Miracle-dz/UniFAR-FTUs huggingface dataset:
Chimerization of the Anti-Viral CD8+ T Cell Response with A Broad Anti-Tumor T Cell Response Reverses Inhibition of Checkpoint Blockade Therapy by Oncolytic Virotherapy

Although immune checkpoint inhibition (ICI) has produced profound survival benefits in a broad variety of tumors, a proportion of patients do not respond. Treatment failure is in part due to immune suppressive tumor microenvironments (TME), which is particularly true of hepatocellular carcinoma (HCC). Since oncolytic viruses (OV) can generate a highly immune-infiltrated, inflammatory TME, we developed a vesicular stomatitis virus expressing interferon-ß (VSV-IFNß) as a viro-immunotherapy against HCC. Since HCC standard of care atezolizumab/bevacizumab incorporates ICI, we tested the hypothesis that pro-inflammatory VSV-IFNß would recruit, prime, and activate anti-tumor T cells, whose activity anti-PD-L1 ICI would potentiate. However, in a partially anti-PD-L1-responsive model of HCC, addition of VSV-IFNß abolished anti-PD-L1 therapy. Cytometry by Time of Flight showed that VSV-IFNß expanded dominant anti-viral effector CD8 T cells with concomitant, relative disappearance of anti-tumor T cell populations which are the target of anti-PD-L1. However, by expressing a range of HCC tumor antigens within VSV, the potent anti-viral response became amalgamated with an anti-tumor T cell response generating highly significant cures compared to anti-PD-L1 ICI alone. Our data provide a cautionary message for the use of highly immunogenic viruses as tumor-specific immune-therapeutics by showing that dominant anti-viral T cell responses can inhibit sub-dominant anti-tumor T cell responses. However, by chimerizing anti-viral and anti-tumor T cell responses through encoding tumor antigens within the virus, oncolytic virotherapy can be purposed for very effective immune driven tumor clearance and can generate anti-tumor T cell populations upon which immune checkpoint blockade can effectively work.
Puerarin protects renal ischemia-reperfusion injury in rats through NLRP3/Caspase-1/GSDMD pathway

ABSTRACT Purpose: To observe the effect of puerarin on renal ischemia-reperfusion (I/R) injury in rats, and to explore its mechanism based on NLRP3/Caspase-1/GSDMD pathway. Methods: Twenty-one Sprague-Dawley rats were divided into three groups: sham-operated group (sham), model group (RIRI), and puerarin treatment group (RIRI + Pue). The model of acute renal I/R injury was established by cutting the right kidney and clamping the left renal pedicle for 45 min. Results: Renal function parameters were statistically significant in group comparisons. The renal tissue structure of rats in sham group was basically normal. Pathological changes were observed in the RIRI group. The renal pathological damage score and apoptosis rate in the RIRI group were higher than those in the sham group, and significantly lower in the RIRI + Pue group than in the RIRI group. Indicators of oxidative stress–superoxide dismutase, malondialdehyde, and glutathione peroxidase–were statistically significant in group comparisons. Compared with the sham group, the relative expressions of NLRP3, Caspase-1 and GSDMD proteins in the RIRI group were increased. Compared with the RIRI group, the RIRI + Pue group had significant reductions. Conclusions: Puerarin can inhibit the activation of NLRP3/Caspase-1/GSDMD pathway, inhibit inflammatory response and pyroptosis, and enhance the antioxidant capacity of kidney, thereby protecting renal I/R injury in rats.
Integration of HIV pre-exposure prophylaxis (PrEP) services for pregnant and breastfeeding women in eight primary care clinics: results of an implementation science study

Background Although HIV vertical transmission (VT) has declined significantly in sub-Saharan Africa, incident HIV infection in pregnant and postpartum women is estimated to account for roughly one-third of VT. Oral pre-exposure prophylaxis (PrEP) for pregnant and breastfeeding women (PBFW) is part of the recommended guidelines in South Africa since 2021; however, integration of PrEP services within antenatal (ANC) and postnatal care (PNC) remains limited. Methods Between March 2022 and September 2023, we evaluated the acceptability, feasibility and sustainability of integrating PrEP for PBFW in high-HIV prevalence clinics after training and mentoring health care providers (HCP). We used the Reach Effectiveness-Adoption Implementation Maintenance (RE-AIM) framework to evaluate the intervention. Acceptability and maintenance were defined as the proportion of PBFW without HIV who initiated PrEP and the proportion of women continuing PrEP at 3 months in ANC or PNC services. Feasibility was defined as the proportion of trained HCPs (HIV lay counsellors and nurses/ midwives) who provided PrEP according to national guidelines, measured through post-training surveys and in-service assessments. Sustainability was defined as number of facilities and providers that continued to provide PrEP for PBFW past the mentoring period. Results In 8 facilities providing ANC and PNC, we trained 224 HCP (127 nurses and 37 counsellors). Of those, we mentored 60 nurses, midwives and HIV counsellors working with PBFW, with 72% of nurse/midwives and 65% of counsellors scoring over 8/10 on the final mentoring assessment Overall, 12% (1493/12,614) of HIV-negative pregnant women started PrEP and 41% of those continued PrEP at 3-months. Among the HIV-negative breastfeeding women in postnatal care, 179/1315 (14%) initiated PrEP and 25% continued PrEP at 3-months. All 8 facilities continued providing PrEP 3-months after handover of the clinics. Conclusion Integration of PrEP services in ANC and services for breastfeeding women was feasible, acceptable and sustainable. Acceptability and PrEP continuation showed improvement over time. Barriers to the PrEP integration were observed including the lack of regular HIV testing of breastfeeding mothers and need for ART-trained nurses to prescribe PrEP. Enablers included motivated and dedicated staff.
Cumulative violence exposures among men who have sex with men living with HIV in India: Psychosocial correlates of HIV care continuum outcomes

Lifetime exposures to violence among men who have sex with men (MSM) are associated with multiple psychosocial health risks and can affect engagement and outcomes of HIV treatment. This study a) explored relationships between levels of exposures to violence and HIV care continuum outcomes among MSM living with HIV in India, and b) identified psychosocial correlates of HIV care continuum outcomes among MSM living with HIV and those with lifetime cumulative exposures to violence (CVE). CVE referred to exposures to violence in both childhood and adulthood. This cross-sectional analysis used survey data collected between August 2016 and May 2017 from 1763 men who have sex with men living with HIV across 10 cities in India, using respondent-driven sampling. We found that higher levels of violence exposure were significantly associated with lower awareness of HIV positive status, and lower likelihood of initiating antiretroviral therapy. Compared with MSM living with HIV that had no CVE, those with CVE were more likely to report perpetration of interpersonal violence, alcohol misuse, depressive symptoms, and HIV transmission risk behaviors and to have two to four co-occurring psychosocial problems. In multivariable analysis with the subset of MSM with CVE, psychosocial correlates significantly associated with at least one HIV care continuum outcome were HIV transmission risk behaviors, perpetration of interpersonal violence, depression, and alcohol misuse. The findings highlight the need for integrating care for lifetime violence exposures and associated behavioral problems in HIV care settings for men who have sex with men living with HIV in India.
The subset of peroxisomal tail-anchored proteins do not reach peroxisomes via ER, instead mitochondria can be involved

Peroxisomes are membrane-enclosed organelles with important roles in fatty acid breakdown, bile acid synthesis and biosynthesis of sterols and ether lipids. Defects in peroxisomes result in severe genetic diseases, such as Zellweger syndrome and neonatal adrenoleukodystrophy. However, many aspects of peroxisomal biogenesis are not well understood. Here we investigated delivery of tail-anchored (TA) proteins to peroxisomes in mammalian cells. Using glycosylation assays we showed that peroxisomal TA proteins do not enter the endoplasmic reticulum (ER) in both wild type (WT) and peroxisome-lacking cells. We observed that in cells lacking the essential peroxisome biogenesis factor, PEX19, peroxisomal TA proteins localize mainly to mitochondria. Finally, to investigate peroxisomal TA protein targeting in cells with fully functional peroxisomes we used a proximity biotinylation approach. We showed that while ER-targeted TA construct was exclusively inserted into the ER, peroxisome-targeted TA construct was inserted to both peroxisomes and mitochondria. Thus, in contrast to previous studies, our data suggest that some peroxisomal TA proteins do not insert to the ER prior to their delivery to peroxisomes, instead, mitochondria can be involved.
Targeting ABCA12-controlled ceramide homeostasis inhibits breast cancer stem cell function and chemoresistance

Cancer stem cells (CSCs) drive tumor growth, metastasis, and chemoresistance. While emerging evidence suggests that CSCs have a unique dependency on lipid metabolism, the functions and regulation of distinct lipid species in CSCs remain poorly understood. Here, we developed a stem cell factor SOX9-based reporter for isolating CSCs in primary tumors and metastases of spontaneous mammary tumor models. Transcriptomic analyses uncover that SOX9high CSCs up-regulate the ABCA12 lipid transporter. ABCA12 down-regulation impairs cancer stemness and chemoresistance. Lipidomic analyses reveal that ABCA12 maintains cancer stemness and chemoresistance by reducing intracellular ceramide abundance, identifying a CSC-associated function of ABCA subfamily transporter. Ceramide suppresses cancer stemness by inhibiting the YAP-SOX9 signaling pathway in CSCs. Increasing ceramide levels in tumors enhances their sensitivity to chemotherapy and prevents the enrichment of SOX9high CSCs. In addition, SOX9high and ABCA12high cancer cells contribute to chemoresistance in human patient-derived xenografts. These findings identify a CSC-suppressing lipid metabolism pathway that can be exploited to inhibit CSCs and overcome chemoresistance.
Prediction models of incontinence and sexual function one year after radical prostatectomy based on data from 20 164 prostate cancer patients

Background Incontinence and sexual dysfunction are long-lasting side effects after surgical treatment (radical prostatectomy, RP) of prostate cancer (PC). For an informed treatment decision, physicians and patients should discuss expected impairments. Therefore, this paper firstly aims to develop and validate prognostic models that predict incontinence and sexual function of PC patients one year after RP and secondly to provide an online decision making tool. Methods Observational cohorts of PC patients treated between July 2016 and March 2021 in Germany were used. Models to predict functional outcomes one year after RP measured by the EPIC-26 questionnaire were developed using lasso regression, 80–20 splitting of the data set and 10-fold cross validation. To assess performance, R2, RMSE, analysis of residuals and calibration-in-the-large were applied. Final models were externally temporally validated. Additionally, percentages of functional impairment (pad use for incontinence and firmness of erection for sexual score) per score decile were calculated to be used together with the prediction models. Results For model development and internal as well as external validation, samples of 11 355 and 8 809 patients were analysed. Results from the internal validation (incontinence: R2 = 0.12, RMSE = 25.40, sexual function: R2 = 0.23, RMSE = 21.44) were comparable with those of the external validation. Residual analysis and calibration-in-the-large showed good results. The prediction tool is freely accessible: https://nora-tabea.shinyapps. io/EPIC-26-Prediction/. Conclusion The final models showed appropriate predictive properties and can be used together with the calculated risks for specific functional impairments. Main strengths are the large study sample (> 20 000) and the inclusion of an external validation. The models incorporate meaningful and clinically available predictors ensuring an easy implementation. All predictions are displayed together with risks of frequent impairments such as pad use or erectile dysfunction such that the developed online tool provides a detailed and informative overview for clinicians as well as patients.
Causes and consequences of the Merriespruit and other tailings‐dam failures

On the night of 22 February 1994, the 31 m high northern wall of the number four tailings dam of the Harmony Gold mine collapsed. The tailings dam is situated 320 m up‐slope of Merriespruit, a suburb of Virginia in the Free State Goldfields of South Africa. More than 2·5 million tonnes of liquefied tailings ripped through the sleeping mining village. Eighty houses were largely swept away and 200 others were severely damaged. Seventeen people were killed.
DNA on the move: mechanisms, functions and applications of transposable elements

Transposons are mobile genetic elements that have invaded all domains of life by moving between and within their host genomes. Due to their mobility (or transposition), transposons facilitate horizontal gene transfer in bacteria and foster the evolution of new molecular functions in prokaryotes and eukaryotes. As transposition can lead to detrimental genomic rearrangements, organisms have evolved a multitude of molecular strategies to control transposons, including genome defense mechanisms provided by CRISPR‐Cas systems. Apart from their biological impacts on genomes, DNA transposons have been leveraged as efficient gene insertion vectors in basic research, transgenesis and gene therapy. However, the close to random insertion profile of transposon‐based tools limits their programmability and safety. Despite recent advances brought by the development of CRISPR‐associated genome editing nucleases, a strategy for efficient insertion of large, multi‐kilobase transgenes at user‐defined genomic sites is currently challenging. The discovery and experimental characterization of bacterial CRISPR‐associated transposons (CASTs) led to the attractive hypothesis that these systems could be repurposed as programmable, site‐specific gene integration technologies. Here, we provide a broad overview of the molecular mechanisms underpinning DNA transposition and of its biological and technological impact. The second focus of the article is to describe recent mechanistic and functional analyses of CAST transposition. Finally, current challenges and desired future advances of CAST‐based genome engineering applications are briefly discussed.
QUANTITATIVE AND QUALITATIVE EVALUATION OF URBAN LAND USE WITH EMPHASIS ON DISTRIBUTION SYSTEM AND PROXIMITY PATTERNS (CASE STUDY: DISTRICT 1 GORGAN CITY)

Introduction Urban land use planning is original core of urban planning system. The purpose of land use planning is for the spatial arrangement and desirable location order for land uses and urban activity, especially in cities that land uses have high combination and variety. To achieve this goal is requires understanding of condition space allocation and land distribution among urban land use that is possible through quality and quantitative evaluation methods. Analysis of compatibility and incompatibility between urban land uses is caused by positive and negative effects that adjacent and neighboring land uses which have on each other. This article is studying quality and quantitative characteristics in district 1 land use of Gorgan city in north of Iran. Recently, researches related to the construction of cities show that without land use planning it is far from reaching to achieve optimal life pattern in cities. Urban land use planning is spatial space organization of activities and urban performances based on demands and needs of urban society especially in those cities that the land uses system has considerable combinations and diversities. The final goal of land use planning is to establish typical ecological balance and social justice in the development process and civil of city and also it should answer to quality objectives like perception of beauty sense of spatial identity and sense of belonging to the environment. Corresponding to failure and limitation of quantitative standards to response to ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ  E-mail: Aliakbariesmaeil@yahoo.com Tel: 09123840594
Wind Effects on Past and Future Regional Sea Level Trends in the Southern Indo-Pacific*

Abstract Global sea level rise due to the thermal expansion of the warming oceans and freshwater input from melting glaciers and ice sheets is threatening to inundate low-lying islands and coastlines worldwide. At present the global mean sea level rises at 3.1 ± 0.7 mm yr−1 with an accelerating tendency. However, the magnitude of recent decadal sea level trends varies greatly spatially, attaining values of up to 10 mm yr−1 in some areas of the western tropical Pacific. Identifying the causes of recent regional sea level trends and understanding the patterns of future projected sea level change is of crucial importance. Using a wind-forced simplified dynamical ocean model, the study shows that the regional features of recent decadal and multidecadal sea level trends in the tropical Indo-Pacific can be attributed to changes in the prevailing wind regimes. Furthermore, it is demonstrated that within an ensemble of 10 state-of-the-art coupled general circulation models, forced by increasing atmospheric CO2 co.
Research Article User-Generated Content Creation and Dissemination in Rural Areas

A majority of the world’s population does not have access to the Internet. Therefore, there is a need for a simple and affordable interaction technology that can enable easy content creation and dissemination for this population. In this paper, we present the design, development, and usage pattern of a VoiKiosk system that provides a voice-based kiosk solution for people in rural areas. This system is accessible by phone and thus meets the affordability and low-literacy requirements. We present usability results gathered from usage by more than 6,000 villagers during nine months of the aeld deployment of the system. The aeld experiments and post-pilot feedback suggest the importance of locally-created content in their own language for this population. The system provides interesting insights about the manner in which this community can create and manage information. Based on the use of the system in the nine months, the VoiKiosk also suggests a mechanism to enable social networking for the rural population.
Three dimensional printed biofilms: Fabrication, design and future biomedical and environmental applications

Abstract Three dimensional printing has emerged as a widely acceptable strategy for the fabrication of mammalian cell laden constructs with complex microenvironments for tissue engineering and regenerative medicine. More recently 3D printed living materials containing microorganisms have been developed and matured into living biofilms. The potential for engineered 3D biofilms as in vitro models for biomedical applications, such as antimicrobial susceptibility testing, and environmental applications, such as bioleaching, bioremediation, and wastewater purification, is extensive but the need for an in‐depth understanding of the structure–function relationship between the complex construct and the microorganism response still exists. This review discusses 3D printing fabrication methods for engineered biofilms with specific structural features. Next, it highlights the importance of bioink compositions and 3D bioarchitecture design. Finally, a brief overview of current and potential applications of 3D printed biofilms in environmental and biomedical fields is discussed.
Assessment of Expression Levels and Localization Patterns of Phospholipase C zeta in Different Grades of HOST in Human Sperm

Background: Phospholipase C zeta (PLC-ζ) deficiency in sperm can underlie oocyte activation failure after intracytoplasmic sperm injection (ICSI). The aim of this study was to determine PLC-ζ expression and location in individual spermatozoa in each host score so that a hypo-osmotic swelling test (HOST) may be used to help routine sperm selection for ICSI. Materials and Methods: In this experimental study, fresh semen samples were randomly obtained from 30 men who were referred to the Andrology Unit of the Infertility Center. Samples were processed by density gradient centrifugation (DGC) and exposed to hypotonic conditions. Seven different tail patterns, classified from ‘a’ to ‘g’ can be detected according to World Health Organization (WHO) criteria. Then, the PLC-ζ protein localization pattern was assessed by quantitative Immunofluorescence in individual sperm Host grades. Moreover, the sperm content of PLC-ζ protein was evaluated by flow cytometry correlated with semen analysis parameters. Results: In the present study, quantitive immunofluorescence analysis indicated that sperm from different host grades exhibited seven localization patterns of PLC-ζ of acrosomal (A); equatorial (EQ), and postacrosomal (PA) patterns. A+EQ=acrosomal and equatorial, A+PA=acrosomal and post-acrosomal, EQ+PA=equatorial and post-crosomal, and A+EQ+PA. The sperm from HOST grade 'd' exhibited significantly higher PLC-ζ (A+PA) and (A+EQ+PA) staining compared to sperm from other grades (P=0.006). The sperm from grade 'd' exhibited higher PLC-ζ (EQ+PA) compared with other grades (P=0.001). However, grade 'd' was not significantly different from 'c' (P=0.087). Analysis of the combined results confirmed that there was a clear reduction in PLC-ζ immunofluorescence in Host grades 'a', 'f' and 'g' sperms. Conclusion: Our data suggest that HOST may represent a useful diagnostic tool for the selection of sperms exhibiting a higher level of PLC-ζ expression.
Vascular flora and gradient analysis of the Natchez Trace Parkway

Vascular Flora and Gradient Analysis of the Natchez Trace Parkway. (August 2006) Nena Mae Monique Phillips, B.S., Texas A&M University Chair of Advisory Committee: Dr. Stephan L. Hatch Vascular plant collections were made on the Natchez Trace Parkway over a 15 month period beginning in August 2004. These collections along with previous work done by the National Park Service (NPS) produced a flora of 750 genera and 2196 species in 167 families. Five collection trips were made so as to include as much of the growing season as possible (August 2004, March, May, July and October 2005). Specimens were collected from 500 sites along the Parkway as well as at 50 quadrat locations. The largest families, by species numbers, are Asteraceae (298 species), Poaceae (236 species), Cyperaceae (148 species), Fabaceae (133 species) and Rosaceae (73 species), which accounted for 40.4% of the flora. A Detrended Correspondence Analysis (DCA) and TWINSPAN analysis were performed on data collected from 49 sites along the length of the Natchez Trace Parkway (NATR). It was found that the major environmental gradient (Axis 1) affecting the species composition of the site was to be the level of disturbance. The sites with high levels of disturbance were characterized as grassland field sites, while those areas with low levels of disturbance were characterized as forested sites. The TWINSPAN analysis produced 29 groupings, of which eight were found to