Miracle-dz/UniFAR-FTUs huggingface dataset:
Thiopurine methyltransferase in red blood cells of dogs, cats, and horses.

Our objective was to determine if thiopurine methyltransferase (TPMT), the enzyme important in the metabolism of azathioprine in human beings, is detectable in red blood cell lysates (RBCL) of healthy dogs, cats, and horses. Values for TPMT activity were determined from blood collected from 20 healthy dogs, cats, and horses. The TPMT activity in each animal's RBCL was determined using a radioenzymatic end point involving TPMT-facilitated metabolism of 6-mercaptopurine to 6-methylmercaptopurine (6-MMP). One unit of TPMT activity represents the formation of 1 nmol of 6-MMP per milliliter of packed red blood cells per hour of incubation at 37 degrees C. TPMT activity in RBCL was detectable in all species, with mean RBC values +/- standard deviation of 17.9 +/- 3.79 U/mL in dogs; 2.76 +/- 0.70 U/mL in cats; and 2.185 +/- 0.36 U/mL in horses. Values for TPMT in the 3 species were significantly (P < .05) different from one another. TPMT values for dogs were significantly higher than the other species, and TPMT values for cats were significantly higher than those for horses. We conclude that RBCL TPMT values are measurable in dogs. cats, and horses and that dogs have higher values than cats or horses. These findings are consistent with the lower tolerance for azathioprine in cats as compared with dogs. It remains to be determined whether RBCL TPMT values in these species correlate with TPMT activity in the liver, where most of the metabolization of azathioprine is believed to occur.
Treatment of Chronic Cough: Single-Institution Experience Utilizing Behavioral Therapy

Objective Chronic cough remains a challenging condition, especially in cases where it persists despite comprehensive medical management. For these particular patients, there appears to be an emerging role for behavior modification therapy. We report a series of patients with refractory chronic cough to assess if there is any benefit of adding behavioral therapy to their treatment regimen. Study Design A case series with planned chart review of patients treated for chronic cough. Setting The review was performed with an outpatient electronic health record system at a tertiary care center. Subjects and Methods The charts of all patients treated for chronic cough by a single laryngologist over a 30-month period were analyzed. Patients’ response to treatment and rate of cough improvement were assessed for those with refractory chronic cough who underwent behavior modification therapy. Results Thirty-eight patients with chronic cough were initially treated empirically for the most common causes of cough, of which 32% experienced improvement. Nineteen patients who did not significantly improve with medical management underwent behavior modification therapy with a speech-language pathologist. Of these patients, 84% experienced resolution or marked improvement of their symptoms. Conclusion Behavioral therapy may be underutilized in practice and could lead to improvement of otherwise recalcitrant cough.
Perceptually Informed Quantification of Speech Rhythm in Pairwise Variability Indices

Abstract Two previous experiments demonstrated that f0 and duration are interdependent in the perception of rhythmic groups in speech and sentence rhythmicality, and that the relative weighting of tonal and durational cues depends on listeners’ native language. The listeners were native speakers of Swiss German, Swiss French, or Metropolitan French (i.e. from France). The experiment reported here investigates a means of applying this perceptual finding to production data from these three languages, to make a rhythm metric, the Pairwise Variability Index (PVI), perceptually informed. The relative weighting that an appropriate duration and an appropriate f0 contributed to listeners’ rhythmicality judgements is calculated, and these language-specific weighting values are incorporated into combined durational- tonal PVIs, to quantify rhythm in the three languages. The results demonstrate that Swiss German and Swiss/Metropolitan French are distinct according to classic durational PVIs, but more similar according to PVIs which are acoustically multidimensional and language-specifically weighted. It is concluded that rhythm produced by speakers, when quantified to account for the acoustic multidimensionality and language-specificity of rhythm perceived by listeners, may be less cross-linguistically divergent than durational rhythm metrics suggest. An evaluation of these language-specifically weighted PVIs concludes that if rhythm metrics remain in use, they should link rhythm perception with rhythm production.
Markers of Cardiovascular Dysfunction in Adolescents With Anorexia Nervosa

Background. Cardiovascular complications contribute to the high morbidity and mortality rate among children with anorexia nervosa (AN). Advances in cardiac imaging permit a more comprehensive assessment of myocardial performance in children that could not be previously obtained with conventional imaging. Myocardial strain analysis is an emerging quantitative echocardiographic technique to characterize global and regional ventricular function in children. Objective. To assess global and regional left ventricular (LV0 function in children newly diagnosed with AN with conventional and quantitative 2-dimensional speckle tracking echocardiographic (2DSTE)–derived strain imaging. Materials. In a cross-sectional study of 30 patients with AN (DSM-5) and 14 age-, sex-, and race-matched healthy children, markers of cardiovascular risk, conventional and 2DSTE measures of LV function, and structure were evaluated and compared. The AN cohort was further stratified by behavioral patterns (restrict, exercise, or purge). Results. Conventional measures and LV global strain were similar between controls and children with AN. A subgroup of AN children with purging behavior had LV remodeling characterized by significantly decreased LV mass index. Regional ventricular function at the apex, as measured by strain, was also decreased in all AN patients. Percent change from ideal body weight, body mass index Z-score, electrolyte profiles, heart rate, and blood pressure were similar. Conclusions. Subclinical regional ventricular dysfunction is present in children with AN. Ventricular remodeling exists in a subgroup of children with AN in association with purging behavior. Future studies may utilize strain imaging to identify those AN patients who are at an increased risk for developing significant cardiac dysfunction.
Secretion of Cell Wall Polymers into the Growth Medium of Lysis-Defective Pneumococci During Treatment with Penicillin and Other Inhibitors of Cell Wall Synthesis

Autolysin-defective pneumococci secrete into the growth medium choline-containing macromolecules during treatment with any one of a large number of inhibitors of cell wall biosynthesis, including beta-lactams, beta-halogeno-d-alanines, cephalosporins, and d-cycloserine. Secretion is closely related to the dose response of the bacteria to the various drugs: (i) secretion can already be detected at the minimum inhibitory concentration; (ii) the rate and extent of secretion is dependent upon the drug concentration; and (iii) secretion commences within minutes after the addition of the antibiotics to the cultures. Reversal of the growth-inhibitory effect of benzylpenicillin (by penicillinase addition) is accompanied by a halt in secretion just at the time when the bacteria resume normal growth. Secretion of the choline-containing macromolecules seems to be a specific consequence of the inhibition of peptidoglycan biosynthesis, since inhibition of growth by drugs affecting protein, ribonucleic acid, or deoxyribonucleic acid synthesis does not cause secretion. The choline-containing macromolecules include both the pneumococcal lipid-containing teichoic acid (Forssman antigen) and wall teichoic acids made after the addition of antibiotics. The appearance of these macromolecules in the growth medium is not due to the hydrolytic activity of an autolysin, since penicillin-induced secretion could be demonstrated in autolysin-defective mutants, in pneumococci grown on ethanolamine-containing medium (such cells are known to have defective autolytic systems), and in wildtype pneumococci grown under conditions nonpermissive for lysis.
Placebo‐corrected efficacy of modern antiepileptic drugs for refractory epilepsy: Systematic review and meta‐analysis

Although adjunctive treatment with modern antiepileptic drugs (AEDs) is standard care in refractory epilepsy, it is unclear how much of the effect can be attributed directly to the AEDs and how much to the beneficial changes seen with placebo. Therefore, we performed a systematic review and meta‐analysis of the evidence to determine the placebo‐corrected net efficacy of adjunctive treatment with modern AEDs on the market for refractory epilepsy. Of 317 potentially eligible articles reviewed in full text, 124 (39%) fulfilled eligibility criteria. After excluding 69 publications, 55 publications of 54 studies in 11,106 adults and children with refractory epilepsy form the basis of evidence. The overall weighted pooled‐risk difference in favor of AEDs over placebo for seizure‐freedom in the total sample of adults and children was 6% [95% confidence interval (CI) 4–8, z = 6.47, p < 0.001] and 21% (95% CI 19–24, z = 17.13, p < 0.001) for 50% seizure reduction. Although the presence of moderate heterogeneity may reduce the validity of the results and limit generalizations from the findings, we conclude that the placebo‐corrected efficacy of adjunctive treatment with modern AEDs is disappointingly small and suggest that better strategies of finding drugs are needed for refractory epilepsy, which is a major public health problem.
Inflation Targeting and the Pass-through Effect in Mongolia

This paper aims to provide empirical evidence on the relationship between inflation targeting and the pass-through effect from exchange rate to consumer prices, focusing on the case of Mongolia. The study estimates a vector-autoregressive model, and examines the impulse responses of consumer prices to the shock of exchange rate for the pre-inflation targeting period and the post-inflation targeting period. The empirical analysis identified the existence of the pass-through effect during the pre-inflation targeting period and the loss of the pass-through during the post-inflation targeting period. It was speculated that the loss of the pass-through comes from the “forward-looking” monetary policy rule in Mongolian inflation targeting, so that it can work on the expectations of domestic agents such that they are less inclined to change prices in response to a given exchange rate shock.
Evaluation of neoplastic nature of keratocystic odontogenic tumor versus ameloblastoma.

OBJECTIVE Although most of odontogenic tumors are benign, some of them will show locally destructive behavior, as keratocystic odontogenic tumor (KCOT) is now known as a benign but aggressive odontogenic neoplasm. The neoplastic characteristics in KCOT have been suggested from clinical as well as pathologic aspects. Matrix metalloproteinase-2 (MMP-2) is a gelatinase form of the MMPs family, which is a group of proteolytic enzymes that degrade many types of collagen. Cysteine aspartic acid-specific protease-3 (caspase-3) is the most downstream enzyme in the apoptosis-inducing protease pathway and is probably the most clearly associated with cell death. The aim of this study is to evaluate and compare the extracellular degradation potentiality (MMP-2) and apoptosis (caspase-3) of the epithelial lining in KCOT versus radicular cysts and ameloblastoma, in order to reinforce its classification as an odontogenic tumor. MATERIAL AND METHODS Twenty-six surgical specimens including keratocyst odontogenic tumor (KCOT; n=11), ameloblastoma (AB; n=8) and radicular cysts (RC; n=7) were examined for expression of MMP-2 and caspase-3 using the immunohistochemical method. RESULTS For MMP-2 immunoexpression, AB showed the statistically significant highest mean area percentage, followed by KCOT, while RC showed the statistically significant lowest mean area percentage. As for caspase- 3, there was no statistically significant difference between KCOT and AB, while RC showed the statistically significantly lowest mean area percentage. CONCLUSION Overexpression of MMP-2 protein related to growth and progression of lesions analyzed and may be one of the factors enhancing the recurrence of KCOT and invasion of AB. In addition, the epithelial lining of KCOT showed a high cell turnover reinforcing its classification as an odontogenic tumor. KEY WORDS Keratocystic odontogenic tumor (KCOT) - Ameloblastoma (AB) - Radicular cyst (RC) - Matrix metalloproteinase-2 (MMP-2) - Caspase-3.
Portal Hyperperfusion after Extended Hepatectomy Does Not Induce a Hepatic Arterial Buffer Response (HABR) but Impairs Mitochondrial Redox State and Hepatocellular Oxygenation

Background & Aims Portal hyperperfusion after extended hepatectomy or small-for-size liver transplantation may induce organ dysfunction and failure. The underlying mechanisms, however, are still not completely understood. Herein, we analysed whether hepatectomy-associated portal hyperperfusion induces a hepatic arterial buffer response, i.e., an adaptive hepatic arterial constriction, which may cause hepatocellular hypoxia and organ dysfunction. Methods Sprague-Dawley rats underwent 30%, 70% and 90% hepatectomy. Baseline measurements before hepatectomy served as controls. Hepatic arterial and portal venous flows were analysed by ultrasonic flow measurement. Microvascular blood flow and mitochondrial redox state were determined by intravital fluorescence microscopy. Hepatic tissue pO2 was analysed by polarographic techniques. Hepatic function and integrity were studied by bromosulfophthalein bile excretion and liver histology. Results Portal blood flow was 2- to 4-fold increased after 70% and 90% hepatectomy. This, however, did not provoke a hepatic arterial buffer response. Nonetheless, portal hyperperfusion and constant hepatic arterial blood flow were associated with a reduced mitochondrial redox state and a decreased hepatic tissue pO2 after 70% and 90% hepatectomy. Microvascular blood flow increased significantly after hepatectomy and functional sinusoidal density was found only slightly reduced. Major hepatectomy further induced a 2- to 3-fold increase of bile flow. This was associated with a 2-fold increase of bromosulfophthalein excretion. Conclusions Portal hyperperfusion after extended hepatectomy does not induce a hepatic arterial buffer response but reduces mitochondrial redox state and hepatocellular oxygenation. This is not due to a deterioration of microvascular perfusion, but rather due to a relative hypermetabolism of the remnant liver after major resection.
Stimulatory effect of growth hormone on in vitro maturation of bovine oocytes is exerted through cumulus cells and not mediated by IGF‐I

A previous study reported that the addition of bovine growth hormone (bGH) during in vitro maturation of bovine oocytes accelerates nuclear maturation and stimulates subsequent embryonic development. The aim of this study was to investigate whether bovine cumulus oocyte complexes (COCs) contain growth hormone receptor (GHR), and whether the stimulatory effect of GH on oocyte maturation is cumulus‐dependent and mediated by insulin‐like‐growth factor (IGF‐I). The expression of growth hormone receptor mRNA in mural granulosa cells, in cumulus cells, and in the oocyte was studied using reverse transcriptase polymerase chain reaction (RT‐PCR). To investigate the importance of cumulus cells for GH‐promoted maturation, COCs and denuded oocytes were cultured for 16 hr in M199 with or without bGH (NIH‐GH‐B18). To investigate whether GH action is mediated by IGF‐I, COCs were cultured in 1) 100 ng/ml bGH, 2) 100 ng/ml bGH plus anti‐IGF‐I, 1:100 dilution, 3) 100 ng/ml h‐IGF‐I, 4) 100 ng/ml h‐IGF‐I plus anti‐IGF‐I, 1:100 dilution, and 5) anti‐IGF‐I, 1:100 dilution. Culture was performed at 39°C in a humidified atmosphere with 5% CO2 in air, and the nuclear stage of oocytes was assessed using 4,6‐diamino‐2‐phenyl‐indole (DAPI) staining. PCR on cDNA of mural granulosa cells, cumulus cells, and oocytes revealed that mRNA for GHR was present in all cell types. Addition of GH (100 ng/ml) to the culture medium of denuded oocytes did not affect the number of metaphase II oocytes after 16 hr, while a significant (P < 0.001) increase was observed, when COCs were cultured in the presence of GH. Addition of the antibody against IGF‐I to the culture medium completely suppressed the stimulatory effect of IGF‐I on oocyte maturation and cumulus expansion, while stimulation by GH was not affected by the antibody. It is con‐ cluded that bovine cumulus cells, mural granulosa, and oo‐ cytes express mRNA for the GH receptor. The stimulatory effect of GH on bovine oocyte maturation is dependent on the cumulus cells and is not mediated by IGF‐I. Mol. Reprod. Dev. 47:175–180, 1997. © 1997 Wiley‐Liss, Inc.
Do Stock Bulletin Board Systems (Bbs) Contain Useful Information? A Viewpoint of Interaction between Bbs Quality and Predicting Ability

This study explores whether information on internet stock bulletin board systems (BBS) is valuable for stock return prediction, taking advantage of data derived from the biggest stock BBS in China. Using a text classification algorithm, we find the online messages significantly predict stock return with negligible R‐squared. However, we find that accuracy of individual BBS posts is below 50 percent and there is no distinction at prediction accuracy between high‐ and low‐quality stock BBS. Due to the autocorrelation of stock returns, we argue that BBS predicts stock returns because of its reflection on the simultaneous stock return rather than revelation on valuable information.
Cutting Edge: CD96 (Tactile) Promotes NK Cell-Target Cell Adhesion by Interacting with the Poliovirus Receptor (CD155)

The poliovirus receptor (PVR) belongs to a large family of Ig molecules called nectins and nectin-like proteins, which mediate cell-cell adhesion, cell migration, and serve as entry receptors for viruses. It has been recently shown that human NK cells recognize PVR through the receptor DNAM-1, which triggers NK cell stimulation in association with β2 integrin. In this study, we show that NK cells recognize PVR through an additional receptor, CD96, or T cell-activated increased late expression (Tactile). CD96 promotes NK cell adhesion to target cells expressing PVR, stimulates cytotoxicity of activated NK cells, and mediates acquisition of PVR from target cells. Thus, NK cells have evolved a dual receptor system that recognizes nectins and nectin-like molecules on target cells and mediates NK cell adhesion and triggering of effector functions. As PVR is highly expressed in certain tumors, this receptor system may be critical for NK cell recognition of tumors.
Interactions of the NPXY microdomains of the low density lipoprotein receptor‐related protein 1

The low density lipoprotein receptor‐related protein 1 (LRP1) mediates internalization of a large number of proteins and protein–lipid complexes and is widely implicated in Alzheimer's disease. The cytoplasmic domain of LRP1 (LRP1‐CT) can be phosphorylated by activated protein‐tyrosine kinases at two NPXY motifs in LRP1‐CT; Tyr 4507 is readily phosphorylated and must be phosphorylated before phosphorylation of Tyr 4473 occurs. Pull‐down experiments from brain lysate revealed numerous proteins binding to LRP1‐CT, but the results were highly variable. To separate which proteins bind to each NPXY motif and their phosphorylation dependence, each NPXY motif microdomain was prepared in both phosphorylated and non‐phosphorylated forms and used to probe rodent brain extracts for binding proteins. Proteins that bound specifically to the microdomains were identified by LC‐MS/MS, and confirmed by Western blot. Recombinant proteins were then tested for binding to each NPXY motif. The NPXY4507 (membrane distal) was found to interact with a large number of proteins, many of which only bound the tyrosine‐phosphorylated form. This microdomain also bound a significant number of other proteins in the unphosphorylated state. Many of the interactions were later confirmed to be direct with recombinant proteins. The NPXY4473 (membrane proximal) bound many fewer proteins and only to the phosphorylated form.
Analysis of ENV V3 sequences from HIV‐1‐infected brain indicates restrained virus expression throughout the disease

The isolation of human immunodeficiency virus type 1 (HIV‐1) from the cerebrospinal fluid (CSF) of asymptomatic virus carriers suggests that the viral infection spreading to the brain occurs early during infection. The aim of the present study was to investigate whether HIV‐1 infection of the brain parenchyma also occurs during the early phase of infection. We also wished to compare the degree of replication of the virus in the brain at different clinical stages associated with HIV‐1 infection. With the use of polymerase chain reaction (PCR), the viral genomes present in seven of eight brain specimens obtained from two asymptomatic HIV‐1 carriers and six AIDS patients were amplified. Thereafter, the number of viral copies present in each brain specimen was quantified, the third variable region (V3) of the gp120 glycoprotein was sequenced and these results compared with the histopathological findings in the tissue.
A tobacco-specific lung carcinogen in the urine of men exposed to cigarette smoke.

BACKGROUND Environmental tobacco smoke has been classified by the Environmental Protection Agency as a carcinogen causally associated with lung cancer in adults, but there have been no reports of lung carcinogens or their metabolites in the body fluids or tissues of nonsmokers exposed to environmental tobacco smoke. METHODS Five male nonsmokers were exposed to sidestream cigarette smoke generated by machine smoking of reference cigarettes for 180 minutes on each of two days, six months apart. Sidestream smoke is the smoke that originates from the smoldering end of a cigarette between puffs. Twenty-four-hour urine samples were collected before and after exposure. The urine samples were analyzed for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide, which are metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a powerful lung carcinogen in rodents. NNAL is also a lung carcinogen in rodents. RESULTS The urinary excretion of the metabolites increased after exposure to sidestream smoke in all the men. The mean (+/- SD) amount of NNAL and NNAL glucuronide was significantly higher after exposure than at base line (33.9 +/- 20.0 vs. 8.4 +/- 11.2 ng per 24 hours [127 +/- 74 vs. 31 +/- 41 pmol per day], P < 0.001) and was correlated with urinary cotinine excretion (r = 0.89, P < 0.001). The nicotine concentrations in the air to which the men were exposed were comparable to those in a heavily smoke-polluted bar. CONCLUSIONS Nonsmokers exposed to sidestream cigarette smoke take up and metabolize a lung carcinogen, which provides experimental support for the proposal that environmental tobacco smoke can cause lung cancer.