Apprehensively, I dialed Mr. M. for an update. Weeks earlier, he and his wife had tested positive for SARS-CoV-2. A few days before this call, Mr. M. had been discharged from the hospital, since his cough and fever were improving. Unfortunately, Ms. M. had developed worsening breathing, needed more…
Tue May 26, 2020 03:00
Abstract P3 amplitude reductions, commonly elicited in oddball paradigms, have been associated with both internalizing (e.g., depression and anxiety) and externalizing problems (e.g., substance use, aggression, and impulsivity). Recent factor analytic models have focused on the shared variance between internalizing and externalizing problems as a potentially important separable psychopathology construct (a general psychopathology factor, or p ‐factor). To assess neurophysiological markers of this...
Mon Jun 01, 2020 18:12
The continuing spread of SARS-CoV-2 remains a Public Health Emergency of International Concern. What physicians need to know about transmission, diagnosis, and treatment is the subject of ongoing updates from infectious disease experts at the Journal. In this audio interview conducted on May 27,…
Thu May 28, 2020 03:00
The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged large parts of the world into a protracted medical, social, and economic crisis. Coronavirus disease 2019 (Covid-19), the respiratory illness caused by SARS-CoV-2 infection, has caused over a quarter…
Wed May 27, 2020 03:00
ABSTRACT Super‐resolution microscopy techniques can provide answers to still pending questions on prokaryotic organisms but are yet to be employed at their full potential for this purpose. To address this, we evaluate the ability of the rhodamine‐like KK114 dye to label various types of bacteria, to enable imaging of fine structural details with Stimulated Emission Depletion Microscopy. We assessed fluorescent labeling with KK114 for eleven Gram‐positive and Gram‐negative bacterial species and observed...
Mon Jun 01, 2020 21:38
Background Povidone‐iodine (PVP‐I) is well known as an antiseptic and exhibits extensive activity against various pathogens. However, due to its uniquely unpleasant nature, it cannot be used locally to deactivate various sinonasal pathogens. Therefore, we developed a PVP‐I composite that blocks the unpleasant odor of PVP‐I for use as a local antiseptic in the sinonasal cavity and evaluated its effect on bacterial biofilm's formation and elimination in in vivo and in vitro models. Methods...
Mon Jun 01, 2020 22:52
Background Recent studies have proposed that handwashing can lead to the development of allergic disease by reducing skin epithelial barrier integrity. The purpose of this study was to evaluate the association between personal hygiene practices and allergic rhinitis (AR) in a nationally representative sample of Korean adolescents. Methods A total of 62,276 adolescent participants (aged 12 to 18 years) were analyzed using the Korea Youth Risk Behavior Web‐based Survey, which was conducted in...
Mon Jun 01, 2020 22:51
Background Drug‐eluting implants are becoming increasingly popular in the treatment of chronic rhinosinusitis (CRS). A previous attempt to make an evidence‐based recommendation was hindered by limited evidence and experience with these implants. Since that time, the body of literature discussing drug‐eluting implants has grown rapidly. The objective of this study was to review drug‐eluting implants designed for use in the sinonasal cavity through an evidence‐based review with recommendations. ...
Mon Jun 01, 2020 22:45
New Findings What is the central question of this study? Does short‐term high intensity interval training alter microbiome composition, and does this associate with exercise‐induced improvements in cardiorespiratory fitness and insulin sensitivity? What is the main finding and its importance? Despite high intensity interval training increasing insulin sensitivity and cardiovascular fitness it did not alter microbiome composition. This suggests microbiome composition changes that...
Mon Jun 01, 2020 13:55
Mon Jun 01, 2020 21:12
Abstract Therapeutic innovation for human papilloma virus‐related (HPV+) head and neck squamous cell carcinomas (HNSCCs) is impaired by inadequate preclinical models and absence of accurate biomarkers. This study establishes the first well‐characterized panel of patient‐derived xenografts (PDXs) and organoids from HPV+ HNSCCs while determining fidelity of the models to the distinguishing genetic features of this cancer type. Despite low engraftment rates, whole exome sequencing showed that PDXs...
Mon Jun 01, 2020 17:55
Abstract The relationship between hepatitis B virus (HBV) and non‐hepatocellular cancers remains inconclusive. This large case‐control study aimed to assess the associations between HBV infection status and multiple cancers. Cases (N = 50 392) and controls (N = 11 361) were consecutively recruited from 2008 to 2016 at the First Affiliated Hospital of Nanjing Medical University. Multivariable adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression...
Mon Jun 01, 2020 17:54
Esophageal squamous cell carcinoma (ESCC) is a disease characterized by a high mutation rate of the TP53 gene, which plays pivotal roles in the DNA damage response (DDR) and is regulated by checkpoint kinase (CHK) 2. CHK1 is another key DDR-related protein, and its selective inhibition is suggested to be particularly sensitive to TP53-mutated cancers, because a loss of both pathways (CHK1 and/or CHK2–p53) is lethal due to the serious impairment of DDR. Such a therapeutic strategy is termed synthetic...
Tue Jun 02, 2020 10:05
Alectinib is used as a first-line treatment for anaplastic lymphoma kinase (ALK)-rearranged non–small cell lung cancer (NSCLC). Whereas other ALK inhibitors have been reported to be involved in resistance to ATP-binding cassette (ABC) transporters, no data are available regarding the association between resistance to alectinib and ABC-transporters. To investigate whether ABC-transporters contribute to alectinib resistance, ABC-transporter expression in alectinib-resistant cell lines derived from...
Tue Jun 02, 2020 10:05
Castration-resistant prostate cancer (CRPC) is a lethal disease with few treatment alternatives once patients become resistant to second-generation antiandrogens. In CRPC, BET proteins are key regulators of AR- and MYC-mediated transcription, while the PLK1 inhibitor potentially downregulates AR and MYC besides influencing the cell cycle. Therefore, synchronous inhibition of BET and PLK1 would be a promising approach for CRPC therapy. This study developed a dual BET and PLK1 inhibitor WNY0824 with...
Tue Jun 02, 2020 10:05
The programmed cell death 1 (PD-1) pathway represents a major immune checkpoint, which may be engaged by cells in the tumor microenvironment to overcome active T-cell immune surveillance. Pembrolizumab (Keytruda®, MK-3475) is a potent and highly selective humanized mAb of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade enhances the functional activity of T cells to facilitate tumor regression and ultimately immune rejection....
Tue Jun 02, 2020 10:05
Metastatic cancer involving spread to the peritoneal cavity is referred to as peritoneal carcinomatosis and has a very poor prognosis. Our previous study demonstrated a Toll-like receptor and C-type lectin receptor agonist pairing of monophosphoryl lipid A (MPL) and trehalose-6,6'-dicorynomycolate (TDCM) effectively inhibits tumor growth and ascites development following TA3-Ha and EL4 challenge through a mechanism dependent on B-1a cell–produced natural IgM and complement. In this study, we investigated...
Tue Jun 02, 2020 10:05
Most patients with osteosarcoma have subclinical pulmonary micrometastases at diagnosis. Mounting evidence suggests that macrophages facilitate metastasis. As the EGFR has been implicated in carcinoma–macrophage cross-talk, in this study, we asked whether gefitinib, an EGFR inhibitor, reduces osteosarcoma invasion and metastatic outgrowth using the K7M2-Balb/c syngeneic murine model. Macrophages enhanced osteosarcoma invasion in vitro, which was suppressed by gefitinib. Oral gefitinib inhibited tumor...
Tue Jun 02, 2020 10:05
TACC3, a transforming acidic coiled-coil (TACC) family member, is frequently upregulated in a broad spectrum of cancers, including breast cancer. It plays critical roles in protecting microtubule stability and centrosome integrity that is often dysregulated in cancers; therefore, making TACC3 a highly attractive therapeutic target. Here, we identified a new TACC3-targeting chemotype, BO-264, through the screening of in-house compound collection. Direct interaction between BO-264 and TACC3 was validated...
Tue Jun 02, 2020 10:05
FGFRs are commonly altered in non–small cell lung cancer (NSCLC). FGFRs activate multiple pathways including RAS/RAF/MAPK, PI3K/AKT, and STAT, which may play a role in the cellular response to radiation. We investigated the effects of combining the selective FGFR 1-3 tyrosine kinase inhibitor AZD4547 with radiation in cell line and xenograft models of NSCLC. NSCLC cell lines were assessed with proliferation, clonogenic survival, apoptosis, autophagy, cell cycle, and DNA damage signaling and repair...
Tue Jun 02, 2020 10:05
Patients with cancer often confront the decision of whether to continue high-dose chemotherapy at the expense of cumulative toxicities. Reducing the dose of chemotherapy regimens while preserving efficacy is sorely needed to preserve the performance status of these vulnerable patients, yet has not been prioritized. Here, we introduce a dual pronged approach to modulate the microenvironment of desmoplastic pancreatic tumors and enable significant dose deescalation of the FDA-approved chemotherapeutic...
Tue Jun 02, 2020 10:05
Renal cell carcinoma bone metastases (RCCBM) are typically osteolytic. We previously showed that BIGH3 (beta Ig-h3/TGFBI), secreted by 786-O renal cell carcinoma, plays a role in osteolytic bone lesion in RCCBM through inhibition of osteoblast (OSB) differentiation. To study this interaction, we employed three-dimensional (3D) hydrogels to coculture bone-derived 786-O (Bo-786) renal cell carcinoma cells with MC3T3-E1 pre-OSBs. Culturing pre-OSBs in the 3D hydrogels preserved their ability to differentiate...
Tue Jun 02, 2020 10:05
Glioblastomas commonly (40%) exhibit epidermal growth factor receptor (EGFR) amplification; half of these tumors carry the EGFRvIII deletion variant characterized by an in-frame deletion of exons 2–7, resulting in constitutive EGFR activation. Although EGFR tyrosine kinase inhibitors had only modest effects in glioblastoma, novel therapeutic agents targeting amplified EGFR or EGFRvIII continue to be developed. Depatuxizumab mafodotin (ABT-414) is an EGFR-targeting antibody–drug conjugate consisting...
Tue Jun 02, 2020 10:05
Platinum-based chemoradiotherapy is a mainstay of organ-preserving therapy for patients with head and neck squamous cell carcinoma cancer (HNSCC). However, the disease eventually becomes resistant to treatment necessitating new therapies. Checkpoint kinase 1 and 2 (CHK1/2) are serine/threonine kinases that activate cell-cycle checkpoints and serve a critical role in the DNA-damage response (DDR). As resistance to cisplatin and radiation may involve a heightened DDR, we hypothesized that prexasertib,...
Tue Jun 02, 2020 10:05
The MYC oncogene is frequently amplified in patients with medulloblastoma, particularly in group 3 patients, who have the worst prognosis. mTOR signaling–driven deregulated protein synthesis is very common in various cancers, including medulloblastoma, that can promote MYC stabilization. As a transcription factor, MYC itself is further known to regulate transcription of several components of protein synthesis machinery, leading to an enhanced protein synthesis rate and proliferation. Thus, inhibiting...
Tue Jun 02, 2020 10:05
KIT or PDGFRA gain-of-function mutations are the primary drivers of gastrointestinal stromal tumor (GIST) growth and progression throughout the disease course. The PI3K/mTOR pathway is critically involved in the transduction of KIT/PDGFRA oncogenic signaling regardless of the type of primary and secondary mutations, and therefore emerges as a relevant targetable node in GIST biology. We evaluated in GIST preclinical models the antitumor activity of copanlisib, a novel pan-class-I PI3K inhibitor with...
Tue Jun 02, 2020 10:05
Patients with prostate cancer with tumors harboring defects in DNA-repair genes (DRD) generally do not respond well to AR-directed therapy. Furthermore, canonical pathways evolve during disease progression and may affect treatment with existing therapies. Due to the limited treatment options after failure of hormonal and taxane therapy, and the tumor heterogeneity induced by DRD, we sought to characterize the alterations in primary and metastatic prostate cancer. Tumors from 1,027 patients with advanced...
Tue Jun 02, 2020 10:05
Abstract New virus SARS‐Cov‐2 infection has spread over the world affecting all daily activities, including functioning of health services. Due to pandemic many hospitals were ordered to re‐organize their work. The aim of the current report was to evaluate the influence of COVID‐19 pandemic on the hospitalizations at the tertiary dermatology department in south‐west Poland. Two corresponding periods of 2019 and 2020 were compared in aspect of number of hospitalizations, sex and age profile of inpatients....
Mon Jun 01, 2020 17:49
Abstract Few studies have reported Fractional Carbon Dioxide (FCO2) laser use in treating Alopecia Areata (AA), yet, effectiveness of this therapy has not been comparatively analyzed. To assess efficacy and safety of FCO2 laser in comparison to traditional intralesional corticosteroids injection (ILCs) in treatment of AA. This study included 20 patients with at least 2 patches of AA. Patients were subjected to history taking, general, dermatological and folliscopic examination. One patch was treated...
Mon Jun 01, 2020 16:20
Abstract Recently 5‐fluorouracil 0.5% / salicylic acid 10% (5‐FU/SA) topical solution has been included in the National Italian portfolio for lesion‐directed treatment of grade I/II actinic keratosis (AKs) located on the face or scalp. To describe the utility of dermoscopy and RCM in treatment response monitoring of a series of AKs treated with 5‐FU/SA as lesion‐directed therapy. Consecutive patients were prospectively treated for a maximum of 12 weeks with 5‐FU/SA for AKs located on the face or...
Mon Jun 01, 2020 16:18
The COVID‐19 pandemic has a strong negative impact on human society world‐wide. Patients with immune‐mediated disease may be prone to an increased risk of infection and/ or more severe course. We review the available data for patients with psoriatic arthritis (PSA) and systemic treatments. Current treatment options are summarized. Based upon the experience with COVID‐19 the following problems are addressed: (a) Can systemic treatment reduce comorbidities of PsA that are also comorbidities for COVID‐19?...
Mon Jun 01, 2020 16:17
Abstract Protecting healthcare workers is crucial during coronavirus disease 2019 (COVID‐19) pandemic and facemask wearing is considered an effective measure to prevent severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. However, long‐time use of a facemask can cause pressure sores on the ears and nose bridge and increase the risk of infection. The topical recombinant human acidic fibroblast growth factor (rh‐aFGF) was used to cure pressure sores for healthcare workers at Zhongfaxincheng...
Mon Jun 01, 2020 16:17
Mon Jun 01, 2020 16:16
Abstract Background Androgenetic alopecia (AGA) is the most common type of baldness affecting both men and women. Studies investigating combination therapies for AGA reported greater efficacy than monotherapy but without rigorous examination. The authors performed a meta‐analysis and systemic review to further verify the evidence. Objective To evaluate the effectiveness of three common combination therapies of minoxidil with finasteride, low‐level laser light therapy (LLLT) or microneedling...
Mon Jun 01, 2020 16:16
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