Miracle-dz/UniFAR-FTUs huggingface dataset:
Humoral and Mucosal Immune Responses to Human Norovirus in the Elderly.

BACKGROUND Most information on mucosal and systemic immune response to norovirus infection is derived from human challenge studies, birth cohort studies, or vaccine trials in healthy adults. However, few data are available on immune responses to norovirus in the elderly. MATERIALS To study the mucosal and systemic immune response against norovirus, 43 long-term care facilities (LTCFs) were enrolled prospectively in 2010-2014. Baseline saliva samples were collected from 17 facilities and from cases and controls up to day 84 from 10 outbreaks as well as acute and convalescent sera. RESULTS Norovirus-specific IgA levels in baseline saliva samples were low and increased in both symptomatic patients and asymptomatic shedders at day 5 after onset. ROC analysis correctly assigned prior norovirus infection in 23 (92%) of 25 participants. Cases and asymptomatic shedders showed seroconversion for IgG (80%), IgA (78%) and blockade antibodies (87%). Salivary IgA levels strongly correlated with increased convalescent serum IgA titers and blockade antibodies. CONCLUSIONS Salivary IgA levels strongly correlated with serum IgA titers and blockade antibodies and remained elevated 3 months after a norovirus outbreak. A single salivary sample collected on day 14 could be used to identify recent infection in a suspected outbreak or to monitor population salivary IgA.
Intravascular lithotripsy to treat an underexpanded coronary stent: 4‐Month angiographic and OCT follow‐up

We report the case of a 79‐year‐old man with stable angina who underwent percutaneous coronary intervention to a severe and calcified left circumflex lesion. Despite extensive preparation of the lesion with high‐pressure balloon predilatation and rotablation, the implanted stent was grossly underexpanded and failed to respond to high‐pressure balloon postdilatation. The patient was readmitted 6 weeks later for intravascular lithotripsy that resulted in excellent stent expansion. Coronary angiography with optical coherence tomography 4 months later revealed sustained acute lumen gain with no evidence of stent recoil or in‐stent restenosis.
Inflammation and Endothelial Function Relevant Genetic Polymorphisms and Carotid Plaque in Chinese Population

Aim: To examine the association between carotid plaque and variants in genes involved in inflammation and endothelial function. Methods: This was a multicenter, cross-sectional survey in southwestern China. The residents aged ≥ 40 years volunteered to participate in the face-to-face survey in eight communities. A total of 2,377 subjects with high stroke risk were enrolled. Carotid plaque and plaque phenotype were assessed by carotid ultrasound. Genotypes of 19 variants in 10 genes related to inflammation and endothelial function were examined. Gene-gene interaction was analyzed by generalized multifactor dimensionality reduction (GMDR). Results: Carotid plaques were found in 852 (35.8%) subjects, and 454 (53.3%) had stable plaques, whereas 398 (46.7%) had vulnerable plaques. PPARA rs4253655, HABP2 rs7923349, and IL1A rs1609682 were associated with the presence of carotid plaque, and NOS2A rs2297518 and PPARA rs4253655 were associated with vulnerable plaque in univariate analysis. The GMDR analysis revealed that there was a significant gene–gene interaction among HABP2 rs7923349, ITGA2 rs1991013, IL1A rs1609682, and NOS2A rs8081248, and the high-risk interactive genotype among the four variants was independently associated with a higher risk of carotid vulnerable plaque after adjusting the covariates (OR, 2.86, 95% CI: 1.32–7.13, P = 0.003). Conclusion: The prevalence of carotid plaque was very high in the high-risk stroke population in southwestern China. Variants in genes involved in the endothelial function and inflammation were associated with the carotid plaque. The high-risk interactive genotype among rs7923349, rs1991013, rs1609682, and rs8081248 was independently associated with a higher risk of vulnerable plaque.
Curcumin derivatives as photosensitizers in photodynamic therapy: photophysical properties and in vitro studies with prostate cancer cells

Photodynamic therapy (PDT) is a minimally invasive approach to treat various forms of cancer, based on the ability of certain non-toxic molecules (photosensitizers) to generate reactive oxygen species (ROS) after excitation by light of a certain wavelength and eventually induce strong phototoxic reactions against malignant cells and other pathogens. Curcumin is one of the most extensively investigated phytochemcals with a wide range of therapeutic properties and has been shown to induce strong photocytotoxic effects in micromolar concentrations against a variety of cancer cell lines. Curcumin (1) is comparatively evaluated with the naturally occurring bisdemethoxy Curcumin (2) , which lacks the two methoxy groups, as well as two newly synthesized curcuminoids, the cinnamaldehyde derivative (3) and the dimethylamino one (4) , designed to increase the absorption maximum and hence the tissue penetration. The synthetic curcuminoids were successfully synthesized in sufficient amounts and their photophysical properties such as absorption, fluorescence, photobleaching and free radical generation were investigated Compound 4 exhibited a significant increase in peak absorption (497 nm) and strong fluorescent emission signals were recorded for all curcuminoids. Photobleaching of 4 was comparable to 1 whereas 2 and 3 showed more extended photobleaching but much higher ROS production in very short irradiation times. Compounds 2 and 4 exhibited specific intracellular localization. After dark and light cytotoxicity experiments against LNCaP prostate cancer cell line for all curcuminoids, concentration of 3 µM and irradiance of 6 mW cm^−2 were selected for the PDT application which resulted in remarkable results with very short LD_50. Curcuminoids 2 and 4 exhibited a significant dose-dependent PDT effect. The biphasic doseresponse photodynamic effect observed for 1 and 3 may provide a strategy against prolonged and sustained photosensitivity.
Activities on acute mental health inpatient wards: a narrative synthesis of the service users' perspective.

BACKGROUND Concern about the lack of activities on mental health inpatient wards is long-standing with reports consistently finding that service users receive insufficient access to a range of activities and report high levels of boredom. There is recognition that little is known about what services users want when admitted to inpatient wards. AIM This review seeks to understand service users' experiences and views in relation to the provision and availability of activities, and to explore the perceived benefits and barriers to service users. METHODS We searched multiple databases (Scopus, Medline, CINHAL, PsychINFO, and Embase) for studies that evaluated activities on acute adult inpatient mental health wards. We identified 12 papers across a range of methodological designs from which the narrative synthesis has been analysed. RESULTS Findings show that the provision of activities is unsatisfactory for many service users which in turn is relates to increased boredom that has a negative impact on service users' wellbeing. We explore the benefits and barriers to engagement, providing an insight into the aspects that make an activity important. CONCLUSION There are few studies exploring the needs of service users regarding activity provision, therefore there is limited knowledge about what is meaningful for individuals.
Differential expression of BMP/SMAD signaling and ovarian-associated genes in the granulosa cells of FecB introgressed GMM sheep

ABSTRACT The present study was conducted to analyze the mRNA expression of the BMP/SMAD signaling and steroidogenesis associated genes in the granulosa cells (GCs) of newly developed Booroola homozygous carrier GMM (FecBBB ) and non-carrier GMM (FecB++ ) ewes through qRT-PCR. Results showed that the expression of BMP2 (P < 0.05) and BMP6 (P < 0.01) was significantly higher in the GCs of the homozygous carrier GMM (FecBBB ) than the non-carrier GMM (FecB++ ) ewes, while the expression of BMP4 was significantly higher (P < 0.001) in the GCs of non-carrier GMM (FecB++ ) than the homozygous carrier GMM (FecBBB ). In comparison, the expression of TGFβR1, BMPR1A, BMPR1B, and BMPRII was not significantly different between GCs of the homozygous carrier GMM (FecBBB ) and non-carrier GMM (FecB++ ) ewes. Similarly, the expression of SMAD1, SMAD2, SMAD3, SMAD4, and SMAD5 was not significantly different between GCs of homozygous carrier GMM (FecBBB ) and non-carrier GMM (FecB++ ). Further, expression of the INHIBIN, P4R, CYP11A1, and 3βHSD1 genes were not significantly different among the GCs of homozygous carrier GMM (FecBBB ) and non-carrier GMM (FecB++ ), while the expression of StAR was significantly higher (P < 0.01) in the GCs of homozygous carrier GMM (FecBBB ) than that of GCs of non-carrier GMM (FecB++ ) ewes. It is concluded that the FecB mutation significantly up-regulates the expression of BMP2, BMP6, and StAR genes and down-regulate the expression of BMP2 in granulosa cells of newly developed GMM ewes. Abbreviations BMP: Bone morphogenetic protein; TGFβ: Transforming growth factor-beta; SMAD: Fusion of Caenorhabditis elegans Sma genes and the Drosophila Mad, Mothers against decapentaplegic; GCs: Granulosa cells; GMM: Garole x Malpura x Malpura; FecB: Booroola fecundity; BMPR: Bone morphogenetic protein receptor; CYP11A1: Cytochrome P450 family 11 subfamily A member 1; StAR (Steroidogenic acute regulatory protein); 3βHSD1: 3 Beta-hydroxysteroid dehydrogenase; IGF: Insulin-like growth factor; ActR2: Activin receptor 2; ACVR1: Activin A receptor, type I; ACVR2: Activin A receptor, type II; ACVRL1: Activin A receptor like type 1; ACVR1B: Activin A receptor type 1B; ACVR1C: Activin A receptor type 1C; RFLP-PCR: Restriction fragment length polymorphism-polymerase chain reaction; qRT-PCR: Quantitative real-time PCR; ANOVA: Analysis of variance; P4R: Progesterone receptor: AMH: Anti mullerian hormone; RT-PCR: Reverse transcriptase-polymerase chain reaction; ER: Estrogen receptor; FSHR: Follicle stimulating hormone receptor.
Losartan ameliorates ovarian ischaemia/reperfusion injury in rats: an experimental study

Abstract This study aimed to investigate the protective and antioxidant role of losartan in ovarian ischaemia and ischaemia/reperfusion injury in an experimental ovarian torsion model. Thirty adult female rats were used. Rats were separated randomly into five groups; Group 1: sham group (abdominal wall was only opened and closed), Group 2: torsion group with 3-hour ischaemia using atraumatic vascular clips. Group 3: torsion + losartan group with 3-hour ischaemia 30 minutes after the administration of 40 mg/kg of losartan via oral gavage. Group 4: torsion-detorsion group with 3-hour ischaemia and 3-hour reperfusion (vascular clips were removed). Group 5: torsion-detorsion + losartan group with 3-hour ischaemia followed by administration of 40 mg/kg of losartan 30 minutes prior to a 3-hour detorsion/reperfusion. Ovarian tissue damage was scored by histopathological analysis. Ovarian tissue malondialdehyde (MDA) and plasma pentraxin 3 (PTX 3) levels were measured biochemically. In comparison with the sham group, both the torsion and torsion-detorsion groups had significantly higher scores for follicular degeneration, vascular congestion, oedema, haemorrhage, and leukocyte infiltration (p < .05). The aforementioned parameters significantly decreased in the torsion-detorsion + losartan group (p < .01) compared to those in the torsion-detorsion group. MDA and plasma PTX 3 levels were notably higher both in the torsion and torsion-detorsion groups compared with those in the sham group (p < .01). The current experimental ovarian torsion study suggests a protective role for losartan upon ischaemia and ischaemia/reperfusion injury in rat ovaries. Losartan may be a novel agent for decreasing ovarian ischaemia/reperfusion injury in ovaries. Impact statement What is already known on this subject? Among gynaecological emergencies, the diagnosis of ovarian torsion is highly difficult. A delayed diagnosis may lead to ovarian necrosis and subsequent loss of ovaries if timely surgical intervention is not performed, which is essential for the fertility and protection of ovarian functions in young patients. However, reperfusion of the ischaemic tissue might leads to more serious damage to the tissue than the damage caused by ischaemia. What the results of this study add? This study found that losartan, an Ang II type 1 receptor blocker which has been currently used for regulation of blood pressure, could be used experimentally to alleviate I/R injury in ovary through improving histological parameters, reducing tissue MDA and plasma PTX3 levels. To date, there is no study regarding the usage of losartan for alleviating I/R on ovary due to torsion. What the implications are of these findings for clinical practice and/or further research? Losartan may be suggested to have therapeutic value in patients with ovarian torsion. Further large clinical studies are necessary to prove the beneficial effect of losartan to prevent I/R injury on human ovaries.
A Study of the Association between Polymorphism of MMP-9 Gene and Atherosclerosis and Cerebral Infarction

Aim:To investigate the association between a 1562 C→T mutation of matrix metalloproteinase-9(MMP-9) gene and atherosclerosis and cerebral infarction of Shanxi.Methods:A case-control study for Shanxi Han Chinese subjects was performed.Polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP) was applied to test the MMP-9-1562 C→T polymorphism.Results:In cerebral infarction,frequencies of C/C,C/T,T/T genotype were 83.03%,16.96% and zero.In the normal control,frequencies of C/C,C/T,T/T genotype were 82.14%,17.86% and zero.The frequencies of genotype and allele showed no significant difference between the control group and the cerebral infarction group(P0.05). Conclusion:The C-1562T polymorphism of MMP-9 gene is not related to cerebral infarction in Shanxi Han Chinese subjects.
Age at natural menopause and development of chronic conditions and multimorbidity: results from an Australian prospective cohort.

STUDY QUESTION Is age at natural menopause (ANM) associated with the development of multiple chronic conditions (multimorbidity) in postmenopausal life? SUMMARY ANSWER Women with premature menopause experience increased odds of developing individual chronic conditions and multimorbidity. WHAT IS KNOWN ALREADY ANM is considered as a marker of age-related morbidity and mortality in postmenopausal life. Multimorbidity affects more than 60% of older women and has been recognized as the most common 'chronic condition'. Few studies have examined the association between ANM and the development of multimorbidity. STUDY DESIGN, SIZE, DURATION A prospective national cohort study of 11 258 Australian women, aged 45-50 years in 1996. Women were followed from 1996 to 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS Information about ANM and 11 chronic conditions (diabetes, hypertension, heart disease, stroke, arthritis, osteoporosis, asthma, chronic obstructive pulmonary disease, depression, anxiety and breast cancer) were estimated approximately every 3 years. Multimorbidity is defined as 2 or more of these 11 conditions. Generalized estimating equations were used to link the categorical ANM with individual chronic conditions and multimorbidity. MAIN RESULTS AND THE ROLE OF CHANCE Among 5107 women reporting ANM, 2.3% experienced premature menopause (≤40 years) and 55.1% developed multimorbidity. Compared with women who experienced menopause at age 50-51 years, women with premature menopause had twice the odds of experiencing multimorbidity by age 60 (OR = 1.98, 95% CI 1.31 to 2.98) and three times the odds of developing multimorbidity in their 60s (OR = 3.03, 95% CI 1.62 to 5.64). Women with premature menopause also experienced higher incidence of most individual chronic conditions. LIMITATIONS, REASONS FOR CAUTION The main limitation of this study was the use of self-reported data, but with repeated assessments from prospective study design and the validity of most of the chronic conditions from hospital data, the potential for non-differential misclassification is minimized. WIDE IMPLICATIONS OF THE FINDINGS To our knowledge, this is the first study to assess the association of premature menopause and development of multimorbidity in a larger national cohort of mid-aged women. Health professionals should consider comprehensive screening and assessment of risk factors for multimorbidity when treating women who experienced premature menopause. STUDY FUNDING/COMPETING INTEREST(S) The Australian Longitudinal Study on Women's Health was supported by the Australian Government Department of Health. X.X. is funded by an International Postgraduate Research Scholarship from the Australian government and a UQ Centennial Scholarship from The University of Queensland. G.D. M. is supported by the National Health and Medical Research Council Principal Research Fellowship (APP1121844). None of the authors has any conflicts of interest to declare.
Blood contains circulating cell‐free respiratory competent mitochondria

Mitochondria are considered as the power‐generating units of the cell due to their key role in energy metabolism and cell signaling. However, mitochondrial components could be found in the extracellular space, as fragments or encapsulated in vesicles. In addition, this intact organelle has been recently reported to be released by platelets exclusively in specific conditions. Here, we demonstrate for the first time, that blood preparation with resting platelets, contains whole functional mitochondria in normal physiological state. Likewise, we show, that normal and tumor cultured cells are able to secrete their mitochondria. Using serial centrifugation or filtration followed by polymerase chain reaction‐based methods, and Whole Genome Sequencing, we detect extracellular full‐length mitochondrial DNA in particles over 0.22 µm holding specific mitochondrial membrane proteins. We identify these particles as intact cell‐free mitochondria using fluorescence‐activated cell sorting analysis, fluorescence microscopy, and transmission electron microscopy. Oxygen consumption analysis revealed that these mitochondria are respiratory competent. In view of previously described mitochondrial potential in intercellular transfer, this discovery could greatly widen the scope of cell‐cell communication biology. Further steps should be developed to investigate the potential role of mitochondria as a signaling organelle outside the cell and to determine whether these circulating units could be relevant for early detection and prognosis of various diseases.
What is a multisensory cortex? A laminar, connectional, and functional study of a ferret temporal cortical multisensory area

Now that examples of multisensory neurons have been observed across the neocortex, this has led to some confusion about the features that actually designate a region as “multisensory. ” While the documentation of multisensory effects within many different cortical areas is clear, often little information is available about their proportions or net functional effects. To assess the compositional and functional features that contribute to the multisensory nature of a region, the present investigation used multichannel neuronal recording and tract tracing methods to examine the ferret temporal region: the lateral rostral suprasylvian sulcal area. Here, auditory‐tactile multisensory neurons were predominant and constituted the majority of neurons across all cortical layers whose responses dominated the net spiking activity of the area. These results were then compared with a literature review of cortical multisensory data and were found to closely resemble multisensory features of other, higher‐order sensory areas. Collectively, these observations argue that multisensory processing presents itself in hierarchical and area‐specific ways, from regions that exhibit few multisensory features to those whose composition and processes are dominated by multisensory activity. It seems logical that the former exhibit some multisensory features (among many others), while the latter are legitimately designated as “multisensory. ”
Current concepts of pharmacotherapy of diabetic macular edema

ABSTRACT Introduction: Diabetic macular edema (DME) is a sight threatening disease and a major cause for blindness for people in working age. The pathogenesis is multifactorial and complex. The pharmacotherapy of DME addresses both the inhibition of vascular endothelial growth factor (VEGF) by the intravitreal injection of VEGF inhibitors and inflammatory processes by the intravitreal application of steroids. Several trials have been published reporting on the efficacy and safety of these treatments. Areas covered: This review discusses original research articles including basic science and clinical studies as well as review articles focusing on the role of inflammation and VEGF expression in DME. It discusses newly published clinical trials on intravitreal pharmacotherapy for DME. The literature was searched using Medline/PubMed and was selected given its relevance for the topic to be discussed. Expert opinion: Our knowledge regarding the pathophysiology of diabetic macular edema has significantly increased. Some of these insights have been successfully transferred into current treatment strategies already including VEGF suppression or anti-inflammatory treatments using steroids. The identification of additional pathophysiological aspects and their relevance as potential treatment targets will be a future challenge in the treatment of DME. A better knowledge on the complex pathophysiology will also help to establish combination strategies.
Genomic and phenotypic effects of inbreeding across two different hatchery management regimes in Chinook salmon

Genomic approaches permit direct estimation of inbreeding and its effect on fitness. We used genomic‐based estimates of inbreeding to investigate their relationship with eight adult traits in a captive‐reared Pacific salmonid that is released into the wild. Estimates were also used to determine whether alternative broodstock management approaches reduced risks of inbreeding. Specifically, 1,100 unlinked restriction‐site associated (RAD) loci were used to compare pairwise relatedness, derived from a relationship matrix, and individual inbreeding, estimated by comparing observed and expected homozygosity, across four generations in two hatchery lines of Chinook salmon that were derived from the same source. The lines are managed as “integrated” with the founding wild stock, with ongoing gene flow, and as “segregated” with no gene flow. While relatedness and inbreeding increased in the first generation of both lines, possibly due to population subdivision caused by hatchery initiation, the integrated line had significantly lower levels in some subsequent generations (relatedness: F2–F4; inbreeding F2). Generally, inbreeding was similar between the lines despite large differences in effective numbers of breeders. Inbreeding did not affect fecundity, reproductive effort, return timing, fork length, weight, condition factor, and daily growth coefficient. However, it delayed spawn timing by 1.75 days per one standard deviation increase in F (~0.16). The results indicate that integrated management may reduce inbreeding but also suggest that it is relatively low in a small, segregated hatchery population that maximized number of breeders. Our findings demonstrate the utility of genomics to monitor inbreeding under alternative management strategies in captive breeding programs.