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Delayed diagnosis and treatment resistance result in high pancreatic ductal adenocarcinoma (PDAC) mortality rates. Identifying molecular subtypes can improve treatment, but current methods are costly and time-consuming. In this study, deep learning models were used to identify histologic features that classify PDAC molecular subtypes based on routine hematoxylin-eosin–stained histopathologic slides. A total of 97 histopathology slides associated with resectable PDAC from The Cancer Genome Atlas project were used to train a deep learning model and test the performance on 44 needle biopsy material (110 slides) from a local annotated patient cohort. The model achieved balanced accuracy of 96.19% and 83.03% in identifying the classical and basal subtypes of PDAC in The Cancer Genome Atlas and the local cohort, respectively. This study provides a promising method to cost-effectively and rapidly classify PDAC molecular subtypes based on routine hematoxylin-eosin–stained slides, potentially leading to more effective clinical management of this disease.

The document discusses two separate topics: tax implications for a specific agency and the tax treatment of overtime payments. In regards to the agency, there is ambiguity regarding whether VAT should be charged on the agency's supplies of accommodation. While the agency argues that they are acting as an agent on behalf of the property owner and therefore should not charge VAT, it is common practice in the industry to include VAT in accommodation charges. As for overtime payments, they are considered taxable income and subject to employees' tax. Employees may choose to receive time off in lieu of overtime payment, but this does not give rise to any taxable benefit. Employers can implement policies to regulate the granting of time off in lieu of payment. [Extracted from the article]

This article provides information on filling in manual information for tax returns. It covers topics such as negotiating discounts for residential complexes, evaluating home security systems, reviewing security contracts, building a strong relationship with security providers, and checking customer support. It also discusses capturing information manually for changes in personal details, business income, rental income, capital gains and losses, and claims against a travel allowance. The article emphasizes the importance of accurately capturing this information to ensure a smooth tax filing process. The text discusses the importance of keeping all supporting documents related to financial matters, such as registration papers and finance agreements. It also mentions that in some cases, the South African Revenue Service (SARS) may request copies of employment agreements to justify the granting of a travel allowance. The text then shifts to retirement planning, noting that female life expectancy in South Africa is almost 70 years and that women in higher income brackets may live even longer. It also highlights the higher prevalence of certain medical conditions in men as they age, raising the question of whether women need to be more concerned about medical costs during retirement. The text briefly mentions the government's planned National Health Insurance but notes that it may take years to implement. [Extracted from the article]

The article focuses on the importance of manually updating personal details on tax returns despite SARS providing pre-populated forms. Topics include the necessity of reporting changes in marital status, the manual update requirements for address and contact details, and the implications of business losses on tax returns.

The article provides guidance for taxpayers on handling tax certificates and submissions during the 2024 Filing Season, stressing the importance of obtaining accurate IRP5 certificates, verifying tax certificate uploads, and requesting detailed tax information from financial institutions. It also discusses the need to ensure correct reporting of investment income, medical scheme membership details.

The article discusses the challenges faced by taxpayers in the 2024 Filing Season due to delays in obtaining IRP5 certificates, resulting in penalties from SARS for late submissions. It also emphasizes the importance of promptly requesting these certificates, especially for lump sum payments like retirement payouts, to avoid complications with tax returns.

The article focuses on preparing for the 2024 Filing Season for personal taxpayers, particularly those with car allowances, highlighting the choice between using 'deemed values' or 'actual costs' when claiming business travel expenses. It explains that while many taxpayers have traditionally opted for 'deemed costs' due to its ease with eFiling.

The concept of intellectual need, which proposes that learning is the result of students wrestling with a problem that is unsolvable by their current knowledge, has been used in instructional design for many years. However, prior research has not described a way to empirically determine whether, and to what extent, students experience intellectual need. In this paper, we present a methodology for identifying students’ intellectual need and report the results of a study that investigated students’ reactions to intellectual need-provoking tasks in first-semester calculus classes. We also explore the relationship between intellectual need, affective need, and students’ learning. Although the overall percentage of students who reported experiencing an intellectual need was low, we found positive associations between intellectual need and learning.

The article focuses on the stagnant tax tables for the 2024/25 fiscal year and the concept of fiscal drag, which leads to increased tax revenue despite no changes in tax rates. Topics discussed include the implications for individual taxpayers, the disproportionate burden on high-income earners, and the broader economic concerns for South Africa.

The article focuses on the importance of having proper policies and procedures in place when relocating employees, including considerations for tax implications for both employers and employees. Topics discussed include the deductibility of relocation costs for employers, tax implications for employees receiving relocation benefits, and strategies for enforcing claw-back provisions in case of employee resignation shortly after relocation.

It has previously been shown that strong flow transients, reaching mm/s flow speeds, are induced when microscopic vapor bubbles nucleate on spatially isolated laser-heated plasmonic nanoantennas supported on a substrate. However, the flow pattern is cylindrically symmetric and always directed toward the nanoantenna at the substrate plane. This limits its applicability in, for example, particle manipulation schemes. Here, we show that the flow direction can be locally reversed by breaking the photothermal symmetry using two nearby nanoantennas that differ either in size or polarization response. The in-plane flow transient is strong enough to push microparticles tens of microns across a surface. Directional flow control may provide the means for rapid and precise mass transport near surfaces for applications in microfluidics, bionanotechnology, and particle sorting.

The article discusses the restrictions on who qualifies for VAT registration on the payments basis and the hardships this causes for small businesses. It explains that VAT registration is required for businesses with an annual turnover exceeding R1 million, and VAT is paid to SARS every two months. The article argues that small businesses that do not qualify for VAT registration on the payments basis face cash flow issues when customers take a long time to pay their accounts. The article suggests that allowing small businesses with a turnover below a specific threshold to register for VAT on the payments basis would alleviate this cash flow squeeze. However, this would require an amendment to the VAT Act. [Extracted from the article]

The document titled "Tax Breaks" discusses various aspects of income tax and capital gains tax (CGT) in South Africa. It explains the implications of withdrawing funds from a retirement annuity, emphasizing the importance of financial planning and avoiding unnecessary tax payments. The document also highlights the specific criteria that small business owners must meet to qualify for CGT exemptions when selling their businesses. Additionally, it mentions that certain retirement benefits, such as retirement annuities and pension funds, are excluded from CGT. The document concludes by mentioning that interest on overdue VAT refunds can be claimed by South African businesses, and it provides information on taxpayers' rights and legal avenues for holding the South African Revenue Service (SARS) accountable. [Extracted from the article]

This document discusses the tax implications of relocation expenses for both employees and employers in South Africa. It explains that foreigners who are physically present in South Africa for a certain period of time may be considered residents for tax purposes. Foreigners are subject to normal tax on income received from a source within South Africa and may be entitled to the same deductions and rebates as residents. The document also mentions that employers may offer to cover certain costs related to employee relocation, and these expenses may be deductible for the employer. However, any payments made to employees that are considered excessive may not be deductible. [Extracted from the article]

This article discusses the tax obligations of foreigners working in South Africa who do not have permanent residence status. It explains that foreigners who earn income from a source within South Africa are subject to normal tax in the country. The article also outlines the tests used to determine whether a foreigner is considered a resident for tax purposes. It emphasizes the importance for employers to ensure that foreign employees have the appropriate work permits and comply with immigration laws. The article concludes by mentioning that the tax position of a foreign employee may be affected by double taxation agreements between South Africa and their home country. [Extracted from the article]

The article discusses the VAT implications for short-term lettings and commissions in the context of acting as an agent or principal. The court ruling emphasizes the importance of actual business operations and economic substance in determining eligibility for tax breaks. The article also addresses the question of whether VAT should be charged on accommodation charges and commissions, providing guidance based on prevailing industry practice. Additionally, the article briefly mentions the tax treatment of overtime payments and the relevant labor legislation. [Extracted from the article]

The article focuses on addressing retirement concerns for individuals approaching their 50s, acknowledging the regret of missed financial opportunities in youth. It suggests low-risk strategies to bolster pension savings at this stage, such as deferring leave payouts, to provide a welcome boost to retirement funds as individuals near the end of their working lives.

The article discusses tax planning opportunities for spouses, focusing on the implications of inter-spouse donations regarding Capital Gains Tax (CGT). Topics include the strategic transfer of assets between spouses to optimize tax liabilities, the application of Paragraph 67 of the Eighth Schedule to the Income Tax Act for CGT rollover provisions in asset transfers, and considerations related to anti-avoidance measures when transferring assets between spouses for tax purposes.

High-throughput total nucleic acid (TNA) purification methods based on solid-phase reversible immobilization (SPRI) beads produce TNA suitable for both genomic and transcriptomic applications. Even so, small RNA species, including miRNA, bind weakly to SPRI beads under standard TNA purification conditions, necessitating a separate workflow using column-based methods that are difficult to automate. Here, an SPRI-based high-throughput TNA purification protocol that recovers DNA, RNA and small RNA, called GSC-modified RLT+ Aline bead-based protocol (GRAB-ALL), which incorporates modifications to enhance small RNA recovery is presented. GRAB-ALL was benchmarked against existing nucleic acid purification workflows and GRAB-ALL efficiently purifies TNA, including small RNA, for next-generation sequencing applications in a plate-based format suitable for automated high-throughput sample preparation.

We theorize that anticipatory thinking (AT) uses the same computational infrastructure as general cognition as described in the Common Model of Cognition. We extend the Common Model with results from research on event cognition. Using these building blocks, we present a five‐step process model of AT as realized in cognitive architecture components. We then revisit simplifying assumptions underlying our model and expand our theory in response. Finally, we make predictions that are entailed by our account of AT, focusing on how computational limits in both natural and artificial cognitive systems can impact support for AT.

Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. The DACH1gene encodes a winged helix/Forkhead DNA-binding protein that competes for binding to FOXM1 sites. Herein, DACH1gene deletion within the 13q21.31-q21.33 region occurs in up to 18% of human PCa and was associated with increased AR activity and poor prognosis. In prostate OncoMice, prostate-specific deletion of the Dach1gene enhanced prostatic intraepithelial neoplasia (PIN), and was associated with increased TGFβ activity and DNA damage. Reduced Dach1increased DNA damage in response to genotoxic stresses. DACH1was recruited to sites of DNA damage, augmenting recruitment of Ku70/Ku80. Reduced Dach1expression was associated with increased homology directed repair and resistance to PARP inhibitors and TGFβ kinase inhibitors. Reduced Dach1expression may define a subclass of PCa that warrants specific therapies.

In this essay, I describe a Human Rights course in which I focused on refugee rights through a service-learning project with a refugee resettlement agency, which I will refer to [...]

Germline structural variants (SVs) are challenging to resolve by conventional genetic testing assays. Long-read sequencing has improved the global characterization of SVs, but its sensitivity at cancer susceptibility loci has not been reported. Nanopore long-read genome sequencing was performed for nineteen individuals with pathogenic copy number alterations in BRCA1, BRCA2, CHEK2and PALB2identified by prior clinical testing. Fourteen variants, which spanned single exons to whole genes and included a tandem duplication, were accurately represented. Defining the precise breakpoints of SVs in BRCA1and CHEK2revealed unforeseen allelic heterogeneity and informed the mechanisms underlying the formation of recurrent deletions. Integrating read-based and statistical phasing further helped define extended haplotypes associated with founder alleles. Long-read sequencing is a sensitive method for characterizing private, recurrent and founder SVs underlying breast cancer susceptibility. Our findings demonstrate the potential for nanopore sequencing as a powerful genetic testing assay in the hereditary cancer setting.

There are few prognostic biomarkers and targeted therapeutics currently in use for the clinical management of oral squamous cell carcinoma (OSCC) and patient outcomes remain poor in this disease. A majority of mutations in OSCC are loss-of-function events in tumour suppressor genes that are refractory to conventional modes of targeting. Interestingly, the chromosomal segment 3q22-3q29 is amplified in many epithelial cancers, including OSCC. We hypothesized that some of the 468 genes located on 3q22-3q29 might be drivers of oral carcinogenesis and could be exploited as potential prognostic biomarkers and therapeutic targets. Our integrative analysis of copy number variation (CNV), gene expression and clinical data from The Cancer Genome Atlas (TCGA), identified two candidate genes: NCBP2, TFRC, whose expression positively correlates with worse overall survival (OS) in HPV-negative OSCC patients. Expression of NCBP2and TFRCis significantly higher in tumour cells compared to most normal human tissues. High NCBP2 and TFRC protein abundance is associated with worse overall, disease-specific survival, and progression-free interval in an in-house cohort of HPV-negative OSCC patients. Finally, due to a lack of evidence for the role of NCBP2 in carcinogenesis, we tested if modulating NCBP2 levels in human OSCC cell lines affected their carcinogenic behaviour. We found that NCBP2 depletion reduced OSCC cell proliferation, migration, and invasion. Differential expression analysis revealed the upregulation of several tumour-promoting genes in patients with high NCBP2expression. We thus propose both NCBP2 and TFRC as novel prognostic and potentially therapeutic biomarkers for HPV-negative OSCC.

The article focuses on tax breaks related to wear and tear allowances for businesses. It mentions that general deductions for capital assets are not allowed, specific provisions in the Income Tax Act allow for deductions based on wear and tear or depreciation of qualifying capital assets. It mentions that the South African Revenue Service (SARS) provides guidelines and rates for wear and tear allowances.

Recent research on integration has shown the importance of quantities-based meanings for integrals. However, this research body is still in need of detailed empirical accounts of howstudents develop such understandings across an entire unit on integration. This paper contributes by providing one such account, based on a quantities-based orientation called adding up pieces(AUP). Our study examines how three separate pairs of students learned definite integrals and integral functions within interview settings over four consecutive interview-lessons, meant to correspond to four consecutive in-class sessions. The first interview developed the partition, target quantity, and sum structure for definite integral, which were solidified in the second interview. The third and fourth interviews extended this AUP structure to a variable upper bound, output, and function structure for integral functions in preparation for the Fundamental Theorem of Calculus (FTC).

Calculus education research on integration is coalescing around the theme that teaching integration based on quantitative reasoning is crucial for robust understanding of and usage of integrals. This paper contributes to this International Journal for Research in Undergraduate Education special issue on the teaching and learning of definite integrals by reviewing the research literature on quantitatively-based approaches to integration, in order to pull together the ideas that are spread across many papers in many outlets. We note that the literature in this area has largely developed along two distinct paradigms, which we call adding up piecesand accumulation from rate. While they are both based in quantitative reasoning, there are critical differences between them that have important ramifications for teaching and learning integration. We use these two paradigms to organize our review and we use the literature to discuss the meanings, formalizations, foci, reasoning, and modeling in these approaches.