Perception versus reality: A National Cohort Analysis of the surgery-first approach for resectable pancreatic cancer

INTRODUCTION: Although surgical resection is necessary, it is not sufficient for long-term survival in pancreatic ductal adenocarcinoma (PDAC). We sought to evaluate survival after up-front surgery (UFS) in anatomically resectable PDAC in the context of three critical factors: (A) margin status; (B) CA19-9; and (C) receipt of adjuvant chemotherapy. METHODS: The National Cancer Data Base (2010-2015) was reviewed for clinically resectable (stage 0/I/II) PDAC patients. Surgical margins, pre-operative CA19-9, and receipt of adjuvant chemotherapy were evaluated. Patient overall survival was stratified based on these factors and their respective combinations. Outcomes after UFS were compared to equivalently staged patients after neoadjuvant chemotherapy on an intention-to-treat (ITT) basis. RESULTS: Twelve thousand and eighty-nine patients were included (n = 9197 UFS, n = 2892 ITT neoadjuvant). In the UFS cohort, only 20.4% had all three factors (median OS = 31.2 months). Nearly 1/3rd (32.7%) of UFS patients had none or only one factor with concomitant worst survival (median OS = 14.7 months). Survival after UFS decreased with each failing factor (two factors: 23 months, one factor: 15.5 months, no factors: 7.9 months) and this persisted after adjustment. Overall survival was superior in the ITT-neoadjuvant cohort (27.9 vs. 22 months) to UFS. CONCLUSION: Despite the perceived benefit of UFS, only 1-in-5 UFS patients actually realize maximal survival when known factors highly associated with outcomes are assessed. Patients are proportionally more likely to do worst, rather than best after UFS treatment. Similarly staged patients undergoing ITT-neoadjuvant therapy achieve survival superior to the majority of UFS patients. Patients and providers should be aware of the false perception of \u27optimal\u27 survival benefit with UFS in anatomically resectable PDAC

Electrostatic Modifications of the Human Leukocyte Antigen-DR P9 Peptide-Binding Pocket and Susceptibility to Primary Sclerosing Cholangitis

The strongest genetic risk factors for primary sclerosing cholangitis (PSC) are found in the human leukocyte antigen (HLA) complex at chromosome 6p21. Genes in the HLA class II region encode molecules that present antigen to T lymphocytes. Polymorphisms in these genes are associated with most autoimmune diseases, most likely because they contribute to the specificity of immune responses. The aim of this study was to analyze the structure and electrostatic properties of the peptide-binding groove of HLA-DR in relation to PSC. Thus, four-digit resolution HLA-DRB1 genotyping was performed in 356 PSC patients and 366 healthy controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. In stepwise logistic regressions, variations at residues 37 and 86 were independently associated with PSC (P = 1.2 × 10−32 and P = 1.8 × 10−22 in single-residue models, respectively). Three-dimensional modeling was performed to explore the effect of these key residues on the HLA-DR molecule. This analysis indicated that residue 37 was a major determinant of the electrostatic properties of pocket P9 of the peptide-binding groove. Asparagine at residue 37, which was associated with PSC, induced a positive charge in pocket P9. Tyrosine, which protected against PSC, induced a negative charge in this pocket. Consistent with the statistical observations, variation at residue 86 also indirectly influenced the electrostatic properties of this pocket. DRB1*13:01, which was PSC-associated, had a positive P9 pocket and DRB1*13:02, protective against PSC, had a negative P9 pocket. Conclusion: The results suggest that in patients with PSC, residues 37 and 86 of the HLA-DRβ chain critically influence the electrostatic properties of pocket P9 and thereby the range of peptides presented. (Hepatology 2011;53:1967-1976

The Brain Tumor Segmentation (BraTS) Challenge 2023: Brain MR Image Synthesis for Tumor Segmentation (BraSyn)

Automated brain tumor segmentation methods have become well-established and reached performance levels offering clear clinical utility. These methods typically rely on four input magnetic resonance imaging (MRI) modalities: T1-weighted images with and without contrast enhancement, T2-weighted images, and FLAIR images. However, some sequences are often missing in clinical practice due to time constraints or image artifacts, such as patient motion. Consequently, the ability to substitute missing modalities and gain segmentation performance is highly desirable and necessary for the broader adoption of these algorithms in the clinical routine. In this work, we present the establishment of the Brain MR Image Synthesis Benchmark (BraSyn) in conjunction with the Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2023. The primary objective of this challenge is to evaluate image synthesis methods that can realistically generate missing MRI modalities when multiple available images are provided. The ultimate aim is to facilitate automated brain tumor segmentation pipelines. The image dataset used in the benchmark is diverse and multi-modal, created through collaboration with various hospitals and research institutions.Comment: Technical report of BraSy

Integrated Mapping of Neglected Tropical Diseases: Epidemiological Findings and Control Implications for Northern Bahr-el-Ghazal State, Southern Sudan

Integrated control of neglected tropical diseases (NTDs) is being scaled up in a number of developing countries, because it is thought to be more cost-effective than stand-alone control programmes. Under this approach, treatments for onchocerciasis, lymphatic filariasis (LF), schistosomiasis, soil-transmitted helminth (STH) infection, and trachoma are administered through the same delivery structure and at about the same time. A pre-requisite for implementation of integrated NTD control is information on where the targeted diseases are endemic and to what extent they overlap. This information is generated through surveys that can be labour-intensive and expensive. In Southern Sudan, all of the above diseases except onchocerciasis require further mapping before a comprehensive integrated NTD control programme can be implemented. To determine where treatment for which disease is required, integrated surveys were conducted for schistosomiasis, STH infection, LF, and loiasis, throughout one of ten states of the country. Our results show that treatment is only required for urinary schistosomiasis and STH in a few, yet separate, geographical area. This illustrates the importance of investing in disease mapping to minimize overall programme costs by being able to target interventions. Integration of survey methodologies for the above disease was practical and efficient, and minimized the effort required to collect these data

A Multicenter Evaluation of Diagnostic Tools to Define Endpoints for Programs to Eliminate Bancroftian Filariasis

Successful mass drug administration (MDA) campaigns have brought several countries near the point of Lymphatic Filariasis (LF) elimination. A diagnostic tool is needed to determine when the prevalence levels have decreased to a point that MDA campaigns can be discontinued without the threat of recrudescence. A six-country study was conducted assessing the performance of seven diagnostic tests, including tests for microfilariae (blood smear, PCR), parasite antigen (ICT, Og4C3) and antifilarial antibody (Bm14, PanLF, Urine SXP). One community survey and one school survey were performed in each country. A total of 8,513 people from the six countries participated in the study, 6,443 through community surveys and 2,070 through school surveys. Specimens from these participants were used to conduct 49,585 diagnostic tests. Each test was seen to have both positive and negative attributes, but overall, the ICT test was found to be 76% sensitive at detecting microfilaremia and 93% specific at identifying individuals negative for both microfilariae and antifilarial antibody; the Og4C3 test was 87% sensitive and 95% specific. We conclude, however, that the ICT should be the primary tool recommended for decision-making about stopping MDAs. As a point-of-care diagnostic, the ICT is relatively inexpensive, requires no laboratory equipment, has satisfactory sensitivity and specificity and can be processed in 10 minutes—qualities consistent with programmatic use. Og4C3 provides a satisfactory laboratory-based diagnostic alternative

Phenotypic Screen of Early-Developing Larvae of the Blood Fluke, Schistosoma mansoni, using RNA Interference

RNA interference (RNAi) represents the only method currently available for manipulating gene-specific expression in Schistosoma spp., although application of this technology as a functional genomic profiling tool has yet to be explored. In the present study 32 genes, including antioxidants, transcription factors, cell signaling molecules and metabolic enzymes, were selected to determine if gene knockdown by RNAi was associated with morphologically definable phenotypic changes in early intramolluscan larval development. Transcript selection was based on their high expression in in vitro cultured S. mansoni primary sporocysts and/or their potential involvement in developmental processes. Miracidia were allowed to transform to sporocysts in the presence of synthesized double-stranded RNAs (dsRNAs) and cultivated for 7 days, during which time developing larvae were closely observed for phenotypic changes including failure/delay in transformation, loss of motility, altered growth and death. Of the phenotypes evaluated, only one was consistently detected; namely a reduction in sporocyst size based on length measurements. The size-reducing phenotype was observed in 11 of the 33 (33%) dsRNA treatment groups, and of these 11 phenotype-associated genes (superoxide dismutase, Smad1, RHO2, Smad2, Cav2A, ring box, GST26, calcineurin B, Smad4, lactate dehydrogenase and EF1α), only 6 demonstrated a significant and consistent knockdown of specific transcript expression. Unexpectedly one phenotype-linked gene, superoxide dismutase (SOD), was highly induced (∼1600-fold) upon dsRNA exposure. Variation in dsRNA-mediated silencing effects also was evident in the group of sporocysts that lacked any definable phenotype. Out of 22 nonphenotype-expressing dsRNA treatments (myosin, PKCB, HEXBP, calcium channel, Sma2, RHO1, PKC receptor, DHHC, PepcK, calreticulin, calpain, Smeg, 14.3.3, K5, SPO1, SmZF1, fibrillarin, GST28, GPx, TPx1, TPx2 and TPx2/TPx1), 12 were assessed for the transcript levels. Of those, 6 genes exhibited consistent reductions in steady-state transcript levels, while expression level for the rest remained unchanged. Results demonstrate that the efficacy of dsRNA-treatment in producing consistent phenotypic changes and/or altered gene expression levels in S. mansoni sporocysts is highly dependent on the selected gene (or the specific dsRNA sequence used) and the timing of evaluation after treatment. Although RNAi holds great promise as a functional genomics tool for larval schistosomes, our finding of potential off-target or nonspecific effects of some dsRNA treatments and variable efficiencies in specific gene knockdown indicate a critical need for gene-specific testing and optimization as an essential part of experimental design, execution and data interpretation

Global Diversity of Sponges (Porifera)

With the completion of a single unified classification, the Systema Porifera (SP) and subsequent development of an online species database, the World Porifera Database (WPD), we are now equipped to provide a first comprehensive picture of the global biodiversity of the Porifera. An introductory overview of the four classes of the Porifera is followed by a description of the structure of our main source of data for this paper, the WPD. From this we extracted numbers of all ‘known’ sponges to date: the number of valid Recent sponges is established at 8,553, with the vast majority, 83%, belonging to the class Demospongiae. We also mapped for the first time the species richness of a comprehensive set of marine ecoregions of the world, data also extracted from the WPD. Perhaps not surprisingly, these distributions appear to show a strong bias towards collection and taxonomy efforts. Only when species richness is accumulated into large marine realms does a pattern emerge that is also recognized in many other marine animal groups: high numbers in tropical regions, lesser numbers in the colder parts of the world oceans. Preliminary similarity analysis of a matrix of species and marine ecoregions extracted from the WPD failed to yield a consistent hierarchical pattern of ecoregions into marine provinces. Global sponge diversity information is mostly generated in regional projects and resources: results obtained demonstrate that regional approaches to analytical biogeography are at present more likely to achieve insights into the biogeographic history of sponges than a global perspective, which appears currently too ambitious. We also review information on invasive sponges that might well have some influence on distribution patterns of the future

SNAPSHOT USA 2019 : a coordinated national camera trap survey of the United States

This article is protected by copyright. All rights reserved.With the accelerating pace of global change, it is imperative that we obtain rapid inventories of the status and distribution of wildlife for ecological inferences and conservation planning. To address this challenge, we launched the SNAPSHOT USA project, a collaborative survey of terrestrial wildlife populations using camera traps across the United States. For our first annual survey, we compiled data across all 50 states during a 14-week period (17 August - 24 November of 2019). We sampled wildlife at 1509 camera trap sites from 110 camera trap arrays covering 12 different ecoregions across four development zones. This effort resulted in 166,036 unique detections of 83 species of mammals and 17 species of birds. All images were processed through the Smithsonian's eMammal camera trap data repository and included an expert review phase to ensure taxonomic accuracy of data, resulting in each picture being reviewed at least twice. The results represent a timely and standardized camera trap survey of the USA. All of the 2019 survey data are made available herein. We are currently repeating surveys in fall 2020, opening up the opportunity to other institutions and cooperators to expand coverage of all the urban-wild gradients and ecophysiographic regions of the country. Future data will be available as the database is updated at eMammal.si.edu/snapshot-usa, as well as future data paper submissions. These data will be useful for local and macroecological research including the examination of community assembly, effects of environmental and anthropogenic landscape variables, effects of fragmentation and extinction debt dynamics, as well as species-specific population dynamics and conservation action plans. There are no copyright restrictions; please cite this paper when using the data for publication.Publisher PDFPeer reviewe