Miracle-dz/UniFAR-FTUs huggingface dataset:
Comprehensive analysis of differential expression profiles reveals potential biomarkers associated with the cell cycle and regulated by p53 in human small cell lung cancer

Small cell lung cancer (SCLC) is the subtype of lung cancer with the highest degree of malignancy and the lowest degree of differentiation. The purpose of this study was to investigate the molecular mechanisms of SCLC using bioinformatics analysis, and to provide new ideas for the early diagnosis and targeted therapy of SCLC. Microarray data were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) in SCLC were compared with the normal lung samples and identified. Gene Ontology (GO) function and pathway analysis of DEGs was performed through the DAVID database. Furthermore, microarray data was analyzed by using the clustering analysis tool GoMiner. Protein-protein interaction (PPI) networks of DEGs were constructed using the STRING online database. Protein expression was determined from the Human Protein Atlas, and SCLC gene expression was determined using Oncomine. In total, 153 DEGs were obtained. Functional enrichment analysis suggested that the majority of DEGs were associated with the cell cycle. CCNB1, CCNB2, MAD2L1 and CDK1 were identified to contribute to the progression of SCLC through combined use of GO, Kyoto Encyclopedia of Genes and Genomes enrichment analysis and a PPI network. mRNA and protein expression were also validated in an integrative database. The present study indicated that the formation of SCLC may be associated with cell cycle regulation. In addition, the four crucial genes CCNB1, CCNB2, MAD2L1 and CDK1, which are downstream of p53, may have important roles in the occurrence and progression of SCLC, and thus may be promising potential biomarkers and therapeutic targets.
Trajectories of life satisfaction after traumatic brain injury: Influence of life roles, age, cognitive disability, and depressive symptoms.

OBJECTIVES (a) Identify life satisfaction trajectories after moderate to severe traumatic brain injury (TBI); (b) establish a predictive model for these trajectories across the first 5 years postinjury; and (c) describe differences in these life satisfaction trajectory groups, focusing on age, depressive symptoms, disability, and participation in specific life roles. RESEARCH METHOD Analysis of the longitudinal TBI Model Systems National Database was performed on data collected prospectively at 1-, 2-, and 5-years post-TBI. Participants (n = 3,012) had a moderate to severe TBI and were 16 years old and older. RESULTS Four life satisfaction trajectories were identified across the first 5 years postinjury, including: stable satisfaction, initial satisfaction declining, initial dissatisfaction improving, and stable dissatisfaction. Age, depressive symptoms, cognitive disability, and life role participation as a worker, leisure participant, and/ or religious participant at 1-year postinjury significantly predicted trajectory group membership. Life role participation and depressive symptoms were strong predictors of life satisfaction trajectories across the first 5 years post-TBI. CONCLUSIONS The previously documented loss of life roles and prevalence of depression after a moderate to severe TBI make this a vulnerable population for whom low or declining life satisfaction is a particularly high risk. Examining individual life role participation may help to identify relevant foci for community-based rehabilitation interventions or supports.
Degrees of Freedom of Multi-Hop MIMO Broadcast Networks with Delayed CSIT

We study the sum degrees of freedom (DoF) of a class of multi-layer relay-aided MIMO broadcast networks with delayed channel state information at transmitters (CSIT). In the assumed network a K-antenna source intends to communicate to K single-antenna destinations, with the help of N-2 layers of K full-duplex single-antenna relays. We assume identical and independent fading channels on every hop. Two practical delayed CSIT feedback scenarios are studied. If the source can obtain the CSI feedback signals from all layers, we prove the optimal sum DoF of the network to be \frac{K}{1+\frac{1}{2}+…+\frac{1}{K}}. If the CSI feedback is only within each hop, we show that when K=2 the optimal sum DoF is \frac{4}{3}, and when K≥ 3 the sum DoF \frac{3}{2} is achieved asymptotically.
Impact of Some Energy Drinks on the Structure and Function of the Kidney in Wistar Albino Rats 1

Three kinds of energy drinks (Power horse, Red bull and Code red) were used to study their possible adverse effects on the structure and function of the kidney in Wistar albino rats. Animals were divided into four groups: group 1 served as control, while animals in groups 2, 3 and 4 each were orally administered with a type of the energy drinks daily for 4 weeks. After two and four weeks of treatment, blood samples were collected for biochemical analysis of kidney function, while small pieces of kidney were removed and quickly fixed to carry out light and electron microscopic investigations. Results of the present study showed that the energy drinks induced an elevation of renal biomarkers urea, uric acid and creatinine.The elevation in these parameters was time dependant and the Power horse was more effective in its action followed by Red bull and to less extend Code red. Histopathological observations of kidney tissue in energy drinks administered animals, revealed distinct pathological lesions as represented by necrosis of renal tubules and glomeruli as well as intertubular hemorrhage and leucocytic infilteration. Moreover, electron microscopic results showed marked ultrastructure alterations in the nucleous and cytoplasmic oraganelles in the cells of proximal and distal tubules as well as in the renal corpuscles. These alterations were more obvious in rats given power horse.The different action of the energy drinks on kidney function could be attributed to the different mixture of their ingredients. [Latifa Khayyat, Amina Essawy, Jehan Sorour and Maisaa Al Rawi. Impact of Some Energy Drinks on the Structure and Function of the Kidney in Wistar Albino Rats. Life Sci J 2014;11(10):1131-1138]. (ISSN:10978135). http://www.lifesciencesite. com. 170
Sex Differences in School Safety and Bullying Experiences Among Sexual Minority Youth

Schools play an integral role in creating safe, supportive environments for students, especially for sexual minority youth (SMY). Using 2016 questionnaire data from seven high schools in a Florida school district, we obtained a sample of 1,364 SMY. Logistic regressions controlling for sex (as applicable), age, grade, race/ethnicity, and school explored differences between SMY and nonsexual minority youth (non-SMY). Sex differences related to school environment perceptions and experiences related to safety, bullying, and hearing homophobic remarks were also explored. SMY were more likely than non-SMY to report several negative school environment perceptions and experiences. Where differences existed within SMY, male SMY were more likely than female SMY to have missed school in the past 30 days (odds ratio [OR] = 1.66, p = .03), report avoiding spaces at school due to safety concerns (OR = 1.38, p = .02), and report hearing homophobic remarks from teachers (OR = 2.00, p = .01). Implications for school nursing are discussed.
A leader-following approach based on probabilistic trajectory estimation and virtual train model

The paper proposes a novel multi-robot leader-following approach that can offer accurate trajectory estimation and tracking control in scenarios where 1) temporary outage of vision detection happens due to the leader robot moving out of view, illumination variation, vision occlusion, motion blurring, etc., and 2) the leader moves at a time-varying linear velocity. The approach estimates the trajectory of the leader robot within the local reference frame of the follower using noise-corrupted odometry information and intermittent inter-robot relative observations based on detection of fiducial markers using an RGBD camera. It also introduces the virtual train model in the trajectory tracking, with which the follower is controlled to keep its linear velocity synchronous with that of the leader and a constant separation distance. Results are obtained based on evaluating the proposed leader-following approach in a test containing sharp turns and a zig-zag pattern in the trajectory, and variation in the speed of the leader robot.
Glycosyl-Phosphatidylinositol-Anchored Anti-HIV Env Single-Chain Variable Fragments Interfere with HIV-1 Env Processing and Viral Infectivity

ABSTRACT In previous studies, we demonstrated that single-chain variable fragments (scFvs) from anti-human immunodeficiency virus (HIV) Env monoclonal antibodies act as entry inhibitors when tethered to the surface of target cells by a glycosyl-phosphatidylinositol (GPI) anchor. Interestingly, even if a virus escapes inhibition at entry, its replication is ultimately controlled. We hypothesized that in addition to functioning as entry inhibitors, anti-HIV GPI-scFvs may also interact with Env in an infected cell, thereby interfering with the infectivity of newly produced virions. Here, we show that expression of the anti-HIV Env GPI-scFvs in virus-producing cells reduced the release of HIV from cells 5- to 22-fold, and infectivity of the virions that were released was inhibited by 74% to 99%. Additionally, anti-HIV Env GPI-scFv X5 inhibited virion production and infectivity after latency reactivation and blocked transmitter/founder virus production and infectivity in primary CD4+ T cells. In contrast, simian immunodeficiency virus (SIV) production and infectivity were not affected by the anti-HIV Env GPI-scFvs. Loss of infectivity of HIV was associated with a reduction in the amount of virion-associated Env gp120. Interestingly, an analysis of Env expression in cell lysates demonstrated that the anti-Env GPI-scFvs interfered with processing of Env gp160 precursors in cells. These data indicate that GPI-scFvs can inhibit Env processing and function, thereby restricting production and infectivity of newly synthesized HIV. Anti-Env GPI-scFvs therefore appear to be unique anti-HIV molecules as they derive their potent inhibitory activity by interfering with both early (receptor binding/entry) and late (Env processing and incorporation into virions) stages of the HIV life cycle. IMPORTANCE The restoration of immune function and persistence of CD4+ T cells in HIV-1-infected individuals without antiretroviral therapy requires a way to increase resistance of CD4+ T cells to infection by both R5- and X4-tropic HIV-1. Previously, we reported that anchoring anti-HIV-1 single-chain variable fragments (scFvs) via glycosyl-phosphatidylinositol (GPI) to the surface of permissive cells conferred a high level of resistance to HIV-1 variants at the level of entry. Here, we report that anti-HIV GPI-scFvs also derive their potent antiviral activity in part by blocking HIV production and Env processing, which consequently inhibits viral infectivity even in primary infection models. Thus, we conclude that GPI-anchored anti-HIV scFvs derive their potent blocking activity of HIV replication by interfering with successive stages of the viral life cycle. They may be effectively used in genetic intervention of HIV-1 infection.
Ultrasound-guided Sciatic Nerve Blocks: Higher and Popliteal Approaches

Background and objective: In modern anaesthetic practice the classical landmark approaches for sciatic nerve blocks have been constantly modified and adjusted to the ultrasound-guided techniques. This huge variety in published ‘new’ ultrasound SNB approaches may be somewhat confusing for the anaesthetic trainee. In this article we compare most popular ultrasound approaches to the landmark techniques trying to systematize them for teaching purposes. Materials and methods: After reviewing the current literature, publications and websites we describe the four most popular groups of ultrasound approaches for sciatic nerve blocks discussing the sonoanatomy, sonotechnique, clinical tips and complications. We start with the most superficial approach-the popliteal and end with the deepest of them-the anterior approach. We also hope that our classification will even accommodate the US approaches developed in the future.
Cutting Edge: Chromatin Accessibility Programs CD8 T Cell Memory

CD8 T cell memory is characterized by rapid recall of effector function, increased proliferation, and reduced activation requirements. Despite the extensive functional characterization, the molecular mechanisms that facilitate these enhanced properties are not well characterized. In this study, the assay for transposase-accessible chromatin sequencing was employed to map the cis-regulatory elements in CD8 T cells responding to acute and chronic lymphocytic choriomeningitis virus infections. Integration of chromatin accessibility profiles with gene expression data identified unique regulatory modules that were enriched for distinct combinations of transcription factor–binding motifs. Memory CD8 T cells displayed a chromatin accessibility structure that was absent from other acute and exhausted cells types and included key effector and proliferative genes. Stimulation of memory cells revealed enhanced transcription of “memory-primed” genes compared with naive cells. Thus, memory CD8 T cells display a preprogrammed chromatin accessibility profile and maintain a molecular history of cis-element usage, thereby reducing the steps necessary to revive effector functions.
Tests for Linear Trends in Proportions and Frequencies

One frequently encounters data consisting of a series of proportions, occurring in groups which fall into some natural order. The question usually asked is then not so much whether the proportions differ significantly, but whether they show a significant trend, upwards or downwards, with the ordering of the groups, In the data shown in Table 1, for, instance, the usual test for a 2 X 3 contingency table yields a x2 equal to 7.89 on 2 degrees of freedom, corresponding to a probability of about 0.02. But this calculation takes no account of the fact that the carrier rate increases with the tonsil size, and it is reasonable to believe that a test specifically designed to detect a trend in the carrier rate as the tonsil size increases would show a much higher degree of significance.
Mapping the Interactome of a Major Mammalian Endoplasmic Reticulum Heat Shock Protein 90

Up to 10% of cytosolic proteins are dependent on the mammalian heat shock protein 90 (HSP90) for folding. However, the interactors of its endoplasmic reticulum (ER) paralogue (gp96, Grp94 and HSP90b1) has not been systematically identified. By combining genetic and biochemical approaches, we have comprehensively mapped the interactome of gp96 in macrophages and B cells. A total of 511 proteins were reduced in gp96 knockdown cells, compared to levels observed in wild type cells. By immunoprecipitation, we found that 201 proteins associated with gp96. Gene Ontology analysis indicated that these proteins are involved in metabolism, transport, translation, protein folding, development, localization, response to stress and cellular component biogenesis. While known gp96 clients such as integrins, Toll-like receptors (TLRs) and Wnt co-receptor LRP6, were confirmed, cell surface HSP receptor CD91, TLR4 pathway protein CD180, WDR1, GANAB and CAPZB were identified as potentially novel substrates of gp96. Taken together, our study establishes gp96 as a critical chaperone to integrate innate immunity, Wnt signaling and organ development.
Equine-Facilitated Prison-Based Programs Within the Context of Prison-Based Animal Programs: State of the Science Review

Equine-facilitated prison programs have become more prevalent and operate in correctional facilities in 13 states throughout the United States. However, there is a deficit of empirical knowledge to guide them. This article reviews 19 studies of prison-based animal programs and centers on patterns in the literature. It reveals how previous studies are relevant and how they can be applied to the examination of equine-facilitated prison-based interventions. Research of this field is warranted in order to study issues, such as the effectiveness of these programs, suitable participants for such programs and contraindications, and the impact of these programs on variables such as recidivism and disciplinary misconduct.
Occupational hazards for home care nurses across the rural‐to‐urban gradient in Ontario, Canada

The purpose of this paper was to describe occupational hazards for nurses working in home care (HC) and explore how they differ across the rural-to-urban gradient. Responses (n = 823) from a cross-sectional survey conducted in 2012 of HC nurses registered to practise nursing in the Province of Ontario, Canada were used. Using chi-square analysis and posthoc pairwise tests with a Bonferroni correction, 14 occupational hazards were individually tested for differences between four geographical settings (rural, town, suburban or urban areas). Our study reports that in addition to common occupational hazards that all HC nurses experience, the frequency of experiencing some hazards varies based on geographic setting. These specific hazards include exposure to: aggressive pets, environmental tobacco smoke, oxygen equipment, unsafe neighbourhoods and pests. Findings from this study suggest that a relationship exists between where a patient's home is located and the types of occupational hazards that may be experienced by HC staff. This research is useful for HC organisations in developing staff training programmes to recognise and manage occupational hazards that workers are likely to encounter. Home healthcare and policy leaders may use these findings to develop and implement educational and other strategies to reduce risk and manage exposures across the rural-to-urban gradient.
MEVVA ion source for uranium high current operation at the GSI accelerator facility

A high particle current is needed to fill the synchrotron (SIS) at GSI to its space charge limit. The high current injector only accepts ions with a mass to charge ratio up to 65 with a space charge limit of the RFQ of 0.25 /spl times/ A//spl zeta/[mA] where A//spl zeta/ is the mass to charge ratio in atomic units. Thus the design ion for accelerator reasons is U/sup 4+/ with a space charge limit of 15 emA at the front end of the accelerator. For the production of high currents of metallic ions in pulsed operation a metal vapor vacuum arc ion source (MEVVA) is used. For accelerator operation the ion source has to provide a stable beam and has to run with high reliability over a long period of time. The results of a long term operation of the source at the high current injector of GSI are presented here revealing plasma parameters, the long term behaviour of beam current, transmission along the low energy beam transport section, lifetime and availability of the ion source.
Bridging the gap: western rock skinks (Trachylepis sulcata) have a short history in South Africa

Phylogeographic patterns in wide‐ranging species in southern Africa remain largely unexplored, especially in areas north of South Africa. Here, we investigate population structuring, demographic history, and the colonization pattern of the western rock skink (Trachylepis sulcata), a rock‐dwelling species with a range extending from southwestern South Africa into Angola. Using 1056 bp from the mitochondrial marker ND2 and > 2.5 kb from three nuclear genes (EXPH5, KIF24, RAG‐1), we constructed allele networks, generated extended Bayesian skyline plots and performed population clustering analyses. Analyses of historical demographic patterns show an overall southward range expansion from Northern Namibia into Southern Namibia and South Africa, although we find contrasting genetic breaks across these geographic regions using nuclear and mitochondrial data. We suggest that mtDNA has introgressed across a nuclear break corresponding to the Knersvlakte region of South Africa, a previously proposed biogeographic barrier for rupicolous species. This pattern of mitochondrial variation contrasts sharply to that of other South African taxa previously investigated, which all show significant mtDNA differentiation across the Knersvlakte region. Additionally, while other taxa show divergences dating to the Pliocene, T. sulcata appears to be a recent arrival in southern Africa, having crossed this barrier and colonized South Africa in the mid‐Pleistocene. The complex phylogeographic history of T. sulcata corroborates the intricate patterns of genetic variation found in South African taxa and provides novel insight into historical processes affecting species distributed across Namibia.
CD40-mediated HIF-1α expression underlying microangiopathy in diabetic nerve pathology

ABSTRACT To understand the pathology and molecular signatures of microangiopathy in diabetic neuropathy, we systemically and quantitatively examined the morphometry of microvascular and nerve pathologies of sural nerves. In the endoneurium of diabetic nerves, prominent microangiopathy was observed, as evidenced by reduced capillary luminal area, increased capillary basement membrane thickness and increased proportion of fibrin(+) blood vessels. Furthermore, capillary basement membrane thickness and the proportion of fibrin(+) blood vessels were correlated with small myelinated fiber density in diabetic nerves. In diabetic nerves, there was also significant macrophage and T cell infiltration, and cluster of differentiation 40 (CD40) expression was increased. The molecular alterations observed were upregulation of hypoxia-inducible factor-1α (HIF-1α), mitogen-activated protein kinase-activated protein kinase 2 (MK2; MAPKAPK2) and phosphatase and tensin homolog (PTEN). In addition, HIF-1α was correlated with small myelinated fiber density and capillary luminal area, while both MK2 and PTEN were correlated with capillary basement membrane thickness. The molecular cascades were further demonstrated and replicated in a cell model of microangiopathy on human umbilical vein endothelial cells (HUVECs) exposed to high-glucose medium by silencing of CD40, PTEN and HIF-1α in HUVECs using shRNA. These data clarified the hierarchy of the molecular cascades, i.e. upregulation of CD40 leading to HIF-1α expression in endothelium and nerve fibers. In conclusion, this study revealed the association of microangiopathy, thrombosis and inflammatory infiltrates with nerve degeneration in diabetic nerves, demonstrating that CD40 is a key molecule for the upregulation of HIF-1α and PTEN underlying the severity of microangiopathy. Summary: This study provides a new therapeutic strategy for diabetic neuropathy, by demonstrating CD40 as a key mediator of microangiopathy leading to HIF-1α expression in endothelial cells.
Multivalency Increases the Binding Strength of RGD Peptidomimetic‐Paclitaxel Conjugates to Integrin αVβ3

Abstract This work reports the synthesis of three multimeric RGD peptidomimetic‐paclitaxel conjugates featuring a number of αVβ3 integrin ligands ranging from 2 to 4. These constructs were assembled by conjugation of the integrin αVβ3 ligand cyclo[DKP‐RGD]‐CH2NH2 with paclitaxel via a 2′‐carbamate with a self‐immolative spacer, the lysosomally cleavable Val‐Ala dipeptide linker, a multimeric scaffold, a triazole linkage, and finally a PEG spacer. Two monomeric conjugates were also synthesized as reference compounds. Remarkably, the new multimeric conjugates showed a binding affinity for the purified integrin αVβ3 receptor that increased with the number of integrin ligands (reaching a minimum IC50 value of 1.2 nm for the trimeric), thus demonstrating that multivalency is an effective strategy to strengthen the ligand–target interactions.