Genome-wide association studies (GWAS) have successfully revealed many disease-associated genetic variants. For a case-control study, the adequate power of an association test can be achieved with a large sample size, although genotyping large samples is expensive. A cost‐effective strategy to boost power is to integrate external control samples with publicly available genotyped data. However, the naïve integration of external controls may inflate the type I error rates if ignoring the systematic differences (batch effect) between studies, such as the differences in sequencing platforms, genotype calling procedures, population stratification, and so forth. To account for the batch effect, we propose an approach by integrating External Controls into the Association Test by Regression Calibration (iECAT-RC) in case-control association studies. Extensive simulation studies show that iECAT-RC not only can control type I error rates but also can boost statistical power in all models. We also apply iECAT-RC to the UK Biobank data for M72 Fibroblastic disorders by considering genotype calling as the batch effect. Four SNPs associated with Fibroblastic disorders have been detected by iECAT-RC and the other two comparison methods. However, our method has a higher probability of identifying these significant SNPs in the scenario of an unbalanced case-control association study.

Sorghum (Sorghum bicolor L.) ranks fifth as the most crucial cereal crop globally, yet its seed morphology remains relatively unexplored. This study investigated seed morphology in sorghum based on 115 mini core and 130 Senegalese germplasms. Eight seed morphology traits encompassing size, shape, and color parameters were assessed. Statistical analyses explored potential associations between these traits and resistance to three major sorghum diseases: anthracnose, head smut, and downy mildew. Furthermore, genome-wide association studies (GWAS) were conducted using phenotypic data from over 24,000 seeds and over 290,000 publicly available single nucleotide polymorphisms (SNPs) through the Genome Association and Prediction Integrated Tool (GAPIT) R package. Significant SNPs associated with various seed morphology traits were identified and mapped onto the reference sorghum genome to identify novel candidate defense genes.

Callus induction (CI) is the critical trait for the transformation of desirable genes in plants. A genome-wide association study (GWAS) analysis was conducted on the rice germplasm of 110 diverse indica rice accessions. Three tissue culture media, including B5, MS, and N6, were used for CI in those rice panels. Seven quantitative trait loci (QTLs) on chromosomes 2, 6, 7, and 11 were found to confer a CI percentage in these three media. For the B5 medium, one QTL (qCI-B5-Chr6) was identified on the rice chromosome 6. For the MS medium, two QTLs were identified on the rice chromosomes 2 and 6 (qCI-MS-Chr2 and qCI-MS-Chr6, respectively). For the N6 medium, four QTLs were identified on the rice chromosomes 6, 7, and 11 (qCI-N6-Chr6.1, qCI-N6-Chr6.2, qCI-N6-Chr7, and qCI-N6-Chr11, respectively). Fifty-five genes were identified within the haplotype blocks corresponding to these QTLs. Thirty-one genes showed haplotypes associated with different CI in those media. The qCI-B5-Chr6 was located in the same region as the qCI-N6-Chr6.2. The caleosin-related family protein was identified in this region. Analysis of the gene-based haplotype reveals the association of this gene with different CI in both B5 and N6 media, suggesting that the gene may play a critical role in the CI mechanism. Moreover, several genes, including the beta-tubulin, the zinc finger proteins, the RNP-1 domain-containing protein, and the Lysophosphatidic acid acyltransferase, were associated with different CI in the N6 media. Results from this study provide insight into the potential QTLs and candidate genes for callus induction in rice that will fulfill the understanding of the physiological and biochemical processes involved in callus formation, which is an essential tool in the molecular breeding of rice.

(1) Background: The goal of our study was to identify SNPs, metabolic pathways (KEGG), and gene ontology (GO) terms significantly associated with calving and workability; (2) Methods: Based on the EuroGenomics reference data set, we analyzed direct (DCE) and maternal (MCE) calving ease, direct (DSB), and maternal (MSB) stillbirth, milking speed (MSP), and temperament (TEM). We estimated SNP effects using a multi-SNP mixed-model. Further, SNP positions were mapped to genes, and GO terms/KEGG pathways of the corresponding genes were assigned. The estimation of GO term/KEGG pathway effects was based on a mixed-model using SNP effects as dependent variables; (3) Results: The number of significant SNPs comprised 59 for DCE, 25 for DSB and MSP, 17 for MCE and MSB, and 7 for TEM. Significant KEGG pathways were found for MSB (2), TEM (2), and MSP (1), while 11 GO terms were significant for MSP, 10 for DCE, 8 for DSB and TEM, 5 for MCE, and 3 for MSB.; (4) Conclusions: From the perspective of a better understanding of the genomic background of the phenotypes, traits with low heritabilities suggest that the focus should be moved from single genes to metabolic pathways or gene ontologies significant for the phenotype.

Powdery mildew (PM), caused by the fungal pathogen Blumeria graminis f. sp. tritici (Bgt), significantly threatens global bread wheat production. Although the use of resistant cultivars is an effective strategy for managing PM, currently available wheat cultivars lack sufficient levels of resistance. To tackle this challenge, we conducted a comprehensive genome-wide association study (GWAS) using a diverse panel of 286 bread wheat genotypes. Over three consecutive years (2020-21, 2021-22, and 2022-23), these genotypes were extensively evaluated for PM severity under field conditions following inoculation with virulent Bgt isolates. The panel was previously genotyped using the Illumina 90K SNP Infinium iSelect SNP assay to obtain genome-wide SNP marker coverage. By applying FarmCPU, a multilocus mixed model, we identified a total of 113 MTAs located on chromosomes 1A, 1B, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 6B, 7A, and 7B at a significance level of p≤0.001. Notably, four novel MTAs on chromosome 6B were consistently detected in 2020-21 and 2021-22 environments. Furthermore, within the confidence intervals of the identified SNPs, we identified 96 candidate genes belonging to different proteins including 12 disease resistance/host-pathogen interactions related protein families. Among these, protein kinases, leucine-rich repeats, and zinc finger proteins, were of particular interest due to their potential roles in PM resistance. These identified loci can serve as targets for breeding programs aimed at developing disease-resistant wheat cultivars.

Background: Thousands of genetic variants have been associated with hematological traits, though target genes remain unknown at most loci. Also, limited analyses have been conducted in African ancestry and Hispanic/Latino populations; hematological trait associated variants more common in these populations have likely been missed. Methods: To derive gene expression prediction models, we used ancestry-stratified datasets from the Multi-Ethnic Study of Atherosclerosis (MESA, including N=229 African American and N=381 Hispanic/Latino participants, monocytes) and the Depression Genes and Networks study (DGN, N = 922 European ancestry participants, whole blood). We then performed a transcriptome-wide association study (TWAS) for platelet count, hemoglobin, hematocrit, and white blood cell count in African (N = 27,955) and Hispanic/Latino (N = 28,324) ancestry participants. Results: Our results revealed 24 suggestive signals (p < 1×10^(-4)) that were conditionally distinct from known GWAS identified variants and successfully replicated these signals in European ancestry subjects from UK Biobank. We found modestly improved correlation of predicted and measured gene expression in an independent African American cohort (the Genetic Epidemiology Network of Arteriopathy (GENOA) study (N=802), lymphoblastoid cell lines) using the larger DGN reference panel; however, some genes were well predicted using MESA but not DGN. Conclusions: These analyses demonstrate the importance of performing TWAS and other genetic analyses across diverse populations and of balancing sample size and ancestry background matching when selecting a TWAS reference panel.

The development of modern genomic tools has sped up the breeding program of food crops. More recently, genomic resources are being developed for tropical forages and will be key resources for developing climate resilient high yielding forage varieties. In this study, we present a genome-wide association study for biomass yield and feed quality traits in buffel grass (Cenchrus ciliaris L. aka Pennisetum ciliare L.,). Genome-wide markers generated using the DArTSeq platform and mapped onto the reference genome of Setaria italica were used for the genome-wide association study. The results revealed several markers associated with biomass yield and feed quality traits. A total of 78 marker trait associations were identified with R2 values ranging from 0.138 to 0.236. The marker trait associations were distributed across different chromosomes. Of these associations, the most marker trait associations (23) were observed on Chr9, followed by Chr5 with 12. The fewest number of marker trait associations were observed on Chr4 with 2. In terms of traits, 17 markers were associated with biomass yield, 24 with crude protein, 26 with TDN, 14 with ADF, 10 with NDF and six with DMI. Twenty of the identified markers were associated with at least two traits. The identified marker trait associations provide a useful genomic resource for future improvement and breeding of buffel grass.

Ningxiang pigs exhibit a diverse array of fatty acids, making them an intriguing model for exploring the genetic underpinnings of Fatty acid metabolism. In this study, we conducted a genome-wide association study using a dataset comprising 50,697 SNPs and samples from over 600 Ningxiang pigs. Our investigation yielded novel candidate genes linked to five saturated fatty acids (SFAs), four monounsaturated fatty acids (MUFAs), and five polyunsaturated fatty acids (PUFAs). Re-markably, 37, 21, and 16 SNPs showed significant associations with SFAs, MUFAs, and PUFAs, respectively. Notably, ALGA0047587, H3GA0046208, DRGA0016063, and ALGA0031262 demonstrated substantial phenotypic variance (≥ 30%) in Arachidic acid (C20:0), Elaidic Acid (C18:1n-9(t)), and Arachidonic acid (C20:4n-6), respectively. Several significant SNPs were posi-tioned proximally to previously reported genes. In total, we identified 11, 6, and 5 candidate genes associated with SFAs, MUFAs, and PUFAs, respectively. These findings hold great promise for advancing breeding strategies aimed at optimizing meat quality and enhancing lipid metabolism within the intramuscular fat (IMF) of Ningxiang pigs.

Background: Telomere length (TL) shortening process is associated with several known environment and individual determinants. DNA methylation is the most studied epigenetic process and may be associated with TL. We investigated the associations between DNA methylation and TL in peripheral blood. Methods: Methylation wide association study was conducted in 47 women (37.1±8.8 years) with different nutritional status. Association between TL and DNA methylation levels were explored by univariate and multiple linear regression models, corrected by age and Body Mass Index. Corrections for multiple comparisons by Benjamini‐Hochberg test was also performed. WEBGestalt was used to identify pathways that are responsible for regulating TL. Results: We found negative correlations between TL and BMI (r = -0.641; p = 0.001), abdominal circumference (r = -0.622; p = 0.001) and fat mass (r = -0.656; p = 0.001). 44 CpGs sites were associated with TL, independent of age and BMI. The most of these sites were negatively correlated with TL. For the 7 remained sites, DNA hypomethylation were associated with shorter TL. These CpGs were related to nine different pathways, including thermogenesis, cancer, glutamatergic and serotonergic synapse. Conclusion: There is an epigenetic contribution in TL, independent of nutritional status and age. Genes related to TL are involved in important metabolic pathways.

At least 50% of factors predisposing to alcohol dependence (AD) are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic functional annotation of associated genomic regions in male and female patients with AD and eight related clinical measures. A genome-wide significant association of rs220677 with AD (p-value = 1.33×10^-8 calculated with the Yates-corrected Chi-square test under the assumption of dominant inheritance) was discovered in female patients. Associations of AD and related clinical measures with seven other single nucleotide polymorphisms listed in previous GWAS of psychiatric and addiction traits were differently replicated in male and female patients. The bioinformatic analysis showed that regulatory elements in the eight associated linkage disequilibrium blocks define the expression of 80 protein-coding genes. Nearly 68% of these and of 120 previously published coding genes associated with alcohol phenotypes directly interact in a single network. This study indicates that a number of genes behind the pathogenesis of AD are different in male and female patients, but implicated molecular mechanisms are functionally connected. The results also suggest the genetic basis of sex-specific psychiatric comorbidities of AD.

Control of Tropical Theileriosis, a tick-borne disease with a strong impact on cattle breeding, can be facilitated by using marker-assisted selection in breeding programs. Genome-wide association studies (GWAS) using high-density arrays are extremely important for the ongoing process of identifying genomic variants associated with resistance to Theileria annulata infection. In this work, Single Nucleotide Polymorphisms (SNPs) were analyzed in the Portuguese autochthonous cattle breeds Alentejana and Mertolenga. In total, 14 SNPs suggestive of significance (p ≤ 10-4) were identified for Alentejana cattle and 20 SNPs for Mertolenga cattle. The genomic regions around these SNPs were further investigated for annotated genes and Quantitative trait loci (QTLs) previously described by other authors. Regarding the Alentejana breed, the MAP3K1, CMTM7, SSFA2, and ATG13 genes are located near suggestive SNPs and appear as candidate genes for resistance to Tropical Theileriosis, considering its action the immune response and resistance to other diseases. On the other hand, in the Mertolenga breed, the UOX gene is also a candidate gene due to its apparent link to the pathogenesis of the disease. These results may represent a first step towards the possibility of including genetic markers for resistance to Tropical Theileriosis in current breed selection programs.

Meloidogyne javanica causing root-knot nematode in soybean is an important problem in soybean areas, leading to several yield losses. Some accessions have been identified carrying resistance loci to this nematode specie. In this study, a set of 317 soybean accessions were characterized for resistance to M. javanica. Genome-wide association study (GWAS) was performed using SNPs from genotyping-by-sequencing (GBS), and a region of 29.2 Kbp on chromosome 13 was identified. The haplotype analysis showed that SNPs were able to discriminate susceptible and resistant accessions, leading to 25 accessions sharing the resistance locus. Furthermore, 5 accessions may be new M. javanica resistance sources. The screening of the SNPs in the USDA soybean germplasm showed that several accessions previous reported as resistance to other nematodes also showed the resistance haplotype on chromosome 13. High levels of concordance among the phenotypes of Brazilian cultivars and the SNPs in chromosome 13 were observed. A in silico analysis of the mapped region on soybean genome revealed a presence of 5 genes with structural similarity with major resistance genes. The expression levels of the candidate genes in the interval demonstrated a potential pseudogene, and other two model genes up-regulated in the resistance source after pathogen infection. The SNPs associated to the region conferring resistance is a important tool for introgression of the resistance by marker-assisted selection in soybean breeding programs.

A genome-wide association study (GWAS) was performed on a set of 260 lines which belong to three different bi-parental flax mapping populations. These lines were sequenced to an averaged genome coverage of 19× using the Illumina Hi-Seq platform. Phenotypic data for 11 seed yield and oil quality traits were collected in eight year/location environments. A total of 17,288 single nucleotide polymorphisms were identified, which explained more than 80% of the phenotypic variation for days to maturity (DTM), iodine value (IOD), palmitic (PAL), stearic, linoleic (LIO) and linolenic (LIN) acid contents. Twenty-three unique genomic regions associated with 33 QTL for the studied traits were detected, thereby validating four genomic regions previously identified. The 33 QTL explained 48-73% of the phenotypic variation for oil content, IOD, PAL, LIO and LIN but only 8-14% for plant height, DTM and seed yield. A genome-wide selective sweep scan for selection signatures detected 114 genomic regions that accounted for 7.82% of the flax pseudomolecule and overlapped with the 11 GWAS-detected genomic regions associated with 18 QTL for 11 traits. The results demonstrate the utility of GWAS combined with selection signatures for dissection of the genetic structure of traits and for pinpointing genomic regions for breeding improvement.

Machine learning, including deep learning, reinforcement learning, and generative artificial intelligence are revolutionising every area of our lives when data is made available. With the help of these methods, we can decipher information from larger datasets while addressing the complex nature of biological systems in a more efficient way. Although machine learning methods have been introduced to human genetic epidemiological research as early as 2004, those were never used to their full capacity. In this review, we outline some of the main applications of machine learning to assigning human genetic loci to health outcomes. We summarise widely used methods and discuss their advantages and challenges. We also identify several tools, such as Combi, GenNet and GMSTool, specifically designed to integrate these methods for hypothesis-free analysis of genetic variation data. We elaborate on the additional value and limitations of these tools from a geneticist’s perspective. Finally, we discuss the fast-moving field of foundation models and large multi-modal omics biobank initiatives.

While DNA serves as the fundamental genetic blueprint for an organism, it is not a static entity. Gene expression, the process by which genetic information is utilized to create functional products like proteins, can be modulated by a diverse range of environmental factors. Epigenetic mechanisms, encompassing DNA methylation, histone modification, and microRNAs, play a pivotal role in mediating the intricate interplay between the environment and gene expression. Intriguingly, alterations in the epigenome have the potential to be inherited across generations. Ethanol abuse poses significant health issues worldwide. Ethanol has the capability to induce changes in the epigenome, which can be inherited by offspring, thus impacting them even in the absence of direct ethanol exposure. This review article reviewed the alterations caused by ethanol on the epigenome. We thoroughly gathered all relevant papers investigating the behavioral and molecular consequences of parental ethanol exposure on their offspring. In conclusion, the comprehensive analysis of the literature supports the notion that ethanol exposure induces lasting epigenetic alterations, which can influence the behavior and health of future generations. This knowledge emphasizes the significance of addressing the potential transgenerational effects of ethanol and highlights the importance of preventive measures to minimize the adverse impact on offspring.

Fat has a high energy density and excessive fatness has been recognized as a problem for egg production and the welfare of chickens. The identification of a genetic polymorphism controlling fat deposition would be helpful to select against excessive fatness in the laying hen. This study aimed to estimate genomic heritability and identify the genetic architecture of abdominal fat deposition in a population of chickens from a Dongxiang blue-shelled local breed crossbred with the White Leghorn. A genome-wide association study wase conducted on abdominal fat percentage, egg production and body weights using a sample of 1534 hens genotyped with a 600K Chicken Genotyping Array. The analysis yielded a heritability estimate of 0.19 ± 0.04 for abdominal fat percentage, 0.56 ± 0.04 for body weight at 72 weeks, 0.11 ± 0.03 for egg production and 0.24 ± 0.04 for body weight gain. The genetic correlation of abdominal fat percentage with egg production between 60 and 72 weeks of age was 0.35 ± 0.18. This implies a potential trade-off between these two traits related to allocation of resource. Strong positive genetic correlations were found between fat deposition and weight traits. A promising locus close to COL12A1 on chromosome 3, associated with abdominal fat percent, was found in the present study. The other region located around HTR2A on chromosome 1, where allele substitution was predicted to be associated with body weight gain, accounted for 2.9% of phenotypic variance. Another region located on chromosome 1, but close to SOX5, was associated with egg production. These results may be used to influence the balanced genetic selection for laying hens.

Japanese apricot (Prunus mume) is a culturally and economically important fruit tree in East Asia. ‘Nanko’, the primary cultivar of the Japanese apricot well known in Japan, usually suffers from scab, a disease caused by Venturia carpophila. Scab results in the development of black spots on the fruit surface, which considerably reduces its commercial value. Despite being an economic concern for Japanese apricot, there have been few reports on the phenotypic variation in scab resistance/susceptibility, the underlying genetic factors, and the development of DNA markers. Therefore, in this study, we performed a comprehensive trait analysis for scab resistance and susceptibility for four years and conducted a genome-wide association study (GWAS) to identify the associated loci. The results showed that significant GWAS peaks were detected in 2017 and 2018. Promising candidate gene encoding domains associated with disease resistance were found at the nine single-nucleotide polymorphisms (SNPs) identified in 2017 and 2018. These SNPs were thought to be associated with scab susceptibility of ‘Nanko’ lineages. These findings shed light on the mechanisms of scab resistance in P. mume and will assist future breeding programs to improve scab resistance in ‘Nanko’ lineages.

Abstract. Introduction: BMD study gives partial information on bone health in patients with TSH suppression therapy due to Differentiated Thyroid Cancer (DTC). TBS, a new parameter of bone microarchitecture is propose for bone quality study. This study analyze their long-term use in patients with DTC. Methods: BMD was measured by DXA and TBS with iNsigth software in 145 postmenopausal DTC patients. Vertebral Fractures (VFs) with a semi-quantitative x-ray method. Results: BMD at the end study was not different from initial. TBS decreased from 1.35±0.1 to 1.27±0.1 (p=0.002). PTH, Osteocalcin, and BAP were increased, suggesting increased bone remodeling. There was an increase in osteoporosis and osteopenia (40.6% and 16.5% to 46.6% and 18.6%); 31% had partially degraded and 15.1% degraded TBS changed to 48,9% and 24,8% at the end study. VFs in 30 patients, was not different in age, BMI, calcium and alcohol ingestion, smoking, radioiodine, or thyroid parameters vs. without VFs. Odds ratio for VFs increased with osteopenia (OR 2.63). Combination of TBS plus TBS did not improve discrimination. Conclusions: TBS was lowered while BMD did not differ. Percentage of osteoporosis and osteopenia and of partially degraded and degraded TBS was higher at the end study. Predominant discordance rate was found in partially degraded microarchitecture, in which the proportion of osteopenia was higher than normal or osteoporotic patients. AUC of TBS plus BMD did not improve discrimination. TBS, radioactive iodine, and sedentary lifestyle were the main differential data for patients with DTC and VFs.

Middle East region experiences a high prevalence of hypovitaminosis D, yet most genetic studies on Vitamin D have focused on European populations. Furthermore, there is a lack of research on the genomic risk factors affecting the elderly population, who are more susceptible to health burden. We investigated the genetic determinants of 25-hydroxyvitamin D levels in elderly Lebanese individuals (n=199) through a whole exome-based genome-wide association study. We identified new loci with suggestive evidence of an association with Vitamin D levels, including rs141064014 in the MGAM gene (P-value of 4.40 × 10−06) and rs7036592 in PHF2 (P-value of 8.43 × 10−06). A meta-analysis of the Lebanese data and the largest European genome-wide association study confirmed consistence replication of numerous variants, including rs2725405 in SLC38A10 (P-value of 3.73 x 10-08). Despite the lower performance of European-derived polygenic risk scores compared to the European estimations, it still effectively predicted Vitamin D deficiency among elderly Lebanese individuals. Our findings provide novel insights into the genetic mechanisms of Vitamin D deficiency in Middle Eastern elderly populations, facilitating the development of personalized approaches for more effective management of hypovitaminosis D. Additionally, we demonstrated that whole exome-based genome-wide association study is an effective method for identifying genetic components associated with phenotypes.

For the different harvest targets, the requirement for the prolificacy trait of maize was also different, so prolificacy is of great significance for modern production. Although some QTLs and genes associated with prolificacy in teosinte have been reported, the genetic mechanism of prolificacy in maize has not been fully elucidated. In this study, two RIL populations and GWAS population were used to genetic research of prolificacy trait in maize, with multi-environment. Combine linkage analysis and Genome-wide association study has identified a total of 13 QTLs and 8 significant SNPs. There were two genes related to tissue differentiation in the stable QTL qP9-2, and two significant SNPs corresponding to three genes were in QTL qP5-1 and QTL qP7-1, respectively. Four candidate genes GRMZM2G317262, GRMZM2G317584, GRMZM5G882364 and GRMZM2G141679 were finally screened out by qRT-PCR analysis. Based on the function of candidate genes, ethylene signaling pathway plays an important role in the formation of prolificacy in maize. It has deepened our understanding of the formation mechanism of prolificacy and laid a foundation for breeding new varieties with various prolificacy in maize.

New flaxseed cultivars differing in seed mucilage content (MC) with low hull content (HC) represent an attractive option to simultaneously target the food and feed markets. Here, a genome-wide association study (GWAS) was conducted for MC and HC in 200 diverse flaxseed accessions genotyped with 1.7 million SNP markers. The data obtained for MC and HC indicated a broad phenotypic variation and high (~70%) and a moderate (~49%) narrow sense heritability, respectively. MC and HC did not differ statistically between fiber and oil morphotypes, but yellow-seeded accessions had 2.7% less HC than brown-seeded ones. The genome wide linkage disequilibrium (LD) decayed to r2 = 0.1 at a physical distance of ~100 Kb. Seven and four QTL were identified for MC and HC, respectively. Promising candidate genes included Linum usitatissimum orthologs of the Arabidopsis thaliana genes TRANSPARENT TESTA 8, SUBTILISIN-LIKE SERINE PROTEASE, GALACTUROSYL TRANSFERASE-LIKE 5, MUCILAGE-MODIFIED 4, AGAMOUS-LIKE MADS-BOX PROTEIN AGL62, GLYCOSYL HYDROLASE FAMILY 17 and UDP-GLUCOSE FLAVONOL 3-O-GLUCOSYLTRANSFERASE that have been shown to play a role in mucilage synthesis and release, seed coat development and anthocyanin biosynthesis in A. thaliana were identified. The favorable alleles will be useful in flaxseed breeding towards the goal of achieving the ideal flaxseed cultivars for food and feed by genomic-based breeding.

Background: Pancreatic neuroendocrine tumors (pNETs) represents a rare subset of pancreatic cancer. Functional tumors caused hormonal changes and clinical syndromes, while non-functional ones are often diagnosed late. Surgical management need a multidisciplinary planning, involving enucleation, distal pancreatectomy with or without spleen preserving, cen-tral pancreatectomy, pancreaticoduodectomy or total pancreatectomy. Minimally invasive ap-proach increased in the last decade compared to the open technique. The aim of this study is to analyze current diagnostic and surgical trends for pNETs, to identify better interventions and their outcomes. Methods: The study adhered to PRISMA guidelines, conducting a systematic review of literature from May 2008 to March 2022 across multiple databases. Several combinations of keywords was used ("NET", "pancreatic", "surgery", "laparoscopic", "minimally invasive", "robotic”, “enuclea-tion”,“parenchima sparing”) and relevant article references was manually checked. Manuscript quality was evaluated. Results: The study screened 3867 manuscripts, twelve studies were selected, primarily from Ita-ly, the United States, and China. A total of 7767 surgical treated patients was collected from 160 included centers. The mean age was 56,3 y.o. Enucleations (EN) and distal pancreatectomy (DP) was the most common performed surgery and represents 43.4% and 38.6% of the total interven-tions, respectively. Pancreatic fistula, post operative bleeding, re-operation and follow up was recorded and analyzed. Conclusions: Enucleation show better postoperative outcomes and lower mortality rates com-pared to pancreaticoduodenectomy (PD) or distal pancreatectomy (DP), despite similar risks of postoperative pancreatic fistula (POPF). DP was preferred over enucleation for pancreas body-tail, while laparoscopic enucleation is better for head pNETs.

Owing to the rising demand for vegetable soybean products, there is an increasing need for high-yield soybean varieties to raise the output. However, complex correlation patterns among quantitative traits with genetic interactions bring a challenge for vegetable soybean breeding. Here, a genome-wide association study (GWAS) was applied for six yield-related traits with 188 vegetable soybean accessions. A total of 81 SNPs were identified for pod length, plant height, pods number, pod thickness, pod width, and seed weight per plant by Blink model. Among these significant SNPs, 79 were novel SNPs, while 2 overlapped with previously reported SNPs. A total of 220 genes were found in 100 kb upstream and downstream regions of significant SNPs, of which 17 genes were functional proteins. Among these function proteins, four candidate genes, Glyma.13G109100, Glyma.03G183200, Glyma.09G102200, and Glyma.09G102300 were analyzed as significant haplotype variations, which encode MYB-related transcription factor, auxin-responsive family protein, F-box protein and CYP450, respectively. In addition, the relative expression with four candidate genes in the V030 and V071 (Among them, the plant height, pod number and fresh pod weight of V030 were lower than V071 strains) vegetable soybean were significantly different and these genes could be involved in plant growth and development via various pathways. Therefore, we proposed four genes from vegetable soybean germplasm that could be the key candidate genes for pod yield and plant height and these studies will accelerate the process of high-yield vegetable soybean breeding.

The emotion of disgust protects individuals against pathogens, and it has been found that during pregnancy, it is elevated. Physiological mechanisms discussed in relation to these changes include immune markers and progesterone levels. The aim of this study is to assess the association between steroids and disgust in pregnancy. In a sample of 179 pregnant women, we have analyzed blood serum steroid concentrations and measured disgust sensitivity by text-based questionnaires in the first and third trimester. We found positive correlations between disgust sensitivity and the levels of C19 steroids, including testosterone, but also its precursors in the Δ5 pathway (androstenediol, DHEA, and their sulfates) and the Δ4 pathway (androstenedione). Furthermore, positive correlations between disgust sensitivity and 5α/β-reduced C19 steroid metabolites were consistently present in both trimesters. In the first trimester, we found a positive association between disgust sensitivity and 17-hydroxypregnanolone as well as some estrogens. In the third trimester, we have observed positive associations between disgust sensitivity and cortisol as well as immunoprotective Δ5 C19 7α/β-hydroxy-steroids. Our study has thus shown that disgust sensitivity is positively correlated with immunomodulatory steroids, and in the third trimester, steroids may reflect potential maternal anxiety-related symptoms.

Pasmo is one of the most widespread diseases threatening flax production. To identify genetic regions associated with pasmo resistance (PR), a genome-wide association study was performed on 370 accessions from the flax core collection. Evaluation of pasmo severity was performed in the field from 2012 to 2016 in Morden, MB, Canada. Genotyping-by-sequencing has identified 258,873 single nucleotide polymorphisms (SNPs) distributed on all 15 flax chromosomes. Marker-trait associations were identified using ten different statistical models. A total of 692 unique quantitative trait nucleotides (QTNs) associated with 500 putative quantitative trait loci (QTL) were detected from six phenotypic PR datasets (five individual years and average across years). Different QTNs were identified with various statistical models and from individual PR datasets, indicative of the complementation between analytical methods and/or genotype × environment interactions of the QTL effects. The single-locus models tended to identify large-effect QTNs while the multi-loci models were able to detect QTNs with smaller effects. Among the putative QTL, 67 had large effects (3-23%), were stable across all datasets and explained 32-64% of the total variation for PR in the various datasets. Forty-five of these QTL spanned 85 resistance gene analogs including a large toll interleukin receptor, nucleotide-binding site, leucine-rich repeat (TNL) type gene cluster on chromosome 8. The number of positive effect QTL (NPQTL) in accessions was significantly correlated with PR (R²=0.55), suggesting additive effects. NPQTL was also significantly associated with morphotype (R²=0.52) and major positive effect QTL were present in the fiber type accessions. The 67 large effect QTL are suited for marker-assisted selection and the 500 QTL for effective genomic prediction in PR molecular breeding.

This paper presents data supporting the IC Regimen for potentiating the effectiveness of lorlatinib in treating ALK positive cancers, and specifically non-small cell lung cancer. Lorlatinib is an effective treatment for ALK driven non-small cell lung cancer and other ALK driven cancers. Lorlatinib inhibits ALK kinase and achieves good brain tissue levels, a common site for metastases in lung cancers. However, resistance to lorlatinib usually supervenes and the cancer awakens and starts growing again, resistant to lorlatinib. This paper analyses data indicating that adding two common generic drugs, itraconazole and cilostazol, to lorlatinib treatment may delay resistance development. Itraconazole is marketed worldwide as a generic antifungal drug that also inhibits Hedgehog signaling, CYP3A4, and the p-gp efflux pump. Cilostazol is a generic anti-thrombosis, phosphodiesterase 3 inhibiting drug that carries minimal bleeding risk. Cilostazol may enhance lorlatinib by deprivation of trophic growth factors supplied by platelets. Itraconazole may enhance lorlatinib effectiveness by reducing or stopping a Hedgehog centered amplifying feedback loop with ALK kinase. The combination of metastatic non-small cell lung cancer being a low-survival disease and the general safety itraconazole plus cilostazol augmentation, make a clinical trial of this trio worthwhile.

Introduction: Known for its persistent blood-feeding behavior from dawn to dusk, Aedes albopictus is recognized as one of the most dangerous mosquito species due to its role as a vector for diseases such as dengue. Studies have demonstrated that Aedes albopictus thrives in micro-breeding sites predominantly located on private properties, including abandoned containers and manholes used for rainwater and irrigation. This study investigates an innovative methodology, the TombiniNet, to mitigate the proliferation of Aedes albopictus by engaging citizens in the active management of micro-breeding sites on their properties. Materials and Methods: The study was conducted in Alessandria, a city with approximately 100,000 inhabitants, focusing on a sample of 200 houses and a population of about 5,000 people. Researchers conducted a comprehensive survey and analysis of micro-breeding sites for Aedes albopictus on both private and communal properties. The larval control measures were conducted from April to October, aligning with the peak mosquito breeding season. The study's sample included 51% of houses that allowed researchers access, and within these, 81% had Aedes albopictus larvae, often found in diverse water Containers holes of which basically manholes on villa garden floors. For monitoring the adult populations were used ovitraps that were not placed in private homes but in public areas to monitor and control the mosquito population. Results: The study identified that up to 70% of micro-breeding sites for Aedes albopictus in northern Alessandria were located on private properties. Citizen participation was critical to the success of the intervention, with a marked decrease in the number of adult tiger mosquitoes observed in areas where residents actively managed breeding sites using the TombiniNet. The TombiniNet was particularly effective in private areas, as it could be regularly maintained by residents, preventing debris accumulation that could hinder drainage. Discussion: The findings highlight the importance of engaging citizens in mosquito control programs to effectively manage Aedes albopictus populations in urban areas. The TombiniNet intervention demonstrated that a simple, cost-effective solution could significantly reduce mosquito breeding sites on private properties. By addressing both communal and private breeding sites, a comprehensive and sustainable approach to mosquito management can be achieved, thereby reducing the risk of disease transmission. Future studies should focus on long-term monitoring and the development of additional innovative solutions to enhance citizen participation and control measures. The study's success also pointed out the limitations of applying such interventions in public areas where debris could impede the net's effectiveness.

Mercury (Hg) pollution not only poses a threat to the environment but also adversely affects the growth and development of plants, with potential repercussions for animals and humans through bioaccumulation in the food chain. Maize, a crucial source of food, industrial materials, and livestock feed, requires special attention in understanding the genetic factors influencing mercury accumulation. Developing maize varieties with low mercury accumulation is vital for both maize production and human health. In this study, a comprehensive genome-wide association study (GWAS) was conducted using an enlarged SNP panel comprising 1.25 million single nucleotide polymorphisms (SNPs) in 230 maize inbred lines across three environments. The analysis identified 111 significant SNPs within 78 quantitative trait loci (QTL), involving 169 candidate genes under the Q model. Compared to the previous study, the increased marker density and optimized statistical model led to the discovery of 74 additional QTL, demonstrating improved statistical power. Gene Ontology (GO) enrichment analysis revealed that most genes participate in arsenate reduction and stress responses. Notably, GRMZM2G440968, associated with the significant SNP chr6.S_155668107 of axis tissue, encodes a cysteine proteinase inhibitor, suggesting its potential role in alleviating Hg toxicity by inhibiting cysteine. Haplotype analyses provided further insights, indicating that lines carrying hap3 exhibited the lowest mercury content compared to other haplotypes. In summary, our study significantly enhances the statistical power of GWAS, identifying additional genes related to mercury accumulation and metabolism. These findings offer valuable insights into unraveling the genetic basis of mercury content in maize and contribute to the development of maize varieties with low mercury accumulation.

Eating disorders (ED) are characterized by alterations in eating behavior. The genetic factors shared between ED diagnoses have been underexplored. The present study aimed to perform a genome-wide association study on individuals with disordered eating behaviors in the Mexican population, blood methylation quantitative trait loci (blood-meQTL) analysis, and in silico function prediction by different algorithms. The analysis included a total of 1803 individuals. Genome-wide association study and blood-meQTL analysis were performed by logistic and linear regression. In silico functional variant prediction, phenome-wide, and transcriptome-wide association studies by different algorithms were analyzed. In the genome-wide association study, we identified 44 single-nucleotide polymorphisms (SNP) associated at a nominal value and 7 blood-meQTL at a genome-wide umbral. The SNPs were enriched in genome-wide associations of the metabolic and immunologic domains. In the in silico analysis, the SNP rs10419198 located on an enhancer mark could change the expression of PRR12 on blood, adipocytes, and brain areas that regulate food intake. The present study supports the previous associations of genetic variation in the metabolic domain with ED.

Our hypothesis that controlled ozone applications interfere into the redox balance of the biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication), has been verified over the last 2 decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes, diabetes-2 and in prevention of intoxications. Low-dose ozone acts as a redox bioregulator: The restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase of the antioxidant repair markers, here mainly shown as glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, relevant data are displayed, evaluated and comprehensively discussed: The repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone treated groups and depending on the indication; the stress markers are simultaneously reduced, the redox system regains its balance.

This study examines the contribution of early executive functions (EFs) in the association between fluency in reading and arithmetic. Kindergarten children (N = 1,185) were assessed on Executive Functions skills and on reading and arithmetic fluency in Grade 1 and Grade 3. The analysis revealed that beyond the connection within each domain there is a unidirectional effect between fluency measures, with Grade 1 reading fluency significantly influencing the development of arithmetic fluency in Grade 3. Furthermore, the findings indicate that kindergarten EFs significantly contribute to arithmetic fluency at both time points and to reading fluency in the first grade. Early EF skills also emerged as a mediator of associations between fluency performance in reading and arithmetic, suggesting that the influence of EFs extends beyond individual academic domains. These findings have implications for understanding the cognitive mechanisms that underlie the relations between these academic skills.

Sea level rise due to global warming is a continuing and, disappointingly, accelerating process, which has already affected and will further impact coastal lowlands and the social and economic activities in these areas. Delos Island, situated in the middle of the Cyclades in the Aegean Sea, was considered the most sacred of all islands in ancient Greek culture and a trading hub for the entire eastern Mediterranean. Uninhabited since the 7th century AD, and consistently the focus of research and touristic attention, the island is designated as an archaeological site and inscribed on the Unesco World Heritage List. Previous studies on the relative sea level (rsl) changes suggest a steadily rsl rise during the last 6,300 years, starting from a sea level at -4.80±0.20m in the Late Neolithic. The seafront of the ancient city of Delos is subject to the effects of the rsl rise, which have caused significant coastline retreat and exposure to the northerly winds and waves, whereas parts of the coastal lowland where the remains of the ancient city lie are inundated, forming extended wetlands. The future impacts of rsl rise on the seafront of ancient Delos are illustrated on very high-resolution digital surface models, evaluating both the flooding risk under different climatic projections, as provided by the IPCC AR6 report, and the ongoing land subsidence, as recorded by GNSS data. An rsl rise ranging from 87cm (SSP1-2.6 scenario) to 148cm (SSP5-8.5 scenario) is anticipated by 2150, requiring both resilience strategies and adaptation solutions as well as mitigation policies to cope with the effects of climate change.

In this article, many experimental similarities between electromagnetic fields (which are applied in systems of electrons, atoms, and liquids) and strong interaction fields (which are applied in systems of quarks, nucleons, and nuclei) are reviewed. The currently accepted theories describing electromagnetic fields differ fundamentally from those describing strong fields. Therefore, the many similarities are quite surprising, and some are not adequately explained even today. Several such unexplained similarities are listed among the top open problems in particle physics, such as the “EMC effect,” the “proton spin crisis,” and the “strong CP problem.” This paper highlights, for the first time, the underlying common characteristics of these problems, potentially offering valuable contribution to future explanations.

Tiller angle (TA) is one of the most important agronomic traits which directly affected plant architecture, photosynthetic efficiency, and planting density of rice. Although many quantitative trait loci (QTL) and associated genes for tiller angle have been identified, the detection of QTL for TA still required emphasis. In this study, 238 micro-core germplasm populations were used for genome-wide association analysis (GWAS) of the tiller angle. The frequency distribution of TA was shown to be continuous in 2018 and 2019, five QTL designated as qTA1, qTA2, qTA6, qTA9, qTA12, and two QTL designated as qTA1, qTA1-1 were detected in 2018 and 2019, respectively. These QTL explained phenotypic variation ranged from 5.94% to 12.38%. Among them, qTA2 and qTA6 are new QTL for TA, and only qTA1 was detected repeatedly in two years. 253 germplasm from the 3K Rice Genome Project were used for candidate gene and haplotypes analysis, the candidate gene and haplotypes analyzed showed LOC_Os01g67770, LOC_Os02g35180 and LOC_Os09g38130 were the candidate gene of qTA1, qTA2, and qTA9, respectively. The results of this study provide insight into the genetic improvement of plant architecture in rice.

Researchers have asserted that, as patients rely on external powerful sources to control their disorders, in addition to their own internal powers and virtues, examining their coping mechanisms can lead to a better understanding of the initiation and progression of chronic diseases and uncover potential opportunities to balance and enhance their psycho-spiritual well-being and possibly their treatment and recovery. This review serves as a user’s manual for investigators who choose to use the CSI-SF to conduct their research on coping behaviors. The CSI-SF that measures four coping strategies based on 16 items was first assessed using the Jackson Heart Study (JHS) cohort in 2007. The reliability and construct validity of the CSI-SF was also later assessed among hemodialysis patients across 13 countries. In this study, the CSI-SF was assessed to be a reliable and valid instrument for measuring coping strategies. The CSI-SF serves the purpose of developing an inner voice that can assist with understanding how people cope with everyday life. The information gathered from administration of the CSI-SF can inform investigators about environmental cues and triggers that can also impact individual health.

The global antibiotic resistance crisis, driven by antibiotic overuse and misuse, is multifaceted. This study aimed to assess the microbiological and genetic characteristics of raw retail pork meat, including the isolation, antibiotic susceptibility testing (AST), whole genome sequencing (WGS) of selected indicator bacteria, antibiotic residue testing, and metagenomic sequencing. Samples were purchased from 10 randomly selected retail stores in Gauteng, South Africa. Samples were aseptically separated, with a portion sent to an external laboratory for isolating indicator bacteria and antibiotic residue testing. Identification of the isolated bacteria was reconfirmed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). AST was performed using the Microscan Walkaway system. WGS and metagenomic sequencing were performed using the Illumina NextSeq 550 instrument. The isolated E. coli and enterococci exhibited little phenotypic resistance, with WGS revealing tetracycline resistance genes. Isolated bacteria and meat samples all harboured tetracycline resistance genes, and the antibiotic residue concentrations were within acceptable limits for human consumption. In the metagenomic context, most identified bacteria were of food/meat spoilage and environmental origin, with the resistome analysis primarily indicating beta-lactam, tetracycline and multidrug resistance genes. Further research is needed to understand the broader implications of these findings on environmental health and antibiotic resistance.

Procurement plays a central and defining role in the efficiency of supply chains. In recent years, the understanding and practice of procurement management have changed significantly due to increasing emphasis on and demand for agility and sustainability within supply chain management systems. Meanwhile, traditional supply chain systems, characterized by siloed processes, limited visibility, and inefficiencies due to manual interventions, can no longer cope with the current dynamic market conditions. Besides, the increasing requirements of sustainability, ethical sourcing, and environmental impact have intensified, making more responsible, transparent, and traceable procurement practices unnegotiable requirements for modern systems. In this paper, we examine the potential of emerging technologies and innovations such as blockchain, artificial intelligence, and the Internet of Things (IoT) in filling these gaps within the supply chain systems of enterprises in the US. The study employs a comprehensive review of relevant literature and case studies to discover and provide insights on how these technologies can improve procurement processes, optimize resource allocation and utilization, and improve sustainability. The findings of this study highlight the need for stakeholders to embrace technological advancements to effectively navigate the dynamic landscape of supply chain management.

In order to integrate genomics in breeding and development of drought tolerant groundnut genotypes, identification of genomic regions/genetic markers for drought surrogate traits is essential. We used SNP markers for a genetic analysis of the ICRISAT groundnut minicore collection for genome wide marker-trait association for some physiological traits and to determine the magnitude of linkage disequilibrium (LD) present in the genetic resources. The LD analysis showed that about 36% of loci pairs were in significant LD (P < 0.05 and r2 > 0.2) and 3.14% of the pairs were in complete LD. There was rapid decline in LD with distance and the LD was <0.2 at a distance of 41635 bp. The marker trait association (MTAs) studies revealed 20 significant MTAs (p <0.001) with 11 markers for leaf area index (4), canopy temperature (13), chlorophyll content (1) and NDVI (2). The markers explained 2 to 21% of the phenotypic variation observed. Most of the MTAs identified on the A subgenome were also identified on the respective homeologous chromosome on the B subgenome. The duplications of effect observed could be due to common ancestor of the A and B genome which explains the linkage detected between markers lying on different chromosomes seen in the current study. The present study identified a total of 20 highly significant marker trait associations with 11 markers for four physiological traits of importance in groundnut; LAI, CT, SCMR and NDVI. The markers identified in this study can serve as useful genomic resources to initiate marker-assisted selection and trait introgression of groundnut for drought tolerance. The identified markers in this study may be useful for marker assisted selection after further validation.

Predictive factors associated with a decline in swallowing function after 2 years were examined in 3,409 Japanese older people aged ≥ 75 years who had undergone a dental checkup in Gifu Prefecture, Japan. Participants with normal swallowing function in a baseline survey in April 2018 were followed for 2 years. Swallowing function was assessed by a repetitive saliva swallowing test. After 2 years, 429 participants (13%) who could not swallow at least three times in 30 seconds were diagnosed as having a decline in swallowing function. Multivariate logistic regression analyses showed the decline in swallowing function after 2 years was associated with male gender (odds ratio [ORs]: 0.772; 95% confidence interval [CIs]: 0.615–0.969), age ≥ 81 years (presence; ORs: 1.523; 95% CIs: 1.224–1.895), support/care-need certification (presence; ORs: 1.815; 95% CIs: 1.361–2.394), periodontal pocket depth (PPD) ≥ 4 mm (presence; ORs: 1.469; 95% CIs: 1.163–1.856), difficulty in biting hard food (yes; ORs: 1.439; 95% CIs: 1.145–1.808), choking on tea and water (yes; ORs: 2.543; 95% CIs: 2.025–3.193), and dry mouth (yes; ORs: 1.316; 95% CIs: 1.052–1.646) at baseline. Therefore, the dental checkup items associated with a decline in swallowing function after 2 years were a PPD ≥ 4 mm, difficulty in biting hard food, choking on tea and water, and dry mouth. PPD status and confirming to the self-administered questionnaire about biting, choking, and dry mouth may be useful in predicting future decline in swallowing function.

Evidence is emerging on the role of maternal diet, gut microbiota, and other lifestyle factors in establishing lifelong health and disease, which are determined by trans-generationally inherited epigenetic modifications. Understanding epigenetic mechanisms may help identify novel biomarkers for pregnancy-related exposure, burden, or disease risk. Such biomarkers are essential for developing tools for the early detection of risk factors and exposure levels. It is necessary to establish the exposure threshold to the fetus due to nutrient deficiencies or other environmental factors that can lead to clinically relevant epigenetic changes that modulate disease risks. This narrative review summarizes the latest updates on the roles of maternal nutrients (n-3 fatty acids, polyphenols, vitamins) and gut microbiota on the placental epigenome and its impacts on fetal brain development.

Many risk-modifying factors affect cancer incidence and mortality rates. We present an ecological study of incidence and/or mortality rates for cancers during 2007–2016 of 17 anatomical sites with respect to solar ultraviolet-B (UVB) doses and obesity prevalence. Solar UVB reduces cancer risk by producing vitamin D, which has many mechanisms to reduce risk of cancer incidence, progression, and metastasis. Obesity increases cancer risk through several mechanisms, including increased systemic inflammation. Data were averaged for 12 geographical regions. Solar UVB doses were significantly inversely correlated with mortality rates for five cancers for males and four for females. Obesity prevalence was directly correlated with mortality rates for three cancers for males and seven for females. The population attributable fraction of cancer mortality rates ascribed to low solar UVB dose was 0.03 for both males and females, whereas that for obesity prevalence was 0.05 for males and 0.08 for females. Thus, cancer mortality rates in France could be reduced through vitamin D supplementation and reducing the prevalence of obesity. Doing so also could reduce risk of other adverse health outcomes.

Oligopeptide transporters (OPTs) are a group of membrane localized proteins that have a broad range of substrate transport capabilities and contribute to numerous biological processes. However, limited information has been reported on OPTs in higher plants. In this study, a comprehensive analysis of the OPT gene family in Medicago truncatula was performed. A total of 26 OPT genes (MtOPT01-MtOPT26) have been identified in the Medicago truncatula genome. Phylogenetic analyses indicated that MtOPTs consisted of two distinct subgroups, 12 MtOPTs belonged to the peptide transport subgroup (PT-OPT) based on their predicted amino acid sequences containing the two highly conserved motifs (NPG and KIPPR) and 14 MtOPTs belonged to yellow stripe subgroup (YS-OPT). The MtOPTs distributed on each of 8 chromosomes in Medicago truncatula. Sequence analysis verified that MtOPTs significant similar to those in other plants. The copy number of MtOPTs was low and the multiply of MtOPTs was simple relatively. Gene structure analysis showed that most of the MtOPTs have various numbers of introns. The multiple of MtOPTs might play different biological roles which were supported by the fact that MtOPTs have a distinct tissue-specific expression pattern. The data obtained in this study will help to better understand the complexity of the MtOPTs gene family and provide new evidence for the function and evolution of the OPT gene family in higher plants.

Shea tree (Vitellaria paradoxa) is an important fruit tree crop because of its oil used for cooking and industrial manufacture of cosmetics. Despite its many benefits, quantitative trait loci linked to the economic traits have not yet been studied. In this study, we performed association mapping on a panel of 374 shea tree accessions using 7,530 single-nucleotide polymorphisms (SNPs) markers for oil yield and seed related traits. Twenty three markers that were significantly (–log10 (p) = 4.87) associated to kernel oil content, kernel length; width and weight were identified. The kernel dry matter oil content and kernel width had the most significant Marker Trait Association (MTA) on chromosomes 1 and 8 respectively. Sixteen candidate genes that condition early induction of flower buds and somatic embryos, seed growth and development, substrate binding, transport, lipid biosynthesis, metabolic processes during seed germination and disease resistance and abiotic stress adaptation were identified. The presence of these genes suggest their role in promoting shea bioactive functions that condition high oil synthesis. This study provides insights into the important marker-linked seed traits with genes controlling them, useful for molecular breeding for improving oil yield in the species.

Advanced genomics, transcriptomics and epigenomics techniques are providing unprecedented insights into the understanding of the molecular underpinnings of the central nervous system, including the neuro-sensory cochlea of the inner ear. Here, we report for the first time a comprehensive and updated overview of the most advanced omics techniques for the study of nucleic acids, and their applications in cochlear research. We describe the available in vitro and in vivo models for hearing research, the principles of genomics, transcriptomics and epigenomics, alongside their most advanced technologies (like single cell omics and spatial omics), which allows to investigate the molecular events that occur at single cell resolution retaining the spatial information.

Lodging poses a significant challenge to rice yield, prompting the need to identify elite alleles for lodging resistance traits to improve cultivated rice varieties. In this study, a natural population of 518 rice accessions was examined to identify elite alleles associated with plant height (PH), stem diameter (SD), stem anti-thrust (AT/S), and various internode lengths: (first (FirINL), second (SecINL), third (ThirINL), fourth (ForINL), and fifth (FifINL) internode lengths). 262 SSR markers linked to these traits were uncovered through association mapping in two environmental conditions. Phenotypic evaluations revealed striking differences among cultivars, and genetic diversity assessments showed polymorphisms across the accessions. Favorable alleles were identified for PH, SD, AT/S, and 1 to 5 internode lengths, with specific alleles displaying considerable effects. Noteworthy alleles include RM6811-160 bp on chromosome 6 (which reduces PH) and RM161-145 bp on chromosome 5 (which increases SD). The study identified a total of 42 novel QTLs. Specifically, seven QTLs were identified for PH, four for SD, five for AT/S, five for FirINL, six for SecINL, five for ThirINL, six for ForINL, and four for FifINL. QTLs qAT/S-2, qPH2.1, qForINL2.1, and qFifINL exhibited the most significant phenotypic variance (PVE) of 3.99% for the stem lodging trait. AT/S, PH, ForINL and FifINL had additive effects of 5.31 kPa, 5.42 cm, 4.27cm and 4.27cm, respectively, offering insights into eight distinct cross-combinations for enhancing each trait. This research suggests the potential for cross-breeding superior parents based on stacked alleles, promising improved rice cultivars with enhanced lodging resistance to meet market demands.

Citrus species essential oils (EOs) are significant sources of bioactive compounds and demonstrate diverse therapeutic effects. However, limited documentation exists regarding the phytochemicals associated with their biological activities. This study aims to assess the antioxidant activity, plant inhibitory properties, and brine shrimp cytotoxic effects of EOs derived from three Citrus species: C. sinensis, C. limon, and C. hystrix. Utilizing chemometric analysis and gas chromatography-mass spectrometry (GC-MS) fingerprints, the volatile components contributing to antioxidant activity were elucidated. The peels of the Citrus samples were hydro-distillated to obtain EOs, and subsequently subjected to antioxidant, plant inhibitory, and brine shrimp cytotoxic assays. The results indicated that C. limon EO exhibited the highest antioxidant activity, while C. hystrix and C. sinensis EOs demonstrated pronounced inhibitory effects against Aetrmia salina and Lactuca sativa, respectively. GC-MS analysis facilitated the identification of key compounds in each EO. Principal component analysis (PCA) and hierarchy cluster analysis (HCA) effectively categorized Citrus EOs based on their antioxidant properties, highlighting the proximity of C. limon and C. sinensis. Among the identified compounds, D-limonene, α-Terpineol, Caryophyllene, (+)-3-Carene, β-Pinene, (-)-Spathulenol, trans-p-Mentha-1(7),8-dien-2-ol, and trans-Verbenol were the most discriminating compounds affected the antioxidant activity of C.limon and C. sinensis EOs.

Infertility is affecting around 20 % of couples in the age of procreation but however in some societies as many as one-third of all couples are unable to conceive. Different factors are contributing to male fertility declining such us endocrine disruptors environmental and professional exposures, oxidative stress and life style changes with risks of de novo epigenetics dysregulation. Since the fantastic development of new technologies of Omes and Omics , the contribution of inherited or de novo genomes and epigenome disorders contributions in male infertility are more elucidated and relevant. More than somatic genome investigation of infertile men (from chromosome to single or multiple gene point mutations) many others techniques become available in molecular andrology laboratory to investigate the genome and epigenome integrity, the maturation and the competency of the spermatozoa and its physiological environment. All those new methods of assessment are demonstrating the role of genetics and epigenetics disorders contribution on reproductive pathology and are helping the professional of assisted reproductive technology to propose different management strategy of male infertility to improve the clinical outcomes and minimize the risk of genetics or metabolic disorders at birth.

Antimicrobial resistance (AMR) is a public health problem exacerbated by the overuse and misuse of antibiotics and an inadequate capacity of laboratories to conduct AMR surveillance. This study assessed the capacity of laboratories in seven faith-based hospitals to conduct bacteriology, AMR testing and surveillance in Zambia. This multi-facility, cross-sectional exploratory study was conducted from February 2024 to April 2024. We collected and analysed data using the self-scoring Laboratory Assessment of Antibiotic Resistance Testing Capacity (LAARC) tool. This study found an overall score of 39%, indicating a low capacity of laboratories to conduct AMR surveillance. The highest capacity score was 47%, while the lowest was 25%. Only one hospital had full capacity (100%) to utilise a Laboratory Information System (LIS). Three hospitals had good capacity to perform data management with scores of 83%, 85%, and 95%. Only one hospital had full capacity (100%) to process specimens, and only one hospital had good safety requirements for a microbiology laboratory, with a score of 89%. This study demonstrates that all the assessed hospitals have a low capacity to conduct AMR surveillance. Therefore, there is an urgent need to strengthen the microbiology capacity of laboratories to enhance surveillance in faith-based hospitals in Zambia.

Bromodomain (BRD)-containing proteins are involved in many biological processes, most notably epigenetic regulation of transcription, and BRD protein dysfunction has been linked to many diseases, including tumorigenesis. However, the role of BRD proteins in the pathogenesis of uterine fibroids (UFs) is entirely unknown. The present study aimed to determine the expression pattern of BRD9 protein in UFs and matching myometrium and further assess the impact of BRD9 inhibitors on UF phenotype and epigenetic/epitranscriptomic changes. Our studies demonstrated that the levels of BRD9 were significantly upregulated in UFs compared to matched myometrium, suggesting that the aberrant BRD protein expression may contribute to the pathogenesis of UFs. We then evaluated the potential roles of BRD9 using its specific inhibitor I-BRD9. Targeted inhibition of BRD9 suppressed the UF tumorigenesis with increased apoptosis and cell cycle arrest, decreased cell proliferation, and extracellular matrix deposition in UF cells. The latter is the key hallmark of UFs. Unbiased transcriptomic profiling coupled with downstream bioinformatics analysis further and extensively demonstrated that targeted inhibition of BRD9 impacted the cell cycle- and ECM-related biological pathways, reprogrammed the UF cell epigenome and epitranscriptome, and altered miRNA-mediated gene regulation in UFs. Taken together, our data support the critical role of BRD9 in UF cells and the strong interconnection between BRD9 and other pathways controlling the UF progression. Targeted inhibition of BRD proteins might provide a non-hormonal treatment option for this most common benign tumor in women of reproductive age.

The number of children diagnosed with autism spectrum disorder (ASD) has increased substantially over the past two decades with current research unable to fully account for this dramatic increase in prevalence. One explanation proposes that both intrinsic (e.g., genetic) and extrinsic (e.g., environmental) risk factors may be involved in the etiology of ASD. The goal of this review paper is to explore modifiable pathways for intervention in children at risk for ASD, specifically examining how early social experience may be correlated with epigenetic change in genes associated with autism. We present an innovative model which proposes that polygenic risk and social experience (via epigenetic mechanisms) may both contribute to the observed ASD phenotype. Previous research on genetic, environmental, and epigenetic mechanisms implicated in the etiology of ASD will be reviewed, with an emphasis on the oxytocin receptor gene, which is epigenetically altered by early social experience, plays a crucial role in mammalian social and cognitive development, and is associated with both genetic and epigenetic risk for ASD. Identifying intrinsic (e.g., genetic) and extrinsic (e.g., social experience) risk markers for ASD, a combination of which has not previously been examined, would transform our understanding of this condition, facilitate earlier identification of ASD risk, and guide early intervention efforts. This may have a far-reaching impact on individuals with ASD, their families, and society.

Genome-wide association studies (GWAS) have identified and reproduced thousands of diseases associated loci but many of them are not directly interpretable due to the strong linkage disequilibrium among variants. Transcriptome-wide association studies (TWAS) incorporated expression quantitative trait loci (eQTL) cohorts as reference panel to detect associations with the phenotype at the gene level and were gaining popularity in recent years. For nicotine addiction, several important susceptible genetic variants were identified by GWAS, but TWAS that detected genes associated with nicotine addiction and unveiled the underlying molecular mechanism were still lacking. In this study, we used eQTL data from the Genotype-Tissue Expression (GTEx) consortium as reference panel to conduct tissue specific TWAS on cigarettes per day (CPD) over 13 brain tissues in two large cohorts: UK Biobank (UKBB; N=142,202) and the GWAS &amp; Sequencing Consortium of Alcohol and Nicotine use (GSCAN; N=143,210), and then meta-analyzed the results across tissues while considering the heterogeneity across tissues. We identified three major clusters of genes with different meta-patterns across tissues consistent in both cohorts, including homogenous genes associated with CPD in all brain tissues, partially homogeneous genes associated with CPD in cortex, cerebellum and hippocampus tissues, and lastly the tissue-specific genes associated with CPD in only few specific brain tissues. Downstream enrichment analyses on each gene cluster identified unique biological pathways associated with CPD and provided important biological insights into the regulatory mechanism of nicotine dependence in the brain.

Space-based gravitational wave detection is extremely sensitive to disturbances. The Keplerian configuration cannot accurately reflect the variations in spacecraft configuration. Planetary gravitational disturbances are one of the main sources. Numerical simulation is an effective method to investigate the impact of perturbation on spacecraft orbits. This study shows that, in the context of the Taiji project, Earth’s gravity is an essential factor in the change in heliocentric formation configuration, contributing to the relative acceleration between spacecrafts in the order of O(10−6)m·s−2. Considering 00:00:00 on October 27, 2032 as the initial orbiting moment, under the influence of Earth’s gravitational perturbation, the maximum relative change in armlengths and variation rates of armlengths for Taiji is 1.6×105km, 32m·s−1 respectively, compared with the unperturbed Keplerian orbit. Additionally, by considering the gravitational perturbations of Venus and Jupiter, the armlength and relative velocity for Taiji are reduced by 16.01% and 17.45%, respectively, compared with when only considering that of Earth. The maximum amplitude of the formation motion indicator changes with the orbit entry time. Results show that the relative velocity increase between the spacecrafts is minimal when the initial orbital moment occurs in July. Moreover, the numerical simulation results are inconsistent when using different ephemerises. The differences between ephemeris DE440 and DE430 are smaller than those between DE440 and DE421.

Gibberella ear rot (GER) caused by Fusarium graminearum (teleomorph Gibberella zeae) is one of the most destructive diseases in maize that severely reduces grain yield and contaminates several potential mycotoxins. However, few efforts had been devoted to dissect the genetic basis of maize GER resistance. In the present study, a genome-wide association study (GWAS) was conducted in a maize association panel consisting of 303 diverse inbred lines. The phenotypes of GER severity were evaluated using kernel bioassay across multiple time points in the laboratory. Then, three models including fixed and random model circulating probability unification model (FarmCPU), general linear model (GLM) and mixed linear model (MLM), were conducted simultaneously in GWAS to identify single-nucleotide polymorphisms (SNPs) significantly associated with GER resistance. A total of four individual significant association SNPs with the phenotypic variation explained (PVE) ranging from 3.51 to 6.42% were obtained. Interestingly, the peak SNP (PUT-163a-71443302-3341) with the greatest PVE value, was co-localized in all models. Subsequently, 12 putative genes were captured from the peak SNP that several of these genes were directly or indirectly involved in disease resistance. Overall, these findings contribute to understand the complex plant-pathogen interactions in maize GER resistance. The regions and genes identified herein provide a list of candidate targets for further investigation, in addition to the kernel bioassay that can be used for evaluating and selecting elite germplasm resources with GER resistance in maize.

Background: Few studies have investigated the longitudinal association between cervical spondylosis (CS) and migraine by using a nationwide population-based database. Methods: We conducted a retrospective cohort study from 2000 to 2011 identifying 27,930 cases of cervical spondylosis and 111,720 control subjects (those without cervical spondylosis) from a single database. The subjects were frequency-matched on the basis of sex, age, and diagnosis date. The non- cervical spondylosis cohort was four times the size of the cervical spondylosis cohort. To quantify the effects of cervical spondylosis on the risk of migraine, univariate and multivariate Cox proportional hazard regression analyses were used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: After a 10-year follow-up controlling for potential confounding factors, overall migraine incidence was higher in the cervical spondylosis cohort than in the non- cervical spondylosis cohort (5.16 and 2.09 per 1,000 people per year, respectively; crude hazard ratio = 2.48, 95% confidence interval = 2.28–2.69) with an adjusted hazard ratio of 2.03 (95% confidence interval = 1.86–2.22) after accounting for sex, age, comorbidities, and medication. Individuals with myelopathy in the cervical spondylosis cohort had a 2.19 times (95% confidence interval = 1.80–2.66) higher incidence of migraine compared than did those in the non- cervical spondylosis cohort. Conclusion: Individuals with cervical spondylosis exhibited a higher risk of migraine than those without cervical spondylosis. The migraine incidence rate was even higher among individuals with cervical spondylotic myelopathy.

Pancreatic cancer is one of the most fatal common cancers affecting both men and women, representing about 3 percent of all new cancer cases in the United States. In this study, we aimed to investigate the association of pancreatic cancer risk with alcohol consumption as well as folate intake. We performed a case-control study of 384 patients diagnosed with pancreatic cancer from May 2004 to December 2009 and 983 primary care healthy controls. Our findings showed no significant association between risk of pancreatic cancer and either overall alcohol consumption or type of alcohol consumed (drinks/day). Our study showed dietary folate intake was modestly but significantly inversely associated with pancreatic cancer (OR=0.99, P <.0001). The current study supports the hypothesis that pancreatic cancer risk is reduced with higher food-based folate intake.

In this paper, single and repetitive frequency UIS characteristics of 1200 V asymmetric (AT)and double trench silicon carbide (DT-SiC) metal–oxide-semiconductor field-effect transistors (MOSFETs) under different working conditions are investigated by experiment and simulation. For asymmetric trench SiC MOSFETs, the failure mode is all thermal runaway under working conditions. However, the failure mode of double trench SiC MOSFETs mostly is gate oxide rupture, which indicates an instable avalanche robustness under UIS stress. The variations of measured parameters are recorded to evaluate typical electrical features of device failure. Furthermore, TCAD simulation is used to reveal the electro-thermal stress inside the device during avalanche. Additionally, failed devices are decapsulated to verify the location of failure point from the perspective of the semiconductor die. Finally, a new type of stepped-oxide vertical power DT MOSFET with P-type shielding and current spread layers is proposed for improvement of gate dielectric reliability.

Millimeter wave wide-band imaging is widely studied for a variety of applications. However real-time millimeter wave wide-band imaging at frequencies above 30GHz for moving targets in a large field of view has not been realized commercially. A 2D sparse array with transmitter multiplexing is a promising solution to this problem. In this article, a method combining compressed sensing and orthogonal coded multiplexing was proposed, and the imaging performance was analyzed for different reconstruction algorithms and observation matrices by imaging simulation for a continuous object. Also the influence on the dynamic range of the original signal introduced by orthogonal coded multiplexing was studied. This work demonstrated that the proposed method was effective in reconstructing the image with a real-time capability. It is shown that different algorithms and matrices resulted in distinct performances, while the evaluation parameter selection also played a role. This work provided useful instructions for both the hardware and software design of a real-time 3D millimeter wave imaging system in the future.

To evaluate genetic variability and seedling plant response to a dominated Warrior (-) race of yellow rust in Northern and Central European germplasm, we used a population of 229 winter wheat cultivars and breeding lines for genome-wide association study (GWAS). A wide variation in yellow rust disease severity (based on infection types 1-9) was observed in this panel. Four breeding lines TS049 (from Austria), TS111, TS185, and TS229 (from Germany) and one cultivar TS158 (KWS Talent) from Germany were found to be resistant to Warrior (-) FS 53/20 and Warrior (-) G 23/19. GWAS identified five significant SNPs associated with yellow rust on chromosomes 1B, 2A, 5B, and 7A for Warrior (-) FS 53/20, while one SNP on chromosome 5B was associated with disease for Warrior (-) G 23/19. For Warrior (-) FS 53/20, we discovered a new QTL for yellow rust resistance associated with the marker Kukri_c5357_323 on chromosome 1B. The resistant allele G at the marker locus Kukri_c5357_323 on chromosome 1B and the susceptible allele T at the marker locus Excalibur_c17489_804 on chromosome 5B showed the largest effects (1.21 and 0.81, respectively) on the severity of yellow rust detected in Warrior (-) FS 53/20 and Warrior (-) G 23/19. Among 144 putative genes within the flanking sequence of the significant SNPs detected by GWAS, the function of the best candidate genes was determined as protein kinase activity and oxidoreductase activity. Our results provide the basis for knowledge-based resistance breeding in the face of the enormous impact of the Warrior (-) race on wheat production in Europe.

The ZIPs (ZRT/IRT-like proteins) play critical roles in the absorption, transport, and intracellular balance of metal ions essential for various physiological processes in plants. However, little is known about the pan-genomic characteristics and properties of ZIP genes in cucumber (Cucumis sativus L.). In this study, we identified 10 CsZIP genes from the pan-genome of 13 C. sativus accessions. Among them, only CsZIP10 showed no variation in protein sequence length. We analyzed the gene structure, conserved domains, promoter cis-elements, and phylogenetic relationships of these 10 CsZIP genes derived from "9930". Based on phylogenetic analysis, the CsZIP genes were classified into three branches. Amino acid sequence comparison revealed the presence of conserved histidine residues in the ZIP proteins. Analysis of promoter cis-elements showed that most promoters contained elements responsive to plant hormones. Expression profiling in different tissues showed that most CsZIP genes were expressed at relatively low levels in C. sativus leave, stem, and tendril, and CsZIP7 and CsZIP10 were specifically expressed in root, indicating their potential involvement in the absorption and transport of metal ions. Transcriptomic data indicated that these 10 ZIP genes displayed responses to both downy mildew and powdery mildew, and CsZIP1 were significantly downregulated after both salt and heat treatments. In conclusion, this study deepens our understanding of the ZIP gene family and enhances our knowledge of the biological functions of CsZIP genes in C. sativus.

Background. Cardiorespiratory fitness (CRF) is a predictor of chronic disease that is impractical to routinely measure in primary care settings. We used a new estimated cardiorespiratory fitness (eCRF) algorithm that uses information routinely documented in electronic health care records to predict abnormal blood glucose incidence. Methods: Participants were adults (17.8% female) 20-81 years old at baseline from the Aerobics Center Longitudinal Study between 1979 and 2006. eCRF was based on sex, age, body mass index, resting heart rate, resting blood pressure, and smoking status. CRF was measured by maximal treadmill testing. Cox proportional hazards regression models were established using eCRF and CRF as independent variables predicting the abnormal blood glucose incidence while adjusting for covariates. Results: Of 8,602 participants at risk at baseline, 3,580 (41.6%) developed abnormal blood glucose during an average of 4.9 years follow-up. The average eCRF of 12.03 ± 1.75 METs was equivalent to the CRF of 12.15 ± 2.40 METs within the 10% equivalence limit. In fully adjusted models, the estimated risks were the same (HRs = 0.96), eCRF (95% CIs = 0.93−0.99), and CRF (95% CI of 0.94−0.98). Each 1-MET increase was associated with a 4% reduced risk. Conclusion: Higher eCRF is associated with a lower risk of abnormal glucose. eCRF can be a vital sign used for research and prevention.

Latest evidence revealed a possible association between Parkinson’s disease (PD) and periodontitis. We explored the causal relationship of this association through two-sample Mendelian randomization (MR) in European ancestry populations. To this end, we used openly accessible data of genome-wide association studies (GWAS) on PD and periodontitis. As instrumental variables for periodontitis, seventeen single-nucleotide polymorphisms (SNPs) from a GWAS of periodontitis (1817 periodontitis cases vs. 2215 controls) and forty-five SNPs from a GWAS of PD (20,184 cases and 397,324 controls). Eight non-overlapping SNPs of periodontitis from an additional GWAS assisted in the validation of association being studied. Multiple approaches of MR were carried-out. There was no evidence of genetic liability of periodontitis being associated with a higher risk of PD (B= -0.0003, Standard Error [SE] 0.0003, P = 0.26). The eight independent SNPs (B= -0.0000, SE 0.0001, P = 0.99) validated this outcome. We found no association of genetically primed PD towards periodontitis (B= -0.0001, SE 0.0001, P = 0.19). This MR study found no conclusive evidence to support a bidirectional causal genetic liability between PD and periodontitis. Further GWAS studies are needed to confirm the consistency of these results.

Wheat dwarf virus (WDV) causes an important vector transmitted virus disease, which leads to significant yield losses in barley production. Due to the fact, that at the moment no plant protection products are approved to combat the vector Psammotettix alienus and this disease cannot be controlled by chemical means, therefore the use of WDV resistant or tolerant genotypes is the most efficient method to control and reduce negative effects of WDV on barley growth and production. In this study, a set of 480 barley genotypes were screened to identify genotypic differences in response to WDV and five traits were assessed under infected and non-infected conditions. In total, 32 genotypes showed resistance or tolerance against WDV. Subsequently, the phenotypic data of 191 out of 480 genotypes combined with 34,408 single nucleotide polymorphisms (SNPs) in a genome wide association study to identify quantitative trait loci (QTLs) and markers linked to resistance/tolerance to WDV, using Tassel, GAPIT, and FARM CPU. In total, 1, 3, 2, 2 and 1 significantly associated markers on chromosomes 3H, 4H, 5H and 7H identified by all three methods for ELISA-60, relative performance of total grain weight, plant height, number of ears per plant and thousand grain weight, respectively.

Pharmacists must acquire the necessary knowledge to provide better drug therapy to patients. In other words, educational programs need to facilitate behavioral changes among pharmacists. Therefore, this study aimed to evaluate how the behavior of pharmacists changed after attending a palliative care educational program. We conducted a web-based questionnaire survey examining the behavior of pharmacists regarding palliative care before participating in the program, two months after participating in the program, and eight months after participating in the program, to determine the behavior and changes over time. For all questions, scores were higher at two and eight months after attending the program than before attending the program (P &lt;0.05). In addition, no significant difference was observed between two and eight months after attending the program for all questions (P =0.504-1.000). The knowledge gained from the educational program was used to repeatedly intervene with patients with cancer, to address the various symptoms they experienced and maintain their behavior. The proven effectiveness of this program serves as a stepping stone for a nationwide rollout across Japan’s 47 prefectures.

Short-range Internet of Things (IoT) sensor nodes operating at 2.4 GHz need to provide ubiquitous wireless sensor networks (WSNs) with energy-efficient, wide-range output power (POUT) and fully integrated on a single chip for wireless body area networks (WBANs) and wireless personal area networks (WPANs) using low-power Bluetooth (BLE) and Zigbee standards. The proposed fully integrated transmitter (TX) utilizes a digitally controllable current-mode class-D (CMCD) power amplifier (PA) with a second harmonic distortion (HD2) suppression to reduce VCO pulling in an integrated system while meeting harmonic limit regulations. The CMCD PA is divided into 7-bit slices that can be reconfigured between differential and single-ended topologies. Duty cycle distortion compensation is performed for HD2 suppression, and an HD2 rejection filter and a modified C-L-C low-pass filter (LPF) reduce HD2 further. Implemented in a 28 nm CMOS process, the TX achieves a wide POUT range of from 12.1 to -31 dBm and provides a maximum efficiency of 39.8% while consuming 41.1 mW at 12.1 dBm POUT. The calibrated HD2 level is -82.2 dBc at 9.93 dBm POUT, resulting in a transmitter figure of merit (TX_FoM) of -97.52 dB. Higher order harmonic levels remain below -41.2 dBm even at 12.1 dBm POUT, meeting regulatory requirements.

The Work Ability Index (WAI) is the most widely used questionnaire for the self-assessment of working ability. Because of its different applications, shorter versions, and widespread use in healthcare activities, it is worthwhile assessing its characteristics. The WAI was distributed online among the workers of a healthcare company; the results were compared with data contained in the workers' personal health records and with absence registers. 340 out of 575 workers (59.1%) participated; 6.5% of them reported poor work ability. Exploratory factor analysis indicated that the one-factor version best described the characteristics of the WAI. The scores of the complete WAI, the shorter form without the list of diseases, and the minimal one-item version (WAS) had equal distribution and were significantly correlated. The WAI score was inversely related to age and significantly lower in women than in men, but it was higher in night workers than in colleagues due to the probable effect of selective factors. The WAI score was also correlated with absenteeism, but no differences were found between males and females in the average number of absences, suggesting that cultural or emotional factors influence the self-rating of the WAI. Workers tended to overreport illnesses in the online survey compared to data collected during occupational health checks. Musculoskeletal disorders were the most frequently reported illnesses (53%). Psychiatric illnesses affected 21% of workers and had the greatest impact on work ability. Multilevel ergonomic and human factor intervention seems to be needed to recover the working capacity of healthcare workers.

While many studies have described the association between cognitive decline and eating habits, little attention has been paid to its association with cheese intake. In this cross-sectional study of 1,035 community-dwelling women aged ≥ 65, we investigated the association between intake/type of cheese and cognitive function. The anthropometry, functional ability, and the frequency of food intake, including cheese, were assessed. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and a score of 20–26 was defined as mild cognitive decline (MCD). We found that MMSE score was significantly different between the presence of cheese intake (cheese intake: 28.3±1.9; non-cheese intake: 27.8±2.2) and between the type of cheese consumed (Camembert cheese: 28.7±1.3; others: 28.3±1.9). After adjusting for confounders, multiple logistic regression revealed four significant independent variables for MCD: Camembert cheese intake (odds ratio [OR] = 0.448, 95% confidence interval [CI] = 0.214–0.936), age (OR = 1.114, 95% CI = 1.059–1.171), usual walking speed (OR = 0.2620, 95% CI = 0.109–0.621), and repetitive saliva swallowing test scores (OR = 0.865, 95% CI = 0.750–0.995). Our results, while based on cross-sectional data from Japanese community-dwelling older women, demonstrated that Camembert cheese intake is significantly associated with MCD.

Diacylglycerol kinase (DGK) is a lipid kinase that phosphorylates diacylglycerol (DAG) to generate phosphatidic acid (PA). Based on converting one important signaling molecule (DAG) to another (PA), DGK plays an important role in plant responses to abiotic stress including waterlogging stress. However, no studies have been reported on the characterization of the DGK gene family in the waterlogging-tolerant kiwifruit germplasm, Actinidia valvata Dunn. Here, we identified 18 AvDGK genes in the A. valvata genome. The phylogenetic analysis showed that AvDGKs can be classified into three clusters, and members within the same cluster have similar domain distribution, exon-intron structures and conserved motif compositions. Chromosome localization analysis revealed that all the AvDGK genes are located across 18 different chromosomes. There were 29 duplicated gene pairs in kiwifruit and all had undergone purifying selection during evolution. Promoter cis-element analysis revealed that the cis-elements within AvDGK genes are associated with multiple functions, including phytohormone signal transduction, stress response, and plant growth and development. The expression pattern analyses indicated that AvDGK play an important role in the fruit development and plant response to waterlogging stress. AvDGKs gene family in the tetraploid A. valvata genome might promote PA synthesis and subsequent signal transduction both under short-term and long-term waterlogging stress. These results provide information regarding the structural characteristics and potential function of DGK genes within kiwifruit and lay a fundamental basis for further research into breeding for enhancing the kiwifruit’s tolerance to waterlogging stress.

We investigated differences in mpox clinical outcomes in people with HIV (PWH) and without HIV (PWoH) and the impact of vaccination in Catalonia, Spain. We used surveillance data and the PISCIS HIV Cohort. We included all confirmed mpox cases (May-December 2022). Of 2122 mpox cases, the majority had mild disease, 56% were Spanish, and 24% from Latin-America. Forty percent were PWH, with median CD4+T-cell 715 cells/µL, 83% had HIV-RNA<50 copies/ml and 1.8% CD4+T-cell<200 cells/L. PWH had no increased risk for complications, except in cases of immunosuppression. PWH with CD4+T-cell<200 cells/µL were more likely to be from Latin-America, had more generalized exanthema, and required hospitalization more frequently (p=0.001). Diagnosis of other sexually transmitted infections (STIs) was common, both at mpox diagnosis (17%) and 2 years before (43%). Dose-sparing smallpox vaccination was accompanied by a sharp decrease in mpox incidence in both populations (p<0.0001). In conclusion, PWH were not at increased risk of severe disease or hospitalization unless immunosuppressed. Mpox is a marker of high-risk sexual behavior and was associated with high HIV and STI rates, supporting the need for screening in all mpox cases. Ethnicity disparities underscore the need for interventions to ensure equitable healthcare access. Dose-sparing smallpox vaccination retained effectiveness.

Vibro-fluidized dry coal beneficiation involves the unavoidable mixing of -1 mm coal dust into the fluidized bed, which compromises the stability and homogeneity of the bed density and reduces the effectiveness of fine-grained coal separation. In order to understand the features of coal powder separation and mixing (-1 mm) in a vibrating fluidized bed, as well as to achieve a uniform and stable bed density, a wide-grained dense medium consisting of -1 mm coal dust and 0.3-0.15 mm magnetite powder was homogeneously mixed in this work. The degree of density separation in the entire bed was examined, as well as the local mixing properties of the Wide-grained Dense Medium. It was discovered that when low vibrational energy was introduced at the same gas velocity, particle separation was enhanced in comparison to the usual fluidized bed. Little bubbles were found to ensnare fine coal dust and migrate upward, increasing density separation. The introduction of high vibrational energy leads to particle disorder within the bed and an increase in the level of particle mixing. The beneficial effects of vibration on the bed are diminished when the gas velocity is gradually increased under specified vibration circumstances. This causes big bubbles to develop more frequently, which increases particle mixing. Among them, the 1-0.5 mm fine-grained coal exhibits the best mixing state; it is less impacted by variations in air velocity and vibration levels, whereas the -0.5 mm coal dust is more affected by each of these variables. Furthermore, a wide range of air velocity regulation without a significant segregation state change was discovered to be achievable by the particle system under vibration circumstances of f=25Hz A=1mm and f=25Hz A=2mm.

Stueckelberg-Horwitz-Piron (SHP) electrodynamics formalizes the distinction between coordinate time (measured by laboratory clocks) and chronology (temporal ordering) by defining 4D spacetime events x^μ as functions of an external evolution parameter τ. Classical spacetime events x^μ (τ) evolve as τ grows monotonically, tracing out particle worldlines dynamically and inducing the five U(1) gauge potentials through which events interact. Since Lorentz invariance imposes time reversal symmetry on x⁰ but not τ, the formalism resolves grandfather paradoxes and related problems of irreversibility. The action involves standard first order field derivatives but includes a higher order τ derivative that while preserving gauge and Lorentz invariance removes certain singularities and makes the related QFT super-renormalizable. The resulting field equations are Maxwell-like but τ-dependent and sourced by a current that represents a statistical ensemble of instantaneous events distributed along the worldline. The width λ of this distribution defines a correlation time for the interactions and a mass spectrum for the photons that carry the interaction. As λ becomes very large, the photon mass goes to zero and the field equations become τ-independent Maxwell’s equations. Maxwell theory thus emerges as an equilibrium limit of SHP, in which λ is larger than any other relevant time scale. Particles and fields are not constrained to mass shells in SHP theory, and by exchanging mass may produce pair creation/annihilation processes at the classical level. On-shell evolution with fixed particle masses is restored through a self-interaction associated with the 5D wave equation.

We assessed depression, anxiety, and stress in healthcare workers (HCWs) in 2023 and the evo-lution of depression in 2023 compared with 2022. In September-November 2023, 181 HCWs from the Infectious Diseases Hospital, Cluj-Napoca, Romania, completed the Depression, Anxiety, and Stress 21 Scale (DASS-21 R), the Patient Health Questionnaire-9 (PHQ-9), and the Hamilton Anxiety Rating Scale (HAM-A). The prevalence of moderate-to-severe levels was 13.81% for DASS-Depression, 18.79% for DASS-Anxiety, 16.02% for DASS-Stress, 19.89% for PHQ-9, and 12.16% for HAM-A. Moderate-to-severe PHQ-9 clinical depression was found in 19.89% of respondents, and moderate-to-severe HAM-A clinical anxiety in 12.16%. Moderate-to-severe PHQ-9 depres-sion was significantly lower in the 2023 study group (19.89%, N=181) compared with 2022 (30.60%, N=114) (p=0.036), also within the 2022-2023 follow-up study group (N=88) (p=0.026). We did not find significant statistical differences between those infected vs. non-infected, vaccinated vs. non-vaccinated, working with vs. non-working with SARS-CoV-2 infected patients. Males were significantly more stressed (p=0.018) and anxious (p=0.034), and physicians in training had the highest prevalence of moderate-to-severe depression (31.60%), followed by physicians (25.64%). In 2023, depression, anxiety, and stress symptoms decreased but remained within a concerning range. By addressing these psychological issues, we can prevent professional crises in the healthcare system.

Increasingly, genomics is being used for the prediction of specific traits and diseases (phenotypes) among humans. Wider availability of genomics data through multiple research projects (such as International HapMap Project1 and 1000 Genomes2) has been a catalyst in that direction. With the recent advances in machine learning and big data analysis, data computation resources and data models needed for genomics data analysis are readily available. However, the prediction of traits and diseases has its own challenges in terms of computational requirements and computational analysis, statistical analysis (example: confounding variables), and limited quality of data collection. Linear Mixed Models (LMM, a type of linear regression) is a common approach for Genome-wide Association Studies (GWAS) for the prediction of common traits among humans using genomics. This paper researches the existing LMM-based approaches for Genome-wide Association Studies (GWAS), describes the experiment performed on FaST-LMM approach from Microsoft Research, and then proposes an enhanced approach (called LMM-22) on how to address computational and statistical issues. LMM-22 focuses on the parallelization of LMM computations and execution of LMM-22 on General Purpose Graphics Processing Units (GPU) as against CPUs to accelerate the LMM approach for GWAS studies.

Insulin-like Growth Factor 2 mRNA binding Protein 1 (IGF2BP1) is a promising candidate gene for influencing economic traits in livestock and poultry. The second intronic region of IGF2BP1 is closely related to growth traits, although the exact mechanism remains unclear. The preliminary resequencing results of goats in our laboratory demonstrated that the IGF2BP1 gene region was subject to strong selection, then we selected multiple single nucleotide polymorphisms (SNPs) to identify. Seven SNPs were located in the conserved region of the second intron, and their functions and relationship with growth traits require further clarification. This study selected 348 Nanjiang Yellow goats as experimental subjects, and chose Time of Flight Mass Spectrometer (MALDI-TOF) as the main method. Our results showed that six SNPs were significantly correlated with the growth traits of the Nanjiang yellow goat by association analysis. Among them, the rs652062749(A>G) was identified as the primary locus affecting the later stage of growth traits of Nanjiang yellow goat. Moreover, there was a strong linkage among three SNPs, and the rs638185407 (T>A) mutant type was observed to increase the luciferase activity in H293T cells extremely significantly. The TTAACT, TTCCCC, and ATCACT combination genotypes were dominant combination genotypes, which provided theoretical references for further genetic co-breeding. The results of our study demonstrate the potential role of the IGF2BP1 gene as a functional genetic marker in the breeding programs of Nanjiang Yellow goats.

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

Global coverage and scale up of interventions to reduce newborn mortality remains low, though progress has been achieved in improving newborn survival in many low-income settings. An important factor in the success of newborn health interventions, and moving to scale, is appropriate design of community-based programs and strategies for local implementation. We report the results of formative research undertaken to inform the design of a newborn health intervention in Cambodia. Information was gathered on newborn care practices over a period of three months using multiple qualitative methods of data collection in the primary health facility and home setting. Analysis of the data indicated important gaps, both at home and facility level, between recommended newborn care practices and those typical in the study area. The results of this formative research have informed strategies for behavior change and improving referral of sick infants in the subsequent implementation study. Collection and dissemination of data on newborn care practices from settings such as these can contribute to efforts to advance survival, growth and development of newborns for intervention research, and for future newborn health programming.

Wide-field (WF) retinal imaging is becoming a standard diagnostic tool for diseases involving the retinal periphery. Technological progress elicited the advent of wide-field optical coherence tomography (WF-OCT) and WF-OCT angiography (WF-OCTA) examinations. This review presents the results of studies that analyzed the implementation of these procedures in clinical practice and refers to them as traditional and ultra-wide-field fluorescein angiography (UWF-FA). The PUBMED search was performed using the terms WF-OCT OR WF-OCTA OR UWF-FA AND the specific clinical entity, including diabetic retinopathy (DR), retinal vein occlusion (RVO), Coats disease, peripheral retinal telangiectasia, peripheral retinal degeneration, lattice degeneration, and posterior vitreous detachment. The analysis only included the studies in which the analyzed field of view for the OCT or OCTA exam was larger than 55 degrees. The evaluation of the extracted studies indicates that WF imaging with OCT and OCTA provides substantial information on retinal disorders involving the retinal periphery. Vascular diseases, such as DR or RVO, can be reliably evaluated using WF-OCTA with results superior to standard-field fluorescein angiography. Nevertheless, UWF-FA provides a larger field of view and still has advantages over WF-OCTA concerning the evaluation of areas of non-perfusion and peripheral neovascularization. Detailed information on the vascular morphology of peripheral changes should be obtained via WF-OCTA, not angiographic examinations. WF-OCT can serve as a valuable tool for the detection and evaluation of vitreoretinal traction, posterior vitreous detachment, and peripheral retinal degeneration, and guide therapeutic decisions on a patient’s eligibility for surgical procedures.

Background: This longitudinal study aimed to investigate the relationship between self-reported chewing status and increases in waist circumference (WC) after 1 year in 10,870 Japanese adults who had received health checkups. Subsequently, 8,068 participants were included in the final analysis at follow-up. Methods: Chewing status was evaluated using a self-reported questionnaire at baseline; 1,080 (13%) respondents were diagnosed as having poor chewing status. We defined an increase in WC of ≥ 5 cm after 1 year as an unhealthy increase; in total, 613 (7.5%) respondents met this criterion. Results: After adjusting for age, gender, WC, body mass index (BMI), and chewing status, an increase in WC ≥ 5 cm was found to be positively associated with gender (females: odds ratios [ORs]: 1.206; 95% confidence intervals [CIs]: 1.008–1.443), WC (ORs: 0.967; 95% CIs: 0.954–0.981), BMI (≥ 25 kg/m2; ORs: 2.194; 95% CIs: 1.715–2.808), and chewing status (poor; ORs: 1.356; 95% CIs: 1.084–1.697). Conclusions: These findings suggest that self-reported poor chewing status is associated with increases in WC after 1 year in Japanese adults.

Abstract Objectives: The purpose of this study was to determine whether breast cancer and diabetes status are related in adult Americans. Methods: We conducted a cross-sectional study of 7,599 individuals from the National Health and Nutrition Examination Survey (NHANES). Diabetes was classified as type 2 diabetes and pre-diabetes. Both prediabetes and diabetes were diagnosed according to ADA 2014 guidelines. Multiple logistic regression analysis was used to explore the relationship between diabetes status and breast cancer. Results: We found that prediabetes (OR = 0. 60, 95% CI:(0. 40, 0. 88), P= 0. 009613) and non-diabetes (OR = 0.05.3,95% CI: (0.34, 0.83), P = 0. 006014) were associated with a reduced risk of breast cancer in comparison to Type 2 diabetes (literature). Prediabetes in non-Hispanic blacks was associated with a reduced risk of breast cancer (OR=0. 55,95%CI:0. 40-0. 75, P<0. 001). Using two segmented linear regression models to fit the relationship between BMI and breast cancer, we found that the relationship between BMI and breast cancer was nonlinear, but there was a threshold effect. The threshold effect analysis found that BMI affcted breast cancer at an inflection point 26. 3 Kg/m2. Adjusted OR (95% CI) on both sides of the turning point was 1. 0799 ( 1. 0029, 1. 1629 ) and 0. 9873 ( 0. 9638, 1. 0115 ), respectively. Conclusions: Diabetes status is associated with the risk of breast cancer development. Moreover, the risk of developing breast cancer steadily increased from nondiabetes to prediabetes and type 2 diabetes. In addition, the prevalence of breast cancer showed a gradual increase withincreasing BMI up to 26. 3 Kg/m2 with the highest prevalence of breast cancer. There was an inverse U-shaped relationship between BMI and the breast cancer prevalence.

Background: Upper respiratory tract infections (URTIs) are a major public health concern due to their high incidence and potential for complications. Pharmacists often serve as the first point of contact for patients with URTIs. This study aims to develop and evaluate the RESP-8 tool to assist pharmacists in determining the need for medical evaluation. Methods: This prospective interventional cohort study was conducted over six months (October 2023 to March 2024) in community pharmacies. Participants included adults aged 18 years and older presenting with URTI symptoms. Pharmacists used the RESP-8 tool, which comprises eight criteria to assess the need for medical referral. Data on medical history, symptom duration, and progression were recorded. The primary outcome was the feasibility of implementing the RESP-8 tool. Secondary outcomes included the accuracy of the tool, the percentage of patients recommended for medical evaluation, and compliance with these recommendations. Results: A total of 64 participants were included, with an average age of 55.7 years. Pharmacists recommended medical evaluation for 75% (48/64) of patients using the RESP-8 tool. Among these, 70.83% (34/48) complied with the recommendation. The tool demonstrated high accuracy in identifying patients needing further medical evaluation, with only two noted errors. All compliant patients received appropriate treatment without complications. The tool was easy to implement, taking less than 5 minutes per patient. Discussion: The RESP-8 tool effectively guided pharmacists in recommending medical evaluations for URTI patients. The high compliance rate indicates patient trust in pharmacists' guidance. While the study's small sample size limits generalizability, the results are promising. Future studies with larger populations are necessary to validate these findings and further refine the tool. Conclusion: The RESP-8 tool shows potential in enhancing pharmacists' ability to make informed decisions about medical referrals for URTIs, ultimately improving patient outcomes and optimizing healthcare resource management.

Wastewater-based surveillance has emerged as an important method for monitoring SARS-CoV-2. This study investigated the presence of SARS-CoV-2 in wastewater in Zambia. We conducted a longitudinal study in the Copperbelt and Eastern provinces of Zambia from October 2023 to December 2023 during which 155 wastewater samples were collected. The samples were subjected to three different concentration methods, namely bag-mediated filtration, skimmed milk flocculation, and polythene glycol-based concentration assays. Molecular detection of SARS-CoV-2 nucleic acid was conducted using real-time PCR. Whole genome sequencing was conducted using Illumina COVIDSEQ assay. Of the 155 wastewater samples, 62 (40%) tested positive for SARS-CoV-2. Of these, 13 sequences of sufficient length to determine SARS-CoV-2 lineages were obtained and two sequences were phylogenetically analyzed. Various Omicron subvariants were detected in wastewater including BA.5, XBB.1.45, BA.2.86, and JN.1. Some of these subvariants have been detected in clinical cases in Zambia. Interestingly, phylogenetic analysis positioned a sequence from the Copperbelt Province in the B.1.1.529 clade, suggesting that earlier Omicron variants detected in late 2021 could still be circulating and may not have been wholly replaced by newer subvariants. This study stresses the need for integrating wastewater surveillance of SARS-CoV-2 into mainstream strategies for monitoring SARS-CoV-2 circulation in Zambia.

Front-of-pack labelling (FOPL) systems, such as the Nutri-Score, play a crucial role in promoting healthy diets and raising consumer awareness. Our study aimed to gather the opinions of Polish experts on the Nutri-Score and its relation to an ideal information system. We conducted a Poland-wide expert opinion study using a cross-sectional design survey with 75 participants, who had an average of 18±13 years of experience and were mainly employed at medical and agricultural universities. The data were collected with CAWI method. The results showed that the most important features of an FOPL system were clarity, simplicity, consistency with healthy eating recommendations, and the ability to objectively compare products within the same group. While more than half of the respondents believed that the Nutri-Score provides an overall assessment of a product’s nutritional value and facilitates quick purchasing decisions, it falls short in helping consumers compose a balanced diet and cannot be applied to all product groups. The experts also expressed concerns about the system’s ability to account for a product’s degree of processing, full nutritional value and carbon footprint. In conclusion, Poland’s current labelling system needs expansion, but the Nutri-Score requires significant and deep changes and validation against national guidelines and expert expectations before implementation.

Background and Objectives Neurofibromatosis 1 (NF1 MIM # 162200), also known as von Recklinghausen disease, is among the most common autosomal dominantly transmitted disorders characterized mainly by neurocutaneous manifestations such as café au lait spots, intertriginous freckling, various types of neurofibromas (cutaneous neurofibromas or plexiform tumors), neurological manifestations, and bone abnormalities. It occurs with an incidence of 1:3000–1:4000 cases. Cone-rod dystrophies belong to the large group of retinal dystrophies, a highly heterogeneous group of disorders clinically manifested mainly by damage to cone and rod cells and have a broad spectrum of clinical manifestations. Many genes are involved in their etiology, with more than 100 currently identified, including the CRX gene responsible for the autosomal dominant form of cone-rod dystrophy (ad CORD). Materials and Methods: The authors present an intriguing case of a patient diagnosed with Neurofibromatosis type 1 (NF1) as an infant and ocular involvement (myopia and astigmatism onset at age 15), which yielded a surprising molecular testing result. Results: Molecular DNA analysis identified a rare occurrence of two mutational variants, including a pathogenic variant in the NF1 gene, c.3871-2A, and a likely pathogenic variant in the CRX gene c.119G>A. Conclusions: The authors present this case to highlight the surprises offered by molecular testing in a condition where the diagnosis is usually based on clinical criteria, thus providing patients with competent genetic advice.

As practiced in Africa, urban agriculture (UA) has been examined in the literature and by architecture and urban planning experts, revealing both advantages and disadvantages for health. While the recognized disadvantages are not negligible, the literature focuses mainly on the positive outcomes about food security and improved socio-economic conditions for farmers. However, little research has focused on farmers' perceptions of the effect of this practice on their psychological well-being. This study seeks to delve into this aspect by surveying 733 farmers in Dar es Salaam and Greater Lomé to map UA's distribution, assess its benefits and challenges, study its psychosocial associations, and demonstrate how architectural design and urban planning can enhance its spatial distribution and overall benefits. The standardized Mental Health Continuum-Short Form (MHC-SF) and non-standardized questionnaires are used to evaluate their responses. Using logistic regression and spatial analysis techniques with Python and QGIS 3.32.2-Lima, the analysis uncovers that farmers attribute improved psychological well-being to their involvement in UA. The study found that farmers' happiness due to UA varies by location within a city, with those on the outskirts generally more satisfied than those in urban centers. Additionally, women farmers reported greater happiness than men farmers, highlighting UA's role in empowering women. The research underscores UA's positive association with practitioners' psychological health in Africa and advocates for its integration into urban planning to promote equitable and beneficial urban spaces.

Early reporting of the introduction and establishment of exotic species is of paramount importance for successful management. Here we report the introduction and rapid spread of the Bare-eyed Pigeon, Patagioenas corensis, on the binational island of Saint-Martin, West Indies. This range-restricted species naturally occurs in the arid coastal areas of Columbia and Venezuela and nearby islands. Its introduction on Saint-Martin represents an expansion of about 1000 km beyond its established native range. Using observations recorded in e-bird and results from a recent field survey, we show that since its introduction, most probably between late 2012 and early 2013, the species is expanding fast in Saint-Martin and has recently broadened its habitat to include anthropized, built areas. The expansion of Bare-eyed Pigeon on Saint-Martin and the neighbouring Leeward Islands, possibly facilitated by climate change in the future, could be a threat to both native columbid species and other bird species, through competition for resources. We therefore recommend to local authorities and stakeholders to rapidly eradicate the species or at least prevent its further spread on Saint-Martin, possibly though listing it as a game species, while it is still possible to do so.

The human gastrointestinal gut contains about 100 trillion of microorganisms including up to 5000 different types of bacteria called the "gut microbiome". Alterations in the composition of gut microorganisms (dysbiosis) can cause threatening for life diseases. This present seeks to evaluate if finally diet and more specifically functional foods affect the intestinal microbiome, and if obesity and the metabolic syndrome (Mets) are associated with the intestinal microbiome. This systematic review was accomplished according to PRISMA guidelines mostly using the key words functional foods, microbiome, obesity, Mets, Mediterranean diet. The search was carried out of recent scien-tific articles from the databases Pubmed, Scopus, and Google Scholar. The most studies discussed in this review showed a potential therapeutic effect of the Mediterranean diet rich in beneficial nutrients, on body weight, fat deposition, in correlation with modulation of the synthesis of gut microbiome. This literature review demonstrates a possible relationship between the metabolites of the microflora, the endotoxemia, obesity and Mets. The role of probiotics, prebiotics, and polyphe-nols in the prevention of obesity and Mets is of high importance in promoting healthy aging. The future challenge is to understand how different dietary patterns can regulate the composition of the gut microflora and whether these changes could be long-term.

Every individual at some point encounters the progressive biological process of aging which is considered one of the major risk factors for common diseases. The main drivers of aging are oxi-dative stress, senescence, and Reactive oxygen species (ROS). The renin-angiotensin-aldosterone system (RAAS) includes several systematic processes for the regulation of blood pressure which is caused by an imbalance of electrolytes. During activation of RAAS, binding of angiotensin II (ANG II) to angiotensin II type I receptor (AGTR1) activates intracellular NADPH oxidase to generate superoxide anions and promote uncoupling of endothelial NO synthase, which in turn decreases NO availability and increases ROS production. Promoting oxidative stress and DNA damage mediated by ANG II is tightly regulated. Individuals with sodium deficiency-associated diseases such as Gitelman syndrome (GS) and Bartter syndrome (BS) show down-regulation of inflammation-related processes and have reduced oxidative stress and ROS. Additionally, the histone deacetylase-Sirtuin-1(SIRT1) has a significant impact on the aging process with reduced activity with age. However, GS/BS patients generally sustain higher levels of SIRT1 activity than aged-matched healthy individuals. In this review, we highlight the importance of the hallmarks of aging, inflammation, and the RAAS system in GS/BS patients and how this might impact healthy aging. We further propose fu-ture research directions for studying the etiology of GS/BS at the molecular level using pa-tient-derived renal stem cells and induced pluripotent stem cells.

This study aimed to present a systematic meta-analysis examining the association between Helicobacter pylori (H. pylori) infection, hemoglobin A1c levels, and the development of type 1 diabetes mellitus. The initial search identified 451 articles related to the association between H. pylori infection and T1DM. Among them, 14 articles had 2,971 participants meeting the inclusion criteria for advanced meta-analysis. A significant association was observed between H. pylori infection and T1DM, with an odds ratio (OR) of 1.87 (95% confidence interval [CI]: 1.27–2.78, p = 0.002). A subgroup analysis on H. pylori status showed that a longer duration of diabetes diagnosis and higher hemoglobin A1c levels were significantly associated with H. pylori infection (p < 0.001 for both). However, there was no significant association between H. pylori infection and the diagnostic age of diabetes (p = 0.306). These findings contribute to the understanding of the association between H. pylori infection and T1DM, thereby highlighting the potential role of H. pylori in influencing the duration and glycemic control of diabetes.

More than two-thirds of death in developing countries are due to non-communicable diseases (NCDs), and tobacco is a leading risk factor. Among different socio-demographic factors, occupation and its corelates have impact on use of smokeless tobacco (SLT) and the evidence in India is limited. The objectives of this study are to find out the overall preva-lence of SLT use and its pattern of association with various occupation and associated variables. Methods: This study used data from Longitudinal Ageing Study in India (LASI) wave 1. Current and ever users of SLT are taken into consideration as target population. For the data analysis, survey-weighted tools have been applied for descriptive statistics and multivariable logistic re-gression model. The weighted data analysis has been done using R. Results and Discussion: From the sample size of 65561, 38% have ever used either smoking or SLT, of them, 40 % use to-bacco in smoke form, 51 % use SLT and 9 % take both. At the population level, 22.8% and 20.4% are ever and current users of SLT respectively. Type, place, and workload in the occupation found to be significantly associated with SLT use. Workplace tobacco-cessation-policy for infor-mal-workers is required to manage this issue.

Cohort studies have identified several genetic determinants that could predict the clinical response to allopurinol. However, they have not been commonly used for genome-wide investigations to identify genetic determinants on allopurinol metabolism and concentrations. We conducted a genome-wide association study of a prior cross-sectional investigation of patients from the Montreal Heart Institute Biobank undergoing allopurinol therapy. Four endpoints were investigated, namely plasma concentrations of oxypurinol, the active metabolite of allopurinol, allopurinol, and allopurinol-riboside, as well as allopurinol daily dosing. A total of 439 participants (mean age 69.4 years; 86.4% male) taking allopurinol (mean daily dose 194.5 mg) and who had quantifiable oxypurinol concentrations were included in the genome-wide analyses. Participants presented multiple comorbidities and received concomitant cardiovascular medications. No association achieved the predefined genome-wide threshold values for any of the endpoints (all p&gt;5 × 10-8). Our results are consistent with prior finding regarding the difficulty in identifying genetic determinants of drug concentrations or pharmacokinetics of allopurinol and its metabolites, and allopurinol daily dosing. Given the size of this genome-wide study, collaborative investigations involving larger and diverse cohorts may be required to further identify pharmacogenomic determinants of allopurinol and measure their clinical relevance to personalize allopurinol therapy.

Studies on the possible association between bacteria and oral squamous cell carcinoma (OSCC) remain inconclusive, largely due to methodological variations/limitations. The objective of this study was to characterize the species composition as well as functional attributes of the bacteriome associated with OSCC. DNA obtained from 20 fresh OSCC biopsies (cases) and 20 deep-epithelium swabs (matched control subjects) were sequenced for the V1-V3 region using Illumina’s 2x300 bp chemistry. High quality, non-chimeric merged reads were classified to species level using a prioritized BLASTN-algorithm. Downstream analyses were performed using QIIME, PICRUSt, and LEfSe. Fusobacterium nucleatum subsp. polymorphum was the most significantly overrepresented species in the tumors followed by Pseudomonas aeruginosa and Campylobacter sp. Oral taxon 44, while Streptococcus mitis, Rothia mucilaginosa and Haemophilus parainfluenzae were the most significantly abundant in the controls. Functionally, genes involved in bacterial mobility, flagellar assembly, bacterial chemotaxis and LPS synthesis were enriched in the tumors while those responsible for DNA repair and combination, purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, ribosome biogenesis and glycolysis/gluconeogenesis were significantly associated with the controls. This is the first epidemiological evidence for association of F. nucleatum and P. aeruginosa with OSCC. Functionally, an “inflammatory bacteriome” is enriched in OSSC.

This paper utilizes the 2020 financial data of A-share listed companies, both ST and non-ST, as the data sample. The model is constructed employing the Factor-Logistic fusion algorithm. Eight key indicator factors were selected from the frameworks of profitability, solvency, operating capacity, development potential, shareholder retained earnings, cash flow and asset growth. An independent indicator system was subsequently established to address the issue of collinearity among risk indicators. The results of model are presented in the form of probabilities, enhancing the interpretability of model. The weights of the features indicate the influence of different features on the final outcome. The model achieves a prediction accuracy of over 89%, with an AUC score exceeding 95%. Finally, by applying the principles of interval estimation theory in statistical hypothesis testing, the risk levels are categorized as A-level representing significant risk, B-level representing moderate risk, C-level representing minor risk and D-level representing no risk. This paper aims to provide a comprehensive definition of a universal financial risk management warning model for enterprises, applicable to all enterprises in China.

Background/Objectives: Concurrent opioid (OPI) and benzodiazepine (BZD) use may exacerbate falls/fractures risk compared to no use or use alone. Yet, patients may need concurrent OPI-BZD use for co-occurring conditions (e.g., pain and anxiety). Therefore, we examined the association between longitudinal OPI-BZD dosing patterns and subsequent injurious falls risk. Methods: We conducted a retrospective cohort study including non-cancer fee-for-service Medicare beneficiaries initiating OPI and/or BZD in 2016-2018. We identified OPI-BZD use patterns during the 3 months following OPI and/or BZD initiation (i.e., trajectory period) using group-based multi-trajectory models. We estimated time to first injurious fall within 3 months post-trajectory period using inverse-probability-of-treatment-weighted Cox proportional hazards models. Results: Among 622,588 beneficiaries (age≥65=84.6%, female=58.1%, White=82.7%; having injurious falls=0.45%), we identified 13 distinct OPI-BZD trajectories: Group(A):Very-low OPI-only (early discontinuation)(44.9% of the cohort); (B):Low OPI-only (rapid decline)(15.1%); (C):Very-low OPI-only (late discontinuation)(7.7%); (D):Low OPI-only (gradual decline)(4.0%); (E):Moderate OPI-only (rapid decline)(2.3%); (F):Very-low BZD-only (late discontinuation)(11.5%); (G):Low BZD-only (rapid decline)(4.5%); (H):Low BZD-only (stable) (3.1%); (I):Moderate BZD-only (gradual decline)(2.1%); (J):Very-low OPI (rapid decline)/Very-low BZD (late discontinuation)(2.9%); (K):Very-low OPI (rapid decline)/Very-low BZD (increasing)(0.9%); (L):Very-low OPI (stable)/Low BZD (stable)(0.6%); and (M):Low OPI (gradual decline)/Low BZD (gradual decline)(0.6%). Compared with Group(A), 6 trajectories had increased 3-month injurious fall risks: (C): HR, 95%CI=1.78, 1.58-2.01; (D): 2.24, 1.93-2.59; (E): 2.60, 2.18-3.09; (H): 2.02, 1.70-2.40; (L): 2.73, 1.98-3.76; and (M): 1.96, 1.32-2.91. Conclusions: Our findings suggest that 3-month injurious fall risk varied across OPI-BZD trajectories, highlighting the importance of considering both dose and duration when assessing fall risks of OPI-BZD use among older adults.

Background: In antibiotic naïve populations, there is a strong association between the use of an antimicrobial and resistance to this antimicrobial. Less evidence is available as to whether this relationship is weakened in populations highly exposed to antimicrobials. Individuals taking HIV PrEP have a high intake of antimicrobials. We previously found that there was no difference in the prevalence of pheno- and genotypic antimicrobial resistance between two groups of PrEP clients who had, and had not, taken antimicrobials in the prior 6-months. Both groups did, however, have a higher prevalence of resistance than a sample of the general population. Methods: In the current study, we used zero-inflated negative binomial regression models to evaluate if there was an individual level association between the consumption of antimicrobials and 1. the minimum inhibitory susceptibilities of oral Neisseria subflava and 2. the abundance of antimicrobial resistance genes in the oropharynges of these individuals. Results: We found no evidence of an association between the consumption of antimicrobials and the minimum inhibitory susceptibilities of oral Neisseria subflava or the abundance of antimicrobial resistance genes in these individuals. Conclusions: We conclude that in high antimicrobial consumption populations, the association between antimicrobial consumption and resistance may be attenuated.

Parkinson’s disease affects a significant number of elderly people around the world, and it is characterized by a variety of motor and non-motor symptoms. Among non-motor symptoms, depression has shown a high prevalence. Nonetheless, complementary therapies have been sought with a view to improving the mental health and quality of life of this population, where spirituality has proven to be a method capable of contributing to the improvement of depression. Accordingly, the objective is to analyze the relationship between spirituality and depression in elderly people with Parkinson’s disease. This is a cross-sectional study, carried out with 35 elderly people living in a municipality in the state of Santa Catarina/Brazil, diagnosed with Parkinson’s disease. It was possible to measure that the higher the general, religious and existential domains of the Spiritual Well-Being Scale, which involve feelings of completeness and satisfaction with life, peace with oneself and the world, and the higher the organizational domain of the Duke University Religion Index, which mainly involves the social component (participation in religious meetings), the lower will be the depression levels in people with Parkinson’s disease. Accordingly, it is concluded that spirituality can, in some way, contribute to the reduction of depression levels in elderly people with Parkinson’s disease.

Purpose The objective of this study was to eliminate any ambiguity by examining the correlation between gut microbiota and both AMD and glaucoma. Methods Mendelian randomization studies were conducted utilizing the data sourced from the GWAS database for the gut microbiome, AMD, and glaucoma. SNP estimates were summarized through five MR methods. We utilized Cochran's Q statistic to evaluate the heterogeneity of the instrumental variables. Additionally, we employed a "leave-one-out" approach to verify the stability of our findings. Results IVW suggests that Eubacterium (oxidoreducens group) and Parabacteroides had a protective effect on AMD. Both weighted median and IVW suggests that Lachnospiraceae (NK4A136 group) and Ruminococcaceae (UCG009) had a protective effect on AMD. However, both weighted median and IVW suggests that Dorea had a risk effect on AMD. Similarly, The IVW of Eubacterium (ventriosum group) showed a risk effect on AMD. The weighted median of Eubacterium (nodatum group), Lachnospiraceae (NC2004 group), and Roseburia had a risk effect on glaucoma. IVW suggested that Ruminococcaceae (UCG004) had a risk effect on glaucoma. Reverse MR analysis found a causal link between Eubacterium (nodatum group) and glaucoma. No causal relationships were found between AMD or glaucoma and the other mentioned bacterial groups. No significant heterogeneity or evidence of horizontal pleiotropy was detected. Conclusions This study found that certain gut bacteria had protective effects on AMD, while others may be risk factors for AMD or glaucoma. Besides, reverse MR found that glaucoma led to increased abundance of certain gut bacteria. Further trials are needed to clarify the specific mechanisms involved.

Aim: This study aimed to investigate the relationship between dental caries, dental anxiety, and salivary cortisol levels in children visiting pediatric dental clinics and their implications on pediatric oral health. Materials and Methods: A cross-sectional study was conducted at a dental university in the UAE. A total of 60 children, aged 4-12 years, were included. Salivary cortisol levels were measured using an Enzyme-Linked Immunosorbent Assay (ELISA) kit. Dental caries status was evaluated, and dental anxiety levels were assessed using the Modified Dental Anxiety Scale (MDAS). Statistical analyses, including Mann-Whitney U test and Pearson's correlation coefficient, were performed to determine significant differences and associations. Results: The study group showed significantly higher salivary cortisol levels compared to the control group (p<0.0001). A strong positive correlation was found between salivary cortisol levels and dental caries status (p<0.001). However, no significant difference in dental anxiety levels was observed between the study and control groups (p=0.85). A strong positive correlation was found between dental anxiety levels and dental caries status (p<0.001). Conclusion: The findings indicate a significant association between salivary cortisol levels and dental caries, suggesting that higher cortisol levels are associated with active caries. Dental anxiety levels were positively correlated with dental caries. Understanding the relationship between these variables can contribute to better oral health strategies and interventions for children, emphasizing the importance of managing dental anxiety and stress in pediatric dental care. Clinical Significance: This study highlights the potential of salivary cortisol as a biomarker for assessing stress and its impact on oral health in children. By addressing dental anxiety and stress, dental professionals can provide child-friendly dental care, enhance preventive measures, and improve oral health outcomes in pediatric patients.

In this paper thermo-mechanical behavior of 4D printed Polylactic Acid (PLA) was investigated, focusing on its response to varying strain rates and temperatures below the glass transition temperature. Dynamic mechanical analysis and uniaxial tensile tests confirmed PLA's dependency on strain rate, showcasing its sensitivity to external stimuli. Stress-strain curves exhibited typical thermoplastic behavior, with yield stresses varying with strain rates, underscoring PLA's responsiveness to different deformation speeds. Clear strain rate dependence was observed, particularly at quasi-static rates, with temperature and strain rate fluctuations significantly influencing PLA's mechanical properties, including yield stress and deformation behavior. Isothermal compression tests demonstrated predictable stress-strain curves with distinct yield points, while adiabatic tests reveal additional complexities such as heat accumulation leading to further softening. Thermal imaging revealed temperature increase during deformation, highlighting the material's thermo-sensitive nature. These findings provide the basis for future research with the focus on advanced modeling techniques and mitigation strategies for self-heating effects, aiming to enhance PLA-based product reliability and performance in applications with deformations at higher strain rates, while also developing models to simulate shape recovery in 4D printed PLA structures at both cold and hot programming temperatures.

Few studies have examined the dietary protein intake and sources in combination with the longitudinal changes in brain structure markers. Our study aimed to examine the association between dietary protein intake and different sources of dietary protein with the longitudinal rate of change in brain structural markers. A total of 2723 and 2679 participants from the UK Biobank were included in the analysis. The relative and absolute amounts of dietary protein intake were calculated through a 24-hour dietary recall questionnaire. The longitudinal change rates of brain structural biomarkers were computed using two waves of brain imaging data. We utilized multiple linear regression to examine the association between dietary protein and different sources and the longitudinal changes in brain structural biomarkers. Restrictive cubic splines were used to explore nonlinear relationships, and stratified and sensitivity analyses were conducted. Increasing the proportion of animal protein in dietary protein intake is associated with a slower reduction in the total hippocampus volume (THV, β: -0.02524, P&lt;0.05), left hippocampus volume (LHV, β: -0.02435, P&lt;0.01) and right hippocampus volume (RHV, β: -0.02544, P&lt;0.05).Higher intake of animal protein relative to plant protein is linked to a lower atrophy rate in THV (β: -0.01249, P&lt;0.05) and LHV (β: -0.01173, P&lt;0.05) and RHV (β: -0.01193, P&lt;0.05). Individuals with higher intake of seafood exhibit lower longitudinal rate of change in HV compared to those with no consume (THV, β: -0.004514; P&lt;0.05; RHV, β: -0.005527, P&lt;0.05). In subgroup and sensitivity analyses, there was not a significantly alteration. A moderate increase in the intake and proportion of animal protein in the diet, especially from seafood, is associated with a lower longitudinal change rate in hippocampus volume.

To address the response of small RNAs (sRNAs) biogenesis to drought stress, we identified sRNAs biogenesis genes, including 11 encoding argonauts (AGO), 8 encoding dicer-like proteins (DCL), and 9 encoding RNA-dependent RNA polymerases (RDR) in the peach genome. Notably, the largest numbers of sRNAs biogenesis genes are located to chromosome 1. The PAZ, PIWI, and MID domains were identified in PpAGOs, while the ribonuclease IIIa and IIIb domains were characterized in PpDCLs. The RDRP domain was recognized in PpRDRs. Orthologous similarity and collinearity analyses between Arabidopsis and peach revealed 5, 1, and 2 collinear blocks in AGOs, DCLs, and RDRs, respectively. Moreover, 41, 40, and 42 cis-acting elements were located in the promoters of PpAGOs, PpDCLs, and PpRDRs, respectively, with the majority related to drought stress response. Analysis of RNA sequencing (RNA-seq) data revealed that sRNAs biogenesis genes were involved in drought stress response in different tissues. Furthermore, the expression of candidate genes was verified in two peach cultivars, Beijing 2-7 (BJ2-7) and Sinai (SN), which are drought tolerance and sensitive, respectively. Interestingly, the expression of PpAGO2b, PpDCL2b, PpDCL4, and PpRDR4 genes was induced in ‘BJ2-7’ but inhibited in ‘SN’ under drought stress. Overall, this study provides insight into the roles of sRNA biogenesis genes in response to drought stress in peach.

Congenital malformations are functional and structural alterations in embryonic or foetal development resulting from a variety of factors including maternal health status. This study aimed to investigate the association between maternal birth weight (MBW) and the prevalence of congenital malformations in the offspring using data from a nationwide birth cohort study in Japan including 103,060 pregnancies. A binary logistic regression model with adjustment for various covariates revealed that MBW of &lt;2,500 g (low MBW) was associated with increased risk of congenital heart disease (adjusted odds ratio: 1.388, [95% confidence interval: 1.075–1.792]), angioma (1.491 [1.079–2.059]), and inguinal hernia (1.746, [1.189–2.565]), while MBW of ≥4,000 g (high MBW) with congenital anomalies of the urinary tract (2.194, [1.261–3.819]), and arrhythmia (1.775, [1.157–2.725]), compared with those with MBW of 3,000-3,499 g. Low MBW was associated with cleft lip and/or palate (1.473, [1.052–2.064]), congenital heart disease (1.615, [1.119–2.332]), genital organs(1.648, [1.130–2.405]), hypospadias (1.804, [1.130–2.881]), and inguinal hernia (1.484, [1.189–1.851]) in male infants and CAKUT (1.619, [1.154–2.273]) in female infants, whereas high MBW was associated with congenital heart disease(1.745, [1.058–2.877]) and CAKUT (2.470, [1.350–4.517]) in male infants. The present study is the first to demonstrate a link between MBW and congenital malformations in Japanese children. While these results must be interpreted with caution, MBW should be considered a major predictor of congenital malformation risk.