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Abstract Placental MRI is increasingly implemented in clinical obstetrics and research. Functional imaging, especially T2*, has been shown to vary across gestation and in pathology. Translation into the clinical arena has been slow because of time taken to mask the region of interest and owing to differences in T2* results depending on field strength. This paper contributes methodology to remove these barriers by utilising data from 0.55, 1.5 and 3T MRI to provide a fully automated segmentation tool; determining field strength dependency of placental assessment techniques; and deriving normal ranges for T2* by gestational age but independent of field strength. T2* datasets were acquired across field strengths. Automatic quantification including fully automatic masking was achieved and tested in 270 datasets across fields. Normal curves for quantitative placental mean T2*, volume and other derived measurements were obtained in 273 fetal MRI scans and z-scores calculated. The fully automatic segmentation achieved excellent quantification results (Dice scores of 0.807 at 3T, 0.796 at 1.5T and 0.815 at 0.55T.). Similar changes were seen between placental T2* and gestational age across all three field strengths (p

In the present article was carried out a research of judicial practice and the procedural-criminal norms regarding the deadline for decalraing the appeal against the decisions of the appeal courts. The presented problem consists in the scientific substantiation and practical regarding of the way of applying in the legal provisions, the need tu meet the requirements of clarity and predictability of the rules regarding the term of appeal, through the lens of ECHR jurisprudence, national practice, including in relation to the amendments to the law from, as well as the analysis of the legislation, resulting in the substantiation of the respective conclusions. Through this study, we want to provoke further analysis and discussion on this topic.

Abstract Copy number variation (CNV) can drive rapid evolution in changing environments. In microbial pathogens, such adaptation is a key factor underpinning epidemics and colonization of new niches. However, the genomic determinants of such adaptation remain poorly understood. Here, we systematically investigate CNVs in a large genome sequencing dataset spanning a worldwide collection of 1104 genomes from the major wheat pathogen Zymoseptoria tritici. We found overall strong purifying selection acting on most CNVs. Genomic defense mechanisms likely accelerated gene loss over episodes of continental colonization. Local adaptation along climatic gradients was likely facilitated by CNVs affecting secondary metabolite production and gene loss in general. One of the strongest loci for climatic adaptation is a highly conserved gene of the NAD-dependent Sirtuin family. The Sirtuin CNV locus localizes to an ~68-kb Starship mobile element unique to the species carrying genes highly expressed during plant infection. The element has likely lost the ability to transpose, demonstrating how the ongoing domestication of cargo-carrying selfish elements can contribute to selectable variation within populations. Our work highlights how standing variation in gene copy numbers at the global scale can be a major factor driving climatic and metabolic adaptation in microbial species.

This investigation examined the Algebra I End-of-Course exam performance of Hispanic boys who were at-risk and those who were not at-risk during the 2016-2017, 2017-2018, and 2018-2019 school years. Data for all students in Texas who took the Algebra I End-of-Course exam during these years were obtained from the Texas Education Agency. The analysis focused exclusively on Hispanic boys. Utilizing secondary data, a causal-comparative or ex post facto study was conducted. The inferential statistical procedures revealed statistically significant differences in performance for at-risk Hispanic boys across all three school years. In each of these years, a significantly lower percentage of at-risk Hispanic boys met the three grade-level standards (Approaches Grade Level, Meets Grade Level, and Masters Grade Level) compared to their not-at-risk peers. On average, at-risk Hispanic boys answered about 13 fewer items correctly than those who were not at-risk. These findings indicate that current instructional practices are not adequately meeting the needs of at-risk Hispanic boys. Policymakers and educational leaders are advised to review current programs and implement necessary changes to better support these students.

Abstract Background Complete surgical removal of pancreatic ductal adenocarcinoma (PDAC) is central to all curative treatment approaches for this aggressive disease, yet this is only possible in patients technically amenable to resection. Hence, an accurate assessment of whether patients are suitable for surgery is of paramount importance. The SCANPatient trial aims to test whether implementing a structured synoptic radiological report results in increased institutional accuracy in defining surgical resectability of non-metastatic PDAC. Methods SCANPatient is a batched, stepped wedge, comparative effectiveness, cluster randomised clinical trial. The trial will be conducted at 33 Australian hospitals all of which hold regular multi-disciplinary team meetings (MDMs) to discuss newly diagnosed patients with PDAC. Each site is required to manage a minimum of 20 patients per year (across all stages). Hospitals will be randomised to begin synoptic reporting within a batched, stepped wedge design. Initially all hospitals will continue to use their current reporting method; within each batch, after each 6-month period, a randomly selected group of hospitals will commence using the synoptic reports, until all hospitals are using synoptic reporting. Each hospital will provide data from patients who (i) are aged 18 or older; (ii) have suspected PDAC and have an abdominal CT scan, and (iii) are presented at a participating MDM. Non-metastatic patients will be documented as one of the following categories: (1) locally advanced and surgically unresectable; (2) borderline resectable; or (3) anatomically clearly resectable (Note: Metastatic disease is treated as a separate category). Data collection will last for 36 months in each batch, and a total of 2400 patients will be included. Discussion Better classifying patients with non-metastatic PDAC as having tumours that are either clearly resectable, borderline or locally advanced and unresectable may improve patient outcomes by optimising care and treatment planning. The borderline resectable group are a small but important cohort in whom surgery with curative intent may be considered; however, inconsistencies with definitions and an understanding of resectability status means these patients are often incorrectly classified and hence overlooked for curative options. Trial registration The SCANPatient trial was registered on 17th May 2023 in the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12623000508673).

Background Altered structural brain development has been identified in fetuses with congenital heart disease (CHD), suggesting that the neurodevelopmental impairment observed later in life might originate in utero. There are many interacting factors that may perturb neurodevelopment during the fetal period and manifest as structural brain alterations, such as altered cerebral substrate delivery and aberrant fetal hemodynamics. Methods and Results We extracted structural covariance networks from the log Jacobian determinants of 435 in utero T2 weighted image magnetic resonance imaging scans, (n=67 controls, 368 with CHD) acquired during the third trimester. We fit general linear models to test whether age, sex, expected cerebral substrate delivery, and CHD diagnosis were significant predictors of structural covariance. We identified significant effects of age, sex, cerebral substrate delivery, and specific CHD diagnosis across a variety of structural covariance networks, including primary motor and sensory cortices, cerebellar regions, frontal cortex, extra‐axial cerebrospinal fluid, thalamus, brainstem, and insula, consistent with widespread coordinated aberrant maturation of specific brain regions over the third trimester. Conclusions Structural covariance networks offer a sensitive, data‐driven approach to explore whole‐brain structural changes without anatomical priors. We used them to stratify a heterogenous patient cohort with CHD, highlighting similarities and differences between diagnoses during fetal neurodevelopment. Although there was a clear effect of abnormal fetal hemodynamics on structural brain maturation, our results suggest that this alone does not explain all the variation in brain development between individuals with CHD.

ABSTRACT In the global efforts to combat antimicrobial resistance and reduce antimicrobial use in pig production, there is a continuous search for methods to prevent and/or treat infections. Within this scope, we explored the relationship between the developing piglet nasal microbiome and (zoonotic) bacterial pathogens from birth until 10 weeks of life. The nasal microbiome of 54 pigs was longitudinally studied over 16 timepoints on 9 farms in 3 European countries (Germany, Ireland, and the Netherlands) using amplicon sequencing targeting the V3-V4 16S rRNA region as well as the tuf gene for its staphylococcal discrimination power. The piglets’ age, the farm, and the litter affected the nasal microbiome, with piglets’ age explaining 19% of the variation in microbial composition between samples. Stabilization of the microbiome occurred around 2 weeks post-weaning. Notably, while opportunistic pathogens were ubiquitously present, they did not cause disease. The piglet nasal microbiome often carried species associated with gut, skin, or vagina, which suggests that contact with the vaginal and fecal microbiomes shapes the piglet nasal microbiome. We identified bacterial co-abundance groups of species that were present in the nasal microbiomes in all three countries over time. Anti-correlation between these species and known bacterial pathogens identified species that might be exploited for pathogen reduction. Further experimental evidence is required to confirm these findings. Overall, this study advances our understanding of the piglet nasal microbiome, the factors influencing it, and its longitudinal development, providing insights into its role in health and disease.IMPORTANCEOur study on the nasal microbiota development in piglets across farms in three European countries found that the microbiomes developed similarly in all locations. Additionally, we observed that the colonization of porcine pathogens was either positively or negatively associated with the presence of other bacterial species. These findings enhance our knowledge of co-colonizing species in the nasal cavity and the identified microbial interactions that can be explored for the development of interventions to control pathogens in porcine husbandry.

ABSTRACT Introduction Traumatic memories (TM) are a core feature of stress‐related disorders, including posttraumatic stress disorder (PTSD). Treatment is often difficult, and specific pharmacological interventions are lacking. We present a novel non‐pharmacological intervention called motor interference therapy (MIT) as a promising alternative for these symptoms. Aims To determine the feasibility of MIT, a brief, audio‐delivered, and non‐pharmacological intervention that uses cognitive and motor tasks to treat TM. Methods We designed a randomized, double‐blind trial. Twenty‐eight participants from an outpatient clinic with at least one TM were included to receive either MIT or progressive muscle relaxation (PMR). Spanish versions of the PTSD symptom severity scale (EGS), visual analog scale for TM (TM–VAS), and quality of life (EQ–VAS) were applied prior to intervention, 1 week, and 1 month following intervention. Results Mean scores on all measures improved from baseline to posttest for both groups. MIT participants showed significantly more positive scores at 1 week and 1 month (TM–VAS baseline: 9.8 ± 0.4; immediate: 6.0 ± 2.0; 1 week: 3.8 ± 3.1 [d = 1.57]; 1 month 2.9 ± 2.8 [d = 1.93]) than PMR participants on measures of distress due to TM, trauma re‐experiencing, anxiety, and a composite measure of PTSD. Conclusion MIT is a simple, effective, and easy‐to‐use tool for treating TM and other stress‐related symptoms. It requires relatively few resources and could be adapted to many contexts. The results provide proof‐of‐principle support for conducting future research with larger cohorts and controls to improve clinical effectiveness and research on brief interventions. Trial Registration ClinicalTrials.gov Identifier: NCT03627078

Abstract Congenital heart disease (CHD) is the most common congenital malformation and is associated with adverse neurodevelopmental outcomes. The placenta is crucial for healthy fetal development and placental development is altered in pregnancy when the fetus has CHD. This study utilized advanced combined diffusion-relaxation MRI and a data-driven analysis technique to test the hypothesis that placental microstructure and perfusion are altered in CHD-affected pregnancies. 48 participants (36 controls, 12 CHD) underwent 67 MRI scans (50 control, 17 CHD). Significant differences in the weighting of two independent placental and uterine-wall tissue components were identified between the CHD and control groups (both pFDR

Abstract Prostatic artery embolization (PAE) has proven to be an efficacious treatment for urinary symptoms of benign prostatic hyperplasia. PAE is performed in a complex and challenging anatomical field which may pose difficulties from procedural standpoint. Cone beam computed tomography (CBCT) has been proposed as an invaluable tool during the PAE procedure. A review of different techniques and advancements, as well as demonstration of CBCT benefits via a pictorial overview of the salient examples is lacking. The techniques of CBCT are discussed herein and the virtual injection technology as an advancement in CBCT is discussed. To show the merits of CBCT in PAE, a pictorial overview of various clinical scenarios is presented where CBCT can be crucial in decision making. These scenarios are aimed at showing different benefits including identification of the origin of the prostatic artery and avoiding non-target embolization. Other benefits may include ensuring complete embolization of entire prostate gland as angiographic appearance alone can be inconclusive if it mimics a severely thickened bladder wall or ensuring adequate embolization of the median lobe to provide relief from “ball-valve” effect. Further examples include verification of embolization of the entire prostate when rare variants or multiple (> 2) arterial feeders are present.

Abstract Background Prenatal bonding describes the emotional connection expectant parents form to their unborn child. Research acknowledges the association between antenatal imaging and enhanced bonding, but the influencing factors are not well understood, particularly for fathers or when using advanced techniques like fetal magnetic resonance imaging (MRI). This study aimed to identify variables which may predict increased bonding after imaging. Methods First-time expectant parents (mothers = 58, fathers = 18) completed a two-part questionnaire (QualtricsXM™) about their expectations and experiences of ultrasound (n = 64) or fetal MRI (n = 12) scans in uncomplicated pregnancies. A modified version of the Prenatal Attachment Inventory (PAI) was used to measure bonding. Qualitative data were collected through open-ended questions. Multivariate linear regression models were used to identify significant parent and imaging predictors for bonding. Qualitative content analysis of free-text responses was conducted to further understand the predictors’ influences. Results Bonding scores were significantly increased after imaging for mothers and fathers (p

Abstract Background Ovarian cancer remains the deadliest of the gynecologic cancers in the United States. There have been limited advances in treatment strategies that have seen marked increases in overall survival. Thus, it is essential to continue developing and validating new treatment strategies and markers to identify patients who would benefit from the new strategy. In this report, we sought to further validate applications for a novel humanized anti-Sialyl Tn antibody-drug conjugate (anti-STn-ADC) in ovarian cancer. Methods We aimed to further test a humanized anti-STn-ADC in sialyl-Tn (STn) positive and negative ovarian cancer cell line, patient-derived organoid (PDO), and patient-derived xenograft (PDX) models. Furthermore, we sought to determine whether serum STn levels would reflect STn positivity in the tumor samples enabling us to identify patients that an anti-STn-ADC strategy would best serve. We developed a custom ELISA with high specificity and sensitivity, that was used to assess whether circulating STn levels would correlate with stage, progression-free survival, overall survival, and its value in augmenting CA-125 as a diagnostic. Lastly, we assessed whether the serum levels reflected what was observed via immunohistochemical analysis in a subset of tumor samples. Results Our in vitro experiments further define the specificity of the anti-STn-ADC. The ovarian cancer PDO, and PDX models provide additional support for an anti-STn-ADC-based strategy for targeting ovarian cancer. The custom serum ELISA was informative in potential triaging of patients with elevated levels of STn. However, it was not sensitive enough to add value to existing CA-125 levels for a diagnostic. While the ELISA identified non-serous ovarian tumors with low CA-125 levels, the sample numbers were too small to provide any confidence the STn ELISA would meaningfully add to CA-125 for diagnosis. Conclusions Our preclinical data support the concept that an anti-STn-ADC may be a viable option for treating patients with elevated STn levels. Moreover, our STn-based ELISA could complement IHC in identifying patients with whom an anti-STn-based strategy might be more effective.

Abstract Knowledge of genetic determinism and evolutionary dynamics mediating host-pathogen interactions is essential to manage fungal plant diseases. Studies on the genetic architecture of fungal pathogenicity often focus on large-effect effector genes triggering strong, qualitative resistance. It is not clear how this translates to predominately quantitative interactions. Here, we use the Zymoseptoria tritici-wheat model to elucidate the genetic architecture of quantitative pathogenicity and mechanisms mediating host adaptation. With a multi-host genome-wide association study, we identify 19 high-confidence candidate genes associated with quantitative pathogenicity. Analysis of genetic diversity reveals that sequence polymorphism is the main evolutionary process mediating differences in quantitative pathogenicity, a process that is likely facilitated by genetic recombination and transposable element dynamics. Finally, we use functional approaches to confirm the role of an effector-like gene and a methyltransferase in phenotypic variation. This study highlights the complex genetic architecture of quantitative pathogenicity, extensive diversifying selection and plausible mechanisms facilitating pathogen adaptation.

Abstract A 47 year old Caucasian female with a background of type 2 diabetes mellitus, hypothyroidism, and autoimmune hepatitis presented with a painful, pruritic, papular eruption in a photosensitive distribution across the upper chest, neck, face, dorsal hands and forearms. On examination, lesions coalesced into annular plaques each with an active, raised margin and an atrophic, yellow centre. Histopathology demonstrated an absence of mucin and elastophagocytosis with giant cells engulfing dermal elastin fibres. These histopathological features favoured a diagnosis of annular elastolytic giant cell granuloma (AEGCG). The patient was managed ciclosporin monotherapy 125 mg twice daily (3 mg/kg/day). At 8 week review, there was a marked improvement in the physical appearance of the dermatosis as well as diminishing of symptoms such as itch and cutaneous pain. AEGCG is a rare inflammatory dermatosis typically affecting sun‐exposed sites. It has been proposed that AEGCG is triggered by a solar induced elastolysis however other theories suggest it is a primary granulomatous disorder and not a photodermatosis. AEGCG appears to be aligned to an autoimmune diathesis, indicated by its frequent association with autoimmune conditions such as Hashimoto’s thyroiditis, vitiligo, giant cell arteritis and, as in our patient, auto‐immune hepatitis. Diabetes mellitus occurring concurrently with AEGCG has also been observed, again like our patient. Histopathological features which distinguish AEGCG from granuloma annulare include absent mucin, absent necrobiosis, giant cells with more nuclei, non‐palisading granulomata and marked loss of elastic tissue. AEGCG is often unresponsive to standard therapies. The literature indicates varying responses to photo‐protection, topical/systemic/intralesional corticosteroids, and oral medications such as methotrexate, hydroxychloroquine, and dapsone. Few case reports have also documented improvement with ciclosporin. In aggressive forms of AEGCG, as in our patient, treatment with ciclosporin may be an effective intervention and should be initiated early in the disease.

Alaska’s boreal forests are experiencing rapid changes in climate that may favor deciduous-dominated systems, with important implications for global biogeochemical and energy cycles. However, aspen (Populus tremuloides Michx.) has experienced substantial defoliation from the aspen leaf miner (Phyllocnistis populiella Cham., hereafter ALM) in Alaska, resulting in significant growth reductions. We conducted a tree-ring and Δ13C study to test the hypothesis that moisture limitation may have predisposed aspen to leaf miner damage. Contrary to our hypothesis, differences in climate-growth correlations between relatively severely and lightly affected trees were negligible during the pre-outbreak decades. Stands with greater summer precipitation had more limited ALM impact, however differences among models were small and multiple climate variables were suitable predictors of ALM impact. The strong negative relationship we detected between tree-ring Δ13C and basal area increment (BAI) suggested that interannual variation in Δ13C was driven primarily by variation in photosynthesis, limiting the utility of Δ13C as a tool to detect stomatal responses to moisture-limitation. Instead, we found that larger, faster-growing individuals on gentler slopes showed a stronger absolute reduction in BAI (pre-ALM BAI−post-ALM BAI), but were similar in relative BAI reduction (pre-ALM BAI/post-ALM BAI), with smaller, slower growing trees. Older trees and stands with greater relative abundance of white spruce [Picea glauca (Moench) Voss] had greater relative ALM impact whereas slower growing trees on steeper slopes were less affected. The significant effect of white spruce abundance on ALM impact was likely due to favorable leaf miner overwintering habitat provided beneath white spruce trees, which can lead to increased leaf miner survival and thus greater reductions in aspen growth. Our results illustrate the subtle but complex biotic interaction between microclimate and pest physiology in determining ALM-induced aspen growth reductions, adding important nuance to a hypothesized increase in deciduous tree cover in Alaska’s boreal forest.

Abstract For nearly two decades, genomic prediction and selection have supported efforts to increase genetic gains in plant and animal improvement programs. However, novel phenomic strategies for predicting complex traits in maize have recently proven beneficial when integrated into across‐environment sparse genomic prediction models. One phenomic data modality is whole grain near‐infrared spectroscopy (NIRS), which records reflectance values of biological samples (e.g., maize kernels) based on chemical composition. Predictions of hybrid maize grain yield (GY) and 500‐kernel weight (KW) across 2 years (2011–2012) and two management conditions (water‐stressed and well‐watered) were conducted using combinations of reflectance data obtained from high‐throughput, F2 whole‐kernel scans and genomic data obtained from genotyping‐by‐sequencing within four different cross‐validation (CV) schemes (CV2, CV1, CV0, and CV00). When predicting the performance of untested genotypes in characterized (CV1) environments, genomic data were better than phenomic data for GY (0.689 ± 0.024—genomic vs. 0.612 ± 0.045—phenomic), but phenomic data were better than genomic data for KW (0.535 ± 0.034—genomic vs. 0.617 ± 0.145—phenomic). Multi‐kernel models (combinations of phenomic and genomic relationship matrices) did not surpass single‐kernel models for GY prediction in CV1 or CV00 (prediction of untested genotypes in uncharacterized environments); however, these models did outperform the single‐kernel models for prediction of KW in these same CVs. Lasso regression applied to the NIRS data set selected a subset of 216 NIRS bands that achieved comparable prediction abilities to the full phenomic data set of 3112 bands predicting GY and KW under CV1 and CV00.

While hydroponics is considered an efficient vegetable production system, there is a compelling need to investigate the efficiency of the current generic nutrient dosing recommendation primarily based on electrical conductivity (EC) measurements. Such information is critical to fine-tune and optimize the current hydroponic management practices for improved nutrient uptake efficiency. This study investigated the dynamics of some micro and macronutrients (N, P, Ca, Mg, K, Fe, and Mn) in a recirculating nutrient film technique (NFT) hydroponic system under lettuce cultivation. The research was conducted in an indoor controlled environment growth chamber with lettuce grown in different EC levels (1.2 and 1.6 dS m−1). Each treatment had four hydroponic cultivation units, each one with 24 plants. Nutrient solution and tissue samples were collected two to three times per week. Nutrient dynamics, including nutrient uptake efficiencies and environmental losses, were calculated using a mass balance approach. The effects of EC level on fresh and dry lettuce biomass and nutrient uptake were insignificant. Observed variations in nutrient solution composition during lettuce cultivation included the almost complete removal of ammonia nitrogen, nitrate decreases towards the end of the experiment, consistent increases in aqueous Ca concentration, and corresponding decreases in K and Mn. Average N losses ranged between 27 and 40 %, presumably through denitrification, while 10–14 % of N was assimilated into the plant biomass. The remaining N in the recirculating nutrient solution was estimated to be between 50 and 59 %. The average P loss was 11–35 %, likely due to precipitation, while 52–77 % remained in the nutrient solution. Nutrient uptake efficiencies averaged 19–31 % K, 12–21 % P, 9–16 % Mn, 4–6 % Ca, 3–4 % Mg, and 2–4 % Fe. These results suggest that elevated nutrient concentrations in recirculating nutrient solutions led to losses and underutilization. Findings from this study provide a comprehensive dataset critical to improving hydroponic nutrient management beyond N and P. Hydroponic nutrient management should target providing essential nutrients needed by plants at the correct proportions considering the plant growth stage.

Inclusive postsecondary education (IPSE) programs provide students with intellectual disabilities (ID) an opportunity to access higher education. As these programs have grown over the decades since their inception in 2010, it is becoming increasingly important that these programs use data-driven interventions to improve student outcomes, both academically and non-academically. Research in the area of non-cognitive skills suggest that focusing students with ID on skills like motivation and engagement or attitudes like action control beliefs can improve their performance in IPSE programs and lead to positive academic and career outcomes in the future. Here, we performed correlation analysis and multiple regression on two non-cognitive skills assessments, the ACES Academic Enablers and Self Determination Inventory, collected from ISPE students. This analysis shows that the degree of a student’s action-control beliefs as measured by the SDI is predictive of their ACES Academic Enablers performance. This suggests that interventions targeting the concept of action control beliefs can improve practical non-cognitive skills that can lead to academic and professional success for students with ID.

Abstract Background Intramuscular fat (IMF) content and its fatty acid (FA) composition are typically controlled by several genes, each with a small effect. In the current study, to pinpoint candidate genes and putative regulators involved in FA composition, we performed a multivariate integrative analysis between intramuscular FA and transcriptome profiles of porcine longissimus dorsi (LD) muscle. We also carried out a combination of network, regulatory impact factor (RIF), in silico prediction of putative target genes, and functional analyses to better support the biological relevance of our findings. Results For this purpose, we used LD RNA-Seq and intramuscular FA composition profiles of 129 Iberian × Duroc backcrossed pigs. We identified 378 correlated variables (13 FA and 365 genes), including six FA (C20:4n-6, C18:2n-6, C20:3n-6, C18:1n-9, C18:0, and C16:1n-7) that were among the most interconnected variables in the predicted network. The detected FA-correlated genes include genes involved in lipid and/or carbohydrate metabolism or in regulation of IMF deposition (e.g., ADIPOQ, CHUK, CYCS, CYP4B1, DLD, ELOVL6, FBP1, G0S2, GCLC, HMGCR, IDH3A, LEP, LGALS12, LPIN1, PLIN1, PNPLA8, PPP1R1B, SDR16C5, SFRP5, SOD3, SNW1, and TFRC), meat quality (GALNT15, GOT1, MDH1, NEU3, PDHA1, SDHD, and UNC93A), and transport (e.g., EXOC7 and SLC44A2). Functional analysis highlighted 54 over-represented gene ontology terms, including well-known biological processes and pathways that regulate lipid and carbohydrate metabolism. RIF analysis suggested a pivotal role for six transcription factors (CARHSP1, LBX1, MAFA, PAX7, SIX5, and TADA2A) as putative regulators of gene expression and intramuscular FA composition. Based on in silico prediction, we identified putative target genes for these six regulators. Among these, TADA2A and CARHSP1 had extreme RIF scores and present novel regulators in pigs. In addition, the expression of TADA2A correlated (either positively or negatively) with C20:4n-6, C18:2n-6, C20:3n-6, C18:1n-9, and that of CARHSP1 correlated (positively) with the C16:1n-7 lipokine. We also found that these two transcription factors share target genes that are involved in lipid metabolism (e.g., GOT1, PLIN1, and TFRC). Conclusions This integrative analysis of muscle transcriptome and intramuscular FA profile revealed valuable information about key candidate genes and potential regulators for FA and lipid metabolism in pigs, among which some transcription factors are proposed to control gene expression and modulate FA composition differences.

Determining the competitive ability of bean cultivars and the economic damage level (EDL) caused by alexandergrass is important for the implementation of integrated weed management. This work aimed to evaluate the interference of alexandergrass and determine the level of economic damage when it competes with seven carioca-type bean cultivars. The experiment was conducted in a completely randomized experimental design, with treatments consisting of the carioca bean varieties IAC Imperador, IPR Curió, ANFC9, IAC Milênio, IPR Tangará, IPR Sabiá, and BRS Pérola and 12 alexandergrass densities for each cultivar, ranging from 0 to 560 plants m−2. Plant density, leaf area, soil cover, and shoot dry matter of alexandergrass were evaluated 35 d after emergence. The variables alexandergrass plant density, grain productivity, control costs, bean price, and herbicide efficiency were used to estimate EDL. The cultivars ANFC9, IAC Milênio, and IPR Tangará were the most competitive, and IAC Imperador, IPR Curió, IPR Sabiá, and BRS Pérola the least competitive against alexandergrass. The highest EDL values were observed in the cultivars ANFC9, IAC Milênio and IPR Tangará, which ranged between 3.80 and 15.70 plants m−2 of alexandergrass. The cultivars IAC Imperador, IPR Curió, IPR Sabiá, and BRS Pérola showed the lowest economic damage with 1.10 to 5.60 plants m−2 of alexandergrass.

Fungi are ubiquitous in most ecosystems and are at the origin of serious pathogen outbreaks in humans and crops. Investigation of pathogen genomes over the past decade led to a paradigm shift of our understanding of the disease agents and provided a fertile ground for fundamental insights into drivers of genome dynamics and expression of traits.

Abstract How novel protein functions are acquired is a central question in molecular biology. Key paths to novelty include gene duplications, recombination or horizontal acquisition. Transposable elements (TEs) are increasingly recognized as a major source of novel domain-encoding sequences. However, the impact of TE coding sequences on the evolution of the proteome remains understudied. Here, we analyzed 1237 genomes spanning the phylogenetic breadth of the fungal kingdom. We scanned proteomes for evidence of co-occurrence of TE-derived domains along with other conventional protein functional domains. We detected more than 13,000 predicted proteins containing potentially TE-derived domain, of which 825 were identified in more than five genomes, indicating that many host-TE fusions may have persisted over long evolutionary time scales. We used the phylogenetic context to identify the origin and retention of individual TE-derived domains. The most common TE-derived domains are helicases derived from Academ, Kolobok or Helitron. We found putative TE co-options at a higher rate in genomes of the Saccharomycotina, providing an unexpected source of protein novelty in these generally TE depleted genomes. We investigated in detail a candidate host-TE fusion with a heterochromatic transcriptional silencing function that may play a role in TE and gene regulation in ascomycetes. The affected gene underwent multiple full or partial losses within the phylum. Overall, our work establishes a kingdom-wide view of putative host-TE fusions and facilitates systematic investigations of candidate fusion proteins.

In the present article was carried out a research of judicial practice and the procedural-criminal norms regarding attributing the quality of successor of the deceased victim to the surviving spouse. The presented problem consists in the scientific substantiation and practical regarding of the way of applying in the legal provisions, which is not currently expressly provided for in art. 81 of the Criminal procedure code of the Republic of Moldova, as well as the analysis of the legislation, resulting in the substantiation of rigorous proposals in order to improve the legislation and jurisprudence. Through this study, we want to provoke further analysis and discussion on this topic.

ABSTRACT Objective: To evaluate symptoms, lung function, and quality of life of a cohort of patients hospitalized for severe COVID-19 12 months after hospital admission. Methods: This was a cross-sectional study. We included severe COVID-19 survivors hospitalized in one of three tertiary referral hospitals for COVID-19 in the city of Belo Horizonte, Brazil. Participants were submitted to lung function and six-minute walk tests and completed the EQ-5D-3L questionnaire. Results: The whole sample comprised 189 COVID-19 survivors (mean age = 59.6 ± 13.4 years) who had been admitted to a ward only (n = 96; 50.8%) or to an ICU (n = 93; 49.2%). At 12 months of follow-up, 43% of patients presented with dyspnea, 27% of whom had a restrictive ventilatory disorder and 18% of whom presented with impaired DLCO. There were no significant differences in FVC, FEV1, and TLC between the survivors with or without dyspnea. However, those who still had dyspnea had significantly more impaired DLCO (14.9% vs. 22.4%; p < 0.020) and poorer quality of life. Conclusions: After one year, survivors of severe COVID-19 in a middle-income country still present with high symptom burden, restrictive ventilatory changes, and loss of quality of life. Ongoing follow-up is needed to characterize long COVID-19 and identify strategies to mitigate its consequences.

Abstract Cyclic carbonates are often produced through catalytic coupling reactions of CO2 with epoxides under harsh conditions. Here, we present a highly active nanoporous copper (np‐Cu) cathode material for the electrosynthesis of cyclic carbonates in mild environments. Np−Cu material was drop casted on glassy carbon (np‐Cu/GC) as cathode electrode to perform galvanostatic electrosynthesis using a magnesium anode in CO2‐saturated acetonitrile with 0.1 M tetraethylammonium iodide. Very good yields have been obtained for 1,2‐butylene carbonate (BC, 74 ± 4 %) and propylene carbonate (PC, 62 ± 6 %). By varying the cathode electrode materials, low yields (≤ 20 %) on bare GC, but similar yields (76 ± 4 % BC and 63 ± 5 % PC) on polycrystalline Cu were achieved. Although the pore‐ligament structure is beneficial to enhance the CO2RR performance, its impact on the yield of cyclic carbonate is minimal. This implies that the activation of CO2 to the CO2⋅− radical anion is not the rate‐limiting step, but rather the ring closure of the final intermediate to form cyclic carbonates. Moreover, the np‐Cu/GC shows very good stability and reusability for the electrochemical‐organic test reaction. This study provides deeper insights into the reaction mechanism of cyclic carbonates formation on Cu‐based electrodes.

Abstract Developing high‐performance carbonaceous anode materials for sodium‐ion batteries (SIBs) is still a grand quest for a more sustainable future of energy storage. Introducing sulfur within a carbon framework is one of the most promising attempts toward the development of highly efficient anode materials. Herein, a microporous sulfur‐rich carbon anode obtained from a liquid sulfur‐containing oligomer is introduced. The sodium storage mechanism shifts from surface‐controlled to diffusion‐controlled at higher synthesis temperatures. The different storage mechanisms and electrode performances are found to be independent of the bare electrode material's interplanar spacing. Therefore, these differences are attributed to an increased microporosity and a thiophene‐rich chemical environment. The combination of these properties enables extending the plateau region to higher potential and achieving reversible overpotential sodium storage. Moreover, in‐operando small‐angle X‐ray scattering (SAXS) reveals reversible electron density variations within the pore structure, in good agreement with the pore‐filling sodium storage mechanism occurring in hard carbons (HCs). Eventually, the depicted framework will enable the design of high‐performance anode materials for sodium‐ion batteries with competitive energy density.

BackgroundThe treatment of preterm and low birth weight (LBW) neonates born with congenital heart disease (CHD) requiring early cardiac intervention remains challenging. We aimed to analyze morbidity and mortality in this combined high-risk patient group.MethodsA retrospective cohort study was conducted of preterm [

ABSTRACT The rapid adaptive evolution of microbes is driven by strong selection pressure acting on genetic variation. How adaptive genetic variation is generated within species and how such variation influences phenotypic trait expression is often not well understood though. We focused on the recent activity of transposable elements (TEs) using deep population genomics and transcriptomics analyses of a fungal plant pathogen with a highly active content of TEs in the genome. Zymoseptoria tritici causes one of the most damaging diseases on wheat, with recent adaptation to the host and environment being facilitated by TE-associated mutations. We obtained genomic and RNA-sequencing data from 146 isolates collected from a single wheat field. We established a genome-wide map of TE insertion polymorphisms in the population by analyzing recent TE insertions among individuals. We quantified the locus-specific transcription of individual TE copies and found considerable population variation at individual TE loci in the population. About 20% of all TE copies show transcription in the genome suggesting that genomic defenses such as repressive epigenetic marks and repeat-induced polymorphisms are at least partially ineffective at preventing the proliferation of TEs in the genome. A quarter of recent TE insertions are associated with expression variation of neighboring genes providing broad potential to influence trait expression. We indeed found that TE insertions are likely responsible for variation in virulence on the host and potentially diverse components of secondary metabolite production. Our large-scale transcriptomics study emphasizes how TE-derived polymorphisms segregate even in individual microbial populations and can broadly underpin trait variation in pathogens.IMPORTANCEPathogens can rapidly adapt to new hosts, antimicrobials, or changes in the environment. Adaptation arises often from mutations in the genome; however, how such variation is generated remains poorly understood. We investigated the most dynamic regions of the genome of Zymoseptoria tritici, a major fungal pathogen of wheat. We focused on the transcription of transposable elements. A large proportion of the transposable elements not only show signatures of potential activity but are also variable within a single population of the pathogen. We find that this variation in activity is likely influencing many important traits of the pathogen. Hence, our work provides insights into how a microbial species can adapt over the shortest time periods based on the activity of transposable elements.

Abstract Background In agricultural ecosystems, outbreaks of diseases are frequent and pose a significant threat to food security. A successful pathogen undergoes a complex and well-timed sequence of regulatory changes to avoid detection by the host immune system; hence, well-tuned gene regulation is essential for survival. However, the extent to which the regulatory polymorphisms in a pathogen population provide an adaptive advantage is poorly understood. Results We used Zymoseptoria tritici, one of the most important pathogens of wheat, to generate a genome-wide map of regulatory polymorphism governing gene expression. We investigated genome-wide transcription levels of 146 strains grown under nutrient starvation and performed expression quantitative trait loci (eQTL) mapping. We identified cis-eQTLs for 65.3% of all genes and the majority of all eQTL loci are within 2kb upstream and downstream of the transcription start site (TSS). We also show that polymorphism in different gene elements contributes disproportionally to gene expression variation. Investigating regulatory polymorphism in gene categories, we found an enrichment of regulatory variants for genes predicted to be important for fungal pathogenesis but with comparatively low effect size, suggesting a separate layer of gene regulation involving epigenetics. We also show that previously reported trait-associated SNPs in pathogen populations are frequently cis-regulatory variants of neighboring genes with implications for the trait architecture. Conclusions Overall, our study provides extensive evidence that single populations segregate large-scale regulatory variation and are likely to fuel rapid adaptation to resistant hosts and environmental change.

Abstract Objectives High-quality species-specific transposable element (TE) libraries are required for studies to elucidate the evolutionary dynamics of TEs and gain an understanding of their impacts on host genomes. Such high-quality TE resources are severely lacking for species in the fungal kingdom. To facilitate future studies on the putative role of TEs in rapid adaptation observed in the fungal wheat pathogen Zymoseptoria tritici, we produced a manually curated TE library. This was generated by detecting TEs in 19 reference genome assemblies representing the global diversity of the species supplemented by multiple sister species genomes. Improvements over previous TE libraries have been made on TE boundary resolution, detection of ORFs, TE domains, terminal inverted repeats, and class-specific motifs. Data description A TE consensus library for Z. tritici formatted for use with RepeatMasker. This data is relevant to other researchers investigating TE-host evolutionary dynamics in Z. tritici or who are interested in comparative studies of the fungal kingdom. Further, this TE library can be used to improve gene annotation. Finally, this TE library increases the number of manually curated TE datasets, providing resources to further our understanding of TE diversity.

Abstract A virus infection can be initiated with very few or even a single infectious virion, and as such can become extinct, i.e. stochastically fail to take hold or spread significantly. There are many ways that a fully competent infectious virion, having successfully entered a cell, can fail to cause a productive infection, i.e. one that yields infectious virus progeny. Though many stochastic models (SMs) have been developed and used to estimate a virus infection’s establishment probability, these typically neglect infection failure post virus entry. The SM presented herein introduces parameter $$\gamma \in (0,1]$$ γ ∈ ( 0 , 1 ] which corresponds to the probability that a virion’s entry into a cell will result in a productive cell infection. We derive an expression for the likelihood of infection establishment in this new SM, and find that prophylactic therapy with an antiviral reducing $$\gamma$$ γ is at least as good or better at decreasing the establishment probability, compared to antivirals reducing the rates of virus production or virus entry into cells, irrespective of the SM parameters. We investigate the difference in the fraction of cells consumed by so-called extinct versus established virus infections, and find that this distinction becomes biologically meaningless as the probability of establishment approaches zero. We explain why the release of virions continuously over an infectious cell’s lifespan, rather than as a single burst at the end of the cell’s lifespan, does not result in an increased risk of infection extinction. We show, instead, that the number of virus released, not the timing of the release, affects infection establishment and associated critical antiviral efficacy.

Electroconvulsive therapy (ECT) is considered one of the most effective treatments for psychiatric disorders. ECT has proven effective in the treatment of depression, mania, catatonia and psychosis. It is presumed that seizures induced during ECT administration cause toxicity and potentially neuronal and glial cell death. A broad range of neurological disorders increase cerebrospinal fluid and serum levels of neuron-specific enolase (NSE) and S-100b protein. This study aims to investigate the effect of ECT on NSE and S-100b levels, which, together, serve as a proxy for neuronal cell damage. Serum concentrations of S-100b and NSE of adult patients who received ECT were measured by immunoluminometric analysis before and after treatment. A two-way ANOVA test was used to estimate the statistical differences in marker concentrations between the subgroups of the study population. Results: A total of 55 patients were included in the analysis: 52.73% (n = 29) were diagnosed with depression, 21.82% (n = 12) with schizophrenia or other psychosis, 16.36% (n = 9) with mania and 9.09% (n = 5) with catatonia. There were no statistically significant changes in NSE (p = 0.288) and S-100b (p = 0.243) levels. We found no evidence that ECT induced neuronal damage based on NSE and S-100b protein levels measured in the serum of patients before and after treatment.

A description of new antimicrobial agents suitable for food industries has become necessary, and natural compounds are being considered as promising sources of new active derivatives to be used with the aim of improving food safety. We have previously described desirable antimicrobial and antibiofilm activities against foodborne bacteria by analogs to A-type proanthocyanidins (PACs) with a nitro (NO2) group at carbon 6 of the A-ring. We report herein the synthesis of eight additional analogs with chloro and bromo atoms at the A-ring and the systematic study of their antimicrobial and antioxidant activities in order to evaluate their possible application as biocides or food preservatives, as well as to elucidate new structure–activity relationships. The results from this study show that halogenated analogs to natural A-type proanthocyanidins rise above the nitro derivatives previously reported in their antimicrobial activities. Gram-positive bacteria are the most sensitive to all the analogs and combinations assayed, showing MICs from 10 to 50 μg/mL in most cases, as well as reductions in biofilm formation and the disruption of preformed biofilms of at least 75%. Some structure–activity relationships previously described have also been corroborated. Analogs with just one OH group at the B-ring show better antimicrobial activities than those with two OH groups, and those analogs with two or three OH groups in the whole structure are more active than those with four OH groups. In addition, the analogs with two OH groups at the B-ring and chloro at the A-ring are the most effective when antibiofilm activities are studied, especially at low concentrations.

Abstract Low skeletal muscle index (SMI) and low skeletal muscle radiodensity (SMD) are associated with reduced survival time in pancreatic ductal adenocarcinoma (PDAC). The negative prognostic impact of low SMI and low SMD is often reported as independent of cancer stage when using traditional clinical staging tools. Therefore, this study sought to explore the relationship between a novel marker of tumour burden (circulating tumour DNA) and skeletal muscle abnormalities at diagnosis of PDAC. A retrospective cross-sectional study was conducted in patients who had plasma and tumour tissue samples stored in the Victorian Pancreatic Cancer Biobank (VPCB) at diagnosis of PDAC, between 2015 and 2020. Circulating tumour DNA (ctDNA) of patients with G12 and G13 KRAS mutations was detected and quantified. Pre-treatment SMI and SMD derived from analysis of diagnostic computed tomography imaging was tested for its association to presence and concentration of ctDNA, as well as conventional staging, and demographic variables. The study included 66 patients at PDAC diagnosis; 53% female, mean age 68.7 years (SD ± 10.9). Low SMI and low SMD were present in 69.7% and 62.1% of patients, respectively. Female gender was an independent risk factor for low SMI (OR 4.38, 95% CI 1.23–15.55, p = 0.022), and older age an independent risk factor for low SMD (OR 1.066, 95% CI 1.002–1.135, p = 0.044). No association between skeletal muscle stores and concentration of ctDNA (SMI r = − 0.163, p = 0.192; SMD r = 0.097, p = 0.438) or stage of disease according to conventional clinical staging [SMI F(3, 62) = 0.886, p = 0.453; SMD F(3, 62) = 0.717, p = 0.545] was observed. These results demonstrate that low SMI and low SMD are highly prevalent at diagnosis of PDAC, and suggest they are comorbidities of cancer rather than related to the clinical stage of disease. Future studies are needed to identify the mechanisms and risk factors for low SMI and low SMD at diagnosis of PDAC to aid screening and intervention development.

Abstract This study examined the effects of maternal and/or post-weaning Bacillus altitudinis supplementation on the microbiota in sow colostrum and faeces, and offspring digesta and faeces. Sows (n = 12/group) were assigned to: (1) standard diet (CON), or (2) CON supplemented with probiotic B. altitudinis spores (PRO) from day (d)100 of gestation to weaning (d26 of lactation). At weaning, offspring were assigned to CON or PRO for 28d, resulting in: (1) CON/CON, (2) CON/PRO, (3) PRO/CON, and (4) PRO/PRO, after which all received CON. Samples were collected from sows and selected offspring (n = 10/group) for 16S rRNA gene sequencing. Rothia was more abundant in PRO sow colostrum. Sow faeces were not impacted but differences were identified in offspring faeces and digesta. Most were in the ileal digesta between PRO/CON and CON/CON on d8 post-weaning; i.e. Bacteroidota, Alloprevotella, Prevotella, Prevotellaceae, Turicibacter, Catenibacterium and Blautia were more abundant in PRO/CON, with Firmicutes and Blautia more abundant in PRO/PRO compared with CON/CON. Lactobacillus was more abundant in PRO/CON faeces on d118 post-weaning. This increased abundance of polysaccharide-fermenters (Prevotella, Alloprevotella, Prevotellaceae), butyrate-producers (Blautia) and Lactobacillus likely contributed to previously reported improvements in growth performance. Overall, maternal, rather than post-weaning, probiotic supplementation had the greatest impact on intestinal microbiota.

Abstract Introduction: In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety. Methods: A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites. Results: We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites. Conclusion: The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.

Objective. This study is aimed at exploring whether the mode of nutrition intervention delivery affected participant goal achievement in a three-arm randomised controlled trial of early and intensive nutrition intervention delivered to upper gastrointestinal cancer patients. Methods. Newly diagnosed upper gastrointestinal cancer patients were recruited from four tertiary hospitals in Melbourne, Australia. Participants in the intervention groups received a regular nutrition intervention for 18 weeks from an experienced dietitian via telephone or mobile application (app) using behaviour change techniques to assist in goal achievement. Univariate and multiple regression models using STATA determined goal achievement, dose, and frequency of contact between groups. A p value

ABSTRACTThe gut microbiota is a key player in the host metabolism. Some bacteria are able to ferment non-digestible compounds and produce short-chain fatty acids that the host can later transform and accumulate in tissue. In this study, we aimed to better understand the relationships between the microorganisms and the short-chain fatty acid composition of the rectal content, including the possible linkage with the fatty acid composition in backfat and muscle of the pig. We studied a Duroc × Iberian crossbred population, and we found significant correlations between different bacterial and archaeal genera and the fatty acid profile. The abundance of n-butyric acid in the rectal content was positively associated with Prevotella spp. and negatively associated with Akkermansia spp., while conversely, the abundance of acetic acid was negatively and positively associated with the levels of Prevotella spp. and Akkermansia spp., respectively. The most abundant genus, Rikenellaceae RC9 gut group, had a positive correlation with palmitic acid in muscle and negative correlations with stearic acid in backfat and oleic acid in muscle. These results suggest the possible role of Prevotella spp. and Akkermansia spp. as biomarkers for acetic and n-butyric acids, and the relationship of Rikenellaceae RC9 gut group with the lipid metabolism, building up the potential, although indirect, role of the microbiota in the modification of the backfat and muscle fatty acid composition of the host.IMPORTANCEThe vital role of the gut microbiota on its host metabolism makes it essential to know how its modulation is mirrored on the fatty acid composition of the host. Our findings suggest Prevotella spp. and Akkermansia spp. as potential biomarkers for the levels of beneficial short-chain fatty acids and the possible influence of Rikenellaceae RC9 gut group in the backfat and muscle fatty acid composition of the pig.

IntroductionUltra-high field MR imaging offers marked gains in signal-to-noise ratio, spatial resolution, and contrast which translate to improved pathological and anatomical sensitivity. These benefits are particularly relevant for the neonatal brain which is rapidly developing and sensitive to injury. However, experience of imaging neonates at 7T has been limited due to regulatory, safety, and practical considerations. We aimed to establish a program for safely acquiring high resolution and contrast brain images from neonates on a 7T system.MethodsImages were acquired from 35 neonates on 44 occasions (median age 39 + 6 postmenstrual weeks, range 33 + 4 to 52 + 6; median body weight 2.93 kg, range 1.57 to 5.3 kg) over a median time of 49 mins 30 s. Peripheral body temperature and physiological measures were recorded throughout scanning. Acquired sequences included T2 weighted (TSE), Actual Flip angle Imaging (AFI), functional MRI (BOLD EPI), susceptibility weighted imaging (SWI), and MR spectroscopy (STEAM).ResultsThere was no significant difference between temperature before and after scanning (p = 0.76) and image quality assessment compared favorably to state-of-the-art 3T acquisitions. Anatomical imaging demonstrated excellent sensitivity to structures which are typically hard to visualize at lower field strengths including the hippocampus, cerebellum, and vasculature. Images were also acquired with contrast mechanisms which are enhanced at ultra-high field including susceptibility weighted imaging, functional MRI, and MR spectroscopy.DiscussionWe demonstrate safety and feasibility of imaging vulnerable neonates at ultra-high field and highlight the untapped potential for providing important new insights into brain development and pathological processes during this critical phase of early life.

ABSTRACT Early COVID-19 convalescent plasma (CCP) transfusion to outpatients with COVID-19 decreases progression to hospitalization, but the mechanism of how CCP reduces severity is unknown. Among 882 COVID-19 participants transfused with CCP or control plasma in a randomized controlled trial, 21 cytokines and chemokines were measured using electrochemiluminescence assays. Wilcoxon rank sum tests were used to evaluate the difference between early (transfused within 5 days of symptom onset) CCP vs early control plasma and late (transfused 6–9 days after symptom onset) CCP vs late control plasma at each visit. Linear mixed-effect models were used to assess the difference in the slope of cytokine change. Median cytokine and chemokine levels were similar between the early CCP and early control groups pre-transfusion. At the day 14 visit, only the median IL-6 (P = 0.014) and IL-16 (P = 0.036) levels were lower in the early CCP group compared to the early control group, but these differences were not statistically significant after correcting for multiple comparisons (requiring P < 0.0024). IL-6 levels decreased significantly faster in the early CCP group from screening to the day 14 visit compared to the early control group (P < 0.001). No difference was observed in the slope of cytokine change from screening to day 90 between early CCP and early control groups. Late control and late CCP arms showed similar cytokine and chemokine levels through study follow-up. One mechanism by which early CCP transfusion reduces hospitalization may be by decreasing IL-6 levels, as the reduction is associated with better recovery from COVID-19. IMPORTANCE This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.

Abstract Human papillomavirus (HPV) infects nearly 85% of sexually active Americans during their lifetime, causing most cervical and five other cancers. Routine HPV vaccination is recommended for adolescents to prevent HPV-attributable cancers, but HPV vaccination coverage remains low, especially in Tennessee. In 2021, 54.6% of the population in Shelby County, Tennessee was Black or African American, reporting higher rates of new cervical cancer cases than other counties in Tennessee. While medical and public health professionals (HPs) play a critical role in promoting vaccination coverage, little is known about the factors HPs perceive to influence HPV vaccination for this population. This study sought to explore HPs’ perceived facilitators and barriers of HPV vaccination among African American adolescents. Qualitative individual interviews with 26 HPs in Shelby County were conducted between October 2019 and February 2020. Interpretive content analysis of the interview data guided by the socio-ecological model revealed several important themes regarding the facilitators and barriers across the individual, interpersonal, and community levels. At the individual level, parental vaccine hesitancy emerged as a leading barrier to HPV vaccination, while appropriate education facilitated the vaccination. At the interpersonal level, a lack of strong provider recommendations impeded HPV vaccination, whereas improved communication skills with patients facilitated the vaccination. Finally, the community-level barriers included a lack of education and social/religious norms; the community-level facilitators included community outreach efforts. HPs should consider development of comprehensive community-based approaches that leverage the facilitators and barriers at multiple levels to increase HPV vaccination among African American adolescents in this region.

Abstract Early life phenology is a crucial factor for population dynamics in a climate change scenario. As such, understanding how the early life cycle of marine fishes is influenced by key oceanic and climate drivers is of chief importance for sustainable fisheries. This study documents interannual changes in early life phenology of two commercial flatfishes: European flounder (Platichthys flesus) and common sole (Solea solea) from 2010 to 2015 based on otolith microstructure. Using GAMs, we looked for correlations of the North Atlantic Oscillation (NAO), Eastern Atlantic pattern (EA), sea surface temperature (SST), chlorophyl a concentration (Chla) and upwelling (Ui) variation with the onset of hatch, metamorphosis, and benthic settlement day. We concluded that higher SST, more intensive upwelling, and EA were coincident with a later the onset of each stage, while increasing NAO induces an earlier onset of each stage. Although similar to S. solea, P. flesus showed a more complex interaction with the environmental drivers, most possibly because it is at its southern limit of its distribution. Our results highlight the complexity of the relationship between climate conditions and fish early life history, particularly those with complex life cycles that include migrations between coastal areas and estuaries.

In recent times, with rapid development in the construction sector, the use of enormous amounts of materials is required for the production of concrete. Fire penetrates concrete, leading to chemical contamination, small cracks, and lightening. These effects can significantly change the properties of concrete’s structure, reduce its strength and durability, and also change the behavior of the structure and lead to effects on the environment. An attempt was made to study the effects of elevated temperature on the mechanical characteristics of self-compacting concrete (SCC) with by-products including fly ash as a partial replacement for cement and waste copper slag as a partial replacement for fine aggregate at 0%, 10%, 20%, 30%, 40%, 50%, 60%, and 70%. The SCC specimens were subjected to elevated temperatures ranging from 200, 400, 600, and 800 °C, respectively, for a steady-state of two hours in a digital muffle furnace. The residual compressive strength, mass loss, ultrasonic pulse velocity, and residual density along with a visual inspection of cracks and color changes were observed. In this study, with over 400 °C temperatures, surface fractures appeared. The residual compressive strength (R-CMS) of all the individual temperatures of the SCC-WCS% mixes exhibited a gain in strength range from 31 to 34 MPa at 400 °C, 26 to 35 MPa at 600 °C, and 22.5 MPa to 33.5 MPa at 800 °C, respectively. Microstructural analysis of SCC-WCS% mixtures subjected to elevated ambient temperatures is carried out with a scanning electron microscope (SEM) and X-ray diffraction (XRD).

Rapid and early detection of infectious diseases in pigs is important, especially for the implementation of control measures in suspected cases of African swine fever (ASF), as an effective and safe vaccine is not yet available in most of the affected countries. Additionally, analysis for swine influenza is of significance due to its high morbidity rate (up to 100%) despite a lower mortality rate compared to ASF. The wide distribution of swine influenza A virus (SwIAV) across various countries, the emergence of constantly new recombinant strains, and the danger of human infection underscore the need for rapid and accurate diagnosis. Several diagnostic approaches and commercial methods should be applied depending on the scenario, type of sample and the objective of the studies being implemented. At the early diagnosis of an outbreak, virus genome detection using a variety of PCR assays proves to be the most sensitive and specific technique. As the disease evolves, serology gains diagnostic value, as specific antibodies appear later in the course of the disease (after 7–10 days post-infection (DPI) for ASF and between 10–21 DPI for SwIAV). The ongoing development of commercial kits with enhanced sensitivity and specificity is evident. This review aims to analyse recent advances and current commercial kits utilised for the diagnosis of ASF and SwIAV.

Maintaining or introducing genetic diversity into plant breeding programs is necessary for continual genetic gain; however, diversity at the cost of reduced performance is not something sought by breeders. To this end, backcross-nested association mapping (BC-NAM) populations, in which the recurrent parent is an elite line, can be employed as a strategy to introgress diversity from unadapted accessions while maintaining agronomic performance. This study evaluates (i) the hybrid performance of sorghum lines from 18 BC1-NAM families and (ii) the potential of genomic prediction to screen lines from BC1-NAM families for hybrid performance prior to phenotypic evaluation. Despite the diverse geographical origins and agronomic performance of the unadapted parents for BC1-NAM families, many BC1-derived lines performed significantly better in the hybrid trials than the elite recurrent parent, R.Tx436. The genomic prediction accuracies for grain yield, plant height, and days to mid-anthesis were acceptable, but the prediction accuracies for plant height were lower than expected. While the prediction accuracies increased when including more individuals in the training set, improvements tended to plateau between two and five lines per family, with larger training sets being required for more complex traits such as grain yield. Therefore, genomic prediction models can be optimized in a large BC1-NAM population with a relatively low fraction of individuals needing to be evaluated. These results suggest that genomic prediction is an effective method of pre-screening lines within BC1-NAM families prior to evaluation in extensive hybrid field trials.