Tunable electroactive oligothiophene-naphthalimide semiconductors via end-capped engineering: cumulative effects beyond the linker

Aiming to obtain novel functional semiconducting materials for their use in organic electronics, the combination of strong donor moieties with electron-withdrawing units is one of the most useful strategies to obtain ambipolar semiconductors with tunable properties. Nowadays most of the efforts headed to efficient materials are based on small changes in the alkyl pendant chains or by replacing single atoms. However, a precise design of new functional materials is still challenging. For this reason, in this work we present a new synthetic approach for achieving redox amphoteric organic semiconductors by tuning their opto-electrochemical properties via rational chemical modifications. All these materials present low-lying LUMO levels, lower than −4.00 eV with broad absorption up to 800 nm in the UV-Vis-NIR spectra. In addition, they have been characterized by DFT, absorption and Raman vibrational spectroscopies, while their charge stabilization abilities are studied by means of spectroelectrochemical techniques. The results point out to a quite complex electronic scenario that goes beyond the expected cumulative effects of the independent molecular units constituting the final molecular assembly.Funding for open access charge: Universidad de Málaga / CBU

Tuning the charge stabilization and transport in naphthalimide-based semiconductors via a fused-ring and core-engineering strategy

The synthesis and characterization of a family of rationally designed compounds based on naphtha- limide units attached, through conjugated nitrogenated linkers (i.e. pyrazine and imidazoline units), to fused thiophene-based moieties is shown. This combination of different donor–acceptor moieties allows fine tuning of the HOMO and LUMO energy levels, and thus the modulation of their electronic properties. A comprehensive physical chemistry study is carried out, in which the nature of the neutral and charged species are analyzed and their electrical performance is understood in terms of molecular and supramolecular characteristics.This work was financially supported by MICINN (PID2022- 138908NB-C33, PID2022-139548NB-I00 and TED2021-129886B- C43) and the UCM (INV.GR.00.1819.10759). R GN thanks the MICINN for a FPI predoctoral fellowship (PRE2020-092327). FSB and MJAN gratefully acknowledge Universidad Rey Juan Carlos for their predoctoral and postdoctoral contracts. Com- puter resources, technical expertise and assistance was pro- vided by the SCBI (Supercomputing and Bioinformatics) center of the University of M´alaga and are gratefully acknowledged. The Vibrational spectroscopy (EVI) lab of the Research Central Services (SCAI) of the University of M´alaga is also gratefully acknowledged. Funding for open access charge: Universidad de Málaga / CBU

V shaped Tröger oligothiophenes boost triplet formation by ct mediation and symmetry breaking

A new family of molecules obtained by coupling Tröger's base unit with dicyanovinylene-terminated oligothiophenes of different lengths has been synthesized and characterized by steady-state stationary and transient time-resolved spectroscopies. Quantum chemical calculations allow us to interpret and recognize the properties of the stationary excited states as well as the time-dependent mechanisms of singlet-to-triplet coupling. The presence of the diazocine unit in Tröger's base derivatives is key to efficiently producing singlet-to-triplet intersystem crossing mediated by the role of the nitrogen atoms and of the almost orthogonal disposition of the two thiophene arms. Spin-orbit coupling-mediated interstate intersystem crossing (ISC) is activated by a symmetry-breaking process in the first singlet excited state with partial charge transfer character. This mechanism is a characteristic of these molecular triads since the independent dicyanovinylene-oligothiophene branches do not display appreciable ISC. These results show how Tröger's base coupling of organic chromophores can be used to improve the ISC efficiency and tune their photophysics.Funding for open Access charge: Universidad de Málaga / CBUA. The authors thank the Spanish Ministry of Science and Innovation (projects MICIN/FEDER PID2021-127127NB- I00, PID2019-109555GB-I00, PID2022-136231NB-I00, PID2022-138908NB-C33, and TED2021-129886B−C43), the Junta de Andalucía (PROYEXCEL-0328), and the Eusko Jaurlaritza (project PIBA19-0004)

Synthesis and electronic properties of nitrogen-doped π-extended polycyclic aromatic dicarboximides with multiple redox processes

In this work, a series of nitrogen-doped polycyclic aromatic mono and dicarboximides was designed, and their synthesis is reported by an innovative synthetic procedure that avoids metal-based cross-coupling reactions. A combined theoretical, electrochemical, optical spectroscopy and material characterization study allows the investigation of the interplay of different effects such as (i) the type of solubilizing chain, (ii) the all-acceptor vs. donor–acceptor nature of the novel systems, and (iii) the molecular ordering, on the ability to stabilize multiple charges and on the OTFT device response characteristics. The amphoteric redox behavior of some of the novel systems allow to obtain ambipolar mobilities while the electron mobility values of the three all-acceptor systems can be rationalized in terms of supramolecular aggregation and enhanced film-forming ability.Funding for open access charge: Universidad de Málaga. This work was financially supported by MICINN (PID2019-106268GB-C33) and the UCM (INV.GR.00.1819.10759). MJAN gratefully acknowledges Universidad Rey Juan Carlos for a predoctoral contract. The university of Ma´laga acknowledges support from Junta de Andalucı´a (projects UMA18-FEDERJA080 and P18-FR-4559) and MICINN (PID2019-110305GB-I00). RPO and AH also thank the Research Central Services (SCAI) of the University of Ma´laga and especially the Vibrational Spectroscopy Laboratory

Comparing the microstructure and photovoltaic performance of 3 perylene imide acceptors with similar energy levels but different packing tendencies

While it is widely recognized that microstructure plays an important role in the performance of organic photovoltaics (OPV), systematic studies are often challenging, as varying the molecular packing through typical chemical means (such as sidechain tuning) often affects the molecular energy levels, thus preventing a clear correlation. In this work we present the synthesis of three perylene imide (PI) based electron acceptors with almost identical energy levels, but distinct packing tendencies. We confirm our initial hypothesis by measuring solution and solid-state absorption, cyclic voltammetry as well as characterizing the films by grazing incident wide angle X-ray scattering (GIWAXS). In a second step, we repeat the characterization of the three materials in blends with two polymer donors, namely PCDTBT or PBDBT, whose energy levels are well aligned with those of the PI acceptors, and which, additionally, exhibit different degrees of structural order. We show how the initial strong difference between acceptors is partially blurred in blends, but still critical. Finally, we correlate our structural data with OPV devices made with the corresponding six blends. Our data suggest that a good donor acceptor marriage should ensure good energy alignment but also exhibit complementary crystallization tendencies of the two components.The authors acknowledge financial support from the Spanish Ministry of Science and Innovation through the Severo Ochoa” Program for Centers of Excellence in R&D (No. CEX2019-000917-S), and projects PGC2018-095411-B-I00, PID2019-106268GB-C33 and PID2019-110305GB-I00, as well as the European Commission through the Horizon 2020 Marie Sklodowska-Curie ITN Programme, SEPOMO, Grant Number: 722651, and the UCM (INV.GR.00.1819.10759). E.G. specially acknowledges Comunidad de Madrid and Universidad Complutense de Madrid for a post-doctoral contract (CT20/19- CT21/19/PEJD-2018-POST/IND-8661PAI). M.J.A.N. acknowledges URJC for a post-doctoral contract. R.P.O and A.H. also acknowledge support from Junta de Andalucía (projects UMA18-FEDERJA-080). We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

HTLV-1 infection in solid organ transplant donors and recipients in Spain

HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy

In vivo screening characterizes chromatin factor functions during normal and malignant hematopoiesis

Bulk ex vivo and single-cell in vivo CRISPR knockout screens are used to characterize 680 chromatin factors during mouse hematopoiesis, highlighting lineage-specific and normal and leukemia-specific functions. Cellular differentiation requires extensive alterations in chromatin structure and function, which is elicited by the coordinated action of chromatin and transcription factors. By contrast with transcription factors, the roles of chromatin factors in differentiation have not been systematically characterized. Here, we combine bulk ex vivo and single-cell in vivo CRISPR screens to characterize the role of chromatin factor families in hematopoiesis. We uncover marked lineage specificities for 142 chromatin factors, revealing functional diversity among related chromatin factors (i.e. barrier-to-autointegration factor subcomplexes) as well as shared roles for unrelated repressive complexes that restrain excessive myeloid differentiation. Using epigenetic profiling, we identify functional interactions between lineage-determining transcription factors and several chromatin factors that explain their lineage dependencies. Studying chromatin factor functions in leukemia, we show that leukemia cells engage homeostatic chromatin factor functions to block differentiation, generating specific chromatin factor-transcription factor interactions that might be therapeutically targeted. Together, our work elucidates the lineage-determining properties of chromatin factors across normal and malignant hematopoiesis

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised