bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody-drug conjugate adverse effects can be understood and addressed based on immune complex clearance mechanisms
Authors: Taylor Ronald P. , Lindorfer Margaret A. 
Published: April 2024

AbstractNumerous antibody-drug conjugates (ADCs) are being developed for cancer immunotherapy. Although several of these agents have demonstrated considerable clinical efficacy and have won Food and Drug Administration (FDA) approval, in many instances, they have been characterized by adverse side effects (ASEs), which can be quite severe in a fraction of treated patients. The key hypothesis in this perspective is that many of the most serious ASEs associated with the use of ADCs in the treatment of cancer can be most readily explained and understood due to the inappropriate processing of these ADCs via pathways normally followed for immune complex clearance, which include phagocytosis and trogocytosis. We review the key published basic science experiments and clinical observations that support this idea. We propose that it is the interaction of the ADC with Fcγ receptors expressed on off-target cells and tissues that can most readily explain ADC-mediated pathologies, which therefore provides a rationale for the design of protocols to minimize ASEs. We describe measurements that should help identify those patients most likely to experience ASE due to ADC, and we propose readily available treatments as well as therapies under development for other indications that should substantially reduce ASE associated with ADC. Our focus will be on the following FDA-approved ADC for which there are substantial literatures: gemtuzumab ozogamicin and inotuzumab ozogamicin; and trastuzumab emtansine and trastuzumab deruxtecan.
TEC-miTarget: enhancing microRNA target prediction based on deep learning of ribonucleic acid sequences
Authors: Yang Tingpeng , Wang Yu , He Yonghong 
Published: April 2024

Abstract
Background
MicroRNAs play a critical role in regulating gene expression by binding to specific target sites within gene transcripts, making the identification of microRNA targets a prominent focus of research. Conventional experimental methods for identifying microRNA targets are both time-consuming and expensive, prompting the development of computational tools for target prediction. However, the existing computational tools exhibit limited performance in meeting the demands of practical applications, highlighting the need to improve the performance of microRNA target prediction models.

Results
In this paper, we utilize the most popular natural language processing and computer vision technologies to propose a novel approach, called TEC-miTarget, for microRNA target prediction based on transformer encoder and convolutional neural networks. TEC-miTarget treats RNA sequences as a natural language and encodes them using a transformer encoder, a widely used encoder in natural language processing. It then combines the representations of a pair of microRNA and its candidate target site sequences into a contact map, which is a three-dimensional array similar to a multi-channel image. Therefore, the contact map's features are extracted using a four-layer convolutional neural network, enabling the prediction of interactions between microRNA and its candidate target sites. We applied a series of comparative experiments to demonstrate that TEC-miTarget significantly improves microRNA target prediction, compared with existing state-of-the-art models. Our approach is the first approach to perform comparisons with other approaches at both sequence and transcript levels. Furthermore, it is the first approach compared with both deep learning-based and seed-match-based methods. We first compared TEC-miTarget’s performance with approaches at the sequence level, and our approach delivers substantial improvements in performance using the same datasets and evaluation metrics. Moreover, we utilized TEC-miTarget to predict microRNA targets in long mRNA sequences, which involves two steps: selecting candidate target site sequences and applying sequence-level predictions. We finally showed that TEC-miTarget outperforms other approaches at the transcript level, including the popular seed match methods widely used in previous years.

Conclusions
We propose a novel approach for predicting microRNA targets at both sequence and transcript levels, and demonstrate that our approach outperforms other methods based on deep learning or seed match. We also provide our approach as an easy-to-use software, TEC-miTarget, at https://github.com/tingpeng17/TEC-miTarget. Our results provide new perspectives for microRNA target prediction.
Interpretable machine learning in predicting drug-induced liver injury among tuberculosis patients: model development and validation study
Authors: Xiao Yue , Chen Yanfei , Huang Ruijian , Jiang Feng , Zhou Jifang , Yang Tianchi 
Published: April 2024

Abstract
Background
The objective of this research was to create and validate an interpretable prediction model for drug-induced liver injury (DILI) during tuberculosis (TB) treatment.

Methods
A dataset of TB patients from Ningbo City was used to develop models employing the eXtreme Gradient Boosting (XGBoost), random forest (RF), and the least absolute shrinkage and selection operator (LASSO) logistic algorithms. The model's performance was evaluated through various metrics, including the area under the receiver operating characteristic curve (AUROC) and the area under the precision recall curve (AUPR) alongside the decision curve. The Shapley Additive exPlanations (SHAP) method was used to interpret the variable contributions of the superior model.

Results
A total of 7,071 TB patients were identified from the regional healthcare dataset. The study cohort consisted of individuals with a median age of 47 years, 68.0% of whom were male, and 16.3% developed DILI. We utilized part of the high dimensional propensity score (HDPS) method to identify relevant variables and obtained a total of 424 variables. From these, 37 variables were selected for inclusion in a logistic model using LASSO. The dataset was then split into training and validation sets according to a 7:3 ratio. In the validation dataset, the XGBoost model displayed improved overall performance, with an AUROC of 0.89, an AUPR of 0.75, an F1 score of 0.57, and a Brier score of 0.07. Both SHAP analysis and XGBoost model highlighted the contribution of baseline liver-related ailments such as DILI, drug-induced hepatitis (DIH), and fatty liver disease (FLD). Age, alanine transaminase (ALT), and total bilirubin (Tbil) were also linked to DILI status.

Conclusion
XGBoost demonstrates improved predictive performance compared to RF and LASSO logistic in this study. Moreover, the introduction of the SHAP method enhances the clinical understanding and potential application of the model. For further research, external validation and more detailed feature integration are necessary.
Role of NT-proBNP and lung ultrasound in diagnosing and classifying heart failure in a hospitalized oldest-old population: a cross-sectional study
Authors: Landolfo Matteo , Spannella Francesco , Giulietti Federico , Di Pentima Chiara , Giordano Piero , Borioni Elisabetta , Landi Laura , Di Rosa Mirko , Galeazzi Roberta , Sarzani Riccardo 
Published: April 2024

Abstract
Aim
Diagnosing and classifying heart failure (HF) in the oldest-old patients has technical and interpretation issues, especially in the acute setting. We assessed the usefulness of both N-terminal pro-brain natriuretic peptide (NT-proBNP) and lung ultrasound (LUS) for confirming HF diagnosis and predicting, among hospitalized HF patients, those with reduced ejection fraction (HFrEF).

Methods
We performed a cross-sectional study on 148 consecutive patients aged ≥ 80 years admitted to our Internal Medicine and Geriatrics ward with at least one symptom/sign compatible with HF and NT-proBNP ≥ 125 pg/mL. We measured serum NT-proBNP levels and performed LUS and transthoracic echocardiography (TTE) on admission before diuretic therapy. We divided our cohort into three subgroups according to the left ventricular ejection fraction (LVEF): reduced (LVEF ≤ 40%), mildly-reduced (LVEF = 41-49%) and preserved (LVEF ≥ 50%).

Results
The mean age was 88±5 years. Male prevalence was 42%. Patients with HFrEF were 19%. Clinical features and laboratory parameters did not differ between the three subgroups, except for higher NT-proBNP in HFrEF patients, which also had a higher number of total B-lines and intercostal spaces of pleural effusion at LUS. Overall, NT-proBNP showed an inverse correlation with LVEF (r = -0.22, p = 0.007) and a direct correlation with age, total pulmonary B-lines, and intercostal spaces of pleural effusion. According to the ROCs, NT-proBNP levels, pulmonary B-lines and pleural effusion extension were poorly predictive for HFrEF. The best-performing cut-offs were 9531 pg/mL for NT-proBNP (SP 0.70, SE 0.50), 13 for total B-lines (SP 0.69, SE 0.85) and one intercostal space for pleural effusion (SP 0.55, SE 0.89). Patients with admission NT-proBNP ≥ 9531 pg/mL had a 2-fold higher risk for HFrEF (OR 2.5, 95% CI 1.3-4.9), while we did not find any association for total B-lines ≥ 13 or pleural effusion ≥ 1 intercostal space with HFrEF. A significant association with HFrEF emerged for the combination of NT-proBNP ≥ 9531 pg/mL, total B-lines ≥ 13 and intercostal spaces of pleural effusion ≥ 1 (adjusted OR 4.3, 95% CI 1.5-12.9).

Conclusions
Although NT-proBNP and LUS help diagnose HF, their accuracy in discriminating HFrEF from non-HFrEF was poor in our real-life clinical study on oldest-old hospitalized patients, making the use of TTE still necessary to distinguish HF phenotypes in this peculiar setting. These data require confirmation in more extensive and longer prospective studies.
Correlation of sonographic with intraoperative findings in laparoscopic managed ectopic pregnancies, a 10-year synopsis: a restrospective observational study
Authors: Mutiso Steve Kyende 
Published: April 2024

Abstract
Background
Ectopic pregnancies (EP) are a common pregnancy complication that’s associated with significant morbidity and rarely mortality if not managed properly. Ultrasound examination forms the cornerstone of diagnosis of EP with some sonographic features occasionally not correlating with intraoperative findings. We set out to conduct an audit of EP managed surgically at our hospital for a 10-year period and discern the correlation and prediction of sonographic findings to intraoperative findings.

Methods
This study was designed as a Retrospective Observational Study based at the Aga Khan University Hospital (AKUH). Study population was all women admitted to AKUH with a diagnosis of ectopic pregnancy that was surgically managed between the period of January 1st 2011 to December 31st 2020. Analysis of data was done against a pre-set checklist. Descriptive statistics for continuous variables was calculated and tabulated in graphs and tables. SPSS version 22 was used for analysis of data.

Results
A total of 337 patients in this study had ultrasound findings. 99.7% (n = 336) of these patients had an intraoperatively confirmed EP. The commonest ultrasound finding was an adnexal mass in 97.1% (n = 309) of patients. These were confirmed surgically in 290 patients at the following locations: 76.6% (n = 222) were ampullary in location; 10.7% (n = 31) were fimbrial in location; 8.6%(n = 25) were isthmic in location; 2.4%(n = 7) were interstitial in location; 1%(n = 3) were abdominal in location; while 0.3% were located in the ovary(n = 1) or round ligament(n = 1) each. Interstitial EP on ultrasound were all (100%) confirmed in the same location intraoperatively, with ampullary EP also correlating fairly well with intraoperative location (75%). The distribution of location in the minor hemoperitoneum (HP) versus major HP groups were similar except for interstitial EP that increased from 1.4% in the minor HP group to 9.5% in the major HP group.

Conclusion
In conclusion, ultrasonography still represents the best imaging modality for EP. The most common finding is usually an adnexal mass with no specific location. Most (99.7%) of the patients with this sonographic finding usually have a confirmed EP. Interstitial EP are the most well localized with ultrasound followed by ampullary EP. Furthermore, the presence of major (> 500mls) hemoperitoneum may act as an adjunct for diagnosis of an interstitial EP.
Incidence and characteristics of aspiration pneumonia in the Nagasaki Prefecture from 2005 to 2019
Authors: Tomonaga Iku , Koseki Hironobu , Imai Chieko , Shida Takayuki , Nishiyama Yuta , Yoshida Daisuke , Yokoo Seiichi , Osaki Makoto 
Published: April 2024

Abstract
Background
Aspiration pneumoniae remains a major health concern, particularly in the older population and has poor prognosis; however, the concept itself remains vague worldwide. This study aimed to determine the actual situation and characteristics of aspiration pneumonia from 2005 to 2019 in Nagasaki Prefecture, Japan.

Methods
Cases of aspiration pneumonia that occurred in the Nagasaki Prefecture between 2005 and 2019 were analyzed using emergency transportation records. The number of occurrences and incidence were analyzed according to age, sex, month, day of the week, and recognition time to clarify the actual situation of aspiration pneumonia.

Results
The total number of new aspiration pneumonia cases was 8,321, and the mean age of the patients was 83.0 years. Annual incidence per 100,000 population increased from 12.4 in 2005 to 65.1 in 2019, with the most prominent increase in the ≥ 80-year-old stratum. Males (55.1%) were more commonly affected than females (44.9%), and 82.2% of the cases involved patients aged ≥ 70 years. No significant correlations were observed between the incidence of aspiration pneumonia and season, month, or day of the week. Aspiration pneumonia occurred frequently in houses (39.8%) and facilities for elderly individuals (40.8%). At 7 days after admission, 80.9% of patients were still hospitalized and 6.5% had died.

Conclusions
The incidence of aspiration pneumonia with risks of severity and mortality is increasing among elderly individuals. Valid preventive measures are urgently needed based on the findings that the disease occurs in both household and elderly care facility settings, regardless of the season.
How are new nurses satisfied with their jobs? From the work value perspective of Generations Y and Z nurses
Authors: Kim Eunkyung , Kim Heejung , Lee Taewha 
Published: April 2024

Abstract
Background
Job satisfaction has garnered significant interest across multiple disciplines as it plays a vital role in shaping human resource strategies. In the field of nursing, enhancing job satisfaction can help prevent workforce shortages. Work values and job-related characteristics are significant predictors of job satisfaction. However, the influence of factors may change as younger generations join the nursing workforce. Although research on generational commonalities and differences in work values is increasing, there is insufficient information on generational differences in the interplay between work values and job satisfaction. This study investigated the factors associated with job satisfaction of new nurses in each generational group based on a work value perspective.

Methods
A total of 280 new nurses (151 from Generation Y and 129 from Generation Z) were selected from the Graduates Occupational Mobility Survey. Multiple linear regression analyses were performed to determine the factors associated with job satisfaction in both groups.

Results
Most participants graduated with a diploma (61.1%), were paid less than the average salary of each group (60.4%), and conducted shift (72.9%) and overtime work (64.3%). Work values and job satisfaction levels were not significantly different between the two groups. Multiple linear regression analyses showed that career growth and task work values were associated with job satisfaction for Generation Z, while task, reputation, and environment work values were associated with job satisfaction for Generation Y. Among the job-related characteristics, nurses’ job tenure was associated with job satisfaction in both groups; salary and overtime had varying relationships with job satisfaction between the two generations.

Conclusions
Understanding generational differences is crucial for improving the effective management of new generational nurses. Our study findings support that different work value dimensions and job-related characteristics were associated with job satisfaction in each generation. Accordingly, it is essential to develop distinct initiatives, such as a well-structured program, to support the continued career growth of the new Generation Z nurses, thereby enhancing their job satisfaction. Furthermore, providing a conducive working environment that helps new-generation nurses overcome challenges and ensures personal lives should be considered.
A scoping review examining patient experience and what matters to people experiencing homelessness when seeking healthcare
Authors: Miller Jean-Philippe , Hutton Jennie , Doherty Claire , Vallesi Shannen , Currie Jane , Rushworth Katrina , Larkin Matthew , Scott Matthew , Morrow James , Wood Lisa 
Published: April 2024

Abstract
Background
Homelessness is associated with significant health disparities. Conventional health services often fail to address the unique needs and lived experience of homeless individuals and fail to include participatory design when planning health services. This scoping review aimed to examine areas of patient experience that are most frequently reported by people experiencing homelessness when seeking and receiving healthcare, and to identify existing surveys used to measure patient experience for this cohort.

Methods
A scoping review was undertaken reported according to the PRISMA-ScR 2020 Statement. Databases were searched on 1 December 2022: MEDLINE, EMBASE, APA PsychINFO and CINAHL. Included studies focused on people experiencing homelessness, healthcare services and patient experience, primary research, published in English from 2010. Qualitative papers and findings were extracted and synthesized against a modified framework based on the National Institute for Health and Care Excellence guidelines for care for people experiencing homelessness, the Institute of Medicine Framework and Lachman’s multidimensional quality model. People with lived experience of homelessness were employed as part of the research team.

Results
Thirty-two studies were included. Of these, 22 were qualitative, seven quantitative and three mixed methods, from the United States of America (n = 17), United Kingdom (n = 5), Australia (n = 5) and Canada (n = 4). Health services ranged from primary healthcare to outpatient management, acute care, emergency care and hospital based healthcare. In qualitative papers, the domains of ‘accessible and timely’, ‘person-centred’, and values of ‘dignity and respect’ and ‘kindness with compassion’ were most prevalent. Among the three patient experience surveys identified, ‘accessible and timely’ and ‘person-centred’ were the most frequent domains. The least frequently highlighted domains and values were ‘equitable’ and ‘holistic’. No questions addressed the ‘safety’ domain.

Conclusions
The Primary Care Quality-Homeless questionnaire best reflected the priorities for healthcare provision that were highlighted in the qualitative studies of people experiencing homelessness. The most frequently cited domains and values that people experiencing homelessness expressed as important when seeking healthcare were reflected in each of the three survey tools to varying degrees. Findings suggest that the principles of ‘Kindness and compassion’ require further emphasis when seeking feedback on healthcare experiences and the domains of ‘safety’, ‘equitable’, and ‘efficiency’ are not adequately represented in existing patient experience surveys.
Bacterial interactome disturbance in chronic obstructive pulmonary disease clinical stability and exacerbations
Authors: Xiao Wei , Chen Yi-long , Du Long-yi , Wu Jiqiu , Wang Zhang , Mao Bing , Wen Fu-qiang , Gibson Peter Gerard , McDonald Vanessa M. , Yu Haopeng , Fu Juan-juan 
Published: April 2024

Abstract
Rationale
Our understanding of airway dysbiosis in chronic obstructive pulmonary disease (COPD) remains incomplete, which may be improved by unraveling the complexity in microbial interactome.

Objectives
To characterize reproducible features of airway bacterial interactome in COPD at clinical stability and during exacerbation, and evaluate their associations with disease phenotypes.

Methods
We performed weighted ensemble-based co-occurrence network analysis of 1742 sputum microbiomes from published and new microbiome datasets, comprising two case-control studies of stable COPD versus healthy control, two studies of COPD stability versus exacerbation, and one study with exacerbation-recovery time series data.

Results
Patients with COPD had reproducibly lower degree of negative bacterial interactions, i.e. total number of negative interactions as a proportion of total interactions, in their airway microbiome compared with healthy controls. Evaluation of the Haemophilus interactome showed that the antagonistic interaction networks of this established pathogen rather than its abundance consistently changed in COPD. Interactome dynamic analysis revealed reproducibly reduced antagonistic interactions but not diversity loss during COPD exacerbation, which recovered after treatment. In phenotypic analysis, unsupervised network clustering showed that loss of antagonistic interactions was associated with worse clinical symptoms (dyspnea), poorer lung function, exaggerated neutrophilic inflammation, and higher exacerbation risk. Furthermore, the frequent exacerbators (≥ 2 exacerbations per year) had significantly reduced antagonistic bacterial interactions while exhibiting subtle compositional changes in their airway microbiota.

Conclusions
Bacterial interactome disturbance characterized by reduced antagonistic interactions, rather than change in pathogen abundance or diversity, is a reproducible feature of airway dysbiosis in COPD clinical stability and exacerbations, which suggests that we may target interactome rather than pathogen alone for disease treatment.