bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enriched environmental exposure reduces the onset of action of the serotonin norepinephrin reuptake inhibitor venlafaxine through its effect on parvalbumin interneurons plasticity in mice
Authors: Coutens Basile , Lejards Camille , Bouisset Guillaume , Verret Laure , Rampon Claire , Guiard Bruno P. 
Published: June 2023

AbstractMood disorders are associated with hypothalamic-pituitary-adrenal axis overactivity resulting from a decreased inhibitory feedback exerted by the hippocampus on this brain structure. Growing evidence suggests that antidepressants would regulate hippocampal excitatory/inhibitory balance to restore an effective inhibition on this stress axis. While these pharmacological compounds produce beneficial clinical effects, they also have limitations including their long delay of action. Interestingly, non-pharmacological strategies such as environmental enrichment improve therapeutic outcome in depressed patients as in animal models of depression. However, whether exposure to enriched environment also reduces the delay of action of antidepressants remains unknown. We investigated this issue using the corticosterone-induced mouse model of depression, submitted to antidepressant treatment by venlafaxine, alone or in combination with enriched housing. We found that the anxio-depressive phenotype of male mice was improved after only two weeks of venlafaxine treatment when combined with enriched housing, which is six weeks earlier than mice treated with venlafaxine but housed in standard conditions. Furthermore, venlafaxine combined with exposure to enriched environment is associated with a reduction in the number of parvalbumin-positive neurons surrounded by perineuronal nets (PNN) in the mouse hippocampus. We then showed that the presence of PNN in depressed mice prevented their behavioral recovery, while pharmacological degradation of hippocampal PNN accelerated the antidepressant action of venlafaxine. Altogether, our data support the idea that non-pharmacological strategies can shorten the onset of action of antidepressants and further identifies PV interneurons as relevant actors of this effect.
A signal-seeking Phase 2 study of olaparib and durvalumab in advanced solid cancers with homologous recombination repair gene alterations
Authors: Thavaneswaran Subotheni , Kansara Maya , Lin Frank , Espinoza David , Grady John P. , Lee Chee Khoon , Ballinger Mandy L. , Sebastian Lucille , Corpuz Theresa , Qiu Min Ru , Mundra Piyushkumar , Bailey Charles G. , Schmitz Ulf , Simes John , Joshua Anthony M. , Thomas David M. 
Published: June 2023

Abstract
Purpose
To determine the safety and efficacy of PARP plus PD-L1 inhibition (olaparib + durvalumab, O + D) in patients with advanced solid, predominantly rare cancers harbouring homologous recombination repair (HRR) defects.

Patients and methods
In total, 48 patients were treated with O + D, 16 with BRCA1/2 alterations (group 1) and 32 with other select HRR alterations (group 2). Overall, 32 (66%) patients had rare or less common cancers. The primary objective of this single-arm Phase II trial was a progression-free survival rate at 6 months (PFS6). Post hoc exploratory analyses were conducted on archival tumour tissue and serial bloods.

Results
The PFS6 rate was 35% and 38% with durable objective tumour responses (OTR) in 3(19%) and 3(9%) in groups 1 and 2, respectively. Rare cancers achieving an OTR included cholangiocarcinoma, perivascular epithelioid cell (PEComa), neuroendocrine, gallbladder and endometrial cancer. O + D was safe, with five serious adverse events related to the study drug(s) in 3 (6%) patients. A higher proportion of CD38 high B cells in the blood and higher CD40 expression in tumour was prognostic of survival.

Conclusions
O + D demonstrated no new toxicity concerns and yielded a clinically meaningful PFS6 rate and durable OTRs across several cancers with HRR defects, including rare cancers.
Episignature analysis of moderate effects and mosaics
Authors: Oexle Konrad , Zech Michael , Stühn Lara G. , Siegert Sandy , Brunet Theresa , Schmidt Wolfgang M. , Wagner Matias , Schmidt Axel , Engels Hartmut , Tilch Erik , Monestier Olivier , Destrėe Anne , Hanker Britta , Boesch Sylvia , Jech Robert , Berutti Riccardo , Kaiser Frank , Haslinger Bernhard , Haack Tobias B. , Garavaglia Barbara , Krawitz Peter , Winkelmann Juliane , Mirza-Schreiber Nazanin 
Published: June 2023

AbstractDNA methylation classifiers (“episignatures”) help to determine the pathogenicity of variants of uncertain significance (VUS). However, their sensitivity is limited due to their training on unambiguous cases with strong-effect variants so that the classification of variants with reduced effect size or in mosaic state may fail. Moreover, episignature evaluation of mosaics as a function of their degree of mosaicism has not been developed so far. We improved episignatures with respect to three categories. Applying (i) minimum-redundancy-maximum-relevance feature selection we reduced their length by up to one order of magnitude without loss of accuracy. Performing (ii) repeated re-training of a support vector machine classifier by step-wise inclusion of cases in the training set that reached probability scores larger than 0.5, we increased the sensitivity of the episignature-classifiers by 30%. In the newly diagnosed patients we confirmed the association between DNA methylation aberration and age at onset of KMT2B-deficient dystonia. Moreover, we found evidence for allelic series, includingKMT2B-variants with moderate effects and comparatively mild phenotypes such as late-onset focal dystonia. Retrained classifiers also can detect mosaics that previously remained below the 0.5-threshold, as we showed forKMT2D-associated Kabuki syndrome. Conversely, episignature-classifiers are able to revoke erroneous exome calls of mosaicism, as we demonstrated by (iii) comparing presumed mosaic cases with a distribution of artificial in silico-mosaics that represented all the possible variation in degree of mosaicism, variant read sampling and methylation analysis.
Single-cell transcriptomics and epigenomics unravel the role of monocytes in neuroblastoma bone marrow metastasis
Authors: Fetahu Irfete S. , Esser-Skala Wolfgang , Dnyansagar Rohit , Sindelar Samuel , Rifatbegovic Fikret , Bileck Andrea , Skos Lukas , Bozsaky Eva , Lazic Daria , Shaw Lisa , Tötzl Marcus , Tarlungeanu Dora , Bernkopf Marie , Rados Magdalena , Weninger Wolfgang , Tomazou Eleni M. , Bock Christoph , Gerner Christopher , Ladenstein Ruth , Farlik Matthias , Fortelny Nikolaus , Taschner-Mandl Sabine 
Published: June 2023

AbstractMetastasis is the major cause of cancer-related deaths. Neuroblastoma (NB), a childhood tumor has been molecularly defined at the primary cancer site, however, the bone marrow (BM) as the metastatic niche of NB is poorly characterized. Here we perform single-cell transcriptomic and epigenomic profiling of BM aspirates from 11 subjects spanning three major NB subtypes and compare these to five age-matched and metastasis-free BM, followed by in-depth single cell analyses of tissue diversity and cell-cell interactions, as well as functional validation. We show that cellular plasticity of NB tumor cells is conserved upon metastasis and tumor cell type composition is NB subtype-dependent. NB cells signal to the BM microenvironment, rewiring via macrophage mgration inhibitory factor and midkine signaling specifically monocytes, which exhibit M1 and M2 features, are marked by activation of pro- and anti-inflammatory programs, and express tumor-promoting factors, reminiscent of tumor-associated macrophages. The interactions and pathways characterized in our study provide the basis for therapeutic approaches that target tumor-to-microenvironment interactions.
Candida albicans exploits N-acetylglucosamine as a gut signal to establish the balance between commensalism and pathogenesis
Authors: Yang Dandan , Zhang Mao , Su Chang , Dong Bin , Lu Yang 
Published: June 2023

AbstractCandida albicans is a benign member of gut microbiota, but also causes life-threatening disseminated infections, suggesting that this fungus commensalism has evolved with retention of virulence traits. Here we reveal that N-acetylglucosamine (GlcNAc) enables C. albicans to balance between commensalism and pathogenesis. Although GlcNAc catabolism is beneficial for commensal growth of C. albicans, deleting GlcNAc sensor-transducer Ngs1 confers enhanced fitness, indicating that GlcNAc signaling is detrimental to commensalism. Interestingly, addition of GlcNAc attenuates commensal fitness of gut-evolved C. albicans but retains its disease-causing potential. We further demonstrate that GlcNAc is a major inducer of hypha-associated transcription in the gut, which represents the key determinant for commensal-pathogenic equilibrium. In addition to yeast-to-hypha morphogenesis, we also identify other factors, including Sod5 and Ofi1, that contribute to the balance. Thus, C. albicans uses GlcNAc to build up a tradeoff between fungal programs supporting commensalism and virulence, which may explain its success as a commensal and pathogen.
The persistence of cognitive biases in financial decisions across economic groups
Authors: Ruggeri Kai , Ashcroft-Jones Sarah , Abate Romero Landini Giampaolo , Al-Zahli Narjes , Alexander Natalia , Andersen Mathias Houe , Bibilouri Katherine , Busch Katharina , Cafarelli Valentina , Chen Jennifer , Doubravová Barbora , Dugué Tatianna , Durrani Aleena Asfa , Dutra Nicholas , Garcia-Garzon Eduardo , Gomes Christian , Gracheva Aleksandra , Grilc Neža , Gürol Deniz Mısra , Heidenry Zoe , Hu Clara , Krasner Rachel , Levin Romy , Li Justine , Messenger Ashleigh Marie Elizabeth , Miralem Melika , Nilsson Fredrik , Oberschulte Julia Marie , Obi Takashi , Pan Anastasia , Park Sun Young , Pascu Daria Stefania , Pelica Sofia , Pyrkowski Maksymilian , Rabanal Katherinne , Ranc Pika , Mekiš Recek Žiga , Symeonidou Alexandra , Tutuska Olivia Symone , Vdovic Milica , Yuan Qihang , Stock Friederike 
Published: June 2023

AbstractWhile economic inequality continues to rise within countries, efforts to address it have been largely ineffective, particularly those involving behavioral approaches. It is often implied but not tested that choice patterns among low-income individuals may be a factor impeding behavioral interventions aimed at improving upward economic mobility. To test this, we assessed rates of ten cognitive biases across nearly 5000 participants from 27 countries. Our analyses were primarily focused on 1458 individuals that were either low-income adults or individuals who grew up in disadvantaged households but had above-average financial well-being as adults, known as positive deviants. Using discrete and complex models, we find evidence of no differences within or between groups or countries. We therefore conclude that choices impeded by cognitive biases alone cannot explain why some individuals do not experience upward economic mobility. Policies must combine both behavioral and structural interventions to improve financial well-being across populations.
Radiological feature heterogeneity supports etiological diversity among patient groups in Meniere’s disease
Authors: Bächinger David , Filidoro Noemi , Naville Marc , Juchler Norman , Kurtcuoglu Vartan , Nadol Joseph B. , Schuknecht Bernhard , Kleinjung Tobias , Veraguth Dorothe , Eckhard Andreas H. 
Published: June 2023

AbstractWe aimed to determine the prevalence of radiological temporal bone features that in previous studies showed only a weak or an inconsistent association with the clinical diagnosis of Meniere’s disease (MD), in two groups of MD patients (n = 71) with previously established distinct endolymphatic sac pathologies; i.e. the group MD-dg (ES degeneration) and the group MD-hp (ES hypoplasia). Delayed gadolinium-enhanced MRI and high-resolution CT data were used to determine and compare between and within (affected vs. non-affected side) groups geometric temporal bone features (lengths, widths, contours), air cell tract volume, height of the jugular bulb, sigmoid sinus width, and MRI signal intensity alterations of the ES. Temporal bone features with significant intergroup differences were the retrolabyrinthine bone thickness (1.04 ± 0.69 mm, MD-hp; 3.1 ± 1.9 mm, MD-dg; p < 0.0001); posterior contour tortuosity (mean arch-to-chord ratio 1.019 ± 0.013, MD-hp; 1.096 ± 0.038, MD-dg; p < 0.0001); and the pneumatized volume (1.37 [0.86] cm3, MD-hp; 5.25 [3.45] cm3, MD-dg; p = 0.03). Features with differences between the affected and non-affected sides within the MD-dg group were the sigmoid sinus width (6.5 ± 1.7 mm, affected; 7.6 ± 2.1 mm, non-affected; p = 0.04) and the MRI signal intensity of the endolymphatic sac (median signal intensity, affected vs. unaffected side, 0.59 [IQR 0.31–0.89]). Radiological temporal bone features known to be only weakly or inconsistently associated with the clinical diagnosis MD, are highly prevalent in either of two MD patient groups. These results support the existence of diverse—developmental and degenerative—disease etiologies manifesting with distinct radiological temporal bone abnormalities.
Creation of a milk oligosaccharide database, MilkOligoDB, reveals common structural motifs and extensive diversity across mammals
Authors: Durham Sierra D. , Wei Zhe , Lemay Danielle G. , Lange Matthew C. , Barile Daniela 
Published: June 2023

AbstractThe carbohydrate fraction of most mammalian milks contains a variety of oligosaccharides that encompass a range of structures and monosaccharide compositions. Human milk oligosaccharides have received considerable attention due to their biological roles in neonatal gut microbiota, immunomodulation, and brain development. However, a major challenge in understanding the biology of milk oligosaccharides across other mammals is that reports span more than 5 decades of publications with varying data reporting methods. In the present study, publications on milk oligosaccharide profiles were identified and harmonized into a standardized format to create a comprehensive, machine-readable database of milk oligosaccharides across mammalian species. The resulting database, MilkOligoDB, includes 3193 entries for 783 unique oligosaccharide structures from the milk of 77 different species harvested from 113 publications. Cross-species and cross-publication comparisons of milk oligosaccharide profiles reveal common structural motifs within mammalian orders. Of the species studied, only chimpanzees, bonobos, and Asian elephants share the specific combination of fucosylation, sialylation, and core structures that are characteristic of human milk oligosaccharides. However, agriculturally important species do produce diverse oligosaccharides that may be valuable for human supplementation. Overall, MilkOligoDB facilitates cross-species and cross-publication comparisons of milk oligosaccharide profiles and the generation of new data-driven hypotheses for future research.
Deep neural network-based analysis of the impact of ambidextrous innovation and social networks on firm performance
Authors: Zhang Xinyuan , Quah Chee Heong , Nazri Bin Mohd Nor Mohammad 
Published: June 2023

AbstractThe motivation for analyzing the impact of deep neural networks on enterprise performance is mainly due to the continuous deepening of enterprise information construction, shifting from traditional paper-based data acquisition methods to electronic data management. The data generated by the sales, production, logistics and other links of enterprises is also becoming increasingly large. How to scientifically and effectively process these massive amounts of data and extract valuable information has become an important issue that enterprises need to solve. The continuous and stable growth of China's economy has promoted the development and growth of enterprises, however, it has also made enterprises face a more complex competitive environment. The question of how to improve the performance of enterprises to enhance their competitiveness in the market has become a major issue to be addressed in the face of fierce competition and to ensure the long-term development of enterprises. In this paper, based on the research of firm performance evaluation, deep neural network is introduced to analyse the influence of ambidextrous innovation and social network on firm performance, and the theories of social network, ambidextrous innovation and deep neural network are sorted out and analysed, and a deep neural network-based firm performance evaluation model is established, and finally the sample data is obtained using crawler technology, and then the response values are analysed. Innovation and the improvement of the mean value of social networks are helpful to firm performance.
Analysis of survival and prognostic factors of clear cell adenocarcinoma of the prostate: a case–control study for a rare cancer entity
Authors: Chen Sijin , Song Wei , Zhang Ruochen , Jin Yiming , Lu Yan , Lin Le , Ye Liefu , Li Tao , Wei Yongbao 
Published: June 2023

AbstractClear cell adenocarcinoma of the prostate (CCPC) is a rare entity compared to acinar carcinoma of the prostate (APC). The survival rate and prognostic factors of CCPC are still unclear and deserve further study. We downloaded data on prostate cancer from the Surveillance, Epidemiology, and End Results database for 1975–2019. After inclusion and exclusion criteria, we compared APC and analyzed cancer-specific mortality (CSM) and overall mortality (OM) in CCPC patients and prognostic risk factors using a propensity score matching (PSM) study and multivariate Cox regression. We included 408,004 cases of APC as a control group and 130 cases of CCPC as a case group. Compared with APC patients, the incidence of CCPC was extremely low, and the median age of diagnosis was older (72.00 years vs. 69.00 years, p < 0.01). In addition, more rates were diagnosed at an earlier stage (1975–1998, 93.1% vs. 50.2%, p < 0.001), more unstaged or unknown stage ratios (87.7% vs. 42.7%, p < 0.001), and more surgical treatments (66.2% vs. 47.6%, p < 0.001), but the prognosis of CCPC patients was worse. After PSM, the median survival time of CCPC patients was shorter (57.50 month vs. 88.00 month, p < 0.01), the rate of CSM was higher (41.5% vs. 27.7%, p < 0.05), and the rate of OM was higher (99.2% vs. 90.8%, p < 0.01). In the adjusted model 2 after PSM, the CSM risk of CCPC patients reached HR 1.76 (95%CI 1.13–2.72), which was 76% higher than that of APC patients (p < 0.05). It was further found that surgical treatment might benefit CSM in CCPC patients (HR 0.39, 95%CI 0.18–0.82, p < 0.05) in Univariate analysis, but it was insignificant in further multivariate analysis. This is the first large-scale case–control report on the survival risk and prognostic factors of CCPC patients. We found that the prognosis of CCPC patients was significantly worse than that of APC. Surgery might be an effective treatment that may improve its prognosis. Clear cell adenocarcinoma, prostate, acinar carcinoma, survival rate, rare cancer, propensity score matching, case–control study.
Association of post-smoking cessation changes in fasting serum glucose with changes in predicted fatty liver score
Authors: Han Saemi , Jeong Seogsong , Ahn Joseph C. , Cho Yoosun , Choi Seulggie , Park Sun Jae , Kim Kyae Hyung , Lee Gyeongsil , Son Joung Sik , Park Sang Min 
Published: June 2023

AbstractMajor post-cessation metabolic changes include weight gain and hyperglycemia. However, the association of post-cessation change in fasting serum glucose (FSG) with risk of fatty liver remains unclear. A total of 111,106 participants aged 40 and above who underwent health screening at least once in two examination periods were extracted from the Korean National Health Insurance Service-National Sample Cohort. Fatty liver status was evaluated using the Korean National Health and Nutrition Examination Survey nonalcoholic fatty liver disease (K-NAFLD) score. Linear and logistic regression were used to calculate the adjusted mean (aMean) and adjusted odds ratio (aOR) with 95% confidence intervals. Compared to stable (aMean 0.10; 95% CI 0.03–0.18) and decline (aMean − 0.60; 95% CI − 0.71 to 0.49) groups, FSG elevation (aMean 1.28; 95% CI 1.16–1.39) was associated with higher K-NAFLD score even within different body mass index change groups. Risk of fatty liver was significantly reduced among participants with stable (aOR 0.38; 95% CI 0.31–0.45) and declined (aOR 0.17; 95% CI 0.13–0.22) FSG levels after smoking cessation compared to FSG elevation group. This study suggests that quitters with elevated FSG are associated with higher NAFLD risk and may benefit from careful monitoring of FSG levels and management of other cardiovascular risk factors.
Neural complexity through a nonextensive statistical–mechanical approach of human electroencephalograms
Authors: Abramov Dimitri Marques , Tsallis Constantino , Lima Henrique Santos 
Published: June 2023

AbstractThe brain is a complex system whose understanding enables potentially deeper approaches to mental phenomena. Dynamics of wide classes of complex systems have been satisfactorily described within q-statistics, a current generalization of Boltzmann-Gibbs (BG) statistics. Here, we study human electroencephalograms of typical human adults (EEG), very specifically their inter-occurrence times across an arbitrarily chosen threshold of the signal (observed, for instance, at the midparietal location in scalp). The distributions of these inter-occurrence times differ from those usually emerging within BG statistical mechanics. They are instead well approached within the q-statistical theory, based on non-additive entropies characterized by the index q. The present method points towards a suitable tool for quantitatively accessing brain complexity, thus potentially opening useful studies of the properties of both typical and altered brain physiology.
Cancer survival analysis and spatial distribution during 2014–2016 in Shandong Province, China
Authors: Jiang Fan , Fu Zhentao , Lu Zilong , Chu Jie , Xu Aiqiang , Guo Xiaolei , Ma Jixiang 
Published: June 2023

AbstractWe aimed to analyse cancer survival and its spatial distribution in Shandong Province. A total of 609,861 cancer cases from 2014 to 2016 were included in the analysis. Survival analysis was performed using strs in Stata. Spatial analysis was performed with GeoDa to determine measures of global and local spatial autocorrelation. Hotspot analysis was used to identify spatial clusters of high values (hotspots) and low values (cold spots) through ArcGIS. The 5-year relative survival rates were 37.85% for all cancers combined, 29.29% for males and 48.88% for females. After age standardisation, the survival rates were 34.47% for all cancers, 28.43% for males and 41.56% for females. Cancers with higher survival rates included thyroid (78.80%), breast (69.52%), uterus (64.51%) and bladder (62.54%) cancers. However, cancers with lower survival rates included pancreatic (11.34%), liver (13.19%), lung (18.39%), bone (19.71%), gallbladder (19.78%), oesophagus (24.52%), and stomach (28.85%) cancers and leukaemia (26.30%). Cancer survival rates in urban areas (37.53%) were higher than those in rural areas (32.83%). From the geographic distribution of cancer survival, we observed that the survival rate displayed a downward trend from east to west and from north to south. The hotspot analysis revealed that some counties of Qingdao, Jinan, Zibo, Dongying and Yantai cities were hotspots, whereas almost all counties of Linyi city and some counties of Weifang, Heze, Rizhao, and Dezhou cities were cold spots. In conclusion, the cancer survival rate in Shandong is still lower than that in China overall. The early diagnosis and treatment of lung and digestive tract cancers need to be further strengthened. Nevertheless, our results reflect a critical first step in obtaining and reporting accurate and reliable estimates of survival in Shandong.