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(3 + 2)-Cycloaddition of bicyclobutanes and thioketones: access to 2-thiabicyclo[2.1.1]hexanes without the use of catalysts or light
No full textA novel approach to the synthesis of a 2-thiabicyclo[2.1.1]hexane scaffold has been described. This method utilizes two highly reactive species: bicyclo[1.1.0]butanes (BCBs) and thioketones. Their high reactivity enabled the formation of the desired product to occur under ambient conditions, without the need for catalysts, additives or light irradiation. To the best of our knowledge, this is the first rational synthesis of this specific skeleton. A variety of carbonyl-substituted BCBs, with or without a substituent at the other bridgehead, and thioketones were examined
A proteotranscriptomic approach to dissect the molecular landscape of human retinoblastoma
No full textBackground: Retinoblastoma is a rare pediatric eye cancer caused by mutations in the RB1 gene, which regulates retinal cell growth. Early detection and treatment are critical for preventing vision loss and improving survival outcomes. This study aimed to perform an integrated proteotranscriptomic characterization of human retinoblastoma to provide a deeper understanding of disease biology and to identify novel therapeutic targets. Methods: Paired tumor and adjacent retinal tissue samples were dissected from seven eyes. RNA sequencing and liquid chromatography-mass spectrometry were performed on the same samples. The spatially resolved cellular landscape was assessed using Imaging Mass Cytometry (IMC). Results: The correlation between RNA and protein level was moderate with variations across different pathways, underscoring the value of an integrated proteotranscriptomic approach. IMC identified more than 67,000 single cells in 11 distinct clusters, including antigen presenting cells, T cells, stroma cells, vascular cells and two clusters of proliferating and CD44/c-Myc positive tumor cells. Antigen presenting cells expressed higher levels of CD68 in retinoblastoma compared to controls.Conclusions: CD44+ and high-c-Myc-expressing tumor cells may represent cancer stem cells with possible involvement in metastasis, warranting further validation. Our multilayered approach could pave the way for enhanced molecular assessments and novel targeted therapies for human retinoblastom
Nationwide assessment of COVID-19 ventilator and non-invasive respiratory support burden during the early pandemic in the United States
No full textIn this nationwide cross-sectional study of 4,055,462 hospital admissions with a diagnosis of coronavirus disease 2019 (COVID-19) from April 2020 to December 2021 identified in the Agency of Healthcare Research and Quality’s Healthcare Cost and Utilization Project National Inpatient Sample in the United States, a total of 489,390 (12.1%) patients experienced endotracheal intubation and mechanical ventilation, with the highest peak in August 2021 (48,735 endotracheal intubations and mechanical ventilation), followed by January 2021 (47,100 endotracheal intubations and mechanical ventilation) and December 2021 (43,835 endotracheal intubations and mechanical ventilation). During the 3-month long large surge from November 2020 to January 2021, a total of 104,750 endotracheal intubations and mechanical ventilation occurred among 1,069,874 COVID-19 admissions. Shock (adjusted-odds ratio 24.21, 95% confidence interval 23.93–24.49) and respiratory failure (adjusted-odds ratio 14.09, 95% confidence interval 13.80–14.38) were the two strongest factors associated with endotracheal intubation and mechanical ventilation. A total of 266,585 (6.6%) patients received non-invasive respiratory support alone without endotracheal intubation and mechanical ventilation during the study period with the highest peak in August 2021 (30,725 cases), followed by January 2021 (28,035 cases), and December 2021 (26,200 cases). The utilization of non-invasive respiratory support without endotracheal intubation and mechanical ventilation increased by nearly three-fold during the 21-month study period (adjusted-odds ratio for the fourth year-quarter of 2021 compared to the second year-quarter of 2020 2.94, 95% confidence interval 2.88–3.00). A total of 515,800 (12.7%) deaths occurred during COVID-19 hospitalization, with highest in the peak of multi-month lasting largest surge (January 2021, 56,775 deaths), followed by August 2021 (47,535 deaths) and December 2021 (46,880 deaths). Among those who deceased following endotracheal intubation and mechanical ventilation, the median time from admission to death was 14 days (interquartile range 7–21). COVID-19 admissions, respiratory intervention approach, and COVID-19 case fatality differed across the nine U.S. census divisions during the study period. In conclusion, these statistics may be useful to inform the national-level preparedness of global pandemic from respiratory illness in the future, possibly exceeding 48,000 endotracheal intubations and mechanical ventilation across the country in a month and 100,000 endotracheal intubations and mechanical ventilation in three months when encountering long-lasting surge with one-million admissions
Eltrombopag in combination with immunosuppressive therapy in pediatric severe aplastic anemia: phase 2 ESCALATE trial
No full textSevere aplastic anemia (SAA) is a rare, life-threatening disease with acquired pancytopenia and hypocellular bone marrow. ESCALATE evaluated eltrombopag in combination with immunosuppressive therapy (IST) in pediatric patients (aged 1 to <18 years) with relapsed/refractory (R/R) or treatment-naïve SAA. The eltrombopag starting dose was 25 mg/d for patients aged 1 to <6 years and 50 mg/d for patients aged 6 to <18 years; dose modifications (maximum dose, 150 mg/d) were allowed to achieve a target platelet count of 50 × 109/L to 200 × 109/L. Eltrombopag was administered with cyclosporine A, with or without horse antithymocyte globulin, for 26 weeks and could be extended if clinically beneficial. Fifty-one patients were treated (R/R SAA, n = 14; treatment-naïve SAA, n = 37). Data were analyzed overall and as 2 cohorts: R/R and treatment-naïve cohorts. The overall response rate (ORR; per North American Pediatric Aplastic Anemia Consortium criteria) at 26 weeks was 54.9% in both cohorts combined and 71.4% and 48.6% in the R/R and treatment-naïve cohorts, respectively; most responders had sustained responses after discontinuing eltrombopag. Among baseline transfusion-dependent patients, 66.7% and 76.7% achieved red blood cell and platelet transfusion independence, respectively, with rates of 70% and 80% for the R/R cohort and 65.6% and 75.8% for the treatment-naïve cohort, respectively. The most common treatment-related adverse events were abnormalities in liver function tests, including increased bilirubin (43.1%), alanine aminotransferase (37.3%), and aspartate aminotransferase (33.3%). Eltrombopag with IST showed a trend toward a favorable ORR in the R/R cohort, with no new safety signals
Examining practices related to ethical aspects in eHealth evaluation research: protocol for a scoping review
No full textEfficacy of a self-guided internet intervention with optional on-demand feedback versus digital psychoeducation on sleep hygiene for university students with insomnia: randomized controlled trial
No full textBackground:Internet-based cognitive behavioral therapy for insomnia (iCBT-I) provides flexibility but requires significant time and includes potentially challenging components such as sleep restriction therapy. This raises questions about its incremental effectiveness compared to less demanding minimal interventions such as sleep hygiene psychoeducation.Objective:This study aimed to assess the incremental efficacy of self-guided iCBT-I with optional on-demand feedback for university students with insomnia compared to a single session of digital psychoeducation on sleep hygiene.Methods:In a randomized controlled trial, 90 students with insomnia (Insomnia Severity Index ≥10) were randomly allocated to self-help–based iCBT-I (45/90, 50%) or one session of digital sleep hygiene psychoeducation with stimulus control instructions (active control group [aCG]: 45/90, 50%). The self-help–based iCBT-I consisted of 6 sessions on psychoeducation, sleep restriction, and stimulus control, including written feedback on demand from an eCoach. Assessments occurred at baseline (T1), 8 weeks after treatment (T2), and at a 6-month follow-up (T3) via web-based self-assessment and diagnostic telephone interviews. The primary outcome was insomnia severity at T2. Analyses of covariance were conducted in an intention-to-treat sample. Secondary outcomes included diagnoses of insomnia and major depression, sleep quality, sleep efficiency, worrying, recovery experiences, recovery activities, presenteeism, procrastination, cognitive irritation, and recuperation in sleep.Results:There was no difference in insomnia severity at T2 between the iCBT-I group (mean 11.27, SD 5.21) and aCG group (mean 12.36, SD 4.16; F1,989.03=1.12; P=.29; d=–0.26; 95% CI 0.68 to 0.17). A significant difference emerged at T3 (iCBT-I: mean 9.43, SD 5.36; aCG: mean 12.44, SD 5.39; F1,426.15=4.72; P=.03), favoring iCBT-I with a medium effect (d=–0.57; 95% CI 1.07 to –0.06). Most secondary outcomes revealed no significant differences between the groups. In total, 51% (23/45) of participants in the iCBT-I group completed all 6 sessions, and 69% (31/45) completed the 4 core sessions.Conclusions:In the short term, students might benefit from low-intensity, easily accessible digital sleep hygiene psychoeducation or iCBT-I. However, it appears that iCBT-I offers superiority over sleep hygiene psychoeducation in the long term
Bridging circuit modeling and signal analysis to understand the risk of crosstalk contamination in brain recordings
No full textAdvancements in the field of implantable neurotechnologies have enabled the integration of hundreds of microelectrodes on ultra-thin and flexible substrates. Besides implantable components, also connectors, headstages and cables have to comply with the high-count demand, resulting in a complex and compact chain with reduced line spacing and smaller safety margins. Here, we show that epicortical recordings acquired from anesthetized rat brains with a state-of-art neural acquisition system are undoubtedly compromised by crosstalk, with signal coherence maps exhibiting a strong dependency to the routing layout. A crosstalk back-correction algorithm is developed, allowing to infer on how signals would look like under a zero-crosstalk scenario. We found that signal coherence between closely routed channels effectively drops after correction, corroborating crosstalk contamination. Our work stresses the importance of validating recorded data against the routing layout as a crucial step of data quality control, helping to come closer to ground truth data
