bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of subphenotypes in critically ill thrombocytopenic patients with different responses to therapeutic interventions: a retrospective study
Authors: Jiang Xuandong , Zhang Weimin , Pan Yuting , Cheng Xuping 
Published: April 2023

IntroductionThe causes of thrombocytopenia (TP) in critically ill patients are numerous and heterogeneous. Currently, subphenotype identification is a popular approach to address this problem. Therefore, this study aimed to identify subphenotypes that respond differently to therapeutic interventions in patients with TP using routine clinical data and to improve individualized management of TP.MethodsThis retrospective study included patients with TP admitted to the intensive care unit (ICU) of Dongyang People’s Hospital during 2010–2020. Subphenotypes were identified using latent profile analysis of 15 clinical variables. The Kaplan–Meier method was used to assess the risk of 30-day mortality for different subphenotypes. Multifactorial Cox regression analysis was used to analyze the relationship between therapeutic interventions and in-hospital mortality for different subphenotypes.ResultsThis study included a total of 1,666 participants. Four subphenotypes were identified by latent profile analysis, with subphenotype 1 being the most abundant and having a low mortality rate. Subphenotype 2 was characterized by respiratory dysfunction, subphenotype 3 by renal insufficiency, and subphenotype 4 by shock-like features. Kaplan–Meier analysis revealed that the four subphenotypes had different in-30-day mortality rates. The multivariate Cox regression analysis indicated a significant interaction between platelet transfusion and subphenotype, with more platelet transfusion associated with a decreased risk of in-hospital mortality in subphenotype 3 [hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.46–0.94]. In addition, there was a significant interaction between fluid intake and subphenotype, with a higher fluid intake being associated with a decreased risk of in-hospital mortality for subphenotype 3 (HR: 0.94, 95% CI: 0.89–0.99 per 1 l increase in fluid intake) and an increased risk of in-hospital mortality for high fluid intake in subphenotypes 1 (HR: 1.10, 95% CI: 1.03–1.18 per 1 l increase in fluid intake) and 2 (HR: 1.19, 95% CI: 1.08–1.32 per 1 l increase in fluid intake).ConclusionFour subphenotypes of TP in critically ill patients with different clinical characteristics and outcomes and differential responses to therapeutic interventions were identified using routine clinical data. These findings can help improve the identification of different subphenotypes in patients with TP for better individualized treatment of patients in the ICU.
The molybdate-binding protein ModA is required for Proteus mirabilis-induced UTI
Authors: Huang Yi , Chen Jinbin , Jiang Qiao , Huang Nan , Ding Xin , Peng Liang , Deng Xiaoyan 
Published: April 2023

BackgroundProteus mirabilis is one of the pathogens commonly causing urinary tract infections (UTIs). The molybdate-binding protein ModA encoded by modA binds molybdate with high affinity and transports it. Increasing evidence shows that ModA promotes the survival of bacteria in anaerobic environments and participates in bacterial virulence by obtaining molybdenum. However, the role of ModA in the pathogenesis of P. mirabilis remains unknown.ResultsIn this study, a series of phenotypic assays and transcriptomic analyses were used to study the role of ModA in the UTIs induced by P. mirabilis. Our data showed that ModA absorbed molybdate with high affinity and incorporated it into molybdopterin, thus affecting the anaerobic growth of P. mirabilis. Loss of ModA enhanced bacterial swarming and swimming and up-regulated the expression of multiple genes in flagellar assembly pathway. The loss of ModA also resulted in decreased biofilm formation under anaerobic growth conditions. The modA mutant significantly inhibited bacterial adhesion and invasion to urinary tract epithelial cells and down-regulated the expression of multiple genes associated with pilus assembly. Those alterations were not due to anaerobic growth defects. In addition, the decreased bacteria in the bladder tissue, the weakened inflammatory damage, the low level of IL-6, and minor weight change was observed in the UTI mouse model infected with modA mutant.ConclusionHere, we reported that in P. mirabilis, ModA mediated the transport of molybdate, thereby affecting the activity of nitrate reductase and thus affecting the growth of bacteria under anaerobic conditions. Overall, this study clarified the indirect role of ModA in the anaerobic growth, motility, biofilm formation, and pathogenicity of P. mirabilis and its possible pathway, and emphasized the importance of the molybdate-binding protein ModA to P. mirabilis in mediating molybdate uptake, allowing the bacterium to adapt to complex environmental conditions and cause UTIs. Our results provided valuable information on the pathogenesis of ModA-induced P. mirabilis UTIs and may facilitate the development of new treatment strategies.
Constructing a prognostic risk model for Alzheimer’s disease based on ferroptosis
Authors: Wang Xiao-Li , Zhai Rui-Qing , Li Zhi-Ming , Li Hong-Qiu , Lei Ya-Ting , Zhao Fang-Fang , Hao Xiao-Xiao , Wang Sheng-Yuan , Wu Yong-Hui 
Published: April 2023

IntroductionThe aim of this study is to establish a prognostic risk model based on ferroptosis to prognosticate the severity of Alzheimer’s disease (AD) through gene expression changes.MethodsThe GSE138260 dataset was initially downloaded from the Gene expression Omnibus database. The ssGSEA algorithm was used to evaluate the immune infiltration of 28 kinds of immune cells in 36 samples. The up-regulated immune cells were divided into Cluster 1 group and Cluster 2 group, and the differences were analyzed. The LASSO regression analysis was used to establish the optimal scoring model. Cell Counting Kit-8 and Real Time Quantitative PCR were used to verify the effect of different concentrations of Aβ1–42 on the expression profile of representative genes in vitro.ResultsBased on the differential expression analysis, there were 14 up-regulated genes and 18 down-regulated genes between the control group and Cluster 1 group. Cluster 1 and Cluster 2 groups were differentially analyzed, and 50 up-regulated genes and 101 down-regulated genes were obtained. Finally, nine common differential genes were selected to establish the optimal scoring model. In vitro, CCK-8 experiments showed that the survival rate of cells decreased significantly with the increase of Aβ1–42 concentration compared with the control group. Moreover, RT-qPCR showed that with the increase of Aβ1–42 concentration, the expression of POR decreased first and then increased; RUFY3 was firstly increased and then decreased.DiscussionThe establishment of this research model can help clinicians make decisions on the severity of AD, thus providing better guidance for the clinical treatment of Alzheimer’s disease.
Nimodipine augments cerebrovascular reactivity in aging but runs the risk of local perfusion reduction in acute cerebral ischemia
Authors: Kecskés Szilvia , Menyhárt Ákos , Bari Ferenc , Farkas Eszter 
Published: April 2023

IntroductionThe efficacy of cerebrovascular reactivity (CVR) is taken as an indicator of cerebrovascular health.Methods and ResultsWe found that CVR tested with the inhalation of 10 % CO2 declined in the parietal cortex of 18-20-month-old rats. The CVR deficit in old rats was coincident with cerebrovascular smooth muscle cell and astrocyte senescence, revealed by the immuno-labeling of the cellular senescence marker p16 in these cells. In a next series of experiments, CVR was severely impaired in the acute phase of incomplete global forebrain ischemia produced by the bilateral occlusion of the common carotid arteries in young adult rats. In acute ischemia, CVR impairment often manifested as a perfusion drop rather than blood flow elevation in response to hypercapnia. Next, nimodipine, an L-type voltage-gated calcium channel antagonist was administered topically to rescue CVR in both aging, and cerebra ischemia. Nimodipine augmented CVR in the aged brain, but worsened CVR impairment in acute cerebral ischemia.DiscussionA careful evaluation of benefits and side effects of nimodipine is recommended, especially in acute ischemic stroke.
Novel patients with NHLRC2 variants expand the phenotypic spectrum of FINCA disease
Authors: Tallgren Antti , Kager Leo , O’Grady Gina , Tuominen Hannu , Körkkö Jarmo , Kuismin Outi , Feucht Martha , Wilson Callum , Behunova Jana , England Eleina , Kurki Mitja I. , Palotie Aarno , Hallman Mikko , Kaarteenaho Riitta , Laccone Franco , Boztug Kaan , Hinttala Reetta , Uusimaa Johanna 
Published: April 2023

PurposeFINCA disease (Fibrosis, Neurodegeneration and Cerebral Angiomatosis, OMIM 618278) is an infantile-onset neurodevelopmental and multiorgan disease. Since our initial report in 2018, additional patients have been described. FINCA is the first human disease caused by recessive variants in the highly conserved NHLRC2 gene. Our previous studies have shown that Nhlrc2-null mouse embryos die during gastrulation, indicating the essential role of the protein in embryonic development. Defect in NHLRC2 leads to cerebral neurodegeneration and severe pulmonary, hepatic and cardiac fibrosis. Despite having a structure suggestive of an enzymatic role and the clinical importance of NHLRC2 in multiple organs, the specific physiological role of the protein is unknown.MethodsThe clinical histories of five novel FINCA patients diagnosed with whole exome sequencing were reviewed. Segregation analysis of the biallelic, potentially pathogenic NHLRC2 variants was performed using Sanger sequencing. Studies on neuropathology and NHLRC2 expression in different brain regions were performed on autopsy samples of three previously described deceased FINCA patients.ResultsOne patient was homozygous for the pathogenic variant c.442G &gt; T, while the other four were compound heterozygous for this variant and two other pathogenic NHLRC2 gene variants. All five patients presented with multiorgan dysfunction with neurodevelopmental delay, recurrent infections and macrocytic anemia as key features. Interstitial lung disease was pronounced in infancy but often stabilized. Autopsy samples revealed widespread, albeit at a lower intensity than the control, NHLRC2 expression in the brain.ConclusionThis report expands on the characteristic clinical features of FINCA disease. Presentation is typically in infancy, and although patients can live to late adulthood, the key clinical and histopathological features are fibrosis, infection susceptibility/immunodeficiency/intellectual disability, neurodevelopmental disorder/neurodegeneration and chronic anemia/cerebral angiomatosis (hence the acronym FINCA) that enable an early diagnosis confirmed by genetic investigations.
Pathogenic variant profile in DNA damage response genes correlates with metastatic breast cancer progression-free survival in a Mexican-mestizo population
Authors: Vázquez-Romo Rafael , Millan-Catalan Oliver , Ruíz-García Erika , Martínez-Gutiérrez Antonio D. , Alvarado-Miranda Alberto , Campos-Parra Alma D. , López-Camarillo César , Jacobo-Herrera Nadia , López-Urrutia Eduardo , Guardado-Estrada Mariano , Cantú de León David , Pérez-Plasencia Carlos 
Published: April 2023

IntroductionMetastatic breast cancer causes the most breast cancer-related deaths around the world, especially in countries where breast cancer is detected late into its development. Genetic testing for cancer susceptibility started with the BRCA 1 and 2 genes. Still, recent research has shown that variations in other members of the DNA damage response (DDR) are also associated with elevated cancer risk, opening new opportunities for enhanced genetic testing strategies.MethodsWe sequenced BRCA1/2 and twelve other DDR genes from a Mexican-mestizo population of 40 metastatic breast cancer patients through semiconductor sequencing.ResultsOverall, we found 22 variants –9 of them reported for the first time– and a strikingly high proportion of variations in ARID1A. The presence of at least one variant in the ARID1A, BRCA1, BRCA2, or FANCA genes was associated with worse progression-free survival and overall survival in our patient cohort.DiscussionOur results reflected the unique characteristics of the Mexican-mestizo population as the proportion of variants we found differed from that of other global populations. Based on these findings, we suggest routine screening for variants in ARID1A along with BRCA1/2 in breast cancer patients from the Mexican-mestizo population.
Aspirin use and bleeding events during thrombocytopenia after autologous stem-cell transplantation for multiple myeloma
Authors: Neuendorff Nina Rosa , Boshikova Boryana , Frankenstein Lutz , Kirchner Marietta , Rohde Christian , Goldschmidt Hartmut , Frey Norbert , Müller-Tidow Carsten , Jordan Karin , Sauer Sandra , Janssen Maike 
Published: April 2023

BackgroundIn patients with cardiovascular (CV) comorbidities that necessitate antiplatelet therapy (APT), its optimal management during chemotherapy-induced thrombocytopenia remains elusive, as the risk of bleeding has to be balanced against the risk of CV events. The purpose of this study was to assess the risk for bleeding with APT during thrombocytopenia in patients with multiple myeloma undergoing high-dose chemotherapy and subsequent autologous stem-cell transplantation (ASCT) with and without acetylsalicylic acid (ASA) as comedication.MethodsWe assessed patients who underwent ASCT at the Heidelberg University Hospital between 2011 and 2020 for bleeding events, management strategies for ASA intake during thrombocytopenia, transfusion requirements, and the occurrence of CV events.ResultsThere were 57/1,113 patients who continued ASA until at least 1 day after ASCT; thus, a continuous platelet inhibition during thrombocytopenia was assumed. Most of the patients (41/57) continued ASA until they had a platelet count of 20–50/nl. This range reflects the kinetics of thrombocytopenia and nondaily measurements of platelets during ASCT. A tendency toward a higher risk for bleeding events in the ASA group was demonstrated (1.9% (control group) vs. 5.3% (ASA), p = 0.082). The risk factors for bleeding in multivariate analysis were the duration of thrombocytopenia &lt; 50/nl, a history of gastrointestinal bleeding, and diarrhea. The factors predicting the duration of thrombocytopenia were age &gt;60 years, a hematopoietic stem-cell transplantation comorbidity index ≥3, and an impaired bone marrow reserve at admission. CV events occurred in three patients; none of them took ASA or had an indication for APT.ConclusionsThe intake of ASA until thrombocytopenia with a platelet count of 20–50/nl appears safe, although an elevated risk cannot be excluded. If ASA is indicated for the secondary prevention of CV events, the evaluation of risk factors for bleeding and a prolonged time of thrombocytopenia before conditioning is crucial to adapt the strategy for ASA intake during thrombocytopenia.
Construction and validation of a risk prediction model for aromatase inhibitor-associated bone loss
Authors: Chu Meiling , Zhou Yue , Yin Yulian , Jin Lan , Chen Hongfeng , Meng Tian , He Binjun , Wu Jingjing , Ye Meina 
Published: April 2023

PurposeTo establish a high-risk prediction model for aromatase inhibitor-associated bone loss (AIBL) in patients with hormone receptor-positive breast cancer.MethodsThe study included breast cancer patients who received aromatase inhibitor (AI) treatment. Univariate analysis was performed to identify risk factors associated with AIBL. The dataset was randomly divided into a training set (70%) and a test set (30%). The identified risk factors were used to construct a prediction model using the eXtreme gradient boosting (XGBoost) machine learning method. Logistic regression and least absolute shrinkage and selection operator (LASSO) regression methods were used for comparison. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the model in the test dataset.ResultsA total of 113 subjects were included in the study. Duration of breast cancer, duration of aromatase inhibitor therapy, hip fracture index, major osteoporotic fracture index, prolactin (PRL), and osteocalcin (OC) were found to be independent risk factors for AIBL (p &lt; 0.05). The XGBoost model had a higher AUC compared to the logistic model and LASSO model (0.761 vs. 0.716, 0.691).ConclusionThe XGBoost model outperformed the logistic and LASSO models in predicting the occurrence of AIBL in patients with hormone receptor-positive breast cancer receiving aromatase inhibitors.
Missed opportunities for immunization among children 0 to 11 months of age that were attended to at debre tabor comprehensive specialized hospital, south gondar zone, Ethiopia
Authors: Kassa Bekalu Getnet , Lul Nhial Char 
Published: April 2023

BackgroundThe World Health Organization's Expanded Immunization Program was established in 1974 and aimed to provide vaccines to children all over the world. Since the inception of this program, numerous initiatives and campaigns have been launched, and millions of children around the world have been saved from death. Many vaccine-preventable diseases, however, remain prevalent in developing countries. This is because most of those countries have low immunization coverage for an unknown number of reasons. As a result, the goal of this study was to examine missed opportunities for immunization among children aged 0 to 11 months.MethodsA cross-sectional survey was carried out from May to August 2022. A structured questionnaire was used to collect data, and the sample was chosen using a simple random sampling technique. Before being entered into the Epidata and exported to the Statistical Package for Social Science for analysis, the data were checked for consistency and completeness. The statistical significance was determined using binary and multiple logistic regression analyses. The statistical level of significance was established at p ≤ 0.05.ResultIn this study, 49.1% of immunization opportunities were missed. Education status [AOR = 2.45, 95% CI = 2.14, 4.22], rural residence [AOR = 4.32, 95% CI = 3.11, 6.38], and perception of caretakers [AOR = 2.13, 95% CI = 1.89, 4.07] were associated with the missed opportunity of immunization.ConclusionWhen compared to previous studies, the proportion of missed immunization opportunities was high in this study. The healthcare staff should be applying the multi-dose vial policy, which is recommended by the World Health Organization to increase the services. The doses for BCG and measles should be minimized to lower doses per vial in order to conduct immunization without having to wait for enough children and without worrying about vaccine waste. All infants who visit the hospital should be linked to immunization services.
Intrinsic drive of medical staff: a survey of employee representatives from 22 hospitals in China
Authors: Zhang Yuqing , Yuan Zheng , Cheng Taozhu , Wang Cunliang , Li Jun 
Published: April 2023

ObjectiveWhile several initiatives, including monetary rewards and performance system reform, are used to inspire medical staff, none are fully effective. We sought to describe the intrinsic drive of medical staff and identify elements that improve work enthusiasm by increasing internal motivation.MethodsA cross-sectional study was conducted in which 2,975 employee representatives from 22 municipal hospitals in Beijing, China were interviewed using a self-made intrinsic motivation scale for medical staff which includes the achievement motivation, self-efficacy, conscientiousness, gratitude level and perceived organizational support. The Kruskal-Wallis analysis of variance and multiple linear regression methods were used to investigate the level of intrinsic motivation and identify any influencing factors. The correlation between employee drive and turnover intention was determined using Spearman rank correlation analysis and Kendall’s tau b rank correlation coefficient.ResultsA total of 2,293 valid answers were obtained, with a valid recovery rate of 77.1%. There were statistically significant differences in intrinsic motivation and its five dimensions by marital status, political status, profession, service year, monthly income, number of working hours per week, and turnover intention (p &lt; 0.05). Being divorced, a CPC member, in the nursing profession, and having a higher monthly income had a positive impact on intrinsic motivation while working a high hours per week had a negative effect. Higher work drive was associated with lower turnover intention. The correlation coefficients of intrinsic drive and its five dimensions with turnover intention ranged from 0.265 to 0.522 (p &lt; 0.001).ConclusionSociodemographic factors and work environment influenced the intrinsic motivation of medical staff. There was a correlation between work drive and turnover intention which indicated that stimulating the intrinsic drive of employees may help to increase staff retention.
Norms and T-scores for screeners of alcohol use, depression and anxiety in the population of Suriname
Authors: de Beurs Edwin , Jadnanansing Raj , Etwaroo Kajal , Blankers Matthijs , Bipat Robbert , Peen Jaap , Dekker Jack 
Published: April 2023

BackgroundThere is a considerable gap between care provision and the demand for care for common mental disorders in low-and-middle-income countries. Screening for these disorders, e.g., in primary care, will help to close this gap. However, appropriate norms and threshold values for screeners of common mental disorders are lacking.MethodsIn a survey study, we gathered data on frequently used screeners for alcohol use disorders, (AUDIT), depression, (CES-D), and anxiety disorders (GAD-7, ACQ, and BSQ) in a representative sample from Suriname, a non-Latin American Caribbean country. A stratified sampling method was used by random selection of 2,863 respondents from 5 rural and 12 urban resorts. We established descriptive statistics of all scale scores and investigated unidimensionality. Furthermore, we compared scores by gender, age-group, and education level with t-test and Mann–Whitney U tests, using a significance level of p &lt; 0.05.ResultsNorms and crosswalk tables were established for the conversion of raw scores into a common metric: T-scores. Furthermore, recommended cut-off values on the T-score metric for severity levels were compared with international cut-off values for raw scores on these screeners.DiscussionThe appropriateness of these cut-offs and the value of converting raw scores into T-scores are discussed. Cut-off values help with screening and early detection of those who are likely to have a common mental health disorder and may require treatment. Conversion of raw scores to a common metric in this study facilitates the interpretation of questionnaire results for clinicians and can improve health care provision through measurement-based care.