Stable, chronic in-vivo recordings from a fully wireless subdural-contained 65,536-electrode brain-computer interface device.

Minimally invasive, high-bandwidth brain-computer-interface (BCI) devices can revolutionize human applications. With orders-of-magnitude improvements in volumetric efficiency over other BCI technologies, we developed a 50-µm-thick, mechanically flexible micro-electrocorticography (µECoG) BCI, integrating 256×256 electrodes, signal processing, data telemetry, and wireless powering on a single complementary metal-oxide-semiconductor (CMOS) substrate containing 65,536 recording and 16,384 stimulation channels, from which we can simultaneously record up to 1024 channels at a given time. Fully implanted below the dura, our chip is wirelessly powered, communicating bi-directionally with an external relay station outside the body. We demonstrated chronic, reliable recordings for up to two weeks in pigs and up to two months in behaving non-human primates from somatosensory, motor, and visual cortices, decoding brain signals at high spatiotemporal resolution.

Assessment of Nucleobase Protomeric and Tautomeric States in Nucleic Acid Structures for Interaction Analysis and Structure-Based Ligand Design.

With increasing interest in RNA as a therapeutic and a potential target, the role of RNA structures has become more important. Even slight changes in nucleobases, such as modifications or protomeric and tautomeric states, can have a large impact on RNA structure and function, while local environments in turn affect protonation and tautomerization. In this work, the application of empirical tools for pKa and tautomer prediction for RNA modifications was elucidated and compared with ab initio quantum mechanics (QM) methods and expanded toward macromolecular RNA structures, where QM is no longer feasible. In this regard, the Protonate3D functionality within the molecular operating environment (MOE) was expanded for nucleobase protomer and tautomer predictions and applied to reported examples of altered protonation states depending on the local environment. Overall, observations of nonstandard protomers and tautomers were well reproduced, including structural C+G:C(A) and A+GG motifs, several mismatches, and protonation of adenosine or cytidine as the general acid in nucleolytic ribozymes. Special cases, such as cobalt hexamine-soaked complexes or the deprotonation of guanosine as the general base in nucleolytic ribozymes, proved to be challenging. The collected set of examples shall serve as a starting point for the development of further RNA protonation prediction tools, while the presented Protonate3D implementation already delivers reasonable protonation predictions for RNA and DNA macromolecules. For cases where higher accuracy is needed, like following catalytic pathways of ribozymes, incorporation of QM-based methods can build upon the Protonate3D-generated starting structures. Likewise, this protonation prediction can be used for structure-based RNA-ligand design approaches.

Exploring the quadriceps muscle architecture variations in various sports disciplines: a comparative analysis of football, taekwondo, and athletics.

BACKGROUND: The purpose of this study was to comprehensively investigate and compare the architecture of the quadriceps muscle in football, taekwondo, and athletics, shedding light on potential differences and providing valuable insights for athletic training and performance enhancement. METHODS: Thirty-five athletes (football[N.]=14. [7 women, 7 men]; taekwondo [N.]=11. [6 women, 5 men]; athletics [N.]=10. [5 women, 5 men]) aged 17-21 years participated in the study. After participant demographic data were collected, 2D real-time B-mode ultrasound (USG) and right (R) and left (L) leg quadriceps muscle group rectus femoris (RF), vastus intermedius (VI), vastus lateralis, pennation angle (PA), RF cross-sectional area (CSA), and subcutaneous fat thickness were determined. RESULTS: In the study, in female athletes, R-RF+VI (P=0.04, ES:4.34), R-VI (P=0.01, ES: 6.1), R-RF: (P=0.009, ES: 7.9), R-CSA (P=0.04, ES: 5.2), L-RF (P=0.002, ES: 10.4) and L-CSA (P=0.007, ES: 7.7) significant differences were found in favor of the Football group. In male athletes, R-CSA (P=0.004, ES: 9.05), L-RF (P=0.05, ES: 3.5) and L-SFT (P=0.00, ES: 13.6), there was a significant difference in favor of the Football group. L-PA (P=0.009, ES: 6.2). L-PA (P=0.009, ES: 6.2) was significantly higher in the male Taekwondo group. CONCLUSIONS: Our research findings show that there is a significant relationship between the type of exercise performed and the structural differences observed in the quadriceps muscle. Consequently, it is highly recommended to consider the outcomes of our study for enhancing the efficacy of training programs in the domains of football, taekwondo, and athletics.

NnU-Net versus mesh growing algorithm as a tool for the robust and timely segmentation of neurosurgical 3D images in contrast-enhanced T1 MRI scans.

PURPOSE: This study evaluates the nnU-Net for segmenting brain, skin, tumors, and ventricles in contrast-enhanced T1 (T1CE) images, benchmarking it against an established mesh growing algorithm (MGA). METHODS: We used 67 retrospectively collected annotated single-center T1CE brain scans for training models for brain, skin, tumor, and ventricle segmentation. An additional 32 scans from two centers were used test performance compared to that of the MGA. The performance was measured using the Dice-Sørensen coefficient (DSC), intersection over union (IoU), 95th percentile Hausdorff distance (HD95), and average symmetric surface distance (ASSD) metrics, with time to segment also compared. RESULTS: The nnU-Net models significantly outperformed the MGA (p < 0.0125) with a median brain segmentation DSC of 0.971 [95CI: 0.945-0.979], skin: 0.997 [95CI: 0.984-0.999], tumor: 0.926 [95CI: 0.508-0.968], and ventricles: 0.910 [95CI: 0.812-0.968]. Compared to the MGA's median DSC for brain: 0.936 [95CI: 0.890, 0.958], skin: 0.991 [95CI: 0.964, 0.996], tumor: 0.723 [95CI: 0.000-0.926], and ventricles: 0.856 [95CI: 0.216-0.916]. NnU-Net performance between centers did not significantly differ except for the skin segmentations Additionally, the nnU-Net models were faster (mean: 1139 s [95CI: 685.0-1616]) than the MGA (mean: 2851 s [95CI: 1482-6246]). CONCLUSIONS: The nnU-Net is a fast, reliable tool for creating automatic deep learning-based segmentation pipelines, reducing the need for extensive manual tuning and iteration. The models are able to achieve this performance despite a modestly sized training set. The ability to create high-quality segmentations in a short timespan can prove invaluable in neurosurgical settings.

Outcomes after surgical revascularization in diabetic patients.

OBJECTIVES: Patients with diabetes mellitus (DM) undergoing coronary artery bypass grafting (CABG) have been repeatedly demonstrated to have worse clinical outcomes compared to patients without DM. The objective of this study was to evaluate the impact of DM on 1-year clinical outcomes after isolated CABG. METHODS: The European DuraGraft registry included 1130 patients (44.6%) with and 1402 (55.4%) patients without DM undergoing isolated CABG. Intra-operatively, all free venous and arterial grafts were treated with an endothelial damage inhibitor. Primary end point in this analysis was the incidence of a major adverse cardiac event (MACE), a composite of all-cause death, repeat revascularization or myocardial infarction at 1 year post-CABG. To balance between differences in baseline characteristics (n = 1072 patients in each group), propensity score matching was used. Multivariable Cox proportional hazards regression was performed to identify independent predictors of MACE. RESULTS: Diabetic patients had a higher cardiovascular risk profile and EuroSCORE II with overall more comorbidities. Patients were comparable in regard to surgical techniques and completeness of revascularization. At 1 year, diabetics had a higher MACE rate {7.9% vs 5.5%, hazard ratio (HR) 1.43 [95% confidence interval (CI) 1.05-1.95], P = 0.02}, driven by increased rates of death [5.6% vs 3.5%, HR 1.61 (95% CI 1.10-2.36), P = 0.01] and myocardial infarction [2.8% vs 1.4%, HR 1.99 (95% CI 1.12-3.53) P = 0.02]. Following propensity matching, no statistically significant difference was found for MACE [7.1% vs 5.7%, HR 1.23 (95% CI 0.87-1.74) P = 0.23] or its components. Age, critical operative state, extracardiac arteriopathy, ejection fraction ≤50% and left main disease but not DM were identified as independent predictors for MACE. CONCLUSIONS: In this study, 1-year outcomes in diabetics undergoing isolated CABG were comparable to patients without DM.

Multiresistant Acinetobacter baumannii causing malignant otitis externa: a case report.

Abstract: Malignant otitis externa is an infection of the skin and soft tissue of the ear canal, spreading to the nearby structures. It causes severe otalgia and otorrhea, and can lead to ominous consequences such as cranial nerve damage and meningitis. The main etiologic agent is Pseudomonas aeruginosa and treatment relies on broad-spectrum intravenous antibiotics. We report a rare case of a woman suffering from Malignant otitis externa caused by Acinetobacter baumannii and requiring the use of colistin.

Clinical outcomes and quality of life after contemporary isolated coronary bypass grafting: a prospective cohort study.

OBJECTIVES: The objective of the European Multicenter Registry to Assess Outcomes in coronary artery bypass grafting (CABG) patients (DuraGraft Registry) was to determine clinical outcomes and quality of life (QoL) after contemporary CABG that included isolated CABG and combined CABG/valve procedures, using an endothelial damage inhibitor (DuraGraft) intraoperatively for conduit preservation. Here, we report outcomes in the patient cohort undergoing isolated CABG. METHODS: The primary outcome was the composite of all-cause death, myocardial infarction (MI), or repeat revascularization (RR) [major adverse cardiac events (MACE)] at 1 year. Secondary outcomes included the composite of all-cause death, MI, RR, or stroke [major adverse cardiac and cerebrovascular events (MACCE)], and QoL. QoL was assessed with the EuroQol-5 Dimension questionnaire. Independent risk factors for MACE at 1 year were determined using Cox regression analysis. RESULTS: A total of 2532 patients (mean age, 67.4±9.2 years; 82.5% male) underwent isolated CABG. The median EuroScore II was 1.4 [interquartile range (IQR), 0.9-2.3]. MACE and MACCE rates at 1 year were 6.6% and 7.8%, respectively. The rates of all-cause death, MI, RR, and stroke were 4.4, 2.0, 2.2, and 1.9%, respectively. The 30-day mortality rate was 2.3%. Age, extracardiac arteriopathy, left ventricular ejection fraction less than 50%, critical operative state, and left main disease were independent risk factors for MACE. QoL index values improved from 0.84 [IQR, 0.72-0.92] at baseline to 0.92 [IQR, 0.82-1.00] at 1 year ( P <0.0001). CONCLUSION: Contemporary European patients undergoing isolated CABG have a low 1-year clinical event rate and an improved QoL.

Cardiac magnetic resonance predictors of left ventricular remodelling following acute ST elevation myocardial infarction: The VavirimS study.

BACKGROUND: Left ventricular (LV) remodelling (REM) ensuing after ST-elevation myocardial infarction (STEMI), has typically been studied by echocardiography, which has limitations, or cardiac magnetic resonance (CMR) in early phase that may overestimate infarct size (IS) due to tissue edema and stunning. This prospective, multicenter study investigated LV-REM performing CMR in the subacute phase, and 6 months after STEMI. METHODS AND RESULTS: patients with first STEMI undergoing successful primary angioplasty were consecutively enrolled. CMR was done at 30-days and 6-months. Primary endpoint was prevalence at 6 months of LV-REM [≥12% increase in LV end-diastolic volume index (LV-REMEDV)]; LV-REM by end-systolic volume index increase ≥12% (LV-REMESV) was also calculated. Of 325 patients enrolled, 193 with a full set of research-quality CMR images were analyzed. LV-REMEDV and LV-REMESV were present in 36/193 (19%) and 34/193 (18%) patients, respectively. At follow up, LV ejection fraction (EF) improved in patients with or without LV-REMEDV, whilst it decreased in those with LV-REMESV (p < 0.001 for interaction). Considering predictors of LV-REM, IS in the highest tertile was clearly separated from the two lower tertiles. In LV-REMEDV, the highest tertile was associated with significantly higher LV-EDV, LV-ESV, and lower EF. CONCLUSIONS: In a contemporary cohort of STEMI patients studied by CMR, prevalence of LV-REMEDV was lower than previously reported. Importantly, our data indicate that LV-REMEDV might not be "adverse" per se, but rather "compensatory", being associated with LV-EF improvement at follow-up. Conversely, LV-REMESV might be an "adverse" phenomenon associated with decreased LV-EF, driven by IS.

Effects of Gradient and Speed on Uphill Running Gait Variability.

BACKGROUND: The aim of this study was to investigate the effects of gradient and speed on running variability (RV) and local dynamic stability (LDS) during uphill running. HYPOTHESES: (1) Both gradient and speed increase metabolic effort, in terms of heart rate (HR) and perceived exertion (CR10), in line with the contemporary literature, and (2) gradient increases RV and impairs LDS. STUDY DESIGN: "Crossover" observational design. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 25 runners completed 10-minute running trials in 3 different conditions and in a randomized order: gradient at 0% (0CON), 2% (2CON), and 2% at isoefficiency speed (2IES). 0CON and 2CON speeds were calculated as the "best 10-km race performance" minus 1 km·h-1, whereas 2IES speed was adjusted to induce the same metabolic expenditure as 0CON. HR and perceived exertion as well as running kinematic variables were collected across all trials and conditions. Running variability was calculated as the standard deviation of the mean stride-to-stride intervals over 100 strides, while LDS was expressed by the Lyapunov exponent (LyE) determined on running cycle time over different running conditions. RESULTS: Increases in HR and CR10 were observed between 0CON and 2CON (P < 0.001) and between 2IES and 2CON (P < 0.01). Higher RV was found in 2CON compared with 0CON and 2IES (both P < 0.001). Finally, the largest LyE was observed in 2IES compared with 0CON and 2CON (P = 0.02 and P = 0.01, respectively). CONCLUSION: Whereas RV seems to be dependent more on metabolic effort, LDS is affected by gradient to a greater extent. CLINICAL RELEVANCE: Running variability could be used to monitor external training load in marathon runners.

Benefits of pre-operative oral Sucrosomial® iron supplementation in cardiac surgery: influence of patient's baseline hemoglobin and gender.

BACKGROUND: The prevalence of low pre-operative hemoglobin (Hb) among cardiac surgery patients is high. As iron homeostasis is often impaired in these patients, restoration of iron availability might over-ride iron-restricted erythropoiesis. This post-hoc analysis of a previously published, large, randomized clinical trial (ClincalTrials.gov NCT03560687; n=1,000) assesses which sub-cohort of patients benefits the most from pre-operative Hb optimization with oral Sucrosomial® iron. MATERIALS AND METHODS: Patients without baseline Hb (n=349) or receiving >5 red blood cell units (n=57) were excluded from the study. Data from the remaining 594 were reanalyzed according to treatment, baseline anemia (Hb <13 g/dL) or gender. Patients (pt) received a one-month course of 60 mg/day Sucrosomial® iron (Iron group, n=309) or routine care (Control group, n=285) prior to elective cardiac surgery. Main end-point variables were increase in Hb from randomization to hospital admission, transfusion requirements, and cost-effectiveness of Sucrosomial® iron administration. RESULTS: At hospital admission, Hb had increased 0.7 g/dL and 0.1 g/dL, for Iron and Control groups, respectively (p<0.001), with no gender-related differences, leading to a decrease in transfusion rate (30 vs 59%, respectively; p<0.001) and transfusion index (0.5 units/patient vs 1.2 units/pt, respectively; p<0.001). Sucrosomial® iron administration was well-tolerated, and yielded cost-savings of €92/pt (p<0.001), particularly in those presenting with baseline Hb <13 g/dL. CONCLUSIONS: This post-hoc analysis confirms pre-operative Sucrosomial® iron administration is a safe and cost-effective strategy to increase preoperative Hb and decrease transfusion requirements in elective cardiac surgery, especially in those anemic at baseline.

Nasal Vestibulitis and Vestibular Furunculosis: a systematic review about two common nasal infections and considerations about correct diagnosis and management.

Background: Nasal vestibulitis (NV) and nasal vestibular furunculosis (NVF) are two infectious processes of the nasal vestibule, sharing common etiology, the same risk of complications, and similar treatment while remaining two different pathological entities. Methods: We performed a comprehensive literature research on NV and NVF in PubMed, Cochrane, and Google Scholar databases, with the aim to review the evidence on these two conditions and discuss the therapeutic approaches. Results: We identified a total of 248 records; according to our inclusion/exclusion criteria, 27 of them, published over a period of 59 years (1962-2021), were included in this review. Conclusion: NV and NVF are reported to be common conditions, with well-known etiological agents and risk factors. The diagnosis is clinical and topical antibiotics are the mainstay of treatment. Complications appear to be infrequent. Further studies are necessary to clarify the pathogenetic mechanisms and the exact prevalence of both conditions.

Effects of intensified training and tapering periods using different exercise modalities on judo-specific physical test performances.

This study investigated the effects of intensified training and tapering periods using different exercise modalities on judo athletes' physical fitness. Fifty-nine adolescent male and female judo athletes (age 15 ± 1 years) were randomly assigned to one of three experimental groups or one control group (CG). Experimental groups (kumi-kata [KG], uchi-komi [UG] and running [RG]) trained four times per week over four weeks of intensified training (in addition to their usual technical-tactical judo training; CG underwent only the usual training) followed by 12 days of tapering. The countermovement jump test (CMJ), isometric and dynamic judogi chin-up tests (JCT), uchi-komi speed test (UST), Special Judo Fitness Test (SJFT) and Judo Physical Fitness Test (JPFT) were administered before and after the intensified period and after tapering. The CMJ performance was superior in KG compared with UG, RG and CG. Isometric JCT performance was superior in KG compared with RG and CG. Regarding UST, performance was superior in UG compared with RG and CG. The same performance was superior with respect to the same groups considering pre-training to tapering change. The SJFT index did not differ between groups or time-points. The JPFT index increased after intensified and tapering periods compared with before training, with KG eliciting higher values compared with CG. Coaches and conditioning coaches could administer kumi-kata high-intensity interval training to enhance athletes' judo-specific physical fitness.

Clinical event rate in patients with and without left main disease undergoing isolated coronary artery bypass grafting: results from the European DuraGraft Registry.

OBJECTIVES: Left main coronary artery disease (LMCAD) is considered an independent risk factor for clinical events after coronary artery bypass grafting (CABG). We have conducted a subgroup analysis of the multicentre European DuraGraft Registry to investigate clinical event rates at 1 year in patients with and without LMCAD undergoing isolated CABG in contemporary practice. METHODS: Patients undergoing isolated CABG were selected. The primary end point was the incidence of a major adverse cardiac event (MACE) defined as the composite of death, myocardial infarction (MI) or repeat revascularization (RR) at 1 year. The secondary end point was major adverse cardiac and cerebrovascular events (MACCE) defined as MACE plus stroke. Propensity score matching was performed to balance for differences in baseline characteristics. RESULTS: LMCAD was present in 1033 (41.2%) and absent in 1477 (58.8%) patients. At 1 year, the MACE rate was higher for LMCAD patients (8.2% vs 5.1%, P = 0.002) driven by higher rates of death (5.4% vs 3.4%, P = 0.016), MI (3.0% vs 1.3%, P = 0.002) and numerically higher rates of RR (2.8% vs 1.8%, P = 0.13). The incidence of MACCE was 8.8% vs 6.6%, P = 0.043, with a stroke rate of 1.0% and 2.4%, P = 0.011, for the LMCAD and non-LMCAD groups, respectively. After propensity score matching, the MACE rate was 8.0% vs 5.2%, P = 0.015. The incidence of death was 5.1% vs 3.7%, P = 0.10, MI 3.0% vs 1.4%, P = 0.020, and RR was 2.7% vs 1.6%, P = 0.090, for the LMCAD and non-LMCAD groups, respectively. Less strokes occurred in LMCAD patients (1.0% vs 2.4%, P = 0.017). The MACCE rate was not different, 8.5% vs 6.7%, P = 0.12. CONCLUSIONS: In this large registry, LMCAD was demonstrated to be an independent risk factor for MACE after isolated CABG. Conversely, the risk of stroke was lower in LMCAD patients. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02922088.

Validation of the COVID-19 Digital Health Literacy Instrument in the Italian Language: A Cross-Sectional Study of Italian University Students.

The Coronavirus Disease 19 (COVID-19) pandemic and the associated "infodemic" have shown the importance of surveillance and promotion of health literacy, especially for young adults such as university students who use digital media to a very high degree. This study aimed to assess the validity and reliability of the Italian version of the COVID-19 adapted version of the Digital Health Literacy Instrument (DHLI). This cross-sectional study is part of the COVID-19 University Students Survey involving 3985 students from two Italian universities. First, item analysis and internal consistency were assessed. Then, Principal Component Analysis (PCA) and Confirmatory Factor Analyses (CFA) were performed comparing different models. The Italian DHLI showed good psychometric characteristics. The protecting privacy subscale was excluded, given the criticalities presented in the validation process. CFA confirmed the four-factor structure, also including a high-order factor. This result allows using the scale to measure a global level of digital health literacy and consider its levels separately for each construct component: searching the web for information, evaluating reliability, determining personal relevance, and adding self-generated content.

Hyperosmia after COVID-19: hedonic perception or hypersensitivity?

OBJECTIVE: COVID-19 has been associated with a wide range of quantitative and qualitative disorders of smell, including hyposmia/anosmia, parosmia, and phantosmia; however, no reports to date have reported hyperosmia as a sequela of SARS-CoV-2 infection. PATIENTS AND METHODS: We present two cases of subjective hyperosmia in a South Tyrolean Alps family, occurring within days after recovery from SARS-CoV-2 infection with transient anosmia. RESULTS: The subjects, a mother and son, exhibited subjective hyperosmia despite normal objective olfactory testing. During independent assessments, the severity of hyperosmia and specific odors affected were highly correlated, consistent with shared genetic and environmental factors. In contrast, two other family members with COVID-19 had no perceptual distortion and normal recovery of smell. CONCLUSIONS: Subjective hyperosmia after COVID-19 infection exhibited striking similarity in two affected family members, suggesting interaction of environment, genetics, and perception.

Case Report: Opsoclonus-Myoclonus Syndrome Associated With Contactin-Associated Protein-Like 2 and Acetylcholine Receptor Autoantibodies in the Setting of Non-Small Cell Lung Carcinoma.

Opsoclonus myoclonus syndrome (OMS) is a rare immune-mediated paraneoplastic or para/-post-infectious syndrome characterized by "dancing" eye movements, myoclonus, and ataxia. Neuropsychiatric symptoms have also been reported. Without treatment, OMS may progress to further neurological impairment and even death. Autoimmune attack of CNS structures in OMS is most commonly mediated by anti-Ri (also known as ANNA2) IgG antibodies, with additional findings implicating antibodies targeting various neurotransmitter receptors. Prompt immunotherapy and neoplasm treatment may result in improvement. We report a novel association of Contactin-Associated Protein-Like 2 (Caspr2) antibodies occurring in association with paraneoplastic OMS. While breast cancer and small cell lung cancer (SCLC) are more commonly associated with OMS among adults, we characterize a novel association between Caspr2 antibody in a patient with mixed non-small cell and small cell lung carcinoma.