Ovarian response and embryo ploidy following oral micronized progesterone-primed ovarian stimulation versus GnRH antagonist protocol. A prospective study with repeated ovarian stimulation cycles.

STUDY QUESTION: Is there any difference in ovarian response and embryo ploidy following progesterone-primed ovarian stimulation (PPOS) using micronized progesterone or GnRH antagonist protocol? SUMMARY ANSWER: Pituitary downregulation with micronized progesterone as PPOS results in higher number of oocytes retrieved and a comparable number of euploid blastocysts to a GnRH antagonist protocol. WHAT IS KNOWN ALREADY: Although the GnRH antagonist is considered by most the gold standard protocol for controlling the LH surge during ovarian stimulation (OS) for IVF/ICSI, PPOS protocols are being increasingly used in freeze-all protocols. Still, despite the promising results of PPOS protocols, an early randomized trial reported potentially lower live births in recipients of oocytes resulting following downregulation with medroxyprogesterone acetate as compared with a GnRH antagonist protocol. The scope of the current prospective study was to investigate whether PPOS with micronized progesterone results in an equivalent yield of euploid blastocysts to a GnRH antagonist protocol. STUDY DESIGN, SIZE, DURATION: In this prospective study, performed between September 2019 to January 2022, 44 women underwent two consecutive OS protocols within a period of 6 months in a GnRH antagonist protocol or in a PPOS protocol with oral micronized progesterone. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 44 women underwent two OS cycles with an identical fixed dose of rFSH (225 or 300 IU) in both cycles. Downregulation in the first cycles was performed with the use of a flexible GnRH antagonist protocol (0.25 mg per day as soon as one follicle of 14 mm) and consecutively, after a washout period of 1 month, control of LH surge was performed with 200 mg of oral micronized progesterone from stimulation Day 1. After the completion of both cycles, all generated blastocysts underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuplody, PGT-A). MAIN RESULTS AND THE ROLE OF CHANCE: Comparisons between protocols did not reveal differences between the duration of OS. The hormonal profile on the day of trigger revealed statistically significant differences between protocols in all the tested hormones except for FSH: with significantly higher serum E2 levels, more elevated LH levels and higher progesterone levels in PPOS cycles as compared with antagonist cycles, respectively. Compared with the GnRH antagonist protocol, the PPOS protocol resulted in a significantly higher number of oocytes (12.7 ± 8.09 versus 10.3 ± 5.84; difference between means [DBM] -2.4 [95% CI -4.1 to -0.73]), metaphase II (9.1 ± 6.12 versus 7.3 ± 4.15; DBM -1.8 [95% CI -3.1 to -0.43]), and 2 pronuclei (7.1 ± 4.99 versus 5.7 ± 3.35; DBM -1.5 [95% CI -2.6.1 to -0.32]), respectively. Nevertheless, no differences were observed regarding the mean number of blastocysts between the PPOS and GnRH antagonist protocols (2.9 ± 2.11 versus 2.8 ± 2.12; DBM -0.07 [95% CI -0.67 to 0.53]) and the mean number of biopsied blastocysts (2.9 ± 2.16 versus 2.9 ± 2.15; DBM -0.07 [95% CI -0.70 to 0.56]), respectively. Concerning the euploidy rates per biopsied embryo, a 29% [95% CI 21.8-38.1%] and a 35% [95% CI 26.6-43.9%] were noticed in the PPOS and antagonist groups, respectively. Finally, no difference was observed for the primary outcome, with a mean number of euploid embryos of 0.86 ± 0.90 versus 1.00 ± 1.12 for the comparison of PPOS versus GnRh antagonist. LIMITATIONS, REASONS FOR CAUTION: The study was powered to detect differences in the mean number of euploid embryos and not in terms of pregnancy outcomes. Additionally, per protocol, there was no randomization, the first cycle was always a GnRH antagonist cycle and the second a PPOS with 1 month of washout period in between. WIDER IMPLICATIONS OF THE FINDINGS: In case of a freeze-all protocol, clinicians may safely consider oral micronized progesterone to control the LH surge and patients could benefit from the advantages of a medication of oral administration, with a potentially higher number of oocytes retrieved at a lower cost, without any compromise in embryo ploidy rates. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by an unrestricted grant from Theramex. N.P.P. has received Research grants from Merck Serono, Organon, Ferring Pharmaceutical, Roche, Theramex, IBSA, Gedeon Richter, and Besins Healthcare; honoraria for lectures from: Merck Serono, Organon, Ferring Pharmaceuticals, Besins International, Roche Diagnostics, IBSA, Theramex, and Gedeon Richter; consulting fees from Merck Serono, Organon, Besins Healthcare, and IBSA. M.d.M.V., F.M., and I.R. declared no conflicts of interest. TRIAL REGISTRATION NUMBER: The study was registered at Clinical Trials Gov. (NCT04108039).

Empirical evaluation of language modeling to ascertain cancer outcomes from clinical text reports.

BACKGROUND: Longitudinal data on key cancer outcomes for clinical research, such as response to treatment and disease progression, are not captured in standard cancer registry reporting. Manual extraction of such outcomes from unstructured electronic health records is a slow, resource-intensive process. Natural language processing (NLP) methods can accelerate outcome annotation, but they require substantial labeled data. Transfer learning based on language modeling, particularly using the Transformer architecture, has achieved improvements in NLP performance. However, there has been no systematic evaluation of NLP model training strategies on the extraction of cancer outcomes from unstructured text. RESULTS: We evaluated the performance of nine NLP models at the two tasks of identifying cancer response and cancer progression within imaging reports at a single academic center among patients with non-small cell lung cancer. We trained the classification models under different conditions, including training sample size, classification architecture, and language model pre-training. The training involved a labeled dataset of 14,218 imaging reports for 1112 patients with lung cancer. A subset of models was based on a pre-trained language model, DFCI-ImagingBERT, created by further pre-training a BERT-based model using an unlabeled dataset of 662,579 reports from 27,483 patients with cancer from our center. A classifier based on our DFCI-ImagingBERT, trained on more than 200 patients, achieved the best results in most experiments; however, these results were marginally better than simpler "bag of words" or convolutional neural network models. CONCLUSION: When developing AI models to extract outcomes from imaging reports for clinical cancer research, if computational resources are plentiful but labeled training data are limited, large language models can be used for zero- or few-shot learning to achieve reasonable performance. When computational resources are more limited but labeled training data are readily available, even simple machine learning architectures can achieve good performance for such tasks.

The Allele Catalog Tool: a web-based interactive tool for allele discovery and analysis.

BACKGROUND: The advancement of sequencing technologies today has made a plethora of whole-genome re-sequenced (WGRS) data publicly available. However, research utilizing the WGRS data without further configuration is nearly impossible. To solve this problem, our research group has developed an interactive Allele Catalog Tool to enable researchers to explore the coding region allelic variation present in over 1,000 re-sequenced accessions each for soybean, Arabidopsis, and maize. RESULTS: The Allele Catalog Tool was designed originally with soybean genomic data and resources. The Allele Catalog datasets were generated using our variant calling pipeline (SnakyVC) and the Allele Catalog pipeline (AlleleCatalog). The variant calling pipeline is developed to parallelly process raw sequencing reads to generate the Variant Call Format (VCF) files, and the Allele Catalog pipeline takes VCF files to perform imputations, functional effect predictions, and assemble alleles for each gene to generate curated Allele Catalog datasets. Both pipelines were utilized to generate the data panels (VCF files and Allele Catalog files) in which the accessions of the WGRS datasets were collected from various sources, currently representing over 1,000 diverse accessions for soybean, Arabidopsis, and maize individually. The main features of the Allele Catalog Tool include data query, visualization of results, categorical filtering, and download functions. Queries are performed from user input, and results are a tabular format of summary results by categorical description and genotype results of the alleles for each gene. The categorical information is specific to each species; additionally, available detailed meta-information is provided in modal popups. The genotypic information contains the variant positions, reference or alternate genotypes, the functional effect classes, and the amino-acid changes of each accession. Besides that, the results can also be downloaded for other research purposes. CONCLUSIONS: The Allele Catalog Tool is a web-based tool that currently supports three species: soybean, Arabidopsis, and maize. The Soybean Allele Catalog Tool is hosted on the SoyKB website ( https://soykb.org/SoybeanAlleleCatalogTool/ ), while the Allele Catalog Tool for Arabidopsis and maize is hosted on the KBCommons website ( https://kbcommons.org/system/tools/AlleleCatalogTool/Zmays and https://kbcommons.org/system/tools/AlleleCatalogTool/Athaliana ). Researchers can use this tool to connect variant alleles of genes with meta-information of species.

Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study.

BACKGROUND: Patritumab deruxtecan (HER3-DXd) is a human epidermal growth factor receptor 3 (HER3)-directed antibody-drug conjugate composed of a fully human anti-HER3 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. TOT-HER3 is a window-of-opportunity study designed to assess the biological activity, measured by CelTIL score [= -0.8 × tumor cellularity (in %)  + 1.3  × tumor-infiltrating lymphocytes (TILs) (in %)], and clinical activity of HER3-DXd during short-term (21 days) pre-operative treatment in patients with primary operable HER2-negative early breast cancer. PATIENTS AND METHODS: Patients with previously untreated hormone receptor-positive/HER2-negative tumors were allocated to one of four cohorts according to baseline ERBB3 messenger RNA expression. All patients received one dose of HER3-DXd 6.4 mg/kg. The primary objective was to evaluate change from baseline in CelTIL score. RESULTS: Seventy-seven patients were evaluated for efficacy. A significant change in CelTIL score was observed, with a median increase from baseline of 3.5 (interquartile range, -3.8 to 12.7; P = 0.003). Among patients assessable for clinical response (n = 62), an overall response rate of 45% was observed (tumor measurement by caliper), with a trend toward an increase in CelTIL score among responders compared with non-responders (mean difference, +11.9 versus +1.9). Change in CelTIL score was independent of baseline ERBB3 messenger RNA and HER3 protein levels. Genomic changes occurred, including switching toward a less proliferative tumor phenotype based on PAM50 subtypes, suppression of cell proliferation genes, and induction of genes associated with immunity. Treatment-emergent adverse events were observed in 96% of patients (14% grade ≥3); most common were nausea, fatigue, alopecia, diarrhea, vomiting, abdominal pain, and neutrophil count decrease. CONCLUSIONS: A single dose of HER3-DXd was associated with clinical response, increased immune infiltration, suppression of proliferation in hormone receptor-positive/HER2-negative early breast cancer, and a tolerable safety profile consistent with previously reported results. These findings support further study of HER3-DXd in early breast cancer.

Association of HER2DX with pathological complete response and survival outcomes in HER2-positive breast cancer.

BACKGROUND: The HER2DX genomic test predicts pathological complete response (pCR) and survival outcome in early-stage HER2-positive (HER2+) breast cancer. Here, we evaluated the association of HER2DX scores with (i) pCR according to hormone receptor status and various treatment regimens, and (ii) survival outcome according to pCR status. MATERIALS AND METHODS: Seven neoadjuvant cohorts with HER2DX and clinical individual patient data were evaluated (DAPHNe, GOM-HGUGM-2018-05, CALGB-40601, ISPY-2, BiOnHER, NEOHER and PAMELA). All patients were treated with neoadjuvant trastuzumab (n = 765) in combination with pertuzumab (n = 328), lapatinib (n = 187) or without a second anti-HER2 drug (n = 250). Event-free survival (EFS) and overall survival (OS) outcomes were available in a combined series of 268 patients (i.e. NEOHER and PAMELA) with a pCR (n = 118) and without a pCR (n = 150). Cox models were adjusted to evaluate whether HER2DX can identify patients with low or high risk beyond pCR status. RESULTS: HER2DX pCR score was significantly associated with pCR in all patients [odds ratio (OR) per 10-unit increase = 1.59, 95% confidence interval 1.43-1.77; area under the ROC curve = 0.75], with or without dual HER2 blockade. A statistically significant increase in pCR rate due to dual HER2 blockade over trastuzumab-only was observed in HER2DX pCR-high tumors treated with chemotherapy (OR = 2.36 (1.09-5.42). A statistically significant increase in pCR rate due to multi-agent chemotherapy over a single taxane was observed in HER2DX pCR-medium tumors treated with dual HER2 blockade (OR = 3.11, 1.54-6.49). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of treatment administered. After adjusting by pCR status, patients identified as HER2DX low-risk had better EFS (P < 0.001) and OS (P = 0.006) compared with patients with HER2DX high-risk. CONCLUSIONS: HER2DX pCR score and risk score might help identify ideal candidates to receive neoadjuvant dual HER2 blockade in combination with a single taxane in early-stage HER2+ breast cancer.

Dynamical Polarization of the Fermion Parity in a Nanowire Josephson Junction.

Josephson junctions in InAs nanowires proximitized with an Al shell can host gate-tunable Andreev bound states. Depending on the bound state occupation, the fermion parity of the junction can be even or odd. Coherent control of Andreev bound states has recently been achieved within each parity sector, but it is impeded by incoherent parity switches due to excess quasiparticles in the superconducting environment. Here, we show that we can polarize the fermion parity dynamically using microwave pulses by embedding the junction in a superconducting LC resonator. We demonstrate polarization up to 94%±1% (89%±1%) for the even (odd) parity as verified by single shot parity readout. Finally, we apply this scheme to probe the flux-dependent transition spectrum of the even or odd parity sector selectively, without any postprocessing or heralding.

Feeding colostrum and transition milk facilitates digestive tract functionality recovery from feed restriction and fasting of dairy calves.

The objective of this study was to evaluate the digestive tract recovery and metabolism of feeding either bovine colostrum (BC), transition milk (TM), or milk replacer (MR) after an episode of feed restriction and fasting (FRF) in dairy calves. Thirty-five Holstein male calves (22 ± 4.8 d old) were involved in a 50-d study. After 3 d of feeding 2 L of rehydration solution twice daily and 19 h of fasting (d 1 of study), calves were randomly assigned to one of the 5 feeding treatments (n = 7): calves were offered either pooled BC during 4 (C4) or 10 (C10) days, pooled TM during 4 (TM4) or 10 (TM10) days, or MR for 10 d (CTRL) at the rate of 720 g/d DM content. Then, all calves were fed the same feeding program, gradually decreasing MR from 3 L twice daily to 2 L once daily at 12.5% DM until weaning (d 42), and concentrate feed, water, and straw were offered ad libitum until d 50. Citrulline, Cr-EDTA, ß-hydroxybutyrate (BHB), and nonesterified fatty acids (NEFA) in serum and complete blood count (CBC) were determined on d -3, 1, 2, 5, and 11 relative to FRF, except BHB and NEFA at d -3. Volatile fatty acids (VFA), lactoferrin (LTF), IgA, and microbiota (Firmicutes to Bacteroidetes ratio and Fecalis prausnitzii) were analyzed in feces on d 5 and 11 before the morning feeding. Health scores were recorded daily from d -3 to d 14 as well as d 23 and 30. Feed concentrate, MR, and straw intake were recorded daily, and body weight on d -3, 1, 2, 5, and 11 and weekly afterward. Calf performance, intake, serum Cr-EDTA, CBC, fecal LTF concentrations and microbiota parameters were similar among treatments throughout the study. Serum NEFA concentrations were greater in TM4, TM10 and C10 calves compared with the CTRL ones from d 2 to 11, and after the FRF, serum concentrations of BHB were lower in CTRL calves than in the other treatments, and on d 11, serum BHB concentrations in the long treatments (C10 and TM10) remained greater than those in the shorter ones (C4 and TM4) and CTRL. Serum citrulline concentrations were similar on d -3 and 1 in all treatments, but they were greater in C4, C10, TM4, and TM10 on d 2 and 5, and on d 11 they were only greater in C10 and TM10 than in CTRL calves. Fecal IgA concentrations tended to be greater in C10 than in CTRL, TM4, and TM10 calves, and in C4 and TM10 than in CTRL animals. Fecal propionate proportion was lesser in C10 than in CTRL, TM4, and TM10 calves, while butyrate was greater in C4 and C10 than in TM4 and CTRL calves. The proportion of non-normal fecal scores of C10 fed calves was greater than TM4 and TM10 calves. Results showed that TM and BC may help to recover intestinal functionality, provide gut immune protection, and increase liver fatty acid oxidation in calves after a FRF episode.

Benefits of barley straw as a forage for dairy calves before and after weaning.

The aim of this study was to assess the potential consequences on calf intake, performance, behavior, ruminal microbiome, and ruminal epithelium development of combining the inclusion of chopped barley straw and alfalfa hay during the pre- and postweaning periods keeping concentrate to forage ratio constant among dietary treatments. Forty-five Holstein calves (44 ± 5.7 kg of body weight [BW] and 3 ± 1.5 d of age) individually penned were blocked by BW and randomly assigned to a common pellet concentrate fed ad libitum along with one of following forage feeding strategies: barley straw before and after weaning (S-S), barley straw before and alfalfa hay after weaning (S-A), or alfalfa hay before and after weaning (A-A). All calves received the same milk replacer regimen. Forage was supplied in a separated bucket at the rate of 7.5% (preweaning) and 15% (postweaning) of total solid feed intake of the previous day. Feed intake and BW were recorded daily and weekly, respectively. Rumen samples were obtained via a stomach tube at 53, 66, and 87 d and were composite in 3 samples of 5 animals each for subsequent rumen microbiome analysis. A rumen epithelium sample was taken by endoscopy at 90 d to assess gene expression of OCLN, CLDN4, SLC9A1, SLC9A3, SLC16A1, SLC16A4, IL6, and TGFB1. Data were analyzed with a mixed-effects model accounting for the fixed effects of block, forage, week of study, and their interaction, and calf as a random effect. The type of forage fed did not affect concentrate feed, forage, or total DM intake before weaning. However, S-A and A-A calves consumed less concentrate feed and S-A calves grew at a lower rate after weaning than S-S calves. Expression of the gene coding for SLC16A1 in the rumen epithelium was greatest in S-S among treatments. Rumen microbiome did not differ among treatments, while the relative abundance of Acidaminococcus and Selenomas genera increased, while Alloprevotella, Bifidobaterium, Olsenella, and Succiclasticum genera decreased with age. In conclusion, feeding barley straw before and after weaning was more effective than feeding alfalfa hay in promoting concentrate feed intake after weaning and fostering an increase in the expression of SLC16A1 in the rumen epithelium.

The 2021 SIIM-FISABIO-RSNA Machine Learning COVID-19 Challenge: Annotation and Standard Exam Classification of COVID-19 Chest Radiographs.

We describe the curation, annotation methodology, and characteristics of the dataset used in an artificial intelligence challenge for detection and localization of COVID-19 on chest radiographs. The chest radiographs were annotated by an international group of radiologists into four mutually exclusive categories, including "typical," "indeterminate," and "atypical appearance" for COVID-19, or "negative for pneumonia," adapted from previously published guidelines, and bounding boxes were placed on airspace opacities. This dataset and respective annotations are available to researchers for academic and noncommercial use.

Pertactin-Deficient Bordetella pertussis with Unusual Mechanism of Pertactin Disruption, Spain, 1986-2018.

Bordetella pertussis not expressing pertactin has increased in countries using acellular pertussis vaccines (ACV). The deficiency is mostly caused by pertactin gene disruption by IS481. To assess the effect of the transition from whole-cell vaccine to ACV on the emergence of B. pertussis not expressing pertactin in Spain, we studied 342 isolates collected during 1986-2018. We identified 93 pertactin-deficient isolates. All were detected after introduction of ACV and represented 38% of isolates collected during the ACV period; 58.1% belonged to a genetic cluster of isolates carrying the unusual prn::del(-292, 1340) mutation. Pertactin inactivation by IS481 insertion was identified in 23.7% of pertactin-deficient isolates, arising independently multiple times and in different phylogenetic branches. Our findings support the emergence and dissemination of a cluster of B. pertussis with an infrequent mechanism of pertactin disruption in Spain, probably resulting from introduction of ACV.

Sociodemographic and Clinical Profile of People Attended in the “Catalonia Suicide Risk Code” Program.

uicide is an issue with a great impact on public health. For this reason, the Catalonia Suicide Risk Code (CSRC) protocol was developed in 2015.

Genetic variation in the body mass index of adult survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort.

BACKGROUND: Treatment characteristics such as cranial radiation therapy (CRT) do not fully explain adiposity risk in childhood acute lymphoblastic leukemia (ALL) survivors. This study was aimed at characterizing genetic variation related to adult body mass index (BMI) among survivors of childhood ALL. METHODS: Genetic associations of BMI among 1458 adult survivors of childhood ALL (median time from diagnosis, 20 years) were analyzed by multiple approaches. A 2-stage genome-wide association study in the Childhood Cancer Survivor Study (CCSS) and the St. Jude Lifetime Cohort Study (SJLIFE) was performed. BMI was a highly polygenic trait in the general population. Within the known loci, the BMI percent variance explained was estimated, and additive interactions (chi-square test) with CRT in the CCSS were evaluated. The role of DNA methylation in CRT interaction was further evaluated in a subsample of ALL survivors. RESULTS: In a meta-analysis of the CCSS and SJLIFE, 2 novel loci associated with adult BMI among survivors of childhood ALL (LINC00856 rs575792008 and EMR1 rs62123082; PMeta < 5E-8) were identified. It was estimated that the more than 700 known loci explained 6.2% of the variation in adult BMI in childhood ALL survivors. Within the known loci, significant main effects for 23 loci and statistical interactions with CRT at 9 loci (P < 7.0E-5) were further identified. At 2 CRT-interacting loci, DNA methylation patterns may have differed by age. CONCLUSIONS: Adult survivors of childhood ALL have genetic heritability for BMI similar to that observed in the general population. This study provides evidence that treatment with CRT can modify the effect of genetic variants on adult BMI in childhood ALL survivors.

Low nitrogen availability inhibits the phosphorus starvation response in maize (Zea mays ssp. mays L.).

BACKGROUND: Nitrogen (N) and phosphorus (P) are macronutrients essential for crop growth and productivity. In cultivated fields, N and P levels are rarely sufficient, contributing to the gap between realized and potential production. Fertilizer application increases nutrient availability, but is not available to all farmers, nor are current rates of application sustainable or environmentally desirable. Transcriptomic studies of cereal crops have revealed dramatic responses to either low N or low P single stress treatments. In the field, however, levels of both N and P may be suboptimal. The interaction between N and P starvation responses remains to be fully characterized. RESULTS: We characterized growth and root and leaf transcriptomes of young maize plants under nutrient replete, low N, low P or combined low NP conditions. We identified 1555 genes to respond to our nutrient treatments, in one or both tissues. A large group of genes, including many classical P starvation response genes, were regulated antagonistically between low N and P conditions. An additional experiment over a range of N availability indicated that a mild reduction in N levels was sufficient to repress the low P induction of P starvation genes. Although expression of P transporter genes was repressed under low N or low NP, we confirmed earlier reports of P hyper accumulation under N limitation. CONCLUSIONS: Transcriptional responses to low N or P were distinct, with few genes responding in a similar way to the two single stress treatments. In combined NP stress, the low N response dominated, and the P starvation response was largely suppressed. A mild reduction in N availability was sufficient to repress the induction of P starvation associated genes. We conclude that activation of the transcriptional response to P starvation in maize is contingent on N availability.

Using compositional mixed-effects models to evaluate responses to amino acid supplementation in milk replacers for calves.

The consequences of supplementing Lys, Met, and Thr in milk replacers (MR) for calves have been widely studied, but scarce information exists about potential roles of other AA (whether essential or not). The effects on growth performance of supplementation of 4 different AA combinations in a mixed ration (25.4% crude protein and 20.3% fat) based on skim milk powder and whey protein concentrate were evaluated in 76 Holstein male calves (3 ± 1.7 d old). The 4 MR were as follows: CTRL with no AA supplementation; PG, supplying additional 0.3% Pro and 0.1% Gly; FY, supplying additional 0.2% Phe and 0.2% Tyr; and KMT, providing additional 0.62% Lys, 0.22% Met, and 0.61% Thr. All calves were fed the same milk allowance program and were weaned at 56 d of study. Concentrate intake was limited to minimize interference of potential differences in solid feed intake among treatments. Animals were weighed weekly, intakes recorded daily, and blood samples obtained at 2, 5, and 7 wk of study to determine serum urea and plasma AA concentrations. Plasma AA concentrations were explored using compositional data analysis, and their isometric log-ratio transformations were used to analyze their potential influence on ADG and serum urea concentration using a linear mixed-effects model. We detected no differences in calf performance and feed intake. Plasma relative concentration of the AA supplemented in the KMT and PG treatments increased in their respective treatments, and, in PG calves, a slight increase in the proportion of plasma Gly, Glu, and branched-chain AA was also observed. The proportions of plasma branched-chain AA, His, and Gln increased, and those of Thr, Arg, Lys, and Glu decreased with calves' age. A specific log-contrast balance formed by Arg, Thr, and Lys was found to be the main driver for lowering serum urea concentrations and increasing calf growth. The use of compositional mixed-effects models identified a cluster formed by the combination of Arg, Thr, and Lys, as a potential AA to optimize calf growth.

Urban areas, human health and technosols for the green deal.

Authors aim to carry out a bibliographic review as an initial approach to state of the art related to the quality of urban soils, as well as its possible link with human health. This concern arises from the need to highlight the consequences that soil could face, derived from the growth and aging of the population, as well as its predicted preference for urban settlement. Urban development may pose a challenge to the health of urban soils, due to degradative processes that it entails, such as land take, sealing, contamination or compaction. A healthy soil is the one which maintains the capacity to support ecosystem services, so it can provide numerous benefits to human health and well-being (carbon sequestration, protection against flooding, retention and immobilization of pollutants and a growth media for vegetation and food production). This article addresses threats facing urban soils, the strategies put forward by the European Union to deal with them, as well as the issues that require further attention. Greening cities could be a consensual solution, so authors analyze whether soils of cities are ready for that challenge and what resources need to maintain soil ecosystem functions. This review proposes to use made by waste Technosols for a sustainable green city. Although the use of Technosols as a type of soil is very recent, the interest of the scientific community in this field continues to grow.

Resonant Inelastic X-Ray Scattering Reveals Hidden Local Transitions of the Aqueous OH Radical.

Resonant inelastic x-ray scattering (RIXS) provides remarkable opportunities to interrogate ultrafast dynamics in liquids. Here we use RIXS to study the fundamentally and practically important hydroxyl radical in liquid water, OH(aq). Impulsive ionization of pure liquid water produced a short-lived population of OH(aq), which was probed using femtosecond x-rays from an x-ray free-electron laser. We find that RIXS reveals localized electronic transitions that are masked in the ultraviolet absorption spectrum by strong charge-transfer transitions-thus providing a means to investigate the evolving electronic structure and reactivity of the hydroxyl radical in aqueous and heterogeneous environments. First-principles calculations provide interpretation of the main spectral features.

Evaluating the potential role of tryptophan in calf milk replacers to facilitate weaning.

Tryptophan is a precursor of serotonin, a neurotransmitter that participates in the control of the affective state of an animal. We hypothesized that Trp supplementation could help dairy calves to cope with weaning stress. Twenty-seven Holstein male calves (48 ± 0.8 d old; 82 ± 2.6 kg of body weight) were used to evaluate the effects of Trp supplementation at a rate of 4.5 g/d via milk replacer (MR) on performance and behavioral parameters around weaning. All calves received the same feeding program (6 L/d at 15% dry matter from d 1 to 7, 4 L/d at 15% dry matter from d 8 to 14, and 2 L/d at 15% dry matter in one feeding until d 21 of study) and were completely weaned 22 d after the beginning of the study (around 70 d of life). Calves were fed a starter feed (19.3% crude protein and 16.2% neutral detergent fiber, on a dry matter basis) and chopped straw ad libitum. Animals were weighed weekly, dry matter intakes were recorded daily, lying behavior was recorded using accelerometers throughout the study, and scan sampling was performed twice a week, 1 h after the morning feeding, to record behavioral activity (nonnutritive oral behaviors, suckling a neighbor calf, standing, resting, rumination, vocalizations, eating, and drinking). Tryptophan supplementation did not affect calf performance or concentrate and MR intake, but straw intake tended to be greater in nonsupplemented compared with Trp-supplemented calves (153 vs. 129 ± 9.0 g/d, respectively). Lying time, lying bouts, and lying duration decreased when changes in the MR feeding program occurred, independent of treatment. Similarly, differences in behavioral observations occurred along days of study, with no effect of Trp supplementation. The main changes observed in calf behavior were an increase in vocalizations and standing time 1 h after the morning feeding at weaning, but again these changes were independent of treatment. Parameters measured in serum and plasma indicated an increase in Trp, kynurenine, and the kynurenine/Trp ratio after feeding in the Trp calves. A tendency for lower plasma glucose concentration after feeding was observed in the Trp group. No changes in stress markers such as cortisol and haptoglobin in serum were detected. In conclusion, supplementing 4.5 g/d of Trp via MR between 48 and 62 d of life had no effect on performance or behavior in calves around weaning.

Short communication: Performance, intestinal permeability, and metabolic profile of calves fed a milk replacer supplemented with glutamic acid.

The objective of this study was to evaluate the potential benefits of supplementing glutamic acid in milk replacers (MR) with respect to calf performance, intestinal permeability, and metabolism. Sixty Holstein male calves (3 ± 1.3 d old and 45 ± 5.9 kg body weight) were individually housed and fed a control MR without AA supplementation (24.8% crude protein and 19.1% fat, dry matter basis), or MR supplemented with 0.3% glutamic acid (25.1% crude protein and 20.3% fat, dry matter basis). Animals followed the same MR feeding program and were weaned at 56 d of the study. The amount of starter concentrate offered was restricted to limit the effect of concentrate intake on calf metabolism. Individual daily consumption and weekly body weight were measured, and 4 h after the morning feeding, blood samples were obtained at 14 and 35 d to determine general biochemical parameters and plasma AA concentrations. On d 10 of the study, we conducted an intestinal permeability test by including 21 g of lactulose and 4.2 g of d-mannitol as markers in the MR. We found no differences in calf performance or in intestinal permeability (measured as lactulose:mannitol ratio). Serum glucose concentration was greater in unsupplemented calves than in Glu-supplemented calves. At 14 d, the proportion of plasma Leu was greater in Glu-supplemented calves; the proportion of Ile tended to be greater in Glu-supplemented calves; and the proportion of Met tended to be greater in unsupplemented calves. We observed no other differences. Small changes occurred in AA metabolism when supplementing calf MR with 0.3% glutamic acid, without leading to improvements in calf performance or changes in intestinal permeability.

DNA methylation and obesity in survivors of pediatric acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study.

Because survivors of pediatric acute lymphoblastic leukemia (ALL) are more likely to be obese than unaffected contemporaries, we compared DNA methylation profiles between normal-weight and obese survivors at adiposity-associated CpG sites previously-reported by epigenome-wide association studies (EWAS) of body mass index (BMI) in the general population. We selected 96 ALL survivors from the Childhood Cancer Survivor Study: 48 obese and 48 normal weight. The Illumina HumanMethylation450 BeadChip was used to compare DNA methylation at 211 loci identified in EWAS of BMI in the general population. Thirty-nine loci were associated (false discovery rate <0.05) with obesity among survivors who only received chemotherapy (n = 49). No loci were significantly associated with obesity among CRT-exposed survivors (n = 47). Our results suggest that previously identified BMI-DNA methylation loci are associated with obesity in ALL survivors who were spared CRT, while no loci were significantly associated with obesity in survivors who received CRT.

Methodological guidelines for preparing a structured therapeutic education program: From design to evaluation. / Guía metodológica para la elaboración de un programa estructurado de educación terapéutica: del diseño a la evaluación.

BACKGROUND AND OBJECTIVE: Therapeutic patient education (TPE) is effective and essential in the context of the growing prevalence of chronic diseases, in which tools are needed for planning structured programs. The objective of this project was to develop guidelines for designing and assessing a TPE program. METHODS: 1) We assembled a multidisciplinary group of 8 leaders in TPE, chronicity, quality and safety from the hospital and the university. 2) We conducted an exhaustive review of the scientific literature on the planning of TPE programs directed at chronically ill patients, their relatives and caregivers. 3) The final text underwent comments and suggestions by participants from the hospital and primary care centre during a course on information and TPE methodology. The recommendations were unanimously agreed upon by the writing group. RESULTS: We obtained a standardised work procedure targeted at professionals involved in planning TPE programs, based on international recommendations. The document is structured into sections: a) Definition of the health problem and analysis of the situation; b) Program structure (human resources and materials); objectives (health-related, behaviour-related and educational) and methodology; c) Path the patient and family/caregiver follows in the program; and d) Assessment and indicators. The assessment of the procedure, in the framework of the methodology courses, was favourable. CONCLUSIONS: The methodology provided by this document serves as an instrument for the standardised and systematic planning of educational programs and unifies the criteria in their drafting. However, the document needs to be adapted to the condition and population to which each program is directed.