Excitation signal optimization for minimizing fluctuations in knock out slow extraction.

The synchrotron is a circular particle accelerator used for high energy physics experiments, material and life science, as well as hadron cancer therapy. After acceleration to the desired energies, particle beams are commonly extracted from the synchrotron using the method of resonant slow extraction. The goal is to deliver a steady particle flux-referred to as spill-to experiments and treatment facilities over the course of seconds while slowly emptying the storage ring. Any uncontrolled intensity fluctuations in the spill are detrimental to the efficiency of beam usage, as they lead to detector pileups or detector interlocks, hindering experiments and cancer treatment. Among the most widely used extraction scheme in medical facilities is the Radio Frequency Knock Out (RF-KO) driven resonant slow extraction, where the stored beam is transversely excited with a radio frequency (RF) field and the spill intensity is controlled by the excitation signal strength. This article presents particle dynamics simulations of the RF-KO system with the focus on finding effective mechanism for minimizing the intensity fluctuations while maintaining a good extraction efficiency and other advantages of KO extraction. An improved beam excitation signal which optimizes these main objectives is found, and is rigorously compared experimentally with other commonly applied techniques.

A Huge Osteochondroma With Chest Wall Deformity Arising From the Ventral Scapula.

Osteochondromas (OC), or exostoses, are developmental defects rather than true neoplasms. Misdirected physeal bone growths give rise to OC. It causes cartilage-capped bony extensions to emerge from the lateral outlines of endochondral bones. We discuss a case of OC in a 35-year-old female who presented with severe chest wall deformity and breathlessness due to compromised left lung function. CT scan showed a vast osteochondroma arising from the ventral surface of the scapula, which was palpable in the supra mammary region on the left side. The tumor mass was completely excised from the base of the stalk. Her breathlessness and compromised left lung function returned to normal in the post-op period. However, the chest deformity was corrected over two months. The article provides insights into the presentation in a patient with such a massive tumor due to its location. Surgical excision should be the treatment of choice for huge osteochondromas.

neuroGPT-X: toward a clinic-ready large language model.

OBJECTIVE: The objective was to assess the performance of a context-enriched large language model (LLM) compared with international neurosurgical experts on questions related to the management of vestibular schwannoma. Furthermore, another objective was to develop a chat-based platform incorporating in-text citations, references, and memory to enable accurate, relevant, and reliable information in real time. METHODS: The analysis involved 1) creating a data set through web scraping, 2) developing a chat-based platform called neuroGPT-X, 3) enlisting 8 expert neurosurgeons across international centers to independently create questions (n = 1) and to answer (n = 4) and evaluate responses (n = 3) while blinded, and 4) analyzing the evaluation results on the management of vestibular schwannoma. In the blinded phase, all answers were assessed for accuracy, coherence, relevance, thoroughness, speed, and overall rating. All experts were unblinded and provided their thoughts on the utility and limitations of the tool. In the unblinded phase, all neurosurgeons provided answers to a Likert scale survey and long-answer questions regarding the clinical utility, likelihood of use, and limitations of the tool. The tool was then evaluated on the basis of a set of 103 consensus statements on vestibular schwannoma care from the 8th Quadrennial International Conference on Vestibular Schwannoma. RESULTS: Responses from the naive and context-enriched Generative Pretrained Transformer (GPT) models were consistently rated not significantly different in terms of accuracy, coherence, relevance, thoroughness, and overall performance, and they were often rated significantly higher than expert responses. Both the naive and content-enriched GPT models provided faster responses to the standardized question set than expert neurosurgeon respondents (p < 0.01). The context-enriched GPT model agreed with 98 of the 103 (95%) consensus statements. Of interest, all expert surgeons expressed concerns about the reliability of GPT in accurately addressing the nuances and controversies surrounding the management of vestibular schwannoma. Furthermore, the authors developed neuroGPT-X, a chat-based platform designed to provide point-of-care clinical support and mitigate the limitations of human memory. neuroGPT-X incorporates features such as in-text citations and references to enable accurate, relevant, and reliable information in real time. CONCLUSIONS: The present study, with its subspecialist-level performance in generating written responses to complex neurosurgical problems for which evidence-based consensus for management is lacking, suggests that context-enriched LLMs show promise as a point-of-care medical resource. The authors anticipate that this work will be a springboard for expansion into more medical specialties, incorporating evidence-based clinical information and developing expert-level dialogue surrounding LLMs in healthcare.

AS1411 aptamer/RGD dual functionalized theranostic chitosan-PLGA nanoparticles for brain cancer treatment and imaging.

Conventional chemotherapy and poor targeted delivery in brain cancer resulting to poor treatment and develop resistance to anticancer drugs. Meanwhile, it is quite challenging to diagnose/detection of brain tumor at early stage of cancer which resulting in severity of the disease. Despite extensive research, effective treatment with real-time imaging still remains completely unavailable, yet. In this study, two brain cancer cell specific moieties i.e., AS1411 aptamer and RGD are decorated on the surface of chitosan-PLGA nanoparticles to improve targeted co-delivery of docetaxel (DTX) and upconversion nanoparticles (UCNP) for effective brain tumor therapy and real-time imaging. The nanoparticles were developed by a slightly modified emulsion/solvent evaporation method. This investigation also translates the successful synthesis of TPGS-chitosan, TPGS-RGD and TPGS-AS1411 aptamer conjugates for making PLGA nanoparticle as a potential tool of the targeted co-delivery of DTX and UCNP to the brain cancer cells. The developed nanoparticles have shown an average particle size <200 nm, spherical in shape, high encapsulation of DTX and UCNP in the core of nanoparticles, and sustained release of DTX up to 72 h in phosphate buffer saline (pH 7.4). AS1411 aptamer and RGD functionalized theranostic chitosan-PLGA nanoparticles containing DTX and UCNP (DUCPN-RGD-AS1411) have achieved greater cellular uptake, 89-fold improved cytotoxicity, enhanced cancer cell arrest even at lower drug conc., improved bioavailability with higher mean residence time of DTX in systemic circulation and brain tissues. Moreover, DUCPN-RGD-AS1411 have greatly facilitated cellular internalization and higher accumulation of UCNP in brain tissues. Additionally, DUCPN-RGD-AS1411 demonstrated a significant suppression in tumor growth in brain-tumor bearing xenograft BALB/c nude mice with no impressive sign of toxicities. DUCPN-RGD-AS1411 has great potential to be utilized as an effective and safe theranostic tool for brain cancer and other life-threatening cancer therapies.

Effect of micro-fractures on gas flow behavior in coal for enhanced coal bed methane recovery and CO2 storage.

This study investigates the impact of micro-fractures on gas flow behavior in coal formations, specifically within the context of CO2-based Enhanced Coal Bed Methane Recovery (ECBMR). Employing comparative analysis, various gas flow models, including Unipore Diffusion Model (UDM), Bidispersed Diffusion Model (BDM), Fractal Fractional Diffusion Model (FFDM), Time-Dependent Diffusivity Model (TDDM), Anomalous Sub-Diffusion Model (ASM), and Free Gas Density Gradient Model (FGDGM), are evaluated for their efficacy in capturing the complexities. The study aims to provide insights into the accuracy and applicability of these models, considering the heterogeneity of coal seams and the influence of micro-fractures on gas flow dynamics. The major findings include the categorization of different gas flow models based on their applicability to CO2-based ECBMR. For instance, the study suggests utilizing BDM and FFDM models while considering the heterogeneity of coal seams. Similarly using the TDDM model for time dynamics of ECBMR will give higher accuracy. The article contributes to a deeper understanding of gas migration processes in coal, particularly in the context of ECBMR, with implications for optimizing recovery strategies and addressing challenges associated with micro-fracture-induced variations in gas flow behavior.

Contrasting functions of ATP hydrolysis by MDA5 and LGP2 in viral RNA sensing.

Cytosolic long dsRNA, among the most potent proinflammatory signals, is recognized by melanoma differentiation-associated protein 5 (MDA5). MDA5 binds dsRNA cooperatively forming helical filaments. ATP hydrolysis by MDA5 fulfills a proofreading function by promoting dissociation of shorter endogenous dsRNs from MDA5 while allowing longer viral dsRNAs to remain bound leading to activation of interferon-ß responses. Here, we show that adjacent MDA5 subunits in MDA5-dsRNA filaments hydrolyze ATP cooperatively, inducing cooperative filament disassembly. Consecutive rounds of ATP hydrolysis amplify the filament footprint, displacing tightly bound proteins from dsRNA. Our electron microscopy and biochemical assays show that LGP2 binds to dsRNA at internal binding sites through noncooperative ATP hydrolysis. Unlike MDA5, LGP2 has low nucleic acid selectivity and can hydrolyze GTP and CTP as well as ATP. Binding of LGP2 to dsRNA promotes nucleation of MDA5 filament assembly resulting in shorter filaments. Molecular modeling identifies an internally bound MDA5-LGP2-RNA complex, with the LGP2 C-terminal tail forming the key contacts with MDA5. These contacts are specifically required for NTP-dependent internal RNA binding. We conclude that NTPase-dependent binding of LGP2 to internal dsRNA sites complements NTPase-independent binding to dsRNA ends, via distinct binding modes, to increase the number and signaling output of MDA5-dsRNA complexes.

Bioactive properties of clove (Syzygium aromaticum) essential oil nanoemulsion: A comprehensive review.

Syzygium aromaticum, commonly called clove, is a culinary spice with medical uses. Clove is utilized in cosmetics, medicine, gastronomy, and agriculture due to its abundance of bioactive components such as gallic acid, flavonoids, eugenol acetate, and eugenol. Clove essential oil has been revealed to have antibacterial, antinociceptive, antibacterial activities, antifungal, and anticancerous qualities. Anti-inflammatory chemicals, including eugenol and flavonoids, are found in clove that help decrease inflammation and alleviate pain. The anti-inflammatory and analgesic qualities of clove oil have made it a popular natural cure for toothaches and gum discomfort. Due to its therapeutic potential, it has been used as a bioactive ingredient in coating fresh fruits and vegetables. This review article outlines the potential food processing applications of clove essential oil. The chemical structures of components, bioactive properties, and medicinal potential of clove essential oil, including phytochemical importance in food, have also been thoroughly addressed.

Recent Progress and Challenges in Clinical Translation of Nanomedicines in Diagnosis and Treatment of Lung Cancer.

Lung cancer is one of the leading causes of death across the world. There are numerous challenges in the early diagnosis and effective treatment of lung cancer, including developing multidrug resistance. However, the diagnosis of lung cancer could be minimally invasive or non-invasive. Nowadays, nanomedicines offer solutions to several emerging challenges in drug delivery research areas. It has the potential to enhance the therapeutic efficacy of biologically and chemically active agents at the site of action. This approach can also be employed in molecular and cellular imaging, precise and early detection, screening, and targeting drugs for lung cancer treatment. A proper understanding of the disease and timely diagnosis using strategically designed effective nanocarriers can be a promising approach to effectively managing cancer. The present review explores issues related to lung cancer chemotherapy and the promises and hurdles of newer approaches like nanomedicine. The article also summarizes the preclinical studies on diagnosis and treatment, pitfalls, and challenges in the clinical translation of nanomedicines for lung cancer therapy.

Prognostic significance of preoperative pyuria & neutrophil to lymphocyte ratio in patients with non-muscle-invasive bladder cancer: A prospective cohort study.

BACKGROUND: The most prevalent cancer of the urinary system and the fourth most frequent cancer in men is bladder cancer. Up to 45% of non-muscle-invasive bladder cancers (NMIBC), may develop into muscle-invasive disease within 5 years after initial diagnosis, depending on the risk profile. The neutrophil to lymphocyte ratio (NLR), which is an emerging marker of host inflammation and can be easily calculated from routine complete blood counts (CBCs) with differentials, has shown to be an independent prognostic factor for a variety of solid malignancies, including urinary tract cancer. Pyuria is a well-documented prognostic factor in urinary tract carcinomas, according to several research. The relationship between preoperative pyuria and recurrence in patients with NMIBC is unclear, even though some studies found that pyuria was a strong predictor of poor prognosis in patients with NMIBC. Our study's objective was to compare the prognostic effect of pre-treatment pyuria and NLR on the likelihood of progression and recurrence in individuals with primary NMIBC. MATERIALS AND METHODOLOGY: Data obtained from 100 bladder cancer patients who underwent transurethral resection of bladder tumor (TURBT) from June 2021 to January 2023 were evaluated prospectively. INCLUSION CRITERIA: Age more than 18 years, having tumor size less than 3 × 3 cm, single tumor, no H/O TURBT. EXCLUSION CRITERIA: Age less than 18 years, size more than 3 × 3 cm, multiple tumors, H/O TURBT. RESULTS: We demonstrated in the current study that, compared to NLR, preoperative pyuria was more substantially linked with intravesical recurrence, higher T stage and disease progression following TURBT for NMIBC.

Modulation of mammary tumour progression using murine model by ethanol root extract of Saussurea costus (falc.) lipsch.

ETHNOPHARMACOLOGICAL RELEVANCE: Breast cancer is a major cause of death among human females across the globe. The anti-neoplastic agents or therapies used for the treatment of cancers can enhance longevity but are subsequently observed to deteriorate the quality of life due to the extensive side effects produced. Saussurea costus is a potential medicinal plant of the Himalayas with noticeable ethnopharmacological properties. The phytochemicals present in Saussurea costus are responsible for anti-carcinogenic potential and warranted nil or minimal side effects of Saussurea costus and directed to use this plant as a preventive or therapeutic drug candidate against cancers. AIM OF THE STUDY: The present study was planned to evaluate the anti-neoplastic activity of Saussurea costus root extract (SL) in rat mammary tumour model. MATERIALS AND METHODS: The anti-neoplastic activity of SL root extract at 3 different doses (100, 250 and 500 mg/kg BW) for 18 weeks against 12-dimethylbenz (a) anthracene (DMBA)-induced mammary tumours in Sprague Dawley (SD) female rats was analyzed through serum biochemistry (ALT, AST, ALP, Total protein, Creatinine and BUN), oxidative stress parameters (Lipid peroxidation, Catalase and Reduced glutathione), pro-inflammatory cytokines (TNF-α and NF-κB), immunohistochemical markers (Ki-67, MMP-9 and VEGF), real-time PCR (PCNA, p53, bax, bcl-2 and caspase-3, genes) and molecular docking. RESULTS: Inhibition of tumour parameters, minimal alteration in the liver (ALT, AST and ALP) and kidney enzymes (Creatinine and BUN), decreased activity of MDA, elevated levels of GSH and catalase, reduction in the levels of pro-inflammatory cytokines i.e. TNF-α and NF-κB, reduced gross and histomorphological changes, declined expression of Ki-67, MMP-9 and VEGF in vivo rat model, mRNA expression of cancer-related genes and docking of dehydrocostus lactone and costunolide with NF-κB and TNF-α demonstrated the chemopreventive action of SL root extract. CONCLUSIONS: The in-vivo trial elucidates anti-neoplastic activity of Saussurea costus root extract as demonstrated through the reduction of biochemical indices, oxidative stress parameters, histological changes, pro-inflammatory cytokines (NF-κB and TNF-α), cellular proliferation (Ki-67), metastases (MMP-9) and neovascularization (VEGF) markers with highest anti-neoplastic effect of SL extract at the dose of 500 mg/kg body weight. Therefore, the present study signifies the need to use the active principles present in the root extract of Saussurea costus against breast cancer as a therapeutic regimen.

Bioactives from medicinal herb against bedaquiline resistant tuberculosis: removing the dark clouds from the horizon.

Tuberculosis is a contagious bacterial ailment that primarily affects the lungs and is brought on by the bacterium Mycobacterium tuberculosis (MTB). An antimycobacterial medication called bedaquiline (BQ) is specified to treat multidrug-resistant tuberculosis (MDR-TB). Despite its contemporary use in clinical practice, the mutations (D32 A/G/N/V/P) constrain the potential of BQ by causing transitions in the structural conformation of the atpE subunit-c after binding. In this study, we have taken the benzylisoquinoline alkaloids from thalictrum foliolosum due to its antimicrobial activity reported in prior literature. We used an efficient and optimized structure-based strategy to examine the wild type (WT) and mutated protein upon molecule binding. Our results emphasize the drastic decline in BQ binding affinity of mutant and WT atpE subunit-c complexes compared to thalirugidine (top hit) from thalictrum foliolosum. The decrease in BQ binding free energy is due to electrostatic energy because nearly every atom in a macromolecule harbors a partial charge, and molecules taking part in molecular recognition will interact electrostatically. Similarly, the high potential mean force of thalirugidine than BQ in WT and mutant complexes demonstrated the remarkable ability to eradicate mycobacteria efficiently. Furthermore, the Alamar blue cell viability and ATP determination assay were performed to validate the computational outcomes in search of novel antimycobacterial. Upon closer examination of the ATP determination assay, it became apparent that both BQ and thalirugidine showed similar reductions in ATP levels at their respective MICs, presenting a potential common mechanism of action.

Emerging role of miR-320a in lung cancer: a comprehensive review.

A specialized biomarker(s) for lung cancer is imperative owing to its high mortality. Continuing our earlier work demonstrating the role of miR-320a as a tumor suppressor, here we discuss the most recent updates on miR-320a in lung cancer pathogenesis. We found that miR-320a modulates levels of diverse cancer-associated molecules and signaling pathways, and is also involved in modulating the immune microenvironment of lung cancer during its pathogenesis. We also discuss how miR-320a encapsulated in exosomes inhibits invasive phenotypes of lung cancer. Therefore, based on the multimodal role of miR-320a in lung cancer development and progression, we believe that miR-320a may be utilized as a potential diagnostic/prognostic marker and therapeutic target for lung cancer patients.

A Comprehensive Review of Postoperative Analgesics Used in Orthopedic Practice.

Orthopedic surgeries, ranging from joint replacements to fracture fixations, are integral procedures that enhance the quality of life for countless individuals. Effective postoperative pain management is crucial in ensuring optimal patient recovery and satisfaction. This comprehensive review analyzes the diverse array of analgesic modalities employed in orthopedic practice for postoperative pain relief. The review systematically explores the pharmacological landscape of analgesics commonly used in orthopedic settings, including opioids, non-steroidal anti-inflammatory drugs, acetaminophen, and adjuvant medications. Emphasis is placed on their mechanisms of action, efficacy profiles, and potential adverse effects. Special attention is given to the evolving role of multimodal analgesia, which combines various agents to achieve synergistic pain control while minimizing individual drug-related complications. Furthermore, the review addresses the emerging trends and advancements in postoperative analgesia within orthopedics, such as integrating regional anesthesia techniques, peripheral nerve blocks, and novel pharmacological agents. A critical evaluation of evidence-based practices and recent clinical trials is incorporated to guide practitioners in making informed decisions regarding postoperative pain management. Consideration is also given to the individualized nature of pain experiences and the importance of patient-centric approaches. The review underscores the significance of tailoring analgesic regimens based on patient characteristics, surgical procedures, and potential complications, fostering a personalized and effective pain management strategy. In conclusion, this comprehensive review is valuable for orthopedic practitioners, anesthetists, and healthcare professionals involved in postoperative care. By synthesizing current knowledge and highlighting evolving trends, the review contributes to the ongoing dialogue on optimizing pain management strategies in orthopedic practice, ultimately improving patient outcomes and satisfaction.

Fabrication, in-silico, in-vitro, and in-vivo characterization of transferrin-targeted micelles containing cisplatin and gadolinium for improved theranostic applications in lung cancer therapy.

The targeted delivery of therapeutic and imaging agents is quite challenging in lung cancer therapy. Thus, lung cancer causes high mortality across the world. Herein, we developed TPGS-PF127 micelles containing cisplatin (CDDP) as a model anticancer drug and gadolinium (Gd) as a diagnostic agent by a slightly modified solvent casting method, further, the surface of the micelles was modified using TPGS-transferrin (TPGS-Tf) conjugate to improve targeted delivery of micelles to the lung cancer cells. Prior to this, the binding affinity of Tf over TfR (1E7U) and TfR (1E8W) was investigated with the help of in-silico studies. In-silico results showed good docking scores -7.8 and -7.2 kcal/mol of Tf -ligand towards 1E8W and 1E7U respectively promoting PI3K inhibition. Micelles have shown an average particle size range of 80-200 nm and have shown spherical morphology. The encapsulation efficiency of cisplatin (CDDP) in the CPT, CGPT, and CGPT-Tf micelles ranged from 75.63 % ± 1.58 % to 85.07 % ± 2.65 %. Furthermore, the encapsulation efficiency of gadolinium (Gd) in the CGPT and CGPT-Tf micelles was found to be 67.50 ± 0.32 % and 62.52 ± 0.52 %, respectively. CGPT-Tf micelles exhibited sustained release fashion for CDDP up to 48 h in physiological conditions. In the cytotoxicity study, CGPT-Tf micelles achieved higher cytotoxicity and caused a more antiproliferative effect in A549 cells compared to a commercial CDDP injection (Ciszest 50), after 24 h of treatment. Furthermore, the pharmacokinetic studies have proven the pharmacological effectiveness of developed CGPT-Tf micelles by achieving higher Cmax, Tmax, t1/2, and MRT of CDDP in systemic circulation compared to its counterparts and Ciszest 50. In lung theranostic observations, a higher internalization of Gd was noted in CGPT-TF compared to free Gd. The biochemical studies have proved the biocompatibility of developed micelles formulations by showing no sign of toxicity in the lungs. The developed micelles have great potential to be utilized in treating and diagnosing a wide variety of cancers.

Imidazo[2,1-b]thiazole based indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor: Structure based design, synthesis, bio-evaluation and docking studies.

Indoleamine-2,3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme known to catalyse the initial and rate limiting step of kynurenine pathway of l-tryptophan metabolism. IDO1 enzyme over expression plays a crucial role in progression of cancer, malaria, multiple sclerosis and other life-threatening diseases. Several efforts over the last two decades have been invested by the researchers for the discovery of different IDO1 inhibitors and the plasticity of the IDO1 enzyme ligand binding pocket provide ample opportunities to develop new heterocyclic scaffolds targeting this enzyme. In the present work, based on the X-ray crystal structure of human IDO1 coordinated with few ligands, we designed and synthesized new fused heterocyclic compounds and evaluated their potential human IDO1 inhibitory activity (compound 30 and 41 showed IC50 values of 23 and 13 µM, respectively). The identified HITs were observed to be non-toxic to HEK293 cells at 100 µM concentration. The observed activity of the synthesized compounds was correlated with the specific interactions of their structures at the enzyme pocket using docking studies. A detailed analysis of docking results of the synthesized analogues as well as selected known IDO1 inhibitors revealed that most of the inhibitors have some reasonable docking scores in at least two crystal structures and have similar orientation as that of co-crystal ligands.

An Overview of Current Progress and Challenges in Brain Cancer Therapy Using Advanced Nanoparticles.

Brain tumors pose significant challenges in terms of complete cure and early-stage prognosis. The complexity of brain tumors, including their location, infiltrative nature, and intricate tumor microenvironment (TME), contributes to the difficulties in achieving a complete cure. The primary objective of brain cancer therapy is to effectively treat brain tumors and improve the patient's quality of life. Nanoparticles (NPs) have emerged as promising tools in this regard. They can be designed to deliver therapeutic drugs to the brain tumor site while also incorporating imaging agents. The NPs with the 10-200 nm range can cross the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) and facilitate drug bioavailability. NPs can be designed by several methods to improve the pharmaceutical and pharmacological aspects of encapsulated therapeutic agents. NPs can be developed in various dosage forms to suit different administration routes in brain cancer therapy. The unique properties and versatility of NPs make them essential tools in the fight against brain tumors, offering new opportunities to improve patient outcomes and care. Having the ability to target brain tumors directly, overcome the BBB, and minimize systemic side effects makes NPs valuable tools in improving patient outcomes and care. The review highlights the challenges associated with brain tumor treatment and emphasizes the importance of early detection and diagnosis. The use of NPs for drug delivery and imaging in brain tumors is a promising approach to improving patient outcomes and quality of life. The versatility and unique properties of NPs make them valuable tools in the fight against brain tumors, and NPs have the potential to revolutionize healthcare.

Snapping ankles: peroneal tendon subluxation and dislocation.

Peroneal tendon dislocation or subluxation is an orthopaedic condition that usually occurs as a result of injury to the superior peroneal retinaculum. The peroneal muscles are located in the lateral compartment of the leg, and their tendons run in the retromalleolar groove anchored by the superior peroneal retinaculum. Peroneal instability is usually classified using the Eckert and Davies classification, which was modified by Oden into a four-point grading system. The mechanism of injury is typically sudden forced dorsiflexion, resulting in aggressive tautness of the peroneal tendons, combined with a forced eversion of the hindfoot. Plain X-ray, ultrasound and magnetic resonance imaging are useful for imaging of the injury and in planning for surgery. Operative management has high success rates and there are multiple surgical techniques available, including superior peroneal retinaculum repair, tenoplasty, bone block procedures, groove deepening and endoscopic approaches, with little variation in outcome found between the approaches.

Force Profile as Surgeon-Specific Signature.

Objective: To investigate the notion that a surgeon's force profile can be the signature of their identity and performance. Summary background data: Surgeon performance in the operating room is an understudied topic. The advent of deep learning methods paired with a sensorized surgical device presents an opportunity to incorporate quantitative insight into surgical performance and processes. Using a device called the SmartForceps System and through automated analytics, we have previously reported surgeon force profile, surgical skill, and task classification. However, an investigation of whether an individual surgeon can be identified by surgical technique has yet to be studied. Methods: In this study, we investigate multiple neural network architectures to identify the surgeon associated with their time-series tool-tissue forces using bipolar forceps data. The surgeon associated with each 10-second window of force data was labeled, and the data were randomly split into 80% for model training and validation (10% validation) and 20% for testing. Data imbalance was mitigated through subsampling from more populated classes with a random size adjustment based on 0.1% of sample counts in the respective class. An exploratory analysis of force segments was performed to investigate underlying patterns differentiating individual surgical techniques. Results: In a dataset of 2819 ten-second time segments from 89 neurosurgical cases, the best-performing model achieved a micro-average area under the curve of 0.97, a testing F1-score of 0.82, a sensitivity of 82%, and a precision of 82%. This model was a time-series ResNet model to extract features from the time-series data followed by a linearized output into the XGBoost algorithm. Furthermore, we found that convolutional neural networks outperformed long short-term memory networks in performance and speed. Using a weighted average approach, an ensemble model was able to identify an expert surgeon with 83.8% accuracy using a validation dataset. Conclusions: Our results demonstrate that each surgeon has a unique force profile amenable to identification using deep learning methods. We anticipate our models will enable a quantitative framework to provide bespoke feedback to surgeons and to track their skill progression longitudinally. Furthermore, the ability to recognize individual surgeons introduces the mechanism of correlating outcome to surgeon performance.

Dual-targeted transferrin and AS1411 aptamer conjugated micelles for improved therapeutic efficacy and imaging of brain cancer.

Brain tumors represent an aggressive form of cancer, posing significant challenges in achieving complete remission. Development of advanced therapies is crucial for improving clinical outcomes in cancer patients. This study aimed to create a novel treatment approach using dual-targeted transferrin (TF) and AS1411 conjugated micelles, designed to enhance therapeutic effectiveness of docetaxel (DTX) and facilitate gadolinium (Gd) based imaging in brain cancer. Micelles were prepared using a slightly modified solvent-casting method, and the dual-targeting ligands were attached to the micelle's surface through a physical adsorption process. Average particle size of micelles ranged from 117.49 ± 3.90-170.38 ± 3.39 nm, with a low polydispersity index. Zeta potential ranged from - 1.5 ± 0.02 to - 18.7 ± 0.04 mV. Encapsulation efficiency of DTX in micelles varied from 92.64 ± 4.22-79.77 ± 4.13 %. Simultaneously, encapsulation of Gd in micelles was found to be 48.27 ± 3.18-58.52 ± 3.17, respectively. In-vitro drug release studies showed a biphasic sustained release profile, with DTX and Gd release continuing up to 72 h with their t50 % at 4.95, 11.29, and 24.14 h for GDTP, GDTP-TF and GDTP-TF-AS1411 micelles, respectively. Cytotoxicity effect of GDTP-TF-AS1411 micelles has shown significant improvement (P < 0.001) and reduced IC50 value up to 0.19 ± 0.14 µg/ml compared to Taxotere® (2.73 ± 0.73 µg/ml). Theranostic study revealed higher accumulation of GDTP-TF and GDTP-TF-AS1411 micelles free GD treated animal brains. The AUC of GDTP-TF-AS1411 micelles exhibited 23.79 ± 17.82 µg.h/ml higher than Taxotere® (14.14 ± 10.59 µg.h/ml). These findings direct enhanced effectiveness in brain cancer therapy leading to improved therapeutics in brain cancer patients. The combined targeted ligands and therapeutic agents strategy can direct advancement in brain cancer therapy and offer improved therapy for patients.

Structural-Based Virtual Screening of FDA-Approved Drugs Repository for NSP16 Inhibitors, Essential for SARS-COV-2 Invasion Into Host Cells: Elucidation From MM/PBSA Calculation.

NSP16 is one of the structural proteins of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) necessary for its entrance to the host cells. It exhibits 2'O-methyl-transferase (2'O-MTase) activity of NSP16 using methyl group from S-adenosyl methionine (SAM) by methylating the 5-end of virally encoded mRNAs and shields viral RNA, and also controls its replication as well as infection. In the present study, we used in silico approaches of drug repurposing to target and inhibit the SAM binding site in NSP16 using Food and Drug Administration (FDA)-approved small molecules set from Drug Bank database. Among the 2 456 FDA-approved molecules, framycetin, paromomycin, and amikacin were found to be significant binders against the SAM binding cryptic pocket of NSP16 with docking score of -13.708, -14.997 and -15.841 kcal/mol, respectively. Classical molecular dynamics (MD) simulation and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA)-based binding free energy calculation depicted that all these three framycetin, paromomycin, and amikacin might be promising therapeutic leads towards SARS-CoV-2 infections via host immune escape inhibition pathway.