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).

Biomarcadores pronósticos en el uso del radio-223 en pacientes con cáncer de próstata metastásico resistente a la castración / Prognostic biomarkers in the use of radium-223 in patients with metastatic castration-resistant prostate cancer

Objetivos Establecer biomarcadores basales en pacientes con cáncer de próstata metastásico resistente a la castración (CPMRC) tratados con Ra-223 que predigan una mejor supervivencia global (SG), así como valorar la toxicidad hematológica y la respuesta. Materiales y métodos Estudio retrospectivo multicéntrico en 151 pacientes con CPMRC tratados con Ra-223 entre 2013 y 2020. Se valoró la SG de acuerdo a: los niveles basales de hemoglobina (Hb), el antígeno prostático específico (PSA), la fosfatasa alcalina (FA), la escala de dolor de la OMS, el Eastern Cooperative Oncology Group (ECOG), el número de lesiones en gammagrafía ósea (GO), el uso de agentes de protección ósea y las dosis recibidas. Se determinó el grado de toxicidad hematológica y la respuesta basada en los cambios de la FA y el dolor pre y postratamiento. Resultados Mediana de SG de 24meses (IC95%: 16,5-31). En el 70% que recibieron tratamiento completo (5-6dosis) la mediana de SG fue de 34,9meses, versus 5,8 en el tratamiento incompleto (1-4dosis). La SG fue mayor en los pacientes con menor PSA, FA, Hb>13g/dl, menor número de metástasis óseas y ECOG 0-1. 52/151pacientes (34%) fallecieron durante el seguimiento. Cerca del 70% de los pacientes presentaron disminución del dolor, y el 66%, reducción de la FA. La mitad de los pacientes presentaron eventos adversos hematológicos leves, y solo el 5%, severos. Conclusiones Los pacientes con CPMRC tratados con Ra-223 que presentan biomarcadores basales como Hb>13g/ml, ECOG 0-1, PSA<20ng/ml y menor número de lesiones en GO muestran mejor SG, con un adecuado perfil de seguridad (AU)

Objectives Establish basal biomarkers in patients with bone metastatic castration-resistant prostate cancer (mCRPC) treated with Ra-223 that predicted a better overall survival (OS), assess hematology toxicity and treatment response. Materials and methods Retrospective multicenter study in 151 patients with mCRPC between 2013 and 2020. OS was assessed according to basal hemoglobin (Hb), PSA, alkaline phosphatase (AP), WHO pain scale, Eastern Cooperative Oncology Group (ECOG), number of metastatic lesions on bone scan (BS), use of protective bone agents and received. Hematological toxicities were evaluated. Treatment response was based on changes in FA and pain. Results Median OS was 24months (95%CI: 16.5-31). OS in 70% of patients who received complete Ra-223 treatment (5-6 doses) was 34.9m vs. 5.8m in patients with incomplete treatment (1-4 doses). OS was longer in patients with lower PSA and AP, Hb>13g/dL, lesser bone metastasis on GO and ECOG 0-1. 52/151 patients (34%) died during follow-up. Nearly 70% of patients experienced decrease in pain and 66% reduction on AP. Half of patients had mild hematological adverse effects and only 5% had severe. Conclusions mCRPC patients treated with Ra-223 who had Hb>13g/mL, ECOG 0-1, low AP, PSA<20ng/ml and lesser bone metastasis on BS shown a better OS with adequate safety profile (AU)

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.

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.

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.

Prognostic biomarkers in the use of radium-223 in patients with metastatic castration-resistent prostate cancer.

OBJECTIVES: This study aimed to establish basal biomarkers in patients with bone metastatic castration-resistant prostate cancer (mCRPC) treated with 223Ra to predict better overall survival (OS), and assess hematologic toxicity and treatment response. MATERIALS AND METHODS: This was a retrospective multicenter study including 151 patients with mCRPC between 2013 and 2020. OS was assessed according to basal hemoglobin (Hb), prostate-specific antigen (PSA), and alkaline phosphatase (AP) values, the World Health Organization pain scale, the Eastern Cooperative Oncology Group (ECOG) performance status scale, the number of metastatic lesions on bone scintigraphy (BS), and the use of protective bone agents and the dose received. The grade of hematological toxicities was evaluated as well as treatment response based on changes in AP and pre- and post-treatment pain. RESULTS: The median OS was 24 months (95% confidence interval 16.5-31). The OS in 70% of patients who received complete (5-6 doses) versus incomplete (1-4 doses) 223Ra treatment was 34.9 vs. 5.8 months, respectively, being longer in patients with lower PSA and AP values, Hb >13 g/dl, lesser bone metastasis on bone scan and with an ECOG 0-1. 52/151 patients (34%) died during follow-up. Pain reduced in nearly 70% of patients and 66% presented a reduction in AP values. Half of the patients presented mild and 5 % severe hematological adverse effects. CONCLUSIONS: mCRPC patients treated with 223Ra with Hb values >13 g/mL, an ECOG 0-1, low AP values, PSA < 20 ng/mL and lesser bone metastasis on BS presented a better OS with an adequate safety profile.

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.

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.

Prognostic value of intrinsic subtypes in hormone-receptor-positive metastatic breast cancer: systematic review and meta-analysis.

BACKGROUND: In hormone receptor-positive (HoR+) breast cancer (BC), gene expression analysis identifies luminal A (LumA), luminal B (LumB), human epidermal growth factor receptor 2 (HER2)-enriched (HER2-E), basal-like (BL) intrinsic subtypes and a normal-like group. This classification has an established prognostic value in early-stage HoR+ BC. Here, we carried out a trial-level meta-analysis to determine the prognostic ability of subtypes in metastatic BC (MBC). MATERIALS AND METHODS: We systematically reviewed all the available prospective phase II/III trials in HoR+ MBC where subtype was assessed. The primary endpoint was progression-free survival (PFS)/time to progression (TTP) of the LumA subtype compared to non-LumA. Secondary endpoints were PFS/TTP of each individual subtype, according to treatment, menopausal and HER2 status and overall survival (OS). The random-effect model was applied, and heterogeneity assessed through Cochran's Q and I2. Threshold for significance was set at P < 0.05. The study was registered in PROSPERO (ID: CRD42021255769). RESULTS: Seven studies were included (2536 patients). Non-LumA represented 55.2% and was associated with worse PFS/TTP than LumA [hazard ratio (HR) 1.77, P < 0.001, I2 = 61%], independently of clinical HER2 status [Psubgroup difference (Psub) = 0.16], systemic treatment (Psub = 0.96) and menopausal status (Psub = 0.12). Non-LumA tumors also showed worse OS (HR 2.00, P < 0.001, I2 = 65%), with significantly different outcomes for LumB (PFS/TTP HR 1.46; OS HR 1.41), HER2-E (PFS/TTP HR 2.39; OS HR 2.08) and BL (PFS/TTP HR 2.67; OS HR 3.26), separately (PFS/TTP Psub = 0.01; OS Psub = 0.005). Sensitivity analyses supported the main result. No publication bias was observed. CONCLUSIONS: In HoR+ MBC, non-LumA disease is associated with poorer PFS/TTP and OS than LumA, independently of HER2, treatment and menopausal status. Future trials in HoR+ MBC should consider this clinically relevant biological classification.

Sex differences in cardiovascular and disease-related features in axial spondyloarthritis. A multicenter study of 912 patients.

OBJECTIVES: To determine the potential impact of sex-specific disease-related characteristics on cardiovascular (CV) disease in axial spondyloarthritis (axSpA). METHODS: Cross-sectional study of the Spanish AtheSpAin cohort to study CV disease in axSpA. Data on carotid ultrasound and CV disease and disease-related features were collected. RESULTS: 611 men and 301 women were recruited. Classic CV risk factors were significantly less prevalent in women, who also showed a lower frequency of carotid plaques (p = 0.001), lower carotid intima-media thickness (IMT) values ​​(p<0.001) and CV events (p = 0.008). However, after adjustment for classic CV risk factors, only the differences with respect to carotid IMT remained statistically significant. Women showed higher ESR at diagnosis (p = 0.038), and more active disease (ASDAS, p = 0.012, and BASDAI, p<0.001). They had shorter disease duration (p<0.001), lower prevalence of psoriasis (p = 0.008), less structural damage (mSASSS, p<0.001), and less mobility limitation (BASMI, p = 0.033). To establish whether these findings could lead to sex differences in CV disease burden, we compared the prevalence of carotid plaques in men and women with the same level of CV risk stratified according to the Systematic Coronary Risk Evaluation (SCORE). Men included in the low-moderate CV risk SCORE category had more carotid plaques (p = 0.050), along with longer disease duration (p = 0.004), higher mSASSS (p = 0.001) and psoriasis (p = 0.023). In contrast, in the high-very high-risk SCORE category, carotid plaques were observed more frequently in women (p = 0.028), who were characterized as having worse BASFI (p = 0.011), BASDAI (p<0.001) and ASDAS (p = 0.027). CONCLUSION: Disease-related features may influence the expression of atherosclerosis in patients with axSpA. This may be especially applicable to women at high CV risk, characterized by greater disease severity and more severe subclinical atherosclerosis than men, suggesting a stronger interaction between disease activity and atherosclerosis in women with axSpA.

Relación entre la cantidad y el tipo de alcohol (destilado versus fermentado) consumido y el riesgo de aparición de deterioro cognitivo compatible con un síndrome demencial en personas mayores de 60 años: revisión sistemática / Relationship between the amount and type of alcohol (distilled versus fermented) consumed and the risk of cognitive impairment compatible with a dementia syndrome in people over 60 years of age: A systematic review

Introducción: el alcohol es la sustancia más consumida en la cultura occidental y su consumo es un factor causal en más de 200 enfermedades y trastornos. El objetivo fue conocer la relación entre la cantidad y el tipo de alcohol (destilado o fermentado) consumido en individuos mayores de 60 años y la aparición del deterioro cognitivo compatible con un síndrome demencial como consecuencia de un consumo excesivo y prolongado.Desarrollo: búsqueda en las bases de datos Medline, PsycInfo y Web of Science. Se acotó la búsqueda a artículos publicados entre los años 2010 y 2021, a partir de la combinación de diversos términos relacionados con la demencia, el consumo y tipo de alcohol y la vejez. Se obtuvieron 157 artículos, se eliminaron aquellos repetidos y los no relacionados con el tema, quedando un total de 9 artículos. Esta revisión sistemática se ha llevado a cabo de acuerdo con los criterios de la declaración PRISMA.Conclusiones: la mayoría de los estudios encontrados (7 de 9) sugirieron una asociación entre el consumo de alcohol y la aparición de la demencia. Respecto al tipo de bebidas, todo y la objetivación de algunos resultados poco concluyentes, en general se sugiere que el consumo de vino (bebida fermentada) se asocia a una disminución del deterioro cognitivo y el consumo de licor (bebida destilada) a un aumento del deterioro cognitivo; no queda claro el papel de la cerveza. Por ello se puede concluir que la asociación entre el consumo de alcohol, y el mayor o menor deterioro cognitivo depende tanto del consumo excesivo y prolongado, como también del tipo de bebidas consumidas (destiladas o fermentadas).(AU)

Introduction: Alcohol is the most consumed substance in Western culture and its consumption is a causal factor in more than 200 diseases and disorders. The objective was to determine the relationship between the amount and type of alcohol (distilled or fermented) consumed, in individuals over 60 years of age, and the appearance of cognitive deterioration compatible with a dementia syndrome as a consequence of excessive and prolonged consumption.Development: Search in Medline, PsycInfo and Web of Science databases. The search was limited to articles published between 2010 and 2021, based on the combination of various terms related to dementia, alcohol consumption and type, and old age. 157 articles were obtained, those repeated and those not related to the topic were eliminated, leaving a total of 9 articles. This systematic review has been carried out in accordance with the criteria of the PRISMA statement.Conclusions: Most of the studies found (7 out of 9) suggested an association between alcohol consumption and the onset of dementia. Regarding the type of beverages, everything and the objectification of some inconclusive results, in general it is suggested that the consumption of wine (fermented beverage) is associated with a decrease of cognitive deterioration and the consumption of liquor (distilled beverage) to a increased cognitive decline; the role of beer is not clear. Therefore, it can be concluded that the association between alcohol consumption and greater or lesser cognitive impairment depends both on excessive and prolonged consumption, as well as on the type of beverages consumed (distilled or fermented).(AU)

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.

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.