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Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia.

Purpose: Height age (HA) and bone age (BA) delay is well known in the patients with short stature. Therefore assessing pituitary hypoplasia based on chronological age (CA) might cause overdiagnosis of pituitary hypoplasia. We aimed to investigate the diagnostic and prognostic value of the PH and PV based on CA, HA, or BA in the patients with GHD. Methods: Fifty-seven patients with severe and 40 patients with partial GHD and 39 patients with ISS assigned to the study. For defining the most accurate diagnosis of pituitary hypoplasia, PH and PV were evaluated based on CA, BA and HA. The relationship of each method with clinical features was examined. Results: The mean PV was significantly larger in patients with ISS compared to the GH-deficient patients. PV was more correlated with clinical features including height SDS, stimulated GH concentration, IGF-1 and IGFBP-3 SDS, height velocity before and after rGH therapy. We found BA-based PV could discriminate GHD from ISS (Sensitivity: 17%, specificity: 98%, positive predictive value: 94%, negative predictive value: 39%), compared to the other methods based on PH or PV respect to CA and HA. 3% of patients with ISS, 17% of patients with GHD had pituitary hypoplasia based on PV-BA. Conclusion: PV based on BA, has the most accurate diagnostic value for defining pituitary hypoplasia. But it should be kept in mind that there might be still misdiagnosed patients by this method. PV is also a significant predictor for the rGH response.

This study investigates the influence of post-oxidation duration on the wear performance and microstructural features of AISI 4140 steel subjected to nitrocarburizing followed by post-oxidation. For this aim, the quenched and tempered AISI 4140 samples were nitrocarburized (NC) and post-oxidized (PO) at various times (45–180 min) under low vacuum. Microstructural features were investigated using optical microscopy, scanning electron microscope (SEM), energy-dispersive X-ray spectrum analysis (EDS), X-ray diffraction (XRD) analysis, and microhardness test. Wear behavior was evaluated using a ball-on-disk tribometer. Experimental results showed that the structures consisting of nitride layer (ε-Fe2–3N) and γ′-Fe4N + iron oxide (Fe3O4) were obtained at the top surfaces of the samples. Increasing post-oxidation times resulted in a notable enhancement in the thickness of the Fe3O4layer. The growing Fe3O4layer has induced the closing of micro porosities for further post-oxidizing times, leading to decreased surface roughness of the samples. It was determined that the post-oxidation times have no significant effect on the hardness profiles of NC + PO samples. The highest (0.375) and lowest (0.276) mean coefficient of friction was obtained in the post-oxidation times of 150 and 180 min, respectively. The best wear rate was obtained in the post-oxidized sample for 150 min.

In this study, the microstructure and mechanical performance of Fe-based composites reinforced by FeTi+B4C at various ratios were determined. The study was based on the production of Fe based nano carbide and boride (B4C, Fe2B, Fe7C3, TiB2) reinforced composites. Mechanical alloying technique was chosen to reduce the reinforcement material to nano size and distribute it homogeneously. Sintering temperature was used as 1,100 °C and sintering time as 2 h. The reionforcement “FeTi+B4C” ratio was raised up to 15 wt.%. The microstructure and phases of the composite samples were descrived by scanning electron microscopy, energy dispersive spectroscopy, X-RD analysis and hardness. The concentration of voids and the stiffness changes of the samples were determined. The size of TiC and TiB2particles reduced significantly with the rise in B4C ratio. Since the hardness of TiB2was less than that of the B4C matrix, the hardness reduced with increasing TiB2ratio.

Extremum seeking, an online model-free optimization algorithm with traditionally exponential convergence, was recently advanced by Poveda and coauthors to fixed-time convergence, using nonsmooth time-invariant feedback. In this article, we introduce an alternative time-varying prescribed-time extremum seeking (PT-ES) approach to reaching the optimum in a user-assignable “prescribed” time (PT), independent of the initial condition of the estimator. Instead of conventional sinusoidal probing signals, we employ “chirpy” perturbations, i.e., sinusoids with growing frequencies. In addition to providing a result for a static input–output map, we provide algorithms for a map in cascade with a delay, a wave partial differential equation (PDE), and a heat/diffusion PDE. The designs are based on the time-varying PT backstepping approach, which transforms the PDE–ordinary-differential-equation cascade into a suitable PT-stabilized target system, and on averaging-based estimates of the gradient and Hessian of the map. Classical averaging does not apply for the analysis of PT-ES algorithms for four reasons: neither is probing periodic, nor is the “average system” exponentially stable, nor is the original system finite-dimensional, nor is the interval of operation infinite. We develop an averaging technique needed for this non-periodic finite-time infinite-dimensional problem. Along with PDE Lyapunov analysis, we show that the input converges to the optimizer in PT. We present three numerical examples to illustrate the effectiveness of the proposed technique for delay-free case as well as for compensation of time-delay and diffusion PDE dynamics.

This study investigated in-hospital outcomes and related factors in patients diagnosed with postearthquake crush syndrome after the earthquakes in Kahramanmaraş, Türkiye. One thousand twenty-four adult patients diagnosed with crush syndrome were analyzed. Data on demographic characteristics, clinical presentation, laboratory values, treatments, and outcomes were collected. A total of 9.8% of patients died during their hospital stay. Nonsurvivors were generally older, more likely to have preexisting chronic kidney disease, and faced more severe injuries and complications, including hypotension-shock, arrhythmias, elevated markers of renal dysfunction, and higher rates of acute kidney injury (AKI) and compartment syndrome. In addition, intensive care unit needs were higher. Multivariate analysis confirmed that age, injury severity, shock, high potassium, uric acid, and lactate levels on admission, development of AKI, compartment syndrome, and intensive care unit admission were significant predictors of mortality. Better disaster preparedness and improved health care infrastructure could be potential explanations for improved in-hospital mortality in the current era, as compared to previous earthquakes.

To evaluate the cardiovascular risk status of patients with endometriosis using serum lipid parameters and atherogenic indices.

Aim: To assess the patterns regarding COVID-19 infection and vaccination, along with the intention and hesitancy towards receiving a booster dose of the COVID-19 vaccine among community pharmacists in Istanbul, Türkiye. Subject and Methods: This was a cross-sectional, descriptive study conducted using a three-part structured validated questionnaire among community pharmacists. Vaccine hesitancy from a booster dose of the COVID-19 vaccine was assessed using the Vaccine Hesitancy Scale. Results: A total of 145 community pharmacists were included, with a mean age of 43.22 ±13.3 years. Ninety-eight percent of the respondents received the COVID-19 vaccine. Most of the participants reported significant agreement to receiving a booster dose of the vaccine (91.7%, P< 0.0001). There was a statistically significant correlation between the intention to receive a booster vaccine dose and female gender (P= 0.0008), pharmacy education degree (bachelor’s degree; P< 0.0001), and work experience more than 10 years (P< 0.0001). Conclusion: Regardless of side effects from the previous dose, most of pharmacists who received the COVID-19 vaccine reported an intention to receive the booster dose, which generally builds trust in vaccine acceptance and undoubtedly plays a significant role in the control of the COVID-19 pandemic.

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The human immunodeficiency virus presents a significant global health challenge due to its rapid mutation and the development of resistance mechanisms against antiretroviral drugs. Recent studies demonstrate the impressive performance of machine learning (ML) and deep learning (DL) models in predicting the drug resistance profile of specific FDA-approved inhibitors. However, generalizing ML and DL models to learn not only from isolates but also from inhibitor representations remains challenging for HIV-1 infection. We propose a novel drug-isolate-fold change (DIF) model framework that aims to predict drug resistance score directly from the protein sequence and inhibitor representation. Various ML and DL models, inhibitor representations, and protein representations were analyzed through realistic validation mechanisms. To enhance the molecular learning capacity of DIF models, we employ a transfer learning approach by pretraining a graph neural network (GNN) model for activity prediction on a data set of 4855 HIV-1 protease inhibitors (PIs). By performing various realistic validation strategies on internal and external genotype–phenotype data sets, we statistically show that the learned representations of inhibitors improve the predictive ability of DIF-based ML and DL models. We achieved an accuracy of 0.802, AUROC of 0.874, and rof 0.727 for the unseen external PIs. By comparing the DIF-based models with a null model consisting of isolate-fold change (IF) architecture, it is observed that the DIF models significantly benefit from molecular representations. Combined results from various testing strategies and statistical tests confirm the effectiveness of DIF models in testing novel PIs for drug resistance in the presence of an isolate.

In atom transfer radical polymerization (ATRP), dormant alkyl halides are intermittently activated to form growing radicals in the presence of a CuI/L/X-CuII/L (activator/deactivator) catalytic system. Recently developed very active copper complexes could decrease the catalyst concentration to ppm level. However, unavoidable radical termination results in irreversible oxidation of the activator to the deactivator species, leading to limited monomer conversions. Therefore, successful ATRP at a low catalyst loading requires continuous regeneration of the activators. Such a regenerative ATRP can be performed with various reducing agents under milder reaction conditions and with catalyst concentrations diminished in comparison to conventional ATRP. Photoinduced ATRP (PhotoATRP) is one of the most efficient methods of activator regeneration. It initially employed UV irradiation to reduce the air-stable excited X-CuII/L deactivators to the activators in the presence of sacrificial electron donors. Photocatalysts (PCs) can be excited after absorbing light at longer wavelengths and, due to their favorable redox potentials, can reduce X-CuII/L to CuI/L. Herein, we present the application of three commercially available xanthene dyes as ATRP PCs: rose bengal (RB), rhodamine B (RD), and rhodamine 6G (RD-6G). Even at very low Cu catalyst concentrations (50 ppm), they successfully controlled PhotoATRP. Well-defined polymers with preserved livingness were prepared under green LED irradiation, with subppm concentrations ([PC] ≥ 10 ppb) of RB and RD-6G or 5 ppm of RD. Interestingly, these PCs efficiently controlled ATRP at wavelengths longer than their absorption maxima but required higher loadings. Polymerizations proceeded with high initiation efficiencies, yielding polymers with narrow molecular weight distributions and high chain-end fidelity. UV–vis, fluorescence, and laser flash photolysis studies helped to elucidate the mechanism of the processes involved in the dual-catalytic systems, comprising parts per million of Cu complexes and parts per billion of PCs.

AbstractIn this study, the structural and anticancer properties of aminopterin, as well as its antiviral characteristics, were elucidated. The preferred conformations of the title molecule were investigated with semiempirical AM1 method, and the obtained the lowest energy conformer was then optimized by using density functional (DFT/B3LYP) method with 6-311++G(d,p) as basis set. The vibrational frequencies of the optimized structure were calculated by the same level of theory and were compared with the experimental values. The vibrational assignments were performed based on the computed potential energy distribution (PED) of the vibrational modes. The molecular electrostatic potential (MEP) and frontier molecular orbitals (HOMO, LUMO) analyses were carried out for the optimized structure and the chemical reactivity has been scrutinized. To enlighten the biological activity of aminopterin as anticancer and anti-COVID-19 agents, aminopterin was docked into DNA, αIIBβ3and α5β1integrins, human dihydrofolate reductase, main protease (Mpro) of SARS-CoV-2 and SARS-CoV-2/ACE2 complex receptor. The binding mechanisms of aminopterin with the receptors were clarified. The molecular docking results revealed the strong interaction of the aminopterin with DNA (−8.2 kcal/mol), αIIBβ3and α5β1integrins (−9.0 and −10.8 kcal/mol, respectively), human dihydrofolate reductase (−9.7 kcal/mol), Mproof SARS-CoV-2 (−6.7 kcal/mol), and SARS-CoV-2/ACE2 complex receptor (−8.1 kcal/mol). Moreover, after molecular docking calculations, top-scoring ligand-receptor complexes of the aminopterin with SARS-CoV-2 enzymes (6M03 and 6M0J) were subjected to 50 ns all-atom MD simulations to investigate the ligand-receptor interactions in more detail, and to determine the binding free energies accurately. The predicted results indicate that the aminopterin may significantly inhibit SARS-CoV-2 infection. Thus, in this study, as both anticancer and anti-COVID-19 agents, the versatility of the biological activity of aminopterin was shown.Communicated by Ramaswamy H. Sarma

The direct electrocatalytic epoxidation of propylene into propylene oxide (PO) is a promising sustainable approach in comparison to current industrial methods for propylene oxidation. However, the yield rates and selectivities of this reaction are too low for industrial requirements. Therefore, it is important to understand the reaction mechanisms for rational catalyst design. In this regard, two noble metal oxides, PtOxand PdOx, are considered in this work for investigating the electrooxidation of propylene into PO. PO is measured in situ via an electrochemical mass spectrometry instrument to overcome the ex situ detection challenges caused by the PO being unstable in aqueous media. In this way, PO could be measured before undergoing hydrolysis or other possible transformations. The selectivity toward PO reaches the maximum at 1.3 V vs RHE on PdOx, whereas on PtOx, the vertex occurs at 1.6 V vs RHE. Moreover, the activity trends of PO production indicate that on PdOx, the rate-determining step for the epoxidation is different whether one is more anodic or more cathodic than 1.3 V vs RHE, while it remains the same in the 1.0–1.6 V vs RHE potential window on PtOx.

This trial investigated the efficacy of artichoke (Cynara scolymus) extract (AE) on the growth performance, immunity, antioxidant parameters, and resistance against Aeromonas hydrophilaof goldfish (Carassius auratus). For this purpose, a total number of 470 goldfish with initial weight 5.70±0.2 g were fed with four experimental diets including 0 (T0), 100 (T1), 150 (T2), and 200 (T3) mg kg−1diet AE for 8 weeks. At the end of feeding trial, growth performances, serum immune parameters, and mucus antioxidant enzymes were measured. Fish were challenged with A. hydrophila, and the antioxidant and immunity-related gene expression were investigated. Based on the results, the highest final weight (FW) and weight gain (WG) were attained in T2 and T3 (P<0.05). Immune factors including ACH50, lysozyme, and total immunoglobulin in T2 and T3 showed the highest values (P<0.05). The expression of GR, IL1β, TNFα, HSC70, HSP70, and HSP90βgenes in T1, T2, and T3 were higher than the control (P<0.05). The GSTexpression was significantly enhanced in T2 (P<0.05). The present study demonstrated that the administration of AE, especially at doses of 150 mg kg−1, could improve the growth, immunity, and antioxidant parameters, as well as enhance disease resistance against A. hydrophilain goldfish.

The ability to identify individuals in the prodromal phase of Parkinson’s disease has improved in recent years, raising the question of whether and how those affected should be informed about the risk of future disease. Several studies investigated prognostic counselling for individuals with isolated REM sleep behavior disorder and have shown that most patients want to receive information about prognosis, but autonomy and individual preferences must be respected. However, there are still many unanswered questions about risk disclosure or early diagnosis of PD, including the impact on personal circumstances, cultural preferences and specific challenges associated with different profiles of prodromal symptoms, genetic testing or biomarker assessments. This narrative review aims to summarize the current literature on prognostic counselling and risk disclosure in PD, as well as highlight future perspectives that may emerge with the development of new biomarkers and their anticipated impact on the definition of PD.

Massive open online courses (MOOCs) have gained popularity as a form of distance education, highlighting the need for additional research. Various studies have systematically examined scholarly research on MOOCs. However, the reviewed academic publications on the use of MOOCs in engineering education are limited. This study aims to examine the implementation of MOOCs in engineering education using systematic review and bibliometric analysis methods. This study examines 68 studies from the Web of Science database that fall within the scope of the systematic review and 257 studies for bibliometric analysis. Since 2018, there has been a growing number of studies exploring the uses of MOOCs in engineering education. The quantitative research method is the most preferred, while the mixed method is the least preferred. The study found that using MOOCs in engineering education resulted in positive student perceptions and satisfaction. However, the lack of interactivity between learners and instructors or among learners was the most frequently reported problem. Moreover, the bibliometric analysis indicates that reviewed studies extensively explore learners' engagement, interactions, and feedback processes. Recently, academic research focused on sentiment analysis, deep learning, educational technology, machine learning, and text mining. There is a need for further investigation into utilizing MOOCs in engineering education. This study's evaluation of MOOCs' pros and cons yields essential insights for optimizing their use in engineering education. By leveraging the positive aspects outlined in the study, educators can enhance engineering students' satisfaction and participation in MOOCs. These findings offer a valuable resource for researchers exploring MOOC‐related topics in engineering education.

This letter presents a novel beam-squint-aware (BSA) channel estimation method for uniform planar array (UPA)-type reconfigurable intelligent surface (RIS)-aided frequency- and spatial-wideband (dual-wideband) massive multiple-input multiple-output (MIMO) systems. The proposed scheme considers the angles of arrival (AoAs), angles of departure (AoDs), and propagation delays as slowly-varying, while treating the channel gains as fast-varying parameters. To estimate these parameters, we divide the estimation procedure into slow-time parameter estimation (ST-PE) and fast-time parameter estimation (FT-PE) modes. During the ST-PE mode, we propose a BSA periodogram for estimating the AoAs at the base station (BS), followed by a BSA orthogonal matching pursuit (OMP) algorithm for estimating the cascaded angles and delays. In the FT-PE mode, we propose a subspace-aware least squares (SA-LS) method to estimate the channel gains. Simulation results demonstrate the superiority of the proposed estimation methods in terms of root mean square error (RMSE) and achievable rate metrics when compared to state-of-the-art approaches.

Abstract: In this study, a pullulan hydrogel is grafted by poly(N-vinylimidazole) (PNVI) in a heterogeneous acidic medium under a nitrogen atmosphere for Methyl Orange (MO) and Acid Green 25 (AG25) dye removal application. The effect of monomer concentration as a significant parameter for grafting yield is investigated thoroughly, and it is demonstrated that 189% grafting yield of PNVI grafted onto epichlorohydrin crosslinked pullulan (pullulan-ECH-graft-PNVI) can be obtained under proper conditions. Equilibrium water absorption capacity values reveal the pH-responsivity of pullulan-ECH-graft-PNVI hydrogels (6000%) as compared to the epichlorohydrin crosslinked pullulan (pullulan-ECH) hydrogel (1000%) counterpart. Further characterization of the samples was performed by Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and X-ray diffraction (XRD). Adsorption of MO and AG25 on pullulan-ECH-graft-PNVI samples was studied at various pH, dye concentration, and time. The optimal adsorption pH value was measured at pH 3.0 with an adsorption capacity of 36.6 mg MO/g adsorbent and 5.72 mg AG25/g adsorbent. Isotherms and kinetic studies describe the adsorption profiles of the samples. The adsorption trends of the samples best fit the Freundlich model, which supports heterolayer dye adsorption and surface heterogeneity. Adsorption kinetic results indicate a pseudo-second-order kinetic model, which shows chemisorption.

This study investigated the impact of parental sensitivity on emerging adults' psychological well-being. Using a moderated mediation model, it explored how adjustment (prosocial and aggressive behavior) mediates the association between perceived parental sensitivity and psychological well-being of emerging adults. Additionally, residential mobility was examined as a moderator in the relationship between parental sensitivity and adjustment. A sample of 445 emerging adults (Mage= 21.46, SDage= 2.33) reported the number of their past moves and rated their parents’ sensitivity, their adjustment, and their psychological well-being. Results revealed that high maternal sensitivity positively predicted psychological well-being through increased prosocial behavior. This indirect relationship was significant only among individuals with lower levels of residential mobility. This pattern was not observed with paternal sensitivity, and the model yielded insignificant results for aggressive behavior. These findings highlight the significance of early maternal sensitivity in influencing the adjustment and psychological well-being of emerging adults.

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Purpose: Lumbar discectomy is among the most common spine procedures in the US, with 300,000 procedures performed each year. Like other surgical procedures, this procedure is not excluded from potential complications. This paper presents a video annotation methodology for microdiscectomy including the development of a surgical workflow. In future work, this methodology could be combined with computer vision and machine learning models to predict potential adverse events. These systems would monitor the intraoperative activities and possibly anticipate the outcomes. Methods: A necessary step in supervised machine learning methods is video annotation, which involves labeling objects frame-by-frame to make them recognizable for machine learning applications. Microdiscectomy video recordings of spine surgeries were collected from a multi-center research collaborative. These videos were anonymized and stored in a cloud-based platform. Videos were uploaded to an online annotation platform. An annotation framework was developed based on literature review and surgical observations to ensure proper understanding of the instruments, anatomy, and steps. Results: An annotated video of microdiscectomy was produced by a single surgeon. Multiple iterations allowed for the creation of an annotated video complete with labeled surgical tools, anatomy, and phases. In addition, a workflow was developed for the training of novice annotators, which provides information about the annotation software to assist in the production of standardized annotations. Conclusions: A standardized workflow for managing surgical video data is essential for surgical video annotation and machine learning applications. We developed a standard workflow for annotating surgical videos for microdiscectomy that may facilitate the quantitative analysis of videos using supervised machine learning applications. Future work will demonstrate the clinical relevance and impact of this workflow by developing process modeling and outcome predictors.

A significant portion of liver transplantations in many countries is conducted via living-donor liver transplantation (LDLT). However, numerous potential donors are unable to donate to their intended recipients due to factors such as blood type incompatibility or size incompatibility. Despite this, an incompatible donor for one recipient may still be a viable donor for another patient. In recent decades, several transplant centers have introduced liver paired exchange (LPE) programs, facilitating donor exchanges between patients and their incompatible donors, thereby enabling compatible transplants. Initially, LPE programs in Asia primarily involved ABO-i pairs, resulting in 2-way exchanges mainly between blood type A and B recipients and donors. This practice has led to a modest 1% to 2% increase in LDLTs at some centers. Incorporating size incompatibility alongside blood type incompatibility further enhances the efficacy and significance of multiple-pair LPEs. Launched in July 2022, a single-center LPE program established at Inonu University Liver Transplant Institute in Malatya, Türkiye, has conducted thirteen 2-way, nine 3-way, four 4-way, two 5-way, and one 6-way LPEs until February 2024. In 2023 alone, this program facilitated 64 LDLTs, constituting 27.7% of the total 231 LDLTs performed. This paper presents the world’s first two 5-way LPEs and the first 6-way LPE.

Deep soil mixing (DSM) applications are one of the widely known soil stabilization techniques which can be applied to a wide range of soil types. Cement and lime are the major materials used as binders for DSM applications. However, as conventional binders lead to emit a large amount of CO2during production, eco-friendly binders suitable for DSM applications have become prominent. Alkali-activated materials are good alternatives to conventional binders. This study was intended to investigate the usability of zeolite rich tuff wastes as an alkali-activated binder in DSM columns. Within this scope, the waste tuff and C-type fly ash mixture were used as an alkali-activated binder, and 10 M NaOH solution was used as an activator. Response surface methodology (RSM) was employed in experimental design to determine optimum components to obtain maximum unconfined compression strength and investigate the interaction between stabilization agents. From the RSM analysis the optimum ratios of activator (X1), waste tuff (X2), and precursor (X3) were determined as; X1= 0.251, X2= 0.548, and X3= 0.538 for maximum UCS. UCS, mineralogical and microstructural characterization (XRF, XRD, SEM, EDX, FTIR) was performed for the DSM samples prepared considering the optimized components. It was determined that the UCS values of the 3, 7, and 28-day cured samples stabilized by considering the optimum values gave UCS values approximately 3 to 5 times higher than the lower limit values recommended by FHWA. As a result of mineralogical and microstructural investigation, the reason for the strength increase in the samples can be attributed to the formation of geopolymeric gel between the soil particles by tuff waste and fly ash activated with alkaline activator. Carbon footprint analyses were performed for 1m3DSM columns produced with alkali-activated binders and ordinary Portland cement (OPC). From the analyses it was seen that the carbon footprint of the DSM column produced using alkali activated binders is lower than that of the DSM column obtained with OPC. After the general evaluation of the study, it is seen that the hypothesis that waste tuff can be used as environmentally safe alkali-activated binders instead of traditional binders is supported.

For over a century, fasting regimens have improved health, lifespan and tissue regeneration in diverse organisms, including humans1–6. However, how fasting and post-fast refeeding affect adult stem cells and tumour formation has yet to be explored in depth. Here we demonstrate that post-fast refeeding increases intestinal stem cell (ISC) proliferation and tumour formation; post-fast refeeding augments the regenerative capacity of Lgr5+ISCs, and loss of the tumour suppressor gene Apcin post-fast-refed ISCs leads to a higher tumour incidence in the small intestine and colon than in the fasted or ad libitum-fed states, demonstrating that post-fast refeeding is a distinct state. Mechanistically, we discovered that robust mTORC1 induction in post-fast-refed ISCs increases protein synthesis via polyamine metabolism to drive these changes, as inhibition of mTORC1, polyamine metabolite production or protein synthesis abrogates the regenerative or tumorigenic effects of post-fast refeeding. Given our findings, fast–refeeding cycles must be carefully considered and tested when planning diet-based strategies for regeneration without increasing cancer risk, as post-fast refeeding leads to a burst in stem-cell-driven regeneration and tumorigenicity.

The accumulation of the 8-kb oncogenic long noncoding MALAT1 RNA in cells is dependent on the presence of a protective triple helix structure at the 3′ terminus. While recent studies have examined the functional importance of numerous base triples within the triplex and its immediately adjacent base pairs, the functional importance of peripheral duplex elements has not been thoroughly investigated. To investigate the functional importance of a peripheral linker region that was previously described as unstructured, we employed a variety of assays including thermal melting, protection from exonucleolytic degradation by RNase R, small-angle X-ray scattering, biochemical ligation and binding assays, and computational modeling. Our results demonstrate the presence of a duplex within this linker that enhances the functional stability of the triplex in vitro, despite its location more than 40 Å from the 3′ terminus. We present a full-length model of the MALAT1 triple helix-containing RNA having an extended rod-like structure and comprising 33 layers of coaxial stacking interactions. Taken together with recent research on a homologous triplex, our results demonstrate that peripheral elements anchor and stabilize triplexes in vitro. Such peripheral elements may also contribute to the formation and stability of some triple helices in vivo.

The design of biocompatible and biodegradable nanostructures with controlled morphological features remains a predominant challenge in medical research. Stimuli-responsive vesicles offer significant advantages in drug delivery, biomedical applications, and diagnostic techniques. The combination of poly(2-oxazoline)s with biodegradable polymers could provide exceptional biocompatibility properties and be proposed as a versatile platform for the development of new medicines. Therefore, poly(2-ethyl-2-oxazoline) (PEtOx) and poly(2-isopropyl-2-oxazoline) (PiPrOx) possessing a hydroxy terminal group that acts as an initiator for the ring-opening polymerization of d,l-lactide (DLLA) have been utilized in this study. The resulting amphiphilic block polymers were used to create polymersomes, which undergo solvent-dependent reorganization into bowl-shaped vesicles or stomatocytes. By blending PEtOx-b-PDLLA and PiPrOx-b-PDLLA copolymers, a thermoresponsive stomatocyte was generated, where the opening narrowed and irreversibly closed with a slight increase in the temperature. Detailed transmission electron microscopy analysis reveals the formation of both closed and fused stomatocytes upon heating the sample above the critical solution temperature of PiPrOx.

ABSTRACTThis study examined how a video-based professional development (VBPD) initiative influenced early childhood teachers’ practices. A purposive sample of 22 early childhood education teachers voluntarily participated in this study. The confidentiality of all participants was assured and their informed consent was obtained prior to the study. The design of the study was qualitative in nature and video based interventions were carried out during the research process. The study data was drawn from a larger study and collected through informal and semi-structured individual interviews. A constant comparative method of data analysis was utilised in the study. The themes identified in the data were guiding teachers’ practices; self-awareness and desire to improve. The teachers expressed that VBPD was supportive for instructional awareness, instructional assessment practices, and the quantity and quality of classroom interaction. Furthermore, from the teachers’ perspectives, the VBPD was found to improve their self-awareness and aid them in staying up-to-date professionally.

Video Abstract1_ymscp0r5Kaltura

Bioactive peptides have been emerging as drug candidates with increasing importance in the last few decades. In this study, to evaluate the anticancer and antiviral properties of EER (Glu‐Glu‐Arg), EPR (Glu‐Pro‐Arg), and PRP (Pro‐Arg‐Pro) tripeptides, firstly their conformation preferences were searched, and the most stable optimized structure of each tripeptide was determined, using the molecular mechanics force field (MMFF) method and the Spartan06 program. Afterwards, each tripeptide was docked to SARS‐CoV‐2 spike protein receptor‐binding domain (6M0J), SARS‐CoV‐2 main protease (6M03, 6LU7), spike glycoprotein (6VXX), DNA (1BNA), integrins (4WK0, 3ZDX, 1JV2) and epidermal growth factor receptor tyrosine kinase (4HJO). Moreover, molecular dynamics (MD) simulations were performed to validate the stability of the EER, EPR and PRP tripeptides docked to SARS‐CoV‐2 main protease, MPro(6M03) and epidermal growth factor receptor tyrosine kinase (4HJO) within 100 ns time scale and ligand‐receptor interactions were evaluated. The metrics root‐mean‐square deviation, root‐mean‐square fluctuation, intermolecular hydrogen bonding, and radius of gyration revealed that the EER, EPR, and PRP tripeptides form energetically stable complexes with the target proteins. The binding free energies were calculated by the combination of Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) and Molecular Mechanics/Poisson‐Boltzmann Surface Area (MM‐PBSA) methods (MM/PB(GB)SA). Principal Component Analysis on MD data was performed to evaluate the energy and structural information of the tripeptide‐protein complexes. Additionally, in‐silico structure‐based pharmacological predictions were made and the anticancer and antibacterial activities of the tripeptides were predicted. The secondary structure plot of the target proteins in complexes.

Diabetes mellitus (DM)‐associated hyperinflammatory host response significantly provokes periodontal tissue destruction. In this context, the support of nonsurgical periodontal therapy in diabetics with host modulation agents is a current field of study. This clinical study aims to investigate the clinical efficacy of melatonin supplementation and discuss its possible biological mechanisms in nonsurgical periodontal treatment in patients with DM and periodontitis through some fundamental markers. In this randomized controlled and single‐blind study, 27 of 55 diabetic patients with periodontitis (stage III/IV and grade C) underwent full‐mouth scaling and root planing (fmSRP) alone and 28 patients underwent melatonin administration (6 mg daily, 30 days) in addition to fmSRP (full‐mouth scaling and root planing plus melatonin, fmSRP‐mel). The potential therapeutic contribution of melatonin was evaluated clinically and biochemically (gingival crevicular fluid RANKL, OPG, MMP‐8, and serum IL‐1β levels) at 3rd and 6th months. Melatonin (tablet, 6 mg daily, 30 days) did not cause any local or systemic side effects. fmSRP alone resulted in significant reduction in serum IL‐1β levels, pocket depths, gingival inflammation, and gingival crevicular fluid RANKL and MMP‐8 levels (p< 0.05). Moreover, melatonin supplementation resulted in a more significant decrease in bleeding and pocket depth scores at probing, especially at 3 months (p< 0.05). Furthermore, RANKL and MMP‐8 levels were significantly lower at 3 months and IL‐1β levels at 6 months compared to the control group (p< 0.05). However, OPG levels were not affected significantly by the treatments (p> 0.05). Melatonin, as a host modulation agent, significantly increases the clinical efficacy of fmSRP. The reduction in periodontal inflammation and pocket depths may be a result of marked suppression of RANKL‐associated osteoclastogenesis and extracellular matrix damage by melatonin.

The bifilar wound switched reluctance motor (BSRM) has transformer-like windings on the stator known as primary and secondary windings and has a unique power converter known as the bifilar converter. In this study, an optimized BSRM winding topology along with the lossless snubber for the converter is proposed. The topology investigates the uneven number of turns on the primary and secondary windings of the BSRM while taking into account the converter switch voltage spike, secondary winding current density, and demagnetization time. A lossless snubber circuit is introduced to suppress the switch voltage spike caused by the leakage inductance while preserving the efficiency of the bifilar converter. Another motivation for this research is that the bifilar converter uses fewer switches and diodes than the asymmetric half-bridge converter, which is promising to reduce costs and improve drive system efficiency. The BSRM drive system is designed and compared with the same size conventionally wound switched reluctance motor (CSRM) drive system in terms of physical structure, and efficiency using a multi-physics circuit and finite element analysis (FEA) simulation tools. The operating principle of the bifilar converter has been thoroughly examined, further, the physical setup of the BSRM drive system is tested, and the experimental results are provided.

Environmental enteric dysfunction (EED) is characterized by reduced absorptive capacity and barrier function of the small intestine, leading to poor ponderal and linear childhood growth.

Environmental Enteric Dysfunction (EED) is an acquired disorder of asymptomatic altered gut function, the etiology of which is unknown. EED is postulated to be a major contributor to growth faltering in early childhood in regions where early-life enteropathogenic carriage is prevalent. Few studies have examined the critical organ (the upper small bowel) with enteropathogens in the evolution of small bowel disease.

Validated biomarkers could catalyze environmental enteric dysfunction (EED) research.

Environmental enteric dysfunction (EED) is an asymptomatic intestinal disorder associated with growth impairment, delayed neurocognitive development, and impaired oral vaccine responses.

Environmental enteric dysfunction (EED) is an inflammatory condition of the small intestine that is prevalent in children residing in low- and middle-income countries. EED is accompanied by profound histopathologic changes in the small bowel, loss of absorptive capacity, increased intestinal permeability, increased microbial translocation, and nutrient loss.

Environmental enteric dysfunction (EED) is a precursor of growth faltering in children living in impoverished conditions who are frequently exposed to environmental toxins and enteropathogens, leading to small bowel inflammatory, malabsorptive, and permeability derangements and low-grade chronic systemic inflammation.

In this paper we study a family of doubled and quadrupled Fibonacci type sequences obtained by distance generalization of Fibonacci sequence. In particular we obtain doubled Fibonacci sequence, doubled and quadrupled Padovan sequence and quadrupled Narayana’s sequence. We give a binomial direct formula for these sequences using graph methods, and also we derive a number of identities. Moreover, we study matrix generators of these sequences and determine connections with the Pascal’s triangle.

Environmental enteric dysfunction (EED), a chronic inflammatory condition of the small intestine, is an important driver of childhood malnutrition globally. Quantifying intestinal morphology in EED allows for exploration of its association with functional and disease outcomes.

The prevalence of penile calcification in the population remains uncertain. This retrospective multicenter study aimed to determine the prevalence and characteristics of penile calcification in a large cohort of male patients undergoing non-contrast pelvic tomography. A total of 14 545 scans obtained from 19 participating centers between 2016 and 2022 were retrospectively analyzed within a 3-months period. Eligible scans (n= 12 709) were included in the analysis. Patient age, penile imaging status, presence of calcified plaque, and plaque measurements were recorded. Statistical analysis was performed to assess the relationships between calcified plaque, patient age, plaque characteristics, and plaque location. Among the analyzed scans, 767 (6.04%) patients were found to have at least one calcified plaque. Patients with calcified plaque had a significantly higher median age (64 years (IQR 56–72)) compared to those with normal penile evaluation (49 years (IQR 36-60) (p< 0.001). Of the patients with calcified plaque, 46.4% had only one plaque, while 53.6% had multiple plaques. There was a positive correlation between age and the number of plaques (r= 0.31, p< 0.001). The average dimensions of the calcified plaques were as follows: width: 3.9 ± 5 mm, length: 5.3 ± 5.2 mm, height: 3.5 ± 3.2 mm, with an average plaque area of 29 ± 165 mm² and mean plaque volume of 269 ± 3187 mm³. Plaques were predominantly located in the proximal and mid-penile regions (44.1% and 40.5%, respectively), with 77.7% located on the dorsal side of the penis. The hardness level of plaques, assessed by Hounsfield units, median of 362 (IQR 250–487) (range: 100–1400). Patients with multiple plaques had significantly higher Hounsfield unit values compared to those with a single plaque (p = 0.003). Our study revealed that patients with calcified plaques are older and have multiple plaques predominantly located on the dorsal and proximal side of the penis.

In this study, we aimed to examine the relationship among cancer gland rupture microenvironment, programmed cell death ligand 1 (PD-L1) expression in CD163+tumor-associated macrophages (TAMs), and prognosis in colon adenocarcinoma. A total of 122 patients were diagnosed with colon adenocarcinoma between 2010 and 2019. PD-L1+(clone 22C3) “macrophage scores” in the microenvironment of cancer gland rupture were calculated. The effects of these variables on prognosis were statistically analyzed. CD163+TAMs were denser in the cancer gland rupture microenvironment. PD-L1+TAMs were observed in the tumor periphery, and there was a significant difference between the rates of PD-L1 expression in TAMs and survival time (log-rank = 10.46, P= 0.015), clinical stage 2 (P= 0.038), and primary tumor 3 and primary tumor 4 cases (P= 0.004, P= 0.013). The risk of mortality was 4.070 times higher in patients with a PD-L1 expression rate of ≥1% in CD163+TAMs. High PD-L1 expression in CD163+TAMs is associated with poor overall survival. Therefore, blocking PD-L1 in CD163+TAMs can be used as a target for immunotherapy.

In regenerative medicine, extracellular vesicles (EVs) possess the potential to repair injured cells by delivering modulatory factors. However, the therapeutic effect of EVs in large-scale tissue defects, which are subject to prolonged timelines for tissue architecture and functional restoration, remains poorly understood. In this study, we introduce EVs and cell-tethering hybrid hydrogels composed of tyramine-conjugated gelatin (GelTA) that can be in-situcrosslinked with EVs derived from human induced pluripotent stem cell-derived myofibers (hiPSC-myofibers) and hiPSC-muscle precursor cells. This hybrid hydrogel sustains the release of EVs and provides a beneficial nano-topography and mechanical properties for creating a favorable extracellular matrix. Secreted EVs from the hiPSC-myofibers contain specific microRNAs, potentially improving myogenesis and angiogenesis. Herein, we demonstrate increased myogenic markers and fusion/differentiation indexes through the combinatory effects of EVs and integrin-mediated adhesions in the 3D matrix. Furthermore, we observe a unique impact of EVs, which aid in maintaining the viability and phenotype of myofibers under harsh environments. The hybrid hydrogel in-situcrosslinked with hiPSCs and EVs is facilely used to fabricate large-scale muscle constructs by the stacking of micro-patterned hydrogel domains. Later, we confirmed a combinational effect, whereby muscle tissue regeneration and functional restoration were improved, via an in vivomurine volumetric muscle loss model.

Graphical Abstract:

This paper aims to contribute to the extant autobiographical memory functions research, which predominantly involves three theoretical constructs being directive, self, and social, mostly tackled on the individual level. In making the general call for foregrounding social identity-related memory functions as a relevant object of study, the present study relies on a particular memory type, that is, of discrimination and denigration against one’s ethnoreligious identity. Findings of interviews with a total of 9 Armenian, Kurdish, and Alevite participants in Turkey reveal in each of the theoretically insulated domains, the real-world operation of these memories renders intertwined functions both on the individual and group level. Particularly, social memory exchanges manifest peculiar constructs pointing at social identity-linked outcomes. As scholarly appeals for investigating autobiographical memory functions’ lived intersectionality continues, this research addresses this agenda for elaborating isolated theoretical considerations revealing memories’ versatile social identity-related usages on individual and group levels.

This experimental study investigates the effects of TiO2nano-particles on the cooling and tribological performance of a vapor compression refrigeration system running on R134a as refrigerant and polyolester oil (POE) as lubricant. Dynamic light scattering analysis was conducted to observe the dispersion of the nano-particles. The heat transfer rate in the evaporator and condenser was taken into consideration to observe the cooling performance of the system charged with combination of 0.1 vol% and 0.5 vol% TiO2incorporated nano-refrigerants (R0.1 & R0.5) and 0.1 vol% and 0.5 vol% TiO2incorporated POE nano-lubricants (P0.1 & P0.5). Coefficient of friction and wear rate analyses were also performed on the piston ring of the compressor by immersing the samples in two different lubricants (P0.1 & P0.5). The compressor’s suction-discharge characteristics were assessed to determine the impact of the nano-fluid combinations. Scanning electron microscopy was used to examine the morphology of the nano-particles and worn surfaces. Atomic force microscopy was utilized to observe the structure of the worn substrates. The chemical composition of the worn surfaces was analyzed using energy-dispersive X-ray and the thermal stability of the nano-additives was ascertained via thermogravimetric analysis and differential scanning calorimeter. The best cooling and tribological performance results were obtained when the system was run on a combination of R0.5 + P0.1. Compared to standard conditions (R134a + POE), the highest increase in COP was 35.86% for R0.5 + P0.1. With the same combination, the cooling time was reduced by 22.25% and the highest decrease in the average coefficient of friction was 8.02% for 0.1 vol% of TiO2incorporated POE lubricant (P0.1).