bluuebunny/crossref_metadata_2025_split huggingface dataset:
Free carnitine concentrations and biochemical parameters in medium‐chain acyl‐CoA dehydrogenase deficiency: Genotype–phenotype correlation
Authors: Weiss Katharina J. , Berger Ursula , Haider Maliha , Wagner Matias , Märtner E. M. Charlotte , Regenauer‐Vandewiele Stephanie , Lotz‐Havla Amelie , Schuhmann Elfriede , Röschinger Wulf , Maier Esther M. 
Published: February 2023

AbstractBiallelic variants in the ACADM gene cause medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD). This study reports on differences in the occurrence of secondary free carnitine (C0) deficiency and different biochemical phenotypes related to genotype and age in 109 MCADD patients followed‐up at a single tertiary care center during 22 years. C0 deficiency occurred earlier and more frequently in c.985A>G homozygotes (genotype A) compared to c.985A>G compound heterozygotes (genotype B) and individuals carrying variants other than c.985A>G and c.199C>T (genotype D) (median age 4.2 vs. 6.6 years; p < 0.001). No patient carrying c.199C>T (genotype C) developed C0 deficiency. A daily dosage of 20–40 mg/kg carnitine was sufficient to maintain normal C0 concentrations. Compared to genotype A as reference group, octanoylcarnitine (C8) was significantly lower in genotypes B and C, whereas C0 was significantly higher by 8.28 μmol/L in genotype C (p < 0.05). In conclusion, C0 deficiency is mainly found in patients with pathogenic genotypes associated with high concentrations of presumably toxic acylcarnitines, while individuals carrying the variant c.199C>T are spared and show consistently mild biochemical phenotypes into adulthood. Low‐dose carnitine supplementation maintains normal C0 concentrations. However, future studies need to evaluate clinical benefits on acute and chronic manifestations of MCADD.
Large Language Models Demonstrate the Potential of Statistical Learning in Language
Authors: Contreras Kallens Pablo , Kristensen‐McLachlan Ross Deans , Christiansen Morten H. 
Published: February 2023

AbstractTo what degree can language be acquired from linguistic input alone? This question has vexed scholars for millennia and is still a major focus of debate in the cognitive science of language. The complexity of human language has hampered progress because studies of language–especially those involving computational modeling–have only been able to deal with small fragments of our linguistic skills. We suggest that the most recent generation of Large Language Models (LLMs) might finally provide the computational tools to determine empirically how much of the human language ability can be acquired from linguistic experience. LLMs are sophisticated deep learning architectures trained on vast amounts of natural language data, enabling them to perform an impressive range of linguistic tasks. We argue that, despite their clear semantic and pragmatic limitations, LLMs have already demonstrated that human‐like grammatical language can be acquired without the need for a built‐in grammar. Thus, while there is still much to learn about how humans acquire and use language, LLMs provide full‐fledged computational models for cognitive scientists to empirically evaluate just how far statistical learning might take us in explaining the full complexity of human language.
Squash smear and fine needle aspiration features of conventional chordoma
Authors: Gajdzis Pawel , Klijanienko Jerzy , Gajdzis Malgorzata 
Published: February 2023

AbstractChordoma is a rare primary central nervous system tumour of notochordal origin. Proper intraoperative or preoperative diagnosis of this entity is crucial for appropriate surgical management. The most common histopathological subtype is conventional chordoma. Cytological characteristics of this subtype are quite distinctive and the diagnosis can be easily made by cytology. There are two particularly important features that are observed in both squash smear and fine needle aspiration specimens: an abundant myxochondroid stroma and cells with large vacuoles, including physaliferous cells. The main differential diagnosis is conventional chondrosarcoma, but in problematic cases immunohistochemical studies are useful to establish the correct diagnosis.
Multiplex protein analysis and ensemble machine learning methods of fine needle aspirates from prostate cancer patients reveal potential diagnostic signatures associated with tumour grade
Authors: Röbeck Pontus , Franzén Bo , Cantera‐Ahlman Rafaele , Dragomir Anca , Auer Gert , Jorulf Håkan , Jacobsson Sven P. , Viktorsson Kristina , Lewensohn Rolf , Häggman Michael , Ladjevardi Sam 
Published: February 2023

AbstractBackgroundImproved molecular diagnosis is needed in prostate cancer (PC). Fine needle aspiration (FNA) is a minimally invasive biopsy technique, less traumatic compared to core needle biopsy, and could be useful for diagnosis of PC. Molecular biomarkers (BMs) in FNA‐samples can be assessed for prediction, eg of immunotherapy efficacy before treatment as well as at treatment decision time points during disease progression.MethodsIn the present pilot study, the expression levels of 151 BM proteins were analysed by proximity extension assay in FNA‐samples from 16 patients, including benign prostate lesions (n = 3) and cancers (n = 13). An ensemble data analysis strategy was applied using several machine learning models.ResultsTwelve potentially predictive BM proteins correlating with International Society of Urological Pathology grade groups were identified, among them vimentin, tissue factor pathway inhibitor 2, and integrin beta‐5. The validity of the results was supported by network analysis that showed functional associations between most of the identified putative BMs. We also showed that multiple immune checkpoint targets can be assessed (eg PD‐L1, CD137, and Galectin‐9), which may support the selection of immunotherapy in advanced PC. Results are promising but need further validation in a larger cohort.ConclusionsOur pilot study represents a “proof of concept” and shows that multiplex profiling of potential diagnostic and predictive BM proteins is feasible on tumour material obtained by FNA sampling of prostate cancer. Moreover, our results demonstrate that an ensemble data analysis strategy may facilitate the identification of BM signatures in pilot studies when the patient cohort is limited.
Study on crack tip opening angle evolutions during dynamic crack propagation of pipelines
Authors: Zhen Ying , Liu Yuanyuan , Cao Yuguang , Niu Ruiyan 
Published: February 2023

AbstractCrack tip opening angle (CTOA) has been used to describe the arrest toughness of high‐grade pipelines. However, its evolutions and influencing factors during pipeline crack propagation are unclear. In view of this, this paper reproduces the full‐scale test using a numerical simulation method that is proven to be reliable. On this basis, the evolutions of CTOA during the dynamic crack propagation of the pipeline are systematically studied, and the effects on CTOA values are clarified. The results show that the critical CTOA of a pipeline is independent of the design factor, the pressure decompression, and the large change in the crack velocity and is also not sensitive to the pipe strength, pipe wall thickness, and the inertial effect of soil, but only related to the pipe diameter and pipe toughness. The above conclusions have laid a foundation for the subsequent establishment of the arrest control method for natural pipelines based on CTOA.
Experimental and analytical study on key factors of rock breaking under a single indenter
Authors: Wang Peng , Yue Zhongwen , Li Akang , Ren Meng , Gao Dan , Bu Wenyang 
Published: February 2023

AbstractRock breaking under impact load has a wide application prospect in hard‐rock roadway excavation because of its environmental protection and strong rock‐breaking ability, but the key factors affecting the rock‐breaking effect are not clear enough. Based on a percussive penetration experimental system (PHPB) into rock by combining the Hopkinson Pressure Bar and a detachable indenter, the effects of impact velocity, waveform and rock strength on the force‐penetration curves, percussive efficiency, and crushing work ratio are studied by model simplification, experimental analysis, and theoretical verification. The results show that the peak percussive force and percussive depth are linearly related to the impact velocity; the penetrative coefficient and crushing work ratio are decayed exponentially with the increase of the thickness‐width ratio of the specimens; the rectangular wave can significantly improve the penetration efficiency; the newly established shear‐tensile model with a double‐V structure can accurately predict each stage of rock breaking, which is consistent with the experimental results. The conclusions can be used to speed up the project progress in mechanical excavation of hard‐rock roadway.
Evenness of soil organic carbon chemical components changes with tree species richness, composition and functional diversity across forests in China
Authors: Wang Hui , Ding Yi , Zhang Yuguang , Wang Jingxin , Freedman Zachary B. , Liu Pengcheng , Cong Wei , Wang Jian , Zang Runguo , Liu Shirong 
Published: February 2023

AbstractHigher tree species richness generally increases the storage of soil organic carbon (SOC). However, less attention is paid to the influence of varied tree species composition on SOC storage. Recently, the perspectives for the stronger persistence of SOC caused by the higher molecular diversity of organic compounds were proposed. Therefore, the influences of tree species richness and composition on the molecular diversity of SOC need to be explored. In this study, an index of the evenness of diverse SOC chemical components was proposed to represent the potential resistance of SOC to decomposition under disturbances. Six natural forest types were selected encompassing a diversity gradient, ranging from cold temperate to tropical forests. We examined the correlations of tree species richness, composition, and functional diversity, with the evenness of SOC chemical components at a molecular level by 13C nuclear magnetic resonance. Across the range, tree species richness correlated to the evenness of SOC chemical components through tree species composition. The negative correlation of evenness of SOC chemical components with tree species composition, and the positive correlation of evenness of SOC chemical components with tree functional diversity were found. These indicate the larger difference in tree species composition and the lower community functional diversity resulted in the higher heterogeneity of SOC chemical components among the communities. The positive correlation of the evenness of SOC chemical components with the important value of indicator tree species, further revealed the specific tree species contributing to the higher evenness of SOC chemical components in each forest type. Soil fungal and bacterial α‐diversity had effect on the evenness of SOC chemical components. These findings suggest that the indicator tree species conservation might be preferrable to simply increasing tree species richness, for enhancing the potential resistance of SOC to decomposition.
Intersectional reflexivity: Fieldwork experiences of ethnic minority women researchers
Authors: Rodriguez Jenny K. , Ridgway Maranda 
Published: February 2023

AbstractIn this paper, we illustrate the usefulness of intersectional reflexivity as an approach for researchers to reflect on their role with more nuance. This approach highlights the importance of reflexivity accounts engaging in more nuanced reflection that considers how intersecting socially constructed categories of difference are mobilized during research exchanges to negotiate positionality and the resulting instances of researcher privilege and disadvantage. We exemplify the value of intersectional reflexivity by using our own experiences as ethnic minority women researchers in patriarchal settings to show that gendered, racio‐ethnicized, aged, and classed dynamics in interactions and exchanges are not immediately obvious. We argue that a purposeful framework that embeds the intersectional lens into reflexive efforts is needed to understand researcher experiences as riddled with both privilege and disadvantage, where both researchers and participants have power and invoke particular intersectional identities to reposition themselves and each other in their interactions. The paper calls for more attention to the co‐constructed nature of research exchanges to inform the way the researcher's self‐accountability is problematized and reported.
Influence of ultrasound intensities on colour, oxidative stability, and texture of Longissimus lumborum steaks from Nellore cattle
Authors: de Lima Loíse Caroline Santos , Salim Ana Paula Amaral de Alcântara , Trezze Isabelle , Ferreira Micheli da Silva , Monteiro Maria Lucia Guerra , Mano Sérgio Borges , Conte‐Junior Carlos Adam 
Published: February 2023

SummaryThis research aimed to evaluate the influence of different high‐intensity ultrasound (HIU) levels (control: 0; low: 276.36; moderate: 422.67; and high: 747.79 W cm−2) and stored in aerobic conditions for 7 days at 4 ± 1 °C on instrumental colour, metmyoglobin reducing activity (MRA), oxidative stability and texture of Longissimus lumborum (LL) from Nellore (Bos indicus) cattle. HIU moderate level samples exhibited higher (P < 0.05) lipid and protein oxidation, whereas high level showed higher MRA than control, low and moderate level counterparts. An increase (P < 0.05) of hue angle, MRA, lipid, and protein oxidation during refrigerated storage. Overall, the HIU levels did not influence pH, colour, texture, lipid, and protein oxidation, whereas HIU high level (HIU‐HL) improved the MRA contributing to beef colour stability.
Breaking the deadlock: How union and employer tactics affect first contract achievement
Authors: Kallas John , Park Dongwoo , Aleks Rachel 
Published: February 2023

AbstractThe United States labour movement faces a potentially transformative moment, as workers have won breakthrough union organizing victories at various high‐profile, private‐sector employers. While winning an election is essential to establishing collective bargaining, unions then need to secure a first contract with employers to make tangible improvements in working conditions. Drawing on a sample of 126 responses about postcertification collective bargaining, we find that both employer and union tactics have significant impacts on first contract achievement. Employers continue to impede first contract achievement by committing unfair labour practices, but unions can improve their chances of establishing an agreement by utilizing tactics that engage the public.
Higher levels of response on clinical atopic dermatitis severity measures are associated with meaningful improvements in patient‐reported symptom and quality of life measures: Integrated analysis of three Upadacitinib phase 3 trials
Authors: Reich K. , de Bruin‐Weller M. S. , Deleuran M. , Calimlim B. M. , Chen N. , Hu X. , Tenorio A. R. , Silverberg J. I. 
Published: February 2023

AbstractBackgroundIt is not fully understood how different degrees of improvements in atopic dermatitis (AD) clinical outcome measures translate to improvements in patient‐reported outcome (PRO) measures, such as those assessing itch, symptoms, sleep, anxiety, depression, quality of life (QoL), and work productivity.ObjectivesThis post hoc analysis of three clinical studies assessed how more robust improvements in clinical responses are associated with improvements in PROs and QoL.MethodsData from three randomized, double‐blind, placebo‐controlled, phase 3 trials in adults and adolescents with moderate to severe atopic dermatitis (Measure Up 1, Measure Up 2, and AD Up) were included. Patients were randomly assigned (1:1:1) to upadacitinib (15 or 30 mg) or placebo once daily (alone or in combination with topical corticosteroids). The mean percentage improvement from baseline to week 16 and percentage of patients achieving responses at week 16 were summarized by the Eczema Area and Severity Index (EASI) and validated Investigator Global Assessment of Atopic Dermatitis (vIGA‐AD) response level categories.ResultsA total of 2392 patients from the three trials were included in the analysis. Increasingly greater mean percentage improvement and proportion of patients achieving response was observed at higher clinical response levels (i.e., stepwise pattern). Mean percentage improvement and proportion of patients achieving response exceeded 69% and 70% at EASI ≥ 90 and vIGA‐AD 0/1, respectively, for most PROs including Worst Pruritus Numeric Rating Scale, Patient Oriented Eczema Measure, and Dermatology Life Quality Index.ConclusionsGreater degrees of clinical responses are related to more robust improvements across multiple dimensions impacted by AD, including itch, skin pain, sleep, anxiety, depression, and QoL.
Integrated diagnosis of nevi with severely atypical features and impact of second opinions
Authors: Uzundere Ceren , Akay Bengu Nisa , Heper Aylin Okcu , Clark Simon P. , Tschandl Philipp , Kittler Harald 
Published: February 2023

AbstractBackgroundA subset of melanocytic proliferations is difficult to classify by dermatopathology alone and their management is challenging.ObjectiveTo explore the value of correlation with dermatoscopy and to evaluate the utility of second opinions by additional pathologists.MethodsFor this single center retrospective study we collected 122 lesions that were diagnosed as atypical melanocytic proliferations, we reviewed dermatoscopy and asked two experienced pathologists to reassess the slides independently.ResultsFor the binary decision of nevus versus melanoma the diagnostic consensus among external pathologists was only moderate (kappa 0.43; 95% CI 0.25–0.61). If ground truth were defined such that both pathologists had to agree on the diagnosis of melanoma, 13.1% of cases would have been diagnosed as melanoma. If one pathologist were sufficient to call it melanoma 29.5% of cases would have been diagnosed as melanoma. In either case, the presence of dermatoscopic white lines was associated with the diagnosis of melanoma. In lesions with peripheral dots and clods, melanoma was not jointly diagnosed by the two pathologists if the patient was younger than 45 years.ConclusionsA considerable number of atypical melanocytic proliferations may be diagnosed as melanoma if revised by other pathologists. The presence of white lines on dermatoscopy increases the likelihood of revision towards melanoma. Peripheral clods indicate growth but are not a melanoma clue if patients are younger than 45 years.
Unintended impacts of a national antipsychotic reduction initiative among nursing facility residents with and without Alzheimer's disease
Authors: Wastila Linda , Qato Danya M. , Fleming Sean , Johnson Abree , Briesacher Becky , McArdle Patrick F. , Holmes Sarah , Lucas Judith A. , Desai Abhilash , Brandt Nicole , Zarowitz Barbara 
Published: February 2023

AbstractBackgroundIn July 2012, the Centers for Medicare & Medicaid services launched an antipsychotic reduction initiative (ARI) to improve care for nursing facility residents with Alzheimer's disease and related dementias (ADRD). We examined the impact of this policy on antipsychotic and psychotropic medication (PM) utilization and diagnosis patterns in long‐stay nursing facility residents with ADRD and other conditions in which antipsychotics are indicated.MethodsUsing an 80% sample of fee‐for‐service Medicare beneficiaries with Part D, we conducted a retrospective cohort study of nursing facility residents with ADRD, bipolar disorder, psychosis, Parkinson's disease, and residents exempt from the policy due to diagnoses of schizophrenia, Tourette syndrome, and/or Huntington's disease. We used interrupted time‐series analyses to compare changes in diagnoses, antipsychotic use, and PM utilization before (January 1, 2011–June 30, 2012) and after (July 1, 2012–September 30, 2015) ARI implementation.ResultsWe identified 874,487 long‐stay nursing facility residents with a diagnosis of ADRD (n = 358,518), exempt (n = 92,859), bipolar (n = 128,298), psychosis (n = 93,402), and Parkinson's disease (n = 80,211). In all cohorts, antipsychotic use declined prior to the ARI; upon policy implementation, antipsychotic use reductions were sustained throughout the study period, including statistically significant ARI‐associated accelerated declines in all cohorts. PM changes varied by cohort, with ARI‐associated increases in non‐benzodiazepine sedatives and/or muscle relaxants noted in ADRD, psychosis, and Parkinson's cohorts. Although anticonvulsant use increased throughout the study period in all groups, with the exception of the bipolar cohort, these increases were not associated with ARI implementation. Findings are minimally explained by increased post‐ARI membership in the psychosis and Parkinson's cohorts.ConclusionsOur study documents antipsychotic use significantly declined in non‐ADRD clinical and exempt cohorts, where such reductions may not be clinically warranted. Furthermore, ARI‐associated compensatory increases in PMs do not offset these reductions. Changes in PM utilization and diagnostic make‐up of residents using PMs require further investigation to assess the potential for adverse clinical and economic outcomes.
Endonuclease VIII‐like 1 deficiency potentiates nigrostriatal dopaminergic neuron degeneration in a male mouse model of Parkinson's disease
Authors: Chen Yu‐Hsuan , Kuo Yi‐Ying , You Yi‐Qian , Lin Ya‐Tin , Chen Pei‐Chun 
Published: February 2023

AbstractParkinson's disease (PD) is a common movement disorder caused by a characteristic loss of dopaminergic neurons in the substantia nigra and degeneration of dopamine terminals in the dorsal striatum. Previous studies have suggested that oxidative stress‐induced DNA damage may be involved in PD pathogenesis, as steady‐state levels of several types of oxidized nucleobases were shown to be elevated in PD brain tissues. These DNA lesions are normally removed from the genome by base excision repair, which is initiated by DNA glycosylase enzymes such as endonuclease VIII‐like 1 (Neil1). In this study, we show that Neil1 plays an important role in limiting oxidative stress‐induced degeneration of dopaminergic neurons. In particular, Neil1‐deficient male mice exhibited enhanced sensitivity to nigrostriatal degeneration after 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) administration, and Neil1‐deficient animals had higher levels of γH2AX‐marked DNA damage than wild‐type (WT) controls, regardless of treatment status. Moreover, MPTP‐treated Neil1−/− male mice had slightly elevated expression of genes related to the nuclear factor erythroid 2‐related factor 2 (Nrf2)‐dependent antioxidant pathway. Treatment with the Nrf2 activator, monomethyl fumarate, reduced PD‐like behaviors and pathology in Neil1−/− male mice, suggesting that Neil1 is an important defense molecule in an oxidative cellular environment. Taken together, these results suggest that Neil1 DNA glycosylase may play an important role in limiting oxidative stress‐mediated PD pathogenesis.image