摘要： Traditional medical publication metrics, such as impact factor, have various well described limitations [1, 2]. Modern, alternative metrics, such as the Altmetric attention score (https://***), provide scores for each publication using an automated algorithm representing a weighted count of the amount of attention for a research output from various sources. Sources include but are not limited to: news articles; blogs; policy documents; patents; engagements on social media platforms; and number of citations. We aimed to use the Altmetric attention score to derive a new performance metric comparable with impact factor, and we applied this metric to journals in peri‐operative medicine, critical care and pain.

摘要： BACKGROUND Anaemia is frequently recorded during preoperative screening and has been suggested to affect outcomes after surgery negatively. OBJECTIVES The objectives were to assess the frequency of moderate to severe anaemia and its association with length of hospital stay. DESIGN Post hoc analysis of the international observational prospective 'Local ASsessment of VEntilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study. PATIENTS AND SETTING The current analysis included adult patients requiring general anaesthesia for non-cardiac surgery. Preoperative anaemia was defined as a haemoglobin concentration of 11 g dl(-1) or lower, thus including moderate and severe anaemia according to World Health Organisation criteria. MAIN OUTCOME MEASURES The primary outcome was length of hospital stay. Secondary outcomes included hospital mortality, intra-operative adverse events and postoperative pulmonary complications (PPCs). RESULTS Haemoglobin concentrations were available for 8264 of 9864 patients. Preoperative moderate to severe anaemia was present in 7.7% of patients. Multivariable analysis showed that preoperative moderate to severe anaemia was associated with an increased length of hospital stay with a mean difference of 1.3 ((95% CI 0.8 to 1.8) days;P < .001). In the propensity-matched analysis, this association remained present, median 4.0 [IQR 1.0 to 5.0] vs. 2.0 [IQR 0.0 to 5.0] days, P = .001. Multivariable analysis showed an increased in-hospital mortality (OR 2.9 (95% CI 1.1 to 7.5);P = .029), and higher incidences of intra-operative hypotension (36.3 vs. 25.3%;P < .001) and PPCs (17.1 vs. 10.5%;P = .001) in moderately to severely anaemic patients. However, this was not confirmed in the propensity score-matched analysis. CONCLUSIONS In this international cohort of non-cardiac surgical patients, preoperative moderate to severe anaemia was associated with a longer duration of hospital stay but not increased intra-operative complications, PPCs

关键词： 8‐   hydroxyquinoline derivatives   Candida spp   chicken embryo   Drosophila melanogaster   zebrafish  

摘要： Aim The purpose of this study was to evaluate the antifungal activity and toxicological parameters of 8-hydroxyquinoline derivatives PH151 and PH153 using alternative animal models, to understand their behaviour when subjected to in vivo experiments. Methods and results We used Toll-deficient Drosophila melanogaster to test the protective effect of compounds against Candida albicans infection. Toxicological parameters were investigated in chicken and zebrafish embryos. PH151 and PH153 showed low toxicity and the treated flies with these compounds had a significantly higher survival rate than untreated flies after 7 days of infection. The compounds did not cause interruption of chicken embryogenesis. Zebrafish embryos exposed to compounds showed dose-dependent toxicity. Conclusions The data supported the potential of PH151 and PH153 for the treatment of systemic candidiasis and demonstrated to be appropriate drug candidates for further studies using mammalian models. Significance and Impact of the Study The increased incidence of Candida infections resistant to antifungals currently available requires acceleration of the discovery of new agents with properties of inhibiting this fungal pathogen. In this study, we have described the antifungal potential and toxicity of two 8-hydroxyquinoline derivatives using in vivo alternative models, and the results confirm their potential to be developed as new drug candidates.

关键词： D-mannitol   dry powder inhaler   particle engineering   spray-congealing   wet-sieving  

摘要： Purpose Traditionally, alpha-lactose monohydrate is the carrier of choice in dry powder inhaler (DPI) formulations. Nonetheless, other sugars, such as D-mannitol, have emerged as potential alternatives. Herein, we explored different particle engineering processes to produce D-mannitol carriers for inhaled delivery. Methods Wet-sieving and spray-congealing were employed as innovative techniques to evaluate the impact of engineering on the particle properties of D-mannitol. To that end, the resulting powders were characterized concerning their solid-state, micromeritics and flowability. Afterwards, the engineered carrier particles were blended with inhalable size beclomethasone dipropionate to form low dose (1 wt%) DPI formulations. The in vitro aerosolization performance was evaluated using the NEXThaler (R), a reservoir multi-dose device. Results Wet-sieving generated D-mannitol particles with a narrow particle size distribution and spray-congealing free-flowing spherical particles. The more uniform pumice particles with deep voids and clefts of wet-sieved D-mannitol (Pearl300_WS) were beneficial to drug aerosolization, only when used in combination with a ternary agent (10 wt% of 'Preblend'). When compared to the starting material, the spray-congealed D-mannitol has shown to be promising in terms of the relative increase of the fine particle fraction of the drug (around 100%), when used without the addition of ternary agents. Conclusions The wet-sieving process and the related aerosolization performance are strongly dependent on the topography and structure of the starting material. Spray-congealing, has shown to be a potential process for generating smooth spherical particles of D-mannitol that enhance the in vitro aerosolization performance in binary blends of the carrier with a low drug dose.

关键词： miR-378   Pgc1-beta   mTOR   Adipogenesis   Autophagy   Gene regulation  

摘要： Over the past decade, medical schools across the United States have increasingly dedicated resources to advancing racial and social justice, such as by supporting diversity and inclusion efforts and by incorporating social medicine into the traditional medical curricula. While these changes are promising, the academic medicine community must apply an anti-racist lens to every aspect of medical education to equip trainees to recognize and address structural inequities. Notably, organizing and scholarly work led by medical students has been critical in advancing anti-racist curricula. In this article, the authors illustrate how student activism has reshaped medical education by highlighting examples of student-led efforts to advance anti-racist curricula at Harvard Medical School (HMS) and at the University of California, San Francisco (UCSF) School of Medicine. HMS students collaborated with faculty to address aspects of existing clinical practice that perpetuate racism, such as the racial correction factor in determining kidney function. They also responded to the existing curricula by noting missed opportunities to discuss structural racism, and they planned supplemental sessions to address these gaps. At UCSF, students identified specific avenues to improve the rigor of social medicine courses and developed new curricula to equip students with skills to confront and work to dismantle racism. The authors describe how HMS students, in an effort to improve the learning environment, developed a workshop to assist students in navigating microaggressions and discrimination in the clinical setting. At UCSF, students partnered with faculty and administration to advocate pass/fail grading for clerkships after university data revealed racial disparities in students' clerkship assessments. In reviewing these examples of students' advocacy to improve their own curricula and learning environments, the authors aim to provide support for students and faculty pursuing anti-racist

关键词： alternative splicing   breast cancer   exon skipping   intrinsically disordered regions  

摘要： Simple Summary Aberrant alternative splicing (AS) regulation plays a pivotal role in breast cancer development, progression, and resistance to therapeutical interventions. Indeed, cancer cells can adapt their own transcriptome by changing different AS programs, thus generating cancer-specific AS isoforms involved in every hallmark of cancer. Here, we investigated global AS errors occurring in human breast cancer cells by using RNA-mediated oligonucleotide annealing, selection, and ligation coupled with next-generation sequencing. Our results identified several dysregulated AS events potentially relevant for breast cancer-related biological processes and that provide a better comprehension of the molecular mechanisms that orchestrate the malignant transformation. Breast cancer is the most frequently occurred cancer type and the second cause of death in women worldwide. Alternative splicing (AS) is the process that generates more than one mRNA isoform from a single gene, and it plays a major role in expanding the human protein diversity. Aberrant AS contributes to breast cancer metastasis and resistance to chemotherapeutic interventions. Therefore, identifying cancer-specific isoforms is the prerequisite for therapeutic interventions intended to correct aberrantly expressed AS events. Here, we performed RNA-mediated oligonucleotide annealing, selection, and ligation coupled with next-generation sequencing (RASL-seq) in breast cancer cells, to identify global breast cancer-specific AS defects. By RT-PCR validation, we demonstrate the high accuracy of RASL-seq results. In addition, we analyzed identified AS events using the Cancer Genome Atlas (TCGA) database in a large number of non-pathological and breast tumor specimens and validated them in normal and breast cancer samples. Interestingly, aberrantly regulated AS cassette exons in cancer tissues do not encode for known functional domains but instead encode for amino acids constituting regions of intrinsically disorde

摘要： A well-developed body of literature demonstrates that lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals experience poorer health outcomes and report worse health care experiences than straight/ cisgender individuals. Many reforms since 2010 have addressed the LGBTQ-related education of future health care professionals at the undergraduate medical education (UME) level;however, reforms at the graduate medical education (GME) level are lagging, and new literature suggests that didactic education at the UME level is not enough to prepare future physicians to properly and compassionately care for LGBTQ patients. Recently, the Accreditation Council for Graduate Medical Education (ACGME) implemented a major revision of its Common Program Requirements that requires residents to demonstrate, as a competence, respect and responsiveness to diverse populations. Given these revisions and the ongoing failure of many GME training programs to adequately prepare future physicians to care for LGBTQ patients, the authors argue that now is the time for the ACGME to develop and implement LGBTQ health-related residency requirements. In addition, the authors outline a path by which the academic medical community may develop and implement these requirements.

关键词： Numerical solution of glioma   Finite difference   Cubic B-Splines   Pseudospectral Chebyshev polynomials   4th-order Runge–   Kutta method  

摘要： In this article, the numerical solution of glioma, or glioblastomas, which is one of the most aggressive forms of cancer is considered. A heterogeneous nonlinear diffusion logistic density model is taken as the main focus. To obtain the numerical results, three different discretization techniques: Pseudospectral method (PSM) using Chebyshev-Gauss-Lobatto collocation points, method of lines (MoL), and cubic B-splines (cBS) are employed on the spatial domain, whereas 4th-order Runge-Kutta (RK4) is considered on the time domain. Adapting cBS and PSM discretization to the glioma model is studied at first in this study. In addition to the theoretical convergence results, detailed comparative computational results are presented. All these methods are compared in terms of their efficiencies in varying time step and mesh discretization not only to one another, but also with the methods given in the literature.

关键词： VITOM   Microscope   COVID-19   Exoscope   PPE   Laryngeal cancer  

摘要： Purpose In the field of microsurgery, the use of conventional operating microscope, adopted in several disciplines, is not suitable with the full adoption of appropriate personal protective equipment (PPE), as goggles and face shields, needing the eyes to be at close contact with oculars. Methods Herein we present an exoscopic surgical setup, implemented for transoral laser microsurgery, by the VITOM (R) 3D-HD system. Results Our proposed exoscopic setting overcomes safety limits of the conventional operating microscope, being suitable with the adoption of full PPE necessary facing with suspected or confirmed positive SARS-CoV-2 patients needing urgent microsurgical procedures. Conclusion The use of protocols to reduce the virus spreading is mandatory to safely treat also patients potentially SARS-CoV-2 infected. The described surgical setup is advisable to manage urgent microsurgical procedures along the duration of the COVID-19 pandemic, being applicable PPE necessary to treat potentially or confirmed SARS-CoV-2-infected patients.