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The Q&U Bolometric Interferometer for Cosmology (QL’BIC) is the first bolometric interferometer designed to measure the primordial B-mode polarization of the Cosmic Microwave Background (CMB). Bolometric interferometry is a novel technique that combines the sensitivity of bolometric detectors with the control of systematic effects that is typical of interferometry, both key features in the quest for the faint signal of the primordial B-modes. A unique feature is the so-called “spectral imaging”, i.e., the ability to recover the sky signal in several sub-bands within the physical band during data analysis. This feature provides an in-band spectral resolution of ∆v/v ~ 0.04 that is unattainable by a traditional imager. This is a key tool for controlling the Galactic foregrounds contamination. In this paper, we describe the principles of bolometric interferometry, the current status of the QU BIC experiment and future prospects.

The liquefaction induced loss of soil strength and stiffness marks a change of soil state, that switches from solid to liquid. Recently, the research has revealed that when liquefaction is attained, the soil behaves as a non-Newtonian fluid. Therefore, the framework of soil mechanics cannot be adopted and then the soil behaviour should be studied using a fluid mechanic approach. Several research works highlighted the large potentiality of the apparent viscosity () as the parameter ruling both the liquefaction triggering and the behaviour of liquefied sands. Mele (2022) showed that liquefied sands exhibit a shear-thinning behavior (i.e. decreasing viscosity with increasing shear strain rate), highlighting the direct link between k and n (parameters of shear-thinning model) to the soil demand (CSR). This paper aims to confirm the proposed correlations of Mele (2022) passing from small to full scale. To do that, the results of 1D non-linear site response analysis of the well-known case study of Treasure Island (California), affected by extensive liquefaction phenomena during the 1989, have been studied and interpreted with a “viscous perspective”. The good agreement of the calibrated pseudo-plastic law with the results of the dynamic analysis confirms, the relevance of as physically based parameter for the correct modeling of the behaviour of liquefied sandy soils.

Background: Perinatal depression has been suggested to adversely impact child neurodevelopment. However, the complexity of the early childhood environment challenges conclusive findings., Objective: To evaluate whether there is an association between perinatal depressive symptoms and child intelligence quotient (IQ) at 5 years of age., Study Design: Secondary analysis of an ancillary study to a multicenter randomized trial of thyroxine therapy for pregnant individuals with subclinical hypothyroidism. Dyads of infants and birthing parent, with completed Center for Epidemiological Studies-Depression (CES-D) screens during pregnancy and postpartum and child neurodevelopment testing completed at five years of age (n=209) were included. CES-D screening was performed at 11-20 weeks, 34-38 weeks, and one-year postpartum. Depressive symptoms were categorized as antenatal (i.e., a positive screen at any point during pregnancy) or postpartum. The primary outcome was child IQ score < 85 at 5 years of age using the Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III) Full Scale test. Secondary outcomes included other assessments of childhood neurodevelopment. Bivariable analyses and multivariable logistic regressions were utilized., Results: Of the 209 birthing people included, 72 (34%) screened positive for depression during pregnancy and 32 (15%) screened positive one year postpartum. Children born to individuals with a positive antenatal depression screen had a higher odds of IQ < 85 at 5 years of age compared with children born to individuals with a CES-D < 16 (35% vs. 18%, OR 2.4, 95% CI 1.2-4.7). Similar findings were seen for children born to individuals with a positive postpartum depression screen (47% vs. 21%, OR 3.3, 95% CI 1.5-7.3). These associations did not persist in multivariable analyses that controlled for social determinants of health and clinical characteristics (adjusted odd ratio [aOR] 1.4, 95% CI 0.7-3.1; aOR 2.1, 95% CI 0.9-5.1, for antenatal and postpartum depressive symptoms, respectively). Similar findings were observed for other adverse neurodevelopmental outcomes., Conclusions: Having a positive perinatal depression screen was not associated with child cognitive outcomes after controlling for covariates including social determinants of health., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: To examine the incidence of overt hypothyroidism 1 and 5 years after pregnancies where screening before 21 weeks identified subclinical hypothyroidism (SH) or hypothyroxinemia (HT). Methods: Secondary analysis of two multicenter treatment trials for either SH or HT diagnosed between 8 and 20 weeks gestation. Current analyses focus only on individuals randomized to the placebo groups in the two parallel studies. SH was diagnosed with thyrotropin (TSH) ≥4.0 mU/L and normal free T4 (fT4) (0.86-1.9 ng/dL). HT was diagnosed with normal TSH (0.08-3.99 mU/L) but fT4 <0.86 ng/dL. Serum from initial testing was stored for later thyroid peroxidase (TPO) antibody assay; results were not returned for clinical management. At 1 and 5 years after delivery, participants were asked whether they had either been diagnosed with or were being treated for a thyroid condition. Maternal serum was collected at these visits and thyroid function measured. Subsequent overt hypothyroidism was defined as TSH ≥4.0 mU/L with fT4 <0.86 ng/dL. Results: Data for 1- and 5-year follow-up were available in 307 of the 338 participants with SH and 229 of the 261 with HT. Subsequent hypothyroidism was more common both at year 1 (13.4% vs. 3.1%, p < 0.001) and year 5 (15.6% vs. 2.6%, p < 0.001) for participants with SH compared with those with HT. This progression was more common in individuals with TSH values >10 mIU/mL. Baseline TPO level >50 IU/mL in participants with SH was associated with higher rates of hypothyroidism at year 1 (26.7% vs. 6.5%, odds ratio [OR] = 5.3 [confidence interval (CI) 2.6-10.7]) and year 5 (30.5% vs. 7.5%, OR = 5.4 [CI: 2.8-10.6]) compared with those with TPO levels ≤50 IU/mL. For participants with HT, no differences in overt hypothyroidism were seen at 1 year related to baseline TPO level >50 IU/mL (1/10 (10%) vs. 6/218 (2.8%), OR = 3.9 [CI: 0.43-36.1]), but more participants with TPO levels >50 IU/mL developed hypothyroidism by year 5 (2/10 (20%) vs. 4/218 (1.8%), OR = 13.4 [CI: 2.1-84.1]). Conclusion: SH is associated with higher rates of overt hypothyroidism or thyroid replacement therapy within 5 years of delivery than is HT when these conditions are diagnosed in the first half of pregnancy.

The outcome of allogeneic hematopoietic stem cell transplantation (HSCT) is significantly influenced by the degree of HLA histocompatibility between donor and recipient. To provide shared indications for required histocompatibility testing and interpretation before HSCT, the Italian Society for Immunogenetics and Transplantation Biology (Associazione Italiana di Immunogenetica e Biologia dei Trapianti [AIBT]) gathered members and created a working group to discuss and develop recommendations for histocompatibility assessment in HSCT.After a review of the literature and multiple panel discussions, AIBT developed up-to-date recommendations for the resolution levels of HLA typing, histocompatibility definitions of patients and donors, importance of anti-HLA antibodies, and significance of NK alloreactivity, which are reported in this document. These recommendations have been shared with the Italian Group for Bone Marrow Transplantation (Gruppo Italiano per il Trapianto di Midollo Osseo, cellule staminali emopoietiche e terapia cellulare [GITMO]) and the Italian National Center for Transplantation (Centro Nazionale Trapianti [CNT]). Notably, the increased use of HLA-mismatched transplantation (i.e., mismatched unrelated, haploidentical) in recent years has made these indications even more relevant for the standardization and improvement of quality of care.This document represents a useful instrument for health care workers involved in the field of HSCT, enhancing synergy with transplant physicians and enabling greater optimization of the available resources.

Background: Sodium-glucose transporter 2 (SGLT2) inhibitors (iSGLT2) are approved medications for type 2 diabetes. Recent studies indicate that iSGLT2 inhibit the growth of some cancer cells. However, the mechanism(s) remains to be fully elucidated., Methods: The SGLT2 levels were determined in normal colon CCD 841 CoN and, HCT 116, HT-29, SW480 and LoVo colorectal cancer (CRC) cell lines by quantitative real-time PCR and western blot. The effect of iSGLT2 canagliflozin on cell proliferation was examined using CCK-8, as its role on CRC cells metabolism and tumorigenesis has been evaluated by XF HS Seahorse Bioanalyzer and flow cytometric analyses. Transient gene silencing experiments and analysis of protein-protein interaction network were conducted to evaluate the SGLT2 molecular targets in CRC cells., Results: Data showed that the treatment with iSGLT2 (50 µM) for 72 h induced cell cycle arrest (p < 0.001), impaired glucose and energetic metabolism (p < 0.001), promoted apoptotic cell death and ER stress flowing into autophagy (p < 0.001) in HCT 116 and HT-29 cells. These cellular events were accompanied by sirtuin 3 (SIRT3) upregulation (p < 0.01), as also supported by SIRT3 transient silencing experiments resulting in the attenuation of the effects of iSGLT2 on the cellular metabolic/energetic alterations and the induction of programmed cell death. The identification and validation of dipeptidyl peptidase 4 (DPP4) as potential common target of SGLT2 and SIRT3 were also assessed., Conclusions: These results deepened knowledge on the iSGLT2 contribution in limiting CRC tumorigenesis unveiling the SGLT2/SIRT3 axis in the cytotoxic mechanisms., (© 2024. The Author(s).)

Objective: The aim of this study was to evaluate whether being small for gestational age (SGA) or large for gestational age (LGA) or having a small or large head circumference (HC) at birth is associated with adverse neurodevelopmental outcomes., Study Design: This is a secondary analysis of a multicenter negative randomized trial of thyroxine therapy for subclinical hypothyroid disorders in pregnancy. The primary outcome was child intelligence quotient (IQ) at 5 years of age. Secondary outcomes included several neurodevelopmental measures. Associations between the outcomes in children with SGA (<10th percentile) or LGA (>90th percentile) birth weights, using ethnicity- and sex-specific population nomogram as well as nomograms from the National Fetal Growth (NFG) study, were compared with the referent of those with appropriate for gestational age (AGA) birth weight. Similar analyses were performed for HC., Results: Using the population nomogram, 90 (8.2%) were SGA and 112 (10.2%) were LGA. SGA neonates were more likely to be born preterm to mothers who were younger, smoked, and were less likely to have less than a high school education, whereas LGA neonates were more likely to be born to mothers who were older and have higher body mass index, compared with AGA neonates. SGA at birth was associated with a decrease in the child IQ at 5 years of age by 3.34 (95% confidence interval [CI], 0.54-6.14) points, and an increase in odds of child with an IQ < 85 (adjusted odds ratio [aOR], 1.9; 95% CI, 1.1-3.2). There was no association between SGA and other secondary outcomes, or between LGA and the primary or secondary outcomes. Using the NFG standards, SGA at birth remained associated with a decrease in the child IQ at 5 years of age by 3.14 (95% CI, 0.22-6.05) points and higher odds of an IQ < 85 (aOR, 2.3; 95% CI, 1.3-4.1), but none of the other secondary outcomes. HC was not associated with the primary outcome, and there were no consistent associations of these standards with the secondary outcomes., Conclusion: In this cohort of pregnant individuals with hypothyroid disorders, SGA birth weight was associated with a decrease in child IQ and greater odds of child IQ < 85 at 5 years of age. Using a fetal growth standard did not appear to improve the detection of newborns at risk of adverse neurodevelopment., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Our objective was to evaluate whether iodine status in pregnant patients with either subclinical hypothyroidism or hypothyroxinemia in the first half of pregnancy is associated with measures of behavior and neurodevelopment in children through the age of 5 years., Study Design: This is a secondary analysis of a multicenter study consisting of two randomized, double-masked, placebo-controlled treatment trials conducted in parallel. Patients with a singleton gestation before 20 weeks' gestation underwent thyroid screening using serum thyrotropin and free thyroxine. Participants with subclinical hypothyroidism or hypothyroxinemia were randomized to levothyroxine replacement or an identical placebo. At randomization, maternal urine was collected and stored for subsequent urinary iodine excretion analysis. Urinary iodine concentrations greater than 150 μg/L were considered iodine sufficient, and concentrations of 150 μg/L or less were considered iodine insufficient. The primary outcome was a full-scale intelligence quotient (IQ) score at the age of 5 years, the general conceptual ability score from the Differential Ability Scales-II at the age of 3 if IQ was not available, or death before 3 years., Results: A total of 677 pregnant participants with subclinical hypothyroidism and 526 with hypothyroxinemia were randomized. The primary outcome was available in 1,133 (94%) of children. Overall, 684 (60%) of mothers were found to have urinary iodine concentrations >150 μg/L. Children of iodine-sufficient participants with subclinical hypothyroidism had similar primary outcome scores when compared to children of iodine-insufficient participants (95 [84-105] vs. 96 [87-109], P adj  = 0.73). After adjustment, there was also no difference in IQ scores among children of participants with hypothyroxinemia at 5 to 7 years of age (94 [85 - 102] and 91 [81 - 100], P adj 1/4 0.11). Treatment with levothyroxine was not associated with neurodevelopmental or behavioral outcomes regardless of maternal iodine status ( p  > 0.05)., Conclusion: Maternal urinary iodine concentrations ≤150 μg/L were not associated with abnormal cognitive or behavioral outcomes in offspring of participants with either subclinical hypothyroidism or hypothyroxinemia., Key Points: · Most pregnant patients with subclinical thyroid disease are iodine sufficient.. · Mild maternal iodine insufficiency is not associated with lower offspring IQ at 5 years.. · Iodine supplementation in subclinical thyroid disease is unlikely to improve IQ.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: This study aimed to measure the association between hypertensive disorders of pregnancy (HDP) and long-term maternal metabolic and cardiovascular biomarkers., Study Design: Follow-up study of patients who completed glucose tolerance testing 5 to 10 years after enrollment in a mild gestational diabetes mellitus (GDM) treatment trial or concurrent non-GDM cohort. Maternal serum insulin concentrations and cardiovascular markers VCAM-1, VEGF, CD40L, GDF-15, and ST-2 were measured, and insulinogenic index (IGI, pancreatic β-cell function) and 1/ homeostatic model assessment (insulin resistance) were calculated. Biomarkers were compared by presence of HDP (gestational hypertension or preeclampsia) during pregnancy. Multivariable linear regression estimated the association of HDP with biomarkers, adjusting for GDM, baseline body mass index (BMI), and years since pregnancy., Results: Of 642 patients, 66 (10%) had HDP: 42 with gestational hypertension and 24 with preeclampsia. Patients with HDP had higher baseline and follow-up BMI, higher baseline blood pressure, and more chronic hypertension at follow-up. HDP was not associated with metabolic or cardiovascular biomarkers at follow-up. However, when HDP type was evaluated, patients with preeclampsia had lower GDF-15 levels (oxidative stress/cardiac ischemia), compared with patients without HDP (adjusted mean difference: -0.24, 95% confidence interval: -0.44, -0.03). There were no differences between gestational hypertension and no HDP., Conclusion: In this cohort, metabolic and cardiovascular biomarkers 5 to 10 years after pregnancies did not differ by HDP. Patients with preeclampsia may have less oxidative stress/cardiac ischemia postpartum; however, this may have been observed due to chance alone given multiple comparisons. Longitudinal studies are needed to define the impact of HDP during pregnancy and interventions postpartum., Key Points: · Hypertensive disorders of pregnancy were not associated with metabolic dysfunction.. · Cardiovascular dysfunction was not consistently seen after pregnancy hypertension.. · Longitudinal studies with postpartum interventions after preeclampsia are needed.., Competing Interests: None declared., (Thieme. All rights reserved.)

Glioblastoma (GBM), the most frequent and lethal brain cancer in adults, is characterized by short survival times and high mortality rates. Due to the resistance of GBM cells to conventional therapeutic treatments, scientific interest is focusing on the search for alternative and efficient adjuvant treatments. S -Adenosylmethionine (AdoMet), the well-studied physiological methyl donor, has emerged as a promising anticancer compound and a modulator of multiple cancer-related signaling pathways. We report here for the first time that AdoMet selectively inhibited the viability and proliferation of U87MG, U343MG, and U251MG GBM cells. In these cell lines, AdoMet induced S and G2/M cell cycle arrest and apoptosis and downregulated the expression and activation of proteins involved in homologous recombination DNA repair, including RAD51, BRCA1, and Chk1. Furthermore, AdoMet was able to maintain DNA in a damaged state, as indicated by the increased γH2AX/H2AX ratio. AdoMet promoted mitotic catastrophe through inhibiting Aurora B kinase expression, phosphorylation, and localization causing GBM cells to undergo mitotic catastrophe-induced death. Finally, AdoMet inhibited DNA repair and induced cell cycle arrest, apoptosis, and mitotic catastrophe in patient-derived GBM cells. In light of these results, AdoMet could be considered a potential adjuvant in GBM therapy.

Objective: To assess whether neonatal morbidities evident by the time of hospital discharge are associated with subsequent cerebral palsy (CP) or death., Study Design: This is a secondary analysis of data from a multicenter placebo-controlled trial of magnesium sulfate for the prevention of CP. The association between prespecified intermediate neonatal outcomes ( n  = 11) and demographic and clinical factors ( n  = 10) evident by the time of discharge among surviving infants ( n  = 1889) and the primary outcome of death or moderate/severe CP at age 2 ( n  = 73) was estimated, and a prediction model was created., Results: Gestational age in weeks at delivery (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.67-0.83), grade III or IV intraventricular hemorrhage (IVH) (OR: 5.3, CI: 2.1-13.1), periventricular leukomalacia (PVL) (OR: 46.4, CI: 20.6-104.6), and male gender (OR: 2.5, CI: 1.4-4.5) were associated with death or moderate/severe CP by age 2. Outcomes not significantly associated with the primary outcome included respiratory distress syndrome, bronchopulmonary dysplasia, seizure, necrotizing enterocolitis, neonatal hypotension, 5-minute Apgar score, sepsis, and retinopathy of prematurity. Using all patients, the receiver operating characteristic curve for the final prediction model had an area under the curve of 0.84 (CI: 0.78-0.89). Using these data, the risk of death or developing CP by age 2 can be calculated for individual surviving infants., Conclusion: IVH and PVL were the only neonatal complications evident at discharge that contributed to an individual infant's risk of the long-term outcomes of death or CP by age 2. A model that includes these morbidities, gestational age at delivery, and gender is predictive of subsequent neurologic sequelae., Key Points: · Factors known at hospital discharge are identified which are independently associated with death or CP by age 2.. · A model was created and validated using these findings to counsel parents.. · The risk of death or CP can be calculated at the time of hospital discharge.., Competing Interests: None declared., (Thieme. All rights reserved.)