Unraveling Brain Synchronisation Dynamics by Explainable Neural Networks using EEG Signals: Application to Dyslexia Diagnosis.

The electrical activity of the neural processes involved in cognitive functions is captured in EEG signals, allowing the exploration of the integration and coordination of neuronal oscillations across multiple spatiotemporal scales. We have proposed a novel approach that combines the transformation of EEG signal into image sequences, considering cross-frequency phase synchronisation (CFS) dynamics involved in low-level auditory processing, with the development of a two-stage deep learning model for the detection of developmental dyslexia (DD). This deep learning model exploits spatial and temporal information preserved in the image sequences to find discriminative patterns of phase synchronisation over time achieving a balanced accuracy of up to 83%. This result supports the existence of differential brain synchronisation dynamics between typical and dyslexic seven-year-old readers. Furthermore, we have obtained interpretable representations using a novel feature mask to link the most relevant regions during classification with the cognitive processes attributed to normal reading and those corresponding to compensatory mechanisms found in dyslexia.

The Cannabis Gray Market: A Case for Cannabis Regulatory Science Research.

The cannabis gray market poses significant public health concerns and remains a major threat to consumer and/or potential consumer uptake of regulated cannabis markets in jurisdictions with legal state-sponsored cannabis programs. In this perspective, we provide an overview of the cannabis gray market, and describe an integrated epidemiological and regulatory science framework to study the gray market. Using tobacco regulatory science as a guide, we introduce example cannabis regulatory science research activities as a means to improve the field's understanding of the cannabis gray market. Cannabis regulatory science is a developing field that can improve our understanding of the cannabis regulatory ecosystem and provide regulatory officials and policymakers alike with much needed data to inform regulatory decision-making and improve the success and uptake of state-sponsored cannabis programs.

Prenatal tobacco and tobacco-cannabis co-exposure: Relationship with attention and memory in middle childhood.

We examined associations between prenatal tobacco exposure (with and without cannabis exposure) and children's performance on laboratory measures of sustained attention, attentional set shifting, and working memory in middle childhood (9-12 years of child age). Participants were recruited in the first trimester of pregnancy and oversampled for prenatal tobacco exposure; with a smaller sample (n = 133; n = 34 non-substance exposed, n = 37 exposed to tobacco only, n = 62 co-exposed) invited (oversampled for co-exposure) to participate in the middle-childhood assessment (M age = 10.6, SD = 0.77; 68% Black, 20% Hispanic). Results for sustained attention indicated lower attention (percent hits) at the first epoch for tobacco only exposed compared to non-exposed and co-exposed; a trend (p = .07) towards increases in impulsive responding across time (a total of 8 epochs) for tobacco exposed (with and without cannabis) compared to non-exposed children; and a significant association between higher number of cigarettes in the first trimester and greater increases in impulsive responding across epochs. However, children prenatally exposed to tobacco (with and without cannabis) demonstrated greater short-term memory compared to children not prenatally exposed, and this difference was driven by higher scores for children prenatally co-exposed to tobacco and cannabis compared to those who were non-exposed. Overall, results suggest that prenatal tobacco exposure, especially in the first trimester, may increase risk for impulsive responding on tasks requiring sustained attention, and that co-use of cannabis did not exacerbate these associations. The higher short-term memory scores among children who were co-exposed compared to non-exposed are perplexing and need replication, particularly in studies with larger sample sizes and samples exposed only to cannabis to examine this more closely.

Tuning the thermostability of GHG gels by salts at different positions on the Hofmeister scale.

The influence of Hofmeister cations (NH4+, Na+, Mg2+) and anions (H2PO4-, CH3COO-, Cl-, NO3-) on the thermostability of a GHG hydrogel was investigated. The combined results of UV circular dichroism (UVCD) and Small Amplitude Oscillatory Shear Rheology experiments reveal that the addition of salt reduces the stability of the gel phase and the underlying fibrils. In line with the cationic Hofmeister hierarchy, the chaotropic Mg2+ ions caused the greatest thermal destabilization of the gel phase with the gel → sol transition temperature Tgs value lowered by 10 °C. In the absence of salt, the gel → sol transition probed by the storage modulus and microscopy is biphasic. In the presence of salt, it becomes monophasic. Contrary to expectations the presence of Hofmeister anions leads to a nearly identical reduction of the gel → sol transition temperatures. However, UVCD spectra suggest that they affect the ππ-stacking between imidazole groups to a different extent. We relate the absence of ion specificity regarding the solubility of fibrils (probed by UVCD) to the observed enthalpy-entropy compensation of the dissolution process. Our results combined show how CD spectroscopy and rheology combined yields a more nuanced picture of the processes underlying the gel → sol transition.

Use of the 445-nm Blue Laser for Management of Early Glottic Carcinoma: Preliminary 1-Year Results.

OBJECTIVE: To analyze oncological efficacy and voice outcomes of the 445-nm blue laser (BL) in the treatment of early glottic carcinoma and compare results with the 532-nm potassium-titanyl-phosphate (KTP) laser. STUDY DESIGN: Single institution, retrospective chart review. METHODS: All patients who underwent microlaryngoscopic KTP or BL laser excision of early glottic carcinoma from 2018 to the present day with at least 1-year follow-up were included. Primary and recurrent disease, including radiation and surgical failures, were included. Demographic data, voice outcomes and oncologic outcomes were compared between the two laser groups. RESULTS: Forty-nine patients met the inclusion criteria for the BL group and 88 for the KTP group, with average follow-up of 635 and 1236 days, respectively. Oncologic outcomes were not significantly different, with disease-specific survival rates of 95.9% for BL and 100% for KTP (p = 0.13), organ preservation rates of 98.0% for BL and 95.6% for KTP (p = 0.39), and local control rates of 93.9% for BL and 92.1% for KTP (p = 0.81). Both BL and KTP groups showed significant improvement in CAPE-V (p = 0.04, 0.006 respectively) and VHI-10 scores (p = 0.003, <0.00001) following surgery. CONCLUSIONS: Photoangiolytic removal of early glottic carcinoma with BL appears to be equally safe and effective as with KTP laser at minimum one-year follow-up, and with excellent voice outcomes. Additional study will be warranted over time to assess long-term outcomes in BL patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Antibody and T-cell response to bivalent booster SARS-CoV-2 vaccines in people with compromised immune function (COVERALL-3).

BACKGROUND: Bivalent mRNA vaccines, designed to combat emerging SARS-CoV-2 variants, incorporate ancestral strains and a new variant. Our study assessed the immune response in previously vaccinated individuals of the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS) following bivalent mRNA vaccination. METHODS: Eligible SHCS and STCS participants received approved bivalent mRNA SARS-CoV-2 vaccines (mRNA-1273.214 or BA.1-adapted BNT162b2) within clinical routine. Blood samples were collected at baseline, 4 weeks, 8 weeks, and 6 months post vaccination. We analyzed the proportion of participants with anti-spike protein antibody response ≥1642 units/ml (indicating protection against SARS-CoV-2 infection), and in a subsample T-cell response (including mean concentrations), stratifying results by cohorts and population characteristics. RESULTS: In SHCS participants, baseline anti-spike antibody concentrations ≥1642 were observed in 87% (96/112), reaching nearly 100% at follow-ups. Among STCS participants, 58% (35/60) had baseline antibodies ≥1642, increasing to 80% at 6 months. Except for lung transplant recipients, all participants showed a five-fold increase in geometric mean antibody concentrations at 4 weeks and a reduction by half at 6 months. At baseline, T-cell responses were positive in 96% (26/27) of SHCS participants and 36% (16/45) of STCS participants (moderate increase to 53% at 6 months). Few participants reported SARS-CoV-2 infections, side-effects, or serious adverse events. CONCLUSIONS: Bivalent mRNA vaccination elicited a robust humoral response in individuals with HIV or solid organ transplants, with delayed responses in lung transplant recipients. Despite a waning effect, antibody levels remained high at 6 months and adverse events were rare.

Donor-derived infections: The Swiss perspective.

While Switzerland has not yet established a systematic approach, the small size of the country and the intensive collaboration between the transplant infectious disease teams facilitate a rapid communication once a donor-derived infection is suspected. Critical information regarding donor infections is shared rapidly, and appropriate measures are discussed. The long-term observational Swiss Transplant Cohort Study, which includes >92% of all solid organ recipients collects all relevant infectious disease episodes and facilitates detection of patterns of potential donor-derived infection.

Molecular and functional mapping of the neuroendocrine hypothalamus: a new era begins.

BACKGROUND: Recent advances in neuroscience tools for single-cell molecular profiling of brain neurons have revealed an enormous spectrum of neuronal subpopulations within the neuroendocrine hypothalamus, highlighting the remarkable molecular and cellular heterogeneity of this brain area. RATIONALE: Neuronal diversity in the hypothalamus reflects the high functional plasticity of this brain area, where multiple neuronal populations flexibly integrate a variety of physiological outputs, including energy balance, stress and fertility, through crosstalk mechanisms with peripheral hormones. Intrinsic functional heterogeneity is also observed within classically 'defined' subpopulations of neuroendocrine neurons, including subtypes with distinct neurochemical signatures, spatial organisation and responsiveness to hormonal cues. AIM: The aim of this review is to critically evaluate past and current research on the functional diversity of hypothalamic neuroendocrine neurons and their plasticity. It focuses on how this neuronal plasticity in this brain area relates to metabolic control, feeding regulation and interactions with stress and fertility-related neural circuits. CONCLUSION: Our analysis provides an original framework for improving our understanding of the hypothalamic regulation of hormone function and the development of neuroendocrine diseases.

Infectious Diseases and Clinical Xenotransplantation.

Xenotransplantation, transplantation into humans of vascularized organs or viable cells from nonhuman species, is a potential solution to shortages of transplantable human organs. Among challenges to application of clinical xenotransplantation are unknown risks of transmission of animal microbes to immunosuppressed recipients or the community. Experience in allotransplantation and in preclinical models suggests that viral infections are the greatest concern. Worldwide, the distribution of swine pathogens is heterogeneous and cannot be fully controlled by international agricultural regulations. It is possible to screen source animals for potential human pathogens before procuring organs in a manner not possible within the time available for surveillance testing in allotransplantation. Infection control measures require microbiological assays for surveillance of source animals and xenograft recipients and research into zoonotic potential of porcine organisms. Available data suggest that infectious risks of xenotransplantation are manageable and that clinical trials can advance with appropriate protocols for microbiological monitoring of source animals and recipients.

Diacylglycerol kinase delta overexpression improves glucose clearance and protects against the development of obesity.

BACKGROUND AND AIM: Diacylglycerol kinase (DGK) isoforms catalyze an enzymatic reaction that removes diacylglycerol (DAG) and thereby terminates protein kinase C signaling by converting DAG to phosphatidic acid. DGKδ (type II isozyme) downregulation causes insulin resistance, metabolic inflexibility, and obesity. Here we determined whether DGKδ overexpression prevents these metabolic impairments. METHODS: We generated a transgenic mouse model overexpressing human DGKδ2 under the myosin light chain promoter (DGKδ TG). We performed deep metabolic phenotyping of DGKδ TG mice and wild-type littermates fed chow or high-fat diet (HFD). Mice were also provided free access to running wheels to examine the effects of DGKδ overexpression on exercise-induced metabolic outcomes. RESULTS: DGKδ TG mice were leaner than wild-type littermates, with improved glucose tolerance and increased skeletal muscle glycogen content. DGKδ TG mice were protected against HFD-induced glucose intolerance and obesity. DGKδ TG mice had reduced epididymal fat and enhanced lipolysis. Strikingly, DGKδ overexpression recapitulated the beneficial effects of exercise on metabolic outcomes. DGKδ overexpression and exercise had a synergistic effect on body weight reduction. Microarray analysis of skeletal muscle revealed common gene ontology signatures of exercise and DGKδ overexpression that were related to lipid storage, extracellular matrix, and glycerophospholipids biosynthesis pathways. CONCLUSION: Overexpression of DGKδ induces adaptive changes in both skeletal muscle and adipose tissue, resulting in protection against HFD-induced obesity. DGKδ overexpression recapitulates exercise-induced adaptations on energy homeostasis and skeletal muscle gene expression profiles.

Weight of evidence evaluation of the metabolism disrupting effects of triphenyl phosphate using an expert knowledge elicitation approach.

Identification of Endocrine-Disrupting Chemicals (EDCs) in a regulatory context requires a high level of evidence. However, lines of evidence (e.g. human, in vivo, in vitro or in silico) are heterogeneous and incomplete for quantifying evidence of the adverse effects and mechanisms involved. To date, for the regulatory appraisal of metabolism-disrupting chemicals (MDCs), no harmonised guidance to assess the weight of evidence has been developed at the EU or international level. To explore how to develop this, we applied a formal Expert Knowledge Elicitation (EKE) approach within the European GOLIATH project. EKE captures expert judgment in a quantitative manner and provides an estimate of uncertainty of the final opinion. As a proof of principle, we selected one suspected MDC -triphenyl phosphate (TPP) - based on its related adverse endpoints (obesity/adipogenicity) relevant to metabolic disruption and a putative Molecular Initiating Event (MIE): activation of peroxisome proliferator activated receptor gamma (PPARγ). We conducted a systematic literature review and assessed the quality of the lines of evidence with two independent groups of experts within GOLIATH, with the objective of categorising the metabolic disruption properties of TPP, by applying an EKE approach. Having followed the entire process separately, both groups arrived at the same conclusion, designating TPP as a "suspected MDC" with an overall quantitative agreement exceeding 85%, indicating robust reproducibility. The EKE method provides to be an important way to bring together scientists with diverse expertise and is recommended for future work in this area.

The impact of surgery clerkship grades on applicant competitiveness for orthopaedic surgery residency match.

Medical school clerkship grades are an important method for applicants to distinguish themselves when applying to residency programs. Given the lack of standardization among medical schools in the clerkship grading process, it has become more challenging for orthopaedic surgery residencies to ascertain the true value of surgery clerkship grades between applicants. This letter to the editor is a response to the article by Hoy et al., "Analysis of variability and trends in medical school clerkship grades," and offers further perspectives on the variability of surgery clerkship grading and its effect on applicants.

Invasive Aspergillosis in Liver Transplant Recipients in The Current Era.

Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multi-center 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in eight cases (13%). 12-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotics usage (adjusted odds ratio [aOR], 4.74; p=0.03) and history of pneumonia (aOR, 48.7; p=0.01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; p=0.01), systemic antibiotics usage (aOR, 5.03; p=0.04), and anti-mold prophylaxis (aOR, 11.9; p=0.02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ration [aHR], 86.9; p<0.001), ICU stay (aHR, 3.67; p=0.02), disseminated IA (aHR, 8.98; p<0.001), and dialysis (aHR, 2.93; p=0.001) were identified as independent risk factors associated with 12-week all-cause mortality; while recent receipt of tacrolimus (aHR, 0.11; p=0.001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted anti-mold prophylactic and appropriate treatment strategies against IA.

Catheter Interventions for Pulmonary Embolism: Mechanical Thrombectomy Versus Thrombolytics.

Pulmonary embolism is a debilitating and potentially life-threatening disease characterized by high mortality and long-term adverse outcomes. Traditional treatment options are fraught with serious bleeding risks and incomplete thrombus removal, necessitating the development of innovative treatment strategies. While new interventional approaches offer promising potential for improved outcomes with fewer serious complications, their rapid development and need for more comparative clinical evidence makes it challenging for physicians to select the optimal treatment for each patient among the many options. This review summarizes the current published clinical data for both traditional treatments and more recent interventional approaches indicated for pulmonary embolism. While published studies thus far suggest that these newer interventional devices offer safe and effective options, more data is needed to understand their impact relative to the standard of care. The studies in progress that are anticipated to provide needed evidence are reviewed here since they will be critical for helping physicians make informed treatment choices and potentially driving necessary guideline changes.

Exploiting intermediate wetting on superhydrophobic surfaces for efficient icing prevention.

HYPOTHESIS: Superhydrophobic surfaces can effectively prevent the freezing of supercooled droplets in technological systems. Droplets on superhydrophobic surfaces commonly not only wet the top asperities (Cassie State), but also partially penetrate into microstructure due to surface properties, environment, and droplet impact occurring in real-world applications. Implications on ice nucleation can be expected and are little explored. It remains elusive how anti-icing surfaces can be designed to exploit intermediate wetting phenomena. EXPERIMENTS: We utilized engineered micro-/nanostructures, specifically micropillars, to modulate the wetting fraction in the microstructure. The behavior of intermediate wetting with supercooling and resulting implications on ice nucleation delay when potential nucleation sites are formed in the microcavities were investigated using experimental, theoretical, and simulation components. FINDINGS: The temperature-dependent wetting fraction in the microstructure increased at supercooled temperatures, partly activated by condensation in the microcavities. At -10/-20 °C, a critical wetting fraction led to maximum ice nucleation delays, with experimental results consistent with theoretical predictions. This critical wetting fraction minimized the effective contact area solid-to-liquid along the partially wetted microstructure. The study establishes physical relations between ice nucleation delays, geometrical surface parameters and wettability properties in the intermediate wetting regime, providing guidance for the design of ice resistant microstructured surfaces.

Multi-center experience with intravascular lithotripsy for treatment of severe calcification during transcarotid artery revascularization for high-risk patients.

OBJECTIVE: Transcarotid artery revascularization (TCAR) offers a safe alternative to carotid endarterectomy (CEA), but severe calcification is currently considered a contraindication in carotid artery stenting. This study aims to describe the safety and effectiveness of TCAR with intravascular lithotripsy (IVL) in patients with traditionally prohibitive calcific disease. METHODS: All consecutive patients who underwent TCAR+IVL from 2018-2022 at nine institutions were identified. IVL was combined with pre-dilatation angioplasty to treat calcified vessels before stent deployment. The primary outcome was a new ipsilateral stroke within 30 days. Secondary outcomes included any new ipsilateral neurologic event (stroke/transient ischemic attack [TIA]) at 30 days, technical success, and <30% residual stenosis. RESULTS: Fifty-eight patients (62% male; mean age, 78 ± 6.6 years) underwent TCAR+IVL, with 22 (38%) for symptomatic disease. Fifty-seven patients (98%) met high-risk anatomical or physiologic criteria for CEA. Forty-seven patients had severely calcific lesions. Fourteen patients (30%) had isolated eccentric plaque, 20 patients (43%) had isolated circumferential plaque, and 13 (27%) had eccentric and circumferential calcification. Mean procedure and flow reversal times were 87 ± 27 minutes and 25 ± 14 minutes. The median number of lithotripsy pulses per case was 90 (range, 30-330), and mean contrast usage was 29 mL. No patients had electroencephalogram changes or new deficits observed intraoperatively. Technical success was achieved in 100% of cases, with 98% having <30% residual stenosis on completion angiography. One patient had an in-hospital post-procedural stroke (1.72%). Four patients total had any new ipsilateral neurologic event (stroke/TIA) within 30 days for an overall rate of 6.8%. One TIA and one stroke occurred during the index hospitalization, and two TIAs occurred after discharge. Preoperative mean stenosis in patients with any postoperative neurologic event was 93% (vs 86% in non-stroke/TIA patients; P = .32), and chronic renal insufficiency was higher in patients who had a new neurologic event (75% vs 17%; P = .005). No differences were observed in calcium, procedural, or patient characteristics between the two groups. The mean follow-up was 132 days (range, 19-520 days). Three stents developed recurrent stenosis (5%) on follow-up duplex; the remainder were patent without issue. There were no reported interventions for recurrent stenosis during the study period. CONCLUSIONS: IVL sufficiently remodels calcified carotid arteries to facilitate TCAR effectively in patients with traditionally prohibitive calcific disease. One patient (1.7%) suffered a stroke within 30 days, although four patients (6.8%) sustained any new neurological event (stroke/TIA). These results raise concerns about the risks of TCAR+IVL and whether it is an appropriate strategy for patients who could potentially undergo CEA.

A referral pathway for treating patients with severe venous disease using mechanical thrombectomy.

BACKGROUND: DVT is associated with clinically significant sequelae, and the most widely used therapies for severe venous disease are often ineffective. Mechanical thrombectomy (MT) offers a promising approach, but most patients with a history of DVT are not evaluated for such intervention. OBJECTIVE: To present overall outcomes and the outcome of a single case after use of an MT procedure to manage advanced deep venous disease. MATERIALS AND METHODS: This retrospective, single-center analysis included all patients with a CEAP score of C6 secondary to DVT who were referred from a wound clinic and underwent an MT-based procedure. RESULTS: Eleven patients with 14 affected limbs were referred for treatment from an associated care network and were treated with MT. As necessary, adjunctive venoplasty and stent placement were also used. The endovascular treatment was successful in removing fibrous obstructions from veins and supporting the improvement or resolution of C6 venous disease in all cases, including the 66-year-old male discussed in the current report. CONCLUSION: Collaboration between endovascular interventionists and local postacute wound care specialists to identify and refer patients with severe venous disease for advanced treatment may lead to improved outcomes.

Stratum Corneum Hydration Measurements with a Bluetooth Wireless Probe: A Real-Life Study at Home Compared to Measurements under Laboratory Conditions.

INTRODUCTION: Non-invasive measurement of the stratum corneum hydration (SCH) with capacitance-based instrumentation is established in dermatological and cosmetic studies. We wanted to test the reliability of non-invasive self-measurements for SCH performed under real-life conditions by volunteers with a Bluetooth-based (wireless) probe Corneometer® (CM 825i) transmitting the data via a smartphone application to a central server. Probes and smartphones communicated using Bluetooth Low Energy. Data from the smartphone were securely transferred to a remote server in a different country with TLS encryption using HTTPS protocols. CM 825i values were correlated with the established CM 825 under laboratory conditions. The primary endpoint was the correlation of the two probes. Secondary endpoints were the coefficient of variation (CV) and delta values (before and after treatment). METHODS: Eighteen healthy volunteers (f: 8; m: 10) participated in the prospective observational study. The real-world home use of the wireless CM 825i was performed before and after treatments with base cream DAC for 7 days. RESULTS: Both instruments showed a significant and relevant correlation (p < 0.0001; Spearman coefficient of r = 0.8647). CM 825i and CM 825 differentiate significantly between normal and high SCH. Both devices showed comparable robustness in repeated measurements with a CV between 5.6% and 9.2%. CONCLUSION: We could show a significant correlation between both devices and a comparable differentiation between low and high SCH and comparable CVs. The real-life use demonstrated adequate acquiring and transmitting of in vivo data to a smartphone and subsequently transmitting to the secure server with low numbers of missed transmissions (<0.2%) and missed measurements (<5%).