pH-Sensitive blue and red N-CDs for L-asparaginase quantification in complex biological matrices.

A novel fluorometric method for the determination of L-asparaginase, an enzyme crucial in cancer therapy and food industry applications, is presented. This sensitive and selective approach utilizes L-asparagine and two pH-sensitive carbon dots (blue-N-CDs and red-N-CDs) as probes. The interaction between L-asparagine and L-asparaginase liberates ammonia, causing an increase in pH. This pH change simultaneously decreases the fluorescence of blue-N-CDs while enhancing the emission of red-N-CDs, enabling ratiometric detection of L-asparaginase. Comprehensive characterization of both carbon dots and investigation of their response mechanism towards L-asparaginase were conducted using ultraviolet-visible spectrophotometry, fluorescence spectroscopy, and transmission electron microscopy (TEM) imaging techniques. The designed approach demonstrates outstanding linearity (20 to 2000 U L-1) and a low detection limit (6.95 U L-1) for L-asparaginase quantification. Moreover, when tested to human serum samples, the detection system exhibits outstanding selectivity and high recovery rates (96.15% to 99.75%) with low standard deviation, underscoring its suitability for practical implementation in clinical diagnostics.

Electrochemical determination of captopril using a disposable graphite electrode modified with a molecularly imprinted film, accompanied by a ratiometric read-out.

In this research paper, a novel "signal on-off" ratiometric-based electrochemical platform was developed for the sensitive and selective detection of captopril. Ratiometric responses were achieved by fabricating molecularly imprinted polymers (MIPs) on the surface of a graphite electrode (GE) decorated with nitrogen (N) and sulfur (S) co-doped porous carbon and silver nanoparticles (Ag). The MIP layer was formed via electropolymerization of copper coordinated with pyrrole-3-carboxylic acid (functional monomer). Silver nanoparticles (Ag) were incorporated to enhance conductivity and surface area and to serve as an internal reference output. Upon the addition of captopril, there was a decrease in the anodic oxidation current of Ag+ at around 0.067 V, coupled with an increase in the oxidation current at 0.54 V (Ag-captopril complex). Under optimized conditions, the electrochemical responses (IAg-captopril/IAg) increased linearly with increasing captopril concentration in the range of 1-450 nM, with a detection limit (S/N = 3) of 0.3 nM. The ratiometric-based MIP electrochemical platform (Cu-MIP/NS-PC@Ag/GE) was successfully applied to detect captopril in complex matrices such as tablets, serum, and urine samples. This platform holds promise for sensitive and selective detection of captopril in various practical applications.

An open-source tool for automated human-level circling behavior detection.

Quantitatively relating behavior to underlying biology is crucial in life science. Although progress in keypoint tracking tools has reduced barriers to recording postural data, identifying specific behaviors from this data remains challenging. Manual behavior coding is labor-intensive and inconsistent, while automatic methods struggle to explicitly define complex behaviors, even when they seem obvious to the human eye. Here, we demonstrate an effective technique for detecting circling in mice, a form of locomotion characterized by stereotyped spinning. Despite circling's extensive history as a behavioral marker, there currently exists no standard automated detection method. We developed a circling detection technique using simple postprocessing of keypoint data obtained from videos of freely-exploring (Cib2-/-;Cib3-/-) mutant mice, a strain previously found to exhibit circling behavior. Our technique achieves statistical parity with independent human observers in matching occurrence times based on human consensus, and it accurately distinguishes between videos of wild type mice and mutants. Our pipeline provides a convenient, noninvasive, quantitative tool for analyzing circling mouse models without the need for software engineering experience. Additionally, as the concepts underlying our approach are agnostic to the behavior being analyzed, and indeed to the modality of the recorded data, our results support the feasibility of algorithmically detecting specific research-relevant behaviors using readily-interpretable parameters tuned on the basis of human consensus.

A novel injectable boron doped-mesoporous nano bioactive glass loaded-alginate composite hydrogel as a pulpotomy filling biomaterial for dentin regeneration.

BACKGROUND: Different materials have been used as wound dressings after vital pulp therapies. Some of them have limitations such as delayed setting, difficult administration, slight degree of cytotoxicity, crown discoloration and high cost. Therefore, to overcome these disadvantages, composite scaffolds have been used in regenerative dentistry. This study aims to construct and characterize the physicochemical behavior of a novel injectable alginate hydrogel loaded with different bioactive glass nanoparticles in various concentrations as a regenerative pulpotomy filling material. METHODS: Alginate hydrogels were prepared by dissolving alginate powder in alcoholic distilled water containing mesoporous bioactive glass nanoparticles (MBG NPs) or boron-doped MBG NPs (BMBG NPs) at 10 and 20 wt% concentrations. The mixture was stirred and incubated overnight in a water bath at 50 0 C to ensure complete solubility. A sterile dual-syringe system was used to mix the alginate solution with 20 wt% calcium chloride solution, forming the hydrogel upon extrusion. Then, constructed hydrogel specimens from all groups were characterized by FTIR, SEM, water uptake percentage (WA%), bioactivity and ion release, and cytotoxicity. Statistical analysis was done using One-Way ANOVA test for comparisons between groups, followed by multiple pairwise comparisons using Bonferroni adjusted significance level (p < 0.05). RESULTS: Alginate/BMBG loaded groups exhibited remarkable increase in porosity and pore size diameter [IIB1 (168), IIB2 (183) (µm)]. Similarly, WA% increased (~ 800%) which was statistically significant (p < 0.05). Alginate/BMBG loaded groups exhibited the strongest bioactive capability displaying prominent clusters of hydroxyapatite precipitates on hydrogel surfaces. Ca/P ratio of precipitates in IIA2 and IIB1 (1.6) were like Ca/P ratio for stoichiometric pure hydroxyapatite (1.67). MTT assay data revealed that the cell viability % of human gingival fibroblast cells have declined with increasing the concentration of both powders and hydrogel extracts in all groups after 24 and 48 h but still higher than the accepted cell viability % of (˃70%). CONCLUSIONS: The outstanding laboratory performance of the injectable alginate/BMBGNPs (20 wt%) composite hydrogel suggested it as promising candidate for pulpotomy filling material potentially enhancing dentin regeneration in clinical applications.

Lack of Efficacy of JNJ-18038683 on Cognitive Impairment in Patients With Stable Bipolar Disorder.

BACKGROUND: The serotonin type 7 (5-HT7) receptor is one of 14 5-HT receptors. It has received attention for its possible role in mood disorders and cognition. The 5-HT7 receptor antagonist, JNJ-18038683, has been reported to be effective in rodent models of depression and REM sleep. Also, 5-HT7 receptor blockade has been postulated to be a key component of cognitive enhancement in a number of drugs. Bipolar disorder (BD) usually endures cognitive impairment (CI); however, no treatment for CI in BD has been approved. This study aimed to evaluate the efficacy of JNJ-18038683 to improve the CI of BD compared to a placebo. METHODS: We conducted a placebo-controlled, 8-week trial of JNJ-18038683 in BD patients. Each patient's data were analyzed and reassessed blindly with a comprehensive neuropsychological battery, depression and hypomania ratings, and overall social and work function measures. RESULTS: Of 60 patients, 38 (63%) were female, 43 (72%) had BD type 1, and most patients were Caucasian and married. The overall time effect for the combined group shows statistically significant improvement from baseline to week 8 for most of the neurocognitive battery measures. This indicates a significant improvement in psychopathology and cognition during the study time in both JNJ-18038683 and placebo groups, but no difference between groups. CONCLUSIONS: This study showed no efficacy for the improvement of CIBD or mood symptoms with JNJ-18038683 compared to the placebo.

Clinical decision support improves autoimmune/paraneoplastic antibody panel utilization.

OBJECTIVES: Selection of autoimmune/paraneoplastic antibody panels remains challenging because health-care professionals often lack familiarity with panel contents, recommended specimen types, and antibody combinations for a given patient. Inappropriate use adds cost, prompts unnecessary additional workup, and delays the identification of the true cause of patient symptoms. In this study, we assessed whether order-entry clinical decision support can improve autoimmune/paraneoplastic antibody panel utilization. METHODS: An order-entry clinical decision support tool was embedded in the electronic health record system. Using a nested panel structure, the decision support tool prompted clinicians to identify their patient's clinical presentation and guided selection of the appropriate tests. In addition, the tool featured a duplicate checking function to alert clinicians when placing multiple orders with substantially similar antibody content within a 3-month period. Panel ordering practices were assessed during the 12 months before implementation and compared with the 6 months immediately following implementation. RESULTS: Clinical decision support significantly reduced the monthly test volume of all orderables from 75.8 per month before implementation to 54.5 per month after implementation (incident rate ratio [IRR], 0.72; 95% CI, 0.63-0.81; P < .001). Placement of multiple orders for panels with substantially overlapping antibody content also decreased significantly, from 7.0 per month to 1.2 per month (IRR, 0.17; 95% CI, 0.07-0.33; P < .001). The number of neural-specific antibodies detected remained unchanged, but the reduction in total test volume increased the neural-specific antibody positivity rate from 4.2% to 6.8% (IRR, 1.61; 95% CI, 0.94-2.70; P = .075). CONCLUSIONS: Order-entry clinical decision support offers an efficient and effective approach to improve the utilization of autoimmune/paraneoplastic antibody panels.

Properties, estimation, and applications of the extended log-logistic distribution.

This paper presents the exponentiated alpha-power log-logistic (EAPLL) distribution, which extends the log-logistic distribution. The EAPLL distribution emphasizes its suitability for survival data modeling by providing analytical simplicity and accommodating both monotone and non-monotone failure rates. We derive some of its mathematical properties and test eight estimation methods using an extensive simulation study. To determine the best estimation approach, we rank mean estimates, mean square errors, and average absolute biases on a partial and overall ranking. Furthermore, we use the EAPLL distribution to examine three real-life survival data sets, demonstrating its superior performance over competing log-logistic distributions. This study adds vital insights to survival analysis methodology and provides a solid framework for modeling various survival data scenarios.

Critical assessment of furrow openers and operational parameters for optimum performance under conservation tillage.

Conservation Agriculture (CA) is an innovative approach that promotes sustainable farming while enhancing soil health. However, residue management challenges often hinder its adoption, causing farmers to burn crop leftovers in fields. This study aimed to evaluate the effectiveness of various furrow openers under simulated soil bin conditions. Three types of furrow openers were examined: single disk (SD), Inverted T-type furrow opener with a plain rolling coulter (ITRC), and double disc (DD) furrow opener. Tests were conducted at different forward speeds (1.5, 2, and 2.5 km h-1) and with three straw densities (1, 2, and 3 t ha-1) at a consistent working depth of 5 cm. Draft measurements were obtained using load cells connected to an Arduino-based data-logging system. Results indicated that draft requirements increased with forward speed and straw density, while straw-cutting efficiency decreased with these factors. Average draft values for SD, ITRC, and DD were 290.3 N, 420 N, and 368.5 N, respectively, and straw-cutting efficiencies were 53.62%, 59.47%, and 74.89%, respectively. The DD furrow opener showed the highest straw-cutting efficiency (81.36%) at a working speed of 1.5 km h-1 and a straw density of 1 t ha-1, demonstrating optimal performance compared to other furrow openers.

Comparative Evaluation of Temporomandibular Joint Parameters in Unilateral and Bilateral Cleft Lip and Palate Patients Using Cone-Beam CT: Focus on Growing vs. Non-Growing Subjects.

BACKGROUND: Morphological differences in the temporomandibular joint (TMJ) are crucial for the treatment of patients with cleft lip and palate (CLP). This study aims to evaluate and compare the TMJ parameters in patients with unilateral and bilateral CLP across growing and non-growing age groups using cone-beam computed tomography (CBCT). METHODS: CBCT records from 57 patients (23 males and 34 females) aged 6-50 years with a diagnosed unilateral or bilateral CLP were analyzed. Patients were categorized into four groups: growing unilateral (UGCLP), growing bilateral (BGCLP), non-growing unilateral (UNGCLP), and non-growing bilateral (BNGCLP). Measurements of TMJ parameters, including the mandibular fossa, articular eminence inclination, joint spaces, and roof thickness of the glenoid fossa, were conducted using CBCT images. RESULTS: Significant differences were observed in the anterior joint space (AJS) and the roof of the glenoid fossa (RGF) between growing and non-growing unilateral cleft patients. Additionally, significant discrepancies were found in the articular eminence angle when comparing the cleft and non-cleft sides within the unilateral growing group. No significant differences were observed in TMJ parameters between the right and left sides among bilateral cleft patients. CONCLUSIONS: The study highlights distinct TMJ morphological differences between growing and non-growing patients with CLP, emphasizing the importance of age-specific considerations in the treatment planning and growth monitoring of these patients.

A novel urease-assisted ratiometric fluorescence sensing platform based on pH-modulated copper-quenched near-infrared carbon dots and methyl red-quenched red carbon dots for selective urea monitoring.

A novel and sensitive fluorescence ratiometric method is developed for urea detection based  on the pH-sensitive response of two fluorescent carbon dot (CD) systems: R-CDs/methyl red (MR) and NIR-CDs/Cu2+. The sensing mechanism involves breaking down urea using the enzyme urease, releasing ammonia and increasing pH. At higher pH, the fluorescence of NIR-CDs is quenched due to the enhanced interaction with Cu2+, while the fluorescence of R-CDs is restored as the acidic MR converts to its basic form, removing the inner filter effect. The ratiometric signal (F608/F750) of the R-CDs/MR and NIR-CDs/Cu2+ intensities changed in response to the pH induced by urea hydrolysis, enabling selective and sensitive urea detection. Detailed spectroscopic and morphological investigations confirmed the fluorescence probe design and elucidated the sensing mechanism. The method exhibited excellent sensitivity (0.00028 mM LOD) and linearity range (0.001 - 8.0 mM) for urea detection, with successful application in milk samples for monitoring adulteration, demonstrating negligible interference and high recovery levels (96.5% to 101.0%). This ratiometric fluorescence approach offers a robust strategy for selective urea sensing in complicated matrices.

A potent formula against triple-negative breast cancer-sorafenib-carbon nanotubes-folic acid: Targeting, apoptosis triggering, and bioavailability enhancing.

Triple-negative breast cancer (TNBC) has short survival rates. This study aimed to prepare a novel formula of sorafenib, carbon nanotubes (CNTs), and folic acid to be tested as a drug delivery system targeting versus TNBC compared with free sorafenib and to evaluate the formula stability, in vitro pharmacodynamic, and in vivo pharmacokinetic properties. The formula preparation was done by the synthesis of polyethylene glycol bis amine linker, CNT PEGylation, folic acid attachment, and sorafenib loading. The prepared formula has been characterized using X-ray diffraction, Flourier-transform infrared, 1HNMR, UV, high resolution-transmission electron microscope, field emission scanning electron microscopy, and Zeta potential. In vitro studies included drug release determination, MTT assay, flow cytometry to determine the apoptotic stage with percent, cell cycle analysis, and apoptotic marker assays for caspase-3, 8, 9, cytochrome c, and BCL-2. The in vivo study was performed to determine bioavailability and half-life in rats. The in vitro MTT antiproliferative assay revealed that the formula was threefold more cytotoxic toward TNBC cells than free sorafenib, and the flow cytometry showed a significant increase in apoptosis and necrosis. The formula has a greater inhibitory effect on BCL-2 and a lessening effect on cytochrome c and caspases 3, 8, and 9 than free sorafenib. In vivo experiments proved that our novel formula was superior to free sorafenib by increasing bioavailability by eight times and prolonging the half-life by three times. These results confirmed the successful preparation of the desired formula with better pharmacodynamic and pharmacokinetic properties. These promising results may show a novel therapeutic strategy for TNBC patients.

Closing the loop: Strengthening course quality of Pharm.D. program via applying a comprehensive four-step review approach.

This study explores the course review process implemented by the College of Pharmacy at King Saud University for its Pharm.D. program. Through a qualitative research design, a dedicated course review committee was established to oversee the evaluation process. The committee gathered and analyzed data from various sources, including course reports, student evaluations, and exam center reports, to achieve a holistic understanding of each course's effectiveness. The evaluation process was structured into a Four-Step Course Evaluation Approach: data collection, data review and recommendations, taking appropriate action, and communicating the outcomes. The "closing the loop" stage ensured that recommendations were effectively implemented, and course evaluation data were systematically archived for future reference. The results of this study, based on the evaluation of 25 courses, revealed significant improvements in course quality, alignment with program learning outcomes, and adherence to accreditation standards. Key findings included the identification of gaps and discrepancies, leading to targeted interventions and enhanced course content. Overall, this study highlights the effectiveness of a structured course review process in enhancing the quality of education and ensuring continuous improvement within the college. The committee focuses on refining evaluation criteria, conducting workshops, and providing training to stay current with emerging accreditation standards and best practices. This systematic course review process demonstrates the College's commitment to providing high-quality education and preparing students for successful careers in pharmacy, with significant implications for the improvement of pharmacy education and the overall student learning experience.

Analysis of fractional solitary wave propagation with parametric effects and qualitative analysis of the modified Korteweg-de Vries-Kadomtsev-Petviashvili equation.

This study explores the fractional form of modified Korteweg-de Vries-Kadomtsev-Petviashvili equation. This equation offers the physical description of how waves propagate and explains how nonlinearity and dispersion may lead to complex and fascinating wave phenomena arising in the diversity of fields like optical fibers, fluid dynamics, plasma waves, and shallow water waves. A variety of solutions in different shapes like bright, dark, singular, and combo solitary wave solutions have been extracted. Two recently developed integration tools known as generalized Arnous method and enhanced modified extended tanh-expansion method have been applied to secure the wave structures. Moreover, the physical significance of obtained solutions is meticulously analyzed by presenting a variety of graphs that illustrate the behaviour of the solutions for specific parameter values and a comprehensive investigation into the influence of the nonlinear parameter on the propagation of the solitary wave have been observed. Further, the governing equation is discussed for the qualitative analysis by the assistance of the Galilean transformation. Chaotic behavior is investigated by introducing a perturbed term in the dynamical system and presenting various analyses, including Poincare maps, time series, 2-dimensional 3-dimensional phase portraits. Moreover, chaotic attractor and sensitivity analysis are also observed. Our findings affirm the reliability of the applied techniques and suggest its potential application in future endeavours to uncover diverse and novel soliton solutions for other nonlinear evolution equations encountered in the realms of mathematical physics and engineering.

Efficacy of the CALM® Algorithm in Reducing Motion-Induced Artifacts in CBCT Imaging: A Fractal Dimension Analysis of Trabecular Bone.

OBJECTIVE: The primary goal of this investigation was to ascertain the efficacy of the CALM® motion artifact reduction algorithm in diminishing motion-induced blurriness in Cone Beam Computed Tomography [CBCT] images. The assessment was conducted through Fractal Dimension [FD] analysis of the trabecular bone. METHODS AND MATERIALS: A desiccated human mandible was subjected to Planmeca ProMax 3D® scanning under eight distinct protocols, marked by variations in motion presence [at 5, 10, and 15 degrees] and the deployment of CALM®. In every scan, five distinct regions of interest [ROIs] were designated for FD analysis, meticulously avoiding tooth roots or cortical bone. The FD was computed employing the box-counting method with Image-J 1.53 software. RESULTS: Our findings reveal that a 5-degree motion does not significantly disrupt FD analysis, while a 10-degree motion and beyond exhibit statistical differences and volatility among the sites and groups. A decreased FD value, signifying a less intricate or "rough" bone structure, correlated with amplified motion blurriness. The utilization of CALM® software seemed to counteract this effect in some instances, reconciling FD values to those akin to the control groups. Nonetheless, CALM®'s efficacy differed across sites and motion degrees. Interestingly, at one site, CALM® application in the absence of motion resulted in FD values considerably higher than all other groups. CONCLUSION: The study indicates that motion, particularly at 10 degrees or more, can considerably impact the FD analysis of trabecular bone in CBCT images. In some situations, the CALM® motion artifact reduction algorithm can alleviate this impact, though its effectiveness fluctuates depending on the site and degree of motion. This underscores the necessity of factoring in motion and the employment of artifact reduction algorithms during the interpretation of FD analysis outcomes in CBCT imaging. More research is necessary to refine the application of such algorithms and to comprehend their influence on different sites under varying motion degrees.

A novel disposable ultrasensitive sensor based on nanosized ceria uniformly loaded carbon nanofiber nanoceramic film wrapped on pencil graphite rods for electrocatalytic monitoring of a tyrosine kinase inhibitor capmatinib.

For the first time, we introduce a novel disposable and ultrasensitive sensing electrode made up of nanosized ceria uniformly loaded carbon nanofibers (CeNPs@CNF) sol-gel nanoceramic film (CF) wrapped on eco-friendly and inexpensive pencil graphite rods (PGRs) to explore their electro-catalytic detection of the anticancer drug capmatinib (CMB). The as-prepared CeNPs@CNF hybrid nanocomposite was described by XRD, SEM, TEM, HRTEM, and EDX analysis. The CV study clearly demonstrated that, the disposable CeNPs@CNF-CF/PGRE sensor exhibited excellent redox activities in the ideal probe [Fe(CN)6]3-/4-. Due to the outstanding electrochemical properties, larger electrochemically active surface area, and tremendous electro-catalytic activity of CeNPs@CNF, the reduction current of CMB on the CeNPs@CNF-CF/PGRE sensor is considerably higher than that of bare PGRE. The detection conditions, such as supporting electrolyte, pH of the buffer solution, amount of modifier, adsorption potential, and time, were studied and optimized. The sensing platform demonstrated high sensitivity (1.2 µA nM-1 cm-2), an ultralow detection limit (0.6 nM), and a wide linear range of 2.0 nM-400 nM of CMB compared to the bare PGRE. Additionally, the CeNPs@CNF-CF/PGRE sensor showed high selectivity, stability, and simple operation, which provided a promising alternative tool for fast detection of CMB in human body fluids with good recoveries.

The ruminant gut microbiome vs enteric methane emission: The essential microbes may help to mitigate the global methane crisis.

Ruminants release enteric methane into the atmosphere, significantly increasing greenhouse gas emissions and degrading the environment. A common focus of traditional mitigation efforts is on dietary management and manipulation, which may have limits in sustainability and efficacy, exploring the potential of essential microorganisms as a novel way to reduce intestinal methane emissions in ruminants; a topic that has garnered increased attention in recent years. Fermentation and feed digestion are significantly aided by essential microbes found in the rumen, such as bacteria, fungi, and archaea. The practical implications of the findings reported in various studies conducted on rumen gut concerning methane emissions may pave the way to understanding the mechanisms of CH4 production in the rumen to enhance cattle feed efficiency and mitigate CH4 emissions from livestock. This review discussed using essential bacteria to reduce intestinal methane emissions in ruminants. It investigates how particular microbial strains or consortia can alter rumen fermentation pathways to lower methane output while preserving the health and productivity of animals. We also describe the role of probiotics and prebiotics in managing methane emissions using microbial feed additives. Further, recent studies involving microbial interventions have been discussed. The use of new methods involving functional metagenomics and meta-transcriptomics for exploring the rumen microbiome structure has been highlighted. This review also emphasizes the challenges faced in altering the gut microbiome and future directions in this area.

Mechanisms of DNA Damage Response in Mammalian Oocytes.

DNA damage poses a significant challenge to all eukaryotic cells, leading to mutagenesis, genome instability and senescence. In somatic cells, the failure to repair damaged DNA can lead to cancer development, whereas, in oocytes, it can lead to ovarian dysfunction and infertility. The response of the cell to DNA damage entails a series of sequential and orchestrated events including sensing the DNA damage, activating DNA damage checkpoint, chromatin-related conformational changes, activating the DNA damage repair machinery and/or initiating the apoptotic cascade. This chapter focuses on how somatic cells and mammalian oocytes respond to DNA damage. Specifically, we will discuss how and why fully grown mammalian oocytes differ drastically from somatic cells and growing oocytes in their response to DNA damage.

Craniofacial and Airway Morphology in Down Syndrome: A Cone Beam Computed Tomography Case Series Evaluation.

Background: Down syndrome (DS) is a genetic condition characterized by an extra copy of chromosome 21, resulting in various physical and cognitive features. This study aimed to comprehensively analyze the dental and craniofacial morphology of individuals with DS using Cone Beam Computed Tomography (CBCT). Methods: Six individuals with DS, comprising five males and one female aged 17 to 35 years, underwent CBCT scanning. Radiographic assessments included dentition, occlusion, paranasal sinuses, airway, skull bones, and suture calcification. Linear and angular cephalometric measurements were performed, and airway analysis was conducted using Dolphin 3D imaging software v.11. Results: The study revealed prognathic maxilla in five patients, prognathic mandible in four, and bimaxillary protrusion in two. Dental findings included microdontia, enamel hypoplasia, and congenitally missing teeth, with maxillary and mandibular third molars most commonly absent. Sinus abnormalities, delayed suture closure, and cervical spine anomalies were also observed. Conclusion: These findings contribute to a deeper understanding of DS-related craniofacial characteristics and emphasize the importance of considering these morphometric features in clinical management strategies for individuals with DS. This study's limited sample size underscores the significance of radiographic assessment in planning interventions such as cosmetic reconstructions, prosthetic rehabilitation, or orthodontic treatment for individuals with DS.

Prefrontal coding of learned and inferred knowledge during REM and NREM sleep.

Idling brain activity has been proposed to facilitate inference, insight, and innovative problem-solving. However, it remains unclear how and when the idling brain can create novel ideas. Here, we show that cortical offline activity is both necessary and sufficient for building unlearned inferential knowledge from previously acquired information. In a transitive inference paradigm, male C57BL/6J mice gained the inference 1 day after, but not shortly after, complete training. Inhibiting the neuronal computations in the anterior cingulate cortex (ACC) during post-learning either non-rapid eye movement (NREM) or rapid eye movement (REM) sleep, but not wakefulness, disrupted the inference without affecting the learned knowledge. In vivo Ca2+ imaging suggests that NREM sleep organizes the scattered learned knowledge in a complete hierarchy, while REM sleep computes the inferential information from the organized hierarchy. Furthermore, after insufficient learning, artificial activation of medial entorhinal cortex-ACC dialog during only REM sleep created inferential knowledge. Collectively, our study provides a mechanistic insight on NREM and REM coordination in weaving inferential knowledge, thus highlighting the power of idling brain in cognitive flexibility.