Synthesis and Characterization of Two Novel Naphthalenediimide/Zinc Phosphonate Crystalline Materials Precipitated from Different Solvents.

Hybrid naphthalenediimide/zinc phosphonate materials (NDI/Zn) were prepared by mixing solutions of N,N'-bis(2-phosphonoethyl)-1,4,5,8-naphthalenediimide (PNDI) and zinc nitrate, resulting in the precipitation of the desired compounds. Samples precipitated from water and N,N-dimethylformamide (DMF) were produced. The obtained samples had the expected elemental composition, and the presence of naphthalenediimides (NDI) was ascertained by infrared and UV-visible spectroscopy. All the samples were crystalline, according to powder X-ray diffraction. Nitrogen adsorption isotherms showed the presence of porosity in the NDI/Zn samples. Mesopores with a diameter = 4.1 nm were present in the sample from DMF, with total pore volume reaching 0.13 cm3/g.

Rashba Spin Splitting Limiting the Application of 2D Halide Perovskites for UV-Emitting Devices.

Layered lead halide perovskites have attracted much attention as promising materials for a new generation of optoelectronic devices. To make progress in applications, a full understanding of the basic properties is essential. Here, we study 2D-layered (BA)2PbX4 by using different halide anions (X = I, Br, and Cl) along with quantum confinement. The obtained cell parameter evolution, supported by experimental measurements and theoretical calculations, indicates strong lattice distortions of the metal halide octahedra, breaking the local inversion symmetry in (BA)2PbCl4, which strongly correlates with a pronounced Rashba spin-splitting effect. Optical measurements reveal strong photoluminescence quenching and a drastic reduction in the PL quantum yield in this larger band gap compound. We suggest that these optical results are closely related to the appearance of the Rashba effect due to the existence of a local electric dipole. The results obtained in ab initio calculations showed that the (BA)2PbCl4 possesses electrical polarization of 0.13 µC/cm2 and spin-splitting energy of about 40 meV. Our work establishes that local octahedra distortions induce Rashba spin splitting, which explains why obtaining UV-emitting materials with high PLQY is a big challenge.

Phenotypic Diversity and Genetic Parameters of Coffea canephora Clones.

The simultaneous analysis of the maximum number of chemical elements present in plant tissues provides more comprehensive information about their chemical constitution and increases the number of characteristics for the selection process in various plant breeding programs. The objective of this study was to analyze productivity, grain yield, and concentration of chemical elements in tissues of Coffea canephora clones to study phenotypic diversity and estimate genetic parameters for use in breeding. This experiment was carried out in Manaus, Amazonas, Brazil, in randomized blocks with four replications. The concentrations of elements in various organs were quantified using total reflection X-ray fluorescence (TXRF). Genetic parameters and genetic divergence were estimated, and genotypes were clustered using the UPGMA hierarchical method and non-metric multidimensional scaling analysis. The study allowed us to differentiate the performance of the clones in terms of the absorption of essential and non-essential chemical elements for plant development and to analyze the correlation of the characteristics in the selection process. TXRF efficiently characterizes the presence and concentration of multiple elements, aiding genotype discrimination for C. canephora improvement.

Multivisceral resection for retroperitoneal liposarcoma-is it worth it? A 20-year single-center experience.

PURPOSE: Soft tissue sarcomas are rare malignant tumors. Liposarcoma constitutes the most frequent histological subtype of retroperitoneal sarcoma. The prognosis of soft tissue sarcomas depends on clinical and histologic characteristics. OBJECTIVE: Evaluate variables that may be related to the overall and local recurrence-free survival in patients with retroperitoneal liposarcoma and discuss the need for visceral resection en-bloc for tumors. METHODS: A retrospective analysis was conducted of the medical records of 60 patients seen between 1997 and 2017 who underwent surgical resection of retroperitoneal liposarcoma. RESULTS: The overall survival rate at 5 years of follow-up was 75.22% (95% confidence interval [CI] 0.58-0.86). The probability of a local recurrence-free survival at 5 years of follow-up was 26.04% (95% CI 0.11-0.44). The multivariate analysis showed that dedifferentiated or pleomorphic tumors and R2/fragmented resection were associated with a shorter time to recurrence. No other characteristics markedly influenced the overall survival (P > 0.05). CONCLUSION: Patients with dedifferentiated or pleomorphic tumors and incomplete resection were associated with higher local recurrence rates than others. This study reinforces the need for complete and en-bloc resection with organs when there is clear involvement or technical surgical difficulty to maintain the tumor integrity.

A autonomia do adolescente em relação ao direto de imunização contra infecções sexualmente transmissíveis: revisão bibliográfica / La autonomía de los adolescentes en relación con la inmunización directa contra las infecciones de transmisión sexual: revisión bibliográfica / The autonomy of adolescents in relation to the direct of immunization against sexually transmitted infections: bibliographic review

O presente estudo trata-se de uma análise na literatura sobre o aspecto bioético da autonomia em relação a imunização contra Hepatite B e HPV na adolescência. Foi realizada uma revisão bibliográfica baseada no método prisma onde foram incluídos artigos em português e inglês os quais foram pesquisados nas plataformas Scientific Electronic Library Online (SciELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e National Library of Medicine (PUBMED), utilizando os seguintes descritores Hepatitis B Vaccines, bioethics, Humans. Os resultados demostraram a eficiência dos profissionais de saúde no contato com o indivíduo e o convencimento deste através de um diálogo aberto e criação de vínculos. Evidenciou-se ainda o estudo evidenciou o direito a autonomia progressiva do paciente, no qual este ganha o direito a algumas escolhas como as imunizações de doenças sexualmente transmissíveis, como é o caso da Hepatite B e HPV, no entanto é necessário que o adolescente seja instruído sobre a imunização. Assim sendo, reconhece-se o direito a autonomia progressiva do adolescente, referente a escolha das imunizações contra a Hepatite B e HPV, entretanto, deve-se considerar que estes indivíduos sejam instruídos sobre os benefícios individuais e/ou coletivos da vacinação, contemplados por atividades de educação em saúde por profissionais qualificados, objetivando ampliar a cobertura global de imunização com doenças que caracterizam problemas de saúde pública.

El presente estudio es un análisis de la literatura sobre el aspecto bioético de la autonomía en relación con la inmunización contra la Hepatitis B y el VPH en la adolescencia. Se realizó una revisión bibliográfica basada en el método del prisma, que incluyó artículos en portugués e inglés que fueron buscados en la Biblioteca Científica Electrónica en Línea (SciELO), Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS) y la Biblioteca Nacional de Medicina (PUBMED), utilizando los siguientes descriptores Vacunas Hepatitis B, bioética, Humanos. Los resultados demostraron la eficiencia de los profesionales de la salud en contactar al individuo y convencerlo a través de un diálogo abierto y creación de vínculos. También se evidenció que el estudio evidenció el derecho del paciente a la autonomía progresiva, en la que adquiere el derecho a algunas opciones como las inmunizaciones de enfermedades de transmisión sexual, como la Hepatitis B y el VPH, sin embargo, es necesario que el adolescente sea educado sobre la inmunización. Por lo tanto, se reconoce el derecho del adolescente a la autonomía progresiva, en cuanto a la elección de las vacunas contra la Hepatitis B y el VPH, sin embargo, se debe considerar que estos individuos sean educados sobre los beneficios individuales y/o colectivos de la vacunación, contemplados por las actividades de educación en salud por profesionales calificados, con el objetivo de ampliar la cobertura mundial de inmunización con enfermedades que caracterizan los problemas de salud pública.

The present study is an analysis of the literature on the bioethical aspect of autonomy in relation to immunization against Hepatitis B and HPV in adolescence. A bibliographic review was carried out based on the prism method, which included articles in Portuguese and English which were searched on the Scientific Electronic Library Online (SCIELO), Latin American and Caribbean Literature on Health Sciences (LILACS) and the National Library of Medicine (PUBMED), using the following descriptors Hepatitis B Vaccines, bioethics, Humans. The results demonstrated the efficiency of health professionals in contacting the individual and convincing him/her through an open dialogue and creation of bonds. It was also evidenced the study evidenced the patient's right to progressive autonomy, in which he gains the right to some choices such as immunizations of sexually transmitted diseases, such as Hepatitis B and HPV, however it is necessary for the adolescent to be educated about immunization. Therefore, the adolescent's right to progressive autonomy is recognized, regarding the choice of immunizations against Hepatitis B and HPV, however, it must be considered that these individuals are instructed on the individual and/or collective benefits of vaccination, contemplated by health education activities by qualified professionals, aiming to expand the global coverage of immunization with diseases that characterize public health problems.

Abordagem epidemiológica e considerações bioéticas sobre a infecção pelo vírus da hepatite b em crianças e adolescentes no estado do acre, Brasil / Enfoque epidemiológico y consideraciones bioéticas sobre la infección por el virus de la hepatitis b en niños y adolescentes en el estado de Acre, Brasil / Epidemiological approach and bioethical considerations on hepatitis b virus infection in children and adolescents in the state of Acre, Brazi

O estudo investiga os aspectos epidemiológicos da hepatite B em crianças e adolescentes, discutindo os resultados encontrados à luz dos princípios da bioética. Trata-se de um estudo transversal, retrospectivo, com base em uma série temporal de casos, cujos dados de notificação foram extraídos do Sistema de Informação de Agravos de Notificação (SINAN) e dados de vacinação do Sistema de Informação do Programa Nacional de Imunizações - SIPNI, no período de 2011 a 2020. Foram notificados 889 casos de hepatite B na população de estudo. A maioria dos participantes encontravam-se na faixa etária de 15 a 19 anos 738 (83%), do sexo feminino 549 (62%), cor da pele parda 637 (72%) residentes na zona urbana 490 (55%) e com ensino fundamental incompleto 279 (31%). A provável fonte de infecção foi por via sexual 450 (51%). A forma clínica mais comum foi a Hepatite Crônica 496 (56%). A maioria dos contaminados com Hepatite B foram indivíduos não vacinados 298 (34%). A luz da bioética os resultados demostram que a prática da vacinação pode contemplar os princípios bioéticos, já que o grau de autonomia depende de um tipo de intervenção planejada e quanto maior a relação entre benefício e ônus, tendo em conta os princípios de beneficência e não maleficência, menos decisiva é essa autonomia.

El estudio investiga los aspectos epidemiológicos de la hepatitis B en niños y adolescentes, discutiendo los resultados encontrados a la luz de los principios bioéticos. Se trata de un estudio transversal, retrospectivo, basado en una serie temporal de casos, cuyos datos de notificación fueron extraídos del Sistema de Información de Enfermedades de Declaración Obligatoria (SINAN) y datos de vacunación del Sistema de Información del Programa Nacional de Inmunizaciones SIPNI, desde 2011 hasta 2020. Se informaron 889 casos de hepatitis B en la población de estudio. La mayoría de los participantes tenían entre 15 y 19 años 738 (83 %), sexo femenino 549 (62 %), color de piel morena 637 (72 %), residentes en zona urbana 490 (55 ) y con educación primaria incompleta 279 (31 %). La fuente probable de infección fue a través de relaciones sexuales 450 (51%). La forma clínica más frecuente fue la Hepatitis Crónica 496 (56%). La mayoría de los infectados con Hepatitis B eran individuos no vacunados 298 (34%). A la luz de la bioética, los resultados muestran que la práctica de la vacunación puede contemplar principios bioéticos, ya que el grado de autonomía depende de un tipo de intervención planificada y mayor la relación entre beneficio y carga, teniendo en cuenta los principios de beneficencia y no maleficencia, menos decisiva es esta autonomía.

The study investigates the epidemiological aspects of hepatitis B in children and adolescents, discussing the results found in the light of bioethical principles. This is a cross-sectional, retrospective study, based on a time series of cases, whose notification data were extracted from the Notifiable Diseases Information System (SINAN) and vaccination data from the National Immunization Program Information System SIPNI, from 2011 to 2020. 889 cases of hepatitis B were reported in the study population. Most participants were aged between 15 and 19 years old 738 (83%), female 549 (62%), brown skin color 637 (72%) living in the urban area 490 (55%) and with incomplete elementary education 279 (31%). The probable source of infection was through sexual intercourse 450 (51%). The most common clinical form was Chronic Hepatitis 496 (56%). Most of those infected with Hepatitis B were unvaccinated individuals 298 (34%). In the light of bioethics, the results show that the practice of vaccination can contemplate bioethical principles, since the degree of autonomy depends on a type of planned intervention and the greater the relationship between benefit and burden, taking into account the principles of beneficence and not maleficence, the less decisive is this autonomy.

COLORECTAL CANCER: ASSOCIATION BETWEEN SOCIODEMOGRAPHIC VARIABLES AND THE ADHERENCE TO CANCER SCREENING.

BACKGROUND: Colorectal cancer (CRC) is a worldwide health problem whose control depends on public policy establishment and effective prevention and screening programs. In Brazil, there are few studies related to adherence to screening methods. AIMS: The aim of this study was to evaluate the association between demographic and socioeconomic to adherence to CRC screening with fecal immunochemical test (FIT) among average-risk individuals for CRC. METHODS: In this prospective cross-sectional study, conducted between March 2015 and April 2016, 1,254 asymptomatic individuals aged 50-75 years, participating in a hospital screening campaign in Brazil, were invited to participate in the study. RESULTS: The adherence rate to FIT was 55.6% (697/1,254). In the multivariable logistic regression analysis, patients aged 60-75 years (odds ratio (OR)=1.30; 95% confidence interval (CI): 1.02-1.66; p=0.03), religious belief (OR=2.04; 95% CI: 1.34-3.11; p<0.01), previous fecal occult blood test (OR=2.07; 95% CI: 1.55-2.76; p<0.01), and full/part-time working status (OR=0.66; 95% CI: 0.49-0.89; p<0.01) were independently associated with adherence to CRC screening. CONCLUSION: The results of the present study highlight the importance of considering the labor aspects when implementing screening programs, suggesting that campaigns conducted in the workplace and repeated over the years may be more effective.

Influence of central sidechain on self-assembly of glycine-x-glycine peptides.

Low molecular weight gelators (LMWGs) are the subject of intense research for a range of biomedical and engineering applications. Peptides are a special class of LMWG, which offer infinite sequence possibilities and, therefore, engineered properties. This work examines the propensity of the GxG peptide family, where x denotes a guest residue, to self-assemble into fibril networks via changes in pH and ethanol concentration. These triggers for gelation are motivated by recent work on GHG and GAG, which unexpectedly self-assemble into centimeter long fibril networks with unique rheological properties. The propensity of GxG peptides to self-assemble, and the physical and chemical properties of the self-assembled structures are characterized by microscopy, spectroscopy, rheology, and X-ray diffraction. Interestingly, we show that the number, length, size, and morphology of the crystalline self-assembled aggregates depend significantly on the x-residue chemistry and the solution conditions, i.e. pH, temperature, peptide concentration, etc. The different x-residues allow us to probe the importance of different peptide interactions, e.g. π-π stacking, hydrogen bonding, and hydrophobicity, on the formation of fibrils. We conclude that fibril formation requires π-π stacking interactions in pure water, while hydrogen bonding can form fibrils in the presence of ethanol-water solutions. These results validate and support theoretical arguments on the propensity for self-assembly and leads to a better understanding of the relationship between peptide chemistry and fibril self-assembly. Overall, GxG peptides constitute a unique family of peptides, whose characterization will aid in advancing our understanding of self-assembly driving forces for fibril formation in peptide systems.

Decisões terapêuticas com pacientes em fim de vida: a visão do residente / Therapeutic decisions with end-of-life patients: the perspective of residents

As mudanças epidemiológicas e demográficas impactam diretamente no aumento das doenças crônicas não transmissíveis e na demanda por cuidados em saúde cada vez mais complexos que englobam a tomada de decisão de forma multidisciplinar e compartilhada entre equipe, família e paciente. Portanto o objeto desta pesquisa foi a visão do aluno da residência multiprofissional a respeito das decisões terapêuticas com pacientes em fim de vida tendo como pano de fundo a bioética por princípios de Beauchamp e Childress. Os objetivos foram: descrever, através do discurso do aluno da residência multiprofissional, como se dá o processo de tomada de decisões terapêuticas com pacientes em fim de vida e quais respaldos morais e bioéticos são utilizados nestas decisões; identificar, a partir do discurso do residente multidisciplinar, a participação dos profissionais da saúde, da família/cuidadores e do próprio paciente nas decisões terapêuticas do fim da vida. Trata-se de uma pesquisa qualitativa, descritiva e exploratória, realizada com 25 alunos de três programas de residência multiprofissional do município do Rio de Janeiro. A técnica para coleta dos dados baseou-se em entrevista semiestruturada realizada no período de 15/07 à 20/09/2022. O método para obtenção dos participantes foi o de bola de neve (snow ball) onde o primeiro participante é escolhido aleatoriamente e os demais são indicados pelo antecessor. Foram observados todos os critérios éticos em pesquisa da Resolução 466/2012 do Ministério da Saúde. Para o tratamento dos dados foi utilizada a análise categorial de Denize Oliveira. Ao final da categorização emergiram três categorias: "Processo de tomada de decisão com pacientes em fim da vida", "Princípios éticos norteadores da tomada de decisão" e "O mundo ideal e o mundo real do processo de tomada de decisão". A primeira categoria buscou detalhar o processo de tomada de decisão com pacientes no fim da vida mostrando a centralização da tomada de decisão, a tomada de decisão de forma multidisciplinar e de forma compartilhada com paciente e família. A segunda categoria relacionou o processo de tomada de decisão com pacientes no fim da vida aos princípios bioéticos de Beaucahmp e Childress demonstrando de forma individualizada a utilização destes para a personalização da tomada de decisão. A terceira categoria apontou os pontos que os residentes entendiam como ideais para o processo de tomada de decisão e as questões relacionadas ao que realmente acontece na prática clínica do dia a dia permeada pelas dificuldades estruturais, sociais e acadêmicas que interferem neste processo. Conclui-se que estamos ainda distantes de um modelo ideal de processo de tomada de decisão que ainda se apresenta de forma médicocentrada, verticalizada e pouco compartilhada com família e pacientes. AU

Epidemiological and demographic changes directly impact the increase in non-communicable chronic diseases and the demand for increasingly complex healthcare, which involves multidisciplinary and shared decision-making among the team, family, and patient. Therefore, the objective of this research was to explore the perspective of residents regarding therapeutic decisions with end-of-life patients, framed within the principles of Beauchamp and Childress' bioethics. The specific aims were to describe, through the discourse of multidisciplinary residents, the process of making therapeutic decisions with end-of-life patients and the moral and bioethical foundations guiding these decisions, as well as to identify the involvement of healthcare professionals, family/caregivers, and the patients themselves in end-of-life therapeutic decisions. This qualitative, descriptive, and exploratory research was conducted with 25 residents from three multidisciplinary residency programs in the city of Rio de Janeiro. Data collection was based on semi-structured interviews conducted from July 15th to September 20th, 2022. The snowball sampling method was used to select participants, where the first participant is chosen randomly and subsequent participants are referred by the preceding ones. The ethical criteria outlined in Resolution 466/2012 of the Ministry of Health were observed throughout the research process. Data analysis was performed using Denize Oliveira's categorical analysis. Three categories emerged from the analysis: "Process of decision-making with end-of-life patients," "Ethical principles guiding decision-making," and "The ideal world and the real world of the decision-making process." The first category aimed to detail the decision-making process with end-of-life patients, highlighting the centralization of decision-making, multidisciplinary decision-making, and shared decision-making with patients and their families. The second category linked the decision-making process with end-of-life patients to Beauchamp and Childress' bioethical principles, demonstrating their individualized application to personalize decision-making. The third category identified the aspects that residents perceived as ideal for the decision-making process, as well as the challenges encountered in the clinical practice influenced by structural, social, and academic difficulties. The findings suggest that we are still far from an ideal model of decision-making, as it remains predominantly physician-centered, hierarchical, and lacking in shared decision-making with families and patients. AU

Câncer colorretal: associação entre variáveis sociodemográficas e a adesão a programas de rastreamento / Colorectal cancer: association between sociodemographic variables and the adherence to cancer screening

ABSTRACT BACKGROUND Colorectal cancer (CRC) is a worldwide health problem whose control depends on public policy establishment and effective prevention and screening programs. In Brazil, there are few studies related to adherence to screening methods. AIMS: The aim of this study was to evaluate the association between demographic and socioeconomic to adherence to CRC screening with fecal immunochemical test (FIT) among average-risk individuals for CRC. METHODS: In this prospective cross-sectional study, conducted between March 2015 and April 2016, 1,254 asymptomatic individuals aged 50-75 years, participating in a hospital screening campaign in Brazil, were invited to participate in the study. RESULTS: The adherence rate to FIT was 55.6% (697/1,254). In the multivariable logistic regression analysis, patients aged 60-75 years (odds ratio (OR)=1.30; 95% confidence interval (CI): 1.02-1.66; p=0.03), religious belief (OR=2.04; 95% CI: 1.34-3.11; p<0.01), previous fecal occult blood test (OR=2.07; 95% CI: 1.55-2.76; p<0.01), and full/part-time working status (OR=0.66; 95% CI: 0.49-0.89; p<0.01) were independently associated with adherence to CRC screening. CONCLUSION: The results of the present study highlight the importance of considering the labor aspects when implementing screening programs, suggesting that campaigns conducted in the workplace and repeated over the years may be more effective.

RESUMO RACIONAL: O câncer colorretal (CCR) é um problema de saúde mundial cujo controle depende do estabelecimento de políticas públicas e programas de prevenção e rastreamento eficazes. No Brasil existem poucos estudos relacionados à adesão métodos de rastreamento. OBJETIVO: Avaliar a associação de características sócio-demográficas à realização de testes de sangue oculto nas fezes do tipo imunoquimicomecanizado (FIM) em população de médio risco para o desenvolvimento de câncer colorretal. MÉTODOS: Estudo observacional transversal, com coleta prospectiva de dados. Entre março de 2015 e abril de 2016, 1.254 indivíduos assintomáticos, com idade entre 50 e 75 anos, foram consecutivamente selecionados a partir de uma campanha hospitalar de rastreamento para neoplasias. RESULTADOS: As taxas de adesão ao teste FIM foi 55.6% (697/1254). Na análise de regressão logística múltipla os fatores independentes associados à adesão ao rastreamento do CCR foram: Idade entre 60-75 anos (oddsratio (OR)=1.30; intervalo de confiança de 95% (IC): 1.02-1.66; p=0.03), crença religiosa (OR=2.04; 95%IC: 1.34-3.11; p<0.01), realização prévia de exame de sangue oculto nas fezes (OR=2.07; 95%IC: 1.55-2.76; p<0.01) e vínculo empregatício em período integral ou parcial (OR=0.66; 95%IC: 0.49-0.89; p<0.01). CONCLUSÃO: Este estudo enfatiza a importância de considerar aspectos laborais ao implementar programas de rastreamento do câncer colorretal e sugere que campanhas de rastreamento implantadas no ambiente de trabalho e de maneira repetida ao longo dos anos podem ser mais efetivas.

Meniscal Bone Angle Is a Strong Predictor of Anterior Cruciate Ligament Injury.

Purpose: To evaluate the influence of lateral posterior tibial slope (LPTS) and meniscal bone angle (MBA) on primary anterior cruciate ligament (ACL) tear risk in an adult population through the LPTS-MBA ratio. Methods: A retrospective case-control study was performed with patients from a tertiary hospital who underwent primary ACL surgery and had preoperative magnetic resonance imaging (MRI). These subjects were matched by age and sex in a 1:1 ratio to patients who had an MRI without ACL tear. LPTS and MBA were measured on MRI scan. Quantitative data are presented in the median ± interquartile range (IQR). Identification of independent risk factors for primary ACL tear was performed using multivariable logistic regression. Receiver operating characteristics curves detected any variable with strong discriminative capacity. Results: In total, 95 patients with primary ACL tear confirmed on MRI were matched with 95 controls (N = 190). Nearly 80% were male subjects, with a median age of 26 years. In the ACL tear group, the median value of LPTS-MBA ratio was 0.20 (IQR 0.11-0.37) versus 0.12 (IQR 0.08-0.19) in the control group (P = .001). LPTS had a median value of 4.20° in the ACL tear group (IQR 2.05-7.35°) and 2.90° in the control group (IQR, 2.05-5.00°) (P = .026), whereas MBA was 19° (IQR, 16-24°) versus 26° (IQR, 24-30°) (P = .001), respectively. Logistic regression showed that LPTS (odds ratio 1.20, 95% confidence interval 1.03-1.42, P = .021) and MBA (odds ratio 0.78, 95% confidence interval 0.71-0.85, P = .001) were independent predictors. The area under the curve (AUC) of LPTS-MBA ratio was 0.69, greater than that of LPTS alone (AUC = 0.61) but lower than that for MBA (AUC = 0.82). Conclusions: In this study, a reduced MBA was the strongest predictive variable associated with a primary ACL tear. A threshold of 22.35° of MBA was associated with an increased risk of ACL tear, with a sensitivity of 70% and specificity of 84%. A cut-off of 0.22 of LPTS-MBA was associated with an increased risk of ACL tear, with a sensitivity of 55% and specificity of 87%. Level of Evidence: Level III, case-control study.

A cross-cohort replicable and heritable latent dimension linking behaviour to multi-featured brain structure.

Identifying associations between interindividual variability in brain structure and behaviour requires large cohorts, multivariate methods, out-of-sample validation and, ideally, out-of-cohort replication. Moreover, the influence of nature vs nurture on brain-behaviour associations should be analysed. We analysed associations between brain structure (grey matter volume, cortical thickness, and surface area) and behaviour (spanning cognition, emotion, and alertness) using regularized canonical correlation analysis and a machine learning framework that tests the generalisability and stability of such associations. The replicability of brain-behaviour associations was assessed in two large, independent cohorts. The load of genetic factors on these associations was analysed with heritability and genetic correlation. We found one heritable and replicable latent dimension linking cognitive-control/executive-functions and positive affect to brain structural variability in areas typically associated with higher cognitive functions, and with areas typically associated with sensorimotor functions. These results revealed a major axis of interindividual behavioural variability linking to a whole-brain structural pattern.

Forbidden Secondary Structures Found in Gel-Forming Fibrils of Glycylphenylalanylglycine.

The zwitterionic l-tripeptide glycylphenylalanylglycine self-assembles into very long crystalline fibrils in an aqueous solution, which causes the formation of an exceptionally strong gel phase (G' ∼ 5 × 106 Pa). The Rietveld refinement analysis of its powder X-ray diffraction (PXRD) pattern reveals a unit cell with four peptides forming a P212121 space group and adopting an inverse polyproline II conformation, that is, a right-handed helical structure that occupies the "forbidden" region of the Ramachandran plot. This unusual structure is stabilized by a plethora of intermolecular interactions facilitated by the large number of different functional groups of the unblocked tripeptide. Comparisons of simulated and experimental Fourier transform infrared and vibrational circular dichroism (VCD) amide I' profiles corroborate the PXRD structure. Our experimental setup reduces the sample to a quasi-two-dimensional network of fibrils. We exploited the influence of this reduced dimensionality on the amide I VCD to identify the main fibril axis. We demonstrate that PXRD, vibrational spectroscopy, and amide I simulations provide a powerful toolset for secondary structure and fibril axis determination.

Liver Abscess Complicated with an Inflammatory Myofibroblastic Tumor.

Inflammatory myofibroblastic tumors have a wide spectrum of biological behaviour and are composed of inflammatory cells and myofibroblastic spindle cells. Tumors may infrequently involve the liver. Imaging findings are non-specific. Teaching Point: Radiologists should be familiar with inflammatory myofibroblastic tumors as a diagnostic consideration to avoid unnecessary surgery.

Evaluation of the polymorphic forms of ritonavir and lopinavir in raw materials and co-milled systems.

Recently, the U.S. Food and Drug Administration (FDA) approved the first oral antiviral drug to treat mild to moderate cases of coronavirus disease. The combination of nirmatrelvir with an already used protease inhibitor class drug, ritonavir, has led to Paxlovid®. Several studies considered drug repositioning as the first trial for new drugs. The precise identification and quantification of polymorphs in raw materials and finished products are important to researchers involved in pharmaceutical development and quality control processes. In this work, we study the solid-state behavior of the antiretroviral drugs ritonavir and lopinavir in raw materials and in milled compositions. The results indicate that mixtures of ritonavir Forms I and II are found in different batches of raw materials from the same manufacturer; besides three equal crystalline samples, an amorphous batch was found in lopinavir. Furthermore, the milling process of the already amorphous lopinavir seems to facilitate the amorphization of ritonavir as well as the production of some unexpected crystalline forms of ritonavir. A phase transition of ritonavir Form I to Form II is only observed when co-milling with amorphous lopinavir. These findings reveal significant variations in phase purity of raw materials that affect the processing and solid-state properties, representing risks for the product quality.

A phase 2 study of first-line nivolumab in patients with locally advanced or metastatic cutaneous squamous-cell carcinoma.

BACKGROUND: Cutaneous squamous-cell carcinoma (CSCC) is among the most frequent malignancies worldwide. For those not amenable to treatment with curative intent, immune checkpoint inhibition (ICI) with anti-programmed death receptor 1 (PD-1) antibodies has emerged as a novel therapeutic option. In this study, the authors sought to investigate the activity of the anti-PD-1 agent nivolumab in patients with advanced CSCC (aCSCC). METHODS: CA209-9JC was an open-label, single-arm, phase 2 study to evaluate the safety and/or efficacy of nivolumab in systemic treatment-naive patients with aCSCC. Nivolumab (3 mg/kg) was administered every 2 weeks until disease progression, unacceptable toxicity, or 12 months of treatment. The primary end point was the best objective response rate (BORR) as per RECIST 1.1 criteria. Secondary end points included safety, progression-free survival (PFS), and overall survival (OS). RESULTS: Twenty-four patients with aCSCC were enrolled with a median age of 74 years (range, 48-93). Among the 24 patients evaluable for response, the BORR was 58.3% (14/24); there were no complete responses. With a median follow-up of 17.6 months, median duration of response has not been reached, and the estimated median PFS and OS were 12.7 and 20.7 months, respectively. Prior exposure to radiotherapy was associated with worse outcomes (p = .035, univariate analysis). Treatment-related adverse events of any grade and grade ≥ 3 occurred in 21 (87.5%) and six (25%) patients, respectively, and one patient discontinued nivolumab due to toxicities. CONCLUSIONS: Nivolumab resulted in robust antitumor activity, sustained responses, and good tolerability in systemic treatment-naive patients with aCSCC. These data provide further evidence to support the use of ICI as the standard treatment of aCSCC.

Mechanisms for the Deactivation of the Electronic Excited States of α-(2-Hydroxyphenyl)-N-phenylnitrone: From Intramolecular Proton and Charge Transfer to Structure Twisting and Aggregation.

The search for new prominent chemosensors is significantly related to the rationalization of possible multiple pathways of excited-state deactivation. We have prepared and studied compound α-(2-hydroxyphenyl)-N-phenylnitrone (Nit-OH), observing that Nit-OH is stable in acetonitrile solution under UV-vis light. The experimentally observed 540 nm fluorescence for Nit-OH was shown to be related to excitation at 360 nm from the highest occupied molecular orbital to the lowest unoccupied molecular orbital (HOMO-LUMO transition). Potential energy curves (PECs) for the S1 state of Nit-OH did show that there are structures associated with excited-state intramolecular proton transfer (ESIPT), and the existence of an intramolecular H-bonding was confirmed using X-ray powder diffraction (XRD). Twisted intramolecular charge transfer (TICT) took place following ESIPT, and a nonradiative deactivation at the S1/S0 conical intersection occurred; aggregation-induced emission was observed at 540 nm associated with the formation of a stacked dimer. Anti-Kasha emission from the S2 was proposed based on the dependence of the fluorescence excitation wavelength on Nit-OH concentration. From the calculation of the PEC for the S2 state, we obtained radiative transitions at 379 and 432 nm, similar to the obtained experimental values of 383 and 453 nm. We proposed a Jablonski-like diagram that depicts all experimental and theoretical electronic transitions for Nit-OH, summarizing the unique intricate photophysical behavior of this nitrone derivative.

Canonical Correlation Analysis and Partial Least Squares for Identifying Brain-Behavior Associations: A Tutorial and a Comparative Study.

Canonical correlation analysis (CCA) and partial least squares (PLS) are powerful multivariate methods for capturing associations across 2 modalities of data (e.g., brain and behavior). However, when the sample size is similar to or smaller than the number of variables in the data, standard CCA and PLS models may overfit, i.e., find spurious associations that generalize poorly to new data. Dimensionality reduction and regularized extensions of CCA and PLS have been proposed to address this problem, yet most studies using these approaches have some limitations. This work gives a theoretical and practical introduction into the most common CCA/PLS models and their regularized variants. We examine the limitations of standard CCA and PLS when the sample size is similar to or smaller than the number of variables. We discuss how dimensionality reduction and regularization techniques address this problem and explain their main advantages and disadvantages. We highlight crucial aspects of the CCA/PLS analysis framework, including optimizing the hyperparameters of the model and testing the identified associations for statistical significance. We apply the described CCA/PLS models to simulated data and real data from the Human Connectome Project and Alzheimer's Disease Neuroimaging Initiative (both of n > 500). We use both low- and high-dimensionality versions of these data (i.e., ratios between sample size and variables in the range of ∼1-10 and ∼0.1-0.01, respectively) to demonstrate the impact of data dimensionality on the models. Finally, we summarize the key lessons of the tutorial.

Describing the Influence of Ball-milling on the Amorphization of Flubendazole Using the PDF and RMC Methods with X-ray Powder Diffraction Data.

Flubendazole (FBZ) is a poorly water-soluble drug, and different methodologies have been proposed to improve its oral bioavailability. Obtaining the amorphous drug phase is an alternative to improve its water solubility. Several techniques for drug amorphization, such as spray drying, lyophilization, melt quenching, solvent-evaporation, and ball milling, can yield various types of structural disorder and possibly render variations in physicochemical properties. Herein, we focus on evaluating the influence of the ball-milling process on the amorphization of FBZ. The characterization of the average global and local structures before, during, and after the milling process is described by sequential Rietveld refinements, pair distribution function analysis, and the Reverse Monte Carlo method. We show that preserving the local structure (nearest molecules) can be responsible for avoiding the fast structure recrystallization commonly observed when using the solvent-evaporation process for the studied drug.