bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determining the role of basophil activation testing in reported type 1 allergy to beta-lactam antibiotics
Authors: Reitmajer Markus , Strauss Antonia , Klinger Christian , Maaß Maximiliane , Kempf Wolfgang E. , Fischer Joerg , Kneilling Manfred , Volc Sebastian 
Published: December 2024

BackgroundAllergy to beta-lactam antibiotics (BLA), especially to penicillin, is the most commonly reported drug allergy by patients. Alternative antibiotics can yield negative consequences, such as extended hospitalization days due to less efficacy and overall higher costs. The basophil activation test (BAT) is an in vitro assay, in which activation of an individual's own basophils is quantified by flow cytometry. It is an increasingly applied in vitro method in allergy testing that is also gaining traction in drug allergies.MethodsWe correlated 37 BAT results with skin test results. The cohort exclusively included patients with suspected type I BLA allergy. In addition, we examined the concordance of these results with clinical symptoms reported in the BLA patients’ medical histories.ResultsBLA-BAT revealed a high specificity of 92.3% [95% confidence interval (CI) 66.7–98.6] but a low sensitivity of only 20.8% (95% CI 9.24–40.47) using BLA-skin tests as a comparator. Negative BLA-BAT in patients with a history of grade I anaphylaxis yielded doubt on the assumption of grading. The exclusion of grade I BLA anaphylaxis increased the sensitivity to 29.4% (95% CI 13.28–53.13) with a still high specificity of 85.7% (95% CI 48.69–97.43). When ImmunoCAP was available, we compared specific IgE and BAT results by using Cohens' kappa (κ) and revealed a moderate level of agreement (κ = 0.538, p = 0.029).ConclusionBAT reveals specific positive results exclusively in patients with cephalosporin anaphylaxis. However, these findings could not be generally confirmed in the heterogeneous group of BLA.
Fumarprotocetraric acid and geraniin were identified as novel inhibitors of human respiratory syncytial virus infection in vitro
Authors: Wang Chao , Huang Yi-Man , Zhao Jun , Bai Yi-Ming , Yan Cai-Qin , Du Guan-Hua , Zheng Li-Shu , Liu Ai-Lin 
Published: December 2024

IntroductionRespiratory syncytial virus (RSV) remains a major international public health concern. However, disease treatment is limited to preventive care with monoclonal antibodies and supportive care. In this study, natural products were screened to identify novel anti-RSV inhibitors.MethodsThe antiviral effect of 320 compounds on RSV in HEp-2 cells was tested using a Cytopathic effect (CPE) inhibition assay. The antiviral effect of fumarprotocetraric acid (FUM) and geraniin (GE) were confirmed by Real-time reverse transcription quantitative PCR (Real-time RT-PCR), plaque reduction test, immunofluorescence assay, and Western blot analysis. Real-time PCR was used to detect inflammatory factor expression. ATP assay and JC-1 stain were used to evaluate mitochondrial protection function. The experiment of administration time was used to determine the stages in the RSV life cycle inhibited by FUM and GE. Human metapneumovirus (HMPV) and human rhinovirus (HRV) were used to evaluate the antiviral activities of other respiratory viruses of FUM and GE. Finally, Air-liquid interface human airway epithelium (ALI-HAE) cells were used to evaluate the antiviral effect and mechanism of FUM and GE to RSV.ResultsThe results showed that FUM and GE can inhibit the replication of RSV in multiple-cell models. Both compounds could dose-dependent inhibit the viral load, RSV nucleic acids level, and RSV-F protein level. Besides, FUM and GE showed good anti-inflammatory activity, mitochondrial protection, and antiviral activity to HMPV and HRV. Meanwhile, our result indicated that FUM and GE can inhibit RSV replication in ALI-HAE cells.ConclusionsFUM and GE were identified as new inhibitors of RSV infection. At the same time, FUM and GE have anti-inflammatory activity, mitochondrial protection function, and broad-spectrum antiviral activity. These results provide evidence that FUM and GE are potential candidates for the development of novel anti-RSV drugs.
Association of the geriatric nutritional risk index with poor outcomes in patients with coronary revascularization: a cohort study
Authors: Xie Beili , Shi Yue , Liu Mingwang , Jin Zhidie , Wen Wei , Yan Yuxin , Gao Mengjie , Jiang Lulian , Yang Lin , Liu Jiangang , Shi Dazhuo , Zhao Fuhai 
Published: December 2024

BackgroundPoor nutritional status may affect outcomes after coronary revascularization, but the association between nutritional status and outcomes in patients undergoing coronary revascularization has not been fully evaluated. This study was based on the MIMIC-IV database to analyze the impact of baseline nutritional status on poor outcomes in patients with coronary revascularization.MethodsPatients with coronary revascularization were screened from the MIMIC-IV database. A geriatric nutritional risk index (GNRI) was calculated and used to divide patients into 4 groups: no malnutrition (Q4: ≥96.79), mild malnutrition (Q3: 90.85–96.78), moderate malnutrition (Q2: 86.37–90.84), and severe malnutrition (Q1: 86.37). The primary outcome measure was 28-day mortality, and the secondary outcome measures were AKI and length of hospital stay. Cox proportional hazards model, Kaplan-Meier survival analysis, restricted cubic spline (RCS), and multiple linear regression model were used for statistical analysis, respectively, to ensure the robustness of study results.ResultsA total of 1,168 patients with coronary revascularization were included. The GNRI demonstrated a significant association with 28-day mortality in patients undergoing coronary revascularization. As a continuous variable, the GNRI exhibited a notable inverse correlation with mortality across unadjusted, partially adjusted, and fully adjusted Cox regression models [hazard ratios (HRs): 0.93, 0.94, 0.96, respectively; all P &lt; 0.001]. When considered as a categorical variable, a low GNRI (first quartile, Q1) was significantly associated with elevated mortality risks (HRs: 2.64, 2.30, 1.82 in the unadjusted, partially adjusted, and fully adjusted models, respectively; all P &lt; 0.05). Subgroup analysis revealed a more pronounced association in patients under 65 years of age (P for interaction = 0.014). Furthermore, reduced GNRI levels were also associated with an increased incidence of AKI and extended hospital lengths of stay.ConclusionGNRI is associated with prognosis in patients with coronary revascularization. Patients with lower GNRI had higher 28-day mortality, greater risk of AKI, and longer hospital stays.
Cardiopulmonary exercise response at high altitude in patients with congenital heart disease: a systematic review and meta-analysis
Authors: Vecchiato Marco , Duregon Federica , Borasio Nicola , Faggian Sara , Bassanello Veronica , Aghi Andrea , Palermi Stefano , Degano Gino , Battista Francesca , Ermolao Andrea , Neunhaeuserer Daniel 
Published: December 2024

BackgroundAn increasing number of patients with congenital heart disease (CHD) engage in physical activities and may exercise at high altitudes (HA). The physiological adaptations required at HA and their implications on individuals with CHD, especially during exercise, remain underexplored. This systematic review aims to investigate cardiopulmonary exercise responses to short-term HA exposure in individuals with CHD.MethodsA literature search was performed across PubMed, Cochrane Library, Scopus, Embase, and SPORTDiscus. The search focused on studies comparing patients with CHD to healthy controls, specifically assessing cardiorespiratory responses during cardiopulmonary exercise testing at HA (≥2,500 m) and low altitude (LA). A meta-analysis of the differences in the main cardiorespiratory adaptations during exercise from LA to HA was performed, comparing patients with CHD and controls.ResultsOf the initial 4,500 articles, four studies met the inclusion criteria, encompassing 150 participants (74 with CHD and 76 controls). Almost all the patients with CHD had lower cardiorespiratory fitness and efficiency both at LA and HA compared to the controls. Nevertheless, the patients with CHD showed a smaller decrease in peak workload [10.61 W (95% CI: 2.33–18.88)] and peak saturation [1.22% (95% CI: 0.14–2.30)] between LA and HA compared to the controls. No participants presented exercise-induced symptoms.ConclusionShort-term exposure to HA appears to be relatively well-tolerated by individuals with low-risk CHD, without a significantly different impact on cardiorespiratory response compared to healthy controls. Further research should confirm these outcomes and explore the long-term effects of higher altitude exposure as comprehensive recommendations for these patients are lacking.
Nonlinear relationship between serum Klotho and chronic kidney disease in US adults with metabolic syndrome
Authors: Lin Xiaobin , Yang Lin 
Published: December 2024

BackgroundCurrent evidence regarding the effects of serum Klotho among patients with metabolic syndrome (MetS) is scarce. This study explored the relationship between serum Klotho levels and the odds of chronic kidney disease (CKD) in middle-aged and older populations with MetS.Materials and methodsThis cross-sectional study analyzed data from 4870 adults aged 40–79 years who participated in the National Health and Nutrition Survey (NHANES) from 2007 to 2016. CKD was identified at urinary albumin to creatinine ratio (UACR) of 30 mg/g or higher and/or an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2. Measurement of serum Klotho concentration was determined via enzyme-linked immunosorbent assay (ELISA) and subsequently divided into four quartiles (Q1-Q4). The NHANES criteria were followed in calculating the sampling weights. Multivariable logistic regression models were employed to assess the correlation between Klotho and CKD, while generalized linear models with cubic spline functions and smooth curve fitting were utilized to detect any nonlinear relationship. Additionally, subgroup analysis and a range of sensitivity analyzes were conducted.ResultsResults showed that a nonlinear L-shaped relationship existed between serum Klotho levels and CKD risk, with the lowest prevalence observed at 9.63–9.94 pg/mL Klotho concentrations. With a two-segment linear regression model, an inflection point of 9.88 pg/mL was noted. Hypertension status was identified as an interaction mediator (Pinteraction = 0.006). Sensitivity analysis showed stable results.ConclusionsA nonlinear L-shaped relationship exists between serum Klotho levels and risks of CKD among middle-aged and older adults with MetS, with the lowest prevalence observed at 9.63 to 9.94 pg/mL Klotho concentrations. Our findings, if replicated, underscore the need to estimate the optimal serum Klotho concentrations and the consequential inverse relationship, thus implying the potential of Klotho as both a serum biomarker and a possible preventive or therapeutic intervention.
The interaction of adverse childhood experiences, sex, and transgender identity as risk factors for depression: disparities in transgender adults
Authors: Balakrishnan Siva , Yang Wei , Weber Ann M. 
Published: December 2024

IntroductionThe intersectionality of sexism, transphobia, and adverse childhood experiences (ACE) on the mental health of transgender adults is poorly understood. We assessed whether the known association between ACE and depression was modified (or differed) by adult transgender identity and by assigned sex at birth, which we used as a proxy for adults' biological (e.g., hormonal changes) and social (e.g., sexism) experiences in childhood.MethodsData from a representative sample of 519 transgender and 127,214 cisgender US adults was retrieved from the 2019 and 2020 Behavioral Risk Factor Surveillance System surveys. The sample was stratified by assigned sex at birth. Adjusted, sample-weighted Poisson regressions and relative excess risk due to interaction (RERI) were used to assess whether transgender identity modified the association between ACE and depression within strata of assigned sex at birth.ResultsWe found 42.4% of transgender compared to 24.9% of cisgender adults experienced 3+ ACE. The association between ACE and depression was stronger for transgender compared to cisgender adults, regardless of assigned sex at birth. However, transgender adults assigned female at birth with 1–2 ACE had a combined risk of depression that was higher than would be expected from the sum of the two risks alone (RERI test of interaction for transgender with 1–2 ACE vs. cisgender with zero ACE: 1.91 [95% confidence interval 0.47–3.36]; p = 0.009). The tests of interaction were not statistically significant (p &gt; 0.05) for those assigned male at birth.DiscussionTransgender adults may benefit more from depression interventions informed by and addressing childhood trauma than their cisgender counterparts, particularly for transgender adults who were assigned female at birth. Our findings suggest a need for greater and improved data collection of gender, experiences associated with assigned sex at birth, and ACE as these relate to the transgender community. This will allow for a better understanding of the intersecting influences of sexism, transphobia, and ACE on adult depression and for identifying particularly vulnerable sub-populations in need of support.
The systemic inflammation response index (SIRI) predicts survival in advanced non-small cell lung cancer patients undergoing immunotherapy and the construction of a nomogram model
Authors: Tang Chunhan , Zhang Min , Jia Hongyuan , Wang Tianlei , Wu Hongwei , Xu Ke , Ren Tao , Liang Long 
Published: December 2024

BackgroundInflammation and immune evasion are associated with tumorigenesis and progression. The Systemic Inflammation Response Index (SIRI) has been proposed as a pre-treatment peripheral blood biomarker. This study aims to compare the relationship between SIRI, various serum biomarkers, and the prognosis of NSCLC patients before and after treatment.MethodsA retrospective study was conducted on advanced NSCLC patients treated with anti-PD-1 drugs from December 2018 to September 2021. Peripheral blood markers were measured pre- and post-treatment, and hazard ratios were calculated to assess the association between serum biomarkers and progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curves and Cox proportional hazards models were employed for survival analysis. A nomogram model was built based on multivariate Cox proportional hazards regression analysis using the R survival package, with internal validation via the bootstrap method (1,000 resamples). Predictive performance was expressed using the concordance index (C-index), and calibration plots illustrated predictive accuracy.The application value of the model was evaluated by decision curve analysis (DCA).ResultsAmong 148 advanced NSCLC patients treated with PD-1 inhibitors, the median PFS was 12.9 months (range: 5.4–29.2 months), and the median OS was 19.9 months (range: 9.6–35.2 months). Univariate analysis identified pre- and post-treatment SIRI, mGRIm-Score, and PNI as independent prognostic factors for both PFS and OS (p &lt; 0.05). Multivariate analysis demonstrated that high post-SIRI and post-mGRIm-Score independently predicted poor PFS (P &lt; 0.001, P = 0.004) and OS (P = 0.048, P = 0.001). The C-index of the nomogram model for OS was 0.720 (95% CI: 0.693–0.747) and for PFS was 0.715 (95% CI: 0.690–0.740). Internal validation via bootstrap resampling (B = 1,000) showed good agreement between predicted and observed OS and PFS at 1, 2, and 3 years, as depicted by calibration plots.ConclusionSIRI is an important independent predictor of early progression in advanced NSCLC patients treated with PD-1 inhibitors and may assist in identifying patients who will benefit from PD-1 inhibitors therapy in routine clinical practice.
Exploring causal relationships between immune cells and age-related macular degeneration through univariable, bidirectional, and multivariable Mendelian analysis
Authors: Wei Xixiang , Yang Hui , Yin Xue , Fu Zheng , Xiong Weiwei 
Published: December 2024

ObjectiveThis study systematically investigates the causal relationships between 731 immune cell phenotypes and age-related macular degeneration (AMD) using comprehensive Mendelian randomization (MR) analyses. The goal is to identify immune cell factors that contribute to or protect against AMD, thereby clarifying the immunological mechanisms underlying AMD pathophysiology and informing prevention and treatment strategies.MethodsUnivariable, bidirectional, and multivariable MR analyses were conducted to evaluate the associations between immune cells and AMD. By utilizing publicly available GWAS datasets, we eliminated the need for individual consents. The large-scale MR approach adhered to STROBE-MR guidelines. Immune cell GWAS data were sourced from a study involving 3,757 Sardinians, encompassing a broad spectrum of immune phenotypes, while AMD summary statistics were derived from a GWAS with over 3,763 cases. Instrumental variables (IVs) were carefully selected to comply with MR assumptions, and multiple MR methods were employed to enhance the robustness of causal inferences. Additionally, we supplemented the data for dry AMD (2,469 cases and 206,221 controls) and wet AMD (2,114 cases and 206,601 controls) for validation purposes.ResultsUnivariable MR analysis identified 17 immune cell phenotypes significantly associated with AMD, including 11 potential risk factors and 6 potential protective factors. Bidirectional MR analysis found no significant effects of AMD on the examined immune cell subsets. Multivariable MR analysis indicated that TD CD4+ %T cells and CD39+ CD8br %T cells likely inhibit AMD development, whereas CD39+ CD8br %CD8br cells and CD45RA on resting Treg cells appear to increase AMD risk. Validation of immune cell subsets in dry and wet AMD revealed significant associations between specific immune cells and both forms of AMD, with some subsets uniquely linked to wet AMD and others to dry AMD.ConclusionThis study addresses a critical gap in understanding the causal relationship between immune cells and AMD, identifying immune cell subsets that may either mitigate or exacerbate AMD risk. Notably, it highlights the potential role of CD39+ CD8+ T cells as anti-inflammatory agents and potential targets for immunotherapy in AMD. The absence of bidirectional causality suggests a complex origin of immune dysregulation in AMD. The differential associations of immune cell subsets with AMD subtypes carry significant implications for precision medicine approaches in ophthalmology, laying a solid foundation for future research focused on understanding the immunological underpinnings of AMD and developing targeted therapeutic strategies.
Development and validation of a risk prediction model for multiple organ dysfunction syndrome secondary to severe heat stroke based on immediate assessment indicators on ICU admission
Authors: Ren Entong , Chen Hao , Guo Chenjiao , Peng Yuanyuan , Tian Li , Yan Lulu , Tong Huasheng , Liu Anwei , Li Weihua 
Published: December 2024

IntroductionEarly prediction of multiple organ dysfunction syndrome (MODS) secondary to severe heat stroke (SHS) is crucial for improving patient outcomes. This study aims to develop and validate a risk prediction model for those patients based on immediate assessment indicators on ICU admission.MethodsTwo hundred eighty-four cases with SHS in our hospital between July 2009 and April 2024 were retrospectively reviewed, and categorized into non-MODS and MODS groups. Logistic regression analyses were performed to identify risk factors for MODS, and then to construct a risk prediction model, which was visualized by a nomogram. The predictive performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), Hosmer-Lemeshow (HL) test, calibration curve, and decision curve analysis (DCA). Finally, the AUCs of the prediction model was compared with other scoring systems.ResultsAcute gastrointestinal injury (AGI), heart rate (HR) &gt;100 bpm, a decreased Glasgow Coma Scale (GCS) score, and elevated total bilirubin (TBil) within the first 24 h of ICU admission are identified as independent risk factors for the development of MODS in SHS patients. The model demonstrated good discriminative ability, and the AUC was 0.910 (95% CI: 0.856–0.965). Applying the predictive model to the internal validation dataset demonstrated good discrimination with an AUC of 0.933 (95% CI: 0.880–0.985) and good fit and calibration. The DCA of this model showed a superior clinical net benefit.DiscussionThe risk prediction model based on AGI, HR, GCS, and TBil shows robust predictive performance and clinical utility, which could serve as a reference for assessing and screening the risk of MODS in SHS patients.
Relationship between sexually transmitted infections knowledge and the sexual behavior of Brazilian future doctors
Authors: Nascimento Maria Clara Sales do , Freitas Junior Luiz Ricardo Cerqueira , Freitas Isabel Carmen Fonseca , Avena Katia de Miranda , Andrade Bruno Bezerril 
Published: December 2024

BackgroundThe prevalence of sexually transmitted infections (STIs) remains alarming, especially among young people and college students, highlighting the vulnerability of this population. In the academic context, it is worth investigating whether medical students, despite their access to information, also engage in risky sexual behaviors.ObjectiveThe present study aims to describe the sexual behavior of Brazilian medical students, analyzing their level of knowledge about HIV/AIDS and other STIs, as well as examining potential correlations between this knowledge and risky behaviors.MethodsThis cross-sectional study was conducted with 193 medical students from a private institution in Salvador, Bahia, Brazil, using a structured, anonymous, self-administered online questionnaire. The questionnaire was adapted from the Brazilian Knowledge, Attitudes, and Practices Survey and a survey on risk behavior and knowledge among university students. Knowledge about STIs and HIV/AIDS was classified as “good” (above 70% correct answers), “average” (50–70% correct answers), and “poor” (below 50% correct answers). The work has been approved by the institutional review board of Bahiana School of Medicine and Public Health.ResultsA total of 77.7% of the students exhibited risky sexual behavior, which was associated with the number of partners (p = 0.0001), engaging in sexual activity within the last 12 months (p = 0.001), lack of a steady partner (p = 0.001), not using condoms during the last sexual encounter with a steady partner (p = 0.0001), and the use of substances such as alcohol (p = 0.0001), marijuana (p = 0.0001), and cigarettes (p = 0.0001) during sexual activity. Most students demonstrated poor (49.2%) or average (48.7%) knowledge about STIs and HIV/AIDS, a pattern that persisted regardless of sexual behavior. Only not using condoms during sexual encounters with casual partners in the past 12 months (p = 0.021) was associated with low levels of knowledge.ConclusionThe prevalence of risky sexual behaviors in this sample was high, as was the low level of knowledge about STIs. However, knowledge of STIs and HIV/AIDS does not appear to be the sole determinant of these behaviors.