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The performance of locally available agricultural carbon media (barley straw and hemp straw) was compared to woodchips for removing nitrate (NO3-N) and orthophosphate (PO4-P) in up-flow laboratory bioreactors. These media were tested in three replicates to quantify variability. The production of greenhouse gases nitrous oxide (N2O), methane (CH4) and carbon dioxide (CO2) were quantified. Influent water with NO3-N and PO4-P flowed continuously through bioreactors at a 4-h hydraulic retention time at 20 °C for 16 weeks. Nitrate removal reached up to 37% across all carbon media after the fifth week, with a removal rate of 64 g N m−3 d−1. Nitrate removal was affected by the type of carbon media in the order of barley straw > hemp straw > woodchips (P < 0.05). Most of the PO4-P rates declined rapidly after the first week for all carbon media meaning none were superior. Greenhouse gas production was dominated by CO2 with less CH4 and N2O produced. Production of N2O relative to nitrate removal for the three media remained low at 0.16 to 0.75%. The findings suggest that agricultural residues could perform better than woodchips for NO3-N removal although there was slightly higher N2O and CO2 production for these residues than woodchips. HIGHLIGHTS Barley straw was more effective in reducing nitrate compared to hemp straw and woodchips.; PO4-P removal efficiencies and rates declined rapidly for the three carbon media.; Greenhouse gas production was dominated by CO2 with less CH4 and N2O produced.; Production of N2O relative to nitrate removal for the three media remained low.;

Objective: There is limited clinical evidence to support any specific parenchymal air leak resolution criteria when using digital pleural drainage devices following lung resection. The aim of this study is to determine an optimal air leak resolution criteria, where duration of chest tube drainage is minimized while avoiding complications from premature chest tube removal. Methods: Airflow data averaged at 10-minute intervals was collected prospectively using a digital pleural drainage device (Thopaz; Medela) in 400 patients from 2015 to 2019. All permutations of air leak resolution criteria from

Abstract Background High expression of the glycosyltransferase UGT2B17 represents an independent adverse prognostic marker in chronic lymphocytic leukemia (CLL). It also constitutes a predictive marker for therapeutic response and a drug resistance mechanism. The key determinants driving expression of the UGT2B17 gene in normal and leukemic B-cells remain undefined. The UGT2B17 transcriptome is complex and is comprised of at least 10 alternative transcripts, identified by previous RNA-sequencing of liver and intestine. We hypothesized that the transcriptional program regulating UGT2B17 in B-lymphocytes is distinct from the canonical expression previously characterized in the liver. Results RNA-sequencing and genomics data revealed a specific genomic landscape at the UGT2B17 locus in normal and leukemic B-cells. RNA-sequencing and quantitative PCR data indicated that the UGT2B17 enzyme is solely encoded by alternative transcripts expressed in CLL patient cells and not by the canonical transcript widely expressed in the liver and intestine. Chromatin accessible regions (ATAC-Seq) in CLL cells mapped with alternative promoters and non-coding exons, which may be derived from endogenous retrotransposon elements. By luciferase reporter assays, we identified key cis-regulatory STAT3, RELA and interferon regulatory factor (IRF) binding sequences driving the expression of UGT2B17 in lymphoblastoid and leukemic B-cells. Electrophoretic mobility shift assays and pharmacological inhibition demonstrated key roles for the CLL prosurvival transcription factors STAT3 and NF-κB in the leukemic expression of UGT2B17. Conclusions UGT2B17 expression in B-CLL is driven by key regulators of CLL progression. Our data suggest that a NF-κB/STAT3/IRF/UGT2B17 axis may represent a novel B-cell pathway promoting disease progression and drug resistance.

Abstract Objective Our objective was to evaluate the relationship between scalp‐EEG and stereoelectroencephalography (SEEG) seizure‐onset patterns (SOP) in patients with MRI‐negative drug‐resistant focal epilepsy. Methods We analyzed retrospectively 41 patients without visible lesion on brain MRI who underwent video‐EEG followed by SEEG. We defined five types of SOPs on scalp‐EEG and eight types on SEEG. We examined how various clinical variables affected scalp‐EEG SOPs. Results The most prevalent scalp SOPs were rhythmic sinusoidal activity (56.8%), repetitive epileptiform discharges (22.7%), and paroxysmal fast activity (15.9%). The presence of paroxysmal fast activity on scalp‐EEG was always seen without delay from clinical onset and correlated with the presence of low‐voltage fast activity in SEEG (sensitivity = 22.6%, specificity = 100%). The main factor explaining the discrepancy between the scalp and SEEG SOPs was the delay between clinical and scalp‐EEG onset. There was a correlation between the scalp and SEEG SOPs when the scalp onset was simultaneous with the clinical onset (p = 0.026). A significant delay between clinical and scalp discharge onset was observed in 25% of patients and featured always with a rhythmic sinusoidal activity on scalp, corresponding to similar morphology of the discharge on SEEG. The presence of repetitive epileptiform discharges on scalp was associated with an underlying focal cortical dysplasia (sensitivity = 30%, specificity = 90%). There was no significant association between the scalp SOP and the epileptogenic zone location (deep or superficial), or surgical outcome. Significance In patients with MRI‐negative focal epilepsy, scalp SOP could suggest the SEEG SOP and some etiology (focal cortical dysplasia) but has no correlation with surgical prognosis. Scalp SOP correlates with the SEEG SOP in cases of simultaneous EEG and clinical onset; otherwise, scalp SOP reflects the propagation of the SEEG discharge. Plain Language Summary We looked at the correspondence between the electrical activity recorded during the start of focal seizure using scalp and intracerebral electrodes in patients with no visible lesion on MRI. If there is a fast activity on scalp, it reflects similar activity inside the brain. We found a good correspondence between scalp and intracerebral electrical activity for cases without significant delay between clinical and scalp electrical onset (seen in 75% of the cases we studied). Visualizing repetitive epileptic activity on scalp could suggest a particular cause of the epilepsy: a subtype of brain malformation called focal cortical dysplasia.

Background: The advent of Deep Learning initiated a new era in which neural networks relying solely on Whole-Slide Images can estimate the survival time of cancer patients. Remarkably, despite deep learning’s potential in this domain, no prior research has been conducted on image-based survival analysis specifically for peritoneal mesothelioma. Prior studies performed statistical analysis to identify disease factors impacting patients’ survival time. Methods: Therefore, we introduce MPeMSupervisedSurv, a Convolutional Neural Network designed to predict the survival time of patients diagnosed with this disease. We subsequently perform patient stratification based on factors such as their Peritoneal Cancer Index and on whether patients received chemotherapy treatment. Results: MPeMSupervisedSurv demonstrates improvements over comparable methods. Using our proposed model, we performed patient stratification to assess the impact of clinical variables on survival time. Notably, the inclusion of information regarding adjuvant chemotherapy significantly enhances the model’s predictive prowess. Conversely, repeating the process for other factors did not yield significant performance improvements. Conclusions: Overall, MPeMSupervisedSurv is an effective neural network which can predict the survival time of peritoneal mesothelioma patients. Our findings also indicate that treatment by adjuvant chemotherapy could be a factor affecting survival time.

AbstractThis paper presents the results of a systematic literature review concerning the actual and future uses of chatbots (artificial conversation agents) in youth bullying cases. The study found that while artificial intelligence is highly regarded as an interesting tool by researchers, the technology is not yet good enough to intervene in crisis cases. Indeed, the studies show that chatbots are still inaccurate regarding emotion detection, their language is not adapted to children’s way of speaking and writing, and they are too predictable. Despite those limitations, the most promising use of chatbots regarding bullying is as a way to raise awareness about it among children and teenagers. Chatbots could then become a tool in preventing bullying cases. This paper also presents a review of researchers’ rhetoric about chatbots, the reasons why youths want to interact with chatbots, and how the use of chatbots in intervention is going to affect the service providers’ work.

Candida auris has emerged as a significant healthcare-associated pathogen due to its multidrug-resistant nature. Ongoing constraints in the discovery and provision of new antifungals create an urgent imperative to design effective remedies to this pressing global blight. Herein, we screened a chemical library and identified aryl-carbohydrazide analogs with potent activity against both C. auris and the most prevalent human fungal pathogen, C. albicans. SPB00525 [N’-(2,6-dichlorophenyl)-5-nitro-furan-2-carbohydrazide] exhibited potent activity against different strains that were resistant to standard antifungals. Using drug-induced haploinsufficient profiling, transcriptomics and metabolomic analysis, we uncovered that Ole1, a Δ(9) fatty acid desaturase, is the likely target of SPB00525. An analog of the latter, HTS06170 [N’-(2,6-dichlorophenyl)-4-methyl-1,2,3-thiadiazole-5-carbohydrazide], had a superior antifungal activity against both C. auris and C. albicans. Both SPB00525 and HTS06170 act as antivirulence agents and inhibited the invasive hyphal growth and biofilm formation of C. albicans. SPB00525 and HTS06170 attenuated fungal damage to human enterocytes and ameliorate the survival of Galleria mellonella larvae used as systemic candidiasis model. These data suggest that inhibiting fungal Δ(9) fatty acid desaturase activity represents a potential therapeutic approach for treating fungal infection caused by the superbug C. auris and the most prevalent human fungal pathogen, C. albicans.

Background. In kidney transplant recipients with positive serology (R+) for the cytomegalovirus (CMV), 2 strategies are used to prevent infection, whose respective advantages over the other are still debated. This study aimed to evaluate the cost-effectiveness and cost utility of antiviral prophylaxis against CMV versus preemptive therapy, considering CMV infection–free survival over the first year posttransplantation as the main clinical outcome. Methods. Clinical, laboratory, and economic data were collected from 186 kidney transplant patients CMV (R+) included in the cohort study (85 patients who benefited from CMV prophylaxis and 101 from preemptive therapy). Costs were calculated from the hospital perspective and quality-adjusted life years (QALYs) using the EQ5D form. Using nonparametric bootstrapping, the incremental cost-effectiveness ratio (ICER) and cost utility were estimated (euros) for each case of infection avoided and each QALY gained for 1 y, respectively. Results. Prophylaxis significantly decreased the risk of CMV infection over the first year posttransplantation (hazard ratio 0.22, 95% confidence interval = 0.12-0.37, P

Summary: Background: Research in healthy young adults shows that characteristic patterns of brain activity define individual “brain-fingerprints” that are unique to each person. However, variability in these brain-fingerprints increases in individuals with neurological conditions, challenging the clinical relevance and potential impact of the approach. Our study shows that brain-fingerprints derived from neurophysiological brain activity are associated with pathophysiological and clinical traits of individual patients with Parkinson’s disease (PD). Methods: We created brain-fingerprints from task-free brain activity recorded through magnetoencephalography in 79 PD patients and compared them with those from two independent samples of age-matched healthy controls (N = 424 total). We decomposed brain activity into arrhythmic and rhythmic components, defining distinct brain-fingerprints for each type from recording durations of up to 4 min and as short as 30 s. Findings: The arrhythmic spectral components of cortical activity in patients with Parkinson’s disease are more variable over short periods, challenging the definition of a reliable brain-fingerprint. However, by isolating the rhythmic components of cortical activity, we derived brain-fingerprints that distinguished between patients and healthy controls with about 90% accuracy. The most prominent cortical features of the resulting Parkinson’s brain-fingerprint are mapped to polyrhythmic activity in unimodal sensorimotor regions. Leveraging these features, we also demonstrate that Parkinson’s symptom laterality can be decoded directly from cortical neurophysiological activity. Furthermore, our study reveals that the cortical topography of the Parkinson’s brain-fingerprint aligns with that of neurotransmitter systems affected by the disease’s pathophysiology. Interpretation: The increased moment-to-moment variability of arrhythmic brain-fingerprints challenges patient differentiation and explains previously published results. We outline patient-specific rhythmic brain signaling features that provide insights into both the neurophysiological signature and symptom laterality of Parkinson’s disease. Thus, the proposed definition of a rhythmic brain-fingerprint of Parkinson’s disease may contribute to novel, refined approaches to patient stratification. Symmetrically, we discuss how rhythmic brain-fingerprints may contribute to the improved identification and testing of therapeutic neurostimulation targets. Funding: Data collection and sharing for this project was provided by the Quebec Parkinson Network (QPN), the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer’s Disease (PREVENT-AD; release 6.0) program, the Cambridge Centre for Aging Neuroscience (Cam-CAN), and the Open MEG Archives (OMEGA). The QPN is funded by a grant from Fonds de Recherche du Québec - Santé (FRQS). PREVENT-AD was launched in 2011 as a $13.5 million, 7-year public-private partnership using funds provided by McGill University, the FRQS, an unrestricted research grant from Pfizer Canada, the Levesque Foundation, the Douglas Hospital Research Centre and Foundation, the Government of Canada, and the Canada Fund for Innovation. The Brainstorm project is supported by funding to SB from the NIH (R01-EB026299-05). Further funding to SB for this study included a Discovery grant from the Natural Sciences and Engineering Research Council of Canada of Canada (436355-13), and the CIHR Canada research Chair in Neural Dynamics of Brain Systems (CRC-2017-00311).

Background: Several strategies were implemented during the Covid-19 pandemic to enhance residency training and patient care. Objective: This study aims to assess the post-pandemic landscape of neurosurgical training and practice. Method: A survey consisting of 28 questions examining the challenges faced in neurosurgery and the adaptive measures was conducted among US neurosurgery residents from May 2022 to May 2023. Results: This study encompassed 59 neurosurgical residents, predominantly male (72.9%) and in later years of training (66.1%) and were distributed across 25 states. Telemedicine and tele-education were pivotal during the pandemic, with virtual lecture series, standalone lectures, and virtual discussions highly favored. Remote didactic learning increased for nearly half of the residents, while 54.2% resumed in-person instruction. Telemedicine was deemed effective by 86.4% for evaluating neurosurgical patients. Access to teaching environments was restricted for 61.0% of residents, impacting their training. The pandemic significantly influenced elective surgeries, with complete cancellations reported by 42.4%. Reduced faculty engagement was noted by 35.6% of residents, while 47.5% reported a negative impact on the overall resident experience. The majority (76.3%) considered changes to their training reasonable given the global health situation. Conclusions: Strategies implemented during the peak of the pandemic remain crucial in shaping neurosurgery training. Telemedicine has become indispensable, with widespread adoption. Tele-education has also expanded, providing additional learning opportunities. However, traditional didactic courses and hands-on experiences remain essential for comprehensive training. Balancing technology-driven methods with established approaches is crucial for optimizing neurosurgical education and maintaining high-quality patient care.

Abstract Background Long-term outcomes of lung transplantation (LTx) remain hampered by chronic lung allograft dysfunction (CLAD). Matrix metalloproteinase 9 (MMP-9) is a secretory endopeptidase identified as a key mediator in fibrosis processes associated with CLAD. The objective of this study was to investigate whether plasma MMP9 levels may be prognostic of CLAD development. Methods Participants were selected from the Cohort in Lung Transplantation (COLT) for which a biocollection was associated. We considered two time points, year 1 (Y1) and year 2 (Y2) post-transplantation, for plasma MMP-9 measurements. We analysed stable recipients at those time points, comparing those who would develop a CLAD within the 2 years following the measurement to those who would remain stable 2 years after. Results MMP-9 levels at Y1 were not significantly different between the CLAD and stable groups (230 ng/ml vs. 160 ng/ml, p = 0.4). For the Y2 analysis, 129 recipients were included, of whom 50 developed CLAD within 2 years and 79 remained stable within 2 years. MMP-9 plasma median concentrations were higher in recipients who then developed CLAD than in the stable group (230 ng/ml vs. 118 ng/ml, p = 0.003). In the multivariate analysis, the Y2 MMP-9 level was independently associated with CLAD, with an average increase of 150 ng/ml (95% CI [0–253], p = 0.05) compared to that in the stable group. The Y2 ROC curve revealed a discriminating capacity of blood MMP-9 with an area under the curve of 66%. Conclusion Plasmatic MMP-9 levels measured 2 years after lung transplantation have prognostic value for CLAD.

Abstract We aim to assess the efficacy and tolerance of cannabidiol as adjunctive therapy for Rett syndrome (RTT) patients with epilepsy. We conducted a longitudinal observational study through a monocentric cohort of 46 patients with RTT. Patients were recruited from March 2020 to October 2022 and were treated with Epidyolex® (cannabidiol, CBD, 100 mg/mL oral solution). In our cohort, 26 patients had associated epilepsy (26/46 [56%]), and 10/26 (38%) were treated with CBD, in combination with clobazam in 50% of cases. The median dose at their last follow‐up was 15 mg/kg/day. The median treatment duration was 13 months (range: 1–32 months). CBD reduced the incidence of seizures in seven out of 10 patients (70%) with one seizure‐free patient, two patients with a reduction of seizures of more than 75%, and four patients with a decrease of more than 50%. No aggravation of symptoms or adverse effects were observed. Only one patient experienced a transitory drooling and somnolence episode at the CBD initiation. Half of the patients showed a reduction in agitation and/or anxiety attacks, and an improvement in spasticity was reported in 4/10 (40%) of patients. CBD appears to have potential therapeutic value for the treatment of drug‐resistant epilepsy in Rett syndrome. CBD is well tolerated and, when used in combination with clobazam, may increase the effectiveness of clobazam alone.

Abstract Arctic ecosystems face increasing risks from vector-borne diseases due to climate-driven shifts in disease patterns and vector distribution. However, species identification challenges impact vector-borne disease surveillance, necessitates accurate identification. Aedes species are predominant among Arctic mosquitoes and pose health risks, with some species potentially carrying Jamestown Canyon and Snowshoe hare viruses. However, identifying Aedes species is challenging, especially under Arctic conditions and with complex adult traits. This study assessed the suitability of DNA barcoding (COI and ITS2 regions) and morphological characteristics for the identification of Arctic black-legged Aedes. It also aimed to evaluate the reliability of publicly available sequences. Our analysis focused on Aedes impiger, Aedes nigripes, and two species from the Punctor subgroup – Aedes hexodontus and Aedes punctor. In our study, the COI barcoding region distinguished Ae. impiger and Ae. nigripes but not within the species of the Punctor subgroup. In addition, the ITS2 barcoding region did not differentiate the species. When we evaluated GenBank and BOLD sequences, we found issues of under-representation and misidentifications, particularly within the Punctor subgroup. Based on these results, we recommend addressing identification difficulties, particularly within the Punctor subgroup, and advocate for more comprehensive morphological and molecular identification strategies. Integrating morphology and DNA barcoding holds promise for robust disease surveillance in Arctic regions, yet challenges persist, especially in complex species groups like the Punctor subgroup. Tackling these issues is pivotal to ensuring accurate vector status determination and reliable disease risk assessments in a rapidly changing Arctic ecosystem.

Considering the harmful effects of cannabis on individuals with a severe mental disorder and the limited effectiveness of current interventions, this case report showcases the beneficial results of a 10-session Avatar intervention for cannabis use disorder (CUD) on a polysubstance user with a comorbid schizoaffective disorder. Virtual reality allowed the creation of an Avatar representing a person significantly related to the patient’s drug use. Avatar intervention for CUD aims to combine exposure, relational, and cognitive behavioral therapies while practicing real-life situations and learning how to manage negative emotions and cravings. Throughout therapy and later on, Mr. C managed to maintain abstinence from all substances. Also, an improvement in the severity of CUD, as well as a greater motivation to change consumption, was observed after therapy. As observed by his mother, his psychiatrist, and himself, the benefits of Avatar intervention for CUD extended to other spheres of his life. The drastic results observed in this patient could be promising as an alternative to the current treatment available for people with a dual diagnosis of cannabis use disorder and psychotic disorder, which generally lack effectiveness. A single-blind randomized control trial comparing the treatment with a classical intervention in a larger sample is currently underway to evaluate whether the results are reproducible on a larger sample.

People with disability face heightened vulnerability during disasters due to functional limitations and inadequate support. This study explores disaster preparedness, capabilities, and support needs among Australians with disability. A cross-sectional survey was conducted, aligned with the Person-Centred Emergency Preparedness (P-CEP) framework: a co-designed and tested framework that helps people with disability assess their capabilities, identify their needs, communicate with others, and plan for different emergency scenarios. Data collection involved self-administered online surveys and interviewer-administered telephone surveys through convenience sampling. Descriptive statistics and regression modelling were employed for data analysis. Of the 138 respondents, most were female (68.1%) and aged 60–69 (23.9%). While 60.3% had emergency plans, motivators included enhancing survival chances (36.7%) and past disaster experiences (22.7%). Barriers included uncertainty about preparation (22.0%) and difficulty obtaining information (11.3%). Those perceiving bushfire risk were more likely to have a plan (p = 0.004), while individuals living alone were less likely (p = 0.019). Common preparedness actions included safely storing important documents (57.5%), but fewer had backup plans for support workers (9.2%) or home generators (9.7%). Respondents with disaster experience highlighted diverse support needs, encompassing health, emotional well-being, and practical assistance. Inclusive disaster risk reduction should involve individuals with disability in assessing their capabilities and support requirements. This study underscores the necessity of tailored emergency preparedness measures to safeguard the well-being of this demographic.

Abstract High-harmonic generation in solids allows probing and controlling electron dynamics in crystals on few femtosecond timescales, paving the way to lightwave electronics. In the spatial domain, recent advances in the real-space interpretation of high-harmonic emission in solids allows imaging the field-free, static, potential of the valence electrons with picometer resolution. The combination of such extreme spatial and temporal resolutions to measure and control strong-field dynamics in solids at the atomic scale is poised to unlock a new frontier of lightwave electronics. Here, we report a strong intensity-dependent anisotropy in the high-harmonic generation from ReS2 that we attribute to angle-dependent interference of currents from the different atoms in the unit cell. Furthermore, we demonstrate how the laser parameters control the relative contribution of these atoms to the high-harmonic emission. Our findings provide an unprecedented atomic perspective on strong-field dynamics in crystals, revealing key factors to consider in the route towards developing efficient harmonic emitters.