Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of Regulatory T Cells Is Increased in Peripheral Blood and Tumor Microenvironment of Patients with Pancreas or Breast Adenocarcinoma1

Regulatory T cells (Treg) that prevent autoimmune diseases by suppression of self-reactive T cells may also suppress the immune response against cancer. In mice, depletion of Treg by Ab therapy leads to more efficient tumor rejection. Treg-mediated suppression of antitumor immune responses may partly explain the poor clinical response to vaccine-based immunotherapy for human cancer. In this study, we measured the prevalence of Treg that coexpress CD4 and CD25 in the PBLs, tumor-infiltrating lymphocytes, and regional lymph node lymphocytes from 65 patients with either pancreas or breast cancer. In breast cancer patients (n = 35), pancreas cancer patients (n = 30), and normal donors (n = 35), the prevalence of Treg were 16.6% (SE 1.22), 13.2% (SE 1.13), and 8.6% (SE 0.71) of the total CD4+ cells, respectively. The prevalence of Treg were significantly higher in breast cancer patients (p < 0.01) and pancreas cancer patients (p < 0.01) when compared with normal donors. In tumor-infiltrating lymphocytes and lymph node lymphocytes, the Treg prevalence were 20.2% (SE 3.93) and 20.1% (SE 4.3), respectively. Treg constitutively coexpressed CTLA-4 and CD45RO markers, and secreted TGF-β and IL-10 but did not secrete IFN-γ. When cocultured with activated CD8+ cells or CD4+25− cells, Treg potently suppressed their proliferation and secretion of IFN-γ. We conclude that the prevalence of Treg is increased in the peripheral blood as well as in the tumor microenvironment of patients with invasive breast or pancreas cancers. These Treg may mitigate the immune response against cancer, and may partly explain the poor immune response against tumor Ags.
The Effect of Strategic Orientation on Organizational Performance: The Mediating Role of Innovation

Survival in today’s dynamic environment requires organizations to have superior performance compared to competitors. In order to achieve this superior performance, this study aimed to examine the effect of both strategic orientation and innovation on organizational performance. It also examined whether innovation acted as a mediator between strategic orientation and organizational performance. Data were gathered from the three telecommunication companies that exist in Jordan. The data were then analysed using Structural Equation Modelling (SEM) and the results revealed that strategic orientation had a significant effect on innovation but not on organizational performance. It was also found that innovation significantly affected organizational performance. Finally, the results indicated that innovation mediated the path between strategic orientation and organizational performance, but only partially.
Expression dynamics, relationships, and transcriptional regulations of diverse transcripts in mouse spermatogenic cells

ABSTRACT Among all tissues of the metazoa, the transcritpome of testis displays the highest diversity and specificity. However, its composition and dynamics during spermatogenesis have not been fully understood. Here, we have identified 20,639 message RNAs (mRNAs), 7,168 long non-coding RNAs (lncRNAs) and 15,101 circular RNAs (circRNAs) in mouse spermatogenic cells, and found many of them were specifically expressed in testes. lncRNAs are significantly more testis-specific than mRNAs. At all stages, mRNAs are generally more abundant than lncRNAs, and linear transcripts are more abundant than circRNAs. We showed that the productions of circRNAs and piRNAs were highly regulated instead of random processes. Based on the results of a small-scale functional screening experiment using cultured mouse spermatogonial stem cells, many evolutionarily conserved lncRNAs are likely to play roles in spermatogenesis. Typical classes of transcription factor binding sites are enriched in the promoters of testis-specific m/lncRNA genes. Target genes of CREM and RFX2, 2 key TFs for spermatogenesis, were further validated by using ChIP-chip assays and RNA-seq on RFX2-knockout spermatogenic cells. Our results contribute to the current understanding of the transcriptomic complexity of spermatogenic cells and provide a valuable resource from which many candidate genes may be selected for further functional studies.
Exogenous Free Ubiquitin Enhances Lily Pollen Tube Adhesion to an in Vitro Stylar Matrix and May Facilitate Endocytosis of SCA1[W]

Pollen tube adhesion and guidance on extracellular matrices within the pistil are essential processes that convey the pollen tube cell and the sperm cells to the ovule. In this study, we purified an additional molecule from the pistil that enhances pollen tube adhesion when combined with the SCA (stigma/stylar cysteine-rich adhesin)/pectin matrix in our in vitro assay. The enhancer of adhesion was identified as free ubiquitin (Ub). This was confirmed by use of bovine Ub as a substitute for lily (Lilium longiflorum Thunb.) stigma Ub. To study the interaction of SCA and Ub with the lily pollen tube, we labeled both proteins with biotin. We observed uptake of biotin-labeled SCA and Ub into the pollen tube cells in vitro using confocal microscopy. For SCA, a strong signal occurred first at the tip of the pollen tube, suggestive of an endocytosis event, and then progressively throughout the tube cytoplasm. SCA was also localized inside the in vivo pollen tube using immunogold electron microscopy and found to be present in endosomes, multivesicular bodies, and vacuoles, all known to be endocytic compartments. It was also confirmed that SCA is endocytosed in the in vitro adhesion assay. Internalization of SCA was increased in pollen tubes treated with exogenous Ub compared to those without Ub, suggesting that Ub may facilitate SCA endocytosis. These results show that Ub can act as an enhancer of pollen tube adhesion in vitro and that it is taken up into the pollen tube as is SCA. The Ub machinery may play a role in pollen tube adhesion and guidance in lily.
Patient-reported autonomic symptoms in Parkinson disease

Objective: There is a wide range of autonomic symptoms (AS) in Parkinson disease (PD), but the full spectrum has never been evaluated with a validated instrument and in comparison with control subjects. In this study a reliable and valid instrument, the SCOPA–AUT, was used to evaluate the occurrence of AS in a large cohort of patients with PD and control subjects and to assess the relations with demographic, disease-related, and clinical variables. Methods: A cohort of 420 patients with PD was evaluated for the occurrence of AS, motor and nonmotor symptoms, as well as for demographic and disease-related characteristics. Results were compared with those of 150 control subjects. Associations between AS and demographic and clinical characteristics were also studied. Results: For all autonomic domains, patients with PD reported more symptoms compared to control subjects, with the greatest differences in the gastrointestinal and urinary domain. Higher age, greater disease severity, and higher doses of dopaminergic medication were related to more autonomic problems. Autonomic symptom severity was associated with more motor dysfunction, depressive symptoms, cognitive dysfunction, psychiatric complications, nighttime sleep disturbances, and excessive daytime sleepiness (all p values < 0.01). Conclusions: Autonomic symptoms (AS) are an important feature of Parkinson disease (PD) and increase with age, disease severity, and medication use. The prominent presence of AS warrants increased clinical awareness and highlights the need for efficacious therapies for the wide spectrum of problems related to this domain of PD.
The Association Between Long-Term Exposure to Particulate Matter and Incidence of Hypertension Among Chinese Elderly: A Retrospective Cohort Study

Background and Objectives: Studies that investigate the links between particulate matter ≤2. 5 μm (PM2.5) and hypertension among the elderly population, especially those including aged over 80 years, are limited. Therefore, we aimed to examine the association between PM2.5 exposure and the risk of hypertension incidence among Chinese elderly. Methods: This prospective cohort study used 2008, 2011, 2014, and 2018 wave data from a public database, the Chinese Longitudinal Healthy Longevity Survey, a national survey investigating the health of those aged over 65 years in China. We enrolled cohort participants who were free of hypertension at baseline (2008) from 706 counties (districts) and followed up in the 2011, 2014, and 2018 survey waves. The annual PM2.5 concentration of 706 counties (districts) units was derived from the Atmospheric Composition Analysis Group database as the exposure variable, and exposure to PM2.5 was defined as 1-year average of PM2.5 concentration before hypertension event occurrence or last interview (only for censoring). A Cox proportional hazards model with penalized spline was used to examine the non-linear association between PM2.5 concentration and hypertension risk. A random-effects Cox proportional hazards model was built to explore the relationship between each 1 μg/m3, 10 μg/m3 and quartile increment in PM2.5 concentration and hypertension incidence after adjusting for confounding variables. The modification effects of the different characteristics of the respondents were also explored. Results: A total of 7,432 participants aged 65–116 years were enrolled at baseline. The median of PM2.5 exposure concentration of all the participants was 52.7 (inter-quartile range, IQR = 29.1) μg/m3. Overall, the non-linear association between PM2.5 and hypertension incidence risk indicated that there was no safe threshold for PM2.5 exposure. The higher PM2.5 exposure, the greater risk for hypertension incidence. Each 1 μg/m3 [adjusted hazard ratio (AHR): 1.01; 95% CI: 1.01–1.02] and 10 μg/m3 (AHR: 1.12; 95% CI: 1.09–1.16) increments in PM2.5, were associated with the incidence of hypertension after adjusting for potential confounding variables. Compared to first quartile (Q1) exposure, the adjusted HRs of hypertension incidence for the Q2, Q3 and Q4 exposure of PM2.5 were 1.31 (95% CI: 1.13–1.51), 1.35 (95% CI: 1.15–1.60), and 1.83 (95% CI: 1.53–2.17), respectively. The effects appear to be stronger among those without a pension, living in a rural setting, and located in central/western regions. Conclusion: We found no safe threshold for PM2.5 exposure related to hypertension risk, and more rigorous approaches for PM2.5 control were needed. The elderly without a pension, living in rural and setting in the central/western regions may be more vulnerable to the effects of PM2.5 exposure.
Class of antiretroviral drugs and the risk of myocardial infarction.

BACKGROUND We have previously demonstrated an association between combination antiretroviral therapy and the risk of myocardial infarction. It is not clear whether this association differs according to the class of antiretroviral drugs. We conducted a study to investigate the association of cumulative exposure to protease inhibitors and nonnucleoside reverse-transcriptase inhibitors with the risk of myocardial infarction. METHODS We analyzed data collected through February 2005 from our prospective observational study of 23,437 patients infected with the human immunodeficiency virus. The incidence rates of myocardial infarction during the follow-up period were calculated, and the associations between myocardial infarction and exposure to protease inhibitors or nonnucleoside reverse-transcriptase inhibitors were determined. RESULTS Three hundred forty-five patients had a myocardial infarction during 94,469 person-years of observation. The incidence of myocardial infarction increased from 1.53 per 1000 person-years in those not exposed to protease inhibitors to 6.01 per 1000 person-years in those exposed to protease inhibitors for more than 6 years. After adjustment for exposure to the other drug class and established cardiovascular risk factors (excluding lipid levels), the relative rate of myocardial infarction per year of protease-inhibitor exposure was 1.16 (95% confidence interval [CI], 1.10 to 1.23), whereas the relative rate per year of exposure to nonnucleoside reverse-transcriptase inhibitors was 1.05 (95% CI, 0.98 to 1.13). Adjustment for serum lipid levels further reduced the effect of exposure to each drug class to 1.10 (95% CI, 1.04 to 1.18) and 1.00 (95% CI, 0.93 to 1.09), respectively. CONCLUSIONS Increased exposure to protease inhibitors is associated with an increased risk of myocardial infarction, which is partly explained by dyslipidemia. We found no evidence of such an association for nonnucleoside reverse-transcriptase inhibitors; however, the number of person-years of observation for exposure to this class of drug was less than that for exposure to protease inhibitors.
RENAL TRANSPLANT REJECTION: TRANSIENT IMMUNODOMINANCE OF HLA MISMATCHES

Many studies have shown long-term benefits of HLA matching in kidney transplantation. By examining rates of graft loss within consecutive posttransplant intervals, using data from the UK Transplant Service, we show that the long-term benefits of HLA matching are due to reduction of the graft failure rate within five months of transplantation. After 5-months, HLA-A,B,DR matching appears to have little impact on graft loss. We suggest that graft losses after 5 months may be attributable to non-HLA targets.
L-methionine decreases dendritic spine density in mouse frontal cortex

Schizophrenia postmortem brain is characterized by γ aminobutyric acid downregulation and by decreased dendritic spine density in frontal cortex. Protracted L-methionine treatment exacerbates schizophrenia symptoms, and our earlier work (Tremolizzo et al. and Dong et al.) has shown that L-methionine decreases reelin and GAD67 transcription in mice which is prevented by co-administration of valproate. In this study, we observed a decrease in spine density following L-methionine treatment, which was prevented by co-administration of valproate. Together with our earlier findings conducted under the same experimental conditions, we suggest that downregulation of spine density in L-methionine-treated mice may be because of the decreased expression of reelin and that valproate may prevent spine downregulation by inhibiting the methylation induced decrease in reelin.
Different Effect of Ouabain on Interferon Production and Action

Summary Ouabain, which inhibits specifically membrane-bound ATPase activity, also inhibits the establishment of the antiviral state induced by interferon. Once the antiviral state is established, ouabain is in-effective. This inhibitory effect is reversed by adding Na/K ions to the cells. On the contrary, interferon production is unaffected by the same concentrations of ouabain. It is of interest that in such interferon-yielding cells, ouabain decreases the antiviral state.
Medicaid, Private Insurance, and the Availability of Smoking Cessation Interventions in Substance Use Disorder Treatment.

OBJECTIVE Integration of smoking cessation services in substance use disorder treatment would benefit many patients. Although prior studies have identified organizational characteristics associated with delivery of these services, less is known regarding associations between financial factors and the availability of smoking cessation services. This study examined whether reliance on Medicaid and private insurance revenues is associated with the availability of a formal counseling-based smoking cessation program and medications (sustained-release bupropion, varenicline, and nicotine replacement) within U.S. specialty treatment organizations. METHODS Administrators of a national sample of 372 treatment organizations participated in face-to-face structured interviews from October 2011 to December 2013. Participants provided data regarding smoking cessation services, revenue sources, and other organizational characteristics. Multiple imputation was used to address missing data, and models were estimated by using logistic regression with adjustment for clustering of organizations within states. RESULTS Greater reliance on Medicaid revenues was positively associated with the odds of offering counseling-based smoking cessation programs, sustained-release bupropion, varenicline, and nicotine replacement. For example, a 10-percentage point increase in Medicaid revenues was associated with a 12% increase in the odds of offering a smoking cessation program. Reliance on private insurance revenues was positively associated with the odds of offering the three medications. CONCLUSIONS The findings point to future potential increases in the availability of smoking cessation services in the context of expanding insurance coverage under health care reform. Longitudinal research will be needed to examine whether this impact is realized.
The Port‐Vendres 4 Shipwreck Cargo: evidence of the Roman wine trade in the western Mediterranean

The Port‐Vendres 4 shipwreck is evidence of coastal export trade between Hispania Citerior and Narbonne in 40/30 BC. The cargo is made up of a particular assemblage of Roman wine amphoras (Pascual 1, Dressel 1B and Lamboglia 2) destined for Gallic markets. Archaeological and archaeometric analyses conducted on a selection of the amphoras allowed the provenance of the cargo to be identified as Hispania Citerior and the central‐southern Tyrrhenian coast of Italy. Iluro and/or Baetulo are proposed as the ports of departure, enabling the reconstruction of the trade route and the historical and economic significance of this shipwreck.
Aggression and violence between siblings.

Two theoretical models are discussed as explanations of why verbal and physical aggression between youthful siblings is so frequent. The sibling rivalry model suggests that aggression between siblings reflects jealousy and nonrealistic conflict. A realistic conflict model, on the other hand, suggests that sibling conflicts arise over tangible goods and the performance of disvalued tasks because proprietary rights and the division of labor within the household are often unclear. These conflicts are likely to become overt if interventionz from parents is anticipated because then younger siblings are willing to fight their more powerfil older siblings. This suggests that siblings fight less when parents take a laissez-jiaire approach because the younger sibling is forced to submit. Recall data collectedfrom college students provide support for the realistic cotnflict model but not the sibling rivalry model.
Tissue tropisms in group A Streptococcus: what virulence factors distinguish pharyngitis from impetigo strains?

Purpose of review Group A streptococci (GAS) are a common cause of pharyngitis and impetigo, and distinct throat strains and skin strains have been long recognized. This review aims to describe recent advances in molecular differences between throat and skin strains, and the pathogenic mechanisms used by virulence factors that may distinguish between these two groups. Recent findings Recent findings include a new typing scheme for GAS strains based on sequence clusters of genes encoding the entire surface-exposed portion of M protein; correlations between emm-based typing schemes, clinical disease and surface adhesins; covalent bond formation mediated by GAS pili and other adhesins in binding to host ligands; a key role for superantigens in oropharyngeal infection via binding major histocompatibility complex class II antigen; and migration of GAS-specific Th17 cells from the upper respiratory tract to the brain, which may be relevant to autoimmune sequelae. Summary The gap between molecular markers of disease (correlation) and virulence mechanisms (causation) in the establishment of tissue tropisms for GAS infection currently remains wide, but the gap also continues to narrow. Whole genome sequencing combined with mutant construction and improvements in animal models for oropharyngeal infection by GAS may help pave the way for new discoveries.
Mass media interventions: effects on health services utilisation.

BACKGROUND The mass media frequently cover health related topics, are the leading source of information about important health issues, and are targeted by those who aim to influence the behaviour of health professionals and patients. OBJECTIVES To assess the effects of mass media on the utilisation of health services. SEARCH STRATEGY We searched the Cochrane Effective Practice and Organisation of Care Group specialised register, MEDLINE, EMBASE, Eric, PsycLit, and reference lists of articles. We hand searched the journals Communication Research (February 1987 to August 1996), European Journal of Communication (1986 to 1994), Journal of Communication (winter 1986 to summer 1996), Communication Theory (February 1991 to August 1996), Critical Studies in Mass Communication (March 1984 to March 1995) and Journalism Quarterly (1986 to summer 1996). SELECTION CRITERIA Randomised trials, controlled clinical trials, controlled before-and-after studies and interrupted time series analyses of mass media interventions. The participants were health care professionals, patients and the general public. DATA COLLECTION AND ANALYSIS Two reviewers independently extracted data and assessed study quality. MAIN RESULTS Seventeen studies were included. All used interrupted time series designs. Fourteen evaluated the impact of formal mass media campaigns, and three of media coverage of health related issues. The overall methodological quality was variable. Six studies did not perform any statistical analysis, and seven used inappropriate statistical tests (ie not taking into account the effect of time trend). All of the studies apart from one concluded that mass media was effective. These positive findings were confirmed by our re-analysis in seven studies. The direction of effect was consistent across studies towards the expected change. The pooled effect sizes for studies assessing the impact of mass media on similar aspects of care revealed an effect upon the utilisation of health services that could not be explained by chance alone, ranging from -1.96 (95%CI -1. 19 to -2.73) for campaigns promoting immunisation programmes, to -1. 12 (95%CI -0.49 to -2.36) for those concerning cancer screening. REVIEWER'S CONCLUSIONS Despite the limited information about key aspects of mass media interventions and the poor quality of the available primary research, there is evidence that these channels of communication may have an important role in influencing the use of health care interventions. Those engaged in promoting better uptake of research information in clinical practice should consider mass media as one of the tools that may encourage the use of effective services and discourage those of unproven effectiveness.