bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Metabolic–Epigenetic Mechanism Directs Cell Fate and Therapeutic Sensitivity in Breast Cancer
Authors: Bernard Matthew J. , Goldstein Andrew S. 
Published: February 2024

Abstract
Over the past decade, studies have increasingly shed light on a reciprocal relationship between cellular metabolism and cell fate, meaning that a cell's lineage both drives and is governed by its specific metabolic features. A recent study by Zhang and colleagues, published in Cell Metabolism, describes a novel metabolic–epigenetic regulatory axis that governs lineage identity in triple-negative breast cancer (TNBC). Among the key findings, the authors demonstrate that the metabolic enzyme pyruvate kinase M2 (PKM2) directly binds to the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the nucleus to silence expression of a set of genes that includes the mitochondrial carnitine transporter SLC16A9. Perturbation of this metabolic–epigenetic regulatory mechanism induces a metabolic shift away from glycolysis and toward fatty acid oxidation. The ensuing influx of carnitine facilitates the deposition of the activating epigenetic mark H3K27Ac onto the promoter of GATA3, driving a committed luminal lineage state. Importantly, this metabolic–epigenetic axis represents a potentially targetable vulnerability for the treatment of TNBC, a subtype that currently lacks effective therapeutic strategies. These findings lend further support for the paradigm shift underlying our understanding of cancer metabolism: that a cellular fuel source functions not only to provide energy but also to direct the epigenetic regulation of cell fate.
Safety Profile and Adverse Event Management for Futibatinib, An Irreversible FGFR1–4 Inhibitor: Pooled Safety Analysis of 469 Patients
Authors: Meric-Bernstam Funda , Hollebecque Antoine , Furuse Junji , Oh Do-Youn , Bridgewater John A. , Shimura Masashi , Anderson Bailey , Hangai Nanae , Wacheck Volker , Goyal Lipika 
Published: February 2024

Abstract

Purpose:
Futibatinib, a covalently-binding inhibitor of fibroblast growth factor receptor (FGFR)1-4 gained approval for the treatment of refractory, advanced intrahepatic cholangiocarcinoma (iCCA) harboring an FGFR2 fusion/other rearrangement. An integrated analysis was performed to evaluate safety and provide guidance on the management of futibatinib-associated adverse events (AEs) in patients with unresectable/metastatic tumors, including iCCA.

Patients and Methods:
Data from three global phase I or II studies of futibatinib (NCT02052778; JapicCTI-142552) were pooled. AEs were graded per NCI CTCAE v4.03, where applicable. Safety was analyzed for patients receiving any futibatinib starting dose (overall population) and in those receiving the approved starting dose of 20 mg once every day.

Results:
In total, 469 patients with one of 33 known tumor types were analyzed, including 318 patients who received futibatinib 20 mg every day. AEs of clinical interest (AECI; any grade/grade ≥3) in the overall population included hyperphosphatemia (82%/19%), nail disorders (27%/1%), hepatic AEs (27%/11%), stomatitis (19%/3%), palmar-plantar erythrodysesthesia syndrome (PPES; 13%/3%), rash (9%/0%), retinal disorders (8%/0%), and cataract (4%/1%). Median time to onset of grade ≥3 AECIs ranged from 9 days (hyperphosphatemia) to 125 days (cataract). Grade ≥3 hyperphosphatemia, hepatic AEs, PPES, and nail disorders resolved to grade ≤2 within a median of 7, 7, 8, and 28 days, respectively. Discontinuations due to treatment-related AEs were rare (2%), and no treatment-related deaths occurred. AE management included phosphate-lowering medication and dose adjustments.

Conclusions:
Futibatinib showed a consistent and manageable safety profile across patients with various tumor types. AECIs were mostly reversible with appropriate clinical management.
Discovery of a Novel Potent EGFR Inhibitor Against EGFR Activating Mutations and On-Target Resistance in NSCLC
Authors: Lee Eun Ji , Oh Seung Yeon , Lee You Won , Kim Ju Young , Kim Min-Je , Kim Tae Ho , Lee Jii Bum , Hong Min Hee , Lim Sun Min , Baum Anke , Woelflingseder Lydia , Engelhardt Harald , Petronczki Mark , Solca Flavio , Yun Mi Ran , Cho Byoung Chul 
Published: February 2024

Abstract

Purpose:
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) serve as the standard first-line therapy for EGFR-mutated non-small cell lung cancer (NSCLC). Despite the sustained clinical benefits achieved through optimal EGFR-TKI treatments, including the third-generation EGFR-TKI osimertinib, resistance inevitably develops. Currently, there are no targeted therapeutic options available postprogression on osimertinib. Here, we assessed the preclinical efficacy of BI-4732, a novel fourth-generation EGFR-TKI, using patient-derived preclinical models reflecting various clinical scenarios.

Experimental Design:
The antitumor activity of BI-4732 was evaluated using Ba/F3 cells and patient-derived cell/organoid/xenograft models with diverse EGFR mutations. Intracranial antitumor activity of BI-4732 was evaluated in a brain-metastasis mouse model.

Results:
We demonstrated the remarkable antitumor efficacy of BI-4732 as a single agent in various patient-derived models with EGFR_C797S-mediated osimertinib resistance. Moreover, BI-4732 exhibited activity comparable to osimertinib in inhibiting EGFR-activating (E19del and L858R) and T790M mutations. In a combination treatment strategy with osimertinib, BI-4732 exhibited a synergistic effect at significantly lower concentrations than those used in monotherapy. Importantly, BI-4732 displayed potent antitumor activity in an intracranial model, with low efflux at the blood–brain barrier.

Conclusions:
Our findings highlight the potential of BI-4732, a selective EGFR-TKI with high blood–brain barrier penetration, targeting a broad range of EGFR mutations, including C797S, warranting clinical development.
Comment on the Article Archaeology, Language, and the Question of Sámi Ethnogenesis
Authors: Piha Minerva , Heikkilä Mikko K. , Häkkinen Jaakko 
Published: February 2024

Abstract
In this response to the article Archaeology, Language, and the Question of Sámi Ethnogenesis by Asgeir Svestad and Bjørnar Olsen (2023), we correct major misunderstandings made by Svestad and Olsen concerning the methodology of historical linguistics and its relation to archaeology. Our comment concerns the following topics: We explain that there cannot be one ethnogenesis that could be approached by different disciplines because different disciplines are independent and meet only momentarily. We also demonstrate that continuity does not disprove migration, nor vice versa, and explain some methods of linguistic substrate studies that the authors have misunderstood. In Svestad and Olsen’s article, there are also some clearly erroneous statements that we correct in our response. In spite of our critical comments, we genuinely encourage multidisciplinary discussion and cooperation because we share the same research interest: to deepen our understanding of the human past.
Towards good practices for research on Acheta domesticus, the house cricket
Authors: Van Peer M. , Berrens S. , Coudron C. , Noyens I. , Verheyen G.R. , Van Miert S. 
Published: February 2024

Abstract
Several alternative approaches have been proposed to address the need for sustainable protein sources within our existing food and feed systems. Insects are regarded as a promising alternative, which has led to increased attention from researchers worldwide. Acheta domesticus, the house cricket, is considered a potential insect species for industrial production and various applications due to its high nutritious value. Since it is expected that A. domesticus and its applications will continue to rise as an important field of study, the standardisation of production techniques are needed. Nowadays, variation in the measurement of parameters and differences in experimental design limit the comparison among studies and, therefore, the ability to build upon existing knowledge. By identifying gaps in current protocols and providing suggestions on rearing practices and reporting, this paper aims to take the first step towards standardisation of the production and characterisation of Acheta domesticus for research purposes. This initiative primarily focusses on research practices evaluating the impact of feed and environmental conditions on the performance of house crickets.
Protocol-Based Standardized Endocrinological Evaluation of Children With Traumatic Brain Injury: A Quality Improvement Initiative
Authors: Bhat Jayalakshmi Narayan , Amato Abbie , Schultz Scott , Gomez Ricardo 
Published: February 2024

Introduction: Traumatic brain injury (TBI) can disrupt the hypothalamo-pituitary axis, causing neuroendocrine dysfunction. As a third of children can develop post-traumatic hypothalamo-pituitary axis dysfunction (HPAD), a longitudinal follow-up is required in children with TBI. Method: The study comprised a pre-quality improvement (QI) phase (baseline phase) and a QI phase (post-intervention phase). Retrospective data were collected on children with TBI at our hospital during the pre-QI phase of the study to estimate the baseline data on HPAD prevalence and pediatric endocrine referral rate. Guidance protocol for standardizing the pediatric endocrine referral, evaluation, and follow-up of children with TBI was implemented. Prospective data were collected to estimate outcome measures (prevalence of HPAD, rate of initial endocrine consultation and outpatient follow-up) and process measures (protocol adherence rate). Result: Twenty-seven children, aged ≤19 years, were admitted with TBI in the pre-QI phase. The median age was 9 years. Motor vehicle accidents predominated. Thirty percent had limited endocrine evaluation, and 4% had transient cranial diabetes insipidus (DI). The QI phase included 8 children. Demographic data were similar to those in the pre-QI phase. Both outcome and process measures increased to 75% from the pre-QI phase following the protocol implementation. Conclusion: A lower prevalence rate of HPAD in the current cohort may be owing to underevaluation and a smaller sample size. The QI initiative incorporating a guidance protocol-based endocrinological approach to children with TBI improved the pediatric endocrinology referral and follow-up rates.
Photos Sculpt the Stories of Youth: Using Photovoice to Holistically Capture the Lived Experiences and Pain of Youth Who Underwent Spinal Fusion Surgery
Authors: Noyek Samantha , Newman Gillian , Jordan Abbie , Birnie Kathryn A. , Noel Melanie 
Published: February 2024

Spinal fusion surgery is one of the most common major surgical procedures in youth. Adolescent idiopathic scoliosis (AIS) is the most frequent reason for corrective spinal fusion. AIS (∼25%–47% of cases) and spinal fusion surgeries are associated with pain, including the development of new onset chronic pain for up to 15% of youth. This research used photovoice approaches to explore the journeys of youth from before, during, and after spinal fusion surgery, to demonstrate their experiences both of and beyond pain. Twenty participants were recruited from a previous study conducted by the senior author’s lab. Participants captured photos/videos in their daily life (Phase 1); collected previously taken photos/videos from before/during/after their surgery (Phase 2); and participated in individual interviews to reflexively discuss the meaning behind photos/videos (Phase 3). Before interviews, a questionnaire was administered to assess pain characteristics. Nineteen girls/women with scoliosis and one boy/man with kyphosis (12–19 years old, M age = 16 years) participated; they identified as white (80%), other (15%), and Southeast Asian (5%). The researchers used a reflexive thematic analysis approach, which generated five themes: (1) body aesthetic versus machine; (2) expectations and anticipation of surgery/outcomes; (3) desire of normalcy and freedom; (4) navigating a hoped-for positive surgery experience; and (5) the journey sculpts identity formation and sense of self. Findings support youth advocacy, underscoring the need to validate youth concerns and inform healthcare professionals of the importance of individualized care. Youth perspectives highlighted opportunities for optimizing surgery/healthcare experiences and the psychosocial impacts of scoliosis on body image and appearance.
Investigating Variations in Medicine Approvals for Attention-Deficit/Hyperactivity Disorder: A Cross-Country Document Analysis Comparing Drug Labeling
Authors: Tanana Laila , Latif Asam , Nishtala Prasad S , Chen Timothy F 
Published: February 2024

Objective: This study aimed to compare the approval of medicines for attention deficit/hyperactivity disorder (ADHD) for pediatric patients across five countries. Method: A document analysis was completed, using the drug labeling for ADHD medicines from five countries; United Kingdom, Australia, New Zealand, Canada and United States (US). Comparisons of available formulations and approval information for ADHD medicine use in pediatric patients were made. Results: The US had the highest number of approved medicines and medicine forms across the studied countries (29 medicine forms for 10 approved medicines). Approved age and dosage variations across countries and missing dosage information were identified in several drug labeling. Conclusions: The discrepancies in approval information in ADHD medicine drug labeling and differing availability of medicine formulations across countries suggest variations in the management of ADHD across countries. The update of drug labeling and further research into reasons for variability and impact on practice are needed.
Metagenomic Analysis Reveals Difference of Gut Microbiota in ADHD
Authors: Wang Ning , Wang Haibin , Bai Yu , Zhao Yilu , Zheng Xiangyu , Gao Xuping , Zhang Zifeng , Yang Li 
Published: February 2024

Objective: Although ADHD is highly heritable, some environmental factors contribute to its development. Given the growing evidence that gut microbiota was involved in psychiatric disorders, we aimed to identify the characteristic composition of the gut microbiota in ADHD. Methods: We recruited 47 medication-naive children and adolescents with ADHD, and 60 healthy controls (HCs). We used shotgun metagenomics to measure the structure of the gut microbiota and analyzed the difference in bacterial taxa between ADHD and HCs. Results: Significant differences were found between the ADHD and HC groups in both alpha diversity indices (Simpson index, p = .025 and Shannon index, p = .049) and beta diversity indices (Euclidean distance, Bray-Curtis distance, and JSD distance, p < 2.2e-16). Nine representative species best explain the difference. Conclusion: Patients with ADHD showed significant differences in the composition of the gut microbiota compared with HCs. These results may help identify potential biomarkers of ADHD.
Real-World Experience of Vitiligo Patients: A Retrospective Chart Review
Authors: Obeng-Asumeng Chelsea , Rodriguez-Bolanos Fabian , Gooderham Melinda 
Published: February 2024

Background: Vitiligo is a common depigmenting skin disorder with an estimated prevalence of 0.5% to 2% worldwide. Objective: We conducted a study to characterize the presentation of vitiligo in community dermatology clinic setting in Ontario, Canada. Methods: A retrospective cross-sectional study was performed through an electronic chart review at a community dermatology clinic with 2 sites in Ontario, Canada. Results: We found a male to female ratio of 1:1.3. The average age at the time of assessment was 40.8 years (ranging from 7 to 75 years). Sixteen percent of the patients were children (less than 18 years of age). Hands were the most common location for vitiligo (55.8%). Conclusions: Our findings are in keeping with previously described epidemiologic data. To our knowledge, this is the first Canadian study looking at the population in a community setting.
Current role of intraoperative cell salvage techniques in the management of renal tumors with level III and IV inferior vena cava thrombus extension
Authors: Surcel Cristian , Dotzauer Robert , Mirvald Cristian , Popa Calin , Olariu Cosmin , Baston Catalin , Harza Mihai , Gangu Constantin , Tsaur Igor , Sinescu Ioanel 
Published: February 2024

Background: En bloc removal of the kidney with tumor thrombus excision in a multidisciplinary team remains the standard treatment for renal cell carcinoma (RCC) with tumor thrombus extension. In order to minimize the hemodynamic impact of the surgical blood loss, intraoperative cell salvage (IOCS) techniques can decrease the need for allogeneic blood and prevent blood transfusion related complications. Objective: In this article, we evaluated the safety of IOCS during radical nephrectomy with inferior vena cava thrombectomy under cardiopulmonary bypass with or without deep hypothermic circulatory arrest. Design and method: In this retrospective comparative multicenter analysis, clinical characteristics of 27 consecutive patients who underwent surgery with or without IOCS between 2012 and 2022 in three referral care units were collected into a database. The need for an allogenic blood transfusion (ABT) was also recorded, defined as any transfusion that occurred either intraoperatively or during the hospital stay. Results: The need for ABT in the cell saver arm was significantly smaller due to the reinfusion of rescued blood ( p < 0.015). In multivariate analysis, no cell saver usage was an independent predictor for complications ⩾3 Clavien 3a [odds ratio (OR) 18.71, 95% CI 1.056–331.703, p = 0.046]. No usage of IOCS was an independent predictor for a lower risk of death (OR 0.277, 95% CI 0.062–0.825, p = 0.024). During follow-up, patients who received salvaged blood did not experience an increased risk for developing local recurrence or distant metastases. Conclusion: Transfusion of autologous blood is safe and can be using during nephrectomy and thrombectomy for advanced RCC.
Treatment patterns and characteristics of patients with migraine: results from a retrospective database study in Japan
Authors: Takizawa Tsubasa , Kitano Takahiro , Iijima Masahiro , Togo Kanae , Yonemoto Naohiro 
Published: February 2024

Abstract
Background
Clinical characteristics and treatment practice of patients with migraine in Japan in real-world setting have not been fully investigated. We conducted a retrospective cohort study using claims database to understand the clinical practice of migraine in recent years and to characterize patients potentially not managed well by current treatment options.

Methods
Our study used data from the large claims database maintained by JMDC Inc. Patients with diagnosis of headache or migraine between January 1, 2018, and July 31, 2022, were defined as the headache cohort, and those with migraine diagnosis and prescription of migraine treatments among the headache cohort were included in the migraine cohort. In the headache cohort, characteristics of medical facilities and status of imaging tests to distinguish secondary headache were examined. Treatment patterns and characteristics of patients potentially not managed well by acute/preventive treatment were described in migraine cohort.

Results
In the headache cohort, 989,514 patients were included with 57.0% females and mean age of 40.3 years; 77.0% patients visited clinics (with ≤ 19 bed capacities) for their primary diagnosis, and 30.3% patients underwent imaging tests (computed tomography and/or magnetic resonance imaging). In the migraine cohort, 165,339 patients were included with 65.0% females and mean age of 38.8 years. In the migraine cohort, 95.6% received acute treatment while 20.8% received preventive treatment. Acetaminophen/non-steroidal anti-inflammatory drugs were most common (54.8%) as the initial prescription for migraine treatment followed by triptan (51.4%). First treatment prescription included preventive treatment in 15.6%, while the proportion increased to 82.2% in the fourth treatment prescription. Among patients with more than 12 months of follow-up, 3.7% had prescription patterns suggestive of risk of medication-overuse headache, and these patients were characterized by a higher percentage of females and a higher prevalence of comorbidities.

Conclusions
This study revealed that approximately one-fifth of the patients with migraine visiting medical facilities use preventive drugs. The presence of potential patients at risk of medication-overuse headache and the role of clinics in migraine treatment were also described.
Offspring of women with hyperemesis gravidarum are more likely to have cardiovascular abnormalities
Authors: Fan Jiao , Yin Minghong 
Published: February 2024

Abstract
Background
Hyperemesis gravidarum (HG) is a severe form of pregnancy-related nausea and vomiting affecting 0.3–2.3% of pregnancies, which can lead to fluid, electrolyte, and acid–base imbalances, nutritional deficiencies, and weight loss, and is usually severe enough to require hospitalization. Abnormally elevated urinary ketones are commonly seen in patients with HG, and ketone bodies are free to pass through the placenta, and maternal hyperketonemia, with or without acidosis, is associated with an increased rate of stillbirth, an increased incidence of congenital anomalies, and impaired neurophysiologic development of the infant. This study investigates the obstetric outcomes of patients with HG and whether HG increases the incidence of cardiovascular disease in the offspring.

Methods
This study included 1020 pregnant women who were hospitalized in our hospital for HG and ultimately delivered in our hospital as well as pregnant women without HG in early gestation and delivered in our hospital from January 2019-January 2020, and we collected and followed up the clinical information of the pregnant women and their offspring.

Results
Pregnant women with HG were more likely to have severe urinary ketones, the rate of early miscarriage and mid-term miscarriage was significantly higher in women with HG compared to pregnant women without HG. Fetal and neonatal head and abdominal circumferences were smaller in HG group than in control group.
Neonatal birth weight and length were also lower in the HG group and cardiovascular anomalies were more likely to occur in the offspring of women with HG when all births were followed up for 3 years.

Conclusions
HG may cause poor obstetric outcomes and was associated with the development of cardiovascular disease in the offspring of women with HG.