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Abstract: To date, no reports have indicated laparoscopic lymph node biopsies using Indocyanine green (ICG) in cases of lymphoproliferative disease. Preliminary data of patients undergoing fluorescence-guided laparoscopic lymph node biopsy (FGLLB) using ICG was retrospectively analysed from the multicentre registry FLABILY study. Between June 2022 and February 2024, 50 patients underwent FGLLB. The surgical biopsy aimed to re-stage lymphoproliferative disease for 25 patients and to establish a diagnosis in 25 patients. The median duration of the procedure was 65 ± 26.5 min. All the procedures were performed laparoscopically. One surgical conversion occurred due to bleeding. Median length of hospitalization was 1 ± 1.7 days. Two unrelated complications occurred in the immediate postoperative course. ICG was administrated preoperatively by means of an inguinal, perilesional, or intravenous injection according to the anatomical sites of the biopsy. Fluorescence was obtained in 43/50 (86%) of patients. A significant difference was highlighted in the appearance of fluorescence in sub-mesocolic lymph nodes compared to supra-mesocolic and mesenteric lymph nodes (41/49 (83.6%) vs. 13/22 (59%), p= 0,012). In 98% of cases, FGLLB provided the information necessary for the correct diagnosis. Fluorescence with ICG offers a simple and safe method for detecting pathological lymph nodes. FGLLB in suspected intra-abdominal lymphoma can largely benefit from this new opportunity which, to date, has not yet been tested. Further studies with a larger case series are needed to confirm its efficacy. Graphical abstract:

Protein–protein interactions (PPIs) are some of the most challenging target classes in drug discovery. Highly sensitive detection techniques are required for the identification of chemical modulators of PPIs. Here, we introduce PPI confocal nanoscanning (PPI-CONA), a miniaturized, microbead based high-resolution fluorescence imaging assay. We demonstrate the capabilities of PPI-CONA by detecting low affinity ternary complex formation between the human CDC34A ubiquitin-conjugating (E2) enzyme, ubiquitin, and CC0651, a small molecule enhancer of the CDC34A–ubiquitin interaction. We further exemplify PPI-CONA with an E2 enzyme binding study on CC0651 and a CDC34A binding specificity study of a series of CC0651 analogues. Our results indicate that CC0651 is highly selective toward CDC34A. We further demonstrate how PPI-CONA can be applied to screening very low affinity interactions. PPI-CONA holds potential for high-throughput screening for modulators of PPI targets and characterization of their affinity, specificity, and selectivity.

Sustainable food consumption may help mitigate the impact that the food industry exerts on the natural environment. To foster sustainable food consumption, it is essential to understand consumers' perceptions related to sustainable food as well as the determinants of the intention to purchase sustainable food. Through an extension of the theory of planned behavior (TPB) with product familiarity (direct and indirect experience) and perceived value (perceived quality and green perceived utility), this study examines the drivers of purchase intention of sustainable biscuits. A survey of 2396 Italian consumers was conducted and structural equation modeling was used to test the developed model. Results show that perceived quality and environmental concern have positive and significant effects on purchase intention, regardless of the specific characteristics of sustainable biscuits, whereas mixed results are obtained about the effect of direct experience and perceived consumer effectiveness. Indirect experience, green perceived utility, perceived behavioral control, and subjective norms do not display any significant effect.

Introduction: Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics. Methods: In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics. Results: Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumanniiodds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01–6.46, p= 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05–72.54, p= 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16–0.91, p= 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-β-lactamase producers, respectively. Conclusions: Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches.

Antibiotic resistance, particularly among Gram-negative bacteria, poses a significant healthcare challenge due to their ability to evade antibiotic action through various mechanisms. In this study, we explore the prediction of small molecule accumulation in Gram-negative bacteria by using machine learning techniques enhanced with statistical descriptors derived from molecular dynamics simulations. We begin by identifying a minimal set of molecular descriptors that maximize the model’s predictive power while preserving human interpretability. We optimize model accuracy, precision, and the area under the receiver operating characteristic curve through an iterative process. We demonstrate that the inclusion of statistical descriptors significantly improves model performance across various prediction metrics. Particularly, the addition of statistical descriptors related to dipole moment and minimum projection radius enhances the model’s predictive capabilities, shedding light on the physicochemical properties crucial for small molecule accumulation. Our findings highlight the importance of considering statistical moments beyond mean values in predictive modeling and suggest avenues for future research. Overall, our study provides insights into the complex dynamics of antibiotic accumulation in Escherichia colibacterial cells, generalizable to other Gram-negative species, offering a promising approach for the discovery of effective antibacterial agents, identifying new hits, and improving them to define effective lead agents.

Integrated photonics is increasingly pivotal across various fields due to its inherent stability, scalability, and compactness. In the landscape of integrated photonic platforms, femtosecond laser writing is a novel microfabrication technique that is swiftly emerging as a strong contender to established photolithographybased methods. This paper presents a primer on the femtosecond laser writing process and explores its capabilities for creating versatile and reprogrammable processors. Furthermore, we examine the application of this technology to the realization of integrated devices designed to leverage the distinctive features of this technology for critical areas such as quantum information processing and astrophotonics.

Graphical AbstractPatients treated with ticagrelor showed increased delta difference in the intracoronary ST-segment elevation during two-step sequential balloon inflations and reduced angina score, compared to clopidogrel.

The nuclear receptor ssDAF-12 has been recognized as the key molecular player regulating the life cycle of the nematode parasite Strongyloides stercoralis. ssDAF-12 ligands permit the receptor to function as an on/off switch modulating infection, making it vulnerable to therapeutic intervention. In this study, we report the design and synthesis of a set of novel dafachronic acid derivatives, which were used to outline the first structure–activity relationship targeting the ssDAF-12 receptor and to unveil hidden properties shared by the molecular shape of steroidal ligands that are relevant to the receptor binding and modulation. Moreover, biological results led to the discovery of sulfonamide 3as a submicromolar ssDAF-12 agonist endowed with a high receptor selectivity, no toxicity, and improved properties, as well as to the identification of unprecedented ssDAF-12 antagonists that can be exploited in the search for novel chemical tools and alternative therapeutic approaches for treating parasitism such as Strongyloidiasis.

The solid state of four novel S-(+)-Naproxen (S-Nap) diastereomeric salts with cis-1-amino-2-indanol (SR-AIand RS-AIenantiomers) is reported. The anhydrous SR-AI_S-Nap_Ais the only obtained phase in all the experimental conditions used, while the kinetically preferred diastereomeric salt RS-AI_S-Nap_A1forms only in certain conditions and undergoes an irreversible phase transition to RS-AI_S-Nap_A2after melting; this second phase was obtained even by dehydration of the monohydrate salt RS-AI_S-Nap_W. The preferred crystallization of SR-AI_S-Nap_Awas observed when S-Napwas introduced in a solution containing equimolar quantity of the racemic cis-1-amino-2-indanol, in spite of the strict similarity of the crystal packings of SR-AI_S-Nap_Aand RS-AI_S-Nap_A1. With the aim of trying to explain the preference of S-Napfor the SR-AIenantiomer, an in-depth analysis and comparison of the diastereomeric salt crystal structures were carried out.

Two-dimensional conjugated polymers (2DCPs) are an emerging class of materials that exhibit properties similar to graphene yet do not have the limitation of zero bandgap. On-surface synthesis provides exceptional control on the polymerization reaction, allowing tailoring properties by choosing suitable monomers. Heteroatom-substituted triangulene 2DCPs constitute a playing ground for such a design and are predicted to exhibit graphene-like band structures with high charge mobility and characteristic Dirac cones in conduction or valence states. However, measuring these properties experimentally is challenging and requires long-range-ordered polymers, preferably with an epitaxial relationship with the substrate. Here, we investigate the electronic properties of a mesoscale-ordered carbonyl-bridged triphenylamine 2DCP (P2TANGO) and demonstrate the presence of a Dirac cone by combining angle-resolved photoemission spectroscopy (ARPES) with density functional theory (DFT) calculations. Moreover, we measure the absolute energy position of the Dirac cone with respect to the vacuum level. We show that the bridging functionality of the triangulene (ether vs carbonyl) does not significantly perturb the band structure but strongly affects the positioning of the bands with respect to the Au(111) states and allows control of the ionization energy of the polymer. Our results provide proof of the controllable electronic properties of 2DCPs and bring us closer to their use in practical applications.

Universal photonic processors (UPPs) are fully programmable photonic integrated circuits that are key components in quantum photonics. With this work, we present a novel platform for the realization of low-loss, low-power, and high-fidelity UPPs based on femtosecond laser writing (FLW) and compatible with a large wavelength spectrum. In fact, we demonstrate different UPPs, tailored for operation at 785 nm and 1550 nm, providing similar high-level performances. Moreover, we show that standard calibration techniques applied to FLW-UPPs result in Haar random polarization-insensitive photonic transformations implemented with average amplitude fidelity as high as 0.9979 at 785 nm (0.9970 at 1550 nm), with the possibility of increasing the fidelity over 0.9990 thanks to novel optimization algorithms. Besides being the first demonstrations of polarization-insensitive UPPs, these devices show the highest level of control and reconfigurability ever reported for a FLW circuit. These qualities will be greatly beneficial to applications in quantum information processing.

Purpose: Type 2 diabetes mellitus (T2DM) stands as the most prevalent metabolic disorder globally. T2DM entails numerous cardiovascular complications, which contribute significantly to morbidity, mortality, and increased public spending worldwide. The real challenge for new diabetes drugs lies not only in reducing blood glucose levels and glycated hemoglobin but also in preventing cardiovascular risk. Emerging receptor agonists for glucagon-like peptide-1 (GLP-1RAs) have demonstrated a pivotal role in diabetes management and mitigating cardiovascular risk. Methods: We conducted a 12-month longitudinal investigation evaluating the cardio-metabolic effects of GLP-1RAs on a cohort of 65 Caucasian patients diagnosed with T2DM who were scheduled for treatment with GLP-1RAs. Fifty-four T2DM patients successfully completed the 12-month study period, with 30 receiving dulaglutide and 24 receiving semaglutide. Results: In our study population, GLP-1RAs resulted in several positive changes beyond the observed weight loss: a shift in fat distribution, indicated by a reduction in the percentage of visceral fat (1.21 vs. 1.17, p< 0.05); a significant decrease in LDL cholesterol levels (p< 0.05) and triglycerides (p< 0.01); and a significant increase in serum adiponectin levels (p< 0.05), potentially indicating a reduction in insulin resistance and inflammation. Additionally, we observed a significant decrease in microalbuminuria and media-intimal thickness at the carotid vessel level (p< 0.05). Conclusions: In patients with T2DM 1-year therapy with GLP-1RAs has a positive effect on the main determinants of cardiovascular risk including body weight, visceral fat, dyslipidemia, and atherosclerosis. Moreover, the increase in adiponectin may play a pivotal role in controlling the inflammatory state and the mechanisms of vascular damage.

ObjectiveTo report real-world experience on the use of anifrolumab (ANI) in refractory systemic lupus erythematosus (SLE).MethodsThe present study is a multicenter, retrospective study involving 9 Italian SLE referral centers participating in a compassionate use program for the use of ANI in adult patients with active SLE in whom all the available treatment choices failed, were not tolerated, or were contraindicated. At baseline and 1, 3, 6, 9, and 12 months of treatment, overall and organ-specific disease activity, flares, daily glucocorticoid (GC) dose, and adverse events were recorded.ResultsA total of 26 patients were enrolled. At 4 weeks after starting ANI, a significant decrease in the Systemic Lupus Erythematosus Disease Activity Index 2000 (P= 0.01), Systemic Lupus Erythematosus–Disease Activity Score (P= 0.01), and physician global assessment (P= 0.001) was recorded, and the same trend was maintained over time. A significant reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index-activity (P< 0.001) and in tender (P= 0.03) and swollen (P= 0.02) joint counts was also recorded. At 3 months of follow-up, 33% of patients already achieved a remission state, whereas 46% were in Lupus Low Disease Activity State (LLDAS); at 6 months, 50% were in remission and 80% were in LLDAS. A significant reduction in the mean GC daily dose was observed, starting from week 4 (P= 0.04). A total of 4 disease flares according to the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index were recorded (3 mild-moderate and 1 severe). Overall, 4/20 patients with at least 24 weeks of follow-up (20%) were considered nonresponders.ConclusionThis study provides real-world experience on the use of ANI in patients with refractory SLE, confirming its rapid effectiveness and an overall acceptable safety profile.

Machine Learning algorithms that perform classification are increasingly been adopted in Information and Communication Technology (ICT) systems and infrastructures due to their capability to profile their expected behavior and detect anomalies due to ongoing errors or intrusions. Deploying a classifier for a given system requires conducting comparison and sensitivity analyses that are time-consuming, require domain expertise, and may even not achieve satisfactory classification performance, resulting in a waste of money and time for practitioners and stakeholders. This paper predicts the expected performance of classifiers without needing to select, craft, exercise, or compare them, requiring minimal expertise and machinery. Should classification performance be predicted worse than expectations, the users could focus on improving data quality and monitoring systems instead of wasting time in exercising classifiers, saving key time and money. The prediction strategy uses scores of feature rankers, which are processed by regressors to predict metrics such as Matthews Correlation Coefficient (MCC) and Area Under ROC-Curve (AUC) for quantifying classification performance. We validate our prediction strategy through a massive experimental analysis using up to 12 feature rankers that process features from 23 public datasets, creating additional variants in the process and exercising supervised and unsupervised classifiers. Our findings show that it is possible to predict the value of performance metrics for supervised or unsupervised classifiers with a mean average error (MAE) of residuals lower than 0.1 for many classification tasks. The predictors are publicly available in a Python library whose usage is straightforward and does not require domain-specific skill or expertise.

The development of high-yielding, resilient cultivars is the primary goal of many crop breeding programmes, but the uptake of these new cultivars is persistently low in low-income countries. We discuss constraints related to the adoption of crop cultivars and stress the importance of participatory approaches in building trust and promoting the adoption of new technologies.

Background: Adrenal lipid-poor adenomas (LPA) are defined by high unenhanced density (≥ 10 HU), and absolute and relative contrast medium washout > 60% and > 40%, respectively, at computerized tomography (CT). To date, no thorough histopathological characterization has been performed in those frequent lesions (one-third of adrenal adenomas). Our aim was to analyze the histopathological characteristics of adrenal LPA. Methods: Patients with LPA (n= 57) were selected among consecutive subjects referred for an adrenal incidentaloma or ACTH-independent Cushing syndrome. FluoroDeoxyGlucose-Positron Emission Tomography (FDG-PET) was performed in 37 patients. In patients treated by adrenalectomy (n= 17), Weiss score and Lin–Weiss–Bisceglia score (in tumors composed entirely or predominantly of oncocytes) were calculated. Results: Radiological parameters did not differ among patients with ACTH-independent Cushing syndrome (n= 6) and those with adrenal incidentalomas associated with primary aldosteronism (n= 2), autonomous cortisol secretion (n= 14), or non-functioning (n= 35). Patients treated by adrenalectomy had larger tumors (28.9 ± 11.2 vs17.3 ± 8.4 mm,P&lt; 0.001), higher CT unenhanced density (29.1 ± 11.0 vs23.1 ± 9.0 HU, P= 0.043), and FDG-PET adrenal uptake (9.0 ± 6.4 vs4.4 ± 2.3 SUV, P= 0.003) than non-operated ones. Oncocytic features > 75% of the tumor were detected in 12/17 cases (70.6%). Five of those showed borderline-malignant histopathological characteristics by Lin–Weiss–Bisceglia score. Among remaining non-oncocytic tumors, 1/5 had a Weiss score ≥ 3. Overall, 6/17 tumors (35.3%) had borderline-malignant potential. Radiological parameters were similar between patients with benign and borderline-malignant tumors. Conclusions: Adrenal LPA are a heterogeneous group of tumors, mostly composed of oncocytomas. Up to 1/3 of those tumors may have a borderline-malignant potential at histopathology.

Aiming at several key problems, such as motion discontinuity, getting stuck and body deformation, and appearing in the motion of wall-pressing pipeline robots (WPPRs) controlled by the differential drive principle, in this article, a smooth motion control policy (SMCP) is proposed. To improve the generality of the SMCP, the relationship between the walking unit driving motor load and the relative attitude of the WPPR is analyzed, and a real-time relative attitude estimation method that only relies on the walking unit driving motor current is proposed. In addition, the WPPR attitude change law when the velocity transmitted to the robot body is not satisfied with the differential drive mode is obtained. Finally, an SMCP based on a PID controller whose feedback signal is the difference between the actual and ideal attitudes of the WPPR is built to reduce the influence of friction fluctuation for the motion. To verify the SMCP, a new WPPR is designed, and a comparative experiment is performed to verify the effect of the SMCP. The experimental results show that the variance of the walking unit driving motor currents is smaller, and the velocity of the robot is larger when the robot adopts the SMCP. Thus, the proposed method can make the WPPR move more smoothly.

Business network agreements (BNA) are an innovative policy tool that allow firms to cooperate on common projects by sharing skills and knowledge. BNA can be set up either by firms working in the same geographical area or by firms geographically distant among each other. Focusing on Italian networks, we conduct a cross-section empirical analysis to investigate the relationship between geographical distance and heterogeneity in firms’ business when forming an interfirm network. It emerges that the geographical agglomeration of network firms is significantly related to a lower value of the entropy index, though in this case the network tends to be composed by a small number of firms. In other words, firms can enjoy the positive externalities arising from cooperation when they are located near each other and carry out similar activities; at the same time, the drawbacks of competition are reduced by limiting the number of partners with whom they share their efforts. On the contrary, we observe more dispersed and big networks among heterogeneous firms.

Abstract: Background: Lymph node dissection and esophageal anastomosis, considered the more demanding steps of laparoscopic gastrectomy for gastric adenocarcinoma, can be performed with the use of a remote-controlled robot. Methods: Thirteen patients with a histologically proved gastric cancer (six stage I, six stage II, and one stage III) were enrolled in a prospective study to assess feasibility and safety of the Da Vinci surgical system in total and partial gastrectomy with extended lymph node dissection. Outcome measures were conversion rate, intra- and postoperative morbidity and mortality, operative time, blood loss, number of lymph nodes harvested, and macroscopic and microscopic evaluation of resection margins. Results: Eight distal, four total, and one proximal laparoscopic gastrectomies were completed without conversion. Extended lymph node dissection, and esophagojejunal and esophagogastric anastomoses were successfully carried out using the da Vinci System. Mean operative time was 286 ± 32.6 min and blood loss was 103 ± 87.5 ml. Mean number of nodes retrieved was 28.1 ± 8.3 and all resection margins were negative. There was no mortality. Trocar bleeding requiring laparoscopy was the only major complication encountered. No recurrence occurred during a mean follow-up time of 12.2 ± 4.5 months. Conclusions: Robot-assisted laparoscopic lymph node dissection and esophageal anastomosis are feasible and safe. Longer follow-up time and randomized studies are needed to evaluate long-term outcome and clinical advantages of this new technology.

Purpose/methods: The determination of tumour biomarkers is paramount to advancing personalized medicine, more so in rare tumours like medullary thyroid carcinoma (MTC), whose diagnosis is still challenging. The aim of this study was to identify non-invasive circulating biomarkers in MTC. To achieve this goal, paired MTC tissue and plasma extracellular vesicle samples were collected from multiple centres and microRNA (miRNA) expression levels were evaluated. Results: The samples from a discovery cohort of 23 MTC patients were analysed using miRNA arrays. Lasso logistic regression analysis resulted in the identification of a set of circulating miRNAs as diagnostic biomarkers. Among them, miR-26b-5p and miR-451a, were highly expressed and their expression decreased during follow-up in disease-free patients in the discovery cohort. Circulating miR-26b-5p and miR-451a were validated using droplet digital PCR in a second independent cohort of 12 MTC patients. Conclusion: This study allowed the identification and validation of a signature of two circulating miRNAs, miR-26b-5p and miR-451a, in two independent cohorts reporting a significant diagnostic performance for MTC. The results of this study offer advancements in molecular diagnosis of MTC proposing a novel non-invasive tool to use in precision medicine.

Antineoplastic drugs (ADs) are essential tools in cancer treatment, but their cytotoxicity poses a risk to workers involved in their handling. In a hospital environment fundamental strategies for minimising exposure involve proper use of safety cabinets and closed-circuit transfer devices, along with personnel training and increased awareness of risks. However, medical gloves remain the first line of defence. In this respect the evaluation of glove materials and best choices can improve hospital safety management and prevent potential hazards and long-term consequences. The aim of this study was to assess contamination of gloves in samples taken from AD administration and preparation units of nine Italian hospitals and to raise awareness of the importance of evaluating chemico-physical properties of gloves. Our findings show that 33 % of the analysed gloves were positive for at least one AD, with contaminations ranging from 0.6 to 20,729 pg/ cm2. We proposed the alert glove values(AGVs) for each AD as a limit value for contamination assessment and good practice evaluation. Our findings also point to multiple AD contamination (43 % of positive findings in preparation units), calculated as total AGV (AGV-T), and confirm that gloves should be replaced after 30 min of AD handling, based on cumulative permeation and area under the curve (AUC), to maintain safety and limit dermal exposure.

The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing on tumor and matched healthy colon tissue, complemented with tumor whole-genome sequencing for further microbiome characterization. A type 1 helper T cell, cytotoxic, gene expression signature, called Immunologic Constant of Rejection, captured the presence of clonally expanded, tumor-enriched T cell clones and outperformed conventional prognostic molecular biomarkers, such as the consensus molecular subtype and the microsatellite instability classifications. Quantification of genetic immunoediting, defined as a lower number of neoantigens than expected, further refined its prognostic value. We identified a microbiome signature, driven by Ruminococcusbromii, associated with a favorable outcome. By combining microbiome signature and Immunologic Constant of Rejection, we developed and validated a composite score (mICRoScore), which identifies a group of patients with excellent survival probability. The publicly available multi-omics dataset provides a resource for better understanding colon cancer biology that could facilitate the discovery of personalized therapeutic approaches.

Background: Rehabilitation is currently the best available treatment for post-stroke disability. There is, however, great variability in the proportion of patients accessing rehabilitation across high-income countries suggesting that factors not explained by facilities availability or guidelines diversity may intervene in decision-making. Objectives: To evaluate which factors are associated with appropriate post-stroke rehabilitation referrals in a tertiary stroke unit setting. Methods: Retrospective single-center cohort study including patients admitted to the Stroke Unit of the “Santa Maria della Misericordia” University Hospital, Udine (IT) from January 1st to December 31st, 2019. Information regarding stroke severity (National Institute of Health Stroke Scale), functional assessment (modified Rankin scale [mRS] and Barthel index [BI]), length of hospital stay, and rehabilitation pathway was collected. Outcome was defined as referral to the appropriate rehabilitation pathway. Appropriateness was assessed comparing patient clinical information at discharge against local criteria for intensive vs. extensive rehabilitation. A mixed-linear effect model was built to explore NIHSS, mRS, and BI variation over time. Multivariable logistic regression was used to estimate the adjusted-odds ratio (OR) and 95% confidence interval (CI 95%) of appropriate assignment to rehabilitation pathways. Results: 288 patients were included in the study (age 73.1 years, males 57.9%) and in 75.7%, the rehabilitation pathway assignment was appropriate. NIHSS at discharge was lower compared to admission but no effect of rehabilitation assignment was evident, while mRS scores at discharge and at three months were 2.6 (CI 95% 2.2; 3.0) and 2.1 (CI 95% 1.8; 2.5) higher compared to admission (p&lt; 0.0001). Rehabilitation assignment effect on mRS was time dependent, resulting in an additional − 0.6 (CI 95% − 1.0; − 0.2) lowering at discharge for those appropriately assigned (p= 0.003), with a trend for significance at three months (p= 0.08). BI score was higher at discharge (p&lt; 0.0001), and appropriate assignment was associated with higher scores (p= 0.01). Multivariate analysis showed that the OR of appropriate rehabilitation pathway assignment were reduced by higher mRS (0.60 [CI 95% 0.48; 0.76], p&lt; 0.0001) and increased by higher NIHSS (1.11 [CI 95% 1.04; 1.19], p= 0.001) scores at discharge. The latter finding might be explained by the rehabilitation assessment focus on post-stroke motor symptoms captured by NIHSS. Conclusions: Higher mRS and lower NIHSS levels at discharge were independent predictors for inappropriate rehabilitation assignment after stroke in our cohort. These findings may reflect a therapeutic bias toward patients with higher post-stroke disability in a rehabilitation framework heavily tilted on post-stroke motor symptoms.

The level of each RNA species depends on the balance between its rates of production and decay. Although previous studies have measured RNA decay across the genome in tissue culture and single-celled organisms, few experiments have been performed in intact complex tissues and organs. It is therefore unclear whether the determinants of RNA decay found in cultured cells are preserved in an intact tissue, and whether they differ between neighboring cell types and are regulated during development. To address these questions, we measured RNA synthesis and decay rates genome wide via metabolic labeling of whole cultured Drosophilalarval brains using 4-thiouridine. Our analysis revealed that decay rates span a range of more than 100-fold, and that RNA stability is linked to gene function, with mRNAs encoding transcription factors being much less stable than mRNAs involved in core metabolic functions. Surprisingly, among transcription factor mRNAs there was a clear demarcation between more widely used transcription factors and those that are expressed only transiently during development. mRNAs encoding transient transcription factors are among the least stable in the brain. These mRNAs are characterized by epigenetic silencing in most cell types, as shown by their enrichment with the histone modification H3K27me3. Our data suggest the presence of an mRNA destabilizing mechanism targeted to these transiently expressed transcription factors to allow their levels to be regulated rapidly with high precision. Our study also demonstrates a general method for measuring mRNA transcription and decay rates in intact organs or tissues, offering insights into the role of mRNA stability in the regulation of complex developmental programs.