Divergent Relationship Research Articles

Pure and mixed Scots pine forests showed divergent responses to climate variation and increased intrinsic water use efficiency across a European-wide climate gradient

AbstractThe present study examined Pinus sylvestris L. growth responses to climatic variations and its relationship with intrinsic water-use efficiency (iWUE) across a water availability gradient and also in pure P. sylvestris and P. sylvestris-Quercus species mixed forests. Study sites were selected in the Mediterranean, temperate, and temperate continental climates in Spain, Italy, and Poland, respectively. A combined tree-ring dendrochronological and stable carbon isotope analysis was used to assess the relationship between tree growth and climate variation. Results showed that P. sylvestris growth is critically affected by summer water availability, regardless of study site and species mixing. Warming temperatures during the early growing season benefit tree growth in Mediterranean and temperate continental climates, while no significant effect was observed in the temperate climatic conditions. At the Mediterranean site, trees in mixed stands showed enhanced growth during wet years when moisture is not limiting. At the temperate continental site, trees in the mixed stand grew at a lower rate than those in pure stands, which suggests that intense interspecific competition for water could overwhelm the benefits of species mixing. Also, we found a divergent growth-iWUE relationship of non-significant and significantly positive and significantly negative correlations at the Polish, Italian, and Spanish sites, respectively. Overall, the negative growth-iWUE relationship at the drier Mediterranean site signifies the risk of tree growth decline, particularly in drier climate conditions. Despite that, elevated iWUE levels would benefit tree radial growth when water is not limited and the admixing tree species have compatible light and water use strategies.

Isolation and whole genomic analysis of mesophilic bacterium Pseudoglutamicibacter cumminsii in epithelial mesothelioma

The relationship between bacteria and tumors has been the hot spot of clinical research in recent years. Pseudoglutamicibacter cumminsii is an aerobic Gram-positive bacterium commonly found in soil. Recent studies have identified P. cumminsii in patients with cutaneous and urinary tract infections. However, little is known on its pathogenesis as well as involvement in other clinical symptoms. In this study, we first report the isolation of P. cumminsii in blood of an epithelial mesothelioma patient. The clinical and laboratory characteristics of P. cumminsii were first described and evaluated. The pure colony of P. cumminsii was then identified using automated microorganism identification system and mass spectrum. The whole genome of the newly identified strain was sequenced with third generation sequencing (TGS). The assembled genome was further annotated and analyzed. Whole genomic and comparative genomic analysis revealed that the isolated P. cumminsii strain in this study had a genome size of 2,179,930 bp and had considerable unique genes compared with strains reported in previous findings. Further phylogenetic analysis showed that this strain had divergent phylogenetic relationship with other P. cumminsii strains. Based on these results, the newly found P. cumminsii strain was named P. cumminsii XJ001 (PC1). Virulence analysis identified a total of 71 pathogenic genes with potential roles in adherence, immune modulation, nutrition/metabolism, and regulation in PC1. Functional analysis demonstrated that the annotated genes in PC1 were mainly clustered into amino acid metabolism (168 genes), carbohydrate metabolism (107 genes), cofactor and vitamin metabolisms (98 genes), and energy metabolism (68 genes). Specifically, six genes including yodJ, idh, katA, pyk, sodA, and glsA were identified within cancer pathways, and their corresponding homologous genes have been documented with precise roles in human cancer. Collectively, the above results first identified P. cumminsii in the blood of tumor patients and further provide whole genomic landscape of the newly identified PC1 strain, shedding light on future studies of bacteria in tumorigenesis.

Internal Psychometric Validation of an International Burden of Illness Survey for Idiopathic Multicentric Castleman Disease.

Idiopathic multicentric Castleman disease (iMCD) is a rare, chronic, debilitating lymphoproliferative disorder where the mainstay of treatment is symptom management. Our recent international patient survey showed that patients with iMCD have a high symptom burden that has a significant negative patient-reported impact on several aspects of daily life. As part of our ongoing work towards the development of an iMCD symptom burden scale, assessing the survey's psychometric properties is a critical step in understanding its adequacy, relevance, and usefulness. As iMCD is a rare disease, there are challenges to conducting such psychometric analyses which we describe. As part of the exploratory psychometric analysis, three a priori hypothesis sets (HS) were generated by interviewing an iMCD-experienced clinician, a patient, and a caregiver to explore the iMCD patient survey's internal construct validity, given no gold standard iMCD measure exists for external construct validation. HS-1hypothesized that a convergent or discriminant relationship exists with the patients' self-assessment of symptom effect on daily life between two potentially related or unrelated symptoms, respectively. HS-2hypothesized that having a greater number of symptoms has a positive convergent relationship with the patients' assessment of symptoms' effect on daily life. Finally, HS-3hypothesized that patients receiving treatment versus no treatment was associated with patients reporting less effect of symptom burden on their daily life. Spearman's rank absolute correlation strength (ACS) was used for HS-1 and HS-2 (convergent relationship, ACS ≥ 0.3 and pvalue < 0.05; divergent relationship, ACS < 0.3), and Cohen's d to quantify standardized absolute effect sizes (AES) for HS-3 (AES ≥ 0.5 and pvalue < 0.05). Our analyses partially supported HS-1. None of the three positive convergent relationships were supported. Of the six discriminant relationships, only dizziness with impaired cognitive function and tiredness with dizziness were supported. HS-2 analyses showed there was convergent validity between the number of symptoms and their effect on aspects of daily life. HS-3 analyses did not provide evidence to support the hypothesis. These internal psychometric construct analyses provide initial support for the bespoke iMCD patient survey and will guide additional work towards the development of the first iMCD-specific symptom burden scale.

Relative Standing and Political Participation

The significance of absolute income has consistently been highlighted in the literature as an important factor shaping individuals’ propensity to engage in political participation. However, considerably less research has been done on the relationship between relative income and individuals’ propensity to engage in both conventional and unconventional forms of political participation. Using relative income to quantify relative standing, this paper explores the relationship between relative standing and political participation in South Africa. Results show that individuals’ relative standing had a divergent relationship with their propensity to engage in voting and protest. More specifically, the results showed that South Africans with a higher relative standing, i.e., those who experienced relative privilege were more likely to engage in voting, while those with a lower relative standing, i.e., those who experienced relative deprivation, were more likely to engage in protest participation.

The complexity of Machiavellian leaders: how and when leader Machiavellianism impacts abusive supervision

AbstractAlthough prior research has documented a divergent relationship between leader Machiavellianism and abusive supervision, it fails to uncover the underlying mechanisms of this relationship. Drawing from trait activation theory as the overarching theory, we develop and test a dual-path model to examine how and when leader Machiavellianism leads to abusive supervision. Specifically, we theorize leader perceived threat to hierarchy (power-threatening process) and perceived power dependence on subordinations (power-sustaining process) as two parallel mechanisms through which leader Machiavellianism affects abusive supervision. We further identify leader position power as a boundary factor that influences the power-threatening and power-sustaining processes. Using multi-wave, multi-source data collected from 175 supervisors and their 763 subordinates, we found that Machiavellian leaders were more likely to perceive high threats from subordinates to the existing hierarchy, though this threat perception was not significantly associated with abusive supervision. Additionally, Machiavellian leaders were also more likely to perceive high power dependence on subordinates, which in turn reduced their abusive supervision. We further found that leader position power strengthened the positive effect of leader Machiavellianism on leader perceived threat to hierarchy, but did not weaken the positive effect of leader Machiavellianism on leader perceived power dependence on subordinates. The implications of our findings are discussed.

The Causal Relationship between PCSK9 Inhibitors and Malignant Tumors: A Mendelian Randomization Study Based on Drug Targeting.

Objective: This study explores the potential causal association between proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors and tumor development using Mendelian randomization (MR) based on drug targets. Methods: Instrumental variables within ±100 kb of the PCSK9 gene locus, impacting low-density lipoprotein cholesterol (LDL-C), were utilized for MR analysis. Coronary heart disease (CHD) served as a positive control to validate the causal relationship between PCSK9 inhibitors and various cancers. We employed reverse MR to address the reverse causation concerns. Data from positive controls and tumors were sourced from OpenGWAS. Results: MR analysis suggested a negative causal relationship between PCSK9 inhibitors and both breast and lung cancers (95%CIBreast cancer 0.81~0.99, p = 2.25 × 10-2; 95%CILung cancer 0.65~0.94, p = 2.55 × 10-3). In contrast, a positive causal link was observed with gastric, hepatic, and oral pharyngeal cancers and cervical intraepithelial neoplasia (95%CIGastric cancer 1.14~1.75, p = 1.88 × 10-2; 95%CIHepatic cancer 1.46~2.53, p = 1.16 × 10-2; 95%CIOral cavity and pharyngeal cancer 4.49~6.33, p = 3.36 × 10-4; 95%CICarcinoma in situ of cervix uteri 4.56~7.12, p = 6.91 × 10-3), without heterogeneity or pleiotropy (p > 0.05). Sensitivity analyses confirmed these findings. The results of MR of drug targets suggested no causal relationship between PCSK9 inhibitors and bladder cancer, thyroid cancer, pancreatic cancer, colorectal cancer, malignant neoplasms of the kidney (except for renal pelvis tumors), malignant neoplasms of the brain, and malignant neoplasms of the esophagus (p > 0.05). Reverse MR helped mitigate reverse causation effects. Conclusions: The study indicates a divergent causal relationship of PCSK9 inhibitors with certain cancers. While negatively associated with breast and lung cancers, a positive causal association was observed with gastric, hepatic, oral cavity, and pharyngeal cancers and cervical carcinoma in situ. No causal links were found with bladder, thyroid, pancreatic, colorectal, certain kidney, brain, and esophageal cancers.

Rewarding Approach Behaviour Attenuates the Return of Pain-Related Avoidance After Successful Extinction with Response Prevention

After successful exposure treatment for chronic pain, pain-related fear and avoidance may return, i.e., relapse may occur. This return of fear and avoidance may be modulated by various post-treatment factors. In this study, we aimed to investigate two potential factors that may affect return of fear and avoidance, i.e. cognitive load and rewarding approach behaviour. In an operant pain-related avoidance conditioning paradigm, healthy pain-free volunteers first learned to fear and avoid an arm-reaching movement that was often paired with painful electrocutaneous stimulation (T1), by performing alternative movements that were less often (T2) or never (T3) paired with pain. During extinction with response prevention, participants were only allowed to perform T1, and pain was omitted. To model relapse, two unexpected painful stimuli were presented (i.e., reinstatement manipulation), after which participants could freely choose among the three arm-reaching movements again. During test, the Low Load group performed an additional easy digit task, whereas the High Load group performed a more cognitively demanding digit task. The Reward group performed the demanding digit task, whilst being rewarded to perform T1. Results showed that pain-related fear and avoidance returned, irrespective of cognitive load imposed. When participants were rewarded to approach T1, however, the return of avoidance, but not fear, was attenuated. Our findings suggest that engaging in rewarding activities may facilitate the maintenance of treatment outcomes, and provide additional support to the growing body of literature indicating a divergent relationship between fear and avoidance. PerspectiveResults of this experiment suggest that engaging in rewarding activities may optimize exposure treatment for chronic pain, by dampening the return of pain-related avoidance – though not of pain-related fear – after extinction.

Extracellular matrix composition alters endothelial force transmission.

Extracellular matrix (ECM) composition is important in a host of pathophysiological processes such as angiogenesis, atherosclerosis, and diabetes, and during each of these processes ECM composition has been reported to change over time. However, the impact ECM composition has on the ability of endothelium to respond mechanically is currently unknown. Therefore, in this study, we seeded human umbilical vein endothelial cells (HUVECs) onto soft hydrogels coated with an ECM concentration of 0.1 mg/mL at the following collagen I (Col-I) and fibronectin (FN) ratios: 100% Col-I, 75% Col-I-25% FN, 50% Col-I-50% FN, 25% Col-I-75% FN, and 100% FN. We subsequently measured tractions, intercellular stresses, strain energy, cell morphology, and cell velocity. Our results revealed that tractions and strain energy are maximal at 50% Col-I-50% FN and minimal at 100% Col-I and 100% FN. Intercellular stress response was maximal on 50% Col-I-50% FN and minimal on 25% Col-I-75% FN. Cell area and cell circularity displayed a divergent relationship for different Col-I and FN ratios. We believe that these results will be of great importance to the cardiovascular field, biomedical field, and cell mechanics.NEW & NOTEWORTHY The endothelium constitutes the innermost layer of all blood vessels and plays an important role in vascular physiology and pathology. During certain vascular diseases, the extracellular matrix has been suggested to transition from a collagen-rich matrix to a fibronectin-rich matrix. In this study, we demonstrate the impact various collagen and fibronectin ratios have on endothelial biomechanical and morphological response.

Border Region Railway Development in Sino- Indian Geopolitical Competition

India and China share about 3,488 km long International Boundary, which has three sectors: Western, Middle and Eastern. The Eastern sector comprises two Northeastern states, that is, Arunachal Pradesh measuring 1,124 kms and Sikkim measuring 219 kms, respectively. Due to recent changes in the geopolitical relationship with China, border management and transport infrastructure development have occupied centre stage. In recent years, the Government of India has taken initiatives to develop railway infrastructure in Northeast India. The study will focus on the role of railway transportation in Sino-Indian geopolitical competition. The study is based on secondary data collected from the office of General Manager, Northeast Frontier Railway, the Census of India and reports of Memorandums of Understanding between India and China. The study reveals that railway infrastructure along the border creates geo-psychological pressures on both countries, influencing the divergent geopolitical relationship between India and China. Railway diplomacy is a tool kit of critical geopolitics which reveals the contours of geopolitical competition in borderlands.

EU Enlarged Countries’ Trade With East Asia: Outliers In Export And Import Time Series

From the standpoint of EU enlarged countries, this empirical study investigates the trade relationship with East Asia via an outlier approach in export and import time series. The results show the exports in trial-and-error progress compared to the imports in a developed adjustment. The outlier patterns clearly demonstrate the divergent trade relationship between the sample countries. This study makes a contribution to the outlier approach in the context of international trade. It concludes that the deeper incorporation of EU enlarged countries into East Asia can lead to significant involvement in the global supply chain and highlight the sustainability of economic growth.

Possibilities of remediation of the personnel substrate of the Slovak public administration

!e public perception and evaluation of the functionality of public authorities depends on the personnel substrate of public administration bodies. !e public is primarily focused on its own problems of everyday life, in the solution of which the public administration and especially its personnel have their share. !e work and attitudes of the personnel of public authorities towards citizens as clients receiving and using speci"c services provided by the public administration organisations naturally also re$ect the public’s attitude towards their own statehood. !ese social relations are inherently highly variable and therefore politically and socially extremely fragile. All the more importance should therefore be attached to the personnel base of the public administration bodies by the public authorities. Public administration reforms are intended to be a means of rationalising the activities of the public administration system. As a rule, however, they are oriented towards revitalising its organisational structure and institutional network, but not towards improving the functioning of the bureaucratic apparatus of the state. Despite the fact that the true essence and goal of its professional activities is such administration of public afairs, which must ideally be carried out solely for the bene"t of the citizens of the state. Since public administration bodies are made up of collectives of people who form an essentially heterogeneous conglomerate in the form of a personnel system, albeit outwardly homogeneous, the state can in fact regulate the guarantees of its operation only to a certain extent and within certain limits. !e decisive place, that is to say, the guarantee and the task of ful"lling the functions attributed to the public administration by the state, therefore belongs to the work portfolio of public administration officials of all levels and types, other managerial employees and the executive bureaucratic apparatus. Officials employed by the state itself in the public administration must therefore meet certain personal, professional and quali"cation criteria. If these requirements are in a divergent relationship with reality, then it is not at all possible for public servants to carry out the internal and external functions of the state in accordance with the political, economic, social and cultural aims of the political power. Although the value of each state as a sovereign political form of organisation of society can be classi"ed according to various indicators, perhaps the most signi"cant are those that can be conceived and monitored on the basis of the establishment and evaluation of the achieved parameters of the quality of life of its population. !e quality of life of the population is also determined by the way in which public affairs are managed. Public administration is therefore a speci"c service of the state provided to the public in its interest and under its responsibility. It is therefore also measurable by the level of satisfaction achieved by the population with its performance. In terms of quality, the performance of public administration is almost exclusively in the hands of the apparatus of public administration bodies, their personnel base (personnel substrate). !is is why the actions of individual officials integrated into the personnel base of the public administration have a signi"cant impact on public opinion. Rersefore, the search for possibilities leading to the improvement of the quality of the activities of the personnel base of the Slovak public administration is still a topical task of both science and practice.

Is there a complementary or a substitutive relationship between climate governance and analyst coverage? Its effect on climate disclosure

AbstractKnowledge of the initiatives that companies are promoting to curb climate change and the impacts resulting from these activities require the disclosure of relevant information that can be used by stakeholders in their decision‐making processes. The objective of this work is to complement previous studies by analysing the effect and type of relationship that exists between internal and market corporate governance mechanisms. We theoretically argue that business transparency related to climate change is explained both by climate governance and by the coverage of the company by financial analysts and that there may be both a complementary and substitutive relationship between the two mechanisms. The results obtained on a global climate governance score show the existence of a substitutive relationship, but the individualised consideration of the components of this score suggests a potential divergent relationship.

Host biology and genomic properties of Plumeria mosaic virus, a tobamovirus discovered in a temple tree in India co-infecting with frangipani mosaic virus.

Temple tree (Plumeria rubra f. acutifolia), an important fragrant-flower tree extensively used in the urban landscaping is known to be infected with a tobamovirus, frangipani mosaic virus (FrMV). In this study, we describe another tobamovirus, Plumeria mosaic virus (PluMV) infecting temple tree in India. PluMV was isolated from an old temple tree co-infected with FrMV. The presence of another tobamovirus was initially realized based on the distinct symptoms on Gomphrena globosa (globe amaranth), a non-host of FrMV. PluMV was highly transmissible through simple rub-inoculation. In host-range study, brinjal (Solanum melongena), chilli (Capsicum annuum), datura (Datura stramonium), globe amaranth and tobacco (Nicotiana benthamiana, N. glutinosa, N. tabacum cv. Xanthi) could differentiate PluMV from FrMV. The complete genome sequence of PluMV was determined (6,688 nucleotides [nt], GenBank KJ395757), which showed the genome structure typical of tobamovirus encoding four proteins: small replicase (3,549 nt/130 kDa), large replicase (5,061 nt/188 kDa), movement protein (770 nt/29 kDa) and coat protein (527 nt/19 kDa). The 5' and 3' UTR of PluMV contained 91 and 284 nt, respectively. The PluMV genome was 45 nts longer than that of FrMV and shared only 71.4-71.6% sequence identity with FrMV and < 50% sequence identity with the rest of the other members of the genus Tobamovirus. PluMV shared a close but a divergent evolutionary relationship with FrMV. Based on the species demarcation guidelines of ICTV (<90% genome sequence identity), PluMV was considered as a new tobamovirus species. As PluMV was serologically related with FrMV, differential diagnostic assays such as simplex and duplex RT-PCR were developed, which revealed that PluMV naturally existed in both the species of temple tree, P. rubra f. acutifolia and P. rubra f. obtusa in India either alone or in mixed infection with FrMV.

Epigenome-Wide Association Study Identified VTI1A DNA Methylation Associated With Accelerometer-Assessed Physical Activity.

Health benefits of physical activity (PA) may be mediated by DNA methylation alterations. The purpose of the current study was to comprehensively identify CpG sites whose methylation levels were associated with accelerometer-assessed total PA in a general Japanese population. The study participants were from the baseline survey of Saga Japan Multi-institutional Collaborative Cohort. PA was objectively measured by a single-axis accelerometer for 7 d. We used a two-stage strategy. In the discovery stage, we performed a meta-analysis of two epigenome-wide association studies of total PA in 898 individuals (a combination of random sample ( n = 507) and case-control study sample ( n = 391)). Peripheral blood DNA methylation levels were measured using Infinium EPIC or HM450 arrays. In the replication stage, we subsequently examined whether CpG sites significantly associated ( P < 1 × 10 -5 ) with total PA were replicated in another sample ( n = 1711), in which methylation levels were measured by pyrosequencing. A multiple linear regression was performed to determine the cross-sectional association between total PA and methylation levels with adjustment for potential confounders, including body mass index. A fixed-effects model was used in the meta-analysis. Correlations between total PA-associated DNA methylation and several inflammatory markers, such as high-sensitivity C-reactive protein, were also conducted. In the meta-analysis, nine CpG sites were significantly associated with total PA ( P < 1 × 10 -5 ). Among the nine sites, one site cg07030336 (annotated to VTI1A/ZDHHC6 gene) was successfully replicated ( P = 0.009). The current study showed that greater accelerometer-assessed total PA was associated with higher DNA methylation levels at cg07030336 ( VTI1A/ZDHHC6 ) in the general population. In addition, we found a divergent relationship between the methylation levels at cg07030336 and several inflammatory biomarkers.

Error aversion or management? Exploring the impact of culture at the sharp-end of production in a mega-project

The research we present in this paper addresses the following question: What type of error culture does the rank-and-file workforce experience during construction, and does it help mitigate rework? We undertake an exploratory case study of an Alliance, which forms part of a transport mega-project. An error culture questionnaire is administered to the Alliance's subcontractors' workforce across four projects. We find that an error management culture positively correlates with reductions in rework and holds a divergent relationship with an error aversion culture. We further reveal a negative association between an error aversion culture and the ability to reduce rework. Consequently, we question the contemporary wisdom that assumes that error prevention should be combined with error management to create an adaptive culture, aiming to minimise the negative and maximise positive error consequences. We finally discuss the study's limitations and implications for future research examining error culture in construction projects.

Genomic Profiling of Antibiotic-Resistant Escherichia coli Isolates from Surface Water of Agricultural Drainage in North-Western Mexico: Detection of the International High-Risk Lineages ST410 and ST617.

Aquatic environments are recognized as one of the main reservoirs for the emergence and dissemination of high-risk lineages of multidrug-resistant (MDR) bacteria of public health concern. However, the genomic characteristics of antibiotic-resistant Escherichia coli isolates from aquatic origins remain limited. Herein, we examined the antibiotic resistance and virulence genomic profiles of three E. coli recovered from surface water in northwest Mexico. Antimicrobial susceptibility testing, whole-genome sequencing (WGS), and in-depth in silico analysis were performed. Two E. coli exhibited MDR phenotypes. WGS-based typing revealed genetic diversity, and phylogenetic analysis corroborated a notable divergent relationship among the studied E. coli. One E. coli strain, harboring enterotoxigenic and extraintestinal pathogenic-associated virulence genes, was assigned to the ST4 lineage. MDR E. coli, belonging to the international high-risk clones ST410 and ST617, carried genes and mutations conferring resistance to aminoglycosides, β-lactams, quinolones, sulfonamides, tetracyclines, and trimethoprim. This study describes, for the first time, the detection and genomic profiling of high-risk lineages of E. coli ST410 and ST617 from surface water in Mexico. Additionally, our results underscore the role of surface water as a reservoir for critical pathogenic and MDR E. coli clones and the need for the surveillance and monitoring of aquatic environments via WGS from the One Health perspective.

Error culture and its impact on rework: An exploration of norms and practices in a transport mega-project

Rework has been and continues to be a problem during the construction of transport mega-projects. This article examines the error culture of an alliance that forms part of a transport mega-project to determine its effectiveness in mitigating rework. Our article reveals that an error management culture positively correlates with reducing rework and holds a divergent relationship with an error aversion culture. We further show a negative association between an error aversion culture and the ability to reduce rework. It is suggested that more can be done to reduce errors and rework despite the prevalence of a strong error management culture in practice. We thus call for an explicit focus on reducing negative error consequences and developing strategies to handle errors. The article argues that providing a psychologically safe work environment, understanding and focusing on what goes right, and coaching to ensure that learning is transferred from an individual to an organizational level can reduce rework. Our study is the first attempt to examine the homogeneity of error culture (i.e., how errors and their consequences are dealt with) in an alliance mega-project setting. In addition, it provides a new line of exploration to address the issue of rework.

Oncogenic Role of Heterogeneous Nuclear Ribonucleoprotein C in Multiple Cancer Types, with a Particular Focus on Lung Adenocarcinoma, Using a Pan-Cancer Analysis and Cell Line Experiments.

Although some evidence has validated the connection between heterogeneous nuclear ribonucleoprotein C (HNRNPC) and the progression of tumors, a pan-cancer investigation is still required. Thus, we explored the oncogenic effect of HNRNPC across many tumors using The Cancer Genome Atlas datasets. Moreover, short hairpin RNAs (shRNAs) were found to repress HNRNPC in lung adenocarcinoma (LUAD) cells, and the effect on LUAD cells proliferation and metastasis was examined using a Cell Counting Kit-8, transwell, and invasion test. HNRNPC was found to be overexpressed in most cancers, and a divergent relationship was observed between the abnormal levels of HNRNPC and tumor prognosis. HNRNPC level was observed to correlate with the cancer-associated fibroblast infiltration, such as lung cancer. Furthermore, higher HNRNPC levels were found in LUAD tissues and cells. Subsequently, Kaplan-Meier analysis revealed that the increased HNRNPC level was connected with worse overall survival and disease-free survival in LUAD patients. Moreover, HNRNPC silencing reduced the progression of A549 and H1299 cells, including proliferation, migration, and invasion. This is the first pan-cancer investigation that presents a relatively systematic finding of the oncogenic effect of HNRNPC among many cancer types. Our data indicate that HNRNPC facilitates the biological processes of LUAD cells; nevertheless, further research on the mechanism underlying the role of HNRNPC in LUAD development is warranted.

A Spheroid Model of Early and Late-Stage Osteosarcoma Mimicking the Divergent Relationship between Tumor Elimination and Bone Regeneration.

Osteosarcoma is the most diagnosed bone tumor in children. The use of tissue engineering strategies after malignant tumor resection remains a subject of scientific controversy. As a result, there is limited research that focuses on bone regeneration postresection, which is further compromised following chemotherapy. This study aims to develop the first co-culture spheroid model for osteosarcoma, to understand the divergent relationship between tumor elimination and bone regeneration. By manipulating the ratio of stromal to osteosarcoma cells the modelled cancer state (early/late) is modified, as is evident by the increased tumor growth rates and an upregulation of a panel of well-established osteosarcoma prognostic genes. Validation of the authors' model is conducted by analyzing its ability to mimic the cytotoxic effects of the FDA-approved chemotherapeutic Doxorubicin. Next, the model is used to investigate what effect osteogenic supplements have, if any, on tumor growth. When their model is treated with osteogenic supplements, there is a stimulatory effect on the surrounding stromal cells. However, when treated with chemotherapeutics this stimulatory effect is significantly diminished. Together, the results of this study present a novel multicellular model of osteosarcoma and provide a unique platform for screening potential therapeutic options for osteosarcoma before conducting in vivo experiments.

Impaired sensory evidence accumulation and network function in Lewy body dementia.

Deficits in attention underpin many of the cognitive and neuropsychiatric features of Lewy body dementia. These attention-related symptoms remain difficult to treat and there are many gaps in our understanding of their neurobiology. An improved understanding of attention-related impairments can be achieved via mathematical modelling approaches, which identify cognitive parameters to provide an intermediate level between observed behavioural data and its underlying neural correlate. Here, we apply this approach to identify the role of impaired sensory evidence accumulation in the attention deficits that characterize Lewy body dementia. In 31 people with Lewy body dementia (including 13 Parkinson’s disease dementia and 18 dementia with Lewy bodies cases), 16 people with Alzheimer’s disease, and 23 healthy controls, we administered an attention task whilst they underwent functional 3 T MRI. Using hierarchical Bayesian estimation of a drift-diffusion model, we decomposed task performance into drift rate and decision boundary parameters. We tested the hypothesis that the drift rate—a measure of the quality of sensory evidence accumulation—is specifically impaired in Lewy body dementia, compared to Alzheimer’s disease. We further explored whether trial-by-trial variations in the drift rate related to activity within the default and dorsal attention networks, to determine whether altered activity in these networks was associated with slowed drift rates in Lewy body dementia. Our results revealed slower drift rates in the Lewy body dementia compared to the Alzheimer’s disease group, whereas the patient groups were equivalent for their decision boundaries. The patient groups were reduced relative to controls for both parameters. This highlights sensory evidence accumulation deficits as a key feature that distinguishes attention impairments in Lewy body dementia, consistent with impaired ability to efficiently process information from the environment to guide behaviour. We also found that the drift rate was strongly related to activity in the dorsal attention network across all three groups, whereas the Lewy body dementia group showed a divergent relationship relative to the Alzheimer’s disease and control groups for the default network, consistent with altered default network modulation being associated with impaired evidence accumulation. Together, our findings reveal impaired sensory evidence accumulation as a specific marker of attention problems in Lewy body dementia, which may relate to large-scale network abnormalities. By identifying impairments in a specific sub-process of attention, these findings will inform future exploratory and intervention studies that aim to understand and treat attention-related symptoms that are a key feature of Lewy body dementia.