The separation of sister chromatids during anaphase is the culmination of mitosis and one of the most strikingly beautiful examples of cellular movement. It consists of two distinct processes: Anaphase A, the movement of chromosomes toward spindle poles via shortening of the connecting fibers, and anaphase B, separation of the two poles from one another via spindle elongation. I focus here on anaphase A chromosome-to-pole movement. The chapter begins by summarizing classical observations of chromosome movements, which support the current understanding of anaphase mechanisms. Live cell fluorescence microscopy studies showed that poleward chromosome movement is associated with disassembly, or ‘melting’ of the kinetochore-attached microtubule fibers that link chromosomes to poles. Microtubule-marking techniques established that kinetochore-fiber disassembly often occurs through a ‘pac-man’ mechanism, where tubulin subunits are lost from kinetochore-attached plus ends and the kinetochore appears to consume its microtubule track as it moves poleward. In addition, kinetochore-fiber disassembly in many cells occurs partly through ‘flux’, where the microtubules flow continuously toward the poles and tubulin subunits are lost from minus ends. Molecular mechanistic models for how load-bearing attachments are maintained to disassembling microtubule ends, and how the forces are generated to drive pac-man and flux-based movements, are discussed.

In recent years, the number of mole species for which the species status has been confirmed using genetic methods has been continuously increasing. Unfortunately, cytogenetic analysis is not available for all species. Here, for the first time, a GTG-banded karyotype of the small-toothed mole from Vietnam, Euroscaptor parvidens, a representative of the eastern clade of the genus Euroscaptor, was described. Through comparative analysis of available Euroscaptor (E. parvidens, E. klossi, and E. malayana) and Oreoscaptor (O.mizura) karyotypes we find cytogenetic signatures. Zoo-FISH with sorted chromosomes of the Siberian mole Talpa altaica on chromosome sets of the small-toothed mole E. parvidens, the small Japanese mole M. imaizumii from the close genus Mogera and the Japanese shrew mole Urotrichus talpoides from the tribe Urotrichini made it possible to identify syntenic regions between species that diverged about 35 million years ago. The low rate of chromosomal changes within the species of the genus Talpa - T.altaica and T.europaea - and the high rate of karyotypic reshuffling within the Asian genera of the tribe were confirmed. The pericentric inversions on four pairs of autosomes are shared between the closely related genera Euroscaptor, Oreoscaptor, and Mogera, while many more apomorphic rearrangements have occurred in each lineage additionally. The highest rate of chromosomal changes was recorded in the lineage of the small-toothed mole.

Human motion analysis using inertial measurement units (IMUs) has recently been shown to provide accuracy similar to the gold standard, marker-based optical motion capture, but at much lower costs and while being less restrictive and time-consuming. However, IMU-based motion analysis requires precise knowledge of the orientation in which the sensor is attached to the body segments. This knowledge is commonly obtained via an anatomical calibration procedure based on precisely defined poses or motions, which is time-consuming and error-prone. In the present work, we propose a self-calibrating approach for magnetometer-free joint angle tracking that is suitable for joints with two degrees of freedom (DoF), such as the elbow, ankle, and metacarpophalangeal finger joints. The proposed methods exploit kinematic constraints to simultaneously identify the joint axes and the heading offset. The experimental evaluation shows that the proposed methods are able to estimate plausible and consistent joint axes from just ten seconds of arbitrary elbow joint motion. Comparison with optical motion capture shows that the proposed methods yield joint angles with similar accuracy as a conventional IMU-based method while being much less restrictive. Therefore, the proposed methods improve the practical usability of IMU-based motion tracking in many clinical and biomedical applications.

Ensuring a protection scheme in DC distribution is more difficult to achieve against pole-to-ground fault than in AC distribution system because of the absence of zero crossing points and low line impedance. To complement the major obstacle of limiting the fault current, several compositions have been proposed related to mechanical switching and solid-state switching. Among them, solid-state circuit breakers(SSCBs) are considered a possible solution to limit fast fault current. However, they may cause problems in circuit complexity, reliability and cost-related troubles due to the use of multiple power semiconductor devices and additional circuit configuration to commutate current. This paper proposes the SSCB with a coupled inductor(SSCB-CI) which has symmetrical configuration. The circuit is comprised of passive components like commutation capacitors, a CI and damping resistors. Thus, proposed SSCB-CI offers the advantages of simple circuit configuration and fewer utilized power semiconductor devices than another typical SSCBs in LVDC microgrid. For analysis, six operation states are described for the voltage across main switches and fault current. The effectiveness of the SSCB-CI against a short-circuit fault is proved via simulation and experimental results in a lab-scale prototype.

There are thousands of rare genetic diseases that could be treated with classical gene therapy strategies such as the addition of the defective gene via viral or non-viral delivery or by direct gene editing. However, several genetic defects are too complex for these approaches. These “genomic mutations” include aneuploidies, intra and inter chromosomal rearrangements, large deletions, or inversion and copy number variations. Chromosome Transplantation (CT) refers to the precise substitution of an endogenous chromosome with an exogenous one. By the addition of an exogenous chromosome and the concomitant elimination of the endogenous one, every genetic defect, irrespective of its nature, could be resolved. In the current review, we analyze the state of the art of this technique and discuss its possible application to human pathology. CT might not be limited to the treatment of human diseases. By working on sex chromosomes, we showed that female cells can be obtained from male cells, since chromosome-transplanted cells can lose either sex chromosome, giving rise to 46,XY or 46,XX diploid cells, a modification that could be exploited to obtain female gametes from male cells. Moreover, CT could be used in veterinary biology, since entire chromosomes containing an advantageous locus could be transferred to animals of zootechnical interest without altering their specific genetic background and the need for long and complex interbreeding. CT could also be useful to rescue extinct species if only male cells were available. Finally, the generation of “synthetic” cells could be achieved by repeated CT into a recipient cell. CT is an additional tool for genetic modification of mammalian cells.

B chromosomes are supernumerary chromosomes which are found in addition to the normal standard chromosomes (A chromosomes). B chromosomes are well known to accumulate several types of repeats. Although the evolution of B chromosomes has been subject of numerous studies, the mechanisms of accumulation and evolution of repetitive sequences is not fully understood. Recently, new genomic approaches have shed light on the origin and accumulation of different classes of repetitive sequences in the process of B chromosome formation and evolution. Here we discuss the impact of repetitive sequences accumulation on the evolution of plant B chromosomes.

In this paper, modelling design and analysis of a triple inverted pendulum have been done using Matlab/Script toolbox. Since a triple inverted pendulum is highly nonlinear, strongly unstable without using feedback control system. In this paper an optimal control method means a linear quadratic regulator and pole placement controllers are used to stabilize the triple inverted pendulum upside. The impulse response simulation of the open loop system shows us that the pendulum is unstable. The comparison of the closed loop impulse response simulation of the pendulum with LQR and pole placement controllers results that both controllers have stabilized the system but the pendulum with LQR controllers have a high overshoot with long settling time than the pendulum with pole placement controller. Finally the comparison results prove that the pendulum with pole placement controller improve the stability of the system.

Vehicle windshield wiper system increases the driving safety by contributing a clear shot viewing to the driver. In this paper, modelling, designing and simulation of a vehicle windshield wiper system with robust control theory is done successfully. H∞ loop shaping and robust pole placement controllers are used to improve the wiping speed by tracking a reference speed signals. The reference speed signals used in this paper are step and sine wave signals. Comparison of the H∞ loop shaping and robust pole placement controllers based on the two reference signals is done and convincing results have been obtained. Finally the comparative results prove the effectiveness of the proposed H∞ Loop Shaping controller to improve the wiping mechanism for the given two reference signals.

Endometrial cancer (EC) is the most frequent gynaecological malignancy. The ESGO/ESTRO/ESP 2020 guidelines identify prognostic groups based on morpho-molecular characteristics. This study aims to evaluate the clinical applicability of NGS analysis to define an appropriate risk class and application for a better diagnostic and prognostic stratification of ECs. Cases of serous carcinoma (OHEC), high (HGEC) and low (LGEC) grade endometrioid carcinoma diagnosed with the morphological and immunohistochemical (IHC) protocols were considered. After a standardized pre-analytical phase, the tumor DNA was semi-automatically extracted and analyzed by NGS with a panel of 14 genes. A total of 63 cases were considered. NGS analysis was successful in 60 cases; all of these were classified according to the new diagnostic algorithm. The molecular risk classification showed a good correlation with the morphological (k=0.8). The study showed that the protocols of the pre-analytical and analytical phases used are robust and can lead to molecular results that fall within the standards required for use in clinical practice for a more precise diagnostic-therapeutic management of patients. The implementation of the classification is particularly relevant for better prognostic stratification of HGECs. In addition, the identification of a suspicious VUS in POLE questions the classification of truncating variants.

With recent developments in fusion engineering, interest has sparked in development of fusion devices for deterrent. Enormous amount of energy generated by combining two light nuclei could be contained and manipulated at will to trigger and accelerate micro explosions (from shock wave, x-rays or ion beam focusing) which finally result in full scale blast. Materials required to make such device are critical. They must possess high strength, high hardness, ductility, formability, drawability, and anisotropic properties. High entropy alloys (HEA) are new class of materials which nicely fulfils this requirement. Essentially, they are solid solutions of multi principal elements (usually > 5) eliminating the need of base metal as in conventional alloys. This gives them many unique properties which may be tailored at will (heat treatment, cold rolling, precipitation, irradiation). They also exhibit excellent directional properties with formation of distinct bands along certain preferred crystallographic planes even in hexagonal close packed structures. These anisotropic properties are strong function of rolling, working, or forging (swaging) direction and can be utilized to benefit. This study encompasses making outer shell of a typical fusion device selected on the basis of the weight, which is a function of area of pay load bay of carrier aircraft.

Mechanisms for somatic chromosomal mosaicism (SCM) and chromosomal instability (CIN) are incompletely understood. During SNP-array molecular karyotyping and bioinformatic analyses of children with neurodevelopmental disorders and congenital malformations (n=612), we observed colocalizaion of regular chromosomal imbalances or copy number variations (CNV) with mosaic ones (n=47 or 7.7%). Analyzing molecular karyotyping data and pathways affected by CNV burdens, we proposed a mechanism for SCM/CIN, which had been designated as “chromohelkosis” (from the Greek chromosome ulceration/open wound). Briefly, structural chromosomal imbalances are likely to cause local instability (“wreckage”) at the breakpoints, which results either to partial/whole chromosome loss (e.g. aneuploidy) or elongation of duplicated regions. Accordingly, a function for classical/alpha satellite DNA (protection from the wreckage towards the centromere) has been hypothesized. Since SCM and CIN are ubiquitously involved in development, homeostasis and disease (e.g. prenatal development, cancer, brain diseases, aging), we have metaphorically (ironically) designate the system explaining chromohelkosis contribution to SCM/CIN as the cytogenomic “theory of everything” like the homonymous theory in physics inasmuch as it might explain numerous phenomena in chromosome biology. Recognizing possible empirical and theoretical weaknesses of this “theory”, we nevertheless believe that studies of chromohelkosis-like processes are required to understand structural variability and flexibility of the genome.

The pine pitch canker pathogen, Fusarium circinatum, is globally regarded as one of the most important threads to commercial pine-based forestry. Although genome sequences of this fungus are available, these remain highly fragmented or structurally ill-defined. Our overall goal was to provide high-quality assemblies for two notable strains of F. circinatum, and to characterize these in terms of coding content, repetitiveness, and the position of telomeres and centromeres. For this purpose, we used Oxford Nanopore Technologies MinION long read sequences, as well as Illumina short sequence reads. By leveraging the genomic synteny inherent to F. circinatum and its close relatives, these sequence reads were assembled to chromosome-level, where contiguous sequences mostly spanned from telomere to telomere. Comparative analyses unveiled remarkable variability in the twelfth and smallest chromosome, which is known to be dispensable. It presented a striking length polymorphism, with one strain lacking substantial portions from the chromosome's distal and proximal regions. These regions, characterized by a lower gene density and G+C content and an increased prevalence of repetitive elements, contrast starkly with the syntenic segments of the chromosome, as well as with the core chromosomes. We propose that these unusual regions might have arisen or expanded due to the presence of transposable elements. Comparison of overall chromosome structure revealed that centromeric elements often underpin intrachromosomal differences between F. circinatum strains, especially at chromosomal breakpoints. This suggested a potential role for centromeres in shaping the chromosomal architecture of F. circinatum and its relatives. The publicly available genome data generated here, together with the detailed metadata provided, represent essential resources for future studies of this important plant pathogen.

The classic, chronic Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPN)- mainly essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF)— represent a heterogeneous group of stem cell disorders characterized by clonal proliferation of one or more hematopoietic cell lineages with organomegaly and constitutional symptoms. Several studies have shown that the presence of chronic inflammation and a dysregulated immune system play indisputable roles in the pathogenesis of these diseases. Lately, the treatment of cancer including hematological malignancy has progressed on the agents targeting the immune system, cytokine milieu, immunomodulatory agents, and targeted immune therapy. Immune checkpoints are the molecules that regulate T cells function in the tumor microenvironment (TME). The fully unraveled primary immune checkpoints are programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4). Immune checkpoint inhibitor therapy (ICIT) is based on blocking the inhibitory pathways in T cells to promote anti-tumor immune responses and has revolutionized cancer treatment paradigms. Despite the impressive clinical success of ICIT, tumor intrinsic resistance remains a daunting challenge for oncologists leading to a low response rate in solid tumors and hematological malignancies. A phase II trial on Nivolumab for patients with Primary Myelofibrosis, post-Essential thrombocythemia myelofibrosis, or post- Polycythemia myelofibrosis has been performed (ClinicalTrials.gov Identifier: NCT02421354). This clinical trial, on the efficacy of PD-1 blockade using the monoclonal antibody Nivolumab, was prematurely terminated due to a lack of efficacy and adverse events. A multicenter, open-label, phase 2, single-arm study was conducted including pembrolizumab in patients with Dynamic International Prognostic Scoring System category of intermediate-2 or greater primary, post-essential thrombocythemia or post-polycythemia vera myelofibrosis that were ineligible for or were previously treated with Ruxolitinib. Pembrolizumab treatment was well tolerated, but there were no objective clinical responses, so the study closed after the first stage was completed. To permit more patients to benefit from immunotherapy, the focus has changed to targeting alternative novel immune checkpoints in the tumor microenvironment such as lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin, and mucin domain 3 (TIM-3), V-domain immunoglobulin-containing suppressor of T-cell activation (VISTA), T cell immunoglobulin and ITIM domain (TIGIT) and human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) forming the basis of next-generation ICIT. Our article aims at emphasizing and discovering the role of next-generation ICIT in MPN as targeted immunotherapy involving monoclonal antibodies, checkpoint inhibitors, or therapeutic vaccines against selected MPN epitopes that could further enhance tumor-specific immune responses. Immunotherapeutic approaches are expanding and hopefully will extend the therapeutic armamentarium in patients with myeloproliferative neoplasms. Preliminary studies from our laboratory showed over-expressed MDSC and over-expressed VISTA in MDSC, and in progenitor and immune cells directing the need for more clinical trials using next-generation ICI in the treatment of MPN.

Anticancer regimens for Hodgkin lymphoma (HL) patients include highly genotoxic drugs that have been very successful in killing tumor cells and providing a 90% disease-free survival at five years. However, these treatments do not have a specific cell target, damaging both cancerous and normal cells. Thus, HL survivors have a high risk of developing new primary cancers, both hematologic and solid tumors, that have been related to treatment. Several studies have shown that after-treatment, HL patients and survivors present persistent chromosomal instability, including non-clonal chromosomal aberrations. The frequency and type of chromosomal abnormalities appear to depend on the type of therapy and the cell type examined. For example, MOPP chemotherapy affects hematopoietic and germ stem cells leading to long-term genotoxic effects and azoospermia, while ABVD chemotherapy affects transiently sperm cells, with most of the patients showing recovery of spermatogenesis. Both regimens have long-term effects in somatic cells, presenting non-clonal chromosomal aberrations and genomic chaos in a fraction of non-cancerous cells. This is a source of karyotypic heterogeneity that could eventually generate a more stable population acquiring clonal chromosomal aberrations and leading towards the development of a new cancer.

Rett Syndrome (RTT) is a severe neurodevelopmental disorder predominately diagnosed in females and primarily caused by pathogenic variants in the X-linked gene Methyl-CpG Binding Protein 2 (MECP2). Most often, the disease causing MECP2 allele resides on the paternal X chromosome while a healthy copy is maintained on the maternal X chromosome with inactivation (XCI) resulting in mosaic expression of one allele in each cell. Preferential inactivation of the paternal X chromosome is theorized to result in reduced disease severity; however, establishing such a correlation is complicated by known MECP2 genotype effects and an age dependent increase in severity. To mitigate these confounding factors, we developed an age- and genotype-normalized measure of RTT severity by modeling longitudinal data collected in the US Rett Syndrome Natural History Study. This model accurately reflected individual increase in severity with age and preserved group-level genotype specific differences in severity allowing for the creation of a normalized clinical severity score. Applying this normalized score to a RTT XCI dataset revealed that XCI influence on disease severity depends on MECP2 genotype with a correlation between XCI and severity observed only in individuals with MECP2 variants associated with increased clinical severity. This normalized measure of RTT severity provides the opportunity for future discovery of additional factors contributing to disease severity that may be masked by age and genotype effects.

Telomeres are specialized structures at the ends of linear chromosomes that protect them from degradation and fusion. Telomere replication is a complex process that involves both DNA polymerases and a specialized enzyme called telomerase. Telomerase is a ribonucleoprotein complex that synthesizes telomeric DNA by using an internal RNA template. However, telomerase alone cannot fully replicate the telomeric DNA, and requires the cooperation of other factors, such as shelterin, CST, and DNA repair proteins. Moreover, telomere replication is tightly regulated by various mechanisms, such as cell cycle checkpoints, telomere length homeostasis, and telomere position effect. Dysregulation of telomere replication can lead to genomic instability, cellular senescence, and cancer. Therefore, understanding the molecular details of telomere replication is crucial for elucidating the role of telomeres in aging and disease.

A bread wheat line (N11) and a disomic 2D(2R) substitution triticale line have been crossed and backrossed four times. At each step electrophoretic selection for the seeds that possessed, simultaneously, the complete set of high molecular weight glutenin subunits of N11 and the two high molecular weight secalins of rye, present in the 2D(2R) line, was carried out. Molecular cytogenetic analyses of the BC4F5 generation have revealed that the selection carried out had produced a disomic addition line (2n=44). The pair of additional chromosomes consisted of the long arm of chromosome 1R (1RL) from rye fused with the satellite body of the wheat chromosome 6B. Rheological analyses revealed that the dough obtained by the new addition line had higher quality characteristics when compared with the two parents. The role of the two additional high molecular weight secalins, present in the disomic addition line, in influencing improved dough characteristics is discussed.

Researchers achieved high torque volume ratios in magnetorheological (MR) fluid braking devices by introducing multiple layers and multiple poles concepts. The number of magnetic poles, pole geometry and placement have a significant effect on these multi-pole MR brake performances. This research work focused on the effect of the pole head geometry in a multi-pole dual-disc MR brake for the enhancement of braking torque. The magnetic field generated by the electromagnetic coil has to penetrate through pole heads and travel orthogonally through the rotor and MR fluid layers to achieve maximum brake torque. This flow depends on the profiles of the magnetic pole head area and corresponding core dimensions. This study considered pentagon, square, hexagon, trapezoid and ellipse pole head profiles in place of the conventional circular pole and the best possible core dimensions were used for each geometry. A three-dimensional electromagnetic analysis of the MR brake is conducted to simulate the brake performance. Results showed that the hexagonal and elliptical pole heads are having better magnetic field area, magnetic intensity distribution and higher magnetic flux lines piercing through the MR fluid perpendicularly than the circular and square pole heads. An increment of 3.88% for braking torque performance is obtained, and the braking torque is significantly enhanced.

Object classification is a crucial task in deep learning, which involves the identification and categorization of objects in images or videos. Although humans can easily recognize common objects, such as cars, animals, or plants, performing this task on a large scale can be time-consuming and error-prone. Therefore, automating this process using neural networks can save time and effort while achieving higher accuracy. Our study focuses on the classification step of human chromosome karyotyping, an important medical procedure that helps diagnose genetic disorders. Traditionally, this task is performed manually by expert cytologists, which is a time-consuming process that requires specialized medical skills. Therefore, automating it through deep learning can be immensely useful. To accomplish this, we implemented and adapted existing preprocessing and data augmentation techniques to prepare the chromosome images for classification. We used ResNet-50 convolutional neural networks and an ensemble approach to classify the chromosomes, obtaining state-of-the-art performance in the tested dataset.

Early in development, placental and marsupial mammals harbouring at least two X chromosomes per nuclei are faced with a choice that affects the rest of their lives: which of those X chromosomes to transcriptionally inactivate. This choice underlies phenotypical diversity in the composition of tissues and organs and in their response to environment, and can determine whether an individual will be healthy or affected by an X-linked disease. Here, we review our current understanding of the process of choice during X-chromosome inactivation and its implications, focusing on the strategies evolved by different mammalian lineages and on the known and unknown molecular mechanisms and players involved. We also call for a revised manner in which to think about choice during random X-inactivation.

Palmer amaranth (Amaranthus palmeri) is a problematic common weed species, especially in cotton (Gossypium hirsutum). With the wide use of chemical herbicide and herbicide-tolerant transgenic cotton lines, Palmer amaranth populations have developed tolerance to commonly used herbicides. It is imperative to develop alternative weed control methods to slow the evolution of herbicide-resistant weed populations and provide new sources for weed management. Eleven chromosome substitution (CS) cotton lines CS-B26lo, CS-T17, CS-B16-15, CS-B17-11, CS-B12, CS-T05sh, CS-T26lo, CS-T11sh, CS-M11sh, CS-B22sh, and CS-B22lo were screened for weed-suppressing abilities in this study. The cotton lines were tested using the established stair-step structure methodology, which provided scope to study the effect of individual CS lines on the growth and development of Palmer amaranth weed without any interference of other external factors in the greenhouse. Height (cm) and chlorophyll concentration (cci) were measured for each plant in the system. The data were analyzed as a randomized complete block design using LSD mean comparisons of the genotypes at the P≤ .05 level. The 14th day after establishment resulted in the most significant variation in Palmer amaranth height reduction among the CS lines. Results indicated that CS-B22sh had the highest effect in reducing Palmer amaranth height and chlorophyll concentration with the most heightened susceptibility for Palmer amaranth. The cluster analysis revealed that Enlist® cotton, CS-CS-B22sh, and CS-T26lo were clustered in one group suggesting similar genetic potential with reference to Palmer amaranth growth and development. CS-B22sh showed novel genetic potential to control the growth and development of Palmer amaranth, a major weed in cotton fields. In the future, it will be interesting to investigate if CS-B22sh exudates from its root contain allelochemicals able to impede the growth and development of Palmer amaranth.

This paper presents a comparison between a kite model with a constant-length tether and a model based on a system identification algorithm. The concept of system identification is applied to predict the uncertainties related to the variation of the wind speed and the shape deformation of the tethered membrane wing during flight. A pole-placement controller is used to ensure that the kite follows the planned flight path. Thus, we can determine the required locations of the closed loop poles, and then enforce them by changing the controller's gains in real-time. The capability of the system identification algorithm to recognize sudden changes in the dynamic model, and the ability of the controller to stabilize the system in the presence of such changes are confirmed. Furthermore, the system identification algorithm is applied to determine the parameters of a kite with variable-length tether used in a flight test of the 20 kW kite power system of TU Delft. Experimental data of this test were compared with the system identification results in real-time and significant changes were observed in the parameters of the dynamic model which heavily affect the resulting response.

Proper bipolar spindle assembly underlies accurate chromosome segregation. A cohort of microtubule-associated proteins orchestrates spindle microtubule formation in a spatiotemporally coordinated manner. Among them, the conserved XMAP215/TOG family of microtubule polymerase plays a central role in spindle assembly. In fission yeast, two XMAP215/TOG members, Alp14 and Dis1, share essential roles in cell viability; however how these two proteins functionally collaborate remains undetermined. Here we show the functional interplay and specification of Alp14 and Dis1. Creation of new mutant alleles of alp14, which display temperature sensitivity in the absence of Dis1, enabled us to conduct detailed analyses of a double mutant. We have found that simultaneous inactivation of Alp14 and Dis1 results in early mitotic arrest with very short, fragile spindles. Intriguingly, these cells often undergo spindle collapse, leading to a lethal “cut” phenotype. By implementing an artificial targetting system, we have shown that Alp14 and Dis1 are not functionally exchangeable and as such are not merely redundant paralogues. Intriguingly, while Alp14 promotes microtubule nucleation, Dis1 does not. Our results uncover that the intrinsic specification, not the spatial regulation, between Alp14 and Dis1 underlies the collaborative actions of these two XMAP215/TOG members in mitotic progression, spindle integrity and genome stability.

This paper presents results of the experiments performed on a nonconventional and extremely interesting in regard to evolution, creature, the European river lamprey Lampetra fluviatilis (Petromyzontiformes, Cyclostomata), one of the oldest taxa of vertebrates. We present detailed immunocytochemical and electron microscopy analyses of chromosome synapsis, the transcription process, and chromatin dynamics in lamprey prophase I, which is the first time for science. We found that not all chromosomes complete synapsis. Rounded structures were detected in chromatin and in some synaptonemal complexes but their nature could not be determined conclusively. An analysis of RNA polymerase II distribution led to the conclusion that transcriptional reactivation in lamprey prophase I is not associated with the completion of chromosome synapsis. Monomethylated histone H3K4 is localized to meiotic chromatin throughout prophase I, and this pattern has not been previously detected in the animals. Thus, the findings made it possible to identify synaptic and epigenetic patterns specific for this group, and to add new pieces of the puzzle to the discussions of the scientific issues under study. The research on lamprey meiotic chromatin and chromosomal dynamics raises many questions leading to new discoveries.

Yam (Dioscorea spp.) is a monocotyledonous herbaceous vine plant grown in the tropics and subtropics. It is a multi-species plant with varied intra- and interspecific ploidy levels. Of the 600 species, 11 are cultivated staple supporting the livelihood of over 300 million people. The paucity of information on ploidy and the genomic constitution is a significant challenge to the crop’s genetic improvement through crossbreeding. The objective of this study was to investigate the ploidy levels of 236 accessions across six cultivated and two wild species using chromosome counting, flow cytometry and genotyping-based ploidy determination methods. Results obtained from chromosome counting and genotyping-based ploidy determination were in agreement. In majority of the accessions, chromosome counting and flow cytometry were congruent, allowing future rapid screening of ploidy levels using flow cytometry. Among cultivated accessions, 168 (71%) were diploid, 50 (21%) were triploid, and 12 (5%) were tetraploid. Two wild species included in the study were diploids. Resolution of ploidy level in yams offers opportunities for implementing successful breeding programmes through intra- and inter-specific hybridization.

The humpback puffer, Tetraodon palembangensis, also known as Pao palembangensis, is a species of poisonous freshwater pufferfish mainly distributed in Southeast Asia (Thailand, Laos, Malaysia and Indonesia). Despite interesting biological features, such as its very inactive nature, tetrodotoxin production and body expansion mechanisms, molecular research on the humpback puffer is still rare because of the lack of a high-quality reference genome. Here, we reported a first chromosome-level genome assembly of an adult humpback puffer, of which the genome size is 362 Mb with ~1.78 Mb contig N50 and ~15.8 Mb scaffold N50s. Based on the genome, ~61.5Mb (18.11%) repeat sequences were also identified, and totally 19,925 genes were annotated, 99.20% of which could be predicted with function using protein-coding function databases. Finally, a phylogenetic tree was constructed with single-copy gene families from ten teleost fishes. The humpback puffer genome will be a valuable genomic resource to illustrate possible mechanisms of tetrodotoxin synthesis and tolerance, providing clues for future detailed studies of biological toxins.

Most Neotropical Psittacidae have a diploid number of 2n=70, and a dichotomy in chromosome patterns. Long-tailed species have biarmed macrochromosomes, while short - tailed ones have telo/acrocentric macrochromosomes. However, the use of chromosome painting with chicken and white hawk probes has demonstrated that karyotype evolution in Psittacidae includes a high number of inter/intrachromosomal rearrangements. Hence, to determine the phylogeny of Long and Short-Tailed species, and to propose a putative ancestral karyotype for this group, we constructed homology maps of Pyrrhura frontalis (PFR) and Amazona aestiva (AAE) and compared them to other previously analyzed long-tailed species. Chromosomes were analyzed by conventional staining and fluorescent in situ hybridization (FISH) using whole chromosome paints of G. gallus (GGA) and L. albicollis (LAL). Conventional staining showed a karyotype with 2n=70 in both species, with biarmed macrochromosomes in Pyrrhura frontalis and telo/acrocentric chromosomes in Amazona aestiva. Comparison of the results with the putative avian ancestral karyotype (PAK) showed fusions in P. frontalis of PAK1p/PAK4q (PFR1) and PAK6/PAK7 (PFR6) with a paracentric inversion in PFR6. However, in A. aestiva there was only the fusion between PAK6/7 (AAE7) with a paracentric inversion. Hybridizations with LAL probes confirmed these results. The results indicate that PFR retained a more basal karyotype than Anodorhynchus hyacinthinus (AHY), Ara macao (AMA) and Ara chloropterus (ACH), because these three species show the fusion PAK8/PAK9 that is not seen in PFR. Hence, we suggest that the ancestral karyotype of species with biarmed chromosomes have the fusions PAK1p/PAK4 and PAK6/PAK7 and, additionally, a pericentric inversion of PAK6/PAK7, while the fusion PAK8/PAK9 would have appeared in the common ancestor of Anodorhynchus hyacinthinus, Ara macao and Ara chloropterus. However, the species A. aestiva shows a characteristic plesiomorphic trait, since PAK1p/PAK4q and PAK8/9 fusions are absent. Our results base on chromosome rearrangements suggest the classification following the criterium of tail length may no reflect the real phylogenetic history of Neotropical Psittacidae.

The technology of left ventricular assist devices (LVADs) requires developing and implementing an intelligent control systems to optimize pump speed to achieve a physiological metabolic demands for heart failure (HF) patients. This work aimed to present an advanced control algorithm to drive an LVAD under different physiological conditions. Pole placement method in conjunction with of sliding mode control approach (PP-SMC) was utilized to design and construct the proposed control method. In this design, the method was adopted to use neural networks to eliminate system uncertainties of disturbances. An elastance function was also developed and used as an input signal to mimic the physiological perfusion of HF patients. Two scenarios ranging from rest to exercise were introduced to evaluate the proposed technique. In this technique, a lumped parameter model of cardiovascular system (CVS) was used for this evaluation. The results demonstrated that the designed controller was robustly tracking the input signal in the presence of the system parameter variations of CVS. In both scenarios, the proposed method shows that the controller automatically drive the LVAD with a minimum flow of 1.7 L/min to prevent suction and 5.7 L/min to prevent over-perfusion.

Miniature sensors are key components for the applications in the Internet of Things (IoT), wireless sensor networks, autonomous vehicles, smart cities and smart manufacturing. As a miniature and self-powered magnetic sensor, Wiegand sensor possesses the advantageous traits including changing-rate-independent output, low cost, and remarkable repeatability and reliability. Typical Wiegand sensor requires hard magnetic pole pieces that provide external fields for triggering voltage outputs that are called Wiegand pulses. However, the wire-shaped sensing element of Wiegand sensor is the critical issue that limits the design, selection, and adoption of the external triggering magnets. Currently, the widely used pole piece materials are rare-earth magnets. However, adopting rare-earth magnets brings strong stray fields, causing electromagnetic interference (EMI) problem. In this study, patterned CoNiP hard magnets were electrodeposited on flexible substrates through microfabrication. Origami magnetization was utilized to control the resultant stray fields, and hence the pole piece of CoNiP magnets can successfully trigger the output of Wiegand pulse. In comparison, the output voltage of the triggered pulse acquired through the patterned CoNiP magnets is comparable to that by using the rare-earth magnets. Furthermore, both the volume (meanwhile the weight) of the Wiegand sensor and the EMI issue can be significantly reduced and mitigated by the CoNiP magnets.

Relapsed acute lymphoblastic leukemia (ALL) represents a continuous challenge for the clinician. Despite recent advances in treatment, the risk of relapse remains significant. The clinical, biological, cytogenetic, and molecular characteristics may be different at the time of relapse. Current comprehensive genome sequencing studies suggest that most relapsed patients, especially those with late relapses, acquire new genetic abnormalities, usually within a minor clone that emerges after ALL diagnosis. We report the case of a 23-year-old young woman diagnosed with Philadelphia chromosome negative B-cell acute lymphoblastic leukemia. The patient underwent allogeneic stem cell transplantation (allo-HSCT) after complete remission. Although having favorable prognostic factors at diagnosis, the disease relapsed early after allo-HSCT. The cytogenetic and molecular exam at relapse was positive for the Philadelphia chromosome, respectively for the bcr-abl transcript. What exactly led to the relapse of this disease in a more aggressive cytogenetic and molecular form, although there were no predictive elements in the diagnosis of this relapse?

Men are more likely to develop cancer than women. In fact, male predominance is one of the most consistent cancer epidemiology findings. Additionally, men have a poorer prognosis and an increased risk of secondary malignancies compared to women. These differences have been investigated in order to better understand cancer and to better treat both men and women. In this review, we discuss factors that may cause this gender difference, focusing on urothelial bladder cancer (UBC) pathogenesis. We consider physiological factors that may cause higher male cancer rates, including differences in X chromosome gene expression. We discuss how androgens may promote bladder cancer development directly by stimulating bladder urothelium and indirectly by suppressing immunity. We are particularly interested in natural killer (NK) cells because they are important, but often overlooked anti-cancer lymphocytes.

Early identification of fetal abnormalities is a huge challenge for modern obstetrics. Quantitative fluorescent polymerase chain reaction (QF-PCR) has quickly become an effective means of chromosome anomaly detection due to its advantages in terms of timing, manpower and accuracy. The QF-PCR results also make a significant change in clinicians’ attitude to some extent, assisting them providing parents with professional and valuable advice on pregnancy management. In this review, the advantages and drawbacks of QF-PCR will be explored. By reviewing studies published in Vietnamese Medical Journals, we conclude QF-PCR can become a potential screening test in the field of prenatal diagnosis.

Background Tropical and subtropical crops such as coffee, cacao, and papaya are valuable commodities and its consumption is a seemingly indispensable part of the daily lives of billions of people across the world. Conventional breeding in these crops is lengthy and yields are threatened by runaway global warming. In this review we propose the application of chromosome engineering and synthetic biology principles in order to enhance synthesis of key metabolites, and transmission of wild traits for resistance to stress and disease. Conclusions It is hoped that the adoption of such technological approaches may enhance the resilience of agricultural communities, lead to economic growth and secure the availability of key resources for generations to come.

In this paper, based on the pseudo-totem pole (PTP) circuit, a family of five-level PTP dual boost converters (PDBC) is proposed. Dual boost converter has some unique advantages such as no bridge arm shoot-through risk and no switch body diode reverse recovery problem, so that it has a good application prospect. Compared with conventional three-level PTP converters, PDBCs has higher power density, higher efficiency, and low voltage and current stress. The topological derivation process, working principle, modulation and strategy of the topology are analyzed firstly. Further, the number of power devices, the switches voltage and current stress of the proposed topology is analyzed. Finally, a representative five-level PDBC experimental prototype is designed with AC input 220V/50Hz, DC output 400V/1kW, and peak efficiency of 98.27%. The experimental results show that the five-level PDBC proposed in this paper has higher efficiency and verify the correctness of the topology.

Typically, a diesel generator on the merchant ship, composed of a wound rotor synchronous generator and a four-stroke diesel engine, supplies electrical power to various loads. Recently, shaft generators for merchant vessels are increasingly replacing diesel generators to reduce CO2 emissions through fuel efficiency improvement. In particular, permanent magnet generators replace induction generators due to their high-efficiency characteristics at light loads. The surface-mounted permanent magnet can be a suitable rotor topology due to the relatively short constant power range. This generator can also operate as a motor according to the propulsion mode, so minimizing the harmonics of the induced voltage and the torque ripple is necessary. This paper proposes an alternative NdFeB magnet pole topology combined with the modular step-skewed rotor. The step-skewed rotor affects to reduce higher-order harmonics, and the modular pole reduces the permanent magnet assembly process and harmonics in voltage and torque. A 2-D finite element method is used to evaluate the harmonics of induced voltage and torque pulsation for the proposed topology. The topology shows harmonic minimization effect by comparing the characteristics of three flatted-bottom magnets. Compared to the tapered bread-loaf magnet, voltage harmonics to the 100th component are almost the same, and the torque ripple is reduced by more than 12% at the same residual flux density. The analysis method is verified by comparing test and analysis results for prototype machines with similar specifications.

Symbolic pole/zero analysis is an important step when designing an analog operational amplifier. Generally, a simplified symbolic analysis of analog circuits suffers from NP-hardness, i.e., an exponential growth of the number of symbolic terms of the transfer function with the circuit size. In this study, we present a mathematical model combined with a heuristic-metaheuristic solution method for the symbolic pole/zero simplification in operational transconductance amplifiers (OTA). At first, the circuit is symbolically solved and an improved root splitting method is applied to extract symbolic poles/zeroes from the exact expanded transfer function. Then, a hybrid algorithm based on heuristic information and a metaheuristic technique using simulated annealing is performed for the simplification of the derived symbolic pole/zero expressions. The developed method has been tested on three analog OTAs. The obtained results show the effectiveness of the proposed method to achieve accurate simplified symbolic pole/zero expressions with the least complexity.

Keywords: Wheat; Speed Breeding; Maize Pollen Induction; Chromosome Elimination; Doubled Haploid (DH)

B chromosomes (Bs) or supernumerary chromosomes are extra chromosomes in the species karyotype that can vary in their copy number. Bs are widespread. Usually, the Bs of specimens collected from natural populations are involved in studies. We applied another approach analyzing the Bs in animals of laboratory cultures. In this study, three species of the Macrostomum genus that underwent a recent whole-genome duplication (WGD) were involved. In laboratory lines of M. lignano and M. janickei, the frequency of Bs was less than 1%, while in the laboratory culture of M. mirumnovem, it was nearer 30%. Their number in specimens of the culture varied from 1 to 14. Mosaicism on Bs was discovered in parts of these animals. We analyzed the distribution of Bs among the worms of the laboratory cultures during long-term cultivation, the transmission rates of Bs in the progeny obtained from crosses of worms with different numbers of Bs, and from self-fertilized isolated worms. The DNA content of the Bs in M. mirumnovem was analyzed with the chromosomal in situ suppression (CISS) hybridization of microdissected DNA probes derived from A chromosomes (As). Bs mainly consisted of repetitive DNA. The cytogenetic analysis also revealed the divergence and high variation in large metacentric chromosomes (LMs) containing numerous regions enriched for repeats. The possible mechanisms of the appearance and evolution of Bs and LMs in species of the Macrostomum genus were also discussed.

Abstract: The purpose of this study was to understand the role of infection in the origin of chromosomal anomalies linked to neurodevelopmental disorders. In patients with neurodevelopmental disorders, DNA’s from viruses and bacteria including known teratogens were tested against chromosome anomalies known to cause the disorders. Results support a theory that parental infections disrupt elaborate multi-system gene coordination needed for neurodevelopment. Genes essential for neurons, lymphatic drainage, immunity, circulation, angiogenesis, barriers, structure, and chromatin activity were all found close together in polyfunctional clusters that were deleted in neurodevelopmental disorders. These deletions account for immune, circulatory, and structural deficits that accompany neurologic deficits. In deleted clusters, specific and repetitive human DNA matched infections and passed rigorous artifact tests. In some patients, epigenetic driver mutations were found and may be functionally equivalent to deleting a cluster or changing topologic chromatin interactions because they change access to large chromosome segments. In three families, deleted DNA sequences were associated with intellectual deficits and were not included in any database of genomic variants. These sequences were thousands of bp and unequivocally matched foreign DNAs. Analogous homologies were also found in chromosome anomalies of a recurrent neurodevelopmental disorder. Viral and bacterial DNAs that match repetitive or specific human DNA segments are thus proposed to interfere with highly active break repair during meiosis, and sometimes delete polyfunctional clusters, and disable epigenetic drivers. Mis-repaired gametes produce zygotes containing rare chromosome anomalies which cause neurologic disorders and accompanying non-neurologic signs. Neurodevelopmental disorders may be examples of assault on the human genome by foreign DNA with some infections more likely tolerated because they resemble human DNA segments. Further tests of this model await new technology.

A new low-pass filter (LPF) circuit with independent adjustment of various, incl. digitally controlled, pole frequency resistors, pole quality factor and transmission coefficient. The proposed low-pass filter is based on the use of the properties of a multi-differential operational amplifier that performs the functions of a signal adder. The peculiarity of the filter is that it has three inputs, with respect to which different transmission coefficients are implemented, incl. inverting (-1) and non-inverting (+1). To check these properties of a low-pass filter in the Micro-Cap environment, computer simulation of a specific circuit was performed on a multi-differential operational amplifier AD 8130. Mathematical expressions are given for the main parameters of the proposed low-pass filter, which allow parametric synthesis of elements of a specific circuit under given restrictions on the used element base.

A new circuit of a low-pass filter (LPF) is considered, which is switched on at the input of analog-to-digital converters to limit the spectrum of input signals. The peculiarity of the proposed low-pass filter is the independent adjustment of the pole frequency, the quality factor of the pole and the transmission coefficient by different resistors. Computer simulation performed in the Micro-Cap environment confirms these properties of the LPF. The basic mathematical expressions are obtained, which make it possible to carry out the parametric synthesis of the LPF circuit. It is shown that the sensitivity of the LPF transmission coefficient to changes in the parameters of the frequency-setting elements of the circuit is close to zero and depends only on the ratio of the resistances of the two resistors in the feedback circuit.

Marek’s Disease (MD) has a significant impact on both the global poultry economy and animal welfare. The disease pathology can include neurological damage and tumour formation. Sexual dimorphism in immunity and known higher susceptibility of females to MD makes the chicken Z chromosome (GGZ) a particularly attractive target to study the chicken MD response. Previously, we used a Hy-Line F6 population from a full-sib advanced intercross line to map MD QTL regions (QTLRs) on all chicken autosomes. Here we mapped MD QTLRs on GGZ in the previously utilized F6 population with individual genotypes and phenotypes, and in eight elite commercial egg production lines with daughter-tested sires and selective DNA pooling (SDP). Four MD QTLRs were found from each analysis. Some of these QTLRs overlap regions from previous reports. All QTLRs were tested by indiviuals from the same eight lines used in the SDP and genotyped with markers located within and around the QTLRs. All QTLRs were confirmed. The results exemplify the complexity of MD resistance in chickens and the complex distribution of P-values and LD pattern and their effect on localization of the causative elements. Considering the fragments and interdigitated LD blocks while using LD to aid localization of causative elements, one must look beyond the insignificant markers, for possible distant markers and blocks in high LD with the significant block. The QTLRs found here may explain at least part of the gender differences in MD tolerance, and provide targets for mitigating the effects of MD.

Fanconi anemia (FA) is a rare genetic disorder caused by pathogenic variants (PV) in at least 22 genes, which cooperate in the FA/BRCA pathway to maintain genome stability. PV in FANCA, FANCC, and FANCG account for most cases (~90%). This study evaluated the chromosomal, molecular, and phenotypic findings of a novel founder FANCG PV, identified in three patients with FA from the Mixe community of Oaxaca, Mexico. All patients presented chromosomal instability and a homozygous PV, FANCG: c.511-3_511-2delCA, identified by next-generation sequencing analysis. Bioinformatics predictions suggest that this deletion disrupts a splice acceptor site promoting the exon 5 skipping. Analysis of Cytoscan 750K arrays for haplotyping and global ancestry supported the Mexican origin and founder effect of the variant, reaffirming the high frequency of founder PV in FANCG. The degree of bone marrow failure and physical findings (described through the acronyms VACTERL-H and PHENOS) were used to depict the phenotype of the patients. Despite having a similar frequency of chromosomal aberrations and genetic constitution, the phenotype showed a wide spectrum of severity. The identification of a founder PV could help for a systematic and accurate genetic screening of patients with FA suspicion in this population.

Sporadic colorectal cancer (CRC) develops through distinct molecular events. Loss of 18q chromosome is a conspicuous event in the progression of adenoma to carcinoma. There is limited information regarding the molecular effectors of this event. Earlier, we had reported ATP8B1 as a novel gene associated with CRC. ATP8B1 belongs to the family of P-type ATPases (P4 ATPase) that primarily function to facilitate the translocation of phospholipids. In this study, we attempt to implicate ATP8B1 gene located on chromosome 18q as a tumor suppressor gene. We studied indigenous patient data and confirmed the reduced expression of ATP8B1 in tumor samples. CRC cell lines were engineered with reduced and enhanced levels of ATP8B1 which provided a tool to study its role on cancer progression. Forced reduction of ATP8B1 expression either by CRISPR/Cas9 or shRNA was associated with increased growth and proliferation of CRC cell line - HT29. In contrast, overexpression of ATP8B1 resulted in reduced growth and proliferation of SW480 cell line. We generated a network of genes that are downstream of ATP8B1. Further, we provide predicted effect of modulation of ATP8B1 levels on this network and possible effect on fatty acid metabolism related genes. These results provide evidence in support of ATP8B1 being a tumor suppressor that may affect fatty acid metabolism in CRC.

Prasinoviruses are large dsDNA viruses commonly found in aquatic systems worldwide, where they can infect and lyse unicellular prasinophyte algae such as Ostreococcus. Host susceptibility is virus strain-specific, but resistance of susceptible Ostreococcus tauri strains to a virulent virus arises frequently. In clonal resistant lines that re-grow, viruses are usually present for many generations, and genes clustered on chromosome 19 show physical rearrangements and differential expression. Here, we investigated changes occurring during the first two weeks after inoculation of viruses. By serial dilutions of cultures at the time of inoculation, we estimated the frequency of resistant cells arising in virus-challenged O. tauri cultures to be 10⁻³–10⁻⁴ of the inoculated population. Re-growing resistant cells were detectable by flow cytometry 3 days post-inoculation (dpi), visible re-greening of cultures occurred by 6 dpi, and karyotypic changes were visually detectable at 8 dpi. Resistant cell lines showed a modified spectrum of host-virus specificities and much lower levels of OtV5 adsorption.

Interior permanent magnets motors are widely used in applications requiring high power den-sity and high efficiency due to their high torque generating capabilities. Recently, given the re-cent price fluctuations and unstable supply of rare-earth permanent magnets, alternative config-urations with reduced use of permanent magnets are being sought. Among the various candi-dates related to this, the consequent-pole type rotor structure can halve the number of perma-nent magnets used compared with conventional structures. However, in the no-load analysis, the waveform of the back electromotive force becomes asymmetric, generating a harmonic component. As a result, there is a disadvantage that the torque ripple increases. To overcome these shortcomings, we propose a novel rotor structure that applies a consequent-pole structure to an embedded permanent-magnet motor structure, wherein a number of permanent magnets are arranged in a flared structure to constitute a single polarity. In the proposed flared-structured magnet arrangement, it is possible to adjust the angle of the permanent magnet and the polar angle to mitigate the asymmetry of the back EMF waveform. The proposed struc-ture was optimized with a genetic algorithm and a prototype of the optimal model was con-structed and experimentally evaluated to verify its validity. Finally, the performance improve-ment and validity of the proposed structure were verified by comparing the analysis results of the optimal model with the experimental results.

Chromosome segregation in female germ cells and early embryonic blastomeres is known to be highly prone to errors. The resulting aneuploidy is therefore the most frequent reason for termination of early development and embryo loss in mammals. And when compatible with embryonic and foetal development, aneuploidy leads into severe developmental disorders. The main surveillance mechanism, essential for protection of cells against aneuploidy, is the Spindle Assembly Checkpoint (SAC). And although all eukaryotic cells are perhaps able to mount SAC response, it is not clear, whether this pathway is active in all cell types, including blastomeres of early embryos. In this review, we will summarize and discuss the published literature with regards to mechanisms controlling chromosome segregation in early embryos. Our conclusion is that early embryos show limited capabilities to react to chromosome segregation defects, which might, at least partially, explain the widespread problem of aneuploidy during early development.

Determination of the fetal gender in the first trimester is important in twin pregnancy cases of familial X-linked genetic syndromes and helps determine chorionicity. We assessed and compared the accuracy of first-trimester ultrasound scans, and circulating cell-free fetal DNA (cffDNA) performed by non-invasive prenatal screening (NIPS) in determining fetal gender in the first trimester of twin pregnancies. For this purpose, we enrolled prospectively pregnant women with twin during the first trimester, gestational week (GA) 11-13. The fetal gender was determined using both ultrasound scans and cffDNA screening. Both results were compared to the newborn gender at delivery. A total of 113 women with twin pregnancies were enrolled. There was 100% sensitivity and specificity in Y chromosome detection using cffDNA. The accuracy of gender assignment using ultrasound in any first-trimester scans was 79.7%. Accuracy level increased from 54.2% in CRL 45-54 mm to 87.7% in CRL 55-67 mm and 91.5% in CRL 67-87 mm. Male fetuses had significantly higher chances of a gender assignment error compared to female fetuses, odds ratio = 23.57 (CI 7.356 - 75.66). This is the first study that compared the accuracy of gender determination in the first trimester by cffDNA and by ultrasound scanning in twin pregnancy. It was concluded that the cffDNA is highly sensitive and specific in determining the presence of the Y chromosome in twin pregnancies in the first trimester. Between CRL 67-87 mm, ultrasound scanning offers a highly accurate determination of fetal gender in twin pregnancies. Larger cohorts of multi-center studies are warranted.

Two X chromosomes of female mammals randomly inactivate one of paternal or maternal X chromosome in early embryonic development and all the daughter cells produced from these cells retain the same feature of X chromosome inactivation, which is called X chromosome inactivation (XCI). Studying the mechanisms of XCI is important for understanding epigenetic that plays an important role in age-associated diseases. The previous studies have demonstrated that binding of RNAs and DNAs may play a role in activating gene expression. In this paper, our study aims to explore whether the mechanisms of XCI involve the RNA binding strength to X chromosome DNAs. The bioinformatics analyses based on big data were used to analyze the simulated binding strength of RNAs (RNA binding strength) to 23 chromosomes (including X chromosome and 22 human autosomes) and the characteristics of repetitive sequences in the X-inactivation centre. The results revealed that RNA binding strength of the long arm of the X chromosome that is almost entirely inactivated in XCI was significantly lower than that of all autosomes and the short arm of X chromosome, meanwhile the RNA binding strengths of inactivation regions in X chromosome were significantly lower than that of regions escaping from XCI. Different repetitive sequence clusters within the center of XCI presented a cross distribution characteristic. To further prove whether the repetitive sequences in human X chromosome involve in XCI, we cloned long interspersed element (LINE-1, L1) and short interspersed element (Alu) from human Xq13, the center of XCI, and constructed expression vectors carrying sense-antisense combination repetitive sequences (L1s or Alus). Effects of combined L1 or combined Alu sequences on expression of EGFP reporter gene were examined in stably transfected HeLa cells, which simulates the effects of repetitive sequences located on chromosomes. The results of experiments revealed transcribed L1 repetitive sequences activated EGFP reporter gene expression, so did the Alus. The experiment results suggested repetitive sequences activated genes by interaction of transcribed RNAs and DNAs. Since the binding of RNAs and DNAs can activate gene, so the low RNA binding strength of human X chromosome may be one of reasons of XCI. The cross distribution characteristics of different repetitive sequence clusters leading to a cascade of gene activation or gene inactivation may be the reason of transcriptional silencing one of the X chromosomes in female mammals.

Large Language Models (LLMs) have proved significant proficiency when comes to code generation especially in Structured Query Language (SQL) for databases and recent successful Text-to-SQL method involves fine-tuning pre-trained LLMs for SQL generation tasks. Transforming natural language text into SQL queries, has been attempted to solve with various learning techniques including Few-shot learning[1], fine tuning. In this paper we propose Supervised fine-tuning (SFT) as a better alternative for learning technique for text-to-SQL generation task using Code-Llama that pushes state of art accuracy on spider test suite to 89.6% on dev set which represent first instance of surpassing the earlier best-in-class with 5.5% higher score and 86.8% of exact match accuracy on dev set. Furthermore, we demonstrate that properly prompted LLM along with SFT provides far fewer hallucinations and much more robust LLM that can be used as a general tool for any text-to-SQL generation use case.

Upland cotton is sensitive to 2,4-dichlorophenoxyacetic acid (2,4-D), and the identification of potentially 2,4-D tolerant cotton chromosome substitution (CS) lines and understanding tolerance mechanisms provide a significant step into the development and genetic improvement of upland cotton to reduce yield loss caused by 2,4-D herbicide effects including the drifts. Experiments were conducted to understand the possible mechanism of herbicide tolerance in CS-T04-15, CS-T07, and CS-B15sh, 2,4-D herbicide-tolerant cotton CS lines compared with TM-1, the 2,4-D herbicide susceptible recurrent parent of the CS line as control, using [14C]2,4-D. Percent absorption rate and translocation patterns of the 14C-labeled herbicide application at 5.17 kBq at 6 to 48 hours after treatment (HAT) were determined. The tolerant cotton CS lines showed 15-19% [14C]2,4-D uptake while TM-1 exhibited a reduced uptake of only 1.4% [14C]2,4-D at 24 HAT. Distribution of the absorbed [14C]2,4-D showed that 2-5% was translocated outside the treated leaf. In TM-1, 77% of the herbicide was translocated above and below the treated leaf, contrasting with the reduced translocation of 14C-labeled herbicide observed in the tolerant CS lines. Interestingly, CS-T04-15 showed a restricted movement of 14C below the treated leaf at 6 to 48 HAT, suggesting a novel mechanism of herbicide tolerance. This finding is the first report on upland cotton demonstrating a complex differential uptake and translocation associated with herbicide tolerance for [14C]2,4-D in cotton CS lines.

Separase is a key cysteine protease to separate sister chromatids through digestion of cohesion ring that inhibits chromosome segregation as trigger of metaphase–anaphase transition in eukaryotes and highly regulated its activity by binding with securin and cyclinB-CDK1 complex. Those bindings prevent proteolytic activity of separase until the onset of anaphase. Chromosome missegregation and aneuploidy are frequently observed in malignancies. However, there are some difficulties for biochemical examinations due to instability of separase in vitro and a few spatiotemporal resolution approaches monitoring live separase activity throughout mitotic processes. Here we have developed FRET-based molecular sensors including GFP variants with separase cleavable sequences as donor and covalently attached fluorescent dye as acceptor molecules applicable to conventional live cell imaging and flow cytometric analysis because of efficient live cell uptake. We investigated performance of equivalent molecular sensors localized or not localized inside nucleus under cell cycle control using flow cytometry. Synchronized cell cycle progression rendered significant separase activity detections in both molecular sensors. We obtained consistent outcomes with localized molecular sensor introduction and cell cycle control by fluorescent microscopic observations. We thus established live cell separase activity monitoring systems specifically or statistically that could lead to elucidate separase properties in detail.

The literature on the causation of multiple sclerosis (MS), both genetic and environmental, extends over hundreds of years, with no firm conclusions on the exact role of autoimmunity and lifestyle. The epidemiology of MS was the basis for this review, but with a new, extensive examination of genes pertaining to each disorder, and disease of first, and second, degree relatives of those with MS. The author’s motivation was to discover some relationship between MS, and notable familial conditions, as the heredity of MS is concluded to be 30%, and the disorders had a chronic and/or idiopathic nature. This investigation hoped to further understand the randomness of MS- who acquires it, and what symptoms develop- after the author’s decades of observing several incidences of multiple members developing MS in a single family. Online databases for the human genome were used to link genes to MS, and symptoms, including excessive depression, fatigue and suicide rates, in coordination with linking genes for specific familial conditions including seizures, stroke, mental illness, bowel disorders, and thyroid conditions. Interesting associations were found, notably a cluster of Th2 cytokines, known to cure the animal model of MS, important receptors for neurotransmitters and hormones, a gene specific to Epstein Barr Virus, and potential genes for mitochondrial dysfunction. The results surprised the author, showing polygenic regions of chromosome 2 and 5, especially a cluster at loci 5q31-q33, may be dysregulated. The conclusion agrees with past hypotheses MS results not from a single gene, but from various genes, including those expressed in glial cells. The individual theories to the causation of MS, starting with Charcot may be explained by multiple pathways converging into a single disease outcome. In coordination with a sunlight factor, chromosome 2 appears to mediate the immune system, and inflammation, through ultraviolet radiation producing vitamin D3 in the skin, but additionally through peptides formed in the melanocyte stimulating and concentrating hormone class. The impact of stress in MS could be primary, given the loci of several stress-related and stress-modulated genes on these chromosomes, and calls for more appreciation of, and greater care for, the MS patients’ state of mind.

The research examines the relationship between self-rated health situation and personal percep-tion of heat waves, and how social linkage of communities would be a moderator variable in residents’ perception of heat waves in Taiwan. This study uses the questionnaire conducted by Sinica “Responsive Capacity under Heat Wave: The Perspectives of the Locals”(2019), using OLS method for estimating the unknown parameters in multiple regression model. The author finds that the correlation of self-rated health situation and perception toward heat is significantly posi-tive. Also, social linkage in communities affects strongly as a moderator variable: While the sat-isfaction to with their community could reduce negative reaction to heat, contacts with neighbors could increase possibility people feel uncomfortable in high-temperature situation. This study ex-hibits the effects of social environment on community, and expects further related researches or practices to strengthen capability to resist heat wavesƒ for Taiwanese residents.

Amebiasis is a disease caused by the unicellular parasite Entamoeba histolytica. In most cases, the infection is asymptomatic but when symptomatic, the infection can cause dysentery and invasive extraintestinal complications. In the gut, E.histolytica feeds on bacteria. Increasing evidences support the role of the gut microbiota in the development of the disease. In this review we will discuss the consequences of E.histolytica infection on the gut microbiota. We will also discuss new evidences about the role of the gut microbiota in regulating the resistance of the parasite to oxi-dative stress and its virulence.

In situ imaging of molecular markers on a physical chromosome is an indispensable tool for refin-ing of genetic maps and validation genome assembly at the chromosomal level. Despite tremen-dous progress in genome sequencing the plant genome assembly at chromosome level still remain a challenge. Recently developed optical and Hi-C mapping aim to assist in genome assembly. For high-confidence in the genome assembly at chromosome level more independent approaches will be required. The present study aimed to refined an ultrasensitive Tyr-FISH technique and to de-velop a reliable and easy method for in situ mapping of a short unique DNA sequences on plant chromosomes. We have carefully analyzed the critical steps of the Tyr-FISH technique to find out the reasons for the failures of using the method. It has been shown that successful visualization of marker/gene depends significantly on method of chromosome slide preparation, probe design and labelling, high stringency washing. Appropriate adjustment of these steps allowed us to detect a short DNA sequence of 1.7Kb with a frequency of 51.6%. Based on our results, we developed a reliable and simple protocol for dual-color Tyr-FISH visualization of short unique DNA sequences on plant chromosomes. New protocol allows more accurate determination of the physical distance between markers and can be applied for faster integration of genetic and cytogenetic maps.

Objective: To explore three novel fasting blood glucose (FBG)-based novel indicators, including FBG-to-albumin ratio (FAR), FBG-to-lymphocytes ratio (FLR), and FBG-to-hemoglobin ratio (FHR), in predicting prognosis and detecting metastasis for patients with pancreatic neuroendocrine neoplasms after resection. Materials and methods: A total of 178 pNEN patients underwent surgical resection were included in this study. Receiver operating characteristic (ROC) curves were used to evaluate the diagnosis values of FAR, FLR, and FHR, and the cut-off values were obtained for further analyses. Univariate and multivariate analyses were conducted to determine the independent predictors. The Kaplan-Meier method was used to evaluate the progression-free survival (PFS) and overall survival (OS) of the pNEN patients. Results: The optimal cut-off values of FAR, FLR, and FHR were 0.17, 2.85, and 0.028, respectively. As for PFS, the area under the curve (AUC) was 0.693 for FAR, 0.690 for FLR, and 0.661 for FHR, respectively. The AUC was 0.770, 0.692, and 0.715 accordingly for OS. The groups with lower FAR, FLR, and FHR were significantly associated with prolonged PFS and OS (p < 0.05). In patients with metastasis, the lower FAR group was correlated with significantly longer PFS and OS (p = 0.022 and 0.002, respectively). The FLR was an independent predictor of PFS in pNEN patients, and the FAR was a predictor of OS. FAR was an independent indicator of PFS in patients with metastasis. Conclusion: Preoperative FAR, FLR, and FHR are effective in predicting the prognosis of pNEN patients and detecting the synchronous metastases.

Objective: The current study aimed to delineate the relationship of furin with inflammation while cervical intraepithelial neoplasia progresses to cancer. Study Design:This cross-sectional study included 81 women who required colposcopic examinations. The study groups were formed based on pathological results: Group I included women with cervical intraepithelial neoplasia (CIN) I (n=30); Group II included women with CIN II-III (n=28); and Group III included women with cervical cancer (CC) (n=23). Furin, ki-67, and p16 levels were evaluated based on immunostaining intensity. The inflammatory indices were calculated parallel with the literature from routine blood samples retrieved within one week before the procedure. Results:Furin expression gradually increased from CIN I to CIN II-III and from CIN II-III to CC, respectively (p < .001, p = .005). The NLR, MLR, PLR, and SII were significantly higher in the CC group (p < .001). ROC curve analysis unveiled that NLR, MLR, PLR and SII predicted the presence of CC with a cutoff value of 2.39 for NLR (sensitivity: 91.3%, specificity: 63.8%, AUROC: 0.79, p < .001); a cutoff value of 0.27 for MLR (sensitivity: 78.3%, specificity: 72.4%, AUROC: 0.77, p = .009); a cutoff value of 123 for PLR (sensitivity: 100%, specificity: 41.4%, AUROC: 0.70, p = .04); and a cutoff value of 747 for SII (sensitivity: 69.6%, specificity: 90.7%, AUROC: 0.71, p = .014). Conclusion:Furin expression increased gradually in parallel to the severity of cervical intraepithelial neoplasia. The inflammatory indices were higher in the presence of CC and denoted good discrimination ability for predicting cervical cancer.

(1) Background: Little research has been done on professionals' perceptions of institutions and governments during epidemics. We aim to create a profile of physicians who feel they can raise public health issues with relevant institutions during a pandemic. (2) Methods: A total of 1285 Romanian physicians completed an online survey as part of a larger study. We used binary logistic regression to profile physicians who felt able to raise public health issues with relevant institutions; (3) Results: Five predictors could differentiate between respondents who tended to agree with the trust statement and those who tended to disagree: feeling safe at work during the pandemic, considering the financial incentive worth the risk, receiving training on the use of protective equipment, having the same values as colleagues, and enjoying work as much as before the pandemic; (4) Conclusions: Physicians who trust the system to raise public health issues with the appropriate institutions feel they share the same values as their colleagues, say they were trained in the use of protective equipment used during the pandemic, felt they were safe at work during the pandemic, enjoyed their work as much as before the pandemic, and felt the financial bonus justified the risk.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

Economic development and population growth lead to increased production of chicken manure (CM), which is a problematic organic waste for its amount, environmental threats, and moisture content. There are different ways of CM, namely anaerobic digestion, composting, combustion, and direct land spreading. Hydrothermal carbonization (HTC) is another emerging way, however. In this study, the HTC of CM was performed to produce energy-rich material called hydrochar (HC). The effects of HTC temperature (180, 240, 300 C) and process time (30, 90, 180 min) were summarized. Proximate and ultimate analysis, as well as heating values (HHV, LHV), have been performed both on raw CM and derived HC. Additionally, the process performance has been examined. The obtained results show that HTC is a feasible method for CM disposal and valorization. Although process time did not influence considerably fuel properties of CM, higher temperature led to significantly higher HHV, reaching 23,880.6734.56 Jg-1 at 300 C and 180 min with an improvement of 8,329 Jg-1 compared with raw CM (15,551.67 Jg-1). The process conducted at 240 C in 30 min has been specified as the most favorable, due to the highest energy gain of HC and relatively low energy consumption.

The increase in the emission of greenhouse gases (GHG) is one of the most important world problems. Decreasing of GHG emission is a big challenge in the future. Transportation sector uses a significant part of petroleum production in the world and it leads to an increase in the emission of GHG. The result of this issue is that population of the world befoul environment of transportation system automatically. Electric Vehicles (EV) have a potentiality to solve a big part of the GHG emission and energy efficiency issues such as stability and reality of energy. The energy actors and their research team determine some targets for 2050; hence, they hope to decrease the world temperature to 6 °C in the best and 2 °C in the normal condition. Fulfillment of these scenarios needs suitable grid infrastructure but in most of the countries, the grid does not have a suitable background to apply those scenarios. In this paper, some problems about energy scenarios, energy storage systems, grid infrastructure and communication systems in supply and demand side of the grid and its solutions have been investigated.

Vehicle to vehicle (V2V) and Vehicle to infrastructure (V2I) or briefly V2X communications are the one of hot topics in automotive industry. Therefore, this situation is providing many advantages of connected vehicles and infrastructures which bring to human life. For instance, vehicles and road infrastructures which shares information with each other, provides a neat flow regulation, more ordered traffic flow and therefore jammed traffic dependent accident’s percentage will be decreased. On the other hand, security is the most important issue for these systems because the operation of V2X networks is completely dependent on uninterrupted and accurate information sharing. In the light of these information, in this paper we review security issues and current solution architectures. We also propose some open problems in this lively field.

Sustaining learners’ motivation to keep learning has been concerned for over 60 years in education and SLA. Most research focusing on Japanese university students has contributed lots of theoretical and practical developments, but research focusing on motivations of non-traditional adult learners and those under 18-year-old to learn Chinese is still little even though previous research findings have proved age is one of the key variables influencing learning besides nationalities and Chinese language levels. In order to find an effective treatment for sustainable Chinese language learning in Japan, this study utilized a survey method to analyze the types of Japanese learners’ motivation to learn Chinese via analysis of a moment structures (AMOS), and to compare the differences of the motivation via one-way ANOVA. This study revealed that Japanese learners’ motivation to learn Chinese consists of eight common types, which are “instrumental motivation”, “personal orientation”, “identified regulation”, “Chinese cultural productions”, “integrating into Chinese community”, “external regulation”, “social responsibility”, and “Chinese for academic purposes”. Also, there are similarities and differences existing in the eight motivation types among the Japanese children, adolescents, (non-) traditional adult learners of Chinese as a foreign language (CFL). The findings contribute the understanding of motivation types and differences among the four aged Japanese learners to teachers of teaching Chinese to speakers of other languages (TCSOL), and to future research further exploring how differently aged Japanese learners can have and use a higher motivation as a main drive to learn Chinese language as a lifelong business.

If genetic gains in wheat yield are to be achieved in today’s breeding, increasing genetic variability of cultivated genotypes is an essential requisite to meet. To this aim, alien gene transfer through chromosome engineering (CE) is a validated and sound strategy. Attempts to incorporate more than one alien segment into cultivated wheat have been rare, particularly for tetraploid durum wheat. Here we present the agronomic and quality performance of the first successful CE-mediated multiple introgression into the latter species. By assembling into 7AL, 3BS and 1AS arms of a single genotype homoeologous segments of Thinopyrum ponticum 7el1L, Aegilops longissima 3SlS, and Triticum aestivum 1DS arms, respectively, we have stacked several valuable alien genes, comprising Lr19+Sr25+Yp (leaf and stem rust resistance and a gene increasing semolina yellowness), Pm13 (powdery mildew resistance) and Gli-D1/Glu-D3 (genes affecting gluten properties), respectively. Advanced progenies of single, double and triple recombinants were field-tested across three years in a typical durum wheat growing area of Central Italy. The results showed that not only all recombinants had normal phenotype and fertility, but also that one of the triple recombinants had the highest yield through all seasons compared with all other recombinants and control cultivars. Moreover, the multiple introgressions enhanced quality traits, including gluten characteristics and semolina yellow index. Presence of effective disease resistance genes confers additional breeding value to the novel and functional CE products, which can greatly contribute to crop security and safety.

A community-level nutrition intervention was implemented among tribal children (3 to 6 years) in Telangana, India. The one-year intervention involved six nutrient-rich formulations of millet-pulse-groundnut based products, suited to local taste preferences. Anthropometric measurements of height, weight and Mid-Upper-Arm -Circumference (MUAC) along with haemoglobin (Hb) levels were monitored at baseline and endline. The treatment group showed considerable gain in height (3.2 cm), weight (1.68 kg) and MUAC (0.33 cm), over the control group. Paired t-test indicated significant differences (p<.01) between pre- and post-intervention anthropometric measurements. Positive shifts were observed in wasting (WHZ; -1.2 ±1.3 to -0.9± 1), stunting (HAZ; -1.8±1.6 to -0.3±1.3) and underweight (WAZ; -1.9±1.2 to -0.7±1) among treatment group. Hb levels in the treatment group also improved significantly from 9.70 ± 0.14 g/dl (moderately-anaemic) to 11.08 ± 0.13 g/dl (non-anaemic). Post-intervention Focus Group Discussions (FGDs) involving mothers and teachers confirmed the positive impact. Thus, nutritional intervention formulated using climate resilient millets, pulses and groundnut, promotes dietary diversity and improves the nutrition & health status of children.

Access to medicines is one of the essential problems in Public Health of low- and middle-income countries (LMICs). The World Health Organization (WHO) defines access to medicines as the possibility of "having continuously accessible and affordable medicines in public or private health facilities that are within a kilometer of the place of residence." Access to medicines, as defined by the WHO, is not fully guaranteed in many LMICs and even in many regions of high-resource countries. The WHO identifies several factors as determinants of limitations in the access to medicines: rational selection, affordable prices, sustainable financing, and reliable health services. The action on these factors makes it possible to improve universal access to medicines with consequent improvement in Public Health. Adequate access to antibiotics and vaccination will avoid a large part of the deaths caused by infectious diseases in the LMICs. However, the emergence of resistance and the difficulties in vaccination campaigns due to socio-political or cultural problems make it challenging to fight many easily treatable infectious diseases. The use and abuse of antibiotics are inevitably associated with the appearance of resistances that make them ineffective. Thus, whereas limited access to antibiotics raises mortality rates from infectious diseases, generalized open access to them ends up eliminating their clinical value. Moreover, the contraction of research in this field for many years has reduced the success in discovering new drugs. Additionally, local market regulations, inadequate selection, inaccessible prices, especially for those of second and third-generation, inefficient health systems, and difficulties of administration and control of prescription compliance, especially in the case of combined therapies, are additional obstacles to universal access to antibiotics. In order to simultaneously improve access to antibiotics and keep resistances under control, it is necessary to develop training and education activities at different social levels (from patients to various Health Care Providers) to complement the national or supranational strategic plans.

The bipolar mitotic spindle drives accurate chromosome segregation by capturing the kinetochore and pulling each set of sister chromatids to the opposite poles. In this review, we describe recent findings on the multiple pathways leading to bipolar spindle formation in fission yeast and discuss these results from a broader perspective. Roles of four mitotic kinesins (Kinesin-5, Kinesin-6, Kinesin-12 and Kinesin-14) in spindle assembly are depicted, and how a group of microtubule-associated proteins, sister chromatid cohesion and the kinetochore collaborates with these motors is shown. We have paid special attention to the molecular pathways that render otherwise essential Kinesin-5 to become non-essential: how cells build bipolar mitotic spindles without the need for Kinesin-5 and where the alternate forces come from are considered. We highlight the force balance for bipolar spindle assembly and explain how outward and inward forces are generated by various ways, in which the proper fine-tuning of microtubule dynamics plays a crucial role. Overall, these new pathways have illuminated remarkable plasticity and adaptability of spindle mechanics. Kinesin molecules are regarded as prospective targets for cancer chemotherapy and many specific inhibitors have been developed. However, several hurdles have arisen against their clinical implementation. This review provides insight into possible strategies to overcome these challenges.

Neuropsychiatric manifestations of COVID-19 include delirium, general malaise, headache, and psychiatric symptoms. These manifestations are related to the neuroinflammatory response to viral antigens and proinflammatory mediators/immune cells. Tetracyclines, such as minocycline, have antibacterial and anti-inflammatory properties. Saiko-keishi-to, a traditional Japanese Kampo medicine, also has anti-inflammatory properties. Given the anti-inflammatory properties of minocycline and Saiko-keishi-to, we describe two cases of COVID-19 with prolonged headaches and general malaise successfully treated with these medications.

This study aims to describe the commitment to national heritage, patriotism, nationalism of elementary school students in the border areas between Indonesia and Timor Leste. This research was conducted in three elementary schools, they are SD Inpres Moto Ain, SD Inpres Class Jau Halimuti, SD Kristen Nanaeklot, and SD Negeri Motabenar from June to August 2018. The subjects of this study were elementary students in the Indonesia-Timor Leste border areas precisely around Motaain City, Belu Regency, East Nusa Tenggara. The research questionnaire was adapted from Karazawa and analyzed with descripriptive statistics. The results of this study showed that the commitment to national heritage, patriotism, and nationalism of elementary students on the Indonesian border areas with Timor Leste is in the very high level.

Aim: To investigate inflammation indices and erythropoietin (EPO) levels for their potential role in distinguishing polycythemia vera (PV) from secondary polycythemia (SP), and to compare different parameter combinations in terms of diagnostic accuracy. Methods: This retrospective cohort was created from patients assessed for polycythemia from January 2020 to December 2023. PV diagnosis was made according to the 2016 WHO criteria (n=145). Those who did not fulfill the criteria were defined as having SP (n=84). Results: NLR, PLR and SII were significantly higher in the PV group (p

The study comprehensively evaluated the prognostic roles of PLR, NLR, MLR, BLR, and ELR in patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD). 619 patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics containing laboratory findings of the AECOPD patients and the blood cell counts (CBCs) of the healthy volunteers were collected. Compared with the healthy volunteers, PLR, NLR, and MLR were elevated in COPD patients in stable condition, and were further ele-vated during exacerbation. ELR showed the opposite trend. PLR, NLR, and MLR were all posi-tively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more serious airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in-hospital mortality while Elevated ELR was associated with decreased in-hospital mortality in AECOPD. A nomogram was construct to predict in-hospital mortality in AECOPD. The nomo-gram had a C-index of 0.850 (95% CI: 0.799 – 0.901) with good predictive value and clinical ap-plicability. In summary, PLR, NLR, MLR, and ELR served as predictors for clinical outcomes in patients with AECOPD.

Background. IgA nephropathy (IgAN) is associated with chronic inflammation. Platelet-related parameters, such as platelet (PLT) count, platelet-to-albumin ratio (PAR) and platelet-to-lymphocyte ratio (PLR), were examined as potential prognostic indicators for renal and cardiovascular (CV) outcomes in IgAN. Methods. 150 IgAN patients were devided into two groups based on the cut-off value of PAR. All-cause mortality, major CV events and end-stage renal disease were the primary combined endpoints. Secondary endpoints, such as CV or renal endpoints, were also analyzed separately. Results. The patient’s mean age was 43.7 ± 13.5 years, and the follow-up time was 124 ± 67 months. The K-M curve showed that PLR, PAR and PLT were strongly associated with primary combined (p = 0.002, p = 0.004, p = 0.001) and renal outcomes (p < 0.001, p < 0.001, p < 0.001), but not with CV outcomes in IgAN. However, when combined with left ventricular hypertrophy (LVH) or metabolic syndrome (MetS) PAR was found to be a significant predictor of both primary (p < 0.001, p < 0.001) and secondary outcomes (p = 0.001 and p = 0.038; p = 0.001 and p = 0.015). Additionally, PLR correlated with microalbuminuria (r = -0.165, p = 0.033) and LVH (r = -0.178, p = 0.025), while PLT correlated with eGFR (r = 0.158, p = 0.040). Conclusion. Elevated PAR and PLR may predict progression to end-stage kidney disease, but in combination with LVH and MetS, they showed CV events also in IgAN. The determination of PAR and PLR can be useful and cost-effective parameters for assessing both cardiovascular and renal risks in CKD.

Background: The aim of this study has been to investigate if inflammatory biomarkers such as the systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have any correlation with the recurrence of pleomorphic adenomas (PA) in patients afflicted by this disease. Methods: A retrospective multicentre study involving two Italian centres, the Maxillofacial Sur-gery at the Policlinico Federico II in Naples and the ENT and Maxillofacial Surgery at the IRCCS G. Pascale National Cancer Institute in Naples, has been performed. The study, involving 608 pa-tients who had received a diagnosis of PA, was conducted between January 2000 and January 2020. A Receiver Operating Characteristic (ROC) curve was used to calculate the optimal cut-off values for the SII, PLR and NLR. A linear regression model (LRM) and a non-linear logistic re-gression model (NLRM) were realized with respect to the NLR, PLR and SII. Results: The highest performance was achieved by the NLR (cut-off 2.960) with the AUC = 0.91, with an accuracy of 96.1%, sensitivity of 78.4% and specificity of 97.2%, PPV = 64.4% and NPV = 98.6%. The LRM and NLRM including all the haematological parameters did not increase the per-formance in terms of recurrence detection. Conclusion: The NLR is an excellent support tool in predicting the recurrence of PA with a cut-off of 2.960. It can be a good reference point for surgical decision-making and follow-up in clinical practice.

Breast cancer (BC) affects millions of women; it is the leading cause of death by neoplasia in wom-en worldwide, with at least 500 thousand deaths each year, 70% of which occur in developing countries. Elastography evaluates tissue stiffness, making this a promising non-invasive real-time technique. BI-RADS is recognized as a standard and helpful technique for establishing BC risk. This study aimed to determine, by strain elastography (SE), the fat-to-lesion index (F/L index), sen-sitivity, specificity, and optimal cut-off to diagnose BC. This prospective study included 216 wom-en who underwent SE, ultrasound, mammography, and breast biopsy; according to mammogra-phy, we recruited BI-RADS category 2 (n= 5), category 3 (n=29), category 4 (n= 94), category 5 (n= 71) and category 6 (n=17); after biopsy, 108 women were classified as negative, and 108 were pos-itive for BC. Three expert BC radiologists performed all imaging interpretations and biopsies. Our results show mean values of the F/L index for negative biopsies of 3.70±2.57 and positive biopsies of 18.10±17.01; we developed two models for the prediction of BC, a logistic regression model with an AUC of 0.893 and a neural network with an AUC of 0.902. The Youden index yielded a F/L index cut-off >5.76, with a sensitivity and specificity of 84.26%. Positive Spearman's Rho cor-relation coefficient was observed between the F/L index and BI-RADS, r=.073 (p< 0.001). ANOVA test showed a difference between F/L index vs. molecular subtypes (p=0.002). SE is helpful as a di-agnostic complement to mammography, or in cases where the latter is contraindicated, elas-tography has an adequate predictive capacity and is a fast and minimally invasive procedure.

It has been proposed that upregulation of the noradrenergic (NA) system through exposure to novelty might be one of the key components for building cognitive reserve and resilience to neurodegeneration. A personality trait that promotes greater interest in novel experiences is Openness to Experience (OE). Individuals who are high in OE exhibit strong curiosity towards novelty and are more likely to be exposed to novel stimuli throughout the lifespan.Performing voxel-based morphometry analyses, we examined whether OE in 135 healthy young adults was associated with Locus Coeruleus (LC) - the main core of the noradrenergic system. We also investigated whether LC mediates the relationship between OE and a key measure of reserve, I.Q. In comparison with other neuromodulators’ seeds (Dorsal and Median Raphe [DR-MR] -5-HT, Ventral Tegmental Area [VTA] -DA- and Nucleus Basalis of Meynert [NBM] -Ach-), results show that greater LC integrity was related to greater OE and IQ. Additionally, mediation analyses revealed that only LC mediated the relationship between OE and IQ. Furthermore, a Bayesian multiple regression was conducted to model the contribution of both isolated and combined neuromodulator seeds to OE trait express. This approach found that the LC + VTA could account for more variance in OE expression compared to the LC alone. Other weaker but significant associations were observed between DR and OE, between LC + NBM and Conscientiousness and between DR + NBM and Extraversion. These results are together suggestive that OE is primarily underpinned by monoaminergic functioning, and that the LC-NA system plays a central role mediating the interdependence between OE expression and cognition (IQ level). While offering further understanding of the neurobiology of human personality, these findings indicate a pivotal role of LC-NA system integrity in novelty seeking in daily life. This provides a psychobiological account for how OE expression may be beneficial for maintaining the noradrenergic system to facilitate cognitive reserve and resilience to neurodegenerative conditions.

This paper compares the performance of three text-to-speech (TTS) models released from June 2021 to January 2022 in order to establish a baseline for Brazilian Portuguese. Those models were trained using dataset for Brazilian Portuguese. The experimental setup considers tts-portuguese dataset to fine-tune the following TTS models: VITS end-to-end model; glowtts and gradtts acoustic models both using hifi-gan vocoder. Performance metrics are arranged into objective and subjective metrics. As subjective metrics, the naturalness and intelligibility are measured based on the mean opinion score (MOS). Results shows that gradtts+hifigan model achieved naturalness of 4.07 MOS, close to performance of current commercial models.

Background: Vaccinating children against COVID-19 is an essential public health strategy in order to reach herd immunity and prevent illness among children and adults. Parents are facing tremendous stress in relation to the COVID-19 pandemic and the effectiveness of the COVID-19 vaccination program for children. In this study, we aimed to investigate parents’ willingness to vaccinate their children against COVID-19 in North Kivu province (DRC). Methods: A cross-sectional survey between December 01, 2021 to January 20, 2022 in 6 health zones (Goma, Karisimbi, Butembo, Beni, Kamango and Katwa) was conducted in the province of North Kivu. In each health zone, we selected 5 clusters (Health area) using the method of probabilistic selection proportional to population size. In total, 522 parents participated in our study. Results: Overall, 32.8% of parents intended to vaccinate their children. In the multivariate analysis, younger age of parents (aOR : 2.40, CI : [1.50-3.83]), higher level of fear that “a member of my family” could contract COVID-19 (aOR : 2.35, CI : [1.38-4.02]), higher level of perceived vulnerability to COVID-19 within the family (aOR : 1.70, CI : [1.005-2.2881]), higher level of perceived susceptibility to COVID-19 within the family (aOR : 3.07, CI : [1.80-5.23]), and history of vaccination against COVID-19 among parents (aOR : 16.47, CI : [8.39-32.33]), were significantly associated with the intention to have their children or adolescents vaccinated. Conclusion: Willingness of parents to vaccinate their children against the COVID-19 vaccination was low in North Kivu. There is undeniably in this region a need to reinsure the populations about vaccine safety for both children and adults. Public health authorities should also address widespread misinformation about vaccines in a timely manner.

With the COVID-19 pandemic continuing and the resulting economic burden increasingly apparent, the Indonesian government began to prepare a "new normal" phase and make peace with COVID-19. From this new decision arises the question of the readiness of businesses and the industrial sector to resume operations amid COVID-19. This article aims to provide concise and precise information about the preparations that can be made by businesses to operate safely amid COVID-19 based on existing scientific studies and literatures. From the literature visits it can be concluded that transmission and danger of a COVID-19 pandemic can be prevented through: creation of infectious disease prevention and response plan, implementing basic infection prevention measures, policies and procedures for proper identification and isolation of sick people, applying flexibilities in policies, and protections in the workplace.

Here we review and describe a set of research priorities to meet present and future challenges posed to farmed animal production that build on progress, successes and resources from the Functional Annotation of ANimal Genomes (FAANG) project.

South America has become the new epicenter of the coronavirus, especially in Brazil where the disease continues to spread exponentially across the country. This text aims to analyze the psychosocial factors of Covid-19 on back to school strategies in Brazil from a bioecological perspective. At the microsystem level, the population is experiencing different levels of stress and fear; at the mesosystem level, changes in routines, separation from family and friends, and closure of schools; and at the macrosystem level, national guidelines to control the pandemic, institutional standards on a national and international scale. Therefore, the main focus for the success of school return must be in the prevention of contagion and with physical and psychological health, and should not only consider the demands of curricula, financial or administrative management. For this reason, it is paramount that greater female representativeness is increased in decision-making levels of the meso and macrosystem, regarding the resumption of school and academic activities in the pandemic period, since the number of female leaders in decision-making, is still insufficient.

The COVID-19 pandemic has presented the world with increased challenges. The response to this pandemic has led to a sudden disruption of routine medical and elective surgical care. Most hospitals across the globe have had to change the way outpatient clinics are carried out and postpone non-urgent elective surgical procedures. NHS England ceased all elective general surgeries to train and re-deploy their staff to support the increased pressures from COVID-19 in an intensive care setting. However, with a decline of reported cases and deaths, the return to undertaking non-urgent elective services is imminent. In May 2020, Radha and Afzal published the first evidence-based guidelines for the resumption of elective orthopaedic services titled “Evidence based suggestions for the return to elective orthopaedic surgery following the COVID-19 Pandemic”. The pathway presented is adapted from the “Evidence based suggestions for the return to elective orthopaedic surgery following the COVID-19 Pandemic” and could potentially be used as a model for other surgical specialities. We present a three-phased return back to urological services. Safe resumption of elective care is possible but needs to be carefully planned.

Most large fibers in central nervous system of vertebrates are decussated. The cause or the evolutionary force of this phenomenon is not convincingly described. Here we show a pattern for this nervous system property that simultaneously is found to a more basic rule in evolution.The idea here is the "function to anatomy" theorem. We claim that functions of physical, biochemical, enzymatic, etc., in lower scale of living organisms "emerge" to anatomy in larger scales. And reversely, the anatomy we see in multicelular organisms are/were functions in microscopic scales.We propose descriptions, predictions, and a probable road map to what this can implicate in biological and medical issues.

In 2014, the outbreak of adenoviral pneumonia occurred in Korean military training center. However, there is limited data on characteristics of fever and its response to antipyretics therapy in immunocompetent adults with adenoviral positive community-acquired pneumonia (CAP). Medical records of patients who were admitted to Armed Forces Chuncheon Hospital for treatment of CAP between January 2014 and December 2016 were retrospectively analyzed. We evaluated demographics, clinico-laboratory findings and radiologic findings at admission were compared between adenovirus positive (Adv) group and adenovirus negative (non-Adv) group. Out of 251 military personnel with CAP during the study periods, 67 were classified into Adv group while 184 were Non-Adv group. Patients with Adv group had a longer duration of fever after admission and symptom onset. Adv group patients had a higher mean temperature at admission and more observed over 40 and 39 to 40℃. Adv group patients had more commonly observed no response to antipyretic treatment and adverse events after antipyretics use. Length of hospital stay had no significant difference between two groups and no patient died in both groups. In our study, Adv positive CAP in patients with immunocompetent military personnel had distinct characteristics of fever and response to antipyretic treatment.

An understanding of the cultural conditions that determine the factors affecting nurses’ intention to leave is important for countries suffering from nurse shortage. Aim: to examine factors influencing intention to leave among female hospital nurses in a large Japanese sample, classified into four generations by age considering economic conditions. Methods: a cross-sectional survey with convenience sampling was conducted. Anonymous self-administered questionnaires were distributed to all nurses in 30 hospitals. To assess intention to leave, basic attributes, life conditions, work characteristics, and factors of psychosocial work environment were addressed. After classifying data into four generations based on age cohorts, we conducted multivariate logistic regression analysis using the completed data (N = 5,074, mean age = 36.24). Results: regardless of generational characteristics influenced by economic conditions, effort and monetary reward were generation-common factors. Over-commitment, social support, and the presence of a role model were generation-common factors in three generations. While having children increased intention to leave in the generation born 1965–1979, having family members in need of caregiving other than children decreased the risk in the generation born in the 1980s. Conclusion: generational countermeasures considering factors of psychosocial work environment and life conditions are needed to avert female nurse turnover.

Microaggressions are subtle verbal and non-verbal slights based on group membership, and they are ubiquitous in the lives of racial minorities, women, and LGBTQ individuals (Sue, 2010). The goal of the current paper is to introduce a role-playing based exercise on effective responses to microaggressions. The workshop draws on the prejudice responding workshops of Plous (2000) and Lawson, et al. (2010) but integrates research-based strategies. The activity was tested in two groups of undergraduate students, and the findings suggested that both groups felt more prepared to deal with microaggressions after participating.

Monochromatic documents claim for much less computer bandwidth for network transmission and storage space than their color or even grayscale equivalent. The binarization of historical documents is far more complex than recent ones as paper aging, color, texture, translucidity, stains, back-to-front interference, kind and color of ink used in handwritting, printing process, digitalization process, etc. are some of the factors that affect binarization. This article presents a new binarization algorithm for historical documents. The new global filter proposed is performed in four steps: filtering the image using a bilateral filter, splitting image into the RGB components, decision-making for each RGB channel based on an adaptive binarization method inspired by Otsu's method with a choice of the threshold level, and classification of the binarized images to decide which of the RGB components best preserved the document information in the foreground. The quantitative and qualitative assessment made with 21 binarization algorithms in three sets of “real world” documents showed very good results.

HER2/neu positive breast tumors predict a high mortality and comprise 25-30% of breast cancer. We have shown that Flavokawain A (FKA) preferentially reduces the viabilities of HER2 overexpressing breast cancer cell lines (i.e. SKBR3 and MCF7/HER2) versus those with less HER2 expression (i.e. MCF7 and MDA-MB-468). FKA at cytotoxic concentrations to breast cancer cell lines also has minimal effect on the growth of non-malignant breast epithelial MCF10 cells. FKA induces G2M arrest in cell cycle progression of HER2 overexpressing breast cancer cell lines through inhibition of Cdc2 and Cdc25C phosphorylation and down-regulation of Myt1 and Wee1expression leading to increased Cdc2 kinase activities. In addition, FKA induces apoptosis in SKBR3 cells by increasing the protein expression of Bim and BAX and decreasing expression of Bcl₂, Bcl_x/L , XIAP and survivin. FKA also down-regulates the protein expression of HER-2 and inhibits AKT phosphorylation. Herceptin plus FKA treatment leads to enhanced growth inhibitory effect on HER-2 overexpressing breast cancer cell lines through down-regulation of Myt1, Wee1, Skp2, Survivin and XIAP. Our results suggest the promise of FKA as a novel apoptosis inducer and G2 checkpoint abrogating agent in combination with Herceptin for treatment of HER2 overexpressing breast cancer.

Neutrophil to lymphocyte ratio (NLR) is a promising predictive and prognostic factor in breast cancer. We investigated its ability to predict disease-free survival (DFS) and overall survival (OS) in patients with luminal A or luminal B-HER2-negative breast cancer who received neoadjuvant chemotherapy (NACT). Pre-treatment complete blood cell counts from 168 consecutive patients with luminal breast cancer were evaluated to assess NLR. The study population was stratified into NLRlow or NLRhigh according to a cut-off value established by receiving operator curve (ROC) analysis. Data on additional pre- and post-treatment clinical-pathological characteristics were also collected. Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models were used for statistical analyses. Patients with pre-treatment NLRlow showed a significantly shorter DFS (HR 6.97, 95% CI 1.65-10.55, p= 0.002) and OS (HR 7.79, 95% CI 1.25-15.07, p= 0.021) compared to those with NLRhigh. Non-ductal histology, luminal B subtype, and post-treatment Ki67≥ 14% were also associated with worse DFS (p= 0.016, p= 0.002, and p= 0.001, respectively). In multivariate analysis, luminal B subtype, post-treatment Ki67≥ 14%, and NLRlow remained independent prognostic factors for DFS, while only post-treatment Ki67≥ 14% and NLRlow affected OS. The present study provides evidence that pre-treatment NLRlow helps identify women at higher risk of recurrence and death among patients affected by luminal breast cancer treated with NACT.

With the unceasing advancement in wide-bandgap (WBG) semiconductor technology, the minimal reverse-recovery charge Qrr and other more powerful natures of WBG transistors enable totem-pole bridgeless PFC to become a dominant solution for energy storage systems (ESS). This paper focuses on design and implementation of a control structure for a totem-pole boost PFC with newfangled enhancement-mode Gallium Nitride (eGaN) FETs, not only to simplify the control implementation, but also to achieve high power quality and efficiency. The converter is designed to convert a 90-264-VAC input to a 385-VDC output for a 2.6-kW output power. Lastly, to validate the methodology, an experimental prototype is characterized and fabricated. The uttermost efficiency at 230 VAC attains 99.14%. The lowest total harmonic distortion in the current (ITHD) at high line condition (230 V) reaches 1.52% while the power factor gains 0.9985.

Chromosome analysis (CA) and chromosomal microarray analysis (CMA) have been successfully used to diagnose genetic disorders. However, many conditions remain undiagnosed due to limitations in resolution (CA) and detection of only unbalanced events (CMA). Optical genome mapping (OGM) has the potential to address these limitations by capturing both structural variants (SVs) resulting in copy number changes and balanced rearrangements with high resolution. In this study, we investigated OGM’s concordance using 87 SVs previously identified by CA, CMA, or Southern blot. Overall, OGM was 98% concordant with only three discordant cases: (1) uncalled translocation with one breakpoint in a centromere; (2) uncalled duplication with breakpoints in the pseudoautosomal region 1; and (3) uncalled mosaic triplication originating from a marker chromosome. OGM provided diagnosis for three previously unsolved cases: (1) disruption of the SON gene due to a balanced reciprocal translocation; (2) disruption of NBEA gene due to an inverted insertion; (3) disruption of the TSC2 gene due to a mosaic deletion. We show that OGM is a valid method for detection of many types of SVs in a single assay and is highly concordant with legacy cytogenomic methods; however, it has limited SV detection capabilities in centromeric and pseudoautosomal regions.

The migration from MATLAB to Python (M-to-PY) has gained significant traction in recent computational research. While MATLAB has long served as a linchpin in myriad scientific endeavors, there's an emerging trend to rejuvenate these projects using Python's extensive AI tools and libraries. This study presents a semi-automated process for M-to-PY conversion, using a detailed case study of an image skeletonization project comprising fifteen MATLAB files and a 1404-image dataset. Skeletonization is foundational for ongoing 3D motion detection research using AI transformers, predominantly developed in Python. The utilization of ChatGPT-4, acting as an AI co-programmer, is pivotal in this conversion. By leveraging the public OpenAI API, we developed an M-to-PY converter prototype, evaluated its efficacy using test cases from the Bard bot, and subsequently employed the converted code in an AI application. The dual contributions encompass a well-tested M-to-PY converter and a Skeleton App capable of sketching and skeletonizing any given image, enriching the AI toolset. This study accentuates how AI resources, like ChatGPT-4, can simplify code transitions, opening doors for innovative AI implementations using primarily MATLAB-coded scientific research.

Waterbomb structures are origami-inspired deformable structural components used in new types of robots. They have a unique radially deployable ability that enables robots to better adapt to their environment. In this paper, we propose a series of new waterbomb structures with square, rectangle, and parallelogram base units. Through quasi-static axial and radial compression experiments and numerical simulations, we prove that the parallelogram waterbomb structure has a twist displacement mode along the axial direction. Compared with the square waterbomb structure, the proposed optimal design of the parallelogram waterbomb structure reduces the critical axial buckling load-to-weight ratio by 55.4% and increases the radial stiffness-to-weight ratio by 67.6%. The significant increase in the radial stiffness-to-weight ratio of the waterbomb structure and decrease in the critical axial buckling load-to-weight ratio make the proposed origami pattern attractive for practical robotics applications.

The world has been highly impacted by the COVID-19 as the virus has spread to all continents – about 200 countries in total. The latest update claims about 4,000,000 confirmed cases and about 300,000 confirmed deaths owing to the COVID-19 pandemic. This probably makes the COVID-19 as the most dangerous contagious disease in the era 2000s. Apart from massive publications on this topic, there is no available qualitative analysis that describes the dynamic spreads of the COVID-19 and its impacts on healthcare and the economy. Through the system archetypes analysis, this paper explains that the dynamic spread of the COVID-19 consists of the limits to growth and the success to successful structures. The limits to growth elucidates that more symptomatic and asymptomatic patients owing to infected droplets may be bounded by self-healing and isolated treatments. The success to successful structure explains that once the COVID-19 affects the economy through the lockdown, there will be a limited fund to support the government aids and the aggregate demand. In overall, this paper gives readers simplified holistic insights into understanding the dynamic spread of the COVID-19.

Background Telomere shortening is related to aging and unfavourable health outcomes. Obesity and metabolic diseases are important factors for accelerating aging. This study aimed to find out the association between obesity, metabolic disease, and telomere length in metabolically healthy adults. Methods 237 adults were enrolled with written consents at a health promotion centre of a tertiary hospital from February 2014 to March 2015. After excluding 99 subjects who met the exclusion criterion, a total of 130 metabolically healthy subjects were selected for final analysis. The subjects were divided into quartile groups according to the telomere lengths of their oral mucosal cells. Results The subjects consisted of 66 (50.8%) males with a mean age of 58.59 years. The body mass index (BMI, kg/m2) increased significantly along with the quartile groups (Q1, 23.00; Q2, 23.96; Q3, 23.70; Q4, 25.20; P-for trend=0.008). Waist circumference (WC, P-for trend=0.022), waist-to-hip ratio (WHR, P-for trend=0.005), and waist-to-height ratio (WHtR, P=0.001) also increased along with the quartile groups. Obesity prevalence (BMI ≥25 kg/m2), abdominal obesity (WC ≥90 cm for men, ≥85 cm for women), WHR 〉1.0 for men or 〉0.85 for women, and WHtR ≥0.5 increased significantly as the telomere length increased (P-for trend <0.05). After adjusting for covariates, the ORs for each obesity markers increased as the telomere length increased (P-for trend <0.05); and the ORs of WHtR were especially meaningful (Q1, 1.00; Q2, 2.53; Q3, 2.97; Q4, 7.81; P-for trend = 0.001). There were no significant trends for metabolic syndrome and its components along with the prevalence of fatty liver disease. Conclusion Obesity markers and telomere length had significant positive correlation despite the established theory. The obesity paradox may exist in metabolically healthy adults with regard to telomere length, However, further studies with larger sample sizes for the association between obesity and telomere length are needed.

Background: The risk to physicians who worked with patients without confirmed COVID-19 testing during the pandemic has been little studied. However, they were at high risk. Methods: A total of 1285 Romanian physicians completed an online survey. We performed Mann-Whitney comparisons between physicians who reported that they knowingly had direct contact with COVID patients and those who didn't regarding their willingness to work. Results: Compared with their colleagues, physicians who reported not knowingly having direct contact with COVID patients reported less access to protective equipment, less overall willingness to respond when asked to work with infected patients, more likely to work out of fear of losing their jobs, and fear of legal repercussions. They received less training in the use of protective equipment. Conclusions: Physicians who worked with patients not yet diagnosed with COVID-19 were significantly less willing to work. The perception of invisible risk may explain the observed differences.

The challenge of accessing finance by entrepreneurs from traditional financial sources is pervasive. The COVID-19 pandemic further exacerbated the problem of limited access to finance from banks. Against this backdrop, the objective of the study was to determine the factors driving crowdfunding success during the COVID-19 pandemic in Africa. The ordinary least squares (OLS) and probit regression models were estimated to analyse 216 crowdfunding projects in Africa. The results of the study documented that targeted amount (TA), and COVID-19 pandemic were negative and significant drivers of crowdfunding success. Furthermore, comments (CMM) and duration (DRN) were negative and significantly affected crowdfunding success. Conversely, images (IM), videos (VD), backers (BCK), and updates (UPD) were positive and significantly affected crowdfunding success. The study contributes to the body knowledge by investigating the drivers of crowdfunding success during the COVID-19 pandemic period which hitherto had not been researched on extenisvely.

Background: Smart transport plays a crucial role in urban planning and the transition from traditional to smart cities in developing countries with sustainability requirements.Traditional cities in developing countries often suffer from traffic congestion,air pollution, and inadequate public transportation systems,which can impede economic growth and negatively impact the quality of life for residents. Smart transport solutions can address these challenges by providing more efficient, sustainable.Here is a possible business model for an ITS system in a high-potential city in Iran,Based on IoT analysis, Mashhad city in Iran selected as a high-potential city to be changed to a smart city in the transportation sector.In the localization business model,the Uber smart transportation business model as a successful world experience is considered the base model. Methods: Based on the literature review,various criteria and sub-criteria were identified and determined in designing a new localized transportation business model.A questionnaire was prepared and filled with the help of 11 experts,method IAHP technique; Results:The present study showed the possibility of monthly payments for customers,software development, and the addition of luxury cars are among the most important sub-criteria with high weights;Conclusions: Working with transport companies,schools and universities as key partners solves reaching a strong and sustainable smart transportation system.

We aimed to explore symptoms severity and adherence to therapy for patients with myelofibrosis treated with ruxolitinib in Bulgaria. It is a prospective, non-interventional study performed at the Specialized hospital for active treatment of hematological diseases in Sofia during 2022 - 2023. Date of diagnosis, demographic characteristics, clinical indicators, ruxolitinib dose, and other data points were collected. Clinical indicators were assessed at baseline, in the middle and at the end of observation. Severity of symptoms was measured with MPN-SAF TSS and adherence to therapy with the Morisky 4 questionnaire 6 times during the observation. The mean age of diagnosis was 58.5 years, with the average duration of disease of 3 years. Pa-tients’ laboratory results were within physiological ranges, with spleen size experiencing a con-stant decrease. The average value for the severity of the symptoms per MPN-SAF TSS results decreased significantly, indicating better disease control. The average adherence to therapy did not change and remained high at around 9 points, except for one patient. In conclusion the treatment of myelofibrosis patients with ruxolitinib decreased symptoms se-verity and spleen size. Patients were adherent to the therapy over the observed period but as treatment duration increases the risk of adherence decreasing.

Recent advances in deep learning technology have led to increased interest in text-to-image technology, which enables computers to create images from text by simulating the human process of forming mental images. The GAN-based text-to-image technology involves the extraction of features from input text, which are combined with noise and then used as input to a GAN that generates images that are similar to the original images through competition between the generator and discriminator. Although generating images from English text is a mature area of research, text-to-image technology based on multilingualism, such as Korean, is still in its early stages of development. Webtoon is a digital comic format that allows comics to be viewed online. The creation process for webtoons is divided into story planning, content/sketching, coloring, and background drawing. Since each stage of webtoon production requires human intervention, it is both time-consuming and expensive. As a result, deep learning technologies such as automatic coloring and automatic line drawing are being used to reduce human involvement. However, there is a shortage of technology that can assist authors with story creation in webtoon production. Therefore, this study proposes a multilingual text-to-image model capable of generating webtoon images when presented with multilingual input text. The proposed model employs Multilingual BERT to extract feature vectors for multiple languages, and trains a DCGAN in conjunction with the images. The experimental results demonstrate that the model can generate images that are similar to the original images when presented with multilingual input text after training.