bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocytic aerobic glycolysis provides lactate to support neuronal oxidative metabolism in the hippocampus
Authors: Dias Cândida , Fernandes Eliana , Barbosa Rui M. , Laranjinha João , Ledo Ana 
Published: April 2023

AbstractUnder physiological conditions, the energetic demand of the brain is met by glucose oxidation. However, ample evidence suggests that lactate produced by astrocytes through aerobic glycolysis may also be an oxidative fuel, highlighting the metabolic compartmentalization between neural cells. Herein, we investigate the roles of glucose and lactate in oxidative metabolism in hippocampal slices, a model that preserves neuron–glia interactions. To this purpose, we used high‐resolution respirometry to measure oxygen consumption (O2 flux) at the whole tissue level and amperometric lactate microbiosensors to evaluate the concentration dynamics of extracellular lactate. We found that lactate is produced from glucose and transported to the extracellular space by neural cells in hippocampal tissue. Under resting conditions, endogenous lactate was used by neurons to support oxidative metabolism, which was boosted by exogenously added lactate even in the presence of excess glucose. Depolarization of hippocampal tissue with high K+ significantly increased the rate of oxidative phosphorylation, which was accompanied by a transient decrease in extracellular lactate concentration. Both effects were reverted by inhibition of the neuronal lactate transporter, monocarboxylate transporters 2 (MCT2), supporting the concept of an inward flux of lactate to neurons to fuel oxidative metabolism. We conclude that astrocytes are the main source of extracellular lactate which is used by neurons to fuel oxidative metabolism, both under resting and stimulated conditions.
Validated liquid chromatography with tandem mass spectrometry method for determination of paxalisib in mouse plasma: An application to pharmacokinetic study in mice
Authors: A. B. Vinod , Das Arunava 
Published: April 2023

AbstractA sensitive and rapid LC–MS/MS method has been developed and validated for the quantification of paxalisib in mouse plasma. A liquid–liquid extraction method was used for the extraction of paxalisib and filgotinib (internal standard, IS) from mouse plasma. A clean chromatographic separation of paxalisib and the IS was achieved on an Atlantis dC18 column using an isocratic mobile phase (10 mM ammonium formate and acetonitrile, 30:70%, v/v) delivered at a flow rate of 0.7 mL/min. The total run time was 2.5 min. Paxalisib and filgotinib were eluted at 1.21 and 0.94 min, respectively. The MS/MS transitions monitored were m/z 383.25 → 309.20 and 426.30 → 291.20 for paxalisib and filgotinib, respectively. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. The method was proved to be accurate and precise at a linearity range of 1.39–2287 ng/mL. The intra‐ and inter‐day precisions for paxalisib in mouse plasma were in the ranges 1.42–9.61 and 4.70–9.63%, respectively. Paxalisib was stable under a series of stability conditions. Post‐oral administration to mice, paxalisib maximum plasma concentrations were attained at 2.0 h. Paxalisib’s half‐life ranged between 3.2 and 4.2 h. Paxalisib exhibited low clearance and moderate volume of distribution. Oral bioavailability was 71%.
Development and validation of a simple HPLC‐MS/MS method for the quantification of methylmalonic acid in human serum without a derivatization step
Authors: Hofmann Sabrina , Gebauer Julian , Krnáč Dušan , Prantz Anja , Reiffová Katarína , Rolinski Boris , Serbin Rastislav 
Published: April 2023

AbstractA simple and rapid HPLC‐MS/MS analytical method was developed and validated for the determination of methylmalonic acid (MMA) in human serum without a derivatization step. Serum samples (200 μl) were pretreated using a simple method based on ultrafiltration using a VIVASPIN 500 ultrafiltration column. Chromatographic separation was achieved on a Luna Omega C18 column with a PS C18 precolumn guard by gradient elution using 0.1% (v/v) formic acid in water (mobile phase A) and 0.5% (v/v) formic acid in acetonitrile (mobile phase B) at a flow rate of 0.2 ml min−1. The total run time of the analysis was 4.5 min. Negative electrospray ionization and multiple reaction monitoring mode were used. The lower limit of detection and lower limit of quantification for MMA were determined to be 13.6 and 42.3 nmol L−1, respectively. The developed method enabled the quantification of MMA in a wide linear range of 42.3–4230 nmol L−1 with a correlation coefficient of 0.9991.
The digital expression profile of BMP7, CDKN2C, HIST1H3G, and PKMYT1 genes improves high‐grade cervical lesion detection in liquid‐based cytology
Authors: Causin Rhafaela Lima , Sussuchi da Silva Luciane , Leal Leticia Ferro , Possati‐Resende Júlio César , Evangelista Adriane Feijó , Matsushita Graziela Macedo , Scapulatempo‐Neto Cristovam , Tavares Guerreiro Fregnani José Humberto , Antônio de Oliveira Marco , Musselwhite Laura W. , Chiquitelli Marques Márcia Maria , Reis Rui Manuel 
Published: April 2023

AbstractBackgroundSome studies reported that differential gene expression could be used as a biomarker for high‐grade cervical lesion identification. The aim was to evaluate the gene expression profile of cervical intraepithelial neoplasia (CIN) to identify a gene expression signature of CIN2+ in liquid‐based cytology (LBC) samples.MethodsLBC samples (n = 85) obtained from women who underwent colposcopy were included with benign (n = 13), CIN1 (n = 26), CIN2 (n = 16), and CIN3 (n = 30) diagnoses. After RNA isolation, gene expression profiling was performed using the nCounter PanCancer Pathways, which consists of 730 cancer‐related genes. The genes identified were in silico expression evaluated using the UALCAN database. An accurate prediction model to discriminate CIN2+ from <CIN2 lesions was determined. Immunohistochemistry was performed to assess the expression of p16 and Ki67 proteins.ResultsThis study identified a gene expression profile that significantly differentiates CIN2+ cases from <CIN2. The gene signature comprised 18 genes, two genes downregulated and 16 upregulated. In silico analysis corroborated the differential expression of 11 of those genes. Further observed was that high expression of BMP7 (odds ratio [OR], 4.202), CDKN2C (OR, 5.326), HIST1H3G (OR, 3.522), PKMYT1 (OR, 4.247), and menarche age (OR, 1.608) were age‐adjusted and associated with CIN2+. This model demonstrates a probability of 43% leading to an area under the curve (of .979; sensitivity of 94.9%, and specificity of 91.2% for CIN2+ prediction. It was observed that p16 expression was significantly associated with CDKN2A mRNA overexpression (p = .0015).ConclusionA gene expression profile that may be helpful in the identification of patients with CIN2+ was identified. This approach could be used together with currently used LBC in a clinical setting, allowing the identification of patients with high risk of CIN2+.
Comprehensive epithelial biomarker analysis of malignant mesothelioma: EpCAM positivity is a potential diagnostic pitfall
Authors: Zhu Yili , Moore Simone , Wang Aihui , George Elizabeth , Allard Grace M. , Libert Diane M. , Lowe Alarice C. 
Published: April 2023

AbstractBackgroundEpithelial cell adhesion molecule (EpCAM) is frequently used to distinguish carcinoma from background mesothelial cells during cytologic examination of body cavity fluids. Previously, the authors identified one malignant mesothelioma case with strong and diffuse membranous EpCAM staining, making it indistinguishable from carcinoma.MethodsIn this study, the authors evaluated all available effusion specimens from patients with malignant mesothelioma, including the above‐mentioned index case, obtained at Stanford Health Care, from 2011 to 2021 (N = 17) as well as control cases (N = 5). Analyses included an immunohistochemistry (IHC) assay for EpCAM and claudin‐4, a multiplexed immunofluorescent (IF) assay for EpCAM, and an RNA in situ hybridization assay targeting EpCAM.ResultsThe authors detected EpCAM positivity of variable intensity and percentage in four malignant mesothelioma cases (23.5%; although only two showed positivity for the epithelial‐specific IHC marker MOC31 in ≥40% of cells) and claudin‐4 negativity in all cases, with two cases displaying focal and weak claudin‐4 staining in <1% of cells. Multiplexed IF staining on the cases with EpCAM IHC positivity showed strong, membranous EpCAM staining in one of four cases. RNA in situ hybridization also was used to assess the correlation between EpCAM positivity by IHC/IF and RNA expression levels. Strong EpCAM RNA expression was detected in the three malignant mesothelioma cases.ConclusionsThe current findings revealed that a subset of epithelioid malignant mesothelioma cases mimic or exhibit the immunophenotypic features of carcinoma when evaluating for EpCAM only. Additional biomarker testing, such as claudin‐4, may help avoid this potential pitfall to yield accurate diagnoses.
Two mechanisms of retinal photoreceptor plasticity underlie rapid adaptation to novel light environments
Authors: Bolstad Kennedy , Novales Flamarique Iñigo 
Published: April 2023

AbstractFishes experience different light environments over short time periods that may require quick modulation of photoreceptor properties to optimize visual function. Previous research has shown that the relative expression of different visual pigment protein (opsin) transcripts can change within several days following exposure to new light environments, but whether such changes are mirrored by analogous modulation in opsin protein expression is unknown. Here, Atlantic halibut larvae and juveniles raised under white light were exposed to blue light for 1 week and their retina compared to that of controls, which remained under white light. Blue light‐treated larvae showed increased expression of all cone opsin transcripts, except rh2, over controls. They also had longer outer segments, and higher density of long wavelength sensitive (L) cones in the dorsal retina. In contrast, only the lws transcript was upregulated in juveniles exposed to blue light compared to controls but their L cone density was greater throughout the retina. These results demonstrate two mechanisms of rapid photoreceptor plasticity as a function of developmental stage associated with improved perception of achromatic or chromatic contrasts in line with the animal's ecological needs.
Distribution of the transcription factor islet‐1 in the central nervous system of nonteleost actinopterygian fish: Relationship with cholinergic and catecholaminergic systems
Authors: Lozano Daniel , Moreno Nerea , Jiménez Sara , Chinarro Adrián , Morona Ruth , López Jesús M. 
Published: April 2023

AbstractIslet‐1 (Isl1) is one of the most conserved transcription factors in the evolution of vertebrates, due to its continuing involvement in such important functions as the differentiation of motoneurons, among other essential roles in cell fate in the forebrain. Although its functions are thought to be similar in all vertebrates, the knowledge about the conservation of its expression pattern in the central nervous system goes as far as teleosts, leaving the basal groups of actinopterygian fishes overlooked, despite their important phylogenetic position. In order to assess the extent of its conservation among vertebrates, we studied its expression pattern in the central nervous system of selected nonteleost actinopterygian fishes. By means of immunohistochemical techniques, we analyzed the Isl1 expression in the brain, spinal cord, and sensory ganglia of the cranial nerves of young adult specimens of the cladistian species Polypterus senegalus and Erpetoichthys calabaricus, the chondrostean Acipenser ruthenus, and the holostean Lepisosteus oculatus. We also detected the presence of the transcription factor Orthopedia and the enzymes tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) to better locate all the immunoreactive structures in the different brain areas and to reveal the possible coexpression with Isl1. Numerous conserved features in the expression pattern of Isl1 were observed in these groups of fishes, such as populations of cells in the subpallial nuclei, preoptic area, subparaventricular and tuberal hypothalamic regions, prethalamus, epiphysis, cranial motor nuclei and sensory ganglia of the cranial nerves, and the ventral horn of the spinal cord. Double labeling of TH and Isl1 was observed in cells of the preoptic area, the subparaventricular and tuberal hypothalamic regions, and the prethalamus, while virtually all motoneurons in the hindbrain and the spinal cord coexpressed ChAT and Isl1. Altogether, these results show the high degree of conservation of the expression pattern of the transcription factor Isl1, not only among fish, but in the subsequent evolution of vertebrates.
A new finite element with variable Young's modulus
Authors: Mazur Katarzyna , Krawczuk Marek , Dąbrowski Leszek 
Published: April 2023

AbstractThe Finite Element Method (FEM) is a numerical technique that is well‐established in the field of engineering. However, in biological sciences, it is just taking its first steps. Bone tissue is an example of biological material which is exposed to high loads in its natural environment. Practically every movement of the body results in changing stress levels in the bone. Nature copes with this very well but when human intervention is necessary (e.g., endoprostheses implants) bone strength has to be determined based on experience since bone tissue has a very heterogeneous structure. The goal of this paper is to demonstrate how standard FEM calculations may be readily modified to provide for variable material properties of such materials as, for example, bone or wood.
First‐line cetuximab + platinum‐based therapy for recurrent/metastatic head and neck squamous cell carcinoma: A real‐world observational study—ENCORE
Authors: Le Tourneau Christophe , Ghiani Massimo , Cau Maria Chiara , Depenni Roberta , Ronzino Graziana , Bonomo Pierluigi , Montesarchio Vincenzo , Leo Luigi , Schulten Jeltje , Salmio Satu , Messinger Diethelm , Sbrana Andrea , Borcoman Edith , Ghi Maria Grazia 
Published: April 2023

AbstractBackgroundENCORE, an observational, prospective, open‐label study, investigated real‐world treatment practices and outcomes with cetuximab plus platinum‐based therapy (PBT) in first‐line (1L) recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).AimsThis multinational study aimed to investigate the long‐term use of cetuximab plus PBT for 1L R/M SCCHN in a clinical setting. In particular, this study aimed to explore clinical considerations such as the decision to prescribe cetuximab plus PBT in R/M SCCHN, the mode and duration of treatment, and patient outcomes.Methods and ResultsPreviously untreated patients with R/M SCCHN whose planned treatment was cetuximab plus PBT were enrolled from 6 countries. Among 221 evaluable patients, planned treatments included cetuximab plus carboplatin (31.2%), cisplatin plus 5‐fluorouracil (31.7%), or carboplatin plus 5‐fluorouracil (23.1%); 3.2% included a taxane, and 45.2% did not include 5‐fluorouracil. Cetuximab treatment was planned for a fixed duration (≤24 weeks) in 15 patients (6.8%) and until disease progression in 206 (93.2%). Median progression‐free survival and overall survival were 6.5 and 10.8 months, respectively. Grade ≥3 adverse events occurred in 39.8% of patients. Serious adverse events occurred in 25.8% of patients; 5.4% were cetuximab‐related.ConclusionIn patients with R/M SCCHN, first‐line cetuximab plus PBT was feasible and modifiable in a real‐world setting with similar toxicity and efficacy as in the pivotal phase III EXTREME trial. Clinical trial registration number: EMR 062202‐566.
Translating corporate social responsibility into financial performance: Exploring roles of work engagement and strategic coherence
Authors: Kim Byung‐Jik , Chang Youngkyun , Kim Tae‐Hyun 
Published: April 2023

AbstractThis study examines how and why corporate social responsibility (CSR) contributes to firms' financial performance. In particular, we investigate the work engagement of employees as a mediator of CSR and firm's financial performance, as well as the moderating role of strategic coherence. With a three‐wave longitudinal survey data of 3343 organizational members from 518 branches and performance records from one of the largest commercial banks, we have found that employees' work engagement mediates the CSR‐financial performance relationship, and strategic coherence, as captured by customer‐ or competitor‐oriented strategy, differentially moderates the mediated relationship. Specifically, the customer‐oriented strategy strengthens the positive influence of CSR on work engagement and subsequent financial performance, whereas the competitor‐oriented strategy weakens the same. Our findings suggest that organizations can maximize financial returns from CSR through employees' work engagement only when CSR, as a non‐market strategy, aligns with the firm's market strategy.
Effects of new anti‐doping measures on sports performance in elite female athletes
Authors: Bezuglov Eduard , Talibov Oleg , Lazarev Artemii , Waśkiewicz Zbigniew , Iljukov Sergei 
Published: April 2023

AbstractStudies examining the effects of new anti‐doping measures on sports performance in elite athletes are scarce. During the last decade, a number of new anti‐doping methods for the detection of anabolic androgenic steroids were developed. We hypothesized that the implementation of these methods may cause a decrease of performance in athletic disciplines where given substances are widely used. For this purpose, the performance results for 10 athletic disciplines from country (Country A), which was widely accused of systematic doping use, were gathered and pooled into the 2012–2015 and 2016–2019 periods. These periods were seen as before and following the implementation periods, where the effects of new anti‐doping methods could be manifested. Also, the performance results of their rival athletes from Country B were analyzed for comparison. The incidence of anti‐doping rule violations for both countries was followed. The analysis revealed a decrease in performance results of Country A athletes in eight of 10 disciplines. The performance results of Country B's athletes in seven of 10 disciplines did not and in three disciplines did demonstrate statistically significant change. The decrease in performance of Country A athletes followed a high incidence of steroid detection cases by means of new anti‐doping methods. It is highly likely that the consequent performance decrease is due to the implementation of new anti‐doping methods. The results of the study bring new facts on the effects of new anti‐doping methods implementation and demonstrate following decrease in performance results in population of athletes from the country widely accused of doping use.
Daily ovarian hormone exposure and loss of control eating in adolescent girls: A registered report
Authors: Pang Raina D. , Morales Jeremy C. , Smith Kathryn E. , Murray Stuart B. , Dunton Genevieve F. , Mason Tyler B. 
Published: April 2023

AbstractObjectiveThe daily biobehavioral factors that precipitate loss of control eating (LOCE) in adolescent girls are not well known. Ovarian hormone levels are key biological factors associated with the etiology of eating disorders in adolescent girls. Yet, models on how daily ovarian hormone exposure predicts LOCE in adolescent girls are underdeveloped. The goal of this study is to examine the daily patterns and mechanisms of ovarian hormone levels on LOCE across the menstrual cycle in adolescent girls and the mediating roles of food‐related reward anticipation and response inhibition. Ecological momentary assessment (EMA) paired with daily hormonal sampling will be used to examine (1) daily associations between within‐person hormones and LOCE, and (2) the mediating role of within‐person food‐related reward anticipation and response inhibition.MethodsNormally cycling adolescent girls who have reached menarche will provide daily saliva samples for hormone analysis and complete EMA for 35 days. During EMA, girls will report LOCE and will complete task‐based and self‐report measures of food‐related response inhibition and reward anticipation.DiscussionThis work has implications for the development of new real‐world biobehavioral models of LOCE in adolescent girls, which will guide theory improvements and treatment for LOCE. Results will provide preliminary evidence for treatment targets for novel interventions for adolescent girls—for example, a response inhibition intervention.Public SignificanceAdolescent eating disorders are severe mental health conditions, often marked by loss of control eating. Estrogen and progesterone play a role in the development and persistence of loss of control eating. The current study will examine how daily exposure to estrogen and progesterone predicts loss of control eating in adolescent girls and identify possible daily mechanisms linking estrogen and progesterone exposure and loss of control eating.
Physiologically vulnerable or resilient? Tropical birds, global warming, and redistributions
Authors: Monge Otto , Maggini Ivan , Schulze Christian H. , Dullinger Stefan , Fusani Leonida 
Published: April 2023

AbstractTropical species are considered to be more threatened by climate change than those of other world regions. This increased sensitivity to warming is thought to stem from the assumptions of low physiological capacity to withstand temperature fluctuations and already living near their limits of heat tolerance under current climatic conditions. For birds, despite thorough documentation of community‐level rearrangements, such as biotic attrition and elevational shifts, there is no consistent evidence of direct physiological sensitivity to warming. In this review, we provide an integrative outlook into the physiological response of tropical birds to thermal variation and their capacity to cope with warming. In short, evidence from the literature suggests that the assumed physiological sensitivity to warming attributed to tropical biotas does not seem to be a fundamental characteristic of tropical birds. Tropical birds do possess the physiological capacities to deal with fluctuating temperatures, including high‐elevation species, and are prepared to withstand elevated levels of heat, even those living in hot and arid environments. However, there are still many unaddressed points that hinder a more complete understanding of the response of tropical birds to warming, such as cooling capacities when exposed to combined gradients of heat and humidity, the response of montane species to heat, and thermoregulation under increased levels of microclimatic stress in disturbed ecosystems. Further research into how populations and species from different ecological contexts handle warming will increase our understanding of current and future community rearrangements in tropical birds.