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BackgroundPediatric renal trauma is rare and lacks sufficient population-specific data to generate evidence-based management guidelines. A nonoperative approach is preferred and has been shown to be safe. However, bleeding risk assessment and management of collecting system injury are not well understood. We introduce the Multi-institutional Pediatric Acute Renal Trauma Study (Mi-PARTS), a retrospective cohort study designed to address these questions. This article describes the demographics and contemporary management of pediatric renal trauma at Level I trauma centers in the United States.MethodsRetrospective data were collected at 13 participating Level I trauma centers on pediatric patients presenting with renal trauma between 2010 and 2019. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Descriptive statistics were used to report on demographics, acute management, and outcomes.ResultsIn total, 1,216 cases were included in this study. Of all patients, 67.2% were male, and 93.8% had a blunt injury mechanism. In addition, 29.3% had isolated renal injuries, and 65.6% were high-grade (American Association for the Surgery of Trauma Grades III-V) injuries. The mean Injury Severity Score was 20.5. Most patients were managed nonoperatively (86.4%), and 3.9% had an open surgical intervention, including 2.7% having nephrectomy. Angioembolization was performed in 0.9%. Collecting system intervention was performed in 7.9%. Overall mortality was 3.3% and was only observed in patients with multiple injuries. The rate of avoidable transfer was 28.2%.ConclusionThe management and outcomes of pediatric renal trauma lack data to inform evidence-based guidelines. Nonoperative management of bleeding following renal injury is a well-established practice. Intervention for renal trauma is rare. Our findings reinforce differences from the adult population and highlights opportunities for further investigation. With data made available through Mi-PARTS, we aimed to answer pediatric specific questions, including a pediatric-specific bleeding risk nomogram, and better understanding indications for interventions for collecting system injuries.Level of evidencePrognostic and Epidemiological; Level IV.

Abstract Highly sensitive and selective gas-sensing materials are critical for applications ranging from environmental monitoring to breath analysis. A rational approach at the nanoscale is urgent to design next-generation sensing devices. In previous work, we unveiled interesting charge transfer channels at the interface between p-type doped graphene and a layer of nickel phthalocyanine (NiPc) molecules, which we believe could be successfully exploited in gas sensing devices. Here, we have investigated the graphene-NiPc interface’s response to adsorbed gas molecules via first-principles calculations. We focused on NH3 and NO2 as test molecules, representing electron donors and acceptors, respectively. Notably, we identified the Ni d z 2 orbital as a key player in mediating the charge transfer and affecting the charge carrier density in graphene. As a proof-of-concept, we then prepared the graphene-NiPc system as a chemiresistor device and exposed it to NH3 and NO2 at room temperature. The sensing tests revealed excellent sensitivity and selectivity, along with a rapid recovery time and a remarkably low detection limit.

Abstract The extended depth-of-focus AcrySof IQ Vivity intraocular lens technology offers promising features for presbyopia management, evaluated in this research in a 6 months real-world setting. Prospective interventional mono-centric study including 40 patients who underwent elective bilateral phacoemulsification. We performed one pre-operative visit (V0) and one evaluation six months post-operatively (V1), evaluating uncorrected and corrected visual acuity for near (UNVA/CNVA), intermediate (UIVA/CIVA) and far (UDVA/UCVA), slit-lamp evaluation, tomography with static pupillometry, endothelial cell count and contrast sensitivity chart. In order to assess post-operative Quality of Life, we administered the patients McAlinden’s Quality of Vision test and Morlock’s Patient-Reported Spectacle Independence Questionnaire. We divided eyes in with Toric-IOL and with non-Toric IOL. A total of 36 eyes received non-tonic IOL implantation, whereas 44 eyes received toric IOL implantation. There were no statistically significant disparities observed in visual outcome measures and contrast sensitivity between the toric group and the non-toric group. Furthermore, we assessed the predictive preoperative refractive astigmatism (PPRA) and residual refractive astigmatism (RRA) in both cohorts, and no statistical significance was found between the two cohorts (p = 0.08). Twenty-one (53%) patients reported total independence from their glasses at all distances. The mean difference between the predicted and measured refractive error, as calculated by spherical equivalent, was 0.09 D. AcrySof IQ Vivity is a well-tolerated and effective IOL with optimal refractive target for both distant and intermediate vision, needing slight spherical addition for the best near vision. Great questionnaire-based satisfaction was reported by the patients.

IntroductionImmune checkpoint inhibitor (ICI)-based immunotherapy targeting programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) has radically changed the management of many types of solid tumors including non-small cell lung cancer (NSCLC). Many clinical trials have demonstrated that ICIs improve the survival and the quality of life of patients with advanced non oncogene NSCLC as compared to standard therapies. However, not all patients achieve a clinical benefit from this immunotherapeutic approach. As a result, real-word validation of the efficacy and safety of ICIs can be useful for defining potential predictive biomarkers as well as for overcoming limitations linked to clinical trial restrictions.MethodsWe retrospectively retrieved the clinical data of patients with advanced non oncogene NSCLC treated with ICIs (anti-PD-1 or anti-PD-L1) as single agent or in combination with chemotherapy at “San Giovanni di Dio e Ruggi D’Aragona” University Hospital from January 2016 to December 2023. Potential correlations between clinical-pathological characteristics and safety or survival outcomes were investigated employing the Fisher’s exact test, Mann-Whitney U test, the Kruskal-Wallis method and log-rank test, as applicable. Multivariate survival analyses were performed using the Cox proportional hazards model.ResultsClinical data of 129 patients were retrieved. At a median follow-up of 29.70 months, progression-free survival (PFS) and overall survival (OS) were 5.27 months and 8.43 months, respectively. At the multivariate analyses, smoking status, presence of bone metastases and the occurrence of immune-related adverse events (irAEs) were correlated with both PFS and OS. Moreover, patients treated with anti-PD-1-based therapy achieved an increased clinical benefit than those treated with anti-PD-L1.DiscussionIn this study we described our real-world experience of ICIs for the treatment of patients with advanced non oncogene NSCLC. A decreased OS in our study population was reported as compared to that of patients included in the clinical trials. Noteworthy, correlations between clinical-pathological characteristics and survival outcomes emerged. Nevertheless, the potential integration of clinical-pathological characteristics as predictive biomarkers in more accurate therapeutic algorithms as well as the underlying biological mechanisms should be further validated in ad hoc studies.

Blinatumomab has remarkable efficacy in patients with relapsed/refractory (r/r) or measurable residual disease (MRD)-positive B-cell acute lymphoblastic leukemia (B-ALL). In many patients, blinatumomab treatment is followed by allogeneic hematopoietic stem cell transplantation (HSCT). However, the influence of blinatumomab on HSCT outcomes in children and young adults (YA) remains to be fully elucidated. We conducted a single-center, retrospective analysis on patients given blinatumomab as last treatment before HSCT. Seventy-eight pediatric and YA patients were evaluated. With a median follow-up of 23.23 months, the 2-year disease-free (DFS) and overall survival (OS) probability were 72.2% and 89.2%, respectively, with a 2-year cumulative incidence (CI) of non-relapse mortality (NRM) of 2.6%. A trend toward improved 2-year DFS, but not OS, was noted in patients transplanted in first complete remission (CR1) (92.9%) compared to those in second or greater remission (CR2/3) (68.5%, p=0.18) due to a lower CI of relapse (0% vs. 29.9%, p=0.05). Among CR2/3 patients, those receiving the sequential combination of inotuzumab and blinatumomab had a significantly lower CI of relapse as compared to those who did not receive inotuzumab (9.5% vs. 40.4%, p=0.023). Relapse after HSCT occurred in 16 patients, all exhibiting CD19-positive blasts; 10 of them received anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy and 2 inotuzumab as salvage therapy, leading to a 2-year post-relapse OS of 52.7%. Our results indicate that HSCT following blinatumomab in children and YA with B-ALL is highly effective, being associated with low NRM and not affecting the efficacy of subsequent salvage immunotherapies, including CAR-T cells.

One of the deepest branches in the tree of life separates the Archaea from the Bacteria. These prokaryotic groups have distinct cellular systems including fundamentally different phospholipid membrane bilayers. This dichotomy has been termed the lipid divide and possibly bestows different biophysical and biochemical characteristics on each cell type. Classic experiments suggest that bacterial membranes (formed from lipids extracted from Escherichia coli, for example) show permeability to key metabolites comparable to archaeal membranes (formed from lipids extracted from Halobacterium salinarum), yet systematic analyses based on direct measurements of membrane permeability are absent. Here, we develop a new approach for assessing the membrane permeability of approximately 10 μm unilamellar vesicles, consisting of an aqueous medium enclosed by a single lipid bilayer. Comparing the permeability of 18 metabolites demonstrates that diether glycerol-1-phosphate lipids with methyl branches, often the most abundant membrane lipids of sampled archaea, are permeable to a wide range of compounds useful for core metabolic networks, including amino acids, sugars, and nucleobases. Permeability is significantly lower in diester glycerol-3-phosphate lipids without methyl branches, the common building block of bacterial membranes. To identify the membrane characteristics that determine permeability, we use this experimental platform to test a variety of lipid forms bearing a diversity of intermediate characteristics. We found that increased membrane permeability is dependent on both the methyl branches on the lipid tails and the ether bond between the tails and the head group, both of which are present on the archaeal phospholipids. These permeability differences must have had profound effects on the cell physiology and proteome evolution of early prokaryotic forms. To explore this further, we compare the abundance and distribution of transmembrane transporter-encoding protein families present on genomes sampled from across the prokaryotic tree of life. These data demonstrate that archaea tend to have a reduced repertoire of transporter gene families, consistent with increased membrane permeation. These results demonstrate that the lipid divide demarcates a clear difference in permeability function with implications for understanding some of the earliest transitions in cell origins and evolution.

Purpose: To evaluate the clinicopathological characteristics and the effectiveness of post-operative high-dose-rate (HDR) interventional radiotherapy (IRT - brachytherapy) in managing advanced ocular surface squamous neoplasia (OSSN) and eyelid tumors. Methods: Nineteen patients with advanced malignancies affecting the ocular surface (stage ≥ T2) and eyelids (staging ≥ T3) were enrolled. Post-operative HDR-IRT treatment followed surgery after multidisciplinary discussion. In our series a total dose of 49 Gy was administered in 14 fractions of 3.5 Gy each, 2 doses per day. Local disease control is the study's main outcome. Death rate, total survival, disease-free survival, and toxicity are secondary outcomes. Results: Local recurrence was observed in 4 cases, 2 were conjunctival melanomas and 2 were conjunctival squamous cell carcinoma. The median OS was 56.3 months. The 12, 24 and 36 months survival rate was respectively 100.00% (IQR: 100.00% - 100.00%), 100.00% (IQR: 100.00% - 100.00%), 100.00% (IQR: 100.00% - 100.00%) respectively . The median DFS was 56.3 months. The 12, 24 and 36 months disease survival rate was respectively 85.71% (IQR: 69.21% - 100.00%), 68.57% (IQR: 42.11% - 100.00%), 68.57% (IQR: 42.11% - 100.00%) respectively. In eyelid tumors, madarosis and eyelid abnormalities are the main side effects, while in OSSNs, dry eye symptoms are frequently reported. Conclusion: Postoperative HDR-IRT has been effective in advanced eyelid cancers control. More challenging appears instead an effective treatment of advanced OSSNs, particularly conjunctival melanomas. Multicenter studies are needed to get a larger patient sample and to evaluate different radiotherapy dosages by different histologic and T types of tumors.

ObjectiveDry eye disease (DED) is a condition associated with a myriad of systemic disorders. According to recent preliminary data, axial spondylarthritis (axial-SpA) could represent a new entity associated with DED. Therefore, this study aimed to assess DED in patients with axial SpA by performing quantitative and qualitative specific tests to investigate the potential association between DED and ocular surface damage in patients with axial-SpA and to identify potential variables associated with DED.MethodsA total of 71 patients with axial-SpA who fulfilled the Assessment of SpondyloArthritis International Society (ASAS) classification criteria and 19 healthy controls were enrolled in this study. Both the patients and the controls underwent a complete ocular assessment aimed at evaluating the tear film and ocular surface, which included the Schirmer test, tear break-up time (TBUT), fluorescein staining, and lissamine green staining. The Ocular Surface Disease Index (OSDI) questionnaire was administered to all patients.ResultsDED symptoms were reported in 46 (64.8%) patients and three (15.8%) healthy controls (p = 0.0004). The odds ratio for receiving a diagnosis of axial-SpA based on the presence of dry-eye-related symptoms was 9.2 (95% C.I. 2.72–42.52, p = 0.001). The Schirmer test values of < 6 mm/5 min were observed in 31 (43.7%) patients with axial-SpA and two (10.5%) healthy controls (p = 0.013); a TBUT of

Tarsocrural osteochondrosis (OCD) is a developmental orthopedic disease commonly affecting young Standardbreds, with different fragment localization and size. Clinically, it is characterized by variable synovial effusion in the absence of lameness, whose determinants are ill-defined. We hypothesized that localization and physical characteristics of the osteochondral fragments like dimensions, multifragmentation, and instability influence joint effusion and correlate with synovial markers of cartilage degradation and inflammation. Clinical data, synovial fluid and intact osteochondral fragments were collected from 79 Standardbred horses, aged between 12 and 18 months, operated for tarsocrural OCD. The severity of tarsocrural joint effusion was assessed semi-quantitatively. The osteochondral fragment site was defined radiographically at the distal intermediate ridge of the tibia (DIRT), medial malleolus (MM) of the tibia, and/or lateral trochlear ridge (LTR) of the talus. Size, stability, and arthroscopic appearance (unique or multi-fragmented aspect) of the fragments were determined intra-operatively. Synovial concentrations of C-terminal cross-linked telopeptides of type II collagen (CTX-II), leukotriene B4 (LTB4), and prostaglandin E2 (PGE2) were quantified. Tarsocrural synovial effusion was significantly affected by localization and stability of the fragments, with MM-located and unstable fragments being associated with highest joint effusion. Concentrations of CTX-II, LTB4, and PGE2 positively correlated with the severity of synovial effusion. This study underlines characteristics of the osteochondral fragments determining higher synovial effusion in OCD-affected tarsocrural joints and suggests both inflammation and extra-cellular matrix degradation are active processes in OCD pathology.

In figure 2, a typo of 'MES > 500 m' was introduced to the third y-axis label from the top when edited to meet house style. This label has been corrected to 'MES < 500 m' in the updated version of figure 2, below. (Figure presented).

Transporter proteins are a vital interface between cells and their environment. In nutrient-limited environments, microbes with transporters that are effective at bringing substrates into their cells will gain a competitive advantage over variants with reduced transport function. Microbial ammonium transporters (Amt) bring ammonium into the cytoplasm from the surrounding periplasm space, but diagnosing Amt adaptations to low nutrient environments solely from sequence data has been elusive. Here, we report altered Amt sequence amino acid distribution from deep marine samples compared to variants sampled from shallow water in two important microbial lineages of the marine water column community-Marine Group I Archaea (Thermoproteota) and the uncultivated gammaproteobacterial lineage SAR86. This pattern indicates an evolutionary pressure towards an increasing dipole in Amt for these clades in deep ocean environments and is predicted to generate stronger electric fields facilitating ammonium acquisition. This pattern of increasing dipole charge with depth was not observed in lineages capable of accessing alternative nitrogen sources, including the abundant alphaproteobacterial clade SAR11. We speculate that competition for ammonium in the deep ocean drives transporter sequence evolution. The low concentration of ammonium in the deep ocean is therefore likely due to rapid uptake by Amts concurrent with decreasing nutrient flux.

The interactions between a virus and its host vary in space and time and are affected by the presence of molecules that alter the physiology of either the host or the virus. Determining the molecular mechanisms at the basis of these interactions is paramount for predicting the fate of bacterial and phage populations and for designing rational phage-antibiotic therapies. We study the interactions between stationary phase Burkholderia thailandensis and the phage ΦBp-AMP1. Although heterogeneous genetic resistance to phage rapidly emerges in B. thailandensis, the presence of phage enhances the efficacy of three major antibiotic classes, the quinolones, the beta-lactams and the tetracyclines, but antagonizes tetrahydrofolate synthesis inhibitors. We discovered that enhanced antibiotic efficacy is facilitated by reduced antibiotic efflux in the presence of phage. This new phage-antibiotic therapy allows for eradication of stationary phase bacteria, whilst requiring reduced antibiotic concentrations, which is crucial for treating infections in sites where it is difficult to achieve high antibiotic concentrations.

La conversazione tra studenti e docenti è un tipo di discorso istituzionale, caratterizzato da un’asimmetria relazionale, basata sui ruoli sociali e sulla diversa distribuzione del sapere. Questo studio si occupa del livello di analisi pragmalinguistico, concentrandosi sulla formulazione dell’atto linguistico di richiesta. Lo studio presenta dati su come gli studenti universitari formulano le richieste e su come le modificano oralmente quando parlano con un professore. Un totale di 398 minuti di conversazione, 92 prodotti da parlanti nativi italiani (PN) e 196 eseguiti da parlanti non nativi italiani (PNN), sono stati analizzati in relazione al tipo e alle prospettive di richiesta, alla quantità e al tipo di mitigazione. I risultati dello studio mostrano che sia gli studenti italiani che quelli internazionali tendono a organizzare conversativamente le richieste secondo scelte preferenziali, in termini di strategie, prospettive e mitigazione delle richieste, riflettendo l'asimmetria dei ruoli studente/insegnante. Tuttavia, le performance degli studenti internazionali sono caratterizzate da fenomeni di verbosità. Speaking at university: a pragmalinguistic analysis of conversations between professors and Italian-speaking and international students The conversation between students and professors is a type of institutional talk, characterized by relational asymmetry, based on social roles and different distribution of knowledge. This study concerns with the pragmalinguistic level of analysis, focusing on the formulation of the linguistic act of request. The study presents data on how academic students formulate requests and how they orally modify them when they talk with a professor. A total of 398 minutes of conversation, 192 produced by Italian native speakers (PN) and 196 performed by Italian non-native speakers (PNN), were analyzed with regard to request type and perspectives, amount and type of mitigation. Findings of the study show that both Italian and international students tend to conversationally organize requests according to preferential choices, in terms of the strategies, perspectives and mitigation of requests, reflecting the asymmetry of student/teacher roles. Nevertheless, the performances of international students are characterized by verbosity phenomena.

Mucosal-associated invariant T (MAIT) cells are innate-like T-cells implicated in the response to fungal and bacterial infections. Their contribution to restoring T-cell immunity and influencing hematopoietic stem cell transplant (HSCT) outcomes remains poorly understood. We retrospectively studied MAIT-cell recovery in 145 consecutive children and young adults with hematological malignancies undergoing allo-HSCT, between April/2019 and May/2022, from unrelated matched donor (MUD, n=52), with standard graft-versus-host-disease (GvHD) prophylaxis, or HLA-haploidentical (Haplo, n=93) donor after in vitro αβT/CD19-cell depletion, without post-HSCT pharmacological prophylaxis. With a median follow-up of 33 months (12-49), overall survival (OS), disease-free survival (DFS) and non-relapse mortality (NRM) were 79.5%, 72% and 7%, respectively; GvHD-free, Relapse-free Survival (GRFS) was 63%, while cumulative incidence of relapse was 23%. While WWT-cells reconstituted 1-2 years post-HSCT, MAIT-cells showed delayed recovery and prolonged functional impairment, characterized by expression of activation (CD25, CD38), exhaustion (PD1, TIM3) and senescence (CD57) markers, and suboptimal ex vivo response. OS, DFS and NRM were not affected by MAIT-cells. Interestingly, higher MAIT-cells at day+30 correlated with higher incidence of grade II-IV acute GvHD (19% vs 7%, p=0.06). Furthermore, a greater MAIT-cell count tended to be associated with a higher incidence of chronic GvHD (17% vs 6%, p=0.07) resulting in lower GRFS (55% vs 73%, p=0.05). Higher MAIT-cells also correlated with greater cytomegalovirus (CMV) reactivation and lower late blood stream infections (BSI) (44% vs 24%, p=0.02 and 9% vs 18%, p=0.08, respectively). Future studies are needed to confirm the impact of early MAIT-cell recovery on cGvHD, CMV reactivation and late BSI.

White dwarfs are the remnants of stars not massive enough to become supernovae. This review explores the concept of strange dwarfs, a unique class of white dwarfs that contain cores of strange quark matter. Strange dwarfs have different sizes, masses, and evolutionary paths with respect to white dwarfs. They might form through the accumulation of normal matter on strange quark stars or by the capture of strangelets. The stability of strange dwarfs has been debated, with initial studies suggesting stability, while later analyses indicated potential instability. This review revisits these discussions, focusing on the critical role of boundary conditions between nuclear and quark matter in determining stability. It also offers insights into their formation, structure, and possible detection in the universe.

Abstract The well-being of students and staff directly affects their output and efficiency. This study presents the results of two focus groups conducted in 2022 within a two-phase project led by the Applied Biomedical and Signal Processing Intelligent e-Health Lab, School of Engineering at the University of Warwick, and British Telecom within “The Connected Campus: University of Warwick case study” program. The first phase, by involving staff and students at the University of Warwick, aimed at collecting preliminary information for the subsequent second phase, about the feasibility of the use of Artificial Intelligence and Internet of Things for well-being support on Campus. The main findings of this first phase are interesting technological suggestions from real users. The users helped in the design of the scenarios and in the selection of the key enabling technologies which they considered as the most relevant, useful and acceptable to support and improve well-being on Campus. These results will inform future services to design and implement technologies for monitoring and supporting well-being, such as hybrid, minimal and even intrusive (implantable) solutions. The user-driven co-design of such services, leveraging the use of wearable devices and Artificial Intelligence deployment will increase their acceptability by the users.