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Introduction: Responses to first-line programmed cell death protein 1 inhibition vary among patients with metastatic NSCLC and a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) greater than or equal to 50%. We previously reported improved clinical outcomes to first-line programmed cell death protein 1 inhibition in patients with metastatic NSCLC with a PD-L1 TPS of greater than or equal to 90% versus 50% to 89% in a pilot study. Here, we report the three-year survival with first-line pembrolizumab and cemiplimab in two large independent cohorts of patients with PD-L1 TPS greater than or equal to 90% versus 50% to 89% and characterize genomic and immunophenotypic differences between these PD-L1 expression groups, which were largely unknown. Methods: We analyzed three-year outcomes of the following two independent cohorts: (1) a multicenter cohort of patients from four academic centers in the United States treated with pembrolizumab and (2) EMPOWER-Lung 1, randomized, phase III trial comparing first-line cemiplimab with chemotherapy. Tumor genomic profiling and multiplexed immunofluorescence were performed to evaluate genomic and immunophenotypic correlates of very high PD-L1 expression. Results: At three years of follow-up, progression-free survival (hazard ratio [HR], 0.69; p < 0.001) and overall survival (HR, 0.70; p < 0.01) to first-line commercial pembrolizumab were significantly improved in patients with a PD-L1 TPS greater than or equal to 90% versus 50% to 89%. In the EMPOWER-Lung 1, patients assigned to the cemiplimab arm with a PD-L1 TPS greater than or equal to 90% also had significant improvements in progression-free survival (HR, 0.53; p < 0.0001) and overall survival (HR, 0.63; p = 0.007) compared with those with a PD-L1 of 50% to 89%. Tumor genomic profiling of 553 NSCLC samples revealed that mutations in STK11 and SMARCA4 were significantly more frequent in tumors with a PD-L1 TPS of 50% to 89% compared with those with a PD-L1 TPS greater than or equal to 90% (Q < 0.15), whereas BRCA2 was enriched in NSCLC samples with a PD-L1 TPS greater than or equal to 90% (Q < 0.15). Multiplexed immunofluorescence on 93 NSCLC samples identified higher intratumoral CD8+PD1+ T cells (p = 0.02) in tumors with PD-L1 TPS greater than or equal to 90% versus 50% to 89%. Conclusion: Pembrolizumab and cemiplimab were found to have long-term survival benefit and favorable genomic and immunophenotypic profile in patients with advanced NSCLC with PD-L1 TPS greater than or equal to 90% compared with TPS 50% to 89%.

Schizophrenia spectrum disorders (SSD) are associated with pervasive cognitive impairments, including deficits in decision-making under risk. However, there is inconclusive evidence regarding specific mechanisms underlying altered decision-making patterns. In this study, participants (33 SSD and 28 non-SSD) completed the Columbia Card Task, an explicit risk-taking task, to better understand risk preference and adjustment in dynamic decision-making. We found that while there is no group difference in overall risk-taking, risk preference, or optimal decision-making, risk adjustment to contextual factors (e.g., loss probability) is blunted in SSD. We also found associations between risk-taking/suboptimal decision-making and disorganized symptoms, excited symptoms, and role functioning, but no associations between decision-making and working memory. These results suggest that during a complex, dynamic risk-taking task, individuals with SSD exhibit less adaption to changing information about risk, which may reflect risk imperception.

Individuals diagnosed with schizophrenia spectrum disorders (SSDs) often demonstrate alterations in the Theory of Mind Network (ToM-N). Here, in this proof-of-concept, single-arm pilot study, we investigate whether participants with an SSD (N = 7) were able to learn to volitionally control regions of the ToM-N (dorso/middle/ventromedial prefrontal cortex [D/M/VMPFC], left temporoparietal junction [LTPJ], precuneus [PC], right superior temporal sulcus [RSTS], and right temporoparietal junction [RTPJ]) using real-time fMRI neurofeedback (rtfMRI-NF). Region-of-interest analyses demonstrate that after neurofeedback training, participants were able to gain volitional control in the following ToM-N brain regions during the transfer task, where no active feedback was given: right temporoparietal junction, precuneus, and dorso/ventromedial prefrontal cortex (neurofeedback effect Fs > 6.17, ps

Metallosis is an uncommon but relevant phenomenon in total hip arthroplasty involving trunnionosis of the contact surfaces. It is understood as the release and deposition of metallic particles (chromium, cobalt and tungsten alloys) in the adjacent tissue, causing inflammation, chronic pain, osteolysis and even implant failure. This reaction brings about new arthroplasty revision surgeries that often present a challenge to the orthopaedic surgeon and an increase in morbimortality. In this report, we present the case of a 61-year-old female patient with a left sub-capital hip fracture who underwent total hip arthroplasty with continued post-operative pain and dysfunction. A revision arthroplasty was performed 16 months later showing abundant metallosis of the surrounding tissues in addition to dissociation of the polyethylene liner with no apparent cup damage, for which head and liner exchange was performed. Due to failure of symptom improvement, a new revision arthroplasty was performed 6 months later consisting of a dual mobility cup replacement and a ceramic-on-ceramic bearing couple. Although this complication rarely affects metal-on-polyethylene contact surfaces, it has been consistently demonstrated that it is not exclusive to metal-on-metal contact surfaces, highlighting the importance of a collaborative approach between surgeons and implant registries to guide operative treatment as well as understanding component design.

A semi-analytical procedure is presented for predicting the complete flexural response of partially interacting steel–concrete composite beams up to failure. The governing equation of the Euler–Bernoulli beam theory is solved wherein concrete, steel and the shear connectors joining the concrete slab to the steel beam are assumed to have nonlinear stress-deformation relationships. The adopted constitutive relationship for the connectors allows for partial or full composite action. The solution is applicable to beams and one-way slabs subjected to concentrated or uniform load and/or their combination. The governing equation is numerically solved by satisfying the equilibrium and compatibility requirements along the member. For the reinforced concrete part of the composite beam, a nonlinear moment–curvature relationship is developed that accounts for concrete nonlinearity in compression and for cracking and tension-stiffening in tension as well as for steel reinforcement nonlinearity. The steel profile is assumed to have a bilinear elasto–plastic strain-hardening moment–curvature relationship. Comparison of the proposed model results with the corresponding experimental load–deflection curves and interfacial shear–slip curves of several beams tested by others shows good agreement. The relative simplicity, efficiency and easy application of the present solution make it possible to accurately predict the failure load, interfacial slip and full nonlinear response of partially interacting composite beams.

Knowledge of the long-term performance of adhesive connections is undoubtedly of paramount importance to enable their deployment in civil, mechanical, and other engineering applications. Over time, adverse environmental conditions can strongly influence the performance of adhesive joints leading to a progressive deterioration of their initial mechanical properties. The use of adhesive connections for secondary structures in offshore applications is a technology that allows for the rapid creation of structural members that, however, cannot ignore the influence of hydrothermal effects on mechanical performance due to environmental conditions. In this context, the investigation of the hygrothermal durability of adhesive connections was undertaken through an extensive experimental programme. More specifically, 130 cylindrical steel joints bonded with a commercially epoxy resin for structural applications were tested in Mode I using an Arcan-modified device. Prior to test, the specimens were placed in climatic ovens capable of combining the effects of temperature and humidity for approximately 320 days. In addition, the glass transition temperature, Tg, was assessed by employing the differential scanning calorimeter (DSC) technique to correctly define the experimental ageing conditions. The experimental results show how ageing conditions influence the mechanical properties of the epoxy resin investigated. Finally, some predictive formulations are proposed to calculate the loss of strength of adhesive joints over time.

Cutaneous bacillary angiomatosis (cBA) is a vascular proliferative disorder due to Bartonella henselae or Bartonella quintana that has been mostly described in people living with HIV. Since cBA is considered to be rare in hosts not affected by major immunosuppression, it could be underdiagnosed in this population. Moreover, antimicrobial treatment of cBA has been poorly validated, thus reporting experiences on this clinical entity is important. We reported a challenging and well-characterized case of an Italian 67-year-old gentleman without a history of major immunocompromizing conditions, although he was affected by conditions that can be associated with impaired immune function. The patient reported herein was diagnosed after a long time since the initiation of symptoms and was successfully treated with combined antibiotic therapy including macrolides and quinolones under the guidance of molecular test results. Physicians should consider cBA as a possible manifestation of Bartonella spp. Infection in patients not suffering from major immunocompromizing conditions. Until evidence-based guidelines are available, molecular tests together with severity and extension of the disease can be useful to personalize the type of treatment and its duration.

Introduction: Patients with metastatic NSCLC (mNSCLC) treated with immune checkpoint inhibitors in clinical practice may often not meet the strict inclusion criteria of clinical trials. Our aim was to assess the trial eligibility of patients with mNSCLC treated with pembrolizumab monotherapy in real-world and to compare the outcome of “trial-ineligible” and “potentially trial-eligible” patients. Methods: Data from the prospective, clinical research platform CRISP were used to compare patient characteristics, treatment, and outcome of patients with programmed cell death-ligand 1 tumor proportion score greater than or equal to 50% tumors treated with pembrolizumab monotherapy who are deemed either “potentially trial-eligible” or “trial-ineligible” according to inclusion and exclusion criteria of the registrational studies (KEYNOTE-024 and -042). Results: Of 746 patients included, 343 patients (46.0%) were classified as “trial-ineligible” and had significantly worse outcomes compared with “potentially trial-eligible” patients (n = 403, 54.0%): median progression-free survival: 6.2 (95% confidence interval [CI]: 5.2–8.4) versus 10.3 (95% CI: 8.4–13.8) months, hazard ratio (trial-ineligible versus potentially trial-eligible) of 1.43 (95% CI: 1.19–1.72), p less than 0.001; median overall survival: 15.9 (95% CI: 11.4–20.3) versus 25.3 (95% CI: 19.8–30.4) months, hazard ratio of 1.36 (95% CI: 1.10–1.67), p equals 0.004. Conclusions: Our data reveal that a considerable proportion of patients with mNSCLC are not eligible to participate in a clinical trial and were found to have worse outcomes than potentially trial-eligible patients, whose outcomes were comparable with those obtained from pivotal clinical trials. This is of substantial clinical relevance for physicians discussing outcomes to be expected with their patients and stresses the need for real-world effectiveness analyses.

The study measured the levels of azoxystrobin (AZ) and thiabendazole (TBZ) in wallboards and metabolite levels of these fungicides in children. The paper covering of wallboard samples contained a higher concentration of AZ and TBZ than the gypsum core, and similar amounts (w/w) of these two fungicides were present in the samples. These data suggest that commercial products containing a 1:1 (w/w) amount of AZ and TBZ, such as Sporgard® WB or Azo Tech™, were applied to the wallboard paper. This is the first detection of TBZ in mold-and-mildew resistant wallboards. The TBZ metabolite, 5OH-TBZ, was detected in 48% of urine samples collected from children aged 40–84 months, and was co-detected with AZ-acid, a common AZ metabolite, in 37.5% of the urine samples. The detection frequency of 5OH-TBZ was positively associated with the detection frequency of AZ-acid. These findings suggest that certain types of wallboards used in homes and commercial buildings may be a potential source of co-exposure to AZ and TBZ in humans.

Summary: Functional precision oncology—a strategy based on perturbing primary tumor cells from cancer patients—could provide a road forward for personalized treatment. Here, we present a comprehensive protocol covering generation and culture of patient-derived colorectal organoids, isolation and expansion of tumor-infiltrating lymphocytes (TILs), and isolation and culture of peripheral blood mononuclear cells (PBMCs). With this protocol, samples fulfilling the demands for performing multi-omics analysis, e.g., RNA sequencing (RNA-seq), whole-exome sequencing (WES), single-cell RNA sequencing (scRNA-seq), and (phospho-)proteomics, can be generated.For complete details on the use and execution of this protocol, please refer to Plattner et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Cervical cancer is one of the most common types of cancer among women and is largely preventable with regular screening using Papanicolau (Pap) tests. In Canada, all provinces have regular screening programs, although with slightly differing recommendations. Previous research has found that immigrant women, who are a large proportion of the Canadian population, are at higher risk of being under-screened, or non-adherent to the recommended screening frequency.Using data from the 2017 Canadian Community Health Survey, this study examined: (1) the extent to which immigration status and time since immigration are associated with Pap test adherence in Ontario, and (2) predictors of Pap test adherence for immigrants and Canadian born populations in Ontario, Canada’s most populous province, with a focus on the role of racial or ethnic identity among immigrants. Estimates of 3-year test adherence were 71.3 % (95 %CI: 66.9–75.7) among immigrant women and 75.4 % (95 %CI: 73.1–77.1) among non-immigrant women. Recent immigrants (6–10 years in Canada) had lower adherence (63.5 %, 95 %CI: 48.0–80.0). Logistic regression models found that immigrant women had lower adherence than Canadian-born women, controlling for age, household income, education, and having a primary care physician. Subgroup analysis found that South Asian immigrant women were least likely to be adherent.These results support targeted programming to increase screening adherence among recent immigrants and raise concerns regarding potential barriers to screening. Data that allow better disaggregation of racial and ethnic identities are important for better understanding the potential implications of these patterns for racial inequities in health.

Summary: Precision oncology approaches for patients with colorectal cancer (CRC) continue to lag behind other solid cancers. Functional precision oncology—a strategy that is based on perturbing primary tumor cells from cancer patients—could provide a road forward to personalize treatment. We extend this paradigm to measuring proteome activity landscapes by acquiring quantitative phosphoproteomic data from patient-derived organoids (PDOs). We show that kinase inhibitors induce inhibitor- and patient-specific off-target effects and pathway crosstalk. Reconstruction of the kinase networks revealed that the signaling rewiring is modestly affected by mutations. We show non-genetic heterogeneity of the PDOs and upregulation of stemness and differentiation genes by kinase inhibitors. Using imaging mass-cytometry-based profiling of the primary tumors, we characterize the tumor microenvironment (TME) and determine spatial heterocellular crosstalk and tumor-immune cell interactions. Collectively, we provide a framework for inferring tumor cell intrinsic signaling and external signaling from the TME to inform precision (immuno-) oncology in CRC.

Is there a way improve our ability to understand the minds of others? Towards addressing this question, here, we conducted a single-arm, proof-of-concept study to evaluate whether real-time fMRI neurofeedback (rtfMRI-NF) from the temporo-parietal junction (TPJ) leads to volitional control of the neural network subserving theory of mind (ToM; the process by which we attribute and reason about the mental states of others). As additional aims, we evaluated the strategies used to self-regulate the network and whether volitional control of the ToM network was moderated by participant characteristics and associated with improved performance on behavioral measures. Sixteen participants underwent fMRI while completing a task designed to individually-localize the TPJ, and then three separate rtfMRI-NF scans during which they completed multiple runs of a training task while receiving intermittent, activation-based feedback from the TPJ, and one run of a transfer task in which no neurofeedback was provided. Region-of-interest analyses demonstrated volitional control in most regions during the training tasks and during the transfer task, although the effects were smaller in magnitude and not observed in one of the neurofeedback targets for the transfer task. Text analysis demonstrated that volitional control was most strongly associated with thinking about prior social experiences when up-regulating the neural signal. Analysis of behavioral performance and brain-behavior associations largely did not reveal behavior changes except for a positive association between volitional control in RTPJ and changes in performance on one ToM task. Exploratory analysis suggested neurofeedback-related learning occurred, although some degree of volitional control appeared to be conferred with the initial self-regulation strategy provided to participants (i.e., without the neurofeedback signal). Critical study limitations include the lack of a control group and pre-rtfMRI transfer scan, which prevents a more direct assessment of neurofeedback-induced volitional control, and a small sample size, which may have led to an overestimate and/or unreliable estimate of study effects. Nonetheless, together, this study demonstrates the feasibility of training volitional control of a social cognitive brain network, which may have important clinical applications. Given the study's limitations, findings from this study should be replicated with more robust experimental designs.

We report the case of a 71-year-old woman diagnosed with giant cell arteritis with bilateral subclavian and axillary obstruction and severe arm claudication that occurred 3 months earlier and was non-regressed after corticosteroids. Before possible revascularization, the patient was initiated to a personalized home-based graded exercise program including walking, hand-bike pedaling, and muscle strength training. During the 9 months of treatment, the patient progressively improved radial pressure values (10 to 85 mmHg), hand temperature values by infrared-thermography (+2.1 °C), arm endurance, and forearm muscle oxygenation by near-infrared spectroscopy. Home-based graded exercise proved to be a noninvasive option for upper limb claudication.

Objective: In brown adipose tissue (iBAT), the balance between lipid/glucose uptake and lipolysis is tightly regulated by insulin signaling. Downstream of the insulin receptor, PDK1 and mTORC2 phosphorylate AKT, which activates glucose uptake and lysosomal mTORC1 signaling. The latter requires the late endosomal/lysosomal adaptor and MAPK and mTOR activator (LAMTOR/Ragulator) complex, which serves to translate the nutrient status of the cell to the respective kinase. However, the role of LAMTOR in metabolically active iBAT has been elusive. Methods: Using an AdipoqCRE-transgenic mouse line, we deleted LAMTOR2 (and thereby the entire LAMTOR complex) in adipose tissue (LT2 AKO). To examine the metabolic consequences, we performed metabolic and biochemical studies in iBAT isolated from mice housed at different temperatures (30 °C, room temperature and 5 °C), after insulin treatment, or in fasted and refed condition. For mechanistic studies, mouse embryonic fibroblasts (MEFs) lacking LAMTOR 2 were analyzed. Results: Deletion of the LAMTOR complex in mouse adipocytes resulted in insulin-independent AKT hyperphosphorylation in iBAT, causing increased glucose and fatty acid uptake, which led to massively enlarged lipid droplets. As LAMTOR2 was essential for the upregulation of de novo lipogenesis, LAMTOR2 deficiency triggered exogenous glucose storage as glycogen in iBAT. These effects are cell autonomous, since AKT hyperphosphorylation was abrogated by PI3K inhibition or by deletion of the mTORC2 component Rictor in LAMTOR2-deficient MEFs. Conclusions: We identified a homeostatic circuit for the maintenance of iBAT metabolism that links the LAMTOR-mTORC1 pathway to PI3K-mTORC2-AKT signaling downstream of the insulin receptor.

Higher-order chromatin structures have functional impacts on gene regulation and cell identity determination. Using high-throughput sequencing (HTS)-based methods like Hi-C, active or inactive compartments and open or closed topologically associating domain (TAD) structures can be identified on a cell population level. Recently developed high-resolution three-dimensional (3D) molecular imaging techniques such as 3D electron microscopy with in situ hybridization (3D-EMSIH) and 3D structured illumination microscopy (3D-SIM) enable direct detection of physical representations of chromatin structures in a single cell. However, computational analysis of 3D image data with explainability and interpretability on functional characteristics of chromatin structures is still challenging. We developed Extracting Physical-Characteristics from Images of Chromatin Structures (EPICS), a machine-learning based computational method for processing high-resolution chromatin 3D image data. Using EPICS on images produced by 3D-EMISH or 3D-SIM techniques, we generated more direct 3D representations of higher-order chromatin structures, identified major chromatin domains, and determined the open or closed status of each domain. We identified several high-contributing features from the model as the major physical characteristics that define the open or closed chromatin domains, demonstrating the explainability and interpretability of EPICS. EPICS can be applied to the analysis of other high-resolution 3D molecular imaging data for spatial genomics studies. The R and Python codes of EPICS are available at https://github.com/zang-lab/epics.

Pleuropulmonary blastoma (PPB) is a rare primitive malignant lung cancer that occurs in pediatric age. Its main differential diagnosis is congenital cystic pulmonary malformation (CPAM).A 30-day-old infant with respiratory failure obtained a chest x-ray and a computed tomography scan (CT) which revealed hypertensive pneumothorax with multifocal bilateral cysts. After thoracic drainage, the patient underwent multiple thoracoscopic pulmonary resections. The first histological diagnosis was of type 2 CPAM.During the radiological follow-up, an increase in the number and dimension of the lesions was detected. Thus, a histological revision was performed, leading to the diagnosis of type I PPB, at nine months. The patient subsequently underwent chemotherapy.At the five-year follow-up appointment, chest magnetic resonance (MR) and CT scans showed a dimensional increase in size of the lesions, with the risk of recurrent pneumothorax. An upper right lobectomy and wedge resection of the residual cysts were performed.Control MR scans showed normalization of the lung parenchyma and the patient showed substantial clinical improvement.

High quality factor (Q) optical biosensors find many applications, from environmental monitoring to food safety and clinical diagnostics. In particular, bound states in the continuum (BICs) can be implemented in planar large-area nanostructures for facile microfluidic integration and straightforward interrogation. In this paper the interference leading to the Friedrich–Wintgen type BIC is engineered to make high-Q flat dispersion bands over a large set of interrogation angles. A thorough numerical study is first carried out to adapt the process to an aptasensor scheme. Then, experiments are carried out tracking the high-Q bands evolution forming around the avoided crossing point as a function of the interaction of ochratoxyn A with the bioprobe. An excellent LOD of 2.3 pg/mL is achieved, and a large FOM > 160 RIU−1 is estimated despite the sub-monolayer adsorbate film of thickness ∼ 10 nm. The proposed sensing architecture can be extended to other mycotoxins and small molecules, finding application in many fields for monitoring physical and biochemical processes.

Background: Oesophageal changes and injuries were recorded after atrial fibrillation(AF) ablation procedures. The reduction of power in the posterior left atrial(LA) wall(closest to the oesophagus) and the monitoring of temperature in the oesophagus(OE) reduced oesophageal injuries. The intracardiac-echocardiography(ICE) with a Cartosound module provides two-dimensional imaging (2D) to assess detailed cardiac anatomy and its relationship with the OE. The aim of this study was to highlight the safety and feasibility of 3D-reconstruction of the oesophageal course in left atrial catheter ablation(CA) procedures without OE temperature probe or quadripolar catheter to guide ICE OE reconstruction. Methods: 180 patients(PT) underwent left atrial ablation. AF ablation were 125(69.5%); incisional left atrial tachycardias(IAFL) were 37(20.6%); left atrial tachycardias(LAT) were 19(10.6%). The LA and pulmonary vein anatomies were rendered by traditional electroanatomic mapping(EAM) and merged with an ICE anatomic map. In 109 PT ICE imaging was used to create a geometry of the OE(group A). A quadripolar catheter was used in 71 PT to show OE course associated to ICE(group B). Results: Ablation energy delivery was performed outside the broadest OE anatomy borders. The duration of procedures was longer in group B vs group A Fluoroscopy time was lower in Group A than Group B(Group A 7 ± 3.2 vs 19.2 ± 2.4 min; p

Syringe pumps are very useful tools to ensure a constant and pulsation-free flow rate, however usability is limited to batch processes. This article shows an open-source method for manufacturing a push pull syringe pump, valid for continuous processes, easy to build, low-cost and programmable.The push–pull syringe pump (PPSP) is driven by an Arduino nano ATmega328P which controls a NEMA 17 in microstepping via the A4988 stepper driver. The Push-Pull Syringe Pump setup is configurable by means of a digital encoder and an oled screen programmed using C ++. A PCB was designed and built to facilitate the assembly of the device. The continuous flow is guaranteed by four non-return valves and a dampener, which has been sized and optimized for use on this device. Finally, tests were carried out to evaluate the flow rates and the linearity of the flow. The device is achievable with a cost of less than 100 €.

The main objective of this research is to fabricate porous mechanical-tuned (low elastic modulus and high strength) Ti-based composites with improved bioactivity for orthopaedic applications. Another objective is to demonstrate the potential of microwave sintering and temporary space alloying technique to synthesize porous Ti-based composites. In this study, porous Ti50Nb50−xHAx (x = 0, 10 and 20) composite was fabricated for orthopaedic applications using a powder metallurgical and rapid microwave sintering (PM-RMS) process. Effects of key PM-RMS parameters on the structural porosity, compressive strength, and elastic modulus of built composite were then analysed. The microstructure, pore characteristics, and mechanical properties were investigated in detail. Using high hydroxyapatite (HA) content (20%), short sintering time (5 min), and high compacting pressure (200 MPa) appears to be the best condition among those studied in terms of yielding a high degree of structural porosity (21%) and low elastic modulus (25 GPa) in the sintered composite. Since size of pores in the synthesized composite is in the range of 20–30 μm, structural porosity not only reduces elastic modulus but also enhances bio-activity of sintered composite. The combination of highly porous structure, low elastic modulus, high compressive strength, improved corrosion resistance, and enhanced bioactivity makes porous Ti-Nb-HA composites fabricated by microwave sintering process potential and promising candidates for orthopedic applications. Keywords: Orthopaedic implants, Porous Ti50Nb50−xHAx composite, Rapid microwave sintering, Porosity, Compressive strength, Elastic modulus

A male patient, 40 years of age, arrived at our Institute with diffuse abdominal tenderness, right flank pain, hematuria and early stage of hemorrhagic shock with anemia and initial hypotension. The immediate clinical history revealed no significant previous trauma, only subsequently was reported inconstant pain in the right flank for 4–5 days with pallor and asthenia, signs and symptoms that the patient had not investigated. Abdominal CT scan with angiographic evaluation was performed showing right kidney mass and perirenal fluid collection by blood component. Immediate nephrectomy was performed and histopathological and further immunohistochemical study, revealed the epithelioid variant of angiomyolipoma.

The zinc complexes 1 and 2 bearing chelating phosphorous based pincer ligands were found to catalyze the ring-opening copolymerization of L-lactide and ε-caprolactone in the melt at 110 °C to obtain a series of random copolymers in which the monomer distributions were coherent with the monomer ratio in the feed. All the obtained copolymers showed high molecular masses with monomodal and moderately narrow distributions. The thermal properties of the achieved copolymers (Tg, glass transition temperature, and Tm, melting temperature) were strongly dependent on their composition. A linear dependence of Tg with molar percentage of lactide in the copolymers was observed over a temperature range from -59 °C (pure polycaprolactone) to 55 °C (pure polylactide).

Background and Objective: Models to count blood cells have been extensively studied, but there are very few for classifying potential blood cells. This is crucial for verifying that what these systems are counting are in fact the correct object of interest. Furthermore, we have very little insight into which features are important for differentiating these classes in computational models.Methods:This paper presents a competitive solution for classifying red blood cells, white blood cells, and platelets from each other.Results:We were able to achieve an overall classification rate of about 99% and outperformed convolutional neural networks by about 10% by using the Blood Cell Count Dataset with a support vector machine, a polynomial kernel, and interpretable and explainable features. Further, we are also able to identify that the important features for classifying the three classes are the number of corners, the proportion of the area of the cell over the relevant area the cell occupies, the major axis relative length of the cell, and the relevant area surrounding the cell.Conclusion: We built a model for blood cell classification that is more interpretable and explainable while also outperforming the state-of-the-art.

Introduction: The development of immune-related adverse events (irAEs) has been associated with improved efficacy of immune checkpoint inhibitors in patients with urothelial cancer, melanoma, and NSCLC. Whether this association exists in patients with SCLC is currently unknown. Methods: We conducted a multicenter retrospective study to evaluate the relationship between irAEs and immunotherapy efficacy in SCLC. To account for the lead-time bias resulting from the time-dependent nature of irAEs, the development of irAEs was considered as a time-varying covariate in univariate and multivariate Cox proportional hazard models. Results: Of the 183 patients treated with immunotherapy, 73 (39.9%) experienced at least one irAE. A total of 42 patients (22.9%) had grade 1 to 2 irAEs, whereas 31 patients (16.9%) had grade 3 to 4 irAEs. The median time of onset to the first irAE was 24 days (interquartile range: 14–55). The baseline clinicopathologic features were well-balanced between patients with and without irAEs. At a median follow-up of 24 months (95% confidence interval [CI]: 17.0–31.6), the median progression-free survival was significantly longer in the irAE group than the non-irAE group (3.8 versus 1.3 mo, p < 0.0001). The median overall survival was also significantly longer among patients with irAEs than patients without irAEs (13.8 versus 2.9 mo, p < 0.0001). When analyzed as a time-varying covariate, the development of irAEs was associated with a significant improvement in progression-free survival (hazard ratio: 0.44 [95% CI: 0.29–0.66], p < 0.001) and overall survival (hazard ratio: 0.47 [95% CI: 0.32–0.71], p < 0.001) in multivariate models. Conclusions: The development of irAEs is associated with improved clinical outcomes for immunotherapy in patients with advanced SCLC.

Composite materials for strengthening existing structural members represent a valid alternative to the traditional strengthening techniques. In particular, Fabric Reinforced Cementitious Matrix (FRCM) composites have been successfully employed to strengthen existing reinforced concrete and masonry structures.Among the different FRCM composites available on the market, the attention of the authors was recently focalized on systems composed of high tensile strength steel cords embedded in a cementitious matrix (systems also well known as Steel Reinforced Grout, SRG).The main failure mechanism of FRCM is represented by the debonding at the matrix-fiber interface. Therefore, the study of the bond behavior of FRCM composites is a key topic to develop reliable design procedures. In this paper, the applicability of different existing bond-slip interface models for FRP-concrete interface to SRG system is studied. The different parameters characterizing the models are calibrated by using an experimental database available by the authors and including results of direct single-lap shear tests on concrete prisms bonded to SRG strips. All the models are calibrated using a classical technique which minimizes the difference between the measured and computed interfacial shear stress values at different slip levels. The results indicate that all the models predict relatively well the slope of the ascending branch of the shear stress-slip curve, but they give substantially different descending branch profiles.The calibrated models are, then, compared with some other laws proposed in the literature for PBO and basalt FRCM systems; some of them are also implemented within a numerical procedure developed by the authors for the estimation of both the maximum axial stress at debonding and the corresponding effective bonded length of the SRG strip. The comparison with the experimental data has allowed for verifying the accuracy of the calibrated bond-slip models.

Automatic event detection from images or wearable sensors is a fundamental step towards the development of advanced sport analytics and broadcasting software. However, the collection and annotation of large scale sport datasets is hindered by technical obstacles, cost of data acquisition and annotation, and commercial interests. In this paper, we present the Soccer Event Recognition (SoccER) data generator, which builds upon an existing, high quality open source game engine to enable synthetic data generation. The software generates detailed spatio-temporal data from simulated soccer games, along with fine-grained, automatically generated event ground truth. The SoccER software suite includes also a complete event detection system entirely developed and tested on a synthetic dataset including 500 min of game, and more than 1 million events. We close the paper by discussing avenues for future research in sports event recognition enabled by the use of synthetic data.

Summary: Background: Host vulnerabilities associated with acute malnutrition could facilitate the ability of specific enteric pathogens to cause diarrhoea and associated mortality. Using data from the Global Enteric Multicenter Study, we assessed whether acute malnutrition modifies the association between common enteric pathogens and moderate-to-severe diarrhoea, and whether associations between enteric pathogens and death were modified by acute malnutrition. Methods: Children with moderate-to-severe diarrhoea and age-matched and community-matched controls were included in this post-hoc analysis if their mid-upper arm circumference had been measured and if they were older than 6 months of age. Acute malnutrition was defined as mid-upper arm circumference below 12·5 cm, capturing both severe acute malnutrition (

We report a series of Pd K-edge and Pt L3-edge X-ray absorption spectra (XAS) collected in situ during thermal treatment of functionalized UiO-67-Pd and UiO-67-Pt metal-organic frameworks in inert and reducing atmospheres. We present raw synchrotron data from three subsequent experiments at different beamlines, normalized XAS spectra and k2-weighted oscillatory χ(k) functions extracted from one of the datasets. Pd K-edge spectra were collected for the samples in 5% H2/He, 3% H2/He and pure He in the temperature range from room temperature (RT) to 450 °C. Pt L3-edge were collected for the samples in 3% H2/He, 10% H2/He and pure He in the temperature range from RT to 300 °C. All spectra are reported together with the used atmosphere and temperature. For the analysis of all reported datasets, please see “Evolution of Pt and Pd species in functionalized UiO-67 metal-organic frameworks”. Fourier-analysis of Pd K-edge is reported in “Formation and growth of Pd nanoparticles in UiO-67 MOF by in situ EXAFS”. Keywords: EXAFS, XANES, MOFs, Nanoparticles

We report the series of Pd K-edge X-ray absorption spectra collected during hydrogenation of ethylene with variable ethylene/hydrogen ratio over carbon supported palladium nanoparticles. The data presented in this article includes normalized X-ray absorption spectra, k2-weighted oscillatory χ(k) functions extracted from the extended X-ray absorption fine structure (EXAFS) and k2-weighted Fourier-transformed EXAFS data, χ(R). Each spectrum is reported together with the hydrogen, ethylene and helium flow rates, adjusted during its collection. In addition, time evolution of the ratio of m/Z signals of 30 and 28 registered by online mass spectrometer is presented. The data analysis is reported in Bugaev et al., Catal. Today, 2019 [1].

Despite the increasing and ubiquitous use of social media for business activities, scholar research on social media marketing strategy is scant and companies deploy their social media marketing strategies guided by intuition or trial and error. This study proposes a comprehensive framework that identifies and classifies social media marketing strategic actions. The conceptual framework covers actions that support both transactional and relationship marketing. This research also positions social media marketing strategy and strategic actions in the context of the marketing organization theory, and discusses the impact of the incorporation of social media on the concept of marketing organization. The study offers valuable theoretical insight on social media marketing actions and the deployment of social media marketing strategies in companies. The investigation also provides hints about how to maximize the benefits from social media marketing for customer-oriented, market-driven organizations.

Since human angiotensin-converting enzyme 2 (ACE2) serves as a primary receptor for SARS-CoV-2, characterizing ACE2 regions that allow SARS-CoV-2 to enter human cells is essential for designing peptide-based antiviral blockers and elucidating the pathogenesis of the virus. We identified and synthesized a 25-mer mimetic peptide (encompassing positions 22-46 of the ACE2 alpha-helix α1) implicated in the S1 receptor-binding domain (RBD)-ACE2 interface. The mimetic (wild-type, WT) ACE2 peptide significantly inhibited SARS-CoV-2 infection of human pulmonary Calu-3 cells in vitro. In silico protein modeling predicted that residues F28, K31, F32, F40, and Y41 of the ACE2 alpha-helix α1 are critical for the original, Delta, and Omicron strains of SARS-CoV-2 to establish the Spike RBD-ACE2 interface. Substituting these residues with alanine (A) or aspartic acid (D) abrogated the antiviral protective effect of the peptides, indicating that these positions are critical for viral entry into pulmonary cells. WT ACE2 peptide, but not the A or D mutated peptides, exhibited significant interaction with the SARS-CoV-2 S 1 RBD, as shown through molecular dynamics simulations. Through identifying the critical amino acid residues of the ACE2 alpha-helix α1, which is necessary for the Spike RBD-ACE2 interface and mobilized during the in vitro viral infection of cells, we demonstrated that the WT ACE2 peptide protects susceptible K18-hACE2 mice against in vivo SARS-CoV-2 infection and is effective for the treatment of COVID-19., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Confidence in perceptual decisions is thought to reflect the probability of being correct. According to this view, confidence should be unaffected or minimally reduced by the presence of irrelevant alternatives. To test this prediction, we designed five experiments. In Experiment 1, participants had to identify the largest geometrical shape among two or three alternatives. In the three-alternative condition, one of the shapes was much smaller than the other two, being a clearly incorrect option. Counter-intuitively, confidence was higher when the irrelevant alternative was present, evidencing that confidence construction is more complex than previously thought. Four computational models were tested, only one of them accounting for the results. This model predicts that confidence increases monotonically with the number of irrelevant alternatives, a prediction we tested in Experiment 2. In Experiment 3, we evaluated whether this effect replicated in a categorical task, but we did not find supporting evidence. Experiments 4 and 5 allowed us to discard stimuli presentation time as a factor driving the effect. Our findings suggest that confidence models cannot ignore the effect of multiple, possibly irrelevant alternatives to build a thorough understanding of confidence., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Radial nerve palsy following fracture of the humeral shaft is common. However, the incidence of nerve transection in the setting of ballistic trauma is unknown. The purpose of this study was to estimate the incidence of radial nerve transection after ballistic fracture of the humerus., Methods: Patients presenting to an urban, level-1 trauma center with a ballistic fracture of the humeral shaft were retrospectively reviewed. Patient demographics, clinical exam on presentation, and operative data were reviewed to determine the incidence of radial nerve palsy on initial examination, the incidence of operative treatment, the incidence of how frequently the nerve was directly visualized, and the incidence of radial nerve transection., Results: One-hundred and thirteen ballistic humeral shaft fractures were identified. Of these, 30 (26.5%) patients had a complete radial nerve palsy on exam. Of patients with a radial nerve palsy, on exam 20 were taken to the operating room and the nerve was visualized in 17 of those cases. There 2 were partially lacerated nerves and 12 nerves were completely transected. Thus, in patients with a complete nerve deficit on examination who underwent operative treatment with nerve exploration, the rate of nerve transection was 70.6%. The lower bound rate of nerve transection for all patients with radial nerve palsy (assuming all unexplored nerves were intact) was 40.0%., Conclusion: The rate of nerve transection in patients with humerus shaft fractures with associated radial nerve palsies is likely higher than the rate of nerve transection in similar injuries caused by blunt mechanisms. The authors recommend early exploration and fixation of these injuries., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Although amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder, some ALS cases can survive beyond 10 years. However, the predictors of long survival in ALS patients remain uncertain., Objective: To define clinical predictors of long survival in a cohort of ALS incident cases., Methods: One hundred-thirty incidents cases, diagnosed in 1998--1999 and classified according to the El Escorial criteria (EEC), were enrolled from a prospective population-based registry established in Puglia, Italy. All but two cases were followed-up until death or November 30, 2006., Results: Thirteen patients (high 10% of the survivors) were classified as long survivors (LS), 13 as short survivors (SS) (low 10%), and 102 as average survivors (AS). LS presented a lower frequency of bulbar onset (8% versus 29% of AS and 39% of SS; p=0.1) and a significantly longer time between symptom onset to diagnosis [(ODI): 13 months versus 10 and 6; p=0.0005]. In multivariate analysis, predictors of long survival were younger age at diagnosis (>65 compared to < or =45 years: odds ratio (OR):18.9; 95%CI: 1.8-194.7; p=0.04), longer interval onset-diagnosis (< or =9 months compared to >9 months, OR: 7.9; 95%CI: 1.3-47; p=0.02) and clinical features with predominant upper motor neuron signs (OR: 8.5; 95%CI: 1.1-64.2; p=0.04)., Conclusions: In this population-based study, younger age, longer interval onset to diagnosis, and clinical features with predominance of upper motor signs predicted long survival, while EEC category at diagnosis did not.

Background: The El Escorial and the revised Airlie House diagnostic criteria for amyotrophic lateral sclerosis (ALS) were introduced to select patients for clinical trials. Heterogeneity of clinical presentation at onset and delay in diagnosis may decrease the likelihood for trial entry., Objective: Identify risk factors for delay in the diagnosis and trial exclusion., Methods: ALS incident cases were identified with El Escorial (EEC) and Airlie House criteria (AHC) through a population-based registry established in Puglia, Southern Italy, in the years 1998-99., Results: 130 ALS incident cases were diagnosed with a median interval between onset of symptoms and diagnosis of 9.3 months and not different across both EEC and AHC categories. Twenty percent of cases were not eligible for clinical trials according to the AHC. About 5% of subjects in this series died with only lower motor neuron signs. Predictors for delay in the diagnosis were age between 65 and 75 years and spinal onset while fasciculations and cramps as first symptoms were predictors of exclusion from trials., Conclusions: In this population-based series, diagnostic delay was longer in subjects with spinal onset and age between 65 and 75 and fasciculation as first symptoms. About 80% of incident cases were trial eligible with AHC criteria. However, a significant number of subjects with ALS, characterized by a limited spread of signs, were not trial eligible while alive.

In the present study, we examined clinical and laser-evoked potentials (LEP) features in a group of chronic tension-type headache (CTTH) patients, in order to perform a topographic analysis of Laser evoked potentials (LEPs) and a correlation with clinical features. Eighteen patients suffering from CTTH [Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders 2nd ed. Cephalalgia 2004; 24 Suppl 1, 1-159.] participated in the study. Twelve age- and sex-matched controls were also examined. We performed a basal evaluation of clinical features, Total Tenderness Score (TTS) and a topographic analysis of LEPs obtained by the hand and the pericranial points stimulation in all patients vs healthy subjects. The later LEPs, especially the P2 component, were significantly increased in amplitude in the CTTH group, specially when the pericranial points were stimulated. The P2 wave amplitude was correlated with TTS levels and anxiety scores. The results of this study confirm that pericranial tenderness is a phenomenon initiating a self-sustaining circuit, involving central sensitization at the level of the cortical nociceptive areas devoted to attentional and emotional components of pain.