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Recent work has focused on developing Raman spectroscopy as a noninvasive probe of DNA interactions with solvents, intercatants, proteins, and other ligands. Here, we report the Raman spectra of thymine in eight solvents and thymidine in nine solvents obtained with visible excitation. Raman spectra under acidic, neutral, and basic conditions were also obtained of both thymine and thymidine. Changes in both the frequencies and intensities of several of the vibrational bands in the 800-1800 [cm.sup.-1] region are observed. No evidence of deprotonation in the different solvents is observed for either thymine or thymidine. Correlations of the observed frequency shifts of specific vibrational modes with characteristic properties of the solvent for both thymine and thymidine show a significant correlation with acceptor and donor numbers, measures of the hydrogen-bonding ability of the solvent, in both thymine and thymidine. These results are interpreted in terms of hydrogen-bonding interactions between the N-H protons of the thymine base and lone pairs of electrons on the solvent molecules and between the solvent hydrogens and lone pairs on C=O sites. The solvent-dependent intensity in vibrational bands of thymine between 1500 and 1800 [cm.sup.-1] indicates a strong interaction between thymine and solvent at the C=O and N-H sites that leads to separation of the C=O stretches from the C=C stretch. The intensity variations with solvent were much smaller for thymidine than for thymine, perhaps as a result of replacing the [N.sub.1] proton by the sugar. These results suggest that Raman spectroscopy is uniquely sensitive to specific interactions of thymine and thymidine with their environment. Key words: Raman spectroscopy, thymine, thymidine, solvent effects, hydrogen bonding.

Introduction: In recent times, Health Professionals (HPs) people may feel a sense of discomfort and nervousness when disconnected from their smartphones, causing the emergence of the new phenomenon of "No Mobile Phone Phobia," or Nomophobia. Objectives: We aim to study lifestyle-related factors that influence HPs' Nomophobia. Methods: From April- June 2023, a global cross-sectional study was conducted using the modified Nomophobia questionnaire (NMP-Q). The original 20 NMP-Q questions (Qs) were reduced to 14 to avoid repetitive Qs with similar meanings. The Qs were categorized into 4 sections, A- Not Being Able to Access Information; B- Losing Connectedness; C- Not Being Able to Communicate; and D- Giving Up Convenience. A new section, "E- Daily Habits", and "F- Smartphone Type", and "Hours Spent Daily" were added. Before the launch, it was internally and externally validated by trained psychiatrists as well as experienced researchers. We utilized social media, WhatsApp, text and emails to share it with HPs of different specialties worldwide. The survey was anonymous and IRB-exempt. Results: Total 105 countries' HPs participation led to 12,253 responses. Total 47.3% of HPs agreed/strongly agreed (A/SA) that they prefer to use their smartphone before bedtime. Over half (57.8%) of HPs A/SA checked their notifications immediately after waking up in the morning. Only 19.4 % of HPs A/SA that woke up in the middle of the night to check notifications. Total 40.5% of HPs A/SA, 22% were neutral, and 37.3% of HPs disagreed /strongly disagreed (D/SD) with using smartphones while eating their meals. A total of 52.7% of HPs preferred smartphone usage over exercising as a break, while 454.9% of HPs A/SA that they chose smartphones over exploring other hobbies for relaxation. A total of 44.2% of respondents A/SA with smartphone usage in the restroom, 39.8% D/SD. 37.4% of participants D/SD with getting distracted by notifications and resisted the urge to answer any calls or texts while performing a focused task, whereas 39.6% A/SA and 23% were neutral. A total of 80% of respondents met the modified criteria for moderate-severe nomophobia. Conclusions: In a large-scale survey-based study on Nomophobia, additional Qs in NMP-Q may help recognize that nomophobia can be a result of daily lifestyle decisions rather than an isolated issue. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

In this paper, we propose the use of non-negative matrix factorization (NMF) for image hashing. In particular, we view images as matrices and the goal of hashing as a randomized dimensionality reduction that retains the essence of the original image matrix while preventing intentional attacks of guessing and forgery. Our work is motivated by the fact that standard-rank reduction techniques, such as QR and singular value decomposition, produce low-rank bases which do not respect the structure (i.e., non-negativity for images) of the original data. We observe that NMFs have two very desirable properties for secure image hashing applications: 1) The additivity property resulting from the non-negativity constraints results in bases that capture local components of the image, thereby significantly reducing misclassification and 2) the effect of geometric attacks on images in the spatial domain manifests (approximately) as independent identically distributed noise on NMF vectors, allowing the design of detectors that are both computationally simple and, at the same time, optimal in the sense of minimizing error probabilities. Receiver operating characteristics analysis over a large image database reveals that the proposed algorithms significantly outperform existing approaches for image hashing. [ABSTRACT FROM PUBLISHER]

Grayscale halftoning converts a continuous-tone image (e.g., 8 bits per pixel) to a lower resolution (e.g., 1 bit per pixel) for printing or display. Grayscale halftoning by error diffusion uses feedback to shape the quantization noise into high frequencies where the human visual system (HVS) is least sensitive. In color halftoning, the application of grayscale error-diffusion methods to the individual colorant planes fails to exploit the HVS response to color noise. Ideally the quantization error must be diffused to frequencies and colors, to which the HVS is least sensitive. Further it is desirable for the color quantization to take place in a perceptual space so that the colorant vector selected as the output color is perceptually closest to the color vector being quantized. This article discusses the design principles of color error diffusion that differentiate it from grayscale error diffusion, focusing on color error diffusion halftoning systems using the red, green, and blue (RGB) space for convenience. [ABSTRACT FROM PUBLISHER]

In the realm of enzymology, Carbonic anhydrase (CA) emerges as a pivotal protagonist orchestrating the rapid conversion of carbon dioxide and water into bicarbonate ions and hydrogen ions, respectively. Carbonic anhydrase inhibitors (CAIs) are the class of drugs that target various isoforms of the enzyme, and these inhibitors play a crucial role in the treatment and management of multiple diseases such as cancer, glaucoma, high altitude sickness, rheumatoid arthritis, obesity, epilepsy, and sleep apnea. Several structural classes of CAIs developed till date possess unique architects of the pharmacophoric requirements around the central core moiety for the selective targeting of various isoforms of the CA. Recent advancements in drug design and development, along with technologies that aid in structure determination, have led to the development of several isoform-selective inhibitors of CA enzymes. However, their clinical development was hampered by the lack of desired therapeutic efficacy, isoform selectivity and safety profile. This review covers the most recent approaches used by different researchers concerned with the development of isoform-selective carbonic anhydrase inhibitors belonging to distinct structural classes like sulphonamides, carbazoles, selenols, coumarin, organotelluride, topiramate, thiophene, triazole, uracil-modified benzylic amines, and thiourea etc. In addition, their structure-activity relationships, biological evaluation, and in silico studies inlcuding the forthcoming avenues of advancements have been discussed. This review serves as a valuable resource for developing potent and efficacious CAIs with remarkable therapeutic implications; offering insights into their potency, specificity, and potential clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Approximately half of patients with localised, high-risk soft tissue sarcoma of the extremity develop metastases. We aimed to assess whether the addition of pembrolizumab to preoperative radiotherapy and surgery would improve disease-free survival., Methods: We completed an open-label, randomised clinical trial in patients with grade 2 or 3, stage III undifferentiated pleomorphic sarcoma or dedifferentiated or pleomorphic liposarcoma of the extremity and limb girdle. Patients were enrolled at 20 academic institutions in Australia, Canada, Italy, and the USA. Patients were randomly assigned to preoperative radiotherapy then surgery (control group) or preoperative pembrolizumab with radiotherapy (initiated 1-14 days after the first dose of pembrolizumab) then surgery and postoperative pembrolizumab (experimental group). Pembrolizumab (200 mg intravenously every 3 weeks) was administered as three neoadjuvant cycles (before, during, and after radiotherapy) and 14 or less adjuvant cycles. Primary endpoint was disease-free survival. This study is registered with ClincialTrials.gov (NCT03092323)., Findings: Between Nov 18, 2017, and Nov 14, 2023, 143 participants were randomly assigned to treatment. A modified intention-to-treat analysis of 127 patients with median follow-up of 43 months showed that the experimental group (n=64) had significantly longer disease-free survival than the control group (n=63; log-rank one-sided p=0·035; hazard ratio [HR] 0·61; 90% CI 0·39-0·96). The 2-year disease-free survival increased by 15% with addition of pembrolizumab: 52% (90% CI 42-64) and 67% (90% CI 58-78) for the control and experimental groups, respectively. Disease-free survival was similarly improved with pembrolizumab for the intention-to-treat patient population (HR 0·61 [90% CI 0·39-0·95]). Grade 3 or higher adverse events occurred more frequently in the experimental group (56%) than the control group (31%)., Interpretation: Addition of pembrolizumab to preoperative radiotherapy and surgery improves disease-free survival for patients with stage III undifferentiated pleomorphic sarcoma and pleomorphic or dedifferentiated liposarcoma of the extremity, which establishes a promising new treatment option for these patients., Funding: Stand Up to Cancer and Merck Sharp & Dohme., Competing Interests: Declaration of interests YMM reports leadership roles in ASTRO and NRG Oncology and an honorarium from the University of Wisconsin–Madison. YMM, KVB, KJW, and DGK report grant funding from Stand Up to Cancer (Merck Catalyst Program) to the institution to support this study. KVB reports funding from SARC and the National Cancer Institute. AMH reports grant funding paid to Australia and New Zealand Sarcoma Association from the GPA Andrew Ursini Charitable Fund to support sample shipment to the USA and grant funding paid from Cancer Australia to Australia and New Zealand Sarcoma Association for clinical research team support for this study in Australia. YMM, AMH, SMS, and CFM report royalties from UpToDate for authorship contributions. AMH reports payment for participating on an advisory board for Teli. SMS reports grant funding from TRACON, Adaptimmune, and GlaxoSmithKline (GSK) to the institution; travel support from the National Comprehensive Cancer Network; and payment for participation in an advisory board for BioAtla. AJW reports a leadership role on the Board of Directors for SARC. VM reports grant funding from Rising Tide Foundation for Cancer Research; honoraria for presentations from Association of Northern California Oncologists and Gundersen Health System; participation in an advisory board for Forma Therapeutics; and funding to the institution from Amgen, Prelude Therapeutics, Jazz Pharmaceuticals, Astex Pharma, Oblato Therapeutics, Orbus Therapeutics, and Novartis. SA reports grant funding to the institution from SARC, Merck, TRACON, Bayer, Novartis, Lilly, Karyopharm, Epizyme, Blueprint, Genmab, CBA Pharma, Philogen, Gradilis, Deciphera, Takeda, Incyte, Springworks, Adaptimmune, Advenchen, Bavarian Nordic, BTG Pharmaceuticals, PTC Therapeutics, GSK, Forma Therapeutics, Ayala Pharma, Trillium, Boehringer Ingelheim, Salarius, Theseus, Monopar, C4 Therapeutics, Inhibrx, Noxopharm, Rain Therapeutics, Shanghai Pharma, PharmaMar, Cogen, and Jazz Therapeutics. SA reports grant funding to himself from Guardant. EC reports consulting fees from Sonata Therapeutics, Adaptimmune, Epizyme, and Bayer; and participation in advisory boards for Adaptimmune and Pfizer. DIP reports honoraria for presentations to Bayer. BAVT reports grant funding from Polaris; a patent on ALEXT3102; a patent on the use of ME1 as a biomarker; licences from Accuronix Therapeutics; consulting fees from Cytokinetics, Bayer, Deciphera Pharmaceuticals, Daiichi Sankyo, EcoR1, Advenchen, Putnam, Salarius Pharmaceuticals, Boxer Capital, Acuta Capital Partners, Aadi Bioscience, Race Oncology, Kronos Bio, Sonata Therapeutics, and Hinge Bio; honoraria for presentations from Iterion Therapeutics, and Total Health Conference; travel support from Adaptimmune, Advenchen Laboratories, Polaris, and Kronos Bio; participation in advisory boards for Apexigen, Daiichi Sankyo, Epizyme, Bayer US Medical Affairs Oncology, PTC Therapeutics, Asdi Biosciences, Boehringer Ingelheim, Agenus, Regeneron Pharmaceuticals, Curis; and an unpaid role on the safety monitoring board for Polaris. GT reports receiving payment for participating on an advisory board for Servier and consulting fees from Daiichi Sankyo. BC reports funding paid to the institution by SARC for support of this study; grant funding for clinical trial support paid to the institution by Bristol Myers Squibb, Macrogenics, Karyopharm Therapeutics, Infinity Pharmaceuticals, Advenchen Laboratories, Xencor, Compugen, Iovance, RAPT Therapeutics, IDEAYA Biosciences, Ascentage, Atreca, Replimune, Instil Bio, Adagene, TriSalus Life Sciences, Kinnate, PTC Therapeutics, Xilio Therapeutics, Kezar Life Sciences, and Immunocore; payment for participation on advisory boards at Novartis, Delcath, Instil Bio, Replimune, Atreca, Regeneron, and Treeline Biosciences; and payment for participation on the data monitoring committee for SpringWorks Therapeutics. AG reports funding to the institution from PharmaMar and Nanobiotix; consulting fees from Novartis, Pfizer, Bayer, Lilly, PharmaMar, SpringWorks, and Boehringer Ingelheim; honoraria for presentations from PharmaMar and Deciphera; travel support from PharmaMar; and leadership roles as the International Representative on the Executive Council of the Society of Surgical Oncology, a member of the Board of Directors of the European Society of Surgical Oncology, and a member of the Board of Directors of the Italian Sarcoma Group. CFM reports consulting fees for participating on advisory boards for Deciphera, Daiichi Sankyo, and Aadi Bioscience. MAD reports funding to the institution from Eli Lilly, Sumitomo Pharma, and Aadi Bioscience. LED reports funding from SARC to the institution to support this study; funding to the institution for clinical trial activities from Salarius, Inhibrx, BioAtla, Adaptimmune, GSK, SpringWorks, Epizyme, BTG Pharmaceuticals, Eisai, and Novartis; consulting fees from GLG Expert Network and Guidepoint Expert Network; educational payment from SpringWorks; payment for participating on advisory boards for Daiichi Sankyo, Inhibrx, Regeneron, and SpringWorks; leadership role on the scientific steering committee for SARC; leadership role on the scientific advisory board for the Osteosarcoma Institute; and a former leadership role on the Northwest Sarcoma Foundation Board of Directors. BEB reports consulting fees from Daiichi Sankyo, Deciphera, and Musculoskeletal Transplant Foundation; participation on a data safety monitoring board for PARITY Trial and SAFETY trial; and serving as a member of the Executive Board for the Musculoskeletal Tumor Society. RFR reports funding to the institution for clinical trial support from Aadi Bioscience, Adaptimmune, AROG, Ayala, BioAtla, Blueprint, Cogent, Daiichi-Sankyo, Deciphera, GlaxoSmithKline, InhibRx, NanoCarrier, Oncternal, PTC Therapeutics, SARC, SpringWorks, TRACON, and Trillium; consulting fees from Aadi Bioscience, Adaptimmune, Bayer, Blueprint, Boehringer Ingelheim, Daiichi-Sankyo, Deciphera, GSK, NanoCarrier, and SpringWorks; honoraria for lectures from SpringWorks; travel support for advisory board participation for Deciphera; leadership role as co-chair of the ECOG-ACRIN Sarcoma Working Group; medical writing assistance from Prescott Medical Communications Group with financial support from SpringWorks Therapeutics; and spouse ownership in Limbguard. DGK reports funding from MSD through the Merck Investigator Studies Program to the institution to support this study; and grant funding to the institution from Bristol Myers Squibb, Varian Medical Systems, the National Institutes of Health, and the Department of Defense. DGK has a licence for an imaging device through Lumicell; patents through Lumicell and XRad Therapeutics; membership on the scientific advisory board of Lumicell; membership on the independent data monitoring committee for the clinical trial SARCO; previous leadership role as the Councillor in Medicine on the Board of Directors of the International Association for Radiation Research; and holding stock in XRad Therapeutics and Lumicell. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

A multitude of plant-derived bioactive compounds have shown significant promise in preventing chronic illnesses, with flavonoids constituting a substantial class of naturally occurring polyphenolic compounds. Apigenin, a flavone identified as 4',5,7-trihydroxyflavone, holds immense promise as a preventative agent against chronic illnesses. Despite its extensive research and recognized nutraceutical value, its therapeutic application remains underexplored, necessitating further clinical investigations. This review delves into the biological sources, nutraceutical prospects, chemistry, pharmacological insights, and health benefits of apigenin. Through multifaceted analytical studies, we explore its diverse pharmacological profile and potential therapeutic applications across various health domains. The manuscript comprehensively examines apigenin's role as a neuroprotective , anti-inflammatory compound, and a potent antioxidant agent. Additionally, its efficacy in combating cardiovascular diseases, anti-diabetic properties, and anticancer potential has been discussed. Furthermore, the antimicrobial attributes and the challenges surrounding its bioavailability, particularly from herbal supplements have been addressed. Available in diverse forms including tablets, capsules, solid dispersions, co-crystals, inclusion complexes and nano formulations. Additionally, it is prevalent as a nutraceutical supplement in herbal formulations. While strides have been made in overcoming pharmacokinetic hurdles, further research into apigenin's clinical effectiveness and bioavailability from herbal supplements remains imperative for its widespread utilization in preventive medicine.

Twelve 3,5-disubstituted-thiazolidine-2,4-dione (TZD) hybrids were synthesized using solution phase chemistry. Continuing our previous work, nine O -modified ethyl vanillin (8a-i) derivatives were synthesized and reacted with the TZD core via Knoevenagel condensation under primary reaction conditions to obtain final derivatives 9a-i. Additionally, three isatin-TZD hybrids (11a-c) were synthesized. The intermediates and final derivatives were characterized using 1 H and 13 C NMR spectroscopy, and the observed chemical shifts agreed with the proposed structures. The in vitro alpha-amylase and alpha-glucosidase inhibitory evaluation of newly synthesized derivatives revealed compounds 9F and 9G as the best dual inhibitors, with IC 50 values of 9.8 ± 0.047 μM for alpha-glucosidase (9F) and 5.15 ± 0.0017 μM for alpha-glucosidase (9G), 17.10 ± 0.015 μM for alpha-amylase (9F), and 9.2 ± 0.092 μM for alpha-amylase (9G). The docking analysis of synthesized compounds indicated that compounds have a higher binding affinity for alpha-glucosidase as compared to alpha-amylase, as seen from docking scores ranging from -1.202 to -5.467 (for alpha-amylase) and -4.373 to -7.300 (for alpha-glucosidase). Further, the molecules possess a high LD 50 value, typically ranging from 1000 to 1600 mg kg -1 of body weight, and exhibit non-toxic properties. The in vitro cytotoxicity assay results on PANC-1 and INS-1 cells demonstrated that the compounds were devoid of significant toxicity against the tested cells. Compounds 9F and 9G showed high oral absorption, i.e. , oral absorption >96%, and their molecular dynamics simulation yielded results closely aligned with the observed docking outcomes. Finally, compounds 9F and 9G were evaluated for in vivo antidiabetic assessment by the induction of diabetes in Wistar rats using streptozotocin. Molecule 9G has been identified as the most effective anti-diabetic molecule due to its ability to modulate several biochemical markers in blood plasma and tissue homogenates. The results were further confirmed by histology investigations conducted on isolated pancreas, liver, and kidney., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)