Atypical low-frequency cortical encoding of speech identifies children with developmental dyslexia.

Slow cortical oscillations play a crucial role in processing the speech amplitude envelope, which is perceived atypically by children with developmental dyslexia. Here we use electroencephalography (EEG) recorded during natural speech listening to identify neural processing patterns involving slow oscillations that may characterize children with dyslexia. In a story listening paradigm, we find that atypical power dynamics and phase-amplitude coupling between delta and theta oscillations characterize dyslexic versus other child control groups (typically-developing controls, other language disorder controls). We further isolate EEG common spatial patterns (CSP) during speech listening across delta and theta oscillations that identify dyslexic children. A linear classifier using four delta-band CSP variables predicted dyslexia status (0.77 AUC). Crucially, these spatial patterns also identified children with dyslexia when applied to EEG measured during a rhythmic syllable processing task. This transfer effect (i.e., the ability to use neural features derived from a story listening task as input features to a classifier based on a rhythmic syllable task) is consistent with a core developmental deficit in neural processing of speech rhythm. The findings are suggestive of distinct atypical neurocognitive speech encoding mechanisms underlying dyslexia, which could be targeted by novel interventions.

New Insights beyond Established Norms: A Scoping Review of Genetic Testing for Infertile Men.

PURPOSE: From a diagnostic standpoint, certain approaches to genetic screening in clinical practice remain ambiguous in the era of assisted reproduction. Even the most current guidelines do not provide definite guidance on testing protocols, leaving clinicians to carefully determine which tests best serve patients struggling with infertility. The lack of uniformity in the current practice of male fertility evaluation can prove to be quite costly, thus necessitating healthcare practitioners to carefully appraise the necessity and weigh the advantages against potential economic and psychological detriments. The objective of this review is to map the existing literature on the general topic of the clinical indications of routine karyotyping and/or AZF screening in infertile men, identify key concepts, determine where the gaps are, and lastly, provide an overview of the conclusions drawn from a body of knowledge that varies widely in terms of methodologies or disciplines. MATERIALS AND METHODS: A thorough search was conducted for the published findings up until July 2023, utilizing PubMed (MEDLINE). This comprehensive search involved the use of specific search keywords, either individually or in combination. The search terms employed were as follows: "Karyotype", "Klinefelter" or "KS" or "47,XXY", "AZF" or "Azoospermi*" and/or "microdeletion*" in the title or abstract. Once the titles and abstracts of selected articles were obtained, the complete texts of linked papers were meticulously scrutinized. RESULTS: A total of 191 records were identified from PubMed. During screening, 161 records (84.3%) were eliminated. Finally, 30 papers were included in this scoping review, which was conducted in 18 countries. The number of sequence tag sites (STSs) used in the studies varied from 5 to 59. The rate of AZF deletions among patients with NOA ranged from 1.3% to 53%. The mean frequency was estimated to be 5.6%. The rate of YCM among patients with XXY karyotype was nil in 19 out of 30 studies (63%), whilst, in the remaining studies, the rate varied from 0.8% to 67%. CONCLUSION: This review provides insights into managing male infertility. The presence of spermatozoa in ejaculation and successful surgical retrieval cannot be excluded for individuals with AZFb/AZFbc microdeletions. Screening for Y chromosome microdeletions is not needed for mosaic or classic KS. Only 1% of individuals with sperm concentration exceeding 1×106 sperm/mL and less than 5×106 sperm/mL exhibit AZF microdeletions; therefore, testing referral for such populations may need reassessment. Individuals with mosaic monosomy X karyotype and certain chromosomal anomalies should be referred for AZF deletion screening. These findings have implications for male infertility management and future research.

Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit. CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.

Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Rapid identification of inflammatory arthritis and associated adverse events following immune checkpoint therapy: a machine learning approach.

Introduction: Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) poses a major clinical challenge to ICI therapy for cancer, with 13% of cases halting ICI therapy and ICI-IA being difficult to identify for timely referral to a rheumatologist. The objective of this study was to rapidly identify ICI-IA patients in clinical data and assess associated immune-related adverse events (irAEs) and risk factors. Methods: We conducted a retrospective study of the electronic health records (EHRs) of 89 patients who developed ICI-IA out of 2451 cancer patients who received ICI therapy at Northwestern University between March 2011 to January 2021. Logistic regression and random forest machine learning models were trained on all EHR diagnoses, labs, medications, and procedures to identify ICI-IA patients and EHR codes indicating ICI-IA. Multivariate logistic regression was then used to test associations between ICI-IA and cancer type, ICI regimen, and comorbid irAEs. Results: Logistic regression and random forest models identified ICI-IA patients with accuracies of 0.79 and 0.80, respectively. Key EHR features from the random forest model included ICI-IA relevant features (joint pain, steroid prescription, rheumatoid factor tests) and features suggesting comorbid irAEs (thyroid function tests, pruritus, triamcinolone prescription). Compared to 871 adjudicated ICI patients who did not develop arthritis, ICI-IA patients had higher odds of developing cutaneous (odds ratio [OR]=2.66; 95% Confidence Interval [CI] 1.63-4.35), endocrine (OR=2.09; 95% CI 1.15-3.80), or gastrointestinal (OR=2.88; 95% CI 1.76-4.72) irAEs adjusting for demographics, cancer type, and ICI regimen. Melanoma (OR=1.99; 95% CI 1.08-3.65) and renal cell carcinoma (OR=2.03; 95% CI 1.06-3.84) patients were more likely to develop ICI-IA compared to lung cancer patients. Patients on nivolumab+ipilimumab were more likely to develop ICI-IA compared to patients on pembrolizumab (OR=1.86; 95% CI 1.01-3.43). Discussion: Our machine learning models rapidly identified patients with ICI-IA in EHR data and elucidated clinical features indicative of comorbid irAEs. Patients with ICI-IA were significantly more likely to also develop cutaneous, endocrine, and gastrointestinal irAEs during their clinical course compared to ICI therapy patients without ICI-IA.

Sampling Real-Time Atomic Dynamics in Metal Nanoparticles by Combining Experiments, Simulations, and Machine Learning.

Even at low temperatures, metal nanoparticles (NPs) possess atomic dynamics that are key for their properties but challenging to elucidate. Recent experimental advances allow obtaining atomic-resolution snapshots of the NPs in realistic regimes, but data acquisition limitations hinder the experimental reconstruction of the atomic dynamics present within them. Molecular simulations have the advantage that these allow directly tracking the motion of atoms over time. However, these typically start from ideal/perfect NP structures and, suffering from sampling limits, provide results that are often dependent on the initial/putative structure and remain purely indicative. Here, by combining state-of-the-art experimental and computational approaches, how it is possible to tackle the limitations of both approaches and resolve the atomistic dynamics present in metal NPs in realistic conditions is demonstrated. Annular dark-field scanning transmission electron microscopy enables the acquisition of ten high-resolution images of an Au NP at intervals of 0.6 s. These are used to reconstruct atomistic 3D models of the real NP used to run ten independent molecular dynamics simulations. Machine learning analyses of the simulation trajectories allow resolving the real-time atomic dynamics present within the NP. This provides a robust combined experimental/computational approach to characterize the structural dynamics of metal NPs in realistic conditions.

Iterative nanoparticle bioengineering enabled by x-ray fluorescence imaging.

Nanoparticles (NPs) are currently developed for drug delivery and molecular imaging. However, they often get intercepted before reaching their target, leading to low targeting efficacy and signal-to-noise ratio. They tend to accumulate in organs like lungs, liver, kidneys, and spleen. The remedy is to iteratively engineer NP surface properties and administration strategies, presently a time-consuming process that includes organ dissection at different time points. To improve this, we propose a rapid iterative approach using whole-animal x-ray fluorescence (XRF) imaging to systematically evaluate NP distribution in vivo. We applied this method to molybdenum-based NPs and clodronate liposomes for tumor targeting with transient macrophage depletion, leading to reduced accumulations in lungs and liver and eventual tumor detection. XRF computed tomography (XFCT) provided 3D insight into NP distribution within the tumor. We validated the results using a multiscale imaging approach with dye-doped NPs and gene expression analysis for nanotoxicological profiling. XRF imaging holds potential for advancing therapeutics and diagnostics in preclinical pharmacokinetic studies.

Proton Affinity and Conformational Integrity of a 24-Atom Triazine Macrocycle across Physiologically Relevant pH.

For 24-atom triazine macrocycles, protonation of the heterocycle leads to a rigid, folded structure presenting a network of hydrogen bonds. These molecules derive from dynamic covalent chemistry wherein triazine monomers bearing a protected hydrazine group and acetal tethered by the amino acid dimerize quantitatively in an acidic solution. Here, lysine is used, and the product is a tetracation. The primary amines of the lysine side chains do not interfere with quantitative yields of the desired bis(hydrazone) at concentrations of 5-125 mg/mL. Mathematical modeling of data derived from titration experiments of the macrocycle reveals that the pKa values of the protonated triazines are 5.6 and 6.7. Changes in chemical shifts of resonances in the 1H NMR spectra corroborate these values and further support assignment of the protonation sites. The pKa values of the lysine side chains are consistent with expectation. Upon deprotonation, the macrocycle enjoys greater conformational freedom as evident from the broadening of resonances in the 1H and 13C NMR spectra indicative of dynamic motion on the NMR time scale and the appearance of additional conformations at room temperature. While well-tempered metadynamics suggests only a modest difference in accessible conformational footprints of the protonated and deprotonated macrocycles, the shift in conformation(s) supports the stabilizing role that the protons adopt in the hydrogen-bonded network.

Detection of Echovirus 11 lineage 1 in wastewater samples in Sicily.

We report the presence of Echovirus 11 (E11) in wastewater in Sicily (Southern Italy), since August 2022. Overall, the 5.4 % of sewage samples (7/130) collected in 2022 were positives for E11 and then the percentage of E11-positive sewage samples reached the value of 27.27(18/66) in the first semester of 2023. Phylogenetic analysis of VP1 sequences showed for most E11-positive samples (16/25: 64 %) close genetic correlation (98.4-99.4 % nucleotide identity) to E11 lineage 1 strains involved in recently reported severe neonatal infections.

Identification of a novel intra-genotype reassortant G1P[8] rotavirus in Italy, 2021.

OBJECTIVES: Rotaviruses G1P[8] are epidemiologically relevant and are targeted by vaccines. The introduction of vaccines has altered rotavirus epidemiology. Hospital-based surveillance conducted in Sicily, Italy, showed a progressive decline in rotavirus prevalence since 2014, along with an increasing vaccine coverage (63.8% in 2020), and a marked decrease in circulation of G1P[8] strains. Surprisingly in 2021, G1P[8] viruses accounted for 90.5% (19/21) of rotavirus infections. This study aimed to understand if the increased activity of G1P[8]'s was related to virus-related peculiarities. DESIGN: In 2021, 266 patients <15 years of age were hospitalized with acute gastroenteritis (AGE) and included in rotavirus surveillance. Viral proteins (VP7 and VP4) genotyping and sequence data were generated from all rotavirus-positive samples. The genetic makeup of G1P[8] rotaviruses was investigated by full-genome sequencing. RESULTS: Peculiar G1P[8] rotaviruses, with VP7 and VP4 belonging to novel sub-lineages, circulated in 2021, accounting for 76.2% (16/21) of all rotavirus infections. On full-genome analysis, the novel G1P[8] variant displayed an intra-genotype (Wa-like) reassortant constellation, involving G12 and G1 strains, into a unique arrangement never observed before. The novel G1P[8] variant showed peculiar amino acid substitutions in 8-1 and 8-3 epitopes of the VP4 with respect to the Rotarix strain. CONCLUSIONS: Prompt identification of virus variants circulating in the human population is pivotal to understanding epidemiological trends and assessing vaccine efficacy.

Stereocontrolled Self-Assembly of a Helicate-Bridged CuI12L4 Cage That Emits Circularly Polarized Light.

Control over the stereochemistry of metal-organic cages can give rise to useful functions that are entwined with chirality, such as stereoselective guest binding and chiroptical applications. Here, we report a chiral CuI12L4 pseudo-octahedral cage that self-assembled from condensation of triaminotriptycene, aminoquinaldine, and diformylpyridine subcomponents around CuI templates. The corners of this cage consist of six head-to-tail dicopper(I) helicates whose helical chirality can be controlled by the addition of enantiopure 1,1'-bi-2-naphthol (BINOL) during the assembly process. Chiroptical and nuclear magnetic resonance (NMR) studies elucidated the process and mechanism of stereochemical information transfer from BINOL to the cage during the assembly process. Initially formed CuI(BINOL)2 thus underwent stereoselective ligand exchange during the formation of the chiral helicate corners of the cage, which determined the overall cage stereochemistry. The resulting dicopper(I) helicate corners of the cage were also shown to generate circularly polarized luminescence.

Laboratory Liquid-Jet X-ray Microscopy and X-ray Fluorescence Imaging for Biomedical Applications.

Diffraction-limited resolution and low penetration depth are fundamental constraints in optical microscopy and in vivo imaging. Recently, liquid-jet X-ray technology has enabled the generation of X-rays with high-power intensities in laboratory settings. By allowing the observation of cellular processes in their natural state, liquid-jet soft X-ray microscopy (SXM) can provide morphological information on living cells without staining. Furthermore, X-ray fluorescence imaging (XFI) permits the tracking of contrast agents in vivo with high elemental specificity, going beyond attenuation contrast. In this study, we established a methodology to investigate nanoparticle (NP) interactions in vitro and in vivo, solely based on X-ray imaging. We employed soft (0.5 keV) and hard (24 keV) X-rays for cellular studies and preclinical evaluations, respectively. Our results demonstrated the possibility of localizing NPs in the intracellular environment via SXM and evaluating their biodistribution with in vivo multiplexed XFI. We envisage that laboratory liquid-jet X-ray technology will significantly contribute to advancing our understanding of biological systems in the field of nanomedical research.

Partial Epididymal Obstruction as a Cause of Idiopathic Oligozoospermia: A Reproductive Urologist's Perspective following 35 Years of Surgical and Clinical Experience.

The role of partial epididymal obstruction as contributing to the development of oligozoospermia has been neglected for decades. In the early 1970s, however, Robert Schoysman, a gynecological surgeon devoted to the surgical and medical management of male factor infertility, dedicated many efforts to study such a pathology and its possible effects on male fertility. Following the studies of this pioneer in the field, we concentrated our attention to the patterns of partial and complete epididymal obstruction during surgical scrotal exploration, once made possible even in oligozoospermic men by diagnostic and therapeutic interventions, such as vasovesciculography or seminal tract washout test, at present considered obsolete and no longer feasible in light of the current guidelines. Interestingly, we found signs of partial epididymal obstruction in about 30% of oligozoospermic men with normal testicular volume and serum FSH level as well as normal spermatogenesis at testis biopsy. We, then, compared the findings of scrotal ultrasound with those of scrotal exploration and found that the ultrasound abnormalities of the epididymis were highly predictive of anatomic alteration of the gland. In the present study, we report our experience, together with a historical review of the literature, on this topic.

Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.

Does Varicocele Repair Improve Conventional Semen Parameters? A Meta-Analytic Study of Before-After Data.

PURPOSE: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. MATERIALS AND METHODS: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). RESULTS: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864. CONCLUSIONS: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele.

Growth performance and feed utilisation of Australian hybrid abalone (Haliotis rubra × Haliotis laevigata) fed increasing dietary protein levels at three water temperatures.

Determining the macronutrient requirements for commercially valuable aquaculture species remains crucial for maximising production efficiency. Yet, such information is lacking for Australian hybrid abalone (Haliotis rubra × Haliotis laevigata), particularly with respect to life stage and water temperatures. The present study aimed to evaluate the effect of dietary protein inclusion level on the growth performance, nutrient utilisation and nutritional quality of juvenile (3·3 g) Australian hybrid abalone reared at three different temperatures representative of winter (12°C), average annual (17°C) and summer (22°C) grow-out periods and fed five diets containing graded dietary protein levels of 35, 38, 41, 44 and 47 %. Abalone growth increased with increasing water temperature with weight gains of approximately 100, 280 and 380 % of their initial weight at 12, 17 and 22°C, respectively. Furthermore, the present study clearly demonstrated that higher dietary protein inclusion levels (41 %) than those currently used commercially (35 %) would significantly improve the growth performance when water temperatures are ≥17°C without any adverse impacts on nutrient utilisation, nutrient deposition or nutritional quality of the abalone soft tissue. For example, at 22°C abalone fed a diet containing 41 % protein obtained a significantly higher weight gain percentage (421 %) compared with those fed a diet containing 35 % protein (356 %). Lastly, it is suggested that maintaining a dietary protein inclusion level of 35 % or implementing a 'least cost' feeding approach during cooler seasons, or where water temperatures are ∼12°C, may be beneficial, considering only marginal growth improvements were observed during these periods of slow growth.

A standardised open science framework for sharing and re-analysing neural data acquired to continuous stimuli.

Neurophysiology research has demonstrated that it is possible and valuable to investigate sensory processing in scenarios involving continuous sensory streams, such as speech and music. Over the past 10 years or so, novel analytic frameworks combined with the growing participation in data sharing has led to a surge of publicly available datasets involving continuous sensory experiments. However, open science efforts in this domain of research remain scattered, lacking a cohesive set of guidelines. This paper presents an end-to-end open science framework for the storage, analysis, sharing, and re-analysis of neural data recorded during continuous sensory experiments. The framework has been designed to interface easily with existing toolboxes, such as EelBrain, NapLib, MNE, and the mTRF-Toolbox. We present guidelines by taking both the user view (how to rapidly re-analyse existing data) and the experimenter view (how to store, analyse, and share), making the process as straightforward and accessible as possible for all users. Additionally, we introduce a web-based data browser that enables the effortless replication of published results and data re-analysis.

Atypical speech production of multisyllabic words and phrases by children with developmental dyslexia.

The prevalent "core phonological deficit" model of dyslexia proposes that the reading and spelling difficulties characterizing affected children stem from prior developmental difficulties in processing speech sound structure, for example, perceiving and identifying syllable stress patterns, syllables, rhymes and phonemes. Yet spoken word production appears normal. This suggests an unexpected disconnect between speech input and speech output processes. Here we investigated the output side of this disconnect from a speech rhythm perspective by measuring the speech amplitude envelope (AE) of multisyllabic spoken phrases. The speech AE contains crucial information regarding stress patterns, speech rate, tonal contrasts and intonational information. We created a novel computerized speech copying task in which participants copied aloud familiar spoken targets like "Aladdin." Seventy-five children with and without dyslexia were tested, some of whom were also receiving an oral intervention designed to enhance multi-syllabic processing. Similarity of the child's productions to the target AE was computed using correlation and mutual information metrics. Similarity of pitch contour, another acoustic cue to speech rhythm, was used for control analyses. Children with dyslexia were significantly worse at producing the multi-syllabic targets as indexed by both similarity metrics for computing the AE. However, children with dyslexia were not different from control children in producing pitch contours. Accordingly, the spoken production of multisyllabic phrases by children with dyslexia is atypical regarding the AE. Children with dyslexia may not appear to listeners to exhibit speech production difficulties because their pitch contours are intact. RESEARCH HIGHLIGHTS: Speech production of syllable stress patterns is atypical in children with dyslexia. Children with dyslexia are significantly worse at producing the amplitude envelope of multi-syllabic targets compared to both age-matched and reading-level-matched control children. No group differences were found for pitch contour production between children with dyslexia and age-matched control children. It may be difficult to detect speech output problems in dyslexia as pitch contours are relatively accurate.

Emergence of the cortical encoding of phonetic features in the first year of life.

Even prior to producing their first words, infants are developing a sophisticated speech processing system, with robust word recognition present by 4-6 months of age. These emergent linguistic skills, observed with behavioural investigations, are likely to rely on increasingly sophisticated neural underpinnings. The infant brain is known to robustly track the speech envelope, however previous cortical tracking studies were unable to demonstrate the presence of phonetic feature encoding. Here we utilise temporal response functions computed from electrophysiological responses to nursery rhymes to investigate the cortical encoding of phonetic features in a longitudinal cohort of infants when aged 4, 7 and 11 months, as well as adults. The analyses reveal an increasingly detailed and acoustically invariant phonetic encoding emerging over the first year of life, providing neurophysiological evidence that the pre-verbal human cortex learns phonetic categories. By contrast, we found no credible evidence for age-related increases in cortical tracking of the acoustic spectrogram.

Biological Specimen Banking as a Time Capsule to Explore the Temporal Dynamics of Norovirus Epidemiology.

Norovirus is recognised as a major cause of epidemic and sporadic acute gastroenteritis (AGE) in all age groups. Information on the genetic diversity of the noroviruses circulating in the 1980s and 1990s, before the development and adoption of dedicated molecular assays, is limited compared with the last decades. Between 1986 and 2020, uninterrupted viral surveillance was conducted in symptomatic children hospitalized with AGE in Palermo, Italy, providing a unique time capsule for exploring the epidemiological and evolutionary dynamics of enteric viruses. A total of 8433 stool samples were tested using real-time RT-PCR. All samples were stored at -20 or -80 °C until processing. In this 35-year long time span, noroviruses of genogroup II (GII) were detected in 15.6% of AGE requiring hospitalization, whilst GI noroviruses were detected in 1.4% of AGE. Overall, the predominant norovirus capsid (Cap) genotype was GII.4 (60.8%), followed by GII.3 (13.3%) and GII.2 (12.4%). Temporal replacement of the GII.4 Cap variants associated with different polymerase (Pol) types were observed over the study period. The chronology of emergence and circulation of the different GII.4 variants were consistent with data available in the literature. Also, for GII.3 and GII.2 NoVs, the circulation of different lineages/strains, differing in either the Cap or Pol genes or in both, was observed. This long-term study revealed the ability of noroviruses to continuously and rapidly modify their genomic makeup and highlights the importance of surveillance activities in vaccine design.