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Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Two years of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in a significant improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) that persisted beyond the 2-year treatment period in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer (EBC). Here, we report 5-year efficacy results from a prespecified overall survival (OS) interim analysis. In the intent-to-treat population, with a median follow-up of 54 months, the benefit of abemaciclib was sustained with hazard ratios of 0.680 (95% CI, 0.599 to 0.772) for IDFS and 0.675 (95% CI, 0.588 to 0.774) for DRFS. This persistence of abemaciclib benefit translated to continuous separation of the curves with a deepening in 5-year absolute improvement in IDFS and DRFS rates of 7.6% and 6.7%, respectively, compared with rates of 6% and 5.3% at 4 years and 4.8% and 4.1% at 3 years. With fewer deaths in the abemaciclib plus ET arm compared with the ET-alone arm (208 v 234), statistical significance was not reached for OS. No new safety signals were observed. In conclusion, abemaciclib plus ET continued to reduce the risk of developing invasive and distant disease recurrence beyond the completion of treatment. The increasing absolute improvement at 5 years is consistent with a carryover effect and further supports the use of abemaciclib in patients with high-risk EBC.

The document is a contents list for the journal CrystEngComm, which focuses on the design and understanding of solid-state and crystalline materials. The contents list includes various articles on topics such as halogen bonding in crown ether chemistry, metal-organic framework-derived materials for enhanced performance of aqueous zinc ion batteries, and the effect of grain boundary doping on the mechanical behavior of Ta bicrystal. The journal is published by The Royal Society of Chemistry, a leading chemistry community. [Extracted from the article]

There is a significant amount of research being conducted in the field of nitrogen-containing heterocycles due to their diverse applications in different industries. Benzimidazole is one of the heterocyclic compounds formed by connecting the benzene and imidazole rings and shows diverse biological activities. Benzimidazole is also an essential compound in agriculture and industry. In this research, the NiFe2O4@SiO2-Pr-S-nBu-SO3H nanocomposite was prepared and used as a heterogeneous catalyst for synthesizing the 2-aryl benzimidazole derivatives. This protocol involved the reaction between orthophenylene diamine and aromatic aldehydes, with iodine as an oxidizing agent. The prepared catalyst was thoroughly examined using various methods, including infrared Fourier transform spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), vibrating sample magnetometry (VSM), and energy dispersive X-ray (EDX) spectroscopy. This protocol offers several advantages such as a short reaction time at room temperature, simple workup, high product yields, simple purification, availability of raw materials, and a catalyst that is both reusable and environmentally friendly. Finally, to characterize the organic compounds, the melting point, FT-IR, and 1H NMR analyses were utilized. [ABSTRACT FROM AUTHOR]

Toxoplasmosis, a disease caused by the apicomplexan parasite Toxoplasma gondii, affects up to one third of the global population. Although immunocompetent individuals rarely experience severe symptoms, those with immunodeficiencies may potentially face fatal disease. The frontline treatments are currently sulphadiazine and pyrimethamine, which suffer from adverse side effects, and lack efficiency in clearing parasite cysts from the muscles and brain of patients. To address the need for novel, more effective, and less toxic treatments, four new ferrocenyl benzimidazole complexes 15–18 were synthesised and evaluated against the ΔKu80:mNeonGreen strain of T. gondii. Complexes 15 and 17 were found to be active with EC50 values of 17.9 and 17.5 μM respectively, with comparable activity to pyrimethamine, which had an EC50 value of 13.8 μM, and less effective than sulphadiazine, which had an EC50 value of 2.56 μM. Additionally, the compounds were found to be relatively non-toxic against HEK 293T and PNT1A human cell lines. Further investigations found that the complexes act by generating reactive oxygen species (ROS) through the ferrocenyl moiety. These complexes show potential for the development of new treatments against Toxoplasmosis. [ABSTRACT FROM AUTHOR]

This study describes the synthesis of N5‐(4‐(1H‐benzo[d]imidazol‐2‐yl)phenyl)‐N2‐phenylpyridine‐2,5‐diamine derivatives from Orthophenylenediamine (1) and 4‐aminobenzoic acid (2) and all the synthesized chemical moieties screened against a panel of cancer cell lines resulted in the identification compound 6 a with good anti‐cancer potential and a GI50 of 2.95 μM, 3.35 μM, 2.27 μM, 8.46 nM and 1.56 μM against MDAMB‐231, MCF‐7, A‐549, NCI‐H23 and A‐498 respectively. As the second greatest cause of death globally, cancer continues to pose a serious threat to public health. An essential enzyme called aromatase catalyses the last, rate‐limiting step in the production of oestrogens. As a well‐researched endocrine therapeutic strategy, aromatase inhibitors (AIs) efficiently block the production of oestrogen, which is necessary for aromatase activity. [ABSTRACT FROM AUTHOR]

Over the course of three decades, benzimidazole as well as benzothiazole and its derivatives have been extensively investigated in oligo‐nucleotide therapy for their properties. These derivatives serve as valuable building blocks for creating pharmaceutical and biologically active molecules. With applications ranging across various therapeutic domains, including antiulcer, anticancer, and anthelmintic treatments, substituted benzimidazole/ benzothiazole derivatives have proven their versatility. This review provides a systematic and comprehensive overview of the latest advancements in benzimidazole/ benzothiazole‐based compounds within medicinal chemistry. These compounds exhibit diverse pharmacological activities such as anticancer, antibacterial, antifungal, anti‐inflammatory, analgesic, anti‐HIV, antioxidant, anticonvulsant, antitubercular, antidiabetic, antileishmanial, antihistaminic, antimalarial properties, among others. By presenting insights into the substitution patterns around the benzimidazole/benzothiazole nucleus, this review aims to assist medicinal chemists in developing structure–activity relationships (SAR) for benzimidazole/benzothiazole‐based drugs and compounds, thereby aiding in the advancement of medicinal research. [ABSTRACT FROM AUTHOR]

Despite the great effort that has gone into developing new molecules as multitarget compounds to treat Alzheimer's disease (AD), none of these have been approved to treat this disease. Therefore, it will be interesting to determine whether benzazoles such as benzimidazole, benzoxazole, and benzothiazole, employed as pharmacophores, could act as multitarget drugs. AD is a multifactorial disease in which several pharmacological targets have been identified—some are involved with amyloid beta (Aβ) production, such as beta secretase (BACE1) and beta amyloid aggregation, while others are involved with the cholinergic system as acetylcholinesterase (AChE) and butirylcholinesterase (BChE) and nicotinic and muscarinic receptors, as well as the hyperphosphorylation of microtubule-associated protein (tau). In this review, we describe the in silico and in vitro evaluation of benzazoles on three important targets in AD: AChE, BACE1, and Aβ. Benzothiazoles and benzimidazoles could be the best benzazoles to act as multitarget drugs for AD because they have been widely evaluated as AChE inhibitors, forming π–π interactions with W286, W86, Y72, and F338, as well as in the AChE gorge and catalytic site. In addition, the sulfur atom from benzothiazol interacts with S286 and the aromatic ring from W84, with these compounds having an IC50 value in the μM range. Also, benzimidazoles and benzothiazoles can inhibit Aβ aggregation. However, even though benzazoles have not been widely evaluated on BACE1, benzimidazoles evaluated in vitro showed an IC50 value in the nM range. Therefore, important chemical modifications could be considered to improve multitarget benzazoles' activity, such as substitutions in the aromatic ring with electron withdrawal at position five, or a linker 3 or 4 carbons in length, which would allow for better interaction with targets. [ABSTRACT FROM AUTHOR]

Objective: Encouraged by the significant anticancer activities of benzimidazole, piperazine, and 1,2,3-triazole containing derivatives and based on the need for the development of new EGFR targeting antibreast cancer agents, our group now interested to synthesize new benzimidazole-piperazine-1,2,3-triazoles (VIIa–VIIn) as in vitro antibreast cancer and anti-EGFR agents. Methods: In this study, we focused on the synthesis of benzimidazole-piperazine-1,2,3-triazoles. As well, the in vitro antibreast cancer activity of compounds (VIIa–VIIn) against MDA-MB-231 and MCF-7 cell lines, and anti-EGFR activity of few compounds were studied via IC50 values. Results and Discussion: Compounds (1-methyl-1H-benzo[d]imidazol-2-yl)(4-((1-(p-tolyl)-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)methanone (VIIb), (4-((1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)(1-methyl-1H-benzo[d]imidazol-2-yl)metha none (VIIe), (4-((1-(3,5-dichlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)(1-methyl-1H-benzo[d]imidazol-2-yl)methanone (VIIh), and (4-((1-(4-chloro-3,5-dimethoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)(1-methyl-1H-benzo[d]imidazol-2-yl)methanone (VIIl) displayed higher activity against two cell lines than the Erlotinib. Furthermore, compounds (VIIb), (VIIe), and (VIIh) displayed greater inhibition against tyrosine kinase EGFR than the Erlotinib. The results of molecular docking studies of (VIIb), (VIIe), (VIIh), and (VIIl) as EGFR (PDB ID: 4HJO) targeting agents were found to be supportive with corresponding IC50 data. Conclusions: We propose that mechanism of in vitro antibreast cancer activity of the investigated compounds, possibly will due to the tyrosine kinase EGFR inhibition. [ABSTRACT FROM AUTHOR]

Herein, we have reported a new series of NNS‐donor ligands coordinated Ni(II) complexes and utilized them as catalytic activator to synthesize N‐alkylated amines and 1,2‐disubstituted benzimidazoles. The reaction of thiophenol/4‐chlorothiophenol/4‐methylthiophenol/4‐methoxythiophenol with 2‐bromo‐N‐quinolin‐8‐yl‐acetamide in presence of sodium hydroxide in ethanol at 80 °C gave [C9H6N‐NH−C(O)−CH2‐S−Ar] [Ar=C6H5 (L1); C6H4Cl‐4 (L2); C6H4Me‐4 (L3) and C6H4‐OMe‐4 (L4)], respectively. The corresponding reaction of L1‐L4 with Ni(OAc)2 in methanol at 80 °C for 3 hours resulted in octahedral nickel complexes [(L1‐H)2Ni] (C1), [(L2‐H)2Ni] (C2), [(L3‐H)2Ni] (C3), and [(L4‐H)2Ni] (C4), respectively. All compounds have been characterized by micro and spectroscopic analysis. The molecular structure of complexes C1–C3 has also been determined by single crystal X‐ray diffraction data. The utility of complexes C1–C4 were evaluated for the N‐alkylation of aniline with benzyl alcohols, and for 1,2‐disubstituted benzimidazoles synthesis. The obtained results indicate that complex C1 showed better catalytic activity in both N‐alkylation of amines with benzyl alcohols [catalyst loading: 2.0 mol %; Yield up to 92 %], and for 1,2‐disubstituted benzimidazoles derivatives [catalyst loading: 2.0 mol %; Yield up to 94 %)]. The mechanistic studies suggested that the reaction works through hydrogen borrowing from benzyl alcohol and its subsequent utilization for in situ reduction of imine. The experimentally observed catalytic reactivity patterns of complexes C1–C4 have found in good agreement with the HOMO‐LUMO energy gaps obtained by DFT analysis of corresponding complexes. [ABSTRACT FROM AUTHOR]

To improve the thermodynamic and mechanical properties of asymmetric polyimide (PI), a method to enhance the linearity of PI by using a structural reorganization approach was designed. First, two novel diamines containing benzimidazole and benzoxazole groups, namely PADBZ and PDBOA, were constructed and synthesized. Thereafter, two new kinds of PI films (PADBZ‐PMDA and PDBOA‐PMDA) were prepared and polymerized with 1,2,4,5‐benzenetetracarboxylic anhydride (PMDA). Based on structural reorganization, PADBZ‐PMDA and PDBOA‐PMDA had repeating units of the same chemical composition and different linearity with PABZ‐BPDA and BOA‐BPDA, respectively. Comparing PADBZ‐PMDA and PABZ‐BPDA, due to the transfer in the position of benzene, PADBZ‐PMDA with high linearity showed the improved heat resistance (Tg up to 448°C), dimensional stability (CTE down to 2.3 ppm/K) and mechanical properties. PDBOA‐PMDA and BOA‐BPDA had the same situation. This study provided a unique solution to enhance the performances of PI by increasing the linearity using a structural reorganization approach. [ABSTRACT FROM AUTHOR]

A novel series of benzimidazole hydrazone‐Schiff bases have been prepared through multi‐step reaction process and structurally confirmed by13C‐,1H‐NMR and HR‐MS (ESI) spectroscopic techniques and evaluated against prolyl oligopeptidase (POP) inhibitory activity. In the series, eleven derivatives 20, 14 15, 19, 10, 9, 11, 4, 5, 18, and 21 revealed excellent inhibition potential having IC50 values from (IC50=1.44±0.08 μM) to (IC50=5.66±0.48 μM). However, six out of twenty compounds 12, 16, 13, 17, 22, and 3 attributed significant activity while, three compounds were found good active in the range of IC50 values 10.43±0.57 to 11.45±0.63 μM. The docking studies indicates that the hydrazone moiety show an imperative part in binding with one of the catalytic residues (Arg643) in the substrate binding region of POP enzyme. The excellent inhibitions of these compounds for POP enzyme may lead them to be a good candidates for drug against neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Three novel Zn(II) mononuclear complexes with the general formula ZnL2Cl2 (L = 2-(4-R-phenylmethylene)benzimidazol-2-hydrazines; R-H (1), R-CH3 (2), and R-OCH3 (3)) were synthesized and fully characterized by various means. These complexes demonstrate excitation-dependent emission, which is detected by a change in the emission color (from blue to green) upon an increase in the excitation wavelength. Moreover complex 1 shows reversible mechanochromic luminescence behavior due to the reversible loss of solvated methanol molecules upon the intense grinding of crystals. In addition, 1 exhibits vapochromic properties, which originate from the adsorption methanol vapor on the crystal surface. The strengthening of anthelmintic activity at the transition from free hydrazones to zinc-based complexes is shown. [ABSTRACT FROM AUTHOR]

Livestock wastewater (LWW) has a complex characteristic of high organic matter content, metals, nutrients, and pharmaceutical compounds. Advanced oxidation processes (AOP) are a potential option for treating this wastewater. This study evaluated real LWW and the performance of UV/H2O2 and UV/peroxymonosulfate (UV/PMS) for its treatment. The experiments were conducted in a UV photoreactor (16 mW/m2, λ = 254 nm). The oxidant agents (Ox) tested were H2O2 and PMS, each at low, medium, and high TOC/Ox molar ratios. A pretreatment based on chemical precipitation was implemented. Annually, the LWW showed total organic carbon (TOC) values of 859 ± 13.37 mg/L, 168.85 ± 1.62 mg/L of total Kjeldahl nitrogen (TKN), and toxicity of 96% v/v. In the dry season, albendazole (ABZ) (95.3 ± 35.16 mg/L), Cu (4.3 ± 0.23 mg/L), Fe (3.8 ± 0.38 mg/L), and suspended solids (SS) (1015 ± 586.9 mg/L) were identified, so pretreatment was implemented. The UV/PMS process with the lowest molar ratio [TOC/Ox 1:0.75] removed significantly lower TOC concentrations (p < 0.05), but toxicity decreased entirely. The study of mineralization and toxicity provided insight into the changes in LWW during treatment with AOP. Furthermore, it contributed to establishing the technical basis for implementing efficient treatment processes. [ABSTRACT FROM AUTHOR]

Background and Objective: Prospective sequential analyses after a new drug approval allow proactive surveillance of new drugs. In the current study, we demonstrate feasibility of frailty-specific sequential analyses for dabigatran, rivaroxaban, and apixaban versus warfarin. Methods: We partitioned Medicare data from 2011 to 2020 into datasets based on calendar year following the date of drug approval. Each calendar year of data was added sequentially for analysis. We used a new-user, active comparative design by comparing the initiators of dabigatran versus warfarin, rivaroxaban versus warfarin, and apixaban versus warfarin. Patients aged ≥ 65 years with atrial fibrillation without contraindication to the anticoagulants were included. Claims-based frailty index ≥ 0.25 was used to define frailty. The initiators of each direct oral anticoagulant were propensity-score matched to the initiators of warfarin within each frailty status. The effectiveness outcome was ischemic stroke or systemic thromboembolism, and the safety outcome was major bleeding. For each calendar year, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazards models using all data available up to that year. Results: As an example of the results, in the 2020 dataset, compared with warfarin, apixaban was associated with a reduced risk of ischemic stroke or systemic thromboembolism (frail: HR 0.73, 95% CI 0.63–0.85; non-frail: HR 0.65, 95% CI 0.59–0.72) and major bleeding (frail: HR 0.63, 95% CI 0.57–0.69; non-frail: HR 0.59, 95% CI 0.56–0.63) in both frail and non-frail patients. We found evidence for apixaban's effectiveness and safety within 1–2 years after the drug approval in frail older patients. Conclusion: Our frailty-specific sequential analyses can be applied to future near-real-time monitoring of newly approved drugs. [ABSTRACT FROM AUTHOR]

The article discusses a 2024 study on the attitudes of patients 65 years and older on the use of routine clinical data in making treatment decisions. Results show participants' interest in such data and in how drugs work for them, and their concerns on confounders like populations' similarity of conditions with them, and on common minor side effects. Also noted are participants' common view that their physicians determine the evidence's applicability to them, and recommend a medication.

.Reductive C−N bond generation strategies of nitroarenes to form N‐arylformamide and azole derivatives were developed under the influences of magnetically separable Pd@rGO‐CuFe2O4 nanoparticle‐catalyzed reaction conditions. These reactions proceed at a very low catalyst loading in H2O as the solvent, which leads to a higher percentage of yields (up to 96 %) of the products. The catalyst is recovered from the reaction medium by using an external magnet and recycled for four consecutive reaction cycles with a less amounts of leaching. [ABSTRACT FROM AUTHOR]

The present study investigates the identification of novel heat shock protein‐90 (HSP90) inhibitors‐modulators employing de novo drug design methodologies. Precisely, a machine learning (ML) assisted de novo design tool, REINVENT4, was employed for generating novel molecules against a given set of known HSP90 inhibitors. Further, a series of cheminformatics analyses were undertaken to assess pharmacokinetic properties, evaluate binding affinity using docking, and predict absolute binding affinity using the KDeep tool to reduce the chemical space. Finally, three novel benzimidazole‐based drug‐like candidates viz. IM1, IM2, and IM3 were selected as potent inhibitors‐modulators for HSP90 protein. Docking‐based binding affinity of IM1, IM2, and IM3 was obtained as −11.30, −11.50, and −11.20 kcal/mol, respectively. Moreover, all identified protein‐ligand complex dynamic behavior has been extensively assessed through MD simulation for a 100 ns span, highlighting overall interaction stability and conformational rearrangements for protein bound with all selected compounds. The MM‐GBSA‐based binding free energy estimation for each complex demonstrated the superiority of identified compounds, as found to be −43.54, −38.34, and −25.50 kcal/mol for IM1, IM2, and IM3. Collectively, pharmacokinetics and drug‐like profile assessment of identified compounds, along with simulation trajectories, explained the potentiality of the compounds for modulating the activity of the HSP90. [ABSTRACT FROM AUTHOR]

In this work, a novel colorimetric chemosensor (BIAD) containing azo chromophore, 1,5dihydroxynaphthalene, and benzimidazole was synthesized and characterized by using IR, 1H,13C NMR, and mass spectral data, and elemental analysis. The cation recognition studies (including fourteen metal cations) exhibited that the synthesized azo dye can act as a rapid, sensitive, and selective colorimetric chemosensor for detecting Cu2+ ions. The addition of Cu2+ ions to the BIAD solution, changed immediately the solution color from purple to blue‐green, which could be observed by the naked eye. Comparison of the UV/Visible spectra of BIAD and (BIAD+Cu2+) revealed a red shift from 543 nm to 616 nm, which confirms the formation of a complex between Cu2+ cations and BIAD molecules. The result of Job's plot indicated that the stoichiometry binding ratio of BIAD to Cu2+ is 1 : 1. The limit of detection (LOD) was found for BIAD toward Cu2+ ion to be 0.10 μM. Furthermore, the BIAD‐based test paper strips were successfully used for the rapid detection of Cu2+ ions (<1 sec) in the aqueous solution (H2O‐DMSO, 9 : 1). [ABSTRACT FROM AUTHOR]

A novel microwave-mediated synthesis method was developed for the rapid and eco-friendly production of pyrimido[1,2-a]benzimidazole in high yields utilizing simple and cost-effective starting materials. This reaction was facilitated by the green organocatalyst guanidine hydrochloride. This protocol offers a metal-free and organocatalysed technique to afford a library of highly fluorescent pyrimido[1,2-a]benzimidazole derivatives. Key features of this synthetic method include its broad compatibility with functional groups, operational simplicity, and scalability, making it a promising technique for various applications. [ABSTRACT FROM AUTHOR]

Objective: Patients with thromboembolic problems, prosthetic valves, or coagulation issues are commonly prescribed anticoagulants and antiplatelets. Anticoagulant and antiplatelet medication might constitute a challenge for dentists and dental hygienists since possible prolonged bleeding might interfere with dental procedures. The aim of the present study was to examine the bleeding durations associated with various anticoagulants and antiplatelets during professional dental hygiene sessions, utilizing a modified Ivy test adapted for the oral context. Materials and methods: Ninety-three consecutive patients undergoing professional oral hygiene were recruited. Debridement during oral hygiene was performed using ultrasonic mechanical instrumentation, and bleeding sites were assessed and treated with gentle pressure using sterile gauzes. The time for bleeding cessation was recorded. Patients were categorized into six groups based on their drug intake, Control: no anticoagulants or antiplatelets DTI: direct thrombin inhibitors (dabigatran) AntiXa: directa factor Xa inhibitors (endoxaban, apixaban, rivaroxaban) VKA: vitamin K antagonists (warfarin, acenocoumarol) SAPT: single anti-platelet therapy (acetylsalicylic acid or clopidogrel) DAPT: dual anti-platelet therapy (acetylsalicylic acid and clopidogrel). Bleeding time was measured in seconds and mean values were assessed among the different groups. Differences between groups were investigated with Kruskal-Wallis test followed by Dunn's post-hoc correction for multiple comparisons or two-way ANOVA followed by Dunnett post-hoc; Results: Control patients presented the lowest bleeding time 50 s, followed by AntiXa (98), SAPT (105), DTI (120), DAPT (190) and VKA (203). A statistically significant difference was present among control and DTI (p = 0.004), VKA (p < 0.001), DAPT (p < 0.001). Conclusions: Based on the present outcomes, an increased risk of prolonged bleeding emerged in patients taking VKA and DAPT. Clinical significance: bleeding did not interfere with the oral hygiene session The optimal period for dental treatment of these patients should be 2–3 h before the next dose, without the need to temporarily suspend the medication. [ABSTRACT FROM AUTHOR]

This review provides a summary of the growth, progress, and characterization studies of benzimidazole single crystals and their derivatives. Various methods, including SEST, Vertical Bridgeman, and Sankaran Narayanan methods, were employed to grow organic nonlinear optical (NLO) single crystals of BMZ derivatives. The developed crystals underwent different characterization analyses such as UV-Vis-NIR spectroscopy, microhardness testing, and Second Harmonic Generation. The focus of this review is specifically on the advancement of the NLO characteristics of the BMZ single crystal. [ABSTRACT FROM AUTHOR]

Simple Summary: Parasitic infections, especially those caused by a particular group of roundworms called gastrointestinal nematodes, are one of the most important diseases of goats worldwide. The widespread and uncontrolled use of deworming drugs (anthelmintics) makes nematodes increasingly resistant, and this phenomenon is called anthelmintic resistance. Romania has one of the highest goat populations in Europe, but little is known about how widespread and resistant gastrointestinal parasites are in this country. That is why we decided to carry out this survey—to find out how Romanian farmers fight parasites in their goats and what their opinion is on the presence of parasites and the effectiveness of deworming drugs in their herds. Our findings are disappointing. Most farmers deworm goats when they think it is necessary, not when laboratory tests show that they really need it. Moreover, they use deworming drugs too often and at too low doses. Such practices are very likely to stimulate parasites to develop anthelmintic resistance, and only intensive education programs for farmers and veterinarians can stop this process. The widespread and uncontrolled use of anthelmintic products has contributed to the emergence of anthelmintic resistance (AR). This phenomenon globally threatens the productivity and welfare of small ruminants. A questionnaire consisting of 34 questions was handed to 234 goat farmers across Romania to gain insight into control practices against internal parasites and the farmers' perception of the parasitic infections present in their herds and the efficacy of anthelmintic treatments. The majority of farmers (88.5%) admitted they had never submitted fecal samples for parasitological laboratory analysis, and 77.4% had treated the animals on their own. In general, the farmers dewormed their goats based on visual body weight estimation. Prophylactic anthelmintic treatment was practiced by more than 85% of the farmers. A traditional control approach based on treating the entire herd at fixed time intervals is widespread among Romanian goat and sheep farmers. The most commonly used anthelmintic drugs in the previous 3 years (2021–2023) were benzimidazoles (85.5%) and macrocyclic lactones (81.6%). Poor anthelmintic efficacy was suspected by 14.5% of farmers, and the minority (18.0%) considered internal parasites as a problem in their herds. Regarding the farmers' perception of the presence of parasites, there was a significant level of uncertainty. This is the first survey carried out in Romanian goat herds, and it provides up-to-date information on practices aimed at controlling internal parasites. [ABSTRACT FROM AUTHOR]

A series of grafted polybenzimidazoles with ratios of flexible links and rigid structures in side chains based on amino polybenzimidazole (AmPBI) was successfully prepared by simple N-substitution reaction. Due to the adequate number of amino groups on the AmPBI backbone, sufficient N–H sites reduce consumption of imidazole group during grafting reactions, while simultaneously elevating the number of proton transfer site. The grafted polybenzimidazole membranes with ratios of flexible links and rigid structures in side chains have excellent properties especially in the phosphoric acid (PA) uptake, pretty swelling ratio and proton conductivity. Importantly, PA uptake, swelling ratio, mechanical property, proton conductivity and power density can be controlled by changing the ratios of flexible links and rigid structures. The grafted membrane (AmPBI-P3) with the longer flexible link in the side chain shows a low swelling ratio of 128.62%, which is lower than that of other AmPBI-PX and AmPBI. Moreover, AmPBI-P3 shows a high proton conductivity of 126.9 mS cm−1 which is about 1.74 times higher than pure AmPBI (73.1 mS cm−1) and still reaches 91.4 mS cm−1 at 180 °C after the PA retention capacity test under 160 °C/0%RH for 240 h. A great power density of 738.5 mW/cm2 at 180 °C with dry H 2 –O 2 and no backpressure is impressive among many reported membranes. [Display omitted] • A series of grafted polybenzimidazoles was successfully prepared. • The proton conductivity of AmPBI-P3 under 180℃ is about 1.74 times higher than AmPBI. • AmPBI-P3 shows pretty retention capacity after the PA retention capacity test under 160 ℃/0%RH for 240 h. • Great power density (738.5 mW/cm2) under 180 °C implies the potential applications in HT-PEMFCs. [ABSTRACT FROM AUTHOR]

The heterocyclic nucleus has a wide range of biological activities with the benzimidazole nucleus having diverse biological activities such as antifungal, antihistaminic, anti-convulsant, anti-inflammatory, analgesic, antiviral agents, etc. From an in-depth literature review, we have complied here a green synthesis of benzimidazole derivatives that are antifungal agents. This review is intended to be of assistance to the scientific community working in the area of heterocyclic nuclei. [ABSTRACT FROM AUTHOR]

Introduction: Venous thromboembolism (VTE) is a major concern following total knee arthroplasty (TKA). The optimal pharmacological prophylaxis remains, however, controversial. The present investigation compared several non-vitamin K antagonist oral anticoagulants commonly employed as VTE prophylaxis following TKA. A Bayesian network meta-analysis was conducted to compare apixaban, aspirin, dabigatran, edoxaban, enoxaparin, fondaparinux, and rivaroxaban. The outcomes of interest were to compare the rate of deep venous thrombosis (DVT), pulmonary embolism (PE), and major and minor haemorrhages. Methods: This study was conducted according to the PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-Analyses of Health Care Interventions. In March 2024, PubMed, Web of Science, and Google Scholar were accessed with no time constraints. All randomised controlled trials (RCTs) comparing two or more drugs for the prevention of VTE following TKA were considered for inclusion. Results: Data from 29,678 patients were collected. Of them, 67% (19,884 of 29,678 patients) were women. The mean age of the patients was 66.8 ± 2.8 years, and the mean BMI was 29.2 ± 1.5 kg/m2. There was comparability in age, sex, and BMI at baseline. Apixaban 5 mg, dabigatran 220 mg, and rivaroxaban 10 mg were the most effective in reducing the rate of DVT. Apixaban 5 mg, enoxaparin 60 mg, and rivaroxaban 40 mg were the most effective in reducing the rate of PE. Apixaban 5 mg, rivaroxaban 10 mg, and apixaban 10 mg were associated with the lowest rate of major haemorrhages. Apixaban 5 mg and 20 mg, and dabigatran 220 mg were associated with the lowest rate of minor haemorrhages. Conclusion: Administration of apixaban 5 mg demonstrated the best balance between VTE prevention and haemorrhage control following TKA. Level of evidence: Level I, network meta-analysis of RCTs. [ABSTRACT FROM AUTHOR]

Introduction: Direct oral anticoagulants (DOACs) reflect anticoagulation agents given to treat or prevent thrombosis, having largely replaced vitamin K antagonists (VKAs) such as warfarin. DOACs are given in fixed daily doses and generally do not need monitoring. However, there may be a variety of reasons that justify measurement of plasma DOAC levels in individual patients. Methods: We report updated findings for DOAC testing in our geographic region, using recent data from the RCPAQAP, an international external quality assessment (EQA) program, currently with some 40–60 participants in each of the different DOAC (rivaroxaban, apixaban, dabigatran) modules, to assess laboratory performance in this area. Data has been assessed for the past 5 years (2019–2023 inclusive), with 20 samples each per DOAC. Results: Data shows a limited repertoire of assays in use, and mostly consistency in reported numerical values when assessing proficiency samples. Available assays mostly comprised reagents from four manufacturing suppliers. There was good consistency across what participants identified as 'DOAC detected', but some variability when participants attempted to grade DOAC levels as low vs moderate vs high. Inter‐laboratory/method coefficient of variation (CVs) were generally <15% for each DOAC, when present at >100 ng/mL. Conclusion: We hope our findings, reflecting on mostly consistent reporting of DOAC levels and interpretation provides reassurance for clinicians requesting these measurements, and helps support their implementation in regions where there is a paucity of test availability. [ABSTRACT FROM AUTHOR]

Benzimidazoles, a class of nitrogen-containing heteroaromatic compounds, play a crucial role in the development of various important drugs. These compounds exhibit diverse biological functionalities. In this study, a novel and environmentally friendly photocatalytic route is proposed for the production of benzimidazoles. This method involves the oxidation of alcohol to aldehyde using air as the oxidant under visible-light conditions. Subsequently, fast condensation with o-phenylenediamine takes place, leading to the formation of 2-substituted benzimidazoles. The key mediator in this process is a newly developed photocatalyst called WO3-ZnS, which is activated by a commercial green laser light with a wavelength of 535 nm. To characterize the nanocomposite, several techniques including FT-IR, XRD, EDS, and FE-SEM were employed. These analyses provided valuable insights into the structure and properties of the nanocomposite. Moreover, Tauc's method was utilized to estimate the optical band gap of the photocatalyst. The proposed photocatalytic process involves a radical pathway including reactive species such as •O2- and OH•, along with h+. Stability and reusability experiments confirmed the reproducibility of the nano-photocatalyst in the reaction medium. Furthermore, the primarily in-vitro cellular toxicity of WO3-ZnS nanoparticles was evaluated using the HCT-116 human cancer cell line through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. The results demonstrated a significant reduction in cell viability, indicating the cytotoxicity of the nanoparticles against these cancerous cells. This finding highlights the potential of the synthesized nanoparticles as effective agents for combating gastrointestinal cancer. [ABSTRACT FROM AUTHOR]

The objective of this study is to investigate a new procedure for specifically reducing the NO2 group present on the aromatic ring along with ester group. We revealed that NaBH4-FeCl2 serves as a crucial reagent in this process. The reduction mediated by NaBH4-FeCl2 exhibited remarkable chemoselectivity, yielding the wanted products in outstanding yields of up to 90-95%. Furthermore, this process was successfully utilized in the synthesis of diamino compound, and in the synthesis of 2-substituted benzimidazole derivatives The diamine compounds was condensed with various aromatic or heterocyclic carboxylic acids in the existence of EDC.HCl and catalyst DMAP. The resulting moiety or product underwent cyclization by using CH3COOH at 100-110°C. Both the reactions (coupling & cyclization) reaction completed effectively, within the minimal reaction times. The structure of created compounds was confirmed using modern spectral techniques like FT-IR, mass spectrometry, NMR. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is a significant global health challenge, creating an urgent need for new therapeutic agents. This study explores benzimidazole derivatives as promising candidates for AD treatment. We conducted a comprehensive analysis of these compounds, focusing on their structure-activity relationship (SAR) in combating AD. The detailed SAR analysis identifies the structural features that enhance therapeutic effectiveness, guiding the design of a series of novel benzimidazole-based molecules. These compounds were thoroughly studied using computational methods, including molecular docking, to predict their binding affinities and interactions with AD-related targets. We also assessed the pharmacokinetic properties, including absorption, distribution, metabolism, and excretion (ADME), of the designed compounds to ensure they exhibit favorable drug-like properties and good bioavailability. The molecular docking studies provided valuable insights into how benzimidazole derivatives interact with key enzymes involved in AD, such as acetylcholinesterase and beta-secretase. Our findings highlight the potential of benzimidazole derivatives as potent anti-Alzheimer agents, offering a promising path for therapeutic development. By integrating SAR analysis, computational modeling, pharmacokinetic profiling, and molecular docking studies, we have established a solid framework for identifying effective compounds for AD treatment. This comprehensive approach not only enhances our understanding of benzimidazole derivatives but also sets the stage for future in vivo studies and clinical trials, ultimately aiming to reduce the global burden of Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Background: Listeria monocytogenes is a bacterial pathogen known for causing listeriosis, a foodborne illness with a wide spectrum of clinical presentations ranging from mild gastroenteritis to severe invasive disease, particularly affecting immunocompromised individuals, pregnant women, newborns, and the elderly. Successful treatment of patients with recurring listeria episodes due to colonised foreign material is often challenging, typically requiring a combination of antimicrobial treatment and surgical removal. Case presentation: Here, we present a particularly complex case of chronic invasive listeriosis with a total of six relapses. After extensive investigations, the patient's ICD device was identified as the focus of infection. Conclusion: The confirmation of relapses through cgMLST analysis highlights the persistence of Listeria monocytogenes and the potential for recurrence even after apparent resolution of symptoms in patients with foreign material. It emphasises the necessity for a comprehensive assessment to identify and mitigate the risk of relapses, thereby ensuring optimal management and outcomes. [ABSTRACT FROM AUTHOR]

Background: Anticoagulant drugs are a valuable tool for minimizing thrombotic risks in at-risk patients. The purpose of this study is to conduct a literature review highlighting the management of these drugs during daily clinical dental practice. Materials and Methods: We limited our search to English-language papers published between 1 January 1989, and 7 March 2024, in PubMed, Scopus and Web of Science that were relevant to our topic. In the search approach, the Boolean keywords "anticoagulant AND dentistry" were used. Results: Twenty-five clinical trials were included for final review from 623 articles obtained from the databases Web of Science (83), PubMed (382), and Scopus (158), eliminating duplicates and 79 off-topic items, resulting in 419 articles after removing 315 entries and confirming eligibility. Overall, these studies support the use of local hemostatic measures to manage the risk of bleeding in patients on anticoagulant therapy undergoing dental procedures and highlight the importance of greater education and collaboration among healthcare professionals. Conclusions: Research and clinical investigation have improved understanding and management of dental procedures in patients undergoing anticoagulant or antiplatelet therapy. Hemostatic agents, clinical protocols, risk factors, and continuous education are essential for navigating the complexities of anticoagulant therapy, ensuring optimal outcomes and enhancing patient well-being. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Activating RAS gene mutations occur in approximately 55% of patients with metastatic colorectal cancer (mCRC) and are associated with poorer clinical outcomes due to epidermal growth factor receptor (EGFR) blockade resistance. Combined EGFR and mitogen-activated protein kinase (MEK) inhibition may extend response to EGFR inhibition and overcome acquired resistance. This phase Ib/II dose escalation trial evaluated the safety and activity of dual inhibition with binimetinib (MEK1/2 inhibitor) and panitumumab (EGFR inhibitor [EGFRi]) in patients with RAS mutant or BRAF wild type (WT)/RAS WT mCRC. METHODS: Phase Ib dose escalation started with binimetinib 45 mg twice daily plus panitumumab 6 mg/kg administered every 2 weeks. In the phase II study, patients with measurable mCRC were enrolled into 4 groups based on previous anti-EGFR monoclonal antibody therapy and RAS mutational status. RESULTS: No patients in the phase Ib portion (n = 10) had a response; 70% of patients had stable disease. In the phase II portion (n = 43), overall response rate (ORR, confirmed) was 2.3% with one partial response in the RAS WT group, DCR was 30.2%, and median progression-free survival was 1.8 months (95%CI, 1.6-3.3). All patients experienced ≥1 adverse event, with the most common being diarrhea (71.7%), vomiting (52.8%), nausea (50.9%), fatigue (49.1%), dermatitis acneiform (43.4%), and rash (41.5%). Most patients required treatment interruption or dose reduction due to difficulties tolerating treatment. CONCLUSIONS: The combination of binimetinib and panitumumab had substantial toxicity and limited clinical activity for patients with mutant or WT RAS mCRC, independent of EGFRi treatment history (Trial registration: NCT01927341).

Abstract The population of South American camelids (SAC) has been steadily growing in Europe, where they are confronted with the regional endoparasite population of ruminants. As there are no anthelmintic drugs registered for use against nematode infections in SACs, anthelmintics (AH) available for ruminants or horses are usually applied. Reports indicating potential failures in administered AH are increasing. However, the generally low egg counts in SACs complicate the application of resistance tests in the field. The present study reports a follow-up study on SAC farms where anthelmintic resistance (AR) was suspected. The aims were (i) to repeat faecal egg count reduction tests (FECRTs) on potentially affected farms identified in a previous study with larger sample sizes, (ii) to verify suspected AR of Haemonchus contortus against benzimidazoles (BZ) by performing a single-nucleotide polymorphism (SNP) analysis using digital polymerase chain reaction (dPCR), and (iii) to apply the mini-FLOTAC technique for more reliable results at low egg counts in line with current recommendations. Seven farms (9–46 animals each) were examined by coproscopy, larval differentiation and SNP analysis. A FECRT was performed on six of these farms with moxidectin (three farms), monepantel (two farms) and ivermectin (one farm). The FEC was calculated according to the current World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines with the clinical protocol (a newly introduced variant of FECRT which can be used for smaller sample sizes and lower egg counts on the cost of sensitivity) and an expected efficacy of 99%. A high level (> 90%) of BZ-resistance-associated SNPs on codon 200 of H. contortus was observed on all farms. With the FECRT, resistance was demonstrated for ivermectin (74% FECR), while it remained inconclusive for one farm for moxidectin treatment. Sustained efficacy was demonstrated for the remaining treatments. This study showed an advanced level of BZ resistance in H. contortus of SACs and the development of AR against macrocyclic lactones on some farms. Thus, constant monitoring of AH treatment and sustainable worm control methods both need to be applied. Graphical Abstract

The purpose of the research is to monitor farms located in the European part of the Russian Federation to identify resistance to effects of benzimidazole anthelmintics in populations of nematodes Haemonchus contortus dwelling in the gastrointestinal tract of small cattle.Materials and methods. The studies were conducted in slaughterhouses located in the Moscow Region in 2023–2024. At the first stage, taxonomic identification of parasitic nematodes and larvae (L3) was made, and Strongylata species was determined from sheep. The study material was the abomasum with duodenum fragments and a distal rectum fragment with feces. For molecular studies, we used mature nematodes and H. contortus L3 larvae isolated from the abomasum and feces of small cattle brought to slaughterhouses in the Moscow Region from 8 regions of the European part of the Russian Federation: Moscow, Astrakhan, Oryol, Lipetsk, Tula, Bryansk regions, Stavropol and Dagestan. The studies were conducted at the premises of the Laboratory of Molecular Biology, the VNIIP – FSC VIEV. Statistical processing of the obtained data was made, and mean infection rates of parasitic nematodes (infection intensity and prevalence) were determined. Fifty-six DNA samples of nematodes H. contortus were examined using nested isothermal amplification (PCR) to identify gene alleles that determine resistance to benzimidazole drugs.Results and discussion. Molecular genetic studies of H. contortus DNA sampled from sheep brought from different Regions only detected homozygous individuals (100%) resistant to benzimidazole in the parasitic nematode population from the Oryol Region. Other regions identified only homozygous and heterozygous individuals susceptible to benzimidazole.

This work describes a novel iron‐catalysed approach for the synthesis of aryl‐substituted benzimidazoles and benzoxazoles. The methodology employs reductive carbonylation using readily available aryl iodides and aryl amines as precursors, with carbon monoxide serving as the efficient carbonyl source. The reaction proceeds under mild conditions with the addition of hydrosilanes and bases. Notably, aryl aldehydes are generated in situ from the aryl iodides, which subsequently react with o‐phenylenediamine or 2‐aminophenol to afford the desired products in high yields. The structures of the synthesized benzimidazoles and benzoxazoles were confirmed using 1H and 13C NMR spectroscopy and mass spectrometry. [ABSTRACT FROM AUTHOR]

Rationale: With the development of matrix‐assisted laser desorption/ionisation (MALDI) mass spectrometry (MS) in spatial localisation omics research on small molecules, the detection sensitivity of the matrix must increase. However, the types of matrices suitable for detecting acidic small molecules in (−) MALDI‐MS mode are very limited and are either not sensitive enough or difficult to obtain. Methods: More than 10 commercially available benzimidazole and benzothiazole derivatives were selected as MALDI matrices in negative ion mode. MALDI‐MS analysis was performed on 38 acidic small molecules and mouse serum, and the matrix effects were compared with those of the common commercial matrices 9‐aminoacridine (9AA), 1,5‐naphthalenediamine (DAN) and 3‐aminoquinoline (3AQ). Moreover, the proton affinity (PA) of the selected potential matrix was calculated, and the relationships among the compound structure, PA value and matrix effect were discussed. Results: In (−) MALDI‐MS mode, a higher PA value generally indicates a better matrix effect. Amino‐substituted 2‐phenyl‐1H‐benzo[d]imidazole derivatives had well‐defined matrix effects on all analytes and were generally superior to the commonly used matrices 9AA, DAN and 3AQ. Among them, 2‐(4‐(dimethylamino‐phenyl)‐1H‐benzo[d]imidazole‐5‐amine (E‐4) has the best sensitivity and versatility for detecting different analytes and has the best ability to detect fatty acids in mouse serum; moreover, the limit of detection (LOD) of some analytes can reach as low as ng/L. Conclusions: Compared to 9AA, DAN and 3AQ, matrix E‐4 is more effective at detecting low‐molecular‐weight acidic compounds in (−) MALDI‐MS mode, with higher sensitivity and better versatility. In addition, there is a clear correlation between compound structure, PA and matrix effects, which provides a basis for designing more efficient matrices. [ABSTRACT FROM AUTHOR]

Dabigatran is an oral anticoagulant that is mainly renally excreted. Despite its efficacy in preventing thromboembolic events, concerns arise regarding bleeding complications in patients with acute kidney injury. Idarucizumab is its specific antidote and reverses quickly and effectively dabigatran anticoagulation effects in situations of severe bleeding or pending surgical procedures, but its benefit beyond these two indications remains uncertain. We present a case of a woman with atrial fibrillation anticoagulated by dabigatran and admitted with Streptococcus agalactiae meningitis, acute kidney injury and dabigatran accumulation. Idarucizumab was not administered initially as she did not meet its current strict indications. However, subsequently, significant bleeding necessitated its use. A rebound increase in dabigatran concentration was associated with an intracranial hemorrhage, but the combination of additional doses of idarucizumab with hemodialysis lowered the dabigatran concentration and prevented significant rebound increases. Further investigation into the optimal management of dabigatran accumulation and acute kidney injury-associated bleeding is needed to enhance patient outcomes and safety. Early initiation of hemodialysis together with idarucizumab administration may be crucial in preventing life-threatening bleeding events in these patients. [ABSTRACT FROM AUTHOR]

The population of South American camelids (SAC) has been steadily growing in Europe, where they are confronted with the regional endoparasite population of ruminants. As there are no anthelmintic drugs registered for use against nematode infections in SACs, anthelmintics (AH) available for ruminants or horses are usually applied. Reports indicating potential failures in administered AH are increasing. However, the generally low egg counts in SACs complicate the application of resistance tests in the field. The present study reports a follow-up study on SAC farms where anthelmintic resistance (AR) was suspected. The aims were (i) to repeat faecal egg count reduction tests (FECRTs) on potentially affected farms identified in a previous study with larger sample sizes, (ii) to verify suspected AR of Haemonchus contortus against benzimidazoles (BZ) by performing a single-nucleotide polymorphism (SNP) analysis using digital polymerase chain reaction (dPCR), and (iii) to apply the mini-FLOTAC technique for more reliable results at low egg counts in line with current recommendations. Seven farms (9–46 animals each) were examined by coproscopy, larval differentiation and SNP analysis. A FECRT was performed on six of these farms with moxidectin (three farms), monepantel (two farms) and ivermectin (one farm). The FEC was calculated according to the current World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines with the clinical protocol (a newly introduced variant of FECRT which can be used for smaller sample sizes and lower egg counts on the cost of sensitivity) and an expected efficacy of 99%. A high level (> 90%) of BZ-resistance-associated SNPs on codon 200 of H. contortus was observed on all farms. With the FECRT, resistance was demonstrated for ivermectin (74% FECR), while it remained inconclusive for one farm for moxidectin treatment. Sustained efficacy was demonstrated for the remaining treatments. This study showed an advanced level of BZ resistance in H. contortus of SACs and the development of AR against macrocyclic lactones on some farms. Thus, constant monitoring of AH treatment and sustainable worm control methods both need to be applied. [ABSTRACT FROM AUTHOR]

The administration of intravenous thrombolysis (IVT) for patients with acute ischemic stroke who have recently ingested direct oral anticoagulants (DOACs) presents a clinical challenge due to the perceived increased risk of intracranial hemorrhage (ICH). Traditional guidelines from the US and European authorities advise against IVT within 48 h of last DOAC ingestion, unless specific coagulation tests indicate safety. However, emerging observational studies suggest that IVT might be safe in selected patients. A US stroke registry study and a global multicenter cohort study both reported no significant increase in symptomatic ICH among patients on DOACs compared to those not on anticoagulants. A systematic review of all published observational studies further supported these findings, showing comparable bleeding rates and functional outcomes in DOAC-treated patients. Reversal agents like idarucizumab for dabigatran have demonstrated potential in facilitating safer IVT administration, though logistical and cost-related barriers limit their widespread use. The variability in global guidelines reflects differing approaches to risk assessment and resource availability, highlighting the need for individualized treatment decisions. In India, the increasing prevalence of atrial fibrillation and stroke as well as prescription of DOACs necessitate adapted guidelines that consider local health-care infrastructure. Despite the promising observational data, the lack of randomized controlled trials underscores the need for further research to establish robust evidence for IVT use in this context. Collaborative international efforts and inclusion of diverse patient populations in future studies will be crucial to refine treatment protocols and improve outcomes for stroke patients on DOACs. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluated direct oral anticoagulants (DOAC) levels in frail older patients with acute illnesses, indicating an essential aspect of their anticoagulant management. Topics discussed include expected rise in DOAC use in frail older patients, patients with higher rates of bleeding, patient demographic and medical data at admission, and a trend observed for rivaroxaban use and DOAC levels above the on-therapy range.

A method for the simultaneous determination of benzimidazoles and their metabolites in dairy products was established using ultra high performance liquid chromatography-tandem mass spectrometry (MS). After extracting the samples with acetonitrile containing 0.2% formic acid, the extracts were centrifuged and purified by solid phase extraction column, and then separated by UPLC HSS T3 chromatographic column, determined in multi reaction monitoring (MRM) method with a positive ESI mode. The results showed that the linear correlation coefficient (r) within the range of 1.0-50 μg/L was greater than 0.995 (except for triclabendazole, which was 0.9578). The method had a limit of detection (LOD) (S/N=3) of 0.002 mg/kg (except for albendazole-2-aminosulfone, thiabendazole, and thiabendazole-5-hydroxy, which were 0.003 mg/kg). The limit of quantitation (LOQ) (S/N=10) was 0.005 mg/kg (except for albendazole-2-aminosulfone, thiabendazole, and thiabendazole-5-hydroxy, which were 0.010 mg/kg). The recoveries at three spiked levels of 0.005, 0.01 and 0.05 mg/kg ranged from 62.5% to 117.6%, with relative standard deviations (RSD) between 1.92% and 12.17%. The method is simple to operate, highly sensitive, and suitable for the quantitative analysis of benzimidazoles and their metabolites in dairy products. [ABSTRACT FROM AUTHOR]

The 2-(2-Chlorophenyl)benzimidazole (CPBZ) vibrational assignments were performed using FT-IR and FT-Raman spectroscopy. The ideal geometrical parameters, IR intensity, and Raman activity of the vibrational bands of CPBZ were determined using the B3LYP functional and 6-311++G(d,p) level of theory, and the findings are compared with experimental findings. To comprehend the charge distribution within the molecule, the Mulliken charges, HOMO-LUMO energies, and molecular electrostatic potential (MEP) are computed. The molecular orbital contributions were evaluated using the total density of states (TDOS). To assess the electronic charge on each atom and the bond order between a pair of atoms, studies on the natural bond orbital (NBO) and the Fukui function were all examined. The 1H and 13C NMR chemical shifts were calculated using gauge-independent atomic orbital (GIAO). The structure and bioactivity of the molecule were validated by the docking research of CPBZ with the breast cancer inhibitors 1A28, 1ERE, 1AQU, and 1M17. The molecule's drug applicability has been determined by using ADMET prediction. Additional research has been done on the molecule's cytotoxicity and antibacterial properties. Ultimately, it appears that CPBZ has promise as a pharmacological option for treating breast cancer. [ABSTRACT FROM AUTHOR]

Given the malignancy of gastric cancer, developing highly effective and low‐toxic targeted drugs is essential to prolong patient survival and improve patient outcomes. In this study, we conducted structural optimizations based on the benzimidazole scaffold. Notably, compound 8 f presented the most potent antiproliferative activity in MGC803 cells and induced cell cycle arrest at the G0/G1 phase. Further mechanistic studies demonstrated that compound 8 f caused the apoptosis of MGC803 cells by elevating intracellular reactive oxygen species (ROS) levels and activating the mitogen‐activated protein kinase (MAPK) signaling pathway, accompanied by corresponding markers change. In vivo investigations additionally validated the inhibitory effect of compound 8 f on tumor growth in xenograft models bearing MGC803 cells without obvious toxicity. Our studies suggest that compound 8 f holds promise as a potential and safe lead compound for developing anti‐gastric cancer agents. [ABSTRACT FROM AUTHOR]

Six organotin(IV) compounds (1–6) have been synthesized by reaction of the polydentate pro-ligands H3L and H2L, respectively, with the corresponding diorganotin chlorides. All of the compounds were characterized by FT-IR spectroscopy, 1H, 13C{1H}, and 119Sn (1H) NMR spectroscopy, HRMS spectrometry, and single-crystal X-ray diffraction. The solid-state structures show that all of the compounds are monomeric (except compound 3) and contain a penta-coordinated tin atom. Compound 3 is a dimer with two hexa-coordinated tin atoms. Compounds 1–3 contain a non-coordinated hydroxymethyl group. All of the compounds have been screened for their catalytic efficacy in the synthesis of 1,2 disubstituted benzimidazoles using o-phenylenediamine and aldehyde derivatives. It has been observed that both the Lewis acidic Sn(IV) centre and the hydroxymethyl group (hydrogen bond donor) catalyse the reactions with a product yield of up to 92%. [ABSTRACT FROM AUTHOR]

Photoactive conjugated microporous polymers (CMPs) as heterogeneous photocatalysts provide a sustainable alternative to classical metal‐based semiconductor photosensitizers. However, previously reported CMPs are typically synthesized through metal catalyzed coupling reactions, which bears product separation, but also increases the price of materials. Herein, a new type of sp2 carbon linked DCM‐CMPs are successfully designed and synthesized by organic base catalyzed Knoevenagel reaction using 2,6‐Dimethyl‐4H‐pyran‐4‐ylidene‐malononitrile and aromatic polyaldehydes as monomers. The new polymers feature inherent porosity, excellent stability, and fully π‐conjugated skeleton with broad visible‐light absorption. They effectively induce the synthesis of benzimidazole compounds under light irradiation, and exhibit wide substrate adaptability with outstanding recyclability. [ABSTRACT FROM AUTHOR]

To make the colorless polyimides (CPIs) suitable for the application of flexible display technology, the polyimide (PI) films need to have both good optical properties and thermal properties. To get the wanted properties, 2‐(2‐methyl‐4‐(2‐methyl‐4‐aminobenzamido)phenyl)‐5‐(2‐methyl‐4‐aminobenzamido)‐N‐phenylbenzimidazol (5a) and 2‐(2‐methyl‐4‐(2‐trifluoromethyl‐4‐aminobenzamido)phenyl)‐5‐(2‐trifluoromethyl‐4‐aminobenzamido)‐N‐phenylbenzimidazol (5b) were synthesized, which both contained benzimidazole and bis‐amide structures. Two kinds of PI films were polymerized with cyclobutane‐1,2,3,4‐tetracarboxylic dianhydride (CBDA). With the contribution of side groups (CH3 or CF3), the resulting PI films presented relatively superior optical properties (transmittance at 400 nm was 59% and 68% respectively) and low coefficient of thermal expansion (CTE = 22 and 25 ppm K−1). These good properties suggest that these PI films have the potential for flexible display usage. [ABSTRACT FROM AUTHOR]

A great deal of attention has been received on developing N‐heterocyclic compounds due to their ambitious biological activities. Many of them are essential footstep to the development and discovery of new drugs. Imidazole/benzimidazole and quinazoline are essential pharmacologically active N‐heterocycles, and one of the molecular framework built up from their combination, imidazo/benzimidazo[1,2‐c]quinazoline, is of great attention in terms of synthesis, reactions, and medicinal applications. The positional variation of hetero N‐atoms and the functional groups acting as substituents in the main scaffold have a direct impact on the properties of imidazo/benzimidazo[1,2‐c]quinazolines. In addition to its physiological activities, this moiety is useful for electrical conductivity, molecules/ions sensing, coordination complex and coordination polymer (CP) formation, and their diverse applications. The major objective of this review is to highlight various synthetic approaches for imidazo/benzimidazo[1,2‐c]quinazolines motif since 2000. Toxicant‐free reaction conditions and the use of an extensive range of inexpensive substrates are two of the main practical benefits of the protocol in accomplishing the sustainable development goals. [ABSTRACT FROM AUTHOR]