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Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome.Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting.Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795.

Summary: Background: Precise enteric fever disease burden data are needed to inform prevention and control measures, including the use of newly available typhoid vaccines. We established the Surveillance for Enteric Fever in Asia Project (SEAP) to inform these strategies. Methods: From September, 2016, to September, 2019, we conducted prospective clinical surveillance for Salmonella enterica serotype Typhi (S Typhi) and Paratyphi (S Paratyphi) A, B, and C at health facilities in predetermined catchment areas in Dhaka, Bangladesh; Kathmandu and Kavrepalanchok, Nepal; and Karachi, Pakistan. Patients eligible for inclusion were outpatients with 3 or more consecutive days of fever in the last 7 days; inpatients with suspected or confirmed enteric fever; patients with blood culture-confirmed enteric fever from the hospital laboratories not captured by inpatient or outpatient enrolment and cases from the laboratory network; and patients with non-traumatic ileal perforation under surgical care. We used a hybrid surveillance model, pairing facility-based blood culture surveillance with community surveys of health-care use. Blood cultures were performed for enrolled patients. We calculated overall and age-specific typhoid and paratyphoid incidence estimates for each study site. Adjusted estimates accounted for the sensitivity of blood culture, the proportion of eligible individuals who consented and provided blood, the probability of care-seeking at a study facility, and the influence of wealth and education on care-seeking. We additionally calculated incidence of hospitalisation due to typhoid and paratyphoid. Findings: A total of 34 747 patients were enrolled across 23 facilitates (six tertiary hospitals, surgical wards of two additional hospitals, and 15 laboratory network sites) during the study period. Of the 34 303 blood cultures performed on enrolled patients, 8705 (26%) were positive for typhoidal Salmonella. Adjusted incidence rates of enteric fever considered patients in the six tertiary hospitals. Adjusted incidence of S Typhi, expressed per 100 000 person-years, was 913 (95% CI 765–1095) in Dhaka. In Nepal, the adjusted typhoid incidence rates were 330 (230–480) in Kathmandu and 268 (202–362) in Kavrepalanchok. In Pakistan, the adjusted incidence rates per hospital site were 176 (144–216) and 103 (85–126). The adjusted incidence rates of paratyphoid (of which all included cases were due to S Paratyphi A) were 128 (107–154) in Bangladesh, 46 (34–62) and 81 (56–118) in the Nepal sites, and 23 (19–29) and 1 (1–1) in the Pakistan sites. Adjusted incidence of hospitalisation was high across sites, and overall, 2804 (32%) of 8705 patients with blood culture-confirmed enteric fever were hospitalised. Interpretation: Across diverse communities in three south Asian countries, adjusted incidence exceeded the threshold for “high burden” of enteric fever (100 per 100 000 person-years). Incidence was highest among children, although age patterns differed across sites. The substantial disease burden identified highlights the need for control measures, including improvements to water and sanitation infrastructure and the implementation of typhoid vaccines. Funding: Bill & Melinda Gates Foundation.

Abstract The first conference of the Vaccination Acceptance Research Network, VARN2022: Shaping Global Vaccine Acceptance with Localized Knowledge, was held virtually, from March 1st to 3rd 2022. This inaugural event brought together a global representation of experts to discuss key priorities and opportunities emerging across the ecosystem of vaccine acceptance and demand, from policies to programs and practice. Convened by the Sabin Vaccine Institute, VARN aims to support dialogue among multidisciplinary stakeholders to enhance the uptake of social and behavioral science-based solutions for vaccination decision-makers and implementers. The conference centered around four key themes: 1) Understanding vaccine acceptance and its drivers; 2) One size does not fit all: community- and context-specific approaches to increase vaccine acceptance and demand; 3) Fighting the infodemic and harnessing social media for good; and 4) Frameworks, data integrity and evaluation of best practices. Across the conference, presenters and participants considered the drivers of and strategies to increase vaccine acceptance and demand relating to COVID-19 vaccination and other vaccines across the life-course and across low-, middle- and high-income settings. VARN2022 provided a wealth of evidence from around the world, highlighting the need for human-centered, multi-sectoral and transdisciplinary approaches to improve vaccine acceptance and demand. This report summarizes insights from the diverse presentations and discussions held at VARN2022, which will form a roadmap for future research, policy making, and interventions to improve vaccine acceptance and demand globally.

Recently, mathematicians, engineers, and scientists have explored the unique characteristics and potential applications of multi-solitons, which is an expanding domain of study. There are various approaches to obtaining multi-soliton solutions of an integrable system, such as the Bäcklund transform, the nonlinear transform method, the Hirota direct method, etc. But each approach has some own characteristics and attributes; however, the Hirota direct method is dominant among them and provides further multi-soliton solutions of nonlinear evolution equations. In this article, we use the Hirota direct method to investigate the single-soliton, double-soliton, and triple-soliton solutions, known as multi-soliton solutions, of the integral Sawada-Kotera equation. We also demonstrate and discuss the effects of amplitude on the fluctuation of wave number in different ranges by comparing 2-D and 3-D plots.

A significant clinical challenge in patients with colorectal cancer (CRC), which adversely impacts patient survival, is the development of therapy resistance leading to a relapse. Therapy resistance and relapse in CRC is associated with the formation of lipid droplets (LD) by stimulating de novo lipogenesis (DNL). However, the molecular mechanisms underlying the increase in DNL and the susceptibility to DNL-targeted therapies remain unclear. Our study demonstrates that colorectal drug-tolerant persister cells (DTPs) over-express Lipin1 (LPIN1), which facilitates the sequestration of free fatty acids into LDs. The increased expression is mediated by the ETS1-PTPN1-c-Src-CEBPβ pathway. Blocking the conversion of free fatty acids into LDs by treatment with statins or inhibiting lipin1 expression disrupts lipid homeostasis, leading to lipotoxicity and ferroptotic cell death in both DTPs and patient-derived organoids (PDOs) in vitro. Ferroptosis inhibitors or N-acetylcysteine (NAC) can alleviate lipid ROS and cell death resulting from lipin1 inhibition. This strategy also significantly reduces tumor growth in CRC DTP mouse xenograft and patient-derived xenograft (PDX) models. Our findings highlight a new metabolic vulnerability in CRC DTPs, PDO, and PDX models and provide a framework for the rational repurposing of statins. Targeting the phosphatidic acid (PA) to diacylglycerol (DAG) conversion to prevent lipid droplet formation could be an effective therapeutic approach for therapy-resistant CRC., 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 Authors. Published by Elsevier B.V. All rights reserved.)

Cardiovascular arrhythmia, characterized by irregular heart rhythms, poses significant health risks, including stroke and heart failure, making accurate and early detection critical for effective treatment. Traditional detection methods often struggle with challenges such as imbalanced datasets, limiting their ability to identify rare arrhythmia types. This study proposes a novel hybrid approach that integrates ConvNeXt-X deep learning models with advanced data balancing techniques to improve arrhythmia classification accuracy. Specifically, we evaluated three ConvNeXt variants-ConvNeXtTiny, ConvNeXtBase, and ConvNeXtSmall-combined with Random Oversampling (RO) and SMOTE-TomekLink (STL) on the MIT-BIH Arrhythmia Database. Experimental results demonstrate that the ConvNeXtTiny model paired with STL achieved the highest accuracy of 99.75%, followed by ConvNeXtTiny with RO at 99.72%. The STL technique consistently enhanced minority class detection and overall performance across models, with ConvNeXtBase and ConvNeXtSmall achieving accuracies of 99.69% and 99.72%, respectively. These findings highlight the efficacy of ConvNeXt-X models, when coupled with robust data balancing techniques, in achieving reliable and precise arrhythmia detection. This methodology holds significant potential for improving diagnostic accuracy and supporting clinical decision-making in healthcare., Competing Interests: Declarations. Competing interests: The authors have no conflicts of interest to declare that they are relevant to the content of this article., (© 2024. The Author(s).)

Introduction: There is no clear consensus on using the response MRI as opposed to the pretreatment MRI for surgical planning in cT4 low rectal cancer. The objective of this study is to determine the safety of using response MRI in surgical planning for T4 rectal cancer., Methods: This study is a retrospective review of a prospectively maintained database of abdominoperineal resections conducted at a single tertiary cancer center. Patients undergoing an abdominoperineal resection were divided into 2 groups: group A (clinical T3, mesorectal fascia positive) and group B (clinical T4), and propensity matching was used to account for uneven distribution of baseline characteristics. Primary outcome was the rate of pathological circumferential resection margin positivity. Secondary outcomes were survival outcomes and recurrence patterns., Results: There were 237 patients in group A and 127 in group B, in the unmatched cohort, with a significantly higher number of females (43.3% vs. 28.7%, p  = 0.005) and anterior circumferential resection margin positivity (68.5% vs. 49%, p  < 0.001), with a lower number of patients receiving neoadjuvant chemotherapy in group B (38.6% vs. 49.8%, p  = 0.041). After propensity matching baseline characters were comparable. There was a higher percentage of extended-total mesorectal excisions in group B (58.5% vs. 40.5%, p  = 0.004). The rate of pathological circumferential positivity was comparable in both groups (20/168 in group A {11.9%} vs. 13/107 in group B {12.1%}, p  = 0.951) with no impact of group on circumferential resection margin positivity on univariate (OR 1.023, p  = 0.951) or multivariate regression (OR 0.993, p  = 0.987). Both the DFS (median DFS 39 months vs. 54 months, p  = 0.970) and OS (3-year OS 72% vs. 67%, p  = 0.798) were comparable between both groups., Conclusion: For T4 low rectal cancers, post-treatment MRI can be used for surgical planning without any detriment in pathological or long-term oncological outcomes., Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-024-02028-3., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2024.)

Background: Our study aims to determine the predictors and patterns of relapses after curative colorectal liver metastasis (CRLM) resection., Methods: A single-centre, retrospective study of CRLM patients operated between 2010 and 2022 was performed. The site of first recurrence was either hepatic (marginal (≤ 1 cm) or extramarginal), extrahepatic, or both. Factors that predicted relapse patterns and overall survival were determined by multivariable Cox regression analysis with backward elimination of variables., Results: The study consisted of 258 patients, with a similar proportion of synchronous (144; 56%) and metachronous(114; 43%) metastasis. At a 43-month median follow-up, 156 patients (60.4%) developed recurrences with 33 (21.1%) in the liver, 62(24.03%) extra-hepatic recurrences, and 58 (22.48%) having both. Isolated marginal liver relapses were seen in seven (9.89%) liver recurrence patients. The median overall and relapse-free survivals were 38 months (30-54) and 13 months (11-16), respectively. The 3-year liver-relapse-free survival was 54.4% (44.9-60.6). Size of liver metastases > 5 cm (HR 2.06 (1.34-3.17), involved surgical margins (HR 2.16 (1.27-3.68)), and adjuvant chemotherapy (HR 1.89 (1.07-3.35)) were predictors of hepatic recurrences. Node positivity of primary (HR 1.61 (1.02-2.56)), presence of baseline extra-hepatic metastases (HR 0.30 (0.18-0.51)), size of liver metastases > 5 cm (HR 2.02 (1.37-2.99)), poorly differentiated histology (HR 2.25 (1.28-3.49)), presence of LVI (HR 2.25 (1.28-3.94)), and adjuvant chemotherapy (HR 2.15 (1.28-3.61)) were predictors of extra-hepatic recurrences., Conclusion: The study found majority relapses occurred at extrahepatic sites whilst isolated marginal recurrences were few. The consistent predictors of recurrence were size and inability to deliver adjuvant therapy. A tailored adjuvant therapy might improve outcomes after liver metastasectomy in colorectal cancers., (© 2024. The Author(s).)

Background: Extramural vascular invasion (EMVI) is a bad prognostic feature in rectal cancer and cancers that remain EMVI positive after neoadjuvant therapy are at high risk for having involved circumferential resection margins. Conventional total mesorectal excision (TME) resections are inadequate in such cases and often lead to positive margins., Methods: We propose a technique for the surgical management of locally advanced tumours with persistent EMVI after neoadjuvant therapy. Ten such tumours were resected using a "beyond TME" (b-TME) approach with or without lateral pelvic lymph node dissection or seminal vesical excision., Results: A b-TME approach, customized to the anatomy of the tumour allowed for an R0 resection with a negative circumferential resection margin (CRM) in all 10 cases., Conclusion: A tailored b-TME approach can achieve good results in cases at high risk for CRM involvement., (© 2024 The Author(s). Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Objective: Early detection of Parkinson's disease (PD) is essential for halting its progression, yet challenges remain in leveraging deep learning for accurate identification. This study aims to overcome these obstacles by introducing a hybrid deep learning approach that enhances PD detection through a combination of autoencoder (AE) and radial basis function neural network (RBFNN)., Methods: The proposed method analyzes the power spectral density (PSD) of preprocessed electroencephalography (EEG) signals, with artifacts removed, to assess energy distribution across EEG sub-bands. AEs are employed to extract features from reconstructed signals, which are subsequently classified by an RBFNN. The approach is validated on UC SanDiego's EEG dataset, consisting of 31 subjects and 93 minutes of recordings., Results: The hybrid model demonstrates promising performance, achieving a classification accuracy of 99%. The improved accuracy is attributed to advanced feature selection techniques, robust data preprocessing, and the integration of AEs with RBFNN, setting a new benchmark in PD detection frameworks., Conclusion: This study highlights the efficacy of the hybrid deep learning framework in detecting PD, particularly emphasizing the importance of using multiple EEG channels and advanced preprocessing techniques. The results underscore the potential of this approach for practical clinical applications, offering a reliable solution for early and accurate PD detection., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objective: Brain tumors are a leading global cause of mortality, often leading to reduced life expectancy and challenging recovery. Early detection significantly improves survival rates. This paper introduces an efficient deep learning model to expedite brain tumor detection through timely and accurate identification using magnetic resonance imaging images., Methods: Our approach leverages deep transfer learning with six transfer learning algorithms: VGG16, ResNet50, MobileNetV2, DenseNet201, EfficientNetB3, and InceptionV3. We optimize data preprocessing, upsample data through augmentation, and train the models using two optimizers: Adam and AdaMax. We perform three experiments with binary and multi-class datasets, fine-tuning parameters to reduce overfitting. Model effectiveness is analyzed using various performance scores with and without cross-validation., Results: With smaller datasets, the models achieve 100% accuracy in both training and testing without cross-validation. After applying cross-validation, the framework records an outstanding accuracy of 99.96% with a receiver operating characteristic of 100% on average across five tests. For larger datasets, accuracy ranges from 96.34% to 98.20% across different models. The methodology also demonstrates a small computation time, contributing to its reliability and speed., Conclusion: The study establishes a new standard for brain tumor classification, surpassing existing methods in accuracy and efficiency. Our deep learning approach, incorporating advanced transfer learning algorithms and optimized data processing, provides a robust and rapid solution for brain tumor detection., (© The Author(s) 2024.)

In this current research, we conceptualized a novel nanotechnology-enabled synthesis approach of targeting HIV-harboring tissues via second-generation (G2) polyamidoamine (PAMAM) mannosylated (MPG2) dendrimers for programmed delivery of anti-HIV drugs efavirenz (EFV) and ritonavir (RTV). Briefly, here mannose served purpose of ligand in this EFV and RTV-loaded PAMAM G2 dendrimers, synthesized by divergent techniques, denoted as MPG2ER. The developed nanocarriers were characterized by different analytical tools FTIR, NMR, zeta potential, particle size, and surface morphology. The results of confocal microscopy showed substantial alterations in the morphology of H9 cells, favored by relatively higher drug uptake through the MPG2ER. Interestingly, the drug uptake study and cytotoxicity assay of MPG2ER demonstrated that it showed no significant toxicity up to 12.5 µM. A typical flow cytometry histogram also revealed that MPG2ER efficiently internalized both drugs, with an increase in drug uptake of up to 81.2 %. It also enhanced the plasma pharmacokinetics of EFV, with C max 7.68 μg/ml, AUC of 149.19 (μg/ml) * hr, and MRT of 26.87 hrs. Subsequently, tissue pharmacokinetics further evidence that MPG2ER accumulated more in distant Human immunodeficiency virus (HIV) reservoir tissues, such as the lymph nodes and spleen, but without exhibiting significant toxicity. Abovementioned compelling evidences strongly favored translational roles of MPG2 as a potential therapeutic strategy in the clinical eradication of HIV from viral reservoir tissue., Competing Interests: 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., (© 2024 The Author(s).)

Background: Digestive issues are recognized as significant contributors to various chronic diseases, including obesity, diabetes, and cardiovascular disease. Barley, a traditional grain, offers considerable promise in addressing these health challenges due to unique nutritional and bioactive compounds., Objective: This review examines the therapeutic potential of various parts of barley, underutilized resource, for chronic disease prevention and management., Method: ology: A comprehensive literature search was conducted across multiple databases like Google Scholar, PubMed, and ISI Web of Science, to identify nutritional components and functional ingredients in barley that contribute to gut health and chronic disease mitigation., Results: The finding suggests that humans digest barley starch more slowly than wheat and rice, which benefits chronic disease management. Barley's high-molecular-weight β-glucan high content acts as a prebiotic, promotes gut health through microbiome modulation and short-chain fatty acid production, potentially preventing colon cancer and boosting immunity. Recent studies on exploring barley grass of high land showed functional ingredients such as flavonoids, saponarin lutonarin, superoxide dismutase, gamma-aminobutyric acid, polyphenols K, Ca, Se, tryptophan chlorophyll, and vitamins, suggesting potential for enhanced antioxidant activity and improved management of chronic conditions like diabetes, cholesterol, hypertension, cardiovascular health, liver protection, and even boosted immunity., Conclusion: This review underscores the therapeutic potential of barley and its components in chronic disease management, highlighting the need for well-designed clinical trials to translate these findings into effective interventions., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors.)

The use of nanosized particles is becoming more popular for the topical treatment of skin conditions. In this research work, we created and investigated the effects of solid lipid nanoparticles (SLN) containing hyaluronic acid and tretinoin. Solvent emulsification diffusion method was used to prepare the SLN formulation and characterized for their physicochemical properties. Fourier transform infrared spectroscopy was used to confirm that hyaluronic acid and tretinoin were incorporated in the SLN. Furthermore, X-ray diffractogram, thermal analysis including DSC and TGA and in vitro dissolution, permeation tests were also performed along with microbial assessment. Clinical studies in human were performed to evaluate the effect of the SLN on skin wrinkles. The SLN was 750 ± 31.29 nm in size, with a zeta potential of 13.07 ± 0.75 mV and a narrow polydispersity index of 0.24 ± 0.12. The entrapment efficiency of tretinoin was found to be 90.07 ± 4.79%. Clinical studies in healthy human volunteers demonstrated that 90% of the tested individuals had improved skin conditions (reduction in wrinkles), by at least one grade after 4 weeks of treatment. Regarding the development on SLN, it was found that the internal phase concentration did not considerably affect the physicochemical and microbiological properties. Therefore, Hyaluronic acid has potential for the development of SLN applicable to cosmetic formulations, especially for skin. These findings show that the developed SLN have potential for use as cosmetics in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mehmood, Shahid, Rizvi, Jamshaid, Arshad, Nur-e-Alam, Hussain and Kazi.)

Cyclooxygenase-2 (COX-2) is critically implicated in various pathologies, including inflammation, cancer, disorders involving the nervous system, and multidrug resistance. In both academic and pharmaceutical research, the development of COX-2 selective drugs as anti-inflammatory and anti-tumor therapeutics is a key focus. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) have ulcerogenic, gastrointestinal adverse effects, and myocardial infarction risk, which resulted in their limited applications. In response to this challenge, we synthesized a series of glycoconjugates featuring six-membered sugar rings and acyl chains of varying lengths attached at the C-6 position. Using molecular docking techniques, we identified galactose esters with optimal acyl chain lengths that selectively and effectively bind to the active site of COX-2 over COX-1. These compounds exhibited enhanced binding affinity and superior inhibition constants (p K i ) for COX-2, thereby offering selective inhibition with potentially reduced ulcerogenic risks, as COX-1 inhibition is thought to contribute to these side effects. The molecular docking study identified two potential compounds, G6 and G8, which were validated via MD simulation for the assessment of their stability and were compared to the complex of the standard drugs, aspirin and rofecoxib. In addition, compound structures were optimized using the DFT method under the B3LYP/6-31+g(d,p) basis set to study their physio-spectral properties, frontier molecular orbitals (HOMO-LUMO), and their energy gap that correlates to their reactivity and stability. ADMET, drug-likeness, and PASS analyses were also carried out to assess their drug-ability and toxicity profiling., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (This journal is © The Royal Society of Chemistry.)

Background and Aim: This is a report from Phase 1 of the prospective, observational, PRECINCT (Pattern of peritoneal dissemination and REsponse to systemic Chemotherapy IN Common and uncommon peritoneal Tumours) study, in which we studied the incidence of disease at pathological evaluation in different morphological appearances of peritoneal malignancies (PM) on imaging., Methods: Radiological findings were captured in a specific format that included a description of the morphological appearance of PM and a correlation performed with pathological findings., Results: In 630 patients enroled at seven centres (September 2022-December 2023), 24 morphological terms were used. Among prespecified terms (N = 8 used in 6350 [92.2%] regions), scalloping was pathologically positive in 93.5%, confluent disease in 78.8%, tumour nodules in 69.6%, thickening in 66.1%, infiltration in 56.3%. Among unspecified appearances (N = 16) for 540 (7.8%) regions, 'enhancement' was positive in 41.5%, micronodules in 65.3% and nodularity in 60.2%. Hierarchal clustering placed gastric cancer and rare tumours together and colorectal cancer, ovarian cancer and peritoneal mesothelioma in one cluster., Conclusions: The incidence of disease at pathological evaluation for most morphological appearances was high (> 50%). Morphological description should be provided in routine radiology reports. A set of standardized terms with their description should be developed by a consensus among experienced radiologists., (© 2024 Wiley Periodicals LLC.)

Polyurethane/hydroxyapatite (PU/HA) composites are well-known for various biomedical applications. This study reports a chemical approach to improve the interaction between HA and PU matrix. HA was surface-modified with 1,6-hexamethylene diisocyanate (HMDI). First, an isocyanate-modified HA (IHA) was synthesized by hydro-thermal method. Second, IHA was incorporated into a separately synthesized thermoplastic PU by a solvent casting technique. A series of PU/IHA composites was prepared by varying PU᾿s soft and hard segments. The IHA was added to PU (5 and 10 %). The FTIR spectra exhibited characteristic bands of urethane and HA, confirming the synthesis of the composites. XRD study showed the crystallite size of IHA (20 Å) with hexagonal geometry and an amorphous to semicrystalline nature of composites. SEM showed that composites displayed porous and granular morphology. The TGA thermograms of the composites revealed the thermal stability up to 400 °C. The IHA addition considerably improved hydrophilicity and degradation of the composites in simulated body fluid (SBF). MTT assay revealed improved cytocompatibility (> 80 %) of the composites. These results demonstrated an appreciable improvement in structure, morphology, hydrophilicity, degradation, and cytocompatibility of PU/IHA composites by chemical modification of HA. Hence, these composites possess remarkable potential for biomedical applications such as tissue regeneration., (© 2024 Misbah Sultan et al., published by Sciendo.)

Background and Aim: In this report from Phase 1 of the prospective, observational, PRECINCT (Pattern of peritoneal dissemination and REsponse to systemic Chemotherapy IN Common and uncommon peritoneal Tumours) study, a correlation was performed between the radiological PCI (peritoneal cancer index; rPCI) and surgical PCI (sPCI). The impact of timing of peritoneal malignancy (PM) and previous abdominal surgery was also studied., Methods: The rPCI and sPCI were considered the 'same' if they differed by ≤ 3 points. The agreement was assessed using Bland-Altman analysis and the strength of the agreement was assessed using the concordance correlation coefficient (CCC). The extent of prior surgery was classified according to prior surgical score (PSS)., Results: In 707 (79.4%) patients, rPCI and sPCI concurred in 280 (39.6%). In the Bland-Altman analysis, < 40% patients were in the ±3 PCI points limit of acceptable difference. The average difference between the two scores was 4.5 points (95% CI- -5.16 to -3.92). The CCC- was 0.59 for the whole cohort ('moderate' concordance) and was not influenced by imaging modality, timing of PM or PSS., Conclusions: The rPCI underestimated sPCI by an average of 4.5 points. The role of peritoneal MRI in patients undergoing iterative procedures and the performance of imaging according to sites of recurrence need further evaluation., (© 2024 Wiley Periodicals LLC.)

Purposes: The objective of this study is to develop a versatile gene carrier based on lipopeptides capable of delivering genetic material into target cells with minimal cytotoxicity., Methods: Two lipopeptide molecules, palmitoyl-CKKHH and palmitoyl-CKKHH-YGRKKRRQRRR-PKKKRKV, were synthesized using solid phase peptide synthesis and evaluated as transfection agents. Physicochemical characterization of the lipopeptides included a DNA shift mobility assay, particle size measurement, and transmission electron microscopy (TEM) analysis. Cytotoxicity was assessed in CHO-K1 and HepG2 cells using the MTT assay, while transfection efficiency was determined by evaluating the expression of the green fluorescent protein-encoding gene., Results: Our findings demonstrate that the lipopeptides can bind, condense, and shield DNA from DNase degradation. The inclusion of the YGRKKRRQRRR sequence, a transcription trans activator, and the PKKKRKV sequence, a nuclear localization signal, imparts desirable properties. Lipopeptide-based TAT-NLS/DNA nanoparticles exhibited stability for up to 20 days when stored at 6-8 °C, displaying uniformity with a compact size of approximately 120 nm. Furthermore, the lipopeptides exhibited lower cytotoxicity compared to the poly-L-lysine. Transfection experiments revealed that protein expression mediated by the lipopeptide occurred at a charge ratio ranging from 4.0 to 8.0., Conclusion: These results indicate that the lipopeptide, composed of a palmitoyl alkyl chain and TAT and NLS sequences, can efficiently condense and protect DNA, form stable and uniform nanoparticles, and exhibit promising characteristics as a potential gene carrier with minimal cytotoxicity., 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 Elsevier B.V. All rights reserved.)

Transdermal microneedles have demonstrated promising potential as an alternative to typical drug administration routes for the treatment of various diseases. As microneedles offer lower administration burden with enhanced patient adherence and reduced ecological footprint, there is a need for further exploitation of microneedle devices. One of the main objectives of this work was to initially develop an innovative biobased photocurable resin with high biobased carbon content comprising isobornyl acrylate (IBA) and pentaerythritol tetraacrylate blends (50:50 wt/wt). The optimization of the printing and curing process resulted in μNe3dle arrays with durable mechanical properties and piercing capacity. Another objective of the work was to employ the 3D printed hollow μNe3dles for the treatment of osteoporosis in vivo. The 3D printed μNe3dle arrays were used to administer denosumab (Dmab), a monoclonal antibody, to osteoporotic mice, and the serum concentrations of critical bone minerals were monitored for six months to assess recovery. It was found that the Dmab administered by the 3D printed μNe3dles showed fast in vitro rates and induced an enhanced therapeutic effect in restoring bone-related minerals compared to subcutaneous injections. The findings of this study introduce a novel green approach with a low ecological footprint for 3D printing of biobased μNe3dles, which can be tailored to improve clinical outcomes and patient compliance for chronic diseases.

Objective: Diabetes is a metabolic disorder that causes the risk of stroke, heart disease, kidney failure, and other long-term complications because diabetes generates excess sugar in the blood. Machine learning (ML) models can aid in diagnosing diabetes at the primary stage. So, we need an efficient ML model to diagnose diabetes accurately., Methods: In this paper, an effective data preprocessing pipeline has been implemented to process the data and random oversampling to balance the data, handling the imbalance distributions of the observational data more sophisticatedly. We used four different diabetes datasets to conduct our experiments. Several ML algorithms were used to determine the best models to predict diabetes faultlessly., Results: The performance analysis demonstrates that among all ML algorithms, random forest surpasses the current works with an accuracy rate of 86% and 98.48% for Dataset 1 and Dataset 2; extreme gradient boosting and decision tree surpass with an accuracy rate of 99.27% and 100% for Dataset 3 and Dataset 4, respectively. Our proposal can increase accuracy by 12.15% compared to the model without preprocessing., Conclusions: This excellent research finding indicates that the proposed models might be employed to produce more accurate diabetes predictions to supplement current preventative interventions to reduce the incidence of diabetes and its associated costs., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: The objective of this systematic review and meta-analysis was to pool randomized trials of patients undergoing left-sided colorectal anastomosis, comparing the use of fluorescence perfusion imaging versus visual inspection in reducing anastomotic leaks., Methods: Databases searched included PubMed, Cochrane Library, Scopus, CINHAL (EBSCO), and Google Scholar based on the concepts: randomized, colorectal, anastomotic leak, and fluorescence imaging. The risk of bias was assessed using RoB2 and the certainty of the evidence with the GRADE Pro tool. The analysis used the log odds ratio for dichotomous data with 95% confidence intervals. Back-transformation of the log odds to odds ratio was performed for the summary of findings. All syntheses used the Random-effects model., Results: Six randomized trials were included with 1949 patients and 204 events (leaks). Three trials included exclusively rectal cancer patients, while the other three involved benign and malignant pathologies of the sigmoid and rectum. The use of ostomy and preoperative radiation was variable. None of the studies had a high risk of bias. The pooled odds ratio for anastomotic leak reduction with Indocyanine Green (ICG) fluorescence was 0.586 (95% CI: 0.434-0.792). An absolute reduction of 4.7% in leak rates was observed, with no statistical heterogeneity (I 2  = 0; p = 0.529). Due to clinical heterogeneity, the quality of evidence was rated moderate., Conclusions: The use of ICG is associated with reduced leak rates following left-sided colorectal anastomosis with moderate confidence. ICG may be considered a standard of care given the clinically significant benefit in decreasing anastomotic leaks., (© 2024 The Author(s). ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Background: Intraoperative unresectability, postoperative deaths and early recurrences remain devastating futile events in the surgical management of Intrahepatic cholangiocarcinomas (iCCA) and Perihilar cholangiocarcinomas (pCCA). The present study aims to determine the preoperative predictors of futile surgery in cholangiocarcinomas., Methods: Consecutive hepatectomies for iCCA and pCCA, between September 2010 and June 2022 were included. Futility of surgery was defined as either intraoperative unresectability, postoperative 30-day mortality or recurrence within six months of surgery. Multivariable logistic regression was used to identify predictors of futility., Results: One hundred and fifty patients of iCCA and pCCA underwent surgery during the time period. Thirty-seven (38.1 %) out of 97 patients of iCCA and 25(47.16 %) out of 53 patients of pCCA underwent futile resection. The predictive factors of futile surgery for iCCA were tumour number (≥2) (OR, 9.705; 95%CI, 2.378-39.614; p = 0.002), serum aspartate transaminase (OR, 8.31; 95%CI, 2.796-24.703; p < 0.001) and serum CA-19.9 (>37 U/ml) (OR, 2.95; 95%CI, 1.051-8.283; p = 0.04). The predictive factors of futility for pCCA were lymph node involvement (OR, 7.636; 95%CI, 1.824-31.979; p = 0.005) and serum alkaline phosphatase (>562.5 U/L) (OR, 11.211; 95%CI, 1.752-71.750; p = 0.011)., Conclusion: Futile surgery was observed in over one third of our patients. Five strong preoperative predictors of futility were identified. Careful analysis of these factors may reduce futile surgical explorations., Competing Interests: Declaration of competing interest The authors of the present study declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The utilization of phytoconstituents in skin care products has emerged as a notable trend due to their recognized safety and therapeutic efficacy. However, the challenge lies in improving the effective delivery of phytoconstituents to specific tissues, primarily attributed to their poor solubility and low permeability. This study endeavors to address this challenge by developing, optimizing and characterizing Cucumis melo var. agrestis (CME) extract loaded nanoemulsion gel (CME-NEG), aiming to enhance the skin permeability and antifungal activity. Herein, nanoemulsions encapsulating the plant extract were prepared using ultrasonication technique and were characterized for droplet size, zeta potential, polydispersity index (PDI) and entrapment efficiency. Further, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) analysis were conducted to characterize the optimized CME extract loaded nanoemulsion (CME-NE 3) formulation. The optimized formulation was blended with Carbopol 940 gel to develop CME-NEG, which was evaluated for release kinetics, in vitro permeation and in vitro antifungal activity. High performance liquid chromatography (HPLC) analysis confirmed the presence of gallic acid, chlorogenic acid, 4-Hydroxy benzoic acid (HB acid), kaempferol, caffeic acid and quercetin. Findings of 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay showed that the ethanolic extract had highest antioxidant activity (88.88 %). The optimized formulation displayed smooth spherical nanodroplets with size of 175.5 ± 1.56 nm, zeta potential of -21.5 ± 0.12 mV, PDI of 0.192 ± 0.06, and highest entrapment efficiency (EE) of 91.35 ± 1.65 %. The release profile of CME-NE exhibited a controlled release characteristic and the release kinetic mechanism was best described by the Korsmeyer-Peppas (Kp) model. In a 24 h permeation study, it was observed that the in vitro permeation of CME-NEG was 58.63 %, significantly higher than that of CME extract loaded plain gel (CME-PG) with an enhancement ratio of 2.12. The prepared CME-NEG formulation also presented enhanced antifungal activity as compared to pure CME extract. In conclusion, the designed CME-NEG offers a promising topical drug delivery system with enhanced skin permeability and antifungal activity., Competing Interests: 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., (© 2024 Published by Elsevier Ltd.)

Extra-pulmonary TB (EPTB) is difficult to diagnose due to paucibacillary nature of disease. Current study evaluated accuracy of Truenat MTB and MTB-Rif Dx (TN), for detection of Mycobacterium tuberculosis and resistance to rifampicin. Samples were collected from 2103 treatment naive adults with presumptive EPTB, and tested by smear microscopy, liquid culture (LC) (MGIT-960) and GeneXpert MTB/RIF (GX) (Microbiological Reference Standards, MRS). TN results were compared to MRS and Composite Reference Standards (CRS, Microbiology, histopathology, radiology, clinical features prompting decision to treat, response to treatment). CRS grouped patients into 551 confirmed, 1096 unconfirmed, and 409 as unlikely TB. TN sensitivity and specificity was 73.7% and 90.4% against GX. Against LC, Overall sensitivity of GX was 67.6%, while that of TN was 62.3%. Highest sensitivity by TN was observed in pus samples (89%) and highest specificity (92%) in CSF samples, similar to GX. TN sensitivity was better in fluid and biopsy samples and slightly inferior for lymph node aspirates compared to GX. TN sensitivity for RIF resistance detection was slightly superior to GX. TN and GX results were further compared to Clinical Reference Standards. TN detected 170 TB patients initiated on treatment missed by GX, while GX detected 113 such patients missed by TN. Of 124 samples with RIF resistance discordance between GX and TN, GX reported 103/124 as sensitive, 3/124 as indeterminate and 18 as resistant (13/18 samples had low/very low DNA load) while TN reported RIF resistance indeterminate in 103/111 low/very low DNA load samples. Due to paucibacillary nature of EPTB samples, culture yield was poor and phenotypic drug susceptibility testing failed to resolve the discordance. The study establishes TN at par with GX and can be utilized for quick and accurate diagnosis of EPTB., (© 2024. The Author(s).)