Mass spectrometry analysis can be performed by introducing samples directly to mass spectrometry, allowing the increase of the analysis throughput; however, some disadvantages of direct-to-mass spectrometry analysis include susceptibility to matrix effects and risk of instrument contamination from inadequate sample preparation. Solid-phase microextraction is one of the most suitable sample preparation methods for direct-to-mass spectrometry analysis, as it offers matrix-compatible coatings which ensure analyte enrichment with minimal or no interference from matrix. One of the ways solid-phase microextraction can be coupled directly to mass spectrometry is via a microfluidic open interface. This manuscript reports improvements made to the initial microfluidic open interface design, where the system components have been simplified to mostly commercially available materials. In addition, the analysis of samples has been automated by implementing software that fully controls the analysis workflow, where the washing procedure is optimized to completely reduce the carryover. Herein, the extraction and desorption time profiles from thin and thick SPME devices was studied where the overall workflow consisted of high-throughput sample preparation of 1.3 min per 96 samples and <1 min per sample instrumental analysis.

We consider the problem of adaptive stabilization for discrete-time, multi-dimensional linear systems with bounded control input constraints and unbounded stochastic disturbances, where the parameters of the system are unknown. To address this challenge, we propose a certainty-equivalent control scheme combining online parameter estimation with saturated linear control. We establish the existence of a high probability stability bound on the closed-loop system, under additional assumptions on the system and noise processes. Numerical examples are presented to illustrate our results.

Objective. The aim of this study was to investigate students’ knowledge, attitudes and hesitancy regarding COVID-19 vaccination. Methods. A cross-sectional questionnaire-based survey was conducted among a total of 1282 medical students and 509 non-medical students at four public universities in Bosnia and Herzegovina: Tuzla, Sarajevo, Banja Luka, and Mostar. Results. A significantly higher rate of vaccination was observed in the group of medical students as well as a higher level of knowledge about vaccination in general and vaccines against the COVID-19 disease. Students who received the COVID-19 vaccine had a higher level of knowledge about vaccination in general and COVID-19 vaccines in particular compared to the non-vaccinated students in the medical and non-medical groups, respectively. Furthermore, vaccinated students, regardless of the course they are taking, showed generally stronger positive attitudes compared to non-vaccinated students, regarding the safety and effectiveness of the COVID-19 vaccine. Both groups of students believe that the rapid development of the vaccine is contributing to refusal or hesitancy to receive a vaccine against COVID-19. Social media/networks were the main sources of information about the COVID-19 vaccine. We did not find any contribution of social media to the reduced level of COVID-19 vaccine coverage. Conclusion. Education of students about the benefits of the COVID-19 vaccine will lead to its better acceptance as well as the development of more positive attitudes towards vaccination in general, especially having in mind that students are the future population of parents, who will make decisions about vaccinating their children.

Background: Schizophrenia is chronic and debilitating psychiatric disorder, characterized by a constellation of clinical signs and symptoms that are categorized into distinct positive, negative, disorganization and cognitive symptom domains. The outcome of the disease is better in female patients compared to male patients who have a higher risk of rehospitalization and twice as long duration of hospital treatment. In male patients with schizophrenia an earlier onset of the disease, negative symptoms and a more severe clinical picture are noted, with a less promising therapeutic response to neuroleptics. The onset of negative symptoms is more variable. Objective: The aim of the study was to determine the correlation of positive and negative symptoms (PANSS scores) in patients with schizophrenia according to gender. Methods: The sample included 40 subjects with schizophrenia (21 males; 19 females). The study was conducted at the Department of Psychiatry Clinical Center University of Sarajevo. Results: All male subjects have a PANSS negative symptoms score of 17 or higher, while all female subjects have a PANSS negative symptoms score of less than 17. While the difference in the variances is not statistically significant, the results show that the difference in the average values of the PANSS symptom score between male and female subjects is statistically significant for both positive and negative symptoms (p=0.026). Conclusion: Diminished sociality, emotional responsiveness, and drive during childhood have been reported in a substantial minority of patients with schizophrenia. This aspect of the illness may account for the low level of emotional expression and neuromotor dysfunction in infants who subsequently have schizophrenia. In other patients, the negative symptoms first occur after the onset of psychosis.

Background Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. Methods In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. Findings Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6–3·4]) compared with the prepandemic phase (2·0 [0·9–3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0–5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0–1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2–1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1–1·7]; p=0·0039). Interpretation Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. Funding None.

The marine environment has a significant impact on life on Earth. Organisms residing in it are vital for the ecosystem but also serve as an inexhaustible source of biologically active compounds. Herein, the biodiversity of two brown seaweeds, Dictyota dichotoma and Dictyota fasciola from the Adriatic Sea, was evaluated. The aim of the study was the determination of differences in compound composition while comparing their activities, including antioxidant, antimicrobial, and enzyme inhibition, in connection to human digestion, dermatology, and neurological disorders. Chemical analysis revealed several terpenoids and steroids as dominant molecules, while fucoxanthin was the main identified pigment in both algae. D. dichotoma had higher protein, carbohydrate, and pigment content. Omega-6 and omega-3 fatty acids were identified, with the highest amount of dihomo-γ-linolenic acid and α-linolenic acid in D. dichotoma. Antimicrobial testing revealed a dose-dependent inhibitory activity of methanolic fraction against Escherichia coli and Staphylococcus aureus. Moderate antioxidant activity was observed for both algae fractions, while the dietary potential was high, especially for the D. fasciola dichloromethane fraction, with inhibition percentages of around 92% for α-amylase and 57% for pancreatic lipase at 0.25 mg/mL. These results suggest that Dictyota species might be a potent source of naturally derived agents for obesity and diabetes.

Introduction Hypoglycaemia is a harmful potential complication in people with type 1 diabetes mellitus (T1DM) and can be exacerbated in patients receiving treatment, such as insulin therapies, by the very interventions aiming to achieve optimal blood glucose levels. Symptoms can vary greatly, including, but not limited to, trembling, palpitations, sweating, dry mouth, confusion, seizures, coma, brain damage or even death if untreated. A pilot study with healthy (euglycaemic) participants previously demonstrated that hypoglycaemia can be detected non-invasively with artificial intelligence (AI) using physiological signals obtained from wearable sensors. This protocol provides a methodological description of an observational study for obtaining physiological data from people with T1DM. The aim of this work is to further improve the previously developed AI model and validate its performance for glycaemic event detection in people with T1DM. Such a model could be suitable for integrating into a continuous, non-invasive, glucose monitoring system, contributing towards improving surveillance and management of blood glucose for people with diabetes. Methods and analysis This observational study aims to recruit 30 patients with T1DM from a diabetes outpatient clinic at the University Hospital Coventry and Warwickshire for a two-phase study. The first phase involves attending an inpatient protocol for up to 36 hours in a calorimetry room under controlled conditions, followed by a phase of free-living, for up to 3 days, in which participants will go about their normal daily activities unrestricted. Throughout the study, the participants will wear wearable sensors to measure and record physiological signals (eg, ECG and continuous glucose monitor). Data collected will be used to develop and validate an AI model using state-of-the-art deep learning methods. Ethics and dissemination This study has received ethical approval from National Research Ethics Service (ref: 17/NW/0277). The findings will be disseminated via peer-reviewed journals and presented at scientific conferences. Trial registration number NCT05461144.

Sleep disorders can impact daily life, affecting physical, emotional, and cognitive well-being. Due to the time-consuming, highly obtrusive, and expensive nature of using the standard approaches such as polysomnography, it is of great interest to develop a noninvasive and unobtrusive in-home sleep monitoring system that can reliably and accurately measure cardiorespiratory parameters while causing minimal discomfort to the user’s sleep. We developed a low-cost Out of Center Sleep Testing (OCST) system with low complexity to measure cardiorespiratory parameters. We tested and validated two force-sensitive resistor strip sensors under the bed mattress covering the thoracic and abdominal regions. Twenty subjects were recruited, including 12 males and 8 females. The ballistocardiogram signal was processed using the 4th smooth level of the discrete wavelet transform and the 2nd order of the Butterworth bandpass filter to measure the heart rate and respiration rate, respectively. We reached a total error (concerning the reference sensors) of 3.24 beats per minute and 2.32 rates for heart rate and respiration rate, respectively. For males and females, heart rate errors were 3.47 and 2.68, and respiration rate errors were 2.32 and 2.33, respectively. We developed and verified the reliability and applicability of the system. It showed a minor dependency on sleeping positions, one of the major cumbersome sleep measurements. We identified the sensor under the thoracic region as the optimal configuration for cardiorespiratory measurement. Although testing the system with healthy subjects and regular patterns of cardiorespiratory parameters showed promising results, further investigation is required with the bandwidth frequency and validation of the system with larger groups of subjects, including patients.