bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumorigenesis Driven by BRAFV600E Requires Secondary Mutations that Overcome it’s Feedback Inhibition of RAC1 and Migration
Authors: Gadal Sunyana , Boyer Jacob A. , Roy Simon F. , Outmezguine Noah A. , Sharma Malvika , Li Hongyan , Fan Ning , Chan Eric , Romin Yevgeniy , Barlas Afsar , Chang Qing , Pancholi Priya , Timaul Neilawattie Merna. , Overholtzer Michael , Yaeger Rona , Manova-Todorova Katia , de Stanchina Elisa , Bosenberg Marcus W. , Rosen Neal 
Published: February 2025

Abstract
BRAFV600E mutations occur in 46% of melanomas and drive high levels of ERK activity and ERK-dependent proliferation. However, BRAFV600E is insufficient to drive melanoma in genetically engineered mouse models, and 82% of human benign nevi harbor BRAFV600E mutations. We found that BRAFV600E inhibited mesenchymal migration by causing feedback inhibition of RAC1 activity. ERK pathway inhibition induced RAC1 activation and restored migration and invasion. In cells with BRAFV600E, mutant RAC1 or PTEN inactivation restored RAC1 activity and cell motility. Together, these lesions occurred in 26% of melanomas with BRAFV600E mutations. Thus, although BRAFV600E activation of ERK deregulates cell proliferation, it prevents full malignant transformation by causing feedback inhibition of RAC1. Secondary mutations are, therefore, required for tumorigenesis. One mechanism underlying tumor evolution may be the selection of lesions that rescue the deleterious effects of oncogenic drivers.
ESR1 Y537S and D538G mutations drive resistance to CDK4/6 inhibitors in estrogen receptor-positive breast cancer
Authors: Lin Chang-Ching A. , Chica-Parrado María Rosario , Unni Nisha , Jaeger Ellen , Fang Yisheng V. , Guo Lei , Napolitano Fabiana , Luna Pamela , Harris Michelle , Chao Calvin , Xu Lin , Arteaga Carlos L. , Hanker Ariella B. 
Published: February 2025

Abstract
Purpose: Breast cancers with ESR1 mutations are resistant to antiestrogen therapy. In this study, we aimed to investigate the association of ESR1 mutations with resistance to CDK4/6 inhibitors (CDK4/6i) using real-world data analysis and experimental validation. Patients and Methods: A total of 3,958 patients with estrogen receptor-positive (ER+) metastatic breast cancer with DNA sequencing data were analyzed. Breast tumor DNA and circulating tumor (ct) DNA were sequenced using the Tempus xT tumor assay and Tempus xF liquid biopsy, respectively. Patients were stratified into either treated with CDK4/6i (tumor tissue: 1,070; ctDNA: 1,885) or CDK4/6i naïve (tumor tissue: 750; ctDNA: 253). Engineered MCF7 cells carrying ESR1 Y537S or D538G knock-in mutations were used to study antitumor efficacy of the CDK4/6i palbociclib in vitro and in vivo. Results: In both xF and xT assays, ESR1 mutations were the only somatic alterations significantly more frequent in patients who received CDK4/6i compared to those who did not. Knock-in of ESR1 Y537S or ESR1 D538G in MCF7 cells resulted in upregulation of cell cycle-related gene signatures upon treatment with CDK4/6i ± antiestrogen compared to cells with non-mutant ESR1. MCF7 xenografts harboring ESR1 Y537S and D538G mutations established in nude mice were resistant to palbociclib. Conclusions: We report herein real-world and preclinical evidence that ESR1 mutations, particularly Y537S and D538G, can drive resistance to CDK4/6 inhibitors.
Kallini et al. (2024) do not compare impossible languages with constituency-based ones
Authors: Hunter Tim 
Published: February 2025

Abstract
A central goal of linguistic theory is to find a precise characterization of the notion “possible human language”, in the form of a computational device that is capable of describing all and only the languages that can be acquired by a typically developing human child. The success of recent large language models (LLMs) in NLP applications arguably raises the possibility that LLMs might be computational devices that meet this goal. This would only be the case if, in addition to succeeding in learning human languages, LLMs struggle to learn “impossible” human languages. Kallini et al. (2024) conducted experiments aiming to test this by training GPT-2 on a variety of synthetic languages, and found that it learns some more successfully than others. They present these asymmetries as support for the idea that LLMs’ inductive biases align with what is regarded as “possible” for human languages, but the most significant comparison has a confound that makes this conclusion unwarranted.
Two-stream approximation in radiative transfer: Average Optical Path Length Estimation
Authors: Stamnes Knut , Kindervatter Tim , Li Wei , Chen Nan , Huang Yuping , Hu Yongxiang , Stamnes Snorre , Lu Xiaomei , Hamre Børge , Tanikawa Tomonori , Lee Jennifer , Weimer Carl , Zeng Xubin , Gatebe Charles K. , Stamnes Jakob J. 
Published: February 2025

Abstract
A general solution based on the two-stream approximation (TSA) to the radiative transfer equation is provided in plane-parallel geometry for an anisotropically scattering slab of arbitrary physical thickness. Conventional two-stream algorithms are used to compute net irradiances and mean radiances, which in turn can be used to estimate heating/cooling rates and photolysis rates. In contrast, our two-stream solution generally applies at arbitrary polar angles, and can be used to estimate average optical path lengths for photons backscattered from a medium such as a cloud, a snowpack, or a vegetation canopy. For a slab consisting of scattering/absorbing particulate matter, the solution is valid for arbitrary values of the optical depth, “observation” polar angle, beam incidence polar angle, single-scattering albedo, backscattering ratio, and slab optical thickness. The upward diffuse radiance is used to estimate the average optical path length for photons reflected from a semi-infinite slab for collimated beam illumination. It is shown that for semi-infinite media, three different two-stream estimates of the average optical path length closely agree with one another. They are also in close agreement with results based on accurate, but computationally more expensive multi-stream radiative transfer simulations. This general TSA solution can be used for spaceborne and airborne lidar measurements of clouds, snowpacks, and vegetation.
SWIFT: A Monotonic, Flux-Form Semi-Lagrangian Tracer Transport Scheme for Flow with Large Courant Numbers
Authors: Bendall Thomas M. , Kent James 
Published: February 2025

Abstract
Local conservation of mass and entropy are becoming increasingly desirable properties for modern numerical weather and climate models. This work presents a Flux-Form Semi-Lagrangian (FFSL) transport scheme, called SWIFT, that facilitates this conservation for tracer variables, whilst maintaining other vital properties such as preservation of a constant, monotonicity and positivity. Importantly, these properties all hold for large Courant numbers and multi-dimensional flow, making the scheme appropriate for use within a dynamical core which takes large time steps. The SWIFT scheme presented here can be seen as an evolution of the FFSL methods of Leonard et al. and Lin and Rood. Two-dimensional and three-dimensional schemes consist of a splitting into a sequence of one-dimensional calculations. The new SWIFT splitting presented here allows monotonic and positivity properties from the one-dimensional calculations to be inherited by the multi-dimensional scheme. These one-dimensional calculations involve separating the mass flux into terms that correspond to integer and fractional parts of the Courant number. Key to achieving conservation is coupling the transport of tracers to the transport of the fluid density, through re-use of the discrete mass flux that was calculated from the fluid density in the transport of the tracers. This work also describes how these properties can still be attained when the tracer is vertically-staggered from the density in a Charney-Phillips grid.
Preventive Effect of Controlled-Release Dexamethasone on Cochlear Ossification in Meningitis Model
Authors: Eravcı Fakih Cihat , Kaplan Ömer , Kılınç Fahriye , Doğan Metin , Arbağ Hamdi , Orhan Miyase 
Published: February 2025

Objective: Despite vaccination and early antibiotic treatment, pneumococcal meningitis remains a disease with significant mortality and morbidity. The resulting inflammatory response can lead to cochlear fibrosis, ossification where cochlear implant surgeries are far challenging. Our study aimed to investigate the preventive effect of controlled-release dexamethasone implant in such cases in terms of structural integrity. Methods: Twenty-four rats were induced with pneumococcal meningitis and randomized into study (n = 16) and control (n = 8) groups. Controlled-release dexamethasone implants were placed transbullarly into the right round window of the study group. Bilateral cochleas underwent histological examination 3 months post-infection. Results: In the study, cochlear effects of pneumococcal meningitis were evaluated. The basal turn was significantly more affected by fibrosis and ossification ( P = .013 and .010, respectively). Compared with control ears, the dexamethasone implant group showed less fibrosis in all turns and less ossification in the basal turn ( P = .014, .003, .044, and .035, respectively). Conclusion: In pneumococcal meningitis, fibrosis and ossification occur more intensively in the basal turn of the cochlea. Controlled-release dexamethasone implants are effective in preventing cochlear ossification and fibrosis. The prevention from the structural damage indicates the potential role of these dexamethasone implants in post-meningitic hearing loss and easing cochlear implant surgeries.
Primary care occupational therapist’s methods of outcome evaluation: Do they align to value-based healthcare?
Authors: Ingham Laura , Cooper Alison , Purcell Catherine 
Published: February 2025

Introduction: Occupational therapy roles are increasing across General Practice in primary care. The evidence base is growing; however, the best way to evaluate outcomes and the impact of practice in this setting remains unclear. Consideration for how methods used align to ambitions of value-based healthcare is also required. This study explored evaluation methods used by occupational therapists, providing services to General Practice in Wales within the context of value-based healthcare. Method: An online focus group was conducted with 13 members of a Welsh Primary Care Occupational Therapy network. Mixed methods were used and Mentimeter results and findings from group discussion were analysed through content and framework analysis. Results: A multifaceted but inconsistent approach to evaluation was reported. Methods used, strengthened by professional core values, broadly aligned practice to shared ambitions of value-based healthcare. The use of validated patient rated scales were most commonly used to evaluate patient experience, whilst cost-effectiveness was least well considered. Conclusion: Further research is required to understand occupational therapy evaluation in this setting to identify what is needed by stakeholders to determine impact and establish value. This could inform care at both an individual level and across populations if consistent data are collected at scale.
Association between headache frequency and risk for fibromyalgia in patients with migraine
Authors: Liao Yen-Hui , Tzeng Yi-Shiang , Chen Shih-Pin , Ling Yu-Hsiang , Chen Wei-Ta , Wang Shuu-Jiun , Wang Yen-Feng 
Published: February 2025

Background The present study aimed to evaluate the risk and impact of fibromyalgia in relation to headache frequency in migraine patients. Methods This cross-sectional study involved migraine patients from a regional hospital and a tertiary medical center. Diagnoses of migraine and fibromyalgia were made according to the International Classification of Headache Disorders, 3rd edition, and the modified 2016 American College of Rheumatology diagnostic criteria, respectively. Clinical data, including Fibromyalgia Symptoms (FS) scale and revised Fibromyalgia Impact Questionnaire (FIQR), were collected systematically by questionnaires-based interviews. Patients were categorized based on monthly headache day (MHD) cut-offs derived from decision tree analysis based on the chi-squared automatic interaction detection algorithm. Results The study involved 2082 migraine patients (1619 female/463 male, mean ± SD age 39.3 ± 12.0 years), including 132 with fibromyalgia (118 female/14 male, mean ± SD age 44.1 ± 12.7 years) (6.3%). Patients were divided into three groups: ≤9 MHDs (n = 924), 10–20 MHDs (n = 745) and ≥21 MHDs (n = 413). The percentage of fibromyalgia increased with headache frequency ( p < 0.001). When compared with patients with ≤9 MHDs (2.8%), those with 10–20 MHDs (6.2%) (odds ratio (OR) = 1.90, 95% confidence interval (CI) = 1.11–3.23, p = 0.019) and ≥21 MHDs (14.5%) (OR = 3.68, 95% CI = 2.08–6.49, p < 0.001) were more likely to have fibromyalgia. Patients with more frequent headaches had higher FS and FIQR scores (all p < 0.001 between MHD categories). Conclusions There was an independent dose–response association between headache frequency and odds, severity, and impact of fibromyalgia in migraine patients. For migraine patients with a higher headache frequency, the potential risk of comorbid fibromyalgia should not be overlooked given its association with more severe clinical manifestations and greater disability.
Clinical Outcomes and Management of Post-varicocelectomy on Male Fertility: A Comprehensive Review
Authors: Hossain Mohammad Akbar 
Published: February 2025

Background Varicocelectomy is one of the main complications that, if left untreated, results in male infertility. Various approaches have been adopted to manage it, but there is a variation in the consensus. Purpose This systematic review aims to summarize the evidence on the various clinical trials and post-varicocelectomy recovery for patients consuming different supplements or regimens. Materials and Methods An organized and systematic literature search was conducted in five electronic databases from their inception till 2021. Upon applying the PICOT format and student inclusion criteria, only n = 13 articles fulfilled the eligibility criteria and were selected for this systematic review. Results A total of 13 studies were included in this systematic review, and different outcomes were measured in all the studies. Generalizing the outcomes measured, they are classified in semen parameters, including sperm count, sperm motility percentage, sperm with standard morphology percentage, semen volume, sperm density, hormonal profile including testosterone (nanograms/liter), follicle-stimulating hormone (international units/liter), luteinizing hormone (international unit/liter), seminal oxidative stress including total antioxidant capacity (mm Trolox equivalent per liter), and pregnancy outcome. Conclusion This systematic review suggests improved sperm count and pregnancy outcomes with pharmacotherapeutic interventions. Oral antioxidants, vitamin C, and vitamin E showed marked improvements in sperm density and reduction in sperm DNA damage. Oral supplements, that is, saffron, were also effective but needed larger, well-conducted randomized clinical trials to validate the findings and estimate the overall impact of these interventions in the post-varicocelectomy period.
Anatomical Study of Nerve Injuries With Minimally Invasive Calcaneus Osteotomies
Authors: Felsberg Maria , Adamik Martha , Schilde Sebastian , Kielstein Heike , Delank Karl-Stefan , Zeh Alexander , Arbab Dariusch , Gutteck Natalia 
Published: February 2025

Background: Calcaneal osteotomy is frequently used in correcting various foot deformities. Minimally invasive procedures such as minimally invasive calcaneus osteotomy (MICO) have become established because of their more favorable risk profile. The literature describes a safe zone for performing the osteotomy to protect the nerve structures. Overall, the existence of a “safe zone” remains controversial. The aim of this anatomical study was to determine the risk of nerve injury in the context of MICO. Methods: Twenty fresh frozen specimens were randomized to a V-shaped and oblique MICO groups. Following the skin incision, the osteotomies were performed with a Shannon burr. The nerve structures were then investigated both medially and laterally. After visualization of the osteotomy plane, standardized distance measurements were taken from the plane to the nerve and injuries were detected. Radiographs were then taken of all specimens, and the safe zone on each was measured and outlined. Results: The evaluation of the safe zone showed that in 17 of 20 cases the osteotomies we performed were located within the safe zone. We found 10 nerve injuries on 8 of 20 specimens. The medial calcaneal nerve was most vulnerable Overall, we found no significant correlation between the frequency of injured nerves and the type of osteotomy ( P  = .361). Conclusion: MICO is a procedure with a low-risk profile. We found that nerve injuries can occur despite compliance with surgical standards and the relative “safe zone” previously described. Other options for protecting the nerve structures and further investigations into the type of osteotomies should be carried out. The clinical relevance of these findings remains to be investigated.
In Vitro Investigation of Microcatheter Behavior During Microsphere Injection in Transarterial Radioembolization
Authors: Snoeijink Tess Josien , van der Hoek Jan Lucas , Mirgolbabaee Hadi , Vlogman Tristan Gerard , Roosen Joey , Nijsen Johannes Frank Wilhelmus , Groot Jebbink Erik 
Published: February 2025

Purpose: To experimentally investigate the behavior of a clinically used microcatheter during transarterial radioembolization (TARE) microsphere injection in a successively bifurcating in vitro model. Materials and Methods: A symmetrical phantom was developed which bifurcated 3 times into 8 outlets. A blood-mimicking fluid was pumped through the phantom using a physiological representative waveform. Holmium-165 microspheres were injected in a pulsed manner at 3 different locations using a standard microcatheter and a rigid counterpart with same dimensions as a control. Motion of the catheter was studied with a top- and side-view camera on the phantom. Microspheres were collected at each outlet and their distribution over the 8 outlets was analyzed. Results: Due to the pulsatile flow in the phantom, strengthened by the pulsatile microsphere injection, the clinical catheter showed maximum displacements of 0.87 mm within a vessel with a diameter of 3.6 mm. This motion resulted in a different microsphere distribution for the clinical catheter compared with the rigid counterpart (75.9% vs 49.4% of the microspheres went to outlet 1–4, respectively). Conclusion: In this in vitro model, the motion of the clinical catheter affected distribution of microspheres. Since the pulsatile administration of microspheres resulted in increased motion of the clinical catheter, standardizing microsphere administration could be beneficial to reduce interprocedural differences in TARE. Clinical Impact Our study demonstrated that microsphere distribution during transarterial radioembolization (TARE) is affected by catheter motion. Furthermore, increased catheter motion was observed as a result of the injection profile. Predictive tools such as the contrast CBCT and scout dose use different injection profiles compared to therapeutic TARE injections, potentially altering catheter tip behaviour and microsphere distribution, which could compromise their predictive values. Additionally, current TARE microsphere injection guidelines provide limited details, which may lead to variability across institutes and interventional radiologists. Standardizing injection techniques could reduce catheter motion variability and may facilitate more consistent and predictable microsphere distribution patterns.
Recurrent isolated sixth cranial nerve palsy as a manifestation of preeclampsia
Authors: Negreanu Daniel , Legault Catherine , El-Messidi Amira , Malhamé Isabelle 
Published: February 2025

Background Isolated sixth nerve palsy is a rare neurologic manifestation of preeclampsia suggesting severity. The purpose of this article is to describe a case of recurrent sixth cranial nerve palsy in the setting of preeclampsia and to highlight its clinical significance, management considerations, and prognosis. Case A 28-year-old woman presented with recurrent left sixth nerve palsy in the setting of preeclampsia at 36 weeks’ gestation. No alternative diagnosis was found in laboratory investigations and cerebral imaging. Symptoms resolved spontaneously within 5 days of delivery. Conclusion A case of recurrent isolated sixth cranial nerve palsy as a manifestation of preeclampsia is described. This rare finding must be recognized by those caring for pregnant individuals.
Machine learning method for damage classification based on acoustic emission waveform analysis in composite lap bar
Authors: Liu Ran , Qiao Shuai , Ye Chao , Liang Yu-jiao , Zhang Peng-fei , Zhou Wei , Li Qing 
Published: February 2025

Carbon fiber reinforced polymer (CFRP), known for their high strength, low density, and excellent corrosion resistance, are widely used in industries such as aerospace, automotive, and wind energy. In recent years, with the growing demand for lightweight solutions in the amusement ride industry, CFRP has gradually been used in non-primary load-bearing components. The lap bar, as a critical component used to secure passengers, has become a primary focus for lightweight design. This paper presents a preliminary study on failure analysis of a composite lap bar using acoustic emission (AE) and machine learning. The main purpose is to analyze the suitability of the prepared composite lap bar in a operational conditions using a classification model. The main challenge, however, is to be able to extract valid descriptors of the damage mechanism from the acquired AE signals. The damage modes of the basic units of the composite lap bar were first characterized individually and information of Hilbert marginal energy spectrum (HMES) about the AE signal associated with each damage mechanism was collected. These spectral features and parameters were then correlated and that is used as a dataset to train the model based on k-nearest neighbor (KNN) algorithm. The model achieved an accuracy of 92% through cross-validation. Then a destructive test was conducted on the composite lap bar, and the failure process was monitored using the AE technique. The acquired AE signals were identified by the classification model. This analysis provides information on the damage process of composite lap bar at different loading stages, with matrix cracking being the more common damage mechanisms. Additionally, the microanalysis of the fracture surface also verified the effectiveness of the classification model. Meanwhile, supervised machine learning shows its potential in handling multi-dimensional data.