bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying key genes in cancer networks using persistent homology
Authors: Ramos Rodrigo Henrique , Bardelotte Yago Augusto , de Oliveira Lage Ferreira Cynthia , Simao Adenilso 
Published: January 2025

Abstract
Identifying driver genes is crucial for understanding oncogenesis and developing targeted cancer therapies. Driver discovery methods using protein or pathway networks rely on traditional network science measures, focusing on nodes, edges, or community metrics. These methods can overlook the high-dimensional interactions that cancer genes have within cancer networks. This study presents a novel method using Persistent Homology to analyze the role of driver genes in higher-order structures within Cancer Consensus Networks derived from main cellular pathways. We integrate mutation data from six cancer types and three biological functions: DNA Repair, Chromatin Organization, and Programmed Cell Death. We systematically evaluated the impact of gene removal on topological voids (
$$\beta _2$$
structures) within the Cancer Consensus Networks. Our results reveal that only known driver genes and cancer-associated genes influence these structures, while passenger genes do not. Although centrality measures alone proved insufficient to fully characterize impact genes, combining higher-order topological analysis with traditional network metrics can improve the precision of distinguishing between drivers and passengers. This work shows that cancer genes play an important role in higher-order structures, going beyond pairwise measures, and provides an approach to distinguish drivers and cancer-associated genes from passenger genes.
SLC1A5 is a key regulator of glutamine metabolism and a prognostic marker for aggressive luminal breast cancer
Authors: Alfarsi Lutfi H. , Ansari Rokaya El , Erkan Busra , Fakroun Ali , Craze Madeleine L. , Aleskandarany Mohammed A. , Cheng Kiu Wai , Ellis Ian O. , Rakha Emad A. , Green Andrew R. 
Published: January 2025

Abstract
Cancer cells exhibit altered metabolism, often relying on glutamine (Gln) for growth. Breast cancer (BC) is a heterogeneous disease with varying clinical outcomes. We investigated the role of the amino acid transporter SLC1A5 (ASCT2) and its association with BC subtypes and patient outcomes. In large BC cohorts, SLC1A5 mRNA (n = 9488) and SLC1A5 protein (n = 1274) levels were assessed and correlated their expression with clinicopathological features, molecular subtypes, and patient outcomes. In vitro SLC1A5 knockdown and inhibition studies in luminal BC cell lines (ZR-75-1 and HCC1500) were used to further explore the role of SLC1A5 in Gln metabolism. Statistical analysis was performed using chi-squared tests, ANOVA, Spearman’s correlation, Kaplan–Meier analysis, and Cox regression. SLC1A5 mRNA and SLC1A5 protein expression were strongly correlated in luminal B, HER2 + and triple-negative BC (TNBC). Both high SLC1A5 mRNA and SLC1A5 protein expression were associated with larger tumour size, higher grade, and positive axillary lymph node metastases (P < 0.01). Importantly, high SLC1A5 expression correlated with poor BC-specific survival specifically in the highly proliferative luminal subtype (P < 0.001). Furthermore, SLC1A5 knockdown by siRNA or GPNA inhibition significantly reduced cell proliferation and glutamine uptake in ZR-75-1 cells. Our findings suggest SLC1A5 plays a key role in the aggressive luminal BC subtype and represents a potential therapeutic target. Further research is needed to explore SLC1A5 function in luminal BC and its association with Gln metabolism pathways.
Illuminating understudied kinases: a generalizable biosensor development method applied to protein kinase N
Authors: Bogomolovas Julius , Chen Ju 
Published: January 2025

Abstract
Protein kinases play crucial roles in regulating cellular processes, making real-time visualization of their activity essential for understanding signaling dynamics. While genetically encoded fluorescent biosensors have emerged as powerful tools for studying kinase activity, their development for many kinases remains challenging due to the lack of suitable substrate peptides. Here, we present a novel approach for identifying peptide substrates and demonstrate its effectiveness by developing a biosensor for Protein Kinase N (PKN) activity. Our method identified a new PKN substrate peptide that we optimized for use in a fluorescent biosensor design. The resulting biosensor shows specificity for PKN family kinases and can detect both overexpressed and endogenous PKN activity in live cells. Importantly, our biosensor revealed sustained basal PKN2 activity at the plasma membrane, identifying it as a PKN2 activity hotspot. This work not only provides a valuable tool for studying PKN signaling but also demonstrates a promising strategy for developing biosensors for other understudied kinases, potentially expanding our ability to monitor kinase activity across the human kinome.
Dark-field X-ray microscopy with structured illumination for three-dimensional imaging
Authors: Gürsoy Doğa , Yay Kaan Alp , Kisiel Elliot , Wojcik Michael , Sheyfer Dina , Last Arndt , Highland Matthew , Fisher Ian Randal , Hruszkewycz Stephan , Islam Zahir 
Published: January 2025

Abstract
Dark-field X-ray microscopy is a lens-based technique that enables real-space imaging of heterogeneous micro- and meso-scale ordered materials. However, achieving accurate three-dimensional (3D) reconstruction often requires meticulous sample alignment or rastering, requiring complex rotational setups and extended acquisition times. To address these challenges, we introduce a structured illumination technique optimized for 3D imaging of ordered materials at sub-micrometer length scales. Our approach employs a coded aperture to spatially modulate the incident X-ray beam, enabling 3D structural reconstruction from images captured at various aperture positions. Unlike current 3D imaging approaches, which often rely on rotational or rastering methods, our technique uses scanning X-ray silhouettes of the coded aperture for depth resolution along the diffraction axis. This eliminates the need for sample rotation or rastering, resulting in a highly stable and efficient imaging modality. We validated the efficacy of this approach through experimental imaging of an isolated twin domain within a bulk single crystal of an iron pnictide using a dark-field X-ray microscope. This advancement aligns with the enhanced brightness upgrades of modern synchrotron radiation facilities, unlocking new possibilities for high-resolution imaging of ordered materials.
Examining Concurrent Associations Between Gesture Use, Developmental Domains, and Autistic Traits in Toddlers With Down Syndrome
Authors: La Valle Chelsea , Mejia Gabriela Davila , Wilkinson Carol L. , Baumer Nicole 
Published: January 2025

Purpose:
Toddlers with Down syndrome (DS) showcase comparable or higher rates of gestures than chronological age– and language-matched toddlers without DS. Little is known about how gesture use in toddlers with DS relates to multiple domains of development, including motor, pragmatics, language, and visual reception (VR) skills. Unexplored is whether gesture use is a good marker of social communication skills in DS or if gesture development might be more reliably a marker of motor, language, pragmatics, or VR skills. This study examined the concurrent association of gesture use on other areas of development and investigated the association of autistic traits with gesture use in toddlers with DS.

Method:

Thirty toddlers with DS (15 females;
M
= 26.12 months,
SD
= 6.42 months) completed the Mullen Scales of Early Learning (MSEL) and the Autism Diagnostic Observation Schedule–Second Edition (ADOS-2). Parents completed the MacArthur–Bates Communicative Development Inventories Words and Gestures form and the Language Use Inventory (LUI; pragmatic language) about their child.

Results:
Controlling for child chronological age and sex, total gestures was strongly positively associated with the LUI total score (pragmatic language) and MSEL language (receptive, expressive) raw scores, moderately positively associated with motor (fine, gross) raw scores, but not significantly associated with VR raw scores. Higher ADOS social affect (SA) calibrated severity scores was strongly negatively associated with total gestures but not significantly associated with restricted and repetitive behaviors.

Conclusions:
Gestures track together with language, pragmatics, and motor skills. Higher ADOS SA calibrated severity scores were associated with fewer gestures in toddlers with DS. Clinicians can consider each child's developmental profile (e.g., motor, pragmatics, language, social communication skills) to better understand their gesture development.

Supplemental Material:

https://doi.org/10.23641/asha.28169186
Effects of ozone and GAC on the removal of acetylsalicylic acid
Authors: Oussama Khemis , Gabriel Racovițeanu , Elena Vulpașu 
Published: January 2025

The presence of pharmaceutical micropollutants from different families in water has become a serious environmental and human health problem. The treatment processes used to eliminate pharmaceutical pollutants are limited, and only some areeffective in removing certain pharmaceutical substances. Our study focused on reducing the pharmaceutical substance acetylsalicylic acid intended for human consumption at various concentrations (1.6 mg/l, 0.8 mg/l, and 0.4 mg/l organic matter (TOC)). The study was developed on two treatment processes (ozonation process (O3) and adsorption process with granular actif carbon) and two different flow rates (1.25 l/min with an EBCTof 6 min, 2.5 l/min with an EBCT of 3 min) applied in a large-scale drinking water treatment pilot.
The O3/AC process obtained good results at a flow rate of 1.25 l/min (EBCT of 6 min) with total elimination at a concentration of 0.4 mg/L and 98.73% and 99.96% for higher concentrations of 1.6 mg/l and 0.8 mg/l respectively, which means that this processis capable of degrading and removing the pharmaceutical substance acetylsalicylic acid.
Does Improvement of Glycemic Control Cause Acute Charcot Foot in
Patients with Diabetes?
Authors: Svendsen Ole Lander , Jansen Rasmus Bo 
Published: January 2025

AbstractRecent studies have suggested that improved
glycemic control in patients with diabetes may cause acute Charcot foot. To
conduct a narrative review of studies investigating whether improved
glycemic control in patients with diabetes causes acute Charcot
foot.Publications found by searching PubMed, EMBASE, and
Cochrane Library as well as reference lists of identified publications were
reviewed.Very few publications were found, primarily
consisting of case reports and case studies without control groups,
documenting instances where cases of acute Charcot foot had been preceded by
improved glycemic control. Recent large multicenter randomized
placebo-controlled clinical trials of anti-hyperglycemic agents in patients
with diabetes, where significant improvement of glycemic control occurred,
have not reported incidences of acute Charcot foot.There is so far no solid evidence to suggest that
improvement of glycemic control in patients with diabetes causes acute
Charcot foot.
Zwischen Hippokrates und Diensteid: Amtsärztliche Begutachtungen von
(angehenden) Beamten im Spannungsfeld von Recht, Moral und
Rollenverständnis
Authors: Schröder-Bäck Peter , Brixius Kerstin 
Published: January 2025

ZusammenfassungBegutachtungen im Öffentlichen Gesundheitsdienst (ÖGD) finden unter anderem in
der Einstellungs- und Dienstunfähigkeitsbegutachtung von Beamten statt. Hier
entstehen möglicherweise Werte- und Normkonflikte für begutachtende Ärzte, denn
diese müssen Entscheidungen treffen, die nicht unbedingt im Interesse der zu
begutachtenden Person liegen. Wie kann man die Begegnungen zwischen Ärzten und
zu Begutachtenden normativ rekonstruieren und deuten? Juristisch sind die
Erwartungen an begutachtenden Ärzte in der öffentlichen Verwaltung weitgehend
definiert. In der amtsärztlichen Praxis erscheinen trotzdem individuelle
normative Rollenkonflikte, es entstehen Gewissensentscheidungen, ob man sich an
rechtliche Vorgaben hält.
A Novel Fibrinolysis Resistance Capacity Assay Can Detect Fibrinolytic Phenotypes in Trauma Patients
Authors: Barrett Christopher D. , Suzuki Yuko , Moore Ernest E. , Moore Hunter B. , Maginot Elizabeth R. , White Collin M. , Siddiqui Halima , Gawargi Flobater I. , Chandler James G. , Sauaia Angela , Urano Tetsumei 
Published: January 2025

Background To evaluate residual fibrinolysis resistance activity (FRA) in plasma, a detergent-modified plasma clot lysis assay time (dPCLT) was established in which α2-antiplasmin (A2AP) and plasminogen activator inhibitor type 1 (PAI-1) are inactivated without impacting protease activity. We applied this novel assay to severely injured trauma patients’ plasma.
Material and Methods Tissue-type plasminogen activator (tPA)-induced plasma clot lysis assays were conducted after detergents- (dPCLT) or vehicle- (sPCLT) treatment, and time to 50% clot lysis was measured (“transition midpoint”, T m). Residual FRA was then calculated as ([sPCLT T m] - [dPCLT T m]/[sPCLT T m]) x100% = Δ Tm PCLT (%). Assay results were compared to rapid thromboelastography (TEG) LY30, tPA TEG LY30, and plasma fibrinolysis biomarkers in polytrauma patients’ plasma (N=43).
Results Δ Tm PCLT(%) in normal plasma (N=5) was 63.0 ± 8.3 whereas in A2AP-depleted plasma was -19.1 ± 1.3%, Plasmin-antiplasmin (PAP) complex increased after complete lysis of sPCLT, whereas that in dPCLT was negligible in normal plasma. In trauma plasma, significant correlations between Δ Tm PCLT and active PAI-1 (r = 0.85, p<0.0001), PAP complex (r = -0.85, p<0.0001), free A2AP (r = 0.66, p<0.0001), total A2AP levels (r = 0.52, p=0.001) and tPA TEG LY30 (r = -0.85, p<0.0001) were found. dPCLT in hyperfibrinolysis patients diagnosed by tPA TEG was significantly shorter than those with low fibrinolysis [10.2 ± 6.4 minutes versus 20.2 ± 2.1 minutes, p=0.0006].
Conclusion Hyperfibrinolysis after trauma is significantly related to exhaustion of FRA, and our novel assay appears to quickly assess this state and may be a useful clinical diagnostic after additional validation.
Key Points
Structural Conformation and the Binding of Factor VIII R2159C (FVIII-Ise) Mutated in the C1 Domain to Phospholipid
Authors: Mizumachi Kuniyoshi , Takeyama Masahiro , Horiuchi Kaoru , Nogami Keiji 
Published: January 2025

Background We previously identified a factor (F)VIII molecular defect associated with an R2159C mutation in the C1 domain (named “FVIII-Ise”) together with undetectable FVIII antigen (FVIII:Ag) levels measured by two-site sandwich ELISA using an anti-C2 domain alloantibody (alloAb). The patient had clinically mild hemophilia A, and his reduced FVIII:C correlated with FVIII:Ag measured by ELISA using monoclonal antibodies (mAbs) with A2 and A2/B domain epitopes, suggesting that the R2159C mutation modified C2 domain antigenicity.
Aim To investigate functional and structural characteristics of the FVIII-R2159C mutant.
Methods and Results ELISAs using a previous anti-C2 domain alloAb confirmed that the antigen level of recombinant FVIII-R2159C mutant prepared in BHK cells was 56% lower relative to wild-type (WT), consistent with our earlier reports. This anti-C2 domain alloAb competitively inhibited FVIII and anti-C1 domain mAb binding, indicating the involvement of specificity for C1 and C2 epitopes. The K
m for FVIII-R2159C with FIXa or FX in the tenase complex was similar to that of FVIII-WT. Thrombin- and FXa-catalyzed cleavage reactions of FVIII-R2159C were similar to those of WT. The K
d for FVIII-R2159C binding to phospholipids was moderately greater than for FVIII-WT, however, while there were no significant differences in von Willebrand factor binding. In silico molecular dynamic simulation analyses revealed subtle differences between FVIII-WT and FVIII-R2159C.
Conclusion The FVIII-R2159C mutation was not different from FVIII-WT in interactions with FIXa, FX, and thrombin, but reduced binding potential to phospholipids and to an anti-C1/C2 domain alloAb was evident apparently due to subtle changes in conformational structure.
The Comorbidity of Lung Cancer and ILD: A Review
Authors: Uhlenbruch Mark , Polke Markus , von Eiff Damian , Koryllos Aris , Krüger Stefan 
Published: January 2025

AbstractPatients with interstitial lung disease (ILD) and especially with idiopathic pulmonary fibrosis(IPF) suffer from reduced survival expectation and risk of exacerbations. Lung cancer is a relevant comorbidity in ILD patients and associated with impaired survival.The most frequent ILD among patients with NSCLC (Non-small cell lung cancer) is idiopathic pulmonary fibrosis (IPF), which is associated with an greater decline in lung function and a higher risk of death.The prevalence of lung cancer in patients with ILD is up to 10% and in autopsy studies a prevalence up to 48% has been found.There are no guidelines for patients with lung cancer and ILD. Moreover, no adequate evidence is available.Therefore, we reviewed currently available literature to present an overview of the state of the art.In this review we focus on staging and treatment of the comorbidity of lung cancer and ILD.
Do Variations in Frontal Recess Anatomy Predispose to Mucocele Formation?
Authors: Varghese Lalee , Bright Rakesh R. , Gunturi Aditya V. A. , Rebekah Grace , Kurien Regi 
Published: January 2025

Abstract
Introduction Mucoceles are benign expansile cystic lesions commonly seen in the frontoethmoidal region.
Objective To see if the distribution of frontal air cells predisposes to mucocele formation.
Methods Retrospective review of all cases of paranasal sinus mucocele from 2011 to 2021. Data on demographics, history of surgery or trauma, clinical features, radiological findings, and outcome were collected and analyzed.
Results Of the 28 cases, 19 (67.9%) were male and 9 (32.1%), female, with a mean age of 40.75 years. Mucocele was unilateral in 26 (92.9%) patients. Twenty patients (71.43%) presented with primary mucocele. The distribution of mucocele was frontal and frontoethmoidal in 8 (28.6%) patients each, maxillary in 6 (21.4%), and ethmoid and sphenoid sinus in 3 (10.7%) patients each. Sixteen (57.1%) patients had frontal sinus involvement. At presentation, 13 (46.4%) patients had nasal symptoms, 17 (60.7%) had orbital symptoms, while 16 (57.1%) had headache. Pain (12; 70.59%) was the predominant orbital symptom, followed by proptosis and diplopia (8; 47.06%). The most common sites of bony erosions were along the frontal sinus floor (14; 50%), followed by lamina papyracea (13; 46.43%), and frontal sinus anterior wall (10; 35.71%). The agger nasi and suprabullar cells were the most common frontal cells encountered in mucoceles involving the frontal sinus, with no significant difference in frontal cell distribution between involved and uninvolved sides. The frontal cell distribution was similar in mucoceles with and without frontal sinus involvement too.
Conclusion Though frontal and frontoethmoidal mucoceles were the most encountered, the type and distribution of frontal cells did not predispose to mucocele formation.
Evaluation of the Nijmegen Cochlear Implant Questionnaire in Danish
Authors: Neumann Charlotte Skov , Schmidt Jesper Hvass 
Published: January 2025

Abstract
Introduction The Nijmegen cochlear implant questionnaire (NCIQ) is a quantifiable self-assessment health-related quality of life (HRQoL) tool used internationally to determine quality of life (QoL) in cochlear implant (CI) users and to evaluate the implant's subjective benefits.
Objective This study aimed to validate the Danish version of the questionnaire (DA-NCIQ) with a test–retest including 60 participants (30 CI users and 30 CI candidates).
Methods The intraclass correlation coefficients (ICC) were calculated to evaluate the temporal stability of the participants' answers and the internal consistency of the questionnaire domains was determined using the Cronbach alpha in order to compare these results with the NCIQ's other language versions.
Results The DA-NCIQ was found to have Cronbach alpha coefficients between 0.7 and 0.91, as well as test–retest reliability with ICC values between 0.7 and 0.92. These findings were similar to the original and other language versions of this questionnaire. The Cronbach alpha coefficients varied between 0.73 and 0.89, while the ICC test–retest reliability varied between 0.64 and 0.85. Furthermore, the present study found that participants with CIs had an improved HRQoL in all subdomains, except for the advanced sound perception one, when compared to the CI candidates.
Conclusion The results supported the DA-NCIQ as a reliable instrument to measure the subjective benefits of CIs in postlingually deafened/hearing-impaired adults.
Plasmatic Levels of Cytokines and Quality of Life among Elderly Individuals with Dizziness
Authors: Moreira Gislaine da Silva , Marchiori Luciana Lozza de Moraes , Ciquinato Daiane Soares de Almeida , Marchiori Glória de Moraes , Okamura Licia Sayuri Tanaka , Branco Braulio Henrique Magnani , Poli-Frederico Regina Célia 
Published: January 2025

Abstract
Introduction Few studies have investigated the relationship between cytokines and dizziness in elderly individuals.
Objective To assess the levels of inflammatory biomarkers and their relationship with quality of life (QoL) among elderly individuals with dizziness.
Methods We conducted a cross-sectional study with 103 participants (90 women and 13 men) who were assessed through the Visual Analogue Scale (VAS) and the Dizziness Handicap Inventory (DHI). The plasma levels of cytokines were measured through the cytometric bead array (CBA) method. Cross-tabulations with the Chi-squared test were used to verify sample homogeneity, and parametric tests were used to analyze the data.
Results Out of the total sample of 103 individuals, dizziness was reported by 40 women and 5 men. A difference between the groups with and without dizziness was observed regarding the levels of interleukin 4 (IL-4; p = 0.011): the group without dizziness presented a higher mean level (2.1 ± 2.8 pg/mL) when compared to the group that presented dizziness (1.0 ± 1.7 pg/mL). Another difference was found between the DHI classifications and the plasma levels of tumor necrosis factor alpha (TNF-α;) p = 0.015): the groups without any losses in QoL presented lower TNF-α levels (1.4 pg/mL) compared to the group that presented moderate QoL loss (6.3 pg/mL).
Conclusion Dizziness affects the functional, physical and emotional dimensions of QoL and plays a role in the decrease in the levels of IL-4 and in the presence of fullness and tinnitus. Higher VAS scores are related to dizziness in the elderly. Moreover, the increased levels of TNF-α were associated to light-to-moderate losses in QoL among elderly patients with dizziness.
The Good and Bad of Regionalizing Colon Cancer Care
Authors: Schaefer Sara L. , Harbaugh Calista M. 
Published: January 2025

AbstractHospitals in the United States continue to merge into expanding hospital networks. As the U.S. health care landscape rapidly evolves toward regionalized hospital networks, there is a critical opportunity for these networks to fulfill their clinical potential toward coordination of care, particularly for cancer patients. While regionalization aims broadly to improve care by distributing services optimally, centralization remains the dominant approach. This article explores regionalization and centralization specific to colon cancer care. We examine the benefits and drawbacks of centralization of colon cancer surgery as a strategy to enhance patient outcomes and access to care. Additional methods for optimizing regional care delivery also exist. In this article, we also present additional strategies for improving regional care delivery and clinical integration for colon cancer patients.