bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing LI-RADS: ancillary features screened from LR-3/4 categories can improve the diagnosis of HCC on MRI
Authors: Zhang Zi-xin , Xv Hui , Du Yan-ni , Lv Zhi-bin , Yang Zheng-han 
Published: March 2024

Abstract
Objective
To determine the high-efficiency ancillary features (AFs) screened from LR-3/4 lesions and the HCC/non-HCC group and the diagnostic performance of LR3/4 observations.

Materials and methods
We retrospectively analyzed a total of 460 patients (with 473 nodules) classified into LR-3-LR-5 categories, including 311 cases of hepatocellular carcinoma (HCC), 6 cases of non-HCC malignant tumors, and 156 cases of benign lesions. Two faculty abdominal radiologists with experience in hepatic imaging reviewed and recorded the major features (MFs) and AFs of the Liver Imaging Reporting and Data System (LI-RADS). The frequency of the features and diagnostic performance were calculated with a logistic regression model. After applying the above AFs to LR-3/LR-4 observations, the sensitivity and specificity for HCC were compared.

Results
The average age of all patients was 54.24 ± 11.32 years, and the biochemical indicators ALT (P = 0.044), TBIL (P = 0.000), PLT (P = 0.004), AFP (P = 0.000) and Child‒Pugh class were significantly higher in the HCC group. MFs, mild-moderate T2 hyperintensity, restricted diffusion and AFs favoring HCC in addition to nodule-in-nodule appearance were common in the HCC group and LR-5 category. AFs screened from the HCC/non-HCC group (AF-HCC) were mild–moderate T2 hyperintensity, restricted diffusion, TP hypointensity, marked T2 hyperintensity and HBP isointensity (P = 0.005, < 0.001, = 0. 032, p < 0.001, = 0.013), and the AFs screened from LR-3/4 lesions (AF-LR) were restricted diffusion, mosaic architecture, fat in mass, marked T2 hyperintensity and HBP isointensity (P < 0.001, = 0.020, = 0.036, < 0.001, = 0.016), which were not exactly the same. After applying AF-HCC and AF-LR to LR-3 and LR-4 observations in HCC group and Non-HCC group, After the above grades changed, the diagnostic sensitivity for HCC were 84.96% using AF-HCC and 85.71% using AF-LR, the specificity were 89.26% using AF-HCC and 90.60% using AF-LR, which made a significant difference (P = 0.000). And the kappa value for the two methods of AF-HCC and AF–LR were 0.695, reaching a substantial agreement.

Conclusion
When adjusting for LR-3/LR-4 lesions, the screened AFs with high diagnostic ability can be used to optimize LI-RADS v2018; among them, AF-LR is recommended for better diagnostic capabilities.
Spatiotemporal modeling of under-five mortality and associated risk factors in Ethiopia using 2000–2016 EDHS data
Authors: Amuka Endashaw , Mitiku Aweke A. , Zeru Melkamu A. 
Published: March 2024

Abstract
Background
The under-five mortality rate serves as a key indicator of the performance of a country’s healthcare system. Despite a minor decline, Ethiopia continues to face a persistently high under-five mortality rate across different zones. Thus, this study aimed to identify the risk factors of under-five mortality and the spatiotemporal variation in Ethiopian administrative zones.

Method
This study used the 2000–2016 Ethiopian Demographic and Health Survey (EDHS) data which were collected using a two-stage sampling method. A total of 43,029 (10,873 in 2000, 9,861 in 2005, 11,654 in 2011, and 10,641 in 2016) weighted sample under-five child mortality were used. The space-time dynamic model was employed to account for spatial and time effects in 65 administrative zones in Ethiopia.

Results
From the result of a general nesting spatial-temporal dynamic model, there was a significant space-time interaction effect [γ = -0.1444, 95% CI(-0.6680, -0.1355)] for under-five mortality. The increase in the percentages of mothers illiteracy [β = 0.4501, 95% CI (0.2442, 0.6559)], not vaccinated[β= 0.7681, 95% CI (0.5683, 0.9678)], unimproved water[β= 0.5801, CI (0.3793, 0.7808)] were increased death rates for under five children while increased percentage of contraceptive use [β= -0.6609, 95% CI (-0.8636, -0.4582)] and antenatal care unit visit > 4 times [β= -0.1585, 95% CI(-0.1812, -0.1357)] were contributed to the decreased under-five mortality rate at the zone in Ethiopia.

Conclusions
Even though the mortality rate for children under five has decreased over time, still there is higher in different zones of Ethiopia. There exists spatial and temporal variation in under-five mortality among zones. Therefore, it is very important to consider spatial neighborhood’s and temporal context when aiming to avoid under-five mortality.
Trends in psychosomatic symptoms among adolescents and the role of lifestyle factors
Authors: Buli Benti Geleta , Lehtinen-Jacks Susanna , Larm Peter , Nilsson Kent W. , Hellström-Olsson Charlotta , Giannotta Fabrizia 
Published: March 2024

Abstract

Background
Adolescent mental health problems are on the rise globally, including in Sweden. One indicator of this trend is increased psychosomatic symptoms (PSS) over time. Lifestyle factors such as physical activity (PA), diet, smoking, and alcohol consumption may influence the time trends in PSS; however, the evidence base is scarce. The aim of this study was to investigate associations between time trends in PSS and lifestyle factors.

Methods
The study was based on data collected from a nationally representative sample of 9,196 fifteen-year-old boys and girls in Sweden using the Health Behavior in School-aged Children (HBSC) symptom checklist. The sample comprised nearly equal proportions of girls (50.5%) and boys. The lifestyle factors examined in this study included PA, regular breakfast intake, consumption of fruits, vegetables, sweets, or soft drinks, smoking, and alcohol drunkenness. We used data from 2002 to 2018 and stratified by family affluence scale (FAS) to demonstrate how the associations varied among the FAS groups. We fitted separate regression models for the high- and low-FAS groups, where interaction terms between the year of survey and each lifestyle factor were used to estimate the level and direction of associations between the factors and trends in PSS.

Results
There was a generally increasing trend in PSS mean scores from 2.26 in 2002 to 2.49 in 2018 (p <.001). The changes in each survey year compared to the average mean scores during the preceding years were significant in all years except 2010. Regular breakfast intake, daily fruit and vegetable consumption, and higher PA were associated with lower PSS mean scores, while smoking and drunkenness had opposite associations with PSS. The only significant interaction between survey year and the lifestyle factors was observed regarding drunkenness in the high FAS group, suggesting that the association between trends in PSS and the experience of getting drunk at least twice got stronger over time (B = 0.057; CI:0.016, 0.097; p <.01).

Conclusions
The results indicate increasing trends in PSS among young people in Sweden from 2002 to 2018, with a significant increase observed among adolescents in the high FAS group who reported getting drunk on at least two occasions.
The association between diet quality index-international and dietary diversity score with preeclampsia: a case–control study
Authors: Hayat Parastoo Tolou , Gargari Bahram Pourghassem , Sarbakhsh Parvin 
Published: March 2024

Abstract
Background
Preeclampsia is a significant complication that occurs during the second half of pregnancy. Recent studies have indicated that dietary factors play a crucial role in the development of preeclampsia. The Diet Quality Index-International (DQI-I) and Dietary Diversity Score (DDS) are appropriate indices for assessing the quality of foods, meals, and diets. This study aimed to investigate the relationship between DQI-I, DDS, and preeclampsia.

Methods
This study utilized a case-control design. A total of 90 newly diagnosed preeclampsia cases and 90 healthy controls were included from a referral hospital in Tabriz, Iran. DQI-I and DDS were calculated based on information obtained from a reliable Food Frequency Questionnaire consisting of 168 food items, which assessed participants’ usual diet. Logistic regression analysis adjusted for age, body mass index, education, family history of preeclampsia, and total energy intake was used to estimate odds ratios (ORs).

Results
The mean age and pre-pregnancy body mass index of the participants were: 27.14 ± 4.40 years and 26.09 ± 3.33 kg/m2, respectively. After adjusting for various confounders, we found significant inverse association between the risk of developing preeclampsia and both DQI-I and DDS. The highest quartile of DQI-I had a significantly lower risk of developing preeclampsia compared to the first quartile (OR = 0.02, 95% CI [0.005, 0.08]) (P < 0.001). Similarly, the highest quartile of DDS had a significantly lower risk of developing preeclampsia compared to the first quartile (OR = 0.09, 95% CI [0.03, 0.31]) (P = 0.001).

Conclusions
Our findings suggest that maintaining a high-quality and diverse diet is associated with a lower risk of preeclampsia. Further studies are needed to confirm these associations and explore potential causal relationships.
CTLs heterogeneity and plasticity: implications for cancer immunotherapy
Authors: Peng Shengkun , Lin Anqi , Jiang Aimin , Zhang Cangang , Zhang Jian , Cheng Quan , Luo Peng , Bai Yifeng 
Published: March 2024

AbstractCytotoxic T lymphocytes (CTLs) play critical antitumor roles, encompassing diverse subsets including CD4+, NK, and γδ T cells beyond conventional CD8+ CTLs. However, definitive CTLs biomarkers remain elusive, as cytotoxicity-molecule expression does not necessarily confer cytotoxic capacity. CTLs differentiation involves transcriptional regulation by factors such as T-bet and Blimp-1, although epigenetic regulation of CTLs is less clear. CTLs promote tumor killing through cytotoxic granules and death receptor pathways, but may also stimulate tumorigenesis in some contexts. Given that CTLs cytotoxicity varies across tumors, enhancing this function is critical. This review summarizes current knowledge on CTLs subsets, biomarkers, differentiation mechanisms, cancer-related functions, and strategies for improving cytotoxicity. Key outstanding questions include refining the CTLs definition, characterizing subtype diversity, elucidating differentiation and senescence pathways, delineating CTL-microbe relationships, and enabling multi-omics profiling. A more comprehensive understanding of CTLs biology will facilitate optimization of their immunotherapy applications. Overall, this review synthesizes the heterogeneity, regulation, functional roles, and enhancement strategies of CTLs in antitumor immunity, highlighting gaps in our knowledge of subtype diversity, definitive biomarkers, epigenetic control, microbial interactions, and multi-omics characterization. Addressing these questions will refine our understanding of CTLs immunology to better leverage cytotoxic functions against cancer.
Impact of professional, recreational and nonsinging on temporomandibular disorders - a comparative study based on a self-assessment questionnaire
Authors: Wollenburg Maja , Wolowski Anne 
Published: March 2024

Abstract
Background
This study investigates the relationship between professional and recreational singing on temporomandibular disorders (TMDs) in women compared to a nonsinging control group.

Methods
A total of 288 female subjects between the ages of 18 and 45 participated in the self-assessment questionnaire including demographic data, as well as questions on vocal practice and TMDs symptoms. Depending on the singing time per week, the (non)vocalists were assigned to the groups professional (n = 96), recreational (n = 96) and nonsingers (n = 96).

Results
The TMDs prevalence in professional singers (42%) was higher than that in recreational singers (31%) and noticeably higher than that in nonsingers (25%). The Fisher-Freeman-Halton exact test showed that the differences between the groups were not noticeable (p = .053) but could be formulated as tendencies. The professionals suffered much more from restricted jaw movement (p = .004; OR = 2.718; 95% CI = 1.409–5.242), temporomandibular joint sounds (p < .009; OR = 2.267; 95% CI = 1.264–4.064) and temporomandibular pain (p = .010; OR = 2.333; 95% CI = 1.264–4.308) than nonsingers.

Conclusions
Singing might have an enhancing effect on the appearance of TMDs. In particular, professional singers suffered more from self-reported TMDs than recreational singers and nonsingers. In addition to the high level of physical workload if participating in professional singing, the psychosocial impact should be investigated more in further studies. No new treatment strategies resulted from this study, as the etiological significance of singing is still unclear. Knowledge about risk factors for multifactorial TMDs can help practitioners and patients prevent and treat TMDs.
No detectable truncating mutations in large T antigen (LT-Ag) sequence of Merkel cell polyomavirus (MCPyV) DNA obtained from porocarcinomas
Authors: Arvia Rosaria , Sollai Mauro , Massi Daniela , Asensio-Calavia Patricia , Urso Carmelo , Zakrzewska Krystyna 
Published: March 2024

AbstractMerkel cell polyomavirus (MCPyV) is associated with Merkel cell carcinoma (MCC). In tumor cells the MCPyV large T antigen (LT-Ag) is frequently found truncated and this is considered a major tumor-specific signature. The role of MCPyV in other, non-MCC tumours, is little known. Viral DNA and/or tumour-specific mutations have been sometimes detected in different tumours, but such data are not unequivocal and the involvement of the virus in the tumorigenesis is not clear. In a previous study, we demonstrated a significantly higher prevalence of MCPyV DNA in formalin fixed paraffin embedded (FFPE) porocarcinoma tissues compared to the normal skin.In the present study, we investigated the presence of truncating mutations in MCPyV LT-Ag coding region in porocarcinoma specimens. Using several overlapped PCR primer pairs, the complete LT-Ag sequence from two biopsies were obtained. No truncating mutations were detected.The lack of truncating mutations in LT-Ag sequence does not seem to support the role of MCPyV in porocarcinoma oncogenesis. However, an oncogenetic mechanism, different from that proposed for MCC and not associated with the LT-Ag mutations/deletions, cannot be excluded. Further studies of more sequences coding for LT-Ag would be needed to verify this hypothesis.
Prognostic value of arterial carbon dioxide tension during cardiopulmonary resuscitation in out-of-hospital cardiac arrest patients receiving extracorporeal resuscitation
Authors: Su Pei-I , Tsai Min-Shan , Chen Wei-Ting , Wang Chih-Hung , Chang Wei-Tien , Ma Matthew Huei-Ming , Chen Wen-Jone , Huang Chien-Hua , Chen Yih-Sharng 
Published: March 2024

Abstract
Background
Current guidelines on extracorporeal cardiopulmonary resuscitation (ECPR) recommend careful patient selection, but precise criteria are lacking. Arterial carbon dioxide tension (PaCO2) has prognostic value in out-of-hospital cardiac arrest (OHCA) patients but has been less studied in patients receiving ECPR. We studied the relationship between PaCO2 during cardiopulmonary resuscitation (CPR) and neurological outcomes of OHCA patients receiving ECPR and tested whether PaCO2 could help ECPR selection.

Methods
This single-centre retrospective study enrolled 152 OHCA patients who received ECPR between January 2012 and December 2020. Favorable neurological outcome (FO) at discharge was the primary outcome. We used multivariable logistic regression to determine the independent variables for FO and generalised additive model (GAM) to determine the relationship between PaCO2 and FO. Subgroup analyses were performed to test discriminative ability of PaCO2 in subgroups of OHCA patients.

Results
Multivariable logistic regression showed that PaCO2 was independently associated with FO after adjusting for other favorable resuscitation characteristics (Odds ratio [OR] 0.23, 95% Confidence Interval [CI] 0.08–0.66, p-value = 0.006). GAM showed a near-linear reverse relationship between PaCO2 and FO. PaCO2 < 70 mmHg was the cutoff point for predicting FO. PaCO2 also had prognostic value in patients with less favorable characteristics, including non-shockable rhythm (OR, 3.78) or low flow time > 60 min (OR, 4.66).

Conclusion
PaCO2 before ECMO implementation had prognostic value for neurological outcomes in OHCA patients. Patients with PaCO2 < 70 mmHg had higher possibility of FO, even in those with non-shockable rhythm or longer low-flow duration. PaCO2 could serve as an ECPR selection criterion.
Factors associated with engraftment success of patient-derived xenografts of breast cancer
Authors: Lee Jongwon , Lee GunHee , Park Hye Seon , Jeong Byung-Kwan , Gong Gyungyub , Jeong Jae Ho , Lee Hee Jin 
Published: March 2024

Abstract
Background
Patient-derived xenograft (PDX) models serve as a valuable tool for the preclinical evaluation of novel therapies. They closely replicate the genetic, phenotypic, and histopathological characteristics of primary breast tumors. Despite their promise, the rate of successful PDX engraftment is various in the literature. This study aimed to identify the key factors associated with successful PDX engraftment of primary breast cancer.

Methods
We integrated clinicopathological data with morphological attributes quantified using a trained artificial intelligence (AI) model to identify the principal factors affecting PDX engraftment.

Results
Multivariate logistic regression analyses demonstrated that several factors, including a high Ki-67 labeling index (Ki-67LI) (p < 0.001), younger age at diagnosis (p = 0.032), post neoadjuvant chemotherapy (NAC) (p = 0.006), higher histologic grade (p = 0.039), larger tumor size (p = 0.029), and AI-assessed higher intratumoral necrosis (p = 0.027) and intratumoral invasive carcinoma (p = 0.040) proportions, were significant factors for successful PDX engraftment (area under the curve [AUC] 0.905). In the NAC group, a higher Ki-67LI (p < 0.001), lower Miller-Payne grade (p < 0.001), and reduced proportion of intratumoral normal breast glands as assessed by AI (p = 0.06) collectively provided excellent prediction accuracy for successful PDX engraftment (AUC 0.89).

Conclusions
We found that high Ki-67LI, younger age, post-NAC status, higher histologic grade, larger tumor size, and specific morphological attributes were significant factors for predicting successful PDX engraftment of primary breast cancer.
Interactive virtual assistance for mental health promotion and self-care management in elderly with type 2 diabetes (IVAM-ED): study protocol and statistical analysis plan for a randomized controlled trial
Authors: da Costa Frederico Ludwig , Matzenbacher Lucas Strassburger , Gheno Vicenzo , Brum Maria Antônia Bertuzzo , de Barros Laura Gomes Boabaid , Maia Isabela Semmelmann , Blank Luiza Machado , Fontoura Lucas Friedrich , Alessi Janine , Telo Gabriela Heiden 
Published: March 2024

Abstract
Background
With one in five individuals aged 65 or older living with type 2 diabetes worldwide, it is crucial to acknowledge and address the challenges faced by this population. In this context, our study aims to evaluate the efficacy of a behavioral intervention model delivered through a smart speaker on mental health and diabetes self-care in the elderly with diabetes.

Methods
This is a single-center, pragmatic, parallel two-arm open randomized clinical trial involving elderly patients with type 2 diabetes. We plan to enroll a total of 112 individuals who will be randomized 1:1 to receive the Smart Speaker EchoDot 3rd Gen device (Amazon Echo®) for home use (intervention arm) or to maintain usual care (control arm). The primary outcome is mental distress, assessed using the 20-item Self Reporting Questionnaire (SRQ-20) after a 12-week intervention period. Secondary outcomes include quality of life, adherence to diabetes self-care behaviors, perception of stress, glycemic control, blood pressure, and lipid profile. Analysis of covariance (ANCOVA) will be used to evaluate the effects of the intervention on the outcomes.

Discussion
This study assesses the effectiveness of an interactive virtual assistance system for enhancing mental health and glycemic control among elderly individuals with type 2 diabetes. The findings may introduce smart speakers as a valuable tool for promoting diabetes-related self-care in this population.

Trial registration
ClinicalTrials.gov NCT05329376. Registered on 15 April 2022. Enrollment began on 20 June 2023 and the last update of protocol was on 13 December 2023.
Diversity of CFTR variants across ancestries characterized using 454,727 UK biobank whole exome sequences
Authors: Ideozu Justin E. , Liu Mengzhen , Riley-Gillis Bridget M. , Paladugu Sri R. , Rahimov Fedik , Krishnan Preethi , Tripathi Rakesh , Dorr Patrick , Levy Hara , Singh Ashvani , Waring Jeffrey F. , Vasanthakumar Aparna 
Published: March 2024

Abstract
Background
Limited understanding of the diversity of variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene across ancestries hampers efforts to advance molecular diagnosis of cystic fibrosis (CF). The consequences pose a risk of delayed diagnoses and subsequently worsened health outcomes for patients. Therefore, characterizing the spectrum of CFTR variants across ancestries is critical for revolutionizing molecular diagnoses of CF.

Methods
We analyzed 454,727 UK Biobank (UKBB) whole-exome sequences to characterize the diversity of CFTR variants across ancestries. Using the PanUKBB classification, the participants were assigned into six major groups: African (AFR), American/American Admixed (AMR), Central South Asia (CSA), East Asian (EAS), European (EUR), and Middle East (MID). We segregated ancestry-specific CFTR variants, including those that are CF-causing or clinically relevant. The ages of certain CF-causing variants were determined and analyzed for selective pressure effects, and curated phenotype analysis was performed for participants with clinically relevant CFTR genotypes.

Results
We detected over 4000 CFTR variants, including novel ancestry-specific variants, across six ancestries. Europeans had the most unique CFTR variants [n = 2212], while the American group had the least unique variants [n = 23]. F508del was the most prevalent CF-causing variant found in all ancestries, except in EAS, where V520F was the most prevalent. Common EAS variants such as 3600G > A, V456A, and V520, which appeared approximately 270, 215, and 338 generations ago, respectively, did not show evidence of selective pressure. Sixteen participants had two CF-causing variants, with two being diagnosed with CF. We found 154 participants harboring a CF-causing and varying clinical consequences (VCC) variant. Phenotype analysis performed for participants with multiple clinically relevant variants returned significant associations with CF and its pulmonary phenotypes [Bonferroni-adjusted p < 0.05].

Conclusions
We leveraged the UKBB database to comprehensively characterize the broad spectrum of CFTR variants across ancestries. The detection of over 4000 CFTR variants, including several ancestry-specific and uncharacterized CFTR variants, warrants the need for further characterization of their functional and clinical relevance. Overall, the presentation of classical CF phenotypes seen in non-CF diagnosed participants with more than one CF-causing variant indicates that they may benefit from current CFTR modulator therapies.