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Background: Although the benefit of supportive care in the postcancer period is now well demonstrated, its implementation in the patient journey remains challenging. This article describes the development, since 2015 and in routine care, of supportive postcancer care comprising a multidisciplinary rehabilitation programme (MRP) based on exercise for patients with early breast cancer., Methods: As part of quality control, we reviewed all patient files since the programme was implemented. Patient data regarding the type of cancer, clinical and pathological factors, and treatment were recorded in a computerised database., Results: From April 2015 to January 2024, 655 patients participated in the MRP. The programme lasts for 14 weeks, totalling 126 hours of face-to-face programme, with a maximum of 8 patients per group, in 5 different centres. A multidisciplinary professional team provide supportive care. The MRP is mainly based on supervised physical exercise and patients also participate in social, psychological, dietary support and educational sessions. Supervised physical exercise includes cardiorespiratory endurance work through specific sessions on ergometers or outdoor walking and adapted physical activity sessions to improve muscular capacities (endurance, strength and flexibility)., Conclusion: We describe here the practical implementation of a routine multidisciplinary supportive care programme, based mainly on physical activity, for post-treatment breast cancer patients. We report almost 9 years of experience with the programme. We show that offering this programme in the postcancer setting and in clinical routine practice is feasible and can be maintained in the long term., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Motivated by recent studies of two-phase lipid vesicles possessing 2D solid domains integrated within a fluid bilayer phase, we study the shape equilibria of closed vesicles possessing a single planar, circular inclusion. While 2D solid elasticity tends to expel Gaussian curvature, topology requires closed vesicles to maintain an average, non-zero Gaussian curvature leading to an elementary mechanism of shape frustration that increases with inclusion size. We study elastic ground states of the Helfrich model of the fluid-planar composite vesicles, analytically and computationally, as a function of planar fraction and reduced volume. Notably, we show that incorporation of a planar inclusion of only a few percent dramatically shifts the ground state shapes of vesicles from predominantly prolate to oblate, and moreover, shifts the optimal surface-to-volume ratio far from spherical shapes. We show that for sufficiently small planar inclusions, the elastic ground states break symmetry via a complex variety of asymmetric oblate, prolate, and triaxial shapes, while inclusion sizes above about 8% drive composite vesicles to adopt axisymmetric oblate shapes. These predictions cast useful light on the emergent shape and mechanical responses of fluid-solid composite vesicles.

In recent decades, the traceless nature of visible photons has been exploited for the development of efficient synthetic strategies for the photoconversion of colourless compounds, namely, photocatalysis, chromophore activation, and the formation of an electron donor/acceptor (EDA) complex. However, the use of photoreactive coloured organic compounds is the optimal strategy to boost visible photons as ideal reagents in synthetic protocols. In view of such premises, the present review aims to provide its readership with a collection of recent photochemical strategies facilitated via direct light absorption by coloured molecules. The protocols have been classified and presented according to the nature of the intermediate/excited state achieved during the transformation.

In contemporary drug discovery, enhancing the sp 3 -hybridized character of molecular structures is paramount, necessitating innovative synthetic methods. Herein, we introduce a deoxygenative cross-electrophile coupling technique that pairs easily accessible carboxylic acid-derived redox-active esters with aldehyde sulfonyl hydrazones, employing Eosin Y as an organophotocatalyst under visible light irradiation. This approach serves as a versatile, metal-free C(sp 3 )-C(sp 3 ) cross-coupling platform. We demonstrate its synthetic value as a safer, broadly applicable C1 homologation of carboxylic acids, offering an alternative to the traditional Arndt-Eistert reaction. Additionally, our method provides direct access to cyclic and acyclic β-arylethylamines using diverse aldehyde-derived sulfonyl hydrazones. Notably, the methodology proves to be compatible with the late-stage functionalization of peptides on solid-phase, streamlining the modification of intricate peptides without the need for exhaustive de-novo synthesis., (© 2024. The Author(s).)

Activated by visible light, arylazo sulfones can serve as multifaceted reactants and are employed in diazenylation, sulfonylation, and arylation reactions under (photo)catalyst-free conditions. Such versatile reactivity enabled us to develop an operationally simple, regioselective, and tunable difunctionalization of styrenes with arylazo sulfones to produce α-sulfonyl arylhydrazones and 1,2-alkoxyarylated products in moderate to excellent yields. Furthermore, such difunctionalized products have been exploited as key building blocks for the synthesis of various heterocycles.

Single-atom catalysis is a field of paramount importance in contemporary science due to its exceptional ability to combine the domains of homogeneous and heterogeneous catalysis. Iron and manganese metalloenzymes are known to be effective in C─H oxidation reactions in nature, inspiring scientists to mimic their active sites in artificial catalytic systems. Herein, a simple and versatile cation exchange method is successfully employed to stabilize low-cost iron and manganese single-atoms in poly(heptazine imides) (PHI). The resulting materials are employed as photocatalysts for toluene oxidation, demonstrating remarkable selectivity toward benzaldehyde. The protocol is then extended to the selective oxidation of different substrates, including (substituted) alkylaromatics, benzyl alcohols, and sulfides. Detailed mechanistic investigations revealed that iron- and manganese-containing photocatalysts work through a similar mechanism via the formation of high-valent M═O species. Operando X-ray absorption spectroscopy (XAS) is employed to confirm the formation of high-valent iron- and manganese-oxo species, typically found in metalloenzymes involved in highly selective C─H oxidations., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Objectives: To assess health-related quality of life (QoL) in caregivers of elderly patients with chronic disabilities receiving, or not receiving, social worker support. Methods: This multicenter open-label randomized study assigned caregivers to receive an information booklet, exclusively, or with social worker support. Caregivers completed Short Form-36 (SF-36) and Hospital Anxiety Depression Scale quarterly, and Zarit Burden Interview each semester, for 24 months. We reported caregiver QoL mean changes at 12 and 24 months (M12, M24). Longitudinal QoL analysis up to M24 used mixed models for repeated measures (MMRM). Results: Among the 179 caregivers randomized from 2015 to 2019, the SF-36 physical and mental component summary showed no significant changes at M12 and M24, in terms of neither anxiety nor burden. However, depression significantly increased (M12: 1.4 ± 4.0; M24: 1.7 ± 4.1) with significant adjusted mean increase using MMRM at M24: 3.4 [0.6-2.5] in the control group, exclusively. Conclusion: These findings call for better recognition of the social support to prevent caregiver QoL deterioration and alleviate their depression early in the course of the disease. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02626377., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Pozet, Darnis, Bonnet, Meurisse, Dabakuyo-Yonli, Lejeune, Fagnoni, Gaimard, Manckoundia, Quibel, Marchand, Anota and Nerich.)

Background: Several cancer immunotherapies that target the PD-L1/PD-1 pathway show promising clinical activity in patients with hepatocellular carcinoma (HCC). However, the standard of care in first-line treatment with atezolizumab (anti-PD-L1 therapy) in combination with bevacizumab is associated with a limited objective response rate. Telomerase reverse transcriptase (TERT) activation meets the criteria of oncogenic addiction in HCC and could be actionable therapeutic target and a relevant tumor antigen. Therefore we hypothesized that combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine might be an attractive therapy in HCC. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (human TERT). UCPVax has been evaluated in a multicenter phase I/II study in non-small cell lung cancers and has demonstrated to be safe and immunogenic, and is under evaluation in combination with atezolizumab in a phase II clinical trial in tumors where telomerase reactivation contributes to an oncogene addiction (HPV +  cancers). The aim of the TERTIO study is to determine the clinical interest and immunological efficacy of a treatment combining the CD4 helper T-inducer cancer anti-telomerase vaccine (UCPVax) with atezolizumab and bevacizumab in unresectable HCC in a multicenter randomized phase II study., Methods: Patients with locally advanced, metastatic or unresectable HCC who have not previously received systemic anti-cancer treatment are eligible. The primary end point is the objective response rate at 6 months. Patients will be allocated to a treatment arm with a randomization 2:1. In both arms, patients will receive atezolizumab at fixed dose of 1200 mg IV infusion and bevacizumab at fixed dose of 15 mg/kg IV infusion, every 3 weeks, according to the standard of care. In the experimental arm, these treatments will be combined with the UCPVax vaccine at 0.5 mg subcutaneously., Discussion: Combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine gains serious consideration in HCC, in order to extend the clinical efficacy of anti-PD-1/PD-L1. Indeed, anti-cancer vaccines can induce tumor-specific T cell expansion and activation and therefore restore the cancer-immunity cycle in patients lacking pre-existing anti-tumor responses. Thus, there is a strong rational to combine immune checkpoint blockade therapy and anticancer vaccine (UCPVax) in order to activate antitumor T cell immunity and bypass the immunosuppression in the tumor microenvironment in HCC. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a CD4 Th1-inducer cancer vaccine derived from telomerase (UCPVax) and atezolizumab plus bevacizumab in unresectable HCC, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials., Trial Registration: NCT05528952., (© 2023. The Author(s).)

Arylazo sulfonates (Ar-N=N-SO 3 Na) have been found to undergo photografting on gold surface through both Au-N sp2 - and Au-C sp2 - bond formation. The functionalized materials have been fully characterized by infrared reflection absorption spectroscopy (IRRAS), Raman, XPS, DFT calculations and UV-Vis absorption spectroscopy. These methods permit to evidence aromatic substituents (IRRAS), the Au-N=N signature (Raman and XPS spectroscopy), and the bond dissociation energy values of the two linkages (DFT calculation). The grafting proceeds through two competitive paths, namely a stepwise reaction involving an aryl radical (for the formation of the Au-Ar bonds) and a concerted reaction on the surface of gold (for Au-N=N-Ar bond formation). The occurrence of an aryl radical upon irradiation has been fully evidenced by EPR spectroscopy. Finally, E/Z photoisomerisation of the N=N bonds present on prepared few layer films has been observed by means of UV-Vis absorption spectroscopy., (© 2023 Wiley-VCH GmbH.)

The selective visible-light-driven generation of a weak acid (sulfinic acid, in nitrogen-purged solutions) or a strong acid (sulfonic acid, in oxygen-purged solutions) by using shelf-stable arylazo sulfones was developed. These sulfones were then used for the green, smooth, and efficient photochemical catalytic protection of several (substituted) alcohols (and phenols) as tetrahydropyranyl ethers or acetals.

The protection of a carbonyl is a standard procedure to mask the reactivity of this group towards nucleophiles and reductants. The present work pointed out the potentialities of arylazo sulfones as non-ionic photoacid generators (PAGs) to promote the efficient conversion of aldehydes and ketones into acetals, ketals, and 1,3-oxazolidines upon visible-light irradiation. This approach employed mild conditions and exhibited an easy scalability and a broad scope (80 examples included)., (© 2022 Wiley-VCH GmbH.)

A set of arylazo sulfones, known to undergo N-S bond cleavage upon light exposure, has been synthesized, and their activity in the dark and upon irradiation towards DNA has been investigated. Their interaction with calf-thymus DNA has been examined, and the significant affinity observed (most probably due to DNA intercalation) was analyzed by means of molecular docking "in silico" calculations that pointed out polar contacts, mainly via the sulfonyl moiety. Incubation with plasmid pBluescript KS II revealed DNA cleavage that has been studied over time and concentration. UV-A irradiation considerably improved DNA damage for most of the compounds, whereas under visible light the effect was slightly lower. Moving to in vitro experiments, irradiation was found to slightly enhance the death of the cells in the majority of the compounds. Naphthylazosulfone 1 showed photo-disruptive effect under UV-A irradiation (IC 50 ~13 μΜ) followed by derivatives 14 and 17 (IC 50 ~100 μΜ). Those compounds were irradiated in the presence of two non-cancer cell lines and were found equally toxic only upon irradiation and not in the dark. The temporal and spatial control of light, therefore, might provide a chance for these novel scaffolds to be useful for the development of phototoxic pharmaceuticals.

Purpose: Universal cancer peptide-based vaccine (UCPVax) is a therapeutic vaccine composed of two highly selected helper peptides to induce CD4+ T helper-1 response directed against telomerase. This phase Ib/IIa trial was designed to test the safety, immunogenicity, and efficacy of a three-dose schedule in patients with metastatic non-small-cell lung cancer (NSCLC)., Patients and Methods: Patients with refractory NSCLC were assigned to receive three vaccination doses of UCPVax (0.25 mg, 0.5 mg, and 1 mg) using a Bayesian-based phase Ib followed by phase IIa de-escalating design. The primary end points were dose-limiting toxicity and immune response after three first doses of vaccine. Secondary end points were overall survival (OS) and progression-free survival at 1 year., Results: A total of 59 patients received UCPVax; 95% had three prior lines of systemic therapy. No dose-limiting toxicity was observed in 15 patients treated in phase Ib. The maximum tolerated dose was 1 mg. Fifty-one patients were eligible for phase IIa. The third and sixth dose of UCPVax induced specific CD4+ T helper 1 response in 56% and 87.2% of patients, respectively, with no difference between three dose levels. Twenty-one (39%) patients achieved disease control (stable disease, n = 20; complete response, n = 1). The 1-year OS was 34.1% (95% CI, 23.1 to 50.4), and the median OS was 9.7 months, with no significant difference between dose levels. The 1-year progression-free survival and the median OS were 17.2% (95% CI, 7.8 to 38.3) and 11.6 months (95% CI, 9.7 to 16.7) in immune responders ( P = .015) and 4.5% (95% CI, 0.7 to 30.8) and 5.6 months (95% CI, 2.5 to 10) in nonresponders ( P = .005), respectively., Conclusion: UCPVax was highly immunogenic and safe and provide interesting 1-year OS rate in heavily pretreated advanced NSCLC.

A versatile, inexpensive and sustainable protocol for the preparation of valuable bis-indolyl methanes via visible light-mediated, metal-free Friedel-Crafts arylation has been developed. The procedure, that exploits the peculiar behavior of arylazo sulfones as non-ionic photoacid generators (PAGs), was applied to the conversion of a variety of aliphatic and aromatic aldehydes into diarylmethanes in good to highly satisfactory yields, employing a low-catalyst loading (0.5 mol%) and irradiation at 456 nm.

The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly modified by the availability of innovative but expensive treatments, increasing the economic burden of prostate cancer. Here, we aimed to systematically identify and review published economic evaluations (EEs) related to the treatment of mHSPC and assess their quality. A systematic search was performed of the PubMed and Cochrane databases. Three reviewers independently selected EEs by defined inclusion and exclusion criteria. They extracted all data from each EE (general information, study population, data about the EE, interventions and comparators, and outcomes). They also assessed the quality of the selected EEs according to Drummond's checklist. Fourteen EEs published between 2016 and 2021 were eligible for the systematic review. The EEs found ADT + docetaxel to be the most cost-effective of all available treatments as a first-line strategy for mHSPC (abiraterone acetate plus prednisone, enzalutamide, and apalutamide). Five EEs showed that a simple price reduction of abiraterone acetate of 50% to 75% could change the results to render this treatment also cost-effective relative to that with docetaxel. Twelve EEs were of high quality, with a Drummond score ≥ 7. Analysis of the 14 EEs identified by our systematic review, amongst which 78.6% met high quality standards, showed that ADT + docetaxel tends to be the most cost-effective alternative for mHSPC. These results were assessed by sensitivity analysis. The data provided by this systematic review help to provide a better understanding of these treatments and the better use of healthcare resources., (Copyright © 2022. Published by Elsevier Inc.)

Health economic regulation and relevance of care are key points for every industrialised country. To get a better medicalised control of expenditure developments, French hospitals contracts with regulation authorities (Agence Régionale de Santé) and healthcare insurance within a "contract for the improvement of the quality and efficiency of care" (CAQES). One of the monitored element is the expenses related to hospital initial prescriptions delivered in community pharmacies (PHEV). The PHEV evolution is driven by prescribing practices (in terms of relevance) But others explanatory factor are structural and more complex to identify. Among these, the characteristics of the health care institution have a strong but unmeasured impact (environment, ambulatory medical demography, etc.). To evaluate the impact of these factors and help healthcare institutions, OMéDIT BFC (Regional Healthcare Products Observatory) and ARS, developed a tool for territorial management and analysis of PHEV named OPTA-PHEV. It makes it possible to individualize their expenditure data and to identify any prescription atypicalities integrating these extrinsic parameters. This will make it possible to compare and put into perspective the different regions in order to optimize PHEV-related expenses., (Copyright © 2022 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

There is an urgent need to develop uncharged radical precursors to be activated under mild photocatalyzed conditions. 2-Substituted-1,3-oxazolidines ( E ox < 1.3 V vs SCE, smoothly prepared from the corresponding aldehydes) have been herein employed for the successful release of tertiary, α-oxy, and α-amido radicals under photo-organo redox catalysis. The reaction relies on the unprecedented C-C cleavage occurring from the radical cation of these heterocyclic derivatives. Such a protocol is applied to the visible-light-driven conjugate radical addition onto Michael acceptors and vinyl (hetero)arenes under mild metal-free conditions., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Neurotrophic keratopathy (NK) is a degenerative corneal disease with a loss of corneal sensitivity and impairment of corneal healing. Low dose insulin eyedrops have been shown to be a simple and effective treatment for refractory NK when the response to the usual treatment is incomplete. At present, there are no commercially available forms, and there is no data regarding the stability of these products as prepared by compounding pharmacies. In this work, we studied the physicochemical and microbiological stability of an insulin ophthalmic formulation obtained by mixing insulin lispro in artificial tears with a polyethylene and propylene glycol base. The stability of this 1IU/mL insulin ophthalmic formulation was analysed for 12 months in low-density polyethylene (LDPE) multidose eye droppers at 4°C. The studied parameters of physicochemical stability were: visual inspection, turbidity, UV spectral absorption, osmolality and pH. In addition, insulin and m-cresol concentrations and quantification of impurities (insulin covalent aggregates and insulin fragments) were studied thanks to the development of a new Size Exclusion Chromatographic method. For unopened eye droppers, all tested physicochemical parameters remained stable for 12 months at 4°C, and excellent microbiological stability was obtained. In conditions of simulated use, these parameters also remained stable for one month at 4°C, and no impact of potential temperature rises on the insulin and m-cresol concentrations in the insulin eyedropper was observed., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

The valorization of alkenoic acids possibly deriving from biomass (fumaric and citraconic acids) was carried out through conversion in important building blocks, such as γ-keto acids and succinic acid derivatives. The functionalization was carried out by addition onto the C=C double bond of radicals generated under photocatalyzed conditions from suitable hydrogen donors (mainly aldehydes) and by adopting a decatungstate salt as the photocatalyst. Syntheses were performed under batch (in a glass vessel) and flow (by using 3D-printed reactors) conditions. The design of the latter reactors allowed for an improved yield and productivity., (© 2022 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Selenium-containing organic molecules have recently found a plethora of applications, ranging from organic synthesis to pharmacology and material sciences. In view of these concepts, the development of mild, efficient, and general protocols for the formation of C-Se bonds is desirable, and light induced approaches are appealing ways. The aim of this Review is to provide the reader with the most recent examples of light promoted selenylation processes., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: There is a strong rational of using anti-programmed cell death protein-1 and its ligand (anti-PD-1/L1) antibodies in human papillomavirus (HPV)-induced cancers. However, anti-PD-1/L1 as monotherapy induces a limited number of objective responses. The development of novel combinations in order to improve the clinical efficacy of an anti-PD-1/L1 is therefore of interest. Combining anti-PD-1/L1 therapy with an antitumor vaccine seems promising in HPV-positive (+) cancers. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (hTERT, human telomerase reverse transcriptase). UCPVax is being evaluated in a multicenter phase I/II study in NSCLC (non-small cell lung cancer) and has demonstrated to be safe and immunogenic. The aim of the VolATIL study is to evaluate the combination of atezolizumab (an anti-PD-L1) and UCPVax vaccine in a multicenter phase II study in patients with HPV + cancers., Methods: Patients with HPV + cancer (anal canal, head and neck, and cervical or vulvar), at locally advanced or metastatic stage, and refractory to at least one line of systemic chemotherapy are eligible. The primary end point is the objective response rate (ORR) at 4 months. Patients will receive atezolizumab every 3 weeks at a fixed dose of 1,200 mg in combination with the UCPVax vaccine at 1 mg subcutaneously., Discussion: Anti-cancer vaccines can restore cancer-immunity via the expansion and activation of tumor-specific T cells in patients lacking pre-existing anti-tumor responses. Moreover, preclinical data showed that specific T H 1 CD4 T cells sustain the quality and homing of an antigen-specific CD8 + T-cell immunity. In previous clinical studies, the induction of anti-hTERT immunity was significantly correlated to survival in patients with advanced squamous anal cell carcinoma. Thus, there is a strong rational to combine an anti-cancer hTERT vaccine and an immune checkpoint inhibitor to activate and promote antitumor T-cell immunity. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a telomerase-based T H 1 inducing vaccine (UCPVax) and an anti-PD-L1 (atezolizumab) immunotherapy in HPV + cancers, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials., Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier NCT03946358., Competing Interests: CB: Research grant from Bayer and Roche, advisory board for Bayer, Sanofi, MSD. FB: Novartis, Seagen, Daiichi Sankyo, Pierre Fabre, Astra-Zeneca, Clovis. SK: reports a consulting or advisory role for Ipsen, Incyte, Boehringer Ingelheim, Sanofi and BeiGene and has received research funding from Pfizer, Roche, Novartis, Bristol-Myers Squibb, Boehringer Ingelheim and Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rebucci-Peixoto, Vienot, Adotevi, Jacquin, Ghiringhelli, de la Fouchardière, You, Maurina, Kalbacher, Bazan, Meynard, Clairet, Fagnoni-Legat, Spehner, Bouard, Vernerey, Meurisse, Kim, Borg and Mansi.)

With the aim of generating new, thermally inaccessible diradicals, potentially able to induce a double-strand DNA cleavage, the photochemistry of a set of chloroaryl-substituted carboxylic acids in polar media was investigated. The photoheterolytic cleavage of the Ar-Cl bond occurred in each case to form the corresponding triplet phenyl cations. Under basic conditions, the photorelease of the chloride anion was accompanied by an intramolecular electron-transfer from the carboxylate group to the aromatic radical cationic site to give a diradical species. This latter intermediate could then undergo CO 2 loss in a structure-dependent fashion, according to the stability of the resulting diradical, or abstract a hydrogen atom from the medium. In aqueous environment at physiological pH (pH=7.3), both a phenyl cation and a diradical chemistry was observed. The mechanistic scenario and the role of the various intermediates (aryl cations and diradicals) involved in the process was supported by computational analysis., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The photochemistry of aryl chlorides having a X-SiMe 3 group (X = O, NR, S, SiMe 2 ) tethered to the aromatic ring has been investigated in detail, with the aim to generate valuable ϭ,π-heterodiradicals. Two competitive pathways arising from the excited triplet state of the aromatics have been observed, namely heterolysis of the aryl-chlorine bond and homolysis of the X-silicon bond. The former path is found in chlorinated phenols and anilines, whereas the latter is exclusive in the case of silylated thiophenols and aryl silanes. A combined experimental/computational approach was pursued to explain such a photochemical behavior.Graphical abstract., (© 2021. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

The preparation of symmetrical (hetero)biaryls via arylazo sulfones has been successfully carried out upon visible light irradiation in the presence of PPh 3 AuCl as the catalyst. The present protocol led to the efficient synthesis of a wide range of target compounds in an organic-aqueous solvent under photocatalyst-free conditions.

Direct photocatalyzed hydrogen atom transfer ( d -HAT) can be considered a method of choice for the elaboration of aliphatic C-H bonds. In this manifold, a photocatalyst (PC HAT ) exploits the energy of a photon to trigger the homolytic cleavage of such bonds in organic compounds. Selective C-H bond elaboration may be achieved by a judicious choice of the hydrogen abstractor (key parameters are the electronic character and the molecular structure), as well as reaction additives. Different are the classes of PCs HAT available, including aromatic ketones, xanthene dyes (Eosin Y), polyoxometalates, uranyl salts, a metal-oxo porphyrin and a tris(amino)cyclopropenium radical dication. The processes (mainly C-C bond formation) are in most cases carried out under mild conditions with the help of visible light. The aim of this review is to offer a comprehensive survey of the synthetic applications of photocatalyzed d -HAT.

Since 2007, a new class of biologic products for human use called "advanced therapy medicinal products (ATMP)" have been legally integrated in the European Medical Agency. They consist of recombinant nucleic acid, engineered cells, cells, or tissues. In the United States, ATMP fall under the regulatory framework of biological products and the term "cell and gene therapy product" is used in the legislative and regulatory documents. Potential clinical applications are broad, particularly, in the field of cancer, inherited genetic disease, and regenerative medicine. Indeed, the benefit conferred by CD19 chimeric antigen receptor T cells led to the first engineered cell therapy products to be approved by the Food and Drug Administration (FDA) in 2017. Gene therapy products to treat orphan diseases are also extensively developed with many clinical trials ongoing in the world. Nevertheless, the use of these therapeutic products is complex and requires careful considerations in the terms of regulatory and hospital setting requirements, such as storage, handling, administration, and disposal which justify the implementation of a secured medication circuit. Through this systematic review of the literature, the authors wanted to compile data on the assessment of environmental exposure related to the use of ATMP in healthcare setting to secure their medication circuit. A literature search was conducted on PubMed and Web of Science, and 32 publications dealing with environmental exposure assessment and ATMP were selected. In addition, marketed ATMPs were identified and data regarding the environmental concerns were extracted from product information sections from European Public Assessment Reports (EPAR). The environmental contamination assessments were mainly addressed in the reviews rather than in original articles related to the use of ATMP. Most of the product information sections from EPAR suggested precautions rather than requirements when dealing with environmental consideration following ATMP handling. Nevertheless, these precautions usually remain elusive especially concerning waste disposal and the detection of biological material on the work surfaces, and mainly relate to the genetically modified organisms (GMO) over non-GMO cellular products. Pharmaceutical oversight and adherence to the good preparation practices and good clinical practices are essential to ensure the safe use in term of environmental concern of these new therapeutic products in healthcare setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Damerval, Fagnoni-Legat, Louvrier, Fischer, Limat, Clairet, Nerich, Madelaine and Kroemer.)

The synthesis of α-arylketones and α-arylazo esters has been achieved in mixed organic-aqueous media under photocatalyst- and metal-free conditions via visible light activation of arylazo sulfones in the presence of enol silyl ethers and ketene silyl acetals, respectively. The process took place efficiently and exhibits an excellent tolerance for a broad variety of functional groups., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: The average hemoglobin content of red cell concentrates (RCC) varies depending on the method of preparation. Surprisingly less data are available concerning the clinical impact of those differences., Study Design and Methods: The effects of two types of RCC (RCC-A, RCC-B) on transfusion regime were compared in a non-blinded, prospective, randomized, two-period, and crossover clinical trial. RCC-A was obtained by whole blood leukoreduction and subsequent plasma removal, RCC-B removing plasma and buffy coat first, followed by leukoreduction. Eligible patients were adult, with transfusion-dependent thalassemia (TDT)., Results: RCC-A contained 63.9 (60.3-67.8) grams of hemoglobin per unit (median with 1 st and 3 rd quartile), RCC-B 54.5 (51.0-58.2) g/unit. Fifty-one patients completed the study. With RCC-B, the average pre-transfusion hemoglobin concentration was 9.3 ± 0.5 g/dl (mean ± SD), the average transfusion interval 14.2 (13.7-16.3) days, the number of RCC units transfused per year 39.3 (35.4-47.3), and the transfusion power index (a composite index) 258 ± 49. With RCC-A, the average pre-transfusion hemoglobin concentration was 9.6 ± 0.5 g/dl (+2.7%, effect size 0.792), the average transfusion interval 14.8 (14.0-18.5) days (+4.1%, effect size 0.800), the number of RCC units transfused per year 34.8 (32.1-42.5) (-11.4%, effect size -1.609), and the transfusion power index 272 ± 61 (+14.1%, effect size 0.997). All differences were statistically highly significant (p < .00001). The frequency of transfusion reactions was 0.59% with RCC-A and 0.56% with RCC-B (p = 1.000)., Conclusion: To reduce the number of RCC units consumed per year and the number of transfusion episodes, TDT patients should receive RCC with the highest average hemoglobin content., (© 2021 The Authors. Transfusion published by Wiley Periodicals LLC. on behalf of AABB.)

The photochemical behaviour of selected aryl sulfonates and phosphates (ArOX) in polar and nonpolar media has been investigated by laser flash photolysis (LFP) experiments. Two main pathways have been identified, namely the photohomolysis of the ArO-X bond or the photoheterolysis of the Ar-OX bond depending on the nature of the leaving group (OX) and on the nature of the substituents on the aromatic ring. In nonpolar solvents the esters are quite photostable due to an efficient triplet deactivation. In polar solvents, the homolytic fragmentation of the ArO-S bond from the exited singlets was found in aryl sulfonates bearing moderately electron-donating groups as well as electron-withdrawing groups. In electron-rich aryl phosphates and sulfonates photoheterolysis of the Ar-OP/Ar-OS bond took place as the exclusive pathway., (© 2021 Wiley-VCH GmbH.)

A visible-light-driven protocol for the synthesis of aryl trifluoromethyl thioethers under photocatalyst- and metal-free conditions has been pursued. The procedure exploits the peculiar properties of arylazo sulfones (having electron-rich or electron-poor substituents on the (hetero)aromatic ring) as photochemical precursors of aryl radicals and S -trifluoromethyl arylsulfonothioates as easy-to-handle trifluoromethylthiolating agents.

A metal-free route for the synthesis of biarenes has been developed. The approach is based on the photoextrusion of a phosphate moiety occurring upon irradiation of biaryl- and triaryl phosphates. The reaction involves an exciplex as the intermediate and it is especially suitable for the preparation of electron-rich biarenes., (Copyright © 2020, Qrareya et al.; licensee Beilstein-Institut.)

The number of research papers that report photocatalyst-free protocols is currently increasing. Among the different approaches proposed, the conversion of a strong C-X bond of a stable substrate into a photolabile reactive moiety has been recently proposed. In this Synopsis, we introduce the so-dubbed dyedauxiliary group strategy by focusing on arylazo sulfones that are bench stable and visible-light responsive derivatives of anilines that have been exploited as precursors of a wide range of intermediates, including carbon-centered radicals as well as aryl cations.

Objectives: Scientific advances in the last decade have highlighted the use of immunotherapy, especially immune checkpoint inhibitors, to be an effective strategy in cancer therapy. However, these immunotherapeutic agents are expensive, and their use must take into account economic criteria. Thus, the objective of the present study was to systematically identify and review published EE related to the use of ipilimumab, nivolumab or pembrolizumab in melanoma, lung cancer, head and neck cancer or renal cell carcinoma, and to assess their quality., Methods: The systematic literature research was conducted on Medline via PubMed and the Cochrane Central Register of Controlled Trials to identify economic evaluations published before July 2018. The quality of each selected economic evaluation was assessed by two independent reviewers using the Drummond checklist., Results: Our systematic review was based on 32 economic evaluations using different methodological approaches, different perspectives and different time horizons. Three-quarters of the economic evaluations are full (n = 24) with a Drummond score ≥ 7, synonymous of "high quality". Among them, 66% reported a strategy that was cost-effective. The most assessed immunotherapeutic agent was nivolumab. In patients with renal cell carcinoma or head and neck cancer, it was less likely to be cost-effective than in patients with melanoma or lung cancer., Conclusions: Whether or not these findings will be confirmed remains to be seen when market approval to cover more indications is extended and new effective immunotherapeutic agents become available.

Venous thromboembolism is highly prevalent in lung cancer patients. Low molecular weight heparins are recommended for long term treatment of cancer associated venous thromboembolism. Direct oral anticoagulants are however an interesting alternative as they are administered orally and don't require monitoring. There are currently studies comparing both their efficacy and tolerance for cancer patients and more and more guidelines suggest considering direct oral anticoagulants for cancer associated venous thromboembolism treatment. The objective of this study was to evaluate the budgetary impact that direct oral anticoagulants use would have for lung cancer associated venous thromboembolism treatment and prevention in France. An economic model was made to evaluate the cost of venous thromboembolism treatment and prevention among patients with primary lung cancer in France by two strategies: current guidelines versus direct oral anticoagulants use. The model was fed with clinical and economic data extracted from the French national health information system. The analysis was conducted from the national mandatory Health insurance point of view. The time horizon of the study was the evaluation of the annual management cost. Lung cancer associated venous thromboembolism management's mean cost was estimated of 836€ per patient, that is a total cost of about 40 million euros per year at a national level. A 76% decrease of this cost can be expected with direct oral anticoagulants use. However, despite their benefits, these treatments raise new issues (medication interactions, bleeding management), and would likely not be recommended for all patients.

Alkyl radicals are key intermediates in organic synthesis. Their classic generation from alkyl halides has a severe drawback due to the employment of toxic tin hydrides to the point that "flight from the tyranny of tin" in radical processes was considered for a long time an unavoidable issue. This review summarizes the main alternative approaches for the generation of unstabilized alkyl radicals, using photons as traceless promoters. The recent development in photochemical and photocatalyzed processes enabled the discovery of a plethora of new alkyl radical precursors, opening the world of radical chemistry to a broader community, thus allowing a new era of photon democracy.

The use of high-valent antimony-oxo porphyrins as visible-light photocatalysts operating via direct hydrogen atom transfer has been demonstrated. Computational analysis indicates that the triplet excited state of these complexes shows an oxyl radical behavior, while the Sb V center remains in a high-valent oxidation state, serving uniquely to carry the oxo moiety and activate the coordinated ligands. This porphyrin-based system has been exploited upon irradiation to catalyze C-H to C-C bond conversion via the addition of hydrogen donors (ethers and aldehydes) onto Michael acceptors in a redox-neutral fashion without the need of any external oxidant. Laser flash photolysis experiments confirmed that the triplet excited state of the photocatalyst triggers the desired C-H cleavage., Competing Interests: The authors declare no competing financial interest.

Direct activation of gaseous hydrocarbons remains a major challenge for the chemistry community. Because of the intrinsic inertness of these compounds, harsh reaction conditions are typically required to enable C(sp 3 )-H bond cleavage, barring potential applications in synthetic organic chemistry. Here, we report a general and mild strategy to activate C(sp 3 )-H bonds in methane, ethane, propane, and isobutane through hydrogen atom transfer using inexpensive decatungstate as photocatalyst at room temperature. The corresponding carbon-centered radicals can be effectively trapped by a variety of Michael acceptors, leading to the corresponding hydroalkylated adducts in good isolated yields and high selectivity (38 examples)., (Copyright © 2020, American Association for the Advancement of Science.)

Phenanthrenes and their aza-analogues have important applications in materials science and in medicine. Aim of this review is to collect recent reports describing their synthesis, which make use of radical cyclizations promoted by a visible light-triggered photocatalytic process., (Copyright © 2020, Del Tito et al.; licensee Beilstein-Institut.)

Background: Venous thromboembolism (VTE) is highly prevalent in cancer patients and can cause severe morbidity. VTE treatment is essential, but anticoagulation increases the risk of major bleeding. The purpose was to evaluate the impact of VTE and major bleeding on survival and to identify significant risk factors for these events in lung cancer patients., Methods: Data were extracted from a permanent sample of the French national health information system (including hospital and out-of-hospital care) from 2009 to 2016. All episodes of VTE and major bleeding events within one year after cancer diagnosis were identified. A Cox model was used to analyse the effect of VTE and major bleeding on the patients' one-year survival. VTE and major bleeding risk factors were analysed with a Fine and Gray survival model., Results: Among the 2553 included patients with lung cancer, 208 (8%) had a VTE episode in the year following diagnosis and 341 (13%) had major bleeding. Almost half of the patients died during follow-up. Fifty-six (60%) of the patients presenting with pulmonary embolism (PE) died, 48 (42%) of the patients presenting with deep vein thrombosis (DVT) alone died and 186 (55%) of those presenting with a major bleeding event died. The risk of death was significantly increased following PE and major bleeding events. VTE concomitant with cancer diagnosis was associated with an increased risk of VTE recurrence beyond 6 months after the first VTE event (sHR = 4.07 95% CI: 1.57-10.52). Most major bleeding events did not appear to be related to treatment., Conclusion: VTE is frequent after a diagnosis of lung cancer, but so are major bleeding events. Both PE and major bleeding are associated with an increased risk of death and could be indicators of lung cancer mortality.

Arylazo sulfones have been exploited as photoactivatable substrates for the simultaneous photografting of both aryl and methanesulfonyl groups on a gold surface. The obtained samples have been characterized by different spectroscopic techniques including ellipsometry and electrochemistry, infrared reflection absorption, surface-enhanced Raman spectroscopy, XPS, and AFM. Grafting occurs through a simple N-S cleavage and not, as usually observed with aromatic precursors, by electron transfer.

The concepts of wavelength dependence and wavelength selectivity have been commonly used by organic photochemists for a long time. The aim of the present article is to offer a selection of relevant cases where the choice of the irradiation wavelength played a key role in the outcome of a photochemical path. Wavelength dependence can be related to the variation in the efficiency (but not the fate) of a process. Herein, three cases have been recognized where a wavelength-selectivity paradigm operates. Indeed, a different wavelength may (i) activate a different chromophore in a single molecule, (ii) induce the population of different reactive excited states and (iii) sequentially populate the excited state of a compound and the excited state of an intermediate photogenerated from it, which show a different reactivity.

The visible-light-driven preparation of (hetero)aryl stannanes was carried out under both photocatalyst- and metal-free conditions via irradiation of arylazo sulfones in the presence of hexaalkyldistannanes. The reaction shows a high efficiency and a wide substrates scope. The resulting crude organotin derivatives can be directly employed in a Stille protocol.

Hydrodeaminated and monodeuterated aromatics were obtained via a visible-light driven reaction of arylazo sulfones. Deuteration occurs efficiently in deuterated media such as isopropanol- d 8 or in THF- d 8 /water mixtures and exhibits a high tolerance to the nature and the position of the aromatic substituents.

The development and investigation of heteroazo switches has flourished in recent years. Because of their specific photophysical and photochemical properties, they find versatile applications from material science to medicine. However, a deep mechanistic understanding is needed to be able to predict the properties of such azoswitches. In particular, the effect of different substituents on the azo chromophore is of great interest as they are often crucial for embedding the molecular switch into a system of interest. Herein, we provide a detailed spectroscopic and computational study on the influence of substituents on 3-phenylazoindoles chosen as models. We will point out changes in absorption properties and analyze the photostationary state of the thermally labile Z isomers through computational means to provide a general structure-property relationship guideline for further use of these compounds.

Background: Infections with antibiotic-resistant pathogens in cancer patients are a leading cause of mortality. Cancer patients are treated with compounds that can damage bacterial DNA, potentially triggering the SOS response, which in turn enhances the bacterial mutation rate. Antibiotic resistance readily occurs after mutation of bacterial core genes. Thus, we tested whether cancer chemotherapy drugs enhance the emergence of resistant mutants in commensal bacteria., Methods: Induction of the SOS response was tested after the incubation of Escherichia coli biosensors with 39 chemotherapeutic drugs at therapeutic concentrations. The mutation frequency was assessed after induction with the SOS-inducing chemotherapeutic drugs. We then tested the ability of the three most highly inducing drugs to drive the emergence of resistant mutants of major bacterial pathogens to first-line antibiotics., Results: Ten chemotherapeutic drugs activated the SOS response. Among them, eight accelerated the evolution of the major commensal E. coli, mostly through activation of the SOS response, with dacarbazine, azacitidine and streptozotocin enhancing the mutation rate 21.3-fold (P < 0.001), 101.7-fold (P = 0.01) and 1158.7-fold (P = 0.02), respectively. These three compounds also spurred the emergence of imipenem-resistant Pseudomonas aeruginosa (up to 6.21-fold; P = 0.05), ciprofloxacin-resistant Staphylococcus aureus (up to 57.72-fold; P = 0.016) and cefotaxime-resistant Enterobacteria cloacae (up to 4.57-fold; P = 0.018)., Conclusions: Our results suggest that chemotherapy could accelerate evolution of the microbiota and drive the emergence of antibiotic-resistant mutants from bacterial commensals in patients. This reveals an additional level of complexity of the interactions between cancer, chemotherapy and the gut microbiota., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The research on heteroaromatic azoswitches has been blossoming in recent years due to their astonishingly broad range of properties. Minimal chemical modifications can drastically change the demeanor of these switches, regarding photophysical and (photo)chemical properties, promoting them as ideal scaffolds for a vast variety of applications based on bistable light-addressable systems. However, most of the characteristics exhibited by heteroaryl azoswitches were found empirically, and only a few works focus on their rationalization. Herein we report on a mechanistic study employing phenylazoindoles as a model reference, combining spectroscopic experiments with comprehensive computational analysis. This approach will elucidate the intrinsic correlations between the molecular structure of the switch and its thermal behavior, allowing a more rational design transferable to various heteroaryl azoswitches.

The photoinduced (by UV or sunlight) catalyst-free radical trifluoromethylation of (hetero)aromatics (up to 87% yield) has been successfully achieved by using N-aryltrifluoromethanesulfonimides as the trifluoromethylating agents. The process likewise occurred under continuous flow conditions.

A mild and selective C(sp 3 )-H aerobic oxidation enabled by decatungstate photocatalysis has been developed. The reaction can be significantly improved in a microflow reactor enabling the safe use of oxygen and enhanced irradiation of the reaction mixture. Our method allows for the oxidation of both activated and unactivated C-H bonds (30 examples). The ability to selectively oxidize natural scaffolds, such as (-)-ambroxide, pregnenolone acetate, (+)-sclareolide, and artemisinin, exemplifies the utility of this new method., (© 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

The growing interest in light-driven molecular switches and optical oscillators led to the development of molecules that are able to interconvert from a stable to a metastable configuration upon photochemical triggering and to return to the thermodynamically stable form as soon as the light stimulus is removed. Controlling a wide range of back-isomerization lifetimes in the dark is a crucial goal for potential application of these compounds such as molecular machines. We herein present a novel class of easily synthesizable azo photoswitches based on the arylazoindole core. Most notably, minimal modifications of the core, such as methylation, dramatically change the Z-to-E thermal isomerization rate from days (Me in position 1) to the nanosecond range (Me in position 2). Moreover, fine-tuning of the Z-to-E lifetimes can be achieved choosing a proper dimethyl sulfoxide-water (or buffered water) solvent mixture. The photochemical and thermal mechanisms have been elucidated by a thorough computational and spectroscopic analysis. This allowed to detect three different pathways of thermal isomerization and to identify the hydrazone tautomer of the phenylazoindole as the major actor in the fast Z-E thermal isomerization of the NH-substituted switch in protic media.