Cross-attention-based saliency inference for predicting cancer metastasis on whole slide images.

Although multiple instance learning (MIL) methods are widely used for automatic tumor detection on whole slide images (WSI), they suffer from the extreme class imbalance WSIs containing small tumors where the tumor may include only a few isolated cells. For early detection, it is important that MIL algorithms can identify small tumors. Existing studies have attempted to address this issue using attention-based architectures and instance selection-based methodologies but have not produced significant improvements. This paper proposes crossattention-based salient instance inference MIL (CASiiMIL), which involves a novel saliency-informed attention mechanism to identify small tumors (e.g., breast cancer lymph node micro-metastasis) on WSIs without needing any annotations. In addition to this new attention mechanism, we introduce a negative representation learning algorithm to facilitate the learning of saliencyinformed attention weights for improved sensitivity on tumor WSIs. The proposed model outperforms the state-ofthe-art MIL methods on two popular tumor metastasis detection datasets. The proposed approach demonstrates great cross-center generalizability, high accuracy in classifying WSIs with small tumor lesions, and excellent interpretability attributed to the saliency-informed attention weights. We expect that the proposed method will pave the way for training algorithms for early tumor detection on large datasets where acquiring fine-grained annotations is is not practical.

Advancements in application of modified biochar as a green and low-cost adsorbent for wastewater remediation from organic dyes.

Synthetic organic dyes, which are resistant to biodegradation, pose a notable health risk, potentially leading to cancer and respiratory infections. Researchers have addressed this concern by exploring physicochemical methods to remove organic dyes from wastewater. A particularly promising solution involves modified biochar adsorbents, which demonstrate high efficiency in organic dye removal. Biochar, a charcoal-like material derived from biomass pyrolysis, offers advantages such as low cost, eco-friendliness, high efficiency and reusability. Beyond its role in sustainable soil remediation, biochar proves effective in removing organic dyes from wastewater after undergoing physical or chemical modification. Acid-base activation or metal-heteroatom impregnation enhances biochar's adsorption capacity. This comprehensive review examines the attributes of biochar, common methods for production and modification, and the impacts of raw materials, pyrolysis temperature, heating rate and residence time. It further elucidates the biochar adsorption mechanism in the removal of organic dyes, assessing factors influencing efficiency, including biochar feedstock, solution pH, adsorption temperature, particle size, initial dye concentration, biochar dosage and reaction time. It explores challenges, opportunities, reusability and regeneration methods of biochar in treating organic dye wastewater. It also discusses recent advances in organic dye removal using adsorption-based biochar. The review ultimately advocates for enhancing biochar's adsorption performance through post-modification.

Cardiomegaly: Navigating the uncharted territories of heart failure - A multimodal radiological journey through advanced imaging, pathophysiological landscapes, and innovative therapeutic frontiers.

Cardiomegaly is among the disorders categorized by a structural enlargement of the heart by any of the situations including pregnancy, resulting in damage to heart muscles and causing trouble in normal heart functioning. Cardiomegaly can be defined in terms of dilatation with an enlarged heart and decreased left or biventricular contraction. The genetic origin of cardiomegaly is becoming more evident due to extensive genomic research opening up new avenues to ensure the use of precision medicine. Cardiomegaly is usually assessed by using an array of radiological modalities, including computed tomography (CT) scans, chest X-rays, and MRIs. These imaging techniques have provided an important opportunity for the physiology and anatomy of the heart. This review aims to highlight the complexity of cardiomegaly, highlighting the contribution of both ecological and genetic variables to its progression. Moreover, we further highlight the worth of precise clinical diagnosis, which comprises blood biomarkers and electrocardiograms (EKG ECG), demonstrating the significance of distinguishing between numerous basic causes. Finally, the analysis highlights the extensive variation of treatment lines, such as lifestyle modifications, prescription drugs, surgery, and implantable devices, although highlighting the critical need for individualized and personalized care.

B cells in perivascular and peribronchiolar granuloma-associated lymphoid tissue and B-cell signatures identify asymptomatic Mycobacterium tuberculosis lung infection in Diversity Outbred mice.

Because most humans resist Mycobacterium tuberculosis infection, there is a paucity of lung samples to study. To address this gap, we infected Diversity Outbred mice with M. tuberculosis and studied the lungs of mice in different disease states. After a low-dose aerosol infection, progressors succumbed to acute, inflammatory lung disease within 60 days, while controllers maintained asymptomatic infection for at least 60 days, and then developed chronic pulmonary tuberculosis (TB) lasting months to more than 1 year. Here, we identified features of asymptomatic M. tuberculosis infection by applying computational and statistical approaches to multimodal data sets. Cytokines and anti-M. tuberculosis cell wall antibodies discriminated progressors vs controllers with chronic pulmonary TB but could not classify mice with asymptomatic infection. However, a novel deep-learning neural network trained on lung granuloma images was able to accurately classify asymptomatically infected lungs vs acute pulmonary TB in progressors vs chronic pulmonary TB in controllers, and discrimination was based on perivascular and peribronchiolar lymphocytes. Because the discriminatory lesion was rich in lymphocytes and CD4 T cell-mediated immunity is required for resistance, we expected CD4 T-cell genes would be elevated in asymptomatic infection. However, the significantly different, highly expressed genes were from B-cell pathways (e.g., Bank1, Cd19, Cd79, Fcmr, Ms4a1, Pax5, and H2-Ob), and CD20+ B cells were enriched in the perivascular and peribronchiolar regions of mice with asymptomatic M. tuberculosis infection. Together, these results indicate that genetically controlled B-cell responses are important for establishing asymptomatic M. tuberculosis lung infection.

Predicting response to neoadjuvant chemotherapy for colorectal liver metastasis using deep learning on prechemotherapy cross-sectional imaging.

BACKGROUND AND OBJECTIVES: Deep learning models (DLMs) are applied across domains of health sciences to generate meaningful predictions. DLMs make use of neural networks to generate predictions from discrete data inputs. This study employs DLM on prechemotherapy cross-sectional imaging to predict patients' response to neoadjuvant chemotherapy. METHODS: Adult patients with colorectal liver metastasis who underwent surgery after neoadjuvant chemotherapy were included. A DLM was trained on computed tomography images using attention-based multiple-instance learning. A logistic regression model incorporating clinical parameters of the Fong clinical risk score was used for comparison. Both model performances were benchmarked against the Response Evaluation Criteria in Solid Tumors criteria. A receiver operating curve was created and resulting area under the curve (AUC) was determined. RESULTS: Ninety-five patients were included, with 33,619 images available for study inclusion. Ninety-five percent of patients underwent 5-fluorouracil-based chemotherapy with oxaliplatin and/or irinotecan. Sixty percent of the patients were categorized as chemotherapy responders (30% reduction in tumor diameter). The DLM had an AUC of 0.77. The AUC for the clinical model was 0.41. CONCLUSIONS: Image-based DLM for prediction of response to neoadjuvant chemotherapy in patients with colorectal cancer liver metastases was superior to a clinical-based model. These results demonstrate potential to identify nonresponders to chemotherapy and guide select patients toward earlier curative resection.

Comparing the differences in quality profiles and antioxidant activity in seven pumpkin cultivars (Cucurbita moschata and Cucurbita maxima) at harvest and during postharvest storage.

Pumpkin, nutritious vegetable, is renowned for its extended shelf life. In this study, seven pumpkin cultivars from Cucurbita moschata and Cucurbita maxima were comparatively characterized for 25 physiochemical quality factors, starch granule structures, antioxidant activity, and correlations at 0-60 days of postharvest (dop). The findings revealed that sucrose and carotenoid contents increased in C. moschata, while they initially increased and then decreased in C. maxima. Additionally, acidity, primarily driven by malic acid, decreased in C. maxima but increased in C. maxima. The starch content of C. moschata and C. maxima reached its maximum value at 30 dop and 20 dop, respectively. The DPPH radical scavenging activity correlated with the carotenoid content in both pumpkin species. Conclusively, C. moschata demonstrated improved nutritional and quality at 20-30 dop, while C. maxima exhibited higher commercial suitability at 10-20 dop. The findings suggested that pumpkin storage was crucial for quality improvement.

Fixation of the proximal flange of a lumen-apposing metal stent using a through-the-scope endoscopic suturing system to prevent stent migration in single-session EUS-directed transgastric ERCP: a pilot study.

BACKGROUND AND AIMS: With the global obesity pandemic, clinical scenarios requiring urgent ERCP in patients with gastric bypass surgery are on the rise, and single-session EUS-directed transgastric ERCP (SS-EDGE) can effectively address these technical challenges. The aim of this study was to evaluate and describe the safe and effective use of a through-the-scope endoscopic suturing system for anchoring the lumen-apposing metal stents (LAMSs) during SS-EDGE. METHODS: Six patients with Roux-en-Y gastric bypass (RYGB) underwent SS-EDGE at our center. A through-the-scope endoscopic suturing system was used for anchoring the LAMSs during SS-EDGE. RESULTS: Clinical and technical success was achieved in all 6 patients without any adverse events related to the procedure. No stent migration, pneumoperitoneum, or GI perforation was noted. At the 4-week follow-up, no stent migration was noted, and the through-the-scope suturing system remained anchored. LAMSs along with tacks were removed, and gastric fistulae were successfully closed endoscopically in all patients to prevent weight gain. CONCLUSIONS: Use of through-the-scope endoscopic suturing can be a safe, reliable, and potentially cost-effective novel technique for LAMS fixation to successfully perform SS-EDGE in RYGB patients.

Invited review: Camel milk-derived bioactive peptides and diabetes-Molecular view and perspectives.

In dairy science, camel milk (CM) constitutes a center of interest for scientists due to its known beneficial effect on diabetes as demonstrated in many in vitro, in vivo, and clinical studies and trials. Overall, CM had positive effects on various parameters related to glucose transport and metabolism as well as the structural and functional properties of the pancreatic ß-cells and insulin secretion. Thus, CM consumption may help manage diabetes; however, such a recommendation will become rationale and clinically conceivable only if the exact molecular mechanisms and pathways involved at the cellular levels are well understood. Moreover, the application of CM as an alternative antidiabetic tool may first require the identification of the exact bioactive molecules behind such antidiabetic properties. In this review, we describe the advances in our knowledge of the molecular mechanisms reported to be involved in the beneficial effects of CM in managing diabetes using different in vitro and in vivo models. This mainly includes the effects of CM on the different molecular pathways controlling (1) insulin receptor signaling and glucose uptake, (2) the pancreatic ß-cell structure and function, and (3) the activity of key metabolic enzymes in glucose metabolism. Moreover, we described the current status of the identification of CM-derived bioactive peptides and their structure-activity relationship study and characterization in the context of molecular markers related to diabetes. Such an overview will not only enrich our scientific knowledge of the plausible mode of action of CM in diabetes but should ultimately rationalize the claim of the potential application of CM against diabetes. This will pave the way toward new directions and ideas for developing a new generation of antidiabetic products taking benefits from the chemical composition of CM.

Frequency of Urinary Tract Infection Among Patients Undergoing Implant Fixation for Acute Trauma.

OBJECTIVE: This study aims to determine the frequency of urinary tract infection (UTI), identify the isolated bacteria, and assess antibiotic sensitivity in patients undergoing orthopedic implant fixation for hip fractures. METHODOLOGY: After ethical approval from the institutional review board, this retrospective cross-sectional study was conducted at the Orthopedic Surgery Department of Dow University Hospital Karachi from June 2022 to June 2023. Through non-probability consecutive sampling, 186 patients above 16 years of age, of either gender, presenting with hip fractures such as intracapsular or extracapsular fractures, who underwent surgical fixation, were included in the study. A urine sample for urinalysis of these patients was sent on admission. Patients who presented with open fractures or those treated with conservative management were excluded from the study. The fracture diagnosis was confirmed on radiographs. All other relevant baseline investigations were also performed before surgery, per protocol, and urine-detailed and cultured reports were followed. In addition, each patient was asked about common symptoms of UTI before surgery and then diagnosed with UTI on positive urine culture and sensitivity (CS). RESULTS: Out of 186 hip fracture patients, 98 (52.7%) were males and 88 (47.3%) were females, with a mean age of 61.03 ± 16.43 (16-96) years. Pre-operative UTI symptoms were reported by 79 patients, including dysuria (16; 20.3%), polyuria (19; 24.0%), and burning (44; 55.7%). UTI was diagnosed on culture and sensitivity report in 65 (34.9%) patients with Escherichia coli as commonly diagnosed bacteria 35 (53.8%), followed by Enterococcus 8 (12.4%), Klebsiella 7 (10.9%), Pseudomonas aeruginosa 3 (4.7%), and Acinetobacter 2 (3.1%) patients. E. coli was sensitive to amikacin, amoxicillin/clavulanic acid, ampicillin, cefixime, ceftriaxone, cefuroxime, ciprofloxacin, colistin, cotrimoxazole, fosfomycin, gentamycin, levofloxacin, meropenem, nitrofurantoin, polymyxin B, and piperacillin-tazobactam. CONCLUSION: Urinary tract infection is common in patients undergoing orthopedic implant fixation for hip fractures, which can lead to potentially serious outcomes. Overall, hygiene, prompt treatment, and standard protocol should be utilized to treat those infected and minimize the spread.

Guar gum/poly ethylene glycol/graphene oxide environmentally friendly hybrid hydrogels for controlled release of boron micronutrient.

The present study was aimed at synthesis of polymeric hydrogels for controlled boron (B) release, as B deficiency is a major factor that decreases crops yield. Thus, graphene oxide incorporated guar gum and poly (ethylene glycol) hydrogels were prepared using the Solution Casting method for boron release. 3-Glycidyloxypropyl trimethoxysilane (GLYMOL) was used as a cross-linker. Characterizations of hydrogels were carried out by Fourier Transform Infrared Spectroscopy (FTIR), Thermo-Gravimetric Analysis and Scanning Electron scope. The FTIR outcomes confirmed the existence of functional groups, bindings and development of hydrogel frameworks from incorporated components. The quantity of GLYMOL directly increased the thermal stability and water retention but decreased the swelling %. The maximum swelling for the hydrogel formulations was observed at pH 7. The addition of GLYMOL changed the diffusion from quasi-Fickcian to non-Fickcian diffusion. The maximum swelling quantities of 3822% and 3342% were exhibited by GPP (control) and GPP-8 in distilled water, respectively. Boron release was determined in distilled water and sandy soil by azomethine-H test using UV-Visible spectrophotometer while 85.11% and 73.65% boron was released from BGPP-16, respectively. In short, water retentive, water holding capacities, swelling performances, biodegradability and swelling/deswelling features would offer an ideal platform for boron release in sustained agricultural applications.

Immunostimulant, hepatoprotective, and nephroprotective potential of Bacillus subtilis (NMCC-path-14) in comparison to dexamethasone in alleviating CFA-induced arthritis.

To investigate and compare efficacy as well as safety of Bacillus subtilis and dexamethasone (Dexa) in complete Freund's adjuvant (CFA)-induced arthritis, we used glucocorticoid monotherapy (Dexa 5 mg/kg/day) and B. subtilis (1 × 108 CFU/animal/day p.o) as pre-treatment and concurrent treatment for a duration of 35 days. Specific emphasis was on chronic aspect of this study since long-term use of Dexa is known to produce undesirable side effects. Treatment with Dexa significantly attenuated the arthritic symptoms but produced severe side effects like weight loss, increased mortality, immunosuppression, and altered histology of liver, kidney, and spleen. Oxidative stress was also elevated by Dexa in these organs which contributed to the damage. Treatment with B. subtilis improved symptoms of arthritis without producing any deleterious side effects as seen with Dexa therapy. Immunohistochemistry (IHC) profile revealed decreased expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1ß, tumor necrosis factor alpha (TNF-α), and increased nuclear factor erythroid 2-related factor 2 (Nrf-2) expression by B. subtilis and Dexa treatment in ankle joint of arthritic mice. Radiological scores were also improved by both treatments. This study concludes that B. subtilis could be an effective alternative for treating arthritis than Dexa since it does not produce life-threatening side effects on prolong treatment.

Exploring the Indications, Levels, and Outcomes of Lower Extremity Amputation at a Tertiary Care Hospital in Pakistan.

BACKGROUND: Lower extremity amputation (LEA) is a surgical procedure performed to remove either a part or the entire lower limb due to medical conditions such as trauma, infection, peripheral vascular disease, or malignancy. The procedure is becoming increasingly common in Pakistan, with a bulk of patients presenting from rural areas in tertiary care centers. Understanding the indications, levels, and outcomes of LEA is essential for improving patient care and adopting preventive strategies, especially in developing countries. METHODOLOGY: This study was conducted at Dow University Hospital in Karachi, Pakistan. Retrospective data of 384 patients who underwent non-traumatic lower extremity amputations between January 2016 and December 2020 was collected to include relevant history and characteristics, amputation indication and level, type of anesthesia used, and outcome within hospital stay. The data was analyzed using descriptive statistics. RESULTS: The data is composed of a wide age range (18 to 91 years) of patients, including a male majority (76.3%, n = 293). The employment status of the patients was taken into consideration, with a reported high number of unemployed individuals (60.4%, n = 232). Diabetes mellitus (84.4%, n = 324) was a commonly reported past medical condition, followed by hypertension (4.4%, n = 17). Indications for amputation exceedingly recorded were diabetic foot ulcers (84.4%, n = 324), followed by infections (9.4%, n = 36) and peripheral arterial disease (3.6%, n = 14). The anesthetic approach that was observed most in these patients was regional anesthesia (74.7%, n = 287). Right-sided amputations (52.9%, n = 203) were dominant, with below-knee amputations leading by the level of amputation performed (42.5%, n = 163). Many patients delayed seeking treatment (71.6%, n = 275) and indicated denial of severity (18%, n = 69) as a reason for the delay. Regarding outcome, many patients were successfully discharged following treatment (85.9%, n = 330). CONCLUSION: Overall, LEAs are being frequently performed in developing countries, such as Pakistan, especially with a large population living with diabetes mellitus. The implications of this disease are reflected in this study population, with the majority of patients reporting delays in treatment due to reasons such as the unknown severity of the disease or financial burdens. The challenges faced by these individuals, especially in this country, can be tackled with widespread affordability and availability of care and education on early management.

Attention2Minority: A salient instance inference-based multiple instance learning for classifying small lesions in whole slide images.

Multiple instance learning (MIL) models have achieved remarkable success in analyzing whole slide images (WSIs) for disease classification problems. However, with regard to giga-pixel WSI classification problems, current MIL models are often incapable of differentiating a WSI with extremely small tumor lesions. This minute tumor-to-normal area ratio in a MIL bag inhibits the attention mechanism from properly weighting the areas corresponding to minor tumor lesions. To overcome this challenge, we propose salient instance inference MIL (SiiMIL), a weakly-supervised MIL model for WSI classification. We introduce a novel representation learning for histopathology images to identify representative normal keys. These keys facilitate the selection of salient instances within WSIs, forming bags with high tumor-to-normal ratios. Finally, an attention mechanism is employed for slide-level classification based on formed bags. Our results show that salient instance inference can improve the tumor-to-normal area ratio in the tumor WSIs. As a result, SiiMIL achieves 0.9225 AUC and 0.7551 recall on the Camelyon16 dataset, which outperforms the existing MIL models. In addition, SiiMIL can generate tumor-sensitive attention heatmaps that is more interpretable to pathologists than the widely used attention-based MIL method. Our experiments imply that SiiMIL can accurately identify tumor instances, which could only take up less than 1% of a WSI, so that the ratio of tumor to normal instances within a bag can increase by two to four times.

Emerging Applications of Nanotechnology in Healthcare and Medicine.

Knowing the beneficial aspects of nanomedicine, scientists are trying to harness the applications of nanotechnology in diagnosis, treatment, and prevention of diseases. There are also potential uses in designing medical tools and processes for the new generation of medical scientists. The main objective for conducting this research review is to gather the widespread aspects of nanomedicine under one heading and to highlight standard research practices in the medical field. Comprehensive research has been conducted to incorporate the latest data related to nanotechnology in medicine and therapeutics derived from acknowledged scientific platforms. Nanotechnology is used to conduct sensitive medical procedures. Nanotechnology is showing successful and beneficial uses in the fields of diagnostics, disease treatment, regenerative medicine, gene therapy, dentistry, oncology, aesthetics industry, drug delivery, and therapeutics. A thorough association of and cooperation between physicians, clinicians, researchers, and technologies will bring forward a future where there is a more calculated, outlined, and technically programed field of nanomedicine. Advances are being made to overcome challenges associated with the application of nanotechnology in the medical field due to the pathophysiological basis of diseases. This review highlights the multipronged aspects of nanomedicine and how nanotechnology is proving beneficial for the health industry. There is a need to minimize the health, environmental, and ethical concerns linked to nanotechnology.

Calcineurin-independent NFATc1 signaling is essential for survival of Burkitt lymphoma cells.

In Burkitt lymphoma (BL), a tumor of germinal center B cells, the pro-apoptotic properties of MYC are controlled by tonic B cell receptor (BCR) signals. Since BL cells do not exhibit constitutive NF-κB activity, we hypothesized that anti-apoptotic NFATc1 proteins provide a major transcriptional survival signal in BL. Here we show that post-transcriptional mechanisms are responsible for the calcineurin (CN) independent constitutive nuclear over-expression of NFATc1 in BL and Eµ-MYC - induced B cell lymphomas (BCL). Conditional inactivation of the Nfatc1 gene in B cells of Eµ-MYC mice leads to apoptosis of BCL cells in vivo and ex vivo. Inhibition of BCR/SYK/BTK/PI3K signals in BL cells results in cytosolic re-location of NFATc1 and apoptosis. Therefore, NFATc1 activity is an integrated part of tonic BCR signaling and an alternative target for therapeutic intervention in BL.

Initial multicenter experience using a novel articulating through-the-scope traction device for endoscopic submucosal dissection.

Background and study aims A single-operator, articulating, through-the-scope (TTS) traction device was recently developed to facilitate endoscopic submucosal dissection (ESD). Clinical data on the performance of this device are limited. We report an initial multicenter experience with ESD using this articulating TTS traction device. Patients and methods Retrospective analysis on all consecutive patients who underwent ESD using this traction device (T-ESD) at five centers between August 2021 and December 2022. Endpoints included: rates of en-bloc resection, R0 resection, curative resection, and adverse events. Results Thirty-six patients (median age 64.8 years; 47.2% women) underwent ESD (median lesion size 40 mm; interquartile range [IRQ]: 27.5-67.5) for lesions in the esophagus (n=2), stomach (n=8), sigmoid colon (n=6), and rectum (n=20). Submucosal fibrosis was encountered in one-third of the lesions (33.3%). Median ESD time was 104.6 minutes (IQR: 65-122). En-bloc, R0 and curative resection were achieved in 94.4%, 91.6%, and 97.2%, respectively. The single patient with non-curative resection of an invasive rectal adenocarcinoma underwent surgery. There were no cases of delayed bleeding or perforation. There was no recurrence on surveillance endoscopy (n=20) at a median of 6 months (IQR: 3.75-6). Conclusions This initial multicenter experience demonstrates high resection rates and excellent safety profile when performing ESD with this novel articulating TTS device. Dynamic real-time traction may lower the technical difficulty of ESD. Additional studies are needed to assess its cost-effectiveness and compare its usefulness with other traction devices and techniques during ESD.

Cerebral Salt Wasting Syndrome Following Right Occipital Craniotomy in a Patient With Metastatic Lung Adenocarcinoma.

Cerebral salt wasting syndrome (CSW) is characterized by excessive natriuresis leading to hyponatremia and hypovolemia. It is commonly encountered among patients who have undergone brain trauma or subarachnoid hemorrhage. The occurrence of CSW after neurosurgical procedures has been frequently reported in the pediatric age group; however, it is a rare phenomenon in adults. We describe the case of a 59-year-old female who developed symptoms of polyuria and polydipsia after a right occipital craniotomy.

Synthesis of New Chromene Derivatives Targeting Triple-Negative Breast Cancer Cells.

Breast cancer continues to be the leading cause of cancer-related deaths among women worldwide. The most aggressive type of breast cancer is triple-negative breast cancer (TNBC). Indeed, not only does TNBC not respond well to several chemotherapeutic agents, but it also frequently develops resistance to various anti-cancer drugs, including taxane mitotic inhibitors. This necessitates the search for newer, more efficacious drugs. In this study, we synthesized two novel chromene derivatives (C1 and C2) and tested their efficacy against a battery of luminal type A and TNBC cell lines. Our results show that C1 and C2 significantly and specifically inhibited TNBC cell viability but had no effect on the luminal A cell type. In addition, these novel compounds induced mitotic arrest, cell multinucleation leading to senescence, and apoptotic cell death through the activation of the extrinsic pathway. We also showed that the underlying mechanisms for these actions of C1 and C2 involved inhibition of microtubule polymerization and disruption of the F-actin cytoskeleton. Furthermore, both compounds significantly attenuated migration of TNBC cells and inhibited angiogenesis in vitro. Finally, we performed an in silico analysis, which revealed that these novel variants bind to the colchicine binding site in ß-tubulin. Taken together, our data highlight the potential chemotherapeutic properties of two novel chromene compounds against TNBC.

Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence.

Reactive oxygen species (ROS) are metabolic byproducts that regulate various cellular processes. However, at high levels, ROS induce oxidative stress, which in turn can trigger cell death. Cancer cells alter the redox homeostasis to facilitate protumorigenic processes; however, this leaves them vulnerable to further increases in ROS levels. This paradox has been exploited as a cancer therapeutic strategy with the use of pro-oxidative drugs. Many chemotherapeutic drugs presently in clinical use, such as cisplatin and doxorubicin, induce ROS as one of their mechanisms of action. Further, various drugs, including phytochemicals and small molecules, that are presently being investigated in preclinical and clinical studies attribute their anticancer activity to ROS induction. Consistently, this review aims to highlight selected pro-oxidative drugs whose anticancer potential has been characterized with specific focus on phytochemicals, mechanisms of ROS induction, and anticancer effects downstream of ROS induction.

How Does Health Uncertainty Impact Greenhouse Gas Emissions in European Union Economies? A Blessing in Disguise.

The global outbreak of COVID-19 caused serious threats to public health and economic growth all around the world, but on the other hand, the betterment of the environment took place. How pandemics' health uncertainty will affect environmental quality is a crucial matter to address. The paper investigates the asymmetric association between pandemics-related health uncertainty and greenhouse gas emissions (GHG) in the top emitter European Union economies (Italy, Germany, France, Poland, Netherlands, Spain, Czech Republic, Belgium, Romania, and Greece). Employing data from 1996 to 2019, a unique approach called 'Quantile-on-Quantile', is adopted to evaluate the influence of various quantiles of the health uncertainty on GHG emissions. According to estimates, health uncertainty enhances environmental quality by minimizing GHG in most of our chosen nations at certain quantiles of data, which makes pandemics a blessing in disguise for environmental quality. Additionally, the estimations indicate that the grades of asymmetry between our variables varies by locality, accentuating the requisite for authorities to give specific consideration while executing health uncertainty and environmental quality policies.