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Department of Pharmacology

 

Managing panic buying-related instabilities in supply chains: A COVID-19 pandemic perspective

Mon, 15/04/2024 - 11:00

IFAC Pap OnLine. 2022;55(10):305-310. doi: 10.1016/j.ifacol.2022.09.405. Epub 2022 Oct 26.

ABSTRACT

Global supply chains (SCs) have been severely impacted by the COVID-19 pandemic on several levels. For example, SCs suffered from panic buying-related instabilities and multiple disruptions of supply, demand, and capacity during the pandemic. This study developed an agent-based model (ABM) to predict the effects of panic buying-related instabilities in SCs and offered strategies to improve them. The ABM model includes a simulation and optimization model of a typical SC of an essential product manufacturer (i.e., toilet paper SC) for the analysis of scenarios and strategies to observe improvements in SCs. Among the four strategies identified, the findings suggest boosting production capacity to the maximum and ensuring optimal reorder points, order sizes, and trucks helped the essential product manufacturers reduce panic buying-related instabilities in their SCs.

PMID:38620991 | PMC:PMC9605711 | DOI:10.1016/j.ifacol.2022.09.405

Sustainability in endoscopy: online endoscopy education platform significantly reduces carbon footprint of patient travel

Sat, 13/04/2024 - 11:00

Clin Med (Lond). 2023 Nov;23 Suppl 6:125-126. doi: 10.7861/clinmed.23-6-s125.

NO ABSTRACT

PMID:38614702 | DOI:10.7861/clinmed.23-6-s125

Reliability of a New Digital Tool for Photographic Analysis in Quantifying Body Asymmetry in Scoliosis

Sat, 13/04/2024 - 11:00

J Clin Med. 2024 Apr 5;13(7):2114. doi: 10.3390/jcm13072114.

ABSTRACT

Background: Advancements in non-ionizing methods for quantifying spinal deformities are crucial for assessing and monitoring scoliosis. In this study, we analyzed the observer variability of a newly developed digital tool for quantifying body asymmetry from clinical photographs. Methods: Prospective observational multicenter study. Initially, a digital tool was developed using image analysis software, calculating quantitative measures of body asymmetry. This tool was integrated into an online platform that exports data to a database. The tool calculated 10 parameters, including angles (shoulder height, axilla height, waist height, right and left waistline angles, and their difference) and surfaces of the left and right hemitrunks (shoulders, waists, pelvises, and total). Subsequently, an online training course on the tool was conducted for twelve observers not involved in its development (six research coordinators and six spine surgeons). Finally, 15 standardized back photographs of adolescent idiopathic scoliosis patients were selected from a multicenter image bank, representing various clinical scenarios (different age, gender, curve type, BMI, and pre- and postoperative images). The 12 observers measured the photographs at two different times with a three-week interval. For the second round, the images were randomly mixed. Inter- and intra-observer variabilities of the measurements were analyzed using intraclass correlation coefficients (ICCs), and reliability was measured by the standard error of measurement (SEM). Group comparisons were made using Student's t-test. Results: The mean inter-observer ICC for the ten measurements was 0.981, the mean intra-observer ICC was 0.937, and SEM was 0.3-1.3°. The parameter with the strongest inter- and intra-observer validity was the difference in waistline angles 0.994 and 0.974, respectively, while the highest variability was found with the waist height angle 0.963 and 0.845, respectively. No test-retest differences (p > 0.05) were observed between researchers (0.948 ± 0.04) and surgeons (0.925 ± 0.05). Conclusion: We developed a new digital tool integrated into an online platform demonstrating excellent reliability and inter- and intra-observer variabilities for quantifying body asymmetry in scoliosis patients from a simple clinical photograph. The method could be used for assessing and monitoring scoliosis and body asymmetry without radiation.

PMID:38610880 | DOI:10.3390/jcm13072114

Syndromic surveillance of population-level COVID-19 burden with cough monitoring in a hospital emergency waiting room

Fri, 12/04/2024 - 11:00

Front Public Health. 2024 Mar 28;12:1279392. doi: 10.3389/fpubh.2024.1279392. eCollection 2024.

ABSTRACT

Syndromic surveillance is an effective tool for enabling the timely detection of infectious disease outbreaks and facilitating the implementation of effective mitigation strategies by public health authorities. While various information sources are currently utilized to collect syndromic signal data for analysis, the aggregated measurement of cough, an important symptom for many illnesses, is not widely employed as a syndromic signal. With recent advancements in ubiquitous sensing technologies, it becomes feasible to continuously measure population-level cough incidence in a contactless, unobtrusive, and automated manner. In this work, we demonstrate the utility of monitoring aggregated cough count as a syndromic indicator to estimate COVID-19 cases. In our study, we deployed a sensor-based platform (Syndromic Logger) in the emergency room of a large hospital. The platform captured syndromic signals from audio, thermal imaging, and radar, while the ground truth data were collected from the hospital's electronic health record. Our analysis revealed a significant correlation between the aggregated cough count and positive COVID-19 cases in the hospital (Pearson correlation of 0.40, p-value < 0.001). Notably, this correlation was higher than that observed with the number of individuals presenting with fever (ρ = 0.22, p = 0.04), a widely used syndromic signal and screening tool for such diseases. Furthermore, we demonstrate how the data obtained from our Syndromic Logger platform could be leveraged to estimate various COVID-19-related statistics using multiple modeling approaches. Aggregated cough counts and other data, such as people density collected from our platform, can be utilized to predict COVID-19 patient visits related metrics in a hospital waiting room, and SHAP and Gini feature importance-based metrics showed cough count as the important feature for these prediction models. Furthermore, we have shown that predictions based on cough counting outperform models based on fever detection (e.g., temperatures over 39°C), which require more intrusive engagement with the population. Our findings highlight that incorporating cough-counting based signals into syndromic surveillance systems can significantly enhance overall resilience against future public health challenges, such as emerging disease outbreaks or pandemics.

PMID:38605877 | PMC:PMC11007176 | DOI:10.3389/fpubh.2024.1279392

Coordinating activation of endo-lysosomal two-pore channels and TRP mucolipins

Wed, 10/04/2024 - 11:00

J Physiol. 2024 Apr 10. doi: 10.1113/JP283829. Online ahead of print.

ABSTRACT

Two-pore channels and TRP mucolipins are ubiquitous endo-lysosomal cation channels of pathophysiological relevance. Both are Ca2+-permeable and regulated by phosphoinositides, principally PI(3,5)P2. Accumulating evidence has uncovered synergistic channel activation by PI(3,5)P2 and endogenous metabolites such as the Ca2+ mobilizing messenger NAADP, synthetic agonists including approved drugs and physical cues such as voltage and osmotic pressure. Here, we provide an overview of this coordination.

PMID:38598430 | DOI:10.1113/JP283829

Intracellular pathways of calcitonin gene-related peptide-induced relaxation of human coronary arteries: A key role for Gβγ subunit instead of cAMP

Sun, 07/04/2024 - 11:00

Br J Pharmacol. 2024 Apr 7. doi: 10.1111/bph.16372. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Calcitonin gene-related peptide (CGRP) is a potent vasodilator. While its signalling is assumed to be mediated via increases in cAMP, this study focused on elucidating the actual intracellular signalling pathways involved in CGRP-induced relaxation of human isolated coronary arteries (HCA).

EXPERIMENTAL APPROACH: HCA were obtained from heart valve donors (27 M, 25 F, age 54 ± 2 years). Concentration-response curves to human α-CGRP or forskolin were constructed in HCA segments, incubated with different inhibitors of intracellular signalling pathways, and intracellular cAMP levels were measured with and without stimulation.

RESULTS: Adenylyl cyclase (AC) inhibitors SQ22536 + DDA and MDL-12330A, and PKA inhibitors Rp-8-Br-cAMPs and H89, did not inhibit CGRP-induced relaxation of HCA, nor did the guanylyl cyclase inhibitor ODQ, PKG inhibitor KT5823, EPAC1/2 inhibitor ESI09, potassium channel blockers TRAM-34 + apamin, iberiotoxin or glibenclamide, or the Gαq inhibitor YM-254890. Phosphodiesterase inhibitors induced a concentration-dependent decrease in the response to KCl but did not potentiate relaxation to CGRP. Relaxation to forskolin was not blocked by PKA or AC inhibitors, although AC inhibitors significantly inhibited the increase in cAMP. Inhibition of Gβγ subunits using gallein significantly inhibited the relaxation to CGRP in human coronary arteries.

CONCLUSION: While CGRP signalling is generally assumed to act via cAMP, the CGRP-induced vasodilation in HCA was not inhibited by targeting this intracellular signalling pathway at different levels. Instead, inhibition of Gβγ subunits did inhibit the relaxation to CGRP, suggesting a different mechanism of CGRP-induced relaxation than generally believed.

PMID:38583945 | DOI:10.1111/bph.16372

Comprehensive machine learning boosts structure-based virtual screening for PARP1 inhibitors

Sat, 06/04/2024 - 11:00

J Cheminform. 2024 Apr 7;16(1):40. doi: 10.1186/s13321-024-00832-1.

ABSTRACT

Poly ADP-ribose polymerase 1 (PARP1) is an attractive therapeutic target for cancer treatment. Machine-learning scoring functions constitute a promising approach to discovering novel PARP1 inhibitors. Cutting-edge PARP1-specific machine-learning scoring functions were investigated using semi-synthetic training data from docking activity-labelled molecules: known PARP1 inhibitors, hard-to-discriminate decoys property-matched to them with generative graph neural networks and confirmed inactives. We further made test sets harder by including only molecules dissimilar to those in the training set. Comprehensive analysis of these datasets using five supervised learning algorithms, and protein-ligand fingerprints extracted from docking poses and ligand only features revealed one highly predictive scoring function. This is the PARP1-specific support vector machine-based regressor, when employing PLEC fingerprints, which achieved a high Normalized Enrichment Factor at the top 1% on the hardest test set (NEF1% = 0.588, median of 10 repetitions), and was more predictive than any other investigated scoring function, especially the classical scoring function employed as baseline.

PMID:38582911 | DOI:10.1186/s13321-024-00832-1

Patterns of failure in patients with nasopharyngeal cancer of Northeastern region of India: a retrospective observational study

Fri, 05/04/2024 - 11:00

Eur Arch Otorhinolaryngol. 2024 Apr 5. doi: 10.1007/s00405-024-08624-x. Online ahead of print.

ABSTRACT

PURPOSE: We aimed to analyze patterns of failure and disease volume-treatment outcomes in patients with Nasopharyngeal carcinoma (NPC) treated with definitive radiation with or without concurrent chemotherapy at a tertiary cancer centre in northeast India.

METHODS: From February 2018 to February 2022, 99 histopathologically proved non-metastatic NPC patients treated with curative-intent RT with or without chemotherapy were retrospectively analyzed. Locally advanced patients received neoadjuvant or adjuvant chemotherapy. The Cox proportional hazards model was used to investigate the impact of various prognostic factors on locoregional free survival (LRFS), distant metastasis free survival (DMFS), progression free survival (PFS) and overall survival (OS). The log-rank test and Kaplan-Meir curves compared outcome variables based on ROC analysis-classified tumor volume.

RESULTS: During a median follow up of 25.4 months (17.3-39.2), 35(35.4%) patients developed recurrence. Twenty-three patients developed locoregional failures, of which 11 were in-field; 12 patient showed an out-field failure. The 3-year LRFS, DMFS, PFS and OS was 71.10%, 70.90%, 64.10% and 74.10% respectively. There was statistically significant difference in LRFS according to T staging (p < 0.0001). Gross tumor volume (GTVp) and gross nodal volume (GTVn) were an independent prognostic factor for OS, PFS, LRFS and DMFS. The cut-off volumes for GTVp and GTVn for distant metastases and locoregional failure, respectively, were found to be 13 and 22.7 mL and 3.7 and 39.2 mL, respectively, by ROC curve analysis. Based on this, 99 patients were divided into three subgroups. OS demonstrated significant differences among patients in different volume subgroups for GTVp (p = 0.03) and GTVn (p = 0.00024).

CONCLUSIONS: For NPC patients who undergo curative IMRT, primary tumour and nodal volumes are independent prognostic indicators. GTVp and GTVn are highly predictive of local control, distant metastases, disease-free survival, and overall survival. This justifies their use as quantitative prognostic indicator for NPC.

PMID:38578506 | DOI:10.1007/s00405-024-08624-x

Manipulating Myc for reparative regeneration

Fri, 05/04/2024 - 11:00

Front Cell Dev Biol. 2024 Mar 21;12:1357589. doi: 10.3389/fcell.2024.1357589. eCollection 2024.

ABSTRACT

The Myc family of proto-oncogenes is a key node for the signal transduction of external pro-proliferative signals to the cellular processes required for development, tissue homoeostasis maintenance, and regeneration across evolution. The tight regulation of Myc synthesis and activity is essential for restricting its oncogenic potential. In this review, we highlight the central role that Myc plays in regeneration across the animal kingdom (from Cnidaria to echinoderms to Chordata) and how Myc could be employed to unlock the regenerative potential of non-regenerative tissues in humans for therapeutic purposes. Mastering the fine balance of harnessing the ability of Myc to promote transcription without triggering oncogenesis may open the door to many exciting opportunities for therapeutic development across a wide array of diseases.

PMID:38577503 | PMC:PMC10991803 | DOI:10.3389/fcell.2024.1357589

Recent Outcomes and Challenges of Artificial Intelligence, Machine Learning, and Deep Learning in Neurosurgery

Fri, 05/04/2024 - 11:00

World Neurosurg X. 2024 Mar 8;23:100301. doi: 10.1016/j.wnsx.2024.100301. eCollection 2024 Jul.

ABSTRACT

Neurosurgeons receive extensive technical training, which equips them with the knowledge and skills to specialise in various fields and manage the massive amounts of information and decision-making required throughout the various stages of neurosurgery, including preoperative, intraoperative, and postoperative care and recovery. Over the past few years, artificial intelligence (AI) has become more useful in neurosurgery. AI has the potential to improve patient outcomes by augmenting the capabilities of neurosurgeons and ultimately improving diagnostic and prognostic outcomes as well as decision-making during surgical procedures. By incorporating AI into both interventional and non-interventional therapies, neurosurgeons may provide the best care for their patients. AI, machine learning (ML), and deep learning (DL) have made significant progress in the field of neurosurgery. These cutting-edge methods have enhanced patient outcomes, reduced complications, and improved surgical planning.

PMID:38577317 | PMC:PMC10992893 | DOI:10.1016/j.wnsx.2024.100301

Handloomed fabrics recognition with deep learning

Thu, 04/04/2024 - 11:00

Sci Rep. 2024 Apr 4;14(1):7974. doi: 10.1038/s41598-024-58750-z.

ABSTRACT

Every nation treasures its handloom heritage, and in India, the handloom industry safeguards cultural traditions, sustains millions of artisans, and preserves ancient weaving techniques. To protect this legacy, a critical need arises to distinguish genuine handloom products, exemplified by the renowned "gamucha" from India's northeast, from counterfeit powerloom imitations. Our study's objective is to create an AI tool for effortless detection of authentic handloom items amidst a sea of fakes. Six deep learning architectures-VGG16, VGG19, ResNet50, InceptionV3, InceptionResNetV2, and DenseNet201-were trained on annotated image repositories of handloom and powerloom towels (17,484 images in total, with 14,020 for training and 3464 for validation). A novel deep learning model was also proposed. Despite respectable training accuracies, the pre-trained models exhibited lower performance on the validation dataset compared to our novel model. The proposed model outperformed pre-trained models, demonstrating superior validation accuracy, lower validation loss, computational efficiency, and adaptability to the specific classification problem. Notably, the existing models showed challenges in generalizing to unseen data and raised concerns about practical deployment due to computational expenses. This study pioneers a computer-assisted approach for automated differentiation between authentic handwoven "gamucha"s and counterfeit powerloom imitations-a groundbreaking recognition method. The methodology presented not only holds scalability potential and opportunities for accuracy improvement but also suggests broader applications across diverse fabric products.

PMID:38575749 | DOI:10.1038/s41598-024-58750-z

The potential of phosphorylated α-synuclein as a biomarker for the diagnosis and monitoring of multiple system atrophy

Thu, 04/04/2024 - 11:00

CNS Neurosci Ther. 2024 Apr;30(4):e14678. doi: 10.1111/cns.14678.

ABSTRACT

INTRODUCTION: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by the presence of glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-Syn). Accurate diagnosis and monitoring of MSA present significant challenges, which can lead to potential misdiagnosis and inappropriate treatment. Biomarkers play a crucial role in improving the accuracy of MSA diagnosis, and phosphorylated α-synuclein (p-syn) has emerged as a promising biomarker for aiding in diagnosis and disease monitoring.

METHODS: A literature search was conducted on PubMed, Scopus, and Google Scholar using specific keywords and MeSH terms without imposing a time limit. Inclusion criteria comprised various study designs including experimental studies, case-control studies, and cohort studies published only in English, while conference abstracts and unpublished sources were excluded.

RESULTS: Increased levels of p-syn have been observed in various samples from MSA patients, such as red blood cells, cerebrospinal fluid, oral mucosal cells, skin, and colon biopsies, highlighting their diagnostic potential. The α-Syn RT-QuIC assay has shown sensitivity in diagnosing MSA and tracking its progression. Meta-analyses and multicenter investigations have confirmed the diagnostic value of p-syn in cerebrospinal fluid, demonstrating high specificity and sensitivity in distinguishing MSA from other neurodegenerative diseases. Moreover, combining p-syn with other biomarkers has further improved the diagnostic accuracy of MSA.

CONCLUSION: The p-syn stands out as a promising biomarker for MSA. It is found in oligodendrocytes and shows a correlation with disease severity and progression. However, further research and validation studies are necessary to establish p-syn as a reliable biomarker for MSA. If proven, p-syn could significantly contribute to early diagnosis, disease monitoring, and assessing treatment response.

PMID:38572788 | DOI:10.1111/cns.14678

Microbiological Analysis and Content of Heavy Metals in Different Candies, Chocolates, and Their Wrappers in Bangladesh

Wed, 03/04/2024 - 11:00

Int J Food Sci. 2024 Mar 26;2024:4536475. doi: 10.1155/2024/4536475. eCollection 2024.

ABSTRACT

Present study investigates 39 brands of candies, chocolate, and litchis, purchased from Dhaka City, Bangladesh, for their moisture content, sulphated ash value, heavy metal, and bacterial contamination. All the brands showed moisture content (0.64%-4.775%) within the BSTI range, but sulphated ash values (18.80%-25.72%) were beyond the accepted value. Pb, Cd, Ni, and Cr ranged from 0.24-2.40 μg/g, 0.071-0.44 μg/g, 0.38-48.10 μg/g, and 0.50-12.79 μg/g, respectively, in the tested brands. Most of the brands contained Pb and Cd beyond the acceptable limits of WHO/FDA. Pb (2.24-2586.75 μg/g) was found in high concentration in the packaging of most brands, and Ni and Cd ranged from 2.10-108.05 μg/g and 1.68-45 μg/g, respectively. Bacterial presence was found in 15 brands, and 4 of them had a total aerobic bacterial count of >1 log CFU/g. Consumption of such contaminated confectionaries holds significant public health risks, specially in children, and demands necessary precautionary steps.

PMID:38566755 | PMC:PMC10987241 | DOI:10.1155/2024/4536475

Efficacy of vestibular rehabilitation program in children with balance disorders and sensorineural hearing loss

Sun, 31/03/2024 - 11:00

Int J Pediatr Otorhinolaryngol. 2024 Mar 28;179:111931. doi: 10.1016/j.ijporl.2024.111931. Online ahead of print.

ABSTRACT

OBJECTIVE: Asses the efficacy of a Vestibular-balance rehabilitation program to minimize or reverse balance disability in children with sensorineural hearing loss.

METHOD: Forty-five hearing-impaired children with balance deficits (i.e., variable degrees of sensorineural hearing loss or auditory neuropathy). Thirty-five were rehabilitated with cochlear implants, and ten with hearing aids. Their age ranged from 4 to 10 years old. A Pre-rehab evaluation was done using questionnaires, neuromuscular evaluation, vestibular and balance office testing, and vestibular lab testing (using cVEMP and caloric test). Customized balances, as well as vestibular rehabilitation exercises, have been applied for three months. That was followed by post-rehab assessment, including the Arabic DHI questionnaire, PBS, BESS, HTT, and DVA test.

RESULTS: There was a statistically significant difference in all measured parameters (including the Arabic DHI questionnaire, PBS, BESS, HTT, and DVA test) after rehabilitation.

CONCLUSIONS: Vestibular-balance rehabilitation intervention positively impacts vestibular and balance functions in hearing-impaired children.

PMID:38555811 | DOI:10.1016/j.ijporl.2024.111931

Brexanolone Treatment in a Real-World Patient Population: A Case Series and Pilot Feasibility Study of Precision Neuroimaging

Fri, 29/03/2024 - 10:00

J Clin Psychopharmacol. 2024 Mar 29. doi: 10.1097/JCP.0000000000001859. Online ahead of print.

ABSTRACT

PURPOSE/BACKGROUND: Brexanolone is approved for postpartum depression (PPD) by the United States Food and Drug Administration. Brexanolone has outperformed placebo in clinical trials, but less is known about the efficacy in real-world patients with complex social and medical histories. Furthermore, the impact of brexanolone on large-scale brain systems such as changes in functional connectivity (FC) is unknown.

METHODS/PROCEDURES: We tracked changes in depressive symptoms across a diverse group of patients who received brexanolone at a large medical center. Edinburgh Postnatal Depression Scale (EPDS) scores were collected through chart review for 17 patients immediately prior to infusion through approximately 1 year postinfusion. In 2 participants, we performed precision functional neuroimaging (pfMRI), including before and after treatment in 1 patient. pfMRI collects many hours of data in individuals for precision medicine applications and was performed to assess the feasibility of investigating changes in FC with brexanolone.

FINDINGS/RESULTS: The mean EPDS score immediately postinfusion was significantly lower than the mean preinfusion score (mean change [95% CI]: 10.76 [7.11-14.40], t(15) = 6.29, P < 0.0001). The mean EPDS score stayed significantly lower at 1 week (mean difference [95% CI]: 9.50 [5.23-13.76], t(11) = 4.90, P = 0.0005) and 3 months (mean difference [95% CI]: 9.99 [4.71-15.27], t(6) = 4.63, P = 0.0036) postinfusion. Widespread changes in FC followed infusion, which correlated with EPDS scores.

IMPLICATIONS/CONCLUSIONS: Brexanolone is a successful treatment for PPD in the clinical setting. In conjunction with routine clinical care, brexanolone was linked to a reduction in symptoms lasting at least 3 months. pfMRI is feasible in postpartum patients receiving brexanolone and has the potential to elucidate individual-specific mechanisms of action.

PMID:38551454 | DOI:10.1097/JCP.0000000000001859

Scalable Large-Area 2D-MoS<sub>2</sub>/Silicon-Nanowire Heterostructures for Enhancing Energy Storage Applications

Fri, 29/03/2024 - 10:00

ACS Appl Energy Mater. 2024 Mar 7;7(6):2299-2308. doi: 10.1021/acsaem.3c03055. eCollection 2024 Mar 25.

ABSTRACT

Two-dimensional (2D) transition-metal dichalcogenides have shown great potential for energy storage applications owing to their interlayer spacing, large surface area-to-volume ratio, superior electrical properties, and chemical compatibility. Further, increasing the surface area of such materials can lead to enhanced electrical, chemical, and optical response for energy storage and generation applications. Vertical silicon nanowires (SiNWs), also known as black-Si, are an ideal substrate for 2D material growth to produce high surface-area heterostructures, owing to their ultrahigh aspect ratio. Achieving this using an industrially scalable method paves the way for next-generation energy storage devices, enabling them to enter commercialization. This work demonstrates large surface area, commercially scalable, hybrid MoS2/SiNW heterostructures, as confirmed by Raman spectroscopy, with high tunability of the MoS2 layers down to the monolayer scale and conformal MoS2 growth, parallel to the silicon nanowires, as verified by transmission electron microscopy (TEM). This has been achieved using a two-step atomic layer deposition (ALD) process, allowing MoS2 to be grown directly onto the silicon nanowires without any damage to the substrate. The ALD cycle number accurately defines the layer number from monolayer to bulk. Introducing an ALD alumina (Al2O3) interface at the MoS2/SiNW boundary results in enhanced MoS2 quality and uniformity, demonstrated by an order of magnitude reduction in the B/A exciton photoluminescence (PL) intensity ratio to 0.3 and a reduction of the corresponding layer number. This high-quality layered growth on alumina can be utilized in applications such as for interfacial layers in high-capacity batteries or for photocathodes for water splitting. The alumina-free 100 ALD cycle heterostructures demonstrated no diminishing quality effects, lending themselves well to applications that require direct electrical contact with silicon and benefit from more layers, such as electrodes for high-capacity ion batteries.

PMID:38550300 | PMC:PMC10966641 | DOI:10.1021/acsaem.3c03055

A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast

Fri, 29/03/2024 - 10:00

Nat Genet. 2024 Mar 28. doi: 10.1038/s41588-024-01688-9. Online ahead of print.

ABSTRACT

Here we use single-cell RNA sequencing to compile a human breast cell atlas assembled from 55 donors that had undergone reduction mammoplasties or risk reduction mastectomies. From more than 800,000 cells we identified 41 cell subclusters across the epithelial, immune and stromal compartments. The contribution of these different clusters varied according to the natural history of the tissue. Age, parity and germline mutations, known to modulate the risk of developing breast cancer, affected the homeostatic cellular state of the breast in different ways. We found that immune cells from BRCA1 or BRCA2 carriers had a distinct gene expression signature indicative of potential immune exhaustion, which was validated by immunohistochemistry. This suggests that immune-escape mechanisms could manifest in non-cancerous tissues very early during tumor initiation. This atlas is a rich resource that can be used to inform novel approaches for early detection and prevention of breast cancer.

PMID:38548988 | DOI:10.1038/s41588-024-01688-9

Exoscope-assisted spine surgery: Current applications and future directions

Thu, 28/03/2024 - 10:00

World Neurosurg X. 2024 Mar 8;23:100335. doi: 10.1016/j.wnsx.2024.100335. eCollection 2024 Jul.

ABSTRACT

Spine surgery is continually evolving, with the application of new technologies often serving as a catalyst for improved clinical outcomes. Exoscope-assisted spinal surgery has recently emerged as a notable technological advancement offering a refined approach to visualisation, thereby potentially contributing to improved surgical precision, reduced complication rates, and optimised patient outcomes. The application of exoscopes have improved spine surgeries such as spinal fusion procedures, decompression surgeries, instrumentation surgeries, minimally invasive and complex surgeries. These improvements include enhanced visualisation, improved ergonomics, improved surgical precision, reduced operation times and postoperative infection rates. The integration of robotics in exoscope-assisted spine surgery enables autofocus function, ensuring the integrity of the sterile field, providing superior image quality, resolution, and three-dimensional perception. However, challenges such as decrease in depth perception and the lack of long-term follow-up data hinder its widespread adoption. Ethical considerations regarding patient safety, technology dependency, and health inequity add another dimension to these challenges. Despite these challenges, exoscope-assisted spine surgery holds significant potential for transforming clinical practice and improving patient outcomes. This review seeks to provide a concise overview of the benefits and limits of exoscope-assisted spine surgeries, while highlighting its challenges and ethical considerations. Addressing these limitations by conducting large-scale clinical trials and exploring the integration of artificial intelligence (AI) could assist in realising the potential of exoscopes in spine surgery."

PMID:38544786 | PMC:PMC10965456 | DOI:10.1016/j.wnsx.2024.100335

Development and validation of a practical clinical risk prediction model for post-endoscopic retrograde cholangiopancreatography pancreatitis

Tue, 26/03/2024 - 10:00

DEN open. 2024 Mar 25;4(1):e355. doi: 10.1002/deo2.355. eCollection 2024 Apr.

ABSTRACT

BACKGROUND: Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) can lead to significant morbidity and mortality. We aimed to develop an accurate post-ERCP pancreatitis risk prediction model using easily obtainable variables.

METHODS: Using prospective multi-center ERCP data, we performed logistic regression using stepwise selection on several patient-, procedure-, and endoscopist-related factors that were determined a priori. The final model was based on a combination of the Bayesian information criterion and Akaike's information criterion performance, balancing the inclusion of clinically relevant variables and model parsimony. All available data were used for model development, with subsequent internal validation performed on bootstrapped data using 10-fold cross-validation.

RESULTS: Data from 3021 ERCPs were used to inform models. There were 151 cases of post-ERCP pancreatitis (5.0% incidence). Variables included in the final model included female sex, pancreatic duct cannulation, native papilla status, pre-cut sphincterotomy, increasing cannulation time, presence of biliary stricture, patient age, and placement of a pancreatic duct stent. The final model was discriminating, with a receiver operating characteristic curve statistic of 0.79, and well-calibrated, with a predicted risk-to-observed risk ratio of 1.003.

CONCLUSIONS: We successfully developed and internally validated a promising post-ERCP pancreatitis clinical prediction model using easily obtainable variables that are known at baseline or observed during the ERCP procedure. The model achieved an area under the curve of 0.79. External validation is planned as additional data becomes available.

PMID:38529515 | PMC:PMC10962486 | DOI:10.1002/deo2.355