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Immunological health has been challenging to characterize but could be defined as the absence of immune pathology. While shared features of some immune diseases and the concept of immunologic resilience based on age-independent adaptation to antigenic stimulation have been developed, general metrics of immune health and its utility for assessing clinically healthy individuals remain ill defined. Here we integrated transcriptomics, serum protein, peripheral immune cell frequency and clinical data from 228 patients with 22 monogenic conditions impacting key immunological pathways together with 42 age- and sex-matched healthy controls. Despite the high penetrance of monogenic lesions, differences between individuals in diverse immune parameters tended to dominate over those attributable to disease conditions or medication use. Unsupervised or supervised machine learning independently identified a score that distinguished healthy participants from patients with monogenic diseases, thus suggesting a quantitative immune health metric (IHM). In ten independent datasets, the IHM discriminated healthy from polygenic autoimmune and inflammatory disease states, marked aging in clinically healthy individuals, tracked disease activities and treatment responses in both immunological and nonimmunological diseases, and predicted age-dependent antibody responses to immunizations with different vaccines. This discriminatory power goes beyond that of the classical inflammatory biomarkers C-reactive protein and interleukin-6. Thus, deviations from health in diverse conditions, including aging, have shared systemic immune consequences, and we provide a web platform for calculating the IHM for other datasets, which could empower precision medicine.

Artificial teeth in dental training have become a valuable tool for students to gain hands-on experience in a safe and controlled environment. This training method allows students to practice various dental procedures and develop their skills without putting patients at risk. Artificial teeth can be used to simulate dental conditions, allowing students to gain experience in dealing with various situations and techniques. Although previous studies in human dentistry have demonstrated the feasibility of using 3D-printed teeth for teaching endodontic procedures such as root canal therapy, similar research has yet to be conducted in the veterinary field. This study aimed to assess the feasibility of creating 3D-printed teeth from an adult dog skull and validate their use as an alternative training tool for root canal therapy in this species. For this, cone beam computed tomography images from a medium-sized dog skull were used to replicate its teeth using a digital 3D printing system. Then, artificial mandibular first molar teeth and a 24-question survey were sent to specialized veterinary dentistry practitioners in Brazil to assess their perception of the model's characteristics during endodontic treatment. In conclusion, it was feasible to create 3D-printed models of dog teeth with high accuracy for the endodontic system. Despite the differences in the properties of the two materials between natural and artificial teeth, it was possible to use the artificial tooth as a training device for conventional endodontic treatment in dogs. The reliability level for the survey was reported as good, displaying a reliability coefficient above 0.86.

Molecules bearing fluorine are increasingly prevalent in pharmaceuticals, agrochemicals, and functional materials. The cyanodifluoromethyl group is unique because its size is closer than that of any other substituted difluoromethyl group to the size of the trifluoromethyl group, but its electronic properties are distinct from those of the trifluoromethyl group. In addition, the presence of the cyano group provides synthetic entry to a wide range of substituted difluoromethyl groups. However, the synthesis of cyanodifluoromethyl compounds requires multiple steps, highly reactive reagents (such as DAST, NSFI, or IF5), or specialized starting materials (such as α,α-dichloroacetonitriles or α-mercaptoacetonitriles). Herein, we report a copper-mediated cyanodifluoromethylation of aryl and heteroaryl iodides and activated aryl and heteroaryl bromides with TMSCF2CN. This cyanodifluoromethylation tolerates an array of functional groups, is applicable to late-stage functionalization of complex molecules, yields analogues of FDA-approved pharmaceuticals and fine chemicals, and enables the synthesis of a range of complex molecules bearing a difluoromethylene unit by transformations of the electron-poor CN unit. Calculations of selected steps of the reaction mechanism by Density Functional Theory indicate that the barriers for both the oxidative addition of iodobenzene to [(DMF)CuCF2CN] and the reductive elimination of the fluoroalkyl product from the fluoroalkyl copper intermediate lie in between those of [(DMF)CuCF3] and [(DMF)CuCF2C(O)NMe2].

The decentralization of formations using onboard sensing is important for multirobot systems, improving the robustness and independence of fleet operations. Bearing measurements (obtainable from embedded cameras) are an attractive choice for use in decentralized formation control, however, this requires that the formation framework be bearing rigid. Rigidity may be checked numerically for a given formation framework, however, it remains difficult to determine the geometric conditions under which otherwise rigid formations become flexible. This article models the sensor and robot constraints in bearing formations of quadrotors as a kinematic mechanism with analogous properties to find geometric conditions for the degeneration of bearing rigidity (singularities) and the resulting uncontrollable motions. A classification of singularities based on graph substructures is developed, and it is shown that arbitrarily large formations may be designed for which all singularities lie within a known set of geometric conditions. An application on how to use the knowledge of all singularity cases in a formation for singularity-free control maintenance is provided.

As the Internet of Things (IoT) continues to expand, the demand for the use of energy-efficient circuits and battery-less devices has grown rapidly. Battery-less operation, zero maintenance, and sustainability are the desired features of IoT devices in fifth-generation (5G) networks and green Industry 4.0 wireless systems. The integration of energy harvesting systems, IoT devices, and 5G networks has the potential impact to digitalize and revolutionize various industries such as Industry 4.0, agriculture, food, and healthcare, by enabling real-time data collection and analysis, mitigating maintenance costs, and improving efficiency. Energy harvesting plays a crucial role in envisioning a low-carbon net zero future and holds significant political importance. This survey aims at providing a comprehensive review on various energy harvesting techniques including radio frequency (RF), multisource hybrid, and energy harvesting using additive manufacturing technologies. However, special emphasis is given to RF-based energy harvesting methodologies tailored for battery-free wireless sensing, and powering autonomous low-power electronic circuits and IoT devices. The key design challenges and applications of energy harvesting techniques, as well as the future perspective of system on chip (SoC) implementation, data digitization in Industry 4.0, next-generation IoT devices, and 5G communications are discussed.

Flexible and adaptive systems for handling and transporting materials within companies and warehouses are increasingly being studied in order to respond to the variability of production and the market. Following this trend, the authors, seeking a simplified design and control, proposed a novel under-actuated modular surface that exploits the friction forces generated by idler rotors inside the modules, for object manipulation. On this subject, the paper concerns the design of two novel measurement set-ups for the determination of parameters fundamental to the single module functioning and the validation of its analytical model. In particular, the test benches are designed to collect the friction forces exchanged between the device rotor and the object moving on top of it, simulating a normal working condition of the surface. The first set-up is specifically dedicated to identify the friction coefficients in the two main directions of the rotor, i.e. along the axis of rotation and in the perpendicular direction. While the second set-up is focused on the validation of the analytical model, thanks to the simultaneous measurement of the two in-plane friction forces caused by the object moving in different directions with respect to the rotor axis. The article describes the operating principles of the test benches and the analytical models for interpreting the data. In addition, some results concerning friction coefficients are introduced. These verify the basic operating assumptions and therefore evidence the module functioning and the quality of the novel test benches, opening their use also for similar transport devices.

Optimal management of septic patients requires accurate assessment of both current severity status and prognosis. Since the 1990s, substantial advances have been made in the use of circulating biomarkers for such assessments. This summary of the session on “Biomarkers: can they really use guide our daily practice?” presented at the 2021 WEB-CONFERENCE OF THE EUROPEAN SHOCK SOCIETY, 6 November 2021. These biomarkers include ultrasensitive detection of bacteremia, circulating soluble urokina-type plasminogen activator receptor (suPAR), C-reactive protein (CRP) and ferritin and procalcitonin. In addition, the potential application of novel multiwavelength optical biosensor technology allows noninvasive monitoring of multiple metabolites that can be used to assess severity and prognosis in septic patients. The application these biomarkers and improved technologies provide the potential for improved personalized management of septic patients.

Certains patients présentent une récidive locale après néphrectomie partielle malgré des marges négatives.

Objectives: The mortality rate in patients with anorexia nervosa (AN) is 5 to 10 times higher than in general population and, suicide is one of the main causes of death. We evaluated the prevalence of suicidality (ideation, self-injurious behaviour, suicidal attempts) in 100 adolescents with onset of AN and we explored the correlation between suicidality, severity of AN symptoms and psychiatric comorbidity. Methods: We subdivided AN patients into restrictive (R-AN; n= 66) and restrictive atypical (A-AN; n= 34), according to the European Guidelines criteria. Assessment was performed using the eating disorder inventory 3rd version, the schedule for affective disorders and schizophrenia for school-age children-present and lifetime version interview, and the Columbia-suicide severity rating scale. Fisher’s exact test and Mann–Whitney test (with correction for multiple testing) were used to compare the distribution of categorical and continuous variables between R-AN and A-AN patients, and between patients with vs. without suicidal behaviours. Results: Twenty-seven patients (27%) presented suicidality as clinical feature, expressed as at least one of the following: suicidal ideation (24%), self-cutting (19%), and suicidal attempt (6%). Patients with suicidality showed greater severity of psychiatric symptoms related to AN psychopathology and presented psychiatric comorbidity, especially depression, more often than patients who did not reported suicidality (70,4% vs 29,6%). No significant differences in terms of suicidal behaviours and AN-specific psychopathology were found between R-AN and A-AN. Conclusions: Suicidality in adolescent patients with R-AN and A-AN seems to be related to ED symptoms. These data highlight the importance of screening for suicidality among adolescents at onset of AN, and confirms that A-AN should not be considered a milder disease. Level of evidence: Level IV: Evidence obtained from multiple time series analysis such as case studies. (NB: Dramatic results in uncontrolled trials might also be regarded as this type of evidence)

Coronavirus disease 2019 is known to impact older people more severely and to cause persistent symptoms during the recovery phase, including cognitive and neurologic ones. We investigated the cognitive and neurologic features of 100 elderly patients with confirmed diagnosis of coronavirus disease 2019 evaluated in the postacute phase through a direct neuropsychological evaluation consisting on Mini Mental State Examination and 8 neuropsychological tests. Overall, a total of 33 participants were found to perform at a level considered to be pathologic; more specifically, 33%, 23%, and 20% failed on Trial Making, Digit Span Backwards, and Frontal Evaluation Battery tests, respectively.

Aim:To analyse the presence and treatment of infections in hospitalised terminal patients by identifying potential risk factors.Methods:We conducted a retrospective study using health data from 229 terminally ill patients (evaluated by our hospital palliative care team (HPCT) hospitalised from January to December 2018.Results:A total of two types of infections were identified: blood flow infection (through blood cultures) and pneumonia (through radiological examinations), while the other cases of infection remained unknown. The most frequently identified microorganism was Staphylococcus spp. The prevalence of infections was higher in patients with non-oncological diseases (n=47, 36.7%; p value 0.009). The potential risk factors identified for infections were the presence of: Parkinson's disease (n=15, 11.7%; p value 0.005), dysphagia (n=49, 38.3%; p value 0.007), bedding (n=15, 11.7%; p value 0.048), pressure ulcers (n=31, 24. 2%); p value 0.018), oxygen therapy (n=60, 46.9%; p value 0.050), urinary catheters (n=95, 74.2%; p value 0.038) and polypathology (2.3 vs 1.7; p value 0.022). Parkinson's disease (OR=5.973; 95% CI=1.292-27.608), dysphagia (OR=2.090; 95% CI=1.080-4.046) and polypathology (OR=1.220; 95% CI=1.015-1.466) were confirmed by a corrected logistic regression analysis.Conclusions:Infections and, consequently, antibiotic therapies, have a high prevalence in hospitalised patients with terminal disease. Potential risk factors for infections in these patients could be polypathology, dysphagia and Parkinson's disease. Patients with these conditions could benefit from prevention programmes.

Flexible ureteroscopy (fURS) is one of the recommended treatments for urinary stones. Urosepsis is one of the most frequent complications of fURS however its predictive factors remain uncertain. Our objective was to assess the septic complications rates of fURS and to determinate predictive factors of these complications in patients undergoing fURS.

Stress, social isolation, and changes in health behaviors during the COVID-19 pandemic period may have a lasting influence on health. Here, the correlation between current or prior demographic, social and health related characteristics, including psychosocial factors with perceived impact of the COVID-19 pandemic assessed by questionnaire during the early pandemic period is evaluated among 770 participants of the Baltimore Longitudinal Study of Aging. In multinomial logistic regression models participants with higher pre-pandemic personal mastery, a construct related to self-efficacy, were more likely to report “both positive and negative” impact of the pandemic than a solely “negative” impact (OR: 2.17, 95% CI: 1.29–3.65). Higher perceived stress and frequent contact with family prior to the pandemic were also associated with pandemic impact. These observations highlight the relevance of psychosocial factors in the COVID-19 pandemic experience and identify characteristics that may inform interventions in future public health crises.

Multi-vehicle aerial robots present great potential in accomplishing manipulation tasks, because of their high payload capacity and full manipulability in 3-dimensional space. Belonging to this class of aerial robots, the Flying Parallel Robot (FPR) is an architecture where a moving platform is supported collectively by a team of quadrotors with passive kinematic chains. While the modelling and control of the FPR in free space has been studied in the previous work, there is lack of consideration in robot-environment interaction, which is however significant to develop the industrial applications of such robots. In this paper, we implement an external wrench estimator and an impedance-based controller with force tracking capability to achieve the disturbance rejection and the physical interaction with the environment. Extensive experimental validations have shown the FPR capable of hovering in presence of additional payload and strong wind perturbations, and performing contact-based interaction tasks.

International governmental networks used to be centralized. However, the formal and informal decentralization of diplomatic relations through local governments and regions has placed the subnational governments as international actors. The subnational parallel pursuit of international relations has been termed paradiplomacy. Knowing “why or how” subnational governments engage in paradiplomacy is relevant because international networks have the potential to foster innovation, cooperation, transfer of knowledge, and international aid. However, not all jurisdictions engage in international relations despite the potential symbolic and material benefits. Scholars have explained local engagement in international relations through economic, cooperative, and political considerations. Without denying their explanatory power, we hypothesize that organizational structures, specifically local pro-international structures, foster paradiplomacy, while political support discourages paradiplomatic activities. To investigate subnational variation in paradiplomacy engagement, we rely on a survey covering all 5565 Brazilian municipalities in 2012. Findings suggest the existence of local pro-international structures is positively correlated with municipal international projects and municipal participation in international networks.

Primary focal and segmental glomerulosclerosis (FSGS) frequently recurs after transplantation and is associated with a poor prognosis. We describe here the successful kidney graft reuse in an adult recipient, 8 months after early primary FSGS recurrence resistant to all available therapeutics. Patient 1, a 23-year-old man, followed for kidney failure secondary to primary FSGS, was first transplanted in 2018 with a deceased donor graft. Unfortunately, we observed an immediate recurrence of biopsy-proven primary FSGS. After 4 lines of treatment (intravenous cyclosporine+corticosteroids, plasma exchanges, immunoadsorption, and rituximab), the patient was still highly nephrotic and kidney function was slowly deteriorating. After approval from both the patient and the health authority (Biomedicine Agency), the graft was detransplanted 8 months after transplantation and reimplanted in patient 2, a 78-year-old nonimmunized and anephric recipient (bi-nephrectomy 2 years previously for bilateral renal carcinoma). We observed immediate kidney function and progressive resolution of proteinuria (serum creatinine of 1.2mg/dL and proteinuria of 0.1 g/d 1 year later). Biopsies performed after surgery showed persistent FSGS lesions with a decrease in overall foot-process effacement. To our knowledge, this is the first reported case showing that kidney graft transfer may still be a viable option for refractory primary FSGS several months after transplantation.

Streptococci still represent common etiologic agents of infective endocarditis (IE). Although renal failure is frequently reported as an aminoglycoside-associated adverse event, last international guidelines recommend a beta-lactam/gentamicin combination therapy. We retrospectively evaluated the use of daptomycin-based aminoglycoside-sparing combination therapy for the treatment of streptococcal IE in seven referral hospitals in Italy. Retrospective, multicenter, observational study. All patients with streptococcal IE admitted from 2016 to 2018 were enrolled. Mortality and incidence of acute kidney injury (AKI) were compared between Group A (standard of care, SoC) and Group B (daptomycin-based aminoglycoside-sparing combination therapy). Fifty-four patients were enrolled, 33 in Group A and 21 in Group B. Mortality was 2/33 (6%) in Group A and 0 in Group B (p = 0.681); AKI incidence was 8/33 (24%) in Group A and 0 in Group B (p = 0.04). Daptomycin-based aminoglycoside-sparing combination therapy appears to be promising for the treatment of streptococcal endocarditis because of similar efficacy compared with SoC and significantly reduced incidence of AKI.

La BCG-thérapie a permis une amélioration des résultats oncologiques des TVNIM de risque intermédiaire et/ou de haut risque. Cependant, les effets secondaires (ES) sont fréquents et peuvent nuire à l’observance. L’objectif de cet article était de décrire les différents effets secondaires liés aux installations de BCG-thérapie et leur prise en charge. La majorité des ES sont classifiés comme mineurs et nécessitent une simple prescription de paracétamol et d’AINS sans arrêt du BCG. Pour les ES de durée plus importante, une introduction d’un traitement par fluoroquinolones améliore la tolérance et donc l’observance. Pour les ES persistants plus de 7 jours, une corticothérapie est indiquée. Dans de très rares cas, une BCGite peut apparaître, imposant une prise en charge en urgence, des mesures réanimatoires, et un traitement antituberculeux prolongé.