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Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma - DIPG), is the primary cause of brain tumor-related death in pediatric patients. DIPG is characterized by a median survival of <12 months from diagnosis, harboring the worst 5-year survival rate of any cancer. Corticosteroids and radiation are the mainstay of therapy; however, they only provide transient relief from the devastating neurological symptoms. Numerous therapies have been investigated for DIPG, but the majority have been unsuccessful in demonstrating a survival benefit beyond radiation alone. Although many barriers hinder brain drug delivery in DIPG, one of the most significant challenges is the blood-brain barrier (BBB). Therapeutic compounds must possess specific properties to enable efficient passage across the BBB. In brain cancer, the BBB is referred to as the blood-brain tumor barrier (BBTB), where tumors disrupt the structure and function of the BBB, which may provide opportunities for drug delivery. However, the biological characteristics of the brainstem's BBB/BBTB, both under normal physiological conditions and in response to DIPG, are poorly understood, which further complicates treatment. Better characterization of the changes that occur in the BBB/BBTB of DIPG patients is essential, as this informs future treatment strategies. Many novel drug delivery technologies have been investigated to bypass or disrupt the BBB/BBTB, including convection enhanced delivery, focused ultrasound, nanoparticle-mediated delivery, and intranasal delivery, all of which are yet to be clinically established for the treatment of DIPG. Herein, we review what is known about the BBB/BBTB and discuss the current status, limitations, and advances of conventional and novel treatments to improving brain drug delivery in DIPG. [Display omitted] [ABSTRACT FROM AUTHOR]

Despite the growing interest in incorporating response time data into item response models, there has been a lack of research investigating how the effect of speed on the probability of a correct response varies across different groups (e.g., experimental conditions) for various items (i.e., differential response time item analysis). Furthermore, previous research has shown a complex relationship between response time and accuracy, necessitating a functional analysis to understand the patterns that manifest from this relationship. In this study, response time data are incorporated into an item response model for two purposes: (a) to examine how individuals' speed within an experimental condition affects their response accuracy on an item, and (b) to detect the differences in individuals' speed between conditions in the presence of within‐condition effects. For these two purposes, by‐variable smooth functions are employed to model differential and functional response time effects by experimental condition for each item. This model is illustrated using an empirical data set to describe the effect of individuals' speed on their reading comprehension ability in two experimental conditions of reading medium (paper vs. digital) by item. A simulation study showed that the recovery of parameters and by‐variable smooth functions of response time was satisfactory, and that the type I error rate and power of the test for the by‐variable smooth function of response time were acceptable in conditions similar to the empirical data set. In addition, the proposed method correctly identified the range of response time where between‐condition differences in the effect of response time on the probability of a correct response were accurate. [ABSTRACT FROM AUTHOR]

We propose a novel Bayesian model framework for discrete ordinal and count data based on conditional transformations of the responses. The conditional transformation function is estimated from the data in conjunction with an a priori chosen reference distribution. For count responses, the resulting transformation model is novel in the sense that it is a Bayesian fully parametric yet distribution-free approach that can additionally account for excess zeros with additive transformation function specifications. For ordinal categoric responses, our cumulative link transformation model allows the inclusion of linear and non-linear covariate effects that can additionally be made category-specific, resulting in (non-)proportional odds or hazards models and more, depending on the choice of the reference distribution. Inference is conducted by a generic modular Markov chain Monte Carlo algorithm where multivariate Gaussian priors enforce specific properties such as smoothness on the functional effects. To illustrate the versatility of Bayesian discrete conditional transformation models, applications to counts of patent citations in the presence of excess zeros and on treating forest health categories in a discrete partial proportional odds model are presented. [ABSTRACT FROM AUTHOR]

The careers of social media content creators, or influencers, live or die by their ability to cultivate and maintain an invested audience-community. To this end, they are encouraged to practise what has been framed as 'emotional labour' (Hochschild, 2002 [1983]) and 'relational labour' (Baym, 2018), commodifying their personalities, lives and tastes in order to build 'authentic' self-brands and intimacy with audiences. Drawing on an ethnographic study of the London influencer industry (2017–2023), this article examines emotional/relational labour through an intersectional feminist lens, foregrounding the ways in which structural inequalities shape relationships between creators and their audiences. The tolls of managing audience relationships are higher for marginalised creators – especially those making stigmatised and less brandable content genres – who find themselves on an uneven playing field in the challenges they face as well as the coping strategies at their disposal. These creators are in an intimacy triple bind, already at higher risk of trolling and harassment, yet under increased pressure to perform relational labour, adversely opening them up to further harms in the form of weaponised intimacy. This article explores four key tactics that creators employ in response to such conditions, as they navigate relational labour and boundaries with audiences: (1) leaning into making rather than being content; (2) (dis)engaging with anti-fans through silence; (3) retreating into private community spaces, away from the exposure of public platforms; and, in parallel, (4) turning off public comments. The adverse experiences of marginalised creators who speak about their identities and experiences online raise serious concerns about the viability of content creation as a career for these groups, as well as the lack of accountability and responsibility that platforms show towards the creators who generate profit for them. [ABSTRACT FROM AUTHOR]

This article considers robust prediction issues in ultrahigh‐dimensional (UHD) datasets and proposes combining quantile regression with sequential model averaging to arrive at a quantile sequential model averaging (QSMA) procedure. The QSMA method is made computationally feasible by employing a sequential screening process and a Bayesian information criterion (BIC) model averaging method for UHD quantile regression and provides a more accurate and stable prediction of the conditional quantile of a response variable. Meanwhile, the proposed method shows effective behaviour in dealing with prediction in UHD datasets and saves a great deal of computational cost with the help of the sequential technique. Under some suitable conditions, we show that the proposed QSMA method can mitigate overfitting and yields reliable predictions. Numerical studies, including extensive simulations and a real data example, are presented to confirm that the proposed method performs well. [ABSTRACT FROM AUTHOR]

Rationale: Preclinical studies report attenuated ethanol-induced conditioned taste aversion (CTA) following chronic ethanol exposure, suggesting that tolerance develops to the aversive properties of ethanol. However, these studies are confounded by pre-exposure to the unconditioned stimulus (US; ethanol), which is well known to hinder conditioning. Objectives: This study was designed to determine whether chronic ethanol exposure produces tolerance to the aversive properties of ethanol in the absence of a US pre-exposure confound. Methods: CTA was performed in adult male and female Long-Evans rats by pairing 0.1% ingested saccharin with an intraperitoneal injection of ethanol (1.5 or 2.0 g/kg) or saline. Rats were then rendered ethanol dependent using chronic intermittent ethanol (CIE) vapor exposure. Controls were exposed to room air (AIR). The effect of chronic ethanol on CTA expression and reconditioning were examined following vapor exposure. Results: Prior to vapor exposure, both sexes developed CTA to a comparable degree with 2.0 g/kg producing greater CTA than 1.5 g/kg ethanol. Following vapor exposure, AIR controls exhibited an increase in CTA magnitude compared to pre-vapor levels. This effect was largely absent in CIE-exposed rats. Re-conditioning after vapor exposure facilitated increased CTA magnitude to a similar degree in AIR- and CIE-exposed males. In contrast, CTA magnitude was unchanged by re-conditioning in females. Conclusions: These data suggest that chronic ethanol does not facilitate tolerance to the aversive properties of ethanol but rather attenuates incubation of ethanol-induced CTA. Loss of CTA incubation suggests that CIE exposure disrupts circuits encoding aversion. [ABSTRACT FROM AUTHOR]

To investigate how and to what extent there are differences in the photosynthetic plasticity of trees in response to different light environments, six species from three successional groups (late successional, mid‐successional, and pioneers) were exposed to three different light environments [deep shade – DS (5% full sunlight – FS), moderate shade – MS (35% FS) and full sunlight – FS].Maximum net photosynthesis (Amax), leaf N partitioning, stomatal, mesophile, and biochemical limitations (SL, ML, and BL, respectively), carboxylation velocity (Vcmax), and electron transport (Jmax) rates, and the state of photosynthetic induction (IS) were evaluated.Higher values of Amax, Vcmax, and Jmax in FS were observed for pioneer species, which invested the largest amount of leaf N in Rubisco. The lower IS for pioneer species reveals its reduced ability to take advantage of sunflecks. In general, the main photosynthetic limitations are diffusive, with SL and ML having equal importance under FS, and ML decreasing along with irradiance. The leaf traits, which are more determinant of the photosynthetic process, respond independently in relation to the successional group, especially with low light availability.An effective partitioning of leaf N between photosynthetic and structural components played a crucial role in the acclimation process and determined the increase or decrease of photosynthesis in response to the light conditions. [ABSTRACT FROM AUTHOR]

When performing movements in rapid succession, the brain needs to coordinate ongoing execution with the preparation of an upcoming action. Here we identify the processes and brain areas involved in this ability of online preparation. Human participants (both male and female) performed pairs of single-finger presses or three-finger chords in rapid succession, while 7T fMRI was recorded. In the overlap condition, they could prepare the second movement during the first response and in the nonoverlap condition only after the first response was completed. Despite matched perceptual and movement requirements, fMRI revealed increased brain activity in the overlap condition in regions along the intraparietal sulcus and ventral visual stream. Multivariate analyses suggested that these areas are involved in stimulus identification and action selection. In contrast, the dorsal premotor cortex, known to be involved in planning upcoming movements, showed no discernible signs of heightened activity. This observation suggests that the bottleneck during simultaneous action execution and preparation arises at the level of stimulus identification and action selection, whereas movement planning in the premotor cortex can unfold concurrently with the execution of a current action without requiring additional neural activity. [ABSTRACT FROM AUTHOR]

A variety of functionalized 3‐arylazoindoles were prepared in good to excellent yields through an iron(III)‐catalyzed C−H azolation of 2‐substituted indoles with arylhydrazines under mild reaction conditions. The reaction underwent an initial TBN‐mediated nitrosation, 1,5‐hydrogen migration, intramolecular condensation, and 1,5‐hydrogen migration over four steps in one pot. A paracyclophane‐derived 3‐phenylazoindole could be prepared in 25% yield over three steps and some prepared 3‐arylazoindoles showed a different fluorescence emission wavelength and existed obvious pH conditions response. The present method highlights broad substrate scope of easily available starting materials, wide range of functional group compatibility, gram scalable preparations, high atom economy, avoidance of unstable and explosive azolation reagents, and simple purification operations by extraction, washing, and recrystallization without flash column chromatography. [ABSTRACT FROM AUTHOR]

Considering the growing interest in clinical applications of neuromodulation, assessing effects of various modulatory approaches is increasingly important. Monosynaptic spinal reflexes undergo depression following repeated activation, offering a means to quantify neuromodulatory influences. Following spinal cord injury (SCI), changes in reflex modulation are associated with spasticity and impaired motor control. To assess disrupted reflex modulation, low-frequency depression (LFD) of Hoffman (H)-reflex excitability is examined, wherein the amplitudes of conditioned reflexes are compared to an unconditioned control reflex. Alternatively, some studies utilize paired-pulse depression (PPD) in place of the extended LFD train. While both protocols induce similar amounts of H-reflex depression in neurologically intact individuals, this may not be the case for persons with neuropathology. We compared the H-reflex depression elicited by PPD and by trains of 3–10 pulses to an 11-pulse LFD protocol in persons with incomplete SCI. The amount of depression produced by PPD was less than an 11-pulse train (mean difference = 0.137). When compared to the 11-pulse train, the 5-pulse train had a Pearson's correlation coefficient (R) of 0.905 and a coefficient of determination (R2) of 0.818. Therefore, a 5-pulse train for assessing LFD elicits modulation similar to the 11-pulse train and thus we recommend its use in lieu of longer trains. [ABSTRACT FROM AUTHOR]

Necrotising enterocolitis (NEC) has a complex pathophysiology but the common end-point is ischaemia reperfusion injury (IRI) and intestinal necrosis. We have previously reported that RIC significantly reduces the intestinal injury in a rat model of NEC. Here we describe the changes in intestinal mRNA occurring in the intestine of animals exposed to IRI, both with and without RIC. Related rat-pups were randomly assigned to four groups: SHAM, IRI only, RIC only and RIC + IRI. IRI animals, underwent 40 min of intestinal ischaemia, and 90 min of reperfusion. Animals that underwent RIC had three cycles of 5 min of alternating ischaemia/reperfusion by means of a ligature applied to the hind limb. Samples from the terminal ileum were immediately stored in RNA-preserving media for later next generation sequencing and transciptome analysis using R v 3.6.1. Differential expression testing showed that 868 genes differentially expressed in animals exposed to RIC alone compared to SHAM and 135 in the IRI and RIC group compared to IRI alone. Comparison between these two sets showed that 25 genes were differentially expressed in both groups. Pro-inflammatory molecules: NF-ĸβ2, Cxcl1, SOD2 and Map3k8 all show reduced expression in response to RIC. Targeted gene analysis revealed increased expression in PI3K which is part of the so-called RISK-pathway which is a key part of the protective mechanisms of RIC in the heart. Overall, this transcriptomic analysis shows that RIC provides a protective effect to the intestine via anti-inflammatory pathways. This could be particularly relevant to treating and preventing NEC. [ABSTRACT FROM AUTHOR]

Acute stress is assumed to affect executive processing of stimulus information, although extant studies have yielded heterogeneous findings. The temporal flanker task, in which a target stimulus is preceded by a distractor of varying utility, offers a means of investigating various components involved in the adjustment of information processing and conflict control. Both behavioral and EEG data obtained with this task suggest stronger distractor-related response activation in conditions associated with higher predictivity of the distractor for the upcoming target. In two experiments we investigated distractor-related processing and conflict control after inducing acute stress (Trier Social Stress Test). Although the stressed groups did not differ significantly from unstressed control groups concerning behavioral markers of attentional adjustment (i.e., Proportion Congruent Effect), or event-related sensory components in the EEG (i.e., posterior P1 and N1), the lateralized readiness potential demonstrated reduced activation evoked by (predictive) distractor information under stress. Our results suggest flexible adjustment of attention under stress but hint at decreased usage of nominally irrelevant stimulus information for biasing response selection. [ABSTRACT FROM AUTHOR]

l -Ascorbic acid (AsA) is an antioxidant with important roles in plant stress physiology, growth, and development. AsA also plays an essential role in human health, preventing scurvy. Humans do not synthesize AsA, which needs to be supplied via a diet rich in fresh produce. Research efforts have provided progress in the elucidation of a complex metabolic network with at least four routes leading to AsA formation in plants. In this review, three alternative pathways, namely the d -galacturonate, the l -gulose, and the myo -inositol pathways, are presented with the supporting evidence of their operation in multiple plant species. We critically discuss feeding studies using precursors and their conversion to AsA in plant organs, and research where the expression of key genes encoding enzymes involved in the alternative pathways showed >100% AsA content increase in the transgenics and in many cases accompanied by enhanced tolerance to multiple stresses. We propose that the alternative pathways are vital in AsA production in response to stressful conditions and to compensate in cases where the flux through the d -mannose/ l -galactose pathway is reduced. The genes and enzymes that have been characterized so far in these alternative pathways represent important tools that are being used to develop more climate-tolerant crops. [ABSTRACT FROM AUTHOR]

Learning outcome is modified by the degree to which the subject responds and pays attention to specific stimuli. Our recent research suggests that presenting stimuli in contingency with a specific phase of the cardiorespiratory rhythm might expedite learning. Specifically, expiration-diastole (EXP-DIA) is beneficial for learning trace eyeblink conditioning (TEBC) compared with inspiration-systole (INS-SYS) in healthy young adults. The aim of this study was to investigate whether the same holds true in healthy elderly adults (n = 50, aged >70 yr). Participants were instructed to watch a silent nature film while TEBC trials were presented at either INS-SYS or EXP-DIA (separate groups). Learned responses were determined as eyeblinks occurring after the tone conditioned stimulus (CS), immediately preceding the air puff unconditioned stimulus (US). Participants were classified as learners if they made at least five conditioned responses (CRs). Brain responses to the stimuli were measured by electroencephalogram (EEG). Memory for the film and awareness of the CS-US contingency were evaluated with a questionnaire. As a result, participants showed robust brain responses to the CS, acquired CRs, and reported awareness of the CS-US relationship to a variable degree. There was no difference between the INS-SYS and EXP-DIA groups in any of the above. However, when only participants who learned were considered, those trained at EXP-DIA (n = 11) made more CRs than those trained at INS-SYS (n = 13). Thus, learned performance could be facilitated in those elderly who learned. However, training at a specific phase of cardiorespiratory rhythm did not increase the proportion of participants who learned. NEW & NOTEWORTHY: We trained healthy elderly individuals in trace eyeblink conditioning, either at inspiration-systole or at expiration-diastole. Those who learned exhibited more conditioned responses when trained at expiration-diastole rather than inspiration-systole. However, there was no difference between the experimental groups in the proportion of individuals who learned or did not learn. [ABSTRACT FROM AUTHOR]

Background: Occipital nerve stimulation (ONS) is a treatment with evidence in refractory chronic cluster headache (CCH). However, the variable response rate and cost make it necessary to investigate predictors of response. Methods: This is a cross-sectional study conducted through the review of medical records of CCH patients from six hospitals in Madrid. Epidemiological and clinical variables were compared between patients with ONS failure and the rest. ONS failure was defined as the need for device withdrawal or switch off because of lack of response or adverse events. Results: From a series of 88 CCH, 26 (29.6%) underwent ONS surgery, of whom 13/26 (50.0%) failed because lack of response. ONS failure group had an earlier headache onset (mean ± SD) of 27.7 ± 6.9 vs. 36.7 ± 11.8 years, p = 0.026) and a higher smoking rate (100% vs. 42.9%, p = 0.006). Stational fluctuations (58.3% vs. 7.7%, p = 0.007) and nocturnal exacerbations (91.7% vs. 53.9%, p = 0.035) were more frequent in the ONS failure group as well. There was no difference between groups in diagnostic delay, years of evolution prior to surgery, mental illness, comorbidity with other headache disorders or chronic pain conditions or prior response to occipital nerves anesthetic blocks. Conclusions: Some clinical features such as an early debut, smoking and seasonal or circadian fluctuations could be related to failure of ONS in refractory CCH. [ABSTRACT FROM AUTHOR]

Background and Aim: The ban on antibiotic growth promoters adversely affects the physiological condition and health of poultry. The aim of this study was to determine the effect of encapsulated Acalypha australis L. leaf extract, chitosan, or a combination of both on the physiological and intestinal conditions of broiler chickens. Materials and Methods: A total of 280 Cobb broiler chicks were randomly distributed into four groups: Basal feed without additives (CNTL), basal feed with 0.01% encapsulated A. australis leaf extract (EALE), 0.01% chitosan (CHIT), and 0.01% EALE and 0.01% chitosan (EACH). Sample collection and data measurement were conducted on day 36. Results: There was a tendency (p = 0.08) for EACH bird to have a higher body weight than the other groups. Feed consumption was higher (p < 0.05) in EACH than in EALE and CHIT. Feed conversion ratio (FCR) was lower (p < 0.05) in EALE, CHIT, and EACH than in CNTL. Erythrocyte numbers were lower (p < 0.05) in EALE than in CNTL and EACH. Hematocrit was lower (p < 0.05) in EALE and CHIT groups than in the other two groups. There was a tendency (p = 0.09) for heterophils to be higher in EACH than in CNTL. Thrombocyte counts were lower (p < 0.05) in EACH group than in the other groups. Serum globulin levels were higher (p < 0.05) in EACH than in CNTL and CHIT. The albumin-to-globulin ratio was higher (p < 0.05) in CNTL than in EALE and EACH. Coliform bacteria tended to be lower (p = 0.05) in the cecum of EACH broilers than that of other broilers. Similarly, the ratio of Lactic acid bacteria to coliforms tended to be higher (p = 0.08) in the cecum of EACH group than that in the other groups. Treatments did not influence the intestinal morphology of broiler chickens (p > 0.05). Conclusion: A combination of EALE and chitosan as feed additives enhanced the final body weight and feed efficiency (FCR) of broilers. These additives also increased the levels of heterophils, serum globulin, the ratio of LAB to coliforms, and reduced thrombocytes, albumin-to-globulin ratio, and cecal coliform bacteria. Hence, EALE and chitosan blend improved the growth performance, immune status, and intestinal health of broiler chickens. [ABSTRACT FROM AUTHOR]

Recent research suggests that insufficient sleep elevates the risk of obesity. Although the mechanisms underlying the relationship between insufficient sleep and obesity are not fully understood, preliminary evidence suggests that insufficient sleep may intensify habitual control of behavior, leading to greater cue-elicited food-seeking behavior that is insensitive to satiation. The present study tested this hypothesis using a within-individual, randomized, crossover experiment. Ninety-six adults underwent a one-night normal sleep duration (NSD) condition and a one-night total sleep deprivation (TSD) condition. They also completed the Pavlovian-instrumental transfer paradigm in which their instrumental responses for food in the presence and absence of conditioned cues were recorded. The sleep × cue × satiation interaction was significant, indicating that the enhancing effect of conditioned cues on food-seeking responses significantly differed across sleep × satiation conditions. However, this effect was observed in NSD but not TSD, and it disappeared after satiation. This finding contradicted the hypothesis but aligned with previous literature on the effect of sleep disruption on appetitive conditioning in animals—sleep disruption following learning impaired the expression of appetitive behavior. The present finding is the first evidence for the role of sleep in Pavlovian-instrumental transfer effects. Future research is needed to further disentangle how sleep influences motivational mechanisms underlying eating. [ABSTRACT FROM AUTHOR]

Summary: A conceptual understanding on how the vegetation's carbon (C) balance is determined by source activity and sink demand is important to predict its C uptake and sequestration potential now and in the future. We have gathered trajectories of photosynthesis and growth as a function of environmental conditions described in the literature and compared them with current concepts of source and sink control. There is no clear evidence for pure source or sink control of the C balance, which contradicts recent hypotheses. Using model scenarios, we show how legacy effects via structural and functional traits and antecedent environmental conditions can alter the plant's carbon balance. We, thus, combined the concept of short‐term source–sink coordination with long‐term environmentally driven legacy effects that dynamically acclimate structural and functional traits over time. These acclimated traits feedback on the sensitivity of source and sink activity and thus change the plant physiological responses to environmental conditions. We postulate a whole plant C‐coordination system that is primarily driven by stomatal optimization of growth to avoid a C source–sink mismatch. Therefore, we anticipate that C sequestration of forest ecosystems under future climate conditions will largely follow optimality principles that balance water and carbon resources to maximize growth in the long term. [ABSTRACT FROM AUTHOR]

Chronic immune activation in tuberculosis (TB) associated with human immunodeficiency virus (HIV) infection (HIV/TB) modifies their clinical course. We prospectively measured osteopontin (OPN), full-length galectin-9 (FL-Gal9), and total-Gal9 (T-Gal9) levels in 32 patients with HIV/TB coinfection treated with anti-tuberculosis and antiretroviral therapies over 6–18 months to determine the amelioration of inflammatory conditions in response to the therapies. We observed a significant time-dependent decrease in FL-Gal9 in both pulmonary TB (PTB, n = 20) and extrapulmonary TB (EPTB, n = 12) patients. The levels of T-Gal9, OPN, and CRP decreased significantly after treatment in only PTB patients. We calculated the inflammatory score (INS) indicating immunologic recovery based on the decline in OPN, FL-Gal9, T-Gal9, and CRP levels. Baseline levels of T-Gal9 and OPN positively correlated with INS in all TB and only PTB patients, respectively, indicating that their levels predict better recovery. In contrast, FL-Gal9 levels at the second visit negatively correlated with INS in EPTB patients. The decrease rate in OPN levels at the second visit also correlated positively with INS in PTB patients. Women showed a higher INS and lower levels of FL-Gal9 than men. The patients with moderate grade severity on chest X-ray had higher CD4 cell numbers than those with limited grade severity. Monitoring these markers will help to predict and assess the response to therapy as well as to devise strategies to reduce the complications caused by chronic immune activation in patients with HIV/TB coinfection. [ABSTRACT FROM AUTHOR]

This study investigated the effects of storage conditions on the quality of chilled ram semen stored at 4°C for 48 h, comparing aerobic and anaerobic conditions. Ejaculates from INRA180 rams were collected and stored under both conditions, with assessments at 0‐, 24‐, and 48‐h intervals. Various sperm parameters were examined, including motility, velocity, viability, morphology, membrane integrity, and lipid peroxidation. Results showed that storage duration significantly impacted sperm quality, leading to a gradual decline from 0 to 24 h and 24 to 48 h. Notably, after the initial 24 h, progressive motility (PM) and membrane integrity (MI) demonstrated distinct responses to storage conditions. Anaerobic storage consistently improved PM and MI values compared to aerobic storage between 24 and 48 h. Anaerobic conditions also enhanced viability and reduced abnormality at the 48‐h mark. Total motility remained stable throughout storage. Velocity parameters (VCL: curvilinear velocity; VSL: straight velocity and VAP: velocity average path) exhibited differences between the 24‐ and 48‐h intervals, with anaerobic storage resulting in higher VAP and VSL values. Moreover, lipid peroxidation exhibited a progressive increase from 0 to 24 h and 24 to 48 h, independent of storage conditions. Remarkably, anaerobic storage consistently yielded lower lipid peroxidation levels compared to aerobic storage, regardless of storage duration. In conclusion, this study highlights that the anaerobic storage proved advantageous for chilled ram semen quality, particularly after the initial 24 h. [ABSTRACT FROM AUTHOR]

Do beliefs about fairness interact with past experiences of labor market shocks to condition redistributive preferences? In a large-scale survey experiment, we investigate the effect of informing individuals that growth in automation could disrupt labor markets in ways that are (possibly) viewed as unfair. We then exploit the COVID-19-induced labor market shock to test for an interaction between treatments and shock exposure. We find that beliefs interact with shock exposure to increase redistributive preferences and commitments to donate potential prize winnings. Our findings suggest this may be motivated by respondents' concerns about their vulnerability to future labor market shocks. • Fairness and inequality concerns increase demand for redistribution. • Lived experience of job loss amplifies informational treatment effects. • Information about luck resonates with experiences of labor shocks. • Personal shock history informs future economic anxiety. [ABSTRACT FROM AUTHOR]

This study determined the proximate composition, cooking and sensory properties of noodles from wheat-tigernut pomace flour blends at optimized condition using response surface methodology (RSM). RSM based on Box–Behnken design was employed for the design of the experiment with three independent variables at three levels of variation resulting in 17 experimental runs. The independent variables are screw speed, barrel temperature and level of tigernut pomace flour added to the wheat flour. The noodles were produced using a single screw laboratory extruder and were analyzed for proximate composition, cooking and sensory properties. The addition of tigernut pomace flour to wheat flour increases the crude fat, crude fiber and carbohydrate, while the moisture and total ash decrease. The cooking properties of the noodles from wheat-tigernut pomace flour blends were also affected significantly by the variables except for the cooking time. However, noodles produced from 10% substitution of wheat with tigernut pomace flour, barrel temperature at 100°C and screw speed at 90 rev/mins were accepted by the panelists. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila is an opportunistic motile pathogen with a broad host range, infecting both terrestrial and aquatic animals. Environmental and geographical conditions exert selective pressure on both geno- and phenotypes of pathogens. Flagellin, directly exposed to external environments and containing important immunogenic epitopes, may display significant variability in response to external conditions. In this study, we conducted a comparative analysis of ~ 150 A. hydrophila genomes, leading to the identification of six subunits of the flagellin gene (fla-1 to fla-4, flaA, and flaB). Individual strains harbored different composition of flagellin subunits and copies. The composition of subunits showed distinct patterns depending on environmental sources. Strains from aquatic environments were mainly comprised of fla-1 to fla-4 subunits, while terrestrial strains predominated in groups harboring flaA and flaB subunits. Each flagellin showed varying levels of expression, with flaA and flaB demonstrating significantly higher expression compared to others. One of the chemotaxis pathways that control flagellin movement through a two-component system was significantly upregulated in flaA(+ 1)/flaB(+ 1) group, whereas flaA and flaB showed different transcriptomic expressions. The genes positively correlated with flaA expression were relevant to biofilm formation and bacterial chemotaxis, but flaB showed a negative correlation with the genes in ABC transporters and quorum sensing pathway. However, the expression patterns of fla-2 to fla-4 were identical. This suggests various types of flagellin subunits may have different biological functions. The composition and expression levels of flagellin subunits could provide valuable insights into the adaptation of A. hydrophila and the differences among strains in response to various external environments. [ABSTRACT FROM AUTHOR]

A dynamic frictional contact problem between a viscoelastic body and a foundation is studied. The contact is modeled with normal damped response and a friction law. The constitutive law with long memory is assumed to be nonlinear. The existence result is proved using nonlinear monotone operators, fixed point argument, and extension procedure. Moreover, the exponential stability of the energy solution is established using the multiplier method. [ABSTRACT FROM AUTHOR]

With over one‐third of terrestrial net primary productivity transferring to the litter layer annually, the carbon release from litter serves as a crucial valve in atmospheric carbon dioxide concentrations. However, few quantitative global projections of litter carbon release rate in response to climate change exist. Here, we combined a global foliar litter carbon release dataset (8973 samples) to generate spatially explicitly estimates of the response of their residence time (τ) to climate change. Results show a global mean litter carbon release rate (k$$ k $$) of 0.69 year−1 (ranging from 0.09–5.6 year−1). Under future climate scenarios, global mean τ is projected to decrease by a mean of 2.7% (SSP 1–2.6) and 5.9% (SSP 5–8.5) during 2071–2100 period. Locally, the alleviation of temperature and moisture restrictions corresponded to obvious decreases in τ in cold and arid regions, respectively. In contract, τ in tropical humid broadleaf forests increased by 4.6% under SSP 5–8.5. Our findings highlight the vegetation type as a powerful proxy for explaining global patterns in foliar litter carbon release rates and the role of climate conditions in predicting responses of carbon release to climate change. Our observation‐based estimates could refine carbon cycle parameterization, improving projections of carbon cycle–climate feedbacks. [ABSTRACT FROM AUTHOR]

Currently, numerical-simulation-based slope reliability analysis (NSB-SRA) considering spatial variability is still a time-consuming task. To address this problem, this study proposed an efficient numerical-simulation-based slope reliability analysis method. Dual dimensionality reduction technique is firstly employed to greatly reduce random variables that are required for establishing a limit-equilibrium-analysis-based multivariate adaptive regression splines (MARS) model. Then, response conditioning method is used to select the failure samples predicted by MARS model as samples for performing NSB-SRA. Finally, the proposed method is validated through two spatially variable slope examples. The results show that MARS + FDM is an efficient solution to perform NSB-SRA, especially for low-probability-level NSB-SRA problem. Besides, NSB-SRA is necessary for cases of horizontal scale of fluctuation, smaller vertical of fluctuation, larger variability of undrained shear strength, and stronger positive cross-correlation between cohesion and internal friction angle because neglecting NSB-SRA will lead to an unreliable assessment on slope reliability. [ABSTRACT FROM AUTHOR]

Background Equine obesity is a significant health and welfare concern. The proportion of domestic horse populations that are overweight are as high as 45%. As the primary decision-makers for their horses' care, owners are theoretically ideally placed to identify whether their horses are appropriately conditioned, however, research in other countries has shown that many owners are unable to accurately judge their horse's body condition. In this study, through the comparison of body condition scoring (BCS) performed by an expert and the horse owners and interviews with owners, we aimed to identify the proportion of horses that were overweight or obese, to assess the accuracy of horse owners' BCS assessment both prior to and after receiving information and instructions on body condition scoring, and to identify common themes amongst owners' views regarding BCS assessment and the Henneke BCS system. Results Forty-five percent of the horses in this study were overweight or obese. The agreement between the owners and an equine veterinarian regarding the horses' BCS was fair to good both prior to (k = .311, P < 0.001; ICC = .502, P < 0.001) and after (k = .381, P < 0.001; ICC = .561, P < 0.001) receiving information and instructions on scoring. Three quarters of the owners who took part in the study did not use any method of monitoring their horse's body condition. Thematic analysis of owner responses was varied, with the most common theme being an awareness of the need to monitor or make changes to their horse's condition with responses in this theme split between owners who felt in control and those who did not. Owner feedback on the utility and useability of the scorning system was that it was useful however parts are too technical or need improvement. Conclusions Equine obesity is a significant problem in this population in Ireland. Horse owners' ability to accurately judge their horse's condition does not improve with provision of instructions on body condition scoring. These results combined with owners' feedback on the Henneke BCS system indicate that it is not a tool that can be reliably used by owners. [ABSTRACT FROM AUTHOR]

Treatments for anorexia nervosa (AN) remain ineffective for many patients. Processes that can account for differential treatment outcomes remain mostly unknown. We propose that the field test the role of associative learning in current psychological treatments. We hold that this line of research could yield actionable information for understanding non‐response and improving long‐term outcomes. To make this argument, we define associative learning and outline its proposed role in understanding psychiatric disorders and their treatment. We then briefly review data exploring associative learning in AN. We argue that associative learning processes are implicitly implicated in existing treatments; by this rationale, baseline differences in learning may interfere with treatment response. Finally, we outline future research to test our hypotheses. Altogether, future research aimed at better understanding how associative learning may contribute to AN symptom persistence has the potential to inform novel directions in intervention research. Public Significance: There is a pressing need to improve outcomes in treatments for anorexia nervosa (AN). We propose that individual differences in associative learning—the ability to form and update associations between cues, contexts, behaviors, and outcomes—may account for differential response to existing treatments. Undertaking this research could provide an understanding of how current treatments work and inform new approaches for those who may be at risk of poor outcomes. [ABSTRACT FROM AUTHOR]

Photoelectric synaptic devices with optical sensing capability are of great importance in simulating human vision systems. Especially realizing all‐in‐one vision neuristor on silicon based new materials and principles is being pursued. 2D van der Waals (vdW) materials have the unique advantage of arbitrary stacking on demand. Herein, a full‐vdW two‐terminal 2D ferroelectric α‐In2Se3/SnSe p–n heterojunction is proposed to construct an optoelectronic neuristor to simulate visual synaptic functions. Implementation of these simulations is attributed to the co‐modulation of the electrical polarization reconfigurable built‐in electric field caused by p–n junction and photo‐inducing ferroelectric polarization switching. These functions include ultra‐high paired‐pulse facilitation index (457%), short synaptic plasticity, long synaptic plasticity, and retina‐like optical adaptations. The high PPF is crucial for high‐precision decoding and processing of visual information. Meanwhile, the classical Pavlovian conditioned reflexes associated with associative learning are also emulated showing the ability of the device to handle complex electrical and optical inputs. This study demonstrates that two‐terminal ferroelectric p–n heterojunctions have great potential in high‐precision multifunctional optoelectronic visual synaptic devices. [ABSTRACT FROM AUTHOR]

Cellular processes are subject to inherent variability, but the extent to which cells can regulate this variability has received little investigation. Here, we explore the characteristics of the rate of cellular protein synthesis in single cells of the eukaryote fission yeast. Strikingly, this rate is highly variable despite protein synthesis being dependent on hundreds of reactions which might be expected to average out at the overall cellular level. The rate is variable over short time scales, and exhibits homoeostatic behaviour at the population level. Cells can regulate the level of variability through processes involving the TOR pathway, suggesting there is an optimal level of variability conferring a selective advantage. While this could be an example of bet-hedging, but we propose an alternative explanation: regulated 'loose' control of complex processes of overall cellular metabolism such as protein synthesis, may lead to this variability. This could ensure cells are fluid in control and agile in response to changing conditions, and may constitute a novel organisational principle of complex metabolic cellular systems. Synopsis: How tightly global cellular metabolic processes are regulated remains unclear. Here, single-cell measurements of amino acid acid flux into nascent proteins reveal high variability of cellular protein synthesis in growing eukaryotic fission yeast, suggesting that a genetically-regulated 'loose' control ensures optimal manoeuvrability. Global protein synthesis rates in exponentially-growing unperturbed fission yeast populations exhibit high cell-to-cell variability. Global protein synthesis is dynamic over short time scales, and exhibits homeostatic behaviour at the population level. Genetic modulation of the TOR pathway and cell-cycle controllers modulates protein translation variability. Amino-acid acid flux into nascent proteins is highly variable and TOR-dependent in growing eukaryotic fission yeast. [ABSTRACT FROM AUTHOR]

Medium-depth geothermal energy mainly consists of two types, hydrothermal and dry-heat rock. With huge resource reserves, its exploration and development are of great significance to the transformation of China's energy structure and the realization of the goal of "Double-Carbon". From the differences in the electrical characteristics between hydrothermal and hot dry rock geothermal resources, this project uses the numerical modeling of the wide field electromagnetic (WFEM) method as a tool to design a model of typical geothermal resources. Then, we summarize and analyze the detection capability of the WFEM by calculating the WFEM response under the conditions of different depths, resistivity values, thickness-to-depth ratios and other parameters. Moreover, aiming at the key problems faced by the WFEM in real applications, we discuss the factors affecting the detection accuracy and give solutions to improve the reliability of the detection results. Finally, the medium-depth geothermal energy detection in the Jiyang Depression of Shandong is presented as an example, showing how the WFEM detection technique was used with the inversion result profile obtained. By comparing the results of geomagnetic and seismic detection on the same survey line, it is demonstrated that the WFEM method has great potential in the exploration of medium-depth geothermal energy and can be the preferred method. [ABSTRACT FROM AUTHOR]

According to the motor learning theory by Albus and Ito, synaptic depression at the parallel fibre to Purkinje cells synapse (pf-PC) is the main substrate responsible for learning sensorimotor contingencies under climbing fibre control. However, recent experimental evidence challenges this relatively monopolistic view of cerebellar learning. Bidirectional plasticity appears crucial for learning, in which different microzones can undergo opposite changes of synaptic strength (e.g. downbound microzones–more likely depression, upbound microzones—more likely potentiation), and multiple forms of plasticity have been identified, distributed over different cerebellar circuit synapses. Here, we have simulated classical eyeblink conditioning (CEBC) using an advanced spiking cerebellar model embedding downbound and upbound modules that are subject to multiple plasticity rules. Simulations indicate that synaptic plasticity regulates the cascade of precise spiking patterns spreading throughout the cerebellar cortex and cerebellar nuclei. CEBC was supported by plasticity at the pf-PC synapses as well as at the synapses of the molecular layer interneurons (MLIs), but only the combined switch-off of both sites of plasticity compromised learning significantly. By differentially engaging climbing fibre information and related forms of synaptic plasticity, both microzones contributed to generate a well-timed conditioned response, but it was the downbound module that played the major role in this process. The outcomes of our simulations closely align with the behavioural and electrophysiological phenotypes of mutant mice suffering from cell-specific mutations that affect processing of their PC and/or MLI synapses. Our data highlight that a synergy of bidirectional plasticity rules distributed across the cerebellum can facilitate finetuning of adaptive associative behaviours at a high spatiotemporal resolution. Author summary: The cerebellum plays a key role in motor learning thanks to synaptic plasticity. While synaptic depression at one cerebellar synaptic type has been long considered the main site for learning, recent experimental findings point out to a critical role for bidirectional plasticity at multiple cerebellar synapses. In this work, we developed a spiking neural network model of the cerebellum and simulated an associative cerebellum-driven task, i.e. classical eyeblink conditioning. Our simulations closely reproduced the behavioural phenotypes of mutant mice with altered cerebellar synapses, shedding light on the underlying neural mechanisms. The results highlight that a synergy of bidirectional plasticity distributed across the cerebellum is necessary for finetuning of adaptive associative behaviours at a high spatiotemporal resolution. [ABSTRACT FROM AUTHOR]

The interpretation of complex biological datasets requires the identification of representative variables that describe the data without critical information loss. This is particularly important in the analysis of large phenotypic datasets (phenomics). Here we introduce Multi-Attribute Subset Selection (MASS), an algorithm which separates a matrix of phenotypes (e.g., yield across microbial species and environmental conditions) into predictor and response sets of conditions. Using mixed integer linear programming, MASS expresses the response conditions as a linear combination of the predictor conditions, while simultaneously searching for the optimally descriptive set of predictors. We apply the algorithm to three microbial datasets and identify environmental conditions that predict phenotypes under other conditions, providing biologically interpretable axes for strain discrimination. MASS could be used to reduce the number of experiments needed to identify species or to map their metabolic capabilities. The generality of the algorithm allows addressing subset selection problems in areas beyond biology. Multi-Attribute Subset Selection is an algorithm for identifying the most descriptive growth conditions in microbial phenotyping experiments. This streamlines high-throughput phenotyping efforts and helps to reveal biological insights. [ABSTRACT FROM AUTHOR]

This concise review navigates the intricate realm of Interleukin-6 (IL-6), an important member of the cytokine family. Beginning with an introduction to cytokines, this narrative review unfolds with the historical journey of IL-6, illuminating its evolving significance. A crucial section unravels the three distinct signaling modes employed by IL-6, providing a foundational understanding of its versatile interactions within cellular landscapes. Moving deeper, the review meticulously dissects IL-6's signaling mechanisms, unraveling the complexities of its pleiotropic effects in both physiological responses and pathological conditions. A significant focus is dedicated to the essential role IL-6 plays in inflammatory diseases, offering insights into its associations and implications for various health conditions. The review also takes a therapeutic turn by exploring the emergence of anti-IL-6 monoclonal inhibitors, marking a profound stride in treatment modalities. Diving into the molecular realm, the review explores small molecules as agents for IL-6 inhibition, providing a nuanced perspective on diverse intervention strategies. As the review embarks on the final chapters, it contemplates future aspects, offering glimpses into potential research trajectories and the evolving landscape of IL-6-related studies. [Display omitted] • IL-6: Versatile cytokine in disease pathways. • IL-6 receptor complex: Intricacies unveiled. • Diverse IL-6 signaling mechanisms explored. • Targeting IL-6: Promising therapies & molecules. [ABSTRACT FROM AUTHOR]

Children with autism spectrum disorder (ASD) who are also minimally verbal may require specialized interventions to promote the development of vocalizations. Preliminary research supports an innovative procedure called response contingent stimulus-stimulus pairing (SSP) as a potentially effective procedure to promote vocalizations. The primary aim of this study was to demonstrate the feasibility of delivering a randomized trial comparing response contingent SSP to a control condition. Secondary aims were to demonstrate the feasibility of deploying to the home environment the Digital Language Processor (DLP), a voice recorder by LENA®, and to examine preliminary efficacy of the intervention. Sixteen minimally verbal children with ASD (ages 2.0 to 3.9 years) were randomly assigned to the intervention or control condition with access to delayed treatment. Feasibility metrics were met in that 14 participants (88%) finished the study and attendance to all assessment time points and treatment sessions was over 90%. The research team conducted treatment sessions with 99% fidelity and collected 83.3% of voice recorder data. Nine of 16 caregiver satisfaction surveys were returned, and scores averaged 5.68 out of a possible 6.00 across all participants. Preliminary treatment data results showed that 8/14 participants (57%) showed significant improvement in target sounds and participants receiving the intervention were 3.5 times as likely to improve compared to control. [ABSTRACT FROM AUTHOR]

Tibetan pig is a geographically isolated pig breed that inhabits high-altitude areas of the Qinghai–Tibetan plateau. At present, there is limited research on viral diseases in Tibetan pigs. This study provides a novel metagenomic exploration of the gut virome in Tibetan pigs (altitude ≈ 3000 m) across three critical developmental stages, including lactation, nursery, and fattening. The composition of viral communities in the Tibetan pig intestine, with a dominant presence of Microviridae phages observed across all stages of development, in combination with the previous literature, suggest that it may be associated with geographical locations with high altitude. Functional annotation of viral operational taxonomic units (vOTUs) highlights that, among the constantly increasing vOTUs groups, the adaptability of viruses to environmental stressors such as salt and heat indicates an evolutionary response to high-altitude conditions. It shows that the lactation group has more abundant viral auxiliary metabolic genes (vAMGs) than the nursery and fattening groups. During the nursery and fattening stages, this leaves only DNMT1 at a high level. which may be a contributing factor in promoting gut health. The study found that viruses preferentially adopt lytic lifestyles at all three developmental stages. These findings not only elucidate the dynamic interplay between the gut virome and host development, offering novel insights into the virome ecology of Tibetan pigs and their adaptation to high-altitude environments, but also provide a theoretical basis for further studies on pig production and epidemic prevention under extreme environmental conditions. [ABSTRACT FROM AUTHOR]

Clustered observations are ubiquitous in controlled and observational studies and arise naturally in multicenter trials or longitudinal surveys. We present a novel model for the analysis of clustered observations where the marginal distributions are described by a linear transformation model and the correlations by a joint multivariate normal distribution. The joint model provides an analytic formula for the marginal distribution. Owing to the richness of transformation models, the techniques are applicable to any type of response variable, including bounded, skewed, binary, ordinal, or survival responses. We demonstrate how the common normal assumption for reaction times can be relaxed in the sleep deprivation benchmark data set and report marginal odds ratios for the notoriously difficult toe nail data. We furthermore discuss the analysis of two clinical trials aiming at the estimation of marginal treatment effects. In the first trial, pain was repeatedly assessed on a bounded visual analog scale and marginal proportional-odds models are presented. The second trial reported disease-free survival in rectal cancer patients, where the marginal hazard ratio from Weibull and Cox models is of special interest. An empirical evaluation compares the performance of the novel approach to general estimation equations for binary responses and to conditional mixed-effects models for continuous responses. An implementation is available in the tram add-on package to the R system and was benchmarked against established models in the literature. [ABSTRACT FROM AUTHOR]

Background: The eosinophil level in peripheral blood increases in response to various conditions, the most common being medication use. Since the outcome of increased levels of eosinophils can range from a benign finding to extensive damage to host organs and systemic consequences, this finding raises concern among clinicians. We aimed to assess the prevalence of prolonged antibiotic-therapy-induced eosinophilia and possible outcomes. Methods: We conducted a retrospective cohort study of diabetic patients admitted to the orthopedic department from December 2016 through December 2020 due to a moderate to severe diabetic foot infection and who received at least 14 days of antibiotic therapy. Patients were identified retrospectively through the orthopedic department registry, and their files were reviewed, extracting demographics, laboratory test results, antibiotic treatment, and outcomes. Results: The cohort included 347 patients; a total of 114 (32.8%) developed eosinophilia during the follow-up period. Patients who developed eosinophilia had a significantly longer duration of antibiotic treatment (p < 0.001) and a significantly longer hospitalization (p = 0.001). For multivariable analysis, the independent risk factors predicting drug-induced eosinophilia included older age, higher eosinophil count on admission (per quantile) and higher platelet count on admission (per quantile) (p = 0.012, p < 0.001, p = 0.009, respectively). There was no evidence of complications in patients who developed eosinophilia compared to patients who did not. No significant association with a specific type of antibiotic was found. Conclusions: We found a higher incidence of drug-induced eosinophilia than expected or previously described. The factors associated with eosinophilia included age and higher baseline eosinophil and platelet levels but not antibiotic type. [ABSTRACT FROM AUTHOR]

Matching‐to‐sample arrangements are commonly used to teach conditional discriminations. In these arrangements, instructors must systematically arrange instruction to ensure that a learner's response comes under the intended sources of stimulus control. Given the multitude of instructional considerations, the instructors' procedural fidelity has been a significant concern. Recently, LeBlanc et al. found that brief training and access to enhanced data sheets produced high levels of fidelity with experienced service providers. The current study extended LeBlanc et al. by examining the effects of a similar training on the fidelity and instructional pacing by participants with and without previous experience. The participants' performance was also compared when using a flashcard or binder (i.e., printed) arrays and relative to a tablet‐delivered instructional program. High levels of fidelity were observed following training, although pacing was slow. Slight differences in performance were observed across comparison arrays; nevertheless, the tablet‐based program outperformed instructors. [ABSTRACT FROM AUTHOR]

An investigation was carried out on humic substances (HSs) isolated from the coal of the Kansk-Achinsk basin (Krasnoyarsk Territory, Russia). The coal HSs demonstrate the main parameters of molecular structure inherent to this class of natural compounds. An assessment was performed for the chemical, microbiological, and pharmacological safety parameters, as well as the biological efficacy. The HS sample meets the safety requirements in microbiological purity, toxic metals content (lead, cadmium, mercury, arsenic), and radionuclides. The presence of 11 essential elements was determined. The absence of general, systemic toxicity, cytotoxicity, and allergenic properties was demonstrated. The coal HS sample was classified as a Class V hazard (low danger substances). High antioxidant and antiradical activities and immunotropic and cytoprotective properties were identified. The ability of the HS to inhibit hydroxyl radicals and superoxide anion radicals was revealed. Pronounced actoprotective and nootropic activities were also demonstrated in vivo. Intragastric administration of the HS sample resulted in the improvement of physical parameters in mice as assessed by the "swim exhaustion" test. Furthermore, intragastric administration in mice with cholinergic dysfunction led to a higher ability of animals with scopolamine-induced amnesia to form conditioned reflexes. These findings suggest that the studied HS sample is a safe and effective natural substance, making it suitable for use as a dietary bioactive supplement. [ABSTRACT FROM AUTHOR]

Rationale: Preclinical research suggests that pharmacologically elevating cannabinoid levels may attenuate fear memory expression and enhance fear extinction. Objectives: We studied the effects of cannabidiol (CBD) on fear memory expression and fear re-extinction in 69 patients with panic disorder with agoraphobia or with social anxiety disorder. Moderation by sex, diagnosis, and serotonergic antidepressant (AD) use was explored. Methods: A cued fear conditioning paradigm was applied before the first treatment session with 300 mg CBD/placebo augmented exposure therapy. Study medication was administered orally preceding 8 weekly sessions. Fear acquisition and suboptimal extinction took place prior to the first medication ingestion (T0). After the first medication ingestion (T1), we investigated effects on fear memory expression at retention and fear re-extinction. Subjective fear, shock expectancy, skin conductance, and startle responses to conditioned (CS+) and safety stimulus (CS−) were measured. Results: Across the sample, CBD reduced shock expectancy at retention under low and ambiguous threat of shock, but fear re-extinction at T1 was unaffected by CBD. However, in AD users, re-extinction of subjective fear was impaired in the CBD condition compared to placebo. In female AD users, CBD interfered with safety learning measured with fear-potentiated startle. Conclusions: The current findings provide no evidence for enhanced fear re-extinction by CBD. However, CBD acutely decreased threat expectation at retention, without affecting other indices of fear. More studies are needed to elucidate possible interactions with AD use and sex, as well as potential effects of CBD on threat expectancies. [ABSTRACT FROM AUTHOR]

Providing adequate water supply to the growing number of urban residents will be a challenge faced by many utility managers throughout the remainder of this century. Though traditionally, water managers have looked toward supply‐based solutions (e.g., expanding reservoirs), recent trends indicate a shift toward demand‐side management (e.g., encouraging conservation behaviors). Here, we present an agent‐based model (ABM) that simulates water supply as a function of the local climatic conditions and water consumption, which is, in part, determined based on water conservation attitudes. Our results indicate the ABM performs well (normalized root mean squared error <10%) for the study area. Further, we explore various hypothetical demand management scenarios by changing the water conservation attitudes of the households (i.e., the archetypes). This scenario testing reveals a statistically significant improvement to water availability after successfully changing water conservation attitudes to be more participatory. Ultimately, this study aims to understand the nuances of water conservation attitudes and aid utilities in their goal to better manage urban water demand. [ABSTRACT FROM AUTHOR]

Objective: This study proposed a model to predict passenger motion sickness under the presence of a visual-vestibular conflict and assessed its performance with respect to previously recorded experimental data. Background: While several models have been shown useful to predict motion sickness under repetitive motion, improvements are still desired in terms of predicting motion sickness in realistic driving conditions. There remains a need for a model that considers angular and linear visual-vestibular motion inputs in three dimensions to improve prediction of passenger motion sickness. Method: The model combined the subjective vertical conflict theory and human motion perception models. The proposed model integrates visual and vestibular sensed 6 DoF motion signals in a novel architecture. Results: Model prediction results were compared to motion sickness data obtained from studies conducted in motion simulators as well as on-road vehicle testing, yielding trends that are congruent with observed results in both cases. Conclusion: The model demonstrated the ability to predict trends in motion sickness response for conditions in which a passenger performs a task on a handheld device versus facing forward looking ahead under realistic driving conditions. However, further analysis across a larger population is necessary to better assess the model's performance. Application: The proposed model can be used as a tool to predict motion sickness under different levels of visual-vestibular conflict. This can be leveraged to design interventions capable of mitigating passenger motion sickness. Further, this model can provide insights that aid in the development of passenger experiences inside autonomous vehicles. [ABSTRACT FROM AUTHOR]

Neuroscience heavily relies on animal welfare in laboratory rodents as it can significantly affect brain development, cognitive function and memory formation. Unfortunately, laboratory animals are often raised in artificial environments devoid of physical and social stimuli, potentially leading to biased outcomes in behavioural assays. To assess this effect, we examined the impact of social and physical cage enrichment on various forms of motor coordination. Our findings indicate that while enriched-housed animals did not exhibit faster learning in eyeblink conditioning, the peak timing of their conditioned responses was slightly, but significantly, improved. Additionally, enriched-housed animals outperformed animals that were housed in standard conditions in the accelerating rotarod and ErasmusLadder test. In contrast, we found no significant effect of enrichment on the balance beam and grip strength test. Overall, our data suggest that an enriched environment can improve motor performance and motor learning under challenging and/or novel circumstances, possibly reflecting an altered state of anxiety. [ABSTRACT FROM AUTHOR]

Our viewpoint is that ethanol could act as a molecular messenger in animal and plant organisms under conditions of hypoxia or other stresses and could elicit physiological responses to such conditions. There is evidence that both animal and plant organisms have endogenous levels of ethanol, but reports on the changes induced by this alcohol at physiological levels are sparse. Studies have shown that ethanol has different effects on cell metabolism at low and high concentrations, resembling a hormetic response. Further studies have addressed the potential cellular and molecular mechanisms used by organisms to sense changes in physiological concentrations of ethanol. This article summarizes the possible mechanisms by which ethanol may be sensed, particularly at the cell membrane level. Our analysis shows that current knowledge on this subject is limited. More research is required on the effects of ethanol at very low doses, in plants and animals at both molecular and physiological levels. We believe that further research on this topic could lead to new discoveries in physiology and may even help us understand metabolic adjustments related to climate change. As temperatures rise more frequently, dissolved oxygen levels drop, leading to hypoxic conditions and consequently, an increase in cellular ethanol levels. [ABSTRACT FROM AUTHOR]

This article contributes to recent research on norms by highlighting the normative agency of non-Western, local recipients of global norms and the plurality of local responses to global norm diffusion. Bringing together insights from norm research and feminist scholarship, this study explores the reception of the global norm on violence against women (the anti-VAW norm) in Turkey, a Muslim majority country, over the past three decades. The study uncovers three different approaches to the global anti-VAW norm adopted by civil societal actors: adoption/compliance, contestation, and rejection. The analysis reveals that the global anti-VAW norm that seeks to unsettle established patriarchal gender hierarchies faces significant resistance in local contexts. The study thus emphasizes the importance of domestic normative frameworks that condition local responses to global norm diffusion. [ABSTRACT FROM AUTHOR]

Following successful treatment in which problem behavior is reduced, it may reemerge as a function of changes in contextual stimuli or the worsening of reinforcement conditions for an alternative response. Although understudied, preliminary research suggests that simultaneous changes in contextual stimuli and reinforcement conditions may represent particularly exigent treatment challenges that create the condition for additive or superadditive relapse. The purpose of the present review was to systematically examine the relapse literature involving simultaneous changes in contextual stimuli and reinforcement conditions in relapse tests and experimental preparations arranged to evaluate their effect on response recovery. We identified 16 empirical articles spanning 27 experiments. Although all experiments included at least one condition that experienced a change in contextual stimuli and worsening of alternative reinforcement conditions, only two experiments included the comparison conditions needed to precisely evaluate additive and superadditive relapse. Our findings establish the preclinical generality of relapse effects associated with simultaneous changes to reinforcement conditions and contextual stimuli across a range of subjects, schedule arrangements, response topographies, reinforcers, and types of contextual changes. We make several recommendations for future research based on our findings from this nascent and clinically relevant subdomain of the relapse literature. [ABSTRACT FROM AUTHOR]

Stable isotopic determination constitutes a useful tool to identify the processes that control the dynamics of the carbon and nitrogen flow in plants, unravelling the mechanisms of their differential investment under different environments. This work aimed to evaluate the spatiotemporal variation of source‐sink patterns of coffee trees under field conditions in response to climatic conditions through the assessment of stable isotopes. For this purpose, stems, leaves, and fruit samples from coffee trees were collected following a temporal pattern based on the region's climatic characteristics and the plant's phenology and a spatial pattern considering different parts of the canopy. The carbon and nitrogen percentage content, the C/N ratio, and the carbon and nitrogen isotopic compositions (δ13C and δ15N) were determined for all samples. The basal portion of the orthotropic branch was also considered for the isotopic analysis of the tree's growth rings. The results obtained were correlated with the climatic variables of the region through a Pearson correlation analysis (p <.05). Coffee plants showed traditional δ13C values of C3 plants. Temporal δ13C variation was associated with the different growth rates between phenological stages and the use of substrates produced at different times under different environmental conditions leading to differences in photosynthetic discrimination. Spatial δ13C variation was observed with heterotrophic tissues isotopically heavier than leaves, with a significant decrease trend in δ13C values from the top (upper third) to the bottom (lower third), associated with ecophysiological differences between the canopy, isotopic fractionation processes downstream of photosynthetic carbon discrimination, and the fixation of C from other pools. Temporal δ15N variation was associated with the precipitation rates in the region and the fertilization distribution across the tree, while the spatial variation was with the plant's nitrogen assimilation and translocation patterns. The tree growth rings isotopic analyses showed isotopic differences between growth rings of the same plant addressed by the climatic conditions, with precipitation being the primary climatic determinant influencing the fixation and discrimination against 13C. Our results highlight the importance of using stable isotope analysis as a reference point for coffee ecophysiological studies to characterize how the temporal and spatial patterns of δ13C and δ15N emerge and signal the influence of climate on the source‐sink relationship of coffee trees under field conditions. [ABSTRACT FROM AUTHOR]

Many animals routinely make energetic trade‐offs to adjust to environmental demands and these trade‐offs often have significant implications for survival. For example, environmental hypoxia is commonly experienced by many organisms and is an energetically challenging condition because reduced oxygen availability constrains aerobic energy production, which can be lethal. Many hypoxia‐tolerant species downregulate metabolic demands when oxygen is limited; however, certain physiological functions are obligatory and must be maintained despite the need to conserve energy in hypoxia. Of particular interest is immunity (including both constitutive and induced immune functions) because mounting an immune response is among the most energetically expensive physiological processes but maintaining immune function is critical for survival in most environments. Intriguingly, physiological responses to hypoxia and pathogens share key molecular regulators such as hypoxia‐inducible factor‐1α, through which hypoxia can directly activate an immune response. This raises an interesting question: do hypoxia‐tolerant species mount an immune response during periods of hypoxia‐induced hypometabolism? Unfortunately, surprisingly few studies have examined interactions between immunity and hypometabolism in such species. Therefore, in this review, we consider mechanistic interactions between metabolism and immunity, as well as energetic trade‐offs between these two systems, in hypoxia‐tolerant animals but also in other models of hypometabolism, including neonates and hibernators. Specifically, we explore the hypothesis that such species have blunted immune responses in hypometabolic conditions and/or use alternative immune pathways when in a hypometabolic state. Evidence to date suggests that hypoxia‐tolerant animals do maintain immunity in low oxygen conditions, but that the sensitivity of immune responses may be blunted. [ABSTRACT FROM AUTHOR]