Fusarium circinatum is an important global pathogen of pine trees. Genome plasticity has been observed in different isolates of the fungus, but no genome comparisons are available. To address this gap, we sequenced and assembled to chromosome level five isolates of F. circinatum. These genomes were analysed together with previously published genomes of F. circinatum isolates FSP34 and KS17. Multi-sample variant calling identified a total of 461683 micro variants (SNPs and small indels) and a total of 1828 macro structural variants of which 1717 were copy number variants and 111 were inversions. Variant density was higher on sub-telomeric regions of chromosomes. Variant annotation revealed that genes involved in transcription, transport, metabolism and transmembrane proteins were overrepresented in gene sets affected by high impact variants. A core genome representing genomic elements conserved in all the isolates and a non-redundant pangenome representing all genomic elements is presented. Whole genome alignments showed that an average of 93% of the genomic elements are present in all isolates. The results of this study reveal that some genomic elements are not conserved within the isolates and some variants are high impact. The described genome-scale variations will help inform novel disease management strategies against the pathogen.

Understanding the role of risk regions identified by genome-wide association studies (GWAS) have made considerable progress lately referred to the post-GWAS era. Annotation of the genes to the GWAS and fine-mapped functional variants, and understanding their biological pathway/gene networks enrichments is expected to give rich dividend by elucidating the mechanisms underlying prostate cancer. To this aim, we compiled and analysed currently available post-GWAS data on genes identified through GWAS and validated through experimental studies in prostate cancer to investigate molecular biological pathways enriched for assigned functional genes. The results highlight some well-known cancer signalling pathways, antigen presentation process and enrichment in cell growth and development gene networks suggesting prostate cancer may result from the accumulation of the effects of functional variants through multiple gene sets and pathways. The upstream analysis identifies critical transcription factors, which supplements the results regarding the regulatory role of the post-GWAS genes. We also identified the common genes between post-GWAS and three well-annotated prostate cancer Oncomine data in patient samples in order to uncover possible main genes in prostate cancer development/progression. Post-GWAS generated knowledge of gene networks and pathways, if analysed further and targeted appropriately, will have an important impact on clinical management of the disease.

The meticulous study of finite automata has produced many important and useful results. Automata are simple yet efficient finite state machines that can be utilized in a plethora of situations. It comes, therefore, as no surprise that they have been used in classic game theory in order to model players and their actions. Game theory has recently been influenced by ideas from the field of quantum computation. As a result, quantum versions of classic games have already been introduced and studied. The PQ penny flip game is a famous quantum game introduced by Meyer in 1999. In this paper we investigate all possible finite games that can be played between the two players Q and Picard of the original PQ game. For this purpose we establish a rigorous connection between finite automata and the PQ game along with all its possible variations. Starting from the automaton that corresponds to the original game, we construct more elaborate automata for certain extensions of the game, before finally presenting a semiautomaton that captures the intrinsic behavior of all possible variants of the PQ game. What this means is that from the semiautomaton in question, by setting appropriate initial and accepting states, one can construct deterministic automata able to capture every possible finite game that can be played between the two players Q and Picard. Moreover, we introduce the new concepts of a winning automaton and complete automaton for either player.

In this study, the effects of combined addition of CeLa and GdY on microstructure and mechanical properties of as-cast Al-4Cu-1Mn alloys were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopies (TEM) and tensile testing. The results show that the minor addition of CeLa and GdY leads to the refinement of grain size. The addition of CeLa results in the formation of supersaturated vacancies in the Al matrix, whereas the addition of GdY leads to a decrease in the precipitation temperature of the Al2Cu phase. The combined CeLa and GdY addition can significantly increase ultimate tensile strength (UTS) while losing only a small amount of elongation (EL). Compared with the unmodified alloy, the grain size and SDAS of the alloy (0.2 wt% CeLa + 0.1 wt% GdY) were diminished by 67.2% and 58.7%, respectively, while maximum hardness and UTS rose by 31.2% and 36.9%, correspondingly.

In this paper, Fe-Cr-C-N-Al-Y wear-resistant surfacing alloy was prepared by open arc surfacing with self-shielded flux-cored wire. The wear properties of the surfacing alloy were analyzed by MLS-23 rubber wheel wet sand wear tester. The phase composition and microstructure of the surfacing alloy were analyzed by XRD, SEM, EBSD and TEM, and the strengthening mechanism and wear mechanism of the alloy were discussed. The results show that the microstructure of Fe-Cr-C-N-Al-Y surfacing alloy is composed of M + γ-Fe + M7C3 + AlN. When the content of nano-Y2O3 is 0.456wt. %, the formability of the surfacing alloy is the best and the wetting angle is the smallest, which is 50.8°, AlN and M7C3 precipitate the most, and the microstructure grain is the smallest. At this time, the hardness value of the surfacing alloy is up to 62.3 HRC, which is 11.8 % higher than that of the unmodified surfacing alloy. The minimum wear weight loss is 0.125 g, and the wear resistance is increased by 41.86 %. The wear mechanism of surfacing alloy is mainly plastic deformation mechanism, and the material removal process is micro cutting and furrow wear.

Salvia ceratophylloides (Ard.) is an endemic, rare, threatened plant species recently rediscovered in very few individuals in two different sites of South Italy. The study of within-plant variation more than among-plant one is fundamental to understand the plant adaptation to the local conditions, especially in rare species, and consequently to preserve plant biodiversity. Here, we reported the variation of the morpho-ecophysiological and metabolic traits between the sessile and petiolate leaf of S. ceratophylloides plants in two different sites for understanding the adaptation strategies for surviving in these habitats. The S. ceratophylloides individuals exhibited different net photosynthetic rate, maximum quantum yield, light intensity for the saturation of the photosynthetic machinery, stomatal conductance, transpiration rate, leaf area, fractal dimension and some VOCs between the different leaf types. This within-plant morpho-physiological and metabolic variation was depended on the site. These results provide empirical evidence of sharply within-plant variation of the morpho-physiological traits and VOCs profiles in S. ceratophylloides which could be because of adaptation to the local conditions.

Searching for neutrinoless double beta decay is a top priority in particle and astroparticle physics, being the most sensitive test of lepton number violation and the only suitable process to probe the Majorana nature of neutrinos. In order to increase the experimental sensitivity for this particular search, ton-scale detectors operated at nearly zero-background conditions with a few keV energy resolution are required. In this scenario, cryogenic detectors have proven effective in addressing many of these issues simultaneously. After long technical developments, the CUORE experiment established the possibility to operate large scale detectors based on this technology. Parallel studies pointed out that scintillating cryogenic detectors represent a suitable upgrade for the CUORE design, directed towards higher sensitivities. In this work, we review the recent development of cryogenic detectors, starting from the status of the art and outlying the path toward next-generation experiments.

In recent years, tremendous progress has been made in the development of rare-earth ion doped tellurite glass laser sources, ranging from watt and multiwatt level fiber lasers to nanowatt level microsphere lasers. Significant success has been achieved in extending the spectral range of tellurite fiber lasers generating at wavelengths beyond 2 μm as well as in theoretical understanding. This review is aimed at discussing the state of the art of neodymium-, erbium-, thulium-, and holmium-doped tellurite glass fiber and microsphere lasers.

Pyrochlore group minerals are the main raw phases in granitic rocks of the Katugin complex-ore deposit that stores Nb, Ta, Y, REE, U, Th, Zr, and cryolite. They are of three main generations: primary magmatic (I), early postmagmatic (II), and supergene (III) pyrochlores. The primary magmatic phase (generation I) is fluornatropyrochlore with high concentrations of Na2O (to 10.5 wt.%), F (to 5.4 wt.%) and REE2O3 (to 17.1 wt.%) but low CaO (0.6-4.3 wt.%), UO2 (to 2.6 wt.%), ThO2 (to 1.8 wt.%), and PbO (to 1.4 wt.%). Pyrochlore of this type is very rare in nature and limited to a few occurrences, such as rare-metal deposits of Nechalacho in syenite and nepheline syenite (Canada) and Mariupol in nepheline syenite (Ukraine). It may have crystallized synchronously with or slightly later than melanocratic minerals (aegirine, biotite, and arfvedsonite) at the late magmatic stage when Fe from the melt became bound making impossible the formation of columbite. Second generation pyrochlore formed at the early postmagmatic stage of the Katugin deposit. It differs from that of first generation in lower Na2O concentrations (2.8 wt.%), relatively low F (4 wt.%), and les occupancy of the A and Y sites at similar contents of other components. Generation III pyrochlore is a product of supergene alteration processes. It is compositionally heterogeneous and contains K, Ba, Pb, Fe, and significant Si concentrations but low Na and F. Its compositions mostly fall within the filed of hydro- and kenopyrochlore.

The separation and enrichment can be targeted to enrich the rare and precious metals in fly ash and reduce the cost of leaching and recovering of fly ash. Regarding their different properties, the single-component separation was used to obtain uncompleted burned carbon, glass microbeads, minerals, and other characteristic components from the ash. Also, the mineral composition of each component was analyzed by electron microscopy. The metal minerals were mainly concentrated in the mineral components. Besides, the electron probe micro-analysis shows that the Pt content in the minerals of fly ash was significantly correlated with the metal contents of Ni and Cu. After the obtainment of the characteristics of fly ash metal enrichment, the heavy minerals with Cu, Ni, Pt, Pd, and other target metal elements were enriched by gravity separation and flotation. The enrichment coefficients of Cu, Ni, Pt, and Pd were 1.45, 1.33, 1.90 and 1.60, respectively, and the recovery rates were 77%, 81%, 97% and 88% respectively. Since the yield of heavy minerals obtained by separation was 62.24%, it indicated the physical separation method could significantly reduce the cost of leaching and recovering of fly ash metal resources.

Modeling and design of fiber lasers facilitate the process of their practical realization. Of particular interest during the last few years is the development of lanthanide ion-doped fiber lasers which operate at wavelengths exceeding 2000 nm. There are two main host glass materials considered for this purpose, namely fluoride and chalcogenide glasses. Therefore, this study concerns comparative modeling of fiber lasers operating within the infrared wavelength region beyond 2000 nm. In particular, the convergence properties of selected algorithms, implemented within various software environments, are studied with a specific focus on the central processing unit (CPU) time and calculation residual. Two representative fiber laser cavities are considered: one is based on a chalcogenide-selenide glass step-index fiber doped with trivalent dysprosium ions whilst the other is a fluoride step-index fiber doped with trivalent erbium ions. The practical calculation accuracy is also assessed by comparing directly the results obtained from the different models.

As SARS-CoV-2 continues to spread among human populations, genetic changes occur and accumulate in the circulating virus. Some of these genetic changes have caused amino acid mutations, including deletions, which may have potential impact on critical SARS-CoV-2 countermeasures, including vaccines, therapeutics, and diagnostics. Considerable efforts have been made to categorize the amino acid mutations of the angiotensin-converting enzyme 2 (ACE2) receptor binding domain (RBD) of the spike (S) protein along with certain mutations in other regions within the S protein as specific variants in an attempt to study the relationship between these mutations and the biological behavior of the virus. However, the currently used whole genome sequencing surveillance technologies can test only a small fraction of the positive specimens with high viral loads and often generate uncertainties in nucleic acid sequencing that needs additional verification for precision determination of mutations. This article introduces a generic protocol to routinely sequence a 437-bp nested RT-PCR cDNA amplicon of the ACE2 RBD and a 490-bp nested RT-PCR cDNA amplicon of the N-terminal domain (NTD) of the S gene for detection of the amino acid mutations needed for accurate determination of all variants of concern and variants of interest according to the definitions published by the U.S. Centers for Disease Control and Prevention. This protocol was able to amplify both nucleic acid targets into cDNA amplicons to be used as templates for Sanger sequencing on all 16 clinical specimens that were positive for SARS-CoV-2.

Morphological and phylogenetic (45S nrDNA+RPB1 gene) analyses of three glomoid spore-producing arbuscular mycorrhizal fungi revealed the presence of two new species be-longing to the genus Glomus in the family Glomeraceae. In the field, Glomus highlandensis sp. nov. was found in a saltmarsh of the Scottish Highlands and in maritime sand dunes of the Baltic Sea in Poland, both saline environments, while G. mongioie sp. nov. originates from the Italian Alps. Phylogenetic placement analysis using environmental sequences indicated that G. highlandensis could have likely worldwide distribution while G. mongioie seems to be a rare species in the world. The molecular and phylogenetic analysis provided important insights about the presence of ribosomal variants in Glomus, with potential negative implication in phylogeny and species recognition.

SOX proteins are transcription factors which play a role in regulating the development of pro-genitor cells and tissue differentiation. Twenty members are known, clustered in eight groups named A to H, and sharing a common DNA-binding domain called the HMG (high-mobility-group) box. Eleven of the SOX genes have been associated with genetic disorders so far, covering a broad spectrum of developmental diseases. SOX4 is a single-exon gene and belongs to the SOXC group together with SOX11 and SOX12. SOX4 variants were recently described to cause a highly penetrant but heterogeneous disorder, with a phenotypic spectrum ranging from mild developmental delay and learning difficulties to intellectual disability with congenital anomalies. Nineteen pathogenic variants were reported to date, generally de novo, heterozygous, and inactivating, either stop-gain or missense, the latter ones primarily targeting the HMG domain. Further, a bi-allelic variant was reported in a single consanguineous family. Copy number variants, leading to whole gene deletion or duplication, are rare and not clearly associated with a neurodevelopmental disorder. Many open questions remain, regarding the definition of variants of unknown significance, a possible role of missense variants outside the HMG domain, genotype-phenotype correlation, the range of phenotypic spectrum and modifying factors, and treatment options.

Some studies show that patients with mutations in the SNCA gene, which codifies for the alpha-synuclein protein, show a particular phenotype. The effects of SNCA Single Nucleotide Polymorphism (SNPs) in recently diagnosed, drug-naïve patients with PD have been less explored. Therefore, we set out to explore the differences in the clinical characteristics of recently diagnosed drug-naïve sporadic PD patients with or without SNCA rs3910105 or rs356181 SNPs. Patients with a clinical diagnosis of PD in the Parkinson’s Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data, dementia, psychiatric conditions, a diagnosis change over the first five years from the initial PD diagnosis, or with a familial history of PD. Subjects were evaluated with the MDS-Unified PD Rating Scale (MDS-UPDRS), DAT imaging, the Geriatric Depression Scale (GDS), the State-Trait Anxiety Inventory (STAI), the Montreal Cognitive Assessment (MoCA), the SCOPA-AUT for autonomic function, the Epworth Sleepiness Scale (ESS), the RBD Questionnaire, and the University of Pennsylvania Smell Identification Test (UPSIT). We included 308 PD patients fulfilling all inclusion and exclusion criteria. A logistic regression analysis and Machine-Learning models did not disclose any difference between patients either with or without the SNCA rs3910105 SNP or with or without the SNCA rs3910105 polymorphism. Our results suggest that the SNCA polymorphisms rs3910105 and rs356181 have no impact on the phenotype of idiopathic, sporadic, recently diagnosed, drug naïve PD patients.

Natural herbs and functional foods contain bioactive molecules capable of augmenting the immune system and mediating anti-viral functions. Functional foods, such as prebiotics, probiotics, and dietary fibers, have been shown to have positive effects on gut microbiota diversity and immune function. The use of functional foods has been linked with en-hanced immunity, regeneration, improved cognitive function, maintenance of gut mi-crobiota, and significant improvement in overall health. The gut microbiota plays a critical role in maintaining overall health and immune function, and disruptions to its balance have been linked to various health problems. SARS-CoV-2 infection has been shown to affect gut microbiota diversity, and the emergence of variants poses new challenges to combat the virus. SARS-CoV-2 recognizes and infects human cells through ACE2 receptors prevalent in lung and gut epithelial cells. Humans are prone to SARS-CoV-2 infection because the respiratory and gastrointestinal tracts are rich in microbial diversity and contain high ACE2 and TMPRSS2. This review article explores the potential use of functional foods in mitigating the impact of SARS-CoV-2 variants on gut microbiota diversity and the potential use of functional foods as a strategy to combat these effects.

Abstract: Infectious bronchitis virus (IBV) induces respiratory and urogenital disease in chickens. Although IBV replicates in the gastrointestinal tract, enteric lesions are uncommon. We have reported a case of runting-stunting syndrome in commercial broilers from which an IBV variant was isolated from the intestines. The isolate, CalEnt, demonstrated an enteric tissue tropism in chicken embryos and SPF chickens experimentally. Here, we determined the full genome of CalEnt and compared it to other IBV strains, in addition to comparing the pathobiology of CalEnt and M41 in commercial broilers. Despite the high whole-genome identity to other IBV strains, CalEnt is rather unique in nucleotide composition. The S gene phylogenetic analyses showed great similarity between CalEnt and Cal 99. Clinically, vent staining was slightly more frequent in CalEnt-infected birds than those challenged with M41. Furthermore, IBV IHC detection was more evident and the viral shedding in feces was overall higher with the CalEnt challenge compared with M41. Despite underlying intestinal lesions caused by coccidiosis and salmonellosis vaccination, microscopic lesions in CalEnt-infected chickens were more severe than in M41-infected chickens or controls, supporting the enteric tropism of CalEnt. Further studies in SPF chickens are needed to determine the pathogenesis of the virus, its molecular mechanisms for the enteric tropism, and its influence in intestinal health.

A signal analysis of the genoma sequenced of coronavirus variants: B.1.1.7, B.1.135, B.1.429-B.1.427, B.1.525 and P1 is presented. We deal with a certain type of finite alternating sum series having independently distributed terms associated with binary (0,1) indicators for the nucleotide bases A,C,G,T. This method provides additional information to conventional Similarity comparisons and Power Spectrum approaches. It leads to uncover distinctive patterns regarding the intrinsic data organization of genomic sequences according to its progression along the nucleotide bases position. Hence, the method could be useful for survelliance of genoma variants.

Germline mutations in predisposition genes account for only 20% of all familial colorectal cancer (CRC) and the remaining genetic burden may be due to rare high-to-moderate-penetrance germline variants that are not explored. With the aim of identifying such potential cancer predisposing variants, we performed whole exome sequencing on three CRC cases and three unaffected members of a Polish family and identified two novel heterozygous variants; a coding variant in APC down-regulated 1 gene (APCDD1, p.R299H) and a non-coding variant in the 5’ untranslated region (UTR) of histone deacetylase 5 gene (HDAC5). Sanger sequencing confirmed the variants segregating with the disease and Taqman assays revealed 8 additional APCDD1 variants in a cohort of 1705 familial CRC patients and no further HDAC5 variants. Proliferation assays indicated an insignificant proliferative impact for the APCDD1 variant. Luciferase reporter assays using the HDAC5 variant resulted in an enhanced promoter activity. Targeting of transcription factor binding sites of SNAI-2 and TCF4 interrupted by HDAC5 variant showed a significant impact of TCF4 on promoter activity of mutated HDAC5. Our findings contribute not only to the identification of unrecognized genetic causes of familial CRC but also underline the importance of 5´UTR variants affecting transcriptional regulation and the pathogenesis of complex disorders.

New insights into the causes and mechanisms of congenital heart disease (CHD) have been gained through the use of next-generation sequencing. Examination of the whole exome sequence detects detrimental gene variations modifying single or contiguous nucleotides, that are characterised as pathogenicity based on statistical assessments of families. and correlates with congenital heart disease, elevated expression during heart development, and reduction of harmful protein-coding mutations in the general population. Patients with CHD and extracardiac abnormalities enriched for gene classes meeting these criteria. CHDs and extracardiac defects, supporting a common set of pathways in the organogenesis of CHDs. Single-cell transcriptomics data reveal the expression of genes associated with CHD in specific cell lineages, and emerging evidence suggests that genetic variants disrupt multicellular genes essential for cardiogenesis. Metrics and units are being tracked in whole genome sequence studies.

Background: Modulator therapies improve weight and body mass index (BMI) in cystic fibrosis (CF) patients. We aimed to compare the nutritional risk index (NRI) in adult CF patients receiving modulator (MT) or only non-modulator (conventional) therapies (non-MT). Methods: A single-center prospective cohort study was conducted between June-December 2023. The NRI based on weight gain and albumin was calculated at beginning and end of a 12 weeks period in both groups. This design was pragmatic, since based on individual patient access to MT for 12 weeks. Results: 107 patients were included [mean (SD) age: 23.85 (4.98) years, 54.7% male, 46.7% MT]. In the MT group, mean (SD) weight (kg) and albumin (g/dL) increased significantly [changes: +3.09 (2.74) and +0.17 (0.37); p

The boosted interest in the use of rare earth elements (REEs) in modern technologies had also increase the necessity of their recovery from various sources, including raw materials and wastes. Though Hydrometallurgy plays a key role in these recovery processes, some drawbacks (apparent or not) of these processes, had led to the development of a more environmental friendship subclass named Solvometallurgy, in which non-aqueous solvents substituted to the aqueous media of the hydrometallurgical processing. The non-aqueous solvents chosen for these usages are, besides ionic liquids (ILs), the so-named Deep Eutectic Solvents (DEEs). The utilization of DEEs included the leaching of REEs from the different sources containing them, and also in the separation-purification steps necessary for the yielding of these elements, normally as oxides or salts, in the most purified form. This work reviewed the most recent literature (2023 year) about the utilization of deep eutectic solvents in the recovery of REEs from various sources, and in the coupling of these two (DESs and REEs) to derived compounds to be used in other fields.

In this study, the extraction of rare earth elements (REEs) from chloride solutions containing mixtures of these metals with solutions of the mixtures of P507 and Cyanex 272 (1:1) of various concentrations was experimentally studied. It was shown that the distribution coefficients of all REEs decrease with increasing concentration of these metals in the initial solution, which is associated with the loading of the organic phase. The most significant improvement in the extraction is observed for heavy group of rare earth elements. The extractability of REEs enhances with increasing atomic number of the element, as is typical for the extraction of these metals with acidic organophosphorus extractants. The data obtained show that separation factors of adjacent rare earth elements mainly decrease with increasing concentration of metals in the initial aqueous solution. Increasing the concentration of the extractant mixture does not have a significant effect on the values of the adjacent REE separation factors. Analysis of the experimental results shows that two commercial products can be obtained from a concentrate of the medium-heavy group. In the first cascade, yttrium can be separated, in the second, a concentrate of dysprosium and terbium can be obtained.

An laboratory procedure has been developed to obtain lanthanum oxide from spent fluid catalytic cracking catalyst, commonly used in the cracking the heavy crude oil process. Two different spent fluid catalytic cracking catalysts, which are mainly formed by silica and alumina, and a certain amount of rare earths were leached under several conditions to recover the rare earth from the solids waste. Subsequently, liquid phases were subjected to a liquid-liquid extraction process, and lanthanum was quantitatively stripped using oxalic acid to obtain the corresponding lanthanum oxalates. After the corresponding thermal treatment, these solids were transformed into lanthanum oxide. Both, lanthanum oxalates and oxides solids have been characterized by wide techniques in order to investigate the purity of the phases.

Emerging of mass-spectroscopy with inductively-coupled plasma (ICP-MS) made possible to study the microelement composition of crude oil and its derivatives (with the limit of detection at the ppt level). We have studied the crude oil composition of some West Siberian and Tatarstan oilfields with the ICP-MS method to detect 50 rare, rare-earth, and other microelements. The elemental composition is reasonably comparable to their concentrations in ultrabasites whereas the contents of most of the elements are low to the limit. On the diagrams of rare-earth elements, one can see the prevalence of light lanthanides and positive europium anomaly. The study shows that crude oils have a specific microelement composition that stands out from other geological systems.

Understanding clinical significance of variants of unknown significance (VUS) reported in next-generation sequencing (NGS) has become essential in cancer treatment. Our study examined six widely used in silico tools: PolyPhen-2, Align-GVGD, MutationTaster2, CADD, REVEL, and Chat-GPT. We utilized a dataset of gene variants known to potentially affect immune therapy. No single tool could comprehensively determine mutation variant pathogenicity. MutationTaster2021 showed the highest overall accuracy and MCC among the tools. Notably, REVEL and Chat-GPT exhibited 100% specificity, suggesting their proficiency in accurately identifying pathogenic variants and minimizing false positives. In contrast, CADD displayed optimal sensitivity, making it suitable for effectively ruling out benign variants.

To better understand anogenital warts (AGW) natural history and dynamic of HPV6/11 infection in regional hairs, 32 newly diagnosed AGW male patients and 32 age-matched healthy controls were closely followed. During enrollment and six follow-up visits (every 2.6 months) 43 AGW tissue and 1,232 anogenital and eyebrow hair samples were collected. This represents the closest longitudinal monitoring of AGW patients to date. Patients were treated according to standard-of-care. HPV6/11 prevalence was 19.9% in patients’ hair samples (HPV6 B1 in 87.5%) and 0% in controls. The highest HPV6/11 prevalence was found in pubic hairs (29.0%) and lowest in eyebrows (7.1%). Odds for HPV6/11-positive hairs increased with smoking, shaving anogenital region and age. A close association between HPV6/11 presence in hairs and clinically visible AGW was observed. The proportion of patients with visible AGW and HPV6/11-positive hairs declined during follow-up with similar trends. No particular HPV6/11 variant was linked with increased AGW recurrence, but sublineage HPV6 B1 showed significantly higher clearance from hairs. Despite treatment, 78.1% and 62.5% of AGW patients experienced one and two/more post-initial AGW episodes, respectively. Patients having HPV6/11-positive hairs or visible AGW at preceding visit demonstrated substantially higher odds for presenting with visible AGW in subsequent visit.

The COVID-19 pandemic has created unique challenges for people with comorbidities, including hereditary diseases and cancer cancers. Several studies have reported a link between the presence of disease-causing genetic variants and the outcome of the COVID-19 infection. In this study, we used clinical exome sequencing in a cohort of 840 COVID-19 patients to identify pathogenic and likely pathogenic genetic variants present in these individuals. While we did not identify any statistically significant differences in the overall burden of pathogenic variants between different patient groups, we discovered three known pathogenic alleles associated with hereditary cancer syndromes, including a frameshift mutation in MSH6 and two missense mutations in TP53. The patients carrying these mutations presented with different severity of the disease and outcome. Thus, a 58-year old male subject with an MSH6 mutation developed a severe form of COVID-19 that resulted in death, even though the patient had few pre-existing conditions and no evidence of malignant tumors. On the other hand, two female subjects carrying pathogenic TP53 variants successfully recovered from the disease despite suffering from various forms of cancer. Our results highlight the importance of personalized approaches to the diagnosis, management and treatment of COVID-19 in patients with specific genetic mutations. Further studies are needed to elucidate the complex relationship between these mutations and COVID-19.

Although the anti-COVID-19 vaccination has proved to be an effective preventive tool, "break-through infections" have been documented in patients with complete primary vaccination course. Most of the SARS-CoV-2 neutralizing antibodies pro-duced after SARS-CoV-2 infection target the spike protein receptor-binding domain which has an important role in facilitating viral entry and infection of the host cells. SARS-CoV-2 has demonstrated the ability to evolve by accumulating mutations in the spike protein to escape the humoral response of the host. The aim of this study is to compare the titers of neutralizing an-tibodies against the variants of SARS-CoV-2 by analyzing the sera of recovered and vaccinated healthcare workers (HCWs). 293 HCWs were enrolled and divided into three cohorts as follows: 91 recovered from SARS-CoV-2 infection (nVP); 102 vac-cinated who became positive after the primary cycle (VP); 100 vaccinated with complete primary cycle who concluded the follow-up pe-riod without becoming positive (VN). Higher neutraliza-tion titers were observed in the vaccinated subjects’ arms com-pared to the nVP arm. Differences in neutralization titers between arms for single variant were statistically significant (p<0.001) except for titers against the Alpha variant (p<0.05) between nVP and VP. Within the nVP group, the number of subjects with the absence of neutralizing antibodies was high. The presence of high-er titers in patients with a complete primary cycle compared to patients recovered from the infec-tion suggests a better efficacy of artificial immunization compared to natural im-munization, further encouraging the promotion of vaccination even in subjects with previous infection.

Coronary artery disease (CAD) is a prevalent cardiovascular condition characterized by the accumulation of plaque within coronary arteries. This plaque accumulation obstructs blood flow to the heart, resulting in a heart attack. While distinct features of CAD have been identified, its causes remain largely unclear, with the exception of environmental and nutritional factors. This study aimed to investigate the connection between genetic factors and CAD, focusing on the thymidylate synthase (TS) gene, a gene involved in one-carbon metabolism. Therefore, our research targeted single nucleotide polymorphisms that could potentially impact TS gene expression and lead to dysfunction. Our findings strongly associate the TS 1100T&gt;C and 1170A&gt;G genotypes with CAD susceptibility. We observed that TS 1100T&gt;C polymorphisms increased disease susceptibility in several groups, while the TS 1170A&gt;G polymorphism displayed a decreasing trend for disease risk when interacting with clinical factors. Furthermore, our results demonstrate the potential contribution of the TS 1100/1170 haplotypes to disease susceptibility, indicating a synergistic interaction with clinical factors in disease occurrence. Based on these findings, we propose that polymorphisms in the 3'-UTR miRNA binding site of the TS gene could serve as clinically useful biomarkers for the prevention, prognosis, and management of CAD.

Patients with Parkinson’s Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD. We compared the rate of genetic mutations in PD patients with or without probable RBD. Patients with a clinical diagnosis of PD in the Parkinson’s Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data or a diagnosis change over the first five years from the initial PD diagnosis. Probable RBD (pRBD) was confirmed by a REM Sleep Behavior Disorder Screening Questionnaire score &gt;5 points. Logistic regression and Machine Learning (ML) algorithms were used to relate Single Nucleotide Polymorphism (SNPs) in PD-related genes with pRBD. We included 330 PD patients fulfilling all inclusion and exclusion criteria. The final logistic multivariate model revealed that the following SNPs increased the risk of pRBD: GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45-7.93), SNCA_A53T_rs104893877 (8.21, 2.26-36.34), ANK2. CAMK2D_rs78738012 (2.12, 1.08-4.10), and ZNF184_rs9468199 (1.89, 1.08-3.33). Conversely, SNP COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15-0.78). The ML algorithms led to similar results. The predictive models were highly specific (95-99%) but lacked sensitivity (9-39%). We found a distinctive genetic signature for pRBD in PD. The high specificity and low sensitivity of the predictive models suggest that genetic mutations are necessary but not sufficient to develop RBD in PD. Additional investigations are needed.

Background: The outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in the global COVID-19 pandemic. The urgency for an effective SARS-CoV-2 vaccine has led to the development of a first series of vaccines at unprecedented speed. The discovery of SARS-CoV-2 spike-glycoprotein mutants, however, and consequentially the potential to escape vaccine-induced protection and increased infectivity, demonstrates the persisting importance of monitoring SARS-CoV-2 mutations to enable early detection and tracking of genomic variants of concern. Results: We developed the CoVigator tool with three components: 1) a knowledge base that collects new SARS-CoV-2 genomic data, processes it and stores its results; 2) a comprehensive variant calling pipeline; 3) an interactive dashboard highlighting the most relevant findings. The knowledge base routinely downloads and processes virus genome assemblies or raw sequenc-ing data from the COVID-19 Data Portal (C19DP) and the European Nucleotide Archive (ENA), respectively. The results of the variant calling pipeline are visualized through the dashboard in the form of tables and customizable graphs, making it a versatile tool for tracking SARS-CoV-2 variants. We put a special emphasis on the identification of intrahost mutations and make available to the community what is, to the best of our knowledge, the largest dataset on SARS-CoV-2 intrahost mutations. In the spirit of open data, all CoVigator results are available for download. The CoVigator dashboard is accessible via covigator.tron-mainz.de. Conclusion: With increasing demand worldwide in genome surveillance for tracking the spread of SARS-CoV-2, CoVigator will be a valuable resource of up-to-date list of mutations, which can be incorporated into global efforts to sustainably prevent or treat infections.

Phagosomal escape and intracellular survival, often accompanied by Small Colony Variants (SCVs) formation, are typical features of infections caused by S. aureus. The survival in macro-phages favours S. aureus dissemination and complicates treatment. RAW 264.7 murine macro-phages infected with S. aureus USA300 and treated with erythromycin and 20mM carnosine, alone and in combination, were used as experimental model. SCVs were isolated from all treat-ment conditions, but only those undergoing the pressure of combined erythromycin and carnosine for 48 hours were stable for at least six passages on blood agar. Nucleic acid extraction was car-ried out for S. aureus USA300 wild-type and stable SCVs. Whole Genome Sequencing (WGS) was performed using Illumina DNA Prep and Illumina MiSeq, and quantitative reverse transcription PCR was performed. WGS analysis did not yield mutations pointing to differences between S. au-reus USA300 and stable SCVs, therefore the focus was shifted to evaluating gene expression vari-ations. Genes such as zur, mntR, uhpt, fur, sdrE were shown to be significantly up-regulated in SCVs compared to S. aureus USA300 wild-type, suggesting a global change that allows adapta-tion to intracellular persistence, including protection from inflammatory response and evasion of the immune system.

Management of inflammatory bowel disease (IBD) often relies on biological and immunomodulatory agents for remission through immunosuppression, raising concerns regarding the SARS-CoV-2 vaccine's effectiveness. The emergent variants have hindered the vaccine neutralization capacity, and whether the third vaccine dose has the capacity to neutralize SARS-CoV-2 variants in this population remains unknown. This study aims to evaluate the humoral response of SARS-CoV-2 variants in patients with IBD 60 days after the third vaccine dose [BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)].56 su bjects with IBD and 12 healthy subjects were recruited. 90% of patients with IBD (49/56) were receiving biologics and/or immunomodulatory therapy. 24 subjects with IBD did not develop effective neutralizing capability against the Omicron variant. 70% (17/24) of those subjects were receiving anti-Tumor Necrosis Factor therapy [10= adalimumab, 7= infliximab], two of them had a history of COVID-19 infection, and one subject did not develop immune neutralization against three other variants: Gamma, Epsilon, and Kappa. All subjects in the control group developed detectable antibodies and effective neutralization against all seven SARS-CoV-2 variants. Our study shows that patients with IBD might not be protected against SARS-CoV-2 variants, and larger studies are needed to evaluate optimal immunity.

From 2008 to 2024, the Newborn Screening Translational Research Network (NBSTRN), part of the National Institute of Child Health and Human Development (NICHD) Hunter Kelly Newborn Screening Program, served as a robust infrastructure to facilitate groundbreaking research in newborn screening (NBS), rare disease, and genomics. Over fifteen years, NBSTRN developed into a significant international network, supporting innovative research on novel technologies to screen, diagnose, treat, manage, and understand the natural history of more than 280 rare diseases. A key component of these efforts has been the development of resources and expertise for the newborn screening community in ethical, legal, and social issues (ELSI). This paper presents findings from a survey conducted by the NBSTRN team with input from one of theNBSTRN's expert workgroups, the Bioethics and Legal Workgroup. With responses from 88 members of the NBS community including researchers and state NBS programs, the survey found that individuals rely on internal and collegial ELSI resources and highlighted a substantial demand for structured, accessible training and resources. The survey’s insights emphasize the importance of privacy and informed consent in NBS research, and suggested a need for improved collaborative tools and educational programs focused on ELSI for the NBS community. The survey results may inform future efforts in ELSI and NBS research including the development of expanded ELSI tools that leverage digital platforms and consultative services.

Background: Circulating rare cells participate in breast cancer evolution as systemic components of the disease and thus, are a source of theranostic information. Exploration of cancer-associated rare cells is in its infancy. We determined the validity of a rare-cell detection platform and demonstrated the usefulness of a certain rare cell subset as a novel approach to characterize the breast cancer system. Methods: Linearity of the Rarmax® platform was established using a spike-in approach. The platform includes red blood cell lysis, leukocyte depletion and high-resolution fluorescence image recording. Rare cell analysis was conducted on 28 samples (before and after surgery) from 14 patients with breast cancer, 20 healthy volunteers and 9 non-cancer control volunteers. In-depth identification of rare cells, including circulating tumor cells, endothelial-like cells, erythroblasts and inflammation-associated cells, was performed using a phenotype and morphology-based classification system. Results: The platform performed linearly over a range of 5-950 spiked cells, with an average recovery of 84.6%. Circulating epithelial and endothelial-like cell subsets have been demonstrated to be associated with or independent of cancer with tumor presence. Furthermore, certain cell patterns may be associated with treatment-related adverse effects. The sensitivity in detecting tumor-presence and cancer-associated abnormality before surgery was 50% and 85.7%, respectively and the specificity was 100% and 96.6%, respectively. Conclusion: The present study supports the idea of a cancer-associated rare cell abnormality to represent tumor entities as well as systemic cancer. The latter is independent of the apparent clinical cancer.

The Sm3+/Gd3+ co-doped glasses in the B2O3–GeO2–PbO and B2O3–GeO2–Bi2O3 systems have been synthesized in the composition range of 40B2O3–40GeO2–(15-17)PbO(Bi2O3)–(3-2)Sm2O3–(2-1)Gd2O3 and 42.5B2O3–42.5GeO2–(11.25-12.75)PbO(Bi2O3)–(2.25-1.5)Sm2O3–(1.5-0.075)Gd2O3. The physical, structural, and spectral properties of the produced glasses have been studied. The fabricated glass samples demonstrated changes in temperature-sensitive luminescence parameters in 298-673 K temperature range. We found out several photoluminescence bands attributed with transitions from different Stark sublevels. By using a combination of two temperature sensitive and one non-sensitive transitions we calculated fluorescence intensities ratio (FIR). This procedure made it possible to increase the sensitivity of luminescence thermometry in several times. Such method could be very useful for the luminescent thermometry materials based on Ln3+ ions with multiplied f-f transitions.

The time required to reach a correct diagnosis is one of the most important problems for rare disease (RD) patients. Diagnostic delay can be intolerably long, to the point that it is usually described as a “diagnostic odyssey” and, sometimes, a diagnosis might never occur. The International Rare Disease Research Consortium proposed, as ultimate goal for 2017-2027, to enable all people with a suspected RD to be diagnosed within one year if the disorder is known, and to enter a globally coordinated diagnostic and research pipeline for the unsolved cases. In-depth analysis of the genotype through next generation sequencing, together with a standardized in-depth phenotype description and sophisticated high-throughput approaches, have been applied as diagnostic tools to increase the chance of a timely and accurate diagnosis. This approach is very fruitful as, according to the Orphanet database, from 2010 to March 2017 more than 600 new RDs have been described and about 3600 genes linked to RDs have been identified. However, combination of -omics and phenotype data and international sharing of this information raise ethical concerns. Values to be assessed include not only patient autonomy but also family implications, beneficence, non-maleficence, justice, solidarity and reciprocity, which must be respected and promoted and, at the same time, balanced among each other. In this work we suggest that, to maximise patients involvement in the search for a diagnosis and identification of new causative genes, undiagnosed patients should have the possibility to: 1) actively participate in the description of their phenotype; 2) choose the level of visibility of their profile in matchmaking databases; 3) express their preferences regarding return of new findings, in particular which level of Variant of Unknown Significance (VUS) significance should be considered relevant to them. The quality of the relation between individual patients and physicians, and between the patient community and the scientific community is critically important for making the best use of available data and combining efforts in the search for matches with similar cases worldwide that will help to solve unsolved cases. The contribution of patients to collecting and coding data comprehensively is critical for efficient use of data downstream of data collection.

A series of novel chiral nonmetallocene pincer-type rare earth metal dialkyl complexes bearing the chiral monoanionic tridentate C2-symmetric 1,3-bis(oxazolinymethylidene)isoindoline (BOXMI) ligand (BOXMI)Ln(CH2SiMe3)2 1-3 (1, Ln = Sc, yield = 57%; 2, Ln = Lu, yield = 55%; 3, Ln = Y, yield = 62%) have been prepared in moderate yields via the acid-base reaction between the BOXMI ligand and rare earth metal tri(trimethylsilylmethyl) complexes. The X-ray diffractions show that both of the complexes 1 and 2 contain one Boxmi ligand and two trimethylsilylmethyl ligands, adopting a distorted-trigonal-bipyramidal configuration. In the presence of cocatalyst such as borate and AlR3, these complexes 1-3 exhibit high activities up to 6.8 × 104 (g of polymer)/(molLn h) and high cis-1,4-selectivities up to 97%) in the polymerization of isoprene in toluene, yielding the cis-1,4-polyisoprenes with high molecular weights (Mn up to 710000 g/mol) and bimodal molecular weight distributions (Mw/Mn = 2.0-4.5).

Pinus occidentalis, Swartz is the primary timber species in the Dominican Republic (DR). Despite its economic importance, studies conducted on this species are very scarce, making it difficult to estimate current inventory levels. This study aims to enhance the accuracy of estimating total bole volume of P. occidentalis in different ecological zones (EZs) within La Sierra, evaluating and comparing two established volume equations—combined variable and Schumacher-Hall—across nine modeling variants (MVs). An indicator variables analysis determined the necessity of distinct equations for two EZs. Fitting included both linear and nonlinear models. Our comprehensive statistical analysis included goodness-of-fit metrics to evaluate each model variant's performance rigorously. Modeling variant SH02 was most effective in the Dry Ecological Zone, showing superior performance in both fitting and validation phases. Similarly, SH03 emerged as the best fit for the Combined Intermediate and Humid Ecological Zones, achieving the lowest overall ranking sum among tested variants. The SH equation variants SH02 and SH03, provide reliable and precise volume estimations, allowing optimization of forestry management practices for P. occidentalis trees. The SH models outperformed the CV model variants' consistency in parameter estimation. This tailored approach employed ensures more accurate volume predictions, which is crucial for sustainable management and conservation efforts.

Analyzing BRCA1/2 tumor pathogenic variants (TPVs) in epithelial tubal/ovarian cancers (EOC) has become an essential part of the diagnostic workflow in many centers to guide treatment options and genetic cascade testing. However, there is no standardization of testing procedures, including techniques, gene assays, or sequencers used, and data on the execution of tumor tests remains scarce. Therefore, we evaluated characteristics of BRCA1/2 tumor testing in advanced-stage EOC with real-world national data. Pathology reports of patients diagnosed with EOC in 2019 in the Netherlands were obtained from the Dutch Pathology Registry (PALGA), and data regarding histological subtype and BRCA1/2 tumor tests were extracted. A total of 999 patients with advanced-stage EOC were included. Tumor tests were performed for 502 patients (50.2%) and BRCA1/2 TPVs were detected in 14.7%. Of all tests, 48.6% used hybrid capture techniques and 26.5% used PCR-based techniques. More than half of the tests (55.0%) analyzed other genes in addition to BRCA1/2. Overall, this study highlights the heterogeneity in the execution of BRCA1/2 tumor tests. Despite a lack of evidence of quality differences, we emphasize that adequate reporting and internal and external quality monitors are essential for high-quality implementation and execution of reliable BRCA1/2 tumor testing, which is crucial for identifying all patients with BRCA1/2 TPVs.

An eight-sided prism sample, obtained from a hot-rolled AZ31 magnesium alloy sheet, was compressed at room temperature along the transverse direction to investigate the influence of local strain on twinning behavior using electron backscatter diffraction (EBSD) measurements. The octagonal surface of the sample was divided into distinct regions based on hardness distribution and metallographic observations. The EBSD maps of different areas show significant variations, suggesting that these areas experienced different local strain conditions. The EBSD measurements provided detailed data from three distinct regions, with the strain state known in two regions and uncertain in the third. The combined analysis of the Schmid factor (SF) and the strain compatibility factor (m') was employed to study twin variant selection. The comparison of twinning behavior in different regions showed that the strain compatibility factor offered a more comprehensive explanation for the observed twinning pattern in the region with local shear strain.

We have developed a simple, rapid, high-throughput RBD-based ELISA to assess the humoral immunity against emerging SARS-CoV-2 virus variants. The cDNAs of the his-tagged RBD proteins of the virus variants were stably engineered into HEK cells secreting the protein into the supernatant, and RBD purification was performed by Ni-chromatography and buffer exchange by membrane filtration. The simplified assay uses single dilutions of sera from finger-pricked native blood samples, purified RBD in 96-well plates, and a chromogenic dye for development. The results of this RBD-ELISA were confirmed to correlate with those of a commercial immunoassay measuring antibodies against the Wuhan strain, as well as direct virus neutralization assays assessing the cellular effects of the Wuhan and the Omicron (BA.5) variants. Here we document the applicability of this ELISA to assess the variant-specific humoral immunity in vaccinated and convalescent patients, as well as to follow the time course of selective vaccination response. This simple and rapid assay, easily modified to detect humoral immunity against emerging SARS-CoV-2 virus variants, may help to assess the level of antiviral protection after vaccination or infection.

Pulmonary arteriovenous malformations (PAVMs) are vascular anomalies resulting in abnormal connection between pulmonary arteries and veins. In 80% of cases, PAVMs are present from birth, but clinical manifestations are rarely seen in childhood. These congenital malformations are typically associated with Hereditary Hemorrhagic Telangiectasia (HHT), a rare disease that affects 1 in 5,000/8,000 individuals. HHT disease is frequently caused by mutations in genes involved in the TGF-β pathway. However, approximately 15% of patients do not have a genetic diagnosis and, among the genetically diagnosed, more than 33% do not meet the Curaçao Criteria. This makes clinical diagnosis even more challenging in the pediatric age group. Here, we introduce an 8 years old patient bearing a severe phenotype of multiple diffuse PAVMs caused by an unknown mutation which ended in lung transplantation. Phenotypically, the case of study follows a molecular pattern HHT-like. Therefore, molecular biology and cellular functional analysis has been performed in primary endothelial cells (ECs) isolated from the explanted lung. The findings revealed a loss of functionality in lung endothelial tissue and a stimulation of endothelial to mesenchymal transition. Understanding the molecular basis of this transition could potentially offer new therapeutic strategies to delay lung transplantation in severe cases.

The R23Cu7Mg4 (R = Ca, Eu) intermetallics, studied by single crystal X-ray diffraction, were found to be isostructural with the Yb23Cu7Mg4 prototype (hP68, k4h2fca, space group P63/mmc), forming a small group inside the bigger 23:7:4 family, otherwise adopting the hP68-Pr23Ir7Mg4 crystal structure. The observed structural peculiarity is connected with the divalent character of the R component and with a noticeable volume contraction, resulting in a clear clustering of title compounds inside the whole 23:7:4 family. The occurrence of fragments typical of similar compounds, particularly Cu-centered trigonal prisms and Mg-centered core-shell polyicosahedral clusters with R at vertices, induced the search of significant structural relationships. In this work, a description of the hexagonal crystal structure of the studied compounds is proposed as a linear intergrowth along the c-direction of the two types of slabs R10CuMg3 (parent type: hP28-kh2ca, SG 194) and R13Cu6Mg (parent type: hR60-b6a2, SG 160). The ratio of these slabs in the studied structure is 2:2 per unit cell, corresponding to the simple equation 2XR10CuMg3 + 2XR13Cu6Mg = 2XR23Cu7Mg4. This description assimilates the studied compounds to the (Ca,Eu,Yb)4CuMg ones, where the same slabs (of p3m1 layer symmetry) are stacked in a different way/ratio, and constitutes a further step towards a structural generalization of R-rich ternary intermetallics.

Many of the potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases such as Alzheimer’s (AD) disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), but also in a seemingly distinct Niemann-Pick type C disease with primarily juvenile-onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets such as microglia, peripheral macrophages, or regulatory T cells (Tregs), the complement system, and other soluble factors. In this review, we will compare these neurodegenerative diseases from a clinical point of view and point out the common pathways and mechanisms of protein aggregation, neurodegeneration and/or neuroinflammation that could potentially lead to shared treatment strategies. We also describe the common therapeutic approaches in treating the immune dysfunctions in these disorders, moving from immunization to microbiome regulation and stem cell treatment.

Al-Zn-Mg-Cu alloy has high specific strength, good corrosion resistance, fracture toughness and fatigue resistance. It is one of the most important structural materials in the fields of aviation, aerospace, weapons, transportation and so on, which plays a huge role in the field of aerospace.In order to optimize the strength, toughness and corrosion properties of Al-Zn-Mg-Cu alloy, alloying has always been the focus of research on Al-Zn-Mg-Cu alloy. The effects of main alloying elements, trace alloying elements and rare earth elements on the microstructure and properties of Al-Zn-Mg-Cu aluminum alloy were briefly introduced in the paper, and the future research directions were prospected.

Quantification of bone loss for follow-up comparisons has not been routinely performed in patients with parietal thinning so far. This study compares different methodological approaches including both 2- and 3-dimensional methods in computerized tomographies of a single patient. The 2-dimensional method provides accurate measurements of bone thickness, while the 3-dimensional method allows for a more comprehensive view of the bone's structure, including parameters like shape, size, and thickness. The techniques provided valuable data for the treating physician and suggest a possible effect of corticosteroids in this individual patient. The study concludes that 3-dimensional reconstruction of computerized tomographies with subsequent 2-dimensional analyses appears justified for routine radiological practice to increase clinical awareness of the size of the parietal bone defects and allow for quantification of bone loss during long-term follow-ups. Further validation of the proposed analytical approaches is warranted in larger studies to investigate patterns of bone thinning across the skull and changes in bone volumes over time, with specialized software to be approved for such analyses.

During the COVID-19 pandemic, individuals with symptoms other than cough or fever have refrained from seeking medical advice. However, a delay in treatment might lead to serious consequences. At the same time, digital health initiatives have emerged to overcome this bottleneck of healthcare. Herein, we report the results of a multi-center initiative using a combination of patient history and artificial intelligence (AI) to identify individuals with rare neuromuscular diseases. First, a questionnaire with 46 items was developed by interviewing patients with muscular dystrophies, amyotrophic lateral sclerosis, Morbus Pompe, neuropathies, and myasthenia gravis. Second, patients with proven neurological diseases answered the questionnaire. Third, a combination of classifiers (artificial neural network, support vector, and random forest) was trained and, finally, the system was challenged with new questionnaires. Users with an abnormal questionnaire pattern received a unique code for data privacy and contact details for a neurologist for further advice. The neurologists confirmed or refuted the AI-based diagnosis. The questionnaire was accessed 3122 times, leading to 853 unique codes. Only for a few patients the computer-based diagnoses and the confirmed final diagnoses were reported to us. However, for these few patients, the genetic testing and high CK levels finally ended their long-lasting diagnostic odyssey.

The problem of effective immobilization of liquid radioactive waste (LRW) is key to the successful development of nuclear energy. The possibility of using magnesium potassium phosphate (MKP) compound for LRW immobilization on the example of nitric acid solutions containing actinides and rare earth elements (REE), including high level waste (HLW) surrogate solution is considered in the research work. Under the study of phase composition and structure of the MKP compounds obtained by the XRD and SEM methods, it was established that the compounds are composed of crystalline phases - analogues of natural phosphate minerals (struvite, metaankoleite). The hydrolytic stability of the compounds was determined according to the semi-dynamic test GOST R 52126-2003. Low leaching rates of radionuclides from the compound are established, including a differential leaching rate of ²³⁹Pu and ²⁴¹Am - 3.5 × 10^-7 and 5.3 × 10^-7 g/(cm²∙day). As a result of the research work it was concluded that the MKP compound is promising for LRW immobilization and can become an alternative material combining the advantages of easy implementation of the technology like cementation and the high physical and chemical stability corresponding to a glass-like compound.

New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOC) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5,007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOC, including Alpha (n =714), Delta (n =1,877), and Omicron (n =1,802). Omicron isolates were further sub-typed as BA.1 (n =899), BA.2 (n =853), and BA.4/BA.5 (n =50); the remaining 614 isolates were classified as “Other”. Approximately 31.5% (1,577/5,007) of the samples were associated with vaccine breakthrough infections, which increased in frequency following the emergence of Delta and Omicron. Severe clinical outcomes included ICU admission (336/5007 = 6.7%), ventilator support (236/5007 = 4.7%), and mortality (430/5007 = 8.6%), with increasing age being the most significant contributor to each (p &lt;0.001). Unvaccinated individuals accounted for 79.7% (268/336) of ICU admissions, 78.3% (185/236) of ventilator cases, and 74.4% (320/430) of deaths. Highly significant (p &lt;0.001) increases in mortality were observed in individuals with cardiovascular disease, hypertension, cancer, diabetes, and hyperlipidemia, but not with obesity, thyroid disease, or respiratory disease. Significant differences (p &lt;0.001) in clinical outcomes were also noted between SARS-CoV-2 variants, including Delta, Omicron BA.1, and Omicron BA.2. Vaccination was associated with significantly improved clinical outcomes in our study, despite an increase in breakthrough infections associated with waning immunity, greater antigenic variability, or both. Underlying comorbidities contributed significantly to mortality in both vaccinated and unvaccinated individuals, with increasing risk based on the total number of comorbidities. Real-time RT-PCR-based screening facilitated timely identification of predominant variants using a minimal number of spike protein mutations, with faster turnaround time and reduced cost compared to WGS. Continued evolution of SARS-CoV-2 variants will likely require ongoing surveillance for new VOCs, with real-time assessment of clinical impact.

The spread of SARS-CoV-2 variants of concern (VOCs), is of great importance to the whole community, since their genetic changes may increase transmissibility, disease severity and reduce effectiveness of vaccines. Moreover, these changes may lead to failure of diagnostic measures, thus variant-specific diagnostic methods are essential. To date, genetic sequencing is the gold standard method to discriminate between variants, however it is time consuming (several days) and expensive. Therefore, the development of rapid diagnostic methods for SARS-CoV-2 in accordance with its genetic modification is of great importance. In this study, we introduce a Mass-Spectrometry (MS)-based methodology for the diagnosis of SARS-CoV-2 in clinical specimens, a methodology which enables universal identification, alongside with variant-specific discrimination. The universal identification of SARS-CoV-2 is based on conserved markers shared by all variants, while the identification of the specific variant relies on variant-specific markers. Determining a specific set of peptides for a given variant consists of a multistep procedure, starting with in-silico search for variant-specific tryptic peptides, followed by tryptic digest of a cell-cultured SARS-CoV-2 variant and identification of these markers by HR-LC-MS/MS analysis. As a proof of concept, this approach was demonstrated for four representative VOCs, in comparison with the wild-type Wuhan reference strain. For each variant, at least two unique markers, derived mainly from the spike (S) and nucleocapsid (N) viral proteins, were identified. This methodology is specific, rapid, easy to perform and inexpensive, therefore can be applied as a general diagnostic tool of pathogenic variants.

The successive waves of the Covid-19 pandemic are driven by SARS-CoV-2 variants that reached critical detection levels in different parts of the world. But how evolved the Wuhan virus since its detection in December 2019 into the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529) variants of concern? This is a story of mice and men, of up to 1,000,000 infected cells in one person, where each cell produces between 10⁵ and 10⁶ viral RNAs, of immune-compromised patients, the digestive tract and viral recombination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic which has been a topic of major concern to global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7, B.1.351, P1 and, B.1.617., which show in-creased transmissibility and resistance towards vaccines and therapies. Importantly, the likelihood of susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response or comorbidities needs greater attention. Herein, we provide a comprehensive perspective regarding ongoing vaccine (mRNA, protein-based, viral vector based etc.) and therapeutic (mono-clonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.

The chemical reaction of ion-adsorption type rare earth during in-situ leaching process is accompanied by ion migration and charge movement, making the leaching process electrochemical in nature. The chemical reaction rate plays an important role in the leaching rate of rare earth elements. In this work, electrochemical impedance spectroscopy (EIS) was used to reveal characteristics of electrical resistance alteration and leaching rate of rare earth elements during in-situ leaching. The equivalent circuit model of the leaching process was established, and two critical parameters of solution resistance Rs and charge transfer resistance Rt were analyzed to reflect the electrochemical characteristics. According to the characteristics of electrical resistance alteration, the leaching process was divided into four stages: wetting, reaction, equilibrium, and top water stage. The resistance parameters Rs and Rt decreased first and then increased during the leaching process. The maximum value of Rs was 1330Ω∙cm2 at the end of the top water stage, and the minimum value was 135Ω∙cm2 at the beginning of the equilibrium stage. The maximum value of Rt was 8310Ω∙cm2 at the beginning of the leaching stage, and the minimum value was 21Ω∙cm2 at the end of the reaction stage. Rs and Rt were negatively correlated with the pore size and chemical reaction rate during leaching. With increasing of pore size and reaction rate , the resistance parameter decrease. This study provide a new idea for intelligent monitoring of rare earth ore.

One of the IRDiRC goals for 2017-2027 is to achieve definitive diagnosis for rare undiagnosed diseases within one year, as diagnosis delay remains one of the pending issues in the rare diseases field. The Spanish Undiagnosed Rare Diseases Program (SpainUDP) was created in response to this challenging scenario to cover patients’ needs and after seeing the success of the UDP in USA. SpainUDP offers a multidisciplinary approach to those patients who have long sought a diagnosis without any success. During a first phase of the protocol, undiagnosed cases are sent to SpainUDP by individual patients, patient organizations or hospitals. After a carefully analysis of phenotype, data from sequencing experiments (WES) is processed with a standard pipeline and a detailed standardized phenotypic information (mapped to HPO) is connected to genetic data. In addition, the participation of SpainUDP in international initiatives such as the European projects RD-Connect and Solve RD, the Undiagnosed Diseases Network International (UDNI), and the MatchMaker Exchange platform, allows the establishment of a global data sharing strategy across multiple projects submitting data to these international initiatives. From the official beginning of the program (at the end of 2015) until early 2018, 147 cases were accepted in SpainUDP. During this time, 37 cases (25 %) dropped out the program due to several reasons. The remaining 110 cases are distributed as follows: phenotypic and genotypic (WES) characterization was finished in 30 cases, of which 20 (67 %) were diagnosed; 21 cases are pending on variants validation by Sanger; in 25 cases, WES is ongoing and 34 cases are in a deep phenotypic characterization. As a conclusion, SpainUDP aims to achieve a diagnosis following two recommendations of the IRDiRC: the patients’ diagnosis in a period of time as short as possible and the promotion of data sharing (especially genomic) at the international level.

SARS-CoV-2, is the cause of the COVID-19 pandemic which has claimed more than six million lives worldwide, devastating the economy and overwhelming healthcare systems globally. The development of new drug molecules and vaccines has played a critical role in managing the pandemic; however, new variants of concern still pose a significant threat as the current vaccines cannot prevent all infections. This situation calls for the collaboration of biomedical scientists and healthcare workers across the world. Repurposing approved drugs is an effective way of fast-tracking new treatments for recently emerged diseases. To this end, we have assembled and curated a database consisting of 7817 compounds from the Compounds Australia Open Drug collection. We developed a set of eight filters based on indicators of efficacy and safety that were applied sequentially to down-select drugs that showed promise for drug repurposing efforts against SARS-CoV-2. Considerable effort was made to evaluate approximately 14000 assay data points for SARS-CoV-2 FDA/TGA-approved drugs and provide an average activity score for 3539 compounds. The filtering process identified 12 FDA approved molecules with established safety profiles that have a plausible mechanism for treating COVID-19 disease. The methodology developed in our study provides a template for prioritising repurposable drug candidates that are safe, efficacious, and cost-effective for the treatment of COVID-19, long COVID, or any other future disease. We present our database in an easy-to-use interactive interface (CoviRx, https://www.covirx.org/) that was also developed to enable scientific community to access to the data of over 7000 potential drugs and to implement alternative prioritisation and down-selection strategies.

In this study, multi-layer ceramic capacitors (MLCCs) detached from lighting sector's waste electrical-electronic equipment (WEEE) are characterised for the presence of rare earth elements (REEs) and precious metals (PMs). Their digestion was carried out with HNO3 & aqua regia on a heating plate and characterised with the use of inductively coupled plasma optical emission spectroscopy (ICP-OES) & scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX). The contents of REEs and PMs are 0.84 wt% and 0.60 wt%, respectively, and create an economic stored value in MLCCs that is essentially defined by PMs of 98.67% and by Pd 78.37%. The content of the main elements is: Nd 0.366 wt%, Y 0.220 wt%, Dy 0.131 wt%, Ag 0.467 wt%, and Pd 0.105 wt%. The results confirm the need of selective removal and separate recycling process of MLCCs from WEEE drivers.

A plant’s health and productivity is influenced by its associated microbes. Although the common microbiome is often thought to be the most influential, significant numbers of rare or uncommon microbes (eg. specialized endosymbionts) may also play an important role in the health and productivity of certain plants in certain environments. To help identify rare/specialized bacteria and fungi in the most important angiosperm plants, we contrasted microbiomes of the shoots, roots and rhizospheres of Arabidopsis, Brachypodium, maize, wheat, sugarcane, rice, tomato, coffee, common bean, cassava, soybean, switchgrass, sunflower, Brachiaria, barley, sorghum, and pea. Plants were grown inside sealed jars on sterile sand or field soil. About 95% and 86% of fungal and bacterial diversity inside plants was uncommon, however judging by read abundance, up to half of the mycobiome consists of uncommon fungal cells, while less than 11% of bacterial endophytes are rare. Uncommon seed transmitted microbiomes consisted mostly of Proteobacteria, Firmicutes, Bacteriodetes, Ascomycetes and Basidiomycetes that most heavily colonized shoots, to a lesser extent roots and least of all rhizospheres. Soil served as a more diverse source of rare microbes than seeds, replacing or excluding the majority of the uncommon seed transmitted microbiome. With the rarest microbes, their colonization pattern could either be the result of stringent biotic filtering by most plants, or uneven/stochastic inoculum distribution in seeds or soil. Several strong plant-microbe associations were observed such as seed transmission to shoots, roots and/or rhizospheres of Sarocladium zeae (maize), Penicillium (pea and Phaseolus), and Curvularia (sugarcane), while robust bacterial colonization from cassava field soil occurred with the cyanobacteria Leptolyngbya into Arabidopsis and Panicum roots, and Streptomyces into cassava roots. Some abundant microbes such as Sakaguchia in rice shoots or Vermispora in Arabidopsis roots appeared in no other samples, suggesting they were infrequent, stochastically deposited propagules from either soil or seed (impossible to know based on the available data). Future experiments with culturing and cross inoculation of these microbes between plants may help us better understand host preferences and their role in plant productivity, perhaps leading to their use in crop microbiome engineering and enhancement of agricultural production.

Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from serosal surface of abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1-WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within 3 years. The dismal survival makes DSRCT an orphan disease with urgent need of new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors have been evaluated in small studies. Recent works using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

Seed bank survival underpins plant population persistence but studies on seed bank trait-environment interactions are few. Changes in environmental conditions relevant to seed banks occur in desert ecosystems owing to solar energy development. We developed a conceptual model of seed bank survival to complement methodologies using in-situ seed bank packets. Using this framework, we quantified the seed bank survival of two closely related annual desert plant species, one rare (Eriophyllum mohavense) and one common (Eriophyllum wallacei) and the seed bank-environment interactions of these two species in the Mojave Desert within a system that emulates microhabitat variation associated with solar energy development. We tracked 4,860 seeds buried across 540 seed packets and found, averaged across both species, that seed bank survival was 21% and 6% for the first and second growing seasons, respectively. After two growing seasons, the rare annual had a significantly greater seed bank survival (10%) than the common annual (2%). Seed bank survival, across both species, was significantly greater in Shade (10%) microhabitats compared to Runoff (5%) microhabitats and Control microhabitats (3%). Our study confers insight into this early life-stage across rare and common congeners and their environmental interactions using a novel conceptual framework for seed bank survival.

To understand functions of biomolecules such as proteins, not only structures but their conformational change and kinetics are important to be characterized but its atomistic details are hard to obtain both experimentally and computationally. We review our recent computational studies using novel enhanced sampling techniques for conformational sampling of biomolecules and calculations of their kinetics. For efficiently characterizing the free energy landscape of a biomolecule, we introduce the multiscale enhanced sampling method, which uses a combined system of atomistic and coarse-grained models. Based on the idea of Hamiltonian replica exchange, we can recover the statistical properties of the atomistic model without any biases. We next introduce the string method as a path search method to calculate the minimum free energy pathways along a multidimensional curve in high dimensional space. Finally we introduce novel methods to calculate kinetics of biomolecules based on the ideas of path sampling: One is the Onsager-Machlup action method, and the other is the weighted ensemble method. Some applications of above methods to biomolecular systems are also discussed and illustrated.

SARS-CoV-2 infection remains a global burden. Despite intensive research, the mechanism and dynamics of early viral replication are not completely understood including the kinetics of formation of genomic RNA (gRNA), sub-genomic RNA (sgRNA) and replication centers/organelles (ROs). We employed single-molecule RNA-fluorescence in situ hybridization (smRNA-FISH) to simultaneously detect viral gRNA and sgRNA, immunofluorescence to detect nsp3 protein, a marker for the formation RO, and carried out a time course analysis. We found that single molecules of gRNA are visible within the cytoplasm at 30 minutes post-infection (p.i.). Starting from 2 hr. p.i., most of the viral RNA existed in clusters/speckles, some of which were surrounded by single molecules of sgRNA. These speckles associated with nsp3 protein starting at 3 hr. p.i., indicating that these were precursors to ROs. Furthermore, RNA replication was asynchronous as cells with RNA at all stages of replication were found at any given time point. Our probes detected the SARS-COV-2 variants of concern, and BA.1 strain exhibited slower rate of replication kinetics than the WA1 strain. Our results provide insights into the kinetics of SARS-CoV-2 early post-entry events, which will facilitate identification of new therapeutic targets to early stage replication to combat COVID-19.

Background: The newly introduced COVID-19 vaccines have reduced disease severity and hospitalizations. However, they do not significantly prevent infection or transmission. In the same context, measuring IgM and IgG antibody levels is important, but it doesn't provide information about the status of the mucosal immune response. This article describes a comprehensive mapping of IgA epitopes of the S protein, its cross-reactivity, and the development of an ELISA-peptide assay. Methods: IgA epitope mapping was conducted using Spot-synthesis and sera from RT-qPCR COVID-19-positive patients. Specific and cross-reacting epitopes were identified, and an evolutionary analysis from the early Wuhan strain to the Omicron variant was performed using bioinformatics tools and a microarray of peptides. The selected epitopes were chemically synthesized and evaluated using ELISA-IgA. Results: 40 IgA epitopes were identified, with 23 in S1 and 17 in the S2 subunit. Among these, at least 23 epitopes showed cross-reactivity with DENV and other organisms and 24 with other associated coronaviruses. Three MAP4 polypeptides were validated by ELISA, demonstrating a sensitivity of 90-99.96% and a specificity of 100%. Among the six IgA-RBD epitopes, only the SC/18 epitope of the Omicron variants (BA.2 and BA.2.12.1) presented a single IgA epitope. Conclusions: This research unveiled the IgA epitome of the S protein and identified many epitopes that exhibit cross-reactivity with DENV and other coronaviruses. The S protein of variants from Wuhan to Omicron retains many conserved IgA epitopes, except for one epitope (#SCov/18). The cross-reactivity with DENV suggests limitations in using the whole S protein or the S1/S2/RBD segment for IgA serological diagnostic tests for COVID-19. The expression of these identified specific epitopes as diagnostic biomarkers could facilitate monitoring mucosal immunity to COVID-19, potentially leading to more accurate diagnoses and alternative mucosal vaccines.

A growing number of emerging SARS-CoV-2 variants is being identified worldwide, potentially impacting the effectiveness of current vaccines. We report the data obtained in several Italian regions involved in the SARS-CoV-2 variant monitoring from the beginning of the epidemic and spanning the period from October 2020 to March 2021.

The altitude of the habitat is one of the important regulators of species survival. Kaçkar Mountains National Park is located in the Eastern Black Sea region of Turkey. This is the first study on the benthic diatom flora of the high mountain lakes in Kaçkar Mountains National Park, which is situated between 2782 and 3075 m a.s.l. A total of 84 diatom species were identified from benthic communities of 15 habitats in summer (19 July, 28 August) and autumn (10 September) months of 2020. The genus Pinnularia (13 species) formed the basis of the taxonomic list followed by Eunotia (5 species), Navicula (5 species), and Frustulia (4 species) genera, respectively. The waters in all the studied lakes were fresh, low-saline, with low-alkaline or circumneutral pH and organically uncontaminated as evidenced by prevailed bioindicator groups. Statistical methods and comparative floristic results confirm the role of the lake altitude for the diatom species distribution. Species richness was higher in lakes with lower altitude, but a statistical approach also revealed a tendency for it to increase with altitude if species richness increased. Further studies will be needed to continue exploring this pattern. In the first round of analysis, diatom species groups were categorized according to IUCN categories, revealing one potentially threatened and one rare species. To protect studied high mountain lakes, their ecological conditions must be constantly monitored in the Kaçkar Mountains National Park.

Traditional population-based metaheuristic algorithms are effective in solving complex real-world problems but require careful strategy selection and parameter tuning. Parameter-less population-based optimization algorithms have gained importance due to their simplicity and efficiency. However, research on their applicability for solving large systems of nonlinear equations is still incipient. In this paper, a systematic review and detailed description of metaphor-less optimization algorithms is made, including the Jaya algorithm, the main Jaya variants for continuous optimization problems, with a focus on the Enhanced Jaya (EJAYA) algorithm, the three Rao algorithms, the best-worst-play (BWP) algorithm, and the very recent max-min-greedy-interaction (MaGI) algorithm. This paper also discusses a few previous parallelizations of the Jaya optimization algorithm, as well as recent GPU-based massively parallel implementations of the Jaya, Enhanced Jaya (EJAYA), Rao, and BWP algorithms developed by the authors. In addition, a novel GPU-accelerated version of the MaGI algorithm is proposed. The GPU-accelerated versions of the metaphor-less algorithms developed by the authors were implemented using the Julia programming language and tested primarily on GeForce RTX 3090 and NVIDIA A100 GPUs, as well as on Tesla V100S and Tesla T4 GPUs, using a set of difficult, large-scale nonlinear equation system problems. The computational experiments carried out produced quite significant speedups, which highlights the efficiency of the GPU-based versions of the metaphor-less algorithms developed for solving large-scale systems of nonlinear equations.

Abstract: The worldwide spread of SARS-CoV-2 has led to a significant economic and social burden on a global scale. Even though the pandemic has concluded, there remains apprehension regarding the emergence of highly transmissible variants capable of evading immunity induced by either vaccination or prior infection. The success of viral penetration is the specific amino acid residues of the Receptor Binding Motif (RBM) involved in viral attachment. This region interacts with the cellular receptor ACE2, triggering a neutralizing antibody (nAb) response. In this study, we have evaluated the immunogenicity of serum from individuals who received either a single dose or a combination of different vaccines against the original SARS-CoV-2 strain and mutated linear RBM. Despite a modest antibody response to the wild-type SARS-CoV-2 RBM, the Omicron variants exhibit four mutations in the RBM (S477N, T478K, E484A, F486V) that result in even lower antibody titers. The primary immune responses observed were directed towards IgA and IgG. While nAbs typically target the RBD, our investigation has unveiled a reduced seroreactivity within the RBD's crucial subregion, the RBM. This deficiency may have implications for the generation of protective nAbs. Evaluation of S1WT and S2WT RBM peptides binding to nAbs using microscale thermophoresis revealed a higher affinity (35 nM) for the S2WT sequence (GSTPCNGVEGFNCYF), which includes the FNCY patch. Our findings suggest that the linear RBM of SARS-CoV-2 is not an immunodominant region in vaccinated individuals. Comprehending the intricate dynamics of the humoral response, its interplay with viral evolution, and host genetics is crucial for formulating effective vaccination strategies, not only targeting SARS-CoV-2 but also anticipating potential future coronaviruses.

Global economic and social burden was caused by the SARS-CoV-2 spread worldwide. Despite the end of the pandemic, there is a concern about virulent evolving variants of the virus which can bypass the humoral immune response induced by vaccination or infection. Crucial to the viral entrance, amino acid residues in the RBM region, which interacts with cellular receptor ACE2, can elicit neutralizing antibody response. Herein we determine the immunogenicity of one-dose or heterologous dose vaccinated serum against wild-type and mutated RBM region. Despite low antibody response to wild-type SARS-CoV-2 RBM, omicron variants possess four mutations in RBM (S477N, T478K, E484A, F486V) that induce even less antibody titers. The most predominant responses were against IgA and IgG. While neutralizing antibodies (nAbs) predominantly target the RBD, our investigation revealed a diminished seroreactivity within the RBD's crucial region, the receptor-binding motif (RBM), potentially impacting the production of protective nAbs. S1WT and S2WT RBM peptides binding to nAbs were evaluated through microscale thermophoresis, and higher affinity (35 nM) was obtained for sequence S2WT (GSTPCNGVEGFNCYF), containing the FNCY patch. Our data indicates that SARS-CoV-2 RBM is not an immunodominant region in vaccinated individuals. Understanding the intricate dynamics of the humoral response and its interplay with viral evolution and host genetics is essential for the formulation of effective vaccination strategies, not only against SARS-CoV-2 but also for future emerging coronaviruses.

The high demand for SARS-CoV-2 tests but limited supply to South African laboratories early in the COVID19 pandemic, resulted in a heterogenous diagnostic footprint of open and closed molecular testing platforms. Novel approaches were required to monitor test quality especially during the introduction of newly circulating variants. The National Health Laboratory Service centrally collected cycle threshold (Ct) values from 1,497,669 test results reported from six commonly used PCR assays in 36 months, and visually monitored changes in their median Ct within a 28-day centered moving average for each assays’ gene targets. This continuous quality monitoring rapidly identified delayed hybridization of RdRp in the Allplex™ SARS-CoV-2 assay due to the Delta (B.1.617.2) variant; S-gene target failure in the TaqPath™ COVID-19 assay due to B.1.1.7 (Alpha) and the B.1.1.529 (Omicron); and recently E-gene delayed hybridization in the Xpert® Xpress SARS-CoV-2 due to XBB.1.5. This near “real-time” monitoring helped inform the need for sequencing and the importance of multiplex molecular nucleic acid amplification technology designs used in diagnostics for patient care. This continuous quality monitoring approach at the granularity of Ct values should be included in ongoing surveillance and with application to other disease use cases that rely on molecular diagnostics.

We explored the outcomes of germline BRCA1/2 pathogenic/likely pathogenic variants (PVs/LPVs) in the endocrine-sensitive disease treated with first line standard of care cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Three studies retrospectively showed a reduction in overall survival (OS) and progression free survival (PFS) in gBRCA1/2m patients compared to both germinal BRCA1/2 wild type (gBRCA1/2wt) and to the untested population. Regarding the efficacy of PI3K inhibitors, there are no subgroup or biomarker analyses in which germinal BRCA status was explored. However, the biological interactions between the PIK3CA/AKT/mTOR pathway and BRCA1/2 at a molecular level could help us to understand the activity of these drugs when used to treat BC in BRCA1/2 PVs/LPVs carriers. The efficacy of trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate (ADC) targeting HER2 for HER2-low and HER2-positive (HER2+) BC, has been increasingly described. Unfortunately, data on T-DXd in HER2+ or HER2-low metastatic BC harboring germinal BRCA1/2 PVs/LPVs is lacking. Including germinal BRCA1/2 status in the subgroup analysis of the registration trials of this ADC would be of great interest, especially in the phase III trial DESTINY-breast04. This trial enrolled patients with HER2-negative (HER2-) and both HR+ and HR- metastatic disease, which can now be categorized as HER2-low. The HER2-low subgroup includes tumors that were previously classified as triple negative, so it is highly likely that some women were germline BRCA1/2 PVs/LPVs carriers and this data was not reported. Germline BRCA1/2 status will be available for a higher number of individuals with BC in the near future and data on the prognostic and predictive role of these PVs/LPVs is needed in order to choose the best treatment options.

Several COVID-19 platforms have been licensed across the world thus far, but vaccine platforms research that can lead to effective antigen delivery is still ongoing. Here, we constructed AdCLD-CoV19 that could modulate humoral immunity by harboring SARS-CoV-2 antigens onto a chimeric adenovirus 5/35 platform that was effective in cellular immunity. By replacing the S1/S2 furin cleavage sequence of the SARS-CoV-2 Spike (S) protein mounted on AdCLD-CoV19 with the linker sequence, high antigen expression was confirmed in various cell lines. The high levels of antigen expression contributed to antigen-specific antibody activity in mice and non-human primates (NHPs) with single vaccination of AdCLD-CoV19. Furthermore, the adenovirus-induced Th1 immune response was specifically raised for the S protein, and these immune responses protected the NHP against live viruses. While AdCLD-CoV19 maintained neutralizing antibody activity against various SARS-CoV-2 variants, it was reduced to single vaccination for β and ο variants, and the reduced neutralizing antibody activity was restored with booster shots. Hence, AdCLD-CoV19 can prevent SARS-CoV-2 with single vaccination, and the new vaccine administration strategy that responds to various variants can maintain the efficacy of the vaccine.

A striking aspect of COVID-19 is the difference in the outcome of the infection between different countries, and different ethnic groups within one country. We surveyed the literature on SARS-CoV-2 complemented with comparative publications on SARS-CoV and other coronaviruses to capture the current understanding of virus – host interactions including virus subtypes, transmission, zoonotic aspects, and potential host determinants.

Studies employing Arellano-Bond and Blundell-Bond GMM estimation for single linear dynamic panel data models are growing exponentially in number. However, for researchers it is hard to make a reasoned choice between many different possible implementations of these estimators and associated tests. By simulation the effects are examined of many options regarding: (i) reducing, extending or modifying the set of instruments; (ii) specifying the weighting matrix in relation to the type of heteroskedasticity; (iii) using (robustified) 1-step or (corrected) 2-step variance estimators; (iv) employing 1-step or 2-step residuals in Sargan-Hansen overall or incremental overidentification restrictions tests. This is all done for models in which some regressors may be either strictly exogenous, predetermined or endogenous. Surprisingly, particular asymptotically optimal and relatively robust weighting matrices are found to be superior in finite samples to ostensibly more appropriate versions. Most of the variants of tests for overidentification restrictions show serious deficiencies. A recently developed modification of GMM is found to have great potential when the cross-sectional heteroskedasticity is pronounced and the time-series dimension of the sample not too small. Finally all techniques are employed to actual data and lead to some profound insights.

Ambitious biodiversity goals to protect 30% or more of the Earth’s surface by 2030 (30x30) require strategic near-term targets. To define areas that must be protected to prevent the most likely and imminent extinctions, we propose Conservation Imperatives—16,825 unprotected sites harboring rare and threatened species and spanning ~164 Mha of the terrestrial realm. We estimate that protecting the Conservation Imperatives would cost approximately US$169 billion [90% probability: $146 — $228 billion]. Globally, 38% of the 16,825 sites are either adjacent to or within 2.5 km of an existing protected area, potentially reducing land acquisition and management costs. These sites should be prioritized for conservation action over the next five years as part of a broader strategy to expand the global protected area network. The expansion of global protected areas between 2018–2023 incorporated only 7% of sites harboring range-limited and threatened species, highlighting a renewed urgency to conserve these habitats. Permanently protecting only 0.74% of land found in the tropics, where Conservation Imperatives are concentrated, could prevent the majority of predicted near-term extinctions once adequately resourced. We estimate this cost to be US$29 billion to US$46 billion per year over the next five years. Multiple approaches will be required to meet long-term protection goals: providing rights and title to Indigenous Peoples and Local Communities (IPLCs) conserving traditional lands, government designation of new protected areas on federal and state lands, and land purchase or long-term leasing of privately held lands.

Abstract: Power generation using dielectric elastomer (DE) artificial muscle is attracting attention because of its light weight, low cost, and high efficiency. Since this method is a system that produces electricity without emitting carbon dioxide nor using rare earths, it would contribute to the goal of environmental sustainability. In this paper, the background of DEs, the associated high-efficient wave energy generation (WEG) systems that we developed using DEs, as well as the latest development of its material are summarized. By covering the challenges we face and the achievements that we’ve reached, we can discuss the opportunities to build the foundation of a recycled energy society through the usage of these WEGs. On the other hand, to make these possibilities commercially successful, the advantages of DEs need to be integrated with traditional technologies. To achieve this, we also consider the method of using DEs alone and a system used in combination with an oscillating water column. Finally, the current status and future of DEGs are discussed.

The current globally dominant SARS-CoV-2 variants are showing immune escape and reduced susceptibility to antiviral drugs. Therefore, agencies responsible for drug evaluation and regula-tion such as the FDA and EMA are revising their emergency authorization use of several COVID-19 neutralizing antibodies. These NAbs proved to be unlikely effective against new variants espe-cially Omicron descendants and several pharmaceutical companies are pursuing the development of more potent neutralizing antibodies. To address the issue of using in silico prediction for the rapid assessment of anti-SARS-CoV-2 MAbs neutralization power, we used a computational method we developed previously, to evaluate 10 SARS-CoV-2 antibodies propensity to neutralize the new Omicron’s subvariants Eris (EG.5) and Pirola (BA.2.86) based on comparative binding affinity and previous experimental and clinical observations. Nine of these MAbs were once granted emergency use authorization, and one is currently under clinical investigation. The rapid, cost-effective in silico evaluation provided reliable predictions consistent with published clinical and experimental data. Furthermore, our data showed new potential therapeutic MAbs combi-nation that could be effective for the treatment countermeasure of the new Omicron’s subvariants Eris (EG.5) and Pirola (BA.2.86).

As variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, assessment of vaccine immunogenicity remains a critical factor to support continued vaccination. To this end, an in vitro microneutralization (MN50) assay was validated to quantitate SARS-CoV-2 neutralizing antibodies against ancestral and variant strains (Beta, Delta, Omicron BA.1, Omicron BA.5 and XBB.1.5) in human serum. For ancestral strain, the MN50 assay met acceptance criteria for inter-/intra-assay precision, specificity, linearity, and selectivity. The assay was robust against changes to virus/serum incubation time, cell seeding density, virus content per well, cell passage number, and serum interference. Analyte in serum samples was stable up to 5 freeze/thaw cycles and for up to 12 months of storage at –80 ± 10 °C. Similar results were observed for the variant-adapted MN50 assays. The conversion factor to convert assay result units to WHO international standard units (IU/mL) was determined to be 0.62 for the ancestral prototype strain. This MN50 assay will be useful for vaccine immunogenicity analyses in clinical trial samples, enabling assessment of vaccine immunogenicity for ancestral and variant strains as variant-adapted vaccines are developed.

Despite successful vaccination efforts, the emergence of new SARS-CoV-2 variants poses ongoing challenges to control COVID-19. Understanding humoral responses concerning SARS-CoV-2 infections and their impact is crucial for developing future vaccines that are effective worldwide. Here, we identified 41 immunodominant linear IgG B-cell epitopes in its Spike glycoprotein with a SPOT synthesis peptide array probed with a pool of serum from hospitalized COVID-19 patients. Bioinformatics showed a restricted set of epitopes unique to SARS-CoV-2 compared to other coronavirus family members. Potential crosstalk was also detected with Dengue virus (DENV), confirmed by screening individuals infected with DENV before the COVID-19 pandemic in a commercial ELISA assay for anti-SARS-CoV-2 antibodies. Higher reactivity indices were often measured in individuals with a pre-pandemic dengue infection than those with COVID-19. A high-resolution evaluation of antibody reactivity against peptides representing epitopes in the spike protein identified ten sequences in the NTD, RBD, and S2 domains. Functionally, antibody-dependent enhancement (ADE) in SARS-CoV-2 infection of monocytes was observed with pre-pandemic dengue-positive sera. A significant increase in viral load was measured compared to controls, with no detectable neutralization or considerable cell death, suggesting its role in viral entry. This study highlights the importance of identifying the epitopes generated during the humoral response to a pathogenic infection to understand the potential interplay of previous and future conditions on disease. Vaccine development and optimization strategies should be mindful of the potential for A.D.E. that could differ geographically due to endemic biological risks.

This proposal was prepared in the very first weeks of 2020 because of the outbreak of COVID-19. There are good reasons to suppose that rotavirus vaccine can be used as protection tool to effectively and safely fight and mitigate SARS-CoV-2 infection and the impact caused by COVID- 19 in adult humans, due to the development of cross and trained immunity following rotavirus vaccination. Up-to-date, some rotavirus vaccines are available and approved, two of them have a large experience in results and safety. Little experience has been achieved in the use of rotavirus vaccine in adults. However, it can be expected that it would be safe and effective in adults and in the elderly as well. This proposal explains the background of this hypothesis based on lungs and intestine relationships.

The use of analytical techniques is important and critical in all areas of REE research such as exploration, mining, extraction, and metallurgical activities at different stages. At every stage of these activities, rock, ore, mineral, and other related materials have to be analysed for their REE contents in terms of elemental, isotopic, and mineralogical concentrations using different analytical techniques. Spectacular developments have taken place in the area of analytical instrumentations during the last four decades, with some of them having shrunk in size and become hand-held. Among laboratory-based techniques, F-AAS, GF-AAS, ICP-OES, and MP-AES have become very popular. Because of high sensitivity, less interference effects, and ease of use. ICP-MS techniques such as quadrupole-ICP-MS, ICP-MS/MS, ICP-TOF-MS, MH-ICP-MS, HR-ICP-MS, and MC-ICP-MS, with both solution nebulisation as well as direct solid analysis using laser ablation sample introduction methods, have become extremely popular for REE analysis. For direct analysis of solids INAA, XRF, and LIBS techniques besides LA-based ICP-MS techniques are being extensively utilised. LIBS technique in particular requires little to no sample preparation. TIMS, SIMS, and SHRIMP techniques are being used for isotopic as well as dating REE depots. Portable analytical techniques such as pXRF, pLIBS, and Raman spectrometers are able to do in situ analysis even in the field helping to take fast decisions during exploration studies. At present hyperspectral remote sensing techniques including hand-held, drone, and satellite-based techniques have become very popular in REE exploration studies because of their ability to cover larger areas in a limited time and thus became very cost-effective. Deployment of microanalytical devices/sensors mounted in remotely operated vehicles (ROV) is being successfully utilized in detecting REE-rich deposits in the deep oceans. Providing updated in-depth information on all these important aspects with suitable examples, especially from the point of view of REE research studies is the focal point of this review article.

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) proteins are a diverse and evolutionarily conserved family of cytidine deaminases that provide a variety of functions from tissue-specific gene expression and immunoglobulin diversity to control of viruses and retrotransposons. APOBEC family expansion has been documented among mammalian species, suggesting a powerful selection for their activity. Enzymes with a duplicated zinc-binding domain often have catalytically active and inactive domains, yet both have antiviral function. Although APOBEC antiviral function was discovered through hypermutation of HIV-1 genomes lacking an active Vif protein, much evidence indicates that APOBECs also inhibit virus replication through mechanisms other than mutagenesis. Multiple steps of the viral replication cycle may be affected, although nucleic acid replication is a primary target. Packaging of APOBECs into virions was first noted with HIV-1, yet is not a prerequisite for viral inhibition. APOBEC antagonism may occur in viral producer and recipient cells. Signatures of APOBEC activity include G-to-A and C-to-T mutations in a particular sequence context. The importance of APOBEC activity for viral inhibition is reflected in the identification of numerous viral factors, including Vif, which are dedicated to antagonism of these deaminases. Such viral antagonists often are only partially successful, leading to selection for viral variants.

Parkinson’s disease (PD) is characterized by motor deficits and a wide variety of non-motor symptoms. The age of onset, rate of disease progression and the precise profile of motor and non-motor symptoms display considerable individual variation. Neuropathologically, the loss of substantia nigra dopaminergic neurons is a key feature of PD. The vast majority of PD patients exhibit alpha-synuclein aggregates in several brain regions, but there is also great variability in the neuropathology between individuals. While the dopamine replacement therapies can reduce motor symptoms, current therapies do not modify the disease progression. Numerous clinical trials using a wide variety of approaches have failed to achieve disease modification. It has been suggested that the heterogeneity of PD is a major contributing factor to the failure of disease modification trials, and that it is unlikely that a single treatment will be effective in all patients. Precision medicine, using drugs designed to target the pathophysiology in a manner that is specific to each individual with PD, has been suggested as a way forward. PD patients can be stratified according to whether they carry one of the risk variants associated with elevated PD risk. In this review we assess current clinical trials targeting two enzymes, leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA), which are encoded by two most common PD risk genes. Because the details of the pathogenic processes coupled to the different LRRK2and GBA risk variants are not fully understood, we ask if these precision medicine-based intervention strategies will prove “precise“ or “personalized“ enough to modify the disease process in PD patients. We also consider at what phases of the disease that such strategies might be effective, in light of the genes being primarily associated with the risk of developing disease in the first place, and less clearly linked to the rate of disease progression. Finally, we critically evaluate the notion that therapies targeting LRRK2 and GBA might be relevant to a wider segment of PD patients, beyond those that actually carry risk variants of these genes.

Currently, there is increasing industrial demand for rare earth elements (REE) as these elements are now integral to the manufacture of many carbon-neutral technologies. The depleting REE ores and increasing mining costs are prompting to look for alternative sources for these valuable metals, particularly from waste streams. Although REE concentrations in most of the alternate resources are lower than current REE ores, some sources such as marine sediments, coal ash, and industrial wastes like red mud are looking promising with significant concentrations of REE in them. This review focuses on the alternative resources for REE such as ocean bottom sediments, continental shelf sediments, river sediments, stream sediments, lake sediments, phosphorites deposits, industrial waste products like red mud, and phosphogypsum, coal, coal fly ash, and related materials, waste rock sources from old and closed mines, acid mine drainage, and recycling of e-waste. Possible future Moon exploration and mining for REE and other valuable minerals are also discussed. It is evident that REE extractions from both primary and secondary ores alone are not adequate to meet the current demand, and sustainable REE recovery from the alternative resources described here is also necessary to meet the growing REE demand. An attempt is made to identify the potential of these alternative resources and sustainability challenges, benefits, and possible environmental hazards to meet the growing challenges in meeting the future REE requirements.

We study here what can be learned from our experience with COVID-19 vaccination for an initially naïve population, that can inform planning for vaccination against the next novel, highly transmissible pathogen. We focus on the first two pandemic years (wild strain through Delta), because after the Omicron wave in early 2022, few people were still SARS-CoV-2-naïve. Almost all were vaccinated, infected, or often both. We review the evidence on COVID-19 vaccine effectiveness (VE), waning effectiveness over time, and what we should expect about VE and waning from a future pathogen. As a basis for our analysis, we conducted a PRISMA-compliant review of all studies on PubMed through August 15, 2022 reporting VE against four endpoints: any infection, symptomatic infection, hospitalization, and death, for the four principal vaccines used in developed Western countries (BNT162b2, mRNA1273, Ad26.CoV2.S, and ChAdOx1-S). The mRNA vaccines (BNT162b2, mRNA1273) had high initial VE against all endpoints but protection waned after approximately six months, with BNT162b2 declining faster than mRNA1273. Both mRNA vaccines initially outperformed the viral vector vaccines. A third “booster” dose, roughly six months after the primary doses, substantially reduced symptomatic infection, severe disease, and mortality, and in hindsight should be seen as part of the normal vaccination schedule.

There are currently around 78 Nuclear Power Plants (NPP) in the world based on Boiling Water Reactors (BWR). The current parameter to assess BWR instability issues is the linear Decay Ratio (DR). However, it is well known that BWRs are complex non-linear dynamical systems that may even exhibit chaotic dynamics that normally preclude the use of the DR when the BWR is working at a specific operating point during instability. In this work a novel methodology based on an adaptive Shannon Entropy estimator and on Noise Assisted Empirical Mode Decomposition variants is presented. This methodology was developed for real-time implementation of a stability monitor. This methodology was applied to a set of signals stemming from several NPPs reactors (Ringhals-Sweden, Forsmark-Sweden and Laguna Verde-Mexico) under commercial operating conditions, that experienced instabilities events, each one of a different nature

Accurate diagnosis for the 400 million people with rare diseases is critical for healthcare decisions, prognosis, understanding disease mechanisms, and identification of treatments. Despite advances in genome sequencing, barriers such as high interpretation costs, diagnostic expertise, throughput associated delays, and uncertain variant classifications persist, with demand exceeding capacity. Many variant classification methods focus narrowly on specific consequences, leading to the use of complex integrative pipelines that often overlook transcript variability and lack prediction transparency. To overcome these limitations, we introduce DITTO. This transparent, transcript-aware machine-learning method demonstrates superior overall performance in accuracy, recall, and precision when compared to existing tools. DITTO is publicly available at https://github.com/uab-cgds-worthey/DITTO

Most of the commonly used Ionic Liquids (ILs) contain bulky organic cations with suitable anions. With our COMPLET (Concept of Melting Point Lowering due to Ethoxylation), we follow a different approach. We use simple, low-toxic, cheap and commercially available anions of the type Cx(EO)yCH2COO– to liquefy presumably any simple metal ion, independently of its charge. In the simplest case, the cation can be sodium or lithium, but synthesis of Ionic Liquids is also possible with cations of higher valences such as transition or rare earth metals. Anions with longer alkyl chains are surface active and form surface active ionic liquids (SAILs), which combine properties of ionic and nonionic surfactants at room temperature. They show significant structuring even in their pure state, i.e. in the absence of water or any other added solvent.

This proposal was prepared in the very first weeks of 2020 because of the outbreak of COVID-19.There is good reason to suppose that rotavirus vaccine can be used as protection tool to effectively and safely fight and mitigate SARS-CoV-2 infection and the impact caused by COVID-19 in adult humans, due to the development of cross and trained immunity following rotavirus vaccination. Up-to-date, some rotavirus vaccines are available and approved, two of them have a large experience in results and safety. Little experience has been achieved in the use of rotavirus vaccine in adults. However, it can be expected that it would be safe and effective in adults and in the elderly as well. This proposal explains the background.

Chromothripsis is a mutational mechanism leading to complex and relatively clustered chromosomal rearrangements resulting in diverse phenotypic outcomes depending on the involved genomic landscapes. It may occur both in the germ and the somatic cells resulting in congenital and developmental disorders and cancer, respectively. Asymptomatic individuals may be carriers of chromotriptic rearrangements and experience recurrent reproductive failures when two or more chromosomes are involved. Several mechanisms are postulated to underly chromothripsis. The most attractive hypothesis involves chromosome pulverization in micronuclei followed by incorrect reassembly of fragments through DNA repair to explain the clustered nature of the observed complex rearrangements. Moreover, exogenous or endogenous DNA damage induction and dicentric bridge formation may be involved. Chromosome instability is commonly observed in the cells of patients with DNA-repair disorders, such as ataxia telangiectasia, Nijmegen breakage syndrome and Bloom syndrome. In addition, germline variations of TP53 have been associated with chromothripsis in Sonic-Hedgehog medulloblastoma and acute myeloid leukemia. In the present review, we focus on the underlying mechanisms of chromothripsis and the involvement of defective DNA-repair genes resulting in chromosome instability and chromothripsis-like rearrangements.

Current prenatal genetic evaluation showed a significantly increase in non-invasive screening and the reduction of invasive diagnostic procedures. To evaluate the diagnostic efficacy on detecting common aneuploidies, structural chromosomal rearrangements and pathogenic copy number variants (pCNV), we performed a retrospective analysis on a case series initially analyzed by aneuvysion fluorescence in situ hybridization (FISH) and karyotyping then followed by array comparative genomic hybridization (aCGH). Of the 386 cases retrieved from the past decade, common aneuploidies were detected in 137 cases (35.5%), other chromosomal structural rearrangements were detected in four cases (1%), and pCNV were detected in five cases (1.3%). The relative frequencies for common aneuploidies suggested a under detection of sex chromosome aneuploidies. Approximately 9.5% of cases with common aneuploidies showed a mosaic pattern. Inconsistent results between FISH and karyotyping were noted in cases with pseudo-mosaicism introduced by culture artifact or variable cellular proliferation from cells with mosaic karyotypic complements under in vitro cell culture. Based on findings from this case series, cell-based FISH and karyotyping should be performed to detect common aneuploidies, structural chromosomal abnormalities, and mosaic pattern. DNA-based aCGH and reflex FISH should be performed to detect and confirm genomic imbalances and pCNV. Practice points to ensure the diagnostic accuracy and efficacy were summarized.