Rejected

Natural language processing (NLP) of unstructured text from Electronic Medical Records (EMR) can improve characterization of COVID-19 signs and symptoms, but large-scale studies demonstrating the real-world application and validation of NLP for this purpose are limited.

Since vaccination remains the only effective protection against orthopox virus-induced diseases such as smallpox or monkeypox, the strategic use and stockpiling of these vaccines remains of significant public health importance. The approved liquid-frozen formulation of Bavarian Nordic's Modified Vaccinia Ankara (MVA-BN) smallpox vaccine has specific cold-chain requirements, while the freeze-dried (FD) formulation of this vaccine provides more flexibility in terms of storage conditions and shelf life. In this randomized phase 3 trial, the immunogenicity and safety of 3 consecutively manufactured lots of the FD MVA-BN vaccine was evaluated. A total of 1129 healthy adults were randomized to 3 treatment groups (lots 1 to 3) and received 2 vaccinations 4 weeks apart. For both neutralizing and total antibodies, a robust increase of geometric mean titer (GMT) was observed across all lot groups 2 weeks following the second vaccination, comparable to published data. For the primary results, the ratios of the neutralizing antibody GMTs between the lot group pairs ranged from 0.936 to 1.115, with confidence ratios well within the pre-specified margin of equivalence. Results for total antibodies were similar. In addition, seroconversion rates were high across the 3 lots, ranging between 99.1 % and 99.7 %. No safety concerns were identified; particularly, no inflammatory cardiac disorders were detected. The most common local solicited adverse events (AEs) reported across lot groups were injection site pain (87.2%) and erythema (73.2%), while the most common general solicited adverse events were myalgia, fatigue, and headache in 40.6% to 45.5% of all participants, with no meaningful differences among the lot groups. No related serious AEs were reported. In conclusion, the data demonstrate consistent and robust immunogenicity and safety results with a freeze-dried formulation of MVA-BN. Clinical Trial Registry Number: NCT03699124.

Transvenous lead extraction (TLE) procedures are now increasingly safe, but there is still a risk of major complications (MC).

Bruxism, a common medical condition characterised by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible, can occur during sleep, when it is known as sleep bruxism (SB), or during wakefulness, when it is known as awake bruxism (AB). Although bruxism often causes headaches, temporomandibular joint pain, masticatory muscle pain, mechanical tooth wear, prosthodontic complications and cracked teeth, there is still not enough data to define and support a standardised approach to its treatment. The aim of this review was to present the pathophysiology, consequences, types and treatment methods of bruxism in order to increase readers' knowledge of this topic. Differences between awake and nocturnal bruxism are included, as well as risk factors and indicators visible during the clinical examination of affected patients. Among the causes we consider are genetics, stress, oral parafunctions and changes in the Central Nervous System (CNS). Potential and common methods of treatment are presented, along with suggested guidelines that should be followed when determining an appropriate treatment method. We draw attention to the notably dynamic development of bruxism in today's society and the importance of informational and preventive projects, especially those targeted at high-risk patients as well as those targeted at specialists, in order to better tackle the bruxism 'epidemic'.

Neurons in the primate lateral habenula fire in response to punishments and are inhibited by rewards. Through its modulation of midbrain monoaminergic activity, the habenula is believed to play an important role in adaptive behavioural responses to punishment and underlie depressive symptoms and their alleviation with ketamine. However, its role in value-based decision-making in humans is poorly understood due to limitations with non-invasive imaging methods which measure metabolic, not neural, activity with poor temporal resolution. Here, we overcome these limitations to more closely bridge the gap between species by recording local field potentials directly from the habenula in 12 human patients receiving deep brain stimulation treatment for bipolar disorder (n = 4), chronic pain (n = 3), depression (n = 3) and schizophrenia (n = 2). This allowed us to record neural activity during value-based decision-making tasks involving monetary rewards and losses. High frequency gamma (60-240 Hertz) activity, a proxy for population level spiking involved in cognitive computations, increased during the receipt of loss, and decreased during receipt of reward. Furthermore, habenula high gamma also encoded risk during decision-making, being larger in amplitude for high compared to low risk. For both risk and aversion, differences between conditions peaked approximately between 400-750 ms after stimulus onset. The findings not only demonstrate homologies with the primate habenula but also extend its role to human decision-making, showing its temporal dynamics and suggesting revisions to current models. The findings suggest that habenula high gamma could be used to optimize real-time closed-looped deep brain stimulation treatment for mood disturbances and impulsivity in psychiatric disorders.

Excess cholesterol accumulation in lesional macrophages elicits complex responses in atherosclerosis. Epsins, a family of endocytic adaptors, fuel the progression of atherosclerosis; however, the underlying mechanism and therapeutic potential of targeting Epsins remains unknown. In this study, we determined the role of Epsins in macrophage-mediated metabolic regulation. We then developed an innovative method to therapeutically target macrophage Epsins with specially designed S2P-conjugated lipid nanoparticles, which encapsulate small-interfering RNAs to suppress Epsins.

A variety of neurological complications have been reported following the widespread use of the COVID-19 vaccines which may lead to vaccine hesitancy and serve as a major barrier to the public health aim of achieving protective herd immunity by vaccination. In this article, we review the available evidence regarding these neurological adverse events reported, to provide clarity regarding the same so that unfounded fears maybe put to rest.

Physiological or pathology-mediated changes in neuronal activity trigger structural plasticity of the action potential generation site-the axon initial segment (AIS). These changes affect intrinsic neuronal excitability, thus tuning neuronal and overall network output. Using behavioral, immunohistochemical, electrophysiological, and computational approaches, we characterized inflammation-related AIS plasticity in rat's superficial (lamina II) spinal cord dorsal horn (SDH) neurons and established how AIS plasticity regulates the activity of SDH neurons, thus contributing to pain hypersensitivity. We show that in naive conditions, AIS in SDH inhibitory neurons is located closer to the soma than in excitatory neurons. Shortly after inducing inflammation, when the inflammatory hyperalgesia is at its peak, AIS in inhibitory neurons is shifted distally away from the soma. The shift in AIS location is accompanied by the decrease in excitability of SDH inhibitory neurons. These AIS location and excitability changes are selective for inhibitory neurons and reversible. We show that AIS shift back close to the soma, and SDH inhibitory neurons' excitability increases to baseline levels following recovery from inflammatory hyperalgesia. The computational model of SDH inhibitory neurons predicts that the distal shift of AIS is sufficient to decrease the intrinsic excitability of these neurons. Our results provide evidence of inflammatory pain-mediated AIS plasticity in the central nervous system, which differentially affects the excitability of inhibitory SDH neurons and contributes to inflammatory hyperalgesia.

Mid-portion Achilles Tendinopathy (AT) is a common musculoskeletal condition with varying rehabilitation success rates. Despite the prevalence of this condition, a considerable proportion of individuals experience persisting pain and functional deficits. Current treatment approaches bias the biomedical model which emphasises physically treating and loading the tendon. Overall, there is a lack of consideration for the central nervous system that is commonly implicated in chronic injuries. The aim of this pilot study was to explore the feasibility of combining Action Observation Therapy (AOT), a treatment technique which targets central changes and influences motor learning, with eccentric exercises in the treatment of mid-portion AT. AOT involves the observation of movements and is commonly followed by the physical performance of these same movements.

In this study, cardiac biomarkers, blood parameters, electrocardiography (ECG), and echocardiography were investigated in children with carbon monoxide (CO) poisoning, and the diagnostic value of these parameters was investigated.