Miracle-dz/UniFAR-FTUs huggingface dataset:
The relation between instrumental musical activity and cognitive aging.

OBJECTIVE Intensive repetitive musical practice can lead to bilateral cortical reorganization. However, whether musical sensorimotor and cognitive abilities transfer to nonmusical cognitive abilities that are maintained throughout the life span is unclear. In an attempt to identify modifiable lifestyle factors that may potentially enhance successful aging, we evaluated the association between musical instrumental participation and cognitive aging. METHOD Seventy older healthy adults (ages 60-83) varying in musical activity completed a comprehensive neuropsychological battery. The groups (nonmusicians, low and high activity musicians) were matched on age, education, history of physical exercise, while musicians were matched on age of instrumental acquisition and formal years of musical training. Musicians were classified in the low (1-9 years) or high (>10 years) activity group based on years of musical experience throughout their life span. RESULTS The results of this preliminary study revealed that participants with at least 10 years of musical experience (high activity musicians) had better performance in nonverbal memory (η2 = .106), naming (η2 = .103), and executive processes (η2 = .131) in advanced age relative to nonmusicians. Several regression analyses evaluated how years of musical activity, age of acquisition, type of musical training, and other variables predicted cognitive performance. CONCLUSIONS These correlational results suggest a strong predictive effect of high musical activity throughout the life span on preserved cognitive functioning in advanced age. A discussion of how musical participation may enhance cognitive aging is provided along with other alternative explanations.
Transection of the hernia sac during laparoscopic totally extraperitoneal inguinal hernioplasty: is it safe and feasible?

BACKGROUND Complete reduction of an indirect inguinal hernia sac during laparoscopic totally extraperitoneal (TEP) repair is not always possible when the sac extends to the scrotum or adheres to adjacent tissues. Laparoscopic TEP repair would be much easier to perform in such cases by transecting the hernia sac. Therefore, the purpose of this study was to determine the safety and efficacy of transection of the hernia sac during laparoscopic TEP. MATERIALS AND METHODS Five hundred twenty laparoscopic TEP repairs were performed on 498 patients by a single surgeon from July 2003 to December 2008. The patients were classified into two groups: the transected sac (TS) group with 269 patients (275 cases) and the completely reduced sac (RS) group with 230 patients (245 cases). RESULTS Statistical analysis between the TS and RS groups showed no significant differences in postoperative pain, length of hospital stay, and recurrence, except for postoperative seromas, which were more frequent in the TS group (24 of 275) than the RS group (6 of 245; P = .002). And the mean operative time was longer in the TS group (23.62 ± 10.25 minutes) than the RS group (21.49 ± 8.17 minutes; P = .010). CONCLUSION Although transection of the hernia sac during laparoscopic TEP repair may cause seromas, our study demonstrated that transection of the hernia sac did not cause significant postoperative complications, including recurrence. Transection of the hernia sac is an alternative technique for laparoscopic TEP repair in cases with difficult hernia sac reduction.
Incidence and Survival in Reproductive-Aged Women with Differentiated Thyroid Cancer: United States SEER18 2000-2016.

BACKGROUND Incidence of differentiated thyroid cancer has increased in the United States (US) and globally with disproportionate increases observed among women. Recent data suggest that factors other than increased detection may underlie this increase. To understand incidence and survival patterns in differentiated thyroid cancer during a time period of increasing imaging, we examined data from a contemporary population-based sample of US reproductive-aged women. METHODS Women aged 20-49 years (N=61,552) diagnosed with papillary thyroid cancer (PTC) or follicular thyroid cancer (FTC) from 2000-2016 were identified from the US National Cancer Institute Surveillance, Epidemiology, and End Results 18 registries database. For each age decade (20-29, 30-39, 40-49 years), we estimated age-adjusted average annual percentage changes in incidence using segmented and unsegmented regression models and fifteen-year survival. Results were stratified by race/ethnicity and cancer stage. RESULTS The estimated incidence of PTC increased during 2000-2016 among women aged 20-29 years and during 2000-2012 among women aged 30-49 years. During 2012-2016, incidence stabilized among women aged 30-39 years and decreased among women aged 40-49 years. For FTC, incidence decreased slightly among women aged 20-29 years and was rather stable among those aged 30-49 years during 2000-2016, although increases were observed among non-Hispanic black women aged 30-49 years. By stage, the percentage increase in PTC incidence was largest for regional disease. Fifteen-year estimated survival was generally high but somewhat lower among women aged 40-49 years than those aged 20-39 years. Survival was similar for PTC and FTC except among women aged 20-29 years, for whom survival was modestly lower with FTC than PTC. CONCLUSIONS Our findings confirm increasing incidence of PTC among US women aged 20-29 years, a recent stabilization of PTC incidence in women 30-49 years, and stable to decreasing incidence of FTC. Increased detection based on imaging is unlikely to fully explain the continued increase in PTC incidence, given increasing incidence of regional disease and routine imaging occurring less often among premenopausal than postmenopausal women. Although survival is generally high, treatment often requires surgery and lifelong medications. Further investigations into contributors to these trends are warranted to reduce future morbidity in reproductive-aged women.
Performance of Apache III over Time in Australia and New Zealand: A Retrospective Cohort Study

The Acute Physiology and Chronic Health Evaluation (APACHE) III-j model has been used for benchmarking intensive care unit (ICU) outcomes in Australia and New Zealand for over a decade. This study assessed performance of the APACHE III-j model in adult patients admitted to Australasian ICUs during a ten-year period. Data were extracted from the Australian and New Zealand Intensive Care Society Adult Patient Database. Performance of APACHE III-j at different time points and within different age strata was evaluated by dividing the whole cohort into five ‘two-year’ groups. Calibration and discrimination were assessed by the Brier score, Hosmer-Lemeshow C and H statistics, Standardised Mortality Ratio (SMR), Cox calibration regression, calibration curves and area under the receiver operating characteristic curve (AUROC). Model performance within diagnostic categories was evaluated. Between 1 January 2000 and 31 December 2009, 558,585 ICU admissions which met inclusion criteria were included in the analysis. The mean (standard deviation) age was 60.8 (18.4) years and 58.3% were male. Overall observed mortality was 12.6%. The mean (standard deviation) APACHE III-j predicted mortality was 14.5% (21.8). Although discrimination (as measured by AUROC) was preserved over time, all other markers of model performance showed deterioration. There was a significant decrease in SMR in eight of ten most common diagnoses examined. This study demonstrates that performance of APACHE III-j model has deteriorated in Australasian hospitals and there is now a clear need for an updated modelling approach to improve mortality prediction, performance monitoring and quality of research undertaken in Australian and New Zealand ICUs.
Gastric Hyperplasia in Mice Lacking the Putative Cdc42 Effector IQGAP1

ABSTRACT Human IQGAP1 is a widely expressed 190-kDa Cdc42-, Rac1-, and calmodulin-binding protein that interacts with F-actin in vivo and that can cross-link F-actin microfilaments in vitro. Recent results have implicated IQGAP1 as a component of pathways via which Cdc42 or Rac1 modulates cadherin-based cell adhesion (S. Kuroda et al., Science 281:832–835, 1998), whereas yeast IQGAP-related proteins have been found to play essential roles during cytokinesis. To identify critical in vivo functions of IQGAP1, we generated deficient mice by gene targeting. We demonstrate that IQGAP1 null mutants arise at normal frequency and show no obvious defects during development or for most of their adult life. Loss of IQGAP1 also does not affect tumor development or tumor progression, but mutant mice exhibit a significant (P < 0.0001) increase in late-onset gastric hyperplasia relative to wild-type animals of the same genetic background. While we cannot exclude that functional redundancy with IQGAP2 contributes to the lack of developmental phenotypes, the restricted expression pattern of IQGAP2 is not obviously altered in adult IQGAP1 mutant mice. Thus, IQGAP1 does not serve any essential nonredundant functions during murine development but may serve to maintain the integrity of the gastric mucosa in older animals.
Monoclonal antibody reveals radial glia in adult avian brain

An antibody prepared against adult canary brain, 40E‐C, stains ventricular zone cells that send long, unbranched processes into the forebrain parenchyma. We identify these cells as radial glia. The same antibody also stains a subset of brain astroglia and reacts with nonbrain material such as mesenchyme, Sertoli cells, and the Z‐line of muscle. A weaker reaction is given by erythrocytes and some endothelial cells. 40E‐C also reacts with the radial glia of the developing rat brain but fails to show any such glia in adult rodent brain. Western blot analysis shows that this antibody recognizes vimentin, a molecule shared by all 40E‐C‐positive cell types. We believe that the presence of radial glia in the adult avian forebrain and their apparent absence in mammals is related to neurogenesis in adulthood, which occurs in birds and much less or not at all in mammals. In addition, the presence of radial glia in adult birds may also relate to other, stillhypothetical, differences in the physiology of adult avian and mammalian brains.
Induction of Proenkephalin Gene Expression in Cultured Bovine Chromaffin Cells Is Dependent on Protein Synthesis of AP‐1 Proteins

Abstract: In bovine chromaffin cells forskolin, phorbol ester, or high potassium levels induce a rapid increase of c‐fos, c‐jun, and junB mRNA levels, which precede an induction of proenkephalin gene expression. Preincubation of the cells with cycloheximide inhibited induction of proenkephalin mRNA levels by each of these agents, indicating that newly synthesized transcription factors are involved. Transient transfection of reporter genes showed that the ENKCRE‐2 element of the proenkephalin promoter was sufficient for basal and second messenger‐induced expression. Gel mobility shift assays revealed that stimulation increased the binding of nuclear proteins to ENKCRE‐2 and AP‐1 oligonucleotides but not to CRE oligonucleotides. Western analysis showed that the induction of AP‐1 binding activity was associated with Fos protein synthesis. Moreover, cotransfection of c‐fos, but not of c‐jun or CREB, expression plasmids transactivated the expression of the PENKCAT reporter genes. These results suggest that Fos and/or other components of AP‐1 transcription factors, rather than CREB or other preexisting proteins, play a specific role in the induction of the proenkephalin gene in bovine chromaffin cells.
An impaired routing of wild‐type aquaporin‐2 after tetramerization with an aquaporin‐2 mutant explains dominant nephrogenic diabetes insipidus

Autosomal recessive and dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin, are caused by mutations in the aquaporin‐2 (AQP2) gene. Missense AQP2 proteins in recessive NDI have been shown to be retarded in the endoplasmic reticulum, whereas AQP2‐E258K, an AQP2 mutant in dominant NDI, was retained in the Golgi complex. In this study, we identified the molecular mechanisms underlying recessive and dominant NDI. Sucrose gradient centrifugation of rat and human kidney proteins and subsequent immunoblotting revealed that AQP2 forms homotetramers. When expressed in oocytes, wild‐type AQP2 and AQP2‐E258K also formed homotetramers, whereas AQP2‐R187C, a mutant in recessive NDI, was expressed as a monomer. Upon co‐injection, AQP2‐E258K, but not AQP2‐R187C, was able to heterotetramerize with wild‐type AQP2. Since an AQP monomer is the functional unit and AQP2‐E258K is a functional but misrouted water channel, heterotetramerization of AQP2‐E258K with wild‐type AQP2 and inhibition of further routing of this complex to the plasma membrane is the cause of dominant NDI. This case of NDI is the first example of a dominant disease in which the ‘loss‐of‐function’ phenotype is caused by an impaired routing rather than impaired function of the wild‐type protein.
Population dynamics of the metacercarial stage of the bucephalid trematode, Labratrema minimus (Stossich, 1887) from Salses-Leucate lagoon (France) during the cercarial shedding period

Abstract The population dynamics of Labratrema minimus (Stossich, 1887) metacercariae (Trematoda, Bucephalidae) were studied in its second intermediate fish host Atherina boyeri from Salses-Leucate lagoon (Northwest Mediterranean Sea, South of France), during the cercarial shedding period. The infection parameters (prevalence and mean abundance of infection) showed the high susceptibility of silversides (juveniles and adults) to infection. The observed variation in the mean abundance of infection with respect to time and host size was explained by (i) the susceptibility of A. boyeri to multiple successive infections (increase in abundance of infection with host length and raising of parasite burden until August) and (ii) the loss, probably by more rapid death, of heavily infected silversides from each host size group (decrease in abundance of infection in September within each host size group, stability of the parasite burden within the older class of hosts over the whole period, premature decrease in the condition factor in August). Finally, it was deduced that the infection pattern observed over the May–September period was a dynamic process controlled by: availability of infective cercariae, influx of newborn silversides free of metacercariae until September, high susceptibility of juvenile and adult A. boyeri to infection, metacercarial loss and probably by parasite-induced host mortality.
A 77 GHz Low LO Power Mixer With a Split Self-Driven Switching Cell in 65 nm CMOS Technology

A low LO power mixer with high gain by using a split self-driven switching cell for automotive applications at 77 GHz is presented. By splitting the switching cell, the required LO power is reduced and the VCO has less capacitive loading. The mixer has a peak conversion gain of 6.8 dB and the input 1 dB compression point is 7 dBm at LO power of 5 dBm. The chip is fabricated in 65 nm CMOS technology and the chip size including a Marchand balun is 790 μm × 590 μm. The total power consumption is 3 mW from a 1.2 V supply.
Long-term persistence after acute Q fever of non-infective Coxiella burnetii cell components, including antigens.

BACKGROUND Previous studies of inciting factors for a prolonged post-infection fatigue syndrome after Q fever (variously termed QFS or Q fever associated CFS/ME in the literature) showed that after the acute infection a high proportion of asymptomatic and QFS patients had Q fever antibody and also low levels in PBMC and bone marrow of Coxiella burnetii (C.b.) DNA with PCR assays directed against three different target sequences in different parts of the coxiella genome. Attempts to isolate a strain of C.b. in A/J mice, and cell culture from PCR positive PBMC and bone marrow were consistently negative. The detailed composition of the persisting coxiella residues remains to be defined. AIM To retest and provide detailed results on selected PCR positive samples from the Birmingham Q fever outbreak patients tested by a highly sensitive method to detect viable organisms and to determine the nature of the residual coxiella cell components. DESIGN Laboratory case study. METHODS NOD/SCID mice were inoculated with samples from the 1989 Q fever outbreak in Birmingham and followed for evidence of infection and the presence of coxiella DNA and specific antigens in spleen and liver macrophages. A significant, unexpected finding of specific antigen was followed by assessment of its ability to provoke production of inflammatory and non-inflammatory cytokines in mice, in THP-1 human macrophage cell cultures and to induce inflammatory lesions in the skin of guinea pigs hyperimmunized against Q fever vaccine. RESULTS Culture of samples from 10 Birmingham Q fever patients in NOD/SCID mice, 12 years from infection did not yield viable Coxiella burnetii, as shown earlier. However complexes of material with coxiella antigens were found in mouse spleens in all cases but in significantly greater amounts in samples from those with post Q fever fatigue syndrome. The antigenic complexes [now designated 'immunomodulatory complexes' (IMC)] were shown to stimulate cytokine release in the mice and in the THP-1 macrophages and to provoke an inflammatory reaction on intradermal injection into the skin of Q fever hyperimmunized guinea pigs. CONCLUSION The study identifies a non-infective complex of C.b. antigens able to survive in the host and provoke aberrant humoral and cell medicated immunity responses - a possible pathogenic link between initial infection and a subsequent long-term post Q fever fatigue syndrome.
Diacylglycerol Kinase δ and Protein Kinase Cα Modulate Epidermal Growth Factor Receptor Abundance and Degradation through Ubiquitin-specific Protease 8*

Many human epithelial cancers are characterized by abnormal activation of the epidermal growth factor receptor (EGFR), which is often caused by its excessive expression in tumor cells. The abundance of EGFR is modulated, in part, by its ubiquitination, which targets it for degradation. The components responsible for adding ubiquitin to EGFR are well characterized, but this is a reversible process, and the mechanisms that modulate the removal of ubiquitin from the EGFR are not well known. We found that de-ubiquitination of EGFR was regulated by diacylglycerol kinase δ (DGKδ), a lipid kinase that terminates diacylglycerol signaling. In DGKδ-deficient cells, ubiquitination of EGFR was enhanced, which attenuated the steady-state levels of EGFR and promoted its ligand-induced degradation. These effects were not caused by changes in the ubiquitinating apparatus, but instead were due to reduced expression of the de-ubiquitinase, ubiquitin-specific protease 8 (USP8). Depletion of protein kinase Cα (PKCα), a target of diacylglycerol, rescued the levels of USP8 and normalized EGFR degradation in DGKδ-deficient cells. Moreover, the effects of PKCα were caused by its inhibition of Akt, which stabilizes USP8. Our data indicate a novel mechanism where DGKδ and PKCα modulate the levels of ubiquitinated EGFR through Akt and USP8.
Thermodynamic properties of the effector domains of MARTX toxins suggest their unfolding for translocation across the host membrane

MARTX (multifunctional autoprocessing repeats‐in‐toxin) family toxins are produced by Vibrio cholerae, Vibrio vulnificus, Aeromonas hydrophila and other Gram‐negative bacteria. Effector domains of MARTX toxins cross the cytoplasmic membrane of a host cell through a putative pore formed by the toxin's glycine‐rich repeats. The structure of the pore is unknown and the translocation mechanism of the effector domains is poorly understood. We examined the thermodynamic stability of the effector domains of V. cholerae and A. hydrophila MARTX toxins to elucidate the mechanism of their translocation. We found that all but one domain in each toxin are thermodynamically unstable and several acquire a molten globule state near human physiological temperatures. Fusion of the most stable cysteine protease domain to the adjacent effector domain reduces its thermodynamic stability ∼ 1.4‐fold (from D G H 2 O 21.8 to 16.1 kJ mol−1). Precipitation of several individual domains due to thermal denaturation is reduced upon their fusion into multi‐domain constructs. We speculate that low thermostability of the MARTX effector domains correlates with that of many other membrane‐penetrating toxins and implies their unfolding for cell entry. This study extends the list of thermolabile bacterial toxins, suggesting that this quality is essential and could be susceptible for selective targeting of pathogenic toxins.
Depressive Symptoms, Social Isolation, and Progression of Coronary Artery Atherosclerosis: The Stockholm Female Coronary Angiography Study

Background: Although both depressive symptoms and social isolation in relation to coronary heart disease have been studied previously, few have examined their joint effects on coronary atherosclerosis progression in women. Method: Among the women enrolled in the Stockholm Female Coronary Angiography Study, Sweden, between 1991 and 1994, 102 were evaluated for coronary atherosclerosis progression using a computer-assisted standardized assessment, repeated quantitative coronary angiographic documentation, of the mean luminal diameter change over 3 years in 10 predefined coronary segments. Depressive symptoms and social isolation were assessed by standard questionnaires. Results: Multivariable controlled mixed model ANOVAs revealed that women who were both depressed and socially isolated had the greatest disease progression: their absolute mean luminal diameter decreased by 0.18 mm [95% confidence interval (CI) = 0.11–0.24] and their percent narrowing was 5.5% (95% CI = 3.6–7.4), whereas in women who lacked both psychological risk factors, the mean luminal diameter decrease was 0.04 mm and their percent narrowing was 0.9%. These associations were independent of the baseline luminal diameter and standard risk factors, including age, smoking history, hypertension, and high-density lipoproteins. Conclusions:In women with coronary disease, depressive symptoms and social isolation in combination accelerated disease progression, suggesting a direct psychosocial effect on the atherosclerotic process. These findings provide an additional opportunity for therapeutic and preventive efforts against progression of coronary disease in women.
The measurement of urinary prostaglandin E in normal subjects and in high-renin states.

Antisera generated toward PGE was obtained from rabbits immunized with PGE2 conjugated to bovine thyroglobulin by the carbodiimide reaction. The specificity of the antibody is such that only PGE1 and PGE2 has significant cross-reactions. 13, 14-Dihydro and 15-keto PG's did not react. An RIA capable of measuring 6 pg of PGE2 was developed to measure PGE in human urine. Urine samples adjusted with buffer to pH-5 are extracted with 5% MeOH in CH2CI2 and chromatographed through Sephadex LH-20 columns. The second-antibody technique is used to separate bound from free. This urine method yields blank values of 2 +/- 2 pg per sample, with a between-assay precision determined by duplicate analysis of 14% and intra-assay precision of 8%. The mean urinary excretion rate is 500 +/- 74 (S.E.), +/- 209 (S.D.) ng/day (n = 8) in men and 300 +/- 70, +/- 242 (n = 12) in women. These values are in agreement with those reported by others using gas chromatography-mass spectrometry of receptor assay with hepatic plasma membranes. Patients in a high-renin state, whether normotensive or hypertensive, have elevated PGE in urine. These studies suggest a relationship between the renin-angiotensin system and renal PG's in man.