UNETR++: Delving into Efficient and Accurate 3D Medical Image Segmentation.

Owing to the success of transformer models, recent works study their applicability in 3D medical segmentation tasks. Within the transformer models, the self-attention mechanism is one of the main building blocks that strives to capture long-range dependencies, compared to the local convolutional-based design. However, the self-attention operation has quadratic complexity which proves to be a computational bottleneck, especially in volumetric medical imaging, where the inputs are 3D with numerous slices. In this paper, we propose a 3D medical image segmentation approach, named UNETR++, that offers both high-quality segmentation masks as well as efficiency in terms of parameters, compute cost, and inference speed. The core of our design is the introduction of a novel efficient paired attention (EPA) block that efficiently learns spatial and channel-wise discriminative features using a pair of inter-dependent branches based on spatial and channel attention. Our spatial attention formulation is efficient and has linear complexity with respect to the input. To enable communication between spatial and channel-focused branches, we share the weights of query and key mapping functions that provide a complimentary benefit (paired attention), while also reducing the complexity. Our extensive evaluations on five benchmarks, Synapse, BTCV, ACDC, BraTS, and Decathlon-Lung, reveal the effectiveness of our contributions in terms of both efficiency and accuracy. On Synapse, our UNETR++ sets a new state-of-the-art with a Dice Score of 87.2%, while significantly reducing parameters and FLOPs by over 71%, compared to the best method in the literature. Our code and models are available at: https://tinyurl.com/2p87x5xn.

Ferroptosis targeting natural compounds as a promising approach for developing potent liver cancer agents.

Liver cancer is the second leading cause of cancer-related death worldwide. However, treatment options, including surgical resection, transplantation, and molecular drug therapies, are of limited effectiveness. Recent studies have demonstrated that suppressing ferroptosis might be a pivotal signal for liver cancer initiation, thus providing a new way to combat liver cancer. Ferroptosis is a distinct form of controlled cell death that differs from conventional cell death routes like apoptosis, necrosis, and pyroptosis. It results from intracellular iron overload, which raises iron-dependent reactive oxygen species. This, in turn, leads to the accumulation of lipid peroxides that further result in oxidative damage to cell membranes, disrupt normal functioning, and ultimately speed up the ferroptosis phenomenon. Ferroptosis regulation is intricately linked to cellular physiological processes, encompassing iron metabolism, lipid metabolism, and the equilibrium between oxygen-free radical reactions and lipid peroxidation. This review intends to summarize the natural compounds targeting ferroptosis in liver cancer to offer new therapeutic ideas for liver cancer. Furthermore, it serves as the foundation for identifying and applying chemical medicines and natural chemicals that target ferroptosis to treat liver cancer efficiently.

Evaluating Catheter Ablation Versus Conventional Management for Ventricular Arrhythmias in Arrhythmogenic Right Ventricular Cardiomyopathy: A Five-Year Retrospective Cohort Study.

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a challenging genetic disorder marked by ventricular arrhythmias and sudden cardiac death, particularly in athletes and young adults. Despite its clinical significance, the relative effectiveness and safety of catheter ablation versus conventional management in ARVC are not fully delineated. Objective This study evaluates the efficacy and safety of catheter ablation compared to conventional management in reducing ventricular arrhythmias and improving patient outcomes over five years in ARVC patients. Methods In a retrospective cohort design at Lady Reading Hospital, Peshawar, we analyzed 120 ARVC patients from January 2018 to December 2023. Patients were divided into two groups: those undergoing catheter ablation and those receiving conventional management. Primary outcomes assessed were recurrence of ventricular arrhythmias, procedural complications, hospitalization duration, and mortality rates. Logistic regression was adjusted for demographics and clinical variables. Results Catheter ablation significantly lowered the recurrence of ventricular arrhythmias (20% vs. 55%, p<0.01) and reduced hospital stay duration (4 ± 2 days vs. 7 ± 3 days, p<0.05). A trend toward reduced five-year mortality was observed in the catheter ablation group (5% vs. 15%, p=0.07). Age, New York Heart Association class, and exercise capacity emerged as significant predictors of outcomes. Conclusions Catheter ablation outperforms conventional management in reducing the recurrence of ventricular arrhythmias and hospitalization in ARVC patients, with a promising trend toward enhanced survival. These findings advocate for personalized management strategies in ARVC, highlighting the necessity for further research to establish the long-term benefits of catheter ablation.

Learnable weight initialization for volumetric medical image segmentation.

Hybrid volumetric medical image segmentation models, combining the advantages of local convolution and global attention, have recently received considerable attention. While mainly focusing on architectural modifications, most existing hybrid approaches still use conventional data-independent weight initialization schemes which restrict their performance due to ignoring the inherent volumetric nature of the medical data. To address this issue, we propose a learnable weight initialization approach that utilizes the available medical training data to effectively learn the contextual and structural cues via the proposed self-supervised objectives. Our approach is easy to integrate into any hybrid model and requires no external training data. Experiments on multi-organ and lung cancer segmentation tasks demonstrate the effectiveness of our approach, leading to state-of-the-art segmentation performance. Our proposed data-dependent initialization approach performs favorably as compared to the Swin-UNETR model pretrained using large-scale datasets on multi-organ segmentation task. Our source code and models are available at: https://github.com/ShahinaKK/LWI-VMS.

The Impact of Age, Comorbidities, and Discharge Timing on Clinical Outcomes Following Elective Percutaneous Coronary Intervention.

Background The adoption of same-day discharge (SDD) in elective percutaneous coronary intervention (PCI) procedures offers potential benefits in terms of patient satisfaction and reduced healthcare costs. Despite these advantages, the safety and efficacy of SDD, especially among patients with diverse health profiles, are not fully understood. This study investigates the effects of patient-specific factors, including age, comorbidities, and discharge timing, on the clinical outcomes of elective PCI, focusing on the viability of SDD. Methods A prospective study was carried out at Lady Reading Hospital, Peshawar, Pakistan, involving 220 patients undergoing elective PCI from January to June 2023. This research compared the clinical outcomes of patients discharged on the same day with those who had extended hospital stays, examining the impact of age, comorbidities, and PCI success. Main outcome measures included post-procedure complications and hospital readmissions within 30 days. Results The study enrolled participants with an average age of 62 years, the majority (88%, n=194/220) of whom had comorbidities. Interestingly, 16% (n=35/220) of the participants were discharged on the same day, while the rest stayed longer in the hospital. Notably, those in the SDD group experienced significantly more complications and readmissions, with 95.14% (n=33/36) compared to only 16.22% (n=30/184) in their counterparts. Factors such as age, comorbidities, success of PCI, timing of discharge, and patient satisfaction emerged as significant predictors of the observed outcomes. Conclusion This study highlights the essential role of personalized care in discharge planning following elective PCI, advocating for a cautious approach towards SDD, especially for older patients and those with multiple health issues.

Review Deciphering the Potential of Nanotherapeutics in Lung Cancer Management.

Lung cancer remains a formidable challenge in oncology, necessitating the develop-ment of more effective prognostic and diagnostic techniques due to inefficient conventional therapeutic approaches and inadequate methods for early lung cancer diagnosis. Despite im-mense progress in the development of innovative strategies to alleviate the impact of this devas-tating disease, the outcomes, unfortunately, remain unsatisfactory, particularly in targeted drug delivery methods. Consequently, nanotechnology has emerged as a revolutionary force in cancer research to develop more effective targeted drug delivery tools due to its extraordinary capacity at the atomic and molecular levels. It has appeared as a beacon of hope in this area of unmet need, providing innovative ways for the prognosis and diagnosis of lung carcinoma. Therefore, this comprehensive review delves into the evolving field of nano-based therapeutics, shedding light on their potential to transform lung cancer treatment. This study meticulously explores the most promising nano-based strategies that have been extensively linked with the treatment of lung carcinoma and mainly emphasizes targeted drug delivery methods and therapies. Addition-ally, this review encapsulates the favorable results of clinical trials, which support the potential pathways for further development of nanotherapeutics in lung cancer management.

Emerging trends of phytochemicals as ferroptosis modulators in cancer therapy.

Ferroptosis, a novel form of regulated cell death characterized by dependence on iron and lipid peroxidation, has been implicated in a wide range of clinical conditions including neurological diseases, cardiovascular disorders, acute kidney failure, and various types of cancer. Therefore, it is critical to suppress cancer progression and proliferation. Ferroptosis can be triggered in cancer cells and some normal cells by synthetic substances, such as erastin, Ras-selective lethal small molecule-3, or clinical pharmaceuticals. Natural bioactive compounds are traditional drug discovery tools, and some have been therapeutically used as dietary additives or pharmaceutical agents against various malignancies. The fact that natural products have multiple targets and minimal side effects has led to notable advances in anticancer research. Research has indicated that ferroptosis can also be induced by natural compounds during cancer treatment. In this review, we focused on the most recent developments in emerging molecular processes and the significance of ferroptosis in cancer. To provide new perspectives on the future development of ferroptosis-related anticancer medications, we also provide a summary of the implications of natural phytochemicals in triggering ferroptosis through ROS production and ferritinophagy induction in a variety of malignancies.

Evaluating the Differential Risk of Contrast-Induced Nephropathy Among Diabetic and Non-diabetic Patients Following Percutaneous Coronary Intervention.

Background Contrast-induced nephropathy (CIN) significantly complicates percutaneous coronary intervention (PCI), with a higher prevalence in diabetic patients. This study compares the incidence of CIN in diabetic and non-diabetic patients undergoing PCI. Material and methods Conducted at Lady Reading Hospital, Peshawar, PAK, from January to December 2023, this observational study involved 450 adult patients with coronary artery disease (CAD) undergoing PCI. The cohort was categorized based on diabetes status, excluding patients with chronic kidney disease and those on renal replacement therapy. Baseline characteristics documented included age, gender, blood pressure, creatinine levels, and the presence of acute coronary syndrome (ACS). CIN was defined as a ≥25% increase in serum creatinine from baseline within 48-72 hours post-PCI. Data analysis was performed using the Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 25.0, Armonk, NY), incorporating descriptive statistics, Chi-square tests, and independent t-tests, with a significance level of p<0.05. Results The median age of the study population was 55 years. The cohort comprised 52% male (n=234) and 48% female (n=216). Notably, 33% (n=149) had ACS. Diabetic patients exhibited a significantly higher incidence of CIN post-PCI compared to non-diabetics. The highest incidence of CIN (17%, n=77) occurred in the 70+ age group. The findings highlight the criticality of renal function monitoring and procedural adjustments for diabetic patients. Conclusion Diabetic patients demonstrate an increased risk of CIN following PCI. This necessitates the development of tailored prevention strategies for this high-risk subgroup.

A mechanistic review of the pharmacological potential of narirutin: a dietary flavonoid.

Flavanones, a type of polyphenol, are found in substantial amounts in citrus fruits. When high- or moderate-dose orange juice consumption occurs, flavanones make up a significant portion of the total polyphenols in plasma. Disaccharide derivative narirutin, mainly dihydroxy flavanone, is found in citrus fruits. The substantial chemotherapeutic potential of narirutin has been amply demonstrated by numerous experimental studies. Consequently, the purpose of this study is to compile the research that has already been done showing narirutin to be a promising anticancer drug, with its mechanism of action being documented in treatment plans for various cancer forms. Narirutin functions in a variety of cancer cells by regulating several pathways that include cell cycle arrest, apoptosis, antiangiogenic, antimetastatic, and DNA repair. Narirutin has been shown to modify many molecular targets linked to the development of cancer, including drug transporters, cell cycle mediators, transcription factors, reactive oxygen species, reactive nitrogen species, and inflammatory cytokines. Taken together, these reviews offer important new information about narirutin's potential as a potent and promising drug candidate for use in medicines, functional foods, dietary supplements, nutraceuticals, and other products targeted at improving the treatment of cancer.

Terpenoid-Mediated Targeting of STAT3 Signaling in Cancer: An Overview of Preclinical Studies.

Cancer has become one of the most multifaceted and widespread illnesses affecting human health, causing substantial mortality at an alarming rate. After cardiovascular problems, the condition has a high occurrence rate and ranks second in terms of mortality. The development of new drugs has been facilitated by increased research and a deeper understanding of the mechanisms behind the emergence and advancement of the disease. Numerous preclinical and clinical studies have repeatedly demonstrated the protective effects of natural terpenoids against a range of malignancies. Numerous potential bioactive terpenoids have been investigated in natural sources for their chemopreventive and chemoprotective properties. In practically all body cells, the signaling molecule referred to as signal transducer and activator of transcription 3 (STAT3) is widely expressed. Numerous studies have demonstrated that STAT3 regulates its downstream target genes, including Bcl-2, Bcl-xL, cyclin D1, c-Myc, and survivin, to promote the growth of cells, differentiation, cell cycle progression, angiogenesis, and immune suppression in addition to chemotherapy resistance. Researchers viewed STAT3 as a primary target for cancer therapy because of its crucial involvement in cancer formation. This therapy primarily focuses on directly and indirectly preventing the expression of STAT3 in tumor cells. By explicitly targeting STAT3 in both in vitro and in vivo settings, it has been possible to explain the protective effect of terpenoids against malignant cells. In this study, we provide a complete overview of STAT3 signal transduction processes, the involvement of STAT3 in carcinogenesis, and mechanisms related to STAT3 persistent activation. The article also thoroughly summarizes the inhibition of STAT3 signaling by certain terpenoid phytochemicals, which have demonstrated strong efficacy in several preclinical cancer models.

Multiparametric Radiogenomic Model to Predict Survival in Patients with Glioblastoma.

BACKGROUND: Clinical, histopathological, and imaging variables have been associated with prognosis in patients with glioblastoma (GBM). We aimed to develop a multiparametric radiogenomic model incorporating MRI texture features, demographic data, and histopathological tumor biomarkers to predict prognosis in patients with GBM. METHODS: In this retrospective study, patients were included if they had confirmed diagnosis of GBM with histopathological biomarkers and pre-operative MRI. Tumor segmentation was performed, and texture features were extracted to develop a predictive radiomic model of survival (<18 months vs. ≥18 months) using multivariate analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regularization to reduce the risk of overfitting. This radiomic model in combination with clinical and histopathological data was inserted into a backward stepwise logistic regression model to assess survival. The diagnostic performance of this model was reported for the training and external validation sets. RESULTS: A total of 116 patients were included for model development and 40 patients for external testing validation. The diagnostic performance (AUC/sensitivity/specificity) of the radiomic model generated from seven texture features in determination of ≥18 months survival was 0.71/69.0/70.3. Three variables remained as independent predictors of survival, including radiomics (p = 0.004), age (p = 0.039), and MGMT status (p = 0.025). This model yielded diagnostic performance (AUC/sensitivity/specificity) of 0.77/81.0/66.0 (training) and 0.89/100/78.6 (testing) in determination of survival ≥ 18 months. CONCLUSIONS: Results show that our radiogenomic model generated from radiomic features at baseline MRI, age, and MGMT status can predict survival ≥ 18 months in patients with GBM.

Burst Image Restoration and Enhancement.

Burst Image Restoration aims to reconstruct a high-quality image by efficiently combining complementary inter-frame information. However, it is quite challenging since individual burst images often have inter-frame misalignments that usually lead to ghosting and zipper artifacts. To mitigate this, we develop a novel approach for burst image processing named BIPNet that focuses solely on the information exchange between burst frames and filter-out the inherent degradations while preserving and enhancing the actual scene details. Our central idea is to generate a set of pseudo-burst features that combine complementary information from all the burst frames to exchange information seamlessly. However, due to inter-frame misalignment, the information cannot be effectively combined in pseudo-burst. Thus, we initially align the incoming burst features regarding the reference frame using the proposed edge-boosting feature alignment. Lastly, we progressively upscale the pseudo-burst features in multiple stages while adaptively combining the complementary information. Unlike the existing works, that usually deploy single-stage up-sampling with a late fusion scheme, we first deploy a pseudo-burst mechanism followed by the adaptive-progressive feature up-sampling. The proposed BIPNet significantly outperforms the existing methods on burst super-resolution, low-light image enhancement, low-light image super-resolution, and denoising tasks. The pre-trained models and source code are available at https://github.com/akshaydudhane16/BIPNet.

Study Deciphering the Crucial Involvement of Notch Signaling Pathway in Human Cancers.

In recent years, dysregulation of the notch pathway has been associated with the development and progression of various cancers. Notch signaling is involved in several cellular processes such as proliferation, differentiation, apoptosis, and angiogenesis, and its abnormal activation can lead to uncontrolled cell growth and tumorigenesis. In various cancers, the Notch pathway has been shown to have both tumor-promoting and tumor-suppressive effects, depending on the context and stage of cancer development. In some cases, activation of the Notch pathway has been shown to promote tumor growth and progression, while in others it has been shown to inhibit tumor growth and induce cell death. The Notch pathway has been found to be particularly important in the development of leukaemia, breast cancer, lung cancer and pancreatic cancer. In leukaemia, the Notch pathway is often activated, which promotes the survival and proliferation of leukaemia cells. In breast cancer, Notch signaling has been implicated in tumor initiation and maintenance of cancer stem cells. In cervical cancer, the Notch signaling pathway has been shown to play a crucial role in the development of the disease. In lung cancer, Notch activation promotes cancer cell proliferation and migration, while in pancreatic cancer, Notch signaling is associated with tumor initiation and resistance to chemotherapy. Understanding the role of the Notch pathway in cancer development and progression may provide new opportunities for the development of targeted therapies for cancer treatment. Several drugs targeting the Notch pathway are currently in preclinical or clinical development and may hold promise for anticancer therapy in the future.

A Case of Bilateral Hyperglycemic Nonketotic Chorea in an 83-year-old Woman With Normal Brain Imaging.

Bilateral hyperglycemic nonketotic chorea is a rare complication of hyperglycemia. In most cases, the literature illustrates patients presenting with unilateral chorea with image findings significant for hyperintense lesions in the basal ganglia on magnetic resonance imaging (MRI) or hyperdensities on computerized tomography (CT). Here, we present a case of an 83-year-old patient who was admitted to the hospital due to acute onset of orofacial and bilateral upper extremity chorea. She had no previous history of infection, genetic mutation, neoplasms, neurodegeneration, stroke, metabolic disease, drug exposure, or autoimmune disease. Surprisingly, her MRI showed only chronic microvascular changes in periventricular white matter without basal ganglia abnormalities. However, she was noted to have marked worsening of her glycemic control over the preceding 12 months based on worsening glycated hemoglobin (HbA1c) levels and elevated serum glucose on presentation. A literature review indicates that chorea caused by hyperglycemia is at times reversible with glycemic control, but as demonstrated in our patient, this is not always necessarily the case. A similar course has only been elaborated in a few other cases in the literature. We will also review the pathogenesis, the usual disease clinical course and standard treatment from the literature.

Hybrids of Benzimidazole-Oxadiazole: A New Avenue for Synthesis, Pharmacological Activity and Recent Patents for the Development of More Effective Ligands.

BACKGROUND: Two significant families of compounds i.e. 1,3,4-oxadiazole and ben-zimidazole, have undergone extensive investigation into their pharmacological characteristics and possible therapeutic applications. Both classes have shown their potential in a variety of ap-plications, and because of their synergistic interactions, they may have an even better therapeutic impact when combined. OBJECTIVES: To produce a specific molecule with potent therapeutic properties, it is now common methods to combine at least two pharmacophores. This facilitates interaction with several targets, enhances biological functions, or eliminates adverse effects associated with them. CONCLUSION: The synthesis of benzimidazole-1,3,4-oxadiazole hybrid compounds has recently involved the use of several synthetic techniques, all of which are detailed in the literature along with the advantages and disadvantages. It has been noted that the structure-activity relationship relates their pharmacological actions to their molecular structure. In order to set the stage for future research, the study aims to provide researchers with an effective toolbox and an under-standing of benzimidazole and 1,3,4-oxadiazole hybrid compounds.

Review Deciphering the Anticancer Efficacy of Resveratrol and their Associated Mechanisms in Human Carcinoma.

The scientific world has recently shown wider attention to elucidating the anticancerous potential of numerous plant-based bioactive compounds. Many research studies have suggested that consuming foods high in polyphenols, which are present in large amounts in grains, legumes, vegetables, and fruits, may delay the onset of various illnesses, including cancer. Normal cells with genetic abnormalities begin the meticulously organized path leading to cancer, which causes the cells to constantly multiply, colonize, and metastasize to other organs like the liver, lungs, colon, and brain. Resveratrol is a naturally occurring stilbene and non-flavonoid polyphenol, a phytoestrogen with antioxidant, anti-inflammatory, cardioprotective, and anticancer properties. Resveratrol makes cancer cells more susceptible to common chemotherapeutic treatments by reversing multidrug resistance in cancer cells. This is especially true when combined with clinically used medications. Several new resveratrol analogs with enhanced anticancer effectiveness, absorption, and pharmacokinetic profile have been discovered. The present emphasis of this review is the modulation of intracellular molecular targets by resveratrol in vivo and in vitro in various malignancies. This review would help future researchers develop a potent lead candidate for efficiently managing human cancers.

SipMaskv2: Enhanced Fast Image and Video Instance Segmentation.

We propose a fast single-stage method for both image and video instance segmentation, called SipMask, that preserves the instance spatial information by performing multiple sub-region mask predictions. The main module in our method is a light-weight spatial preservation (SP) module that generates a separate set of spatial coefficients for the sub-regions within a bounding-box, enabling a better delineation of spatially adjacent instances. To better correlate mask prediction with object detection, we further propose a mask alignment weighting loss and a feature alignment scheme. In addition, we identify two issues that impede the performance of single-stage instance segmentation and introduce two modules, including a sample selection scheme and an instance refinement module, to address these two issues. Experiments are performed on both image instance segmentation dataset MS COCO and video instance segmentation dataset YouTube-VIS. On MS COCO test-dev set, our method achieves a state-of-the-art performance. In terms of real-time capabilities, it outperforms YOLACT by a gain of 3.0% (mask AP) under the similar settings, while operating at a comparable speed. On YouTube-VIS validation set, our method also achieves promising results. The source code is available at https://github.com/JialeCao001/SipMask.

Insights on the Correlation between Mitochondrial Dysfunction and the Progression of Parkinson's Disease.

The aetiology of a progressive neuronal Parkinson's disease has been discussed in several studies. However, due to the multiple risk factors involved in its development, such as environmental toxicity, parental inheritance, misfolding of protein, ageing, generation of reactive oxygen species, degradation of dopaminergic neurons, formation of neurotoxins, mitochondria dysfunction, and genetic mutations, its mechanism of involvement is still discernible. Therefore, this study aimed to review the processes or systems that are crucially implicated in the conversion of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) into its lethal form, which directly blockades the performance of mitochondria, leading to the formation of oxidative stress in the dopaminergic neurons of substantia nigra pars compacta (SNpc) and resulting in the progression of an incurable Parkinson's disease. This review also comprises an overview of the mutated genes that are frequently associated with mitochondrial dysfunction and the progression of Parkinson's disease. Altogether, this review would help future researchers to develop an efficient therapeutic approach for the management of Parkinson's disease via identifying potent prognostic and diagnostic biomarkers.

Role of Actin Dynamics and GhACTIN1 Gene in Cotton Fiber Development: A Prototypical Cell for Study.

Cotton crop is considered valuable for its fiber and seed oil. Cotton fiber is a single-celled outgrowth from the ovule epidermis, and it is a very dynamic cell for study. It has four distinct but overlapping developmental stages: initiation, elongation, secondary cell wall synthesis, and maturation. Among the various qualitative characteristics of cotton fiber, the important ones are the cotton fiber staple length, tensile strength, micronaire values, and fiber maturity. Actin dynamics are known to play an important role in fiber elongation and maturation. The current review gives an insight into the cotton fiber developmental stages, the qualitative traits associated with cotton fiber, and the set of genes involved in regulating these developmental stages and fiber traits. This review also highlights some prospects for how biotechnological approaches can improve cotton fiber quality.