T cells in testicular germ cell tumors: new evidence of fundamental contributions by rare subsets.

BACKGROUND: Immune cell infiltration is heterogeneous but common in testicular germ cell tumors (TGCT) and pre-invasive germ cell neoplasia in situ (GCNIS). Tumor-infiltrating T cells including regulatory T (Treg) and follicular helper T (Tfh) cells are found in other cancer entities, but their contributions to TGCT are unknown. METHODS: Human testis specimens from independent patient cohorts were analyzed using immunohistochemistry, flow cytometry and single-cell RNA sequencing (scRNA-seq) with special emphasis on delineating T cell subtypes. RESULTS: Profound changes in immune cell composition within TGCT, shifting from macrophages in normal testes to T cells plus B and dendritic cells in TGCT, were documented. In most samples (96%), the CD4+ T cell frequency exceeded that of CD8+ cells, with decreasing numbers from central to peripheral tumor areas, and to tumor-free, contralateral testes. T cells including Treg and Tfh were most abundant in seminoma compared to mixed tumors and embryonal carcinoma. CONCLUSION: Despite considerable heterogeneity between patients, T cell subtypes form a key part of the TGCT microenvironment. The novel finding of rare Treg and Tfh cells in human testis suggests their involvement in TGCT pathobiology, with implications for understanding tumor progression, to assess patients' prognosis, and as putative targets for personalized immunotherapy.

Differential Fairness: An Intersectional Framework for Fair AI.

We propose definitions of fairness in machine learning and artificial intelligence systems that are informed by the framework of intersectionality, a critical lens from the legal, social science, and humanities literature which analyzes how interlocking systems of power and oppression affect individuals along overlapping dimensions including gender, race, sexual orientation, class, and disability. We show that our criteria behave sensibly for any subset of the set of protected attributes, and we prove economic, privacy, and generalization guarantees. Our theoretical results show that our criteria meaningfully operationalize AI fairness in terms of real-world harms, making the measurements interpretable in a manner analogous to differential privacy. We provide a simple learning algorithm using deterministic gradient methods, which respects our intersectional fairness criteria. The measurement of fairness becomes statistically challenging in the minibatch setting due to data sparsity, which increases rapidly in the number of protected attributes and in the values per protected attribute. To address this, we further develop a practical learning algorithm using stochastic gradient methods which incorporates stochastic estimation of the intersectional fairness criteria on minibatches to scale up to big data. Case studies on census data, the COMPAS criminal recidivism dataset, the HHP hospitalization data, and a loan application dataset from HMDA demonstrate the utility of our methods.

Long Non-Coding RNAs in Kidney Disease.

Non-coding RNA species contribute more than 90% of all transcripts and have gained increasing attention in the last decade. One of the most recent members of this group are long non-coding RNAs (lncRNAs) which are characterized by a length of more than 200 nucleotides and a lack of coding potential. However, in contrast to this simple definition, lncRNAs are heterogenous regarding their molecular function-including the modulation of small RNA and protein function, guidance of epigenetic modifications and a role as enhancer RNAs. Furthermore, they show a highly tissue-specific expression pattern. These aspects already point towards an important role in cellular biology and imply lncRNAs as players in development, health and disease. This view has been confirmed by numerous publications from different fields in the last years and has raised the question as to whether lncRNAs may be future therapeutic targets in human disease. Here, we provide a concise overview of the current knowledge on lncRNAs in both glomerular and tubulointerstitial kidney disease.

A Brief Overview of lncRNAs in Endothelial Dysfunction-Associated Diseases: From Discovery to Characterization.

Long non-coding RNAs (lncRNAs) are a novel class of regulatory RNA molecules and they are involved in many biological processes and disease developments. Several unique features of lncRNAs have been identified, such as tissue-and/or cell-specific expression pattern, which suggest that they could be potential candidates for therapeutic and diagnostic applications. More recently, the scope of lncRNA studies has been extended to endothelial biology research. Many of lncRNAs were found to be critically involved in the regulation of endothelial function and its associated disease progression. An improved understanding of endothelial biology can thus facilitate the discovery of novel biomarkers and therapeutic targets for endothelial dysfunction-associated diseases, such as abnormal angiogenesis, hypertension, diabetes, and atherosclerosis. Nevertheless, the underlying mechanism of lncRNA remains undefined in previous published studies. Therefore, in this review, we aimed to discuss the current methodologies for discovering and investigating the functions of lncRNAs and, in particular, to address the functions of selected lncRNAs in endothelial dysfunction-associated diseases.

An empirical study of construction and demolition waste generation and implication of recycling.

Associated with the continuing increase of construction activities such as infrastructure projects, commercial buildings and housing programs, Bangladesh has been experiencing a rapid increase of construction and demolition (C&D) waste. Till now, the generation rate of C&D waste has not been well understood or not explicitly documented in Bangladesh. This study aims to provide an approach to estimate C&D waste generation using waste generation rates (WGR) through regression analysis. Furthermore, analyses the economic benefit of recycling C&D waste. The results revealed that WGR 63.74 kg/m2 and 1615 kg/m2 for construction and demolition activities respectively. Approximately, in financial year (FY) 2016, 1.28 million tons (0.149 construction and 1.139 demolition) waste were generated in Dhaka city, of which the three largest proportions were concrete (60%), brick/block (21%) and mortar (9%). After collection they were dumped in either landfills or unauthorized places. Therefore, it can be summarized as: waste is a resource in wrong place. The results of this study indicate that rapid urbanization of Dhaka city would likely experience the peak in the generation of C&D waste. This paper thus designates that C&D waste recycling is an entrepreneurial activity worth venturing into and an opportunity for extracting economic and environmental benefits from waste. The research findings also show that recycling of concrete and brick waste can add economic value of around 44.96 million USD. In addition, recycling of C&D waste leads to important reductions in CO2 emissions, energy use, natural resources and illegal landfills. Therefore, the findings of WGR and economic values provide valuable quantitative information for the future C&D waste management exercises of various stakeholders such as government, industry and academy.

Long non-coding RNAs in hematological malignancies: translating basic techniques into diagnostic and therapeutic strategies.

Recent studies have revealed that non-coding regions comprise the vast majority of the human genome and long non-coding RNAs (lncRNAs) are a diverse class of non-coding RNAs that has been implicated in a variety of biological processes. Abnormal expression of lncRNAs has also been linked to different human diseases including cancers, yet the regulatory mechanisms and functional effects of lncRNAs are still ambiguous, and the molecular details also need to be confirmed. Unlike protein-coding gene, it is much more challenging to unravel the roles of lncRNAs owing to their unique and complex features such as functional diversity and low conservation among species, which greatly hamper their experimental characterization. In this review, we summarize and discuss both conventional and advanced approaches for the identification and functional characterization of lncRNAs related to hematological malignancies. In particular, the utility and advancement of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system as gene-editing tools are envisioned to facilitate the molecular dissection of lncRNAs via different knock-in/out strategies. Besides experimental considerations specific to lncRNAs, the roles of lncRNAs in the pathogenesis and progression of leukemia are also highlighted in the review. We expect that these insights may ultimately lead to clinical applications including development of biomarkers and novel therapeutic approaches targeting lncRNAs.