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Abstract Investigating ligand-protein complexes is essential in the areas of chemical biology and drug discovery. However, detailed information on key reagents such as fluorescent tracers and associated data for the development of widely used bioluminescence resonance energy transfer (BRET) assays including NanoBRET, time-resolved Förster resonance energy transfer (TR-FRET) and fluorescence polarization (FP) assays are not easily accessible to the research community. We created tracerDB, a curated database of validated tracers. This resource provides an open access knowledge base and a unified system for tracer and assay validation. The database is freely available at https://www.tracerdb.org/ .

Gynecomastia is a benign glandular proliferation that can affect adolescents causing significant psychological discomfort. Generally, it is idiopathic but underlying endocrinological conditions must be excluded. Different surgical techniques are available, the surgical correction with subareolar incision achieves the goal of satisfactory aesthetic result for patients. We studied all patients treated for gynecomastia in two centers of pediatric surgery. After collection of a detailed family history, we evaluated the presence of early onset of puberty, congenital abnormalities of the external genitalia, use of drugs, eating habits and the presence of genetic disorders. Laboratory tests and ultrasound were made to exclude endocrinological disorders. The surgical treatment was performed by a subareolar incision with gland and adipose tissue excision. A Body - Q chest module to evaluate patient satisfaction has been proposed to everyone before and after surgery. 47 adolescents with median age of 15 years were surgically treated. Three presented endocrinological disorders. Grade of gynecomastia for surgery was: III in 40 patients and IIb in 7 patients. Postoperative complications occurred in 5 patients. The Body - Q chest module was completed by 42 patients and showed good results for all points analyzed, except for social feelings. Gynecomastia in adolescents can be surgically treated with subareolar incision, reporting good aesthetic results and low incidence of complications. Specific tests are useful to assess patient satisfaction.

Prostate cancer is a frequent malignancy in older men and has a very high 5‐year survival rate if diagnosed early. The prognosis is much less promising if the tumor has already spread outside the prostate gland. Targeted treatments mainly aim at blocking androgen receptor (AR) signaling and initially show good efficacy. However, tumor progression due to AR‐dependent and AR‐independent mechanisms is often observed after some time, and novel treatment strategies are urgently needed. Dysregulation of the PI3K/AKT/mTOR pathway in advanced prostate cancer and its implication in treatment resistance has been reported. We compared the impact of PI3K/AKT/mTOR pathway inhibitors with different selectivity profiles on in vitro cell proliferation and on caspase 3/7 activation as a marker for apoptosis induction, and observed the strongest effects in the androgen‐sensitive prostate cancer cell lines VCaP and LNCaP. Combination treatment with the AR inhibitor darolutamide led to enhanced apoptosis in these cell lines, the effects being most pronounced upon cotreatment with the pan‐PI3K inhibitor copanlisib. A subsequent transcriptomic analysis performed in VCaP cells revealed that combining darolutamide with copanlisib impacted gene expression much more than individual treatment. A comprehensive reversal of the androgen response and the mTORC1 transcriptional programs as well as a marked induction of DNA damage was observed. Next, an in vivo efficacy study was performed using the androgen‐sensitive patient‐derived prostate cancer (PDX) model LuCaP 35 and a superior efficacy was observed after the combined treatment with copanlisib and darolutamide. Importantly, immunohistochemistry analysis of these treated tumors showed increased apoptosis, as revealed by elevated levels of cleaved caspase 3 and Bcl‐2‐binding component 3 (BBC3). In conclusion, these data demonstrate that concurrent blockade of the PI3K/AKT/mTOR and AR pathways has superior antitumor efficacy and induces apoptosis in androgen‐sensitive prostate cancer cell lines and PDX models.

BackgroundPleuropulmonary blastoma (PPB) is the most common lung cancer of infancy and early childhood. Type I PPB is a purely cystic lesion that has a microscopic population of primitive small cells with or without rhabdomyoblastic features and may progress to type II or III PPB, whereas type Ir lacks primitive small cells.MethodsChildren with suspected PPB were enrolled in the International PPB/DICER1 Registry. Pathology was centrally reviewed, and follow-up was ascertained annually.ResultsBetween 2006 and 2022, 205 children had centrally reviewed type I or Ir PPB; 39% of children with type I and 5% of children with type Ir PPB received chemotherapy. Outcomes were favorable, although 11 children (nine with type I and two with type Ir PPB) experienced progression to type II/III (n = 8) or regrowth of type I PPB at the surgical site (n = 3), none of whom received chemotherapy before progression. Age and cyst size in combination were more suitable than either factor alone in predicting whether a particular lesion was type I or Ir PPB.ConclusionsFor young children with type I PPB, outcomes are favorable, but complete resection is indicated because of the risk for progression. Chemotherapy may be useful in a subset of children at increased risk for recurrence/progression. Efforts to risk stratify children with type I PPB to optimize outcomes while reducing treatment-related side effects are underway.

Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase that is activated by phosphorylation events downstream of FcR, B-cell and T-cell receptors, integrins, and C-type lectin receptors. When the tandem Src homology 2 (SH2) domains of SYK bind to phosphorylated immunoreceptor tyrosine-based activation motifs (pITAMs) contained within these immunoreceptors, or when SYK is phosphorylated in interdomain regions A and B, SYK is activated. SYK gain-of-function (GoF) variants were previously identified in six patients that had higher levels of phosphorylated SYK and phosphorylated downstream proteins JNK and ERK. Furthermore, the increased SYK activation resulted in the clinical manifestation of immune dysregulation, organ inflammation, and a predisposition for lymphoma. The knowledge that the SYK GoF variants have enhanced activity was leveraged to develop a SYK NanoBRET cellular target engagement assay in intact live cells with constructs for the SYK GoF variants. Herein, we developed a potent SYK-targeted NanoBRET tracer using a SYK donated chemical probe, MRL-SYKi, that enabled a NanoBRET cellular target engagement assay for SYK GoF variants, SYK(S550Y), SYK(S550F), and SYK(P342T). We determined that ATP-competitive SYK inhibitors bind potently to these SYK variants in intact live cells. Additionally, we demonstrated that MRL-SYKi can effectively reduce the catalytic activity of SYK variants, and the phosphorylation levels of SYK(S550Y) in an epithelial cell line (SW480) stably expressing SYK(S550Y).

Summary: Humans are the most versatile tool users among animals. Accordingly, our manual skills evolved alongside the shape of the hand. In the future, further evolution may take place: humans may merge with their tools, and technology may integrate into our biology in a way that blurs the line between the two. So, the question is whether humans can embody a bionic tool (i.e., experience it as part of their body) and thus if this would affect behavior. We investigated in virtual reality how the substitution of the hand with a virtual grafting of an end-effector, either non-naturalistic (a bionic tool) or naturalistic (a hand), impacts embodiment and behavior. Across four experiments, we show that the virtual grafting of a bionic tool elicits a sense of embodiment similar to or even stronger than its natural counterpart. In conclusion, the natural usage of bionic tools can rewire the evolution of human behavior.

Background: A knee injury in an athlete leads to periods of forced exercise interruption. Myocardial work (MW) assessed by echocardiographic and cardiopulmonary exercise testing (CPET) are two essential methods for evaluating athletes during the period following injury. However, compared to pre-surgery evaluations, the variations in cardiovascular parameters and functional capacity assessed by these methods after surgery remain unclear. Methods: We evaluated 22 non-professional athletes aged 18–52, involved in prevalently aerobic or alternate aerobic/anaerobic sports activities, who were affected by a knee pathology requiring surgical treatment. The evaluation was performed at rest using transthoracic echocardiography, including MW assessment, and during exercise using CPET. Each athlete underwent the following two evaluations: the first before surgery and the second after surgery (specifically at the end of the deconditioning period). Results: Resting heart rate (HR) increased significantly (from 63.3 ± 10.85 to 71.2 ± 12.52 beats per minute, p = 0.041), while resting diastolic and systolic blood pressure, forced vital capacity, and forced expiratory volume in the first second did not show significant changes. Regarding the echocardiographic data, global longitudinal strain decreased from −18.9 ± 1.8 to −19.3 ± 1.75; however, this reduction was not statistically significant (p = 0.161). However, the global work efficiency (GWE) increased significantly (from 93.0% ± 2.9 to 94.8% ± 2.6, p = 0.006) and global wasted work (GWW) reduced significantly (from 141.4 ± 74.07 to 98.0 ± 50.9, p = 0.007). Additionally, the patients were able to perform maximal CPET at both pre- and post-surgery evaluations, as demonstrated by the peak respiratory exchange ratio and HR. However, the improved myocardial contractility (increased GWE and decreased GWW) observed at rest did not translate into significant changes in exercise parameters, such as peak oxygen consumption and the mean ventilation/carbon dioxide slope. Conclusions: After surgery, the athletes were more deconditioned (as indicated by a higher resting HR) but exhibited better resting myocardial contractility (increased GWE and reduced GWW). Interestingly, no significant changes in exercise capacity parameters, as evaluated by CPET, were found after surgery, suggesting that the improved myocardial contractility was offset by a greater degree of muscular deconditioning.

Current small-molecule inhibitors of KRAS(G12C) bind irreversibly in the switch-II pocket (SII-P), exploiting the strong nucleophilicity of the acquired cysteine as well as the preponderance of the GDP-bound form of this mutant. Nevertheless, many oncogenic KRAS mutants lack these two features, and it remains unknown whether targeting the SII-P is a practical therapeutic approach for KRAS mutants beyond G12C. Here we use NMR spectroscopy and a cellular KRAS engagement assay to address this question by examining a collection of SII-P ligands from the literature and from our own laboratory. We show that the SII-Ps of many KRAS hotspot (G12, G13, Q61) mutants are accessible using noncovalent ligands, and that this accessibility is not necessarily coupled to the GDP state of KRAS. The results we describe here emphasize the SII-P as a privileged drug-binding site on KRAS and unveil new therapeutic opportunities in RAS-driven cancer.

Abstract Background Systemic inflammation has been proposed as a relevant mechanism in amyotrophic lateral sclerosis (ALS). Still, comprehensive data on ALS patients' innate and adaptive immune responses and their effect on the clinical phenotype are lacking. Here, we investigate systemic immunity in a population‐based ALS cohort using readily available hematological indexes. Methods We collected clinical data and the complete blood count (CBC) at diagnosis in ALS patients from the Piemonte and Valle d'Aosta Register for ALS (PARALS) from 2007 to 2019. Leukocytes populations, neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), systemic‐immune‐inflammation index (SII), and lymphocyte‐to‐monocyte ratio (LMR) were derived from CBC. All variables were analyzed for association with clinical features in the entire cohort and then in sex‐ and age‐based subgroups. Results Neutrophils (P = 0.001) and markers of increased innate immunity (NLR, P = 0.008 and SII, P = 0.006) were associated with a faster disease progression. Similarly, elevated innate immunity correlated with worse pulmonary function and shorter survival. The prognosis in women also correlated with low lymphocytes (P = 0.045) and a decreased LMR (P = 0.013). ALS patients with cognitive impairment exhibited lower monocytes (P = 0.0415). Conclusions and Relevance The dysregulation of the systemic immune system plays a multifaceted role in ALS. More specifically, an elevated innate immune response is associated with faster progression and reduced survival. Conversely, ALS patients with cognitive impairment showed a reduction in monocyte count. Additionally, immune response varied according to sex and age, thus suggesting that involved immune pathways are patient specific. Further studies will help translate those findings into clinical practice or targeted treatments.

Transfer of cognitive abilities has often been described in regard to Working Memory, while little has been said about Cognitive Control. Recent studies have proposed that congruency cues can be used to investigate learning-guided cognitive control adaptations in a trial-by-trial fashion during conflict tasks. In the present study, we employed congruency cues within an inducer/diagnostic paradigm to (1) induce a control learning between cue and string congruency in a Flanker task variant and (2) test whether this learning could transfer to a different Flanker variant. Results provided evidence that participants can learn to strategically employ congruency cues to adapt their cognitive control and that these learned control strategies/routines can be transferred to a very similar task variant (near transfer). Further experiments will be performed to explore the extent of this transfer.

While all childhood cancers are rare, tumors that are particularly infrequent or underrepresented within pediatrics are studied under the umbrella of the Children’s Oncology Group Rare Tumor committee, divided into the Retinoblastoma and Infrequent Tumor subcommittees. The Infrequent Tumor subcommittee has traditionally included an emphasis on globally rare tumors such as adrenocortical carcinoma, nasopharyngeal carcinoma, or those tumors that are rare in young children, despite being common in adolescents and young adults, such as colorectal carcinoma, thyroid carcinoma, and melanoma. Pleuropulmonary blastoma, gonadal stromal tumors, pancreatic tumors including pancreatoblastoma, gastrointestinal stromal tumor, nonmelanoma skin cancers, neuroendocrine tumors, and desmoplastic small round cell tumors, as well as other carcinomas are also included under the heading of the Children’s Oncology Group Rare Tumor committee. While substantial challenges exist in rare cancers, inclusion and global collaboration remain key priorities to ensure high quality research to advance care.

Neurological disorders such as stroke, Parkinson’s disease (PD), and severe traumatic brain injury (sTBI) are leading global causes of disability and mortality. This study aimed to assess the ability to walk of patients with sTBI, stroke, and PD, identifying the differences in dynamic postural stability, symmetry, and smoothness during various dynamic motor tasks. Sixty people with neurological disorders and 20 healthy participants were recruited. Inertial measurement unit (IMU) sensors were employed to measure spatiotemporal parameters and gait quality indices during different motor tasks. The Mini-BESTest, Berg Balance Scale, and Dynamic Gait Index Scoring were also used to evaluate balance and gait. People with stroke exhibited the most compromised biomechanical patterns, with lower walking speed, increased stride duration, and decreased stride frequency. They also showed higher upper body instability and greater variability in gait stability indices, as well as less gait symmetry and smoothness. PD and sTBI patients displayed significantly different temporal parameters and differences in stability parameters only at the pelvis level and in the smoothness index during both linear and curved paths. This study provides a biomechanical characterization of dynamic stability, symmetry, and smoothness in people with stroke, sTBI, and PD using an IMU-based ecological assessment.

The present paper aims to discuss the discursive strategies of otherization, legitimation, and normalization typically found in extracts from the author’s video corpus of US Presidents’ selected official statements at the height of actual or potential armed conflicts between the First Gulf War (1990-1991) and the end of the Obama Administration (2016). The underlying working assumption is that, to consolidate asymmetrical power relationships and monitor dissent and/or win domestic consent about the use of force, the US Administration systematically resorts to a relatively restricted inventory of political myths and cultural constructs sustained by strategic storytelling and powerful master narratives, or Intertextual Thematic Formations. The qualitative analysis, informed by a systemic functional, critical discourse approach, is undertaken at both the macro- and micro-levels, with a view to highlighting how master narratives project distinct/conflicting standpoints and socio-institutional roles and identities (e.g. the-President-as-Father-of-the-Nation; the-Community-as-Protector-of-its-Members'-Interests; the-West-as-Civilizer), while feeding the myth of a ‘super-empowered’ President and ultimately sustaining the ideological square. The final contention is that awareness-raising pedagogical models are needed which work upwards from the bottom of the hierarchical narrative structure, contextualizing the master narrative and linking it to the audience’s individual narratives, so that discourse can fulfil its critical function of dismantling potentially manipulative and/or normalizing discourse practices and foster civil society-led, personal counter-narratives that remove stereotyping and oversimplification.

Introduction: The pterional approach and anterior interhemispheric approach are both valid surgical routes for the treatment of anterior skull base meningiomas. Comparative studies of these two surgical routes are not yet reported in the literature. Research question: This retrospective study aims to compare the surgical outcome of both approaches, pros, and cons as well as potential postoperative complications. Materials and methods: In this retrospective study the following variables were evaluated: age, sex, meningioma location, symptoms, post-surgical complications, Simpson grade, follow-up/Outcome (maximum six months), hospital stay (days), Intraoperative time (minutes), intra-operative blood loss (mL). Results: This retrospective study included a total of 22 patients (18 females and 4 males) with a female/male ratio of 4,5/1. The mean age was 59,5 ± 12,59 years. In 13 patients (59%) an anterior interhemispheric approach was performed; in 9 (41%) patients an extended pterional approach. Comparing the two surgical techniques operative time it was found a significant difference between the two approaches (p = 0,03), and a significant difference (p = 0,016) was found in blood losses during surgical procedures: a lower operative time with a higher blood loss was found performing the anterior interhemispheric approach. Discussion and conclusion: The pterional approach and anterior interhemispheric approach are two possible surgical options for the treatment of anterior skull base meningiomas. Both approaches have achieved optimal results, with total tumor resection in most patients and a low complication rate, and that the best approach depends mainly on the experience of the surgeons. A larger cohort of patients with a longer follow-up is needed to propose an algorithm to select the most suitable surgical route for surgical resection, thus reducing the risks.

Respiratory failure assessment is among the most debatable research topics in amyotrophic lateral sclerosis (ALS) clinical research due to the wide heterogeneity of its presentation. Among the different pulmonary function tests (PFTs), maximal voluntary ventilation (MVV) has shown potential utility as a diagnostic and monitoring marker, able to capture early respiratory modification in neuromuscular disorders. In the present study, we explored calculated MVV (cMVV) as a prognostic biomarker in a center-based, retrospective ALS population belonging to the Piemonte and Valle d’Aosta registry for ALS (PARALS). A Spearman’s correlation analysis with clinical data and PFTs showed a good correlation of cMVV with forced vital capacity (FVC) and a moderate correlation with some other features such as bulbar involvement, ALSFRS-R total score, blood oxygen (pO2), carbonate (HCO3−), and base excess (BE), measured with arterial blood gas analysis. Both the Cox proportional hazard models for survival and the time to non-invasive ventilation (NIV) measurement highlighted that cMVV at diagnosis (considering cMVV(40) ≥ 80) is able to stratify patients across different risk levels for death/tracheostomy and NIV indication, especially considering patients with FVC% ≥ 80. In conclusion, cMVV is a useful marker of early respiratory failure in ALS, and is easily derivable from standard PFTs, especially in asymptomatic ALS patients with normal FVC measures.

Respiratory failure is the most common cause of death in patients with amyotrophic lateral sclerosis (ALS) and occurs with great variability among patients according to different phenotypic features. Early predictors of respiratory failure in ALS are important to start non-invasive ventilation (NIV). Venous serum chloride values correlate with carbonate (HCO3-) blood levels and reflect metabolic compensation of respiratory acidosis. Despite its wide availability and low cost, few data on serum chloride as a prognostic marker exist in ALS literature. In the present study, we evaluated serum chloride values at diagnosis as prognostic biomarkers for overall survival and NIV adaptation in a retrospective center-based cohort of ALS patients. We collected all ALS patients with serum chloride assessment at diagnosis, identified through the Piemonte and Valle d’Aosta Register for ALS, evaluating the correlations among serum chloride, clinical features, and other serum biomarkers. Thereafter, time-to-event analysis was modeled to predict overall survival and NIV start. We found a significant correlation between serum chloride and inflammatory status markers, serum sodium, forced vital capacity (FVC), ALS functional rating scale-revised (ALSFRS-R) item 10 and 11, age at diagnosis, and weight loss. Time-to-event analysis confirmed both in univariate analysis and after multiple confounders’ adjustment that serum chloride value at diagnosis significantly influenced survival and time to NIV start. According to our analysis, based on a large ALS cohort, we found that serum chloride analyzed at diagnosis is a low-cost marker of impending respiratory decompensation. In our opinion, it should be added among the serum prognostic biomarkers that are able to stratify patients into different prognostic categories even when performed in the early phases of the disease.

BackgroundAn esophageal duplication cyst (EDC) is a rare malformation resulting from the embryonic foregut. VACTERL syndrome is a genetic disorder affecting many systems of the human body. We report the first case of VACTERL syndrome associated to asymptomatic double EDC.Case reportA girl with anorectal malformation and rectovestibular fistula, kidney malformation, and various vertebral defects came to our attention at the time of birth. VACTERL disease was diagnosed. She underwent Peña anoplasty at 4 months of life without complications. MRI was conducted at the age of 2. It accidentally showed a double esophageal duplication (12 mm × 35 mm × 10 mm) at the D7–D9 level. We planned a thoracoscopy; previous intraoperative esophagogastroduodenoscopy showed an external compression of the native esophagus. Two duplicated esophageal lesions were removed. The patient made an uneventful recovery and was completely asymptomatic at long-term follow-up.ConclusionsVACTERL syndrome is still a not well-defined disease. Based on the current literature, this is the first case of a double esophageal duplication in a patient affected by VACTERL syndrome. According to us, the thoracoscopic approach of esophageal duplications can be followed by experts. Complete surgical excision is possible even if the cyst shares a common muscular wall with the esophagus. For this reason, we suggest to close the muscular wall by a simple interrupted suture.

Background: Gangliocytic Paraganglioma is rarely reported in the paediatric age. We describe a case of a 4-month-old infant presenting with an intestinal obstruction from ileocolic intussusception led by Meckel's diverticulum. Case presentation: A 4-month-old male infant with intestinal obstruction underwent explorative laparotomy. An intussusception of a small mass in the diverticulum wall was found at surgery, which revealed to be a Gangliocytic Paraganglioma. Conclusions: The occurrence of this type of tumour is peculiar in children and has never been reported in infants and in association with Meckel's diverticulum and intestinal intussusception.

Psychosis can occur at high rates in individuals with autism spectrum disorder (ASD). However, the detection of prodromal psychotic symptoms, including attenuated psychosis syndrome (APS), conditions at high risk of converting to full psychosis, has not been extensively investigated in ASD. We longitudinally evaluate a sample of young ASD individuals (age, mean ± SD: 13 ± 2.9) with (n = 13) or without (n = 18) concomitant APS through a standardized assessment of autistic (Autism Diagnostic Observation Schedule–Second Edition; ADOS−2) and psychotic (Structured Interview for Psychosis-Risk Syndromes, SIPS) symptoms and cognitive and adaptive skills. Individuals with other neuropsychiatric disorders were excluded. We estimated the conversion rate to full psychosis (according to SIPS criteria) over time (39.6 ± 11.5 months) and explored the role of clinical variables at baseline in the transition to full psychosis. A conversion rate to full psychosis of 30.7% was found in ASD/APS. Conversion to full psychosis was not affected by the severity of the autistic and psychotic symptoms. At baseline, young individuals with ASD/APS who later converted to full psychosis showed lower cognitive performance (d = 2.05) and greater impairment of adaptive social functioning profile (d = 1.2) than those with ASD. The results of this preliminary report revealed that nearly a third of young individuals with ASD/APS convert to full psychosis over time. Conversion to full psychosis is affected by decreased cognitive and adaptive skills. Further investigations are needed to confirm the utility of APS detection and to better characterize the psychotic developmental trajectory in ASD, with consequent important implications on prognosis and therapeutic strategies.

This paper presents the results of the activities related to the subtask “Building and process optimization” of the IEA SHC Task 65. The main topic of this activity was the integration of solar cooling in retrofitted HVAC systems. Based on the current conventional HVAC systems, the integration may present difficulties concerning cold distribution and refrigerants. Cold supply systems can also reduce airflow in air-based systems and enhance thermal comfort in buildings. The best technical actions for specific scenarios were mentioned considering both technical and economic aspects. Unfortunately, not all the analyses that were planned provide useful data. Results show that there are few recent projects that consider the application of solar cooling systems in buildings and most of them are based on simulation. Moreover, not much data about the characteristics of the buildings (envelope, other cooling systems, comfort conditions, etc.) are reported in the studies. This is because many of them are more focused on the plants’ configurations, and the performance of the different plants is in general assessed by testing the prototype in a single room. Despite this, the information provided could be used as baseline cases in order to study the potential energy savings achievable by applying solar cooling systems.

The automotive industry seeks innovative solutions for energy-efficient and sustainable vehicles. Conventional air-conditioning systems consume significant energy and have environmental impacts. Adsorption technology offers a promising alternative with higher energy efficiency and reduced emissions. This review analyzes recent advancements in adsorption air-conditioning for automotive applications, including material selection and system integration. It discusses the benefits, challenges, environmental impact, and waste heat recovery potential of adsorption systems. This review explores emerging trends like hybridization with vapour-compression (VC) systems to optimize energy efficiency and sustainability. By evaluating the existing literature, this review provides insights into thermally driven technologies for automotive air-conditioning.

Since the spinal cord has traditionally been considered a bundle of long fibers connecting the brain to all parts of the body, the study of its role has long been limited to peripheral sensory and motor control. However, in recent years, new studies have challenged this view pointing to the spinal cord’s involvement not only in the acquisition and maintenance of new motor skills but also in the modulation of motor and cognitive functions dependent on cortical motor regions. Indeed, several reports to date, which have combined neurophysiological techniques with transpinal direct current stimulation (tsDCS), have shown that tsDCS is effective in promoting local and cortical neuroplasticity changes in animals and humans through the activation of ascending corticospinal pathways that modulate the sensorimotor cortical networks. The aim of this paper is first to report the most prominent tsDCS studies on neuroplasticity and its influence at the cortical level. Then, a comprehensive review of tsDCS literature on motor improvement in animals and healthy subjects and on motor and cognitive recovery in post-stroke populations is presented. We believe that these findings might have an important impact in the future making tsDCS a potential suitable adjunctive approach for post-stroke recovery.

Gamification, which refers to the use of game design elements in non-game contexts, provides similar experiences and motivations as games do; this makes gamification a useful approach to promote positive behaviors. As a useful tool for keeping users motivated, engaged and active, there is a wide interest in adopting gamification solutions for supporting and promoting positive behaviors and behavior change (e.g. quit smoking, ecological behaviors, food choices, civic engagement, mental healthcare, sustainability, etc.).In this study, we use the CiteSpace software to examine 984 publications and their 46,609 unique references on gamification applied for behavior change. The corpus of studies was downloaded from the Scopus database and refers to studies published between 2011 and the beginning of 2022. Several methods were used to analyze these data: (1) document co-citation analysis (DCA) was performed to identify the pivotal researches and the research areas; (2) author cocitation analysis (ACA) was performed to identify the main authors; (3) and keyword analysis was performed to detect the most influential keywords and their change over time.The results of the analysis provide an overview of the influential documents, authors and keywords that have given shape to the literature of the field, and how it has evolved, showing an initial interest in motivational and persuasion techniques, and in the gamification design, and subsequently in the development of more rigorous methodologies for both design and use.As the first scientometric review of gamification applied to behavior change, this study will be of interest to junior and senior researchers, graduate students, and professors seeking to identify research trends, topics, major publications, and influential scholars.

Abstract Background A few literatures reported that the outcomes of total knee replacement (TKR) in posttraumatic osteoarthritis (PTOA) were lower compared to TKR in primary osteoarthritis (primary OA). The study’s purpose was to compare the comorbidity and outcome of TKR among fracture PTOA, ligamentous PTOA, and primary OA. The secondary aim was to identify the effect of postoperatively lower limb mechanical axis on an 8-year survivorship after TKR between PTOA and primary OA. Methods Seven hundred sixteen patients with primary OA, 32 patients with PTOA (knee fracture subgroup), and 104 PTOA (knee ligamentous injury subgroup) were recruited. Demography, comorbidities, Charlson Comorbidity Index (CCI), operative parameters, mechanical axis, functional outcome assessed by WOMAC, and complications were compared among the three groups. Results PTOA group was significantly younger (p

Since the COVID-19 outbreak began, an association between COVID-19 and thrombotic diseases has been underlined. Although this association is more frequent with venous thromboembolism, ischaemic stroke has also been reported as a thrombotic complication in several cohorts of affected patients. Furthermore, the association between ischaemic stroke and COVID-19 has been considered a risk factor for early mortality. On the other hand, after the successful vaccination campaign, the incidence and the virulence of SARS-CoV-2 decreased, though it has been observed that COVID-19 may induce a severe infection in specific cohorts of frail subjects. For this reason, different drugs have been introduced of an antiviral action in order to improve the disease outcome of frail patients. In this field, with the arrival of a neutralizing monoclonal antibody against SARS-CoV-2, in particular, sotrovimab, a further chance to treat high-risk patients with mild-to-moderate COVID-19 arrived, achieving a concrete reduction in the risk of disease progression. We here report our clinical experience of an ischaemic stroke occurring a few minutes after the administration of sotrovimab for the treatment of moderate COVID-19 in a frail patient with chronic lymphocytic leukaemia. Other causes of ischaemic stroke were ruled out, and in order to evaluate the probability of a rare side effect, the Naranjo probability scale has also been utilized. In conclusion, among several side effects that have been described during the treatment of COVID-19 with sotrovimab, ischaemic stroke was not reported. Therefore, we here report a rare case of ischaemic stroke with early clinical manifestation after the administration of sotrovimab for the treatment of moderate COVID-19 in an immunocompromised patient for the first time.