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Childhood is the most crucial stage in human life, as well as for the cognitive and technological development of our species. However, earlier traditional archaeological studies have often neglected the role of children in prehistoric societies and focused on the primary socio-economic elements of daily life in prehistory (e.g. agriculture, animal husbandry, hunting-gathering, and various crafts). The picture of a Neolithic village portrayed by archaeologists mostly comprised adults who were engaged in production and subsistence. Children, were seen as passive until they reached a certain age when they became active in production. Increasing ethnographic and archaeological studies however, portray a contrasting picture as they yield insights into the learning and transmission processes of know-how and skills regarding socio-economic activities, technologies, and craft production which suggest that social roles and identities are all formed during childhood. Thus, although the state of research shows that we still have further steps to go, it is clear that a deeper understanding of childhood and children in prehistory is as essential as understanding the world of adults. In such an attempt, this article focuses on the children of Aşıklı Höyük, an Early Neolithic community in Central Anatolia. We briefly discuss the skeletal evidence emerging from the anthropological analyses, and attempt to approach the roles and identities of children through the lens of grave goods and lithic production technologies.

Heart transplantation is associated with major hurdles, including the limited number of available organs for transplantation, the risk of rejection due to genetic discrepancies, and the burden of immunosuppression. In this study, we demonstrated the feasibility of permanent genetic engineering of the heart during ex vivo perfusion. Lentiviral vectors encoding for short hairpin RNAs targeting beta2-microglobulin (shβ2m) and class II transactivator (shCIITA) were delivered to the graft during two hours of normothermic EVHP. Highly efficient genetic engineering was indicated by stable reporter gene expression in endothelial cells and cardiomyocytes. Remarkably, swine leucocyte antigen (SLA) class I and SLA class II expression levels were decreased by 66% and 76%, respectively, in the vascular endothelium. Evaluation of lactate, troponin T, and LDH levels in the perfusate and histological analysis showed no additional cell injury or tissue damage caused by lentiviral vectors. Moreover, cytokine secretion profiles (IL-6, IL-8, and TNF-α) of non-transduced and lentiviral vector-transduced hearts were comparable. This study demonstrated the ex vivo generation of genetically engineered hearts without compromising tissue integrity. Downregulation of SLA expression may contribute to reduce the immunogenicity of the heart and support graft survival after allogeneic or xenogeneic transplantation.

The sedimentation at low Reynolds numbers of large, non-interacting spherical inclusions in networks of model monodisperse, slender colloidal rods is investigated. The influence of rod concentration, rod length, and inclusion stress on the inclusion's creeping motion is investigated. The decrease in sedimentation speeds as a function of rod concentration is compared to the Stokes law, using the zero-shear viscosity from the Doi–Edwards theory for semi-dilute colloidal rod solutions. The experimental speeds display the same concentration dependence as the zero-shear viscosity and are, thus, strongly dependent on the rod length. The speed is, however, a fraction of 2 and 4 lower than expected for rods of 0.88 μm and 2.1 μm, respectively. The results for both rod lengths superimpose when plotted against the overlap concentration, hinting at an extra dependence on the entanglement. [ABSTRACT FROM AUTHOR]

In the title molecular salt, C26H24N3S+·Br−, the dihedral angles between the thiazole ring and its attached phenyl and benzoyl rings are 54.81 (7) and 85.51 (7)°, respectively. In the crystal, ion pairs are linked by C—H...Br and N—H...Br hydrogen bonds and are connected into helical chains extending along the c-axis direction by weak, electrostatic S...Br− interactions. A Hirshfeld surface analysis was performed, which showed the dominant role of H...H contacts (51.3%).

Bu araştırmanın amacı öz düzenlemeli öğrenme yaklaşımının görsel sanatlar öğretmeni adaylarının sanat eleştirisi dersine yönelik akademik başarılarına ve kalıcılığa etkisini incelemektir. Nicel araştırma yöntemlerinden deneysel yöntemin ön test son test kontrol gruplu yarı deneysel modeli ile gerçekleştirilen araştırmanın çalışma grubunu, 2014-2015 Güz Döneminde, Atatürk Üniversitesi Kazım Karabekir Eğitim Fakültesi Resim İş Eğitimi Ana Bilim Dalı’nda öğrenim gören 38 öğretmen adayı oluşturmaktadır. Araştırmada öz düzenlemeli öğrenmenin görsel sanatlar öğretmeni adaylarının akademik başarılarına etkisini kontrol etmek için akademik başarı testi kullanılmıştır. Dersler deney grubunda öz düzenlemeli öğrenme yaklaşımına uygun olarak, kontrol grubuna ise sunuş yoluyla öğrenme yaklaşımına dayalı olarak işlenmiştir. Verilerin analizinde SPSS 19 Paket Programı kullanılmıştır. Non-parametrik verilerin toplanması için "İlişkisiz Ölçümler İçin Mann Whitney U-Testi", öntest-sontest, son test- kalıcılık puanlarını karşılaştırmak için non-parametrik istatistik tekniklerinden "İlişkili Ölçümler İçin Wilcoxon İşaretli Sıralar Testi" kullanılmıştır. Araştırma bulgularına göre; deney ve kontrol gruplarının son test puanlarına bakıldığında her iki öğrenme ortamında da akademik başarıda belli bir artış gözlenmiştir. Deney grubu ile kontrol grubu son test puanları karşılaştırıldığında; deney grubundakilerin akademik başarılarının kontrol grubundakilere göre daha yüksek olduğu görülmektedir. Bu bulgu; öz düzenlemeye dayalı öğretimin daha etkili bir öğrenme ortamı sağladığını ve öğrencilerin akademik başarılarını arttırmada daha etkili olduğunu göstermektedir. Ayrıca; deney ve kontrol gruplarının kalıcılık puanlarına bakıldığında her iki öğrenme ortamında da yapılan öğretimin kalıcılığını sürdürdüğü görülmüştür. Deney grubu ile kontrol grubu kalıcılık puanları karşılaştırıldığında; deney grubunun kalıcılık puanları kontrol grubuna göre daha yüksektir. Araştırma sonuçlarına dayanarak; öz düzenlemeli öğrenme yaklaşımının öğretmen adaylarının akademik başarılarına ve sanat eleştirisi dersi tutumlarına olumlu yönde etki ettiği söylenebilir.

In the title molecule, C28H27N3O3S, the heterocyclic portion of the tetrahydroisoquinoline unit is planar and an intramolecular N—H...N hydrogen bond and a C—H...π(ring) interaction help to determine the overall conformation. In the crystal, a layer structure with the layers parallel to (10\overline{1}) is generated by O—H...O and C—H...O hydrogen bonds.

In an effort to develop a potent antidiabetic drug, new quinoxaline derivative, 2-(4-((3-methyl-2-oxoquinoxalin-1(2H)-yl)methyl)-4,5-dihydro-1H-1,2,3-triazol-1-yl)-N-(p-tolyl)acetamide (MOQTA) was synthesized and characterized by XRD and various spectroscopic tools (IR, 1H &13C NMR, ESI-MS). The geometric optimization of the molecule was calculated with Density Functional Theory (DFT) method by B3LYP with a 6–311++G(d,p) basis set. Frontier Molecular Orbitals (FMOs) and Molecular Electrostatic Potential (MEP) surfaces of the title compound were generated. Furthermore, Hirshfeld surface analysis (HSA) and 2D fingerprint plots were presented. The calculated MEP and HSA surface interactions were compared in terms of hydrogen bonds and π-π stacking interactions obtained by X-ray packing analyses. X-ray crystallographic structure analysis revealed that the N—HN, C—HO and C—HN intermolecular hydrogen bonds were in agreement with those obtained by HSA. Moreover, MOQTA was assessed for its in vitro anti-diabetic activity. Likewise, molecular docking analyses were conducted to examine the binding mode between MOQTA and the enzymes α-glucosidase and α-amylase. Finally, the physicochemical, pharmacokinetic and toxicological properties of MOQTA have been evaluated by using in silico absorption, distribution, metabolism, excretion and toxicity analysis prediction.

Interfacially stabilized nonaqueous lipid-based foams, which we name here oleofoams, are rarely encountered as opposed to the large number of aqueous foams stabilized by molecular or particulate emulsifiers. There is no case well described in the literature with a convincing characterization of the interfacial contribution to oleofoam stability. Methods for filling this gap are described here, which reach out to a large part of the lipid phase diagram. We bring here complete evidence that lipidic crystals made of a high fraction of fully soluble monoglyceride (MG) in oil do not only adsorb at the oil-air interface but also can easily form a jammed, closely packed layer of crystals around the bubbles of a foam produced by whipping (Pickering effect). Very fine bubbles, soft textures, or firmer ones such as for shaving foams could be obtained, with a high air fraction (up to 75%), which is unprecedented. A thin, jammed layer of crystals on bubbles can cause bubbles to retain nonspherical shapes in the absence of bulk effects for times much longer than the characteristic capillary relaxation time for bare bubbles, which is actual evidence for Pickering-type interfacial stabilization. By comparing to foams obtained by depressurization, we show that whipping is necessary for bubble wrapping with a layer of crystals. The origin of high stability against Ostwald ripening at long times is also discussed. Furthermore, we show that these Pickering whipped foams have rheological properties dominated by interfacial or film contributions, which is of high interest for food and cosmetics applications because of their high moduli. This system can be considered to be a model of the crystallization behavior of MG in oil, which is similar to that in many fats. Our methods are very general in the context of lipid-based foaming, in particular, from food materials, and were used in patent applications. [ABSTRACT FROM AUTHOR]

This study reports the synthesis, characterization and importance of a novel diethyl 2-(2-(2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetyl)hydrazono)malonate (MQOAHM). Two independent molecular structures of the disordered MQOAHM have been established by XRD‑single‑crystal analysis in a ratio of 0.596(3)/0.404(3), MQOAHM (a) and MQOAHM (b), respectively. MQOAHM was characterized by means of various spectroscopic tools ESI-MS, IR, 1H &13C NMR analyses. Density Functional Theory (DFT) method, B3LYP, 6–311++G(d,p) basis set was used to optimize MQOAHM molecule. The obtained theoretical structure and experimental structure were superimposed on each other, and the correlation between them was calculated. The Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) were created, and the energy gap between these orbitals was calculated. For analyzing intermolecular interactions, Molecular Electrostatic Potential (MEP) and Hirshfeld Surface Analysis were studied. For a fair comparative study, the two forms of the title compound were docked together with 18 approved drugs and N3 under precisely the same conditions. The disordered molecule structure's binding scores against 7BQY were −7.0 and −6.9 kcal/mol−1 for MQOAHM (a) and MQOAHM (b), respectively. Both the forms show almost identical superimposed structures and scores indicating that the disorder of the molecule, in this study, has no obvious effect. The high binding score of the molecule was attributed to the multi-hydrogen bond and hydrophobic interactions between the ligand and the receptor's active amino acid residues. Worth pointing out here that the aim of using the free energy in Silico molecular docking approach is to rank the title molecule compared to the wide range of approved drugs and a well-established ligand N3. The binding scores of all the molecules used in this study are ranged from −9.9 to −4.5 kcal/mol−1. These results and the supporting statistical analyses suggest that this malonate-based ligand merits further research in the context of possible therapeutic agents for COVID-19. Cheap computational techniques, PASS, Way2drug and ADMET, online software tools, were used in this study to uncover the title compound's potential biological activities and cytotoxicity.

In this study, two new salicylideneaniline derivative compounds which are an isomer of each other have been synthesized and characterized by X-Ray Diffraction (XRD) technique, IR spectroscopy, and theoretical method. While (E)-4-(dihydroxyamino)-2-(((4-fluorophenyl)imino) methyl)phenol (1), crystalizes triclinic P-1 space group, (E)-4-(dihydroxyamino)-2-(((3-fluorophenyl)imino)methyl)phenol (2) crystalizes monoclinic P21/c space group. Both of the molecules which adopt (E) configuration with respect to the central C=N bond have strong intermolecular O―H∙∙∙N hydrogen bonds. These O―H∙∙∙N hydrogen bonds create S(6) motifs according to graph set notation. The optimized geometries of the molecules have been calculated by using Density Functional Theory (DFT) with the 6-31G(d,p) basis set. Molecular Electrostatic Potential (MEP) map and Frontier Molecular Orbitals have been made for the optimized geometries. In addition to these studies, the theoretical IR spectra of the compounds, the experimental IR spectra of which have been recorded at 4000-400 cm-1 interval, have also been calculated with same level theory. The experimental and theoretical results were compared to each other.

Two new one-dimensional coordination polymers of barium (II) and strontium (II)-acesulfamato complexes such as [Ba(C4H4NO4S)2(H2O)]n (1) and [Sr(C4H4NO4S)2(H2O)]n (2) have been synthesized and their molecular structures were identified by X-ray diffraction technique. Both barium (II) and strontium (II) complexes crystallize in the centrosymmetric monoclinic space group P121/c1 and barium (II) and strontium (II) ions, which are surrounded by O- and N-atoms, have the coordination number of nine. Each complex forms a structure like a polymer extending parallel to the a-axis. The molecular structures of those complexes were stabilized by O―H···O and C―H···O hydrogen bonds. Besides identifying their crystallographic structures, the geometric parameters were also calculated using density functional theory (B3LYP) with 6-31G base sets for the asymmetric units of the complexes. The calculated geometrical parameters were also compared to the geometric parameters of X-ray diffraction technique. Furthermore, molecular electrostatic potential maps were constructed and frontier molecular orbital calculations were done for the synthesized complexes. The results of the experimental and theoretical IR studies were also compared.

This paper presents an analysis of the possible performance of a proposed airborne rotor type electricity generator wind turbine design. The innovative design proposal by inventor is based on the rotation of the airborne structure with blades attached to the airborne zeppelin and thus it is called an airborne rotor generator. In this paper computational fluid dynamics analysis of a model close to the proposed design is carried out and the results are presented. The proposed design examples are set to produce 10-100KW. The electrical energy generated through two symmetrically placed alternators at both ends of the zeppelin is transferred to the ground-based system through the tethered cords used to also stabilize the system. Thus, an airborne rotor generator is formed.

In the title molecule, C18H16N2O3, the five-membered ring has an envelope conformation, with the substituted C atom deviating by 0.342 (4) Å from the mean plane P calculated for the remainder of the non-H atoms of the 2,3-dihydro-1H-indene fragment. The mean planes of quinazoline-2,4(1H,3H)-dione fragment and P form a dihedral angle of 59.08 (4)°. In the crystal, pairs of N—H...O hydrogen bonds link molecules into inversion dimers, and weak C—H...O hydrogen bonds and π–π interactions between the benzene rings of the quinazoline ring systems [centroid–centroid distance = 3.538 (3) Å] further consolidate the packing.

In the title compound, C12H17N3O2S, the 4-methyl-2-methylsulfanyl-6-oxo-1,6-dihydropyrimidine-5-carbonitrile part of the molecule is almost planar (r.m.s deviation = 0.062 Å). In the crystal, molecules form centrosymmetric dimers via pairs of N—H...O hydrogen bonds.

In the title molecule, C17H21FN2S, the mean planes of the benzene ring and the thiourea fragment form a dihedral angle of 61.93 (9)°. In the crystal, pairs of weak N—H...S interactions link the molecules, forming inversion dimers.

In the crystal structure of the title compound, [Cu(C4H4NO4S)2(C2H8N2)2], the Cu2+ ion resides on a centre of symmetry. The environment of Cu2+ ion is a distorted octahedron. The axial bond lengths between the CuII ion and the N atoms are considerably longer than the equatorial bond distances between the CuII ion and the N atoms of the ethylenediamine ligand as a consequence of the Jahn–Teller effect. The molecular conformation is stabilized by intramolecular N—H...O hydrogen bonds. In the crystal, molecules are connected by intermolecular N—H...O hydrogen bonds into chains running along the a axis.

Subunit vaccines containing universal tumor associated antigens (TAAs) present an attractive treatment modality for cancer primarily due to their safety and potential to generate long-term immunological responses that can safeguard against recurrences. However, TAA-based subunit vaccines require potent adjuvants for therapeutic efficacy. Using a novel form of the 4-1BBL costimulatory molecule, SA-4-1BBL, as the adjuvant of choice, we previously demonstrated that a single vaccination with survivin (SVN) as a bona fide self TAA was effective in eradicating weakly immunogenic 3LL tumors in >70% of C57BL/6 mice. The present study was designed to i) assess the therapeutic efficacy of a prime-boost vaccination and ii) investigate the mechanistic basis of vaccine efficacy. Our data shows that a prime-boost vaccination strategy was effective in eradicating 3LL lung carcinoma in 100% of mice. The vaccine efficacy was correlated with increased percentages of CD8(+) T cells expressing IFN-γ as well as potent killing responses of both CD8(+) T and NK cells in the absence of detectable antibodies to ssDNA as a sign of autoimmunity. Antibody depletion of CD8(+) T cells one day before vaccination completely abrogated therapeutic efficacy, whereas depletion of CD4(+) T cells had no effect. Importantly, NK cell depletion had a moderate (∼50% reduction), but significant (p

The title compound, C7H6O5·H2O, is a new polymorph of the structures reported by Jiang et al. (2000) [Acta Cryst. C56, 594–595] and Okabe et al. (2001) [Acta Cryst. E57, o764–o766]. The gallic acid molecule is essentially planar (r.m.s. deviation = 0.550 Å). An intramolecular O—H...O hydrogen bond occurs in the gallic acid molecule, which is linked to the water molecule by a further O—H...O hydrogen bond. In the crystal, the components are linked by O—H...O hydrogen bonds. The hydrogen-bonding pattern differs from those reported for the previous polymorphs.

In the title compound, [Zn(C7H3NO4)(C10H9N3)(H2O)]·H2O, the ZnII atom has a distorted octahedral coordination geometry. One of the water molecules is coordinated with the ZnII ion and this molecule forms an O—H...O interaction with the lattice water molecule. The pyridine-2,6-dicarboxylate ligand is almost planar (r.m.s. deviation = 0.0242 Å). In the crystal, C—H...O, C—H...N, O—H...O and N—H...O hydrogen bonds are present.

In the title compound, C14H8INO2, the dihedral angle between the isoindole ring and the phenyl ring of the 1-iodobenzene group is 84.77 (15)°. There is a short intermolecular I...O contact of 3.068 (3) Å in the crystal.

The asymmetric unit of the title compound, [Ni(C2H8N2)3](C5H2N2O4)·1.67H2O, consists of three [Ni(en)3]2+ dications (en is ethylenediamine), three [(pzdc)3]2− dianions (pzdc is pyrazole-3,5-dicarboxylate) and five water molecules. In each complex dication, the NiII atom is coordinated by six N atoms from three en ligands forming a distorted octahedral coordination geometry. In the crystal, the ions and water molecules are linked into a three-dimensional framework by a large number of N—H...O and O—H...O hydrogen bonds.

In the title compound, C13H9N3S2, the thiophene and phenyl rings are oriented at dihedral angles of 8.00 (7) and 6.31 (7)°, respectively, with respect to the central thiadiazole ring. No significant C—H...S and π–π interactions exist in the crystal structure.

Background/objectives: Phenylketonuria is a hereditary metabolic disorder characterized by a deficiency of phenylalanine hydroxylase. The main treatment for PKU is a phenylalanine-restricted diet. The exclusion of protein rich natural foods and inclusion of low-Phe substitutes may give rise to an imbalanced diet, and the increased risk of overweight and obesity in PKU is a cause for concern. We aimed to evaluate the body composition and nutritional biochemical biomarkers in adult PKU patients who are on Phe-restricted and essential amino acid-supplemented nutrition therapy and to investigate the relationships between these parameters and patient gender, adherence to dietary therapy, and disease type, defined as mild or classic PKU., Methods: The study group comprised 37 PKU patients and 26 healthy siblings as controls. The participants were assessed based on an analysis of anthropometric parameters, body composition, and biochemical test results., Results: PKU patients do not have a higher incidence of overweight and obesity than healthy controls, the proportion of energy derived from carbohydrates in their diets was below the recommended level, and their total energy intake was below the recommended daily allowance. It was remarkable that patients with a treatment adherence ratio of <50% displayed a higher prevalence of overweight and abdominal obesity in comparison to those with a more favorable treatment adherence ratio., Conclusions: In view of the growing prevalence of overweight in the general population, PKU patients should be kept under close long-term follow-up. Particularly in the group with low treatment compliance, more caution should be taken in terms of adverse outcomes.

Phenothiazines (PTZ) are antipsychotics known to modulate a variety of neurotransmitter activities that include dopaminergic and cholinergic signaling and have been identified as potential anticancer agents in vitro. However, it is important to also test whether a highly cytotoxic, repurposed, or novel PTZ has low toxicity and neuromodulatory activity in vivo using vertebrate model organisms, such as zebrafish. In this study, we synthesized novel phenothiazines and screened them in vitro in liver cancer and in vivo in zebrafish embryos/larvae. The syntheses of several intermediate PTZ 10-yl acyl chlorides were followed by elemental analysis and determination of 1 H NMR and 13 C NMR mass (ESI + ) spectra of a large number of novel PTZ 10-carboxamides. Cytotoxicities of 28 PTZ derivatives (1-28) screened against Hep3B and SkHep1 liver cancer cell lines revealed five intermediate and five novel leads along with trifluoperazine (TFP), prochlorperazine (PCP), and perphenazine, which are relatively more cytotoxic than the basic PTZ core. Overall, the derivatives were more cytotoxic to Hep3B than SkHep1 cells. Moreover, in silico target screening identified cholinesterases as some of the commonest targets of the screened phenothiazines. Interestingly, molecular docking studies with acetylcholinesterase (AChE) and butyrylcholinesterase proteins showed that the most cytotoxic compounds 1 , 3 , PCP, and TFP behaved similar to Huprin W in their amino acid interactions with the AChE protein. The highly cytotoxic intermediate PTZ derivative 1 exhibited a relatively lower toxicity profile than those of 2 and 3 during the zebrafish development. It also modulated in vivo the cholinesterase activity in a dose-dependent manner while significantly increasing the total cholinesterase activity and/or ACHE mRNA levels, independent of the liver cancer cell type. Our screen also identified novel phenothiazines, i.e., 8 and 10 , with significant cytotoxic and cholinesterase modulatory effects in liver cancer cells; yet both compounds had low levels of toxicity in zebrafish. Moreover, they modulated the cholinesterase activity or expression of ACHE in a cancer cell line-specific manner, and compound 10 significantly inhibited the cholinesterase activity in zebrafish. Accordingly, using a successful combination of in silico, in vitro, and in vivo approaches, we identified several lead anticancer and cholinesterase modulatory PTZ derivatives for future research., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Gold standard method for the treatment of critical-sized bone defects is the autogenous bone grafting procedure. A number of new and potentially useful adjuncts currently are being investigated to enhance the success of bone grafting. We propose to evaluate the effect of the most known and easily obtained 2 biological materials, fat graft and platelet-rich plasma (PRP), on bone graft healing. Twenty-seven New Zealand male rabbits were included in this randomized, controlled study. Two-sided 15-mm diameter bone defects were created in the parietal bones and the bones taken were replaced right-to-left and vice versa with 1 control group, 1 fat graft applied group, and the last one PRP applied group. Histologic evaluation and 3-dimensional maxillofacial computerized tomography were performed and bone density was calculated. In radiologic analysis, bone density was significantly different in the PRP group compared with the control and fat graft group in the 12th week ( P <0.05). In histologic scoring analysis, the PRP group had a better score than the control and fat graft group, while the fat graft group was worse than the control group in the 6th week ( P <0.05). The addition of PRP had a positive effect whereas fat graft had a negative effect on bone graft healing compared with the control group., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Introduction: Delays in the diagnosis and referral of aortic stenosis (AS) during the coronavirus disease 2019 (COVID-19) pandemic may have affected the haemodynamic status of AS patients. We aimed to compare clinical and haemodynamic characteristics of severe AS patients referred for transcatheter aortic valve implantation (TAVI) or balloon aortic valvuloplasty (BAV) before the pandemic versus two subsequent periods., Methods: This study compared three 1‑year historical cohorts: a pre-COVID-19 group (PCOV), a 1st-year COVID-19 group (COV-Y1) and a 2nd-year COVID-19 group (COV-Y2). The main parameters were baseline New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (LVEDP). Demographics, procedural characteristics and 30-day clinical outcomes were assessed. The transition time between heart team decision and TAVI was examined. Pairwise group comparisons were performed (PCOV vs COV-1Y and COV-1Y vs COV-2Y)., Results: A total of 720 patients were included with 266, 249 and 205 patients in the PCOV, COV-Y1 and COV-Y2 groups, respectively. BAV was performed in 28 patients (4%). NYHA class did not differ across the cohorts. Compared to PCOV, LVEF was slightly lower in COV-Y1 (58% (49-60%) vs 57% (45-60%), p = 0.03); no difference was observed when comparing COV-Y1 and COV-Y2. LVEDP was higher in COV-Y1 than in PCOV (20 mm Hg (16-26 mm Hg) vs 17 mm Hg (13-24 mm Hg), p = 0.01). No difference was found when comparing LVEDP between COV-Y1 and COV-Y2. Thirty-day mortality did not differ between groups. Transition time was reduced in the COVID era. Duration of hospital stay declined over the study period., Conclusions: Patients undergoing TAVI during the COVID-19 pandemic had more advanced AS illustrated by lower LVEF and higher LVEDP, but there were no differences in clinical outcome. The TAVI pathway became more efficient., (© 2023. The Author(s).)

Background: Mitochondrial diseases are the most common group of inherited metabolic disorders, causing difficulties in definite diagnosis due to clinical and genetic heterogeneity. Clinical components are predominantly associated with pathogenic variants shown in nuclear or mitochondrial genomes that affect vital respiratory chain function. The development of high-throughput sequencing technologies has accelerated the elucidation of the genetic etiology of many genetic diseases that previously remained undiagnosed. Methods: Thirty affected patients from 24 unrelated families with clinical, radiological, biochemical, and histopathological evaluations considered for mitochondrial diseases were investigated. DNA isolated from the peripheral blood samples of probands was sequenced for nuclear exome and mitochondrial DNA (mtDNA) analyses. MtDNA sequencing was also performed from the muscle biopsy material in one patient. For segregation, Sanger sequencing is performed for pathogenic alterations in five other affected family members and healthy parents. Results: Exome sequencing revealed 14 different pathogenic variants in nine genes encoding mitochondrial function peptides ( AARS2, EARS2, ECHS1, FBXL4, MICOS13, NDUFAF6, OXCT1, POLG , and TK2 ) in 12 patients from nine families and four variants in genes encoding important for muscle structure ( CAPN3, DYSF, and TCAP ) in six patients from four families. Three probands carried pathogenic mtDNA variations in two genes ( MT-ATP6 and MT-TL1 ). Nine variants in five genes are reported for the first time with disease association: ( AARS2 : c.277C>T/p.(R93*), c.845C>G/p.(S282C); EARS2 : c.319C>T/p.(R107C), c.1283delC/p.(P428Lfs*); ECHS1 : c.161G>A/p.(R54His); c.202G>A/p.(E68Lys); NDUFAF6 : c.479delA/p.(N162Ifs*27); and OXCT1 : c.1370C>T/p.(T457I), c.1173-139G>T/p.(?). Conclusion: Bi-genomic DNA sequencing clarified genetic etiology in 67% (16/24) of the families. Diagnostic utility by mtDNA sequencing in 13% (3/24) and exome sequencing in 54% (13/24) of the families prioritized searching for nuclear genome pathologies for the first-tier test. Weakness and muscle wasting observed in 17% (4/24) of the families underlined that limb-girdle muscular dystrophy, similar to mitochondrial myopathy, is an essential point for differential diagnosis. The correct diagnosis is crucial for comprehensive genetic counseling of families. Also, it contributes to making treatment-helpful referrals, such as ensuring early access to medication for patients with mutations in the TK2 gene., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gedikbasi, Toksoy, Karaca, Gulec, Balci, Gunes, Gunes, Aslanger, Unverengil, Karaman, Basaran, Demirkol, Gokcay and Uyguner.)

Herein, new polyborosiloxanes (PBSs) were prepared using a straightforward synthetic approach to obtain a core-shell structure as a material with various features such as better adhesion ability to the applied surface and enhanced thermal properties. In this concept, in situ core-shell formation was allowed by sequential addition of ingredients with fixed conversions. First, pre-condensed polysiloxane was synthesized, with a 60% conversion, as a core by the reaction of phenyltriethoxysilane in the presence of water in an acidic condition. Subsequent addition of boric acid into the pre-condensate and a further condensation reaction resulted in the formation of the shell layer through the introduction of the -Si-O-B- bonds to the network of the PBS. The resulting resin was used as a binder for heat-resistant paint in combination with an aluminum pigment, and the paint applied on a metal plate was found to be resistant up to 600 °C in terms of adhesion strength. It was also demonstrated that the incorporation of boron in the core-shell structure showed better adhesion strength than the one-pot preparation of PBS. Using this method, not only the heat resistance requirement of the industrial coating was achieved but also the flame-retardant ability was introduced., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Even though the effect of several factors on sit-to-stand (STS) performance of children with CP has been previously explored, the potential role of lower extremity selective control, trunk control and sitting function on the performance of STS has not been examined. This study aimed to investigate the association of trunk control and lower extremity selective motor control with STS performance in children with CP. We recruited 28 children with CP aged between 4 and 10 years whose Gross Motor Function Classification System levels were I and II and 32 age-matched typically developing (TP) children. Trunk control, sitting function, selective control of the lower extremities and STS were evaluated with Trunk Control Measurement Scale (TCMS), sitting section of Gross Motor Function Measure-88 (GMFM-88), Selective Control Assessment of the Lower Extremity (SCALE) and the STS outcomes of a force platform [weight transfer time, rising index, and center of gravity (COG) sway velocity], respectively. In all evaluations, children with CP demonstrated lower scores than TD children. A moderate correlation was found between total scores of TCMS, GMFM-88 sitting section scores and COG sway velocity during STS and a fair correlation between SCALE total scores and COG sway velocity in the CP group ( r = -0.51, r = -0.52, r = -0.39, respectively). A fair correlation was found between SCALE total scores and the weight transfer time during STS in children with CP ( r = -0.39). Based on these results, improving trunk and lower extremity selective control may enhance STS performance in children with CP., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aminophylline has been demonstrated to be effective in improving renal functions of the infants suffering from acute kidney injury (AKI) due to perinatal asphyxia. We aimed to evaluate the effect of a single-dose aminophylline on estimated glomerular filtration rate (eGFR), urine output (UO), and incidence and severity of AKI according to the pediatric-modified RIFLE and neonatal RIFLE criteria in newborns with perinatal asphyxia under therapeutic hypothermia. This was a single-center, retrospective cohort study including newborns (gestational age ≥36 weeks) who underwent therapeutic hypothermia due to hypoxic ischemic encephalopathy between 2016 and 2019. Demographic and clinical data were obtained from electronic medical records and patient files. Two patient groups were established: aminophylline group and control group which were only under therapeutic hypothermia. Twenty-one newborns were in the aminophylline group and 13 newborns were in the control group. Our study revealed that on the third day of life (DOL), eGFR was significantly higher in the control group (p=0.025), but UO was significantly higher in the aminophylline group (p=0.021). In the aminophylline group, eGFR on the first DOL was higher than the value on the second DOL (p=0.017) while UO was higher on the second and third DOL compared to the first DOL (1-2 DOL p=0.006, and 1-3 DOL p=0.004). However, in the control group, there was no statistically significant difference in UO over the four DOL. Both groups were similar in the presence, severity, and outcome of AKI.Conclusion: This study demonstrated that aminophylline increases UO even in the infants under therapeutic hypothermia. However, the eGFR did not significantly increase in the aminophylline group. Understanding how therapeutic hypothermia affects pharmacokinetics may help us improve our results in future studies. What is known: • Therapeutic hypothermia (TH) reduces the incidence of acute kidney injury in asphyxiated newborns. • Aminophylline is effective in improving renal functions in asphyxiated newborns. What is new: • This is the first study evaluating the effect of a single dose of aminophylline on renal functions in newborns under TH. • A single dose of aminophylline administration in newborns under TH was associated with increased urine output especially on the third day of life. However, no significant increase was detected in glomerular filtration rate associated with aminophylline administration., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Cholinergic signals can be important modulators of cellular signaling in cancer. We recently have shown that knockdown of nicotinic acetylcholine receptor subunit alpha 5, CHRNA5, diminishes the proliferative potential of breast cancer cells. However, modulation of CHRNA5 expression in the context of estrogen signaling and its prognostic implications in breast cancer remained unexplored., Methods: Meta-analyses of large breast cancer microarray cohorts were used to evaluate the association of CHRNA5 expression with estrogen (E2) treatment, estrogen receptor (ER) status and patient prognosis. The results were validated through RT-qPCR analyses of multiple E2 treated cell lines, CHRNA5 depleted MCF7 cells and across a breast cancer patient cDNA panel. We also calculated a predicted secondary (PS) score representing direct/indirect induction of gene expression by E2 based on a public dataset (GSE8597). Co-expression analysis was performed using a weighted gene co-expression network analysis (WGCNA) pipeline. Multiple other publicly available datasets such as CCLE, COSMIC and TCGA were also analyzed., Results: Herein we found that CHRNA5 expression was induced by E2 in a dose- and time-dependent manner in breast cancer cell lines. ER - breast tumors exhibited higher CHRNA5 expression levels than ER + tumors. Independent meta-analysis for survival outcome revealed that higher CHRNA5 expression was associated with a worse prognosis in untreated breast cancer patients. Furthermore, CHRNA5 and its co-expressed gene network emerged as secondarily induced targets of E2 stimulation. These targets were largely downregulated by exposure to CHRNA5 siRNA in MCF7 cells while the response of primary ESR1 targets was dependent on the direction of the PS-score. Moreover, primary and secondary target genes were uncoupled and clustered distinctly based on multiple public datasets., Conclusion: Our findings strongly associate increased expression of CHRNA5 and its co-expression network with secondary E2 signaling and a worse prognosis in breast cancer.

Rapidly accumulating literature has proven feasibility of the zebrafish xenograft models in cancer research. Nevertheless, online databases for searching the current zebrafish xenograft literature are in great demand. Herein, we have developed a manually curated database, called ZenoFishDb v1.1 (https://konulab.shinyapps.io/zenofishdb), based on R Shiny platform aiming to provide searchable information on ever increasing collection of zebrafish studies for cancer cell line transplantation and patient-derived xenografts (PDXs). ZenoFishDb v1.1 user interface contains four modules: DataTable , Visualization , PDX Details , and PDX Charts . The DataTabl e and Visualization pages represent xenograft study details, including injected cell lines, PDX injections, molecular modifications of cell lines, zebrafish strains, as well as technical aspects of the xenotransplantation procedures in table, bar, and/or pie chart formats. The PDX Details module provides comprehensive information on the patient details in table format and can be searched and visualized. Overall, ZenoFishDb v1.1 enables researchers to effectively search, list, and visualize different technical and biological attributes of zebrafish xenotransplantation studies particularly focusing on the new trends that make use of reporters, RNA interference, overexpression, or mutant gene constructs of transplanted cancer cells, stem cells, and PDXs, as well as distinguished host modifications.

Primary coenzyme Q10 deficiency-6 (COQ10D6) is a rare autosomal recessive disorder caused by COQ6 mutations. The main clinical manifestations are infantile progressive nephrotic syndrome (NS) leading to end-stage renal disease and sensorineural deafness. A 7-year-old girl was diagnosed with steroid-resistant NS (SRNS) and an audiological work-up revealed bilateral sensorineural deafness. A renal biopsy demonstrated focal segmental glomerulosclerosis. Despite immunosuppressive therapy, her serum levels of creatinine increased and haemodialysis was indicated within 1 year after the diagnosis. Living-donor kidney transplantation was performed in the eighth month of haemodialysis. A diagnostic custom-designed panel-gene test including 30 genes for NS revealed homozygous c.1058C > A [rs397514479] in exon nine of COQ6. Her older brother, who had sensorineural hearing loss with no renal or neurological involvement, had the same mutation in homozygous form. COQ6 mutations should be considered not only in patients with SRNS with sensorineural hearing loss but also in patients with isolated sensorineural hearing loss with a family history of NS. The reported p.His174 variant of COQ8B was suggested to be a risk factor for secondary CoQ deficiency, while p.Arg174 appeared to improve the condition in a yeast model. Family segregation and the co-occurrence of biallelic p.Arg174 of COQ8B in a brother with hearing loss implied that the interaction of the altered COQ8B with the mutant COQ6 alleviated the symptoms in this family. CoQ10 replacement therapy should be initiated for these patients, as primary CoQ10 deficiency is considered the only known treatable mitochondrial disease., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Population-based studies report that children with epilepsy have relatively better prognosis than those with an onset at infancy, though studies about this period are limited. We aimed to evaluate the etiology in infant epilepsy less than 2 years of age and foreseeable risk factors for anti-epileptic drug resistance. We evaluated the patients who were presented to the division of pediatric neurology in our university hospital with seizures when they were between 1 and 24 months of age and diagnosed as epilepsy. Two hundred and twenty-nine patients (110 male and 119 female) who were diagnosed between the ages of 1-24 months were included in the study. The etiologies were structural (n = 55;24%), genetic (n = 29;12.7%), metabolic (n = 27;11.7%), and infectious (n = 8;3.5%), and it was unknown in 110 patients (48%). One-hundred and forty (61%) patients met the criteria for drug-resistant epilepsy (DRE). Multivariate logistic regression analysis showed that developmental delay at onset (OR 3.9, 95% CI 1.22, 12.47, p = 0.021), multifocal epileptiform discharges (OR 2.8, 95% CI 1.1, 7.44, p = 0.031), and history of status epilepticus (OR 32.9, 95% CI 3.8, 285.35, p = 0.001) were strong predictive factors for DRE. The epilepsy in children under 2 years of age is highly resistant to the anti-epileptic drugs, which could be related to the history of status epilepticus, developmental delay at onset, and multifocal epileptiform discharges.

Dispersed systems are important in many applications in a wide range of industries such as the petroleum, pharmaceutical and food industries. Therefore the ability to control and non-invasively measure the physical properties of these systems, such as the dispersed phase size distribution, is of significant interest, in particular for concentrated systems, where microscopy or scattering techniques may not apply or with very limited output quality. In this paper we show how reciprocal space data acquired using both 1D magnetic resonance imaging (MRI) and 2D X-ray micro-tomographic (X-ray μCT) data can be analysed, using a Bayesian statistical model, to extract the sphere size distribution (SSD) from model sphere systems and dispersed food foam samples. Glass spheres-in-xanthan gels were used as model samples with sphere diameters (D) in the range of 45μm⩽D⩽850μm. The results show that the SSD was successfully estimated from both the NMR and X-ray μCT with a good degree of accuracy for the entire range of glass spheres in times as short as two seconds. After validating the technique using model samples, the Bayesian sphere sizing method was successfully applied to air/water foam samples generated using a microfluidics apparatus with 160μm⩽D⩽400μm. The effect of different experimental parameters such as the standard deviation of the bubble size distribution and the volume fraction of the dispersed phase is discussed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Block copolymers made from a poly(dimethyl siloxane) (Si) and a poly(meth)acrylate carrying oxyethylene (EG) or fluoroalkyl (AF) side chains were synthesized and incorporated as surface-active components into a silicone matrix to produce cross-linked films with different surface hydrophilicity/phobicity. Near-edge X-ray absorption fine structure (NEXAFS) studies showed that film surfaces containing Si-EG were largely populated by the siloxane, with the oxyethylene chains present only to a minor extent. In contrast, the fluorinated block was selectively segregated to the polymer-air interface in films containing Si-AF as probed by NEXAFS and X-ray photoelectron spectroscopy (XPS) analyses. Such differences in surface composition were reflected in the biological performance of the coatings. While the films with Si-EG showed a higher removal of both Ulva linza sporelings and Balanus amphitrite juveniles than the silicone control, those with Si-AF exhibited excellent antifouling properties, preventing the settlement of cyprids of B. amphitrite.