV IgG before transplantation. However, it has been observed that some patients who test positive for CMV-specific humoral response before kidney transplantation (KT) exhibit a weak or absent CMV-specific cellular response. The significance of this observation in LT is still unknown.MethodsThis prospective, multicenter, observational study evaluated the agreement between CMV IgG serology and specific cell-mediated response (specific T cell Enzyme-Linked ImmunoSpot Assay, ELISPOT, against CMV pp65 and IE-1 antigens) in 121 patients on the waiting list for LT.ResultsOne hundred and four (86%) patients were seropositive for CMV. Discordant humoral and cellular immunologic responses were observed, 29% of seropositive patients had a weak ELISPOT response to IE-1 and 39% to pp65. In 22% of seropositive patients, there was a weak or no response to both antigens. All seronegative patients did not respond to either antigen.ConclusionsTherefore, over 20% of CMV seropositive LT candidates showed weak CMV-specific cellular immune responses despite detectable serological memory against CMV. This may be important in assessing the risk of developing a CMV infection after transplantation.
Baricitinib treatment for hospitalized patients with severe COVID-19 on invasive mechanical ventilation: a propensity score-matched and retrospective analysis
Authors: Mao Yanxiong , Guo Anyi , Zhang Ying , Lai Jianxing , Yuan Dian , Zhang Hao , Diao Wenqi , Chen Weisong , Yan Fugui 
Published: January 2025

IntroductionBaricitinib is a selective inhibitor of Janus kinase (JAK)1 and JAK2, which is associated with clinical improvement in non-severe COVID-19 patients. But in severe COVID-19 patients, the effectiveness of baricitinib is still controversial.MethodsA propensity score-matched and retrospective study was conducted to evaluate the effectiveness of baricitinib in severe COVID-19 patients requiring invasive mechanical ventilation (IMV).ResultsA total number of 48 patients treated with baricitinib were included, and 48 patients were assigned to control group by propensity score matching. The mean ages were high in both group (baricitinib group vs. control group: 78.80 ± 9.04 vs. 82.57 ± 9.27), and most were unvaccinated (62.5% vs. 66.7%. Baricitinib group had a higher proportion of patients with hypertension (73.9% vs. 45.5%, p = 0.006). Control group had higher level of creatine kinase-myocardial band (247.50 vs. 104.50, p = 0.021). Patients in the baricitinib group were more likely to receive nirmatrelvir/ritonavir (39.6% vs. 16.7%, p = 0.017) and intravenous immunoglobin (14.6% vs. 0, p = 0.007). Baricitinib group had significantly lower all-cause 28-days mortality than control group (72.9% vs. 89.6%, p = 0.004).ConclusionThe present study revealed baricitinib reduced 28-days mortality in severe COVID-19 patients on IMV. The effectiveness of baricitinib in treating patients with severe COVID-19 on IMV needs to be further investigated through future studies.
Hypomagnesemia, insulin secretion and action in patients without diabetes, 1 year after kidney transplantation
Authors: Carlsen Rasmus K. , Åsberg Anders , Svensson My , Birkeland Kåre I. , Jørgensen Hanne S. , Bressendorff Iain , Gulseth Hanne L. , Midtvedt Karsten , Nordheim Espen , Jenssen Trond G. 
Published: January 2025

IntroductionHypomagnesemia after kidney transplantation has been reported as a potential risk factor for development of post-transplant diabetes mellitus.MethodsIn kidney transplant recipients undergoing an oral glucose tolerance test during one-year surveillance follow-up we estimated insulin sensitivity with the Matsuda index, a modified Stumvoll index, and HOMA-2IR. First and second phase insulin secretion was assessed using the Stumvoll equation. Participants were categorized into tertiles by plasma magnesium levels, (&lt;0.7, 07–0.78,&gt;0.78 mmol/L).ResultsWe included 208 patients (62% men, median age 51 years). Patients in the lowest compared to the highest magnesium tertile had higher measured GFR (mean 59 vs. 49 mL/min, p = 0.002), tacrolimus trough concentration (mean 6.7 vs. 5.5 μg/L, p &lt; 0.001), and fasting plasma glucose (mean 5.5 vs. 5.3 mmol/L, p = 0.03). There was no significant difference in the Matsuda index between magnesium tertiles, nor in insulin sensitivity assessed by modified Stumvoll index, HOMA-2IR, first or second phase insulin. Results indicate a non-significant trend toward lower disposition index in the lowest vs. highest tertile (p = 0.052).ConclusionIn kidney transplant recipients with lower compared to normal plasma magnesium levels we found a higher fasting plasma glucose but no differences in insulin sensitivity indexes nor dynamic insulin measurements.
Comparison of the conceive-design-implement-operate model and lecture-based learning in teaching the “healthcare-associated infections” course
Authors: Chen Yu , Zhang Rui , Zhou Zhenke , Hong Min , Huang Zheng , Wen Heling , Peng Lei 
Published: January 2025

BackgroundHealthcare-associated infections (HAI) are infections acquired by patients during treatment in various healthcare institutions. These infections significantly increase morbidity, mortality, and healthcare costs. Enhancing HAI education for nurses can improve patient safety and medical quality.AimThe study aimed to assess the effectiveness of the new conceive-design-implement-operate (CDIO) teaching model on nursing students’ HAI learning outcomes and compare it with the traditional LBL model, providing valuable insights for future HAI education in nursing.MethodsA total of 110 nursing students were randomly assigned to one of two groups for HAI training during the 2022–2023 academic year: a group that engaged in the CDIO model and another that received traditional lecture-based learning (LBL). The effectiveness of these pedagogical approaches was evaluated by comparing pre-and post-training test scores, and we used the Course Experience Questionnaire (CEQ) to collect students’ feedback on the course and teaching.ResultsCompared to traditional LBL method, the CDIO model significantly improved the overall scores and practical application scores of nursing students in the HAI course, with these advantages still retained after 24 weeks. Additionally, preliminary results show that students in the CDIO model scored higher on CEQ categories such as good teaching, clear goals and standards, appropriate assessment, generic skills, and independence, but they also reported an increased workload.ConclusionOur research is the first to apply the CDIO framework to nursing education in HAI courses, enhancing nursing students’ practical application skills, particularly in the sustained retention in this area. Our study indicates that the CDIO teaching model has significant advantages in enhancing course experience and teaching effectiveness.
Detection of macular and peripheral ocular microvascular changes after carotid artery revascularization using widefield SS-OCTA
Authors: Luo Ting , Wang Lu , Zhang Li 
Published: January 2025

PurposeThis study aims to investigate microvascular changes in the macular and peripheral regions, as well as alterations in the foveal avascular zone (FAZ) of the ipsilateral eye using widefield swept-source optical coherence tomography angiography (SS-OCTA) in patients with severe carotid artery stenosis (SCAS) after carotid artery revascularization (CAR).DesignThis study employed a prospective study design.MethodsSCAS patients were examined using widefield SS-OCTA, which covered an area of 16 × 16 mm centered on the fovea. These examinations were conducted both before and after CAR to assess changes in retinal and choroidal blood flow in the macular and peripheral regions, as well as alterations in the characteristics of the FAZ.ResultsA total of 56 patients and their corresponding 56 ipsilateral eyes were included in this study. In the macular area, a significant increase in the vessel density of the retinal superficial vascular complex (VDRSVC) was found, while a significant decrease was noted in the vessel density of the retinal deep vascular complex (VDRDVC) after CAR. Additionally, both the area and circumference of the FAZ decreased significantly after CAR. In the peripheral regions, significant increases were detected in both VDRSVC and the three-dimensional choroidal vascularity index (3D-CVI) post-CAR.ConclusionThe findings of this study demonstrated that CAR can improve perfusion in both the macular and peripheral fundus and lead to a decreased area and circumference of the FAZ in the ipsilateral eye. The observed decrease in the VDRDVC after CAR may be attributed to microvascular embolization and ischemia within the deep capillary plexus (DCP).
Intercropping of Saccharum spp. with Dictyophora indusiata: effects on microbial communities and metabolite profiles during bagasse degradation
Authors: Duan Mingzheng , Wu Xiaojian , Long Shengfeng , Huang Hairong , Li Xiang , Li Yijie , Li Changning , Feng Bin , Chen Jiafu , Zhong Defa , Chen Zhendong , Wang Zeping 
Published: January 2025

BackgroundIntercropping Saccharum spp. (sugarcane) with the fungus Dictyophora indusiata together with bagasse amendment represents an innovative circular agriculture method that can enhance soil health, boost sugarcane yields, and increase farm profitability. Understanding the process by which D. indusiata degrades bagasse is key to optimizing this method.AimsThis study aims to clarify the microbial and metabolic processes involved in bagasse degradation by D. indusiata in the sugarcane intercropping system.MethodsChemical composition analysis, metabarcoding sequencing, and metabolomic profiling were conducted on D. indusiata-degraded bagasse (DIBA) and naturally degraded bagasse (BA).ResultsAnalysis of chemical composition revealed that only acid detergent fiber (ADF) and crude protein content differed significantly between the DIBA and BA treatments. Metabarcoding sequencing showed that DIBA significantly altered the bacterial and fungal communities, reducing microbial diversity. Metabolomic analysis indicated an enhancement of biological metabolism, particularly carbohydrate breakdown, in the DIBA treatment. Key metabolites, such as glucose, cellobiose, and D-mannose, were more abundant in DIBA samples. In addition, unique metabolites such as L-alanine, serine, and oxaloacetate were detected in the DIBA treatment, suggesting more efficient bagasse degradation compared with natural processes.ConclusionThe use of macrofungi such as D. indusiata can play a pivotal role in circular agriculture by transforming agricultural waste into valuable soil amendments. Future research should focus on the long-term impact of this system on soil quality and crop yield, as well as the underlying mechanisms, to further optimize intercropping systems and the use of fungi in agricultural waste management.
Mesalazine: a novel therapeutic agent for periodontitis via regulation of periodontal microbiota and inhibiting Porphyromonas gingivalis
Authors: Wang Yuqi , Ma Jun , Wang Haoyu , Yi Jingzheng , Bai Yuxin , Hu Min , Yan Jiaqing 
Published: January 2025

IntroductionPeriodontitis and inflammatory bowel disease are chronic inflammatory diseases with shared epidemiological, biological, and therapeutic associations. Given the similarities in their pathogenic factors, this study hypothesized that mesalazine, a key treatment agent for inflammatory bowel disease, could also be effective in managing periodontitis.MethodsThe antimicrobial effect of mesalazine on Porphyromonas gingivalis was investigated in vitro, including observations of morphological changes on the surface of P. gingivalis. Additionally, the impact of mesalazine on both the formation and established plaque biofilms was examined. The antimicrobial mechanism was elucidated by assessing the expression of P. gingivalis virulence genes and by determining the disruptive effect on P. gingivalis cell membranes. An in vivo rat model of periodontitis was constructed to evaluate mesalazine’s efficacy and its influence on the periodontal bacterial flora in the context of periodontitis.Results and discussionOur results demonstrated that mesalazine concentrations ranging from 0.5 to 2 mg/mL significantly inhibited P. gingivalis proliferation over 72 h. Flow cytometry revealed a marked reduction in the number of viable cells following mesalazine treatment. At the nanometer scale, mesalazine induced crumpling and rupture of the P. gingivalis surface, compromising cell membrane integrity. Mesalazine not only suppressed the formation of plaque biofilms by P. gingivalis and polymicrobial communities but also disrupted pre-existing biofilms. The data also suggested that mesalazine could disrupt the integrity of the P. gingivalis cell membrane and inhibit the expression of virulence factors. An animal model of periodontitis in rats was successfully constructed in vivo. Mesalazine treatment inhibited alveolar bone resorption, alleviated inflammation of periodontal tissues, and improved the composition of the periodontal flora to a healthier state. This study establishes that mesalazine can treat periodontitis through modulation of the periodontal flora and its anti-inflammatory properties, thus broadening its classical therapeutic applications.
Labeling tumor-associated extracellular vesicles with antibody-DNA conjugates for quantitative analysis
Authors: Du Xiao , Li Hongxiu , Shen Shiyi , Tian Chao , Cao Xiaohuan , Xu Xingang , Xu Nan , Wang Shuling , Tian Qingchang 
Published: January 2025

IntroductionExtracellular vesicles (EVs) shed from tumor cells into peripheral circulation or other body fluids are promising biomarkers for cancer diagnosis with enormously long circulation. Consequently, precise methods for differentiating normal and tumor-associated EVs (TAEs) are required.MethodsThis study used quantifiable antibody-DNA conjugate-assisted quantitative methods combined with proximity ligation technology to detect TAEs. The antibody-DNA conjugate contained one antibody associated with three oligonucleotides for signal amplification. The antibody in the conjugate can recognize the surface tumor antigens of TAEs. Simultaneously, DNA in the conjugate is attached to the surfaces of TAEs and holds the signal amplification post, converting protein identities to DNA amplification for protein detection, even at the molecular level.ResultsThese findings revealed that TAEs can be quantitatively detected using DNA-mediated quantitative polymerase chain reaction (qPCR). Antibody-DNA conjugates were used to recognize the epithelial cell adhesion molecule (EpCAM) antigen on the TAE surface and quantify the antigen using qPCR for cancer analysis.DiscussionThis method proposed a new quantitative detection approach for TAEs, which aim to identify specific EV-associated markers for diagnostic or therapeutic, this method could inspire a new idea for tumor diagnosis and detection of other diseases.
Electrophysiological properties of melanin-concentrating hormone neuron subpopulations defined by anatomical localization and CART expression
Authors: Adekunle Rafiat Damilola , Chowdhury Mohammed Sohel , Fang Lisa Z. , Hirasawa Michiru 
Published: January 2025

IntroductionMelanin-concentrating hormone (MCH) neurons are essential regulators of energy and glucose homeostasis, sleep–wake behaviors, motivation, learning and memory. These neurons are anatomically distributed across the medial (MH) and lateral hypothalamus (LH), and the adjacent zona incerta (ZI), which may represent functional subgroups with distinct connectivity with different brain regions. Furthermore, MCH neurons can be classified according to co-expression of neuropeptides, such as cocaine and amphetamine- regulated transcript (CART).MethodsTo identify functional similarities and differences of MCH subpopulations, we characterized their intrinsic electrophysiological properties using whole cell current clamp recording on acute brain slices from male and female mice.ResultsMCH neurons were classified into subgroups according to their anatomical localization in three MCH-rich brain areas: MH, LH and ZI. Among the three brain regions, ZI MCH neurons were the least excitable while LH MCH neurons were the most excitable. Furthermore, grouping MCH neurons according to CART co-expression revealed that MCH/CART− cells are uniquely depolarized and excitable, and display H-currents. These MCH/CART− cells were mainly found in the LH, which may in part explain why LH MCH neurons are more excitable. While some sex differences were found, the majority of parameters investigated were not different.DiscussionOur results suggest that MCH/CART− cells are electrophysiologically distinct, whereas MCH/CART+ cells are largely similar despite their diffuse distribution in the hypothalamus. It is therefore a combination of intrinsic electrophysiological properties and neurochemical identities, in addition to anatomy and connectivity that are likely to be critical in defining functional subpopulations of MCH neurons.
Neural activity responsiveness by maturation of inhibition underlying critical period plasticity
Authors: Matsumoto Ibuki , Nobukawa Sou , Kanamaru Takashi , Sakemi Yusuke , Sviridova Nina , Kurikawa Tomoki , Wagatsuma Nobuhiko , Aihara Kazuyuki 
Published: January 2025

IntroductionNeural circuits develop during critical periods (CPs) and exhibit heightened plasticity to adapt to the surrounding environment. Accumulating evidence indicates that the maturation of inhibitory circuits, such as gamma-aminobutyric acid and parvalbumin-positive interneurons, plays a crucial role in CPs and contributes to generating gamma oscillations. A previous theory of the CP mechanism suggested that the maturation of inhibition suppresses internally driven spontaneous activity and enables synaptic plasticity to respond to external stimuli. However, the neural response to external stimuli and neuronal oscillations at the neural population level during CPs has not yet been fully clarified. In the present study, we aimed to investigate neuronal activity responsiveness with respect to the maturation of inhibition at gamma-band frequencies.MethodWe calculated inter-trial phase coherence (ITPC), which quantifies event-related phase modulations across trials, using a biologically plausible spiking neural network that generates gamma oscillations through interactions between excitatory and inhibitory neurons.ResultsOur results demonstrated that the neuronal response coherence to external periodic inputs exhibits an inverted U-shape with respect to the maturation of inhibition. Additionally, the peak of this profile was consistent with the moderate suppression of the gamma-band spontaneous activity.DiscussionThis finding suggests that the neuronal population's highly reproducible response to increased inhibition may lead to heightened synaptic plasticity. Our computational model can help elucidate the underlying mechanisms that maximize synaptic plasticity at the neuronal population level during CPs.