Summary The attrition rate of anticancer drugs during the clinical development remains very high. Interspecies extrapolation of anticancer drug pharmacodynamics (PD) could help to bridge the gap between preclinical and clinical settings and to improve drug development. Indeed, when combined with a physiologically-based-pharmacokinetics (PBPK) approach, PD interspecies extrapolation could be a powerful tool for predicting drug behavior in clinical trials. The present study aimed...
07:29
Abstract ATP-binding castle protein G2 (ABCG2) is thought to inhibit the activities of certain gefitinib transporters, thereby affecting drug pharmacokinetics. The C421A polymorphism affects the function and expression of ABCG2 on the cell membrane. Previous studies have shown that proton-pump inhibitors (PPIs) inhibit gefitinib absorption, as well as the function of ABCG2. We evaluated the plasma concentrations of gefitinib in patients with and without the ABCG2 C421A polymorphism,...
07:29
Summary Background PF-06840003 is a highly selective indoleamine 2, 3-dioxygenase (IDO1) inhibitor with antitumor effects in preclinical models. This first-in-human phase 1 study evaluated safety, pharmacokinetics/pharmacodynamics, and preliminary efficacy in recurrent malignant glioma to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Methods Patients (N = 17) received oral PF-06840003 in four dose-escalation groups: 125 mg once-daily (QD; n = 2);...
07:29
Summary Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, and most patients die within one year after diagnosis. This cancer is resistant to almost all current therapies, so there is an urgent need to identify novel druggable targets. Ubiquitin-specific protease 7 (USP7) is a deubiquitinase that functions in carcinogenesis, but its role in PDAC is unknown. Our experiments indicated that several subtypes of PDAC cells are sensitive to USP7 inhibition....
07:29
Summary Introduction Afatinib is used to treat patients with advanced non-small cell lung cancer (NSCLC) harboring common EGFR mutations; however, the clinicopathological factors that predict this drug’s effectiveness in real-world settings remain unclear. We therefore evaluated the effectiveness of afatinib in such patients and assessed potential prognostic factors. Methods We retrospectively investigated patients with NSCLC who received first-line afatinib between July 2014...
07:29
British Journal of Cancer, Published online: 21 October 2020; doi:10.1038/s41416-020-01117-8Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
03:00
Summary The attrition rate of anticancer drugs during the clinical development remains very high. Interspecies extrapolation of anticancer drug pharmacodynamics (PD) could help to bridge the gap between preclinical and clinical settings and to improve drug development. Indeed, when combined with a physiologically-based-pharmacokinetics (PBPK) approach, PD interspecies extrapolation could be a powerful tool for predicting drug behavior in clinical trials. The present study aimed...
06:43
Abstract ATP-binding castle protein G2 (ABCG2) is thought to inhibit the activities of certain gefitinib transporters, thereby affecting drug pharmacokinetics. The C421A polymorphism affects the function and expression of ABCG2 on the cell membrane. Previous studies have shown that proton-pump inhibitors (PPIs) inhibit gefitinib absorption, as well as the function of ABCG2. We evaluated the plasma concentrations of gefitinib in patients with and without the ABCG2 C421A polymorphism,...
06:43
Summary Background PF-06840003 is a highly selective indoleamine 2, 3-dioxygenase (IDO1) inhibitor with antitumor effects in preclinical models. This first-in-human phase 1 study evaluated safety, pharmacokinetics/pharmacodynamics, and preliminary efficacy in recurrent malignant glioma to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Methods Patients (N = 17) received oral PF-06840003 in four dose-escalation groups: 125 mg once-daily (QD; n = 2);...
06:43
Summary Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, and most patients die within one year after diagnosis. This cancer is resistant to almost all current therapies, so there is an urgent need to identify novel druggable targets. Ubiquitin-specific protease 7 (USP7) is a deubiquitinase that functions in carcinogenesis, but its role in PDAC is unknown. Our experiments indicated that several subtypes of PDAC cells are sensitive to USP7 inhibition....
06:43
Summary Introduction Afatinib is used to treat patients with advanced non-small cell lung cancer (NSCLC) harboring common EGFR mutations; however, the clinicopathological factors that predict this drug’s effectiveness in real-world settings remain unclear. We therefore evaluated the effectiveness of afatinib in such patients and assessed potential prognostic factors. Methods We retrospectively investigated patients with NSCLC who received first-line afatinib between July 2014...
06:43
Radix Aconiti Lateralis Preparata (Fuzi) is a traditional Chinese medicine. Its alkaloids are both cardiotonic and cardiotoxic; however, the underlying mechanisms are unclear. Compatibility testing and processing are the primary approaches used to reduce the toxicity of aconite preparations. The purpose of this study was to compare the effects of crude Fuzi (CFZ), CFZ combined with Glycyrrhiza (Gancao) (CFZ+GC), and prepared materials of CFZ (PFZ) on heart failure (HF) in C57BL/6J mice and explore...
Tue Oct 20, 2020 18:50
A recent position paper published by the EACMFS1 on the management of the clinically N0 neck in early oral squamous cell carcinoma has come as a reminder that this 30-year-old plus debate is far from over. The authors of this paper eloquently describe the evolution of the neck management, from the early Weiss2 mathematic network modelling, to the landmark D’Cruz RCT3 and the UK SEND trial4 (and the other randomised trials combined in a meta-analysis4) and the establishment of the sentinel node biopsy...
Tue Oct 20, 2020 03:00
This systematic review aims to examine whether the incidence of osteonecrosis differs between patients who have dental extractions performed prior to or following radiotherapy.
Tue Oct 20, 2020 03:00
Tue Oct 20, 2020 11:35
Abstract Countless evidence suggests that long noncoding RNAs (lncRNAs) are involved in human malignant cancers, including esophageal squamous cell carcinoma (ESCC), although their exact function remains unclear. In the present study, we aimed to investigate the roles and molecular mechanisms of the lncRNA LOC440173 in ESCC progression. Microarray analysis and quantitative real‐time polymerase chain reaction were conducted to measure the expression levels of LOC440173 and miR‐30d‐5p. The biological...
Tue Oct 20, 2020 16:48
The submental island flap (SIF) is a reliable option for reconstructing defects in the facial region and offers several advantages when compared to free-flap alternatives. While the reconstructive applications...
Tue Oct 20, 2020 03:00
The management of recurrent ischemic priapism is unclear in contemporary practice. Yet, if left untreated, the condition may evolve into an acute ischemic priapism and in some cases result in erectile dysfunct...
03:00
Anastomotic recurrences of the colon are postulated to arise due to inadequate margins, tumor implantation by exfoliated cells, altered biological properties of bowel anastomosis, and missed synchronous lesion...
Tue Oct 20, 2020 03:00
The article by Remington et al1 in this issue of the journal addresses a key question that individuals with food allergy and their families often ask: “Can I go out to eat?” There is tremendous anxiety in patients with food allergy over the possibility of an allergic reaction.2 Patients often worry about when their next allergic reaction will occur and are often afraid to eat out of their home because of a possibility of a reaction to a single bite.3 Most studies have indicated that many allergic...
05:37
Despite the remarkable advances in our understanding of the phenotypes and endotypes of allergic diseases, there remains no cure for the treatment of allergic diseases, and the global burden of allergic diseases is enormous.1,2 The yardsticks for asthma, anaphylaxis, and atopic dermatitis (AD) published in the Annals of Allergy, Asthma & Immunology have offered diagnostic and treatment guidance for the management of these complex diseases.3-5 However, hopes to reduce the prevalence of allergic...
05:37
AbstractPectus excavatum is a chest wall deformity with an incidence of around 1 in 400 live births. The Nuss procedure is a surgical intervention that aims to restore functional integrity in these patients. We report the first case of bar migration into the stomach necessitating further surgical intervention for removal. Our case presents a rare complication of pectus excavatum repair and highlights the importance of vigilant follow-up in these patients. If bar migration does occur, imaging in the...
03:00
AbstractThe prevalence of transmesocolic hernias, a subtype of internal hernias (IHs), is generally low. Its clinical consequences, including strangulation, ischemia and even death, however, necessitate awareness. IHs are classified as congenital or acquired as resulting from surgery, trauma or intraperitoneal inflammation. This is a case of a 37-year-old male victim of a motor vehicle collision 1 month prior to the index admission. The trauma-related injuries were managed conservatively and then...
03:00
ABSTRACTTransarterial embolization (TAE) is a useful option for anterior cranial fossa–dural arteriovenous fistula (ACF–dAVF) as endovascular devices have progressed. Liquid agents are usually injected via a microcatheter positioned just proximal to the shunt pouch beyond the ophthalmic artery; however, high blood flow from the internal maxillary artery (IMA) often impedes penetration of embolic materials into the shunt pouch. Therefore, reducing blood flow from the IMA before embolization can increase...
Tue Oct 20, 2020 03:00
Antiretrovirals belonging to the HIV protease inhibitor (HIV-PI) class exert inhibitory effects across several cancer types by targeting tumor cells and its microenvironment. Cervical carcinoma (CC) represents a leading cause of morbidity and mortality, particularly in women doubly infected with high-risk human papillomaviruses (HR-HPV) and the human immunodeficiency virus (HIV); of note, combined antiretroviral therapy has reduced CC onset and progression in HIV-infected women. We evaluated the...
Tue Oct 20, 2020 20:41
Treatment-free remission (TFR) is one of the therapeutic goals for patients with chronic phase chronic myeloid leukemia (CML-CP). Although previous reports indicated that anti-tumor immunity contributes to TFR, its determinants are still unclear. We previously reported that allelic polymorphisms of killer immunoglobulin-like receptors (KIRs) and human leukocyte antigens (HLAs) are associated with achievement of deep molecular response (DMR) in patients with CML-CP. Here, we examined the association...
Tue Oct 20, 2020 20:41
Agents targeting metabolic pathways form the backbone of standard oncology treatments, though a better understanding of differential metabolic dependencies could instruct more rationale-based therapeutic approaches. We performed a chemical biology screen that revealed a strong enrichment in sensitivity to a novel dihydroorotate dehydrogenase (DHODH) inhibitor, AG-636, in cancer cell lines of hematologic versus solid tumor origin. Differential AG-636 activity translated to the in vivo setting, with...
Tue Oct 20, 2020 20:41
Pretargeted radioimmunotherapy (PRIT) has been investigated as a multi-step approach to decrease relapse and toxicity for high-risk acute myeloid leukemia (AML). Relevant factors including endogenous biotin and immunogenicity, however, have limited the use of PRIT with an anti-CD45 antibody (Ab)-streptavidin (SA) conjugate and radiolabeled DOTA-biotin. To overcome these limitations we designed anti-murine and anti-human CD45 bispecific antibody (Ab) constructs using 30F11 and BC8 Ab, respectively,...
Tue Oct 20, 2020 20:41
Non-proteinogenic amino acids, such as the proline analog L-azetidine-2-carboxylic acid (AZC), are detrimental to cells because they are mis-incorporated into proteins and lead to proteotoxic stress. Our goal was to identify genes that show chemical-genetic interactions with AZC in Saccharomyces cerevisiae and thus also potentially define the pathways cells use to cope with amino acid mis-incorporation. Screening the yeast deletion and temperature sensitive collections, we found 72 alleles with negative...
00:40
Abstract Acne vulgaris is the most recurring skin condition in the world, causing great harm to the physical and psychological well-being of many patients. Antimicrobial photodynamic therapy (aPDT) has broad therapeutic applicability. The purpose was to evaluate in vitro the photodynamic inactivation against Propionibacterium acnes (P. acnes) biofilms by using different concentrations of hypericin (Hypericum perforatum) photosensitizer associated with different energies of low-level...
03:00
Abstract In the last few decades, there has essentially been an explosion in the use of lasers in medicine, especially in the area of cosmetic dermatology. Potentially harmful substances are liberated when tissues are vaporized with laser. This creates numerous risks, including the spread of infectious disease. Smoke evacuators are devices that capture and filter laser plume, thereby maintaining a safe environment for the surgical team and patient. Our aim was to characterize...
Tue Oct 20, 2020 03:00
Targeting of poly(ADP-ribose)polymerase (PARP) enzymes has emerged as an effective therapeutic strategy to selectively target cancer cells with deficiencies in homologous recombination (HR) signaling. Currently used to treat BRCA-mutated cancers, PARP inhibitors (PARPi) have demonstrated improved outcome in various cancer types as single agents. Ongoing efforts have seen the exploitation of PARPi combination therapies, boosting patient responses as a result of drug synergisms. Despite great successes...
Tue Oct 20, 2020 16:31
Purpose: The RET proto-oncogene encodes a receptor tyrosine kinase which is activated by gene fusion in 1-2% of non-small cell lung cancers (NSCLC) and rarely in other cancer types. Selpercatinib is a highly selective RET kinase inhibitor that has recently been approved by the FDA in lung and thyroid cancers with activating RET gene fusions and mutations. Molecular mechanisms of acquired resistance to selpercatinib are poorly understood. Patients and Methods: We studied patients treated on the first-in-human...
Tue Oct 20, 2020 16:31
Background: Despite the expansion of immune checkpoint inhibitor (ICI) indications, the relationship between ICI dose and toxicity or response is not well established. To understand this correlation, we performed a meta-analysis of ICI trials that used dose-escalation. Methods: We searched PubMed and abstracts presented at (inter)national meetings for trials using FDA-approved ICIs. The reported rates of grade 3-5 adverse events (G3-5AEs), immune-related adverse events (irAEs), and response were...
Tue Oct 20, 2020 16:31
Purpose: Women with hormone-receptor-positive early breast cancers have a persistent risk of relapse and biomarkers for late recurrence are needed. We sought to identify tumor genomic aberrations associated with increased late recurrence risk. Experimental Design: In a secondary analysis of Study of Letrozole Extension (SOLE) trial, a case-cohort-like sampling selected 598 primary breast cancer for targeted next-generation sequencing (NGS) analysis of gene mutations and copy number gains (CNG). Correlations...
Tue Oct 20, 2020 16:31
Purpose: Nijmegen breakage syndrome (NBS) is a DNA repair disorder with a high predisposition to hematological malignancies. Experimental Design: We describe the natural history of NBS, including cancer incidence, risk of death and the potential effectiveness of hematopoietic stem cell transplantation (HSCT) in preventing both pathologies: malignancy and immunodeficiency. Results: Among two hundred forty-one (n=241) patients with NBS enrolled in the study from 11 countries, 151 (63.0%) patients were...
Tue Oct 20, 2020 16:31
Purpose: To evaluate somatic mutations, circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in the PDAC patients with pathological complete response (pCR) to neoadjuvant therapy (NAT) and find their associations with outcome. Design: Thirty-six PDAC patients with pCR were identified from 2009 to 2017. Macro-dissection was performed on resected specimens to isolate DNA from 332 regions of interest including fibrosis, normal duct, normal parenchyma, and undefined ductal cells (UDCs). Cell-free...
Tue Oct 20, 2020 16:31
T cell-engagers are a rapidly evolving novel group of treatments that have in common the concurrent engagement of a T cell-surface molecule and a tumoral cell antigen. Bispecific antibodies and genetically engineered adoptive cell therapies, as chimeric antigen receptor or T cell receptor T cells, have similarities and differences among their mechanisms of action, toxicity profiles, and resistance pathways. Nevertheless, the success observed in the hematological field has not been obtained with solid...
Tue Oct 20, 2020 16:31
We are grateful to Haas RL and Gronchi A for their interest in our manuscript and the expert-based constructive comments. We propose to incorporate our joint vision into an update of the practice-changing guidelines.
Tue Oct 20, 2020 03:00
Lung cancer is the leading cause of cancer mortality, representing 13% of new cancer diagnoses in men and women, and accounting for 25% of cancer-related mortality [1]. The 5-year overall survival (OS) in patients with lung cancer is poor (19%) [1]. Radiotherapy forms a critical aspect of the curative treatment of non-small cell lung cancer, particularly in Stage III disease, and medically inoperable patients with Stage I/II disease. Although a number of clinical factors that predict outcome for...
Tue Oct 20, 2020 03:00
Proton therapy (PT) is becoming a more widely available treatment option for cancer. Compared to conventional photon-based radiotherapy, the primary advantage of PT is the markedly reduced low-to-intermediate dose-bath, which significantly reduces the exposure of the normal tissues and organs at risk (OARs) close to the tumour [1].
Tue Oct 20, 2020 03:00
Stereotactic body radiotherapy (SBRT) has become a standard local treatment modality for early stage, medically inoperable non-small cell lung cancer (NSCLC) and an emerging local treatment option for recurrent and metastatic lung cancer [1,2]. Stereotactic techniques can provide excellent local tumor control by the delivery of high doses to a small planning target volume (PTV) while minimizing exposure to organs at risk (OAR) including lung [3].
Tue Oct 20, 2020 03:00
Standard local curative treatment options in patients with prostate cancer (PCa) without distant metastases comprise Radical Prostatectomy (RP) and Definitive Radiotherapy (Def-RT) with or without androgen deprivation therapy (ADT) [1,2].
Tue Oct 20, 2020 03:00
Knowledge of biological responses to proton therapy (PT) in comparison to X-ray remains in its infancy. Identification of PT specific molecular signals is an important opportunity for the discovery of biomarkers and synergistic drugs and improved PT clinical usage. As PT can be used for lymphoma treatment, we study here lymphoma cell lines transcriptomic response to PT vs X-ray to identify potential drugable target.
Tue Oct 20, 2020 03:00
The COVID-19 pandemic has posed serious challenges for the delivery of quality care in healthcare systems. This is acutely felt in the oncology setting, where patients are a high-risk population often being older or challenged with significant comorbidities and having systematic immunosuppression due to treatments. Cancer patients and those with a cancer history have been found to be at serious risk for complications and death from this disease[1–3], and also may be more vulnerable to contracting...
Tue Oct 20, 2020 03:00
Abstract Background Restless legs syndrome [RLS] is known as a disease of iron and dopaminergic dysregulation but inflammatory processes might also have a role in the pathogenesis. In this study, we compared the circulating levels of hsCRP, IL-1β, IL-6, and TNF-α in patients with primary restless legs syndrome [RLS] and healthy control subjects. Methods ...
03:00
Abstract Purpose To evaluate the inflammatory profile of premenopausal women with anovulatory cycles, regular menstrual cycles, or using contraceptives, and the associations with sleep and health-related parameters. Methods Subjects completed questionnaires including the Pittsburgh Sleep Quality Index and the Epworth sleepiness scale, underwent whole-night...
Tue Oct 20, 2020 03:00
To evaluate the maxillary dentition effects of the extrusion arch for anterior open bite (AOB) correction in mixed dentition patients.
Tue Oct 20, 2020 03:00
Gradenigo’s Syndrome and Bacterial Meningitis in a Patient with a Petrous Apex Cholesterol Granuloma
Gradenigo’s syndrome (GS) classically involves a triad of ear pain due to acute or chronic otitis media (OM), facial or retro-orbital pain in the distribution of the trigeminal nerve, and an abducens nerve palsy. The simultaneous presentation of all three components has become less common in cases of GS reported in the literature, particularly in the era of antibiotics effective against typical organisms attributed to OM and petrous apicitis. In addition to infectious petrous apicitis arising directly...
Tue Oct 20, 2020 17:05
Orbital compartment syndrome is an ophthalmologic emergency that requires timely surgical intervention. The authors present a rare case of orbital compartment syndrome in a 30-year-old male injured by forceful entry of air-gasoline mixture into the orbit, secondary to inadvertent firing of the piston from running mechanical diagnostics on an automobile internal combustion engine. Orbital CT revealed extensive orbital emphysema with both pre- and postseptal involvement and diffuse chemical cellulitis....
Fri Oct 16, 2020 03:00
Purpose: To evaluate the presentation, treatment, and outcome for patients with peribulbar dermolipomas and describe a reliable technique for excision of large lesions. Patients and methods: Retrospective chart review for patients seen at Moorfields Eye Hospital between 1976 and 2019. Patient demographics, clinical features, imaging (CT or MRI, where available), histopathology, and surgical outcomes were reviewed. Results: One hundred and ninety-six eyes of 187 patients (117...
Fri Oct 16, 2020 03:00
Vaccinations for shingles are recommended for most adults over 60 years of age and are typically well tolerated. The present case describes acute onset of unilateral ptosis, proptosis, and orbital myositis developing within days after administration of shingles vaccination. The episode resolved to baseline after 1 week of treatment with steroids. To the authors' knowledge, this is first reported case of orbital inflammation following shingles vaccination. Given the temporal relationship and rapid...
Fri Oct 16, 2020 03:00
Primary melanoma of the lacrimal sac is a rare entity, with high mortality and a propensity for recurrence. This report details a patient with widely metastatic melanoma discovered after biopsy of abnormal lacrimal sac tissue during routine dacryocystorhinostomy. The patient subsequently underwent local excision and treatment with pembrolizumab. At the time of this writing, it has been 24 months since the original diagnosis with resolution of his lacrimal and orbital lesions and improvement in all...
Fri Oct 16, 2020 03:00
Abstract Background Oral myofunctional therapy (MFT) is an effective treatment for mild‐to‐moderate obstructive sleep apnea (OSA) in middle‐aged patients. However, few reports have described its use in elderly patients with moderate and severe OSA. Moreover, no studies have examined the relationship between changes in tongue pressure with MFT and the severity of OSA. Objective We conducted an interventional study using MFT to evaluate the effect of MFT on middle‐ to senior‐aged patients...
Tue Oct 20, 2020 11:01
Journal of Investigative Medicine High Impact Case Reports, Volume 8, Issue , January-December 2020. Membranous glomerulonephritis is one of the common causes of nephrotic syndrome in the adult population. It is idiopathic in the majority of patients, but the secondary forms can be seen in the setting of autoimmune disease, cancer, infection, and following exposure to certain medications. However, subclinical syphilis-related membranous nephropathy remains a particularly rare clinicopathologic entity...
Tue Oct 20, 2020 14:33
Journal of Investigative Medicine High Impact Case Reports, Volume 8, Issue , January-December 2020. Syncope is a sudden but reversible brief loss of consciousness secondary to an acute reduction of cerebral perfusion. Reflex syncope denotes neurologically mediated syncope, which includes vasovagal, carotid sinus syndrome, and other situational syncope. The most frequent form of syncope is vasovagal, which is triggered by emotional stress or prolonged standing, and may be diagnosed with the tilt...
Tue Oct 20, 2020 14:32
Journal of Investigative Medicine High Impact Case Reports, Volume 8, Issue , January-December 2020. This study reported 2 new patients and 16 historical cases with pathologically proven intraocular infiltration with adult T-cell leukemia and lymphoma (ATLL) to know the timing of intraocular infiltration in the disease course. The first case was a 67-year-old woman who developed bilateral vitreous opacity about half a year after the onset of acute type of ATLL that had been unresponsive to chemotherapy....
Tue Oct 20, 2020 14:32
Cochlear implants are a groundbreaking technology that has changed the lives of many people living with severe to profound hearing loss. University of Sydney School of Biomedical Engineering researcher, Dr Greg Watkins, hears with the assistance of two cochlear implants after experiencing profound deafness in both ears following a 30-year career as an electrical engineer.Despite his profound deafness, with the help of his cochlear implant he has been able to complete a PhD in biomedical engineering.Dr...
Tue Oct 20, 2020 10:06
This year's Academy of Doctors of Audiology (ADA) annual convention, AuDacity 2020, goes outside the box--in format and themes—with contemporary topics and a completely virtual platform."The AuDacity 2020 Planning Committee, co-chaired by Dr. David Citron and Dr. Amyn Amlani, dreamed up a conference program so big and so innovative, it cannot be contained in Texas or confined to any physical location," read an announcement from the ADA.The event, which took place on October 16 and 17 (US Eastern...
Mon Oct 19, 2020 13:44
Although uncommon, sudden permanent hearing loss seems to be linked to COVID-19 infection in some people, warn doctors, reporting the first UK case in the journal BMJ Case Reports.Awareness of this possible side effect is important, because a prompt course of steroid treatment can reverse this disabling condition, they emphasise.Sudden hearing loss is frequently seen by ear, nose and throat specialists, with around 5-160 cases per 100,000 people reported every year. It's not clear what the causes...
Mon Oct 19, 2020 12:22
This year's Academy of Doctors of Audiology (ADA) annual convention, AuDacity 2020, goes outside the box--in format and themes—with contemporary topics and a completely virtual platform."The AuDacity 2020 Planning Committee, co-chaired by Dr. David Citron and Dr. Amyn Amlani, dreamed up a conference program so big and so innovative, it cannot be contained in Texas or confined to any physical location," read an announcement from the ADA.The event, which took place on October 16 and 17 (US Eastern...
Mon Oct 19, 2020 13:44
Although uncommon, sudden permanent hearing loss seems to be linked to COVID-19 infection in some people, warn doctors, reporting the first UK case in the journal BMJ Case Reports.Awareness of this possible side effect is important, because a prompt course of steroid treatment can reverse this disabling condition, they emphasise.Sudden hearing loss is frequently seen by ear, nose and throat specialists, with around 5-160 cases per 100,000 people reported every year. It's not clear what the causes...
Mon Oct 19, 2020 12:22
The first case of coronavirus disease 2019 (COVID-19) was declared in December in Wuhan, before becoming a global pandemic in a few weeks. Several complications of this infection have been reported. However, a spontaneous pneumomediastinum has rarely been described. We report the fourth case of this extremely rare complication in a 65-year-old male patient with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pneumonia, discovered during his therapeutic management by a CT scan control.
Tue Oct 20, 2020 18:35
Dating back to the last universal common ancestor (LUCA), the P-loop NTPases and Rossmanns now comprise the most ubiquitous and diverse enzyme lineages. Intriguing similarities in their overall architecture and phosphate binding motifs suggest common ancestry; however, due to a lack of sequence identity and some fundamental structural differences, these families are considered independent emergences. To address this longstanding dichotomy, we systematically searched for 'bridge proteins' with structure...
Tue Oct 20, 2020 03:00
Increasingly, predicting and even controlling evolutionary processes is a sought after goal in fields ranging from agriculture, artificial intelligence, astrobiology, oncology, and infectious diseases. However, our ability to predict evolution and plan such interventions in real populations is limited in part by our understanding of how spatial structure modulates evolutionary dynamics. Among current clinical assays applied to predict drug response in infectious diseases, for instance, many do not...
Tue Oct 20, 2020 03:00
Studies of convergence in wild populations have been instrumental in understanding adaptation by providing strong evidence for natural selection. At the genetic level, we are beginning to appreciate that the re-use of the same genes in adaptation occurs through different mechanisms and can be constrained by underlying trait architectures and demographic characteristics of natural populations. Here, we explore these processes in naturally adapted high- (HP) and low-predation (LP) populations of the...
Tue Oct 20, 2020 03:00
Apicomplexa is a diverse protistan phylum composed almost exclusively of metazoan-infecting parasites, including the causative agents of malaria, cryptosporidiosis, and toxoplasmosis. A single apicomplexan genus, Nephromyces, was described in 2010 as a mutualist partner to its tunicate host. Here we present genomic and transcriptomic data from the parasitic sister species to this mutualist, Cardiosporidium cionae, and its associated bacterial endosymbiont. Cardiosporidium cionae and Nephromyces both...
Tue Oct 20, 2020 03:00
128 years ago, August Weismann proposed that the only source of inherited genetic variation in animals is the germline1. Julian Huxley reasoned that if this were true, it would falsify Jean-Baptiste Lamarck's theory that acquired characteristics are heritable2. Since then, scientists have discovered that not all animals segregate germline cells from somatic cells permanently and early in development3. In fact, throughout their lives, Cnidaria4-6 and Porifera7 maintain primordial stem cells that continuously...
Tue Oct 20, 2020 03:00
Abstract Objective The present study summarizes the current knowledge on the role of bacterial extracellular signaling systems, known as quorum sensing (QS), in oral biofilm formation, and on the possibility of blocking these microbial communication systems as a potential approach to prevent and treat oral infectious diseases. Methods A detailed literature review of the current knowledge of QS in the oral cavity was performed, using the databases MEDLINE (through PubMed) and Web of Science....
Tue Oct 20, 2020 19:16
Abstract Objectives To investigate whether serum amylase can predict the recovery of salivary volume and determine the correlation of the level of cytokines, including epidermal growth factor, hepatocyte growth factor, and keratinocyte growth factor, with oral mucositis during chemoradiotherapy for oral cancer Subjects and Methods This study included 84 patients treated with preoperative chemoradiotherapy followed by curative surgery, following a phase II study protocol. We measured and...
Tue Oct 20, 2020 18:21
Abstract Objectives To investigate pathogenic variants of the paired box 9 (PAX9) gene in patients with non‐syndromic oligodontia, and the functional impact of these variants. Subjects and Methods Whole exome sequencing and Sanger sequencing were utilised to detect gene variants in a cohort of 80 patients diagnosed with non‐syndromic oligodontia. Bioinformatic and conformational analyses, fluorescence microscopy and luciferase reporter assay were employed to explore the functional impact....
Tue Oct 20, 2020 11:43
Abstract Objective To determine whether risk factors other than hyperglycemia lead to failed osseointegration in patients with type 2 diabetes mellitus (T2DM) during the healing period. Materials and Methods We compared the success rates between patients with and without T2DM during the healing period at our center. Bone marrow mesenchymal stem cells (BMSCs) were cultured from subjects. Proteomics was used to detect differentially expressed proteins (DEPs) among the DM failure (DM‐F), DM...
Tue Oct 20, 2020 11:27
The cover image is based on the Original Article Notch activation leads to loss of myoepithelial differentiation and poor outcome in solid adenoid cystic carcinoma by Ye Zhang et al., https://doi.org/10.1111/odi.13480.
Mon Oct 19, 2020 15:15
Alloplastic replacement of the temporomandibular joint (TMJ) is the treatment of choice in cases of TMJ end-stage disease. Improvements in computer-aided design/computer-aided manufacturing (CAD/CAM) translated into the possibility ongf designi very precise TMJ prostheses based on the anatomy of each single patient. Custom-made TMJ prostheses are described in the most recent literature and provide facilitations in terms of ease of placement and accuracy. Although before the era of custom-made surgical...
Tue Oct 20, 2020 03:00
Abstract We investigated neural correlates of traumatic experience related to the lack of family care in adults with a history of institutionalization (IC) using the Emotional Stroop paradigm. The goals of our study were two‐fold: we investigated whether adults with IC history (n=24; Mage = 22.17, SD = 6.7) demonstrate atypical processing of emotionally‐salient words in general, and whether they exhibit selective processing bias towards family‐related words compared to adults raised in biological...
Tue Oct 20, 2020 22:45
Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c09103
Tue Oct 20, 2020 07:00
Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c07013
Tue Oct 20, 2020 07:00
Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c05920
Tue Oct 20, 2020 07:00
Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c09222
Tue Oct 20, 2020 07:00
Miquel Llorente es Doctor en Psicología por la Universitat Ramon Llull (Blanquerna) y Licenciado en Psicología por la Universitat de Barcelona. Premio extraordinario de doctorado. Profesor Serra Húnter en el área de Psicología Básica en la Universitat de Girona (www.udg.edu), donde imparte cursos de Psicobiología y de Psicología Básica y del Desarrollo. Actualmente es el Director Científico de IPRIM (www.institutprimatologia.com) y ha sido Research Manager de la Fundació MONA (www.fundaciomona.org)...
Tue Oct 20, 2020 21:51
A team of scientists report a new method for identifying any genome sequence located next to a known sequence. Sonication Inverse PCR (SIP) can be used to characterize any DNA sequence (near a known sequence) and can be applied across genomics applications within a clinical setting as well as molecular evolutionary analyses.
Mon Oct 19, 2020 17:34
Peritoneal metastasis (PM) is an important pathological process in the progression of gastric cancer (GC). The metastatic potential of tumor and stromal cells is governed by hypoxia, which is a key molecular f...
Tue Oct 20, 2020 03:00
An amendment to this paper has been published and can be accessed via the original article.
Tue Oct 20, 2020 03:00
Internalising problems, such as depression and anxiety, are common and represent an important economical and societal burden. The effectiveness of parenting interventions in reducing the risk of internalising ...
Mon Oct 19, 2020 03:00
The exponential growth of the biomedical literature necessitates investigating strategies to reduce systematic reviewer burden while maintaining the high standards of systematic review validity and comprehensi...
Mon Oct 19, 2020 03:00
Occupational exposure to cytotoxic drugs is associated with various unfavorable health outcomes. This protocol reports a methodology for a systematic review and meta-analysis that aims to systematically review...
Mon Oct 19, 2020 03:00
Abstract Fulminant hepatitis (FH) is an acute clinical disease with a poor prognosis and high mortality rate. The purpose of this study was to determine the protective effect of the Toll-like receptor 4 (TLR4) inhibitor TAK-242 on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced explosive hepatitis and explore in vivo and in vitro mechanisms. Mice were pretreated with TAK-242 for 3 h prior to LPS (10 μg/kg)/D-GalN (250 mg/kg) administration. Compared to the LPS/D-GalN...
Tue Oct 20, 2020 03:00
The aim of the study was to determine the antioxidant activity and assess the lipophilicity and skin penetration of eugenyl chloroacetate (EChA), eugenyl dichloroacetate (EDChA), and eugenyl trichloroacetate (...
Mon Oct 19, 2020 03:00
Confidence in any Covid-19 vaccine that is made available under an emergency use authorization (EUA) will depend on the rigor of the clinical criteria, including the duration of follow-up, used to evaluate it. Recently published guidance from the Food and Drug Administration (FDA) recommends that…
Fri Oct 16, 2020 03:00
There were two intensive care unit (ICU) physician teams and countless nurses and respiratory therapists outside Mr. K.’s room when I arrived on the unit. The attending intensivist filled me in. "He’s maxed out on ECMO and pressors. He has a tension pneumothorax. My fellow is about to do a needle…
Wed Oct 14, 2020 03:00
Abstract Cystic neoplasms of the pancreas are an increasingly important public health problem. The majority of these lesions are benign but some progress to invasive pancreatic ductal adenocarcinoma (PDAC). There is a dearth of mouse models of these conditions. The orphan nuclear receptor NR5A2 regulates development, differentiation, and inflammation. Germline Nr5a2 heterozygosity sensitizes mice to the oncogenic effects of mutant Kras in the pancreas. Here, we show that ‐ unlike constitutive Nr5a2...
Tue Oct 20, 2020 18:35
The aim of this study was to evaluate via finite element analysis (FEA) the biomechanical behavior of conventional small-fragment screws reinforced by a patient-specific plate in type p condylar head.
Mon Oct 19, 2020 03:00
Abstract Objectives Percutaneous bone anchored hearing devices (pBAHDs) are the most commonly used bone conduction implants (BCI). Concerns surround the long‐term complications, notably skin‐related, in patients with percutaneous abutments. The active transcutaneous BCI Bonebridge system can help avoid some of these pitfalls but is often considered a second line option due to various factors including perceived increased overall costs. Design Longitudinal economic analysis of Bonebridge...
Sat Oct 17, 2020 17:45
Abstract Introduction This review discusses how nasal congestion may have benefits as a mechanism of defence against respiratory viruses. Methods A literature research was conducted on respiratory viruses and nasal congestion, following a recently published review on how temperature sensitivity is important for the success of common respiratory viruses. Results The literature reported that common respiratory viruses are temperature sensitive and replicate well at the cooler temperatures...
Fri Oct 16, 2020 18:45
This article describes the protocols used to produce a novel vaccine delivery platform, "polybubbles," to enable delayed burst release. Polyesters including poly(lactic-co-glycolic acid) and polycaprolactone were used to form the polybubbles and small molecules and antigen were used as cargo.
Tue Oct 20, 2020 19:41
Introduction: Deep brain stimulation (DBS) of the globus pallidus internus has become an accepted treatment for severe isolated idiopathic and inherited dystonia. Patients who had other forms of surgery earlier, such as radiofrequency lesioning or selective peripheral denervation, however, usually are not considered candidates for DBS. Objective: The aim of this study was to evaluate the long-term outcome of pallidal DBS in a rare subgroup of patients who had undergone both pallidotomy and selective...
Tue Oct 20, 2020 15:44
Background: Directional leads are increasingly used in deep brain stimulation. They allow shaping the electrical field in the axial plane. These new possibilities increase the complexity of programming. Thus, optimized programming approaches are needed to assist clinical testing and to obtain full clinical benefit. Objectives: This simulation study investigates to what extent the electrical field can be shaped by directional steering to compensate for lead malposition. Method: Binary volumes of tissue...
Tue Oct 20, 2020 10:15
Abstract Acute undifferentiated leukemia (AUL) is a very rare hematologic neoplasm that expresses no markers specific for either myeloid or lymphoid lineages. While commonly observed in several acute leukemias, KMT2A rearrangements in AUL have been rarely reported in the literature. We report the third case to our knowledge of AUL harboring a KMT2A rearrangement. Furthermore, the KMT2A/GIMAP8 gene fusion identified in this case represents a novel KMT2A rearrangement. This article is protected by...
Tue Oct 20, 2020 12:36
Abstract Chromosome translocations involving the RUNX1 gene at 21q22 are recurring abnormalities in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), i.e., t(8;21) and t(3;21) and in B‐cell acute lymphoblastic leukemia with t(12;21). These translocations result in the fusion of RUNX1 with RUNX1T1, MECOM, and ETV6, respectively, and are implicated in leukemogenesis. Here we describe 10 rare RUNX1 fusion gene partners, including six novel fusions, in myeloid neoplasia. Comprehensive...
Tue Oct 20, 2020 12:13
Abstract Pathogenic variants in the BRCA1 and BRCA2 genes are well known causes of hereditary breast and ovarian cancer. Other genes involved in the homologous recombination pathway can also be associated with increased probability of cancer development, for example, breast and ovarian cancer, prostate and pancreatic cancer, colorectal cancer and even childhood tumors like medulloblastoma. Traditionally, patients and families likely to harbor a genetic predisposition have been identified using...
Tue Oct 20, 2020 11:59
Publication date: Available online 20 October 2020Source: Journal of Neuroscience MethodsAuthor(s): J.R. Bourgeois, G. Kalyanasundaram, C. Figueroa, A. Srinivasan, A.M. Kopec
Tue Oct 20, 2020 18:52
Heart failure (HF) is not uncommon among patients with hematologic malignancies (HM) undergoing hematopoietic stem cell transplantation (HSCT) and is associated with an increased mortality. Among HSCT patients without signs or symptoms of HF, groups with elevated and normal N-terminal probrain natriuretic peptide (NT-proBNP) levels have been poorly characterized in previous literature. Herein, we reviewed consecutive admissions for HM undergoing HSCT (). Based on NT-proBNP levels and clinical signs...
Tue Oct 20, 2020 09:20
Abstract A progressive increase in copy number variation (CNV) characterizes the natural history of cutaneous melanoma progression towards later disease stages, but our understanding of genetic drivers underlying chromosomal arm‐level CNVs remains limited. To identify candidate progression drivers, we mined the TCGA SKCM dataset and identified HDGF as a recurrently amplified gene whose high mRNA expression correlates with poor patient survival. Using melanocyte specific overexpression in the zebrafish...
Fri Oct 16, 2020 19:08
Abstract Introduction In bone tissue, bone resorption by osteoclasts and bone formation by osteoblasts are repeated continuously. Osteoclasts are multinucleated cells that derive from monocyte-/macrophage-lineage cells and resorb bone. In contrast, osteoblasts mediate osteoclastogenesis by expressing receptor activator of nuclear factor-kappa B ligand (RANKL), which is expressed as a membrane-associated cytokine. Osteoprotegerin (OPG)...
Tue Oct 20, 2020 03:00
Abstract Introduction Recent studies have indicated the potential of stem cell therapy in combination with cytokines to restore the bone repair via migration and homing of stem cells to the defected area. The present study aimed to investigate the mobilization and recruitment of mesenchymal stem cells (MSCs) in response to SDF-1. Materials and Methods ...
Tue Oct 20, 2020 03:00
Abstract Optical coherence tomography (OCT) has shown potential in differentiating normal colonic mucosa from neoplasia. In this study of 33 fresh human colon specimens, we report the first use of texture features and computer‐vision‐based imaging features acquired from en face scattering coefficient maps to characterize colorectal tissue. En face scattering coefficient maps were generated automatically using a new fast integral imaging algorithm. From these maps, a gray‐level co‐occurrence matrix...
Fri Oct 16, 2020 16:53
Abstract Photodynamic therapy (PDT) with Rose Bengal has previously achieved eradication of Trichophyton rubrum infections causing toenail onychomycosis, however, its antifungal activity against other clinically relevant dermatophytes has yet to be studied. Here, we test the efficacy of PDT using Rose Bengal (140 μM) and 532 nm irradiation (101 J cm−2) against Trichophyton mentagrophytes and Trichophyton interdigitale spores, in comparison to T. rubrum. A significant reduction (>99%) of T. mentagrophytes...
Thu Oct 15, 2020 17:21
Abstract Although nivolumab, a programmed cell death 1 (PD‐1) inhibitor, is a standard therapy for platinum‐refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), no definitive biomarkers have been reported thus far. This study aimed to select promising prognostic markers in nivolumab therapy and to create a novel prognostic scoring system. In this retrospective cohort study, we reviewed patients with R/M HNSCC who were treated with nivolumab from April 2017 to April...
Tue Oct 20, 2020 11:41
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