Explore the vast range of titles available.

PurposeComplementary and alternative medicine (CAM) use is common amongst cancer patients. However, there is growing concern about its safety and efficacy. Online crowdfunding campaigns represent a unique avenue to understand the cancer patient’s perspective for using CAM or declining conventional cancer therapy (CCT).MethodsFive hundred GoFundMe campaigns from 2012 to 2019 detailing financial need for cancer treatment were randomly selected and reviewed for endorsement of CAM use, reasons for using CAM, and reasons for declining CCT. Descriptive statistics were used to compare patient and campaign characteristics between 250 CAM users and 250 non-CAM users.ResultsCompared to non-CAM users, CAM users were more likely to be female (70% vs. 54%, p < 0.01), to report more stage IV cancer (54% vs. 12%, p < 0.01), and to have a history of delayed, missed, or misdiagnosis (10% vs. 4%, p < 0.01). Reasons for using CAM include endorsing curative/therapeutic effects 212 (85%), pain/stress reduction 137 (55%), and dissatisfaction with current or past medical treatment options 105 (42%). 87 (35%) CAM users that declined CCT reported that they wanted to try to fight off cancer using CAM first 57 (61%), that CCT was too “toxic” to the body 39 (42%), and cancer was already too advanced, so that CCT would be futile or too aggressive 25 (27%).ConclusionCancer patients on GoFundMe using CAM highly value quality of life, comfort, and autonomy. Physicians should educate themselves on CAM to set realistic expectations and provide comprehensive counseling of the risks and benefits of CAM usage to patients who choose to use CAM to either augment or completely replace CCT.

Point-scanning imaging systems are among the most widely used tools for high-resolution cellular and tissue imaging, benefiting from arbitrarily defined pixel sizes. The resolution, speed, sample preservation and signal-to-noise ratio (SNR) of point-scanning systems are difficult to optimize simultaneously. We show these limitations can be mitigated via the use of deep learning-based supersampling of undersampled images acquired on a point-scanning system, which we term point-scanning super-resolution (PSSR) imaging. We designed a ‘crappifier’ that computationally degrades high SNR, high-pixel resolution ground truth images to simulate low SNR, low-resolution counterparts for training PSSR models that can restore real-world undersampled images. For high spatiotemporal resolution fluorescence time-lapse data, we developed a ‘multi-frame’ PSSR approach that uses information in adjacent frames to improve model predictions. PSSR facilitates point-scanning image acquisition with otherwise unattainable resolution, speed and sensitivity. All the training data, models and code for PSSR are publicly available at 3DEM.org.Point-scanning super-resolution imaging uses deep learning to supersample undersampled images and enable time-lapse imaging of subcellular events. An accompanying ‘crappifier’ rapidly generates quality training data for robust performance.

ObjectiveThe clinical presentation and course of Crohn's disease (CD) is highly variable. We sought to better understand the cellular and molecular mechanisms that guide this heterogeneity, and characterise the cellular processes associated with disease phenotypes.DesignWe examined both gene expression and gene regulation (chromatin accessibility) in non-inflamed colon tissue from a cohort of adult patients with CD and control patients. To support the generality of our findings, we analysed previously published expression data from a large cohort of treatment-naïve paediatric CD and control ileum.ResultsWe found that adult patients with CD clearly segregated into two classes based on colon tissue gene expression—one that largely resembled the normal colon and one where certain genes showed expression patterns normally specific to the ileum. These classes were supported by changes in gene regulatory profiles observed at the level of chromatin accessibility, reflective of a fundamental shift in underlying molecular phenotypes. Furthermore, gene expression from the ilea of a treatment-naïve cohort of paediatric patients with CD could be similarly subdivided into colon-like and ileum-like classes. Finally, expression patterns within these CD subclasses highlight large-scale differences in the immune response and aspects of cellular metabolism, and were associated with multiple clinical phenotypes describing disease behaviour, including rectal disease and need for colectomy.ConclusionsOur results strongly suggest that these molecular signatures define two clinically relevant forms of CD irrespective of tissue sampling location, patient age or treatment status.

Bacterial immunoglobulin A1 (IgA1) proteases may sabotage the protective effects of IgA. In vitro, both exogenous and endogenously produced IgA1 protease inhibited phagocytic killing of Streptococcus pneumoniae by capsule-specific IgA1 human monoclonal antibodies (hMAbs) but not IgA2. These IgA1 proteases cleaved and reduced binding of the the effector Fcα1 heavy chain but not the antigen-binding F(ab)/light chain to pneumococcal surfaces. In vivo, IgA1 protease-resistant IgA2, but not IgA1 protease-sensitive IgA1, supported 60% survival in mice infected with wild-type S. pneumoniae. IgA1 hMAbs protected mice against IgA1 protease-deficient but not -producing pneumococci. Parallel mouse sera with human IgA2 showed more efficient complement-mediated reductions in pneumococci with neutrophils than did IgA1, particularly with protease-producing organisms. After natural human pneumococcal bacteremia, purified serum IgG inhibited IgA1 protease activity in 7 of 11 patients (64%). These observations provide the first evidence in vivo that IgA1 protease can circumvent killing of S. pneumoniae by human IgA. Acquisition of IgA1 protease-neutralizing IgG after infection directs attention to IgA1 protease both as a determinant of successful colonization and infection and as a potential vaccine candidate.

Abstract Objectives Parents of children with medical complexity are often expected to implement complicated plans of care, such as enteral tube feeding, to support the health of their child. Enteral feeding can have psychosocial implications for the parent, child, and family. Blenderized tube feeding (BTF) refers to the administration of pureed food and drinks through a feeding tube. Little is known regarding parents’ experiences with BTF. Therefore, the purpose of this qualitative study was to understand the lived experience of BTF from the parent’s perspective. Methods This qualitative study was a grounded theory analysis utilizing semi-structured interviews of parents who provided at least 50% of their child’s diet through BTF. Participants were recruited using purposive sampling from the Complex Care Program at a tertiary care paediatric centre. Interviews were conducted until thematic saturation was achieved. Themes were identified using constant comparative analysis of transcribed interviews. Results Parents (n=10) felt that BTF positively affected the experience of tube feeding and enhanced their child’s health and wellbeing. Parents described BTF as a means of self-empowerment and a mechanism to normalize feeding and care for the entire family. Despite reporting BTF as more time consuming than formula feeding, all parents were satisfied with having made the change, and planned on continuing the diet. Conclusion BTFs can improve the experience of tube feeding and positively address some of the negative psychosocial implications of enteral tube feeding, providing a sense of normalcy and control for parents caring for a child with medical complexity. Graphical Abstract

Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is vital to addressing the regions rising burden of disease. Tissue from unselected Nigerian patients was analyzed with a multigene, next-generation sequencing assay. The rate of microsatellite instability is significantly higher among Nigerian CRC patients (28.1%) than patients from The Cancer Genome Atlas (TCGA, 14.2%) and Memorial Sloan Kettering Cancer Center (MSKCC, 8.5%, P  < 0.001). In microsatellite-stable cases, tumors from Nigerian patients are less likely to have APC mutations (39.1% vs. 76.0% MSKCC P  < 0.001) and WNT pathway alterations (47.8% vs. 81.9% MSKCC, P  < 0.001); whereas RAS pathway alteration is more prevalent (76.1% vs. 59.6%, P  = 0.03). Nigerian CRC patients are also younger and more likely to present with rectal disease (50.8% vs. 33.7% MSKCC, P  < 0.001). The findings suggest a unique biology of CRC in Nigeria, which emphasizes the need for regional data to guide diagnostic and treatment approaches for patients in West Africa. Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is important for early detection and treatment. Here, the authors use a multigene next-generation sequencing panel to identify genomic differences in Nigerian CRCs compared to those from TCGA and MSKCC cohorts.

Loss of lamina propria (LP) macrophage tolerance to the enteric microbiota is a central event in the pathogenesis of Crohn’s disease (CD). IL-10 drives homeostatic effects in the mucosal immune system. Mice and humans with a defective IL-10 pathway have severe CD driven in part by enteric microbial stimulation of macrophage signaling. We hypothesized that functional adaptations of LP macrophages to the enteric microbiota are attributed to modified regulatory activity at key gene loci, and defects in this transcriptional program lead to loss of microbial tolerance, resulting in CD.MethodsUsing FAIRE-seq (Formaldehyde-Assisted Isolation of Regulatory Elements), we catalogued accessible chromatin regions (regulatory elements) and gene expression (RNA-seq) in germ-free (GF) and enteric-microbiota-colonized (CNV) wild-type (WT) and colitis-prone (Il10-/-) murine LP macrophages genome-wide. To determine regulatory elements driving LP macrophage tolerance, FAIRE-seq and RNA-seq were performed on murine WT and Il10−/− bone marrow derived macrophages (BMMs) stimulated with lipopolysaccharide (LPS). Available ChIP-seq data from BMMs stimulated with LPS were incorporated into the genomic analysis to annotate regions of accessible chromatin and reveal specific transcription factor interactions. FAIRE-seq was performed in colon biopsy samples obtained from genotyped CD and control patients. Electrophoretic mobility shift assays (EMSA) were performed with human THP1 macrophage nuclear extract to characterize underlying allelic variation in CD-specific open chromatin.ResultsFAIRE-seq revealed 3 accessible chromatin states (“inducible,” “reducible,” or “IL10-blocked”) in BMMs based on LPS stimulation and underlying genotype (WT versus Il10−/−). We annotated post-translational modifications of histones associated with these chromatin states that are active, repressed, or poised for transcriptional activation, including H3K4me3, H3K4me1 and H3K27ac. IL10-blocked regions had aberrantly accessible chromatin in Il10−/− mice and represented putative LPS-responsive enhancers bound by PU.1, JunB, and NFkB. These data indicate that BMMs harbor a chromatin signature suggestive of the classical cytokine response. LP macrophages isolated from GF and CNV WT and Il10−/− mice also revealed these 3 accessible chromatin states. The IL10-blocked state was the predominant chromatin profile observed in LP macrophages. Unlike BMMs, accessible and LPS-responsive chromatin was observed at key phagocytic gene loci consistent with the known bactericidal capabilities of LP macrophages. Analysis of genome wide chromatin accessibility in WT LP macrophages, colitis-prone LP macrophages and BMMs revealed distinct regions of open chromatin. These accessible regions contained PU.1, JunB, Stat3, and NFkB binding sites. To translate findings to human CD, we performed FAIRE-seq on mucosal biopsies from the non-inflamed section of the colon in genotyped CD patients. We identified and characterized one key accessible region upstream of Il7r/IL7R that was functionally conserved in these specimens and overlapped a previously uncharacterized sequence variant (rs185659576). EMSA revealed an allele-specific preference in protein binding at this site of CD-specific open chromatin.ConclusionsWe demonstrate that different genomic loci exhibit distinct chromatin changes that play active roles in shaping the response in LP macrophages to the enteric microbiota. These chromatin features are dynamic and regulated by IL-10 and the enteric microbiota. These findings introduce the possibility of modulating chromatin regulators with small molecules for the treatment of CD.

Organized into six thematic rubrics, this book demonstrates that Yiddish, always a border-crossing language, continues to puch boundaries with vigorous disciplinary exchange.