bluuebunny/crossref_metadata_2025 huggingface dataset:
The dual face of structural object case: on Lithuanian genitive of negation
Authors: SIGURÐSSON EINAR FREYR , ŠEREIKAITĖ MILENA
Published: June 2023

We analyze genitive of negation (GN) in Lithuanian. When the verb is negated, GN is realized on an object that would otherwise be realized as accusative. We demonstrate that Lithuanian GN is a syntactic (in line with Arkadiev 2016) and morphological phenomenon in contrast to Russian GN, whose realization is influenced by semantic factors (e.g. Kagan 2013). It differs from Russian (Pesetsky 1982) in that (i) it is always assigned to a DP which would otherwise bear structural accusative regardless of its semantic properties, and (ii) it cannot affect a structural nominative DP regardless of whether it is an external or internal argument. Lithuanian GN, in this respect, is similar to Polish GN (e.g. Przepiórkowski 2000, Witkoś 2008). We offer a three-layered approach to case, arguing that GN is a reflection of structural object case, assigned in syntax, then translated to morphological genitive case at PF and, finally, realized at Vocabulary Insertion (Halle & Marantz 1993). Thus, structural object case has two morphological realizations: as genitive under negation or as accusative in the absence of negation. Lithuanian also exhibits long-distance GN (Arkadiev 2016), showing that case boundaries can cross non-finite clauses without an overt CP element, suggesting these are not phases.
Dead rats, dopamine, performance metrics, and peacock tails: Proxy failure is an inherent risk in goal-oriented systems
Authors: John Yohan J. , Caldwell Leigh , McCoy Dakota E. , Braganza Oliver
Published: June 2023

When a measure becomes a target, it ceases to be a good measure. For example, when standardized test scores in education become targets, teachers may start “teaching to the test,” leading to breakdown of the relationship between the measure – test performance – and the underlying goal – quality education. Similar phenomena have been named and described across a broad range of contexts, such as economics, academia, machine learning, and ecology. Yet it remains unclear whether these phenomena bear only superficial similarities, or if they derive from some fundamental unifying mechanism. Here, we propose such a unifying mechanism, which we label proxy failure. We first review illustrative examples and their labels, such as the “cobra effect,” “Goodhart's law,” and “Campbell's law.” Second, we identify central prerequisites and constraints of proxy failure, noting that it is often only a partial failure or divergence. We argue that whenever incentivization or selection is based on an imperfect proxy measure of the underlying goal, a pressure arises that tends to make the proxy a worse approximation of the goal. Third, we develop this perspective for three concrete contexts, namely neuroscience, economics, and ecology, highlighting similarities and differences. Fourth, we outline consequences of proxy failure, suggesting it is key to understanding the structure and evolution of goal-oriented systems. Our account draws on a broad range of disciplines, but we can only scratch the surface within each. We thus hope the present account elicits a collaborative enterprise, entailing both critical discussion as well as extensions in contexts we have missed.
Heterogeneity in Spatiotemporal Variability of High Mountain Asia's Runoff and Its Underlying Mechanisms
Authors: Zhu Yanxin , Sang Yan‐Fang , Wang Bin , Lutz Arthur , Hu Shi , Chen Deliang , Singh Vijay P.
Published: June 2023

High Mountain Asia (HMA) is the headwater area for major Asian rivers, providing a vast amount of freshwater to billions of people in Asia. These rivers also make their surrounding areas highly vulnerable to destructive water‐related disasters. However, the complex spatiotemporal variability of runoff over HMA and its underlying mechanisms are poorly understood. This study investigates into the spatial heterogeneity of HMA's runoff variability at three timescales (interannual, interdecadal, and multidecadal) and the roles played by climate conditions and catchment properties. We find significant interannual and multidecadal variability of runoff in west and central HMA, and significant interdecadal variability in central and east HMA. At interannual and multidecadal timescales, the runoff variability tends to be more significant in dryer basins. The variability of runoff at the three timescales is largely controlled by climate variations, especially precipitation. The catchment properties, including groundwater storage and glacier‐snow meltwater, also play important roles in regulating the effect of precipitation. In particular, the high contributions of glacier‐snow meltwater in east HMA can weaken the response of runoff variability to precipitation at interannual and multidecadal timescales. The space‐time patterns of runoff variability over HMA are driven by atmospheric drivers including El Niño‐Southern Oscillation, Interdecadal Pacific Oscillation, and Atlantic Multidecadal Oscillation across timescales. The results of this study provide a better understanding of HMA's runoff variability and its physical mechanisms, which have critical implications for sustainable freshwater management and effective risk mitigation in this densely populated and ecologically vulnerable region.
Inverse Modeling for Subsurface Flow Based on Deep Learning Surrogates and Active Learning Strategies
Authors: Wang Nanzhe , Chang Haibin , Zhang Dongxiao
Published: June 2023

Inverse modeling is usually necessary for prediction of subsurface flows, which is beneficial to characterize underground geologic properties and reduce prediction uncertainty. Considering the intensive computational effort required for repeated simulation runs when solving inverse problems, surrogate models can be built to substitute for the simulator and improve inversion efficiency. Deep learning models have been widely used for surrogate modeling of subsurface flow. However, a large amount of training data is usually needed to train the models, especially for constructing globally accurate surrogate models, which would bring large computational burden. In fact, the local accuracy of surrogate models in regions around the true solution of the inverse problem and the potential searching path of the solution is more important for the inversion processes. The local accuracy of surrogate models can be enhanced with active learning. In this work, active learning strategies based on likelihood or posterior information are proposed for inverse modeling, including both offline and online learning strategies. In the offline strategy, a pre‐trained model is utilized to select samples with higher likelihood, which can produce model responses closer to the observations, and then the selected samples can be used to retrain the surrogate. The retrained surrogate is further integrated with the iterative ensemble smoother (IES) algorithm for inversion. In the online strategy, the pre‐trained model is adaptively updated and refined with the selected posterior samples in each iteration of IES to continuously adapt to the solution searching path. Several subsurface flow problems, including both single‐phase groundwater flow and two‐phase (oil‐water) flow problems, are introduced to evaluate the performance of the proposed active learning strategies. The results show that the proposed strategies achieve better inversion performance than the original surrogate‐based inversion method without active learning, and the number of required simulation runs can also be reduced.
Ionospheric Vertical Correlation Distance Calculation Based on COSMIC Electron Density Profile Data
Authors: Zhang Simin , Wu Xiaocheng , Hu Xiong
Published: June 2023

Background error covariance is an important part of ionospheric assimilation and contains correlation information of the ionospheric background field and error information of the model background field, determines the influence degree of observations on models, and controls the vertical electron density distribution of assimilation results. For more accurate background error covariance determination along the ionosphere vertical direction, we used Constellation Observing System for Meteorology Ionosphere and Climate occultation electron density profile data for vertical correlation distance calculation considering IRI 2016 model errors. The vertical direction correlations are asymmetrical above and below the reference altitude, and with increasing altitude, the vertical correlation distance growth rate may decline or remain unchanged. There are correlation differences in different solar activity years, varying with local time, geomagnetic latitude, and altitude. The vertical correlation distances in high‐solar activity years are greater than that in low‐solar activity years. The correlation distances difference at different times decreases with latitude, with the largest correlation distances at low latitudes. The nighttime distances vary slightly with latitude, while the sunrise correlation distances vary the most relative to other periods. At the same altitude, the correlation distances in the daytime low‐latitude region are the smallest overall, while the correlation distances between the daytime mid‐latitude region and sunrise time are the largest. The point where vertical correlation distances growth stabilize may be correlated with ionospheric hmF2 and upper transition. The IRI model is the most widely used background model in ionospheric assimilation, and the study results could facilitate more accurate vertical background error covariance for ionospheric assimilation.
Adnp-mutant mice with cognitive inflexibility, CaMKIIα hyperactivity, and synaptic plasticity deficits
Authors: Cho Heejin , Yoo Taesun , Moon Heera , Kang Hyojin , Yang Yeji , Kang MinSoung , Yang Esther , Lee Dowoon , Hwang Daehee , Kim Hyun , Kim Doyoun , Kim Jin Young , Kim Eunjoon
Published: June 2023

ADNP syndrome, involving the ADNP transcription factor of the SWI/SNF chromatin-remodeling complex, is characterized by developmental delay, intellectual disability, and autism spectrum disorders (ASD). Although Adnp-haploinsufficient (Adnp-HT) mice display various phenotypic deficits, whether these mice display abnormal synaptic functions remain poorly understood. Here, we report synaptic plasticity deficits associated with cognitive inflexibility and CaMKIIα hyperactivity in Adnp-HT mice. These mice show impaired and inflexible contextual learning and memory, additional to social deficits, long after the juvenile-stage decrease of ADNP protein levels to ~10% of the newborn level. The adult Adnp-HT hippocampus shows hyperphosphorylated CaMKIIα and its substrates, including SynGAP1, and excessive long-term potentiation that is normalized by CaMKIIα inhibition. Therefore, Adnp haploinsufficiency in mice leads to cognitive inflexibility involving CaMKIIα hyperphosphorylation and excessive LTP in adults long after its marked expressional decrease in juveniles.
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

Mood 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

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

DNA 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

Metastasis 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

Candida 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

While 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

We 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

The 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

The 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

Clear 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

Major 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

The 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

We 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.
Dose–effects in behavioural responses of moths to light in a controlled lab experiment
Authors: Jägerbrand Annika , Andersson Petter , Nilsson Tengelin Maria
Published: June 2023

Insects play a critical role in providing numerous ecosystem services. However, insect diversity and biomass have been declining dramatically, with artificial light being suggested as a contributing factor. Despite the importance of understanding the dose–effect responses of insects to light emissions, these responses have been rarely studied. We examined the dose–effect responses of the greater wax moth (Galleria mellonella L.) to different light intensities (14 treatments and a dark control) by observing their behavioural responses in a light-tight box equipped with a LED light source (4070 K) and infrared cameras. Our findings reveal dose–effect responses to light, as the frequency of walking on the light source increased with higher light intensity. Additionally, moths exhibited jumps in front of the light source and jump frequency increased with light intensity. No direct flight-to-light behaviour or activity suppression in response to light was observed. Based on our analysis of the dose–effect responses, we identified a threshold value of 60 cd/m2 for attraction (walking on the light source) and the frequency of jumps. The experimental design in this study offers a valuable tool for investigating dose–effect relationships and behavioural responses of various species to different light levels or specific light sources.
A novel computational method enables RNA editome profiling during human hematopoiesis from scRNA-seq data
Authors: Wu Yan , Hao Shijie , Xu Xiaojing , Dong Guoyi , Ouyang Wenjie , Liu Chao , Sun Hai-Xi
Published: June 2023

RNA editing is a post-transcriptional modification with a cell-specific manner and important biological implications. Although single-cell RNA-seq (scRNA-seq) is an effective method for studying cellular heterogeneity, it is difficult to detect and study RNA editing events from scRNA-seq data because of the low sequencing coverage. To overcome this, we develop a computational method to systematically identify RNA editing sites of cell types from scRNA-seq data. To demonstrate its effectiveness, we apply it to scRNA-seq data of human hematopoietic stem/progenitor cells (HSPCs) with an annotated lineage differentiation relationship according to previous research and study the impacts of RNA editing on hematopoiesis. The dynamic editing patterns reveal the relevance of RNA editing on different HSPCs. For example, four microRNA (miRNA) target sites on 3ʹ UTR of EIF2AK2 are edited across all HSPC populations, which may abolish the miRNA-mediated inhibition of EIF2AK2. Elevated EIF2AK2 may thus activate the integrated stress response (ISR) pathway to initiate global translational attenuation as a protective mechanism to maintain cellular homeostasis during HSPCs’ differentiation. Besides, our findings also indicate that RNA editing plays an essential role in the coordination of lineage commitment and self-renewal of hematopoietic stem cells (HSCs). Taken together, we demonstrate the capacity of scRNA-seq data to exploit RNA editing events of cell types, and find that RNA editing may exert multiple modules of regulation in hematopoietic processes.
Honey bees (Apis mellifera) preselected for Varroa sensitive hygiene discriminate between live and dead Varroa destructor and inanimate objects
Authors: Sprau Lina , Traynor Kirsten , Rosenkranz Peter
Published: June 2023

Varroa destructor is one of the main causes of colony losses of the western honey bee (Apis mellifera). Many efforts exist to breed honey bees resistant to V. destructor. Varroa sensitive hygiene (VSH) is a commonly selected behavioural trait; VSH workers remove the pupae of mite infested brood cells with high efficiency, interrupting the reproduction of the mite. The cues and triggers for this behaviour are not yet fully understood. To determine what elicits this removal behaviour, we examined preselected VSH workers´ responses to four different groups of objects inserted into freshly capped cells: live mites, dead mites, odour reduced mites, and glass beads. These were also compared to control cells that were opened and closed without inserting any object. The pupae in cells containing inorganic objects (glass beads) were removed at similar rates to the control, demonstrating that an object alone does not trigger a removal response. Dead and odour reduced mites were removed at a higher frequency than control cells, but less frequently than live mites. Workers sometimes removed items resting near the top of the cell without removing the pupa. Our results demonstrate that although mite odour from dead mites triggers removal behaviour, the pupa of cells containing live mites were removed more frequently, suggesting that other cues (i.e. odour from feeding wound) or signals (i.e. pupal movement to signal distress) are important. Future research should focus on elucidating these other cues or signals from the brood and mites, as mite presence alone seems to be insufficient.
Neuropsychological deficits in patients with persistent COVID-19 symptoms: a systematic review and meta-analysis
Authors: Sobrino-Relaño Saioa , Balboa-Bandeira Yolanda , Peña Javier , Ibarretxe-Bilbao Naroa , Zubiaurre-Elorza Leire , Ojeda Natalia
Published: June 2023

Long-term persistent symptoms of COVID-19 affect 30–80% of patients who have recovered from the disease and may continue for a long time after the disease has been overcome. The duration of these symptoms over time might have consequences that affect different aspects of health, such as cognitive abilities. The main objective of this systematic review and meta-analysis was to objectify the persistent COVID-19 cognitive deficits after acute phase of infection and to summarize the existing evidence. Additionally, we aimed to provide a comprehensive overview to further understand and address the consequences of this disease. Our protocol was registered in PROSPERO (CRD42021260286). Systematic research was conducted in the Web of Science, MEDLINE, PubMed, PsycINFO, Scopus, and Google Scholar databases from January 2020 to September 2021. Twenty-five studies were included, six of which were analyzed for the meta-analysis, and consisted of 175 patients who had recovered from COVID-19 and 275 healthy individuals. Analyses of cognitive performance of post-COVID-19 patients and healthy volunteers were compared using a random-effects model. The results showed an overall medium–high effect size (g = −.68, p = .02) with a 95% CI (−1.05 to −.31), with a significantly moderate level of heterogeneity among studies (Z = 3.58, p < .001; I2 = 63%). The results showed that individuals who had recovered from COVID-19 showed significant cognitive deficits compared to controls. Future studies should carefully assess the long-term progression of cognitive impairments in patients with persistent COVID-19 symptoms, as well as the effectiveness of rehabilitation interventions. Nevertheless, there is an urgent need to know the profile to speed up development of prevention plans as well as specific interventions. Since more information is being obtained and more studies are being conducted on the subject, the need to examine this symptomatology multidisciplinary to achieve greater scientific evidence of its incidence and prevalence has become increasingly clear.
Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy
Authors: Lumpkin Casey J. , Harris Ashlee W. , Connell Andrew J. , Kirk Ryan W. , Whiting Joshua A. , Saieva Luciano , Pellizzoni Livio , Burghes Arthur H. M. , Butchbach Matthew E. R.
Published: June 2023

Proximal spinal muscular atrophy (SMA) is a leading genetic cause for infant death in the world and results from the selective loss of motor neurons in the spinal cord. SMA is a consequence of low levels of SMN protein and small molecules that can increase SMN expression are of considerable interest as potential therapeutics. Previous studies have shown that both 4-phenylbutyrate (4PBA) and trichostatin A (TSA) increase SMN expression in dermal fibroblasts derived from SMA patients. AR42 is a 4PBA-tethered TSA derivative that is a very potent histone deacetylase inhibitor. SMA patient fibroblasts were treated with either AR42, AR19 (a related analogue), 4PBA, TSA or vehicle for 5 days and then immunostained for SMN localization. AR42 as well as 4PBA and TSA increased the number of SMN-positive nuclear gems in a dose-dependent manner while AR19 did not show marked changes in gem numbers. While gem number was increased in AR42-treated SMA fibroblasts, there were no significant changes in FL-SMN mRNA or SMN protein. The neuroprotective effect of this compound was then assessed in SMNΔ7 SMA (SMN2+/+;SMNΔ7+/+;mSmn−/−) mice. Oral administration of AR42 prior to disease onset increased the average lifespan of SMNΔ7 SMA mice by ~ 27% (20.1 ± 1.6 days for AR42-treated mice vs. 15.8 ± 0.4 days for vehicle-treated mice). AR42 treatment also improved motor function in these mice. AR42 treatment inhibited histone deacetylase (HDAC) activity in treated spinal cord although it did not affect SMN protein expression in these mice. AKT and GSK3β phosphorylation were both significantly increased in SMNΔ7 SMA mouse spinal cords. In conclusion, presymptomatic administration of the HDAC inhibitor AR42 ameliorates the disease phenotype in SMNΔ7 SMA mice in a SMN-independent manner possibly by increasing AKT neuroprotective signaling.
Integrated bioinformatics and wet-lab analysis revealed cell adhesion prominent genes CDC42, TAGLN and GSN as prognostic biomarkers in colonic-polyp lesions
Authors: Tabatabaei Elmira Sadat , Mazloomnejad Radman , Rejali Leili , Forouzesh Flora , Naderi-Noukabadi Fatemeh , Khanabadi Binazir , Salehi Zahra , Nazemalhosseini-Mojarad Ehsan
Published: June 2023

Colorectal cancers are derived from intestinal polyps. Normally, alterations in cell adhesion genes expression cause deviation from the normal cell cycle, leading to cancer development, progression, and invasion. The present study aimed to investigate the elusive expression pattern of CDC42, TAGLN, and GSN genes in patients with high and low-risk polyp samples, and also colorectal cancer patients and their adjacent normal tissues. In upcoming study, 40 biopsy samples from Taleghani Hospital (Tehran, Iran) were collected, consisting of 20 colon polyps and 20 paired adjacent normal tissues. The expression of the nominated genesCDC42,TAGLN, andGSNwas analyzed using quantitative polymerase chain reaction (Q-PCR) and relative quantification was determined using the 2−ΔΔCtmethod. ROC curve analysis was performed to compare high-risk and low-risk polyps for the investigated genes. The expression of adhesion molecule genes was also evaluated using TCGA data and the correlation between adhesion molecule gene expression and immunophenotype was analyzed. The role of mi-RNAs and lncRNAs in overexpression of adhesion molecule genes was studied. Lastly, GO and KEGG were performed to identify pathways related to adhesion molecule genes expression in healthy, normal adjacent, and COAD tissues. The results showed that the expression patterns of these genes were significantly elevated in high-risk adenomas compared to low-risk polyps and normal tissues and were associated with various clinicopathological characteristics. The estimated AUC for CDC42, TAGLN, and GSN were 0.87, 0.77, and 0.80, respectively. The study also analyzed COAD cancer patient data and found that the selected gene expression in cancer patients was significantly reduced compared to high-risk polyps and healthy tissues. Survival analysis showed that while the expression level of the GSN gene had no significant relationship with survival rate, the expression of CDC42 and TAGLN genes did have a meaningful relationship, but with opposite effects, suggesting the potential use of these genes as diagnostic or prognostic markers for colorectal cancer. The present study's findings suggest that the expression pattern of CDC42, TAGLN, and GSN genes was significantly increased during the transformation of normal tissue to polyp lesions, indicating their potential as prognostic biomarkers for colorectal polyp development. Further results provide valuable insights into the potential use of these genes as diagnostic or prognostic markers for colorectal cancer. However, further studies are necessary to validate these findings in larger cohorts and to explore the underlying mechanisms of these genes in the development and progression of colorectal cancer.