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Background: This study analyzed the Quality of Life (QoL) and cost-effectiveness of laparoscopic (LDP) versus robotic distal pancreatectomy (RDP). Methods: Consecutive patients submitted to LDP or RDP from 2010 to 2020 in four high-volume Italian centers were included, with a minimum of 12 months of postoperative follow-up were included. QoL was evaluated using the EORTC QLQ-C30 and EQ-5D questionnaires, self-reported by patients. After a propensity score matching, which included BMI, gender, operation time, multiorgan and vascular resections, splenic preservation, and pancreatic stump management, the mean differential cost and Quality-Adjusted Life Years (QALY) were calculated and plotted on a cost-utility plane. Results: The study population consisted of 564 patients. Among these, 271 (49%) patients were submitted to LDP, while 293 (51%) patients to RDP. After propensity score matching, the study population was composed of 159 patients in each group, with a median follow-up of 59 months. As regards the QoL analysis, global health and emotional functioning domains showed better results in the RDP group (p = 0.037 and p = 0.026, respectively), whereas the other did not differ. As expected, the median crude costs analysis confirmed that RDP was more expensive than LDP (16,041 Euros vs. 10,335 Euros, p < 0.001). However, the robotic approach had a higher probability of being more cost-effective than the laparoscopic procedure when a willingness to pay more than 5697 Euros/QALY was accepted. Conclusion: RDP was associated with better QoL as explored by specific domains. Crude costs were higher for RDP, and the cost-effectiveness threshold was set at 5697 euros/QALY. [ABSTRACT FROM AUTHOR]

When surveys contain direct questions about sensitive topics, participants may not provide their true answers. Indirect question techniques incentivize truthful answers by concealing participants' responses in various ways. The Crosswise Model aims to do this by pairing a sensitive target item with a non-sensitive baseline item, and only asking participants to indicate whether their responses to the two items are the same or different. Selection of the baseline item is crucial to guarantee participants' perceived and actual privacy and to enable reliable estimates of the sensitive trait. This research makes the following contributions. First, it describes an integrated methodology to select the baseline item, based on conceptual and statistical considerations. The resulting methodology distinguishes four statistical models. Second, it proposes novel Bayesian estimation methods to implement these models. Third, it shows that the new models introduced here improve efficiency over common applications of the Crosswise Model and may relax the required statistical assumptions. These three contributions facilitate applying the methodology in a variety of settings. An empirical application on attitudes toward LGBT issues shows the potential of the Crosswise Model. An interactive app, Python and MATLAB codes support broader adoption of the model. [ABSTRACT FROM AUTHOR]

Introduction: Oral squamous cell carcinoma (OSCC), while common and with a favorable prognosis in early stages, presents a marked reduction in survival rate upon metastasis to lymph nodes. Early detection of lymph node metastasis via biomarkers could enhance the therapeutic strategy for OSCC. Here, we explored dendritic cells (DCs) and cytotoxic T-cells in tumour-draining lymph nodes (TDLNs) as potential biomarkers. Method: Dendritic cells and cytotoxic T-cells in 33 lymph nodes were analyzed with multi-parameter flow cytometry in TDLNs, regional non-TDLNs surgically excised from 12 OSCC patients, and compared to 9 lymph nodes from patients with benign conditions. Results: Our results displayed a higher proportion of conventional cDC1s with immunosuppressive features in TDLN. Further, high PD-L1 expression on cDC1 in TDLNs was associated with metastasis and/or recurrent disease risk. Also, elevated levels of memory CD8+ T-cells and terminally exhausted PD-1+TCF-1−CD8+ T-cells were observed in TDLNs and non-TDLNs compared to healthy lymph nodes. Conclusions: We conclude that TDLNs contain cells that could trigger an anti-tumor adaptive response, as evidenced by activated cDC1s and progenitor-like TCF-1+ T-cells. The detection of high PDL1 expression on cDC1s was indicative of TDLN metastasis and an adverse prognosis, proposing that PD-L1 on dendritic cells in TDLN could serve as a predictive biomarker of OSCC patients with a worse prognosis. [ABSTRACT FROM AUTHOR]

Jackiw–Teitelboim dilaton quantum gravity localizes on a double-scaled random-matrix model, whose perturbative free energy is an asymptotic series. Understanding the resurgent properties of this asymptotic series, including its completion into a full transseries, requires understanding the nonperturbative instanton sectors of the matrix model for Jackiw–Teitelboim gravity. The present work addresses this question by setting-up instanton calculus associated with eigenvalue tunneling (or ZZ-brane contributions), directly in the matrix model. In order to systematize such calculations, a nonperturbative extension of the topological recursion formalism is required—which is herein both constructed and applied to the present problem. Large-order tests of the perturbative genus expansion validate the resurgent nature of Jackiw–Teitelboim gravity, both for its free energy and for its (multi-resolvent) correlation functions. Both ZZ and FZZT nonperturbative effects are required by resurgence, and they further display resonance upon the Borel plane. Finally, the resurgence properties of the multi-resolvent correlation functions yield new and improved resurgence formulae for the large-genus growth of Weil–Petersson volumes. [ABSTRACT FROM AUTHOR]

Clustering is an unsupervised machine learning method grouping data samples into clusters of similar objects, used as a system support tool in numerous applications such as banking customers profiling, document retrieval, image segmentation, and e-commerce recommendation engines. The effectiveness of several clustering techniques is sensible to the initialization parameters, and different solutions have been proposed in the literature to overcome this limitation. They require high computational memory consumption when dealing with big data. In this paper, we propose the application of a recent object detection Deep Learning model (YOLO-v5) for assisting the initialization of classical techniques and improving their effectiveness on two-variate datasets, leveraging the accuracy and reducing dramatically the memory and time consumption of classical clustering methods. [ABSTRACT FROM AUTHOR]

Background: Compassionate drug use (CDU) provides early access to not yet authorised medicines and is funded by pharmaceutical companies. The observational retrospective study Compass-O monitored the CDU of onco-haematological drugs, managed by seven Italian units for cytotoxic drug preparations (Unità Farmaci Antiblastici [UFA]), between 1 January, 2016 and 31 December, 2021. Objective: We aimed to evaluate the CDU of onco-haematological drugs managed by seven Italian UFA, between 2016 and 2021. Methods: The seven UFA provided anonymised data concerning CDU approved in the study period. The early access and potential cost savings for the National Health System (Servizio Sanitario Nazionale [SSN]) were analysed for CDU concerning drug-therapeutic indication combinations with complete data and reimbursed by SSN up to December 2023 (date of study execution), according to the executive decision of the Italian Medicines Agency (Agenzia Italiana del Farmaco [AIFA]). Both analyses distinguished solid/liquid tumours and categorised the combinations as innovative (fully/conditionally) or non-innovative based on AIFA assessments. Results: Compass-O collected 783 CDU authorisations, with 572 (73.1%) analysable in terms of early access and cost savings. On average, early access amounted to 514 days and the total cost savings was €376,115,801. Compassionate drug use approvals involved mainly solid tumours (93.7% vs 6.3% for liquid tumours), and the combination of trastuzumab emtansine-breast cancer was the most dispensed (n = 73; early access = 426 days; potential cost savings: €610,388). Out of 572 CDU approvals, 200 (35%) were innovative drug-therapeutic indication combinations, with 598 days of early access and a total potential saving of €113,124,069. Conclusions: The study Compass-O showed a significant economic burden of CDU and a relevant need for early access, particularly for innovative drugs. However, there is currently no structured monitoring of CDU in Italy, suggesting the need for a national observatory, of which Compass-O can be the pilot phase. [ABSTRACT FROM AUTHOR]

To date, evidence supporting the efficacy of tricuspid valve (TV) repair in interrupting the progression of systemic right ventricular (RV) adverse remodeling in hypoplastic left heart syndrome (HLHS) is conflicting. We conducted a systematic review and meta-analysis of scientific literature to assess the impact of TV repair in effectively modifying the prognosis of patients with HLHS. We conducted a systematic review of PubMed, Web of Science, and Scopus databases. A random-effect meta-analysis was performed and transplant-free survival, freedom from TV regurgitation, and TV reoperation data were reconstructed using the published Kaplan–Meier curves. Nine studies were included, comprising 203 HLHS patients undergoing TV repair and 323 HLHS controls. The estimated transplant-free survival at 1, 5, and 10 years of follow-up was 75.5% [95% confidence interval (CI) = 67.6–84.3%], 63.6% [95% CI = 54.6–73.9%], and 61.9% [95% CI = 52.7–72.6%], respectively. Transplant-free survival was comparable to HLHS peers without TV regurgitation (p = 0.59). Five-year freedom from recurrence of TV regurgitation and freedom from TV reoperation was 57% [95% CI = 46.7–69.7%] and 63.6% [95% CI = 54.5–74.3%], respectively. Younger age and TV repair at the time of Norwood operation increased the risk of TV regurgitation recurrence and the need for TV reoperation. Our meta-analysis supports the efficacy of TV repair in favorably modifying the prognosis of patients with HLHS and TV regurgitation, reestablishing a medium-term transplant-free survival which is comparable to HLHS peers. However, durability of surgery and long-term fate of TV and RV performance are still unclear. [ABSTRACT FROM AUTHOR]

The Software Heritage (SWH) dataset represents an invaluable source of open-source code as it aims to collect, preserve, and share all publicly available software in source code form ever produced by humankind. Although designed to archive deduplicated small files thanks to the use of a Merkle tree as the underlying data structure, querying the SWH dataset presents challenges due to the nature of these structures, which organize content based on hash values rather than any locality principle. The magnitude of the repository, coupled with the resource-intensive nature of the download process, highlights the need for specialized infrastructure and computational resources to effectively handle and study the extensive dataset housed within SWH. Currently, there is a lack of infrastructures specifically tailored for running analytics on the SWH dataset, leaving users to handle these issues manually. To address these challenges, we implemented the SWH-Analytics (SWHA) framework, a development environment that transparently runs custom analytic applications on publicly available software data preserved over time by SWH. Specifically, this work shows how SWHA can be effectively exploited to study usage patterns of free and open-source software licenses, highlighting the need to improve license literacy among developers. [ABSTRACT FROM AUTHOR]

Down syndrome is one of the most common genetic diseases, generally associated with an increased probability of congenital heart diseases. This increased risk contributes to escalated levels of morbidity and mortality. In this study, we sought to analyze nationwide data of pediatric and adult patients with Down syndrome and congenital heart disease over a 15-year period. Data obtained from the hospital discharge form between 2001 and 2016 of patients diagnosed with Down syndrome in Italy and at least one congenital heart disease were included. Information on 12362 admissions of 6527 patients were included. Age at first admission was 6.2 ± 12.8 years and was a predictor of mortality (HR = 1.51, 95% CI 1.13–2.03, p = 0.006). 3923 (60.1%) patients underwent only one admission, while 2604 (39.9%) underwent multiple (> 1) admissions. There were 5846 (47.3%) admissions for cardiac related symptoms. Multiple admissions (SHR: 3.13; 95% CI: 2.99, 3.27; P < 0.01) and cardiac admissions (SHR: 2.00; 95% CI: 1.92, 2.09; P < 0.01) were associated with an increased risk of additional potential readmissions. There was an increased risk of mortality for patients who had cardiac admissions (HR = 1.45, 95% CI: 1.08–1.94, p = 0.012), and for those who underwent at least 1 cardiac surgical procedure (HR = 1.51, 95% CI 1.13–2.03, p = 0.006). Conclusions: A younger age at first admission is a predictor for mortality in patients with Down syndrome and congenital heart disease. If patients undergo more than one admission, the risk of further readmissions increases. There is a pivotal role for heart disease in influencing the hospitalization rate and subsequent mortality. What is Known: • Down syndrome individuals often face an increased risk of congenital heart diseases. • Congenital heart diseases contribute significantly to morbidity and mortality in Down syndrome patients. What is New: • This study analyzes nationwide data covering a 15-year period of pediatric and adult patients in Italy with Down syndrome and congenital heart disease. • It identifies a younger age at first admission as a predictor for mortality in these patients, emphasizing the criticality of early intervention. • Demonstrates a correlation between multiple admissions, particularly those related to cardiac issues, and an increased risk of further readmissions, providing insights into the ongoing healthcare needs of these individuals. [ABSTRACT FROM AUTHOR]

Pinus pinea is an interesting species due to its pine nuts. Tuber borchii, a fungus that produces truffles, is a delicacy. Both species association offers a new productive opportunity. This work evaluated the effect of fertilization and inoculation with T. borchii on stone pine seedling growth in nursery and one year after field establishment in Chile, as well as mycorrhizal persistence. A factorial trial with two factors, inoculation and fertilization, was conducted in nursery. Mycorrhization, seedling growth, biomass and needle nutrient concentration after one growing season were measured. Mycorrhization and plant growth were measured one year after establishment a multi-environment trial involving seven sites. In nursery, inoculated seedlings presented over 50% of mycorrhized root apexes, with no differences between fertilized and non-fertilized plants. Under fertilization, inoculated plants had 16.5% higher height than non-inoculated ones. Fertilization increased seedling growth independently of inoculation. Inoculation did not modify the aerial to root biomass ratio. Inoculated and non-fertilized plants showed statistically higher P and lower K in needles than non-inoculated seedlings. One year after establishment, inoculation favored plant growth, and plants presented on average 88% of root apexes mycorrhized with T. borchii. Fertilization did not affect plant growth or mycorrhization levels. Stone pine inoculation with T. borchii was successful to produce abundantly mycorrhized roots in nursery. One year after field establishment, plant height and crown diameter were enhanced by inoculation, and high mycorrhization level suggests future truffle harvests. Both P. pinea and T. borchii showed high adaptability to different environments. Key message: Stone pine (Pinus pinea) seedlings non-inoculated and inoculated with Tuber borchii were produced in nursery with and without fertilization, and established in seven field trials in central-southern Chile. Before planting, inoculated seedlings presented abundantly mycorrhized root systems, and fertilized plants showed higher height and root collar diameter, independently of inoculation, than non-fertilized ones. One year after plant field establishment, mycorrhization had a positive effect on plant growth, and T. borchii colonization was higher than in nursery. Fertilization did not affect growth or mycorrhization level. The results have practical implications for trufficulture and pine nut production in non-native habitats. [ABSTRACT FROM AUTHOR]

Body mass results from a complex interplay between genetics and environment. Previous studies of the genetic contribution to body mass have excluded repetitive regions due to the technical limitations of platforms used for population scale studies. Here we apply genome-wide approaches, identifying an association between adult body mass and the copy number (CN) of 47S-ribosomal DNA (rDNA). rDNA codes for the 18 S, 5.8 S and 28 S ribosomal RNA (rRNA) components of the ribosome. In mammals, there are hundreds of copies of these genes. Inter-individual variation in the rDNA CN has not previously been associated with a mammalian phenotype. Here, we show that rDNA CN variation associates with post-pubertal growth rate in rats and body mass index in adult humans. rDNA CN is not associated with rRNA transcription rates in adult tissues, suggesting the mechanistic link occurs earlier in development. This aligns with the observation that the association emerges by early adulthood. Many genetic variants have been associated with body size, but the contribution of copy number of rDNA is unknown. Here, the authors explore the association between rDNA copy number and body size in both rats and humans, finding that lower rDNA CN is associated with higher weight and BMI. [ABSTRACT FROM AUTHOR]

Up to the beginning of the twenty-first century, most of quasi-brittle structures, in particular the ones composed by concrete or masonry frames and walls, were designed and built according to codes that totally ignored fracture mechanics theory. The structural load capacity predicted by strength-based theories, such as plastic analysis and limit analysis, do not exhibit size-effect. Within the framework of fracture mechanics theory, this paper deals with the analysis of the effect of non proportional loadings on the strength reduction with the structural scaling. In particular, this study investigates the size-effect of quasi-brittle materials subjected to self-weight. Although omnipresent, gravity-load is often considered negligible in most studies in the field of fracture mechanics. This assumption is obviously not valid for large structures and in particular for geometries in which the dead load is a major driving force leading to fracture and structural failure. In this study, an analytical formulation expressing the relation between the strength-reduction and the structural scaling and accounting for self-weight, was derived for both notched and unnotched bodies. More specifically, a closed form expression for size and self-weight effects was first derived for notched specimens from equivalent linear elastic fracture mechanics. Next, equivalent linear elastic fracture mechanics theory being not applicable to unnotched bodies, a cohesive model formulation was considered. Particularly, the cohesive size effect curve and the generalized cohesive size effect curves, originally obtained via cohesive crack analysis for weightless bodies with sharp and blunt/unnotched notches, respectively, were equipped of an additional term to account for the effect of gravity. All the resulting formulas were compared with the predictions of numerical simulation resulting from the adoption of the Lattice Discrete Particle Model. The results point out that the analytical formulas match very well the results of the numerical model for both notched and unnotched samples. Furthermore, the analytical formulas predict a vertical asymptote for increasing size, in the typical double-logarithm strength versus structural size representation. The asymptote corresponds to a characteristic size at which the structure fails under its own weight. For large structural sizes approaching this characteristic size, the newly developed formulas deviate significantly from previously proposed size-effect formulas. The practical relevance of this finding was demonstrated by analyzing size and self-weight effect for several quasi-brittle materials such as concrete, wood, limestone and carbon composites. Most importantly, the proposed formulas were applied to the failure of semi-circular masonry arches under spreading supports with different slenderness ratios. Results show that analytical formulas well predict numerical simulations and, above all, that for vaulted structures it is mandatory accounting for the effect of self-weight. [ABSTRACT FROM AUTHOR]

The aim of the present study was to individuate and compare specific machine learning algorithms that could predict postoperative anterior elevation score after reverse shoulder arthroplasty surgery at different time points. Data from 105 patients who underwent reverse shoulder arthroplasty at the same institute have been collected with the purpose of generating algorithms which could predict the target. Twenty-eight features were extracted and applied to two different machine learning techniques: Linear regression and support vector regression (SVR). These two techniques were also compared in order to define to most faithfully predictive. Using the extracted features, the SVR algorithm resulted in a mean absolute error (MAE) of 11.6° and a classification accuracy (PCC) of 0.88 on the test-set. Linear regression, instead, resulted in a MAE of 13.0° and a PCC of 0.85 on the test-set. Our machine learning study demonstrates that machine learning could provide high predictive algorithms for anterior elevation after reverse shoulder arthroplasty. The differential analysis between the utilized techniques showed higher accuracy in prediction for the support vector regression. Level of Evidence III: Retrospective cohort comparison; Computer Modeling. [ABSTRACT FROM AUTHOR]

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Detecting thermal Unruh radiation from accelerated electrons has presented a formidable challenge due not only to technical difficulties but also for lack of conceptual clarity about what is actually seen by a laboratory observer. We give a summary of the current interpretations along with a simpler heuristic description that draws on the analogy between the Unruh effect and radiation from a two-level atomic system. We propose an experiment to test whether there is emission of thermal photons from an accelerated electron. [ABSTRACT FROM AUTHOR]

Novel psychoactive substances (NPS) represent a broad class of drugs new to the illicit market that often allow passing drug-screening tests. They are characterized by a variety of structures, rapid transience on the drug scene and mostly unknown metabolic profiles, thus creating an ever-changing scenario with evolving analytical targets. The present study aims at developing an indirect screening strategy for NPS monitoring, and specifically for new synthetic opioids (NSOs), based on assessing changes in endogenous urinary metabolite levels as a consequence of the systemic response following their intake. The experimental design involved in-vivo mice models: 16 animals of both sex received a single administration of morphine or fentanyl. Urine was collected before and after administration at different time points; the samples were then analysed with an untargeted metabolomics LC-HRMS workflow. According to our results, the intake of opioids resulted in an elevated energy demand, that was more pronounced on male animals, as evidenced by the increase in medium and long chain acylcarnitines levels. It was also shown that opioid administration disrupted the pathways related to catecholamines biosynthesis. The observed alterations were common to both morphine and fentanyl: this evidence indicate that they are not related to the chemical structure of the drug, but rather on the drug class. The proposed strategy may reinforce existing NPS screening approaches, by identifying indirect markers of drug assumption. [ABSTRACT FROM AUTHOR]

Rationale: The 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT, known online as "Moxy") is a new psychedelic tryptamine first identified on Italian national territory in 2014. Its hallucinogen effects are broadly well-known; however, only few information is available regarding its pharmaco-toxicological effects. Objectives: Following the seizure of this new psychoactive substances by the Arm of Carabinieri and the occurrence of a human intoxication case, in the current study we had the aim to characterize the in vivo acute effects of systemic administration of 5-MeO-MiPT (0.01–30 mg/kg i.p.) on sensorimotor (visual, acoustic, and overall tactile) responses, thermoregulation, and stimulated motor activity (drag and accelerod test) in CD-1 male mice. We also evaluated variation on sensory gating (PPI, prepulse inhibition; 0.01–10 mg/kg i.p.) and on cardiorespiratory parameters (MouseOx and BP-2000; 30 mg/kg i.p.). Lastly, we investigated the in silico ADMET (absorption, distribution, metabolism, excretion, toxicity) profile of 5-MeO-MiPT compared to 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) and N,N-dimethyltryptamine (DMT). Results: This study demonstrates that 5-MeO-MiPT dose-dependently inhibits sensorimotor and PPI responses and, at high doses, induces impairment of the stimulated motor activity and cardiorespiratory changes in mice. In silico prediction shows that the 5-MeO-MiPT toxicokinetic profile shares similarities with 5-MeO-DIPT and DMT and highlights a cytochrome risk associated with this compound. Conclusions: Consumption of 5-MeO-MiPT can affect the ability to perform activities and pose a risk to human health status, as the correspondence between the effects induced in mice and the symptoms occurred in the intoxication case suggests. However, our findings suggest that 5-MeO-MiPT should not be excluded from research in the psychiatric therapy field. [ABSTRACT FROM AUTHOR]

The findings of the study demonstrate the impact of low-intensity laser and quasi-monochromatic light on the biosynthetic activity of the edible medicinal fungus L. edodes during submerged cultivation. An artificial lighting installation based on matrices of light-emitting diodes (LED) emitting light at 470 nm (blue), 530 nm (green), 650 nm (red), and argon gas laser (488 nm) was used. Irradiation with blue and red LED and laser led to a shortening of the lag phase by 2 days and an increase in the mycelial mass. Irradiation with laser light resulted in the highest mycelial mass yield (14.1 g/L) on the 8th day of cultivation. Irradiation in all used wavelength ranges caused an increase in the synthesis of both extracellular and intracellular polysaccharides. Laser light at 488 nm and LED at 470 nm proved to be the most effective. Irradiation with red, green, and blue laser light caused an increase in the total amount of fatty acids in the mycelial mass compared to the control. A significant distinction in qualitative composition was observed: short-chain acids C6‒C12 compounds were produced under red light irradiation, whereas long-chain C20‒C24 were formed under green light irradiation. The most significant changes in the aromatic profile of the mycelial mass and culture liquid were recorded upon irradiation with green light. The content of aromatic components increased 24.6 times in the mycelial mass and 38.5 times in the culture liquid. The results suggest the possibility of using low-intensity quasi-monochromatic light for targeted regulation of L. edodes biosynthetic activity. [ABSTRACT FROM AUTHOR]

Stone pine (Pinus pinea) produces a highly demanded dried fruit, the pine nuts; Tuber borchii produces a well-known commercialized truffle. Thus, the co-culture of P. pinea and T. borchii may represents an interesting productive option. This work evaluated the effect of T. borchii inoculation on stone pine tree growth, survival, health, entry into cone production, and mycorrhization level during the first 3 years after establishment along a 2000 km gradient in Chile. We tested two treatments (inoculation and non-inoculation) in a multi-environment trial (MET) involving seven sites along Chile. Plantations were repeatedly measured during 3 years after establishment. In all environments, inoculation enhanced tree height, root collar diameter (RCD) and crown diameter (6.9, 10 and 8.3% higher for inoculated than for non-inoculated plants). Vigor was also favored (14.1% more vigorous trees). Stone pine performance was enhanced in all sites, but mainly in those with extreme environmental conditions. T. borchii mycorrhizae were abundant (over 60% of mycorrhized root apexes) 3 years after establishment. The truffle-host plant combination was not previously evaluated in Chile. The results showed high root colonization levels and the persistence of mycorrhization 3 years after establishment, and an enhanced effect of mycorrhization on tree growth and vigor under different soil and climate conditions, confirming the high plasticity of both species. [ABSTRACT FROM AUTHOR]

Purpose: Left ventricular (LV) fibrosis has a key role in arrhythmogenesis in patients with mitral valve prolapse (MVP). Cardiac magnetic resonance identifies LV fibrosis by using late gadolinium enhancement (LGE) technique. LGE assessment and quantification in patients with MVP lacks of standardization protocols. Methods: 66 MVP patients with normal systolic function and without significant regurgitation were enrolled. Semi-automated gray-scale thresholding techniques using full width at half maximum (FWHM) and 2, 3 and 5 standard deviation (SD) above the remote myocardium were used and compared with the visual assessment, considered as the gold standard. Results: LGE was identified in 41 MVP patients (62%) and quantified. The mean quantity of LGE visually assessed was 2.40 ± 1.07% or 1.40 ± 0.82 g. With FWHM, LGE resulted 3.56 ± 1.23% or 1.99 ± 1.13 g. Using thresholding, the mean LGE quantity was 9.2 ± 3.1% or 4.82 ± 2.28 g for 2-SD, 5.72 ± 1.75% or 3.06 ± 1.47 g for 3-SD and 2.36 ± 0.99% or 1.29 ± 0.79 g for 5-SD. The 5-SD measurement in percentage demonstrated a good correlation with LGE quantification visually assessed (2.40 ± 1.07 vs. 2.363 ± 0.9909, p = 0.543). When compared with the gold standard, the 5-SD threshold quantification, both in percentage and in grams, revealed the least intra-observer (respectively, ICC: 0.976 and 0.966) and inter-observer variability (respectively ICC: 0.948 and 0.935). Conclusion: The 5-SD gray-scale threshold technique in percentage revealed the best correlation with the visual assessment and an optimal reproducibility in MVP patient. [ABSTRACT FROM AUTHOR]

Arroyo Verde epithermal deposit, in the North Patagonia region of Argentina, is located within the Lower Chon Aike volcanism and is developed between 192.6 ± 2.5 Ma (mineralization host rock) and 189.5 ± 2.6 Ma (overlying lava). Marifil volcanic complex is the host rock for these veins, veinlets and breccias. This particular small deposit has developed low to intermediate sulphidation characteristics, with gangue mineral textures associated with several ore minerals. Electron probe microanalysis determines electrum, silver minerals such as acanthite, and tetrahedrite, related Ag-Cu minerals like jalpaite, mckinstryite, stromeyerite, and base metals like chalcopyrite, sphalerite, galena and pyrite. Fluid inclusions in quartz of two out of five events indicate that these Low Jurassic veins were formed due to subtle boiling and dilution mechanisms and by low-salinity (3.4 wt.% to 6.7 wt.% NaCl Eq) magmatic-hydrothermal fluid at 225 to 310 °C. The fluid inclusion measurements that indicate boiling (Event 3) were plotted, and based on this data, we interpret that the Arroyo Verde deposit has been eroded between 550 and 700 m. This particular character has not been previously recorded for other sectors of the eastern north Patagonian region. [ABSTRACT FROM AUTHOR]

Introduction: An increased midnight cortisol (MC) has been described in end-stage kidney disease (ESKD) and type 1 diabetes (T1D). Lower circulating levels of the cytokine soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) have been found in T1D and ESKD and associated with cardiovascular (CV) events in the latter. We aimed to study MC and sTWEAK in simultaneous pancreas-kidney transplant (SPKT) recipients, and the association of these markers with CV risk factors and transplant outcomes. Methods: This was a retrospective cohort study including subjects with T1D who received a first SPKT between 2008 and 2020. MC and sTWEAK at baseline were correlated with CV risk factors and evolution 1 year after SPKT. Results: We included 29 subjects (58.6% women, mean age 43.5 ± 7.5 years, diabetes duration 31.9 ± 9.4 years). Systolic blood pressure (SBP) increased directly with MC quartiles, despite similar hypertension prevalence (p < 0.05). At 1 year, antihypertensive treatment was deintensified in those in lower MC quartiles (p < 0.05). Diabetic neuropathy prevalence decreased progressively in higher cortisol quartiles (p for trend = 0.005). Low MC was associated with delayed kidney graft function (p for trend = 0.044), and high sTWEAK with kidney graft rejection (p for trend = 0.018). In multivariate analyses, MC (standardized-β 0.505, p = 0.004) and age (standardized-β − 0.460, p = 0.040) were independently correlated with SBP, and MC was independently associated with the presence of diabetic neuropathy (OR 0.633, 95% CI 0.425–0.944, p = 0.025), adjusted for confounders. Conclusions: In this exploratory study, lower MC was associated with a lower baseline SBP, an improvement of antihypertensive treatment 1 year after transplant, and a higher diabetic neuropathy prevalence in SPKT recipients. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42% < 5 years), and a minority (15.6%) had a history of cardiovascular events. Importantly, oral semaglutide was started in subjects with various disease durations and background therapies. Notably, its initiation was accompanied by de-prescription of sulfonylureas, pioglitazone, DPP-4 inhibitors, and insulin. Choice of oral semaglutide was influenced by patient profiles and ongoing glucose-lowering regimens. Factors such as younger age, higher HbA1c, and ongoing SGLT-2 inhibitor therapy drove the choice of oral semaglutide with the aim of improving glycemic control. Projected glycemic effectiveness analysis revealed that oral semaglutide could potentially lead HbA1c to target in > 60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management. [ABSTRACT FROM AUTHOR]

English language development is a critical component for young children's school readiness. In this study, we examined the effect of Read it again-Pre-K! (Justice and McGinty in Read it again!-Prek: a preschool curriculum supplement to promote language and literacy foundations, Crane Center for Early Childhood Research and Policy, Columbus, 2013), a literacy curriculum designed to prepare young children's school readiness on the English literacy skills of Korean dual language learners in general education. Using a multiple probe design, eight 4- to 5-year-old Korean dual language learners (1 female, 7 males) received 1:1 online synchronous daily instruction over 2 months during the summer before entering their kindergarten programs. Through the intervention, all eight children demonstrated increases in the use of English vocabulary, story comprehension, and oral fluency. Post-intervention data on vocabulary and reading fluency through three standardized tests, Dynamic Indicators of Basic Early Literacy Skills, Peabody Picture Vocabulary Test, and Expressive Vocabulary Test, showed improvement over baseline for most children. Discussion and implications for future research were provided. [ABSTRACT FROM AUTHOR]

Although the precise clinical indication for initiation of PMX-HA is widely debated in the literature, a proper patient selection and timing of treatment delivery might play a critical role in the clinical course of a specific subphenotype of septic shock (endotoxic shock). In light of this view, since 2019, we have introduced in our clinical practice a diagnostic-therapeutic flowchart to select patients that can benefit the most from the treatment proposed. In addition, we reported in this study our experience of PMX-HA in a cohort of critically ill patients admitted to our intensive care unit (ICU). We analyzed a single centre, retrospective, observational web-based database (extracted from the EUPHAS2 registry) of critically ill patients admitted to the ICU between January 2016 and May 2021 who were affected by endotoxic shock. Patients were divided according to the diagnostic-therapeutic flowchart in two groups: Pre-Flowchart (Pre-F) and Post-Flowchart (Post-F). From January 2016 to May 2021, 61 patients were treated with PMX-HA out of 531 patients diagnosed with septic shock and of these, fifty patients (82%) developed AKI during their ICU stay. The most common source of infection was secondary peritonitis (36%), followed by community-acquired pneumonia (29%). Fifty-five (90%) out of 61 patients received a second PMX-HA treatment, with a statistically significant difference between the two groups (78% of the Pre-F vs. 100% of the Post-F group, p = 0.005). In both groups, between T0 and T120, the Endotoxin Activity Assay (EAA) decreased, while the SOFA score, mean arterial pressure (MAP), and Vasoactive Inotropic Score (VIS) improved with no statistically significant difference. Furthermore, when performing a propensity score matching analysis to compare mortality between the two groups, statistically significant lower ICU and 90-day mortalities were observed in the Post-F group [p = 0.016]. Although in this experienced centre data registry, PMX-HA was associated with organ function recovery, hemodynamic improvement, and current EAA level reduction in critically ill patients with endotoxic shock. Following propensity score-matched analysis, ICU mortality and 90-day mortalities were lower in the diagnostic-therapeutic flowchart group when considering two temporal groups based on strict patient selection criteria and timing to achieve PMX. Further Randomised Control Trials focused on centre selection, adequate training and a flowchart of action when assessing extracorporeal blood purification use should be performed. [ABSTRACT FROM AUTHOR]

Aim: To analyze if the 1mg-dexamethasone suppression test (DST) is a reliable marker of glucocorticoid excess and cardiometabolic risk in patients with adrenal incidentalomas (AIs). Methods: Cross-sectional study of patients with nonfunctioning adrenal incidentalomas (NFAIs, defined by cortisol post-DST ≤ 1.8 µg/dL) and patients with autonomous cortisol secretion (ACS, defined by cortisol post-DST > 1.8 µg/Dl). The urinary steroid profile (USP) was determined by gas chromatography coupled to mass spectrometry. Both groups were matched by sex, age and body mass index. Results: Forty-nine patients with AIs (25 with ACS and 24 with NFAI) were included. As a whole, AIs showed a high excretion of β-cortolone, tetrahydro-11-deoxycortisol (THS), α-cortolone, α-cortol, tetrahydrocortisol (THF) and tetrahydrocortisone (THE). A positive yet modest correlation between post-DST cortisol and total excretion of glucocorticoid metabolites (r = 0.401, P = 0.004) was observed, with the stronger being observed with total THS (r = 0.548, P < 0.001) and THF (r = 0.441, P = 0.002). Some of the metabolites that were elevated in patients with AIs, were higher in patients with ACS-related comorbidities than in those without comorbidities. Post-DST cortisol showed a fair diagnostic accuracy for the prediction of ACS-related comorbidities (AUC 0.767 [95% CI 0.634–0.882]). However, post-DST diagnostic accuracy improved when combined with urinary cortisone, α-cortol, THS and serum DHEAS (0.853 [0.712‒0.954]). Conclusion: The DST has a positive, but modest, correlation with urinary glucocorticoid excretion. Similarly, the diagnostic accuracy of the DST for the prediction of ACS-related comorbidities is only fair, but it may be improved if combined with the results of the USP and serum DHEAS. Significance statement: This is the first study aimed to evaluate if 1mg-dexamethasone suppression test (DST) is a reliable marker of glucocorticoid excess and cardiometabolic risk in patients with adrenal incidentalomas (AIs) and if urinary steroid profile was measured by GS-MS could improve such a prediction. We found a positive yet modest correlation between post-DST cortisol and total excretion of glucocorticoid metabolites, with the stronger being observed with total tetrahydro-11-deoxycortisol (THS) and tetrahydrocortisol. Post-DST cortisol showed a fair diagnostic accuracy for the prediction of ACS-related comorbidities (AUC 0.767). However, post-DST diagnostic accuracy improved when combined with urinary cortisone, α-cortol, THS and serum DHEAS (0.853). [ABSTRACT FROM AUTHOR]

Since the beginning of Coronavirus Disease 2019 (COVID-19) pandemic, many drugs have been purposed for the treatment of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Remdesivir emerged as an encouraging antiviral drug for patients with documented severe COVID-19-related pneumonia. Although several studies about remdesivir effectiveness exist, no study investigated the effect of the combination of remdesivir with the vaccination status. The aim of this study was to assess whether the administration of remdesivir could show some differences in terms of clinical outcomes in patients vaccinated against SARS-CoV-2 versus those who were not. The primary outcome was the in-hospital mortality. The secondary outcomes were 30-days mortality, the need for ICU admission and for oxygen supplementation. This is a retrospective cohort study including all consecutive adult patients hospitalized for severe COVID-19 at the Padua University Hospital (Italy), between September 1st, 2020, and January 31st, 2022, and who received a 5-days course of remdesivir. A total of 708 patients were included, 467 (66%) were male, and the median age was 67 (IQR: 56-79) years. To better estimate the outcomes of interest, a propensity score weighted approach was implemented for vaccination status. A total of 605/708 patients (85.4%) did not complete the vaccination schedule. In-hospital mortality rate was 5.1% (n = 36), with no statistically significant difference between the unvaccinated (n=29, 4.8%) and vaccinated (n=7, 6.8%; p=0.4) patients. After propensity score matching, mortality between the two groups remained similar. However, both the need for ICU and oxygen supplementation were significantly lower in the vaccinated group. Our finding suggests that a complete vaccination course could have an impact in reducing the need for transfer in ICU and for high-flow therapy in moderate-to-severe COVID-19 patients treated with remdesivir. [ABSTRACT FROM AUTHOR]

This study investigated whether a systematic instruction package was effective in child acquisition of question answering using an iPad-based speech generating device (SGD). The study was conducted with two children with autism using a multiple probe across behaviors design. Results demonstrated that the systematic instruction package consisting of graduated guidance, discrete trial teaching, time delay, and reinforcement resulted in acquisition of answering all questions. Follow-up data were collected one, three, and five weeks after instruction ended. For all participants, skills maintained during follow-up and generalized to novel settings and skills. Social validity data were also collected and indicated that teachers without experience using SGDs found them to be effective and feasible for teaching communication skills. [ABSTRACT FROM AUTHOR]

Early childhood special education teachers require training and support in implementing function-based intervention for challenging behavior. Yet, teacher professional development practices are not universally effective,and teachers may benefit from differentiated supports. The purpose of this study was to pilot and evaluate a multilevel approach to teacher professional development for function-based intervention. The multilevel approach included behavioral skills training, practice-based coaching, and teacher self-monitoring and was evaluated using a multiple baseline across participants single-case research design. Results demonstrated that while all teachers benefited from the professional development, teachers required different levels of support within the multilevel approach. These findings support a growing body of work suggesting that teachers may require varying levels of support to implement evidence-based practices. [ABSTRACT FROM AUTHOR]

Breast cancer is the leading cause of cancer in women in Spain and its annual incidence is rapidly increasing. Thanks to the screening programs in place, nearly 90% of breast cancer cases are detected in early and potentially curable stages, despite the COVID-19 pandemic possibly having impacted these numbers (not yet quantified). In recent years, locoregional and systemic therapies are increasingly being directed by new diagnostic tools that have improved the balance between toxicity and clinical benefit. New therapeutic strategies, such as immunotherapy, targeted drugs, and antibody–drug conjugates have also improved outcomes in some patient subgroups. This clinical practice guideline is based on a systematic review of relevant studies and on the consensus of experts from GEICAM, SOLTI, and SEOM. [ABSTRACT FROM AUTHOR]

The experience of the COVID-19 pandemic showed the importance of timely monitoring of admissions to the ICU admissions. The ability to promptly forecast the epidemic impact on the occupancy of beds in the ICU is a key issue for adequate management of the health care system. Despite this, most of the literature on predictive COVID-19 models in Italy has focused on predicting the number of infections, leaving trends in ordinary hospitalizations and ICU occupancies in the background. This work aims to present an ETS approach (Exponential Smoothing Time Series) time series forecasting tool for admissions to the ICU admissions based on ETS models. The results of the forecasting model are presented for the regions most affected by the epidemic, such as Veneto, Lombardy, Emilia-Romagna, and Piedmont. The mean absolute percentage errors (MAPE) between observed and predicted admissions to the ICU admissions remain lower than 11% for all considered geographical areas. In this epidemiological context, the proposed ETS forecasting model could be suitable to monitor, in a timely manner, the impact of COVID-19 disease on the health care system, not only during the early stages of the pandemic but also during the vaccination campaign, to quickly adapt possible preventive interventions. [ABSTRACT FROM AUTHOR]

Background: Technological development has offered laparoscopic colorectal surgeons new video systems to improve depth perception and perform difficult task in limited space. The aim of this study was to assess the cognitive burden and motion sickness for surgeons during 3D, 2D-4 K or 3D-4 K laparoscopic colorectal procedures and to report post-operative data with the different video systems employed. Methods: Patients were assigned to either 3D, 2D-4 K or 3D-4 K video and two questionnaires (Simulator Sickness Questionnaire-SSQ- and NASA Task Load Index -TLX) were used during elective laparoscopic colorectal resections (October 2020-August 2022) from two operating surgeons. Short-term results of the operations performed with the three different video systems were also analyzed. Results: A total of 113 consecutive patients were included: 41 (36%) in the 3D Group (A), 46 (41%) in the 3D-4 K Group and 26 (23%) in the 2D-4 K Group (C). Weighted and adjusted regression models showed no significant difference in cognitive load amongst the surgeons in the three groups of video systems when using the NASA-TLX. An increased risk for slight/moderate general discomfort and eyestrain in the 3D-4 K group compared with 2D-4 K group (OR = 3.5; p = 0.0057 and OR = 2.8; p = 0.0096, respectively) was observed. Further, slight/moderate difficulty focusing was lower in both 3D and 3D-4 K groups compared with 2D-4 K group (OR = 0.4; p = 0.0124 and OR = 0.5; p = 0.0341, respectively), and higher in the 3D-4 K group compared with 3D group (OR = 2.6; p = 0.0124). Patient population characteristics, operative time, post-operative staging, complication rate and length of stay were similar in the three groups of patients. Conclusions: 3D and 3D-4 K systems, when compared with 2D-4 K video technology, have a higher risk for slight/moderate general discomfort and eyestrain, but show lower difficulty focusing. Short post-operative outcomes do not differ, whichever imaging system is used. [ABSTRACT FROM AUTHOR]

We investigate the long-run relationship between de jure trade openness and economic growth as well as between de jure financial openness and economic growth for a panel of 118 developed and developing countries in the period 1970–2017. We fit a cross-sectional autoregressive distributed lag model and unveil the positive association between both liberalizations and economic growth in the global panel and for the more developed countries. Conversely, only trade liberalization is linked with larger output growth in less developed nations. We complement these results with a long-run causality analysis, which reveals that for the whole sample and for the two subsamples both de jure trade and de jure financial openness jointly cause economic growth. These outcomes may be indicative that during the time span under scrutiny developing countries faced current account crises when they stuck to the early prescriptions of the Washington Consensus. Yet, they later adopted a more nuanced view of economic liberalism putting in place a number of capital controls, which protected them from sudden stops and capital reversals. [ABSTRACT FROM AUTHOR]

Genetic parameters were estimated for egg production, egg quality, and eggshell colors in eight lineages of Brazilian laying hens. Age at first egg (AFE), total egg production up to the 45th week (PROD), egg weight (EW), albumen height (AH), yolk color (YC), the Haugh units (HU), eggshell strength (ESS), eggshell thickness (EST), yolk weight (YW), eggshell weight (ESW), and eggshell color (L*, a*, and b*) were measured in 2030 eggs obtained from 645 laying hens. Variance components were estimated from a mixed animal model, which included the fixed effects of contemporary groups, cage location, and hen line, and the additive genetic, permanent environmental, and residual as random effects. In general, heritabilities were low to moderate (h2 = 0.11 to 0.48). Genetic correlations among eggshell quality traits were moderate to high (0.36 and 0.69). High genetic correlations were obtained between the eggshell color traits [rg = −0.90 (L* and a*); rg = −0.64 (L* and b*); and rg = 0.65 (a* and b*)]. Results suggest that EW is strongly correlated with ESW, but the genetic correlations between EW and ESS and between EW and EST were low. Genetic correlations between L* and eggshell quality traits were low to moderate, suggesting that L* has little or no relation with external egg quality. However, genetic correlations between a* and b* values and eggshell quality traits were high. The genetic correlations between eggshell color and eggshell quality traits were low, suggesting that the eggshell color does not influence external egg quality. Genetic correlations between PROD and egg quality traits were negative and varied between −0.42 and −0.05. This antagonistic relationship emphasizes the importance of adopting breeding schemes that allow the simultaneous genetic progress of these traits by considering their genetic correlation and economic relevance, such as the selection index. [ABSTRACT FROM AUTHOR]

In children with congenital heart disease (CHD), pulmonary blood flow (Qp) contributes to alterations of pulmonary mechanics and gas exchange, while cardiopulmonary bypass (CPB) induces lung edema. We aimed to determine the effect of hemodynamics on lung function and lung epithelial lining fluid (ELF) biomarkers in biventricular CHD children undergoing CPB. CHD children were classified as high Qp (n = 43) and low Qp (n = 17), according to preoperative cardiac morphology and arterial oxygen saturation. We measured ELF surfactant protein B (SP-B) and myeloperoxidase activity (MPO) as indexes of lung inflammation and ELF albumin as index of alveolar capillary leak in tracheal aspirate (TA) samples collected before surgery and in 6 hourly intervals within 24 h after surgery. At the same time points, we recorded dynamic compliance and oxygenation index (OI). The same biomarkers were measured in TA samples collected from 16 infants with no cardiorespiratory diseases at the time of endotracheal intubation for elective surgery. Preoperative ELF biomarkers in CHD children were significantly increased than those found in controls. In the high Qp, ELF MPO and SP-B peaked 6 h after surgery and tended to decrease afterward, while they tended to increase within the first 24 h in the low Qp. ELF albumin peaked 6 h after surgery and decreased afterwards in both CHD groups. Dynamic compliance/kg and OI significantly improved after surgery only in the High Qp. Conclusion: In CHD children, lung mechanics, OI, and ELF biomarkers were significantly affected by CPB, according to the preoperative pulmonary hemodynamics. What is Known: • Congenital heart disease children, before cardiopulmonary run, exhibit changes in respiratory mechanics, gas exchange, and lung inflammatory biomarkers that are related to the preoperative pulmonary hemodynamics. • Cardiopulmonary bypass induces alteration of lung function and epithelial lining fluid biomarkers according to preoperative hemodynamics. What is New: • Our findings can help to identify children with congenital heart disease at high risk of postoperative lung injury who may benefit of tailored intensive care strategies, such as non-invasive ventilation techniques, fluid management, and anti-inflammatory drugs that can improve cardiopulmonary interaction in the perioperative period. [ABSTRACT FROM AUTHOR]

Purpose: Hydrocephalus is a multifactorial neurological disorder and one of the most common neurosurgical conditions characterized by excessive cerebrospinal fluid (CSF) accumulation within the brain's ventricles. It can result in dilatation of the ventricular system caused by the inadequate passage of CSF from its point of production within the ventricles to its point of absorption into the systemic circulation. Recent findings on the genetics and molecular studies of hydrocephalus have the potential to improve treatment and quality of life. Methods: Review of literature on the novel studies of the pathogenesis of hydrocephalus. Conclusion: Molecular studies on the pathogenesis of hydrocephalus have provided a means to improve the treatment and follow-up of patients with hydrocephalus. [ABSTRACT FROM AUTHOR]

Cirrhosis is a complex diffuse process whereby the architecture of the liver is replaced by abnormal nodules because of the presence of fibrosis. Several pediatric diseases such as extrahepatic portal vein obstruction, biliary atresia, alpha-1-antitrypsin deficit and autoimmune hepatitis can lead to cirrhosis and portal hypertension in children. In this article the authors describe interventional radiology procedures that can facilitate the diagnosis and treatment of diseases associated with liver cirrhosis and portal hypertension in the pediatric population. These procedures include image-guided liver biopsy, mesenteric–intrahepatic left portal vein shunts, balloon-occluded retrograde transvenous obliteration, transjugular intrahepatic portosystemic shunts and splenic embolization. [ABSTRACT FROM AUTHOR]

Caregiver-implemented interventions are increasingly utilized to address the needs of families of autistic children. The purpose of this systematic review was to synthesize the studies evaluating interventions implemented by caregivers of autistic teens and young adults. We identified 10 studies that evaluated the efficacy of a caregiver-implemented intervention for autistic adolescents and young adults. We analyzed information related to participant and methodological characteristics, dependent variables, caregiver involvement, caregiver implementation fidelity, social validity, design quality, and strength of the results. In the included studies, daily living skills were the most common outcome targeted for intervention. Caregiver training often consisted of some or all of the components of behavioral skills training. Seven of the ten included studies (70%) met the What Works Clearinghouse methodological design standards. Across studies, results suggest caregiver-implemented interventions improved outcomes for autistic individuals and caregivers rated the interventions as socially valid. The current body of literature provides initial support for the use of caregiver-implemented interventions to improve outcomes for autistic adolescents and young adults, although additional research in this area is warranted. [ABSTRACT FROM AUTHOR]

Sequential multiple assignments randomized trials (SMARTs) are a type of experimental design where patients may be randomised multiple times according to pre-specified decision rules. The present work investigates the state-of-the-art of SMART designs in oncology, focusing on the discrepancy between the available methodological approaches in the statistical literature and the procedures applied within cancer clinical trials. A systematic review was conducted, searching PubMed, Embase and CENTRAL for protocols or reports of results of SMART designs and registrations of SMART designs in clinical trial registries applied to solid tumour research. After title/abstract and full-text screening, 33 records were included. Fifteen were reports of trials' results, four were trials' protocols and fourteen were trials' registrations. The study design was defined as SMART by only one out of fifteen trial reports. Conversely, 13 of 18 study protocols and trial registrations defined the study design SMART. Furthermore, most of the records considered each stage separately in the analysis, without considering treatment regimens embedded in the trial. SMART designs in oncology are still limited. Study powering and analysis is mainly based on statistical approaches traditionally used in single-stage parallel trial designs. Formal reporting guidelines for SMART designs are needed. [ABSTRACT FROM AUTHOR]

Feed-efficient cattle selection is among the most leading solutions to reduce cost for beef cattle production. However, technical difficulties in measuring feed efficiency traits had limited the application in livestock. Here, we performed a Bivariate Genome-Wide Association Study (Bi-GWAS) and presented candidate biological mechanisms underlying the association between feed efficiency and meat quality traits in a half-sibling design with 353 Nelore steers derived from 34 unrelated sires. A total of 13 Quantitative Trait Loci (QTL) were found explaining part of the phenotypic variations. An important transcription factor of adipogenesis in cattle, the TAL1 (rs133408775) gene located on BTA3 was associated with intramuscular fat and average daily gain (IMF-ADG), and a region located on BTA20, close to CD180 and MAST4 genes, both related to fat accumulation. We observed a low positive genetic correlation between IMF-ADG (r = 0.30 ± 0.0686), indicating that it may respond to selection in the same direction. Our findings contributed to clarifying the pleiotropic modulation of the complex traits, indicating new QTLs for bovine genetic improvement. [ABSTRACT FROM AUTHOR]

Background: Thoracic mesenchymal hamartomas are rare benign lesions. Rarely symptomatic, they may compress pulmonary parenchyma, leading to respiratory distress. Although spontaneous regression has been documented, the more common outcome is progressive growth. The treatment of choice is en bloc excision of the involved portion of the chest wall, frequently leading to significant deformity. Objective: The aim of our study was to describe percutaneous techniques to treat these lesions. Materials and methods: We collected data of children with thoracic mesenchymal hamartomas who were treated at our institution from 2005 to 2020 using various percutaneous techniques. Techniques included radiofrequency thermoablation, microwave thermoablation (microwave thermoablation) and cryoablation. Results: Five children were treated for chest wall hamartomas; one child showed bilateral localization of the mass. Two children underwent microwave thermoablation, one radiofrequency thermoablation and two cryoablation; one child treated with cryoablation also had radiofrequency thermoablation because mass volume increased after the cryoablation procedure. The median reduction of tumor volume was 69.6% (24.0–96.5%). One child treated with microwave thermoablation showed volumetric increase of the mass and underwent surgical removal of the tumor. No major complication was reported. Conclusion: Percutaneous ablation is technically feasible for expert radiologists and might represent a valid and less invasive treatment for chest wall chondroid hamartoma, avoiding skeletal deformities. [ABSTRACT FROM AUTHOR]

Background: Inflammation plays an important role in tumor growth. Novel serum blood biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), have been proposed as useful prognostic indexes in cancer patients. However, their role in rectal cancer is controversial. Methods: A comprehensive literature review was conducted including MEDLINE/Pubmed, EMBASE, SCOPUS, and the Cochrane Database of Systematic Reviews through May 2022. The systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Quality was appraised with the Methodological Index for Non-Randomized Studies (MINORS) tool. Aim of the study was to summarize available literature on PLR, NLR, and LMR in patients with rectal cancer undergoing resection. Results: Forty-seven observational studies (14,205 patients) were included; there were 42 retrospective and 5 prospective cohort studies with an average MINORS score of 14.6 (range: 12–18). Worse overall survival was associated with high NLR (HR 1.81; 95%CI 1.52–2.15; p < 0.001), high PLR (HR 1.24; 95%CI 1.06–1.46; p = 0.009), and low LMR (HR 0.67; 95%CI 0.49–0.91; p = 0.01). High NLR and low LMR were also associated with disease-free-survival (HR 1.68; 95%CI 1.35–2.08; p < 0.001 and HR 0.71; 95%CI 0.58–0.87; p < 0.001, respectively). Conclusions: NLR, PLR, and LMR are independent clinical predictors for overall survival in patients with rectal cancer treated with curative surgery. NLR and LMR are also good predictors for disease free survival. These biomarkers, which are readily available, appear optimal prognostic indexes and may help clinicians predict the prognosis of rectal cancer and develop individualized treatment strategies. [ABSTRACT FROM AUTHOR]

Due to the high milk production of Holstein cows, many countries have chosen to import semen to improve local dairy herds. This strategy would be more effective if this semen was used in the same environment conditions in which the bulls were selected. If the effect of genotype by environment (G × E) interaction is not considered, the estimated breeding values (EBVs) may vary, potentially reducing the selection response. We evaluate the impact of heat stress on selection for milk yield and composition of Holstein cows using random regression models. To verify the interference of heat stress in milk yield (MY) and composition traits (fat, protein, total saturated, and total unsaturated fatty acids content in milk), temperature–humidity index (THI) on test-day milk records was used. The threshold value to divide the environments using test-day information from Brazilian Holstein cows was 72 units of THI, i.e., < 72 represented no heat stress and > 72 represented heat stress. Legendre polynomials of second-order (Leg 2) model and two lactation points (33 and 122 DIM) were used to estimate heritabilities and EBVs for five important dairy traits. The heritabilities of milk components and fatty acids were low (0.09–0.29), regardless of lactation period and degree of heat stress, with the exception of protein content (0.30–0.35). Fat content was the only milk component that was reduced according to the degree of heat stress and lactation period. The EBVs tended to decrease in heat stress conditions, thus animals with high genetic potential demonstrated evidence of G × E interaction. However, acclimatization of dairy cows to heat stress in the farm production systems may have been responsible for the low differences among genetic parameters and EBVs with and without heat stress found in this study. [ABSTRACT FROM AUTHOR]

Challenging behavior tends to increase in levels during adolescence for individuals with developmental disabilities (DD). If not addressed, this can lead to negative post-school outcomes for adolescents with DD. The purposes of this meta-analysis were to examine the effects of behavioral intervention in reducing challenging behaviors of adolescents with DD and to identify variables that could potentially moderate these effects. This meta-analysis included thirty single-case design studies that met standards for methodological rigor and experimental control. Overall, behavioral interventions were found to yield moderate effects for adolescents with DD (overall Tau-U = 0.68, SD = 0.04, [0.62, 0.73]) across settings and types of challenging behaviors. With regards to participant and setting characteristics, verbal ability and classroom setting were found to moderate the effects of the intervention outcomes with statistical significance. No other variables produced similar findings. Furthermore, statistically significant differences were found between interventions that included or did not include planned reinforcement as an intervention component. Several implications for research and practice are discussed. [ABSTRACT FROM AUTHOR]

Background: Standard laparoscopic colorectal surgery relies on 2D image systems in most centers. However, 3D vision has gained popularity and is used nowadays in a constantly rising number of units. Right hemicolectomy with intracorporeal anastomosis and lymph node dissection represents a surgical procedure that may benefit the most from 3D vision. The aim of the study was to summarize the available literature on the use of 2D vs. 3D video imaging in patients undergoing laparoscopic right hemicolectomy. Methods: A comprehensive literature review was conducted including Medline/PubMed, Embase, and Scopus (PROSPERO registration number CRD 42022344764) through October 2022. The systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The risk of bias was evaluated using the ROBINS-I tool. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines and GRADEpro to develop a summary of evidence tables. Random-effects meta-analyses were conducted. Results: Five observational retrospective studies (496 patients, 275 2D and 216 3D) were included. One study was rated as having a critical risk of bias; the remaining had low to moderate risk. 2D laparoscopic right hemicolectomy patients showed longer anastomotic time in 3/3 studies (MD = 3.32; 95%CI, 1.58–5.05; p = 0.002) and an upward trend in operative time in 4/5 studies (MD = 9.98; 95%CI, −1.42, 21.37; p = 0.086) compared to 3D. The two image video systems had similar short-term outcomes, including the number of lymph nodes harvested (MD = −0.67; 95%CI, −2.47, 1.13; p = 0.47), morbidity (OR post-operative complications = 1.12; 95%CI, 0.71–1.77; p = 0.62), and length of stay (MD = 0.27; 95%CI, −0.59, 1.13; p = 0.9). Conclusions: 2D and 2D laparoscopic right hemicolectomy had similar complications rate, with a shorter anastomotic time along with a downward trend in overall operative time for 3D. Larger prospective randomized trials are awaited before definitive conclusions can be drawn. [ABSTRACT FROM AUTHOR]

Background: There are few studies focused on the short-term results of laparoscopic right hemicolectomy performed with 2D (two-dimension) or 3D (three-dimension) video technology and none on the oncologic effects. The aim of the study was to assess the long-term results of laparoscopic right hemicolectomy (LRH) with intracorporeal anastomosis using 3D or 2D video in patients with right colon cancer with at least three years of oncologic follow-up. Methods: Data from patients undergoing laparoscopic right hemicolectomy (LRH) with intracorporeal anastomosis for cancer in an 11-year period (June 2008–June 2019) and ≥ 3 years of follow-up were prospectively collected. Surgical procedures were performed by two expert laparoscopic surgeons. Results: 111 patients were included in the study: 56 (50.5%) in the 3D group and 55 (49.5%) in the 2D group. Tumor stage and number of lymph nodes harvested were similar. Overall and disease-free survival were not different in the two groups. Local recurrence occurred in none of the patients, and distant metachronous metastases were similar in the two groups. A propensity score weighting approach was used to account for potential confounding related to patients’ nonrandom allocation to the 2 groups. The effects of the intervention on postoperative outcomes were assessed with a weighted regression approach. Conclusions: Laparoscopic 3D technology allows similar oncological results as 2D vision in LRH with intracorporeal anastomosis. Larger prospective randomized studies might confirm these results in the long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: Patient empowerment through pharmacological self-management is a common strategy in some chronic diseases such as diabetes, but it is rarely used for controlling blood pressure. Objective: This study aimed to assess self-monitoring plus self-titration of antihypertensive medication versus usual care for reducing systolic blood pressure (SBP) at 12 months in poorly controlled hypertensive patients. Design: The ADAMPA study was a pragmatic, controlled, randomized, non-masked clinical trial with two parallel arms in Valencia, Spain. Participants: Hypertensive patients older than 40 years, with SBP over 145 mmHg and/or diastolic blood pressure (DBP) over 90 mmHg, were recruited from July 2017 to June 2018. Intervention: Participants were randomized 1:1 to usual care versus an individualized, pre-arranged plan based on self-monitoring plus self-titration. Main Measure: The primary outcome was the adjusted mean difference (AMD) in SBP between groups at 12 months. Key Results: Primary outcome data were available for 312 patients (intervention n=156, control n=156) of the 366 who were initially recruited. The AMD in SBP at 12 months (main analysis) was −2.9 mmHg (95% CI, −5.9 to 0.1, p=0.061), while the AMD in DBP was −1.9 mmHg (95% CI, −3.7 to 0.0, p=0.052). The results of the subgroup analysis were consistent with these for the main outcome measures. More patients in the intervention group achieved good blood pressure control (<140/90 mmHg) at 12 months than in the control group (55.8% vs 42.3%, difference 13.5%, 95% CI, 2.5 to 24.5%, p=0.017). At 12 months, no differences were observed in behavior, quality of life, use of health services, or adverse events. Conclusion: Self-monitoring plus self-titration of antihypertensive medication based on an individualized pre-arranged plan used in primary care may be a promising strategy for reducing blood pressure at 12 months compared to usual care, without increasing healthcare utilization or adverse events. Trial Registration: EudraCT, number 2016-003986-25 (registered 17 March 2017) and clinicaltrials.gov, NCT03242785. [ABSTRACT FROM AUTHOR]