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Recent research indicates that human observers can perform high-level cognitive tasks typically associated with working memory processes (e.g. learning of complex item sequences, reading, arithmetic or delayed visual discrimination) independently of conscious awareness of the relevant information. However, the neural basis of this phenomenon is not known. Here we show neuroimaging and neurostimulation evidence that the dorsolateral and anterior prefrontal cortex can operate on non-conscious information in a manner that goes beyond automatic forms of sensorimotor priming and which may support implicit working memory processes and higher-level cognitive function. •Tested the relationship between working memory and conscious awareness.•Probed the neural basis of working memory without awareness.•PFC mediates successful working memory performance for non-conscious cues.•Non-conscious working memory processes can be modulated by PFC-tDCS.

Infection control guidelines for cystic fibrosis (CF) stress cleaning of environmental surfaces and patientcare equipment in CF clinics. This multicenter study measured cleanliness of frequently touched surfaces in CF clinics using an ATP bioluminescence assay to assess the effectiveness of cleaning/disinfection and the impact of feedback. Eight surfaces were tested across 19 clinics (10 pediatric, 9 adult) over 5 rounds of testing. Rounds 1 and 2 served as uncleaned baseline, and Round 3 occurring after routine cleaning. Rounds 4 and 5 were performed after feedback provided to staff and measured after cleaning. Pass rates defined as <250 relative light units were the primary outcome. Of the 750 tests performed, 72% of surfaces passed at baseline, and 79%, 83%, and 85% of surfaces passed in Rounds 3, 4, and 5, respectively. The overall pass-rate was significantly higher in adult compared to pediatric clinics (86% vs 71%; < 0.001). In pediatric clinics, blood pressure equipment and computer keyboards in the pulmonary function lab consistently passed, but the exam room patient/visitor chairs consistently failed in all rounds. In adult clinics blood pressure equipment, keyboards in exam rooms and exam tables passed in all rounds and no surface consistently failed. We demonstrate the feasibility of an ATP bioluminescence assay to measure cleanliness of patient care equipment and surfaces in CF clinics. Pass rates improved after cleaning and feedback for certain surfaces. We found that surfaces are more challenging to keep clean in clinics taking care of younger patients.

ObjectivesDevelop an individualised prognostic risk prediction tool for predicting the probability of adverse COVID-19 outcomes in patients with inflammatory bowel disease (IBD).Design and settingThis study developed and validated prognostic penalised logistic regression models using reports to the international Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease voluntary registry from March to October 2020. Model development was done using a training data set (85% of cases reported 13 March–15 September 2020), and model validation was conducted using a test data set (the remaining 15% of cases plus all cases reported 16 September–20 October 2020).ParticipantsWe included 2709 cases from 59 countries (mean age 41.2 years (SD 18), 50.2% male). All submitted cases after removing duplicates were included.Primary and secondary outcome measuresCOVID-19 related: (1) Hospitalisation+: composite outcome of hospitalisation, ICU admission, mechanical ventilation or death; (2) Intensive Care Unit+ (ICU+): composite outcome of ICU admission, mechanical ventilation or death; (3) Death. We assessed the resulting models’ discrimination using the area under the curve of the receiver operator characteristic curves and reported the corresponding 95% CIs.ResultsOf the submitted cases, a total of 633 (24%) were hospitalised, 137 (5%) were admitted to the ICU or intubated and 69 (3%) died. 2009 patients comprised the training set and 700 the test set. The models demonstrated excellent discrimination, with a test set area under the curve (95% CI) of 0.79 (0.75 to 0.83) for Hospitalisation+, 0.88 (0.82 to 0.95) for ICU+ and 0.94 (0.89 to 0.99) for Death. Age, comorbidities, corticosteroid use and male gender were associated with a higher risk of death, while the use of biological therapies was associated with a lower risk.ConclusionsPrognostic models can effectively predict who is at higher risk for COVID-19-related adverse outcomes in a population of patients with IBD. A free online risk calculator (https://covidibd.org/covid-19-risk-calculator/) is available for healthcare providers to facilitate discussion of risks due to COVID-19 with patients with IBD.

Abstract Deep learning has shown significant promise in surrogate modeling for engineering simulations. However, when applied to structural and thermal response prediction, deep neural networks often suffer from performance degradation due to data imbalance—where low-magnitude responses dominate, and critical high-response regions are underrepresented. To address this challenge, we propose an imbalance-aware deep surrogate modeling framework that integrates convolutional neural networks (CNNs) with two imbalance mitigation strategies: stratified sampling and label transformation. The framework is applied across three representative case studies: (1) stress prediction in 2D cantilever beams, (2) transient thermal and thermal stress responses in heat-transfer fins, and (3) 3D stress prediction in cantilever beams under variable loading. We demonstrate that stratified sampling improves performance on small datasets by balancing rare and frequent response values, while label transformations reshape skewed label distributions to reduce model bias. Our results show consistent improvements in accuracy, particularly in predicting maximum response values, which are critical for design and safety applications. The proposed framework offers a scalable and adaptable approach for improving surrogate modeling in structural and thermal analysis and can be extended to more advanced architecture and complex simulations. Graphical Abstract Graphical Abstract

Albendazole (ABZ) is a weakly basic drug that undergoes extensive presystemic metabolism after oral administration and converts to its active form albendazole sulfoxide (ABZ_SO). The absorption of albendazole is limited by poor aqueous solubility, and dissolution is the rate-limiting step in the overall exposure of ABZ_SO. In this study, PBPK modeling was used to identify formulation-specific parameters that impact the oral bioavailability of ABZ_SO. In vitro experiments were carried out to determine pH solubility, precipitation kinetics, particle size distribution, and biorelevant solubility. A transfer experiment was conducted to determine the precipitation kinetics. A PBPK model for ABZ and ABZ_SO was developed using the Simcyp™ Simulator based on parameter estimates from in vitro experiments. Sensitivity analyses were performed to assess the impact of physiological parameters and formulation-related parameters on the systemic exposure of ABZ_SO. Model simulations predicted that increased gastric pH significantly reduced ABZ absorption and, subsequently, ABZ_SO systemic exposure. Reducing the particle size below 50 µm did not improve the bioavailability of ABZ. Modeling results illustrated that systemic exposure of ABZ_SO was enhanced by increasing solubility or supersaturation and decreasing the drug precipitation of ABZ at the intestinal pH level. These results were used to identify potential formulation strategies to enhance the oral bioavailability of ABZ_SO.

Background: Treatment of multidrug-resistant tuberculosis (MDR-TB) in the Programmatic Management of Drug-resistant TB program involves a standard regimen with a 6-month intensive phase and an 18-month continuation phase. However, the local drug resistance patterns in high MDR regions such as Mumbai may not be adequately reflected in the design of the regimen for that particular area. Setting: The study was carried out at a private Tertiary Level Hospital in Mumbai in a mycobacteriology laboratory equipped to perform the second-line drug susceptibility testing (DST). Objective: We attempted to analyze the impact of prescribing the standardized Category IV regimen to all patients receiving a DST at our mycobacteriology laboratory. Materials and Methods: All samples confirmed to be MDR-TB and tested for the second-line drugs at Hinduja Hospital′s Mycobacteriology Laboratory in the year 2012 were analyzed. Results: A total of 1539 samples were analyzed. Of these, 464 (30.14%) were MDR-TB, 867 (56.33%) were MDR with fluoroquinolone resistance, and 198 (12.8%) were extensively drug-resistant TB. The average number of susceptible drugs per sample was 3.07 ± 1.29 (assuming 100% cycloserine susceptibility). Taking 4 effective drugs to be the cut or an effective regimen, the number of patients receiving 4 or more effective drugs from the standardized directly observed treatment, short-course plus regimen would be 516 (33.5%) while 66.5% of cases would receive 3 or less effective drugs. Conclusion: Our study shows that a high proportion of patients will have resistance to a number of the first- and second-line drugs. Local epidemiology must be factored in to avoid amplification of resistance.

Formal lectures have been a traditional part of medical and dental education, but there is debate as to their compulsory status. This study was designed to explore dental and medical students’ views on compulsory lectures and the use of Video-Recorded Lectures (VRL). A cross-sectional study of University of Bristol students in Years 2 to 4 was conducted using an online questionnaire. The majority of both dental (76%) and medical (66%) students felt lectures should be non-compulsory. The most common learning resources used by both dental and medical students were live lectures, lecture handouts and VRL. The majority of both dental (84%) and medical (88%) students used VRL. Most students attended lectures all of the time both before and after the introduction of VRL, even though most dental and medical students believe lectures should be non-compulsory. VRL is a popular learning resource. These findings tie-in with General Dental Council and General Medical Council recommendations that encourage self-directed learning. Dental and Medical schools should offer a range of learning resources and make use of current technology, including the use of VRL.

Abstract BACKGROUND Due to the critical neurovascular structures that surround the pulvinar, deciding the best surgical approach can be challenging, with multiple options available. OBJECTIVE To analyze and compare the ipsilateral vs the contralateral version of the 2 main approaches to the cisternal pulvinar surface: paramedian supracerebellar infratentorial (PSCI) and interhemispheric occipital transtentorial (IOT). METHODS The PSCI and IOT approaches were performed on 7 formalin-fixed adult cadaveric heads to evaluate qualitatively and quantitatively the microsurgical exposure of relevant anatomic structures. We quantitatively measured the corridor distance to our target with each approach. RESULTS The ipsilateral PSCI approach provided an easier access and a better exposure of the anteromedial portion of the cisternal pulvinar surface. The contralateral approach provided a wider and more accessible exposure of the posterolateral portion of the cisternal pulvinar surface. When protrusion of the posterior parahippocampal gyrus above the free edge of the tentorium was present, the contralateral PSCI approach provided an unobstructed view to both areas. The IOT approach provided a better view of the anteromedial portion of the cisternal pulvinar surface, especially with a contralateral approach. CONCLUSION Multiple approaches to the pulvinar have been described, modified, and improved. Based on this anatomic study we believe that although the corridor distance with a contralateral approach is longer, the surgical view and access can be better. We recommend the use of a PSCI contralateral approach especially when a significant protrusion of the posterior parahippocampal gyrus is present.

Background: Accessing the hippocampus for amygdalohippocampectomy and minimally invasive procedures, such as depth electrode placement, require an accurate knowledge regarding the location of the hippocampus. Methods: The authors removed 10 human cadaveric brains from the cranium and observed the relationships between the lateral temporal neocortex and the underlying hippocampus. They then measured the distance between the hippocampus and superficial landmarks. The authors also validated their study using magnetic resonance imaging (MRI) scans of 10 patients suffering from medial temporal lobe sclerosis where the distance from the hippocampal head to the anterior temporal tip was measured. Results: In general, the length of the hippocampus was along the inferior temporal sulcus and inferior aspect of the middle temporal gyrus. Although the hippocampus tended to be more superiorly located in female specimens and on the left side, this did not reach statistical significance. The length of the hippocampus tended to be shorter in females, but this too failed to reach statistical significance. The mean distance from the anterior temporal tip to the hippocampal head was identical in the cadavers and MRIs of patients with medial temporal lobe sclerosis. Conclusions: Additional landmarks for localizing the underlying hippocampus may be helpful in temporal lobe surgery. Based on this study, there are relatively constant anatomical landmarks between the hippocampus and overlying temporal cortex. Such landmarks may be used in localizing the hippocampus during amygdalohippocampectomy and depth electrode implantation in verifying the accuracy of image-guided methods and as adjuvant methodologies when these latter technologies are not used or are unavailable.