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Here we used deep neural network + hidden Markov model (DNN+HMM) to provide a computational account for the relationship among holistic processing (HP), face scanning pattern and face recognition performance. The model accounted for the positive associations between HP and eyes-focused face scanning pattern/face recognition performance observed in the literature regardless of the version of the composite task used to measure HP. Interestingly, we observed a quadratic relationship between HP and face scanning pattern, where models being highly eyes-focused or highly nose-focused had lower HP. By inspecting fixation locations and associated attention window size in the model and XAI methods, we found that the eyes- and nose-focused models both developed local and holistic internal representations during training, and their difference was in the temporal dynamics of how these representations were used. Our findings demonstrated how computational modeling could unravel the mechanisms underlying cognition not readily observable in human data.

Large language models (LLMs) were trained to predict words without having explicit semantic word representations as humans do. Here we compared LLMs and humans in re-solving semantic ambiguities at the word/token level by ex-amining the case of segmenting overlapping ambiguous strings in Chinese sentence reading, where three characters “ABC” could be segmented in either “AB/C” or “A/BC” depending on the context. We showed that although LLMs performed worse than humans, they demonstrated a similar interaction effect between segmentation structure and word frequency order, suggesting that this effect observed in humans could be accounted for by statistical learning of word/token occurrence regularities without assuming an explicit semantic word representation. Nevertheless, across stimuli LLMs' responses were not correlated with any hu-man performance or eye movement measures, suggesting differences in the underlying processing mechanisms. Thus, it is essential to understand these differences through XAI methods to facilitate LLM adoption.

Here we present a new Explainable AI (XAI) method to probe the functional partition in AI models by comparing features attended to at different layers with human attention driven by diverse task demands. We applied this method to explain an object detector Yolo-v5s in multi-category and single-category object detection tasks. We found that the model's neck showed higher similarity to human attention during object detection, indicating a reliance on diagnostic features in the neck, whereas its backbone showed higher similarity to attention during passive viewing, indicating salient local features encoded. With this understanding of its functional partition, using Yolo-v5s as a model for human cognition, our comparative analysis against human attention when providing explanations for object detection revealed that humans attended to a combination of diagnostic and salient features during explaining multi-category general object detection but attended to mainly diagnostic features when explaining single-category human/vehicle detection in driving scenarios.

The recent surge in online learning demands better ways to monitor students' mind wandering (MW) episodes. We examined whether different eye movement measures were associated with MW in tasks with different cognitive demands. We found that a reduced number of fixations was associated with MW in tasks involving searching for information without clearly defined strategies. A larger variance in pupil diameter, as well as reduced eye movement consistency, were associated with MW when imagining a scenario with a central fixation. Reduced eye movement consistency, as well as reduced joint attention with another participant, were both associated with MW in tasks involving a clearly defined strategy. Interestingly, none of these eye movement measures was associated with MW in tasks involving well-learned visual routines such as face and scene identification, suggesting idiosyncrasy in eye movement behavior in these tasks. These findings have important implications for developing effective methods for detecting MW.

A major limitation to developing chimeric antigen receptor (CAR)-T cell therapies for solid tumors is identifying surface proteins highly expressed in tumors but not in normal tissues. Here, we identify Tyrosinase Related Protein 1 (TYRP1) as a CAR-T cell therapy target to treat patients with cutaneous and rare melanoma subtypes unresponsive to immune checkpoint blockade. TYRP1 is primarily located intracellularly in the melanosomes, with a small fraction being trafficked to the cell surface via vesicular transport. We develop a highly sensitive CAR-T cell therapy that detects surface TYRP1 in tumor cells with high TYRP1 overexpression and presents antitumor activity in vitro and in vivo in murine and patient-derived cutaneous, acral and uveal melanoma models. Furthermore, no systemic or off-tumor severe toxicities are observed in an immunocompetent murine model. The efficacy and safety profile of the TYRP1 CAR-T cell therapy supports the ongoing preparation of a phase I clinical trial.

IntroductionFemale reproductive function depends on a choreographed sequence of hormonal secretion and action, where specific stresses such as inflammation exert profound disruptions. Specifically, acute LPS-induced inflammation inhibits gonadotropin production and secretion from the pituitary, thereby impacting the downstream production of sex hormones. These outcomes have only been observed in acute inflammatory stress and little is known about the mechanisms by which chronic inflammation affects reproduction. In this study we seek to understand the chronic effects of LPS on pituitary function and consequent luteinizing and follicle stimulating hormone secretion.MethodsA chronic inflammatory state was induced in female mice by twice weekly injections with LPS over 6 weeks. Serum gonadotropins were measured and bulk RNAseq was performed on the pituitaries from these mice, along with basic measurements of reproductive biology.ResultsSurprisingly, serum luteinizing and follicle stimulating hormone was not inhibited and instead we found it was increased with repeated LPS treatments.DiscussionAnalysis of bulk RNA-sequencing of murine pituitary revealed paracrine activation of TGFβ pathways as a potential mechanism regulating FSH secretion in response to chronic LPS. These results provide a framework with which to begin dissecting the impacts of chronic inflammation on reproductive physiology.

In recent decades, the governance of educational systems has experienced dramatic changes in many countries. Schools have been given more autonomy whilst being held increasingly accountable at the central level through standardized testing and other forms of external evaluation. The mechanisms of performance-based accountability (PBA) and the consequences attached to test results vary. In high-stakes systems, teachers' careers are more directly connected to students' performance, and low performing schools might risk closure, whereas in lower-stakes systems, the official administrative consequences of accountability for school actors are more symbolic than material. The main aim of this paper is to understand the impact of different forms of PBA on teachers' work from a comparative perspective. Most research on this topic is based on single-context case studies, which makes it difficult to understand the impact of policy factors and professional contexts in teachers' decisions and autonomy. To address this challenge, we review recent investigations (2017-2020) on the topic and compare their findings in different teachers' regulatory contexts. The review includes 101 articles from the SCOPUS and Web of Science databases. We find that evidence on the impact of PBA on teachers' perceptions and beliefs are variegated, and that the implications of PBA on teachers' autonomy does not only depend on the level of accountability stakes, but on teachers' professional regulation.

Technology in the digital era is currently progressing very rapidly. This is marked by the increasingly massive number of social media users in everyday life. Survey results from the Indonesian Internet Service Providers Association (APJII) in 2022 recorded that the number of internet users in Indonesia reached 196.7 million people. This number increased by 23.5 million or 8.9% compared to 2018. With information technology and the internet, information is now becoming more easily spread and can be accessed by all levels of society thanks to the internet, not just people in urban areas, but people living there. in rural areas too. The Ogan Ilir Regency Government initiated information technology infrastructure including village internet or Digital Village to solve the problem of inequality in digitalization of society in rural and urban areas. Development and implementation of a digital village is a program that implements electronic-based government system (SPBE) services to the community and empowers the community based on the use of technology. This research aims to conduct a survey of information technology infrastructure to identify village potential, marketing and accelerating access and public services. Apart from that, this research also identifies digital-based life patterns of people in rural and urban areas, as well as to advance economic development in rural areas to improve SPBE services in Ogan Ilir Regency. The method used is a quantitative method for surveying and mapping the use of information technology in villages and ultimately producing the concept of an independent digital village. Research data was obtained from surveys and FGDs with the Ogan Ilir district government, village heads, village communities and micro, small and medium enterprises. Meanwhile, secondary data will be obtained through the results of MSME and village profiles from the Central Statistics Agency.

Canopy base height (CBH) and canopy bulk density (CBD) are forest canopy fuel parameters that are key for modeling the behavior of crown wildfires. In this work, we map them at a pan-European scale for the year 2020, producing a new dataset consisting of two raster layers containing both variables at an approximate resolution of 100 m. Spatial data from Earth observation missions and derived down-stream products were retrieved and processed using artificial intelligence to first estimate a map of aboveground biomass (AGB). Allometric models were then used to estimate the spatial distribution of CBH using the canopy height values as explanatory variables and CBD using AGB values. Ad-hoc allometric models were defined for this study. Data provided by FIRE-RES project partners and acquired through field inventories was used for validating the final products using an independent dataset of 804 ground-truth sample plots. The CBH and CBD raster maps have, respectively, the following accuracy regarding specific metrics reported from the modeling procedures: (i) coefficient of correlation (R) of 0.445 and 0.330 (p-value < 0.001); (ii) root mean square of error (RMSE) of 3.9 m and 0.099 kg m−3; and (iii) a mean absolute percentage error (MAPE) of 61% and 76%. Regarding CBD, the accuracy metrics improved in closed canopies (canopy cover > 80%) to R = 0.457, RMSE = 0.085, and MAPE = 59%. In short, we believe that the degree of accuracy is reasonable in the resulting maps, producing CBH and CBD datasets at the pan-European scale to support fire mitigation and crown fire simulations.

Abstract Background This pilot study aimed to provide supportive evidence for the feasibility of conducting a full-scale intervention trial with patients newly diagnosed with head and neck cancer (HNC). This included assessing the acceptability and potential usefulness of the PTSD Coach mobile app as an early self-management intervention that gives information about anxiety symptoms, offers self-assessment of symptoms with feedback, tools to self-manage anxiety, and connects to support. Methods A three-arm randomized controlled trial was conducted. The primary pilot study questions related to feasibility were: (1) can we recruit enough (i.e., n = 60 over 8 months or 8/month) and retain a sufficient proportion (i.e., ≥ 85% at three months post-randomization, having completed the primary outcome) of patients with HNC in all trial arms? (2) Will there be at least a 90% completion rate of PTSD Coach within 3 weeks from randomization? (3) Will at least 85% of the content for each module of PTSD Coach be completed? (4) Will there be at least a 90% completion rate of the attention-control tasks (i.e., 45 min/week over 3 weeks)? (5) What would be the anticipated sample size for a full study? (6) We also explored a signal for intervention effects on 1-, 3-, and 6-month levels of cancer-related anxiety, quality of life, anxiety and depression, self-stigma of seeking help, and professional psycho-oncology service uptake. Results Participants comprised 39 patients (11 experimental group (EG), 13 attention-control (AC), 15 usual care (UC)), primarily male (82%). Enrolment was lower than expected, with strategies implemented to increase the study’s participation rate (i.e., shortening the questionnaire, more relevant AC games, pacing study components, and enlarging eligibility to 4 weeks post-diagnosis instead of 2). Retention rates, intervention completion rates, and completion time were adequate. The intervention was acceptable with all patients (100%) who received PTSD Coach reporting it a positive experience and that they would recommend it to others. When compared to UC, there was a signal for the PTSD Coach group to report lower 3-month cancer-related anxiety (PCL-S; eta squared = 0.013), lower anxiety and depression (HADS; eta squared = 0.015), anxiety (HADS-A; eta squared = 0.028), and higher functional wellbeing (FACT-FW; eta squared = 0.09), based on effect sizes calculated across all three groups. The sample size for a full study was estimated to be 118 to 154 per group. Conclusion A repeat pilot study with an expanded oncology population is warranted to further investigate feasibility prior to a full Phase III study. PTSD Coach could be a valuable self-management tool as an initial stepped-care approach intervention in patients newly diagnosed with HNC. Trial registration ClinicalTrials.gov, NCT03651570 . Registered June 26, 2018.

Abstract Background The increased degradation of the insulin receptor β subunit (InsRβ) in lysosomes contributes to the development of insulin resistance and type 2 diabetes mellitus. Endoplasmic reticulum (ER) stress contributes to insulin resistance through several mechanisms, including the reduction of InsRβ levels. Here, we examined how peroxisome proliferator-activated receptor (PPAR)β/δ regulates InsRβ levels in mouse skeletal muscle and C2C12 myotubes exposed to the ER stressor tunicamycin. Methods Wild-type (WT) and Ppard −/− mice, WT mice treated with vehicle or the PPARβ/δ agonist GW501516, and C2C12 myotubes treated with the ER stressor tunicamycin or different activators or inhibitors were used. Results Ppard −/− mice displayed reduced InsRβ protein levels in their skeletal muscle compared to wild-type (WT) mice, while the PPARβ/δ agonist GW501516 increased its levels in WT mice. Co-incubation of tunicamycin-exposed C2C12 myotubes with GW501516 partially reversed the decrease in InsRβ protein levels, attenuating both ER stress and the increase in lysosomal activity. In addition, the protein levels of the tyrosine kinase ephrin receptor B4 (EphB4), which binds to the InsRβ and facilitates its endocytosis and degradation in lysosomes, were increased in the skeletal muscle of Ppard −/− mice, with GW501516 reducing its levels in the skeletal muscle of WT mice. Conclusions Overall, these findings reveal that PPARβ/δ activation increases InsRβ levels by alleviating ER stress and lysosomal degradation.

Circulating fluidized bed combustion (CFBC) fly ash has the potential as a precursor to making geopolymer concrete because of its rich silica and alumina content. However, there is a problem in utilizing CFBC fly ash caused by its chemical and physical properties that differ from the widely used pulverized coal combustion (PCC) fly ash. CFBC fly ash has a higher water requirement than PCC fly ash due to its angular particle shape, and higher sulfur and lime contained also caused a different reaction in the geopolymer system. Mechanical activation by milling the CFBC fly ash could decrease the water requirement in the mixture and make good quality CFBC fly sh-based geopolymer concrete. Three CFBC fly ash samples from different power plants in Indonesia with different chemical compositions were used in this research. The first had a low lime and no sulfur content, the second had high lime and no sulfur content, and the third had high lime and sulfur content. The milling process using a ball mill for two hours decreased the water requirement, as shown in the lower normal consistency of the fly ash. The reactivity also was increased, shown by the faster initial setting time. Besides its higher reactivity, lower water requirement increased the compressive strength of geopolymer mortar produced. This study also showed that the existence of calcium and sulfur content in the CFBC fly ash could cause unexpected results shown by the change of initial setting time, water requirement, and compressive strength.

Abstract Background Attention-deficit/hyperactivity disorder (ADHD) is a common neuro-developmental disorder that often persists into adulthood. Moreover, it is frequently accompanied by bipolar disorder (BD) as well as borderline personality disorder (BPD). It is unclear whether these disorders share underlying pathomechanisms, given that all three are characterized by alterations in affective states, either long or short-term. BD is characterized by infrequent but intense mood shifts, while ADHD and BPD involve more dynamic emotional fluctuations. It is yet to be determined whether these disorders represent distinct phenomena or different points on a spectrum of affective dysregulation. Methods This study seeks to distinguish the emotional dysregulation of BPD, ADHD, and BD by using digital phenotyping, a measurement burst electronic-diary method with different sampling rates, and accelerometry to measure participants’ activity. Our study will include 480 participants aged 14 to 50 (120 each from BPD, ADHD, BD, and healthy control groups) from five European sites. Participants’ smartphones will provide continuous data on their digital phenotypes, i.e., by indicators of physical activity and communication, for one year, along with daily evening ratings of mood and sleep. Moreover, five intensive measurement periods of five days each, called measurement bursts, will occur throughout the year, with electronic diaries asking participants to report on mood, self-esteem, impulsivity, life events, social interactions, and dysfunctional behaviors ten times a day. Moreover, participants will wear activity sensors during the five measurement bursts. Statistical analysis aims to identify whether affective dysregulation aspects share or differ across disorders. Specifically, data analysis aims to investigate the differences in parameters of affect fluctuation such as attractor strength and variability between disorders and to test the association of genetic risk factors for psychiatric disorders and resilience factors with critical parameters of affect modulation. Discussion The results of this study offer the potential to link patients’ external exposures with their affective state, reduce misdiagnosis, and determine the best timing for therapeutic interventions. Potential limitations of the study include insufficient recruitment of patients and drop-outs due to various protocol violations. Trial registration Study code: DRKS00028917, registered 27.07.2022, https://drks.de/search/de/trial/DRKS00028917 .

Abstract We studied nosocomial transmission of multidrug-resistant bla NDM-1-containing Klebsiella pneumoniae ST147 in a Dutch pediatric oncology center. Whole-genome multilocus sequence typing revealed two genetic clusters consisting of 2 and 5 K. pneumoniae isolates, both from Ukrainian medical evacuees and Dutch patients. Ukrainian patients were colonized at admission, and two Dutch patients developed bacteremia. Temporal and spatial transmission links were assessed and sampling of sinks revealed environmental contamination of bla NDM-1-containing K. pneumoniae with genetic relatedness to cluster isolates. Phylogenetic analysis of 163 K. pneumoniae ST147 isolates from the Dutch national surveillance revealed that transmission-related isolates formed a unique phylogenetic branch. In conclusion, we demonstrate nosocomial transmission of unique bla NDM-1-containing K. pneumoniae ST147 strains introduced by Ukrainian patients. Sink drains colonized by genetically similar bla NDM-1-containing strains in rooms designated as spatial links within the cluster were considered the potential source of transmission. Healthcare professionals should be aware of these risks, particularly in settings with susceptible patients exposed to antibiotic pressure.

Abstract This study presents characterisation of diatom’s PtLPCAT1 (acyl-CoA: lysophosphatidylcholine acyltransferase) activity in phospholipid remodelling. In this research microsomal fractions of yeast Δale1 mutant overexpressing PtLPCAT1 were used as a source of the tested enzyme. In the assays evaluating remodelling of different phospholipids by PtLPCAT1 not modified microsomal fractions of the tested yeast were used. The enzyme most intensively remodelled fatty acid composition of microsomal phosphatidylcholine (PC), however, it was also able to remodel phosphatidylethanolamine (PE) and phosphatidic acid (PA). To study the ability of the tested enzyme to remodel PC molecules containing fatty acids from the VLC-PUFA biosynthetic pathway the tested microsomes were enriched biochemically with: sn-1-18:1-sn-2-18:3(n-3)-PC, sn-1-18:1-sn-2-18:3(n-6)-PC, sn-1-18:1-sn-2-18:4(n-3)-PC, sn-1-18:1-sn-2-20:4(n-3)-PC and sn-1-18:1-sn-2-20:5(n-3)-PC. Further on it was shown that PtLPCAT1 was able to remodel PC of such modified microsomes with higher intensity than PC of unmodified microsomes. The remodelling efficiency of PtLPCAT1 was affected also by fatty acid donors; the process was most efficient when acyl-CoAs with unsaturated fatty acids were in the assays. In comparative studies the properties of Arabidopsis AtLPCAT1 and yeast ALE1 were tested. Effect of the temperature and pH values on the remodelling activity of PtLPCAT1 was also examined.

La recuperació de l’autogovern de Catalunya va ser possible amb l’aprovació de la Constitució de 1978 i del primer Estatut de 1979. Sobre aquestes bases jurídiques, les institucions catalanes han pogut exercir un poder polític important, però limitat, tenint en compte el potencial que permetia desenvolupar el marc jurídic. La insatisfacció sobre el contingut de l’autogovern i sobre el reconeixement de Catalunya com a entitat nacional diferenciada dins l’Estat ha portat en aquests darrers anys a diverses iniciatives per superar les limitacions existents, singularment la reforma de l’Estatut i l’opció per la independència. Aquests intents no han assolit els resultats previstos, la qual cosa comporta la necessitat que les institucions i les forces polítiques afrontin el futur de l’autogovern des de noves perspectives.

La hisenda és una de les peces clau de l’autogovern. És a dir, la determinació de quins són els recursos de què disposa el govern territorial i de quin és l’abast de les responsabilitats normatives i administratives sobre aquests recursos. El finançament de la Generalitat de Catalunya ha estat objecte de successives reformes des de les primeres eleccions autonòmiques l’any 1980, culminant amb la reforma de 2009. En el fons del debat sobre el finançament hi ha subjacent el debat sobre el model d’Estat i, concretament, sobre dues qüestions fonamentals. Per una banda, la pulsió entre la visió pròpia d’un Estat unitari, on el poder polític està concentrat en el govern central, i la visió pròpia d’un Estat federal, on el poder polític està repartit (i, en alguns punts, és compartit) entre el govern central i els governs territorials d’àmbit intermedi. I, per una altra banda, les tensions derivades d’una realitat que manifesta de forma palesa l’asimetria existent entre els diferents territoris quant a voluntat d’autogovern i grau d’autoconsciència nacional. Aquestes dues qüestions incideixen de manera determinant en el model d’hisenda i en l’orientació de les possibles reformes, que haurien de tenir un sentit o un altre segons quin sigui el model d’estat que es persegueixi.