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Jiachen Yu,1,* Yingchun Zhang,1,* Rong Ran,2,* Zixiao Kong,3 Duoyi Zhao,1 Wei Zhao,1 Yingxin Yang,4 Lianbo Gao,5 Zhiyu Zhang1 1Department of Orthopedics, the Fourth Affiliated Hospital of China Medical University, China Medical University, Shen Yang, 110032, People’s Republic of China; 2Department of Anesthesia, the Fourth Affiliated Hospital of China Medical University, China Medical University, Shen Yang, 110032, People’s Republic of China; 3China Medical University, Shen Yang, 110032, People’s Republic of China; 4General Hospital of Northern Theater Command, China Medical University, Shen Yang, 110032, People’s Republic of China; 5Department of Neurology, the Fourth Affiliated Hospital of China Medical University, China Medical University, Shen Yang, 110032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiyu Zhang; Lianbo Gao, The Fourth Affiliated Hospital of China Medical University, No. 4 Chongshan Road, Huanggu District, Shenyang, Liaoning, People’s Republic of China, Email zyzhang@cmu.edu.cn; lbgao@cmu.edu.cnAbstract: The development of therapeutic drugs and methods has been greatly facilitated by the emergence of tumor models. However, due to their inherent complexity, establishing a model that can fully replicate the tumor tissue situation remains extremely challenging. With the development of tissue engineering, the advancement of bioprinting technology has facilitated the upgrading of tumor models. This article focuses on the latest advancements in bioprinting, specifically highlighting the construction of 3D tumor models, and underscores the integration of these two technologies. Furthermore, it discusses the challenges and future directions of related techniques, while also emphasizing the effective recreation of the tumor microenvironment through the emergence of 3D tumor models that resemble in vitro organs, thereby accelerating the development of new anticancer therapies.Keywords: bioprinting, bioink, organoids, tumor spheroids, tumor chips

Rui-Huan Gao,1,&ast; Boyang Liu,2,&ast; Ying Yang,1 Ruoxi Ran,1 Yidan Zhou,1,&ast; Song-Mei Liu1,&ast; 1Department of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, People’s Republic of China; 2Department of Computer Science and Engineering, Michigan State University, East Lansing, MI, USA&ast;These authors contributed equally to this workCorrespondence: Song-Mei Liu; Yidan Zhou, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, Hubei Province, 430071, People’s Republic of China, Email smliu@whu.edu.cn; Yzhou12@whu.edu.cnPurpose: Diabetic nephropathy (DN) is a common complication of type 2 diabetes mellitus (T2DM) that significantly impacts the quality of life for affected patients. Dyslipidemia is a known risk factor for developing cardiovascular complications in T2DM patients. However, the association between serum lipoprotein(a) (Lp(a)) and high-density lipoprotein cholesterol (HDL-C) with DN requires further investigation.Patients and Methods: For this cross-sectional study, we randomly selected T2DM patients with nephropathy (DN, n = 211) and T2DM patients without nephropathy (T2DM, n = 217) from a cohort of 142,611 patients based on predefined inclusion and exclusion criteria. We collected clinical data from the patients to identify potential risk factors for DN using binary logistic regression and machine learning. After obtaining the feature importance score of clinical indicators by building a random forest classifier, we examined the correlations between Lp(a), HDL-C and the top 10 indicators. Finally, we trained decision tree models with top 10 features using training data and evaluated their performance with independent testing data.Results: Compared to the T2DM group, the DN group had significantly higher serum levels of Lp(a) (p < 0.001) and lower levels of HDL-C (p = 0.028). Lp(a) was identified as a risk factor for DN, while HDL-C was found to be protective. We identified the top 10 indicators that were associated with Lp(a) and/or HDL-C, including urinary albumin (uALB), uALB to creatinine ratio (uACR), cystatin C, creatinine, urinary ɑ1-microglobulin, estimated glomerular filtration rate (eGFR), urinary β 2-microglobulin, urea nitrogen, superoxide dismutase and fibrinogen. The decision tree models trained using the top 10 features and with uALB at a cut-off value of 31.1 mg/L showed an average area under the receiver operating characteristic curve (AUC) of 0.874, with an AUC range of 0.870 to 0.890.Conclusion: Our findings indicate that serum Lp(a) and HDL-C are associated with DN and we have provided a decision tree model with uALB as a predictor for DN.Keywords: type 2 diabetes mellitus, diabetic nephropathy, high density lipoprotein cholesterol, lipoprotein(a), machine learning

Information-seeking behavior in humans is often viewed as irrational rather than utility maximizing. Here the authors describe data obtained in Spring 2020 showing that participants’ concern about COVID-19 was related not only to their drive to seek information about the virus, but also to their curiosity about other more general topics.

Abstract Humans exhibit complex arithmetic skills, often attributed to our exceptionally large neocortex. However, the past decade has provided ample evidence that the functional domain of the subcortex extends well beyond basic functions. Using a sensitive behavioral method, for the first time, we explored the contributions of lower-order visual monocular channels to symbolic arithmetic operations, addition and subtraction. The pattern of results from 4 different experiments provides converging evidence for a causal relation between mental arithmetic and primitive subcortical regions. The results have major implications for our understanding of the neuroevolutionary development of general numerical abilities–subcortical regions, which are shared across different species, are essential to complex numerical operations. In a bigger conceptual framework, these findings and others call for a shift from the modal view of the exclusive role of the neocortex in high-level cognition to a view that emphasizes the interplay between subcortical and cortical brain networks.

Predicting the future is essential for organisms like Homo sapiens, who live in a dynamic and ever-changing world. Previous research has established that conscious stimuli can lead to non-conscious predictions. Here we examine whether masked stimuli can also induce such predictions. We use masked movement-with and without obstacles-to examine predictions from masked stimuli. In six experiments a moving object was masked using continuous flash suppression (CFS). A few hundred milliseconds after the object had disappeared, a conscious probe appeared in a location that was either consistent with the masked stimulus or not. In Experiments 1-3 the movement was linear, and reaction times (RTs) indicated predictions that were based on direction and speed of movement. In Experiment 4, the masked moving object collided with an obstacle and then disappeared. Predictions in this case should reflect deflection, and indeed reaction times revealed predictions on the deflection route. In Experiments 5 and 6 we introduce an innovative way of using eye-tracking during continuous flash suppression (CFS) and report physiological evidence-in the forms of eye-movements-for masked stimuli induced predictions. We thus conclude that humans can use dynamic masked stimuli to generate active predictions about the future, and use these predictions to guide behavior. We also discuss the possible interpretations of these findings in light of the current scientific discussion regarding the relation between masked presentation, subliminal perception and awareness measurement methods.

Conscious awareness to the events and stimuli around us is a central part of our everyday experience. Yet, are humans the only species that experiences conscious awareness? Since non-verbal species cannot report their internal states, philosophers and scientists have long debated whether the question of animal consciousness is empirically testable, and it still remains a topic of speculation (Dawkins, 2015; Gutfreund, 2017). In the large spectrum of views, some advocate that consciousness may require complex processes like language, a capacity that is unique to adult humans (Dennett, 1995) or a human-like theory of mind (Carruthers, 1998), which may extend to only a few selected species such as great apes (e.g., Krupenye, Kano, Hirata, Call, & Tomasello, 2016; but see Horschler, MacLean, & Santos, 2020). In contrast, others have used neuroanatomical similarities to argue that a number of species (including some birds and octopuses) are likely to be capable of generating conscious experience (see, for example, the Cambridge declaration on consciousness, 2012). Others argue that non-human animals are conscious on the basis of intelligent behaviors which, at least in humans, seem to coincide with conscious awareness as supporting evidence for animal consciousness. These include behaviors such as planning (Osvath & Osvath, 2008), or metacognition (Hampton, Engelberg, & Brady, 2020; Rosati & Santos, 2016), for review see Boly et al., 2013; Griffin & Speck, 2004. Yet, since many complex human behaviors and high-level functions can be performed outside of conscious awareness (i.e., Hassin, 2013), it is difficult to determine whether non-human animals that display intelligent behaviors are indeed conscious or not (Carruthers, 2018). Furthermore, given the ambiguity and difficulty in disentangling conscious from non-conscious processes in non-verbal species, many consider the question of animal consciousness as far from having been resolved (Dawkins, 2015; Gutfreund, 2017). For many, the gap in evidence needed to unambiguously infer animal consciousness is considered “as wide as ever” (Dawkins, 2012).

The Zr55Cu30Al10Ni5 amorphous alloy with thickness 0.5 mm and width of 75 mm was fabricated by twin-roll casting. Due to high rolling force, the alloy exhibited high energy state, high free volume and microstructure inhomogeneity. However, the friction property is not clear because of excellent plasticity and high free volume. The present study tested the friction property of the alloy by rotating pin-on-disk method and investigated the friction behavior and wear mechanism. Besides, the abrasive resistance was improved by subsequent annealing treatment. The results show that the wear mechanisms are mainly abrasive wear, adhesion wear, delamination wear and fatigue wear. The wear law is in accordance with the Archard's empirical wear law. The structural stability and uniformity of that cast strip can be increased by annealing the cast strip at the glass transition temperature. Meanwhile, the wear resistance of the amorphous alloy is improved, and the wear rate in the annealed state is reduced to 88.7 percent of that in the as-cast state, so that abrasive resistance is improved. This study provides a little theoretical basis for amorphous alloy as wear-resistant material and expands the application of amorphous alloy in engineering materials. [ABSTRACT FROM AUTHOR]

Abstract Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid. Thirty-three patients received BPX-601 with or without rimiducid, 24 patients with mPDAC and 9 with mCRPC. Two dose-limiting toxicities and two treatment-related deaths occurred in the highest-dose mCRPC cohort, after which the study was terminated, without determination of the RP2D. Two mCRPC patients experienced partial responses (one unconfirmed), and 56% of mCRPC patients achieved ≥50% reduction in prostate-specific antigen. BPX-601 cell expansion, long-term persistence in peripheral blood, and tumor infiltration were observed. Rimiducid increased circulating inflammatory cytokines/chemokines consistent with GoCAR-T® cell activation. These results suggest that pharmacological activation of GoCAR-T® cells is feasible and may offer a promising avenue to control chimeric antigen receptor-T cell activity with continued dose-optimization to improve tolerability.

Fluency, the subjective experience of ease associated with information processing, has been shown to affect a host of judgments. Previous research has typically focused on specific factors that affect the use of a single, specific fluency source. In the present study we examine how cognitive mindsets, or processing modes, moderate fluency emanating from two simultaneous sources of fluency. As a cognitive mindset manipulation, participants performed Jacoby's process dissociation paradigm. Subsequently, participants engaged in a metamemory task that incorporates (and can separately measure the influence of) two simultaneous sources of fluency: familiarity and accessibility. Our results confirmed that our content-unrelated mindset procedure had affected the use of fluency. Moreover, the use of both fluency sources was attenuated, demonstrating the generality of the effect. The findings highlight the causal dependency of fluency on a complex, cognitively-rich environment. (Contains 1 figure.)

We propose that experience of emotion is a mental phenomenon, which requires resources. This hypothesis implies that a concurrent cognitive load diminishes the intensity of feeling since the 2 activities are competing for the same resources. Two sets of experiments tested this hypothesis. The first line of experiments (Experiments 1-4) examined the intensity of participants' feelings as they performed a secondary (backward counting) task. The results showed that the intensity of both negative and positive feelings diminished under a cognitive load and that this attenuation of feeling was not mediated by either distraction from external stimuli or demand characteristics. In the second set of experiments (Experiments 5-6), load was created by asking the participants to focus on the feelings. Even in these circumstances, the participants who were under load reported a lower intensity of feeling than those who were not under load. We explain these findings in terms of a resource-dependent model of emotional experience. Possible implications of our findings for a broader class of phenomenological experiences are succinctly discussed. (Contains 4 footnotes, 4 tables, and 4 figures.)

Abstract Background Different hormone receptor (HR) expression patterns have significant biological and therapeutic implications in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, the distinction between HR-positive /HER2-positive (HR+/HER2+) and HR-negative/HER2-positive (HR-/HER2+) subtypes remains unclear. Methods This retrospective study analyzed 828 patients with HER2-positive breast cancer at the First Affiliated Hospital of Xi’an Jiaotong University from 2012 to 2022. Baseline characteristics were compared by chi-square test. Survival outcomes were estimated by Kaplan-Meier method. Results In total, 56.3% (n = 466) had HR-positive and 43.7% (n = 362) had HR-negative disease. Comparatively, HR+/HER2 + breast cancers presented favorable clinicopathological features. At a median follow-up of 49 months, 199 disease-free survival (DFS) events and 99 deaths were observed. HR+/HER2 + patients had significantly better survival outcomes than HR-/HER2 + patients. HR-positive status was an independent protective factor for overall survival (OS) [P = 0.032; hazard ratio, 0.61; 95% confidence interval (CI), 0.39–0.96] and DFS (P = 0.001; hazard ratio, 0.61; 95% CI, 0.46–0.81). HR+/HER2 + patients were significantly less sensitive to neoadjuvant therapy than HR-/HER2 + patients. In the first-line treatment for HR+/HER2 + advanced breast cancer, receiving endocrine therapy significantly improved advanced-OS (P

Numerous studies have demonstrated that Huntington's disease mutation-carriers have deficient explicit recognition of isolated facial expressions. There are no studies, however, which have investigated the recognition of facial expressions embedded within an emotional body and scene context. Real life facial expressions are typically embedded in contexts which may dramatically change the emotion recognized in the face. Moreover, a recent study showed that the magnitude of the contextual bias is modulated by the similarity between the actual expression of the presented face and the facial expression that would typically fit the context, e.g. disgust faces are more similar to anger than to sadness faces and, consequently, are more strongly influenced by contexts expressing anger than by contexts expressing sadness. Since context effects on facial expression perception are not explicitly controlled, their pattern serves as an implicit measure of the processing of facial expressions. In this study we took advantage of the face-in-context design to compare explicit recognition of face-expressions by Huntington's disease mutation-carriers, with evidence for processing the expressions deriving from implicit measures. In an initial experiment we presented a group of 21 Huntington's disease mutation-carriers with standard tests of face-expression recognition. Relative to controls, they displayed deficits in recognizing disgust and anger faces despite intact recognition of these emotions from non-facial images. In a subsequent experiment, we embedded the disgust faces on images of people conveying sadness and anger as expressed by body language and additional paraphernalia. In addition, sadness and anger faces were embedded on context images conveying disgust. In both cases participants were instructed to categorize the facial expressions, ignoring the context. Despite the deficient explicit recognition of isolated disgust and anger faces, the perception of the emotions expressed by the faces was affected by context in Huntington's disease mutation-carriers in a similar manner as in control participants. Specifically, they displayed the same sensitivity to face-context pairings. These findings suggest that, despite their impaired explicit recognition of facial expressions, Huntington's disease mutation-carriers display relatively preserved processing of the same facial configurations when embedded in context. The results also show intact utilization of the information elicited by contextual cues about faces expressing disgust even when the actually presented face expresses a different emotion. Overall, our findings shed light on the nature of the deficit in facial expression recognition in Huntington's disease mutation-carriers as well as underscore the importance of context in emotion perception.

Abstract The tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR), such as osimertinib and gefitinib, aumolertinib have been widely used in EGFR mutation‐positive non‐small cell lung cancer (NSCLC) patients. However, the discrepancy of pharmacokinetic features and distributions in important tissues between these EGFR‐TKIs remains obscure. In this study, an ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) method with specificity and accuracy was established. After a single equivalent dose ratio or equal dose gavage, aumolertinib displayed the shortest elimination half‐life time (t1/2), while it showed the largest area under the concentration–time curve in mouse plasma and bone marrow among these 3 EGFR‐TKIs. Furthermore, at the time of reaching maximum concentration (tmax) after single equivalent dose ratio gavage, the concentrations of aumolertinib were significantly higher than that of osimertinib and gefitinib in 9 important tissues of mice. Moreover, after single oral administration, aumolertinib displayed the highest concentration in plasma samples from EGFR mutation‐positive NSCLC patients. Collectively, our findings manifest that the bioavailability and tissue distribution features of aumolertinib are superior to those of osimertinib and gefitinib, providing a pharmacokinetic basis for the clinical application of aumolertinib and the development of next‐generation EGFR‐TKIs.

Perovskite oxides with high oxygen ionic conductivity have played major roles in five important devices of significance for clean energy future and automated manufacturing, i.e., solid oxide fuel cell, solid oxide electrolysis cell, oxygen permeable membranes, gas sensors, and oxygen pumps, all of which exhibit different performance requirements and challenges. Although improving the oxygen ion transport within the perovskite lattice serves as the key to increasing the efficiencies of perovskites’ components in these devices, the different criteria, structures, and/or physicochemical properties often become the complicating factors. It is understood that the oxygen ion transport performance of perovskite is mainly determined by the crystal structure, the A/B-site cations and their content, and the oxygen vacancies. This perspective overviews these factors, which can be manipulated to adapt the needs for different devices. Brief discussions are then made on the concepts, status, and outlook of each device together with the strategies for improving the device performance. The summaries and insights provided in this review are anticipated to promote more strategic research and development directions and activities in these important applications.