Preparation of tetrahydro-1H-xanthen-1-one and chromen-1-one derivatives via a Morita-Baylis-Hillman/oxa-Michael/elimination cascade

The Morita-Baylis-Hillman (MBH) reaction is a carbon-carbon bond forming transformation between an electrophile, typically an aldehyde, and an activated olefin. MBH adducts obtained from 2-hydroxy- benzaldehydes and cyclic enones are potential substrates for the synthesis of xanthenone and chromenone derivatives. In this work, we investigated conditions to obtain tetrahydro-1H-xanthen-1-ones and chromen- 1-ones directly via a Morita-Baylis-Hillman/oxa-Michael/elimination cascade catalyzed by a bifunctional, bicyclic imidazolyl alcohol (BIA), which proved to be an effective catalyst for this transformation. The reactions were performed at room temperature in water to give the products in 10-74 % yield

Do interventions to improve adherence to antiretroviral therapy recognise diversity? A systematic review

People living with HIV (PLWH) are often culturally and linguistically diverse populations; these differences are associated with differing barriers to antiretroviral therapy (ART) adherence. Cultural competence measures the extent to which trial design recognises this diversity. This systematic review aimed to determine whether adherence trial participants represent the diversity of PLWH. Randomised Controlled Trials in Organisation for Economic Co-operation and Development countries to improve ART adherence were eligible. We searched MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews. For all included trials, we searched for their development, testing and evaluation studies. We compared trial participant characteristics with nationally reported PLWH data. We appraised trial cultural competence against ten criteria; scoring each criterion as 0, 1 or 2 indicating cultural blindness, pre-competence or competence respectively. For 80 included trials, a further 13 studies presenting development/testing/evaluation data for the included trials were identified. Only one of the 80 included studies reported trial participants representative of the country's population of PLWH. The median (IQ) cultural competence score was 2.5 (1.0, 4.0) out of 20. HIV adherence trial participants are not reflective of the population with HIV, which may be due to limited adoption of culturally competent research methods

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Exploring the Advantages of Layout Procedure with Fully‐Connected Quantum Computing Technologies

Even though quantum algorithms are designed using an idealised high-levelquantum circuit description, the execution on real devices must consider thebackend physical properties. Contemporary noisy intermediate-scale quantum(NISQ) computers are characterized by limited inter-qubit connectivity and anexclusive set of native gates, whose execution is affected by non-negligibleerrors and non-idealities. Quantum compilation, consisting of logic and layoutsynthesis, aims to recast the original circuit description to the target hardwareby solving the coupling-constraint and to minimize the execution time and theerror rate. While a previous article addresses the first phase, the second one isthe aim of this manuscript. Currently available layout tools mainly targetsuperconducting technology. This article tries to match the unmet need for alayout synthesis library supporting a wider range of technologies. The mostpromising algorithms already present in the state of the art are adapted toextend the compatibility to all the supported technologies, and newapproaches, which exploit the awareness of the coupling strength infully-connected topologies, are proposed. The integrated procedures arebenchmarked against IBM’s Qiskit and Cambridge Quantum Computing’st|ket⟩compilation toolchains, and even though these strategies can be furtherimproved, the results are encouraging

Palladium-mediated oxidative annulation of δ-indolyl-α,β-unsaturated compounds toward the synthesis of cyclopenta[b]indoles and heterogeneous hydrogenation to access fused indolines

The cyclopenta[b]indole moiety represents a key skeletal unit in several natural and synthetic compounds that exhibit diverse biological properties. We described herein a two-step sequence for synthesizing cyclopenta[b]indoles with great structural diversity in overall yields up to 37%. The key step was a palladium-catalyzed oxidative annulation of 3-alkylindoles (Fujiwara-Moritani reaction). The obtained cyclopenta[b]indoles were used as substrates in heterogeneous hydrogenation reactions to afford new fused indolines in moderate yields. An acid-catalyzed intramolecular cyclization of three such indolines gave tetracyclic lactams in 89, 90, and 61% yields84955645581CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP307840/2014-0; 422880/2016-22013/07600-3; 2013/10449-5; 2018/02611-

Synthesis, characterization, crystal structure and in vitro antiproliferative assays of the 2-thiouracilato(triphenylphosphine) gold(I) complex

A gold(I) complex with triphenylphosphine and 2-thiouracil, named 2-thiouracilato(triphenylphosphine) gold(I) (Ph3P-Au-tuH), was synthesized and characterized by a set of chemical and spectroscopic techniques. By elemental and mass spectrometric (ESI-QTOF-MS) analyses, the molecular formula AuC22H18N2OSP was proposed, corresponding to a 1:1 metal/ligand composition. Spectroscopic studies based on the infrared (IR) and nuclear magnetic resonance (NMR) of H-1, C-13 and P-31 evidenced the conversion of the chlorido(triphenylphosphine)gold(I) into the 2-thiouracilato(triphenylphosphine) gold(I), with substitution of Cl- by thiouracil. The crystal structure of the Ph3P-Au-tuH complex was determined by single crystal X-ray diffraction and shows the coordination of 2-thiouracil to gold(I) by the thiol group. Further, the in vitro antiproliferative assays of the 2-thiouracilato(triphenylphosphine)gold(I) complex showed its high activity when compared to the chlorido(triphenylphosphine)gold(I) one against lung (NCI-H460) and colon (HT29) tumor cell lines, with total growth inhibition (TGI) values of 26.7 and 28.5 mu g mL(-1), respectively, and also high selectivity towards tumor cells when compared to the normal cell line (HaCat). In addition, the Ph3P-Au-tuH complex showed a TGI value lower than 0.25 mu g mL(-1) for the leukemia cell line (K-562) with a selectivity index (SI) of 24.4, exhibiting a better in vitro cytotoxicity and selectivity than doxorubicin against this specific cell1178169178CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP442123/2014-0não tem2015/25114-

Revealing the Dynamic of Excited State Proton Transfer of a π‑Conjugated Salicylidene Compound: An Experimental and Theoretical Study

Excited state intramolecular proton transfer (ESIPT) in a novel salicylidene sal-3,4-benzophen chromophore is studied by white-light femtosecond pump–probe and time-resolved fluorescence techniques, as well as by theoretical calculations under the time dependent density functional theory framework. We show that when the sal-3,4-benzophen chromophore (in <i>enol</i> form) is excited (at 390 nm) to the <i>cis-enol*</i> form, it is quickly converted to the hot <i>cis-keto*</i> (hK*) form due to the fast ESIPT process (τ_ESIPT = 150 fs). Subsequently, cooling from the hot <i>cis-keto*</i> (hK*) to cold <i>cis-keto*</i> (cK*) state takes place with a characteristic time constant of ∼600 fs, with following relaxation decay time of 37 ps related with the photodynamic from sal-3,4-benzophen due to the occurrence of the <i>cis → trans</i> photoisomerization and intersystem crossing mechanisms. Finally, we observed the fluorescence emission from the <i>cis-keto*</i> at 575 nm. The dynamics of the optical process was modeled using rate equations with the proper energy level diagram and supported by theoretical calculations