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Testing for DNA mismatch repair deficiency (MMRd) is recommended for all colorectal cancers (CRCs). Automating this would enable precision medicine, particularly if providing information on etiology not captured by deep learning (DL) methods. We present AIMMeR, an AI-based method for determination of mismatch repair (MMR) protein expression at a single-cell level in routine pathology samples. AIMMeR shows an area under the receiver-operator curve (AUROC) of 0.98, and specificity of ≥75% at 98% sensitivity against pathologist ground truth in stage II/III in two trial cohorts, with positive predictive value of ≥98% for the commonest pattern of somatic MMRd. Lower agreement with microsatellite instability (MSI) testing (AUROC 0.86) reflects discordance between MMR and MSI PCR rather than AIMMeR misclassification. Analysis of the SCOT trial confirms MMRd prognostic value in oxaliplatin-treated patients; while MMRd does not predict differential benefit of chemotherapy duration, it correlates with difference in relapse by regimen (P Interaction  = 0.04). AIMMeR may help reduce pathologist workload and streamline diagnostics in CRC., Competing Interests: Declaration of interests D.N.C. has participated in advisory boards for MSD and has received research funding on behalf of the TransSCOT consortium from HalioDx for analyses independent of this study. V.H.K. has served as an invited speaker on behalf of Indica Labs, SPCC, and Takeda and has received project-based research funding from The Image Analysis Group and Roche outside of the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Solitary fibrous tumors (SFTs) belonging to a distinct group of mesenchymal tumors, was originally described by Klemper and Rabin in the pleura in year 1931. However, it can also be extra-pleural in origin. With tongue being the most common site involved in this region, epiglottis, larynx, thyroid, external auditory canal, lacrimal sac, hypoglossal nerve, parotid gland, sublingual gland, Para pharyngeal space, nasopharynx, scalp, gingiva, orbit and infratemporal fossa as well as paranasal sinuses and nasal cavities can also get involved. But SFTs involving nasal cavities and nasopharynx are quite uncommon, accounting for < 0.1% of all Sino-nasal neoplasms. Until now there have only been 40 cases of nasal SFT reported in literature. We report the case of an extraserosa solitary fibrous tumor arising from the nasal cavity with extension to the sphenoid sinus, a much rarer presentation of its type. Our case report is one of its type, emphasizing the need conducting further studies on the nature and management of the disease., Competing Interests: Conflict of interestAll authors declare that there is no conflict of interest., (© Association of Otolaryngologists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

In the present study, the commercially available three different fabrics cotton, nylon and cotton/nylon were modified by chitosan and silver nanoparticles using a crosslinker triethyl orthoformate (TEOF). Resulted cotton‑silver (Ag-Cs-Cot), nylon‑silver (Ag-Cs-Nyl) and cotton-nylon silver (Ag-Cs-Cot-Nyl) fabrics showed significant anti-bacterial activity even after 50 washing cycles. Silver nanoparticles were prepared by reducing silver nitrate through sodium borohydride at 0 °C. In FTIR spectra the peak at near 1650 cm -1 confirmed that TEOF mediated attachment of chitosan with fabrics (due to C=N) and the stretching of secondary amine near the 3375 cm -1 indicated the silver attachment to the amine group of the chitosan. In Scanning Electron Microscope (SEM) images smooth surfaces of fabrics without any damage by modification process were observed. The antibacterial activity was Analyzed by agar diffusion and broth dilution assays against Escherichia coli and Staphylococcus aureus bacterial strains and results showed 90% bacterial inhibition against E. coli and 89% bacterial inhibition against S. aureus. For testing the antibacterial durability, the modified fabrics were washed with non-ionic detergent (10g/l) for 15 minutes under aggressive stirring (100 rpm) at room temperature. The modified fabrics retained antibacterial activity over the 50 washing cycles. Finally, the commercial potential of cotton-silver fabric was evaluated by stitching it with the socks of football players and interestingly results showed that the modified fabric on the socks showed more than 90% bacterial inhibition as compared to the plain fabric after 70 minutes of playing activity., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Osteoporosis is a common condition associated with an increased risk of bone fractures due to fragility. Bone mineral density (BMD) is lower in menopausal women due to estrogen deficiency, age-related decline in osteoblast function, decreased calcium absorption, and reduced synthesis of vitamin D, which lead to osteoporosis. The aim of this study was to determine the correlation between serum vitamin D levels and BMD assessed using radiofrequency echographic multi-spectrometry technology (REMS) in menopausal women. A cross-sectional study was conducted at Prof. Dr. Chairuddin P. Lubis Hospital of Universitas Sumatera Utara, Medan, Indonesia, from May 2023 to August 2023. Consecutive sampling method was employed to sample menopausal women with no history of hysterectomy or oophorectomy (unilateral or bilateral), and no history of hormone replacement therapy or vitamin D supplementation. Interviews and physical examinations were conducted to obtain the characteristics of the subjects (age, duration of menopause, and body mass index). The 25(OH)D level was measured using immunoassay and REMS examination was conducted to assess BMD. The Spearman correlation test was used to assess the correlation between serum vitamin D levels and BMD. A total of 32 menopausal women were included in this study with the average vitamin D level was 18.05±5.81 ng/mL, and the mean BMD level was -2.13±1.23. The data showed a significant positive correlation between serum vitamin D levels and BMD in menopausal women ( r =0.710; p =0.020). This study highlights that REMS could be useful as an alternative to dual-energy x-ray absorptiometry (DXA) to assess DMD in postmenopausal women., Competing Interests: The authors declare that there is no conflict of interest., (© 2024 by the authors.)

Introduction: COVID-19 seriously impacted routine immunization (RI) in Iraq. Coverage declined to a 6-year low in 2021, and COVID-19 vaccination uptake was slow. In response, government implemented intensification of integrated immunization services (3IS), a nationwide approach comprising regular outreach sessions of COVID-19 vaccination and RI for children who had either missed doses or never commenced scheduled vaccination (zero-dose children). We describe the 3IS and its impact on vaccination coverage in Iraq., Methods: 3IS comprised new outreach sessions for urban and rural communities where administrative data suggested there were gaps in coverage. Groups of six personnel from each of 1,321 primary healthcare centres implemented six outreach sessions per month during February-November 2022. Community engagement was an integral component. We compared RI administrative data (2019-2022) and data reported during 3IS activities to assess its impact., Results: In total 4,189,859 vaccine doses were administered during 72,495 3IS outreach sessions, over one-fifth of 19,106,849 vaccine doses administered in Iraq over these 10 months. Among them, 957,874 (22.9 %) were COVID-19 vaccines, adding slightly to national coverage, and 3,231,985 (77.1 %) were RI vaccines, dramatically reducing zero-dose children, adding 18 %, 25 %, 21 %, and 31 % to 2022 penta1, penta3, measles first-dose and MMR1 vaccine coverage, and contributing to national coverage of 102.2 %, 94.5 %, 91.8 % and 96.3 % for these vaccines during February-November, respectively. Moreover, 3IS sessions delivered 133,528 doses of tetanus toxoid, 16,353 doses of adult HepB vaccine, and 315,032 vitamin A doses to eligible individuals., Conclusion: In the context of global encouragement to integrate vaccination services, Iraq's 3IS approach enabled dramatic improvements in RI coverage, virtual elimination of zero-dose status among children born during the pandemic, and small improvements in COVID-19 and adult vaccination. Our findings provide lessons for future integrated primary care towards universal health coverage in Iraq, and for other countries yet to undertake integration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To compare the etiology, phenomenology and motor subtype of delirium in patients with and without an underlying dementia., Methods: A combined dataset (n = 992) was collated from two databases of older adults (>65 years) from liaison psychiatry and palliative care populations in Ireland and India. Phenomenology and severity of delirium were analysed using the Delirium Symptom Rating Scale Revised (DRS-R98) and contributory etiologies for the delirium groups were ascertained using the Delirium Etiology Checklist (DEC). Delirium motor subtype was documented using the abbreviated version of the Delirium Motor Subtype Scale (DMSS4)., Results: Delirium superimposed on dementia (DSD) showed greater impairment in short term memory, long term memory and visuospatial ability than the delirium group but showed significantly less perceptual disturbance, temporal onset and fluctuation. Systemic infection, cerebrovascular and other Central nervous system etiology were associated with DSD while metabolic disturbance, organ insufficiency and intracranial neoplasm were associated with the delirium only group., Conclusion: The etiology and phenomenology of delirium differs when it occurs in the patient with an underlying dementia. We discuss the implications in terms of identification and management of this complex condition., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Accurate annotation of vertebral bodies is crucial for automating the analysis of spinal X-ray images. However, manual annotation of these structures is a laborious and costly process due to their complex nature, including small sizes and varying shapes. To address this challenge and expedite the annotation process, we propose an ensemble pipeline called VertXNet. This pipeline currently combines two segmentation mechanisms, semantic segmentation using U-Net, and instance segmentation using Mask R-CNN, to automatically segment and label vertebral bodies in lateral cervical and lumbar spinal X-ray images. VertXNet enhances its effectiveness by adopting a rule-based strategy (termed the ensemble rule) for effectively combining segmentation outcomes from U-Net and Mask R-CNN. It determines vertebral body labels by recognizing specific reference vertebral instances, such as cervical vertebra 2 ('C2') in cervical spine X-rays and sacral vertebra 1 ('S1') in lumbar spine X-rays. Those references are commonly relatively easy to identify at the edge of the spine. To assess the performance of our proposed pipeline, we conducted evaluations on three spinal X-ray datasets, including two in-house datasets and one publicly available dataset. The ground truth annotations were provided by radiologists for comparison. Our experimental results have shown that the proposed pipeline outperformed two state-of-the-art (SOTA) segmentation models on our test dataset with a mean Dice of 0.90, vs. a mean Dice of 0.73 for Mask R-CNN and 0.72 for U-Net. We also demonstrated that VertXNet is a modular pipeline that enables using other SOTA model, like nnU-Net to further improve its performance. Furthermore, to evaluate the generalization ability of VertXNet on spinal X-rays, we directly tested the pre-trained pipeline on two additional datasets. A consistently strong performance was observed, with mean Dice coefficients of 0.89 and 0.88, respectively. In summary, VertXNet demonstrated significantly improved performance in vertebral body segmentation and labeling for spinal X-ray imaging. Its robustness and generalization were presented through the evaluation of both in-house clinical trial data and publicly available datasets., (© 2024. The Author(s).)

Background: Tumour-infiltrating CD8 + cytotoxic T cells confer favourable prognosis in colorectal cancer. The added prognostic value of other infiltrating immune cells is unclear and so we sought to investigate their prognostic value in two large clinical trial cohorts., Methods: We used multiplex immunofluorescent staining of tissue microarrays to assess the densities of CD8 + , CD20 + , FoxP3 + , and CD68 + cells in the intraepithelial and intrastromal compartments from tumour samples of patients with stage II-III colorectal cancer from the SCOT trial (ISRCTN59757862), which examined 3 months versus 6 months of adjuvant oxaliplatin-based chemotherapy, and from the QUASAR 2 trial (ISRCTN45133151), which compared adjuvant capecitabine with or without bevacizumab. Both trials included patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1. Immune marker predictors were analysed by multiple regression, and the prognostic and predictive values of markers for colorectal cancer recurrence-free interval by Cox regression were assessed using the SCOT cohort for discovery and QUASAR 2 cohort for validation., Findings: After exclusion of cases without tissue microarrays and with technical failures, and following quality control, we included 2340 cases from the SCOT trial and 1069 from the QUASAR 2 trial in our analysis. Univariable analysis of associations with recurrence-free interval in cases from the SCOT trial showed a strong prognostic value of intraepithelial CD8 (CD8 IE ) as a continuous variable (hazard ratio [HR] for 75th vs 25th percentile [75vs25] 0·73 [95% CI 0·68-0·79], p=2·5 × 10 -16 ), and of intrastromal FoxP3 (FoxP3 IS ; 0·71 [0·64-0·78], p=1·5 × 10 -13 ) but not as strongly in the epithelium (FoxP3 IE ; 0·89 [0·84-0·96], p=1·5 × 10 -4 ). Associations of other markers with recurrence-free interval were moderate. CD8 IE and FoxP3 IS retained independent prognostic value in bivariable and multivariable analysis, and, compared with either marker alone, a composite marker including both markers (CD8 IE -FoxP3 IS ) was superior when assessed as a continuous variable (adjusted [a]HR 75 vs 25 0·70 [95% CI 0·63-0·78], p=5·1 × 10 -11 ) and when categorised into low, intermediate, and high density groups using previously published cutpoints (aHR for intermediate vs high 1·68 [95% CI 1·29-2·20], p=1·3 × 10 -4 ; low vs high 2·58 [1·91-3·49], p=7·9 × 10 -10 ), with performance similar to the gold-standard Immunoscore. The prognostic value of CD8 IE -FoxP3 IS was confirmed in cases from the QUASAR 2 trial, both as a continuous variable (aHR 75 vs 25 0·84 [95% CI 0·73-0·96], p=0·012) and as a categorical variable for low versus high density (aHR 1·80 [95% CI 1·17-2·75], p=0·0071) but not for intermediate versus high (1·30 [0·89-1·88], p=0·17)., Interpretation: Combined evaluation of CD8 IE and FoxP3 IS could help to refine risk stratification in colorectal cancer. Investigation of FoxP3 IS cells as an immunotherapy target in colorectal cancer might be merited., Funding: Medical Research Council, National Institute for Health Research, Cancer Research UK, Swedish Cancer Society, Roche, and Promedica Foundation., Competing Interests: Declaration of interests DK has patents related to use of digital pathology algorithms, and serves as an advisor and has stock in Oxford Cancer Biomarkers. MPS has received honoraria from Merck, Server, Bayer, Takeda, and Amgen for meetings or lectures. WK has received royalties from Room4. DNC has participated in advisory boards for MSD and has received research funding on behalf of the TransSCOT consortium from HalioDx for analyses independent of this study. VHK has served as an invited speaker on behalf of Sharing Progress in Cancer Care and Indica Labs, and has received project-based research funding from The Image Analysis Group and Roche outside of the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The prolonged hypoxic conditions hinder chronic wounds from healing and lead to severe conditions such as delayed re-epithelialization and enhanced risk of infection. Multifunctional wound dressings are highly required to address the challenges of chronic wounds. Herein, we report polyurethane-coated sodium per carbonate-loaded chitosan hydrogel (CSPUO 2 ) as a multifunctional dressing. The hydrogels (Control, CSPU, and CSPUO 2 ) were prepared by freeze gelation method and the developed hydrogels showed high porosity, good absorption capacity, and adequate biodegradability. The release of oxygen from the CSPUO 2 hydrogel was confirmed by the increase in pH and a sustained oxygen release was observed over the period of 21 days, due to polyurethane (CSPU) coating. The CSPUO 2 hydrogel exhibited around 2-fold increased angiogenic potential in CAM assay when compared with Control and CSPU dressing. CSPUO 2 also showed good level of antibacterial efficacy against E. coli and S. aureus. In a full-thickness rat wound model, CSPUO 2 hydrogel considerably accelerated wound healing with exceptional re-epithelialization granulation tissue formation less inflammatory cells and improved skin architecture highlighting the tremendous therapeutic potential of this hydrogel when compared with control and CSPU to treat chronic diabetic and burn wounds., (© 2023 Wiley Periodicals LLC.)