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The James Webb Space Telescope has discovered a surprising population of bright galaxies in the very early Universe (≲500 Myr after the Big Bang) that is hard to explain with conventional galaxy-formation models and whose physical properties are not fully understood. Insight into their internal physics is best captured through nebular lines, but at these early epochs, the brightest of these spectral features are redshifted into the mid-infrared and remain elusive. Using the mid-infrared instrument onboard the James Webb Space Telescope, here we present a detection of Hα and doubly ionized oxygen ([O iii] 4959,5007 Å) from the bright, ultra-high-redshift galaxy candidate GHZ2/GLASS-z12. Based on these emission lines, we infer a spectroscopic redshift of z = 12.33 ± 0.04, placing this galaxy just ~400 Myr after the Big Bang. These observations provide key insights into the conditions of this primaeval, luminous galaxy, which shows hard ionizing conditions rarely seen in the local Universe and probably driven by a compact and young burst (≲30 Myr) of star formation. The galaxys oxygen-to-hydrogen abundance is close to a tenth of the solar value, indicating a rapid metal enrichment. This study establishes the unique conditions of this notably bright and distant galaxy and the huge potential of mid-infrared observations to characterize these primordial systems.

This study investigates the integration of hydrochar, derived from municipal solid waste, into cement-lime-based plasters to enhance their thermo-acoustic and mechanical properties. The research begins by analyzing the thermo-physical properties of hydrochar, revealing its exceptional thermal stability exceeding 200 °C. The porous nature of hydrochar proves to be advantageous, positively impacting the thermal characteristics of the plasters. Notably, the innovative plaster exhibits a significant reduction in thermal conductivity, dropping from 1 Wm−2K−1 to approximately 0.7 Wm−2K−1. Despite a lower density of about 10% compared to the standard plaster, the hydrochar-modified plaster maintains good acoustic and mechanical performance. Transmission loss remains stable at 60 dB varying the thickness of the plaster while compressive and flexural strengths reduce by 2%, due to the higher percentage of water used (from 22% to 26%) to guarantee the same workability of the plasters and to distribute the hydrochar uniformly in the mix design.

In the past decade, precise targeting through genome editing has emerged as a promising alternative to traditional therapeutic approaches. Genome editing can be performed using various platforms, where programmable DNA nucleases create permanent genetic changes at specific genomic locations due to their ability to recognize precise DNA sequences. Clinical application of this technology requires the delivery of the editing reagents to transplantable cells ex vivo or to tissues and organs for in vivo approaches, often representing a barrier to achieving the desired editing efficiency and safety. In this review, authored by members of the GenE-HumDi European Cooperation in Science and Technology (COST) Action, we described the plethora of delivery systems available for genome-editing components, including viral and non-viral systems, highlighting their advantages, limitations, and potential application in a clinical setting.

Abstract Dutch elm disease (DED) is a destructive tracheomycosis caused by Ophiostoma novo‐ulmi, an ascomycete that is devastating natural elm populations throughout Europe, North America, and part of Asia. The fungus is mainly spread by elm bark beetles (EBBs) (Coleoptera: Curculionidae, Scolytinae) that complete their life cycle between healthy and diseased elms. It has recently been shown that certain fungi of the genus Geosmithia, vectored by bark beetles, are involved in the DED pathosystem. Not only it has been observed that the two fungi share the same habitat in the host plant and during each developmental stage of the insect, but also there appears to be a parasitic association between them. By analyzing the presence and quantity of the two fungi on the bodies of elm beetles by a qPCR duplex TaqMan assay, this work aimed to explore the dynamic of the relationship among the adults of Scolytus multistriatus, O. novo‐ulmi, and Geosmithia spp. at sites characterized by different DED severity levels during the elm growing season. We observed that, regardless of the epidemiological conditions, both fungi are always present on adult flickering insects. The proportion of the two fungal populations varies among sampling sites, with Geosmithia spp. being predominant in the non‐epidemic sites. The hyperparasitism of Geosmithia toward O. novo‐ulmi within this tri‐trophic system should be investigated further for potential use as biological control agent.

Abstract We explored the impact of luspatercept therapy on overall survival (OS) and possible predictors of response in low‐risk (LR) myelodysplastic syndrome (MDS) patients. We evaluated 331 anemic patients treated with luspatercept. Hematological response (HI) was defined as (i) hemoglobin (Hb) increase of ≥1.5 g/dL in nontransfusion‐dependent (NTD) patients, and (ii) red blood cell (RBC) transfusion independence (TI) with a concomitant Hb increase of ≥1.5 g/dL, or RBC‐TI without an Hb increase of 1.5 g/dL, or >50% reduction in RBC transfusion burden (TB) for TD patients. Response was observed in 166 patients (50.2%), with significantly higher response in NTD and low TB versus high TB patients (p

Este estudo teve como objetivo (re)conhecer as situações estressoras de pais no contexto da unidade de terapia intensiva neonatal. Trata-se de estudo misto realizado em duas unidades de terapia intensiva neonatal. Participaram da entrevista treze pais e/ou mães de recém-nascidos e os dados quantitativos foram coletados pela escala parental Stress scale: neonatal intensive care unit. Para a análise temática foi utilizado Bardin. Os dados resultaram em quatro categorias temáticas e uma tabela falante que integra os dados de abordagem quantitativa e qualitativa. O estresse é presente pelas duas facetas metodológicas de análise com ênfase ao domínio papel de pai e mãe, com maior média de score. Os achados reforçam a necessidade de promover uma assistência singular ao recém-nascido, levando em consideração a família. Além da comunicação eficiente, promover e fortalecer a corresponsabilização dos pais pelo cuidado, respeitar os princípios familiares são essenciais para a recuperação e reabilitação do neonato.

BackgroundMyelodysplastic neoplasms (MDS) are characterized by ineffective hematopoiesis, peripheral blood cytopenias, and an increased risk of progression to acute myeloid leukemia. One of the main treatment goals is improving quality of life (QoL), particularly for patients with lower-risk MDS (LR-MDS) who may live longer with compromised QoL. The QOL-E© is a patient-reported outcome (PRO) measure specifically developed to address the lack of a health-related QoL questionnaire for patients with MDS. The objective of this study was to evaluate the psychometric performance of the QOL-E in patients with LR-MDS.MethodsData from four clinical trials in MDS (MEDALIST, DARB-MDS, EQoL-MDS, and RevMDS trials) were used to assess construct validity, reliability, and responsiveness. The QOL-E was validated by the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire – Core 30 (QLQ-C30) and clinical outcomes. It contains 29 items with the first two items assessing the patient’s general well-being and the 27 remaining items grouped into six domain scores: physical well-being (QOL-FIS), functional well-being (QOL-FUN), social/family well-being (QOL-SOC), sexual well-being (QOL-SEX), fatigue (QOL-FAT), and MDS-specific disturbances (QOL-MDSS). Additionally, meaningful within-patient change (MWPC) thresholds were determined for the domains and summary scores of the QOL-E using anchor-based analyses, supported by distribution-based analyses.ResultsA total of 458 patients were included in the analyses. The QOL-E domain/summary scores demonstrated acceptable convergent/divergent and known-groups validity. Test-retest reliability and internal consistency was confirmed with intraclass correlation coefficients and Cronbach alpha exceeding 0.70 across most QOL-E domains/summary scores. The QOL-E domains/summary scores, except for QOL-SEX, had an adequate ability to detect change from baseline to Week 24. MWPC thresholds were proposed for all other domains and summary scores.ConclusionThe study results demonstrate that the QOL-E is generally fit for purpose to assess treatment effects in populations with LR-MDS and the proposed MWPC thresholds can be used to assess within-patient treatment effect on PROs, as assessed by the QOL-E, in future studies.

Abstract The lignocellulosic materials of some plant species are rich in chemical compounds that can serve as a source of natural and environmentally less aggressive biocides for treating wood. The aim of this study was to verify the potential of the lignocellulosic materials (wood and bark) of Ateleia glazioviana and Hovenia dulcis as a natural wood preservative. The extracts were prepared by heating the materials to 100 °C at a concentration of 10%. The wood samples were treated in a laboratory autoclave using the empty cell method. Control samples (untreated) and samples treated with chromated copper borate - CCB (2.5%) were used as a comparison. The accelerated rot test in the laboratory was carried out using a sample of the colony of the white rot fungus, Trametes versicolor. Mass loss, solubility in 1% NaOH, scanning electron spectroscopy (SEM) and attenuated total reflection infrared spectroscopy (ATR-FTIR) were evaluated. A rotting field test was also carried out in a forest fragment for 180 days and the mass loss, apparent specific mass, ATR-FTIR, and dynamic bending of the wood samples were evaluated. In laboratory tests, natural extractive solutions from the bark and wood of Hovenia dulcis and only from the bark of Ateleia glazioviana have fungitoxic potential against the white rot fungus, when compared to material without preservative impregnations. The resistance of the wood in the field to rot did not obtain significant results with the application of the natural preservatives, and future studies will need to increase the concentration of the extracts in an attempt to improve their performance as natural biocides.

Introduction Muscle volume is a crucial indicator of muscle strength and neuromuscular health, traditionally assessed using Magnetic Resonance Imaging (MRI). While MRI provides high accuracy, it is costly and time-consuming. Three-dimensional ultrasonography (3DUS) offers a more accessible alternative but requires rigorous validation due to setup dependent accuracy. This study evaluates the validity and reliability of a custom 3DUS setup for measuring lower limb muscle volumes, compares it to MRI, and documents the methodology for broader research adoption. Methods We recruited 10 healthy participants (5 males, 5 females; 18–40 years). The protocol included two 3DUS sessions and one MRI session spaced one week apart. The 3DUS scans were acquired by one experienced operator, while two operators analyzed the captured volumes from the second scanning timepoint. Target muscles—biceps femoris, gastrocnemius medialis and lateralis, tibialis anterior, and vastus lateralis—were scanned using a linear probe (12L3, Siemens, Erlangen, Germany) integrated with a motion capture system (Optitrack Flex 3, NaturalPoint, Corvallis, OR, USA). Data synchronization and reconstruction were performed using 3D Slicer. MRI scans were acquired using a 3T whole-body scanner (MAGNETOM Prisma, Siemens, Erlangen, Germany), and muscle volumes were segmented using Dafne and 3D-Slicer software. Validation was enhanced with phantom models (100–600 mL) scanned via both modalities. Reliability metrics included intra-class correlation (ICC), coefficients of variation (CV%), standard error of measurement (SEM), minimal detectable change (MDC) and standardized mean bias. Results Test-retest reliability of 3DUS was high for all muscles, with ICCs ranging from 0.97 to 0.99 (95% confidence intervals between 0.86–0.99) and CV% values between 2.0 and4.6% (95% CI between 1.3–6.7%). MDC values were below 5 mL for all muscles, indicating sensitivity to detect small volume changes. The biceps femoris exhibited the highest test-retest reliability, while the gastrocnemius medialis showed lower but acceptable agreement. Inter-rater reliability was similarly high, with ICCs exceeding 0.97 (95% CIs between 0.51–0.99) for all assessed muscles and minimal variability between operators (CV%: 2.1–3.2%, 95% CIs between 1.1–4.7%). Tibialis anterior yielded the highest inter-rater reliability results, vastus lateralis the lowest. Compared to MRI, 3DUS underestimated muscle volumes, with mean biases ranging from -15.4% to -44.6%. Agreement was highest for the tibialis anterior and lowest for the gastrocnemii. Standardized mean biases were classified as moderate to very large, ranging from -0.92 to -2.64. In contrast, phantom scans confirmed high accuracy for both 3DUS and MRI, suggesting measurement errors in vivo were likely due to probe pressure and sweep inconsistencies. Discussion/Conclusion Our 3DUS system demonstrated excellent reliability for assessing muscle volumes between sessions and raters, but showed limited comparability to MRI, systematically underestimating volumes. The magnitude of underestimation appeared to be influenced by muscle architecture and location. Calibration refinements, including reduced probe pressure and optimized sweep protocols, are underway to improve accuracy. Nonetheless, 3DUS is a promising, cost-effective tool for longitudinal muscle assessments, particularly for detecting intervention-induced changes. Our openly accessible documentation of the methodology supports reproducibility and further innovation in the field.

ABSTRACT Backgroud Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with a generally dismal prognosis and no standard of care established, despite a known association with epidermal growth factor receptor 2 (HER2) and androgen receptor (AR) over‐expression. Case We report the case of a 64‐year‐old female with extra‐ and intracranial metastases of SDC with evidence of AR and HER2 overexpression. After progression on first line chemotherapy, was administered neratinib, a pan‐Erb2 receptor tyrosine kinase inhibitor. Even with central nervous system involvement at diagnosis, a durable clinical response was obtained with a PFS of 11 months and no significant toxicities to manage. Best response observed during tratment was partial response. Conclusions This case confirms the potential efficacy of neratinib in HER2‐positive SDC and underlines the need to define the best therapeutic sequence and potential biomarkers for these rare patients.

Abstract Background We present a systematic review and meta‐analysis of randomized clinical trials (RCTs) with PARPi either as monotherapy or in combination with an androgen receptor‐targeted agent (ARTA) in first‐ and second‐line settings. Methods Primary endpoints are radiographic progression free survival (rPFS) and overall survival (OS) in patients with mCRPC and either unselected, homologous recombination repair wild‐type (HRR−), homologous recombination repair mutated (HRR+) or with BRCA1, BRCA2, or ATM mutation. The effect of PARPi + ARTA in the second‐line setting is also explored. Safety is a secondary end‐point. Results A total of five phase III (first line: MAGNITUDE, PROpel, TALAPRO‐2; second line: PROfound, TRITON3) and two phase II RCTs (second line: NCT01972217, NCT01576172) were selected. In the first‐line setting, rPFS was significantly improved in PARPi + ARTA arm in all comers (HR 0.70, p

In the last few years, we have seen the gradual spread of a new treadmill training modality, which involves walking not on the flat but downhill, also known as "downhill". This review aims to qualitatively assess the efficacy of downhill treatment on different patient populations and outline treatment routes for future efficacy studies. We searched five different databases: MEDLINE, SCOPUS, Web of Science, PEDro, and LILACS for studies to include. Only randomized controlled trials (RCTs) published in English were considered. PEDro scales and Risk of Bias 2 (RoB 2) assessment were used to evaluate the risk of bias. Forty-one RCTs were included, and three articles remained to be analyzed; the included studies showed 110 participants for three RCTs; of these, two were performed on patients diagnosed with chronic obstructive pulmonary disease (COPD), while one was for treating people with multiple sclerosis (MS). The outcome measures used in the studies were the pulmonary function test, the cardiopulmonary exercise test, the 6-Minute Walking Test, and the St. George Respiratory Questionnaire. In patients diagnosed with COPD, downhill training appears effective on functional capacity and symptoms of dyspnea and fatigue, while in people with MS, it increases strength and activity performance when compared to other walking training modalities. RoB 2 tool shows good methodological quality for all studies included in the review; when evaluated with the PEDro scale, all presented a score of 8. Downhill could be such an effective, safe, and feasible eccentric training modality that it can be considered a new rehabilitation strategy that could be implemented for patients with low exercise tolerance.