Abstract
To date, more than 263 million people have been infected with SARS-CoV-2 during the COVID-19 pandemic. In many countries, the global spread occurred in multiple pandemic waves characterized ...by the emergence of new SARS-CoV-2 variants. Here we report a sequence and structural-bioinformatics analysis to estimate the effects of amino acid substitutions on the affinity of the SARS-CoV-2 spike receptor binding domain (RBD) to the human receptor hACE2. This is done through qualitative electrostatics and hydrophobicity analysis as well as molecular dynamics simulations used to develop a high-precision empirical scoring function (ESF) closely related to the linear interaction energy method and calibrated on a large set of experimental binding energies. For the latest variant of concern (VOC), B.1.1.529 Omicron, our Halo difference point cloud studies reveal the largest impact on the RBD binding interface compared to all other VOC. Moreover, according to our ESF model, Omicron achieves a much higher ACE2 binding affinity than the wild type and, in particular, the highest among all VOCs except Alpha and thus requires special attention and monitoring.
Merkel Cell Carcinoma (MCC) is a highly aggressive neuroendocrine neoplasm of the skin. Due to its rarity, the management of MCC is not standardized across centers. In this article, we present the ...experience of the Veneto region in the North-East of Italy, where a committee of skin cancer experts has proposed a clinical pathway for the diagnosis and treatment of MCC. Putting together the evidence available in the international literature, we outlined the best approach to the management of patients affected with this malignancy step- by- step for each possible clinical situation. Crucial in this pathway is the role of the multidisciplinary team to deal with the lack of robust information on each aspect of the management of this disease.
Melanoma of unknown primary (MUP), accounts for up to 3% of all melanomas and consists of a histologically confirmed melanoma metastasis to either lymph nodes, (sub)cutaneous tissue, or visceral ...sites without any evidence of a primary cutaneous, ocular, or mucosal melanoma. This study aimed to investigate the characteristics, treatment strategies, and prognostic factors of MUP patients, in order to shed some light on the clinical behavior of this malignancy.
All the consecutive patients with a diagnosis of MUP referring to our institutions between 1985 and 2018 were considered in this retrospective cohort study. The records of 173 patients with a suspected diagnosis of MUP were retrospectively evaluated for inclusion in the study. Patient selection was performed according to the Das Gupta criteria, and a total of 127 MUP patients were finally included in the study, representing 2.7% of the patients diagnosed with melanoma skin cancer at our institutions during the same study period. A second cohort of all consecutive 417 MKP patients with AJCC stages IIIB-IV, referring tions in the period considered (1985-2018), was included in the study to compare survival between MUP and MKP patients. All the diagnoses were based on histopathologic, cytologic and immunohistochemical examination of the metastases. All tumors were re-staged according to the 2018 American Joint Committee on Cancer (AJCC) 8
Edition.
Median follow-up was 32 months (IQR: 15-84). 3-year progression-free survival (PFS) was 54%, while 3-year overall survival (OS) was 62%. Worse OS and PFS were associated with older age (P = 0.0001 for OS; P = 0.008 for PFS), stage IV (P < 0.0001 for OS; P = 0.0001 for PFS) and higher Charlson Comorbidity Index (P < 0.0001 for OS and P = 0.01 for PFS). Patients with lymph node disease showed longer PFS (P = 0.001) and OS (P = 0.0008) than those with (sub)cutis disease. Complete lymph node dissection (CLND) was the most common surgical treatment; a worse OS in these patients was associated with the number of positive lymph nodes (P = 0.01), without significant association with the number of retrieved lymph nodes (P = 0.79). Survival rates were lower in patients undergoing chemotherapy (CT) and target therapy (TT), and higher in those receiving immunotherapy (IT). 417 patients with AJCC stages IIIB-IV of Melanoma Known Primary (MKP) were included for the survival comparison with MUP. 3-year PFS rates were 54 and 58% in MUP and MKP, respectively (P = 0.30); 3-year OS rates were 62 and 70% in MUP and MKP, respectively (P = 0.40).
The most common clinical scenario of our series was a male patient around 59 years with lymph node disease. We report that CLND associated with IT was the best treatment in terms of survival outcome. In the current era of IT and TT for melanoma, new studies have to clarify the impact of novel drugs on MUP.
Three-dimensional liver modeling can lead to substantial changes in choosing the type and extension of liver resection. This study aimed to explore whether 3D reconstruction helps to better ...understand the relationship between liver tumors and neighboring vascular structures compared to standard 2D CT scan images.
Contrast-enhanced CT scan images of 11 patients suffering from primary and secondary hepatic tumors were selected. Twenty-three experienced HBP surgeons participated to the survey. A standardized questionnaire outlining 16 different vascular structures (items) having a potential relationship with the tumor was provided. Intraoperative and histopathological findings were used as the reference standard. The proper hypothesis was that 3D accuracy is greater than 2D. As a secondary endpoint, inter-raters' agreement was explored.
The mean difference between 3D and 2D, was 2.6 points (SE: 0.40; 95 % CI: 1.7-3.5; p < 0.0001). After sensitivity analysis, the results favored 3D visualization as well (mean difference 1.7 points; SE: 0.32; 95 % CI: 1.0-2.5; p = 0.0004). The inter-raters' agreement was moderate for both methods (2D: W = 0.45; 3D: W = 0.44).
3D reconstruction may give a significant contribution to better understanding liver vascular anatomy and the precise relationship between the tumor and the neighboring structures.
Axonal count is the base for efficient nerve transfer; despite its capital importance, few studies have been published on human material, most research approaches being performed on experimental ...animal models of nerve injury. Thus, standard analysis methods are still lacking.
Quantitative data obtained have to be reproducible and comparable with published data by other research groups. To share results with the scientific community, the standardization of quantitative analysis is a fundamental step. For this purpose, the experiences of the Italian, Austrian, German, Greek, and Iberian-Latin American groups have been compared with each other and with the existing literature to reach a consensus in the fiber count and draw up a protocol that can make future studies from different centers comparable.
The search for a standardization of the methodology was aimed to reduce all the factors that are associated with an increase in the variability of the results. All the preferential methods to be used have been suggested. On the other hand, alternative methods and different methods have been identified to achieve the same goal, which in our experience are completely comparable; therefore, they can be used indifferently by the different centers according to their experience and availability.
OBJECTIVE:To examine the difference between outcomes in the administration of concurrent endoscopic sinus surgery (ESS), septoplasty (SP), and rhinoplasty (RP) and concurrent ESS and SP in 1 single ...surgical session.
METHODS:Patients who underwent concurrent ESS and SP from September 2004 to July 2015 were identified. Furthermore, patients among them who underwent functional primary RP were selected. Subjects who had been administered concurrent ESS, SP, and RP (primary RP) were matched for sex, age, sinonasal surgical procedures for treatment of chronic rhinosinusitis with patients underwent concurrent ESS and SP, used as control subjects. A literature review was performed to find previous articles describing results of concurrent procedures among ESS, SP, and RP.
RESULTS:Twenty subjects, who underwent concurrent ESS, SP, and RP, were compared with a matched control group made of 20 patients who underwent concurrent ESS and SP, evaluating different postoperative outcomes (postoperative complications, postoperative improvement of respiratory symptoms, persistence of chronic rhinosinusitis symptoms 6 months to 1 year postoperative, need of revision surgery, satisfaction of the patient). Obtained P values showed that there was no statistically significant difference (P > 0.05) as regards the different outcomes, except for postoperative complications, increased because of the invasiveness proper of RP (P < 0.05).
CONCLUSIONS:Therefore, execution of concurrent ESS, SP, and RP seems to be safe and effective, and additional RP does not modify postoperative outcomes of concurrent ESS and SP except for a little increase of postoperative complications, even if most of them had low impact on result of procedures.
Introdução: As infecções de corrente sanguínea por fungos do gênero Candida, também denominadas candidemias, são uma importante causa de sepse tardia em pacientes hospitalizados. Durante o período ...pandêmico, diversos estudos apontaram aumento de sua incidência em pacientes com covid-19. Objetivo: Este estudo teve o obejtivo de avaliar a incidência das candidemias durante a pandemia da covid19 e os fatores associados a esta co-infecção em um hospital de ensino. Método: Foi analisada uma coorte retrospectiva de 89 pacientes com hemocultura positiva para fungos do gênero Candida, internados entre março de 2020 e fevereiro de 2022, no Hospital das Clínicas da Faculdade de Medicina de Botucatu – UNESP. O diagnóstico da covid-19 foi confirmado por reação em cadeia da polimerase em tempo real, sendo os pacientes analisados segundo a presença ou não da infecção pelo SARS-Cov-2. Teste Exato de Fisher foi usado para comparar as densidades de incidência e os fatores categóricos associados a co-infecção, enquanto que para as variáveis contínuas foi usado o Teste U de Mann-Whitney. Foram considerados significativos valores de p menores que 0,05. Resultados: Dos 89 pacientes com candidemia, 26 (29,2%) tinham infecção pela covid-19. A densidade de incidência de candidemia foi de 2,26 casos/ 1000 pacientes-dia nos pacientes com covid19 e 0,23 casos/ 1000 pacientes-dia nos demais OR = 9,69 (5,89 – 15,53), p < 0,01. As principais espécies causadoras da candidemia foram C. albicans, C. glabrata e C. tropicalis tanto nos pacientes com covid19 como nos demais. Houve uma tendência em maior incidência de C. krusei nos pacientes com covid19 (15,4 vs 3,2%, p = 0,06). Na análise dos fatores associados à co-infecção, os pacientes com covid19 e candidemia foram mais submetidos a corticoterapia (92,3 vs 18,5%, p < 0,01) e mais internação em terapia intensiva (92,3 vs 55,6%, p = 0,03) que os demais pacientes, enquanto que estes últimos foram mais submetidos a cirurgia abdominal (0,0 vs 44,4%, p < 0,01). A mortalidade em 30 dias foi semelhante entre os grupos, com 30,8% nos pacientes covid19 e 40,7% nos demais (p = 0,73). Conclusão: Estes achados corroboram a elevada incidência de candidemia em pacientes com covid-19 e sua associação com o uso de corticoides e necessidade de cuidados intensivos.
The UAE Pavilion will be a major attraction at Expo 2020 in Dubai. The roof of the building consists of 28 operable wings made of carbon and glass fiber, having masses ranging from 5 to 18 tons and ...total lengths in the range of 30 to 65 m that have to be actuated by a dedicated mechanism. In this paper we present the turn-key project for the design, manufacturing, installation, test and commissioning of the Roof Wing Opening System, which represents a unique system world-wide for operating the wings. It consists of one Hydraulic Power Unit with approximately 1 MW of installed power, 2 km of piping working at the nominal pressure of 210 bar, 46 hydraulic cylinders with 1.5 tons of mass each and the complete automation and control subsystem that includes 9 separate PLCs, dedicated software, 2.000 sensors and control points, and over 20 km of harness. One major challenge is the control of the wings. Part of them, due to their huge dimensions and masses, are actuated using two or three hydraulic cylinders that have to be properly synchronized during the movement, preventing unwanted displacements in order to avoid stresses on the wing mechanical structure and ultimately permanent damages. Due to the nature of the project, a final validation of the control algorithms can be done only at system level during the commissioning phase. Therefore, particular care has to be devoted to the verification strategy, anticipating the behavior of the system in the early validation stages and following a V-model approach, in order to identify critical situations and reduce the overall risk. After a brief system description, we will explain how the verification has been approached by using system level simulations and dedicated testing activities on specific subsystems. In particular, we will detail the verification of the control algorithms that has been performed on a dedicated Hardware-Inthe- Loop system first, followed then by dedicated tests on a reduced wing mock-up, allowing the study of the system behavior under the most critical conditions. These include the application of external forces with specified profiles. Finally, we will provide the actual status of the system installation, testing and commissioning activities that have been running in Dubai since January 2019.
O presente trabalho teve como objetivo determinar a temperatura de armazenamento que proporciona melhor manutenção da qualidade de tangores 'Murcote' minimamente processados. O processamento mínimo ...constou da separação do fruto em segmentos e acondicionamento dos mesmos em bandeja de polietileno rígida. O armazenamento foi realizado a 2, 6 e 12ºC. Foram realizadas análises físico-químicas e sensoriais a cada 3 dias, durante 9 dias. A aparência foi considerada boa até o 9º dia para os segmentos armazenados a 2ºC. A acidez total titulável (ATT), o teor de sólidos solúveis totais (SST) e a relação "SST/ATT" não foram afetados pelos tratamentos. A intensificação da coloração nos segmentos dos frutos ocorreu de forma gradual ao longo do armazenamento. A qualidade de tangores 'Murcote' minimamente processados pode ser mantida por até 9 dias de armazenamento a 2ºC.
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