Test fairness is critical to the validity of group comparisons involving gender, ethnicities, culture, or treatment conditions. Detection of differential item functioning (DIF) is one component of ...efforts to ensure test fairness. The current study compared four treatments for items that have been identified as showing DIF: deleting, ignoring, multiple-group modeling, and modeling DIF as a secondary dimension. Results of this study provide indications about which approach could be applied for items showing DIF for a wide range of testing environments requiring reliable treatment.
Esophageal cancer: emerging therapeutics Rogers, Jane E; Sewastjanow-Silva, Matheus; Waters, Rebecca E ...
Expert opinion on therapeutic targets,
02/2022, Letnik:
26, Številka:
2
Journal Article
Recenzirano
Esophageal cancer (EC) is a worldwide healthcare concern and represents an aggressive malignancy. Squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) are the two primary histological subtypes but ...have yet to vastly differ in management. Outcomes remain poor with current treatment approaches; however, recent progress is focused on distinguishing separate targets based on thistology.
Here we provide an overview of EC management via a historical review and recent discoveries. As noted in this review, targeted therapy has lagged behind other solid tumors. Over the previous decade, for EACs there were only two targeted therapies used in the advanced setting with limited benefits. ESCC progress was rather non-existent. We present current ongoing advancements that have occurred in the realm of immunotherapy and emerging new agents.
It is becoming clearer that segregating these two histological subtypes in trials should be the goal of future trial designs. ESCC appears to be more amenable to immune modulation than EAC; however, we are navigating in exciting times as molecular interrogations of EC has expanded with the hope of making more rapid progress. There is still hard work ahead of us to painfully define subsets representing heterogeneity and then finding appropriate agents.
Gastric adenocarcinoma (GAC) continues to be a prevalent worldwide malignancy and a leading cause of cancer death, and it is frequently cited as incurable. Targeted therapy in GAC has lagged behind ...other solid tumors. The human epidermal growth factor receptor-2 (HER-2) represented the single target in GACs for many years, seen in approximately 20% of patients with advanced GAC. Recent advances in management now include the addition of immunotherapy checkpoint inhibition to select front-line advanced GACs. Unfortunately, outcomes remain poor for most patients. We anticipate finding a key to future discoveries in GACs in next-generation sequencing and more targeted approaches. Claudin 18.2 (CLDN18.2) has emerged as a therapeutic target in GACs. CLDN18.2 is reportedly expressed in 14-87% of GACs, and CLDN18.2 is available for monoclonal antibody (mAb) binding as it is expressed on the outer cell membrane. Here, we review the exploration of CLDN18.2 as a target in GACs via the use of zolbetuximab (IMAB362). Zolbetuximab is now under priority FDA review for GACs, and we eagerly await the review outcome.
Summary
Until recently, achieving a reference‐quality genome sequence for bread wheat was long thought beyond the limits of genome sequencing and assembly technology, primarily due to the large ...genome size and > 80% repetitive sequence content. The release of the chromosome scale 14.5‐Gb IWGSC RefSeq v1.0 genome sequence of bread wheat cv. Chinese Spring (CS) was, therefore, a milestone. Here, we used a direct label and stain (DLS) optical map of the CS genome together with a prior nick, label, repair and stain (NLRS) optical map, and sequence contigs assembled with Pacific Biosciences long reads, to refine the v1.0 assembly. Inconsistencies between the sequence and maps were reconciled and gaps were closed. Gap filling and anchoring of 279 unplaced scaffolds increased the total length of pseudomolecules by 168 Mb (excluding Ns). Positions and orientations were corrected for 233 and 354 scaffolds, respectively, representing 10% of the genome sequence. The accuracy of the remaining 90% of the assembly was validated. As a result of the increased contiguity, the numbers of transposable elements (TEs) and intact TEs have increased in IWGSC RefSeq v2.1 compared with v1.0. In total, 98% of the gene models identified in v1.0 were mapped onto this new assembly through development of a dedicated approach implemented in the MAGAAT pipeline. The numbers of high‐confidence genes on pseudomolecules have increased from 105 319 to 105 534. The reconciled assembly enhances the utility of the sequence for genetic mapping, comparative genomics, gene annotation and isolation, and more general studies on the biology of wheat.
Significance Statement
This new release of bread wheat cv. Chinese Spring reference genome sequence, IWGSC RefSeq v2.1, features correction of assembly errors affecting approximately 10% of the prior IWGSC RefSeq v1.0 release using genome‐wide optical maps and filling of gaps with single‐molecule long‐reads as well as incorporating re‐annotation of TEs and re‐computation of gene coordinates. These refinements enhance the sequence utility for breeding and research applications.
Cancer diagnosed during pregnancy has increased because of delayed child‐bearing and the known occurrence of age‐dependent malignancies. Cases of colorectal cancer (CRC) in pregnancy have recently ...been reported. With the expected rise in CRC diagnosed in young adults coupled with the current trend of delayed child‐bearing, CRC during pregnancy is likely to increase. Treating pregnant women with CRC by using antineoplastics presents a dilemma because there are many unknowns to guide treatment decisions. We review the issues regarding the use of 10 CRC‐approved agents in pregnancy.
Implications for Practice:
Colorectal cancer (CRC) in pregnancy is likely to become more common because of the current population trend in delayed child‐bearing and the increase in CRC incidence expected among young adults. Practitioners should become familiar with the challenges associated with systemic treatment of a pregnant patient with CRC. This review addresses concerns surrounding the 10 systemic agents approved for CRC to help provide treatment guidance when such a case arises.
摘要
在妊娠期间诊断为癌症的病例越来越多, 这是由于生育年龄推迟以及已知年龄依赖的恶性肿瘤的发生。近期有研究报告了妊娠期结直肠癌 (CRC) 病例。鉴于预期CRC诊断在较年轻的成年人中出现升高, 加之当前生育推迟的趋势, 妊娠期间CRC很可能会增加。对患有CRC的妊娠女性使用抗肿瘤治疗是一个两难问题, 因为在治疗决策指导中存在太多未知因素。我们对10种获批可用于妊娠期治疗的抗CRC药物的相关问题进行了回顾。The Oncologist 2016;21:563–570
对临床实践的提示: 由于目前人群的生育年龄有推迟趋势, 并且预期较年轻成年人中的结直肠癌 (CRC) 发生率会增加, 因此妊娠期间 CRC 很可能变得更为常见。临床医生应熟悉这一问题及妊娠期 CRC 患者系统治疗的相关挑战。本综述介绍了 10 种获批的 CRC 系统性治疗药物的相关问题, 可能有助于此类病例出现时的治疗指导。
Although infrequent, cases of colorectal cancer (CRC) during pregnancy have been reported in the last decade. With the trend in delayed child‐bearing, CRC during pregnancy will likely rise in incidence. This review focuses on CRC antineoplastics and the challenges that are present when their use is considered during pregnancy.
Unresectable metastatic colorectal cancer (mCRC) has a poor prognosis. Emerging treatment paradigms have improved outcomes in selected unresectable mCRC cases. Recent therapeutic advancements are due ...in part to a shift in trial designs. By examining CRC as a heterogeneous group of various tumor subtypes, researchers have identified molecular distinctions that have led to promising targets.
Nineteen antineoplastic agents are included in the National Comprehensive Cancer Network guidelines for the palliative management of mCRC. However, not all patients will be candidates for each agent. New therapies for rare mCRC subtypes have emerged. Herein, the authors review these rare mCRC subtypes: microsatellite instability-high/deficient mismatch repair, BRAFV600E-mutant, and human epidermal growth factor receptor 2-positive tumors. Additionally, they provide an overview of unresectable mCRC management and future directions.
Treatment in the majority of mCRC patients (RAS wild-type or RAS-mutant, microsatellite instability-stable or -low/mismatch repair-proficient, BRAFV600E wild-type, or HER2-negative) needs further advancement and remains an unmet need. The authors believe that the key to identifying more breakthroughs in these mCRC patients is to continue to differentiate their tumors molecularly and clinically.
In the dairy region of northern Victoria, Australia, the performance of temperate perennial dairy pastures is often poor over summer due to a combination of high temperatures and limited water ...availability that can restrict dry matter production and plant survival. This review summarizes published and unpublished research on perennial ryegrass, mostly undertaken in the northern Victoria region over the past decade, to help determine its future role in this environment. It includes information from a series of field experiments or case studies where the effects of heat and restricted irrigation on the growth and nutritive characteristics of perennial ryegrass were examined. This research involved investigations on whether plant survival under the stressed experimental conditions could be influenced by plant genotype, irrigation, and grazing management strategies, as well as by the presence of endophyte. In conclusion, it was difficult to identify any irrigation, grazing management or plant genotype effect that consistently improved the performance of perennial ryegrass in the hot, dry summers of northern Victoria, Australia. The incidences of extreme heat events and low water availability in this region are increasing, and the role of C3 perennial grasses as major suppliers of feed for dairy cows is diminishing. A major focus for the dairy industry in this region is now to identify new farming systems and alternative species that may be better adapted to the climate environment than perennial ryegrass, as well as be capable of adapting to year‐to‐year variations in irrigation water supply.
An ordered draft sequence of the 17-gigabase hexaploid bread wheat (Triticum aestivum) genome has been produced by sequencing isolated chromosome arms. We have annotated 124,201 gene loci distributed ...nearly evenly across the homeologous chromosomes and subgenomes. Comparative gene analysis of wheat subgenomes and extant diploid and tetraploid wheat relatives showed that high sequence similarity and structural conservation are retained, with limited gene loss, after polyploidization. However, across the genomes there was evidence of dynamic gene gain, loss, and duplication since the divergence of the wheat lineages. A high degree of transcriptional autonomy and no global dominance was found for the subgenomes. These insights into the genome biology of a polyploid crop provide a springboard for faster gene isolation, rapid genetic marker development, and precise breeding to meet the needs of increasing food demand worldwide.
•Delayed severe toxicities can occur after fluoropyrimidine exposure in patients with heterozygous DPYD mutation genotypes, especially with DPD c.557A>G (p.Y186C) variant in patients of African ...descent and female sex.•Uridine triacetate treatment should not be limited to patients with early-onset fluoropyrimidine toxicities or homozygous DPYD mutations.
The Wheat@URGI portal has been developed to provide the international community of researchers and breeders with access to the bread wheat reference genome sequence produced by the International ...Wheat Genome Sequencing Consortium. Genome browsers, BLAST, and InterMine tools have been established for in-depth exploration of the genome sequence together with additional linked datasets including physical maps, sequence variations, gene expression, and genetic and phenomic data from other international collaborative projects already stored in the GnpIS information system. The portal provides enhanced search and browser features that will facilitate the deployment of the latest genomics resources in wheat improvement.
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