Whole genome sequencing of viruses directly from clinical samples is integral for understanding the genetics of host-virus interactions. Here, we report the use of sample sparing target enrichment ...(by hybridisation) for viral nucleic acid separation and deep-sequencing of herpesvirus genomes directly from a range of clinical samples including saliva, blood, virus vesicles, cerebrospinal fluid, and tumour cell lines. We demonstrate the effectiveness of the method by deep-sequencing 13 highly cell-associated human herpesvirus genomes and generating full length genome alignments at high read depth. Moreover, we show the specificity of the method enables the study of viral population structures and their diversity within a range of clinical samples types.
Appropriate assessment is essential for the management of chemotherapy-induced peripheral neuropathy (CIPN), an intractable symptom that cannot yet be palliated, which is high on the list of causes ...of distress for cancer patients. However, objective assessment by medical staff makes it easy to underestimate the symptoms and effects of CIPN in cancer survivors. As a result, divergence from subjective evaluation of cancer survivors is a significant problem. Therefore, there is an urgent need to develop a subjective scale with high accuracy and applicability that reflects the experiences of cancer patients. We developed a comprehensive assessment scale for CIPN in cancer survivors, named the Comprehensive Assessment Scale for Chemotherapy-Induced Peripheral Neuropathy in Survivors of Cancer (CAS-CIPN), and demonstrated its reliability and validity.
We developed a questionnaire based on qualitative studies of peripheral neuropathy in Japanese cancer patients and literature review. Twelve cancer experts confirmed the content validity of the questionnaire. A draft version comprising 40 items was finalized by a pilot test on 100 subjects. The participants in the present study were 327 Japanese cancer survivors. Construct validity was determined by factor analysis, and internal validity by confirmation factor analysis and Cronbach's α.
Factor analysis showed that the structure consisted of 15 items in four dimensions: "Threatened interference in daily life by negative feelings", "Impaired hand fine motor skills", "Confidence in choice of treatment/management," and "Dysesthesia of the palms and soles." The CAS-CIPN internal consistency reliability was 0.826, and the reliability coefficient calculated using the Spearman-Brown formula q = 2r/(1 + r) was 0.713, confirming high internal consistency and stability. Scores on this scale were strongly correlated with Gynecologic Oncology Group-Neurotoxicity scores (r = 0.714, p < 0.01), confirming its criterion-related validity.
The CAS-CIPN is an assessment tool with high reliability and validity for the comprehensive evaluation of CIPN in cancer survivors. The CAS-CIPN is simple to use, and can be used by medical professionals for appropriate situational assessment and intervention.
Chitinase 3-like 1 (CHI3L1), one of the mammalian members of the chitinase family, is expressed in several types of human cancer, and elevated serum level of CHI3L1 is suggested to be a biomarker of ...poor prognosis in advanced cancer patients. However, the overall biological function of CHI3L1 in human cancers still remains unknown. Studies were performed to characterize the role of CHI3L1 in cancer pathophysiology utilizing human colorectal cancer samples and human cell lines. Plasma protein and tissue mRNA expression levels of CHI3L1 in colorectal cancer were strongly upregulated. Immunohistochemical analysis showed that CHI3L1 was expressed in cancer cells, and CHI3L1 expression had a significant association with the number of infiltrated macrophages and microvessel density (MVD). By utilizing transwell migration and tube-formation assays, overexpression of CHI3L1 in SW480 cells (human colon cancer cells) enhanced the migration of THP-1 cells (human macrophage cells) and HUVECs (human endothelial cells), and the tube formation of HUVECs. The knockdown of CHI3L1 by RNA interference or the neutralization of CHI3L1 by anti-CHI3L1 antibody displayed strong suppression of CHI3L1-induced migration and tube formation. Cell proliferation assay showed that CHI3L1 overexpression significantly enhanced the proliferation of SW480 cells. Enzyme-linked immunosorbent assay (ELISA) analysis showed that CHI3L1 increased the secretion of inflammatory chemokines, IL-8 and monocyte chemoattractant protein-1 (MCP-1), from SW480 cells through mitogen-activated protein kinase (MAPK) signaling pathway. Both neutralization of IL-8 or MCP-1 and inhibition or knockdown of MAPK in SW480 cells significantly inhibited CHI3L1-induced migration and tube formation. In a xenograft mouse model, overexpression of CHI3L1 in HCT116 cells (human colon cancer cells) enhanced the tumor growth as well as macrophage infiltration and MVD. In conclusion, CHI3L1 expressed in colon cancer cells promotes cancer cell proliferation, macrophage recruitment and angiogenesis. Thus, the inhibition of CHI3L1 activity may be a novel therapeutic strategy for human colorectal cancer.
Varicella zoster virus (VZV) is the etiological agent of chickenpox and shingles, diseases characterized by epidermal skin blistering. Using a calcium-induced keratinocyte differentiation model we ...investigated the interaction between epidermal differentiation and VZV infection. RNA-seq analysis showed that VZV infection has a profound effect on differentiating keratinocytes, altering the normal process of epidermal gene expression to generate a signature that resembles patterns of gene expression seen in both heritable and acquired skin-blistering disorders. Further investigation by real-time PCR, protein analysis and electron microscopy revealed that VZV specifically reduced expression of specific suprabasal cytokeratins and desmosomal proteins, leading to disruption of epidermal structure and function. These changes were accompanied by an upregulation of kallikreins and serine proteases. Taken together VZV infection promotes blistering and desquamation of the epidermis, both of which are necessary to the viral spread and pathogenesis. At the same time, analysis of the viral transcriptome provided evidence that VZV gene expression was significantly increased following calcium treatment of keratinocytes. Using reporter viruses and immunohistochemistry we confirmed that VZV gene and protein expression in skin is linked with cellular differentiation. These studies highlight the intimate host-pathogen interaction following VZV infection of skin and provide insight into the mechanisms by which VZV remodels the epidermal environment to promote its own replication and spread.
The adverse effects of climate change on agriculture have been felt across the globe. Smallholder farmers in sub-Sahara Africa are particularly more vulnerable to the effects of climate change ...leading to loss of income and livelihood thus affecting global food security. Rainwater harvesting (RWH) is emerging as a viable option to mitigate the negative effects of climate change by supporting rain-fed agriculture through supplemental irrigation. However, smallholder farmers are still grappling with a myriad of challenges hindering them from reaping the benefits of their investment in RWH systems. This review explores some of the factors behind the poor performance of RWH systems in Kenya and also seeks to suggest techniques that can be applied to optimize the design parameters for improved performance and the adoption of RWH systems. According to the review, RWH has the potential to mitigate the adverse effects of climate change among smallholder farmers. It allows for crop production beyond the growing season through supplemental irrigation. However, their impacts have been minimal due to the consistent poor performance of RWH systems. This is attributed to inefficiencies in design and construction brought about by lack of required technical skills among RWH system designers and implementers. Proper design and implementation are therefore paramount for better performance and adoption of RWH systems in the region. This will ensure that RWH systems are reliable, technically and economically feasible as well as possess a desirable water-saving efficiency. HIGHLIGHTS Improved design of rainwater harvesting system (RWH).; Increased adoption of RWH systems.; Improved resilience to climate change among smallholder farmers.; Enhanced food security and access to clean water.; Improved performance of RWH systems.;
Endogenous retroviruses (ERV), or the remnants of past retroviral infections that are no longer active, are found in the genomes of most vertebrates, typically constituting approximately 10% of the ...genome. In some vertebrates, particularly in shorter-lived species like rodents, it is not unusual to find active endogenous retroviruses. In longer-lived species, including humans where substantial effort has been invested in searching for active ERVs, it is unusual to find them; to date none have been found in humans. Presumably the chance of detecting an active ERV infection is a function of the length of an ERV epidemic. Intuitively, given that ERVs or signatures of past ERV infections are passed from parents to offspring, we might expect to detect more active ERVs in species with longer generation times, as it should take more years for an infection to run its course in longer than in shorter lived species. This means the observation of more active ERV infections in shorter compared to longer-lived species is paradoxical. We explore this paradox using a modeling approach to investigate factors that influence ERV epidemic length. Our simple epidemiological model may explain why we find evidence of active ERV infections in shorter rather than longer-lived species.
Multilayered piezoelectric MEMS energy harvesters based on sputtering depositions are designed and fabricated. To obtain high endurance and output power, the unimorph cantilever structure with ...totally 10 μm-thick multilayered PZT thin films and 80 μm-thick Si elastic layer is designed. In addition, the cantilever is designed to undergo a uniform stress on the PZT. The output power and voltage was 90 μW and 1.0 Vrms under the input acceleration of approximately 1.2 G (=11.76 m/s2) and optimum load resistance.
Rainwater harvesting (RWH) is emerging as a promising alternative source of water in sub-Saharan Africa. It can be an alternative source of good-quality water to substitute other freshwater sources, ...to enable crop production beyond the growing season through supplemental irrigation as well as to improve the environment by minimizing the effect of drought and floods. The Rachuonyo North Sub-County of Kenya experiences low rainfall coupled with high population with limited access to reliable water sources. The study assessed the RWH potential of the Rachuonyo North Sub-Catchment with the aim of providing information on alternative water resources to meet the water demands for agriculture as well as domestic use in the region. The Australian water balance model (AWBM) was used to simulate the RWH potential of the Rachuonyo North Sub-Catchment using the area rainfall, evapotranspiration and river flow data. The calibration and validation of the model were performed with calibration and validation results yielding Nash–Sutcliffe efficiency (NSE) values of 0.503 and 1.00, respectively. Research findings indicated that the area has a potential for RWH with runoff harvest of between 104,496 and 43,646,142 m3/month, which can significantly support the residential and irrigation water demands for the area. Policymakers and development agencies in the region should pro-actively put in place measures to promote RWH interventions as a tool for increasing access to water. The methodology in the study is suitable for adaption for rainfall–runoff simulation in other sub-Saharan African regions where data are limiting. HIGHLIGHTS Resilience to climate change.; Increased access to clean water.; Increased access to irrigation water.; Flood management.; Integrated water resources management.;
We analysed associations between exposure to nightlife businesses and severe acute respiratory syndrome coronavirus 2 PCR test results at a tertiary hospital in Tokyo between March and April 2020. A ...nightlife group was defined as those who had worked at or visited the businesses. We included 1517 individuals; 196 (12.9%) were categorised as the nightlife group. After propensity score matching, the proportion of positive PCR tests in the nightlife group was significantly higher than that in the non-nightlife group (nightlife, 63.8%; non-nightlife, 23.0%; P < 0.001). An inclusive approach to mitigate risks related to the businesses needs to be identified.
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