Small open reading frames (smORFs), which encode proteins under 100 amino acids, represent an underexplored dimension of the human gut microbiome, despite growing evidence of their essential biological roles. Due to small size and poor annotation, smORFs are typically excluded from metagenomic/metaproteomic analyses. Here, we present a high-resolution multi-omic workflow that integrates smORF prediction into metaproteome searches and enables ultra-deep detection of smORF-encoded proteins (SEPs), without experimental size-based enrichment, utilizing state-of-the-art mass spectrometry instrumentation. Applied to human gut microbiomes, this approach resulted in the largest number of detected SEPs to date, allowing identification of over 25,000 SEPs in the metaproteome, alongside the measurements of the larger proteins. Our multi-omics integrative strategy is critical for advancing human metaproteome research. It also provides a generalizable strategy for comprehensive SEP discovery across diverse microbial ecosystems greatly expanding the previously hidden proteomic landscape.

Clinicians can use fixational eye movements to gain more information about the state of their patients: these measures have great potential as biomarkers of health conditions and might facilitate the early and differential diagnosis of disease. Objective measurements of fixational eye movements are also increasingly used to quantify fatigue and other traits or symptoms. However, the validity of such assessments depends on our ability to identify and control for factors that potentially alter fixational eye movements and that thereby may confound the results. Because eye movements can drive neural activity, cognition, and perception, these potentially confounding factors should be addressed, even in tasks and conditions where eye movements are not the focus of the assessment. In this chapter, we review altered or abnormal microsaccade dynamics in neurologic and ophthalmic conditions. We also review various factors that are known to alter fixational eye movement measurements, including arousal, fatigue, substance use, and various other states that are common among patient and control populations. Taking these different factors into consideration may help clarify existing findings, help refine assessment and diagnostic tools, and help us to better understand human neurology.

The Bereitschaftspotential (BP) is a slow negative-going deflection in the scalp electrical potential that appears before self-initiated movements that has been considered a neural sign of motor preparation. Besides neuroscience, this brain potential has also generated significant interest in philosophy regarding free will, in law concerning culpability discussions, and in sociology for shaping views on agency and responsibility. Its amplitude varies considerably across tasks and populations, and is influenced by diseases, stage of development, and cognitive factors. However, the factors relevant to this variation have never been systematically reviewed. There have been many studies on some aspects of the BP and fewer on others. In this narrative review, we analyze whether there might be a general factor, explaining most results, despite their differences of purpose. A structured literature search on PubMed revealed many peer-reviewed studies that used a task that might illuminate the significance of the amplitude. We found studies comparing different types of movement and different populations. We conclude that the factor of attention appears to be the most consistent across the studies reviewed.

Research suggests some individuals with progressive supranuclear palsy (PSP) have socioemotional deficits, typically characterized as reduced emotion recognition, difficulty with perspective taking, and increased apathy. However, the variability of these deficits across individuals and the pattern of impairments across the spectrum of social cognition have not been quantified in larger samples. The present study used multiple face-to-face and informant-based social cognition, neuropsychiatry, and personality measures to identify socioemotional changes occurring as a result of PSP. Data were collected from 287 individuals: 113 with early-stage PSP (Clinical Dementia Rating scale global score < 2) and 174 older healthy controls (HC). Though there was a high degree of individual variability, on average those with PSP had a pervasive pattern of deficits across tests of social cognition compared to HC, including emotion reading, social inferencing, theory of mind, and identifying and applying social behavior rules. Worse neuropsychiatric functioning was reported on both self- and informant-report measures, including increased depression, apathy, and anxiety. Changes in personality, including reduced conscientiousness, openness, and extraversion, from pre-morbid to current presentation were also found. Our analyses revealed that the social withdrawal typical of PSP is not simply a reflection of apathy or emotion reading deficits, but is directly correlated with the degree of the patient's depression and self-reported sense of hopelessness. These results reveal more clinically significant socioemotional deficits and personality shifts in early-stage PSP than are generally recognized, and suggest face-to-face testing and informant reports of socioemotional functioning may provide critically important information to guide clinical care.

Accurate subthalamic beta activity could guide deep brain stimulation programming in Parkinson's disease, but bipolar recordings complicate contact selection. In 39 patients, we validated three methods to estimate pseudo-monopolar beta power. Distance-weighted methods (Euclidean, Strelow) agreed consistently with the externalized "ground-truth" beta distribution. Maximal beta power across 20s windows was more stable in ring than in directional channels. Beta-contacts from all methods aligned with clinically active stimulation contacts one year after surgery.

Sensory and motor difficulties are common in autism. Altered excitation-inhibition (E-I) balance is a putative framework for understanding atypical sensory and motor function. We investigated whether sensory differences of autism mediate motor difficulties of autism via differences in E-I balance. 106 children were included in the study (Autism n = 44, Typical development children (TDC) n = 62, age 10.32 ± 1.49). E-I balance was assessed through magnetic resonance spectroscopy (MRS), quantifying Glutamate and Glutamine (Glx) and Gamma-Aminobutyric Acid (GABA) in primary sensorimotor cortex (SM1) and thalamus (Thal). Sensory function was evaluated using both objective vibrotactile perceptual sensitivity assessments and subjective parent ratings via the Sensory Experience Questionnaire (SEQ). Motor ability was assessed objectively through the Movement Assessment Battery for Children-second edition (MABC-2) and the Physical and Neurological Examination for Subtle Signs (PANESS). Our findings reveal that lower sensory reactivity and lower tactile thresholds are both predictive of better motor ability (Rsig range between 0.32 and 0.57) with higher sensory scores reflecting poorer sensory filtering predicting worse motor function (Rsig range -0.22 and -0.63). We identified significant associations between MRS-measured Glx and GABA+ levels and sensory reactivity (p < 0.001). Importantly, sensory reactivity sub-scores were found to fully mediate E-I balance to motor associations in domain-specific patterns: Hyper-reactivity mediated the impact of SM1 Glx levels, while hypo-reactivity mediated the impact of SM1 GABA levels. Additionally, sensory seeking mediated the impact of Thalamic GABA levels with all indirect paths ab p < 0.01. These results propose a model where regional metabolite-specific markers of E-I balance explain patterns of autism-associated sensory and motor difficulties, and where subsequently, distinct sensory phenotypes differentially mediate metabolite-motor associations (see Graphical Abstract for detail).

Chronic musculoskeletal pain is an occupational health concern among surgeons, with spinal pain being commonly reported. Exercise-based physiotherapy is recommended for reducing chronic spinal pain; however, the treatment effects are modest and may vary across clinical subgroups. Mechanical Diagnosis and Therapy (MDT) is a classification-based approach that uses a standardised clinical examination to guide exercise-based interventions and self-management strategies, and may offer advantages over non-direction-specific generalised exercise in selected patients.