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Advancements in Artificial Intelligence (AI) will produce “reasonable disagreements” between human operators and machine partners. A simulation study investigated factors that may influence compromise between human and robot partners when they disagree in situation evaluation. Eighty-seven participants viewed urban scenes and interacted with a robot partner to make a threat assessment. We explored the impacts of multiple factors on threat ratings and trust, including how the robot communicated with the person, and whether or not the robot compromised following dialogue. Results showed that participants were open to compromise with the robot, especially when the robot detected threat in a seemingly safe scene. Unexpectedly, dialogue with the robot and hearing robot inner speech reduced compromise and trust, relative to control conditions providing transparency or signaling benevolence. Dialogue may change the human’s perception of the robot’s role in the team, indicating a design challenge for design of future systems.

History tells us that some problems are admired so deeply that we forget to solve them. But then, there are also times when we move to solve them too quickly, without having admired them enough.So, what about employee engagement?For several decades motivational theorists admired the problem with great fascination and offered the world a whole host of theories that we continue to fall back on. Then in the last few decades, consulting companies have offered the world their own models of motivation under the umbrella of engagement.Given that the context has changed so enormously and so much water has flown under the bridge, I believe it is time to step back and admire the problem once again. That is the purpose of my article.

Introduction: Chronic hepatitis B (CHB) infection is accountable for nearly 240 million cases worldwide. Hepatitis B virus (HBV) has a propensity to show a divergent phase, and isolated measure of high HBV DNA level may not reflect the stage of the disease. In this background, this study was done to detect hepatitis B e antigen (HBeAg) and HBV DNA levels among hepatitis B surface antigen (HBsAg)-positive CHB cases and to determine the stage of disease with viral markers and biochemical parameters such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels.Materials and Methods: Blood samples were collected from 50 participants with CHB (HBsAg positive for more than 6 months) tested for HBe Ag by enzyme-linked immunosorbent assay, HBV DNA, ALT, and AST levels.Results: Among the 50 cases, 31 (62%) were HBeAg negative. Among these 31 HBeAg-negative groups, 16 (52%) had HBV DNA levels >2000 IU/mL. In these 16 patients, six had ALT >40IU/mL.Conclusion: HBsAg, HBeAg, ALT levels, and HBV DNA are important markers to determine the clinical stage of the disease. Since it is a chronic disease, patients need long-term follow-up. Further, emergence of viral mutants among vaccinated and those on lamivudine aggravates the existing problem.

* The AAAI 2019 Spring Symposium Series was held Monday through Wednesday, March 25-27, 2019, on the campus of Stanford University, adjacent to Palo Alto, California. The titles of the [...]

Artificial general intelligence revived in recent years after people achieved significant advances in machine learning and deep learning. This leads to the thinking of how real intelligence could be created. Consciousness theories believe that general intelligence is essentially conscious, yet no universal definition is agreed upon. In this work, global workspace (GW) theory is implemented and integrated with crucial cognitive components. With the focus on episodic memory and inspiration from the nature of episodic memory in psychology and neuroscience, the episodic memory component is implemented within the GW framework. In our experiment, the robotic agent operates in a real-world interactive context, forming episodic memory and demonstrating static, temporal, and context memory capabilities during interactions. Consciousness in this work engages in all formation, maintenance, and retrieval processes of episodic memory. The novelty and contributions of this work are: 1) this work is implementing episodic memory within the consciousness framework, suggesting the sustainable potential of such an integrated approach to cognitive agents with artificial general intelligence (AGI); 2) regarding the limited examples in consciousness-based cognitive architectures, this work attempts to contribute to the diversity of perspectives and approaches; 3) extant episodic memory implementations are suffering from various limitations, while this work summarises some key features for modeling episodic memory within a cognitive architecture; and 4) authors discuss the relationship between episodic memory, consciousness, and general intelligence, proposing the compatibility and relationship between machine consciousness and other AGI research. It is believed that a better alignment between them would further boost the fusion of diverse research for achieving desired cognitive machines.

Background: Solid lipid nanoparticles (SLNs) have emerged as effective carriers for the simultaneous delivery of two drugs. Moreover, the surface modification of SLNs enhances their targetability and minimizes side effects, rendering them a promising and dynamic strategy for addressing various life-threatening diseases. The assessment of pharmacokinetic parameters is a critical aspect of this approach. In the present study, we report the development and validation of an LC-MS/MS-based bioanalytical method for the quantification of Atorvastatin (ATR) and Quercetin (QUER) encapsulated in folic acid-modified SLNs as a drug delivery system to estimate their pharmacokinetics and tissue distribution. Method: FA-SLNs were synthesized by amide linkage formation (carbodiimide reaction) and tested for their haemocompatibility. Further, an LC-MS/MS method was developed on a C18 (3 × 100 mm, 2.7 μm) column using 0.1% v/v formic acid in water and acetonitrile as the mobile phase with a 0.3 mL min−1flow rate. For detection, analytes were ionized using an electron spray ionization (ESI) source in multiple reaction monitoring (MRM) mode. MRM for the ATR (559.0 → 440.2) m/zand IS (482.1 → 257.8) m/zin positive polarity, and QUER (301.9 → 151.0) m/zin negative polarity were optimized. Results: Pharmacokinetics studies demonstrated an increase in the half-lives of ATR and QUER of about 6.4-fold and 5.7-fold, respectively, from FA-SLN compared to pure drugs. Further, the active targeting facilitated by FA conjugation showed increased mean residence time (MRT) and decreased clearance time, resulting in long circulation time without the enhanced retention of drugs in the tissues of rats. These findings underscore the potential of FA-modified ATR and QUER-loaded SLNs as an advanced drug delivery strategy in improving the therapeutic outcomes.

The paper focuses on how the neoliberal economy is changing the agriculture and traditional food system of the Kondh tribes of Odisha, India. As Kondhs’ culture and the ritual system moves around agriculture, its increasing commercialization has led to changes in the larger socioeconomic structure. The paper discusses the immediate impacts of neoliberalism on the Kondhs’ youths and rising materialism. Widespread cultivation of Bt. Cotton and GM seeds in the region are one of the ways to trace the impact of the neoliberal market system. Most commercial exchanges performed by Kondhs and nontribal middlemen are a site for multiple negotiations and terms for trading, in which Kondhs most loose, both ecologically and economically. The paper uses ethnographic data and experiences to discuss socioeconomic distress among Kondhs, changing from barter to a cash system. It concludes by discussing if local NGOs and food movements can become a solution.

Sympathetic activation during cold exposure increases adipocyte thermogenesis via the expression of mitochondrial protein uncoupling protein 1 (UCP1)1. The propensity of adipocytes to express UCP1 is under a critical influence of the adipose microenvironment and varies between sexes and among various fat depots2–7. Here we report that mammary gland ductal epithelial cells in the adipose niche regulate cold-induced adipocyte UCP1 expression in female mouse subcutaneous white adipose tissue (scWAT). Single-cell RNA sequencing shows that glandular luminal epithelium subtypes express transcripts that encode secretory factors controlling adipocyte UCP1 expression under cold conditions. We term these luminal epithelium secretory factors ‘mammokines’. Using 3D visualization of whole-tissue immunofluorescence, we reveal sympathetic nerve–ductal contact points. We show that mammary ducts activated by sympathetic nerves limit adipocyte UCP1 expression via the mammokine lipocalin 2. In vivo and ex vivo ablation of mammary duct epithelium enhance the cold-induced adipocyte thermogenic gene programme in scWAT. Since the mammary duct network extends throughout most of the scWAT in female mice, females show markedly less scWAT UCP1 expression, fat oxidation, energy expenditure and subcutaneous fat mass loss compared with male mice, implicating sex-specific roles of mammokines in adipose thermogenesis. These results reveal a role of sympathetic nerve-activated glandular epithelium in adipocyte UCP1 expression and suggest that mammary duct luminal epithelium has an important role in controlling glandular adiposity.

Thinking to oneself is a prerogative of man when he needs to think about or repeat what he is doing or experiencing. It is a way of processing information and setting in motion a decision-making process. When this is done aloud, there is also a chance that someone else will understand the meaning or reasons for the action. Equipping an agent with the ability to reveal the reasons for its decisions is both a way to improve human interaction and a way to improve the triggering of a decision process. In this work, we propose to use the speech act to enable a coalition of agents to exhibit inner speech capabilities to explain their behavior, but also to guide and reinforce the creation of an inner model. The BDI agent paradigm, Jason, and CArtAgO are used to give agents the ability to act in a human-like manner. The BDI reasoning cycle has been extended to include inner speech. The proposed solution continues the research path that started with the definition of a cognitive model and architecture for human-robot teaming interaction and aims to integrate the believable interaction paradigm in it.

Background and Objective: Many naturally available dietary molecules such as curcumin have not seen the market due to poor solubility, bioavailability, and photodegradability. Successful development of a lipid-based dry emulsion may overcome these issues and help in reaching the markets for natural dietary molecules such as curcumin. The current study aims to develop a dry emulsion formulation of curcumin using natural oil and evaluate its dissolution, photostability, pharmacokinetics, and anti-inflammatory activity. Methods: Dry emulsions were prepared using emu oil and corn oil as the lipid phase, Caproyl 90 and Cremophor RH 40 as surfactants, and dextrin as a hydrophilic carrier. Results: Microscopic studies showed the formation of spherical porous particles, and solid-state characterization using differential scanning calorimetry and powder X-ray diffraction showed the conversion of curcumin to an amorphous form. About 80% drug release was observed from formulation, whereas pure drug showed only 50% drug release in 30 min. In vivo pharmacokinetic studies showed fivefold improvement in the maximum concentration of curcumin in plasma (Cmax) and sevenfold improvement in the area under the concentration-time curve of curcumin from emu oil formulation compared with pure curcumin. Significant differences were observed in the anti-inflammatory activity of curcumin dry emulsion and plain curcumin. Emu-oil-based formulations showed synergistic anti-inflammatory activity over corn-oil-based formulations with improved photostability. Conclusion: The present study suggests that the dry emulsion may enhance the bioavailability with synergistic anti-inflammatory activity and photostability of curcumin when given orally.

•The analysis of ctDNA in NSCLC patients is challenging, due to its high variability in shedding, giving high probability of false negative results.•65 % of patients who were mEGFR shedders in ctDNA at baseline, had higher ECOG PS, bilateral localization of primary tumor, and presence of intrathoracic/extrathoracic disease.•Liquid biopsy testing of EGFR mutation offers valuable insights for clinical applicability and a better understanding of clinical characteristics associated to ctDNA shedding may reduce the risk of false negative results.

The construction industry generates a huge amount of concrete waste that needs to be recycled, which is said to be recycled aggregate (RA) being used for partial or total substitution of natural aggregate. Upscaling recycled aggregate in concrete production reduces dumped waste and decreases energy consumption in the extraction of new materials. However, the high water demand and poor interfacial transition zone of recycled aggregate contribute to inferior compressive strength and durability properties of concrete. Therefore, in this study, the inherent properties of recycled aggregate are improved by precoating it with pond ash material discarded from the thermal power plant industries. The pretreated recycled aggregate is then used in the replacement of natural coarse aggregate at various substitution levels (0%, 30%, 50%, 70%, and 100%), and the effects of these replacements on the mechanical and durability aspects of concrete are explored. The compressive strength, flexural strength, elastic modulus, water absorption, water sorptivity, and carbonation properties are assessed in pretreated recycled aggregate concrete. Test results indicate an increase in compressive strength (20.68%) and flexural strength (13.33%) in concrete with 50% pretreated recycled aggregate, while the elastic modulus in the same replacement shows marginal improvement. Durability aspects such as water absorption and sorptivity were enhanced with the precoated RCA and fell within permissible limits. Recycling construction and demolition waste using this pretreatment technique can help to protect the environment and reduce the depletion of natural resources, contributing to sustainable development goals.

We tested whether aspects of the childhood/adolescent home environment mediate genetic risk for alcohol problems within families across generations. Parental relationship discord and parental divorce were the focal environments examined. The sample included participants of European ancestry (N= 4806, 51% female) and African ancestry (N= 1960, 52% female) from the high-risk Collaborative Study on the Genetics of Alcoholism. Alcohol outcomes in the child generation included lifetime criterion counts for DSM-5 Alcohol Use Disorder (AUD), lifetime maximum drinks in 24 h, age at initiation of regular drinking, and age at first alcohol intoxication. Predictors in the parent generation included relationship discord, divorce, alcohol measures parallel to those in the child generation, and polygenic scores for alcohol problems. Parental polygenic scores were partitioned into alleles that were transmitted and non-transmitted to the child. The results from structural equation models were consistent with genetic nurture effects in European ancestry families. Exposure to parental relationship discord and parental divorce mediated, in part, the transmission of genetic risk for alcohol problems from parents to children to predict earlier ages regular drinking (βindirect= −0.018 [−0.026, −0.011]) and intoxication (βindirect= −0.015 [−0.023, −0.008]), greater lifetime maximum drinks (βindirect= 0.006 [0.002, 0.01]) and more lifetime AUD criteria (βindirect= 0.011 [0.006, 0.016]). In contrast, there was no evidence that parental alleles had indirect effects on offspring alcohol outcomes via parental relationship discord or divorce in the smaller number of families of African ancestry. In conclusion, parents transmit genetic risk for alcohol problems to their children not only directly, but also indirectly via genetically influenced aspects of the home environment. Further investigation of genetic nurture in non-European samples is needed.

Introduction:Suicidal thoughts and behaviors have partially distinct genetic etiologies. Methods:We used PRS-CS to create polygenic risk scores (PRSs) from GWAS of non-suicidal self-injury, broad-sense self-harm ideation, nonfatal suicide attempt, death by suicide, and depression. Using mixed-effect models, we estimated whether these PRSs were associated with a range of suicidal thoughts and behaviors in the Collaborative Study on the Genetics of Alcoholism (N= 7,526). Results:All PRSs were significantly associated with suicidal ideation and suicide attempt (betas = 0.08–0.44, false discovery rate [FDR] <0.023). All PRSs except non-suicidal self-injury PRS were associated with active suicidal ideation (betas = 0.14–0.22, FDR <0.003). Several associations remained significant in models where all significant PRSs were included as simultaneous predictors, and when all PRSs predicted suicide attempt, the PRS together explained 6.2% of the variance in suicide attempt. Significant associations were also observed between some PRSs and persistent suicidal ideation, non-suicidal self-injury, compounded suicide attempt, and desire to die. Conclusion:Our findings suggest that PRS for depression does not explain the entirety of the variance in suicidal thoughts and behaviors, with PRS specifically for suicidal thoughts and behaviors making additional and sometimes unique contributions.

Cutaneous T-cell lymphoma (CTCL) is a devastating lymphoid malignancy characterized by the accumulation of malignant T cells in the dermis and epidermis. Skin lesions cause serious symptoms that hamper quality of life and are entry sites for bacterial infection, a major cause of morbidity and mortality in advanced diseases. The mechanism driving the pathological processes that compromise the skin barrier remains unknown. Here, we report increased transepidermal water loss and compromised expression of the skin barrier proteins filaggrin and filaggrin-2 in areas adjacent to TOX-positive T cells in CTCL skin lesions. Malignant T cells secrete mediators (including cytokines such as interleukin 13 [IL-13], IL-22, and oncostatin M) that activate STAT3 signaling and downregulate filaggrin and filaggrin-2 expression in human keratinocytes and reconstructed human epithelium. Consequently, the repression of filaggrins can be counteracted by a cocktail of antibodies targeting these cytokines/receptors, small interfering RNA–mediated knockdown of JAK1/STAT3, and JAK1 inhibitors. Notably, we show that treatment with a clinically approved JAK inhibitor, tofacitinib, increases filaggrin expression in lesional skin from patients with mycosis fungoides. Taken together, these findings indicate that malignant T cells secrete cytokines that induce skin barrier defects via a JAK1/STAT3-dependent mechanism. As clinical grade JAK inhibitors largely abrogate the negative effect of malignant T cells on skin barrier proteins, our findings suggest that such inhibitors provide novel treatment options for patients with CTCL with advanced disease and a compromised skin barrier.

Recent genome-wide association studies (GWAS) have identified genetic markers of post-traumatic stress disorder (PTSD) in civilian and military populations. However, studies have yet to examine the genetics of PTSD while factoring in risk for alcohol dependence, which commonly co-occur. We examined genome-wide associations for DSM-IV PTSD among 4,978 trauma-exposed participants (31% with alcohol dependence, 50% female, 30% African ancestry) from the Collaborative Study on the Genetics of Alcoholism (COGA). We also examined associations of polygenic risk scores (PRS) derived from the Psychiatric Genomics Consortium (PGC)-PTSD Freeze 2 (N= 3533) and Million Veterans Program GWAS of PTSD (N= 5200) with PTSD and substance dependence in COGA, and moderating effects of sex and alcohol dependence. 7.3% of COGA participants met criteria for PTSD, with higher rates in females (10.1%) and those with alcohol dependence (12.3%). No independent loci met genome-wide significance in the PTSD meta-analysis of European (EA) and African ancestry (AA) participants. The PGC-PTSD PRS was associated with increased risk for PTSD (B= 0.126, p< 0.001), alcohol dependence (B= 0.231, p< 0.001), and cocaine dependence (B= 0.086, p< 0.01) in EA individuals. A significant interaction was observed, such that EA individuals with alcohol dependence and higher polygenic risk for PTSD were more likely to have PTSD (B= 0.090, p< 0.01) than those without alcohol dependence. These results further support the importance of examining substance dependence, specifically alcohol dependence, and PTSD together when investigating genetic influence on these disorders.

Adding keyword and number descriptors to book titles using the All My Books database improves the user-friendliness of library catalog searching, especially for books in a series. Widely used cataloging [...]

Wireless Sensor Network (WSN) is composed of different sensors attached to the same wireless medium. Sensor node data is usually forwarded to the base station, where it has been stored, evaluated, and processed. Ring Routing, a new energy-efficient distributed routing protocol aimed at larger-scale WSN applications with mobile sink and motionless sensor nodes. The structure ring is quickly converted, and they are capable of switching positions with regular nodes in a simple and effective manner, thereby minimizing the hotspot problem. In the network system, the central node is considered, and ring nodes with a certain distance are established while creating a ring structure. Since the sink nodes are powered by batteries, they deplete their batteries quicker than the other nodes, which is attributable to the accumulation of data traffic into the sink. Furthermore, when the ring configuration is disrupted due to ring node expiration, data transfer becomes tedious and causes significant delay. As a ring node starts to exhaust, its neighbor takes over as the ring node, and this selection of the regular node as the ring node is done optimally based on Multiple-Fitness Parameters such as Four-level energy consumption (4En), Distance (distance between the ring node and the regular node Distring− regand distance between network centers to regular node ΔDistC−ring${\Delta}Dis{t}_{C-ring}$) and delay S. Moreover, this optimal selection of the regular node to act as ring node will be carried out by a new hybrid algorithm referred to as Cuckoo Search Updated Sealion’s Attacking Technique (CSUSAT) that combines the standard crow search and sea lion optimization algorithm. At last, the supremacy of the presented approach is proved over other models.

Plant extract mediated biogenic synthesis of silver nanoparticles (AgNPs) has garnered considerable attention in nanotechnology due to its promising wound healing properties. This eco-friendly and cost-effective approach utilizes natural sources, such as the ethyl acetate extract of Nigella sativaL. (N. sativa) seeds, as a reducing agent. In this study, AgNPs were synthesized biogenically using N. sativaextract, and their wound healing potential was systematically assessed. Several methods for characterization are employed, incorporating ultraviolet-visible (UV-Vis) spectroscopy, fourier-transform infrared (FTIR) spectrometry, X-ray diffraction (XRD), scanning electron microscope (SEM) and dynamic light scattering (DLS) analysis were utilized to confirm successful synthesis and provide insight into the chemical and physical properties of AgNPs. When compared to a control group, human keratinocytes treated with AgNPs exhibited significantly enhanced proliferation and migration. Additionally, AgNPs were observed to increase the expression of wound-healing factors, (such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF)) as evidenced by western blot analysis. As a potent and naturally derived medicine for wound healing, AgNPs synthesized using N. sativaseed extract (ethyl acetate extract) potentially utilize the PDGF and VEGF signaling pathways to induce their therapeutic effects. Nevertheless, additional research is necessary to clarify the underlying mechanisms and assess the long-term safety and efficacy of this environmentally friendly method for producing AgNPs, which demonstrate remarkable wound-healing capabilities.

Type 1 diabetes is an organ-specific autoimmune disease resulting from the interaction of several genetic elements and yet undetermined environmental factors. It is characterized by a predominantly T-cell-mediated destruction of [...], The major predisposing genetic component in type 1 diabetes maps to the major histocompatibility complex locus in both mice and humans. To verify the HLA class II association with disease pathogenesis, we adopted the transgenic approach. Expression of HLA-DQ8, the molecule showing the strongest association with human type 1 diabetes, in the diabetes-predisposing milieu of NOD mice in the absence of the endogenous class II molecule I-[A.sup.g7] did not render susceptibility to type 1 diabetes. To study if providing a local proinflammatory environment would lead to diabetes in these mice, Aβ°.NOD.DQ8 were bred with C57BL/6 mice expressing tumor necrosis factor (TNF)-α in the β-cells of the islets of Langerhans. Surprisingly, although diabetes was evident in the F1 intercross expressing rat insulin promoter (RIP)-TNF, offspring lacking either endogenous or transgenic class II molecules developed accelerated diabetes with high frequency in both sexes. Moreover, expression of any functional class II molecule seemed to confer significant protection from diabetes in this model. Thus, neonatal expression of TNF-α in an islet-specific manner bypassed the requirement of [CD4.sup.+] T-cells and resulted in diabetes that could be mediated by [CD8.sup.+] T-cells. We also show for the first time that diabetes in NOD.RIP-TNF mice can occur independent of inheritance of NOD-derived idd1.

The compliance mechanism plays a crucial role in the MEMS (Micro-Electro-Mechanical Systems) device design as it provides elastic body deformation through respective force and motion transmission. This paper presents, an electrothermal compliant mechanism using V-beam combo structure. Design methodology, fabrication process flow, characterization results and future scope of the proposed device are elaborated. The limited elasticity of Silicon material resulted in limited response of the fabricated device compared to the FEM tool results. Hence an extended optimization for the design structure through POLYMUMPs process is recommended to overcome the limitation. The proposed device finds an application in RF switch domain with its low power consumption feature.

Early identification of individuals at high risk for alcohol use disorder (AUD) coupled with prompt interventions could reduce the incidence of AUD. In this study, we investigated whether Polygenic Risk Scores (PRS) can be used to evaluate the risk for AUD and AUD severity (as measured by the number of DSM‐5 AUD diagnostic criteria met) and compared their performance with a measure of family history of AUD. We studied individuals of European ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA). DSM‐5 diagnostic criteria were available for 7203 individuals, of whom 3451 met criteria for DSM‐IV alcohol dependence or DSM‐5 AUD and 1616 were alcohol‐exposed controls aged ≥21 years with no history of AUD or drug dependence. Further, 4842 individuals had a positive first‐degree family history of AUD (FH+), 2722 had an unknown family history (FH?), and 336 had a negative family history (FH−). PRS were derived from a meta‐analysis of a genome‐wide association study of AUD from the Million Veteran Program and scores from the problem subscale of the Alcohol Use Disorders Identification Test in the UK Biobank. We used mixed models to test the association between PRS and risk for AUD and AUD severity. AUD cases had higher PRS than controls with PRS increasing as the number of DSM‐5 diagnostic criteria increased (p‐values ≤ 1.85E−05) in the full COGA sample, the FH+ subsample, and the FH? subsample. Individuals in the top decile of PRS had odds ratios (OR) for developing AUD of 1.96 (95% CI: 1.54 to 2.51, p‐value = 7.57E−08) and 1.86 (95% CI: 1.35 to 2.56, p‐value = 1.32E−04) in the full sample and the FH+ subsample, respectively. These values are comparable to previously reported ORs for a first‐degree family history (1.91 to 2.38) estimated from national surveys. PRS were also significantly associated with the DSM‐5 AUD diagnostic criterion count in the full sample, the FH+ subsample, and the FH? subsample (p‐values ≤6.7E−11). PRS remained significantly associated with AUD and AUD severity after accounting for a family history of AUD (p‐values ≤6.8E−10). Both PRS and family history were associated with AUD and AUD severity, indicating that these risk measures assess distinct aspects of liability to AUD traits. We calculated polygenic risk scores (PRS) using variants having the same directions of effects in discovery datasets to exclude study‐specific findings and findings due to random variations. The PRS were significantly associated with AUD and AUD severity. Those in the top decile of PRS had odds ratios of 1.96 to develop AUD, comparable to odds ratios of the family history of AUD. PRS were also independent of family history and especially useful when family history information is not available.

There are many developed theories and implemented artificial systems in the area of machine consciousness, while none has achieved that. For a possible approach, we are interested in implementing a system by integrating different theories. Along this way, this paper proposes a model based on the global workspace theory and attention mechanism, and providing a fundamental framework for our future work. To examine this model, two experiments are conducted. The first one demonstrates the agent’s ability to shift attention over multiple stimuli, which accounts for the dynamics of conscious content. Another experiment of simulations of attentional blink and lag-1 sparing, which are two well-studied effects in psychology and neuroscience of attention and consciousness, aims to justify the agent’s compatibility with human brains. In summary, the main contributions of this paper are (1) Adaptation of the global workspace framework by separated workspace nodes, reducing unnecessary computation but retaining the potential of global availability; (2) Embedding attention mechanism into the global workspace framework as the competition mechanism for the consciousness access; (3) Proposing a synchronization mechanism in the global workspace for supporting lag-1 sparing effect, retaining the attentional blink effect.

Synonymous and noncoding single nucleotide polymorphisms (SNPs) in the KCNJ6gene, encoding G protein-gated inwardly rectifying potassium channel subunit 2 (GIRK2), have been linked with increased electroencephalographic frontal theta event-related oscillations (ERO) in subjects diagnosed with alcohol use disorder (AUD). To identify molecular and cellular mechanisms while retaining the appropriate genetic background, we generated induced excitatory glutamatergic neurons (iN) from iPSCs derived from four AUD-diagnosed subjects with KCNJ6variants (“Affected: AF”) and four control subjects without variants (“Unaffected: UN”). Neurons were analyzed for changes in gene expression, morphology, excitability and physiological properties. Single-cell RNA sequencing suggests that KCNJ6AF variant neurons have altered patterns of synaptic transmission and cell projection morphogenesis. Results confirm that AF neurons express lower levels of GIRK2, have greater neurite area, and elevated excitability. Interestingly, exposure to intoxicating concentrations of ethanol induces GIRK2 expression and reverses functional effects in AF neurons. Ectopic overexpression of GIRK2 alone mimics the effect of ethanol to normalize induced excitability. We conclude that KCNJ6variants decrease GIRK2 expression and increase excitability and that this effect can be minimized or reduced with ethanol.

Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N= 15,134. Our analyses included participants of European (NEUR= 12,659) and African (NAFR= 2475) ancestries. SUD outcomes included: (1) alcohol dependence, (2) nicotine dependence; (3) drug dependence, and (4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 01.37–1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11–1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09–1.18). The full model explained 6–13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86–8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.

Type 1 diabetes (T1D) is an organ-specific autoimmune disease characterized by immune-mediated destruction of the insulin-producing β-cells of the islets of Langerhans that results in life-long insulin dependence (1). Given [...]

Invasive thymoma, a malignant tumor of the thymus gland, constitutes between 0.2 percent and 1.5 percent of all cancers. This cancer is generally treated with surgery followed by radiation to kill any cancer cells that may have spread beyond the boundary of the surgically removed tissues. However, invasive thymoma often penetrates tissues in the chest and neck which are not surgically removable; if these areas are also outside of the region receiving radiotherapy, then relapse is certain. It is natural, therefore, that attempts be made to improve the results of treatment for invasive thymoma by including chemotherapy. A study was conducted to evaluate neoadjuvant chemotherapy for invasive thymoma. Neoadjuvant chemotherapy is administered prior to surgery not only to destroy deposits of cancer cells which may not be surgically removed, but also to reduce the size of the primary tumor and render it more amenable to surgical resection. A total of seven patients with invasive thymoma were treated with cisplatin, epirubicin, and etoposide prior to surgery. Following surgery, radiotherapy was administered in doses ranging from 4,600 to 6,000 cGy. (A Gy, or Gray, is a dose of radiation equivalent to one joule of energy absorbed per kilogram of tissue; cGy is 1/100th of a Gray.) All seven patients achieved partial responses to the neoadjuvant chemotherapy. (A partial response is defined as a reduction in tumor mass of at least 50 percent.) In four cases, it was possible to completely remove the tumor mass. In only one case was it impossible to remove the complete tumor as determined by gross examination. In the remaining two cases, only microscopic examination revealed that the entire tumor had not been removed. One patient died of a brain tumor; he was found to be free of thymoma at autopsy. The remaining six patients are currently alive and free of disease at follow-up periods ranging from 8 to 24 months. It is estimated that the two-year survival for this group of patients may be around 80 percent. (Consumer Summary produced by Reliance Medical Information, Inc.)

Aberrant connectivity of large-scale brain networks has been observed among individuals with alcohol use disorders (AUDs) as well as in those at risk, suggesting deficits in neural communication between brain regions in the liability to develop AUD. Electroencephalographical (EEG) coherence, which measures the degree of synchrony between brain regions, may be a useful measure of connectivity patterns in neural networks for studying the genetics of AUD. In 8810 individuals (6644 of European and 2166 of African ancestry) from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a Multi-Trait Analyses of genome-wide association studies (MTAG) on parietal resting-state theta (3–7 Hz) EEG coherence, which previously have been associated with AUD. We also examined developmental effects of GWAS findings on trajectories of neural connectivity in a longitudinal subsample of 2316 adolescent/young adult offspring from COGA families (ages 12–30) and examined the functional and clinical significance of GWAS variants. Six correlated single nucleotide polymorphisms located in a brain-expressed lincRNA (ENSG00000266213) on chromosome 18q23 were associated with posterior interhemispheric low theta EEG coherence (3–5 Hz). These same variants were also associated with alcohol use behavior and posterior corpus callosum volume, both in a subset of COGA and in the UK Biobank. Analyses in the subsample of COGA offspring indicated that the association of rs12954372 with low theta EEG coherence occurred only in females, most prominently between ages 25 and 30 (p< 2 × 10-9). Converging data provide support for the role of genetic variants on chromosome 18q23 in regulating neural connectivity and alcohol use behavior, potentially via dysregulated myelination. While findings were less robust, genome-wide associations were also observed with rs151174000 and parieto-frontal low theta coherence, rs14429078 and parieto-occipital interhemispheric high theta coherence, and rs116445911 with centro-parietal low theta coherence. These novel genetic findings highlight the utility of the endophenotype approach in enhancing our understanding of mechanisms underlying addiction susceptibility.

Background:Suicidal thoughts and behaviors (STBs) and nonsuicidal self-injury (NSSI) behaviors are moderately heritable and may reflect an underlying predisposition to depression, impulsivity, and cognitive vulnerabilities to varying degrees. Objectives:We aimed to estimate the degrees of association between genetic liability to depression, impulsivity, and cognitive performance and STBs and NSSI in a high-risk sample. Methods:We used data on 7,482 individuals of European ancestry and 3,359 individuals of African ancestry from the Collaborative Study on the Genetics of Alcoholism to examine the links between polygenic scores (PGSs) for depression, impulsivity/risk-taking, and cognitive performance with 3 self-reported indices of STBs (suicidal ideation, persistent suicidal ideation defined as ideation occurring on at least 7 consecutive days, and suicide attempt) and with NSSI. Results:The PGS for depression was significantly associated with all 4 primary self-harm measures, explaining 0.6–2.5% of the variance. The PGS for risk-taking behaviors was also associated with all 4 self-harm behaviors in baseline models, but was no longer associated after controlling for a lifetime measure of DSM-IV alcohol dependence and abuse symptom counts. Polygenic predisposition for cognitive performance was negatively associated with suicide attempts (q= 3.8e−4) but was not significantly associated with suicidal ideation nor NSSI. We did not find any significant associations in the African ancestry subset, likely due to smaller sample sizes. Conclusions:Our results encourage the study of STB as transdiagnostic outcomes that show genetic overlap with a range of risk factors.

African Americans (AA) have lower prevalence of alcohol dependence and higher subjective response to alcohol than European Americans. Genome‐wide association studies (GWAS) have identified genes/variants associated with alcohol dependence specifically in AA; however, the sample sizes are still not large enough to detect variants with small effects. Admixture mapping is an alternative way to identify alcohol dependence genes/variants that may be unique to AA. In this study, we performed the first admixture mapping of DSM‐IV alcohol dependence diagnosis, DSM‐IV alcohol dependence criterion count, and two scores from the self‐rating of effects of ethanol (SRE) as measures of response to alcohol: the first five times of using alcohol (SRE‐5) and average of SRE across three times (SRE‐T). Findings revealed a region on chromosome 4 that was genome‐wide significant for SRE‐5 (pvalue = 4.18E‐05). Fine mapping did not identify a single causal variant to be associated with SRE‐5; instead, conditional analysis concluded that multiple variants collectively explained the admixture mapping signal. PPARGC1A, a gene that has been linked to alcohol consumption in previous studies, is located in this region. Our finding suggests that admixture mapping is a useful tool to identify genes/variants that may have been missed by current GWAS approaches in admixed populations.

Predictive models have succeeded in distinguishing between individuals with Alcohol use Disorder (AUD) and controls. However, predictive models identifying who is prone to develop AUD and the biomarkers indicating a predisposition to AUD are still unclear. Our sample (n= 656) included offspring and non-offspring of European American (EA) and African American (AA) ancestry from the Collaborative Study of the Genetics of Alcoholism (COGA) who were recruited as early as age 12 and were unaffected at first assessment and reassessed years later as AUD (DSM-5) (n= 328) or unaffected (n= 328). Machine learning analysis was performed for 220 EEG measures, 149 alcohol-related single nucleotide polymorphisms (SNPs) from a recent large Genome-wide Association Study (GWAS) of alcohol use/misuse and two family history (mother DSM-5 AUD and father DSM-5 AUD) features using supervised, Linear Support Vector Machine (SVM) classifier to test which features assessed before developing AUD predict those who go on to develop AUD. Age, gender, and ancestry stratified analyses were performed. Results indicate significant and higher accuracy rates for the AA compared with the EA prediction models and a higher model accuracy trend among females compared with males for both ancestries. Combined EEG and SNP features model outperformed models based on only EEG features or only SNP features for both EA and AA samples. This multidimensional superiority was confirmed in a follow-up analysis in the AA age groups (12–15, 16–19, 20–30) and EA age group (16–19). In both ancestry samples, the youngest age group achieved higher accuracy score than the two other older age groups. Maternal AUD increased the model’s accuracy in both ancestries’ samples. Several discriminative EEG measures and SNPs features were identified, including lower posterior gamma, higher slow wave connectivity (delta, theta, alpha), higher frontal gamma ratio, higher beta correlation in the parietal area, and 5 SNPs: rs4780836, rs2605140, rs11690265, rs692854, and rs13380649. Results highlight the significance of sampling uniformity followed by stratified (e.g., ancestry, gender, developmental period) analysis, and wider selection of features, to generate better prediction scores allowing a more accurate estimation of AUD development.

Aggression often occurs alongside alcohol and drug misuse. However, it is not clear whether the latent and manifest relations among alcohol‐related, drug‐related, and non–substance‐related aggression are separate manifestations of a single construct or instead are 3 distinct constructs. To examine these associations, we conducted a preregistered analysis of 13,490 participants in the Collaborative Study on the Genetics of Alcoholism. In a structured interview, participants reported their lifetime perpetration of these 3 aggression phenotypes. The data were better fit by a model that treated these aggression phenotypes as 3 distinct latent factors, as compared to models in which the items all loaded onto 1 (“general”) or 2 (“substance‐related” and “non–substance‐related”) aggression factors. This 3‐factor model fit better for men than women. Subsequent exploratory analyses then showed that among these 3 factors, alcohol‐related aggression explained the variance of overall aggression better than the other 2 factors. Our findings suggest that these 3 forms of aggression are distinct phenotypes (especially among men). Yet, people’s alcohol‐related aggression can accurately characterize their overall aggressive tendencies across these domains. Future research will benefit from articulating the unique and shared pathways and risk factors underlying each of these facets of aggression. This figure depicts the results of a factor analysis that shows how alcohol‐related aggression (ARA), drug‐related aggression (DRA), and non‐substance‐related aggression (NSRA) are best modeled as distinct constructs, instead of reflecting a general aggressive tendency.

Pleural effusions are among the first clinical manifestations of malignant pleural mesothelioma (MPM) and often constitute the only available material for diagnosis. Although an MPM diagnosis can be reliable on cytology, the reported sensitivity is low (30% to 75%). Particularly, it can be hard to discriminate epithelioid MPM, the most common histotype, from reactive mesothelial hyperplasia (MH). Currently, BRCA1-associated protein 1 (BAP1) and CDKN2A(p16), evaluated by immunohistochemistry and fluorescent in situhybridization, respectively, are the most valuable markers to discriminate MPM and MH. Both markers have a high specificity, but their sensitivity is not always satisfying, even when used together. We have recently developed a 117-gene expression panel, based on Nanostring technology, able to differentiate epithelioid MPM from MH pleural tissues better than BAP1 and p16. Herein, we evaluated the efficacy of the same panel on an independent retrospective cohort of 23 MPM and 11 MH pleural effusions (cell blocks and smears). The overall sensitivity and specificity of the panel were equal to 0.9565 and 1, respectively. Moreover, the panel performance was compared with BAP1 and p16 on 25 cell blocks. Sensitivity levels of gene panel, BAP1 alone, p16 alone, and BAP1 plus p16 were 1, 0.5882, 0.4706, and 0.7647, respectively. Specificity was always 1. Although further validation is needed, this gene panel could really facilitate patients' management, allowing a definitive MPM diagnosis directly on pleural effusions.

There are gaps in the literature on service use (help‐seeking and treatment utilization) for alcohol problems among those with alcohol use disorder (AUD). First, policy changes and cultural shifts (e.g., insurance) related to AUD have occurred over the last few decades, making it important to study generational differences. Second, multiple studies have found that females receive fewer services than males, and exploring whether these sex differences persist across generations can inform public health and research endeavors. The current study examined service use for alcohol problems among individuals with AUD. The aims were as follows: (i) to describe service use for alcohol problems; (ii) to assess generational differences (silent [b. 1928 to 1945], boomer [b. 1946 to 1964], generation X [b. 1965 to 1980], millennial [b. 1981 to 1996]) in help‐seeking and treatment utilization; and (iii) to examine sex differences across generations. Data were from affected family members of probands who participated in the Collaborative Study on the Genetics of Alcoholism (N= 4,405). First, frequencies for service use variables were calculated across generations. Pearson chi‐square and ANOVA were used to test for differences in rates and types of service use across generations, taking familial clustering into account. Next, Cox survival modeling was used to assess associations of generation and sex with time to first help‐seeking and first treatment for AUD, and time from first onset of AUD to first help‐seeking and first treatment. Interactions between generation and sex were tested within each Cox regression. Significant hazards were found in all 4 transitions. Overall, younger generations used services earlier than older generations, which translated into higher likelihoods of these behaviors. Regardless of generation, younger females were less likely to use services than males. There are generational and sex differences in service use for alcohol problems among individuals with AUD. Policy and clinical implications are discussed. Generational (silent, baby boomer, generation X, millennial) and sex (male, female) differences in service use for alcohol problems were found among individuals with alcohol use disorder. Overall, generation X and millennial individuals were more likely to use services than baby boomers. Young females were less likely than their male counterparts to use services. These differences broadly map onto policy (e.g., insurance) and social (e.g., decreasing stigma) shifts. Potential clinical implications for public health and intervention efforts are explored.

Family history (FH) is an important risk factor for the development of alcohol use disorder (AUD). A variety of dichotomous and density measures of FH have been used to predict alcohol outcomes; yet, a systematic comparison of these FH measures is lacking. We compared 4 density and 4 commonly used dichotomous FH measures and examined variations by gender and race/ethnicity in their associations with age of onset of regular drinking, parietal P3 amplitude to visual target, and likelihood of developing AUD. Data from the Collaborative Study on the Genetics of Alcoholism (COGA) were utilized to compute the density and dichotomous measures. Only subjects and their family members with DSM‐5 AUD diagnostic information obtained through direct interviews using the Semi‐Structured Assessment for the Genetics of Alcoholism(SSAGA) were included in the study. Area under receiver operating characteristic curves were used to compare the diagnostic accuracy of FH measures at classifying DSM‐5 AUD diagnosis. Logistic and linear regression models were used to examine associations of FH measures with alcohol outcomes. Density measures had greater diagnostic accuracy at classifying AUD diagnosis, whereas dichotomous measures presented diagnostic accuracy closer to random chance. Both dichotomous and density measures were significantly associated with likelihood of AUD, early onset of regular drinking, and low parietal P3 amplitude, but density measures presented consistently more robust associations. Further, variations in these associations were observed such that among males (vs. females) and Whites (vs. Blacks), associations of alcohol outcomes with density (vs. dichotomous) measures were greater in magnitude. Density (vs. dichotomous) measures seem to present more robust associations with alcohol outcomes. However, associations of dichotomous and density FH measures with different alcohol outcomes (behavioral vs. neural) varied across gender and race/ethnicity. These findings have great applicability for alcohol research examining FH of AUD. Using Collaborative Study on the Genetics of Alcoholism (COGA) data, we compared the predictability of four density and four dichotomous family history measures on three outcomes: age of onset of regular drinking, visual P3 amplitude, and likelihood of developing alcohol use disorder (AUD) across gender and race/ethnicity. Density measures had greater diagnostic accuracy at classifying AUD. Both measures significantly predicted all three outcomes, but density measures were more robust among males (vs. females) and Whites (vs. Blacks) for all outcomes.

Trending features brief essays on current issues or new ideas in public librarianship. In my last few months of undergraduate study, I realized that I had a decision to make. [...]

Materials-based drug delivery approaches have garnered substantial attention in recent years due to their potential to revolutionize pharmaceutical interventions. This abstract provides a concise overview of recent advancements and future prospects in this rapidly evolving field. Materials such as nanoparticles, liposomes, polymers, and hydrogels have emerged as versatile carriers for drug delivery. These materials facilitate precise control over drug release kinetics, enabling targeted and sustained therapeutic effects. Smart materials with responsiveness to external stimuli or physiological conditions have further enhanced drug delivery precision. Personalized medicine approaches are gaining traction, tailoring drug delivery systems to individual patient profiles and needs. The horizon for materials-based drug delivery is bright. Ongoing research is focused on refining material design, streamlining production processes, and ensuring safety profiles. Collaborative efforts among researchers, clinicians, and industry stakeholders are crucial for translating these advancements into clinical practice. Additionally, the convergence of drug delivery with diagnostics and imaging holds immense potential for personalized and efficient healthcare solutions. As materials-based drug delivery continues to evolve, it stands poised to reshape the landscape of pharmaceuticals, offering the promise of more effective and patient-centered therapies for a wide range of medical conditions.

This paper outlines an augmented robotic architecture to study the conditions of successful Human-Humanoid Interaction (HHI). The architecture is designed as a testable model generator for interaction centred on the ability to emit, display and detect honest signals. First we overview the biological theory in which the concept of honest signals has been put forward in order to assess its explanatory power. We reconstruct the application of the concept of honest signalling in accounting for interaction in strategic contexts and in laying bare the foundation for an automated social metrics. We describe the modules of the architecture, which is intended to implement the concept of honest signalling in connection with a refinement provided by delivering the sense of co-presence in a shared environment. Finally, an analysis of Honest Signals, in term of body postures, exhibited by participants during the preliminary experiment with the Geminoid Hi-1 is provided.