bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic and serologic assessments of responses to mRNA-1273 and BNT162b2 vaccines in human recipient sera
Authors: Hickey Thomas E. , Mudunuri Uma , Hempel Heidi A. , Kemp Troy J. , Roche Nancy V. , Talsania Keyur , Sellers Brian A. , Cherry James M. , Pinto Ligia A. 
Published: January 2025

IntroductionThe first vaccines approved against SARS-CoV-2, mRNA-1273 and BNT162b2, utilized mRNA platforms. However, little is known about the proteomic markers and pathways associated with host immune responses to mRNA vaccination. In this proof-of-concept study, sera from male and female vaccine recipients were evaluated for proteomic and immunologic responses 1-month and 6-months following homologous third vaccination.MethodsAn aptamer-based (7,289 marker) proteomic assay coupled with traditional serology was leveraged to generate a comprehensive evaluation of systemic responsiveness in 64 and 68 healthy recipients of mRNA-1273 and BNT162b2 vaccines, respectively.ResultsSera from female recipients of mRNA-1273 showed upregulated indicators of inflammatory and immunological responses at 1-month post-third vaccination, and sera from female recipients of BNT162b2 demonstrated upregulated negative regulators of RNA sensors at 1-month. Sera from male recipients of mRNA-1273 showed no significant upregulation of pathways at 1-month post-third vaccination, though there were multiple significantly upregulated proteomic markers. Sera from male recipients of BNT162b2 demonstrated upregulated markers of immune response to doublestranded RNA and cell-cycle G(2)/M transition at 1-month. Random Forest analysis of proteomic data from pre-third-dose sera identified 85 markers used to develop a model predictive of robust or weaker IgG responses and antibody levels to SARS-CoV-2 spike protein at 6-months following boost; no specific markers were individually predictive of 6-month IgG response. Thirty markers that contributed most to the model were associated with complement cascade and activation; IL-17, TNFR pro-apoptotic, and PI3K signaling; and cell cycle progression.DiscussionThese results demonstrate the utility of proteomics to evaluate correlates or predictors of serological responses to SARS-CoV-2 vaccination.
Systematic review and quantitative meta-analysis of age-dependent human T-lymphocyte homeostasis
Authors: Kulesh Victoria , Peskov Kirill , Helmlinger Gabriel , Bocharov Gennady 
Published: January 2025

ObjectiveTo evaluate and quantitatively describe age-dependent homeostasis for a broad range of total T-cells and specific T-lymphocyte subpopulations in healthy human subjects.MethodsA systematic literature review was performed to identify and collect relevant quantitative information on T-lymphocyte counts in human blood and various organs. Both individual subject and grouped (aggregated) data on T-lymphocyte observations in absolute and relative values were digitized and curated; cell phenotypes, gating strategies for flow cytometry analyses, organs from which observations were obtained, subjects’ number and age were also systematically inventoried. Age-dependent homeostasis of each T-lymphocyte subpopulation was evaluated via a weighted average calculation within pre-specified age intervals, using a piece-wise equal-effect meta-analysis methodology.ResultsIn total, 124 studies comprising 11722 unique observations from healthy subjects encompassing 20 different T-lymphocyte subpopulations – total CD45+ and CD3+ lymphocytes, as well as specific CD4+ and CD8+ naïve, recent thymic emigrants, activated, effector and various subpopulations of memory T-lymphocytes (total-memory, central-memory, effector-memory, resident-memory) – were systematically collected and included in the final database for a comprehensive analysis. Blood counts of most T-lymphocyte subpopulations demonstrate a decline with age, with a pronounced decrease within the first 10 years of life. Conversely, memory T-lymphocytes display a tendency to increase in older age groups, particularly after ~50 years of age. Notably, an increase in T-lymphocyte numbers is observed in neonates and infants (0 – 1 year of age) towards less differentiated T-lymphocyte subpopulations, while an increase into more differentiated subpopulations emerges later (1 – 5 years of age).ConclusionA comprehensive systematic review and meta-analysis of T-lymphocyte age-dependent homeostasis in healthy humans was performed, to evaluate immune T-cell profiles as a function of age and to characterize generalized estimates of T-lymphocyte counts across age groups. Our study introduces a quantitative description of the fundamental parameters characterizing the maintenance and evolution of T-cell subsets with age, based on a comprehensive integration of available organ-specific and systems-level flow cytometry datasets. Overall, it provides the most up-to-date view of physiological T-cell dynamics and its variance and may be used as a consistent reference for gaining further mechanistic understanding of the human immune status in health and disease.
Immunomodulatory effects of Lactiplantibacillus plantarum CCFM8661 + stachyose on cyclophosphamide-induced immunosuppression mice
Authors: Ma Weiwei , Sun Hang , Lian Lian , Guo Lidong , Wang Yanyan , Huang Lili 
Published: January 2025

IntroductionThe increasing stress of modern life has led to a decline in immunity, sparking widespread interest in new strategies to boost immune function. Lactiplantibacillus plantarum and stachyose have gained attention for their immune-regulating effects, but the mechanisms of their combined application remain unclear. This study aims to investigate the immunoregulatory effects of Lactiplantibacillus plantarum CCFM8661 combined with stachyose in cyclophosphamide-induced immunocompromised mice.MethodsMice were divided into the normal control group, model control group (normal saline), positive drug control group (levamisole hydrochloride, 10 mg/kg), and low, medium, and high-dose groups (1.5×105, 1.5×106, and 1.5×107 CFU of Lactiplantibacillus plantarum CCFM8661 + 1.5 mg stachyose). Each treatment group received continuous oral gavage administration for 28 days. On days 23 and 24, except for the normal control group, all other groups were intraperitoneally injected with cyclophosphamide (40 mg/kg) to establish an immunosuppressed model. On day 28, 30 minutes after the final administration, the mice were euthanized to collect the thymus, spleen, serum, ileum, and feces for subsequent analysis of immune indicators, intestinal barrier function, serum cytokines, and intestinal microbiota.ResultsThe combination significantly improved immune organ atrophy, restored intestinal morphology, and normalized cytokine levels in immunosuppressed mice, indicating enhanced immune function. Additionally, it restored intestinal microbiota diversity by increasing the abundance of Muribaculaceae while reducing Lachnospiraceae, potentially promoting intestinal homeostasis.DiscussionThe combination of Lactiplantibacillus plantarum CCFM8661 and stachyose has immune-enhancing effects, potentially achieved by regulating inflammation levels and maintaining intestinal homeostasis.
A preoperative predictive model based on multi-modal features to predict pathological complete response after neoadjuvant chemoimmunotherapy in esophageal cancer patients
Authors: Qi Yana , Hu Yanran , Lin Chengting , Song Ge , Shi Liting , Zhu Hui 
Published: January 2025

BackgroundThis study aimed to develop a multi-modality model by incorporating pretreatment computed tomography (CT) radiomics and pathomics features along with clinical variables to predict pathologic complete response (pCR) to neoadjuvant chemoimmunotherapy in patients with locally advanced esophageal cancer (EC).MethodA total of 223 EC patients who underwent neoadjuvant chemoimmunotherapy followed by surgical intervention between August 2021 and December 2023 were included in this study. Radiomics features were extracted from contrast-enhanced CT images using PyrRadiomics, while pathomics features were derived from whole-slide images (WSIs) of pathological specimens using a fine-tuned deep learning model (ResNet-50). After feature selection, three single-modality prediction models and a combined multi-modality model integrating two radiomics features, 11 pathomics features, and two clinicopathological features were constructed using the support vector machine (SVM) algorithm. The performance of the models were evaluated using receiver operating characteristic (ROC) analysis, calibration plots, and decision curve analysis (DCA). Shapley values were also utilized to explain the prediction model.ResultsThe predictive capability of the multi-modality model in predicting pCR yielded an area under the curve (AUC) of 0.89 (95% confidence interval [CI], 0.75-1.00), outperforming the radiomics model (AUC 0.70 [95% CI 0.54-0.85]), pathomics model (AUC 0.77 [95% CI 0.53-1.00]), and clinical model (AUC 0.63 [95% CI 0.46-0.80]). Additionally, both the calibration plot and DCA curves support the clinical utility of the integrated multi-modality model.ConclusionsThe combined multi-modality model we propose can better predict the pCR status of esophageal cancer and help inform clinical treatment decisions.
Recombinase-based amplification coupled with lateral flow chromatography for the specific and sensitive detection and identification of Leishmania major in cutaneous leishmaniasis patients
Authors: Bel Hadj Ali Insaf , Saadi-Ben Aoun Yusr , Khammeri Imen , Souguir Hejer , Harigua-Souiai Emna , Chouaieb Hamed , Chakroun Ahmed S. , Lemrani Meryem , Kallel Aicha , Kallel Kalthoum , Haddad Nabil , El Dbouni Oussaima , Coler Rhea N. , Reed Steven G. , Fathallah-Mili Akila , Guizani Ikram 
Published: January 2025

IntroductionCutaneous leishmaniases (CL), a wide range of cutaneous diseases caused by diverse species of Leishmania genus parasites, are among the most neglected infectious diseases. While they are non-fatal, CL are highly morbid with disfiguring lesions, which could be chronic, leaving lifelong unsightly scars; they are combined with psychological distress and social stigma. The efficiency of treatment highly depends on the infecting Leishmania species. Diagnosis is mainly based on microscopic direct examination (DE) of Giemsa-stained smears needing experienced microscopists. It can be laborious and time-consuming when the parasite load is low. DE is poorly sensitive and does not identify Leishmania species. So far, only DNA assays accurately identify the species. Despite their wide use for generic detection, PCR methods also require equipment and additional steps to identify causal Leishmania species. L. major is hyperendemic in many countries in Africa, the Middle East, and Asia, where other species co-occur with different endemicity levels according to the situations. This complicates disease management and treatment, particularly as distribution and epidemiology of leishmaniases remain poorly understood. Here, we aimed for a simple and rapid molecular diagnostic test to detect and identify L. major, a predominant CL causal species, which could be prone to become a control tool at the point of care, in endemic areas, using isothermal recombinase DNA amplification (recombinase polymerase amplification, RPA, or recombinase aided amplification, RAA) coupled to detection by the lateral flow (LF) chromatography on a PCRD cassette.MethodsTo develop an L. major species-specific RPA-LF assay, computational analysis of 70 Leishmania DNA targets, identified through bibliography and database searches, selected five targets. We designed and tested 7 primer pairs/probe sets to specifically amplify L. major DNAs. First, the primers were tested for species specificity and sensitivity using basic RPA chemistry. Then, to develop RPA-coupled LF detection, we shifted to the nfo chemistry.ResultsThis way, we retained one set for further investigation, which confirmed it is L. major species-specific. Tested on 86 human cutaneous samples, this selected set was able to detect 100% of L. major infections in confirmed CL patients. We did not observe any cross-reactivity with lesions due to L. infantum or L. tropica.
Brain anatomy differences in Chinese children who stutter: a preliminary study
Authors: Ma Dan , Wang Lingling , Liu Sai , Ma XinMao , Jia Fenglin , Hua Yimin , Liao Yi , Qu Haibo 
Published: January 2025

Background and purposeIt is unknown the neural mechanisms of developmental stuttering (DS). The aim of this study was to investigate the changes in the structural morphology of the brain in Chinese children who stutter.MethodsA case–control study was conducted to collect magnetic resonance imaging data from stuttering and non-stuttering children, thereby analyzing whole-brain gray matter volume and cortical morphological changes in stuttering children.ResultsA total of 108 subjects were recruited (stuttering group: control group = 1:1). Comparing to healthy controls, the gray matter volume was significantly decreased in right temporal gyrus and bilateral cerebellum. Additionally, there was a significant reduction in cortical folds in the right insula and right superior temporal gyrus. Moreover, the gray matter volume of the right cerebellum and right temporal gyrus is related to the severity score of stuttering.ConclusionThe present study proposes that the neural mechanisms underlying DS are intricately linked to the cortico-basal ganglia-thalamo-cortical loop and the dorsal language pathway. This finding is expected to provide reference value for the clinical treatment of DS.
Exploring the association between pro-inflammatory diets and chronic liver diseases: evidence from the UK Biobank
Authors: Pan Lili , Xu Zhengrong , Li Yining , Cai Guoen , Gao Haibing , Lin Shenglong 
Published: January 2025

BackgroundChronic liver diseases (CLD) continue to pose a significant global burden, potentially exacerbated by pro-inflammatory diets. This study explores the relationship between the Dietary Inflammatory Index (DII), a measure of dietary inflammatory potential, and CLD risk.MethodsUtilizing data from the UK Biobank cohort, we assessed the dietary information and calculated the DII for each participant. Cox proportional hazards models and Fine-Gray competing risk models were employed to evaluate the association between DII and CLD incidence, adjusting for potential confounders.ResultsOur analysis included 121,329 participants with a median follow-up of 604.43 weeks, during which 4,018 developed CLD. A higher DII, indicating a more inflammatory diet, was associated with a 16% increased risk of CLD [hazard ratio (HR) = 1.162, P = 0.001], with each unit increase in DII elevating the risk by 3.3% (HR: 1.033, P &lt; 0.001). A significant linear association between DII and CLD was observed. Competing risk analyses, which accounted for cirrhosis, liver cancer, and death, supported these findings. Subgroup analyses confirmed the robustness of the DII's association across various demographic and lifestyle factors. Moreover, a higher DII was positively associated with the progression of CLD to cirrhosis. Sensitivity analyses, including energy-adjusted DII and typical dietary DII, reinforced our results. Additionally, adherence to anti-inflammatory dietary patterns, as indicated by higher Healthy Eating Index 2020 and Mediterranean Diet Score values, was inversely associated with CLD risk.ConclusionOur study highlights the potential benefits of adopting anti-inflammatory diets as a strategy for the prevention and management of CLD. Comprehensive dietary interventions may play a pivotal role in mitigating the global burden of CLD.
RET inhibition overcomes resistance to combined CDK4/6 inhibitor and endocrine therapy in ER+ breast cancer
Authors: Kindt Charlotte K. , Ehmsen Sidse , Traynor Sofie , Policastro Benedetta , Nissen Nikoline , Jakobsen Mie K. , Hundebøl Monique F. , Johansen Lene E. , Bak Martin , Arbajian Elsa , Staaf Johan , Ditzel Henrik J. , Alves Carla L. 
Published: January 2025

BackgroundCombined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy significantly improve the outcome of patients with advanced estrogen receptor-positive (ER+) breast cancer. However, resistance to this treatment and disease progression remains a major clinical challenge. High expression of the receptor tyrosine kinase REarranged during Transfection (RET) has been associated with resistance to endocrine therapy in breast cancer, but the role of RET in CDK4/6i treatment response/resistance remains unexplored.MethodsTo identify gene expression alterations associated with resistance to combined endocrine therapy and CDK4/6i, we performed RNA sequencing of two ER+ breast cancer cell models resistant to this combined therapy. The functional role of RET was assessed by siRNA-mediated RET silencing and targeted inhibition with the FDA/EMA-approved RET-selective inhibitor selpercatinib in resistant breast cancer cells and patient-derived organoids (PDOs). RET silencing was evaluated mechanistically using global gene expression and pathway analysis. The clinical relevance of RET expression in ER+ breast cancer was investigated by gene array analysis of primary tumors treated with endocrine therapy and by immunohistochemical scoring of metastatic lesions from patients who received combined CDK4/6i and endocrine therapy.ResultsWe show that RET is upregulated in ER+ breast cancer cell lines resistant to combined CDK4/6i and fulvestrant compared to isogenic cells resistant to fulvestrant alone. siRNA-mediated silence of RET in high RET-expressing, combined CDK4/6i- and fulvestrant-resistant cells reduced their growth partially by affecting cell cycle regulators of the G2-M phase and E2F targets. Notably, targeting RET with selpercatinib in combination with CDK4/6i inhibited the growth of CDK4/6i-resistant cell lines and resensitized ER+ breast cancer patient-derived organoids resistant to CDK4/6i. Finally, analysis of RET expression in ER+ breast cancer patients treated with endocrine therapy showed that high RET expression correlated with poor clinical outcomes. We further observed a shorter median survival to combined CDK4/6i and endocrine therapy in patients with RET-positive compared to RET-negative tumors, but this difference did not reach statistical significance.ConclusionsOur findings show that RET is overexpressed in ER+ metastatic breast cancer resistant to combined CDK4/6i and endocrine therapy, rendering RET inhibition a promising therapeutic approach for patients who experience disease progression on combined CDK4/6i and endocrine therapy.
Prognostic factors for successful extubation in newborns with congenital diaphragmatic hernia
Authors: Rannebro A. , Mesas-Burgos C. , Fläring U. , Eksborg S. , Berner J. 
Published: January 2025

IntroductionNeonates with congenital diaphragmatic hernia (CDH) have an associated high mortality and morbidity. The European CDH EURO consortium has developed guidelines for initial and perioperative ventilatory management. There are, however, no recommendations on how to wean these patients from the ventilator. Extubation failure is more frequent in this group of patients than in other neonates. The aim of this study was to describe patient characteristics and risk factors for failed extubation and to evaluate predictive factors for successful weaning.MethodsWe performed a retrospective study in a single centre tertiary pediatric intensive care unit in Stockholm, Sweden. CDH-patients (n = 38), aged 0–28 days, with extubation events were identified from 2017 to 2019. Eight patients (21.1%) needed reintubation within 24 h after the first extubation attempt. Patient demographics, surgical repair with patch, oxygenation saturation index (OSI), rapid shallow breathing index (RSBI), ventilatory settings, fluid balance and sedation on the day of extubation were recorded.ResultsPatients in the failed extubation group (FE) had lower birth weight (p &lt; 0.05), surgical patch repair (p &lt; 0.05), longer length of stay in intensive care (p &lt; 0.05), longer time on the ventilator (p &lt; 0.05) and other comorbidities (p &lt; 0.001). Using logistic regression we identified OSI, RSBI and inspiratory pressure (Pinsp) as factors predicting a successful extubation, AUCROC 0.95 (95% CI: 0.87 to 1.00). Patients in the FE-group had significantly more often pulmonary hypertension requiring treatment (p &lt; 0.05), a higher fraction of inspired oxygen (FiO2) (p &lt; 0.05) and hypercapnia (p &lt; 0.001) prior to extubation and an oxygen demand exceeding 40% two hours after extubation (p &lt; 0.05).ConclusionUseful predictors of successful extubation in CDH patients are OSI, RSBI and Pinsp. Low birth weight, patch repair and comorbidity also appear to be important factors. Prospective studies are required to confirm findings in the present study.
Incidence of hyperkalemia RAASi and SGLT-2i treatment in individuals with diabetic kidney disease: a systematic review and network meta-analysis
Authors: Yuan Yahui , Chen Chun , Lin Yuping , Luo Yehao , Yang Zhaojun , Guo Jingyi , Liu Qiaoyun , Sun Lu , Fan Guanjie 
Published: January 2025

BackgroundThis study aims to evaluate the incidence of hyperkalemia and serum potassium levels associated with the use of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), renin‐angiotensin‐aldosterone system inhibitors (RAASi) and concurrent use of these medications in individuals with diabetic kidney disease (DKD).MethodsA comprehensive systematic search was performed in EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, and PubMed database, covering studies up to March 2024. Relevant randomized controlled trials (RCT) included adults with DKD who were treated with SGLT-2i and RAASi or their combination, with a minimum follow-up duration of 12 weeks. The primary outcomes assessed were the incidence of hyperkalemia and serum potassium levels were the primary outcomes assessed. The surface under the cumulative ranking curves (SUCRA) was utilized for ranking purposes.ResultsThe study included 36 trials, encompassing 45,120 participants, comparing various interventions. SGLT-2i (SUCRA = 88.5%) was found to significantly reduce the risk of hyperkalemia. In contrast, the combination of ACEI/ARB + MRA (SUCRA = 5.7%) increased the risk of hyperkalemia. However, when SGLT-2i was added to the ACEI/ARB + MRA regimen, the incidence of hyperkalemia was found to decrease. Subgroup analyses on MRA showed that ACEI/ARB + spironolactone posed the highest risk of hyperkalemia. ACEI/ARB + SGLT-2i mitigated serum potassium level.ConclusionSGLT-2i was effective in reducing the incidence of hyperkalemia incidence, whereas a combination of ACEI/ARB and MRA might elevate the incidence of hyperkalemia in individuals with DKD.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42024552810.