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Computational strategies for protein conformational outfit recognition.
Sacituzumab govitecan (sacituzumab govitecan-hziy; Trodelvy™) is a Trop-2-directed antibody conjugated to a topoisomerase I inhibitor (SN-38) that is being developed by Immunomedics for the treatment of solid tumours, including breast cancer. In April 2020, sacituzumab govitecan received accelerated approval in the USA for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Sacituzumab govitecan is undergoing phase III development for breast cancer in the USA and EU, and phase II development for urothelial cancer. It is also being explored for brain metastases, glioblastoma, endometrial cancer and prostate cancer. This article summarizes the milestones in the development of sacituzumab govitecan leading to this first approval for mTNBC.Purpose Cryoablation is a minimally-invasive percutaneous procedure that is capable of reducing the psychosocial burden of surgical delay while also decreasing the morbidity of breast cancer therapy. The purpose of this editorial is to discuss the potential role of cryoablation for reducing the psychosocial burden of surgical delay during the COVID-19 pandemic by expediting the management of breast cancer while also lessening demand on limited healthcare resources. Methods This editorial critiques current expert opinion recommendations that aim to reduce viral transmission and preserve healthcare resources during the COVID-19 pandemic by advocating delay of elective breast cancer surgery. Results The editorial summarizes the current state of the evidence that supports the selective use of cryoablation as a definite or stopgap measure in the management of breast cancer during the COVID-19 pandemic or when healthcare resources are limited. Conclusions As an office-based procedure performed under local anesthesia, cryoablation eliminates the need for operating room personnel and equipment while also reducing the psychosocial impact of delayed breast cancer surgery. By reducing the number of patient and healthcare provider interactions, cryoablation not only decreases the risk of viral transmission but also the need for personal protective devices during resource-limited times.Purpose This study evaluates the oncogenic role of PIBF1 in triple-negative breast cancer (TNBC). TNBC is considered to have a poorer prognosis than other types of breast cancer and is associated with high risk of recurrence and distant metastasis. Currently, there are no effective therapies for the TNBC patients with distant metastasis due to the lack of targeted therapeutic options. Methods The effects of PIBF1 knockdown on the cell viability and motility of TNBC cell lines were investigated. Effects of PIBF1 overexpression on tumorigenicity and cell motility were confirmed using Ba/F3 cell line and xenograft study on BALB/c nude mice. Results In TNBC cell lines that highly express PIBF1, knockdown of PIBF1 induces apoptosis and suppresses cell viability and motility with activation of the ATR/CHK1 signaling pathway. Moreover, the oncogenic function of PIBF1 was confirmed using the Ba/F3 cell line. Conclusion For the first time, these findings clarify the role of PIBF1 in regulating ATR/CHK1 signaling pathway and inhibiting the proliferation and migration of TNBC cell lines. These results demonstrate the oncogenic roles of PIBF1 and provide new insights into the function and the molecular mechanism of PIBF1 in malignant TNBC.Programs designed to educate farmers on the safe use and application of agrochemicals, and to train them in integrated pest management, are common in developing countries, where the agricultural workers overuse pesticides and fail to use adequate protection. In this study, I evaluate the effects of exposure to both types of programs-the use of pesticides and protection. The data are from the Mekong Delta, which is the most fertile region of Vietnam, produces most of the country's rice and vegetables. The Vietnamese government began such educative campaigns in the late 1990s. The results show that while the abovementioned programs are effective in promoting the use of personal protection, they have less success in reducing the use of pesticides. Moreover, the evidence suggests that the two types of program are substitutes rather than complements.COVID-19 is a global pandemic that is wreaking havoc with the health and economy of much of human civilization. In this document from the American Autonomic Society, we identify the potential risks of exposure to patients, physicians, and allied healthcare staff. We provide guidance for conducting autonomic function testing safely in this environment.Recently, hybrid glenoid components have been developed, consisting of cementless highly porous metal central peg, monoblock keel or cage along with cemented backside polyethylene surface. The aims of this study were twofold (1) to determine the revision and complication rates of hybrid glenoid components, consisting of porous metal pegs or coatings attached to the polyethylene, for aseptic loosening in TSA and (2) to evaluate the rate of radiolucent lines in patients who underwent TSA with hybrid glenoid components consisting of porous metal pegs or coatings attached to the polyethylene. The US National Library of Medicine (PubMed/MEDLINE), EMBASE and the Cochrane Database of Systematic Reviews were queried for publications utilizing the following keywords "hybrid" OR "bone-ingrowth" OR "bone ingrowth" AND "TSA" OR "total" AND "shoulder" AND "arthroplasty" OR "replacement". Five articles were included for analysis (470 operated shoulders, mean follow-up 47.5 months). The overall weighted mean modified methodology Coleman score was 51.2/100, indicating a moderate level of overall methodological quality. The survival rate of hybrid glenoid components was 97.4% (458 out of 470 cases), while the rate of glenoid-related complications was 2.8% (13 cases). Finally, there were 54 cases (out of 313 reported; 17.3%) with glenoid radiolucency (none of them required revision). TSA with hybrid fixation glenoid components was associated with high survivorship and low rate of glenoid component-related complications at 4 years mean follow-up. In addition, there was limited evidence to show that the short- to mid-term outcome of TSA using hybrid glenoid components is not inferior to the outcome of cemented all-polyethylene glenoid components.Purpose This paper aims to report the impact of COVID-19 outbreak on Emergency Ear nose and Throat (ENT) activity, in Lombardy (Italy), during COVID-19 pandemic. Methods The number of accesses to Emergency Department requiring ENT consultations between February 21st and May 7th, 2020, was retrospectively collected, along with the conditions treated. Data were stratified in 1-week time spans, to evaluate the evolving trends during the on-going epidemic and a comparison with the two previous years was performed. Results A significant reduction in the number of consultations performed during the pandemic was observed, as high as - 91% compared to the same period of 2018. Conclusion Multiple reasons can explain such a reduction of Emergency ENT consultations, not least the fear of potentially being infected by SARS-CoV-2 by while accessing the hospital. The analysis performed might be useful as a starting point for a future reorganization of first aid consultations once the epidemic will be resolved.Purpose Differences in the definition and classification of cholesteatoma hinders comparing of surgical outcomes of cholesteatoma. Uniform registration is necessary to allow investigators to share and compare their findings. For many years surgical cholesteatoma procedures were divided into two main groups canal wall up mastoidectomy (CWU) and canal wall down mastoidectomy (CWD). Recently, mastoid obliteration can be added to both procedures. Because of great variation within these main groups, the International Otology Outcome Group (IOOG) proposed the new SAMEO-ATO classification system to categorize tympanomastoid operations. The aim of our study was to correlate the mastoid bone extirpation (M-stage) with the contemporary (CWU, CWD with or without obliteration) system. Methods Demographic characteristics and type of performed surgery were registered for 135 cholesteatoma patients from sixteen hospitals, both secondary and tertiary care institutions, across the Netherlands. In addition, the surgical reports were collected, retrospectively classified according to the contemporary system and the new system and compared. Correlations of the outcomes were calculated. Results In total, there were 112 CWU and 14 CWD (both with or without obliteration) suitable for correlation analysis. Z test for correlation between the M-stage and CWU procedure was significant for M1a and M1b procedure and significant for M2c with the CWD procedure. Conclusion The newly proposed SAMEO-ATO classification seems to be more detailed in the registration of surgical procedures than surgeons currently are used to. All M-stages of the SAMEO-ATO system are correlating well to the standard CWU and CWD except one 'in between' M-stage.Objective To present and analyse the radiological findings, surgical findings, pre-implantation and post-implantation speech and hearing outcomes of nine children with SMS Type III cochleovestibular malformation. Study design Retrospective case series of nine children with pre-lingual profound sensorineural hearing loss who underwent cochlear implantation (Jan 2012 to July 2019). These children had been classified as Type III malformation according to the SMS Classification of cochleovestibular anomalies. Stenoparib concentration Facial nerve anomalies, CSF leaks and any other significant surgical finding were noted. Meaningful Auditory Integration Scale (MAIS) was used to report the child's pre-operative and two-year post-implantation auditory and speech abilities. Any significant improvement was assessed using the Wilcoxon signed rank test. P value less then 0.05 was considered significant. Results Out of nine patients, five patients sustained CSF gushers, while three patients had mild CSF leak, which were plugged adequately. No facial nerve anomalies were encountered. Post-op course was uneventful for all nine patients. MAIS scores at a two-year follow-up showed significant statistical improvement (P less then 0.05) when compared to pre-operative scores. Conclusion Cochlear implant is the treatment of choice for children with type III cochleovestibular malformation. There are significant auditory and speech improvements expected. However, the surgeon should bear in mind the risk of CSF leak and subsequent meningitis.Pistachio contains polyphenolic compounds including flavonoids and anthocyanins which have antioxidant and antiinflammatory activity. Present study was aimed to evaluate the protective effects of pistachio on neurobehavioral and neurochemical changes in rats with Parkinson's disease (PD). Animal model of PD was induced by the injection of rotenone (1.5 mg/kg/day, s.c.) for 8 days. Pistachio (800 mg/kg/day, p.o.) was given for two weeks in both pre- and post-treatment. At the end of treatment brain was dissected out and striatum was isolated for biochemical and neurochemical analysis. Memory was assessed by Morris water maze (MWM) and novel object recognition (NOR) test while open field test (OFT), Kondziela inverted screen test (KIST), pole test (PT), beam walking test (BWT), inclined plane test (IPT) and footprint (FP) test were used to observe motor behavior. Rotenone administration significantly (p less then 0.01) impaired the memory but pistachio in both pre- and post-treatment groups significantly (p less then 0.
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