Miracle-dz/UniFAR-FTUs huggingface dataset:
The human colonic monocarboxylate transporter Isoform 1: its potential importance to colonic tissue homeostasis.

BACKGROUND & AIMS Butyrate serves as the major source of energy for colonic epithelial cells, and has profound effects on their proliferation, differentiation, and apoptosis. Transport of butyrate across the colonocyte luminal membrane is mediated by the monocarboxylate transporter, MCT1; the expression of which is down-regulated dramatically during colon carcinogenesis. We have proposed that the decline in MCT1 expression during colon carcinogenesis may reduce the intracellular availability of butyrate required to regulate expression of genes associated with the processes maintaining tissue homeostasis within the colonic mucosa. METHODS To test this hypothesis we used the technique of RNA interference to inhibit MCT1 expression specifically, and determined the consequences of this inhibition on the ability of butyrate to exert its recognized effects in vitro using flow cytometry, immunofluorescence, Northern analysis, and Western analysis. RESULTS We show that inhibition of MCT1 expression, and hence butyrate uptake, has profound inhibitory effects on the ability of butyrate to regulate expression of key target genes: p21waf1/cip1 (p21), intestinal alkaline phosphatase (IAP), and cyclin D1, and their associated processes of proliferation and differentiation. In contrast, inhibition of MCT1 expression had no effect on the ability of butyrate to modulate expression of either bcl-XL or bak, and this was reflected in a corresponding lack of effect on butyrate induction of apoptosis. CONCLUSIONS Collectively, these results show the importance of MCT1 to the ability of butyrate to induce cell-cycle arrest and differentiation, and suggest fundamental differences in the mechanisms by which butyrate modulates specific aspects of cell function.
A motivational model of alcohol use.

The final, common pathway to alcohol use is motivational. A person decides consciously or unconsciously to consume or not to consume any particular drink of alcohol according to whether or not he or she expects that the positive affective consequences of drinking will outweigh those of not drinking. Various factors (e.g., past experiences with drinking, current life situation) help to form expectations of affective change from drinking, these factors always modulated by a person's neurochemical reactivity to alcohol. Such major influences include the person's current nonchemical incentives and the prospect of acquiring new positive incentives and removing current negative incentives. Our motivational counseling technique uses nonchemical goals and incentives to help the alcoholic develop a satisfying life without the necessity of alcohol. The technique first assesses the alcoholic's motivational structure and then seeks to modify it through a multicomponent counseling procedure. The counseling technique is one example of the heuristic value of the motivational model.
A family study of obsessive-compulsive disorder.

OBJECTIVE The goal of this study was to determine 1) whether obsessive-compulsive disorder is familial, 2) whether there is a familial relationship between obsessive-compulsive disorder and Gilles de la Tourette's syndrome and chronic tics, and 3) whether different familial types of obsessive-compulsive disorder exist. METHOD In this family study, all available first-degree relatives of 100 probands with obsessive-compulsive disorder were interviewed directly with structured interviews, and best-estimate diagnoses were assigned. In addition to the 466 first-degree relatives of the probands, 113 comparison subjects who were first-degree relatives of 33 psychiatrically unaffected subjects were studied with the same interviews. RESULTS The rates of obsessive-compulsive disorder and subthreshold obsessive-compulsive disorder were significantly greater among the relatives of the probands with obsessive-compulsive disorder (10.3% and 7.9%, respectively) than among the comparison subjects (1.9% and 2.0%, respectively). Furthermore, the rate of tics (Tourette's disorder and chronic tics) was also significantly greater among the relatives of the probands (4.6%) than among the comparison subjects (1.0%). The relatives of female probands with obsessive-compulsive disorder were more likely to have tics, and the relatives of probands with early onset were at higher risk for both obsessive-compulsive disorder and tics. CONCLUSIONS Obsessive-compulsive disorder is a heterogeneous condition. Some cases are familial and related to tic disorders, some cases are familial and unrelated to tics, and in other cases there appears to be no family history of either obsessive-compulsive disorder or tics.
6‐Methylangelicins: new monofunctional photochemotherapeutic agents for psoriasis

The monofunctional furocoumarins, the 6‐methylangelicins, were tested for their antiproliferative activity with various animal models and for genotoxicity in micro‐organisms and in mammalian cells. The most active compound was 6,4,4′‐trimethylangelicin, which showed a high antiproliferative effect and reduced genotoxicity in comparison with 8‐methoxypsoralen (8‐MOP). Some of these compounds were also tested clinically by topical application on 17 patients with psoriasis. They appeared to be more active than 8‐MOP in clearing psoriasis without inducing skin phototoxicity. The methylangelicins also caused skin pigmentation.
Is bigger really better? Relative and absolute body size influence individual growth rate under competition

Abstract Models suggest that the mechanism of competition can influence the growth advantage associated with being large (in absolute body size or relative to other individuals in the population). Large size is advantageous under interference, but disadvantageous under exploitative competition. We addressed this prediction in a laboratory experiment on Rana temporaria tadpoles competing for limited food. There were 166 target individuals spanning a 10‐fold range in body mass reared for 3 days with three other individuals that were either the same size, half as large, or twice as large as the target. Relative growth rate (proportion per day) declined with size, and absolute growth rate (mass per day) reached a peak at intermediate size and declined thereafter. Tadpoles grew slowly if they were large relative to their competitors, although relative body size was less important than absolute size. As a result, size variation declined in groups that were initially composed of individuals of variable size. Thus, bigger was not better under exploitative competition. Our results help connect individual‐level behavior with individual growth and the size distribution of the population.
The orexin component of fasting triggers memory processes underlying conditioned food selection in the rat

To test the selectivity of the orexin A (OXA) system in olfactory sensitivity, the present study compared the effects of fasting and of central infusion of OXA on the memory processes underlying odor–malaise association during the conditioned odor aversion (COA) paradigm. Animals implanted with a cannula in the left ventricle received ICV infusion of OXA or artificial cerebrospinal fluid (ACSF) 1 h before COA acquisition. An additional group of intact rats were food-deprived for 24 h before acquisition. Results showed that the increased olfactory sensitivity induced by fasting and by OXA infusion was accompanied by enhanced COA performance. The present results suggest that fasting-induced central OXA release influenced COA learning by increasing not only olfactory sensitivity, but also the memory processes underlying the odor–malaise association.
Relation Between Splenectomy and Subsequent Infection

Six years ago, in a treatise on 'Splenic Function', Hayhoe and Whitby (1955) stated as one of their conclusions that 'the spleen can be removed with relative impunity and low mortality and is not in any way essential to life'. The present study, however, provides evidence to prove that the spleen may be essential to life; that its absence, in infancy particularly, may result in serious and overwhelming infection. Such a relation was suggested first by King and Schumacker (1952), and later by Smith and his colleagues (Smith, Erlandson, Schulman and Stern, 1956; Smith, Erlandson, Schulman and Stern, 1957; Smith, Erlandson, Stern and Schulman, 1960), Gofstein and Gellis (1956), Robinson and Sturgeon (1960) and Lucas and Krivit (1960). On the other hand, this view has been opposed by certain authors, particularly by Gross (1953), and Laski and MacMillan (1959). When the present study was commenced, a critical review of the relevant English and French literature indicated that the essential problem remained unsolved: does splenectomy itself significantly increase the susceptibility of the child to serious infection? To the clinician there seem to be very important reasons for obtaining a definite answer to this question. One is that the recent developments in anaesthetic and surgical techniques and in antibiotic therapy have made the operation of splenectomy far safer than it was a generation ago, when the operative mortality was three or four times as high as it is today. As a result, splenectomy may appear to be justifiable far more often nowadays, even in the neonatal period. Another reason is that in certain disorders, for which splenectomy in infancy was hitherto advocated in some centres, medical treatment has now been developed to the stage where it may effectively replace splenectomy, at least until the later years of childhood when the operation carries less surgical risk. For such cogent and practical reasons it was decided to assess critically the evidence in the literature and to investigate further the problem of the relation between splenectomy and subsequent serious infection. The present study involved a follow-up of 142 patients in whom splenectomy had been performed in childhood. The purposes were first to determine whether there was a significant incidence of serious infections following this operation, secondly to determine whether the incidence of such infections was influenced by the age of the patient at operation, and thirdly to determine whether the incidence was influenced by the nature of the condition for which splenectomy was performed. The incidence of serious bacterial infections following splenectomy in this series was 12-0%. A statistically significant relation of infection to age was shown in infancy: of 10 infants aged 8 months or less at the time of operation, five developed serious infections, three of which were fatal. The findings suggested also that when splenectomy was performed for an underlying disease, it carried a greater risk of subsequent infection than when it was performed for traumatic rupture.
The Effect of Oral Processing on the Viscosity of Thickened Drinks for Patients With Dysphagia

Objective To determine whether a gum-containing thickener maintains its viscosity better during oral processing than a completely starch-based thickener. Methods Thirty-five healthy volunteers participated in a double-blind, cross-over study. Artificial tap water was thickened to honey-like consistency (effective viscosity of 1,300±100 mPa·s at a shear rate of 50 per second at 20℃) with a starch-based thickener (SB) or a gum-containing thickener (GC). Bolus viscosity was determined after standardized oral processing of the thickened water by the subjects for 10 and 20 seconds. Significant effects were determined by ANOVA analysis and pairwise comparisons. Results Both thickeners were susceptible to breakdown during oral processing. However, GC-thickened water retained its viscosity significantly better than SB-thickened water. Conclusion The presence of gums has a protective effect on the starch hydrolysis by salivary amylase in thickened drinks, which may facilitate safer swallowing.
1 " " eIF 4 A is stimulated by the pre-initiation complex and enhances recruitment of mRNAs regardless of structural 1 " complexity 2 " 3 "

13" eIF4A is a DEAD-box RNA-dependent ATPase thought to unwind RNA secondary structure in the 5'-untranslated 14" regions (UTRs) of mRNAs to promote their recruitment to the eukaryotic translation pre-initiation complex (PIC). We 15" show that eIF4A’s ATPase activity is markedly stimulated in the presence of the PIC, independently of eIF4E•eIF4G, 16" but dependent on subunits i and g of the heteromeric eIF3 complex. Surprisingly, eIF4A accelerated the rate of 17" recruitment of all mRNAs tested, regardless of their degree of structural complexity. Structures in the 5'-UTR and 3' of 18" the start codon synergistically inhibit mRNA recruitment in a manner relieved by eIF4A, indicating that the factor does 19" not act solely to melt hairpins in 5'-UTRs. Our findings that eIF4A functionally interacts with the PIC and plays 20" important roles beyond unwinding 5’-UTR structure is consistent with a recent proposal that eIF4A modulates the 21" conformation of the 40S ribosomal subunit to promote mRNA recruitment. 22" 23" INTRODUCTION 24" The goal of translation initiation is to assemble the ribosomal initiation complex containing the methionyl initiator 25" tRNA (Met-tRNAi) at the translation start site on an mRNA. The process begins when the small (40S) subunit of the 26" ribosome binds eIF1, eIF1A, eIF2, GTP, Met-tRNAi, eIF3, and eIF5, to assemble the 43S PIC (Dever et al., 2016). eIF1 27" and eIF1A bind near the P and A sites of the 40S subunit, respectively, and promote loading of the ternary complex 28" (TC) comprising eIF2, GTP, and Met-tRNAi. eIF5 is the GTPase-activating protein (GAP) for eIF2 and stimulates GTP 29" . CC-BY 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi. org/10.1101/147959 doi: bioRxiv preprint first posted online Jun. 13, 2017;
Eczematous skin reaction to atopy patch testing with cockroach in patients with atopic dermatitis.

BACKGROUND Aeroallergens from house dust mite (HDM) may be an important trigger in a subgroup of patients with atopic dermatitis (AD). HDM and cockroach (CR) contain cross-reactive allergens, such as tropomyosin. OBJECTIVE To investigate the diagnostic value of patch testing with an aeroallergen and the role of CR allergen and HDM allergen in persons with AD. METHODS We performed skin prick tests (SPT) with a panel of common aeroallergens and total serum immunoglobulin (Ig)E and specific IgE tests for CR and HDM on 23 patients with AD and 9 nonatopic control participants. Atopy patch tests (APT) were performed with CR and HDM extracts on clinically uninvolved skin on the back, and evaluated after 48 and 72 hours. RESULTS A positive APT reaction to CR was found in 10/23 (43%) patients with AD. No positive reactions were observed in the nonatopic control participants. Positive APT reactions for CR showed no significant correlation with SPT or specific IgE levels for this allergen. Twelve of the 23 (52%) patients with AD were also sensitized to HDM. There was no significant correlation between positive results for SPT, APT, and specific IgE to CR and HDM. CONCLUSION We demonstrate that CR allergens can induce positive patch test reactions in patients with AD. The absence of a significant correlation to SPT and specific IgE antibodies suggests that T-cell- and IgE-sensitization may be mediated by different allergens. There was no significant relationship between CR and HDM sensitivity, thus indicating no major cross-reactivity.
Tracheal extension in respiration.

It has long been known that the lower end and bifurcation of the trachea are displaced downwards during inspiration. Macklin (1925) described a vertical respiratory displacement of 21 mm. in a healthy young adult female. Bruckner (1952), in a radiological study, demonstrated an inspiratory descent of the carina of about one thoracic vertebral body in young adults of 19 to 25 years of age. Holden and Ardran (1957), in a meticulous examination of bronchograms from subjects aged 12 to 65 years, concluded that "in deep inspiration the trachea increased in length up to one fifth and in diameter by about one tenth. " In a personal observation, on inspiration the carina descended 30 mm. in a young adult male with a full inspiratory movement. Thus, in young adults, the carina descends by about 1 in. (2.5 cm.) with deep inspiration, i.e., about 20% of the unextended length of the trachea. There are no references in the literature to similar observations in infants and young children in whom the technical difficulty of securing a full inspiratory and expiratory movement for radiographic investigation is obvious. Also, most observers have examined only the movement of the carina and have not considered changes in the whole length of the trachea. Keith (1909) drew attention to the fact that certain parts of the lung are expanded more readily than others. The bases and sterno-costal surfaces related to the more mobile parts of the thoracic wall expand more readily than the apices, mediastinal surfaces, and posterior margins, related to less mobile parts. These areas he described as areas of direct or of indirect expansion. The thoracic wall does not move uniformly during inspiration; the parts which move most are the diaphragmatic and sterno-costal surfaces. Thus the lung tends to expand in a downward and forward direction. Now the lung root must obviously descend to facilitate this movement. In
Glycemic control and sliding scale insulin use in medical inpatients with diabetes mellitus.

OBJECTIVE To identify predictors of hypoglycemic and hyperglycemic episodes in hospitalized patients with diabetes with special attention to the effectiveness of sliding scale insulin regimens. DESIGN Prospective cohort study. SETTING Urban university hospital. PARTICIPANTS One hundred seventy-one adults with diabetes mellitus as a comorbid condition admitted consecutively to medical inpatient services during a 7-week period. MEASUREMENTS Demographic, clinical, and laboratory data from inpatient medical records. MAIN OUTCOMES Rates of hypoglycemic (capillary blood glucose, < or = 3.3 mmol/L [< or = 60 mg/dL]) and hyperglycemic (capillary blood glucose, > or = 16.5 mmol/L [> or = 300 mg/ dL]) episodes. RESULTS Of the patients, 23% experienced hypoglycemic episodes, and 40% experienced hyperglycemic episodes. The overall rates of hypoglycemic and hyperglycemic episodes were 3.4 and 9.8 per 100 capillary blood glucose measurements, respectively. Independent predictors of hypoglycemic episodes included African American race (relative risk [RR], 2.13) and low serum albumin level (RR, 1.92 per 100-g/L decrease); corticosteroid use was associated with a reduced risk of hypoglycemic episodes (RR, 0.32; P < .05). Independent predictors of hyperglycemic episodes included female gender (RR, 1.67), severity of illness (RR, 1.22 per 10 Acute Physiology and Chronic Health Evaluation III units), severe diabetic complications (RR, 2.32), high admission glucose level (RR, 1.33 per 5.5 mmol/L), admission for infectious disease (RR, 2.14), and corticosteroid use (RR, 3.74; P < .05). Of 171 patients, 130 (76%) were placed on a sliding scale insulin regimen. When used alone, sliding scale insulin regimens were associated with a 3-fold higher risk of hyperglycemic episodes compared with individuals following no pharmacologic regimen (RRs, 2.85 and 3.25, respectively; P < .05). CONCLUSIONS Suboptimal glycemic control is common in medical inpatients with diabetes mellitus. The risk of suboptimal control is associated with selected demographic and clinical characteristics, which can be ascertained at hospital admission. Although sliding scale insulin regimens are prescribed for the majority of inpatients with diabetes, they appear to provide no benefit; in fact, when used without a standing dose of intermediate-acting insulin, they are associated with an increased rate of hyperglycemic episodes.
Mixture Effects of Estrogenic Pesticides at the Human Estrogen Receptor α and β

Consumers of fruits and vegetables are frequently exposed to small amounts of hormonally active pesticides, some of them sharing a common mode of action such as the activation of the human estrogen receptor α (hERα) or β (hERβ). Therefore, it is of particular importance to evaluate risks emanating from chemical mixtures, in which the individual pesticides are present at human-relevant concentrations, below their corresponding maximum residue levels. Binary and ternary iso-effective mixtures of estrogenic pesticides at effect concentrations eliciting a 1 or 10% effect in the presence or absence of 17β-estradiol were tested experimentally at the hERα in the yeast-based estrogen screen (YES) assay as well as in the human U2-OS cell-based ERα chemical-activated luciferase gene expression (ERα CALUX) assay and at the hERβ in the ERβ CALUX assay. The outcome was then compared to predictions calculated by means of concentration addition. In most cases, additive effects were observed with the tested combinations in all three test systems, an observation that supports the need to expand the risk assessment of pesticides and consider cumulative risk assessment. An additional testing of mixture effects at the hERβ showed that most test substances being active at the hERα could also elicit additive effects at the hERβ, but the hERβ was less sensitive. In conclusion, effects of the same ligands at the hERα and the hERβ could influence the estrogenic outcome under physiological conditions.
Understanding the Complex Etiologies of Developmental Disorders: Behavioral and Molecular Genetic Approaches

Objective: This article has 2 primary goals. First, a brief tutorial on behavioral and molecular genetic methods is provided for readers without extensive training in these areas. To illustrate the application of these approaches to developmental disorders, etiologically informative studies of reading disability (RD), math disability (MD), and attention-deficit hyperactivity disorder (ADHD) are then reviewed. Implications of the results for these specific disorders and for developmental disabilities as a whole are discussed, and novel directions for future research are highlighted. Method: Previous family and twin studies of RD, MD, and ADHD are reviewed systematically, and the extensive molecular genetic literatures on each disorder are summarized. To illustrate 4 novel extensions of these etiologically informative approaches, new data are presented from the Colorado Learning Disabilities Research Center, an ongoing twin study of the etiology of RD, ADHD, MD, and related disorders. Conclusions: RD, MD, and ADHD are familial and heritable, and co-occur more frequently than expected by chance. Molecular genetic studies suggest that all 3 disorders have complex etiologies, with multiple genetic and environmental risk factors each contributing to overall risk for each disorder. Neuropsychological analyses indicate that the 3 disorders are each associated with multiple neuropsychological weaknesses, and initial evidence suggests that comorbidity between the 3 disorders is due to common genetic risk factors that lead to slow processing speed.