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The Virus HIV-1 infection still represents a serious disease even if actually it is transformed in chronic pathology. Considering the crucial role of the enzyme Protease in life cycle of HIV many efforts have been made in the research of new organic compounds showing inhibitory activity. After development of several series of non peptidic inhibitors we report here the synthesis of novel simple HIV-Protease inhibitors containing heteroaryl carboxamides and their antiviral activity in vitro and in HEK293 cells. Benzofuryl- benzothienyl- and indolyl rings as well as aryl sulfonamides with different electronic properties have been introduced by efficient synthetic procedures. All compounds showed inhibitory activity similar to the commercial drug Darunavir, effective against both wild-type HIV-1 protease and that containing the V32I or V82A mutations. ADME properties were also evaluated, showing the potential of such compounds to be developed as drugs.

Microvascular flow imaging is a new ultrasound technique with better ability than color Doppler imaging to identify small vessels that have slow blood flow, and it permits better evaluation of the features, especially microvascular architecture, of various lesions. We describe a case of inguinal hidradenitis suppurativa in a patient with positive risk factors (young age, female, smoker, and obese), diagnosed by ultrasonography using B-Mode, color Doppler, and finally also with microvascular flow imaging. Our aim is to demonstrate the usefulness of this new technique in characterization of lesions.

Introduction: Since breast imaging requires very close contact with patients, a protocol is needed to perform safe daily screening activities during the COVID-19 pandemic. Materials and methods: Patients were triaged and separated into three different clinical scenarios by performing a telephone questionnaire before each diagnostic exam or a nasopharyngeal swab before every recovery. Specific procedures for each scenario are described. Results: From July to October 2020, 994 exams were performed. A total of 16 cancers and 7 suspected COVID-19 patients were identified. No medical were was infected. Conclusion: This protocol is an example of the practical use of guidelines applied to a breast unit to assist specialists in preventing COVID-19 infection and optimizing resources for breast cancer diagnosis., Lay abstract On March 11th, 2020, the WHO officially declared the COVID-19 infection pandemic. Since breast cancer represents the most frequent cancer in women of all ages, and breast imaging examinations require very close contact with patients, a protocol was designed to optimize the management of patients and healthcare workers, performing strict COVID-19 screening and avoiding any impairment of survival of patients with breast cancer. Patients were separated into three different clinical scenarios (non-COVID-19 patients, suspected COVID-19 patients and confirmed COVID-19 patients) by performing a telephone questionnaire before each diagnostic exam or a nasopharyngeal swab before every recovery. Specific procedures for each scenario are described. Confirmed or suspected patients are rescheduled if not urgent. From July to October 2020, 994 exams were performed. A total of 16 cancers and 7 suspected COVID-19 patients were identified. No medical staff were infected. This study demonstrates efficacy in terms of continuity in the provision of an essential level of care in a breast cancer screening and ambulatory setting, providing an example of the practical use of guidelines applied to a breast unit, to assist specialists in preventing COVID-19 infection and optimizing resources for breast cancer diagnosis.

Purpose Methods and materials Results Conclusion Personal information and conflict of interest References, Purpose: Ultrasound (US) is the first-line screening technique in young women and complementary to mammography in women with dense breast. Furthermore, it is useful to guide biopsy of suspicious breast lesions (BLs). The sensitivity and specificity of breast...

Portal vein thrombosis (PVT) is a common complication of liver cirrhosis and is often the first sign of undetected hepatocellular carcinoma. It is crucial to differentiate malignant from benign thrombosis in determining prognosis and treatment. We describe a case of malignant PVT, detected for the first time by a new ultrasound technology, microvascular flow imaging, which can depict low flow in small vessels.

In this review, we summarize the most used natural products as useful adjuvants in BC by clarifying how these products may play a critical role in the prevention, treatment and progression of this disease. BC is the leading cancer, in terms of incidence, that affects women. The epidemiology and pathophysiology of BC were widely reported. Inflammation and cancer are known to influence each other in several tumors. In the case of BC, the inflammatory component precedes the development of the neoplasm through a slowly increasing and prolonged inflammation that also favors its growth. BC therapy involves a multidisciplinary approach comprising surgery, radiotherapy and chemotherapy. There are numerous observations that showed that the effects of some natural substances, which, in integration with the classic protocols, can be used not only for prevention or integration in order to prevent recurrences and induce a state of chemoquiescence but also as chemo- and radiosensitizers during classic therapy.

Background: The assessment of breast density is one of the main goals of radiologists because the masking effect of dense fibroglandular tissue may affect the mammographic identification of lesions. The BI-RADS 5th Edition has revised the mammographic breast density categories, focusing on a qualitative evaluation rather than a quantitative one. Our purpose is to compare the concordance of the automatic classification of breast density with the visual assessment according to the latest available classification. Methods: A sample of 1075 digital breast tomosynthesis images from women aged between 40 and 86 years (58 ± 7.1) was retrospectively analyzed by three independent readers according to the BI-RADS 5th Edition. Automated breast density assessment was performed on digital breast tomosynthesis images with the Quantra software version 2.2.3. Interobserver agreement was assessed with kappa statistics. The distributions of breast density categories were compared and correlated with age. Results: The agreement on breast density categories was substantial to almost perfect between radiologists (κ = 0.63–0.83), moderate to substantial between radiologists and the Quantra software (κ = 0.44–0.78), and the consensus of radiologists and the Quantra software (κ = 0.60–0.77). Comparing the assessment for dense and non-dense breasts, the agreement was almost perfect in the screening age range without a statistically significant difference between concordant and discordant cases when compared by age. Conclusions: The categorization proposed by the Quantra software has shown a good agreement with the radiological evaluations, even though it did not completely reflect the visual assessment. Thus, clinical decisions regarding supplemental screening should be based on the radiologist’s perceived masking effect rather than the data produced exclusively by the Quantra software.

Testicular metastasis are rare findings and bilateral metastasis of testes are extremely rare. Here we are describing for the first time a case of bilateral testicular metastasis in a patient with a known ileocecal valve NET using an in-depth ultra-sound studying including microvascular flow imaging (MV-flow), ultra-sound new technique, able to detect small vessel slow-signal.

Supplemental material, sj-doc-1-jvu-10.1177_15443167211033599 for Microvascular Flow Imaging in a case of Portal Vein Thrombosis by Marika Santarsiere, Mariateresa Rumolo, Emilia Vergara, Arturo Brunetti and Pietro Gisonni in Journal for Vascular Ultrasound

Purpose To assess clinician satisfaction with structured (SR) and conventional (CR) radiological reports for chest CT exams in coronavirus disease 2019 (COVID-19) patients, objectively comparing both reporting strategies. Method We retrospectively included 68 CTs (61 patients) with COVID-19. CRs were collected from the digital database while corresponding SRs were written by an expert radiologist, including a sign checklist, severity score index and final impressions. New CRs were prepared for a random subset (n = 10) of cases, to allow comparisons in reporting time and word count. CRs were analyzed to record severity score and final impressions inclusion. A random subset of 40 paired CRs and SRs was evaluated by two clinicians to assess, using a Likert scale, readability, comprehensiveness, comprehensibility, conciseness, clinical impact, and overall quality. Results Overall, 19/68 (28%) and 9/68 (13%) of CRs included final impressions and severity score, respectively. SR writing required significantly (p < 0.001) less time (mean = 308 s; SD ± 60 s) compared to CRs (mean = 458 s; SD ± 72 s). On the other hand, word count was not significantly different (p = 0.059, median = 100 and 106, range = 106-139 and 88-131 for SRs and CRs, respectively). Both clinicians expressed significantly (all p

Introduction: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is uncommon but is associated with poor outcomes. In selected high risk patients (pts), high dose methotrexate (HDMTX) is often used as CNS prophylaxis with frontline (1L) DLBCL therapy despite uncertain efficacy, optimum dose and timing of delivery. A recent UK study (Wilson et al 2020) showed that intercalated HDMTX (i-HDMTX) was associated with increased toxicity and R-CHOP delays compared to end of treatment (EOT) delivery. Although hypothesis generating, the study size was insufficient to determine whether EOT was non-inferior in terms of CNS relapse risk. Methods: We conducted an international, multicentre retrospective analysis of consecutive DLBCL or high grade BCL pts between 2007-20 from 47 centers in Europe, Australia and N. America. Pts were included if they received R-CHOP or R-CHOP-like 1L therapy with curative intent as well as HDMTX CNS prophylaxis (≥1 cycle). Concurrent intrathecal (IT) prophylaxis was permitted. Pts with known CNS involvement at baseline and those treated with more intensive protocols (e.g. R-DA-EPOCH) were excluded. i-HDMTX was defined as any pt receiving a HD-MTX cycle before the final R-CHOP cycle. CNS relapse events were excluded if occurring after first systemic lymphoma relapse/progression. Time to event endpoints were measured from diagnosis to first event or censor and analysed using Kaplan-Meier and Cox regression methods. Time to CNS relapse was analysed using competing risk Fine and Gray method (for death and non-synchronous systemic relapse). To mitigate for possible immortality bias in the EOT arm, a landmark analysis for pts alive and free from progression at 6 months was conducted. We aimed to exclude a 5% difference in 2-year (y) CNS relapse rates. Results: 1,384 pts were analysed. 750 received i-HDMTX and 634 received EOT HDMTX. Key baseline characteristics are summarised in Table 1. Median follow up was 37.9 months. 44.2% had high CNS IPI (4-6) with no significant difference between i-HDMTX and EOT groups (45.1% vs 43.1%, p=0.087). ≥2 cycles of HDMTX were used in 86.6% with no difference between groups (85.6% vs 87.9%, p=0.22). Concurrent IT prophylaxis use was higher for EOT pts (55.6% vs 38.1% p 78 CNS relapses (42 i-HDMTX, 36 EOT) were observed: parenchymal in 41 (53%), parenchymal and leptomeningeal in 16 (21%) and isolated leptomeningeal in 21 (27%). There was no significant difference in 2y CNS relapse rates between i-HDMTX and EOT in all pts: 5.2% vs 3.9%, adjusted hazard ratio (HR) 0.92 (95% CI 0.58-1.47), p=0.74, 2y difference -0.2% (-2.0-2.5) or landmark analysis: 2.8% vs 4.1%, HR: 0.93 (0.56-1.55), p=0.79, 2y difference: -0.3% (-1.8-2.2%) (Fig 1a/b). Exploratory analyses focusing on pts with isolated CNS relapse (n=57) demonstrated similar results (2y rates 3.6% vs 3.0%, p=0.99). On multivariable analysis (MVA) of risk factors for CNS relapse, renal/adrenal involvement was the only variable associated with increased CNS relapse risk (adjusted HR 1.74 (1.03-2.92), p=0.038). Notably, IT prophylaxis was not associated with reduction in CNS relapse. In 600 high CNS IPI (4-6) pts, there was no difference in CNS relapse risk between i-HD-MTX and EOT (3y rates 9.4% vs 8.6%, HR 0.92 (95% CI 0.52-1.62)). In a composite high risk group including CNS IPI 4-6 and/or any of the following: ≥3 extranodal sites, renal, adrenal, testicular or breast involvement (n=885) there was no difference in 3y CNS relapse rates between groups (i-HDMTX 7.6% vs EOT 7.4%, HR 0.94 (0.58-1.53)). Progression-free survival (PFS) and overall survival (OS) in the i-HDMTX and EOT groups were as follows: 3y PFS 70.7% vs 76.7% (p=0.098), 3y OS 79.9% vs 87.0% (p=0.0016). However, there were no PFS/OS differences between groups on landmark analysis (n=1259) (Fig 1c). On analysis of pts experiencing ≥1 R-CHOP delay of ≥7 days, use of i-HDMTX was the only factor on MVA associated with increased delays (p Discussion: We found no evidence that EOT delivery increases CNS relapse risk when compared to i-HDMTX in this large analysis of pts treated with 1L R-CHOP. Delays to R-CHOP cycles were increased with i-HDMTX. Findings in a high risk subgroup were unchanged and rates of CNS relapse in this HDMTX treated group were similar to published comparable high risk cohorts receiving infrequent CNS prophylaxis. Where HDMTX prophylaxis is used, delivery could be deferred until R-CHOP completion. Figure 1 Figure 1. Disclosures Wilson: Takeda: Other: Conference fees; Janssen: Other: Conference fees; Abbvie: Honoraria. Eyre: Janssen: Honoraria; Secura Bio: Consultancy, Honoraria; Gilead/KITE: Honoraria, Other: Travel support for conferences, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel to conferences; AstraZeneca: Honoraria, Research Funding; Loxo Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Beigene: Honoraria, Research Funding. Ahearne: Pfizer: Research Funding; Takeda: Honoraria; Roche: Honoraria. Schorb: Roche: Research Funding; Riemser Pharma GmbH: Honoraria, Research Funding; AbbVie: Research Funding. Ku: Antegene: Consultancy; Roche: Consultancy; Genor Biopharma: Consultancy. Narkhede: Genentech/Roche: Research Funding; Gilead: Research Funding; Genmab: Other: Medical writing support, Research Funding; TG Therapeautics: Research Funding. Lewis: AstraZeneca: Consultancy, Honoraria; Janssen: Honoraria, Patents & Royalties; Novartis: Patents & Royalties; Roche: Consultancy, Honoraria. Øvlisen: Abbvie: Other: Travel expenses. Santarsiere: Janssen: Honoraria. Shah: Abbvie, Janssen and Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Roulin: Janssen: Other: Travel and meetings. Manos: Bristol-Myers Squibb: Other: Travel and meetings. Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lopez-Garcia: Roche: Other: Speaker Honoraria, Travel and accommodation grants; Janssen: Other: Speaker Honoraria, Advisor, Travel and accommodation grants, Research Funding; Abbvie: Other: Speaker Honoraria, Advisor, Travel and accommodation grants; Celgene: Other: Speaker Honoraria; Fresenius: Other: Speaker Honoraria; Novonordisk: Other: Speaker Honoraria. El-Galaly: ROCHE Ltd: Ended employment in the past 24 months; Abbvie: Other: Speakers fee. Cheah: Beigene: Consultancy, Honoraria, Other: advisory; AbbVie: Research Funding; Celgene: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: advisory; Loxo/Lilly: Consultancy, Honoraria, Other: advisory; TG Therapeutics: Consultancy, Honoraria, Other: advisory; Roche: Consultancy, Honoraria, Other: advisory and travel expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: advisory; MSD: Consultancy, Honoraria, Other: advisory, Research Funding; Gilead: Consultancy, Honoraria, Other: advisory; Ascentage pharma: Consultancy, Honoraria, Other: advisory. Ferreri: Gilead, Novartis, Juno, PletixaPharm, Roche, Incyte: Membership on an entity's Board of Directors or advisory committees; BMS, Beigene, Pharmacyclics, Hutchison Medipharma, Amgen, Genmab, ADC Therapeutics, Gilead, Novartis, Pfizer: Research Funding. Fox: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Other: speaker fees. Cwynarski: Gilead: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Atara: Consultancy; Celgene: Consultancy; Takeda: Consultancy, Other: travel to scientific conferences, Speakers Bureau; Kite, a Gilead Company: Consultancy, Other: travel to scientific conferences, Speakers Bureau; Janssen: Consultancy, Other: travel to scientific conferences; Roche: Consultancy, Other: travel to scientific conferences, Speakers Bureau; BMS/Celgene: Other: travel to scientific conferences. McKay: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Other: Travel Support; KITE: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Janssen: Honoraria, Other: Travel Support; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior The spectral analysis and asynchronous cellular automata subjects are relevant among the cellular automata scientific community. Asynchronous cellular automata are variants of cellular automata at which the cells have their state shifted at distinct time paces, instead of being all updated at the same global pace, as in the conventional model. The asynchronous updates, deterministic or probabilistic, have been receiving a progressive rise of attention by the pertinent scientific community, due to the bigger flexibility the cellular automata acquire concerning computability as well as for the better suitability to model natural systems. Spectral analysis is a set of techniques to transpose data from the space domain to the frequency domain. Among its many applications, this technique is applied to the study the limit behavior of the cellular automata rules, which consist in calculating the Fourier spectrum of these cellular automata, for a given lattice size, number of iterations, and set of lattices as a sampling. At the present dissertation are done studies concerning the impact that distinct deterministic updating sequences have over the shape of the elementary space rules’ Fourier spectra. There have been defined three distinct asynchrony patterns families, each one displaying itself at ten distinct asynchrony patterns, for all the rules of the elementary space of cellular automata. There are described and classified the shape shifts of the spectra obtained by the lattice asynchronous updating, as well as other phenomena described with the experiment. The newly obtained spectra were groped in spectral similarity classes for study as well. The focus of the dissertation is to document, by means of computational explorations, how the presence of asynchrony effects the formation of the asynchronous automata Fourier spectra, and identify reasons for these phenomena. Os tópicos autômatos celulares assíncronos e análise espectral são relevantes em meio à comunidade científica de autômatos celulares. Autômatos celulares assíncronos são variantes de autômatos celulares nos quais as células têm seu estado alterado em diferentes passos de tempo, em vez de serem todas atualizadas em um mesmo passo global, como no modelo convencional. As atualizações assíncronas, determinísticas ou probabilísticas, têm recebido um aumento progressivo de atenção na comunidade científica pertinente, em função da maior flexibilidade que os autômatos celulares adquirem tanto do ponto de vista de computabilidade quanto pela maior naturalidade para modelagem de sistemas naturais. Análise espectral é um conjunto de técnicas para transportar dados do domínio do espaço para o domínio da frequência. Dentre suas muitas aplicações, esta técnica é aplicada ao estudo do comportamento limite das regras dos autômatos celulares, que consiste em calcular o espectro de Fourier destes autômatos celulares, para determinado tamanho de reticulado, número de iterações, e conjunto de reticulados como amostra. Na presente dissertação são efetuados estudos sobre o impacto que sequências de atualização determinísticas distintas têm sobre a forma dos espectros de Fourier das regras do espaço elementar de autômatos celulares. São aqui definidas três famílias distintas de padrões de assincronia, cada qual se apresentando com dez padrões de assincronia distintos, para todas as regras do espaço elementar. São descritas e classificadas as mudanças de forma dos espectros obtidas com a evolução assíncrona do reticulado, bem como outros fenômenos observados com o experimento. Os novos espectros obtidos também foram agrupados em classes de similaridade espectral para estudo. O foco da dissertação é documentar, por meio de explorações computacionais, como a presença da assincronia afeta a formação dos espectros de Fourier dos autômatos assíncronos, e identificar razões para tais fenômenos.