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Simple Summary: Most birds' eggs are products of consumer demand (for direct consumption or used to produce edible birds, mostly chickens). Many scientists are thus engaged in analyzing their shape to help improve quality, productivity and marketability, and these studies open up prospects for the use of artificial intelligence (AI). Deep learning (DL) is a form of AI concerned with computers taking data and extrapolating them to new ideas without direct human guidance. DL is based on the workings of animal brains, and specifically performs classification, analysis and further scholarly tasks by learning from existing datasets. We first consider the "state of the art" of DL in the poultry industry, including image recognition and applications for detecting cracks, egg content and freshness. We comment on how AI algorithms need to be properly trained and consider egg profile geometry. We revisit previous publications' egg shape mathematics, commenting on the pros/cons of each. Examining weight, volume, surface area and air cell calculations, we consider how DL might be applied to these. The future value of DL is in egg sorting before incubation, storage/incubation and dimension calculation. Combining mathematical models with AI/DL means that we are on the threshold of many scientific discoveries, technological achievements and industrial successes. Avian eggs are products of consumer demand, with modern methodologies for their morphometric analysis used for improving quality, productivity and marketability. Such studies open up numerous prospects for the introduction of artificial intelligence (AI) and deep learning (DL). We first consider the state of the art of DL in the poultry industry, e.g., image recognition and applications for the detection of egg cracks, egg content and freshness. We comment on how algorithms need to be properly trained and ask what information can be gleaned from egg shape. Considering the geometry of egg profiles, we revisit the Preston–Biggins egg model, the Hügelschäffer's model, universal egg models, principles of egg universalism and "The Main Axiom", proposing a series of postulates to evaluate the legitimacy and practical application of various mathematical models. We stress that different models have pros and cons, and using them in combination may yield more useful results than individual use. We consider the classic egg shape index alongside other alternatives, drawing conclusions about the importance of indices in the context of applying DL going forward. Examining egg weight, volume, surface area and air cell calculations, we consider how DL might be applied, e.g., for egg storage. The value of DL in egg studies is in pre-incubation egg sorting, the optimization of storage periods and incubation regimes, and the index representation of dimensional characteristics. Each index can thus be combined to provide a synergy that is on the threshold of many scientific discoveries, technological achievements and industrial successes facilitated through AI and DL. [ABSTRACT FROM AUTHOR]

Disease-causing variants in key immune homeostasis genes can lead to monogenic autoimmune diabetes. Some individuals carrying disease-causing variants do not develop autoimmune diabetes, even though they develop another autoimmune disease. We aimed to determine whether type 1 diabetes polygenic risk contributes to phenotypic presentation in monogenic autoimmune diabetes. We used a 67 single nucleotide polymorphism type 1 diabetes genetic risk score (T1D-GRS) to determine polygenic risk in 62 individuals with monogenic autoimmune diabetes and 180 control individuals with nonautoimmune neonatal diabetes (NDM). We used population-based control participants (n = 10,405) and individuals with type 1 diabetes (n = 285) as a comparator. Individuals with monogenic autoimmune diabetes had higher T1D-GRSs compared with individuals with nonautoimmune NDM (mean 11.3 vs. 9.8; P = 1.7 × 10−5) and controls (mean 10.3; P = 7.5 × 10−6), but the levels were markedly lower than those for individuals with type 1 diabetes (14.9; P = 3.3 × 10−21). These differences were explained by individuals with monogenic autoimmune diabetes having higher class II HLA genetic risk, specifically from the DRB1* 03:01 -DQA1 *05:01 -DQB1 *02:01 haplotype (DR3-DQ2) (P < 0.01). In the presence of monogenic autoimmunity, the polygenic class II HLA susceptibility contributes to development of autoimmune diabetes. This suggests a role of class II HLA in targeting the dysregulated immune response toward the β-cell. Article Highlights: There is variability in early-onset autoimmune diabetes presentation in individuals with monogenic autoimmunity; the mechanism(s) underlying this is unclear. We examined whether type 1 diabetes (T1D) polygenic risk contributes to clinical phenotype in monogenic autoimmune diabetes. Individuals with monogenic autoimmune diabetes had higher T1D genetic risk scores compared with control cohorts, driven largely by increased presence of T1D-risk DR3-DQ2 haplotype. Established T1D polygenic risk alleles, particularly class II HLA genes, contribute to clinical presentation in monogenic autoimmunity. [ABSTRACT FROM AUTHOR]

The arterial switch operation for d-transposition of the great arteries achieves anatomic repair but creates the potential for right ventricular outflow tract obstruction as a result of the LeCompte maneuver. The resultant right ventricular hypertension is generally well tolerated but a select group are referred for cardiac catheterization. The outcomes of these catheterizations have not been well described. The objective of this study was to describe the degree and nature of right ventricular outflow tract obstruction found during cardiac catheterization among patients following the arterial switch operation as well as determine the rate of intervention and assess the acute impact of any catheter intervention undertaken. We conducted a retrospective study of patients after arterial switch operation with the LeCompte maneuver and subsequent right heart catheterization. Descriptive statistics were reported, and paired sample t tests were used for analysis. 544 children had an arterial switch operation, of which 110 children (20%) had a cardiac catheterization procedure after surgery and 11% had a right heart catheterization. Of the right heart catheterizations, 90% had an intervention (balloon and/or stent). In the interventional group, the right ventricle to systemic pressure ratio decreased modestly, from 2/3 to half systemic, after balloon dilation and/or stent placement (p < 0.01). No serious complications were observed. [ABSTRACT FROM AUTHOR]

Black men suffer disproportionately from prostate cancer (PCa) compared to men of other races and ethnicities. Comparing the molecular landscape of PCa among Black and White patients has the potential to identify targets for development of new precision medicine interventions. Herein, we conducted transcriptomic analysis of prostate tumors and paired tumor-adjacent normals from self-reported Black and White PCa patients and estimated patient genetic ancestry. Clinical follow-up revealed increased biochemical recurrence (BCR) among Black patients compared to White patients with high-grade PCa. Transcriptomic analysis identified differential alternative RNA splicing events (ARSs) between Black and White PCa patients. Genes undergoing genetic ancestry-concordant ARSs in high-grade or low-grade tumors involved cancer promoting genes. Most genes undergoing genetic ancestry-concordant ARSs did not exhibit differential aggregate gene expression or alternative polyadenylation. A number of the genetic ancestry-concordant ARSs associated with BCR; thus, genetic ancestry-concordant RNA splice variants may represent unique targets for PCa precision oncology. [ABSTRACT FROM AUTHOR]

Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, so together may provide a more complete picture of sleep health, while illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches. GWASs of these six SHSs identify 28 significant novel loci adjusting for multiple testing on six traits (p < 8.3e-9), along with 341 previously reported loci (p < 5e-08). The heritability of the first three SHS-PCs equals or exceeds that of SHS-ADD (SNP-h2 = 0.094), while revealing sleep-domain-specific genetic discoveries. Significant loci enrich in multiple brain tissues and in metabolic and neuronal pathways. Post-GWAS analyses uncover novel genetic mechanisms underlying sleep health and reveal connections (including potential causal links) to behavioral, psychological, and cardiometabolic traits. Data-driven composite sleep health scores, combining self-reported sleep duration, snoring, chronotype, insomnia, and sleepiness, provide heritable, interpretable phenotypes and novel GWAS discoveries elucidating regulatory pathways. [ABSTRACT FROM AUTHOR]

Palladium-doped silver nanoclusters (NCs) have been highlighted for their unique physicochemical properties and potential applications in catalysis, optics, and electronics. Anion-directed synthesis offers a powerful route to control the morphology and properties of these NCs. Herein, we report a novel Pd-doped Ag NC, [Pd(H)Ag13(S){S2P(OiPr)2}10] (PdHAg13S), synthesized through the inclusion of sulfide and hydride anions. This NC features a unique linear S-Pd-H axis enclosed in a 4-5-4 stacked arrangement of silver atoms. The distinctive hydride environment was characterized by NMR spectroscopy, and the total structure was determined by single-crystal X-ray diffraction (SCXRD) and supported by computational studies. Mass spectrometry and X-ray photoelectron spectroscopy (XPS) further confirmed the assigned composition. This unique construct exhibits promising hydrogen evolution reaction (HER) activity. Our findings highlight the potential of anion-directed synthesis for creating novel bimetallic NCs with tailored structures and catalytic properties. [ABSTRACT FROM AUTHOR]

Simple Summary: Asiatic mouflon (Ovis gmelini) and urial (O. vignei) are two species of wild sheep that occur throughout the mountains of Iran. At the moment, phylogenetic ("family tree") relationships between populations of wild sheep in this region remain unclear. Three subspecies of the Asiatic mouflon and three subspecies of the urial were described in Iran. In our study, utilizing molecular genetic tools, we, for the first time, investigated the phylogenetic status of the Kerman wild sheep, as this has long been considered to be a hybrid of Asiatic mouflon and urial. We examined three specimens of Kerman sheep using nuclear and mitochondrial DNA approaches. Our results demonstrated that Kerman sheep were different from other groups and occupy an intermediate position between the two wild breeds. We demonstrated that the maternal line ancestor of the Kerman sheep belonged to the urial. In our opinion, therefore, Kerman wild sheep can be recognized as a separate subspecies of the urial. Two species of wild sheep inhabit Iran: Asiatic mouflon (Ovis gmelini) and urial (O. vignei). Phylogenetic relationships between populations distributed in this country are complex and still remain unclear. This study aimed to clarify, by genetic assessment, the phylogenetic status of Kerman wild sheep, considered to be a hybrid of the two species. For this purpose, we created a dataset that included specimens of O. gmelini, O. vignei, and Kerman sheep. We applied genome-wide SNP genotyping technology to analyze population structure and genetic diversity of these groups. Using Neighbor-Net and PCA plots, it was demonstrated that Kerman sheep were differentiated from other groups and occupy an intermediate position between O. gmelini and O. vignei. Using Admixture analysis, two ancestral components were identified in this population; however, admixed ancestry was not confirmed by f3 statistics. Genetic diversity in Kerman wild sheep was significantly higher than in any group of O. vignei, but lower than in O. gmelini. Additionally, we examined complete mitochondrial genomes and it was demonstrated that the matrilineal ancestor of Kerman sheep belonged to O. vignei. Our results lead to the conclusion that Kerman wild sheep can be recognized as a separate subspecies of O. vignei. [ABSTRACT FROM AUTHOR]

Brain glymphatic activity, as indicated by diffusion-tensor imaging analysis along the perivascular space (ALPS) index, is involved in developmental neuropsychiatric and neurodegenerative diseases, but its genetic architecture is poorly understood. Here, we identified 17 unique genome-wide significant loci and 161 candidate genes linked to the ALPS-indexes in a discovery sample of 31,021 individuals from the UK Biobank. Seven loci were replicated in two independent datasets. Genetic signals located at the 2p23.3 locus yielded significantly concordant effects in both young and aging cohorts. Genetic correlation and polygenic overlap analyses indicate a common underlying genetic mechanism between the ALPS-index, ventricular volumes, and cerebrospinal fluid tau levels, with GMNC (3q28) and C16orf95 (16q24.2) as the shared genetic basis. Our findings enhance the understanding of the genetics of the ALPS-index and provide insight for further research into the neurobiological mechanisms of glymphatic clearance activity across the lifespan and its relation to neuropsychiatric phenotypes. Here, the authors perform a genome-wide association study of the ALPS-index, identifying 17 unique genome-wide significant loci, unraveling mechanisms of brain glymphatic activity and providing insight for its relation to neuropsychiatric phenotypes. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have detected several susceptibility variants for urinary bladder cancer, but how gene regulation affects disease development remains unclear. To extend GWAS findings, we conducted a transcriptome-wide association study (TWAS) using PrediXcan to predict gene expression levels in whole blood using genome-wide genotype data for 6180 bladder cancer cases and 5699 controls included in the database of Genotypes and Phenotypes (dbGaP). Logistic regression was used to estimate adjusted gene-level odds ratios (OR) per 1-standard deviation higher expression with 95% confidence intervals (CI) for bladder cancer risk. We further assessed associations for individual single-nucleotide polymorphisms (SNPs) used to predict expression levels and proximal loci for genes identified in gene-level analyses with false-discovery rate (FDR) correction. TWAS identified four genes for which expression levels were associated with bladder cancer risk: SLC39A3 (OR = 0.91, CI = 0.87–0.95, FDR = 0.015), ZNF737 (OR = 0.91, CI = 0.88–0.95, FDR = 0.016), FAM53A (OR = 1.09, CI = 1.05–1.14, FDR = 0.022), and PPP1R2 (OR = 1.09, CI = 1.05–1.13, FDR = 0.049). Findings from this TWAS enhance our understanding of how genetically-regulated gene expression affects bladder cancer development and point to potential prevention and treatment targets. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled trials (RCTs) represent the highest level of evidence in guiding the management of clavicle fractures. They are conducted to ensure that evidence drives the basis of treatment algorithms. Relying solely on P values to assess orthopedic RCTs may be deceptive and challenge the validity of the studies. Objective: To evaluate the degree of statistical fragility in the clavicle fracture literature using the fragility index (FI) and fragility quotient (FQ). Methods: A systematic search strategy using the Medline, PubMed, and Embase databases was used to find all dichotomous data for randomized controlled trials (RCTs) in clavicle fracture research from 2000 to 2024. The FI of each outcome was calculated by reversing a single outcome event until significance was reversed. The FQ was calculated by dividing each fragility index by the study sample size. The interquartile range (IQR) was also calculated for the FI and FQ. Results: Of the 3646 articles screened, 81 met the search criteria, with 30 RCTs evaluating clavicle fractures included for analysis. There were 250 total outcomes, where 62 significant and 188 nonsignificant outcomes were identified. The overall FI and FQ were 4 (IQR 3–5) and 0.045 (IQR 0.024–0.080). Statistically significant and nonsignificant outcomes had an FI of 3.5 (IQR 2–7) and 4 (IQR 3–5), respectively. Regarding loss to follow-up (LTF), 63.3% (19) reported LTF greater or equal to the overall FI of 4. Conclusion: When scrutinizing management algorithms relying on statistical analysis, we recommend including the FI and FQ alongside the P value. [ABSTRACT FROM AUTHOR]

Background ROS1 tyrosine kinase inhibitors are one of the primary immunotherapies for ROS1 fusion-positive cancers. Tyrosine kinase inhibitors have markedly improved outcomes for advanced cancers previously with poor prognosis. Entrectinib is an example of an ROS1 inhibitor that can be used for lung adenocarcinoma. There are numerous adverse effects with rare cardiac side effects reported, such as heart failure and myocarditis. Case summary A 27-year-old male being treated for lung adenocarcinoma who presented new congestive heart failure 2 weeks after starting Entrectinib. He developed refractory ventricular tachycardia, cardiogenic shock with an endomyocardial biopsy that showed active lymphohistiocytic myocarditis. With antiarrhythmic therapy, heavy sedation, mechanical circulatory support, and high-dose steroids, the patient had complete resolution of symptoms and return to baseline status. Discussion This is a rare case with a severe complication after starting Entrectinib for lung adenocarcinoma. In the literature, this is the first case of its kind presenting with myocarditis and severe heart failure after treatment with Entrectinib. This case highlights not only using cardiac imaging, and biopsy to help guide the diagnosis, but also describe the appropriate management. [ABSTRACT FROM AUTHOR]

Simple Summary: New programs and tools are needed in pig production as societal pressure to reduce antibiotic use leads to increasingly restrictive regulations. Neonatal diarrhea among newborn piglets is one of the key challenges in reducing antibiotic consumption. In this 4-week farm trial, we compared the use of a complementary feed containing a tannin extract derived from the wood of sweet chestnut with the standard antibiotic treatment used on the farm. All 18 litters in the study required treatment due to a high incidence of diarrhea among the piglets. The piglets in the nine litters of the control group received an oral antibiotic treatment. In contrast, the nine litters in the test group were initially treated with the complementary feed containing hydrolyzable tannins. If diarrhea persisted after three days, piglets were treated with antibiotics. The results showed that antibiotic consumption for diarrhea in the test group was reduced by 84% compared to the control group. Mortality rates were identical in both groups, with six piglets dying in each group. We conclude that the complementary feed containing a tannin extract has the potential to significantly reduce antibiotic use for neonatal diarrhea in newborn piglets while maintaining similar health outcomes. The objective of this farm trial was to investigate if the consumption of antibiotics could be reduced when piglets showing early signs of neonatal diarrhea were treated with an oral dose of tannin extract derived from sweet chestnut wood. The farm had a very high incidence of neonatal diarrhea among gilt litters. Gilts were randomized into test or control groups in a 1:1 ratio to compare the consumption of antibiotics used for piglets and piglet mortality during the four-week trial period. Control litters were treated with the oral antibiotic paromomycin, while test litters were treated with the complementary feed O-Nella-Protect. The farm trial included 18 gilt litters comprising 254 piglets. In the control group, 100% of the piglets received antibiotic treatment. In the test group, consumption of antibiotics used against diarrhea was reduced by 84% (p = 0.001) and consumption of antibiotics used for other illnesses was reduced by 45% (p = 0.045). In both test and control groups, six piglets died. Microbiological analysis identified both potential bacterial and viral pathogens. In conclusion, the farm trial indicates that even under the challenge of potentially serious bacterial and viral pathogens, a complimentary feed containing a tannin extract can support piglet health and reduce antibiotic consumption. [ABSTRACT FROM AUTHOR]

It is thought that cells surviving ionizing radiation exposure repair DNA double-strand breaks (DSBs) and restore their genomes. However, the recent biochemical and genetic characterization of DSB repair pathways reveals that only homologous recombination (HR) can function in an error-free manner and that the non-homologous end joining (NHEJ) pathways canonical NHEJ (c-NHEJ), alternative end joining (alt-EJ), and single-strand annealing (SSA) are error-prone, and potentially leave behind genomic scars and altered genomes. The strong cell cycle restriction of HR to S/G2 phases and the unparalleled efficiency of c-NHEJ throughout the cell cycle, raise the intriguing question as to how far a surviving cell "reaches" after repairing the genome back to its pre-irradiation state. Indeed, there is evidence that the genomes of cells surviving radiation treatment harbor extensive genomic alterations. To directly investigate this possibility, we adopted next-generation sequencing (NGS) technologies and tested a normal human fibroblast cell line, 82-6 hTert, after exposure up to 6 Gy. Cells were irradiated and surviving colonies expanded and the cells frozen. Sequencing analysis using the Illumina sequencing platform and comparison with the unirradiated genome detected frequent genomic alterations in the six investigated radiation survivor clones, including translocations and large deletions. Translocations detected by this analysis and predicted to generate visible cytogenetic alterations were frequently (three out of five) confirmed using mFISH cytogenetic analysis. PCR analysis of selected deletions also confirmed seven of the ten examined. We conclude that cells surviving radiation exposure tolerate and pass to their progeny a wide spectrum of genomic alterations. This recognition needs to be integrated into the interpretation of biological results at all endpoints, as well as in the formulation of mathematical models of radiation action. NGS analysis of irradiated genomes promises to enhance molecular cytogenetics by increasing the spectrum of detectable genomic alterations and advance our understanding of key molecular radiobiological effects and the logic underpinning DSB repair. However, further developments in the technology will be required to harness its full potential. [ABSTRACT FROM AUTHOR]

The article discusses Stephen Wolfe's book "The Case for Christian Nationalism" and its impact on debates surrounding the concept of Christian nationalism in American politics. Wolfe's vision of a Christian nation is analyzed through the lens of Oakeshottian concepts of civil association and enterprise association. The article also explores Oakeshott's distinction between civil and enterprise associations, highlighting how civil law can coexist with individual freedom. The analysis compares Wolfe's Christian nationalism with Oakeshott's views on government and individual autonomy, offering a critical perspective on the theological and political implications of Wolfe's thesis. [Extracted from the article]

Large databases of cyclic tests on flexure‐ or shear‐critical concrete members and shear‐critical connections of columns to beams or slabs are used to estimate the uncertainty inherent in experimental data in literature—as read by users. To this end, the predictions of two different, presumably independent, design‐oriented models for the properties of interest are used to establish the "central tendency" of data, against which individual tests or small groups thereof are assessed. Properties considered are: (a) the cyclic ultimate chord‐rotation of flexure‐controlled members with continuous or lap‐spliced deformed bars, (b) the cyclic shear strength of shear‐critical members, (c) the chord‐rotation at yielding of rectangular columns with plain bars, and (d) the cyclic shear strength of shear‐controlled beam‐column and slab‐column joints. Results suggest that the data from each test campaign have a certain degree of bias, specific to it. Test campaigns with ratio of estimated average deviation from the "central tendency" to the standard deviation of campaign deviations (called "data uncertainty") which is far into the tail of the Normal distribution may be excluded as questionable. This systematic bias, along with other types of "data uncertainty" addressed in this work, seem to contribute to the apparent scatter of model predictions with respect to cyclic test results the equivalent of a coefficient of variation of model‐to‐test‐ratio of at least 10% and possibly as high as 25%–30%. Model uncertainty seems to contribute to this scatter the equivalent of a coefficient of variation of at least 15% in shear‐controlled connections, or as much as 25% in the case of flexural deformation capacity of members with deformed bars; the cyclic shear resistance of members and—with the reservation of the small number of tests—the chord‐rotation at yielding of members with plain bars, are in‐between. [ABSTRACT FROM AUTHOR]

In this paper, we review the derivation of the Gauss–Levenberg–Marquardt (GLM) algorithm and its extension to ensemble parameter estimation. We explore the use of graphical methods to provide insights into how the algorithm works in practice and discuss the implications of both algorithm tuning parameters and objective function construction in performance. Some insights include understanding the control of both parameter trajectory and step size for GLM as a function of tuning parameters. Furthermore, for the iterative Ensemble Smoother (iES), we discuss the importance of noise on observations and show how iES can cope with non‐unique outcomes based on objective function construction. These insights are valuable for modelers using PEST, PEST++, or similar parameter estimation tools. [ABSTRACT FROM AUTHOR]

Worldwide museums hold collections of eggshells representing material for descriptive studies. However, an obstacle to this is the lack of information about the original contents and weight of the entire egg (W). This study aimed to fill this gap though development of a methodological mechanism for calculating the volume of the egg interior (Vi), its density (Di) and W. To determine Vi, it is sufficient to measure four geometric dimensions of the egg and shell thickness. The Di value depends on the surface area-to-volume ratio (S/V) and can be calculated from an empirical relationship. For its derivation, data on 454 eggs from 447 avian species, 95 families and 13 orders were used. Imputing data on the contents and shell weight (Ws), we proposed a theoretical relationship for calculating W. We found a negative correlation between Di and S/V (which reflects the egg metabolism level) and suggest that a female in most species maintains the duration of egg incubation at a constant level that has practically an unchanged value for the respective species. A mathematical algorithm for calculating the Di value depending on the S/V ratio provides the missing link in calculating W of a whole egg from archived collection material. [ABSTRACT FROM AUTHOR]

A Type 1 Diabetes Genetic Risk Score (T1DGRS) aids diagnosis and prediction of Type 1 Diabetes (T1D). While traditionally derived from imputed array genotypes, Whole Genome Sequencing (WGS) provides a more direct approach and is now increasingly used in clinical and research studies. We investigated the concordance between WGS-based and array-based T1DGRS across genetic ancestries in 149,265 UK Biobank participants using WGS, TOPMed-imputed, and 1000 Genomes-imputed array genotypes. In the overall cohort, WGS-based T1DGRS demonstrated strong correlation with TOPMed-imputed array-based score (r = 0.996, average WGS-based score 0.0028 standard deviations (SD) lower, p < 10− 31), while showing lower correlation with 1000 Genomes-imputed array-based scores (r = 0.981, 0.043 SD lower in WGS, p < 10− 300). Ancestry-stratified analyses between WGS-based and TOPMed-imputed array-based score showed the highest correlation with European ancestry (r = 0.996, 0.044 SD lower in WGS, p < 10− 300) followed by African ancestry (r = 0.989, 0.0193 SD lower in WGS, p < 10− 14) and South Asian ancestry (r = 0.986, 0.0129 SD lower in WGS, p < 10 − 6). These differences were more pronounced when comparing WGS based score with 1000 Genomes-imputed array-based scores (r = 0.982, 0.975, 0.957 for European, South Asian, African respectively). Population-level analysis using WGS-based T1DGRS revealed significant ancestry-based stratification, with European ancestry individuals showing the highest scores, followed by South Asian (average 0.28 SD lower than Europeans, p < 10− 58) and African ancestry individuals (average 0.89 SD lower than Europeans, p < 10− 300). Notably, when applying the European ancestry-derived 90th centile risk threshold, only 0.71% (95% CI 0.41–1.13) of African ancestry individuals and 6.4% (95% CI 5.6–7.2) of South Asian individuals were identified as high-risk, substantially below the expected 10%. In conclusion, while WGS is viable for generating T1DGRS, with TOPMed-imputed genotypes offering a cost-effective alternative, the persistence of ancestry-based variations in T1DGRS distribution even using whole genome sequencing emphasises the need for ancestry-specific or pan-ancestry standards in clinical practice. [ABSTRACT FROM AUTHOR]

The lungs of patients with cystic fibrosis (CF) are vulnerable to persistent polymicrobial colonization by bacterial pathogens including Pseudomonas aeruginosa, Staphylococcus aureus , and the non-tuberculous mycobacterium (NTM) Mycobacterium abscessus. The polymicrobial milieu within the CF lung impacts individual species fitness, influences biofilm-forming capabilities, pathogenicity, production of virulence factors and even antimicrobial responses, all potentially compromising therapeutic success. Interaction studies among these CF pathogens are very limited, especially studies on the influences of P. aeruginosa and S. aureus on M. abscessus co-existence and virulence. Based on the little known thus far about coinfection of these pathogens, we hypothesize that the co-existence of P. aeruginosa and S. aureus alters M. abscessus virulence and phenotypic characteristics. We evaluated the direct (co-culture) and indirect (using supernatant) effects of P. aeruginosa and S. aureus on M. abscessus growth rate, biofilm formation, macrophage internalization and glycopeptidolipids (GPL) expression. Our observations indicate that P. aeruginosa and S. aureus exert a competitive behavior toward M. abscessus during direct contact or indirect interaction in-vitro , probably as is the case of polymicrobial infections in the lungs of patients with CF. This is the first report that demonstrates S. aureus inhibitory effects on M. abscessus growth and biofilm forming capabilities. Collectively, co-culture studies enhance our understanding of polymicrobial interactions during coinfection and can guide to establish better management of coinfections and treatment strategies for M. abscessus. [ABSTRACT FROM AUTHOR]

The major histocompatibility complex class I related protein (MR1) presents microbially derived vitamin B2 precursors to mucosal-associated invariant T (MAIT) cells. MR1 can also present other metabolites to activate MR1-restricted T cells expressing more diverse T cell receptors (TCRs), some with anti-tumor reactivity. However, knowledge of the range of the antigen(s) that can activate diverse MR1-reactive T cells remains incomplete. Here, we identify pyridoxal (vitamin B6) as a naturally presented MR1 ligand using unbiased mass spectrometry analyses of MR1-bound metabolites. Pyridoxal, and the related compound, pyridoxal 5-phosphate bound to MR1 and enabled cell surface upregulation of wild type MR1*01 and MR1 expressing the Arg9His polymorphism associated with the MR1*04 allotype in a manner dependent on Lys43-mediated Schiff-base formation. Crystal structures of MR1*01 in complex with pyridoxal and pyridoxal 5-phosphate showed how these ligands were accommodated within the A-pocket of MR1. T cell lines transduced with the 7.G5 TCR, which has reported "pan-cancer" specificity, were specifically activated by pyridoxal presented by antigen-presenting cells expressing MR1*01 and MR1 allotypes bearing the less common Arg9His polymorphism. 7.G5 T cells also recognized, to a lesser extent, pyridoxal 5-phosphate and, importantly, recognition of both vitamers was blocked by an anti-MR1 antibody. 7.G5 TCR reactivity toward pyridoxal was enhanced when presented by the Arg9His polymorphism-bearing MR1 allotypes. Vitamin B6, and vitamers thereof, have been associated with various cancers, and here we describe a link between this ligand, MR1, and its allomorphs, and the pan-cancer 7.G5 TCR. This work identifies an MR1 ligand that can activate a diverse MR1-restricted TCR. [ABSTRACT FROM AUTHOR]

Mucosal-associated invariant T (MAIT) cells are known for their rapid effector functions and antibacterial immune protection. Here, we define the plasticity of interferon-γ (IFN-γ)–producing MAIT1 and interleukin-17A (IL-17A)–producing MAIT17 cell subsets in vivo. Whereas T-bet+ MAIT1 cells remained stable in all experimental settings, after adoptive transfer or acute Legionella or Francisella infection, RORγt+ MAIT17 cells could undergo phenotypic and functional conversion into both RORγt+T-bet+ MAIT1/17 and RORγt−T-bet+ MAIT1 cells. This plasticity ensured that MAIT17 cells played a dominant role in generating antibacterial MAIT1 responses in mucosal tissues. Single-cell transcriptomics revealed that MAIT17-derived MAIT1 cells were distinct from canonical MAIT1 cells yet could migrate out of mucosal tissues to contribute to the global MAIT1 pool in subsequent systemic infections. Human IL-17A–secreting MAIT cells also showed similar functional plasticity. Our findings have broad implications for understanding the role of MAIT cells in combatting infections and their potential utility in MAIT cell–targeted vaccines. Editor's summary: During development, mucosal-associated invariant T (MAIT) cells develop into MAIT1 and MAIT17 subsets with poised effector functions that support homeostatic and antimicrobial responses. Using transcription factor reporter and fate-mapping mice, Wang et al. examined the plasticity of MAIT1 and MAIT17 cells during homeostasis and bacterial infection. RORγt+T-bet− MAIT17 cells rapidly converted into RORγt−T-bet+ MAIT1-like cells, whereas canonical MAIT1 cells were largely resistant to phenotypic conversion. MAIT17 cell–derived MAIT1 cells accumulated in a tissue-specific manner and provided protection against systemic F. tularensis infection. Together, these findings demonstrate that specific patterns of MAIT cell plasticity support their functional adaptation and mucosal protection during bacterial infection. —Claire Olingy [ABSTRACT FROM AUTHOR]

Chemical investigation of the Antarctic sponge Suberites sp. has previously led to the identification of new suberitane derivatives, some of which show bioactivity toward respiratory syncytial virus (RSV). Our ongoing NMR-guided investigation of new specimens of the sponge resulted in the isolation of five new analogs (1–5), previously reported suberitenones A–D (6–9), and oxaspirosuberitenone (10). Suberitenone K (1) was characterized as the 8-keto derivative of 6, while three new phenols, suberitandiol (2), abeosuberitandiol (3), and furanosuberitandiol (4), and the degraded sesterterpene norsuberitenone B (5) were also found. Compound 3 displays a ring contraction while 4 has a new dihydrofuran ring. Structural characterization was achieved by a combination of NMR, HR-MS, and X-ray diffraction (XRD). Moderate activity towards RSV was reported for 9 and the new metabolite 1, with IC50 values of 15.0 μM and 39.8 μM, respectively. [ABSTRACT FROM AUTHOR]

Background/Objectives: A combination of increased human presence in the Arctic zone alongside climate change has led to a decrease in the number of wild reindeer (Rangifer tarandus). Studying the genetic potential of this species will aid in conservation efforts, while simultaneously promoting improved meat productivity in domestic reindeer. Alongside reducing feed costs, increasing disease resistance, etc., acquiring genetic variation information is a crucial task for domestic reindeer husbandry. This study thus identified highly informative molecular genetic markers usable for assessing genetic diversity and breeding purposes in reindeer. Methods: We analyzed gene polymorphism that may potentially affect animal growth and development in populations of wild (Taimyr Peninsula) and domestic reindeer, including Nenets and Evenk breeds. We screened these populations for polymorphisms by sequencing the GH, GHR, LCORL and BMP2 genes. Results: Following generation of gene sequences, we compared the alleles frequency in the surveyed populations and their genetic divergence. Some loci lacked polymorphism in wild reindeer, unlike domestic breeds. This could suggest a selection-driven microevolutionary divergence in domestic reindeer populations. An isolated domestic population from Kolguyev Island appeared to be genetically remote from continental reindeer. Conclusions: Molecular genetic markers associated with economically important traits in reindeer can be further developed using the data obtained. Monitoring wild reindeer populations and better utilizing the genetic potential of domestic animals will depend on a panel of these marker genes. By using this marker panel, the amount of time spent on selection efforts will be greatly reduced to enhance meat performance during reindeer breeding. [ABSTRACT FROM AUTHOR]

We investigate a data‐driven dynamic inventory control problem involving fixed setup costs and lost sales. Random demand arrivals stem from a demand distribution that is only known to come out of a vast ambiguity set. Lost sales and demand ambiguity would together complicate the problem through censoring, namely, the inability of the firm to observe the lost portion of the demand data. Our main policy idea advocates periodically ordering up to high levels for learning purposes and, in intervening periods, cleverly exploiting the information gained in learning periods. By regret, we mean the price paid for ambiguity in long‐run average performances. When demand has a finite support, we can accomplish a regret bound in the order of 풪(T2/3·(lnT)1/2) which almost matches a known lower bound as long as inventory costs are genuinely convex. Major policy adjustments are warranted for the more complex case involving an unbounded demand support. The resulting regret could range between 풪(T0.779) and 풪(T0.889) depending on the nature of moment‐related bounds that help characterize the degree of ambiguity. These are improvable to 풪(T2/3·(lnT)2) when distributions are light‐tailed. Our simulation demonstrates the merits of various policy ideas. [ABSTRACT FROM AUTHOR]

Background: Globally, almost one-third of adults with chronic non-cancer pain (CNCP) are prescribed opioids. Prevention of opioid dependence among these patients is a public health priority. Aim: To synthesise the evidence on the effectiveness of primary care-based interventions for secondary prevention of opioid dependence in patients with CNCP who are taking pharmaceutical opioids. Design & setting: Systematic review of randomised controlled trials (RCTs) and comparative non-randomised studies of interventions from high-income countries. Method: We searched five databases for studies on non-tapering secondary prevention interventions, such as tools for predicting dependence, screening tools for early recognition of dependence, monitoring of prescribing or medication, and specialist support. We examined multiple outcomes, including reduction in opioid dosage. Primary analyses were restricted to RCTs with data synthesised using an effect direction plot. Risk of bias was assessed using the Cochrane risk of bias (RoB2) tool. Results: Of 7102 identified reports, 18 studies were eligible (eight of which were RCTs). Most used multiple interventions or components. Of the seven RCTs at low risk of bias or with 'some concerns', five showed a positive intervention effect on at least one relevant outcome, four of which included a nurse care manager and/or other specialist support. The remaining two RCTs showed no positive effect of automated symptom monitoring and optimised analgesic management by a nurse care manager or a physician pain specialist team, or of a mobile opioid management app. Conclusion: We identify a clear need for further adequately powered high-quality studies. The Conclusions that can be drawn on the effectiveness of interventions are limited by the sparsity and inconsistency of available data. [ABSTRACT FROM AUTHOR]

Simple Summary: It has been established that exposure to trace amounts of the herbicide glyphosate, even in low quantities, may have serious negative consequences for the health of poultry. The purpose of this study was to examine changes in growth and in the expression of key genes in the cecum of broiler chickens after adding glyphosate (a herbicide), antibiotics and an anticoccidial (a drug used to prevent and control infections of intracellular parasites called coccidia) into their food. At 7, 14, and 40 control days of raising, samples were taken. The results showed that at the age of 7 days, there was a stimulating effect on the expression of the TLR2 gene following exposure to glyphosate, either alone or in combination with antibiotics or an anticoccidial drug. Glyphosate increased the expression of genes IGF1, IGF2, and MSTN associated with broiler performance by 3.7-foldat the age of 7 days and, conversely, decreased the expression of the same ones at later ages (14 and 40 days). Our findings suggest that, in agricultural practice, it is necessary to observe a number of measures to minimize the use of glyphosate and similar compounds that exceed the recommended levels. Studies have shown the presence of residual amounts of the herbicide glyphosate in poultry feed, which leads to its bioaccumulation in the body. Recently, it has been established that exposure to low levels of glyphosate over a long period may have serious negative effects on poultry health. Moreover, combined exposure to several toxicants can potentially lead to additive and/or synergistic effects. The purpose of this study was to analyze changes in meat productivity and the expression dynamics of key genes (IGF1, IGF2, MYOG, MYOZ2, SLC2A1, SLC2A2, MSTN, MUC2, OCLN, CLDN1, TLR2, TLR4, CAT, SOD1, PRDX6, and HMOX1) in the cecum of broilers as affected by glyphosate, antibiotics and a coccidiostat (anticoccidial drug). Day-old Ross 308 broiler chickens (n = 260) were divided into four groups, including a control group (CONT) fed the basic diet (BD), and three experimental groups: GLY (BD + glyphosate), GLY+ANT (BD + glyphosate and antibiotics enrofloxacin and colistin methanesulfonate), and GLY+CS (BD + glyphosate and the coccidiostat ammonium maduramycin). Samples were collected at control 7, 14, and 40 days of rearing, 50 mg each from three birds from each group. The mean body weight in each group was determined after the individual weighing of the entire flock. At 7 days of age, an upregulating effect on the expression of the immune-related TLR2 gene was detected in Groups GLY+ANT and GLY+CS compared to Group CONT (p = 0.044 and p = 0.042, respectively) and Group GLY (p = 0.049 and p = 0.044, respectively). At 40 days of age, this gene expression, conversely, decreased in Groups GLY+ANT and GLY+CS compared to Group CONT (p = 0.041 and p = 0.038, respectively). Glyphosate (Group GLY) upregulated the mRNA level of genes associated with productivity (IGF1, IGF2, and MSTN) at 7 days of age by 3.7 times (p = 0.041, p = 0.036 and p = 0.039, respectively) and, conversely, decreased it at a later age (14 and 40 days) compared to Group CONT (p = 0.024, p = 0.049 and p = 0.047, respectively, at 14 days, and p = 0.037 and p = 0.036 and p = 0.035, respectively, at 40 days of age). Thus, we identified detrimental changes in the expression of key broiler genes as influenced by glyphosate, as well as its combinations with antibiotics and a coccidiostat, which may have negative consequences for the poultry industry. [ABSTRACT FROM AUTHOR]

SUMMARY: The current Ukrainian native chicken gene pool is experiencing a decline in the number of breeds and maintained flocks. The major chicken breeds and lines of Ukrainian selection currently involve the Poltava Clay, Birkivska Barvysta, White Plymouth Rock and Rhode Island Red, representing different utility purpose types (i.e. layer and dual purpose). The local germplasm conservation agenda implies, among other measures, exploration of the genetic diversity of Ukrainian native chicken breeds using various types of molecular markers (e.g. indels, PCR-RFLPs and microsatellites). The purpose of this article is to review recent results of the complex genetic studies for assessing the features of population structure and variation in local breeds and lines. In particular, native gene pool stocks were examined for polymorphisms of the following genes: PRL, PRLR, GH, GHR, IGF1, PIT1, TGF-β1, TGF-β2, TGF-β3 and Mx. Based on these results, association of the identified polymorphic loci with productive traits (i.e. egg and meat performance) was investigated. For each of the experimental chicken lines, promising genotypes were established for further implementation in marker-assisted selection programs. Using microsatellites, the main variability parameters were established in the experimental populations, their genetic differentiation was analysed, and genetic distances were calculated between the experimental lines. [ABSTRACT FROM AUTHOR]

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Introduction: A growing literature has shown that exposure to adverse life events during childhood or adolescence is associated with the presence of psychotic-like experiences (PLEs), which is in turn associated with the risk of psychotic outcomes. Ruminative thinking, i.e., the tendency to dwell on particular issues or ideas, may affect the perceived aversiveness and ability to cope with adverse life events. However, the role that rumination plays in the relationship between adverse life events and the presence of PLEs remains unclear. The purpose of this study is to assess the association between adverse life events and PLEs in a longitudinal sample of young adults and adolescents, and to investigate whether this relationship is mediated by ruminative thinking. Methods: We used a longitudinal naturalistic sample of 706 volunteers assessed at ages 18 and 22 years, within the Imagen consortium. Lifetime occurrence of adverse life events (i.e., events perceived as strongly negative by participants) was investigated using the Life Events Questionnaire. The Community Assessment of Psychic Experience (CAPE-42) served to assess the presence of PLEs, while ruminative thinking was investigated through the Ruminative Response Scale. Results: Results showed that both frequency of PLEs and their persistence over time were associated with greater adverse life events exposure (r = 0.32, p < 0.001 and F 1 = 9.8; p < 0.001, respectively) and greater ruminative response (r = 0.66, p < 0.001 and F 1 = 94.9; p < 0.001, respectively). Mediation analyses showed that relationship between adverse life events and PLEs frequency was partially mediated by rumination (direct effect Z: 5.4, p < 0.001; indirect effect Z: 6.9, p < 0.001; total effect Z: 5.9, p < 0.001). Considering changes between the two assessment timepoints, relationship between PLEs variation between 18 and 22 years and adverse life events occurred during the same period was partially mediated by changes in rumination (direct effect Z: 2.8, p < 0.005; indirect effect Z: 4.3, p < 0.001; total effect Z: 4.3; p < 0.001). Discussion: Overall, our findings confirm that the presence of adverse life events may increase the risk of experiencing PLEs in healthy individuals and suggest that dysfunctional coping strategies, such as ruminative thinking, may be related to psychosis proneness. Results do not disentangle whether individuals with greater risk for psychosis tend to ruminate more or whether rumination exacerbates psychosis risk. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinomas (CCA) are a group of aggressive malignancies with poor prognosis. The distinct subtypes are related to different etiologies and genetic aberrations that are subject to targeted therapies. Mouse double minute 2 homolog (MDM2) is a potent inhibitor of tumor suppressor p53 and is proven to be altered in certain carcinomas. Novel targeted drugs, such as the MDM2-p53 antagonist Brigimadlin, have shown promising results for therapeutic efficacy in patients with MDM2 amplification and wild-type TP53. Objectives: This study therefore aimed to characterize CCAs regarding their MDM2 status, compare the concordance between fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methods, and elucidate the role of MDM2 amplification in prognosis and other clinicopathological characteristics. Design: Retrospective cohort study. Methods: All patients (n = 52) were diagnosed with CCA and received surgical resection with curative intention at the University Hospital of Cologne. Samples were analyzed retrospectively for MDM2 amplification with FISH and IHC. We correlated results with pre-existing molecular as well as clinical data. Results: We included 52 patients with primary CCA, three of which showed positive MDM2 amplification (5.8%). MDM2 amplification was present only in the intrahepatic CCA type and all patients with positive MDM2 amplification exhibited normal p53 status. Among the large-duct subtypes of intrahepatic CCAs, patients with positive MDM2 amplification demonstrated better survival than patients with negative MDM2 amplification (p = 0.041). Of the patients with MDM2 amplification, two underwent adjuvant therapy post-surgery (66.7%). There was a strong correlation between MDM2 amplification and positive protein expression in IHC. There were no identifiable molecular co-alterations of MDM2 with FGFR2 or SWI/SNF complex alterations. Conclusion: Real-world evidence in our Caucasian patient population confirmed that a significant number of intrahepatic CCAs showcase MDM2 amplification, qualifying for a personalized therapy option with Brigimadlin. MDM2 amplification must therefore be considered in the context of personalized molecular testing in CCA. [ABSTRACT FROM AUTHOR]

In conventional optical microscopes, image contrast of objects mainly results from the differences in light intensity and/or color. Muller matrix optical microscopes (MMMs), on the other hand, can provide significantly enhanced image contrast and rich information about objects by analyzing their interactions with polarized light. However, state‐of‐the‐art MMMs are fundamentally limited by bulky and slow polarization state generators and analyzers. Here, the study demonstrates a metasurface‐based MMM, i.e., Meta‐MMM, which is equipped with a chip‐integrated, single‐shot metasurface polarization state analyzer (Meta‐PSA). The Meta‐MMM is featured with high‐speed measurement (≈2s per Muller matrix (MM) image), superior operation stability, dual‐color operation, and high measurement accuracy (measurement error 1–2%) for MM imaging. The Meta‐MMM is applied to nanostructure characterization, surface morphology analysis, and discovering birefringent structures in honeybee wings. The Meta‐MMMs hold the promise to revolutionize various applications from biological imaging, medical diagnosis, and material characterization to industry inspection and space exploration. [ABSTRACT FROM AUTHOR]

Background and aims: Chronic non‐cancer pain (CNCP) is one of the most common causes of disability globally. Opioid prescribing to treat CNCP remains widespread, despite limited evidence of long‐term clinical benefit and evidence of harm such as problematic pharmaceutical opioid use (POU) and overdose. The study aimed to measure the prevalence of POU in CNCP patients treated with opioid analgesics. Method: A comprehensive systematic literature review and meta‐analysis was undertaken using MEDLINE, Embase and PsycINFO databases from inception to 27 January 2021. We included studies from all settings with participants aged ≥ 12 with non‐cancer pain of ≥ 3 months duration, treated with opioid analgesics. We excluded case–control studies, as they cannot be used to generate prevalence estimates. POU was defined using four categories: dependence and opioid use disorder (D&OUD), signs and symptoms of D&OUD (S&S), aberrant behaviour (AB) and at risk of D&OUD. We used a random‐effects multi‐level meta‐analytical model. We evaluated inconsistency using the I2 statistic and explored heterogeneity using subgroup analyses and meta‐regressions. Results: A total of 148 studies were included with > 4.3 million participants; 1% of studies were classified as high risk of bias. The pooled prevalence was 9.3% [95% confidence interval (CI) = 5.7–14.8%; I2 = 99.9%] for D&OUD, 29.6% (95% CI = 22.1–38.3%, I2 = 99.3%) for S&S and 22% (95% CI = 17.4–27.3%, I2 = 99.8%) for AB. The prevalence of those at risk of D&OUD was 12.4% (95% CI = 4.3–30.7%, I2 = 99.6%). Prevalence was affected by study setting, study design and diagnostic tool. Due to the high heterogeneity, the findings should be interpreted with caution. Conclusions: Problematic pharmaceutical opioid use appears to be common in chronic pain patients treated with opioid analgesics, with nearly one in 10 experiencing dependence and opioid use disorder, one in three showing signs and symptoms of dependence and opioid use disorder and one in five showing aberrant behaviour. [ABSTRACT FROM AUTHOR]

Geospatial expertise draws on and recognizes a vast array of seemingly unrelated interconnections allowing the geographer to find solutions to otherwise incomprehensible problems. Geospatial thinking involves both time and space, acknowledges cause-and-effect relationships of geographic phenomena at multiple scales, and recognizes the impact of spatial and temporal scale on processes. The complexity of geographic thinking necessitates an equally complex set of learning experiences that collectively are characterized by the professional geographer. Due to the inherent complexity of geospatial expertise, its nuanced relationship to spatial thinking, and a lack of research on how individuals attain geospatial expertise, we organized an interdisciplinary group of experts to present their perspectives on developing geospatial expertise in this special edition. In this introduction, we review geospatial expertise and distinguish it from spatial thinking, review research on developing geospatial expertise, and end with recommendations for future research. Through these reviews and recommendations, this introduction provides background context for the articles in this special edition and elucidates their connections. Given the complexity of geospatial expertise, it is only through connecting researchers and educators across multiple disciplines that the nature of one of the most integrative professional disciplines – that of the geographer – can be fully understood. [ABSTRACT FROM AUTHOR]

Background/Objectives: Orenburg goats are renowned for their soft down that acts as a substrate for warm clothing, particularly shawls that have an international reputation. As with many local livestock breeds, however, the Orenburg is presently at risk of extinction, an issue that can be addressed by assessing population genetic diversity and, thereafter, encouraging as much outbreeding as possible. Using single-nucleotide polymorphism (SNP)-based data, therefore, we analyzed the genetic diversity and population structure of modern Orenburg goats using samples collected from an expedition to Orenburg Oblast in 2024. Methods: We applied the Goat SNP50 BeadChip (Illumina, San Diego, CA, USA) for the genotyping of Orenburg goats from modern and archived populations. SNP genotypes of three Orenburg populations sampled in 2017 and 2019, Altai Mountain, Altai White, and Soviet Mohair breeds, were added to the dataset. Results: Principal component analysis and network and admixture analyses demonstrated that the genetic background inherent to the archived group of Orenburg goats was maintained in all modern populations. Values of genetic diversity indicators in modern populations were compatible with those obtained in comparison groups. Runs of homozygosity (ROH) were found in all the Orenburg goat populations (with a mean ROH length of 72.6–108.9 Mb and mean ROH number of 28–36). Genomic inbreeding based on ROH was low in all the Orenburg populations (FROH = 0.03–0.045). Conclusions: We showed that the ancestral background is retained in present-day Orenburg goats sampled in 2024. We provide the genetic basis through which certain breeder animals may be selected and bred traditionally or ex situ through a conservation program of gamete preservation. [ABSTRACT FROM AUTHOR]

There is a significant need to develop decision support tools capable of delivering accurate representations of environmental conditions, such as ground and surface water solute concentrations, in a timely and computationally efficient manner. Such tools can be leveraged to assess a large number of potential management strategies for mitigating non‐point source pollutants. Here, we assess the effectiveness of the impulse‐response emulation approach to approximate process‐based groundwater model estimates of solute transport from MODFLOW and MT3D over a wide range of model inputs and parameters, with the goal of assessing where in parameter space the assumptions underlying this emulation approach are valid. The impulse‐response emulator was developed using the sensitivity analysis utilities in the PEST++ software suite and is capable of approximating MODFLOW/MT3D estimates of solute transport over a large portion of the parameter space tested, except in cases where the Courant number is above 0.5. Across all runs tested, the highest percent errors were at the plume fronts. These results suggest that the impulse‐response approach may be suitable for emulation of solute transport models for a wide range of cases, except when high‐resolution outputs are needed, or when very low concentrations at plume edges are of particular interest. [ABSTRACT FROM AUTHOR]

In last 100 years or so, much information has been accumulated on avian karyology, genetics, physiology, biochemistry and evolution. The chicken genome project generated genomic resources used in comparative studies, elucidating fundamental evolutionary processes, much of it funded by the economic importance of domestic fowl (which are also excellent model species in many areas). Studying karyotypes and whole genome sequences revealed population processes, evolutionary biology, and genome function, uncovering the role of repetitive sequences, transposable elements and gene family expansion. Knowledge of the function of many genes and non-expressed or identified regulatory components is however still lacking. Birds (Aves) are diverse, have striking adaptations for flight, migration and survival and inhabit all continents most islands. They also have a unique karyotype with ~ 10 macrochromosomes and ~ 30 microchromosomes that are smaller than other reptiles. Classified into Palaeognathae and Neognathae they are evolutionarily close, and a subset of reptiles. Here we overview avian molecular cytogenetics with reptilian comparisons, shedding light on their karyotypes and genome structure features. We consider avian evolution, then avian (followed by reptilian) karyotypes and genomic features. We consider synteny disruptions, centromere repositioning, and repetitive elements before turning to comparative avian and reptilian genomics. In this context, we review comparative cytogenetics and genome mapping in birds as well as Z- and W-chromosomes and sex determination. Finally, we give examples of pivotal research areas in avian and reptilian cytogenomics, particularly physical mapping and map integration of sex chromosomal genes, comparative genomics of chicken, turkey and zebra finch, California condor cytogenomics as well as some peculiar cytogenetic and evolutionary examples. We conclude that comparative molecular studies and improving resources continually contribute to new approaches in population biology, developmental biology, physiology, disease ecology, systematics, evolution and phylogenetic systematics orientation. This also produces genetic mapping information for chromosomes active in rearrangements during the course of evolution. Further insights into mutation, selection and adaptation of vertebrate genomes will benefit from these studies including physical and online resources for the further elaboration of comparative genomics approaches for many fundamental biological questions. [ABSTRACT FROM AUTHOR]

The motor cortex is essential for controlling the flexible movements underlying complex behaviors. Behavioral flexibility involves the ability to integrate and refine new movements, thereby expanding an animal’s repertoire. This review discusses recent strides in motor learning mechanisms across spatial and temporal scales, describing how neural networks are remodeled at the level of synapses, cell types, and circuits and across time as animals’ learn new skills. It highlights how changes at each scale contribute to the evolving structure and function of neural circuits that accompanies the expansion and refinement of motor skills. We review new findings highlighted by advanced imaging techniques that have opened new vistas in optical physiology and neuroanatomy, revealing the complexity and adaptability of motor cortical circuits, crucial for learning and control. At the structural level, we explore the dynamic regulation of dendritic spines mediating corticocortical and thalamocortical inputs to the motor cortex. We delve into the role of perisynaptic astrocyte processes in maintaining synaptic stability during learning. We also examine the functional diversity among pyramidal neuron subtypes, their dendritic computations and unique contributions to single cell and network function. Further, we highlight how cortical activation is characterized by increased consistency and reduced strength as new movements are learned and how external inputs contribute to these changes. Finally, we consider the motor cortex’s necessity as movements unfold over long time scales. These insights will continue to drive new research directions, enhancing our understanding of motor cortical circuit transformations that underpin behavioral changes expressed throughout an animal’s life. [ABSTRACT FROM AUTHOR]

There has been a long-standing interest in targeting the type 1 insulin-like growth factor receptor (IGF-1R) signaling system in breast cancer due to its key role in neoplastic proliferation and survival. However, no IGF-1R targeting agent has shown substantial clinical benefit in controlled phase 3 trials, and no biomarker has been shown to have clinical utility in the prediction of benefit from an IGF-1R targeting agent. IGFBP7 is an atypical insulin-like growth factor binding protein as it has a higher affinity for the IGF-1R than IGF ligands. We report that low IGFBP7 gene expression identifies a subset of breast cancers for which the addition of ganitumab, an anti-IGF-1R monoclonal antibody, to neoadjuvant chemotherapy, substantially improved the pathological complete response rate compared to neoadjuvant chemotherapy alone. The pCR rate in the chemotherapy plus ganitumab arm was 46.9% in patients in the lowest quartile of IGFBP7 expression, in contrast to only 5.6% in the highest quartile. Furthermore, high IGFBP7 expression predicted increased distant metastasis risk. If our findings are confirmed, decisions to halt the development of IGF-1R targeting drugs, which were based on disappointing results of prior trials that did not use predictive biomarkers, should be reviewed. [ABSTRACT FROM AUTHOR]