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In this study, we report a novel platinum–doxorubicin conjugate that demonstrates superior therapeutic indices to cisplatin, doxorubicin, or their combination, which are commonly used in cancer treatment. This new molecular structure (1) was formed by conjugating an amphiphilic Pt(IV) prodrug of cisplatin with doxorubicin. Due to its amphiphilic nature, the Pt(IV)–doxorubicin conjugate effectively penetrates cell membranes, delivering both cisplatin and doxorubicin payloads intracellularly. The intracellular accumulation of these payloads was assessed using graphite furnace atomic absorption spectrometry and fluorescence imaging. Since the therapeutic effects of cisplatin and doxorubicin stem from their ability to target nuclear DNA, we hypothesized that the amphiphilic Pt(IV)–doxorubicin conjugate (1) would effectively induce nuclear DNA damage toward killing cancer cells. To test this hypothesis, we used flow the cytometric analysis of phosphorylated H2AX (γH2AX), a biomarker of nuclear DNA damage. The Pt(IV)–doxorubicin conjugate (1) markedly induced γH2AX in treated MDA-MB-231 breast cancer cells, showing higher levels than cells treated with either cisplatin or doxorubicin alone. Furthermore, MTT cell viability assays revealed that the enhanced DNA-damaging capability of complex 1 resulted in superior cytotoxicity and selectivity against human cancer cells compared to cisplatin, doxorubicin, or their combination. Overall, the development of this amphiphilic Pt(IV)–doxorubicin conjugate represents a new form of combination therapy with improved therapeutic efficacy. [ABSTRACT FROM AUTHOR]

In this work, we have demonstrated agar and oxidized bacterial cellulose cryogels as a potential hemostatic dressing material. TEMPO-oxidized bacterial cellulose (OBC) was incorporated into the agar matrix, improving its mechanical and hemostatic properties. The oxidation of bacterial cellulose (BC) was evidenced by chemical characterization studies, confirming the presence of carboxyl groups. The in vitro blood clotting test conducted on agar/OBC composite cryogels demonstrated complete blood clotting within 90 seconds, indicating their excellent hemostatic efficacy. The cryogels exhibited superabsorbent properties with a swelling degree of 4200%, enabling them to absorb large amounts of blood. Moreover, the compressive strength of the composite cryogels was appreciably improved compared to pure agar, resulting in a more stable physical structure. The platelet adhesion test proved the significant ability of the composite cryogels to adhere to and aggregate platelets. Hemocompatibility and cytocompatibility tests have verified the safety of these cryogels for hemostatic applications. Finally, the material exhibited remarkable in vivo hemostatic performance, achieving clotting times of 64 seconds and 35 seconds when tested in the rat tail amputation model and the liver puncture model, respectively. The experiment results were compared with those of commercial hemostat, Axiostat, and Surgispon, affirming the potential of agar/OBC composite cryogel as a hemostatic dressing material. [ABSTRACT FROM AUTHOR]

Text classification involves organizing textual information into predefined classes, a task which is particularly useful in domains like sentiment analysis, spam detection, and content labeling. In India, where a massive amount of information is generated daily through newspapers and social media, Hindi is one of the most widely used and spoken languages. However, there is limited research on Hindi text classification and, particularly, regarding Hindi news classification. This paper presents a research study to classify Hindi news articles published in Hindi-language newspapers in India by using and comparing various Machine Learning (ML) and Deep Learning (DL) algorithms. To prepare the textual news data for classification, pre-processing and feature engineering techniques, such as count vectorizer, Tf-Idf vectorizer and Doc2Vec, were used and applied to convert texts into vectors. This pre-processing step on the textual data was very challenging due to the presence of multimodal words, conjunctions, punctuation, and special characters in Hindi texts. The study considered Hindi news headlines from predetermined categories (Science, Sports, Entertainment and Business) and, among the different ML and DL models tested and evaluated, Linear Regression with Doc2Vec vectorizer and SGD classifier with Tf-Idf vectorizer produced best accuracies of 97.04% and 96.59%, respectively. The best performing DL model was found to be the Bi-LSTM with an accuracy of approximately 97% on the testing data. [ABSTRACT FROM AUTHOR]

Objective: To compare the safety and efficacy of the en bloc technique with the standard 2-lobe technique for holmium laser enucleation of the prostate (HoLEP). Methods: This prospective study included patients with benign prostatic hyperplasia (BPH) who underwent HoLEP from September 2020 to March 2022, by en bloc or 2-lobe technique. Patient demographics, prostate volume, enucleation, morcellation and operative time, and incidence of postoperative incontinence were compared between the 2 groups. Results: We included 64 patients (30 en bloc and 34 2-lobe techniques) who underwent HoLEP in this study. The mean age, prostate volume, creatinine, and PSA of patients were comparable in both groups [(68.53 vs. 67.55 years; P = .62), (79.43 vs. 79.88 g, P = .92), (1.08 mg/dL vs. 1.20 mg/dL, P = .35), (3.78 vs. 4.63 ng/mL; P = .376), respectively]. The enucleation time was significantly shorter in the en bloc group than in the 2-lobe group (54.2 vs. 61.67; P = .03). Additionally, the mean operative time was also comparatively shorter in the en bloc group than the 2-lobe group (72.36 vs. 80.50; P = .057). The improvement in the quality-of-life (QoL) score was significantly better with en bloc than the 2-lobe group (3.80 vs. 2.11; P = .01). There was a significant difference in stress urinary incontinence on days 1, 7, and 30 (P < .001) with en bloc compared to the two-lobe technique. Conclusion: Although the outcomes of en bloc and 2-lobe endoscopic enucleation of prostate techniques were comparable, the en bloc technique seems to be a better option in most patients undergoing HoLEP due to less enucleation and operative time and lowered stress urinary incontinence incidence. [ABSTRACT FROM AUTHOR]

HLA‐DQA1*05:05:17:03 differs from HLA‐DQA1*05:05:01:02 by a single base substitution in exon 1 and HLA‐DQA1*05:05:17:01 within introns 1 and 2. [ABSTRACT FROM AUTHOR]

HLA‐B*41:84 has a single base substitution in exon 2, altering glutamic acid to glutamine'. [ABSTRACT FROM AUTHOR]

8-oxoguanines (8-oxoG) in cells form compromised G-quadruplexes (GQs), which may vary GQ mediated gene regulations. By mimicking molecularly crowded cellular environment using 40% DMSO or sucrose, here it is found that oxidized human telomeric GQs have stabilities close to the wild-type (WT) GQs. Surprisingly, while WT GQs show negative formation cooperativity between a Pt(II) binder and molecularly crowded environment, positive cooperativity is observed for oxidized GQ formation. Single-molecule mechanical unfolding reveals that 8-oxoG sequence formed more diverse and flexible structures with faster folding/unfolding transition kinetics, which facilitates the Pt(II) ligand to bind the best-fit structures with positive cooperativity. These findings offer new understanding on structures and properties of oxidized G-rich species in crowded environments. They also provide insights into the design of better ligands to target oxidized G-rich structures formed under oxidative cell stress., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Objective: To compare the safety and efficacy of the en bloc technique with the standard 2-lobe technique for holmium laser enucleation of the prostate (HoLEP)., Methods: This prospective study included patients with benign prostatic hyperplasia (BPH) who underwent HoLEP from September 2020 to March 2022, by en bloc or 2-lobe technique. Patient demographics, prostate volume, enucleation, morcellation and operative time, and incidence of postoperative incontinence were compared between the 2 groups., Results: We included 64 patients (30 en bloc and 34 2-lobe techniques) who underwent HoLEP in this study. The mean age, prostate volume, creatinine, and PSA of patients were comparable in both groups [(68.53 vs. 67.55 years; P=.62), (79.43 vs. 79.88 g, P=.92), (1.08 mg/dL vs. 1.20 mg/dL, P=.35), (3.78 vs. 4.63 ng/mL; P=.376), respectively]. The enucleation time was significantly shorter in the en bloc group than in the 2-lobe group (54.2 vs. 61.67; P=.03). Additionally, the mean operative time was also comparatively shorter in the en bloc group than the 2-lobe group (72.36 vs. 80.50; P=.057). The improvement in the quality-of-life (QoL) score was significantly better with en bloc than the 2-lobe group (3.80 vs. 2.11; P=.01). There was a significant difference in stress urinary incontinence on days 1, 7, and 30 (P .001) with en bloc compared to the two-lobe technique., Conclusion: Although the outcomes of en bloc and 2-lobe endoscopic enucleation of prostate techniques were comparable, the en bloc technique seems to be a better option in most patients undergoing HoLEP due to less enucleation and operative time and lowered stress urinary incontinence incidence.