bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accounting for time-varying exposures and covariates in the relationship between obesity and diabetes: analysis using parametric g-formula
Authors: Park Boyoung , Yoon Junghyun , Tran Thi Xuan Mai 
Published: July 2024

Background
Previous studies investigating the association between obesity and diabetes often did not consider the role of time-varying covariates affected by previous obesity status. This study quantified the association between obesity and diabetes using parametric g-formula.

Methods

We included 8924 participants without diabetes from the Korean Genome and Epidemiology Study—Ansan and Ansung study(2001–2002)—with up to the seventh biennial follow-up data from 2015 to 2016. Obesity status was categorised as normal (body mass index (BMI) <23.5 kg/m
2
), overweight (23.5–24.9 kg/m
2
), obese 1 (25.0–27.4 kg/m
2
) and obese 2 (≥27.5 kg/m
2
). Hazard ratios (HRs) comparing baseline or time-varying obesity status were estimated using Cox models, whereas risk ratio (RR) was estimated using g-formula.

Results
The Cox model for baseline obesity status demonstrated an increased risk of diabetes in overweight (HR 1.85; 95% CI=1.48–2.31), obese 1 (2.40; 1.97–2.93) and obese 2 (3.65; 2.98–4.47) statuses than that in normal weight status. Obesity as a time-varying exposure with time-varying covariates had HRs of 1.31 (1.07–1.60), 1.55 (1.29–1.86) and 2.58 (2.14–3.12) for overweight, obese 1 and obese 2 statuses. Parametric g-formula comparing if everyone had been in each obesity category versus normal over 15 years showed increased associations of RRs of 1.37 (1.34–1.40), 1.78 (1.76–1.80) and 2.42 (2.34–2.50).

Conclusions
Higher BMI classification category was associated with increased risk of diabetes after accounting for time-varying covariates using g-formula. The results from g-formula were smaller than when considering baseline obesity status only but comparable with the results from time-varying Cox model.
Targeting the Sodium–Potassium Pump as a Therapeutic Strategy in Acute Myeloid Leukemia
Authors: Schneider Constanze , Spaink Hermes , Alexe Gabriela , Dharia Neekesh V. , Meyer Ashleigh , Merickel Lucy A. , Khalid Delan , Scheich Sebastian , Häupl Björn , Staudt Louis M. , Oellerich Thomas , Stegmaier Kimberly 
Published: July 2024

Abstract
Tissue-specific differences in the expression of paralog genes, which are not essential in most cell types due to the buffering effect of the partner pair, can make for highly selective gene dependencies. To identify selective paralogous targets for acute myeloid leukemia (AML), we integrated the Cancer Dependency Map with numerous datasets characterizing protein–protein interactions, paralog relationships, and gene expression in cancer models. In this study, we identified ATP1B3 as a context-specific, paralog-related dependency in AML. ATP1B3, the β-subunit of the sodium–potassium pump (Na/K-ATP pump), interacts with the α-subunit ATP1A1 to form an essential complex for maintaining cellular homeostasis and membrane potential in all eukaryotic cells. When ATP1B3’s paralog ATP1B1 is poorly expressed, elimination of ATP1B3 leads to the destabilization of the Na/K-ATP pump. ATP1B1 expression is regulated through epigenetic silencing in hematopoietic lineage cells through histone and DNA methylation in the promoter region. Loss of ATP1B3 in AML cells induced cell death in vitro and reduced leukemia burden in vivo, which could be rescued by stabilizing ATP1A1 through overexpression of ATP1B1. Thus, ATP1B3 is a potential therapeutic target for AML and other hematologic malignancies with low expression of ATP1B1.
Significance: ATP1B3 is a lethal selective paralog dependency in acute myeloid leukemia that can be eliminated to destabilize the sodium–potassium pump, inducing cell death.
Reconstitution of the Multiple Myeloma Microenvironment Following Lymphodepletion with BCMA CAR-T Therapy
Authors: Yang Yazi , Qin Sen , Yang Mengyu , Wang Ting , Feng Ru , Zhang Chunli , Zheng Enrun , Li Qinghua , Xiang Pengyu , Ning Shangyong , Xu Xiaodong , Zuo Xin , Zhang Shuai , Yun Xiaoya , Zhou Xuehong , Wang Yue , He Lin , Shang Yongfeng , Sun Luyang , Liu Hui 
Published: July 2024

Abstract

Purpose:
The purpose of this study was to investigate the remodeling of the multiple myeloma microenvironment after B-cell maturation antigen (BCMA)–targeted chimeric antigen receptor T (CAR-T) cell therapy.

Experimental Design:
We performed single-cell RNA sequencing on paired bone marrow specimens (n = 14) from seven patients with multiple myeloma before (i.e., baseline, “day −4”) and after (i.e., “day 28”) lymphodepleted BCMA CAR-T cell therapy.

Results:
Our analysis revealed heterogeneity in gene expression profiles among multiple myeloma cells, even those harboring the same cytogenetic abnormalities. The best overall responses of patients over the 15-month follow-up are positively correlated with the abundance and targeted cytotoxic activity of CD8+ effector CAR-T cells on day 28 after CAR-T cell infusion. Additionally, favorable responses are associated with attenuated immunosuppression mediated by regulatory T cells, enhanced CD8+ effector T-cell cytotoxic activity, and elevated type 1 conventional dendritic cell (DC) antigen presentation ability. DC re-clustering inferred intramedullary-originated type 3 conventional DCs with extramedullary migration. Cell–cell communication network analysis indicated that BCMA CAR-T therapy mitigates BAFF/GALECTIN/MK pathway–mediated immunosuppression and activates MIF pathway–mediated anti–multiple myeloma immunity.

Conclusions:
Our study sheds light on multiple myeloma microenvironment dynamics after BCMA CAR-T therapy, offering clues for predicting treatment responsivity.
Heart Failure Events After Long-term Continuous Screening for Atrial Fibrillation: Results From the Randomized LOOP Study
Authors: Xing Lucas Yixi , Højberg Søren , Kriegerg Derk W. , Graff Claus , Olesen Morten S. , Healey Jeff S. , McIntyre William F. , Brandes Axel , Køber Lars , Haugan Ketil Jørgen , Svendsen Jesper Hastrup , Diederichsen Søren Zöga 
Published: July 2024

BACKGROUND:
Mounting evidence indicates that even device-detected subclinical atrial fibrillation is associated with a higher risk of heart failure (HF). However, the potential impact of atrial fibrillation screening on HF remains unknown.

METHODS:
The LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) evaluated the effects of atrial fibrillation screening on stroke prevention using an implantable loop recorder (ILR) versus usual care in older individuals with additional stroke risk factors. In this secondary analysis, we explored the following HF end points: (1) HF event or cardiovascular death; (2) HF event; (3) event with HF with reduced ejection fraction (HFrEF); and (4) HFrEF event or cardiovascular death. Outcomes were assessed in a Cox model both as time-to-first events and as total (first and recurrent) events analyzed using the Andersen-and-Gill method.

RESULTS:
Of 6004 participants (mean age 74.7 and 52.7% men), 1501 were randomized to ILR screening and 4503 to the control group. In total, 77 (5.1%) in the ILR group versus 295 (6.6%) in the control group experienced the primary outcome of an HF event or cardiovascular death. Compared with usual care, ILR screening was associated with a nonsignificant reduction in the primary outcome for the time-to-first event analysis (hazard ratio, 0.78 [95% CI, 0.61–1.01]) and the total event analysis (hazard ratio, 0.77 [95% CI, 0.59–1.01]). Similar results were obtained for the HF event. A significant risk reduction in total events was observed in the ILR group for the composite of HFrEF event or cardiovascular death and for HFrEF event (hazard ratio, 0.74 [95% CI, 0.56–0.98] and 0.65 [95% CI, 0.44–0.97], respectively).

CONCLUSIONS:
In an older population with additional stroke risk factors, ILR screening for atrial fibrillation tended to be associated with a lower rate of total HF events and cardiovascular death, particularly those related to HFrEF. These findings should be considered hypothesis-generating and warrant further investigation.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02036450.
Speaker Demographics Modulate Listeners' Neural Correlates of Spoken Word Processing
Authors: Wu Hanlin , Duan Xufeng , Cai Zhenguang G. 
Published: July 2024

Abstract
In language comprehension, listeners expect a speaker to be consistent in their word choice for labeling the same object. For instance, if a speaker previously refers to a piece of furniture as a “couch,” in subsequent references, listeners would expect the speaker to repeat this label instead of switching to an alternative label such as “sofa.” Moreover, it has been found that speakers' demographic backgrounds, often inferred from their voice, influence how listeners process their language. The question in focus, therefore, is whether speaker demographics influence how listeners expect the speaker to repeat or switch labels. In this study, we used ERPs to investigate whether listeners expect a child speaker to be less likely to switch labels compared to an adult speaker, given the common belief that children are less flexible in language use. In the experiment, we used 80 pictures with alternative labels in Mandarin Chinese (e.g., yi1sheng1 vs. dai4fu, “doctor”). Each picture was presented twice over two experimental phases: In the establishment phase, participants listened to an adult or a child naming a picture with one of the labels and decided whether the label matched the picture they saw; in the test phase, participants listened to the same speaker naming the same picture by either repeating the original label or switching to an alternative label and, again, decided whether the label matched the picture they saw. ERP results in the test phase revealed that, compared to repeated labels, switched labels elicited an N400 effect (300–600 msec after label onset) and a P600 effect (600–1000 msec after label onset). Critically, the N400 effect was larger when listeners were exposed to the child speaker than to the adult speaker, suggesting that listeners found a switched label harder to comprehend when it was produced by a child speaker than an adult speaker. Our study shows that the perceived speaker demographic backgrounds influence listeners' neural responses to spoken words, particularly in relation to their expectations regarding the speaker's label switching behavior. This finding contributes to a broader understanding of the relationship between social cognition and language processing.
Identifying vital nodes for yeast network by dynamic network entropy
Authors: Liu Jingchen , Wang Yan , Men Jiali , Wang Haohua 
Published: July 2024

Abstract
Background
The progress of the cell cycle of yeast involves the regulatory relationships between genes and the interactions proteins. However, it is still obscure which type of protein plays a decisive role in regulation and how to identify the vital nodes in the regulatory network. To elucidate the sensitive node or gene in the progression of yeast, here, we select 8 crucial regulatory factors from the yeast cell cycle to decipher a specific network and propose a simple mixed K2 algorithm to identify effectively the sensitive nodes and genes in the evolution of yeast.

Results
Considering the multivariate of cell cycle data, we first utilize the K2 algorithm limited to the stationary interval for the time series segmentation to measure the scores for refining the specific network. After that, we employ the network entropy to effectively screen the obtained specific network, and simulate the gene expression data by a normal distribution approximation and the screened specific network by the partial least squares method. We can conclude that the robustness of the specific network screened by network entropy is better than that of the specific network with the determined relationship by comparing the obtained specific network with the determined relationship. Finally, we can determine that the node CDH1 has the highest score in the specific network through a sensitivity score calculated by network entropy implying the gene CDH1 is the most sensitive regulatory factor.

Conclusions
It is clearly of great potential value to reconstruct and visualize gene regulatory networks according to gene databases for life activities. Here, we present an available algorithm to achieve the network reconstruction by measuring the network entropy and identifying the vital nodes in the specific nodes. The results indicate that inhibiting or enhancing the expression of CDH1 can maximize the inhibition or enhancement of the yeast cell cycle. Although our algorithm is simple, it is also the first step in deciphering the profound mystery of gene regulation.
Perturbation of periodic spot-generation balance leads to diversified pigmentation patterning of harlequin Phalaenopsis orchids: in silico prediction
Authors: Lu Ti-Wen , Chen Wen-Huei , Chen Pao-Yang , Shu Yu-Chen , Chen Hong-Hwa 
Published: July 2024

Abstract
Background
A retrotransposon HORT1 in the promoter of the anthocyanin activator gene PeMYB11, microRNA858 (miR858) that targets PeMYB11, and a repressor PeMYBx have been implicated in pigmentation patterning diversity of harlequin Phalaenopsis orchids. However, the interrelationship among them remains to be elucidated.

Results
To understand how these factors interact to generate anthocyanin spots in Phalaenopsis, we successfully developed a mathematical model based on the known reaction–diffusion system to simulate their interplay and refined the conceptual biological model. Intriguingly, the expression of both PeMYBx and PeMYB11 were in phase for purple spot formation, even though they showed adverse effects on anthocyanin accumulations. An increase in the self-activation rate of PeMYB11 resulted in the increased size of purple spots, but no effects on spot fusion. Decreased degradation rate of miR858 in the purple regions, led to disruption of the formation of spotted pigmentation patterning and a full-red pigmentation pattern. Significantly, the reduced miR858 level promotes the fusion of large dark purple dots induced by the solo-LTR of HORT1, eventually generating the purple patches. In addition, the spatially heterogeneous insertion of HORT1 caused by the remnant solo-LTR of HORT1 derived from random homologous unequal recombination of HORT1 in individual cells of floral organs could explain the diverse pigmentation patterning of harlequin Phalaenopsis.

Conclusions
This devised model explains how HORT1 and miR858 regulate the formation of the pigmentation patterning and holds great promise for developing efficient and innovative approaches to breeding harlequin Phalaenopsis orchids.
Diagnostic agreement between emergency medical service and emergency department physicians, a prospective multicentre study
Authors: Veldhuis Lars I. , Gouma P. , Nanayakkara Prabath W. B. , Ludikhuize J. 
Published: July 2024

Abstract
Introduction
Early and adequate preliminary diagnosis reduce emergency department (ED) and hospital stay and may reduce mortality. Several studies demonstrated adequate preliminary diagnosis as stated by emergency medical services (EMS) ranging between 61 and 77%. Dutch EMS are highly trained, but performance of stating adequate preliminary diagnosis remains unknown.

Methods
This prospective observational study included 781 patients (> 18years), who arrived in the emergency department (ED) by ambulance in two academic hospitals. For each patient, the diagnosis as stated by EMS and the ED physician was obtained and compared. Diagnosis was categorized based on the International Classification of Diseases, 11th Revision.

Results
The overall diagnostic agreement was 79% [95%-CI: 76–82%]. Agreement was high for traumatic injuries (94%), neurological emergencies (90%), infectious diseases (84%), cardiovascular (78%), moderate for mental and drug related (71%), gastrointestinal (70%), and low for endocrine and metabolic (50%), and acute internal emergencies (41%). There is no correlation between 28-day mortality, the need for ICU admission or the need for hospital admission with an adequate preliminary diagnosis.

Conclusion
In the Netherlands, the extent of agreement between EMS diagnosis and ED discharge diagnosis varies between categories. Accuracy is high in diseases with specific observations, e.g., neurological failure, detectable injuries, and electrocardiographic abnormalities. Further studies should use these findings to improve patient outcome.
Fetuin-A: a relevant novel serum biomarker for non-invasive diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD): a retrospective case-control study
Authors: Elhoseeny Mohamed M. , Abdulaziz Badawy A. , Mohamed Mohamed A. , Elsharaby Radwa M. , Rashad Ghadeer M. , Othman Amira A. A. 
Published: July 2024

Abstract
Objectives
To determine how fetuin-A contributes to diagnosing and assessing MASLD severity.

Methods
Fifty MASLD patients and fifty healthy control participants were involved in this retrospective case-control research. Abdominal ultrasonography, fibroscan with controlled attenuated parameter scan (CAP scan), laboratory investigation (including fetuin-A assessment), clinical examination, and history-taking were performed on every case.

Results
Fetuin-A level was considerably higher in the Cases group (1154.85 ± 629.89) than in the Control group (505.29 ± 150.4) (p < 0.001). Fetuin-A had significant validity in the prediction of MASLD at a cut-off > 702.5 with 82% sensitivity, 90% specificity, and 86% overall accuracy.

Conclusion
One possible marker for MASLD diagnosis could be fetuin-A. Furthermore, a substantial association between such marker and the severity of the disease as it revealed a significant correlation with ultrasound grading and fibroscan with controlled attenuated parameters.
Trial registration
1- Pan African Clinical Trial Registry.
Unique Identifying number/registration ID: PACTR202309644280965.
URL: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=26860.
Registration Approval date: 21/09/2023.
2- ClinicalTrials.gov.
Unique Identifying number /registration ID: NCT06097039.
URL: https://clinicaltrials.gov/study/NCT06097039?cond=NCT06097039&rank=1.
Registration Approval date: 25/10/2023.
Diagnostic accuracy, reliability, and construct validity of the German quick mild cognitive impairment screen
Authors: Manser Patrick , de Bruin Eling D. 
Published: July 2024

Abstract
Background
Early detection of cognitive impairment is among the top research priorities aimed at reducing the global burden of dementia. Currently used screening tools have high sensitivity but lack specificity at their original cut-off, while decreasing the cut-off was repeatedly shown to improve specificity, but at the cost of lower sensitivity. In 2012, a new screening tool was introduced that aims to overcome these limitations – the Quick mild cognitive impairment screen (Qmci). The original English Qmci has been rigorously validated and demonstrated high diagnostic accuracy with both good sensitivity and specificity. We aimed to determine the optimal cut-off value for the German Qmci, and evaluate its diagnostic accuracy, reliability (internal consistency) and construct validity.

Methods
We retrospectively analyzed data from healthy older adults (HOA; n = 43) and individuals who have a clinical diagnosis of ‘mild neurocognitive disorder’ (mNCD; n = 37) with a biomarker supported characterization of the etiology of mNCD of three studies of the ‘Brain-IT’ project. Using Youden’s Index, we calculated the optimal cut-off score to distinguish between HOA and mNCD. Receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic accuracy based on the area under the curve (AUC). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Reliability (internal consistency) was analyzed by calculating Cronbach’s α. Construct validity was assessed by analyzing convergent validity between Qmci-G subdomain scores and reference assessments measuring the same neurocognitive domain.

Results
The optimal cut-off score for the Qmci-G was ≤ 67 (AUC = 0.96). This provided a sensitivity of 91.9% and a specificity of 90.7%. The PPV and NPV were 89.5% and 92.9%, respectively. Cronbach’s α of the Qmci-G was 0.71 (CI95% [0.65 to 0.78]). The Qmci-G demonstrated good construct validity for subtests measuring learning and memory. Subtests that measure executive functioning and/or visuo-spatial skills showed mixed findings and/or did not correlate as strongly as expected with reference assessments.

Conclusion
Our findings corroborate the existing evidence of the Qmci’s good diagnostic accuracy, reliability, and construct validity. Additionally, the Qmci shows potential in resolving the limitations of commonly used screening tools, such as the Montreal Cognitive Assessment. To verify these findings for the Qmci-G, testing in clinical environments and/or primary health care and direct comparisons with standard screening tools utilized in these settings are warranted.
Nausea and vomiting in pregnancy (NVP) in Chinese pregnant women: a cross-sectional study
Authors: Zou Tong , Long Zhiwen , Wang Silu , Yao Qiang 
Published: July 2024

Abstract
Background
This study addresses the scarcity of research on nausea and vomiting in pregnancy (NVP) in China. It aims to explore the current NVP status in the country using validated questionnaires, analyze associated factors, and provide a useful reference for future research. The study also compares results from different assessment tools.

Methods
Online questionnaires were utilized to gather data from 535 pregnant women across 24 provinces. Demographic, pregnancy, and NVP-related information were collected. NVP severity was assessed using Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) and the Rhodes Index of Nausea, Vomiting, and Retching (RINVR) scales. Ordinal logistic regression identified factors linked to NVP severity. Differences between PUQE and RINVR assessments were compared.

Results
NVP prevalence exceeded 90%, with 96.1% assessed by PUQE and 90.8% by RINVR. Incidence decreased from nausea to retching and vomiting. Severe NVP correlated with reduced gestational weight gain, younger age, fewer gestational weeks, and living in North (all P values < 0.05). There was moderate consistency between PUQE and RINVR assessments. The NVP prevalence assessed by the PUQE is higher than that assessed by the RINVR in the same population. However, the proportion of NVP levels above moderate assessed by RINVR is greater than that assessed by PUQE.

Conclusions
NVP is highly prevalent among Chinese pregnant women, with nausea being predominant. RINVR assessments may be better able to identify severe NVP, thereby improving the low treatment rates for severe NVP.