Trust-based health decision-making recruits the neural interoceptive saliency network which relates to temporal trajectories of Hemoglobin A1C in Diabetes Type 1.

Experimental approaches in neuroeconomics generally involve monetary utility. Utility in the health domain is relevant in diabetes because constant daily life decisions are critical for self-consequential long-term outcomes. We used fMRI to investigate self-consequent decision-making in the health and economic domains in Type 1 Diabetes Mellitus and controls (N = 50). We focused on two critical phases of decision-making: Investment and Feedback (Positive or Negative). Patients showed larger BOLD activation of limbic, and reward/dopaminergic regions in particular in the health trust game. Importantly, the worse the trajectory of metabolic control (increasing HbA1C), the higher the BOLD activity in regions of the interoceptive saliency network. This was manifested by positive correlations between brain activity during investment in anterior cingulate cortex and insula and HbA1c blood level progression. We conclude that the neural correlates of health-consequent decision-making domain involve limbic and reward related dopaminergic regions in Type 1 Diabetes Mellitus. Furthermore, the temporal trajectory of HbA1C blood levels is correlated with neural risk processing in the saliency network. Evidence for differential risk processing in the health versus the neuroeconomic context, and the discovery of a role for the saliency interoceptive network in metabolic control trajectories suggests a new perspective on the development of personalized interventions.

Genomic profiling of primary and metastatic thyroid cancers.

The genetic repertoire of primary thyroid cancers (TCs) is well documented, but there is a considerable lack of molecular profiling in metastatic TCs. Here, we retrieved and analyzed the molecular and clinical features of 475 primary and metastatic TCs subjected to targeted DNA sequencing, from the cBioPortal database. The cohort included primary and metastatic samples from 276 papillary thyroid carcinomas (PTCs), 5 follicular thyroid carcinomas, 22 Hürthle cell carcinomas (HCCs), 127 poorly differentiated thyroid carcinomas (PDTCs), 30 anaplastic thyroid carcinomas (ATCs) and 15 medullary thyroid carcinomas. The ATCs had the highest tumor mutational burden and the HCCs the highest fraction of the genome altered. Compared to primary PTCs, the metastases had a significantly higher frequency of genetic alterations affecting TERT (51% vs 77%, P < 0.001), CDKN2A (2% vs 10%, P < 0.01), RET (2% vs 7%, P < 0.05), CDKN2B (1% vs 6%, P < 0.05) and BCOR (0% vs 4%, P < 0.05). The distant metastases had a significantly lower frequency of BRAF (64% vs 85%, P < 0.01) and a significantly higher frequency of NRAS (13% vs 3%, P < 0.05) hotspot mutations than the lymph node metastases. Metastases from HCCs and PDTCs were found to be enriched for NF1 (29%) and TP53 (18%) biallelic alterations, respectively. The frequency of subclonal mutations in ATCs was significantly higher than in PTCs (43% vs 25%, P < 0.01) and PDTCs (43% vs 22%, P < 0.01). Metastatic TCs are enriched in clinically informative genetic alterations such as RET translocations, BRAF hotspot mutations and NF1 biallelic losses that may be explored therapeutically.

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.

2023 UPDATE: Luso-Brazilian evidence-based guideline for the management of antidiabetic therapy in type 2 diabetes.

BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

From Bariatric Surgery to Conception: The Ideal Timing to Optimize Fetal Weight.

PURPOSE: Bariatric surgery (BS) increases the risk of small for gestational age (SGA) neonates. Guidelines recommend postponing pregnancy for 12-24 months, but optimal surgery-to-conception interval (BSCI) remains uncertain. We aimed to evaluate the impact of BSCI on birth weight and SGA. MATERIALS AND METHODS: Retrospective cohort study of 42 pregnancies following BS, including Roux-en-Y gastric bypass, gastric sleeve, adjustable gastric banding and biliopancreatic diversion. Neonates were classified as SGA if birth weight < 10th percentile. Optimal BSCI was obtained from the analysis of ROC curves, and pregnancies were compared by that cut-off. RESULTS: There was a linear association between BSCI and birth weight and an inverse association with SGA, with each additional month of BSCI translating into additional 4.5 g (95%CI: 2.0-7.0) on birth weight and -6% risk of SGA (95%CI: 0.90-0.99). We established a cut-off of 24.5 months of BSCI for lower risk of SGA. Pregnancies conceived in the first 24 months had a more than tenfold increased risk of SGA (OR 12.6, 95%CI: 2.4-66.0), even when adjusted for maternal age, gestational diabetes and inadequate gestational weight gain. CONCLUSION: BSCI was associated with birth weight and SGA. Our results are in line with the recommendations of BSCI of at least 24 months to reduce the risk of SGA.

Correlational study on novelty factor, immersive tendencies, purchase intention and memory in immersive VR e-commerce applications.

E-commerce is a field that changed how consumers purchase and interact with products. Although, inherent limitations such as the difficulty of testing the products "first-hand" before a purchase can compromise consumers' trust in online purchases. Virtual Reality (VR) has been investigated as a tool to solve limitations in several fields and how we can harness its potential to improve the overall user experience. This study analysed how immersive VR (IVR) could solve these limitations by allowing consumers to test products beforehand. We have studied how the Novelty Factor (evaluated by the users' past VR experience) and Immersive Tendencies correlate with the users' Purchase Intention and Memory (how well they remember the product's characteristics). We have analysed a sample of 38 participants (21 males) from 18 to 28 years old. Participants experienced a refrigerator with an interactive touchscreen in an IVR setup and were guided through its functionalities. Results indicated that memory of the product's characteristics was positively correlated with how recently they experienced VR. No correlations were found in the female sample. A negative correlation between Purchase Intention and Memory of the product's characteristics was found in the male sample. We concluded that IVR applications could become helpful for both consumers and online shops in an e-commerce context regardless of the Novelty Factor and Immersive Tendencies of consumers. However, differences between genders should be further investigated.

Acute kidney injury: a strong risk factor for hypoglycaemia in hospitalized patients with type 2 diabetes.

AIMS: Acute kidney injury (AKI) is highly prevalent during hospitalization of patients with type 2 diabetes (T2D). We aimed to assess the impact of AKI and its severity and duration on the risk of hypoglycaemia in hospitalized patients with T2D. METHODS: Retrospective cohort analysis of patients with T2D, admitted at a University Hospital in 2018-2019. AKI was defined as an increase in serum creatinine by ≥ 0.3 mg/dl (48 h) or ≥ 1.5 times baseline (7 days), and hypoglycaemia as blood glucose concentration < 70 mg/dl. Patients with chronic kidney disease stage ≥ 4 were excluded. We registered 239 hospitalizations with AKI and randomly selected 239 without AKI (control). Multiple logistic regression was used to adjust for confounding factors and ROC curve analysis to determine a cutoff for AKI duration. RESULTS: The risk of hypoglycaemia was higher in the AKI group (crude OR 3.6, 95%CI 1.8-9.6), even after adjusting for covariates (OR 4.2, 95%CI 1.8-9.6). Each day of AKI duration was associated with a 14% increase in the risk of hypoglycaemia (95%CI 1.1-1.2), and a cutoff of 5.5 days of AKI duration was obtained for increased risk of hypoglycaemia and mortality. AKI severity was also associated with mortality, but showed no significant association with hypoglycaemia. Patients with hypoglycaemia had 4.4 times greater risk of mortality (95%CI 2.4-8.2). CONCLUSIONS: AKI increased the risk of hypoglycaemia during hospitalization of patients with T2D, and its duration was the main risk factor. These results highlight the need for specific protocols to avoid hypoglycaemia and its burden in patients with AKI.

Studying the Influence of Multisensory Stimuli on a Firefighting Training Virtual Environment.

How we perceive and experience the world around us is inherently multisensory. Most of the Virtual Reality (VR) literature is based on the senses of sight and hearing. However, there is a lot of potential for integrating additional stimuli into Virtual Environments (VEs), especially in a training context. Identifying the relevant stimuli for obtaining a virtual experience that is perceptually equivalent to a real experience will lead users to behave the same across environments, which adds substantial value for several training areas, such as firefighters. In this paper, we present an experiment aiming to assess the impact of different sensory stimuli on stress, fatigue, cybersickness, Presence and knowledge transfer of users during a firefighter training VE. The results suggested that the stimulus that significantly impacted the user's response was wearing a firefighter's uniform and combining all sensory stimuli under study: heat, weight, uniform, and mask. The results also showed that the VE did not induce cybersickness and that it was successful in the task of transferring knowledge.

ARAM: A Technology Acceptance Model to Ascertain the Behavioural Intention to Use Augmented Reality.

The expansion of augmented reality across society, its availability in mobile platforms and the novelty character it embodies by appearing in a growing number of areas, have raised new questions related to people's predisposition to use this technology in their daily life. Acceptance models, which have been updated following technological breakthroughs and society changes, are known to be great tools for predicting the intention to use a new technological system. This paper proposes a new acceptance model aiming to ascertain the intention to use augmented reality technology in heritage sites-the Augmented Reality Acceptance Model (ARAM). ARAM relies on the use of the Unified Theory of Acceptance and Use of Technology model (UTAUT) model's constructs, namely performance expectancy, effort expectancy, social influence, and facilitating conditions, to which the new and adapted constructs of trust expectancy, technological innovation, computer anxiety and hedonic motivation are added. This model was validated with data gathered from 528 participants. Results confirm ARAM as a reliable tool to determine the acceptance of augmented reality technology for usage in cultural heritage sites. The direct impact of performance expectancy, facilitating conditions and hedonic motivation is validated as having a positive influence on behavioural intention. Trust expectancy and technological innovation are demonstrated to have a positive influence on performance expectancy whereas hedonic motivation is negatively influenced by effort expectancy and by computer anxiety. The research, thus, supports ARAM as a suitable model to ascertain the behavioural intention to use augmented reality in new areas of activity.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear feature: clinical, pathological, and molecular update 5 years after the nomenclature revision.

The term non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was proposed in 2016 and incorporated as a new entity in the World Health Organization (WHO) classification of tumours of endocrine organs in 2017. Since then, there has been debate regarding the histological criteria for the diagnosis, the need for molecular studies or the risk of lymph node metastasis or recurrence associated with this entity. Over the years, the concept of NIFTP evolved, now including both small (<1 cm) and large (>4 cm) tumours and oncocytic lesions. On the other hand, recent data on NIFTP in the setting of thyroid follicular nodular disease or frequent coexistence of malignant tumours raised concerns regarding the follow-up of these patients. Today, both pathologists and clinicians still face several challenges in the diagnosis, treatment, and follow-up of patients with NIFTP.

Using Heart Rate Variability for Comparing the Effectiveness of Virtual vs Real Training Environments for Firefighters.

The use of Virtual Reality (VR) technology to train professionals has increased over the years due to its advantages over traditional training. This paper presents a study comparing the effectiveness of a Virtual Environment (VE) and a Real Environment (RE) designed to train firefighters. To measure the effectiveness of the environments, a new method based on participants' Heart Rate Variability (HRV) was used. This method was complemented with self-reports, in the form of questionnaires, of fatigue, stress, sense of presence, and cybersickness. An additional questionnaire was used to measure and compare knowledge transfer enabled by the environments. The results from HRV analysis indicated that participants were under physiological stress in both environments, albeit with less intensity on the VE. Regarding reported fatigue and stress, the results showed that none of the environments increased such variables. The results of knowledge transfer showed that the VE obtained a significant increase while the RE obtained a positive but non-significant increase (median values, VE: before - 4 after - 7, p = .003; RE: before - 4 after - 5, p = .375). Lastly, the results of presence and cybersickness suggested that participants experienced high overall presence and no cybersickness. Considering all results, the authors conclude that the VE provided effective training but that its effectiveness was lower than that of the RE.

SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World's Population.

Fifty ~20-amino acid (aa)-long peptides were selected from functionally relevant SARS-CoV-2 S, M, and E proteins for trial B-21 and another 53 common ones, plus some new ones derived from the virus' main genetic variants for complementary trial C-21. Peptide selection was based on tremendous SARS-CoV-2 genetic variability for analysing them concerning vast human immunogenetic polymorphism for developing the first supramutational, Colombian SARS-protection (SM-COLSARSPROT), peptide mixture. Specific physicochemical rules were followed, i.e., aa predilection for polyproline type II left-handed (PPIIL) formation, replacing ß-branched, aromatic aa, short-chain backbone H-bond-forming residues, π-π interactions (n→π* and π-CH), aa interaction with π systems, and molecular fragments able to interact with them, disrupting PPIIL propensity formation. All these modified structures had PPIIL formation propensity to enable target peptide interaction with human leukocyte antigen-DRß1* (HLA-DRß1*) molecules to mediate antigen presentation and induce an appropriate immune response. Such modified peptides were designed for human use; however, they induced high antibody titres against S, M, and E parental mutant peptides and neutralising antibodies when suitably modified and chemically synthesised for immunising 61 major histocompatibility complex class II (MHCII) DNA genotyped Aotus monkeys (matched with their corresponding HLA-DRß1* molecules), predicted to cover 77.5% to 83.1% of the world's population. Such chemically synthesised peptide mixture represents an extremely pure, stable, reliable, and cheap vaccine for COVID-19 pandemic control, providing a new approach for a logical, rational, and soundly established methodology for other vaccine development.

Hypoglycemia unawareness in type 1 diabetes patients using intermittent continuous glucose monitoring: Identification of risk factors and glycemic patterns.

BACKGROUND: Hypoglycemia unawareness designates failure to detect eminent hypoglycemia. Clarke's questionnaire is one of the most used systems to evaluate this problem. AIMS: To relate Clarke's questionnaire (QQ) results with continuous glucose monitoring data. METHODS: Application of the questionnaire in a sample of type 1 diabetes mellitus (T1DM) patients using intermittent continuous glucose monitoring (iCGM). RESULTS: 111 T1DM patients were evaluated, 56.8% female, mean age 35.0 ± 12.4 years and mean disease duration 18.8 ± 10.5 years. According to CQ, 13.5% had unawareness, 76.6% awareness and 9.9% indeterminate awareness to hypoglycemia. Those with unawareness had longer disease duration (25.1 ± 10.4 vs 18.2 ± 10.3 for awareness and 14.9 ± 9.9 for indeterminate awareness, p = 0.047), more time below range (10.3 ± 4.9% vs 6.3 ± 5.1 and 6.3 ± 4.8; p = 0.009) and higher mean duration of hypoglycemia (131.7 ± 38.6 vs 116.6 ± 49.6 and 131.7 ± 38.6; p = 0.008). In multivariate analysis, mean duration of hypoglycemia was an independent predictor of CQ results. In a receiver operating curve (AUC 0.746; p = 0.004) a mean duration of hypoglycemia ≥106.5 min showed 84.6% sensitivity/64.4% specificity for unawareness. CONCLUSIONS: Our sample had a significative prevalence of hypoglycemia unawareness which increased with longer diabetes duration. iCGM data can be indicative of this problem, with a mean hypoglycemia duration ≥106.5 min being suggestive, albeit unspecific.

Do Multisensory Stimuli Benefit the Virtual Reality Experience? A Systematic Review.

The majority of virtual reality (VR) applications rely on audiovisual stimuli and do not exploit the addition of other sensory cues that could increase the potential of VR. This systematic review surveys the existing literature on multisensory VR and the impact of haptic, olfactory, and taste cues over audiovisual VR. The goal is to identify the extent to which multisensory stimuli affect the VR experience, which stimuli are used in multisensory VR, the type of VR setups used, and the application fields covered. An analysis of the 105 studies that met the eligibility criteria revealed that 84.8 percent of the studies show a positive impact of multisensory VR experiences. Haptics is the most commonly used stimulus in multisensory VR systems (86.6 percent). Non-immersive and immersive VR setups are preferred over semi-immersive setups. Regarding the application fields, a considerable part was adopted by health professionals and science and engineering professionals. We further conclude that smell and taste are still underexplored, and they can bring significant value to VR applications. More research is recommended on how to synthesize and deliver these stimuli, which still require complex and costly apparatus be integrated into the VR experience in a controlled and straightforward manner.

The clinical spectrum of X-linked adrenoleukodystrophy: from Addison's-only in men to middle-age neurologic manifestations in women.

X-linked adrenoleukodystrophy (X-ALD) is caused by a mutation in the ABCD1 gene which encodes for a peroxisomal very long-chain fatty acid (VLCFA) transporter. Clinically, X-ALD can present a wide range of phenotypes, from slowly progressive myelopathy to rapid demyelination of brain white matter (cerebral X-ALD-CALD). Adrenocortical insufficiency (AI) occurs mainly in the pediatric age group, and it can be the first manifestation of the disease. Female carriers may also develop manifestations of myelopathy, but later in life. We present two cases of patients who show the heterogeneous clinical manifestations of X-ALD. Case 1 was a man with AI diagnosed at 6 years old and with the first manifestations of myelopathy at 44 years old, which led to the diagnosis of X-ALD. At 47 years, he developed rapidly progressive CALD. Case 2 was a woman with progressive spastic gait disturbance that started at 49 years old. The diagnosis of X-ALD was confirmed at 54 years old after the discovery of a family history of the disease. Mild progression of the neurologic manifestations was noted, but with no signs of AI nor CALD. She is currently 60 years old and under surveillance. We review the current knowledge on X-ALD as concerns its genetic and pathophysiological mechanisms, clinical presentations, diagnosis, treatment, and follow-up. This condition is a real diagnostic challenge. The early detection of AI and CALD, potentially life-threatening complications in men, is very difficult. The surveillance of these complications in female patients still raises controversy.

Flash glucose monitoring and glycemic control in type 1 diabetes with subcutaneous insulin infusion.

AIMS: To analyze the association between scan frequency and glycemic measures in continuous subcutaneous insulin infusion (CSII) treated type 1 diabetes (T1DM) adults. METHODS: This retrospective study included 140 patients (> 18 years) with T1DM who used flash glucose monitoring (FGM). For each patient, we analyzed the Ambulatory Glucose Profile data over a period of 90 days. Data regarding glucose management indicator (GMI), time above, below and within range (TIR) and coefficient of variation (CV) were correlated with the number of daily scans. The effect of each additional test on glucose parameters was also evaluated. RESULTS: Users performed a mean of 8.6 ± 4.4 scans per day. There was an inverse correlation between scanning frequency and GMI (r = - 0.431, p < 0.001), CV (r = - 0.440, p < 0.001), time above and below range (r = - 0.446, p < 0.001 and r = - 0.200, p = 0.018, respectively). The number of daily scans correlated positively with TIR (r = 0.554, p < 0.001). For each additional scan per day, the mean GMI decreased 0.09% and TIR increased 1.60%. CONCLUSIONS: In patients with T1DM and CSII, higher rates of scanning correlated with improved glycemic markers, including reduced GMI and CV and increased TIR. For each test performed, there was a significant effect on the improvement of all glucose parameters.

Heterogeneity amongst GLP-1 RA cardiovascular outcome trials results: can definition of established cardiovascular disease be the missing link?

Atherosclerotic cardiovascular diseases are the leading cause of adverse outcomes in patients with type 2 diabetes, and all new anti-diabetic agents are mandated to undergo cardiovascular outcome trials (CVOTs). Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are incretin mimetics that reduce blood glucose levels with a low associated risk of hypoglycaemia. CVOTs with different GLP-1 RAs yielded different results in terms of major cardiovascular composite outcome (MACE), with some trials showing superiority in the treatment arm, whereas other simply displayed non-inferiority. More importantly, the significance of each component of MACE varied between drugs. This begs the question of whether these differences are due to dissimilarities between drugs or other factors, namely trial design, are at the root of these differences. We analyse the trial designs for all CVOTs with GLP-1 RAs and highlight important differences between them, namely in terms of definition of established cardiovascular disease, and discuss how these differences might explain the disparate results of the trials and preclude direct comparisons between them. We conclude that a fair comparison between GLP-1 RA CVOTs would involve post-hoc analysis re-grouping the patients into different cardiovascular risk categories based upon their baseline clinical parameters, in order to even out the criteria used to classify patients.

Genetic Determinants for Prediction of Outcome of Patients with Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) usually presents an excellent prognosis, but some patients present with aggressive metastatic disease. BRAF, RAS, and TERT promoter (TERTp) genes are altered in PTC, and their impact on patient outcomes remains controversial. We aimed to determine the role of genetic alterations in PTC patient outcomes (recurrent/persistent disease, structural disease, and disease-specific mortality (DSM)). The series included 241 PTC patients submitted to surgery, between 2002-2015, in a single hospital. DNA was extracted from tissue samples of 287 lesions (primary tumors and metastases). Molecular alterations were detected by Sanger sequencing. Primary tumors presented 143 BRAF, 16 TERTp, and 13 RAS mutations. Isolated TERTpmut showed increased risk of structural disease (HR = 7.0, p < 0.001) and DSM (HR = 10.1, p = 0.001). Combined genotypes, BRAFwt/TERTpmut (HR = 6.8, p = 0.003), BRAFmut/TERTpmut (HR = 3.2, p = 0.056) and BRAFmut/TERTpwt (HR = 2.2, p = 0.023) showed increased risk of recurrent/persistent disease. Patients with tumors BRAFwt/TERTpmut (HR = 24.2, p < 0.001) and BRAFmut/TERTpmut (HR = 11.5, p = 0.002) showed increased risk of structural disease. DSM was significantly increased in patients with TERTpmut regardless of BRAF status (BRAFmut/TERTpmut, log-rank p < 0.001; BRAFwt/TERTpmut, log-rank p < 0.001). Our results indicate that molecular markers may have a role in predicting PTC patients' outcome. BRAFmut/TERTpwt tumors were prone to associate with local aggressiveness (recurrent/persistent disease), whereas TERTpmut tumors were predisposed to recurrent structural disease and DSM.

Hands-free interaction in immersive virtual reality: A systematic review.

Hands are the most important tool to interact with virtual environments, and they should be available to perform the most critical tasks. For example, a surgeon in VR should keep his/her hands on the instruments and be able to do secondary tasks without performing a disruptive event to the operative task. In this common scenario, one can observe that hands are not available for interaction. The goal of this systematic review is to survey the literature and identify which hands-free interfaces are used, the performed interaction tasks, what metrics are used for interface evaluation, and the results of such evaluations. From 79 studies that met the eligibility criteria, the voice is the most studied interface, followed by the eye and head gaze. Some novel interfaces were brain interfaces and face expressions. System control and selection represent most of the interaction tasks studied and most studies evaluate interfaces for usability. Despite the best interface depending on the task and study, the voice was found to be versatile and showed good results amongst the studies. More research is recommended to improve the practical use of the interfaces and to evaluate the interfaces more formally.