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We present a joint experimental and theoretical study of the through-space charge transfer (CT) TADF molecule TpAT-tFFO. The measured fluorescence has a singular Gaussian line shape but two decay components, coming from two distinct molecular CT conformers, energetically only 20 meV apart. We determined the intersystem crossing rate (1 × 107 s–1) to be 1 order of magnitude faster than radiative decay, and prompt emission (PF) is therefore quenched within 30 ns, leaving delayed fluorescence (DF) observable from 30 ns onward as the measured reverse intersystem crossing (rISC) rate is >1 × 106 s–1, yielding a DF/PF ratio >98%. Time-resolved emission spectra measured between 30 ns and 900 ms in films show no change in the spectral band shape, but between 50 and 400 ms, we observe a ca. 65 meV red shift of the emission, ascribed to the DF to phosphorescence transition, with the phosphorescence (lifetime >1 s) emanating from the lowest 3CT state. A host-independent thermal activation energy of 16 meV is found, indicating that small-amplitude vibrational motions (∼140 cm–1) of the donor with respect to the acceptor dominate rISC. TpAT-tFFO photophysics is dynamic, and these vibrational motions drive the molecule between maximal rISC rate and high radiative decay configurations so that the molecule can be thought to be “self-optimizing” for the best TADF performance.

Background Salivary gland tumors (SGT) are rare with limited systemic treatments. We aimed to evaluate the activity of selinexor, an oral selective inhibitor of nuclear export, in patients with recurrent unresectable or metastatic SGT. Methods GEMS-001 is an open-label phase 2 study for patients with recurrent or metastatic SGT with two parts. In part 1 of the protocol, patients had tumor samples profiled with targeted next generation sequencing as well as immunohistochemistry for androgen receptor, HER-2 and ALK. For part 2, patients with no targetable alterations identified or no matched agents available are eligible to receive selinexor 60 mg given twice weekly every 28 days. The primary endpoint was objective response rate. Secondary endpoints included progression-free survival (PFS) and prevalence of druggable alterations across SGT. Results Between July 2014 and September 2021, 100 patients were enrolled in GEMS-001 and underwent genomic and proteomic profiling. A total of 21 patients (12 female) with a median age of 61 years (range 36–79) who lacked actionable alterations or available matched therapies were treated with selinexor. Histological subtypes (World Health Organization classification) included adenoid cystic carcinoma (n = 10), salivary duct carcinoma (n = 3), acinic cell carcinoma (n = 2) and other (n = 6). Fourteen patients were treatment naïve and 7 patients had received 1 or more lines of treatment prior to enrollment. Of 18 evaluable patients, stable disease as best response was observed in 17 patients (94%) (stable disease ≥ 6 months in 7 patients (39%)). Tumor reduction of target lesions was observed in 11 patients (61%). However, no partial or complete responses were observed. The median PFS was 4.9 months (95% confidence interval, 3.4–10). The most common treatment-related grade 1–2 adverse events were nausea [17 patients (81%)], fatigue [16 patients (76%)] and dysgeusia [12 patients (57%)]. Most common treatment-related grade 3–4 adverse events were hyponatremia [3 patients (14%)], neutrophil count decrease [3 patients (14%)] and cataracts [2 patients (10%)]. No treatment-related deaths were observed. Conclusions Although tumor reduction was observed across participants single agent selinexor antitumor activity was limited. Trial registration This clinical trial is registered at ClinicalTrials.gov (NCT02069730) first posted February 24 2014.

BACKGROUND People with spinal cord injury (SCI) report feeling unprepared to manage their disability upon discharge to the community. This situation is exacerbated when they return to settings where self-management support and resources are sparse, thus increasing the risk of costly secondary conditions and rehospitalizations. These factors make a compelling case for implementing innovative community-based SCI self-management programs that empower and engage individuals with SCI. Using a community-engaged research (CEnR) approach, we developed a peer-supported SCI self-management intervention, known as PHOENIX (Peer-supported Health Outreach, Education, and Information Exchange), which integrates online educational content and support from peer navigators (PNs) through telehealth, to promote health and community participation after SCI. OBJECTIVE The objective of this pilot study is to evaluate the feasibility and acceptability of PHOENIX and the study design, and to obtain estimates of the variability of relevant outcome measures. METHODS We conducted a pilot randomized waitlist-controlled trial (n=30) in collaboration with the South Carolina Spinal Cord Injury Association (SCSCIA), our long-standing community-based nonprofit organization research partner. We recruited 4 PNs through our SCSCIA collaboration using its existing network of trained peer mentors. Our study design supported comparison of the following 2 randomly assigned groups: PHOENIX intervention group and waitlist enhanced usual care (EUC) group. The PHOENIX intervention was administered online by PNs over 16 weeks through scheduled “video visits.” The EUC group participated in the study for 16 weeks with usual community services and no navigation, and received 4 monthly newsletters from the SCSCIA on a variety of SCI-relevant topics. At the end of the waitlist period, the waitlist EUC group received the full PHOENIX intervention. Measures of feasibility included PN and participant recruitment and retention, PN workload, protocol adherence, and incidence of technical issues. We conducted qualitative interviews with participants and PNs to evaluate the acceptability of PHOENIX and the study design. Outcome measures, including community participation, quality of life, and the occurrence and subjective impact of medically serious secondary conditions and rehospitalizations, were assessed at baseline after randomization and at subsequent time points to allow between-group comparisons. RESULTS PN hiring and training were completed in August 2018. Recruitment began in November 2018. A total of 30 participants were recruited across South Carolina, and 28 participants completed follow-up by August 2020. An analysis of the results is being finalized, and the results are expected to be published in 2023. CONCLUSIONS This study will provide valuable information to guide future research seeking to address unmet self-management needs and improve outcomes in individuals with SCI. Feasibility findings of this study will provide evidence from CEnR guided by people with SCI and SCI service providers to inform further development, testing, and dissemination of effective and scalable self-management strategies for people with SCI. INTERNATIONAL REGISTERED REPORT RR1-10.2196/42688

BACKGROUND: Many hazardous drugs (HDs) are excreted in urine and feces, and evidence has shown that bathrooms of patients receiving chemotherapy at home are contaminated with HDs. However, little information exists on bathroom contamination in ambulatory clinics where HDs are administered. OBJECTIVES: This project aimed to determine the presence of HD residue in the patient and staff bathrooms of an ambulatory cancer center. METHODS: A quality improvement project was initiated to examine potential contamination by the HDs 5-fluorouracil and oxaliplatin in a patient bathroom and a secured badge-access staff bathroom in the infusion department of an ambulatory comprehensive cancer center. Twice-daily wipe testing was conducted on the floor in front of the toilet and the flush handle for five consecutive days. FINDINGS: Sixty-five percent of the samples from the floor of the patient bathroom were positive for at least one of the HDs. In the staff bathroom, 35% of the floor samples were positive for at least one HD. None of the flush handle samples were above the level of detection.

Atraves das analises dos filmes documentais Um passaporte hungaro (2001), Elena (2012) e Os dias com ele (2013) demonstramos como as cineastas, ao desdobrarem-se tambem como personagens em seus filmes, rompem com uma pratica de representacao de alteridades no cinema. As praticas autoritarias da representacao do outro sao desmontadas a partir do deslocamento de perspectiva adotado, da valorizacao da historia em “h” minuscula frente aquela oficial, frequentemente autoritaria. Nossa contribuicao reside na analise de como a presenca fisica dessas diretoras no espaco diegetico de seus filmes desestruturam discursos hegemonicos, construindo novas estrategias na reconstrucao de memorias privadas e politicas. Ao articular o individual dentro do campo cinematografico, essas cineastas atualizam o preceito feminista de que a esfera privada e expressivamente politica; ao faze-lo, elas tambem se consolidam como sujeitos-criadoras apoderando-se de uma autoridade dentro da industria cenografica nacional, lugar onde a participacao de mulheres e o reconhecimento por suas obras ainda e restrito.

Objective Class 3 semaphorins are reduced in the synovial tissue of RA patients and these proteins are involved in the pathogenesis of the disease. The aim of this study was to identify the transcription factors involved in the expression of class 3 semaphorins in the synovium of RA patients. Methods Protein and mRNA expression in synovial tissue from RA and individuals at risk (IAR) patients, human umbilical vein endothelial cells (HUVEC) and RA fibroblast-like synoviocytes (FLS) was determined by ELISA, immunoblotting and quantitative PCR. TCF-3, EBF-1 and HOXA5 expression was knocked down using siRNA. Cell viability, migration and invasion were determined using MTT, calcein, wound closure and invasion assays, respectively. Results mRNA expression of all class 3 semaphorins was significantly lower in the synovium of RA compared with IAR patients. In silico analysis suggested TCF-3, EBF-1 and HOXA5 as transcription factors involved in the expression of these semaphorins. TCF-3, EBF-1 and HOXA5 silencing significantly reduced the expression of several class 3 semaphorin members in FLS and HUVEC. Importantly, HOXA5 expression was significantly reduced in the synovium of RA compared with IAR patients and was negatively correlated with clinical disease parameters. Additionally, TNF-α down-regulated the HOXA5 expression in FLS and HUVEC. Finally, HOXA5 silencing enhanced the migratory and invasive capacities of FLS and the viability of HUVEC. Conclusion HOXA5 expression is reduced during the progression of RA and could be a novel therapeutic strategy for modulating the hyperplasia of the synovium, through the regulation of class 3 semaphorins expression.

Objective: Semaphorin 3B (Sema3B) decreases the migratory and invasive capacities of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) and suppresses expression of matrix metalloproteinases. We undertook this study to examine the role of Sema3B in a mouse model of arthritis and its expression in RA patients. Methods: Clinical responses, histologic features, and FLS function were examined in wild-type (WT) and Sema3B−/− mice in a K/BxN serum transfer model of arthritis. Protein and messenger RNA expression of Sema3B in mouse joints and murine FLS, as well as in serum and synovial tissue from patients with arthralgia and patients with RA, was determined using enzyme-linked immunosorbent assay, immunoblotting, quantitative polymerase chain reaction, and RNA sequencing. FLS migration was determined using a wound closure assay. Results: The clinical severity of serum-induced arthritis was significantly higher in Sema3B−/− mice compared to WT mice. This was associated with increased expression of inflammatory mediators and increased migratory capacity of murine FLS. Administration of recombinant mouse Sema3B reduced the clinical severity of serum-induced arthritis and the expression of inflammatory mediators. Sema3B expression was significantly lower in the synovial tissue and serum of patients with established RA compared to patients with arthralgia. Serum Sema3B levels were elevated in patients with arthralgia that later progressed to RA, but not in those who did not develop RA; however, these levels drastically decreased 1 and 2 years after RA development. Conclusion: Sema3B expression plays a protective role in a mouse model of arthritis. In RA patients, expression levels of Sema3B in the serum depend on the disease stage, suggesting different regulatory roles in disease onset and progression.

In the present article, I examine Daniela Thomas and Walter Salles's Linha de passe (2008) and Anna Muylaert's Que horas ela volta? (2015). I argue that these films create new representational possibilities for subjects withincontemporary Brazilian culture by breaking with the dominant model of the favela as a predominantly masculine space that is essentially "out of control." This renegotiation brings with it a valorization of the subjectivity of women who work in the city. I argue that this valorization takes place in both films through the physical displacement of those who traditionally do not enjoy subject status and yet dare to enter territories previously denied to them.

Posterior reversible encephalopathy syndrome (PRES) is a neurological condition with a wide range of symptoms, including visual disturbances, headache, vomiting, seizures, and altered consciousness. This review describes the pathophysiology of PRES, as well as the clinical, diagnostic, and therapeutic intervention during pregnancy. The gold standard for diagnosis of PRES is Magnetic Resonance Imaging (MRI), helping to differentiate it from other similar conditions. The aim of this paper is to review the principal aspects of PRES, general care, blood pressure control, and seizures prevention while avoiding potential injuries to the mother and fetus in the event of pregnancy. We concluded that PRES can be effectively treated and reversed if prompt diagnostic action is made, and adequate care is initiated.

Fluorescent sensors with selectivity and sensitivity to metal ions are an active field in supramolecular chemistry for biochemical, analytical, and environmental problems. Mg2+ is one of the most abundant divalent ions in the cell, and it plays a critical role in many biological processes. Coumarin-based sensors are widely used as desirable fluorophore and binding moieties showing a remarkable sensitivity and fluorometric enhancement for Mg2+ . In this work, density functional theory/multireference configuration interaction (DFT/MRCI) calculations were performed in order to understand the sensing behavior of the organic fluorescent sensor 7-hydroxy-4-methyl-8-((2-(pyridin-2-yl)hydrazono)methyl)-2H-chromen-2-one (PyHC) in ethanol to solvated Mg2+ ions. The computed optical properties reproduce well-reported experimental data. Our results suggest that after photoexcitation of the free PyHC, a photo-induced electron transfer (PET) mechanism may compete with the fluorescence decay to the ground state. In contrast, this PET channel is no longer available in the complex with Mg2+ making the emissive decay more efficient. © 2019 Wiley Periodicals, Inc.

espanolEn este articulo se realiza un analisis sobre las condiciones sociales y productivas de las familias pertenecientes a tres asociaciones campesinas que surgen en el marco del conflicto armado, como propuestas comunitarias de resistencia pacifica y construccion de paz en Colombia. Los resultados cuantitativos de esta investigacion se obtienen a traves de un instrumento estructurado aplicado a 102 hogares pertenecientes a familias asociadas en el departamento de Santander y la zona del Magdalena Medio, seleccionados por muestreo aleatorio simple. Se destacan las ventajas sociales, educativas y productivas que estos modelos asociativos, surgidos como defensa ante el conflicto armado, brindan a sus familias y que pueden ser capitalizados como modelos productivos en el postconflicto. Tambien se encontraron carencias en la asistencia estatal y dificultades en la formalizacion de la tenencia de la propiedad de la tierra y la comercializacion de la produccion. EnglishIn this article, an analysis is made about the social and productive conditions of families belonging to three peasant associations that arise in the framework of the armed conflict, as community proposals of peaceful resistance and peace building in Colombia. The quantitative results of this research were obtained through a structured instrument applied to 102 households belonging to associated families in the Department of Santander and the Magdalena Medio area, selected by simple random sampling. It highlights the social, educational, productive advantages that these associative models, emerged as a defense to the armed conflict, provide to the families, and how they can be can be capitalized as productive models in the post-conflict. There were also shortcomings in state assistance and difficulties in formalizing tenure of land ownership and commercialization of production.

The vitamin D receptor (VDR) is responsible for mediating the effects of vitamin D through regulation of other gene transcriptions. There are several polymorphisms that alter the gene expression or the function of this protein. We aimed to analyze the association between two SNPs of VDR gene and melanoma cancer in Colombian patients.We included 120 healthy individual as controls and 120 melanoma cancer patients as cases . Patients in both groups were matched in terms of gender and age. The genotyping of rs731236 and rs2228570 polymorphisms was performed using PCR-RFLP. The SNPStats program was used to carry out the statistical analysis through a logistic regression model.Under dominant model, we found that rs2228570 polymorphism was associated with melanoma cancer risk (C/C vs C/T-T/T, OR: 5.10, 95% CI: 2.85-9.14), whereas rs731236 polymorphism was associated with a protective effect against this cancer (T/T vs T/C, OR: 0.27, 95% CI: 0.14-0.53).Our results suggested that both polymorphisms were involved in the development of melanoma cancer, increasing or decreasing this risk.

Multireference quantum chemical calculations were performed in order to investigate the (reverse) intersystem crossing ((R)ISC) mechanisms of 4,5-di(9H-carbazol-9-yl)-phthalonitrile (2CzPN). A combination of density funcional theory (DFT) and multireference configuration interaction methods (MRCI) was used. The excellent agreement of the computed absorption spectrum with available experimental absorption spectra lends confidence to the chosen computational protocol. Vertically, two triplet excited states (T1 and T2) are found below the S1 state. At the excited state minima, the calculated adiabatic energies locate only the T1 state below the S1 state. The enhanced charge transfer (CT) character of the geometrically relaxed excited states causes their mutual (direct) spin–orbit coupling (SOC) interaction to be low. Contributions of vibronic SOC to the (R)ISC probability, evaluated by a Herzberg–Teller-like procedure for a temperature of 300 K, are small but not negligible. For ISC, the S1 → T1 channel is the fastest (8 × 106 s−1), while the S1 → T2 channel is found to be thermally activated (9 × 104 s−1) and less efficient when proceeding from the adiabatic S1 state. Our calculations also reveal, however, a barrierless S1 → T2 ISC pathway near the Franck–Condon region. RISC is found to essentially proceed via the T1 → S1 channel, with a rate constant of (3 × 104 s−1) if our adiabatic singlet–triplet energy gap in vacuum (ΔEST = 0.12 eV) is employed. Shifting the potentials to match two experimentally reported singlet–triplet energy gaps in toluene (ΔEST = 0.21 and 0.31 eV, respectively) leads to a drastic reduction of the computed rate constant by up to 4 orders of magnitude. The T2 state is not expected to play a major role in mediating triplet–singlet transitions in 2CzPN unless it is directly populated by hot excitons. No indication for a strong vibronic coupling of the T2 and T1 potentials is found, which could help overcome the negative exponential dependence of the RISC rate constant on the magnitude of the energy gap.

Unidad de excelencia María de Maeztu MdM-2015-0552 Most of the literature on the causes of tropical deforestation has focused on the proximate and distal causes. However, research exploring the psychological drivers of deforestation, i.e., motivations, is still scant despite being crucial to understand the processes of land-use change and individual decision making within social-ecological systems. We studied the combined effect of structural and individual causes of deforestation, with particular emphasis on motivations, for a sample of rural households in Colombia's foremost tropical deforestation frontier. We implemented a new instrument based on self-determination theory to measure five different types of motivations to protect the forests: intrinsic, guilt/regret, social, extrinsic motivations, and amotivation (lack of motivation). Our findings show that, controlling for the structural and household drivers widely identified in the deforestation literature, intrinsic motivations positively correlate with less self-reported deforestation. Also, amotivated people and those with extrinsic motives, such as expected payments for conservation, are more likely to deforest. Our results show that motivations can explain variation in land-use decisions and thus should be considered when designing, implementing, and evaluating conservation policies aiming to halt deforestation.

Objective Approximately 10% of stillbirths are attributed to fetal anomalies, but anomalies are also common in live births. We aimed to assess the relationship between anomalies, by system and stillbirth. Design Secondary analysis of a prospective, case-control study. Setting Multicentre, 59 hospitals in five regional catchment areas in the USA. Population or sample All stillbirths and representative live birth controls. Methods Standardised postmortem examinations performed in stillbirths, medical record abstraction for stillbirths and live births. Main outcome measures Incidence of major anomalies, by type, compared between stillbirths and live births with univariable and multivariable analyses using weighted analysis to account for study design and differential consent. Results Of 465 singleton stillbirths included, 23.4% had one or more major anomalies compared with 4.3% of 1871 live births. Having an anomaly increased the odds of stillbirth; an increasing number of anomalies was more highly associated with stillbirth. Regardless of organ system affected, the presence of an anomaly increased the odds of stillbirth. These relationships remained significant if stillbirths with known genetic abnormalities were excluded. After multivariable analyses, the adjusted odds ratio (aOR) of stillbirth for any anomaly was 4.33 (95% CI 2.80-6.70) and the systems most strongly associated with stillbirth were cystic hygroma (aOR 29.97, 95% CI 5.85-153.57), and thoracic (aOR16.18, 95% CI 4.30-60.94) and craniofacial (aOR 35.25, 95% CI 9.22-134.68) systems. Conclusions In pregnancies affected by anomalies, the odds of stillbirth are higher with increasing numbers of anomalies. Anomalies of nearly any organ system increased the odds of stillbirth even when adjusting for gestational age and maternal race. Tweetable abstract Stillbirth risk increases with anomalies of nearly any organ system and with number of anomalies seen.

Resumen Se investigó el espectro electrónico vertical de la oxoglaucina utilizando el método de interacción de configuraciones multi-referencial (DFT/MRCI). Se analizó el efecto de los grupos metilo y metoxilo sobre la geometría y la distribución energética de los estados excitados de baja energía utilizando la base TZVP. Se encontró que, en los mínimos del estado fundamental de oxoglaucina, oxoglaucina sin grupos metilo y sin grupos metoxilo, los estados excitados singulete de más baja energía son de tipo nП* (S1) y ПП* (S2) y que los estados triplete ПП* (T1) y nП* (T2) son energéticamente accesibles desde S1 Desde el punto de vista energético, se encontró que el canal más eficiente para el entrecruzamiento de sistemas singulete-triplete es 1(nП*)3(ПП*). Aunque la presencia de los grupos metilo y metoxilo distorsionan la planaridad del sistema de anillos, su efecto en la distribución (vertical) de los estados singulete y triplete de más baja energía es mínimo. Abstract The vertical electronic spectrum of oxoglaucine by means of a multireference configuration interaction method (DFT/ MRCI) was studied. The effect of both methyl and methoxy groups on the geometries and energetic distribution of the low-lying excited states was analyzed. The results show that, by means of the TZVP basis set, at the ground state minima of oxoglaucine, oxoglaucine without methyl and methoxy groups, the lowest excited singlet states are of nП* (S1) and ПП* (S2) type. Triplet states of ПП* (T1) and nП* (T2) type are energetically accessible from S1. From the energetic point of view, it can be proposed that the channel for an efficient intersystem crossing 1(nП*)3(ПП*) is plausible. Although the presence of the methyl and methoxyl groups distort the planarity of the rings system, the effect in the vertical distribution of the lowest lying singlet and triplet states can be considered as negligible. Resumo O espectro eletrônico vertical da oxoglaucina foi investigado por meio do método de interação de configurações multi referência (DFT/MRCI). Foi estudado o efeito dos grupos metilo e metoxi nas geometrias e na distribuição energética dos estados excitados de baixa energia utilizando a base TZVP. Os resultados mostram que nos mínimos do estado fundamental da oxoglaucina, a oxoglaucina sem grupos metilo e metoxi os estados excitados singletos de mais baixa energia são de tipo nП* (S1) y ПП* (S2) e que os estados tripletos do tipo ПП* (T1) e nП* (T2) são energeticamente acessíveis a partir de S1 Do ponto de vista energético, pode-se propor que o canal para um cruzamento intersistema eficiente 1(nП*)3(ПП*) seja plausível. Embora a presença dos grupos metilo e metoxilo distorçam a planaridade do sistema de anéis, o efeito na distribuição vertical dos estados de singleto e de tripleto de mais baixa energía pode ser considerado negligenciável.

Background Salivary gland tumors (SGT) are rare and heterogeneous diseases with limited systemic options available. Results from recent basket trials including SGT cohorts for specific actionable alterations (AA) have described promising outcomes with molecularly targeted approaches (TA). Methods The GEMS-001 study (NCT02069730) is an ongoing multi-arm trial with two phases. In part 1, recurrent or metastatic (R/M) SGT patients (pts) undergo comprehensive immunohistochemistry (IHC) including HER2, androgen receptor (AR) and ALK translocation and multigene panel testing (NGS). Based on the molecular profiling results in part 1, R/M SGT pts are matched to available targeted therapies on disease progression. Here, we present the efficacy results for the matched cohort of the GEMS-001 study. Results As of July 2021, 100 pts underwent molecular profiling within part 1. According to the SGT subtype (WHO 2017): 49% adenoid cystic carcinoma (ACC), 18% salivary duct carcinoma (SDC), 9% acinic (ACI) and 24% other subtypes (O). Overall, on IHC HER2 overexpression was present in 10%, AR 24% and ALK translocation 0%. On NGS, PIK3CA mutation (mut) was in 10%, HRAS mut 7%, ERBB2/3 alterations (alt) 5%, NOTCH1-3 mut 2% and ETV6-NTRK3 fusion 2%. Up to 45% pts displayed at least 1 AA and 25% had ≥2 AA. AA were enriched in SDC (100% ≥1 AA) as compared to ACI (33% ≥1 AAs), O (58% ≥1 AA) or ACC (22% ≥1 AA) (p Citation Format: Alberto Hernando-Calvo, Eoghan Malone, Daphne Dai, Amy Prawira, Ilan Weinreb, Anneli Eliason, Angela Rodriguez, Katherine Lajkosz, Sarah Jennings, Anna Spreafico, Lillian L. Siu, Aaron Hansen. Genomic profiling and matched therapy for recurrent or metastatic salivary gland neoplasms. Results from the matched cohort of the GEMS-001 clinical trial [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P154.