bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individual variation in field metabolic rates of wild living fish have phenotypic and ontogenetic underpinnings: insights from stable isotope compositions of otoliths
Authors: Jones Joseph , Hunter Ewan , Hambach Bastian , Wilding Megan , Trueman Clive N. 
Published: June 2023

IntroductionIndividual metabolism has been identified as a key variable for predicting responses of individuals and populations to climate change, particularly for aquatic ectotherms such as fishes. Predictions of organism standard metabolic rate (SMR), and the thermal sensitivity of metabolic rate are typically based on allometric scaling rules and respirometry-based measures of respiratory potential under laboratory conditions. The relevance of laboratory-based measurement and theoretical allometric rules to predict performance of free-ranging animals in complex natural settings has been questioned, but determining time averaged metabolic rate in wild aquatic animals is challenging.MethodsHere we draw on stable isotope compositions of aragonite in fish otoliths to estimate time averaged experienced temperature and expressed field metabolic rate (FMR) simultaneously and retrospectively at an individual level. We apply the otolith FMR proxy to a population of European plaice (Pleuronectes platessa) from the North Sea during a period of rapid warming between the 1980s to the mid-2000s, sampling otolith tissue grown in both juvenile and adult stages.ResultsAmong-individual variations in realized mass-specific FMR were large and independent of temperature and scaled positively with body size in adult life stages, contradicting simplistic assumptions that FMR follows scaling relationships inferred for standard metabolic rates (SMR). In the same individuals, FMR in the first summer of life co-varied positively with temperature.DiscussionWe find strong evidence for the presence of consistent metabolic phenotypes within the sampled population, as FMR in the first year of life was the strongest single predictor for among individual variation in FMR at the point of sampling. Nonetheless, best fitting models explained only 20% of the observed variation, pointing to large among-individual variation in FMR that is unexplained by body mass, temperature or metabolic phenotype. Stable isotope-derived estimates of field metabolic rate have great potential to expand our understanding of ecophysiology in general and especially mechanisms underpinning the relationships between animal performance and changing environmental and ecological conditions.
Identification of a novel candidate HSD3B2 gene variant for familial hypospadias by whole-exome sequencing
Authors: Almaramhy Hamdi Hameed , Abdul Samad Firoz , Al-Harbi Ghadeer , Zaytuni Dimah , Imam Syed Nazar , Masoodi Tariq , Shamsi Monis Bilal 
Published: June 2023

Introduction: Hypospadias [MIM: 300633] is one of the most frequent congenital malformations of male external genitalia. The spectrum of genetic variants causing hypospadias is varied, with studies commonly implicating genes critical in the fetal steroidogenic pathway. This is the first genetic study on hypospadias from the Yemen ethnicity and the second to report HSD3B2 mutations in more than one affected individual from the same family.Material and methods: Surgical hypospadias repair was performed on two hypospadias-affected siblings from a consanguineous family. Whole-exome sequencing (WES) was performed to identify the potential pathogenic variant for hypospadias, which was later confirmed by Sanger sequencing. The identified variant was further analyzed for its pathogenicity by using in silico tools such as SIFT, PolyPhen-2, MutationAssessor, MutationTaster, FATHMM, and ConSurf.Results: We identified a novel missense mutation (Chr1:119964631T&gt;A, c.507T&gt;A, p. N169K) in 3β-hydroxysteroid 2-dehydrogenase (HSD3B2) gene by WES. Sanger sequencing confirmed that the variant segregated the disease in the family between the affected and non-affected individuals. Both patients are homozygous, while parents and two unaffected siblings are heterozygous carriers, indicating an autosomal recessive pattern of inheritance. The in silico analysis by all six in silico tools (SIFT, PolyPhen-2, MutationAssessor, MutationTaster, FATHMM, and ConSurf) predicted the variant to be pathogenic/deleterious.Discussion: An abnormal fetal steroidogenic pathway due to genetic influences may affect the development of the male genital tract, including the urethral tract closure and morphogenesis of male genitalia. Furthermore, the pathogenicity of the observed variant in this study, confirmed by multiple in silico tools, characterizes the influence HSD3B2 gene variants may have in the etiology of hypospadias.Conclusion: Understanding of pathogenic manifestation and inheritance of confounding genetic variants in hypospadias is a matter of great concern, especially in familial cases.
Articulatory speech measures can be related to the severity of multiple sclerosis
Authors: Kieling Maiara Laís Mallmann , Finkelsztejn Alessandro , Konzen Viviana Regina , dos Santos Vanessa Brzoskowski , Ayres Annelise , Klein Iasmin , Rothe-Neves Rui , Olchik Maira Rozenfeld 
Published: June 2023

BackgroundDysarthria is one of the most frequent communication disorders in patients with Multiple Sclerosis (MS), with an estimated prevalence of around 50%. However, it is unclear if there is a relationship between dysarthria and the severity or duration of the disease.ObjectiveDescribe the speech pattern in MS, correlate with clinical data, and compare with controls.MethodsA group of MS patients (n = 73) matched to healthy controls (n = 37) by sex and age. Individuals with neurological and/or systemic conditions that could interfere with speech were excluded. MS group clinical data were obtained through the analysis of medical records. The speech assessment consisted of auditory-perceptual and speech acoustic analysis, from recording the following speech tasks: phonation and breathing (sustained vowel/a/); prosody (sentences with different intonation patterns) and articulation (diadochokinesis; spontaneous speech; diphthong/iu/repeatedly).ResultsIn MS, 72.6% of the individuals presented mild dysarthria, with alterations in speech subsystems: phonation, breathing, resonance, and articulation. In the acoustic analysis, individuals with MS were significantly worse than the control group (CG) in the variables: standard deviation of the fundamental frequency (p = 0.001) and maximum phonation time (p = 0.041). In diadochokinesis, individuals with MS had a lower number of syllables, duration, and phonation time, but larger pauses per seconds, and in spontaneous speech, a high number of pauses were evidenced as compared to CG. Correlations were found between phonation time in spontaneous speech and the Expanded Disability Status Scale (EDSS) (r = − 0.238, p = 0.043) and phonation ratio in spontaneous speech and EDSS (r = −0.265, p = 0.023), which indicates a correlation between the number of pauses during spontaneous speech and the severity of the disease.ConclusionThe speech profile in MS patients was mild dysarthria, with a decline in the phonatory, respiratory, resonant, and articulatory subsystems of speech, respectively, in order of prevalence. The increased number of pauses during speech and lower rates of phonation ratio can reflect the severity of MS.
Application of codon usage and context analysis in genes up- or down-regulated in neurodegeneration and cancer to combat comorbidities
Authors: Khandia Rekha , Pandey Megha Katare , Zaki Magdi E. A. , Al-Hussain Sami A. , Baklanov Igor , Gurjar Pankaj 
Published: June 2023

IntroductionNeurodegeneration and cancer present in comorbidities with inverse effects due to the expression of genes and pathways acting in opposition. Identifying and studying the genes simultaneously up or downregulated during morbidities helps curb both ailments together.MethodsThis study examines four genes. Three of these (Amyloid Beta Precursor Protein (APP), Cyclin D1 (CCND1), and Cyclin E2 (CCNE2) are upregulated, and one protein phosphatase 2 phosphatase activator (PTPA) is simultaneously downregulated in both disorders. We investigated molecular patterns, codon usage, codon usage bias, nucleotide bias in the third codon position, preferred codons, preferred codon pairs, rare codons, and codon context.ResultsParity analysis revealed that T is preferred over A, and G is preferred over C in the third codon position, suggesting composition plays no role in nucleotide bias in both the upregulated and downregulated gene sets and that mutational forces are stronger in upregulated gene sets than in downregulated ones. Transcript length influenced the overall %A composition and codon bias, and the codon AGG exerted the strongest influence on codon usage in both the upregulated and downregulated gene sets. Codons ending in G/C were preferred for 16 amino acids, and glutamic acid-, aspartic acid-, leucine-, valine-, and phenylalanine-initiated codon pairs were preferred in all genes. Codons CTA (Leu), GTA (Val), CAA (Gln), and CGT (Arg) were underrepresented in all examined genes.DiscussionUsing advanced gene editing tools such as CRISPR/Cas or any other gene augmentation technique, these recoded genes may be introduced into the human body to optimize gene expression levels to augment neurodegeneration and cancer therapeutic regimens simultaneously.
Prognostic and predictive values of the grading system of lymph node status in patients with advanced-stage gastric cancer
Authors: Zhang Xue-Mei , Shen Wei-Wei , Song Ling-Jun 
Published: June 2023

BackgroundLymph node metastasis is one of the most important prognostic factors of gastric cancer. However, the effect of germinal centers in lymph nodes on the prognosis of patients with gastric cancer has not been reported. This study aimed to investigate the contribution of germinal center generation to prognostic parameters and clinicopathological significance in gastric cancer.MethodsWe retrospectively reviewed gastric cancer patients who underwent surgery from October 2012 to June 2022. We analyzed 5484 lymph nodes (210 patients) and calculated the lymph node metastasis rate (LNMR) and the proportion of non-metastatic lymph nodes containing three or more germinal centers (NML-GCP).ResultsUsing a grading system that incorporated LNMR and NML-GCP. The tumors were classified into three groups based on this system, which was found to be significantly associated with prognosis. The TNM stage and grading system of lymph node status were independent risk factors for overall survival (OS) and disease-free survival (DFS). The 5-year OS rates for patients with advanced gastric cancer were 85.07% (n=50), 58.34% (n=42), and 24.44% (n=21) for Grades 1, 2, and 3, respectively (p&lt;0.0001). The 5-year DFS rates were 65.32% (n=58), 40.85% (n=51), and 5.88% (n=34), respectively (p&lt;0.0001). Patients with Grade 1 advanced gastric cancer had higher 5-year OS and DFS rates compared to those with Grade 2 or 3 in TNM stage II and III. Furthermore, the 5-year OS and DFS rates differed significantly among patients with different grades of advanced gastric cancer who received chemotherapy (p&lt;0.0001).ConclusionThese findings suggest that the grading system may be valuable for predicting prognosis and guiding clinical management in patients with gastric cancer, and provides good prognostic stratification for OS and DFS in patients with TNM stage II and III.
Impact of microRNA polymorphisms on high-dose methotrexate-related hematological toxicities in pediatric acute lymphoblastic leukemia
Authors: Zhan Min , Liu Ting , Zhang Zhou , Wang Guoqiang , Cao Zhongqiang , Li Xuejuan , Zeng Hongwu , Mai Huirong , Chen Zebin 
Published: June 2023

ObjectivesIt is well known that transporter and enzyme genes could be regulated by microRNA (miRNA) at the post-transcriptional level, and single-nucleotide polymorphisms (SNPs) in miRNA, which are involved in the miRNA production and structure, may impact the miRNA expression level and then influence drug transport and metabolism. In this study, we aim to evaluate the association between miRNA polymorphisms and high-dose methotrexate (HD-MTX) hematological toxicities in Chinese pediatric patients with acute lymphoblastic leukemia (ALL).MethodA total of 181 children with ALL were administered with 654 evaluable cycles of HD-MTX. Their hematological toxicities were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5. The association between 15 candidate SNPs of miRNA and hematological toxicities (leukopenia, anemia, and thrombocytopenia) was analyzed using Fisher's exact test. Further multiple backward logistic regression analysis was used to explore the independent risk factors for grade 3/4 hematological toxicities.ResultRs2114358 G&gt;A in pre-hsa-miR-1206 was related to HD-MTX-related grade 3/4 leukopenia after multiple logistic regression [GA + AA vs. GG: odds ratio (OR): 2.308, 95% CI: 1.219–4.372, P = 0.010], and rs56103835 T &gt; C in pre-hsa-mir-323b was associated with HD-MTX-related grade 3/4 anemia (TT + TC vs. CC: OR: 0.360, 95% CI: 0.239–0.541, P = 0.000); none of the SNPs were significantly associated with grade 3/4 thrombocytopenia. Bioinformatics tools predicted that rs2114358 G&gt;A and rs56103835 T&gt;C would impact the secondary structure of pre-miR-1206 and pre-miR-323b, respectively, and then probably influence the expression level of mature miRNAs and their target genes.ConclusionRs2114358 G&gt;A and rs56103835 T&gt;C polymorphism may potentially influence HD-MTX-related hematological toxicities, which may serve as candidate clinical biomarkers to predict grade 3/4 hematological toxicities in pediatric patients with ALL.
Clinician perception of care at the end of life in a quaternary neonatal intensive care unit
Authors: Imai Lauren , Gray Megan M. , Kim Brennan J. H. , Lyle Allison N. J. , Bock Amber , Weiss Elliott Mark 
Published: June 2023

IntroductionCare for neonates at the end of life (EOL) is often challenging for families and medical teams alike, performed suboptimally, and requires an experienced and compassionate clinician. Much literature exists on adult and pediatric EOL care, but limited studies examine the neonatal process.MethodsWe aimed to describe clinicians' experiences around EOL care in a single quaternary neonatal intensive care unit as we implemented a standard guideline using the Pediatric Intensive Care Unit-Quality of Dying and Death 20 tool.ResultsSurveys were completed by 205 multidisciplinary clinicians over three time periods and included 18 infants at EOL. While most responses were high, a meaningful minority were below goal (&lt;8 on 0–10 scale) for troubling symptom management, conflict between parents and staff, family access to resources, and parent preparation of symptoms. Comparison between Epochs revealed improvement in one symptom management and four communication categories. Satisfaction scores related to education around EOL were better in later Epochs. Neonatal Pain, Agitation, and Sedation Scale scores were low, with few outliers.DiscussionThese findings can guide those aiming to improve processes around neonatal EOL by identifying areas with the greatest challenges (e.g., conflict management) and areas that need further study (e.g., pain management around death).
Propofol inhibits neuroinflammation and metabolic reprogramming in microglia in vitro and in vivo
Authors: Guan Shuyuan , Sun Lingbin , Wang Xihua , Huang Xirui , Luo Tao 
Published: June 2023

Microglial activation-induced neuroinflammation is closely related to the development of sepsis-associated encephalopathy. Accumulating evidence suggests that changes in the metabolic profile of microglia is crucial for their response to inflammation. Propofol is widely used for sedation in mechanically ventilated patients with sepsis. Here, we investigate the effect of propofol on lipopolysaccharide-induced neuroinflammation, neuronal injuries, microglia metabolic reprogramming as well as the underlying molecular mechanisms. The neuroprotective effects of propofol (80 mg/kg) in vivo were measured in the lipopolysaccharide (2 mg/kg)-induced sepsis in mice through behavioral tests, Western blot analysis and immunofluorescent staining. The anti-inflammatory effects of propofol (50 μM) in microglial cell cultures under lipopolysaccharide (10 ng/ml) challenge were examined with Seahorse XF Glycolysis Stress test, ROS assay, Western blot, and immunofluorescent staining. We showed that propofol treatment reduced microglia activation and neuroinflammation, inhibited neuronal apoptosis and improved lipopolysaccharide-induced cognitive dysfunction. Propofol also attenuated lipopolysaccharide-stimulated increases of inducible nitric oxide synthase, nitric oxide, tumor necrosis factor-α, interlukin-1β and COX-2 in cultured BV-2 cells. Propofol-treated microglia showed a remarkable suppression of lipopolysaccharide-induced HIF-1α, PFKFB3, HK2 expression and along with downregulation of the ROS/PI3K/Akt/mTOR signaling pathway. Moreover, propofol attenuated the enhancement of mitochondrial respiration and glycolysis induced by lipopolysaccharide. Together, our data suggest that propofol attenuated inflammatory response by inhibiting metabolic reprogramming, at least in part, through downregulation of the ROS/PI3K/Akt/mTOR/HIF-1α signaling pathway.
Increased plasma renin by vasodilators promotes the progression of abdominal aortic aneurysm
Authors: Liu Yu , Liu Shuai , Zhao Jiani , Wu Kemin , Xu Baohui , Wang Wei 
Published: June 2023

Background: It is well-accepted that antihypertensive therapy is the cornerstone of treatment for abdominal aortic aneurysm (AAA) patients with hypertension. Direct-acting vasodilators were used in the treatment of hypertension by directly relaxing vascular smooth muscle but may have destructive effects on the aortic wall by activating the renin–angiotensin system axis. Their roles in AAA disease remain to be elucidated. In this study, we used hydralazine and minoxidil, two classical direct-acting vasodilators, to investigate their influence and potential mechanisms on AAA disease.Methods and results: In this study, we investigated the plasma renin level and plasma renin activity in AAA patients. Simultaneously, age and gender ratio-matched patients diagnosed with peripheral artery disease and varicose veins were selected as the control group using a ratio of 1:1:1. Our regression analysis suggested both the plasma renin level and plasma renin activity are positively associated with AAA development. In view of the well-established relationship between direct-acting vasodilators and increased plasma renin concentration, we established a porcine pancreatic elastase-infused AAA mouse model, followed by oral administration of hydralazine (250 mg/L) and minoxidil (120 mg/L) to investigate effects of direct-acting vasodilators on AAA disease. Our results suggested both hydralazine and minoxidil promoted the progression of AAA with increased aortic degeneration. Mechanistically, the vasodilators aggravated aortic inflammation by increased leukocyte infiltration and inflammatory cytokine secretion.Conclusion and relevance: The plasma renin level and plasma renin activity are positively associated with AAA development. Direct vasodilators aggravated experimental AAA progression, which raised cautionary concerns about their applications in AAA disease.
Breaking the boundaries: the power of ligatures in visual-word recognition
Authors: Fernández-López María , Perea Manuel , Marcet Ana 
Published: June 2023

IntroductionCurrent neurobiological-inspired models of visual-word recognition propose that letter detectors in the word recognition system can tolerate some variations in the visual form of the letters. However, it is unclear whether this tolerance extends to novel ligatures, which combine two letters into a single glyph.MethodsTo investigate this, the present study utilized a masked priming experiment with a lexical decision task to examine whether primes containing novel ligatures are effective in activating their corresponding base word, relative to omitted-letter primes, in the initial stages of word processing. For each target word (e.g., VIRTUAL), were created an identity prime (virtual), a prime containing a novel ligature of two of the letters (e.g., virtual; “ir” in a single glyph), and an omitted-letter prime where one letter was removed (e.g., vrtual [omitted-vowel] in Experiment 1; vitual [omitted-consonant] in Experiment 2).ResultsResults showed that the presence of a novel ligature in the prime resulted in faster lexical decision times compared to a prime with an omitted vowel (Experiment 1), but not with an omitted consonant (Experiment 2). Furthermore, the performance with the primes containing the novel ligature was not different from that of the identity primes.DiscussionThese results suggest that the word recognition system can quickly enable separate letter detectors for novel ligatures. These findings have important implications for our understanding of the front-end of visual-word recognition.
Self-esteem and professional identity among male nurses and male nursing students: mediating roles of perceived prejudice and psychological distress
Authors: Wu Xiaoqin , You Xu , Pu Jinyuan , Li Junping , Wu Wenzhi , Ma Xiao , Long Qing , Zhang Yunqiao , Zhao Xinling , Guo Zeyi , Cao Xiang , Tu Fangjun , Zeng Yong 
Published: June 2023

IntroductionThere are not enough nurses around the world, and there are even fewer male nurses. It has not been easy for men to become nurses because of stereotypes about the roles of men and women in the workplace, which lead to prejudice and discrimination. This study explored how the self-esteem of male nurses and male nursing students affects their professional identity in an environment where stereotypes and social prejudice exist. This study also examined the differences of relevant variables in different sociodemographic characteristics of the research subjects in a Chinese social context.MethodsBy purposive and snowball sampling, 464 male nurses and male nursing students were surveyed through questionnaires from November 2021 to January 2022. Data analysis was performed using SPSS 25.0 and PROCESS Macro 3.3.ResultsSelf-esteem could indirectly affect professional identity through perceived prejudice and psychological distress. Nonetheless, self-esteem still had a significant direct effect on professional identity. The total mediating effect accounted for 32.816% of the total effect, and the direct effect accounted for 67.184% of the total effect. Also of note was that 81.7% of participants reported experiencing psychological distress.DiscussionTo improve the professional identity of male nurses and male nursing students, nursing educators and administrators should do the following: protect and improve their self-esteem; take steps to reduce social prejudice against them; value their mental health and alleviate their psychological distress.