Purpose: Several aggressive pediatric cancers harbor alterations in SMARCB1, including rhabdoid tumors, epithelioid sarcoma and chordoma. As tumor profiling has become more routine in clinical care, we investigated the relationship between SMARCB1 genetic variants identified by next-generation sequencing (NGS) and INI1 protein expression. Therapeutic approaches for INI1-deficient tumors are limited. Early reports suggest a potential role for immune checkpoint inhibition in these patients. Thus, we...
Mon Mar 02, 2020 16:20
Purpose: ROS1 tyrosine kinase inhibitors (TKIs) provide significant benefit in lung adenocarcinoma (LUAD) patients with ROS1 fusions. However, as observed with all targeted therapies, resistance arises. Detecting mechanisms of acquired resistance (AR) is crucial to finding novel therapies and improve patient outcomes. Experimental Design: ROS1 fusions were expressed in in HBEC and NIH-3T3 cells either by cDNA overexpression (CD74/ROS1, SLC34A2/ROS1) or CRISPR-Cas9-mediated genomic engineering (EZR/ROS1)....
Mon Mar 02, 2020 16:20
Circulating cell-free DNA (cfDNA) is rapidly transitioning from discovery research to an important tool in clinical decision making. However, the lack of harmonization of preanalytical practices across institutions may compromise the reproducibility of cfDNA-derived data and hamper advancements in cfDNA testing in the clinic. Differences in cellular genomic contamination, cfDNA yield, integrity, and fragment length have been attributed to different collection tube types and anticoagulants, processing...
Mon Mar 02, 2020 16:20
Purpose: Cytarabine is an effective treatment for AML with associated toxicities including treatment related mortality (TRM). The purpose is to determine the clinical relevance of single-nucleotide polymorphisms (SNPs) identified through the use of HapMap lymphoblastoid cell-based models, in predicting cytarabine response and toxicity in AML. Experimental Design: We tested clinical significance of SNPs associated with cytarabine sensitivity in children with AML treated on Children's Oncology Group...
Mon Mar 02, 2020 16:20
Purpose: Broadly expressed, highly differentiated tumor-associated antigens (TAA) can elicit anti-tumor immunity. However, vaccines targeting TAAs have demonstrated disappointing clinical results, reflecting poor antigen selection and/or immunosuppressive mechanisms. Experimental Design: Here, a panel of widely expressed, novel colorectal TAAs were identified by performing RNA sequencing of highly purified colorectal tumor cells in comparison to patient-matched colonic epithelial cells; tumor cell...
Mon Mar 02, 2020 16:20
Purpose: The histone-methyl transferase EZH2, catalytic subunit of the PRC2 complex involved in transcriptional regulation is mutated in approximately 25% of germinal center B-cell lymphomas. Aberrant proliferative dependency on EZH2 activity can be targeted by the orally available EZH2 inhibitor tazemetostat (EPZ-6438). We report the results of the phase Ib tazemetostat plus R-CHOP combination (NCT02889523), in patients 60-80 years with newly diagnosed diffuse large B cell lymphoma. Experimental...
Mon Mar 02, 2020 16:20
Purpose: RNA splicing is a fundamental biological process that generates protein diversity from a finite set of genes. Recurrent somatic mutations of splicing factor genes are common in some hematological cancers but are relatively uncommon in Acute Myeloid Leukemia (AML, < 20% of patients). We examined whether RNA splicing differences exist in AML, even in the absence of splicing factor mutations. Experimental Design: We developed a bioinformatics pipeline to study alternative RNA splicing in...
Mon Mar 02, 2020 16:20
Abstract Child soldiers have been heavily involved in contemporary African warfare. Since the 1990s, the ‘child soldier crisis’ has become a major humanitarian and human rights project. The figure of the child soldier has often been taken as evidence of the ‘barbarism’, dehumanization and trauma generated by modern warfare, but such images can obscure the complex reality of children’s experiences of being part of armed groups during conflict. This article uses the published memoirs...
Mon Mar 02, 2020 02:00
Abstract The current article focused on examining the potential benefits of the End-of-Life (EoL) informal caregiving, communication, and ritualistic behaviors in adaptation to the conjugal bereavement across two different cultural-background contexts: France and Togo, West Africa. The investigation adopted a transnational approach including a total of 235 bereaved spouses. Despite the variation in the length of time since death, no significant difference was found between the...
Mon Mar 02, 2020 02:00
(Source: Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry)
Sat Feb 29, 2020 07:41
(Source: Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry)
Sat Feb 29, 2020 07:41
(Source: Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry)
Sat Feb 29, 2020 07:41
(Source: Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry)
Sat Feb 29, 2020 07:41
(Source: Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry)
Sat Feb 29, 2020 07:41
(Source: Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry)
Sat Feb 29, 2020 07:41
(Source: Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry)
Sat Feb 29, 2020 00:00
The Pharmacogenomics Journal, Published online: 03 March 2020; doi:10.1038/s41397-020-0164-3Association of MICA-129Met/Val polymorphism with clinical outcome of anti-TNF therapy and MICA serum levels in patients with rheumatoid arthritis
02:00
Cancer Gene Therapy, Published online: 03 March 2020; doi:10.1038/s41417-020-0170-2Transcription factors in ferroptotic cell death
02:00
The geographic expansion of chronic wasting disease (CWD) in U.S. white-tailed deer (Odocoileus virginianus) has been largely unabated by best management practices, diagnostic surveillance, and depopulation of positive herds. Using a custom Affymetrix Axiom® single nucleotide polymorphism (SNP) array, we demonstrate that both differential susceptibility to CWD, and natural variation in disease progression, are moderately to highly heritable ( among farmed U.S. white-tailed deer, and that loci other...
Mon Mar 02, 2020 23:36
Innovative tools are essential for advancing malaria control and depend on an understanding of molecular mechanisms governing transmission of malaria parasites by Anopheles mosquitoes. CRISPR/Cas9-based gene disruption is a powerful method to uncover underlying biology of vector-pathogen interactions and can itself form the basis of mosquito control strategies. However, embryo injection methods used to genetically manipulate mosquitoes (especially Anopheles) are difficult and inefficient, particularly...
Mon Mar 02, 2020 23:36
Cotton is an important crop that has made significant gains in production over the last century. Emerging pests such as the reniform nematode have threatened cotton production. The rare African diploid species Gossypium longicalyx is a wild species that has been used as an important source of reniform nematode immunity. While mapping and breeding efforts have made some strides in transferring this immunity to the cultivated polyploid species, the complexities of interploidal transfer combined with...
Mon Mar 02, 2020 23:36
Theoretical work predicts that sexual selection can enhance natural selection, increasing the rate of adaptation to new environments and helping purge harmful mutations. While some experiments support these predictions, remarkably little work has addressed the role of sexual selection on compensatory adaptation-populations' ability to compensate for the costs of deleterious alleles that are already present. We tested whether sexual selection, as well as the degree of standing genetic variation, affect...
Mon Mar 02, 2020 23:36
The Hippo pathway regulates growth and apoptosis. We identify RhoBTB proteins as novel regulators of Hippo signaling. RhoBTB depletion in the Drosophila wing disc epithelium cooperated with Yki to drive hyperplasia into neoplasia. Depletion of RhoBTB2 caused elevated YAP activity in human cells. RhoBTB2 deficiency resulted in increased colony formation in assays for anchorageindependent growth. We provide evidence that RhoBTBs acts on Hippo signaling through regulation of the kinase LKB1. LKB1 protein...
Fri Feb 28, 2020 23:57
The RB51 vaccine strain of Brucella abortus, which confers safe and effective protection of cattle from B. abortus infection, was originally generated via serial passage of B. abortus 2308 to generate spontaneous, attenuating mutations. While some of these mutations have been previously characterized, such as an insertional mutation in the wboA gene that contributes to the rough phenotype of the strain, a comprehensive annotation of genetic differences between RB51 and B. abortus 2308 genomes has...
Fri Feb 28, 2020 23:57
Drought stress causes the greatest soybean [Glycine max (L.) Merr.] yield losses among the abiotic stresses in rain-fed U.S. growing areas. Because less than 10% of U.S. soybean hectares are irrigated, combating this stress requires soybean plants which possess physiological mechanisms to tolerate drought for a period of time. Phenotyping for these mechanisms is challenging, and the genetic architecture for these traits is poorly understood. A morphological trait, slow or delayed canopy wilting,...
Fri Feb 28, 2020 23:57
Inflammation and oxidative stress play key roles in the process of aging and age-related diseases. Since serine availability plays important roles in the support of antioxidant and anti-inflammatory defense system, we explored whether serine deficiency affects inflammatory and oxidative status in D-galactose-induced aging mice. Male mice were randomly assigned into four groups: mice fed a basal diet, mice fed a serine- and glycine-deficient (SGD) diet, mice injected with D-galactose and fed a basal...
Mon Mar 02, 2020 16:35
Xuebijing injection is a Chinese herb compound to treat sepsis in China, but it contains many different kinds of components, and each component may have different effects in treating sepsis. The present study was performed to investigate the effect of three ingredients of Xuebijing, safflor yellow A (SYA), hydroxysafflor yellow A (HSYA), and anhydrosafflor yellow B (AHSYB), in lipopolysaccharide- (LPS-) induced acute lung injury (ALI). LPS (10 mg/kg) was injected intratracheally to induce acute lung...
Sat Feb 29, 2020 13:05
Smoking is a major risk factor for pulmonary diseases that include chronic obstructive pulmonary diseases (COPD) and cancer. Nicotine is the toxic and addictive component of tobacco products, like cigarettes, that negatively affects the immune system. Here, we examined the effect of nicotine on the IL-22 pathway that protects lung function by increasing transepithelial resistance and epithelial cell regeneration and repair. Our results indicate that exposure to nicotine impairs the regenerative capacity...
Sat Feb 29, 2020 10:05
Abstract Background The anti‐tumour necrosis factor (TNF)‐α adalimumab is the only licenced biologic for moderate‐to‐severe hidradenitis suppurativa (HS). No predictors of response have been identified so far. Objective To identify clinical parameters predicting response to adalimumab and confirm its efficacy/ safety. Methods Data of 389 HS patients treated with adalimumab in 21 Italian centres were reviewed. Sex, ages at onset/diagnosis/baseline, body mass index, smoking,...
04:11
Abstract Dermatology‐specific quality‐of‐life instruments such Dermatology Life Quality Index (DLQI), as well as vitiligo‐specific instruments are available to study the quality of life of patients with vitiligo. Vitiligo Impact Scale (VIS)‐22 is a validated vitiligo‐specific instrument, and clinical meaning has been assigned to its absolute scores.1,2 The minimal important change (MIC) is the smallest difference in a score that is considered significant by the patient and/or physician. We conducted...
04:11
Abstract Keratinocyte cancers (KC) are the commonest malignancies in the UK population, with rates increasing annually. Nicotinamide (vitamin B3) has recently been reported to reduce the incidence of KC in high‐risk patients. It is a precursor of nicotinamide adenine dinucleotide (NAD+) which replenishes cellular energy levels and enhances efficient repair of ultraviolet light (UV) induced DNA damage within keratinocytes.
04:11
Abstract Alopecia areata (AA) is one of the most common autoimmune diseases; however, the pathogenesis of the condition has yet to be fully elucidated. A recent study reported a case of severe AA associated with atopic dermatitis (AD) which was successfully treated with dupilumab, a monoclonal antibody against the α subunit of IL‐4/IL‐13 receptor.
04:11
Abstract Introduction Pityriasis lichenoides (PL) is a papulosquamous dermatosis affecting both children and adults for which no standard treatment currently exists. The aims of our systematic review were to characterize different treatment options and develop an evidence‐based treatment algorithm for PL. Methods A systematic search of published literature on PL treatments was performed on December 23rd, 2017 via the Medline, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, and the EU Clinical...
Sat Feb 29, 2020 13:16
Abstract Patch testing is a common procedure, where the baseline series is frequently used as a first screening. The number and the specific allergens of these series varies from country to country and keep changing over the years. Although the European Society of Contact Dermatitis (ESCD) made recommendations about patch testing1, the decisions about the European baseline series were traditionally delegated to the European Environmental Contact Dermatitis Research Group (EECDRG)2. A different,...
Sat Feb 29, 2020 13:16
Summary Epidermolysis bullosa (EB) is a complex rare condition that affects the skin and many parts of the body. Those born with EB have skin so fragile they are called ‘butterfly children’, their skin is quite simply as fragile as the wing of a butterfly. In the UK it is estimated that there are more than 5,000 people living with EB and 500,000 worldwide. Little clinical guidance for care existed until DEBRA International started a programme to develop clinical practice guidelines (CPGs). There...
Sat Feb 29, 2020 13:16
Summary The incidence of skin cancers is increasing worldwide. The epidermis is the surface layer of the skin and the main cell type is the keratinocyte. Keratinocyte‐derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic (meaning it can spread) skin cancer and it is responsible for 20% of skin cancer related deaths. The main risk factor for cSCC includes long term exposure to sun ultraviolet radiation. The progression of cSCC is as follows: it starts in a premalignant...
Sat Feb 29, 2020 13:16
Summary The disease pachyonychia congenita (PC) is a rare skin condition affecting approximately 900 people worldwide, according to the International PC Research Registry. PC is caused by inherited mutations (abnormalities) in a subset of genes called keratin intermediate filament genes (keratin 6A, keratin 6B, keratin 6C, keratin 16, and keratin 17), which are normally found in skin structures like hair follicles, the nail bed, and sweat glands. PC has many symptoms, but the most common and...
Sat Feb 29, 2020 13:16
Summary Pachyonychia congenita (PC) is a rare genetic skin disease which is estimated to affect between 5,000 and 10,000 people worldwide. PC can cause severe pain, especially affecting weight‐bearing areas, which accompanies thickening of the skin on the feet (keratoderma). Although there are options for treating the various symptoms of PC, most of them are not especially effective at improving the keratoderma and the pain. The successful use of botulinum toxin (Btx) injections for treating...
Sat Feb 29, 2020 13:16
Summary Pemphigus vulgaris (PV) and mucous membrane pemphigoid (MMP) are rare and potentially serious conditions that cause painful blisters or erosions to develop in the mouth, nose, throat, oesophagus, genitalia and skin. One of the main complications unique to MMP is that it may scar affected sites, particularly the eyes. Both diseases generally occur in older adults. To confirm the diagnosis of PV and MMP, a biopsy has traditionally been taken from near the affected area (perilesional). Where...
Sat Feb 29, 2020 13:16
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