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COVID-19 remains a severe condition for many including immunocompromised individuals. There remains a need for effective measures against this and other respiratory infections, which transmit via virus-laden droplets that reach the nasal or oral mucosae. Nasal sprays offer potential protection against viruses. Such formulations should preserve normal nasal mucociliary function. The antiviral barrier efficacy and effects on mucociliary function of astodrimer sodium nasal spray (AS-NS) were evaluated and compared with other available nasal sprays-low pH hydroxypropyl methylcellulose (HPMC-NS), iota-carrageenan (Carr-NS), nitric oxide (NO-NS), and povidone iodine (PI-NS). Assays simulated clinical conditions. Antiviral barrier function and cell viability were assessed in airway cell monolayers, while a model of fully differentiated human nasal epithelium (MucilAir™) was utilized to evaluate tissue integrity, cytotoxicity, cilia beating frequency, and mucociliary clearance. AS-NS reduced infectious virus in cell monolayers and demonstrated a benign cytotoxicity profile. In human nasal epithelium ex vivo, AS-NS had no impact on mucociliary function (cilia beating nor mucociliary clearance). Carr-NS, HPMC-NS, NO-NS and PI-NS demonstrated limited antiviral effects, while HPMC-NS caused inhibition of mucociliary function. Astodrimer sodium nasal spray demonstrates an acceptable nonclinical efficacy and safety profile as a barrier nasal spray against respiratory viral infection in the nasal cavity.

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Depuración Mucociliar , Mucosa Nasal , Rociadores Nasales , SARS-CoV-2 , Humanos , Mucosa Nasal/virología , Mucosa Nasal/efectos de los fármacos , Mucosa Nasal/metabolismo , SARS-CoV-2/efectos de los fármacos , Depuración Mucociliar/efectos de los fármacos , Antivirales/farmacología , Antivirales/administración & dosificación , COVID-19/virología , COVID-19/metabolismo , Tratamiento Farmacológico de COVID-19 , Supervivencia Celular/efectos de los fármacos

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INTRODUCTION: Cervical artery dissection (CeAD) is considered a non-atherosclerotic arteriopathy, but atherosclerosis of the cervical arteries may co-exist. We explored the frequency and clinical importance of co-existent atherosclerosis in patients with CeAD. PATIENTS AND METHODS: Single-center exploratory study from the Stroke Center Basel, Switzerland. We re-reviewed duplex ultrasound images at (i) baseline and (ii) last follow-up visit for the presence versus absence of the following atherosclerotic manifestations in the carotid arteries: (i) abnormal carotid intima-media thickness, (ii) plaques, and (iii) atherosclerotic stenosis. We investigated whether CeAD patients with versus without co-existing atherosclerosis differ regarding (a) recurrence of CeAD and (b) occurrence of vascular events (myocardial infarction, peripheral artery disease, or ischemic stroke) using logistic regression with adjustment for age and follow-up time. RESULTS: Among 294 CeAD patients (median age 46 [IQR 37-53], 41.8% women), 35 (12%) had any atherosclerotic signs at baseline. Among 196 patients with available follow-up, another 21/196 (11%) patients developed atherosclerosis during a median follow-up of 55.7 months. Patients with atherosclerosis had decreased odds of recurrent CeADs when compared to patients without atherosclerosis (OR 0.03, 95% CI = 0.00-0.30). During follow-up, 6 (15%) vascular events occurred among 40 CeAD patients with atherosclerosis and 13 (8.5%) among 153 patients without atherosclerosis (OR 1.38, 95% CI = 0.39-4.55, data for 3 patients were missing). DISCUSSION AND CONCLUSION: Signs of atherosclerosis in the carotid artery were detectable in 12% of CeAD patient at baseline. Additionally, 11% of CeAD patients developed new signs of atherosclerosis within the following 5 years. The presence of atherosclerosis may suggest a lower risk for recurrent CeAD. Whether it might indicate an increased risk for late clinical vascular events deserves further studies.

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Partial remission (PR) occurs in only half of people with new-onset type 1 diabetes (T1D) and corresponds to a transient period characterized by low daily insulin needs, low glycemic fluctuations and increased endogenous insulin secretion. While identification of people with newly-onset T1D and significant residual beta-cell function may foster patient-specific interventions, reliable predictive biomarkers of PR occurrence currently lack. We analyzed the plasma of children with new-onset T1D to identify biomarkers present at diagnosis that predicted PR at 3 months post-diagnosis. We first performed an extensive shotgun proteomic analysis using Liquid Chromatography-Tandem-Mass-Spectrometry (LCMS/MS) on the plasma of 16 children with new-onset T1D and quantified 98 proteins significantly correlating with Insulin-Dose Adjusted glycated hemoglobin A1c score (IDAA1C). We next applied a series of both qualitative and statistical filters and selected protein candidates that were associated to pathophysiological mechanisms related to T1D. Finally, we translationally verified several of the candidates using single-shot targeted proteomic (PRM method) on raw plasma. Taken together, we identified plasma biomarkers present at diagnosis that may predict the occurrence of PR in a single mass-spectrometry run. We believe that the identification of new predictive biomarkers of PR and ß-cell function is key to stratify people with new-onset T1D for ß-cell preservation therapies.

Asunto(s)

Biomarcadores , Diabetes Mellitus Tipo 1 , Proteómica , Humanos , Diabetes Mellitus Tipo 1/sangre , Biomarcadores/sangre , Niño , Proteómica/métodos , Masculino , Femenino , Adolescente , Preescolar , Espectrometría de Masas en Tándem , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Cromatografía Liquida , Proteínas Sanguíneas/análisis , Proteínas Sanguíneas/metabolismo , Inducción de Remisión , Insulina/sangre

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Much of our understanding of how the brain processes dynamic faces comes from research that compares static photographs to dynamic morphs, which exhibit simplified, computer-generated motion. By comparing static, video recorded, and dynamic morphed expressions, we aim to identify the neural correlates of naturalistic facial dynamism, using time-domain and time-frequency analysis. Dynamic morphs were made from the neutral and peak frames of video recorded transitions of happy and fearful expressions, which retained expression change and removed asynchronous and non-linear features of naturalistic facial motion. We found that dynamic morphs elicited increased N400 amplitudes and lower LPP amplitudes compared to other stimulus types. Video recordings elicited higher LPP amplitudes and greater frontal delta activity compared to other stimuli. Thematic analysis of participant interviews using a large language model revealed that participants found it difficult to assess the genuineness of morphed expressions, and easier to analyse the genuineness of happy compared to fearful expressions. Our findings suggest that animating real faces with artificial motion may violate expectations (N400) and reduce the social salience (LPP) of dynamic morphs. Results also suggest that delta oscillations in the frontal region may be involved with the perception of naturalistic facial motion in happy and fearful expressions. Overall, our findings highlight the sensitivity of neural mechanisms required for face perception to subtle changes in facial motion characteristics, which has important implications for neuroimaging research using faces with simplified motion.

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Clinical mental health researchers may understandably struggle with how to incorporate biological assessments in clinical research. The options are numerous and are described in a vast and complex body of literature. Here we provide guidelines to assist mental health researchers seeking to include biological measures in their studies. Apart from a focus on behavioral outcomes as measured via interviews or questionnaires, we advocate for a focus on biological pathways in clinical trials and epidemiological studies that may help clarify pathophysiology and mechanisms of action, delineate biological subgroups of participants, mediate treatment effects, and inform personalized treatment strategies. With this paper we aim to bridge the gap between clinical and biological mental health research by (1) discussing the clinical relevance, measurement reliability, and feasibility of relevant peripheral biomarkers; (2) addressing five types of biological tissues, namely blood, saliva, urine, stool and hair; and (3) providing information on how to control sources of measurement variability.

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BACKGROUND: The use of bibliometric analysis studies allows for the precise assessment of high impact contributions to various fields of study. A bibliometric assessment of academic works cited in filed patents enables tracking the academic studies which have been most influential in development of new technologies in spine surgery. METHODS: The Lens database was utilized to retrieve scholarly articles related to the field of spine surgery, with special focus on spinal fusion and biologics. Scholarly works cited in patents were organized by the publishing journal, article topic, study type, publishing institution, and author information. We categorized such publications in terms of their country of origin and, for patents within the US, region of origin. RESULTS: The search criteria yielded 37,005 scholarly works related to spine surgery published between 1889-2023 and a total of 947 scholarly works cited in patents from 1968-2023. Many of the top contributing authors were orthopedic surgeons while the top 3 authors were biomedical engineers. The region in the US with the most citations in patents and the most scholarly work overall was the middle-Atlantic region. CONCLUSIONS: We assessed trends in spine surgery innovation over time, evaluated regional contributions to spine surgery innovation in the United States and worldwide, and examined the top institutions driving innovation in spine surgery. Our results have historical importance and scientific value insofar as the identified trends and other insights provided by our data may influence future decisions in terms of research efforts and allocation of research funds.

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Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.LIBRETTO-001 is a registrational phase I/II, single-arm, open-label study of selpercatinib in patients with RET (REarranged during Transfection)-activated cancers (ClinicalTrials.gov identifier: NCT03157128). We present long-term safety and efficacy from LIBRETTO-001 in patients with RET-mutant medullary thyroid cancer (MTC; n = 324) and RET fusion-positive thyroid cancer encompassing different histological subtypes (TC; n = 66). At the data cutoff of January 2023, the objective response rate was 82.5% among patients with cabozantinib/vandetanib-naïve MTC and 95.8% among patients with treatment-naïve TC. At a median follow-up time of 42.4 and 44.0 months in patients with cabozantinib/vandetanib-naïve and pretreated MTC, the median progression-free survival (PFS) was not reached and 41.4 months, respectively. At a median follow-up time of 24.9 and 30.4 months in patients with treatment-naïve and pretreated TC, the median PFS was not reached and 27.4 months, respectively. Three-year PFS rates were 75.2% and 87.3% among patients with cabozantinib/vandetanib-naïve MTC and treatment-naïve TC, respectively. Median PFS was similar to median duration of response for each patient group. The safety profile of selpercatinib was consistent with previous reports. With an additional follow-up of 37 months and 228 more patients from the last disclosure, selpercatinib continued to provide durable and robust responses in treatment-naïve and previously treated patients with RET-mutant MTC and RET fusion-positive TC.

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Proteínas Proto-Oncogénicas c-ret , Pirazoles , Piridinas , Neoplasias de la Tiroides , Humanos , Proteínas Proto-Oncogénicas c-ret/genética , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Masculino , Persona de Mediana Edad , Femenino , Adulto , Anciano , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Piridinas/uso terapéutico , Piridinas/efectos adversos , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/patología , Adulto Joven , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Anciano de 80 o más Años , Supervivencia sin Progresión , Mutación , Anilidas

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OBJECTIVE: Postural abnormalities are a debilitating symptom of Parkinson disease (PD) that may require spinal intervention. Camptocormia is a unique abnormality most seen in PD, defined by a severe forward flexion of the trunk that completely resolves when supine. The condition presents a challenge due to an undefined pathophysiology and optimal therapeutic approach in a high-risk patient population. In this study, we systematically reviewed the literature regarding the use of spine surgery for the treatment of camptocormia in PD. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were systematically queried for studies involving spine surgery as treatment of PD-associated camptocormia. Studies involving nonsurgical management, involving deep brain stimulation, involving noncamptocormic PD patients undergoing surgery, or were out of scope were excluded. RESULTS: The search resulted in 5 studies, with a total of 19 patients with PD with camptocormia who underwent spine surgery (73.7% women). The mean age was 69.5 years (range, 59-83), and the mean PD duration was 69.5 months (range, 36-84). Of 19 patients, 11 required surgical revision (57.9%), with an average of 0.68 revisions per patient (range, 0-2). Radiographic and patient-reported outcomes were inconsistently reported yet showed improvement. Ultimately, 18 patients were reported to have positive outcomes. CONCLUSIONS: Despite an increased risk of complication and revision that is inherent to patients with PD, spine surgery has been proven as a reasonable alternative that should be prospectively studied further because 18 of 19 patients had favorable outcomes.

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The Solanaceae plant family contains at least 98 genera and over 2700 species. The Duboisia genus stands out for its ability to produce pyridine and tropane alkaloids, which are relatively poorly characterized at the phytochemical level. In this study, we analyzed dried leaves of Duboisia spp. using supercritical CO2 extraction and ultra-high-pressure liquid chromatography coupled to high-resolution tandem mass spectrometry, followed by feature-based molecular networking. Thirty-one known tropane alkaloids were putatively annotated, and the identity of six (atropine, scopolamine, anisodamine, aposcopolamine, apoatropine, and noratropine) were identified using reference standards. Two new granatane alkaloids connected in the molecular network were highlighted from Duboisia myoporoides, and their α-granatane tropate and α-granatane isovalerate structures were unambiguously established by semisynthesis.

Asunto(s)

Alcaloides , Hojas de la Planta , Solanaceae , Solanaceae/química , Estructura Molecular , Hojas de la Planta/química , Alcaloides/química , Tropanos/química , Cromatografía Líquida de Alta Presión , Espectrometría de Masas en Tándem

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BACKGROUND: Acne vulgaris is a common chronic inflammatory disorder of the pilosebaceous unit, characterized by papules, pustules and/or nodules manifesting primarily on the face and/or upper back that can leave scars, post-inflammatory hyperpigmentation (PIH) and erythema (PIE). OBJECTIVE: To evaluate the anti-inflammatory properties of a protein-free sap extruded from Rhealba® oat plantlets and a Garcinia mangostana extract on Cutibacterium acnes-induced inflammation in vitro and assess the tolerability and efficacy of a dermocosmetic product containing these actives in subjects with mild-to-moderate acne. METHODS: Monocyte-derived dendritic cells (Mo-DCs) from acne patients were stimulated with a planktonic culture of C. acnes and cytokine production was evaluated before and after addition of the test extracts by RT-PCR and ELISA. The clinical study was conducted in subjects with mild-to-moderate acne who applied the product to their face and upper back twice-daily for 2 months. RESULTS: Cutibacterium acnes-induced IL-6, IL-12p40, IL-10 and TNFα synthesis was reduced by the addition of the Garcinia mangostana extract and oat sap in vitro. The clinical study included 54 subjects. The 2-month, twice-daily application of the test product to the whole face and acne-affected areas on the upper back was well tolerated. It led to significant decreases in the number of retentional (-21% for 69% of subjects at D57) and inflammatory (-35% for 79% of subjects at D57) acne lesions, as well as a decrease in Global Acne Evaluation severity scores (2.5 at D1, 2.2 at D29 and 2.1 at D57). The dermatologist also rated the product as effective or very effective in most subjects with PIE (82%; n = 33/40) and PIH (70%; n = 8/11) at D57. CONCLUSION: The actives demonstrated anti-inflammatory effects in vitro, and the dermocosmetic product showed good clinical efficacy and tolerability in subjects with mild-to-moderate acne, supporting the use of this product in acne management.

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Acné Vulgar , Avena , Garcinia mangostana , Extractos Vegetales , Humanos , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/microbiología , Garcinia mangostana/química , Extractos Vegetales/farmacología , Femenino , Masculino , Adulto , Adulto Joven , Adolescente , Índice de Severidad de la Enfermedad , Propionibacterium acnes/efectos de los fármacos

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Cyclophilins (Cyps), characterized as peptidyl-prolyl cis-trans isomerases (PPIases), are highly conserved and ubiquitous, playing a crucial role in protein folding and cellular signaling. This review summarizes the biochemical pathways mediated by Cyps, including their involvement in pathological states such as viral replication, inflammation, and cancer progression, to underscore the therapeutic potential of Cyp inhibition. The exploration of Cyp inhibitors (CypI) in this review, particularly non-immunosuppressive cyclosporine A (CsA) derivatives, highlights their significance as therapeutic agents. The structural and functional nuances of CsA derivatives are examined, including their efficacy, mechanism of action, and the balance between therapeutic benefits and off-target effects. The landscape of CypI is evaluated to emphasize the clinical need for targeted approaches to exploit the complex biology of Cyps and to propose future directions for research that may enhance the utility of non-immunosuppressive CsA derivatives in treating diseases where Cyps play a key pathological role.

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Associations between the fat mass and obesity-associated (FTO) gene and obesity are well-established. However, recent studies have linked FTO to addiction phenotypes and dopaminergic signaling, thus suggesting broader psychiatric implications. We explored this assumption by conducting a phenome-wide association study across 4756 genome-wide association studies, identifying 23-26 psychiatric traits associated with FTO at the multiple-corrected significance level. These traits clustered into four categories: substance use, chronotype/sleep, well-being, and neuroticism. To validate these findings, we analyzed a functionally suggestive FTO variant (rs1421085) in a separate cohort, examining its impact on (i) alcohol use based on the Alcohol Use Disorders Identification Test (AUDIT), (ii) subjective well-being based on the WHO (Ten) Well-Being Index, and (iii) neuroticism based on Schafer's Five Factor Model or the Karolinska Scales of Personality. Our results confirmed a direct association between rs1421085 and neuroticism that was independent of age, sex, alcohol use, body mass index (BMI), and childhood adversities. Interestingly, while no direct association with alcohol intake was observed, both cross-sectional and lagged longitudinal mediation analyses uncovered indirect relationships between rs1421085 and problematic alcohol use (AUDIT-P), with increased neuroticism acting as the intermediary. Mediation analyses also supported an indirect effect of rs1421085 on lower well-being through the pathways of increased neuroticism and BMI. Our study is the first to validate a direct association between FTO and neuroticism. However, additional studies are warranted to affirm the causal pathways linking FTO to well-being and alcohol use through neuroticism.

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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Estudio de Asociación del Genoma Completo , Neuroticismo , Humanos , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Masculino , Femenino , Adulto , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Alcoholismo/genética , Consumo de Bebidas Alcohólicas/genética , Índice de Masa Corporal , Predisposición Genética a la Enfermedad

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BACKGROUND: Inflammatory bowel disease (IBD) is characterized by recurrent inflammation of the gastrointestinal tract and has been linked to an imbalance in gut bacteria. Synbiotics, which combine probiotics and prebiotics, are emerging as potential IBD treatments. AIM: To examine the effects of four synbiotic formulations on intestinal inflammation and peripheral biomarkers in a rodent IBD model of both sexes. METHODS: Colitis was induced in male and female C57BL/6 mice using 1% dextran sulfate sodium (DSS). Concurrently, a non-exposed control group was maintained. Starting on day 4 post-induction, DSS-exposed mice received one of four synbiotic preparations (Synbio1-4 composed of lactic acid bacteria, Bifidobacterium and dietary fibres), an anti-inflammatory drug used to treat IBD (mesalazine), or placebo (water) until day 14. Clinical symptoms and body weight were monitored daily. Blood samples (taken on days -3, 4, and 14, relative to DSS introduction), were used to analyze plasma biomarkers. At the end of the study, intestinal tissues underwent histological and morphological evaluation. RESULTS: Compared to placebo, the Synbio1-, 2- and 3-treated groups had improved clinical scores by day 14. Synbio1 was the only preparation that led to clinical improvements to scores comparable to those of controls. The Synbio1-and 3-treated groups also demonstrated histological improvements in the colon. Plasma biomarker analyses revealed significant Synbio1-induced changes in plasma IL17A, VEGFD, and TNFRSF11B levels that correlated with improved clinical or histological scores. Sex-stratified analyses revealed that most therapeutic-like effects were more pronounced in females. CONCLUSION: Our findings underscore the potential therapeutic benefits of specific synbiotics for IBD management. However, further research is needed to validate these outcomes in human subjects.

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Encefalitis , Trastornos Psicóticos , Receptor del Glutamato Metabotropico 5 , Humanos , Receptor del Glutamato Metabotropico 5/metabolismo , Trastornos Psicóticos/etiología , Encefalitis/complicaciones , Encefalitis/inmunología , Mioclonía/etiología , Ataxia , Femenino , Masculino , Adulto

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Background: Prednisolone and prednisone are recommended treatment options for adults with congenital adrenal hyperplasia (CAH); however, there is no randomised comparison of prednis(ol)one with hydrocortisone. Design: Six-month open-label randomised phase 3 study and interim analysis of a single-arm extension study was the design of the study. Methods: The method of the study was hydrocortisone dose equivalent and 09:00-h 17-hydroxyprogesterone (17OHP) from 48 patients taking prednis(ol)one at baseline. Results: At baseline, the median hydrocortisone dose equivalent was 30 mg/day and 17OHP was < 36 nmol/L (3× upper limit of normal) in 56% of patients. Patients were randomised to continue prednis(ol)one or switch to modified-release hydrocortisone capsule (MRHC) at the same hydrocortisone-equivalent dose. At 4 weeks, 94% on MRHC and 71% on prednis(ol)one had 17OHP < 36 nmol/L. At 18 months in the extension study of MRHC, the median MRHC dose was 20 mg/day and 82% had 17OHP < 36 nmol/L. The per cent of patients with 17OHP < 36 nmol/L on a hydrocortisone dose equivalent ≤ 25 mg/day was greater at 18 months in the extension study on MRHC than while on prednis(ol)one at baseline: 57% vs 27%, P = 0.04. In the randomised study, no patients had an adrenal crisis on MRHC and one on prednisolone. In the extension study (221 patient years), there were 12 adrenal crises in 5 patients (5.4/100 patient years). Conclusion: MRHC reduces 17OHP at 09:00 h compared to prednis(ol)one and the dose of MRHC can be down-titrated over time in the majority of patients.

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RATIONALE: Novel therapeutic approaches are needed in stroke recovery. Whether pharmacological therapies are beneficial for enhancing stroke recovery is unclear. Dopamine is a neurotransmitter involved in motor learning, reward, and brain plasticity. Its prodrug levodopa is a promising agent for stroke recovery. AIM AND HYPOTHESIS: To investigate the hypothesis that levodopa, in addition to standardized rehabilitation therapy based on active task training, results in an enhancement of functional recovery in acute ischemic or hemorrhagic stroke patients compared to placebo. DESIGN: ESTREL (Enhancement of Stroke REhabilitation with Levodopa) is a randomized (ratio 1:1), multicenter, placebo-controlled, double-blind, parallel-group superiority trial. PARTICIPANTS: 610 participants (according to sample size calculation) with a clinically meaningful hemiparesis will be enrolled ⩽7 days after stroke onset. Key eligibility criteria include (i) in-hospital-rehabilitation required, (ii) capability to participate in rehabilitation, (iii) previous independence in daily living. INTERVENTION: Levodopa 100 mg/carbidopa 25 mg three times daily, administered for 5 weeks in addition to standardized rehabilitation. The study intervention will be initiated within 7 days after stroke onset. COMPARISON: Matching placebo plus standardized rehabilitation. OUTCOMES: The primary outcome is the between-group difference of the Fugl-Meyer-Motor Assessment (FMMA) total score measured 3 months after randomization. Secondary outcomes include patient-reported health and wellbeing (PROMIS 10 and 29), patient-reported assessment of improvement, Rivermead Mobility Index, modified Rankin Scale, National Institutes of Health Stroke Scale (NIHSS), and as measures of harm: mortality, recurrent stroke, and serious adverse events. CONCLUSION: The ESTREL trial will provide evidence of whether the use of Levodopa in addition to standardized rehabilitation in stroke patients leads to better functional recovery compared to rehabilitation alone.

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Video recordings accurately capture facial expression movements; however, they are difficult for face perception researchers to standardise and manipulate. For this reason, dynamic morphs of photographs are often used, despite their lack of naturalistic facial motion. This study aimed to investigate how humans perceive emotions from faces using real videos and two different approaches to artificially generating dynamic expressions - dynamic morphs, and AI-synthesised deepfakes. Our participants perceived dynamic morphed expressions as less intense when compared with videos (all emotions) and deepfakes (fearful, happy, sad). Videos and deepfakes were perceived similarly. Additionally, they perceived morphed happiness and sadness, but not morphed anger or fear, as less genuine than other formats. Our findings support previous research indicating that social responses to morphed emotions are not representative of those to video recordings. The findings also suggest that deepfakes may offer a more suitable standardized stimulus type compared to morphs. Additionally, qualitative data were collected from participants and analysed using ChatGPT, a large language model. ChatGPT successfully identified themes in the data consistent with those identified by an independent human researcher. According to this analysis, our participants perceived dynamic morphs as less natural compared with videos and deepfakes. That participants perceived deepfakes and videos similarly suggests that deepfakes effectively replicate natural facial movements, making them a promising alternative for face perception research. The study contributes to the growing body of research exploring the usefulness of generative artificial intelligence for advancing the study of human perception.

Asunto(s)

Emociones , Expresión Facial , Reconocimiento Facial , Grabación en Video , Humanos , Emociones/fisiología , Femenino , Masculino , Adulto , Reconocimiento Facial/fisiología , Adulto Joven , Estimulación Luminosa , Percepción Social

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Basophil activation test (BAT) or the mast cell activation test (MAT) are two in vitro tests that are currently being studied in food allergy as diagnostic tools as an alternative to oral food challenges (OFCs). We conducted a meta-analysis on BAT and MAT, assessing their specificity and sensitivity in diagnosing peanut allergy. Six databases were searched for studies on patients suspected of having peanut allergy. Studies using BAT or MAT to peanut extract and/or component as diagnostic tools with results given in percentage of CD63 activation were included in this meta-analysis. Study quality was evaluated with the QUADAS-2 tool. On the 11 studies identified, eight focused exclusively on children, while three included a mixed population of adults and children. Only one study provided data on MAT, precluding us from conducting a statistical analysis. The diagnostic accuracy of BAT was higher when stimulated with peanut extract rather than Ara h 2 with a pooled specificity of 96% (95% CI: 0.89-0.98) and sensitivity of 0.86 (95% CI: 0.74-0.93). The sensitivity and specificity of BATs in discriminating between allergic and sensitized patients were studied as well, with pooled analysis revealing a sensitivity of 0.86 (95% CI: 0.74; 0.93) and a specificity of 0.97 (95% CI: 0.94, 0.98). BATs, when stimulated with peanut extracts, exhibit a satisfactory sensitivity and specificity for the diagnosis of peanut allergy and can help to discriminate between allergic individuals and those only sensitized to peanuts. More investigations on the potential for MATs diagnostic methods are warranted.

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Hipersensibilidad al Cacahuete , Sensibilidad y Especificidad , Hipersensibilidad al Cacahuete/diagnóstico , Hipersensibilidad al Cacahuete/inmunología , Humanos , Basófilos/inmunología , Arachis/inmunología , Niño , Mastocitos/inmunología , Prueba de Desgranulación de los Basófilos/métodos , Alérgenos/inmunología , Adulto

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WHAT IS THIS SUMMARY ABOUT?: This summary describes the results from a phase 2 study called FOENIXCCA2. The study evaluated treatment with futibatinib in people with a rare form of advanced bile duct cancer called intrahepatic cholangiocarcinoma (or iCCA), where the tumors have changes in the structure of a gene called FGFR2. These changes include FGFR2 gene fusions. Bile duct cancer often returns after surgery or cannot be treated by surgery because the tumor has spread, so it requires treatment with chemotherapy. People live for a median of 1 year after their first chemotherapy treatment and 6 months after their second treatment. This study included people whose cancer had grown/spread after one or more chemotherapy treatments. The aims of the study were to see if futibatinib could shrink the size of tumors and stop the cancer from growing/spreading and to see how long people lived when treated with futibatinib. Clinicians also looked at side effects from taking futibatinib and at how it affected people's quality of life. WHAT WERE THE RESULTS?: Futibatinib treatment shrank tumors in over 80% of people who received treatment. Tumors shrank by at least 30% in 42% of people. Futibatinib stopped tumors from growing/spreading for a median of 9.7 months. People who took the medicine lived for a median of 21.7 months, and 72% of people were still alive after 1 year. Side effects from taking futibatinib were like those reported for similar medicines, and clinicians considered the side effects to be manageable by adjusting the dose of futibatinib or treating the side effects. Most people reported that their quality of life stayed the same or improved during the first 9 months of taking futibatinib. WHAT DO THE RESULTS MEAN?: The results support the use of futibatinib for treating people with advanced bile duct cancer. Based on the results of this study, futibatinib is now approved in the US, Europe, and Japan. Futibatinib is approved for treating adults with advanced bile duct cancer who have received previous treatment for their cancer, and whose tumors have a gene fusion or other change in the FGFR2 gene.Clinical Trial Registration: NCT02052778 (FOENIX-CCA2).

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Apparent parallels between natural language and antibody sequences have led to a surge in deep language models applied to antibody sequences for predicting cognate antigen recognition. However, a linguistic formal definition of antibody language does not exist, and insight into how antibody language models capture antibody-specific binding features remains largely uninterpretable. Here we describe how a linguistic formalization of the antibody language, by characterizing its tokens and grammar, could address current challenges in antibody language model rule mining.

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Anticuerpos , Lingüística , Humanos , Anticuerpos/inmunología