Miracle-dz/UniFAR-FTUs huggingface dataset:
Knockdown of PKM2 and GLS1 expression can significantly reverse oxaliplatin-resistance in colorectal cancer cells

Clinical treatment for colorectal cancer (CRC) thus far encounters a huge challenge due to oxaliplatin-resistance. As crucial rate-limiting enzymes in aerobic glycolysis and glutaminolysis, pyruvate kinase M2 type (PKM2) and kidney-type glutaminase (GLS1) are proposed to carry important implications in colorectal carcinogenesis and drug-resistance. This study aimed to explore the possible association of oxaliplatin-resistance with aerobic glycolysis/glutaminolysis indexed by PKM2/GLS1 expression. PKM2 and GLS1 expression was quantified by polymerase chain reaction (PCR) and Western blot techniques in CRC cell lines. The abilities of cell formation, kinetics, migration, invasion, survival and apoptosis, as well as permeability glycoprotein (Pgp) expression were inspected before and after knocking-down PKM2/GLS1 expression. In addition, the influence of knocking-down PKM2/GLS1 expression was evaluated in vivo. Differentiated PKM2 and GLS1 expression in both THC8307 and THC8307/Oxa cell lines was identified. In the THC8307 cell line, PKM2 and GLS1 can accelerate malignant behaviors, increase oxaliplatin-resistance, upregulate Pgp expression, and inhibit cell apoptosis. Contrastingly in the THC8307/Oxa cell line, knockdown of PKM2/GLS1 expression can restrain malignant behaviors, reestablish oxaliplatin-sensitivity, downregulate Pgp expression, and induce cell apoptosis. In xenograft, knockdown of PKM2/GLS1 expression can significantly inhibit tumor growth, reduce Pgp expression, and increase tumor apoptosis. Taken together, the present findings enriched our knowledge by demonstrating a significant association of PKM2 and GLS1 with oxaliplatin-resistance in CRC. We further propose that knockdown of PKM2/GLS1 expression may constitute a novel therapeutic strategy toward effective treatment for CRC.
Individual vocal production in a sperm whale (Physeter macrocephalus) social unit

The vocal repertoires of group-living animals may communicate individual or group identity. Female and juvenile sperm whales live in long-term social units that can be assigned to vocal clans based on the pattern of clicks in coda vocalizations. An unusual set of circumstances allowed us to record the vocalizations of photo-identified individuals within a single social unit over a 41 d period. Using click interpulse intervals, we were able to assign codas to individuals and investigate coda production at the individual level within a social unit for the first time. Adult females in the unit vocalized at approximately equal rates. A calf and juvenile, both male, vocalized less often than the adult females. Repertoires were indistinguishable for all unit members apart from a mother and her calf, which possessed significantly different repertoires—even from one another. We suggest that similarity among the coda repertoires of most unit members indicates a function in advertising unit identity. In contrast, the distinctive repertoires of the calf and its mother may facilitate reunions between these whales. We hypothesize that sperm whales may be able to vary their vocal repertoires as their reproductive status alters the trade-off between the benefits of individual and group identification.
Comparison of Illumina and 454 Deep Sequencing in Participants Failing Raltegravir-Based Antiretroviral Therapy

Background The impact of raltegravir-resistant HIV-1 minority variants (MVs) on raltegravir treatment failure is unknown. Illumina sequencing offers greater throughput than 454, but sequence analysis tools for viral sequencing are needed. We evaluated Illumina and 454 for the detection of HIV-1 raltegravir-resistant MVs. Methods A5262 was a single-arm study of raltegravir and darunavir/ritonavir in treatment-naïve patients. Pre-treatment plasma was obtained from 5 participants with raltegravir resistance at the time of virologic failure. A control library was created by pooling integrase clones at predefined proportions. Multiplexed sequencing was performed with Illumina and 454 platforms at comparable costs. Illumina sequence analysis was performed with the novel snp-assess tool and 454 sequencing was analyzed with V-Phaser. Results Illumina sequencing resulted in significantly higher sequence coverage and a 0.095% limit of detection. Illumina accurately detected all MVs in the control library at ≥0.5% and 7/10 MVs expected at 0.1%. 454 sequencing failed to detect any MVs at 0.1% with 5 false positive calls. For MVs detected in the patient samples by both 454 and Illumina, the correlation in the detected variant frequencies was high (R2 = 0.92, P<0.001). Illumina sequencing detected 2.4-fold greater nucleotide MVs and 2.9-fold greater amino acid MVs compared to 454. The only raltegravir-resistant MV detected was an E138K mutation in one participant by Illumina sequencing, but not by 454. Conclusions In participants of A5262 with raltegravir resistance at virologic failure, baseline raltegravir-resistant MVs were rarely detected. At comparable costs to 454 sequencing, Illumina demonstrated greater depth of coverage, increased sensitivity for detecting HIV MVs, and fewer false positive variant calls.
Evidence-based systematic review: effects of nonspeech oral motor exercises on speech.

PURPOSE The purpose of this systematic review was to examine the current evidence for the use of oral motor exercises (OMEs) on speech (i.e., speech physiology, speech production, and functional speech outcomes) as a means of supporting further research and clinicians' use of evidence-based practice. METHOD The peer-reviewed literature from 1960 to 2007 was searched for articles examining the use of OMEs to affect speech physiology, production, or functional outcomes (i.e., intelligibility). Articles that met selection criteria were appraised by 2 reviewers and vetted by a 3rd for methodological quality, then characterized as efficacy or exploratory studies. RESULTS Fifteen studies met inclusion criteria; of these, 8 included data relevant to the effects of OMEs on speech physiology, 8 on speech production, and 8 on functional speech outcomes. Considerable variation was noted in the participants, interventions, and treatment schedules. The critical appraisals identified significant weaknesses in almost all studies. CONCLUSIONS Insufficient evidence to support or refute the use of OMEs to produce effects on speech was found in the research literature. Discussion is largely confined to a consideration of the need for more well-designed studies using well-described participant groups and alternative bases for evidence-based practice.
Factors Associated with Male Partner Involvement in Programs for the Prevention of Mother-to-Child Transmission of HIV in Rural South Africa

Male partner involvement (MPI) can contribute to the success of programs aimed at preventing mother-to-child transmission (PMTCT) of HIV. However, the definition and measures of MPI differ according to context. This study utilized secondary cross-sectional data to investigate the prevalence and determinants of MPI among 463 male partners of HIV-infected pregnant women in rural South Africa. Results indicated that 44.1% of male partners reported involvement in most or all specified male partner involvement activities (i.e., scores of 7 to 9). Descriptive, correlation and multiple linear-regression analyses were conducted. Positive predictors of MPI included relationship status, own HIV status, awareness of female partner’s positive HIV status, female partner’s desire to have more children, having family planning discussions with provider, condom use to prevent HIV and sexually transmitted infections (STIs), and partner reasoning skills. Negative predictors included partner verbal aggression. Overall, although MPI is low, the study underlines important information that could be used to develop interventions aimed at improving maternal and infant health in PMTCT programs in South Africa.
Regulation of alpha 6 beta 1 integrin laminin receptor function by the cytoplasmic domain of the alpha 6 subunit

The alpha 6 beta 1 integrin is expressed on the macrophage surface in an inactive state and requires cellular activation with PMA or cytokines to function as a laminin receptor (Shaw, L. M., J. M. Messier, and A. M. Mercurio. 1990. J. Cell Biol. 110:2167-2174). In the present study, the role of the alpha 6 subunit cytoplasmic domain in alpha 6 beta 1 integrin activation was examined. The use of P388D1 cells, an alpha 6-integrin deficient macrophage cell line, facilitated this analysis because expression of either the alpha 6A or alpha 6B subunit cDNAs restores their activation responsive laminin adhesion (Shaw, L. S., M. Lotz, and A. M. Mercurio. 1993. J. Biol. Chem. 268:11401-11408). A truncated alpha 6 cDNA, alpha 6-delta CYT, was constructed in which the human cytoplasmic domain sequence was deleted after the GFFKR pentapeptide. Expression of this cDNA in P388D1 cells resulted in the surface expression of a chimeric alpha 6-delta CYT beta 1 integrin that was unable to mediate laminin adhesion or increase this adhesion in response to PMA under normal conditions, i.e., in medium that contained physiological concentrations of Ca++ and Mg++. The alpha 6A-delta CYT transfectants adhered to laminin, however, when Ca++/Mg++ was replaced with 150 microM Mn++. We also assessed the role of serine phosphorylation in the regulation of alpha 6A beta 1 integrin function by site-directed mutagenesis of the two serine residues present in the alpha 6A cytoplasmic domain because this domain is phosphorylated on serine residues in response to stimuli that activate the laminin receptor function of alpha 6 A beta 1. Point mutations were introduced in the alpha 6A cDNA that changed either serine residue #1064 (M1) or serine residue #1071 (M2) to alanine residues. In addition, a double mutant (M3) was constructed in which both serine residues were changed to alanine residues. P388D1 transfectants which expressed these serine mutations adhered to laminin in response to PMA to the same extent as cells transfected with wild-type alpha 6A cDNA. These findings provide evidence for a novel mode of integrin regulation that is distinct from that reported for other regulated integrins (O'Toole, T. E., D. Mandelman, J. Forsyth, S. J. Shattil, E. F. Plow, and M. H. Ginsberg. 1991. Science (Wash. DC). 254:845-847. Hibbs, M. L. , H. Xu, S. A. Stacker, and T. A. Springer. 1991. Science (Wash. DC). 251:1611-1613), and they demonstrate that serine phosphorylation of the alpha 6A cytoplasmic domain is not involved in this regulation.
Forecasting Distributional Responses of Limber Pine to Climate Change at Management-Relevant Scales in Rocky Mountain National Park

Resource managers at parks and other protected areas are increasingly expected to factor climate change explicitly into their decision making frameworks. However, most protected areas are small relative to the geographic ranges of species being managed, so forecasts need to consider local adaptation and community dynamics that are correlated with climate and affect distributions inside protected area boundaries. Additionally, niche theory suggests that species' physiological capacities to respond to climate change may be underestimated when forecasts fail to consider the full breadth of climates occupied by the species rangewide. Here, using correlative species distribution models that contrast estimates of climatic sensitivity inferred from the two spatial extents, we quantify the response of limber pine (Pinus flexilis) to climate change in Rocky Mountain National Park (Colorado, USA). Models are trained locally within the park where limber pine is the community dominant tree species, a distinct structural-compositional vegetation class of interest to managers, and also rangewide, as suggested by niche theory. Model forecasts through 2100 under two representative concentration pathways (RCP 4.5 and 8.5 W/m2) show that the distribution of limber pine in the park is expected to move upslope in elevation, but changes in total and core patch area remain highly uncertain. Most of this uncertainty is biological, as magnitudes of projected change are considerably more variable between the two spatial extents used in model training than they are between RCPs, and novel future climates only affect local model predictions associated with RCP 8.5 after 2091. Combined, these results illustrate the importance of accounting for unknowns in species' climatic sensitivities when forecasting distributional scenarios that are used to inform management decisions. We discuss how our results for limber pine may be interpreted in the context of climate change vulnerability and used to help guide adaptive management.
Phylogeny and polymorphism in the long control regions E6, E7, and L1 of HPV Type 56 in women from southwest China

Globally, human papillomavirus (HPV)-56 accounts for a small proportion of all high-risk HPV types; however, HPV-56 is detected at a higher rate in Asia, particularly in southwest China. The present study analyzed polymorphisms, intratypic variants, and genetic variability in the long control regions (LCR), E6, E7, and L1 of HPV-56 (n=75). The LCRs, E6, E7 and L1 were sequenced using a polymerase chain reaction and the sequences were submitted to GenBank. Maximum-likelihood trees were constructed using Kimura's two-parameter model, followed by secondary structure analysis and protein damaging prediction. Additionally, in order to assess the effect of variations in the LCR on putative binding sites for cellular proteins, MATCH server was used. Finally, the selection pressures of the E6-E7 and L1 genes were estimated. A total of 18 point substitutions, a 42-bp deletion and a 19-bp deletion of LCR were identified. Some of those mutations are embedded in the putative binding sites for transcription factors. 18 single nucleotide changes occurred in the E6-E7 sequence, 11/18 were non-synonymous substitutions and 7/18 were synonymous mutations. A total 24 single nucleotide changes were identified in the L1 sequence, 6/24 being non-synonymous mutations and 18/24 synonymous mutations. Selective pressure analysis predicted that the majority of mutations of HPV-56 E6, E7 and L1 were of positive selection. The phylogenetic tree demonstrated that the isolates distributed in two lineages. Data on the prevalence and genetic variation of HPV-56 types in southwest China may aid future studies on viral molecular mechanisms and contribute to future investigations of diagnostic probes and therapeutic vaccines.
Results of the Implementation of a Pilot Model for the Bidirectional Screening and Joint Management of Patients with Pulmonary Tuberculosis and Diabetes Mellitus in Mexico

Background Recently, the World Health Organisation and the International Union Against Tuberculosis and Lung Disease published a Collaborative Framework for the Care and Control of Tuberculosis (TB) and Diabetes (DM) (CFTB/DM) proposing bidirectional screening and joint management. Objective To evaluate the feasibility and effectiveness of the CFTB/DM in Mexico. Design. Prospective observational cohort. Setting. 15 primary care units in 5 states in Mexico. Participants: Patients aged ≥20 years diagnosed with DM or pulmonary TB who sought care at participating clinics. Intervention: The WHO/Union CFTB/DM was adapted and implemented according to official Mexican guidelines. We recruited participants from July 2012 to April 2013 and followed up until March 2014. Bidirectional screening was performed. Patients diagnosed with TB and DM were invited to receive TB treatment under joint management. Main outcome measures. Diagnoses of TB among DM, of DM among TB, and treatment outcomes among patients with DM and TB. Results Of 783 DM patients, 11 (1.4%) were unaware of their TB. Of 361 TB patients, 16 (4.4%) were unaware of their DM. 95 TB/DM patients accepted to be treated under joint management, of whom 85 (89.5%) successfully completed treatment. Multiple linear regression analysis with change in HbA1c and random capillary glucose as dependent variables revealed significant decrease with time (regression coefficients (β) = −0.660, (95% confidence interval (CI), −0.96 to −0.35); and β = −1.889 (95% CI, −2.77 to −1.01, respectively)) adjusting by sex, age and having been treated for a previous TB episode. Patients treated under joint management were more likely to experience treatment success than patients treated under routine DM and TB programs as compared to historical (adjusted OR (aOR), 2.8, 95%CI 1.28–6.13) and same period (aOR 2.37, 95% CI 1.13–4.96) comparison groups. Conclusions Joint management of TB and DM is feasible and appears to improve clinical outcomes.
Effect of nano-SiO_2 on the properties of cement-based decorative mortars

The properties of cement-based decorative mortars modified with nano-SiO2 were studied and microstructure of mortars was analyzed with environment scanning electron microscope.The results indicated that the compressive strength,flexural strength and tensile bond strength of mortars with 1.5%～2.5% nano-SiO2 were significantly improved(max growth rate all over 60%);the capillary water absorption of mortars with 0.5%～1.5% nano-SiO2 were significantly reduced by 40%;the resistance to efflorescence of mortars with 1.0%～3.0% nano-SiO2 were significantly improved;the resistance to stain of mortars with 0.5%～3.0% nano-SiO2 were better than the plain mortar.Nano-SiO2 can digest the pore structure of the mortar and reduce its Ca(OH)2 crystal size,making the microstructure of mortar more compact.
The Anti-inflammatory and Matrix Restorative Mechanisms of Platelet-Rich Plasma in Osteoarthritis

Background: Intra-articular (IA) treatment with platelet-rich plasma (PRP) for osteoarthritis (OA) results in improved patient-reported pain and function scores. Purpose: To measure the effects of PRP and high molecular weight hyaluronan (HA) on the expression of anabolic and catabolic genes and on the secretion of nociceptive and inflammatory mediators from OA cartilage and synoviocytes. Study Design: Controlled laboratory study. Methods: Synovium and cartilage harvested from patients undergoing total knee arthroplasty were co-cultured with media of PRP or HA. Tumor necrosis factor–α (TNF-α), interleukin-6 (IL-6), and IL-1β were measured in the media by enzyme-linked immunosorbent assay. Hyaluronan synthase–2 (HAS-2), matrix metalloproteinase–1 (MMP-1), MMP-13, and TNF-α genes were measured in synoviocytes by reverse transcription polymerase chain reaction (RT-PCR). Collagen type I α1 (COL1A1), COL2A1, aggrecan (ACAN), and MMP-13 gene expression were measured in cartilage by quantitative RT-PCR. Results: Media TNF-α concentration was decreased in PRP and HA compared with control cultures (PRP = 6.94 pg/mL, HA = 6.39 pg/mL, control = 9.70 pg/mL; P ≤ .05). Media IL-6 concentration was decreased in HA compared with PRP and control (HA = 5027 pg/mL, PRP = 5899 pg/mL, control = 5613 pg/mL; P ≤ .05). Media IL-1β was below detectable concentrations (<0.1 pg/mL) in all samples. Synoviocyte MMP-13 expression was decreased in PRP compared with HA and control (PRP = 10.1, HA = 12.8, control = 13.5; P ≤ .05). Synoviocyte HAS-2 expression was increased in PRP compared with HA and control (PRP = 12.1, HA = 9.8, control = 8.7; P ≤ .05). Cartilage ACAN expression was increased in PRP compared with HA, but neither was different from control (PRP = 8.8, HA = 7.7, control = 7.6; P ≤ .05); COL1A1 expression was increased in HA compared with PRP, but neither was different from control (PRP = 14.9, HA = 13.5, control = 12.9; P ≤ .05). Neither platelet nor leukocyte concentration had a significant effect on outcome measurements (gene or protein expression data) in cartilage or synoviocytes (P > .05). Conclusion: Both PRP and HA treatments of OA joint tissues result in decreased catabolism, but PRP treatment also resulted in a significant reduction of MMP-13, an increase in HAS-2 expression in synoviocytes, and an increase in cartilage synthetic activity compared with HA. These results indicate that PRP acts to stimulate endogenous HA production and decrease cartilage catabolism. Platelet-rich plasma showed similar effects as HA in the suppression of inflammatory mediator concentration and expression of their genes in synoviocytes and cartilage. Clinical Relevance: The antinociceptive and anti-inflammatory activities of PRP support its use in OA joints to reduce pain and modulate the disease process. This study supports further clinical investigations of IA PRP for the treatment of OA.
Bernoulli Robust dimension-free Gram operator estimates

In this paper we investigate the question of estimating the Gram operator by a robust estimator from an i.i. d. sample in a separable Hilbert space and we present uniform bounds that hold under weak moment assumptions. The approach consists in first obtaining non-asymptotic dimension-free bounds in finite-dimensional spaces using some PAC-Bayesian inequalities related to Gaussian perturbations of the parameter and then in generalizing the results in a separable Hilbert space. We show both from a theoretical point of view and with the help of some simulations that such a robust estimator improves the behavior of the classical empirical one in the case of heavy tail data distributions.
Ethanol extract of Allium fistulosum inhibits development of non-alcoholic fatty liver disease

BACKGROUND/OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is closely associated with metabolic syndrome. In the present study, we observed the effect of ethanol extract of Allium fistulosum (EAF) on NAFLD and have suggested the possibility of using EAF as a natural product for application in the development of a treatment for NAFLD. MATERIALS/METHODS The preventive effect on hepatic lipid accumulation was estimated by using an oleic acid (OA)-induced NAFLD model in vitro and a Western diet (high-fat high-sucrose; WD)-induced obese mouse model. Animals were divided into three groups (n = 7): normal diet group (ND), WD group, and WD plus 1% EAF group. RESULTS EAF reduced OA-stimulated lipid accumulation in HepG2 cells in the absence of cellular cytotoxicity and significantly blocked transcriptional activation of sterol regulatory element-binding protein 1 and fatty acid synthase genes. Subsequently, we investigated these effects in vivo in mice fed either ND or WD in the presence or absence of EAF supplementation. In comparison to the ND controls, the WD-fed mice exhibited increases in body weight, liver weight, epididymal fat weight, and accumulation of fat in hepatocytes, and these effects were significantly attenuated by EAF supplementation. CONCLUSIONS Allium fistulosum attenuates the development of NAFLD, and EAF elicits anti-lipogenic activity in liver. Therefore, EAF represents a promising candidate for use in the development of novel therapeutic drugs or drug combinations for the prevention and treatment of NAFLD.