Notes

Niclosamide exerts anticancer effects by means of hang-up with the FOXM1-mediated Genetic harm reaction within cancer of the prostate.
d inflammation.
To test the hypothesis that many patients presenting with congenital insensitivity to pain have lesser known or unidentified mutations not captured by conventional genetic panels, we performed whole-exome sequencing in a cohort of well-characterized patients with a clinical diagnosis of congenital hereditary sensory and autonomic neuropathy with unrevealing conventional genetic testing.

We performed whole-exome sequencing (WES) in 13 patients with congenital impaired or absent sensation to pain and temperature with no identified molecular diagnosis from a conventional genetic panel. Patients underwent a comprehensive phenotypic assessment including autonomic function testing, and neurologic and ophthalmologic examinations.

We identified known or likely pathogenic genetic causes of congenital insensitivity to pain in all 13 patients, spanning 9 genes, the vast majority of which were inherited in an autosomal recessive manner. These included known pathogenic variants (3 patients harboring mutations in
and
), suspected pathogenic variants in genes described to cause congenital sensory and autonomic syndromes (7 patients harboring variants in
,
,
, and
), and likely pathogenic variants in novel genes (4 patients harboring variants in
and
).

Our results expand the genetic landscape of congenital sensory and autonomic neuropathies. Further validation of some identified variants should confirm their pathogenicity. WES should be clinically considered to expedite diagnosis, reduce laboratory investigations, and guide enrollment in future gene therapy trials.
Our results expand the genetic landscape of congenital sensory and autonomic neuropathies. Further validation of some identified variants should confirm their pathogenicity. WES should be clinically considered to expedite diagnosis, reduce laboratory investigations, and guide enrollment in future gene therapy trials.The COVID-19 pandemic put most in-person pathology electives on-hold as departments adapted to changes in education and patient care. To address the subsequent void in pathology education, we created a free, virtual, modular, and high-quality pathology elective website. Website traffic from June 1, 2020, to October 1, 2020, was monitored using the built-in analyses on Squarespace. Twitter engagement was analyzed using Twitter analytics and the Symplur Social Graph Score. A voluntary satisfaction survey was sent to all PathElective users and results were analyzed. During this time, the site saw 25 467 unique visitors, over 34 988 visits, 181 302 page views, and 4449 subscriptions from 99 countries. Countries with the highest traffic are the United States (14 682), India (5210), and the Philippines (2195). PathElective's Twitter social graph score increased from 63.59 to 89.3 with the addition of 1637 followers. Data from surveyed users (n = 177) show most to be pathology residents (41%). Most subscribers (89%) are committed to a career in pathology. The majority heard of the website via Twitter (55%). Almost half of those surveyed engaged with the PathTwitter community on Twitter and of those who participated, 99% found that interaction useful. In all survey questions surrounding satisfaction and usefulness, a large majority of the users were either satisfied or very satisfied. PathElective is a novel pathology elective that offers a unique opportunity to educate medical students and residents from around the globe and demonstrates high effectiveness and satisfaction among users.The Coronavirus 2019 pandemic has strained nearly every aspect of pathology practice, including preanalytic, analytic, and postanalytic processes. Much of the challenges result from high demand for limited severe acute respiratory syndrome coronavirus 2 testing capacity, a resource required to facilitate patient flow throughout the hospital system and society at large. At our institution, this led to unprecedented increases in inquiries from providers to laboratory staff relating to the expected time to result for their patients. The demand was great enough to require redeployment of staff to handle the laboratory call volume. Although these data are available in our laboratory information system, the data do not interface to our electronic health record system. We developed systems using the R statistical programming language that abstract the necessary data regarding severe acute respiratory syndrome coronavirus 2 polymerase chain reaction testing from our lab system in real time, store it, and present it to clinicians for on demand querying. These data have been accessed over 2500 times by over 100 distinct users. Median length of each user session is approximately 4.9 minutes. Because our lab information system does not persistently store tracking information while our system does, we have been able to iteratively recalculate time to result values for each tracking stop as workflows have changed over time. Facility with informatics and programming concepts coupled with clinical understanding have allowed us to swiftly develop and iterate on applications which provide efficiency gains, allowing laboratory resources to focus on generating test results for our patients.The COVID-19 pandemic created new challenges in health care, and pathology departments have led with innovations in testing and education. While the medical community and public showed great interest in gross and histologic findings in COVID-affected patients, paradoxically many autopsy services nationwide closed due to uncertainties surrounding the proximity to infected patient tissue, shortages in personal protective equipment, and pressures to discontinue perceived nonessential hospital operations. These disruptions furthermore negatively impacted pathology trainee education. The autopsy division at Northwestern Memorial Hospital, with the belief that a fully functioning autopsy service is especially crucial at this time, adopted a framework for continuing at full capacity for both clinical care and education. New operations were modeled on national protocols by the Centers for Disease Control and Prevention and the College of American Pathologists, and the service continually adjusted policies to reflect rapidly changing guidelines and feedback from trainees and staff. Between January and December 2020, we performed 182 adult autopsies including 45 COVID-19 autopsies. Twelve residents, 4 staff, and 5 attendings rotated through the service. In exit interviews, participants expressed (1) improved comfort managing both COVID-related and general autopsies; (2) sense of personal safety on service (despite the increased risk of exposure); (3) belief that both COVID-related and general autopsies contributed to their personal education and to the medical community. There have been zero known autopsy-related COVID-19 infections to date. We hope that our innovative autopsy service restructuring can serve as a framework for other academic programs during the current and in future pandemics.The COVID-19 pandemic has forced educational programs, including pathology residency, to move to a physically distanced learning environment. Tandem microscopic review (also known as "double-scoping") of pathology slides is a traditional cornerstone of pathology education. However, this requires the use of a double- or multi-headed optical light microscope which is unfortunately not amenable to physical distancing. The loss of double-scoping has forced educational innovation in order to continue teaching microscopy. Digital pathology options such as whole slide imaging could be considered; however, financial constraints felt by many departments often render this option cost-prohibitive. Alternatively, a shift toward teaching via dynamic virtual microscopy offers a readily available, physically distanced, and cost-conscious alternative for pathology education. Required elements include a standard light microscope, a mounted digital camera, computers, and videoconferencing software to share a slide image with the learner(s). Through survey data, we show immediate benefits include maintaining the essence of the traditional light microscope teaching experience, and additional gains were discovered such as the ability for educators and learners to annotate images in real time, among others. Existing technology may not be initially optimized for a dynamic virtual experience, resulting in lag time with image movement, problems focusing, image quality issues, and a narrower field of view; however, these technological barriers can be overcome through hardware and software optimization. Herein, we share the experience of establishing a dynamic virtual microscopy educational system in response to the COVID-19 pandemic, utilizing readily available technology in the pathology department of a major academic medical center.Whipple's disease is a bacterial infection caused by Tropheryma whipplei and is known to cause perplexing clinical presentations, making its diagnosis challenging. The beginning by the involvement of the gastrointestinal tract, Whipple's disease can slowly progress to affect almost any organ system and lead to chronic multi-system inflammatory disease. Enfortumab vedotin-ejfv in vivo Hereby, we present a middle age man who initially manifested with shortness of breath and chronic weight loss. He subsequently developed pleuro-pericardial effusion, ascites, mesenteric lymphadenopathy, possible myocarditis, and severe osteopenia with multiple vertebral fractures during his illness. Esophagogastroduodenoscopy with the biopsy and subsequent molecular confirmation of disease led to the confirmation of WD. Therapeutic management included two separate antibiotic regimens in an attempt to address the refractory course of WD in this patient.Nanoparticle-based targeted drug delivery holds promise for treatment of cancers. However, most approaches fail to be translated into clinical success due to ineffective tumor targeting in vivo. Here, the delivery potential of mesoporous silica nanoparticles (MSN) functionalized with targeting ligands for EGFR and CCR2 is explored in lung tumors. The addition of active targeting ligands on MSNs enhances their uptake in vitro but fails to promote specific delivery to tumors in vivo, when administered systemically via the blood or locally to the lung into immunocompetent murine lung cancer models. Ineffective tumor targeting is due to efficient clearance of the MSNs by the phagocytic cells of the liver, spleen, and lung. These limitations, however, are successfully overcome using a novel organ-restricted vascular delivery (ORVD) approach. ORVD in isolated and perfused mouse lungs of Kras-mutant mice enables effective nanoparticle extravasation from the tumor vasculature into the core of solid lung tumors. In this study, ORVD promotes tumor cell-specific uptake of nanoparticles at cellular resolution independent of their functionalization with targeting ligands. Organ-restricted vascular delivery thus opens new avenues for optimized nanoparticles for lung cancer therapy and may have broad applications for other vascularized tumor types.[This corrects the article DOI 10.18632/oncoscience.519.].Metastatic renal cell carcinoma (mRCC) treatments have rapidly evolved in the last few years. While vascular endothelial growth factor (VEGF) inhibition had previously been the mainstay of treatment for first-line advanced RCC therapy in the past decade, it has now rapidly changed into combination checkpoint inhibitors with or without VEGF TKIs, although there remains a role for VEGF tyrosine kinase inhibitor monotherapy for patients with favorable-risk disease and for those with intermediate and poor-risk disease with the use of cabozantinib. Perspectives on the Quality-adjusted survival Time without Symptoms of disease or Toxicity (Q-TWiST) analysis for the CABOSUN trial, as well as different aspects of efficacy regarding different first-line therapy for advanced or metastatic RCC are discussed herein.
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