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1.
Clin Appl Thromb Hemost ; 28: 10760296221127275, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124369

RESUMO

BACKGROUND: Iliac vein compression syndrome (IVCS) diagnosis heavily relies on an imaging test. However, non-invasive and contrast-free imaging test for the diagnosis of IVCS remains a big challenge. To address this issue, this prospective study aimed to assess the image quality and diagnostic performance of a magnetic resonance imaging technique, black-blood venous imaging (BBVI), in detecting IVCS by comparing it with contrast-enhanced computed tomography venography (CTV) and using invasive digital subtraction angiography (DSA) as the reference. METHODS: We enrolled 105 patients, and all patients underwent BBVI, CTV, and DSA examinations. We compared the consistency of CTV and BBVI image quality and their consistency in diagnosing the rate of iliac vein stenosis in IVCS patients. Using the consensus DSA as a reference, the sensitivity, specificity, positive and negative predictive values, and accuracy of BBVI and CTV and their diagnostic agreement with DSA were calculated. RESULTS: BBVI demonstrated high sensitivity, specificity, and accuracy for the diagnosis of IVCS, without contrast agents. BBVI and CTV are quite in diagnosis IVCS. Quite SE (67.8% vs 68.3%), SP (94.8% vs 94.8%), PPV (98.0% vs 98.0%), NPV (46.2% vs 46.9%) and ACC (75.3% vs 75.7%) were obtained by BBVI in comparison with CTV. CONCLUSION: BBVI has comparable diagnostic performance with CTV. It may be a viable alternative to CTV techniques in screening the IVCS without contrast agents and free of ionizing radiation.


Assuntos
Síndrome de May-Thurner , Meios de Contraste , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Estudo de Prova de Conceito , Estudos Prospectivos
2.
Crit Care Med ; 50(9): e731-e732, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35984068
3.
BMC Neurol ; 22(1): 293, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931957

RESUMO

BACKGROUND: Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), a rare disorder affecting young adults, causes gradual weakness of the limbs, areflexia and impaired sensory function. New CIDP phenotypes without pathogenic antibodies but with modified cell profiles have been described. Treatments include corticotherapy, intravenous immunoglobulins, and plasmapheresis but the latter's action mechanisms remain unclear. Plasmapheresis supposedly removes toxic agents like antibodies from plasma but it is uncertain whether it has an immune-modulating effect. Also, the refining mechanisms of the two main plasmapheresis techniques-single plasma exchange and double filtration plasmapheresis (DFPP) - are different and unclear. This study aims to compare the evolution of peripheral lymphocyte profiles in patients with CIDP according to their treatment (single centrifugation plasmapheresis or DFPP) to better grasp the action mechanisms of both techniques. METHOD: In this proof-of-concept, monocentric, prospective, Single-Case Experimental Design study, 5 patients are evaluated by alternating their treatment type (single plasma exchange or DFPP) for 6 courses of treatment after randomization to their first treatment type. Each course of treatment lasts 2-4 weeks. For single plasma exchange, 60 ml/kg plasma will be removed from the patient and replaced with albumin solutes, with a centrifugation method to avoid the immunological reaction caused by the membrane used with the filtration method. For DFPP, 60 ml/kg plasma will be removed from the patient with a plasma separator membrane, then processed via a fractionator membrane to remove molecules of a greater size than albumin before returning it to the patient. This technique requires no substitution solutes, only 20 g of albumin to replace what would normally be lost during a session. The primary outcome is the difference between the two plasmapheresis techniques in the variation of the TH1/TH17 ratio over the period D0H0-D0H3 and D0H0-D7. Secondary outcomes include the variation in lymphocyte subpopulations at each session and between therapeutic plasmapheresis techniques, the clinical evolution, tolerance and cost of treatments. DISCUSSION: Understanding the action mechanisms of single plasma exchange and DFPP will help us to offer the right treatment to each patient with CIPD according to efficacy, tolerance and cost. TRIAL REGISTRATION: ClinicalTrials.gov under the no. NCT04742374 and date of registration 10 December 2020.


Assuntos
Troca Plasmática , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Albuminas , Humanos , Linfócitos , Fenótipo , Plasmaferese/métodos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Estudo de Prova de Conceito , Estudos Prospectivos , Projetos de Pesquisa
4.
J Biotechnol ; 357: 47-55, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-35963593

RESUMO

The red palm weevil (RPW), Rhynchophorus ferrugineus, is considered a severe pest of palms. Usually, the early stages of infection are without visible signs. An attractive early sensing approach of non-visible infections is based on volatile organic compounds (VOCs). In this study, a whole-cell bacterial biosensor was used for the identification of RPW in date palm (Phoenix dactylifera). The cells are genetically modified to produce light in the presence of general stresses. The bioluminescent bacterial panel is based on three genetically engineered Escherichia coli strains that are sensitive to cytotoxicity (TV1061), genotoxicity (DPD2794), or quorum-sensing (K802NR). The bioluminescent bacterial panel detects the presence of VOCs and a change in the light signal is then generated, reflecting the health status of the date palm tree. The bioreporter bacteria cells are immobilized in calcium alginate tablets and placed in a sealed jar without direct contact with the tested sample, thereby exposing them only to the VOCs in the surrounding air. The immobilized bacteria cells were exposed to the air near infected by RPW or uninfected sugar canes, date palm tree pieces, and on date palm trees. Commercial plate reader was used for signal measurement. The findings show that quorum-sensing was induced by all the tested samples of infected sugar canes, date palm tree pieces, and date palm trees. While, cytotoxicity was induced only by infected date palm tree pieces, and genotoxicity was induced only by infected date palm trees. The bacterial monitoring results enable the identification of specific signatures that will allow a quick and accurate diagnosis.


Assuntos
Técnicas Biossensoriais , Phoeniceae , Compostos Orgânicos Voláteis , Gorgulhos , Animais , Bactérias , Estudo de Prova de Conceito , Açúcares , Gorgulhos/microbiologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-36012059

RESUMO

The aim of this study was to assess the acceptability and feasibility of offering risk-based breast cancer screening and its integration into regular clinical practice. A single-arm proof-of-concept trial was conducted with a sample of 387 women aged 40-50 years residing in the city of Lleida (Spain). The study intervention consisted of breast cancer risk estimation, risk communication and screening recommendations, and a follow-up. A polygenic risk score with 83 single nucleotide polymorphisms was used to update the Breast Cancer Surveillance Consortium risk model and estimate the 5-year absolute risk of breast cancer. The women expressed a positive attitude towards varying the frequency of breast screening according to individual risk and, especially, more frequently inviting women at higher-than-average risk. A lower intensity screening for women at lower risk was not as welcome, although half of the participants would accept it. Knowledge of the benefits and harms of breast screening was low, especially with regard to false positives and overdiagnosis. The women expressed a high understanding of individual risk and screening recommendations. The participants' intention to participate in risk-based screening and satisfaction at 1-year were very high.


Assuntos
Neoplasias da Mama , Detecção Precoce de Câncer , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Estudos de Viabilidade , Feminino , Humanos , Mamografia , Programas de Rastreamento , Estudo de Prova de Conceito
6.
Lung Cancer ; 171: 97-102, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35933915

RESUMO

INTRODUCTION: Exposure to osimertinib, a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for treatment of non-small cell lung cancer (NSCLC) and a sensitizing EGFR mutation, can be substantially below average. We evaluated whether plasma levels could be boosted by co-administration of cobicistat, a strong Cytochrome P450 3A-inhibitor. METHODS: This was a pharmacokinetic, proof-of-concept clinical trial (the OSIBOOST trial, NCT03858491). NSCLC-patients with osimertinib were eligible if their steady state osimertinib plasma trough concentration was low (≤195 ng/mL). On day 1, the area under the plasma curve (AUC0-24,ss) of osimertinib and its metabolite (AZ5104) was calculated using a limited sampling strategy (four samples). Cobicistat co-treatment (150 mg, once daily) was started on day 2. Between day 22-26, a second AUC was determined. Cobicistat dose could be escalated if the osimertinib trough concentration was still ≤ 195 ng/mL, in the absence of toxicity. Primary endpoint was the increase in osimertinib exposure, secondary endpoint was toxicity. Cobicistat could be continued during the expanded access phase, with follow-up (2-4 months) of the boosting effect. RESULTS: The mean baseline osimertinib trough concentration for the eleven enrolled patients was 154 ng/mL. In all patients, cobicistat addition led to an increase in osimertinib exposure. Mean increase in total AUC0-24ss (AUC osimertinib + AUC AZ5104) was 60%, (range 19%-192%). The boosting effect was consistent over time. No grade ≥ 2 toxicity was observed. CONCLUSION: Pharmacokinetic boosting of osimertinib with cobicistat in patients with NSCLC is feasible without increasing toxicity, although the degree of boosting is variable.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Acrilamidas/farmacocinética , Compostos de Anilina/uso terapêutico , Antineoplásicos/farmacocinética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Cobicistat/farmacocinética , Receptores ErbB/genética , Humanos , Indóis , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação/genética , Estudo de Prova de Conceito , Inibidores de Proteínas Quinases/farmacocinética , Pirimidinas
7.
J Hazard Mater ; 439: 129403, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-35908393

RESUMO

In situ burning (ISB) hasn't been widely used for offshore oil spill response for various reasons. We present a feasibility study for a new ISB method - the Burning Tongue (BT) concept. We conducted scaled experiments in the Ohmsett wave tank to demonstrate its feasibility. We produced a 35-m long "tongue" of burnable oil (average oil thickness 4.2 mm - above the thickness needed for ISB) by towing a conventional boom (with a 12″ (0.3 m) deep skirt) partially filled with crude oil and then released the oil through a 6″ (0.15 m) wide opening at the apex. We found that the boom movement produced a convergence zone just downstream that kept released oil thick and also pulled oil that entrained under the boom skirt into the thick "tongue" of oil. CFD modeling was performed to explain the flow hydrodynamics and the formation of the convergence zone, which indicates the phenomenon is universal. We used small harbor boom only partially filled with oil for this study and believe that a full-scale marine boom filled with oil would achieve an even thicker "burning tongue." The BT concept could make ISB more widely used for oil spill response in offshore areas.


Assuntos
Queimaduras , Poluição por Petróleo , Petróleo , Humanos , Poluição por Petróleo/análise , Estudo de Prova de Conceito
8.
Sci Rep ; 12(1): 11469, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35794460

RESUMO

Sepsis has been called the graveyard of pharmaceutical companies due to the numerous failed clinical trials. The lack of tools to monitor the immunological status in sepsis constrains the development of therapies. Here, we evaluated a test based on whole plasma peptidome acquired by MALDI-TOF-mass spectrometer and machine-learning algorithms to discriminate two lipopolysaccharide-(LPS) induced murine models emulating the pro- and anti-inflammatory/immunosuppression environments that can be found during sepsis. The LPS group was inoculated with a single high dose of LPS and the IS group was subjected to increasing doses of LPS, to induce proinflammatory and anti-inflammatory/immunosuppression profiles respectively. The LPS group showed leukopenia and higher levels of cytokines and tissue damage markers, and the IS group showed neutrophilia, lymphopenia and decreased humoral response. Principal component analysis of the plasma peptidomes formed discrete clusters that mostly coincided with the experimental groups. In addition, machine-learning algorithms discriminated the different experimental groups with a sensitivity of 95.7% and specificity of 90.9%. Data reveal the potential of plasma fingerprints analysis by MALDI-TOF-mass spectrometry as a simple, speedy and readily transferrable method for sepsis patient stratification that would contribute to therapeutic decision-making based on their immunological status.


Assuntos
Lipopolissacarídeos , Sepse , Animais , Citocinas , Humanos , Contagem de Leucócitos , Camundongos , Estudo de Prova de Conceito
9.
Clin Nutr ESPEN ; 50: 238-246, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35871930

RESUMO

BACKGROUND AND AIMS: Severe obesity (BMI ≥60 kg/m2) in multimorbid patients can be acutely life-threatening. While emergency weight-loss surgery is urgently needed to preserve life, most patients are in an inoperable state. Pre-surgical bridging therapy is required to achieve technical operability through weight reduction. Standard bridging using an intragastric balloon (IB) can achieve operability in 6 months but is unsuitable for some patients in a critical condition. A non-invasive fast-track rescue therapy to achieve very rapid operability is urgently needed. We investigated whether a rescue weight reduction therapy (RWR) consisting of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, a leucine-rich amino acid infusion and a hypocaloric diet, can accelerate readiness for emergency surgery in patients with acutely life-threatening severe obesity. METHODS: In this proof-of-concept study, prospective data from patients treated with RWR (intervention group 1, n = 26) were mathematically matched with retrospective biometric data of 26 patients with severe obesity (historic control group 2) who underwent standard 6-month bridging with IB. A rating scale was developed to identify patients needing urgent fast-track bridging. RESULTS: Rapid weight loss was observed in all patients on the RWR therapy. All achieved operability after a mean RWR bridging duration of 20.7 ± 6.9 days. Baseline weight was 236.3 ± 35.8 kg in group 1 compared with 230.1 ± 32.7 kg in group 2. Mean body weight loss during RWR was 27.5 ± 14.1 kg, compared with 20.9 ± 10.5 kg in group 2 (P = 0.0629). CONCLUSIONS: Pre-operative bridging using liraglutide in combination with a leucine-rich amino acid infusion and hypocaloric diet was effective in all cases of acutely life-threatening severe obesity, achieving technical operability within only ca. 2-4 weeks. This therapy has potential as a life-saving rescue therapy for multimorbid patients with severe obesity who were previously untreatable. This study is registered at ClinicalTrials.gov (identifier: NCT02616003).


Assuntos
Cirurgia Bariátrica , Balão Gástrico , Obesidade Mórbida , Dieta Redutora , Humanos , Leucina , Liraglutida , Obesidade/cirurgia , Obesidade Mórbida/cirurgia , Estudo de Prova de Conceito , Estudos Prospectivos , Estudos Retrospectivos , Redução de Peso
10.
Sensors (Basel) ; 22(14)2022 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-35890831

RESUMO

Ankle spasticity is clinically assessed using goniometry to measure the angle of muscle reaction during the Modified Tardieu Scale (MTS). The precision of the goniometric method is questionable as the measured angle may not represent when the spastic muscle reaction occurred. This work proposes a method to accurately determine the angle of muscle reaction during the MTS assessment by measuring the maximum angular velocity and the corresponding ankle joint angle, using two affordable inertial sensors. Initially we identified the association between muscle onset and peak joint angular velocity using surface electromyography and an inertial sensor. The maximum foot angular velocity occurred 0.049 and 0.032 s following the spastic muscle reaction for Gastrocnemius and Soleus, respectively. Next, we explored the use of two affordable inertial sensors to identify the angle of muscle reaction using the peak ankle angular velocity. The angle of muscle reaction and the maximum dorsiflexion angle were significantly different for both Gastrocnemius and Soleus MTS tests (p = 0.028 and p = 0.009, respectively), indicating that the system is able to accurately detect a spastic muscle response before the end of the movement. This work successfully demonstrates how wearable technology can be used in a clinical setting to identify the onset of muscle spasticity and proposes a more accurate method that clinicians can use to measure the angle of muscle reaction during the MTS assessment. Furthermore, the proposed method may provide an opportunity to monitor the degree of spasticity where the direct help of experienced therapists is inaccessible, e.g., in rural or remote areas.


Assuntos
Articulação do Tornozelo , Espasticidade Muscular , Tornozelo , Humanos , Extremidade Inferior , Espasticidade Muscular/diagnóstico , Músculo Esquelético , Estudo de Prova de Conceito
11.
Medicina (Kaunas) ; 58(7)2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35888586

RESUMO

Background and Objectives: In dentistry, the assessment of the histomorphometric features of periodontal (PD) and peri-implant (PI) lesions is important to evaluate their underlying pathogenic mechanism. The present study aimed to compare manual and digital methods of analysis in the evaluation of the inflammatory biomarkers in PI and PD lesions. Materials and Methods: PD and PI inflamed soft tissues were excised and processed for histological and immunohistochemical analyses for CD3+, CD4+, CD8+, CD15+, CD20+, CD68+, and CD138+. The obtained slides were acquired using a digital scanner. For each marker, 4 pictures per sample were extracted and the area fraction of the stained tissue was computed both manually using a 594-point counting grid (MC) and digitally using a dedicated image analysis software (DC). To assess the concordance between MC and DC, two blinded observers analysed a total of 200 pictures either with good quality of staining or with non-specific background noise. The inter and intraobserver concordance was evaluated using the intraclass coefficient and the agreement between MC and DC was assessed using the Bland-Altman plot. The time spent analysing each picture using the two methodologies by both observers was recorded. Further, the amount of each marker was compared between PI and PD with both methodologies. Results: The inter- and intraobserver concordance was excellent, except for images with background noise analysed using DC. MC and DC showed a satisfying concordance. DC was performed in half the time compared to MC. The morphological analysis showed a larger inflammatory infiltrate in PI than PD lesions. The comparison between PI and PD showed differences for CD68+ and CD138+ expression. Conclusions: DC could be used as a reliable and time-saving procedure for the immunohistochemical analysis of PD and PI soft tissues. When non-specific background noise is present, the experience of the pathologist may be still required.


Assuntos
Peri-Implantite , Periodontite , Antígenos CD20 , Biomarcadores/análise , Humanos , Peri-Implantite/patologia , Estudo de Prova de Conceito
13.
Sensors (Basel) ; 22(15)2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35898009

RESUMO

In this paper, the combination of using an anti-resonant hollow-core fiber (ARHCF), working as a gas absorption cell, and an inexpensive, commercially available watch quartz tuning fork (QTF), acting as a detector in the quartz-enhanced photothermal spectroscopy (QEPTS) sensor configuration is demonstrated. The proof-of-concept experiment involved the detection of methane (CH4) at 1651 nm (6057 cm-1). The advantage of the high QTF Q-factor combined with a specially designed low-noise amplifier and additional wavelength modulation spectroscopy with the second harmonic (2f-WMS) method of signal analysis, resulted in achieving a normalized noise-equivalent absorption (NNEA) at the level of 1.34 × 10-10 and 2.04 × 10-11 W cm-1 Hz-1/2 for 1 and 100 s of integration time, respectively. Results obtained in that relatively non-complex sensor setup show great potential for further development of cost-optimized and miniaturized gas detectors, taking advantage of the combination of ARHCF-based absorption cells and QTF-aided spectroscopic signal retrieval methods.


Assuntos
Metano , Quartzo , Amplificadores Eletrônicos , Estudo de Prova de Conceito , Análise Espectral/métodos
14.
BMC Med Inform Decis Mak ; 22(1): 181, 2022 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-35836174

RESUMO

BACKGROUND: Predicting treatment outcome in major depressive disorder (MDD) remains an essential challenge for precision psychiatry. Clinical prediction models (CPMs) based on supervised machine learning have been a promising approach for this endeavor. However, only few CPMs have focused on model sparsity even though sparser models might facilitate the translation into clinical practice and lower the expenses of their application. METHODS: In this study, we developed a predictive modeling pipeline that combines hyperparameter tuning and recursive feature elimination in a nested cross-validation framework. We applied this pipeline to a real-world clinical data set on MDD treatment response and to a second simulated data set using three different classification algorithms. Performance was evaluated by permutation testing and comparison to a reference pipeline without nested feature selection. RESULTS: Across all models, the proposed pipeline led to sparser CPMs compared to the reference pipeline. Except for one comparison, the proposed pipeline resulted in equally or more accurate predictions. For MDD treatment response, balanced accuracy scores ranged between 61 and 71% when models were applied to hold-out validation data. CONCLUSIONS: The resulting models might be particularly interesting for clinical applications as they could reduce expenses for clinical institutions and stress for patients.


Assuntos
Transtorno Depressivo Maior , Algoritmos , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Estudo de Prova de Conceito , Resultado do Tratamento
15.
Sensors (Basel) ; 22(11)2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35684600

RESUMO

There is growing interest in monitoring gait patterns in people with neurological conditions. The democratisation of wearable inertial sensors has enabled the study of gait in free living environments. One pivotal aspect of gait assessment in uncontrolled environments is the ability to accurately recognise gait instances. Previous work has focused on wavelet transform methods or general machine learning models to detect gait; the former assume a comparable gait pattern between people and the latter assume training datasets that represent a diverse population. In this paper, we argue that these approaches are unsuitable for people with severe motor impairments and their distinct gait patterns, and make the case for a lightweight personalised alternative. We propose an approach that builds on top of a general model, fine-tuning it with personalised data. A comparative proof-of-concept evaluation with general machine learning (NN and CNN) approaches and personalised counterparts showed that the latter improved the overall accuracy in 3.5% for the NN and 5.3% for the CNN. More importantly, participants that were ill-represented by the general model (the most extreme cases) had the recognition of gait instances improved by up to 16.9% for NN and 20.5% for CNN with the personalised approaches. It is common to say that people with neurological conditions, such as Parkinson's disease, present very individual motor patterns, and that in a sense they are all outliers; we expect that our results will motivate researchers to explore alternative approaches that value personalisation rather than harvesting datasets that are may be able to represent these differences.


Assuntos
Marcha , Doença de Parkinson , Humanos , Aprendizado de Máquina , Doença de Parkinson/diagnóstico , Estudo de Prova de Conceito , Análise de Ondaletas
16.
Eur J Pain ; 26(8): 1665-1678, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35671086

RESUMO

BACKGROUND: Painful diabetic peripheral neuropathy (PDPN) affects up to 26% of patients with diabetes mellitus, with major impacts on their general health and well-being. Most available drugs fail to deliver acceptable pain reduction in the majority of patients and are often poorly tolerated. NRD.E1 is a novel product that has shown anti-nociceptive preclinical effects and good tolerability in healthy volunteer studies. METHODS: This phase 2a, randomized, dose-finding, Proof of Concept study enrolled patients with PDPN of ≥3 months duration. After at least one treatment-free week (WO week), 88 patients entered a 1-week single-blind (SB)-placebo run-in period, followed by 3 weeks' double-blind (DB) treatment, during which they received NRD.E1 at 10, 40 or 150 mg/day or placebo. RESULTS: The primary endpoint (change from SB-placebo run-in week to week 3 in weekly mean of daily average numerical rating scale [NRS] pain intensity) showed clinically relevant placebo-corrected treatment effect pain reductions at 40 mg and 150 mg/day of 0.82 (95% CI: 0.07, 1.58, p = 0.034) and 0.66 (95% CI: -0.03, 1.35; p = 0.061) NRS points, respectively, though did not meet the pre-specified value of p = 0.016 required due to multiplicity. An additional post hoc endpoint looking at the change from WO baseline to week 3 in weekly mean of daily average NRS showed the placebo-corrected treatment effect was 1.46 (95% CI: 0.26, 2.66), and 1.20 (95% CI: 0.10, 2.29) NRS points, respectively. Secondary and post hoc analyses of NRS pain data (including 30 & 50% responder rate and NNT), sleep interference, Short-form McGill pain questionnaire (especially pain intensity assessed on Visual Analogue Scale), Patient's and Clinician's Global Impression of Change showed effects consistent with the primary findings. NRD.E1 was well tolerated, with only headache reported in more than two patients and more frequently on NRD.E1 than placebo. CONCLUSIONS: The data suggest that NRD.E1 potentially represents a novel non-opioid therapeutic option for patients with PDPN, with at least similar efficacy and better tolerability than available therapies, justifying its further evaluation in larger-scale confirmatory studies. SIGNIFICANCE: NRD.E1 is a novel non-opioid therapeutic which is being developed for the treatment of PDPN. In this randomized, controlled, dose-finding, Proof of Concept study, NRD.E1 induced a clinically relevant pain reduction and it was well tolerated. Available data suggest that NRD.E1 has at least similar efficacy and better tolerability than the currently available therapies, potentially offering a promising new therapeutic option to patients with PDPN and possibly other neuropathic pain indications.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Neuralgia , Neuropatias Diabéticas/tratamento farmacológico , Método Duplo-Cego , Humanos , Neuralgia/tratamento farmacológico , Medição da Dor , Estudo de Prova de Conceito , Método Simples-Cego , Resultado do Tratamento
17.
Depress Anxiety ; 39(8-9): 646-656, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35708131

RESUMO

OBJECTIVE: Underdeveloped cognitive control (CC)-the capacity to flexibly adjust to changing environments-may predispose some children to early onset anxiety disorders and represents a promising intervention target. The current study established and pilot-tested "Camp Kidpower"-a novel group-based, interactive CC training intervention-and assessed its impacts on behavioral and neurophysiological indices of CC among preschool children with elevated anxiety symptoms. METHODS: Forty-four anxious children (4-6 years) were enrolled in Camp Kidpower, delivered in four sessions over 10 days. Before and after camp, children's capacity for CC was measured using well-validated, non-trained behavioral tasks and error-related negativity (ERN). Child anxiety symptoms were measured by parent report on the Spence Preschool Anxiety Scale. RESULTS: Thirty-two children completed the study, as defined by completion of pre- and follow-up assessments and at least three camp sessions. From baseline to after camp, performance on behavioral tests of CC improved, ERN amplitude increased, and anxiety symptoms decreased. CONCLUSION: Results provide initial evidence that play-based cognitive training targeted to behavioral and brain markers of CC reduces anxiety in preschoolers.


Assuntos
Transtornos de Ansiedade , Ansiedade , Ansiedade/terapia , Transtornos de Ansiedade/psicologia , Transtornos de Ansiedade/terapia , Encéfalo , Pré-Escolar , Cognição , Potenciais Evocados/fisiologia , Humanos , Estudo de Prova de Conceito
18.
J Magn Reson ; 341: 107237, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35714389

RESUMO

PURPOSE: A framework for supervised design of MR sequences for any given target contrast is proposed, based on fully automatic acquisition and reconstruction of MR data on a real MR scanner. The proposed method does not require any modeling of MR physics and thus allows even unknown contrast mechanisms to be addressed. METHODS: A derivative-free optimization algorithm is set up to repeatedly update and execute a parametrized sequence on the MR scanner to acquire data. In each iteration, the acquired data are mapped to a given target contrast by linear regression. RESULTS: It is shown that with the proposed framework it is possible to find an MR sequence that yields a predefined target contrast. In the present case, as a proof-of principle, a sequence mapping absolute creatine concentration, which cannot be extracted from T1 or T2-weighted scans directly, is discovered. The sequence was designed in a comparatively short time and with no human interaction. CONCLUSIONS: New MR contrasts for mapping a given target can be discovered by derivative-free optimization of parametrized sequences that are directly executed on a real MRI scanner. This is demonstrated by 're-discovery' of a chemical exchange weighted sequence. The proposed method is considered to be a paradigm shift towards autonomous, model-free and target-driven sequence design.


Assuntos
Algoritmos , Imageamento por Ressonância Magnética , Humanos , Estudo de Prova de Conceito
19.
Thorac Cancer ; 13(15): 2180-2191, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35708207

RESUMO

BACKGROUND: CT scans are used in routine clinical practice for the diagnosis and treatment surveillance of non-small cell lung cancer (NSCLC). However, more sensitive methods are desirable. Liquid biopsy analyses of RNA and DNA can offer more sensitive diagnostic approaches. Cell-free RNA (cfRNA) has been described in several malignancies, but its clinical utility has not previously been explored. METHODS: We evaluated the clinical utility of cfRNA for early detection and surveillance of tumor disease in a proof-of-concept study. Using real-time-droplet digital polymerase chain reaction we characterized a candidate transcript (MORF4L2) in plasma samples from 41 advanced stage, 38 early stage NSCLC and 39 healthy samples. We compared its diagnostic performance with tumor markers and evaluated its utility for disease monitoring. RESULTS: MORF4L2 cfRNA was more abundant in patients than in healthy donors (p < 0.0001). Using the Youden index approach (cutoff value of 537 copies/ml was established) with a sensitivity of 0.73 (95% CI: 0.61-0.82) and a specificity of 0.87 (95% CI: 0.73-0.96). Positive and negative predictive values of 0.92 (95% CI: 0.83-0.95) and 0.59 (95% CI: 0.47-0.83) were achieved. Combination of cfRNA and Cyfra21-1 improved its predictive value from 89.5% to 94.7%. Low baseline MORF4L2 levels were associated with better overall survival (HR:0.25, 95% CI: 0.09-0.7, p = 0.009) and progression-free survival for patients treated with tyrosine kinase inhibitors (p = 0.011) and chemotherapy (p = 0.019). MORF4L2 profile between baseline and follow-up mirrored radiological response and tumor dynamics better than tumor markers. cfRNA transcripts allowed monitoring tumor dynamics in patients without tumor-reported genetic alterations. CONCLUSION: Our data support clinical utility of cfRNA for detection and surveillance of NSCLC. Further studies with larger cohorts are required.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Ácidos Nucleicos Livres , Neoplasias Pulmonares , Antígenos de Neoplasias , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Ácidos Nucleicos Livres/genética , Receptores ErbB/genética , Humanos , Queratina-19 , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Estudo de Prova de Conceito , Fatores de Transcrição/genética
20.
Acta Derm Venereol ; 102: adv00750, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35758514

RESUMO

Research relating to machine learning algorithms, including convolutional neural networks, has increased during the past 5 years. The aim of this pilot study was to investigate how accurately a convolutional neural network, trained on Swedish registry data, could perform in predicting cutaneous invasive and in situ melanoma (CMM) within 5 years. A cohort of 1,208,393 individuals was used. Registry data ranged from 4 July 2005 to 31 December 2011, predicting CMM between 1 January 2012 and 31 December 2016. A convolutional neural network with one-dimensional convolutions with respect to time was trained using healthcare databases and registers. The algorithm was trained on 23,886 individuals. Validation was performed on a holdout validation set including 6,000 individuals. After training and validation, the convolutional neural network was evaluated on a test set (1,000 individuals with an CMM occurring within 5 years and 5,000 without). The area under the receiver-operating characteristic curve was 0.59 (95% confidence interval (95% CI) 0.57-0.61). The point on the receiver-operating characteristic curve where sensitivity equalled specificity had a value of 56% (sensitivity 95% CI 53-60% and specificity 95% CI 55-58%). Albeit at an early stage, this pilot investigation demonstrates potential usefulness for machine learning algorithms in predicting melanoma risk.


Assuntos
Melanoma , Redes Neurais de Computação , Algoritmos , Humanos , Melanoma/epidemiologia , Projetos Piloto , Estudo de Prova de Conceito , Sistema de Registros
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