bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical impact of UV mutational signatures in Veterans with cancer
Authors: Wu Ni-Chi , Huang Richard S P , Tseng Chin-Lin , Sokol Ethan S , Serway Christine N , Chadwick Gregory , Mitchell Jerry , Kelley Michael J 
Published: December 2024

Abstract

Background
UV-related DNA damage signature (UVsig) is highly specific for cutaneous cancers. The prevalence of UVsig among tumors without a primary site and tumors of extracutaneous origin were previously reported, suggesting potential misclassification of cancers. Our study aims to assess if the knowledge of UVsig at diagnosis would change first-line treatment recommendation.

Methods
The main outcome was the potential clinical impact (PCI) of UVsig. High PCI was defined as UVsig leading to change in diagnosis and first-line therapy. Medium PCI was a change in diagnosis, but appropriate therapy was offered. Low PCI group had diagnosis modified by clinicians and treated as cutaneous cancer independently of UVsig.

Results
Among 5565 cases, 650 (12%) were positive for a UVsig. In the cancer of unknown primary group: 20 (49%), 9 (22%), and 12 (29%) cases were categorized in the high, medium, and low PCI group, respectively. In the cancer of extracutaneous origin cohort: 22 (54%), 15 (36%), and 4 (10%) cases were high, medium, and low PCI, respectively. The diagnosis would have changed in 14% of Veterans with UVsig positive tumor. Among all high PCI cases, 37 (88%) received chemotherapy that was not indicated based on a UVsig-informed diagnosis of cutaneous malignancy.

Conclusion
Our study suggested that UVsig would lead to revision of the working clinical diagnosis and significantly alter the first-line treatment in at least half of cancers of unknown primary or extracutaneous origin with UVsig. Knowledge of UVsig could lead to more effective and less toxic therapy for patients with cancer.
Second-line therapies in advanced hepatocellular carcinoma following first-line atezolizumab and bevacizumab: multicenter single institution cohort experience
Authors: Marell Paulina , Kournoutas Ioannis , Gile Jennifer , Peersen Anina , Shah Priyanshi , Babiker Hani , Kankeu Lionel Fonkoua , Washburn Leslie , Graham Rondell , Truty Mark , Starlinger Patrick , Halfdanarson Thorvardur , Jin Zhaohui , Jatoi Aminah , McWilliams Robert , Borad Mitesh , Bekaii-Saab Tanios S , Mahipal Amit , Ou Fang-Shu , Tran Nguyen H 
Published: December 2024

Abstract

Background
Atezolizumab plus bevacizumab (A/B) received FDA approval as the first-line therapy for patients with advanced hepatocellular carcinoma (HCC) in 2020. However, optimal subsequent treatment options are unclear. Here, we describe clinical outcomes of advanced HCC patients following first-line treatment with A/B.

Patients and Methods
We conducted a multi-site analysis of patients with HCC treated with first-line A/B between January 2018 and December 2022 at Mayo Clinic. This study cohort included all patients receiving second-line systemic therapy after A/B. Median overall survival (OS) and time-to-treatment discontinuation (TTD) were estimated using the Kaplan-Meier method. Child Pugh (CP) scores are also described at diagnosis, prior to first line, and prior to second-line therapy.

Results
Of the 342 patients who received A/B, 107 (31.3%) received second-line treatments including anti-VEGF therapy or immune checkpoint inhibitor (ICI) and were included in the final analysis. Median OS for all patients was 11.1 months from initiation of second-line therapy. Median OS was 10.7 months (95% CI: 7.2-12.8) and 15.7 months (95%CI: 6.8-NE) for those receiving anti-VEGF inhibitors and ICI ( P = .50). Median TTD for second-line therapies was 2.4 months (95% CI: 1.7-3.3) and 2.6 months (95% CI: 1.5-5.1) for anti-VEGF inhibitors and ICI, respectively (P = .87). In multivariate analyses, CP was significantly associated with survival.

Conclusion
Following first-line A/B treatment, there is no statistically significant difference in survival between ICI and anti-VEGF therapy, nor in time to treatment discontinuation. CP score remains an important prognostic tool.
Experience with sociodemographic data collection in the Canadian paediatric surgical context: A quality improvement initiative
Authors: So Jeannette P , Wiebe Kayla , Kelley Simon , Matava Clyde , Kirsch Roxanne 
Published: December 2024

ABSTRACT
Groups that experience social inequities have poorer health outcomes; however, Canadian healthcare institutions do not routinely collect data to identify those with health inequities. This quality improvement initiative assessed response rates for different methods of sociodemographic data collection using a questionnaire developed to support the ethical prioritization of paediatric non-urgent surgery. Of the 329 families contacted, 85.4% (281/329) completed the questionnaire and of those, 79.7% (224/281) provided sociodemographic data. Surgeon asking in the clinic had the highest response rate (100.0%, 5/5), followed by phone calls from surgical booking administrators (81.6%, 93/114), and a research assistant asking in the clinic (81.0%, 34/42). Sociodemographic data collection is feasible in a Canadian paediatric hospital setting and response rates were higher when completed in person and by staff supporting the care of the patient. The next steps will be to incorporate patient social determinants of health data into decision-making for surgical prioritization.
The Logic of Potential Infinity
Authors: Cook Roy T 
Published: December 2024

Abstract
Michael Dummett argues that acceptance of potentially infinite collections requires that we abandon classical logic and restrict ourselves to intuitionistic logic. In this paper we examine whether Dummett is correct. After developing two detailed accounts of what, exactly, it means for a concept to be potentially infinite (based on ideas due to Charles McCarty and Øystein Linnebo, respectively), we construct a Kripke structure that contains a natural number structure that satisfies both accounts. This model supports a logic much stronger than intuitionistic logic, demonstrating that Dummett was wrong. We conclude by briefly examining ways to extend the account(s) in question to indefinitely extensible concepts such as Cardinal, Ordinal, and Set.
Vitamin B12 intake during pregnancy linked to child speech development and intelligence quotient
Authors: Hrezova Eliska , Jiskrova Gabriela Ksinan , Prusa Tomas , Andryskova Lenka , Pikhart Hynek 
Published: December 2024

Abstract

Background
Nutrient deficiencies during pregnancy may affect offspring development. We aim to examine the association between prenatal vitamin B12 intake and children’s cognitive development.

Methods
A total of 5151 mother–child pairs from the Czech part of ELSPAC study were included in the analysis. Dietary information was obtained during pregnancy using food frequency questionnaire. Parents reported on their child’s speech and language development at 18 months, 3, 5 and 7 years. Intelligence quotient (IQ) was measured at 8 years in subcohort of 854 children.

Results
Children of mothers with higher vitamin B12 intake demonstrated higher scores in language (B = 0.20, 95% CI 0.06, 0.34) and talking and understanding (B = 2.39, 95% CI 0.97, 3.80) in a fully adjusted model at 18 months. Additionally, they were more likely to get maximum points in the intelligibility test at age 3 (OR = 1.05, 95% CI 1.01, 1.09) in unadjusted model, however, not in fully adjusted model. We found a positive effect of higher vitamin B12 intake on verbal IQ (B = 1.08, 95% CI 0.09, 2.08).

Conclusions
We identified consistent associations between prenatal vitamin B12 intake and children’s cognitive development. The results suggest that inadequate vitamin B12 during pregnancy may negatively affect children’s cognitive development, particularly in speech and language.
When tomorrow comes too late—the silent threat: why people delay needed medical care in Türkiye
Authors: Uzun Süleyman Utku , Akın Merve 
Published: December 2024

Abstract

Background
Healthcare demand procrastination is a public health concern in Türkiye, with limited research available. This study examines the prevalence of healthcare procrastination and identifies associated factors among patients at Pamukkale University Hospital.

Methods
This cross-sectional study was conducted from 2 to 13 February 2023 in Denizli and involved 503 patients from 15 outpatient clinics. Data on sociodemographic characteristics, healthcare utilization and procrastination behaviors were collected via a structured questionnaire, including the Healthcare Demand Procrastination Scale (HDPS). Descriptive statistics and linear regression were used for analysis.

Results
The participants had a mean age of 41.46 years (±15.34), with 52.9% being female. A significant 77.3% reported delaying healthcare despite needing it. The primary reasons for delays were difficulty in getting appointments (51.5%), long waiting times (21.9%) and COVID-19 concerns (19.9%). The mean HDPS score was 2.29 ± 0.65, indicating moderate procrastination. Regression analysis revealed that younger age (≤35 years) and rural residence significantly predicted higher HDPS scores, whereas receiving health information from professionals was linked to lower procrastination.

Conclusions
Healthcare procrastination is common among patients in Türkiye, particularly among younger individuals and rural residents. Improving healthcare accessibility, reducing wait times and implementing targeted interventions are essential to mitigate this issue and enhance health outcomes.
Age-period-cohort modeling of oesophageal carcinoma risk in a middle eastern country: 1980–2019
Authors: Akhtar Saeed , Al-Shammari Ahmad , Al-Huraiti Mohammad , Al-Anjery Fouzan 
Published: December 2024

Abstract

Background
Understanding of the factors influencing oesophageal cancer trends is crucial. Therefore, this cross-sectional cohort study sought to disentangle the age, period and cohort effects on the trends of oesophageal cancer in Kuwait.

Methods
The data on incident oesophageal carcinoma cases diagnosed between January 1, 1980, through December 31, 2019, and reference population were obtained. Age-period-cohort (APC) analysis was conducted using a loglinear Poisson regression model.

Results
A total of 496 oesophageal carcinoma cases in 12.8 million person-years (i.e. squamous-cell carcinoma, 269, 54.23%), adenocarcinoma,147, 29.64% and unspecified cases, 80,16.13%) were diagnosed. The overall age-standardized incidence rate (per 105 person-years) of oesophageal carcinoma during the study period was 10.51 (95% CI: 6.62–14.41). The APC analysis results showed that the age and birth cohort effects were the significant determinants of declining, and subsequently steadying the oesophageal carcinoma incidence rates.

Conclusions
A substantial decline in oesophageal carcinoma incidence rates was recorded, which significantly varied in all three temporal dimensions. The observed birth cohort patterns suggest changing lifestyle and dietary patterns seem to be responsible for decreasing oesophageal carcinoma risk in Kuwait. Future studies may look for the component causes maintaining the endemicity of oesophageal carcinoma risk in this and similar countries in the region.
Has a Phenomenon Been Born? Causes, Consequences, and Strategies of Gendering De-democratization in Turkey
Authors: Fernandes Raquel Santos 
Published: December 2024

Abstract
This article examines how the de-democratization process influences gendered politics and how opposition to gender equality assisted democratic backsliding in Turkey. Drawing on a grounded theory methodology study, this article contends that anti-gender equality policy aided the Justice and Development Party in de-democratizing the political regime. At the same time, women experience different consequences of gendering de-democratization. The evidence from in-depth fieldwork, including fifty-three semistructured interviews, demonstrates that antithetical groups are more exposed to the phenomenon. Findings suggest that anti-gender equality policy influences women’s participation in the labor market, which goes along with further exposure to domestic violence.
Group II Introns in Archaeal Genomes and the Evolutionary Origin of Eukaryotic Spliceosomal Introns
Authors: Mattick J. S. A. , Malik S.-B. , Delwiche C. F. 
Published: December 2024

AbstractA key attribute of eukaryotic genomes is the presence of abundant spliceosomal introns that break up many protein-coding genes into multiple exons and must be spliced out during the process of gene expression. These introns are believed to be evolutionarily derived from group II introns, which are known to be widespread in bacteria. One prominent hypothesis is that the spliceosomal intron arose after the endosymbiotic origin of the mitochondrion, as a consequence of transfer of genes containing group II introns from the organelle to nuclear genome; in this model, transfer of group II introns into the ancestral eukaryotic genome set the stage for evolution of the spliceosomal form. However, the recent discovery and sequencing of asgard archaea — the closest archaeal relatives of extant eukaryotes — has shed significant light on the composition of the early eukaryotic genome and calls that model into question. Using sequence analysis and structural modeling, we show here the presence of group II intron maturases in the genomes of Heimdallarchaeia and other asgard archaea, and demonstrate by phylogenetic inference that these are closely related to both eukaryotic mitochondrial group II intron maturases and the spliceosome protein PRP8. This suggests that the first intron-containing eukaryotic common ancestor (FIECA) inherited selfish group II introns from its ancestral archaeal genome – the progenitor of the nuclear genome – rather than from the mitochondrial endosymbiont. These observations suggest that the spread and diversification of introns may have occurred independently of the acquisition of the mitochondrion. To better understand the context for intron evolution, we investigate the broader occurrence of group II introns in archaea, identify archaeal clades enriched in group II introns, and perform structural modeling to examine the relationship between the archaeal group II intron maturase and the eukaryotic spliceosome. We propose a model of intron acquisition and expansion during early eukaryotic evolution that places the spread of introns prior to the acquisition of mitochondria, possibly facilitated by the separation of transcription and translation afforded by the nucleus.
Elevated FGF23 levels predict cardiovascular and cerebrovascular events in acute ischaemic stroke patients
Authors: Gu Lingyun , Shen Liping , Li Weizhang , Zhou Jinfeng , Jin Qi , Yang Jiangsheng , Cui Junyou , Zhu Zufu , Xu Zhuowen , Weng Yulong 
Published: December 2024

AbstractBACKGROUNDThere have been recent studies on fibroblast growth factor 23 (FGF23) and acute ischaemic stroke (AIS), but some of the results were conflicting. Therefore, the objective of this study was to assess whether baseline FGF23 was associated with the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in AIS patients.METHODSThis study enrolled 394 patients with AIS and followed for a median period of 43 months. 130 people who underwent health check-ups in our hospital were selected as the control group. The study endpoint was the first occurrence of MACCE outside the hospital. Serum FGF23 levels were quantified using an enzyme-linked immunosorbent assay.RESULTSSerum FGF23 levels were found to be significantly higher in the AIS group than in the control group (525.14±167.40 vs 338.62±161.71,P<0.05). Furthermore, serum FGF23 levels were observed to be elevated in the MACCE group in comparison to the no MACCE group (646.09±164.05 vs 491.87±152.54,P<0.05). According to the receiver operating characteristic curve analysis, the predictive value of the combination of the three [FGF23, National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS)] for the occurrence of MACCE in AIS was higher than that of any of them (P<0.05), while the difference between the three was not statistically significant. The cumulative MACCE-free survival was found to be significantly higher in the group with low FGF23 levels than in the group with high FGF23 levels, as demonstrated by Kaplan-Meier analysis (P<0.05). The multifactorial Cox analysis revealed that the elevated baseline serum FGF23 level (HR: 3.731, 95% CI: 2.157-6.452) was a significant predictor of MACCE in AIS patients.CONCLUSIONSElevated baseline serum FGF23 levels were considered to be a valid predictor of MACCE in patients with AIS.
Subjective experience of women with childbirth in hospitals after COVID-19 outbreak: Insights from Babies Born Better survey
Authors: Greškovičová Katarína , Němcová Mariana , Šiková Tereza 
Published: December 2024

AbstractAfter COVID-19 outbreak, there has been changes in maternity care suggesting that childbirth experience was also change. This study thus investigates the impact of the COVID-19 pandemic on childbirth experiences in Slovak hospitals, focusing on women’s perspectives to childbirth experience. Utilizing data from the Babies Born Better survey, we analyzed responses from 810 women who gave birth in Slovakia between March 2020 and June 2022. Via inductive content analysis we identified 4 main themes: Compassionate and Supportive Care, Medical Expertise and Care, Autonomy and Empowerment, and External Conditions. Our research has provided further evidence of the multifaceted nature of childbirth experience. The childbirth experience in a period of general adversity (such as pandemics) may have not been captured in this research or it may not significantly differ from periods of non-adversity. What is important for women remain unchanged - compassionate and supportive care from healthcare providers. Based on our findings we propose improvements in maternal healthcare during childbirth. These improvements aim not only to improve womeńs childbirth experience but also foster better healthcare outcomes for professionals and hospitals.
PREVALENCE OF ANEMIA, IRON DEFICIENCY ANEMIA, AND ASSOCIATED FACTORS AMONG DIABETICS IN THE WEST REGION of CAMEROON
Authors: Tedong Leonard , Mekieje Maï-Pamela Tumchou , Djeukamgang Melisa Mene , De Manfouo Romaric Tuono , Tchoumke Marius Mbiandjeu ,   Pascal Blaise Well a Well a Koul, Simo Josué Louokdom , Chuisseu Djamen Pascal Dieudonne 
Published: December 2024

ABSTRACTAims and objectiveAnemias are a burden for management because they are associated with the worsening of the pathophysiology of diseases. They can be multifactorial, including micronutrient deficiencies including iron deficiencies. This study aimed to biologically characterize anemias and iron deficiency anemias during diabetes and to identify the associated factors.MethodsOver 4 months, we conducted an analytical cross-sectional study from August to November 2024. 210 diabetic patients, attending the diabetology unit of the regional hospital in West Cameroon were studied, their age range between <20 and > 70 years. Blood samples were taken for biological tests including blood count, glycemia, glycated hemoglobin, ferritin, and serum following standard assay protocols. The results obtained were analyzed using the R statistical tool version 4.1.1.ResultsThe sex ratio was 0.89 and the mean age was 48.32±18.19 years. 48.6% of patients were overweight. The frequency of anemia was observed in 72 females (53%) and 63 males (46.7%) with a total frequency of 64.3%. 11.4% were found to have iron deficiency anemias. The blood count revealed hematological abnormalities characterized by leukopenia (41.4%), granulocytopenia (35.7%), and thrombocytopenia (2.86%) with macroplateletosis (40.0%). Anemias were characterized by microcytosis (11.1% in anemic patients versus none in non-anemic patients (p<0.001), hypochromia (88.9% in anemic patients versus 72% in non-anemic patients (p<0.001)) and greater regeneration in anemic patients versus non-anemic patients (p<0.001). Macroplateletosis and high Hb1AC were identified as predictive factors for iron deficiency anemia in diabetes with (Or=2.83, 95% CI= [1.17;6.80];p=0.021) and Or=2.38, 95% CI= [0.14;3.09],p=0.045, respectively.ConclusionThis study reports a significant frequency of anemia and iron deficiency anemia in diabetic patients; the latter is associated with worsening clinical manifestations in patients. This study raises the need for regular exploration of iron status in diabetics to prevent complications related to iron deficiency.
Leucine Aminopeptidase LyLAP enables lysosomal degradation of membrane proteins
Authors: Jain Aakriti , Heremans Isaac , Rademaker Gilles , Detomasi Tyler C. , Hernandez Grace A. , Zhang Justin , Gupta Suprit , Linde Teresa von , Lange Mike , Spacci Martina , Rohweder Peter , Anderson Dashiell , Citron Y. Rose , Olzmann James A. , Dawson David W. , Craik Charles S. , Bommer Guido , Perera Rushika M. , Zoncu Roberto 
Published: December 2024

AbstractProteolysis of hydrophobic helices is required for complete breakdown of every transmembrane protein trafficked to the lysosome and sustains high rates of endocytosis. However, the lysosomal mechanisms for degrading hydrophobic domains remain unknown. Combining lysosomal proteomics with functional genomic data mining, we identify Lysosomal Leucine Aminopeptidase (LyLAP; formerly Phospholipase B Domain-Containing 1) as the hydrolase most tightly associated with elevated endocytic activity. Untargeted metabolomics and biochemical reconstitution demonstrate that LyLAP is not a phospholipase, but a processive monoaminopeptidase with strong preference for N-terminal leucine – an activity necessary and sufficient for breakdown of hydrophobic transmembrane domains. LyLAP is upregulated in pancreatic ductal adenocarcinoma (PDA), which relies on macropinocytosis for nutrient uptake, and its ablation led to buildup of undigested hydrophobic peptides, which compromised lysosomal membrane integrity and inhibited PDA cell growth. Thus, LyLAP enables lysosomal degradation of membrane proteins, and may represent a vulnerability in highly endocytic cancer cells.One sentence summaryLyLAP degrades transmembrane proteins to sustain high endocytosis and lysosomal membrane stability in pancreatic cancer.