A novel Skin lesion prediction and classification technique: ViT-GradCAM.

BACKGROUND: Skin cancer is one of the highly occurring diseases in human life. Early detection and treatment are the prime and necessary points to reduce the malignancy of infections. Deep learning techniques are supplementary tools to assist clinical experts in detecting and localizing skin lesions. Vision transformers (ViT) based on image segmentation classification using multiple classes provide fairly accurate detection and are gaining more popularity due to legitimate multiclass prediction capabilities. MATERIALS AND METHODS: In this research, we propose a new ViT Gradient-Weighted Class Activation Mapping (GradCAM) based architecture named ViT-GradCAM for detecting and classifying skin lesions by spreading ratio on the lesion's surface area. The proposed system is trained and validated using a HAM 10000 dataset by studying seven skin lesions. The database comprises 10 015 dermatoscopic images of varied sizes. The data preprocessing and data augmentation techniques are applied to overcome the class imbalance issues and improve the model's performance. RESULT: The proposed algorithm is based on ViT models that classify the dermatoscopic images into seven classes with an accuracy of 97.28%, precision of 98.51, recall of 95.2%, and an F1 score of 94.6, respectively. The proposed ViT-GradCAM obtains better and more accurate detection and classification than other state-of-the-art deep learning-based skin lesion detection models. The architecture of ViT-GradCAM is extensively visualized to highlight the actual pixels in essential regions associated with skin-specific pathologies. CONCLUSION: This research proposes an alternate solution to overcome the challenges of detecting and classifying skin lesions using ViTs and GradCAM, which play a significant role in detecting and classifying skin lesions accurately rather than relying solely on deep learning models.

Diagnostic potential of various laboratory tests for Irritable Bowel Syndrome (IBS): A systematic review.

Objective: To identify possible tests along with their accuracies that may be used to diagnose irritable bowel syndrome. METHODS: The systematic review comprised literature search on Cochrane Library, PubMed, Science Direct and Elsevier databases for randomised controlled trials and cohort studies conducted from January 1, 2015, to December 31, 2022, using appropriate key words and Boolean operators. Focus was kept on studies that reported irritable bowel syndrome diagnosis as the primary outcome. The risk of bias was assessed using quality assessment, data abstraction, and synthesis version 2. RESULTS: Of the 2,798 studies initially identified, 10(0.35%) were analysed in detail. Of them, 4(40%) used enzyme-linked immunosorbent assay kits to test for anti-cytolethal distending toxin B and anti-vinculin levels, 2(20%) used the kits for serum cytokine profiling and serum calprotectin levels, and 4(40%) used either magnetic resonance imaging scans, faecal metabolic profiling, intestinal biopsy analysis with immunostaining or polymerase chain reaction for differential transferribonucleic acid-derived small ribonucleic acid. Out of the 4(40%) studies on anti-cytolethal distending toxin B and anti-vinculin levels, optical densities >1.56 and >1.60 recorded 100% specificity for irritable bowel syndrome with diarrhoea, but sensitivity was 22%. In contrast, rectal biopsies for cell densities of somatostatin and peptide YY showed high sensitivity and specificity for irritable bowel syndrome ranging 80-90%. Conclusion: Enzyme-linked immunosorbent assay testing for anti-cytolethal distending toxin B and anti-vinculin as well as rectal biopsies for cell densities could be potential diagnostic tests for irritable bowel syndrome.

Attenuation of acute postoperative pain and opioid requirement with the use of magnesium sulfate in patients undergoing limb amputations.

OBJECTIVE: To compare the effects of magnesium sulphate on the total dose of intravenous morphine consumption postoperatively following limb amputations along with rescue analgesia requirement, pain scores and side effects. METHODS: This prospective, triple-blinded, randomised controlled study was conducted from October 2021 to May 2022 at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised of patients scheduled for limb amputations. They were randomised into 2 equal groups. The anaesthesia protocol was uniform for all patients. Intervention group A was administered 30mg/kg loading dose and 10mg/kg/hr maintenance dose of magnesium sulphate intravenously, while patients in control group B received the same amount of plain isotonic saline. Morphine consumption, including that used for rescue analgesia and patient-controlled analgesia, was measured for 24 hours postoperatively. Numeric rating scale was used for the evaluation of postoperative pain in both groups at 15min, 1h, 2h, at discharge from the post-anaesthesia care unit and at 12h and 24h in the ward. Data was analysed using SPSS 23. RESULTS: Of the 24 patients enrolled, the study was completed by 20(83.33%). There were 10(50%) patients in group A; 8(40%) males and 2(20%) females with mean age 24.8±14.14 years and mean surgery time 130.5±47.86 minutes. There were 10(50%) patients in group B; 8(40%) males and 2(20%) females with mean age 23.2±7.4 years and mean surgery time 117±23.85 minutes (p>0.05). Total morphine used over 24 hours in group A was 16±3.1 mg compared to 29.6±11.2 mg in group B (p<0.05). The time for first use of patient-controlled analgesia after arriving in the postanaesthesia care unit was significantly delayed in group A (72.2±24.95 minutes) compared to that in group B (25±26.68 minutes) (p<0.05). Pain scores were significantly higher in the group B at 15min compared to group A (p<0.05), but not at the rest of the time points (p>0.05). CONCLUSIONS: Intravenous magnesium sulphate proved to be effective in lowering postoperative opioid requirement following limb amputations.

Integrative metagenomic dissection of last-resort antibiotic resistance genes and mobile genetic elements in hospital wastewaters.

Hospital wastewater is a critical source of antimicrobial resistance (AMR), which facilitates the proliferation and spread of clinically significant antimicrobial resistance genes (ARGs) and pathogenic bacteria. This study utilized metagenomic approaches, including advanced binning techniques, such as MetaBAT2, MaxBin2, and CONCOCT, which offer significant improvements in accuracy and completeness over traditional binning methods. These methods were used to comprehensively assess the dynamics and composition of resistomes and mobilomes in untreated wastewater samples taken from two general hospitals and one cancer hospital. This study revealed a diverse bacterial landscape, largely consisting of Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria, with notable variations in microbial composition among hospitals. Analysis of the top 15 genera showed unique microbial pattern distribution in each hospital: Aeromonas was predominant in 1stHWTS (49.39 %), Acidovorax in the CAHWTS at 16.85 %, and Escherichia and Bacteroides in the 2ndHWTS at 11.44 % and 11.33 %, respectively. A total of 114 pathogenic bacteria were identified, with drug-resistant Aeromonas caviae and Escherichia coli being the most prevalent. The study identified 34 types and 1660 subtypes of ARGs, including important last-resort antibiotic resistance genes (LARGs), such as blaNDM, mcr, and tet(X). Using metagenomic binning, this study uncovered distinct patterns of host-resistance associations, particularly with Proteobacteria and Firmicutes. Network analysis highlighted the complex interactions among ARGs, mobile genetic elements (MGEs), and bacterial species, all contributing to the dissemination of AMR. These findings emphasize the intricate nature of AMR in hospital wastewater and the influence of hospital-specific factors on microbial resistance patterns. This study provides support for implementing integrated management strategies, including robust surveillance, advanced wastewater treatment, and strict antibiotic stewardship, to control the dissemination of AMR. Understanding the interplay among bacterial communities, ARGs, and MGEs is important for developing effective public health measures against AMR.

Quantification and polymeric characterization of microplastics in composts and their accumulation in lettuce.

Organic fertilizers have become a vector for the transport of microplastics (MPs), which pose human health concerns through the food chain. This study aimed to quantify and characterize MPs in eight different compost samples of various raw materials and their subsequent translocation to lettuce (Lacuta sativa) grown on contaminated composts. The results revealed that the MP abundance ranged from 3810 to 16530 MP/kg. Municipal solid waste compost (MSWC) had highest abundance (16082 ± 632 MP/kg), followed by leaf compost (LC) and organic compost (OC) (6299 ± 1011 and 3680 ± 419 MP/kg, respectively). MPs of <100 µm in size were most dominant in MSWC and LC. Fragments and fibers were the prevalent shape types, with white/transparent colored MPs being more abundant. Polyethylene (PE), polypropylene (PP) and polyethylene terephthalate (PET) were the dominant polymers. MPs accumulation in the lettuce leaves was greatest in the lettuce plants grown on MSWC, followed by those grown on LC and OC, indicating that MSWC grown lettuce is not suitable for human consumption. The decrease in the growth (leaf length, number of leaves, leaf fresh and weights) and physiological (membrane stability index, relative water contents) parameters of lettuce was in line with the trend of MP accumulations. Hence, it is highly important to regulate the plastic contents in compost because it is a threat to ecosystems and human health.

Exploring the mechanism of action of spirooxindoles as a class of CDK2 inhibitors: a structure-based computational approach.

Cyclin-dependent kinase 2 (CDK2) regulates cell cycle checkpoints in the synthesis and mitosis phases and plays a pivotal role in cancerous cell proliferation. The activation of CDK2, influenced by various protein signaling pathways, initiates the phosphorylation process. Due to its crucial role in carcinogenesis, CDK2 is a druggable hotspot target to suppress cancer cell proliferation. In this context, several studies have identified spirooxindoles as an effective class of CDK2 inhibitors. In the present study, three spirooxindoles (SOI1, SOI2, and SOI3) were studied to understand their inhibitory mechanism against CDK2 through a structure-based approach. Molecular docking and molecular dynamics (MD) simulations were performed to explore their interactions with CDK2 at the molecular level. The calculated binding free energy for the spirooxindole-based CDK2 inhibitors aligned well with experimental results regarding CDK2 inhibition. Energy decomposition (ED) analysis identified key binding residues, including I10, G11, T14, R36, F82, K89, L134, P155, T158, Y159, and T160, in the CDK2 active site and T-loop phosphorylation. Molecular mechanics (MM) energy was identified as the primary contributor to stabilizing inhibitor binding in the CDK2 protein structure. Furthermore, the analysis of binding affinity revealed that the inhibitor SOI1 binds more strongly to CDK2 compared to the other inhibitors under investigation. It demonstrated a robust interaction with the crucial residue T160 in the T-loop phosphorylation site, responsible for kinase activation. These insights into the inhibitory mechanism are anticipated to contribute to the development of potential CDK2 inhibitors using the spirooxindole scaffold.

BC-QNet: A quantum-infused ELM model for breast cancer diagnosis.

The timely and accurate diagnosis of breast cancer is pivotal for effective treatment, but current automated mammography classification methods have their constraints. In this study, we introduce an innovative hybrid model that marries the power of the Extreme Learning Machine (ELM) with FuNet transfer learning, harnessing the potential of the MIAS dataset. This novel approach leverages an Enhanced Quantum-Genetic Binary Grey Wolf Optimizer (Q-GBGWO) within the ELM framework, elevating its performance. Our contributions are twofold: firstly, we employ a feature fusion strategy to optimize feature extraction, significantly enhancing breast cancer classification accuracy. The proposed methodological motivation stems from optimizing feature extraction for improved breast cancer classification accuracy. The Q-GBGWO optimizes ELM parameters, demonstrating its efficacy within the ELM classifier. This innovation marks a considerable advancement beyond traditional methods. Through comparative evaluations against various optimization techniques, the exceptional performance of our Q-GBGWO-ELM model becomes evident. The classification accuracy of the model is exceptionally high, with rates of 96.54 % for Normal, 97.24 % for Benign, and 98.01 % for Malignant classes. Additionally, the model demonstrates a high sensitivity with rates of 96.02 % for Normal, 96.54 % for Benign, and 97.75 % for Malignant classes, and it exhibits impressive specificity with rates of 96.69 % for Normal, 97.38 % for Benign, and 98.16 % for Malignant classes. These metrics are reflected in its ability to classify three different types of breast cancer accurately. Our approach highlights the innovative integration of image data, deep feature extraction, and optimized ELM classification, marking a transformative step in advancing early breast cancer detection and enhancing patient outcomes.

Biosynthesized metallic nanoparticles: A new era in cancer therapy.

Cancer remains a global health crisis, claiming countless lives throughout the years. Traditional cancer treatments like chemotherapy and radiation often bring about severe side effects, underscoring the pressing need for innovative, more efficient, and less toxic therapies. Nanotechnology has emerged as a promising technology capable of producing environmentally friendly anticancer nanoparticles. Among various nanoparticle types, metal-based nanoparticles stand out due to their exceptional performance and ease of use in methods of imaging. The widespread accessibility of biological precursors for synthesis based on plants of metal nanoparticles has made large-scale, eco-friendly production feasible. This evaluation provides a summary of the green strategy for synthesizing metal-based nanoparticles and explores their applications. Moreover, this review delves into the potential of phyto-based metal nanoparticles in combating cancer, shedding light on their probable mechanisms of action. These insights are invaluable for enhancing both biomedical and environmental applications. The study also touches on the numerous potential applications of nanotechnology in the field of medicine. Consequently, this research offers a concise and well-structured summary of nanotechnology, which should prove beneficial to researchers, engineers, and scientists embarking on future research endeavors.

Methacrylated gelatin and platelet-rich plasma based hydrogels promote regeneration of critical-sized bone defects.

Physiological repair of large-sized bone defects requires instructive scaffolds with appropriate mechanical properties, biocompatibility, biodegradability, vasculogenic ability and osteo-inductivity. The objective of this study was to fabricate in situ injectable hydrogels using platelet-rich plasma (PRP)-loaded gelatin methacrylate (GM) and employ them for the regeneration of large-sized bone defects. We performed various biological assays as well as assessed the mechanical properties of GM@PRP hydrogels alongside evaluating the release kinetics of growth factors (GFs) from hydrogels. The GM@PRP hydrogels manifested sufficient mechanical properties to support the filling of the tissue defects. For biofunction assay, the GM@PRP hydrogels significantly improved cell migration and angiogenesis. Especially, transcriptome RNA sequencing of human umbilical vein endothelial cells and bone marrow-derived stem cells were performed to delineate vascularization and biomineralization abilities of GM@PRP hydrogels. The GM@PRP hydrogels were subcutaneously implanted in rats for up to 4 weeks for preliminary biocompatibility followed by their transplantation into a tibial defect model for up to 8 weeks in rats. Tibial defects treated with GM@PRP hydrogels manifested significant bone regeneration as well as angiogenesis, biomineralization, and collagen deposition. Based on the biocompatibility and biological function of GM@PRP hydrogels, a new strategy is provided for the regenerative repair of large-size bone defects.

A deep learning-based theoretical protocol to identify potentially isoform-selective PI3Kα inhibitors.

Phosphoinositide 3-kinase alpha (PI3Kα) is one of the most frequently dysregulated kinases known for their pivotal role in many oncogenic diseases. While the side effects linked to existing drugs against PI3Kα-induced cancers provide an avenue for further research, the significant structural conservation among PI3Ks makes it extremely difficult to develop new isoform-selective PI3Kα inhibitors. Embracing this challenge, we herein designed a hybrid protocol by integrating machine learning (ML) with in silico drug-designing strategies. A deep learning classification model was developed and trained on the physicochemical descriptors data of known PI3Kα inhibitors and used as a screening filter for a database of small molecules. This approach led us to the prediction of 662 compounds showcasing appropriate features to be considered as PI3Kα inhibitors. Subsequently, a multiphase molecular docking was applied to further characterize the predicted hits in terms of their binding affinities and binding modes in the targeted cavity of the PI3Kα. As a result, a total of 12 compounds were identified whereas the best poses highlighted the efficiency of these ligands in maintaining interactions with the crucial residues of the protein to be targeted for the inhibition of associated activity. Notably, potential activity of compound 12 in counteracting PI3Kα function was found in a previous in vitro study. Following the drug-likeness and pharmacokinetic characterizations, six compounds (compounds 1, 2, 3, 6, 7, and 11) with suitable ADME-T profiles and promising bioavailability were selected. The mechanistic studies in dynamic mode further endorsed the potential of identified hits in blocking the ATP-binding site of the receptor with higher binding affinities than the native inhibitor, alpelisib (BYL-719), particularly the compounds 1, 2, and 11. These outcomes support the reliability of the developed classification model and the devised computational strategy for identifying new isoform-selective drug candidates for PI3Kα inhibition.

Genome-wide in-silico analysis of ethylene biosynthesis gene family in Musa acuminata L. and their response under nutrient stress.

Ethylene is a gaseous phytohormone involved in plants' growth and developmental processes, including seed germination, root initiation, fruit ripening, flower and leaf senescence, abscission, and stress responses. Ethylene biosynthesis (EB) gene analysis in response to nitrogen (N) and potassium (K) stress has not yet been conducted in Musa acuminata (banana) roots. The genome mining of banana (Musa acuminata L.) revealed 14 putative 1-aminocyclopropane-1-carboxylate synthase (ACS), 10 1-aminocyclopropane-1-carboxylate oxidase (ACO), and 3 Ethylene overproducer 1 (ETO1) genes. ACS, ACO, and ETO1 proteins possessed amino acid residues ranging from 422-684, 636-2670, and 893-969, respectively, with molecular weight (Mw) ranging from 4.93-7.55 kD, 10.1-8.3 kD and 10.1-10.78 kD. The number of introns present in ACS, ACO, and ETO1 gene sequences ranges from 0-14, 1-6, and 0-6, respectively. The cis-regulatory element analysis revealed the presence of light-responsive, abscisic acid, seed regulation, auxin-responsive, gibberellin element, endosperm-specific, anoxic inducibility, low-temperature responsiveness, salicylic acid responsiveness, meristem-specific and stress-responsive elements. Comprehensive phylogenetic analyses ACS, ACO, and ETO1 genes of Banana with Arabidopsis thaliana revealed several orthologs and paralogs assisting in understanding the putative functions of these genes. The expression profile of Musa acuminata genes in root under normal and low levels of nitrogen and potassium shows that MaACS14 and MaACO6 expressed highly at normal nitrogen supply. MaACS1 expression was significantly upregulated at low potassium levels, whereas, MaACO6 gene expression was significantly downregulated. The functional divergence and site-specific selective pressures on specific gene sequences of banana have been investigated. The bioinformatics-based genome-wide assessment of the family of banana attempted in the present study could be a significant step for deciphering novel ACS, ACO, and ETO1 genes based on genome-wide expression profiling.

Association of Wilms Tumor with Crossed Fused Renal Ectopia in Children: A Case Report.

Introduction: Wilms tumor is the most common renal malignancy in children. The occurrence of Wilms tumor with various congenital genitourinary anomalies has been reported, particularly in horseshoe kidneys, hypospadias, disorder of sexual development, and double collecting system. However, Wilms tumor with crossed renal ectopia is a rare finding. Case Description: We are reporting a case report of Wilms tumor in a 3-year-old girl who presented with a huge left flank mass with cross-fused renal ectopia. After the initial workup and triphasic computed tomography scan of the chest, abdomen, and pelvis for confirmation of diagnosis and metastasis, the patient underwent image-guided tissue biopsy, followed by neoadjuvant chemotherapy, left radical nephrectomy with separation of fused right ectopic renal moiety, and adjuvant chemoradiation. Practical Implication: This report shows an association of Wilms tumor with cross-fused renal ectopia, a rare combination. Unusual findings on imaging with unilateral flank mass should be considered as part of the differential diagnosis for this rare finding. Adjuvant chemotherapy and modern imaging helped delineate the anatomy and ease the surgery for safe resection, improving the overall outcome.

Complications and Outcome of Bone Sarcoma Patients with Limb Salvage using Liquid Nitrogen-treated Bone for Reconstruction.

Introduction: The recommended treatment method for bone sarcoma is wide local excision and reconstruction to preserve limb function. Established methods of reconstruction are mega prosthesis or biological reconstruction. This study aimed to determine the complications and functional outcomes associated with limb salvage surgery using liquid nitrogen-treated bone. Materials and Methods: We retrospectively observed the short-term outcome of limb salvage surgeries where liquid nitrogen bone was used for reconstruction. A total of 15 patients underwent reconstruction with liquid nitrogen auto graft from January 2018 to December 2020. We used the free freezing method of liquid nitrogen treatment after wide local excision of sarcoma. We observed short-term outcomes after liquid nitrogen-treated bone reconstruction in limb salvage surgery. Survival of the auto grafts was recorded using the Kaplan-Meier method with a 95% confidence interval. Results: The mean follow-up was 19.83 ± 4.5 months. The mean musculoskeletal tumor society score was 62.4 ± 7.9%, while the average Toronto extremity score was 59.6 ± 5.7%. Three patients died during the study duration due to visceral metastasis. Skin necrosis and wound breakdown were major complications in 9 (60%) patients. Deep infection was observed in 4 (26.7%). Similarly, 4 (26.7%) patients had non-union at either the proximal or distal osteotomy site, while the average time of bone union in the rest of the patients was 6.3 ± 1.7 months. A total of 6 (40%) patients underwent reoperation after liquid nitrogen treatment, either due to infection or non-union at the osteotomy site. Recurrence was observed in 3 (20%) of patients. Conclusion: We observed a high complication rate with liquid nitrogen-treated autograft reconstruction. Vascularized fibula with liquid nitrogen-treated autograft or endoprosthesis should be encouraged.

Rare presentation of pneumothorax in a young woman with underlying congenital pulmonary airway malformation.

Congenital pulmonary airway malformation (CPAM) is the most common among a rare group of congenital anomalies of the lower respiratory tract. It has variable presentation depending on its subtype and the patient's age. It may lead to respiratory distress in neonates. It can be a particularly challenging diagnosis in children born asymptomatic but present with complications later in life such as haemoptysis, recurrent chest infections, breathlessness and pneumothorax. Prenatal ultrasound, chest X-ray, CT scan and MRI are helpful in making a radiological diagnosis.A woman in her late teens presented with shortness of breath and right pleuritic chest pain. CT's chest showed a number of bullae of varying sizes on the right, including one huge bulla compressing all three lobes. She underwent lung volume reduction surgery via video-assisted thoracoscopy, and the histology specimen confirmed the diagnosis of CPAM type 1.

Exposure Assessment of Essential and Potentially Toxic Metals in Wheat-Based Sweets for Human Consumption: Multivariate Analysis and Risk Evaluation Studies.

In recent years, there has been a growing concern about the negative impact of unforeseen contaminants such as metals in commonly consumed food items, which pose a threat to human well-being. Therefore, it is of utmost importance to evaluate the levels of these contaminants to guarantee the safe consumption of these food items. The goal of the current research is to determine the levels of essential (EMs: Mg, Ca, Mn, Fe, Co, Cu, and Zn) and potentially toxic metals (PTMs: Al, Cr, Ni, As, Cd, and Pb) in various brands of wheat-based sweets. One hundred samples were collected and analysed via flame atomic absorption spectrometry (FAAS) and inductively coupled plasma-optical emission spectrometry (ICP-OES). Also, the current study was to investigate the distribution, correlation, and multivariate analysis of 13 metals (Mg, Ca, Mn, Fe, Co, Cu, Zn, Al, Cr, Ni, As, Cd, and Pb). Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were used to interpret the metals' association. The concentration (mg/kg) ranges of EMs were, in order, Mg (12.70-65.67), Ca (24.02-209.12), Mn (1.32-9.61), Fe (4.55-111.23), Co (0.32-8.94), Cu (2.12-8.61), and Zn (2.60-19.36), while the concentration (mg/kg) ranges of PTMs were, in order, Al (0.32-0.87), Cr (0.17-5.74), Ni (0.36-1.54), Cd (0.16-0.56), and Pb (0.14-0.92), and As was not detected in any sample under investigation. The HCA data revealed that Co, Al, and Ni form clusters with other metals. Sweets are prepared at high temperatures, and the elevated temperatures can increase the likelihood of Ni and Al leaching from stainless steel. Tolerable dietary intake (TDI) values for Ni were higher than the values established by the European Food Safety Authority (EFSA). The CR value found for the Ni and Cr was at the threshold level of cancer risk, if an amount of 25 g were to be used over a lifetime. In a nutshell, this study highlights the monitoring of EM and PTM levels in wheat-based sweets, and from a food safety perspective, the study is important for consumers of wheat-based sweets.

Limb Salvage Surgery in a Voluminous Malignant Quadriceps Tumor.

It is uncommon for soft tissue sarcomas to develop after adenocarcinoma of the rectum. In a treated rectal adenocarcinoma patient, we encountered a huge malignant quadriceps tumor as leiomyosarcoma and salvaged the limb. A 49-year-old male known case of treated moderately differentiated adenocarcinoma of the rectum presented in the Orthopedic Clinic with a new swelling in his left thigh. MRI of the left lower limb was obtained, and it demonstrated a large 15.8 x 13.2 x 30 cm well-defined mixed solid cystic lesion in the anterolateral aspect of the left mid-thigh without the involvement of adjacent bony cortex. Limb salvage surgery with wide local excision of the tumor was done. The patient was ambulated full weight from the very next day with a Musculoskeletal Tumor Society Score (MSTS) score of 20. Despite the massive size of the tumor, limb salvage was attempted successfully and achieved good functional status.

Epidemiology and antifungal susceptibilities of clinically isolated Aspergillus species in South China.

Aspergillosis is a rising concern worldwide; however, its prevalence is not well documented in China. This retrospective study determined Aspergillus's epidemiology and antifungal susceptibilities at Meizhou People's Hospital, South China. From 2017 to 2022, the demographic, clinical, and laboratory data about aspergillosis were collected from the hospital's records and analysed using descriptive statistics, chi-square test, and ANOVA. Of 474 aspergillosis cases, A. fumigatus (75.32%) was the most common, followed by A. niger (9.92%), A. flavus (8.86%), and A. terreus (5.91%). A 5.94-fold increase in aspergillosis occurred during the study duration, with the highest cases reported from the intensive care unit (52.74%) - chronic pulmonary aspergillosis (79.1%) and isolated from sputum (62.93%). Only 38 (8.02%) patients used immunosuppressant drugs, while gastroenteritis (5.7%), haematologic malignancy (4.22%), and cardiovascular disease (4.22%) were the most prevalent underlying illnesses. In A. fumigatus, the wild-type (WT) isolates against amphotericin B (99.1%) were higher than triazoles (97-98%), whereas, in non-fumigatus Aspergillus species, the triazole (95-100%) WT proportion was greater than amphotericin B (91-95%). Additionally, there were significantly fewer WT A. fumigatus isolates for itraconazole and posaconazole in outpatients than inpatients. These findings may aid in better understanding and management of aspergillosis in the region.

SEC24D gene as a biomarker in human cancers and its association with CD8+ T cell immune cell infiltration.

OBJECTIVE: The SEC24D (SEC24 Homolog D, COPII Coat Complex Component) gene belongs to the SEC24 subfamily of genes. The protein encoded by this gene, along with its other binding partners, mediates the transport of newly-synthesized proteins from the endoplasmic reticulum to the Golgi apparatus. METHODS: A pan-cancer analysis of this gene, as well as its diagnostic and prognostic implications, are lacking in the medical literature. First, we analyzed SEC24D gene expression, its prognostic effect, promoter methylation level, genetic alteration landscape, pathways, CD8+ T immune cell infiltration, and gene-drug network in various types of cancer through various online databases and bioinformatic tools. Then, we performed the expression and methylation validation analysis of the SEC24D gene on cell lines using RNA sequencing (RNA-seq) and targeted bisulfite sequencing (bisulfite-seq) techniques. RESULTS: Bioinformatic analysis showed that the SEC24D gene was overexpressed in metastasis across Kidney Renal Clear Cell Carcinoma (KIRC), Lung Squamous Cell Carcinoma (LUSC), and Stomach Adenocarcinoma (STAD) patients and was a prognostic risk factor. Then, using RNA sequencing and targeted bisulfite sequencing analysis, it was validated in cell lines that SEC24D was overexpressed and hypomethylated in KIRC patients. Mutational analysis revealed that SEC24D was mutated less frequently in KIRC, LUSC, and STAD patients. It was further observed that CD8+ T cell infiltration levels were increased in SEC24D-overexpressed KIRC, LUSC, and STAD samples. Pathway enrichment analysis of SEC24D-associated genes revealed their participation in two important pathways. Moreover, we suggested a few valuable drugs for treating KIRC, LUSC, and STAD patients with respect to overexpressed SEC24D. CONCLUSION: This is the first pan-cancer study that details the oncogenic roles of SEC24D among different cancers.

Six-Year Retrospective Analysis of Epidemiology, Risk Factors, and Antifungal Susceptibilities of Candidiasis from a Tertiary Care Hospital in South China.

Candidiasis is a life-threatening disease that increases mortality in critically ill patients. However, such epidemiological data are still lacking in underdeveloped regions of China. A retrospective analysis (2016 to 2021) was conducted in Meizhou People's Hospital, China to study the burden of candidiasis, particularly candidemia, and antifungal susceptibilities of the species among hospitalized patients. Of the 7,864 candidiasis cases, 461 (5.86%) were candidemia cases. Candida albicans (64.25%) was the most identified species, followed by C. tropicalis (12.61%), C. glabrata (10.79%), and C. parapsilosis (9.79%). In non-C. albicans (NCA) candidemia cases, the number of C. glabrata cases was higher (102/461, 22.37%) than C. tropicalis (64/461, 14.04%). Gastrointestinal pathology, respiratory dysfunctions, septic shock, and malignancies were common underlying comorbidities, respectively. A central venous catheter was an independent risk factor for both C. albicans and NCA candidemia. The mortality rate was not statistically significant for either C. albicans or NCA. Amphotericin B and 5-flucytosine were highly effective (98 to 100%), while azoles were least effective (67.74 to 95.66%). Candidemia cases caused by C. tropicalis and C. glabrata had significantly lower azole susceptibility than non-candidemia-causing isolates. This study provides valuable information for prescribers to choose the right empirical therapy, for researchers to explore different resistance mechanisms, and for health care managers to control candidiasis better. IMPORTANCE This study provides important information on the burden of candidiasis, particularly candidemia, and the antifungal susceptibility of Candida species among hospitalized patients in an underdeveloped region of China. First, the finding that azoles were least effective against Candida species causing candidemia is particularly noteworthy, as it suggests the possibility of resistance to this class of antifungal agents. This information can guide the choice of empirical therapy and help in the selection of appropriate antifungal agents for the treatment of candidemia, thereby reducing the risk of resistance development. Second, the study provides important information for researchers to explore different resistance mechanisms in Candida species. Finally, the study has important implications for health care managers in controlling the spread of candidiasis. The high prevalence of candidemia cases in the study highlights the need for appropriate infection control measures to prevent the spread of the disease.