Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of tricyclic antidepressants on drug metabolism

The effects of chronic treatment with amitriptyline and nortriptyline on the elimination from plasma of warfarin, dicumarol, phenytoin, and tolbutamide were examined in man. No alteration of plasma half‐life of warfarin, phenytoin, or tolbutamide was observed following dosage with the tricyclic antidepressants used. There was no consistent effect on the metabolism of dicumarol following treatment with amitriptyline or nortriptyline although the bioavailability of dicumarol appeared to be increased. In some subjects, this increased bioavailability was associated with significant prolongation of the plasma half‐life of dicumarol due to its dose‐dependent kinetics.
Mitochondrial HEP27 Is a c-Myb Target Gene That Inhibits Mdm2 and Stabilizes p53

ABSTRACT The ever-expanding knowledge of the role of p53 in cellular metabolism, apoptosis, and cell cycle control has led to increasing interest in defining the stress response pathways that regulate Mdm2. In an effort to identify novel Mdm2 binding partners, we performed a large-scale immunoprecipitation of Mdm2 in the osteosarcoma U2OS cell line. One significant binding protein identified was Hep27, a member of the short-chain alcohol dehydrogenase/reductase (SDR) family of enzymes. Here, we demonstrate that the Hep27 preprotein contains an N-terminal mitochondrial targeting signal that is cleaved following mitochondrial import, resulting in mitochondrial matrix accumulation of mature Hep27. A fraction of the mitochondrial Hep27 translocates to the nucleus, where it binds to Mdm2 in the central domain, resulting in the attenuation of Mdm2-mediated p53 degradation. In addition, Hep27 is regulated at the transcriptional level by the proto-oncogene c-Myb and is required for c-Myb-induced p53 stabilization. Breast cancer gene expression analysis correlated estrogen receptor (ER) status with Hep27 expression and p53 function, providing a potential in vivo link between estrogen receptor signaling and p53 activity. Our data demonstrate a unique c-Myb-Hep27-Mdm2-p53 mitochondria-to-nucleus signaling pathway that may have functional significance for ER-positive breast cancers.
Most Highly Exposed Seronegative Men Lack HIV-1-Specific, IFN-γ-Secreting T Cells 1

Naturally acquired cellular immunity in individuals who have been exposed to HIV-1 but have remained uninfected may hold clues for the design of an effective HIV vaccine. To determine the presence and nature of such an HIV-1-specific immune response, we evaluated the quantity and fine specificity of HIV-1-reactive IFN-γ-secreting T cells in a group of highly exposed seronegative men having sex with men. All 46 ES reported frequent unprotected anal sex with known HIV-1-infected partners at enrollment, and high risk activities continued in at least one-half of the volunteers for up to >6 years of observation. Despite the high frequency of unprotected anal intercourse and potential HIV-1 exposure, the vast majority of individuals demonstrated no or very low numbers of HIV-1-specific, IFN-γ-secreting T cells. Even when HIV-1 epitopes were presented by peptide-pulsed autologous dendritic cells in 15 of the highest risk volunteers, HIV-1-specific T cells remained infrequent, and the proportion of responders was not significantly different from that in a lower risk seronegative control cohort. Only PBMC from two individuals who have remained uninfected to date exhibited distinctly positive responses. However, these responses rarely persisted over time, single epitope specificities were identified in only one volunteer, and HIV-1-specific memory T cell clones did not expand in vitro. HIV-1-specific, IFN-γ-secreting T cells are thus unlikely to substantially contribute to resistance against infection in most exposed seronegative men having sex with men.
Case-mix adjustment of the National CAHPS benchmarking data 1.0: a violation of model assumptions?

OBJECTIVE To compare models for the case-mix adjustment of consumer reports and ratings of health care. DATA SOURCES The study used the Consumer Assessment of Health Plans (CAHPS) survey 1.0 National CAHPS Benchmarking Database data from 54 commercial and 31 Medicaid health plans from across the United States: 19,541 adults (age > or = 18 years) in commercial plans and 8,813 adults in Medicaid plans responded regarding their own health care, and 9,871 Medicaid adults responded regarding the health care of their minor children. STUDY DESIGN Four case-mix models (no adjustment; self-rated health and age; health, age, and education; and health, age, education, and plan interactions) were compared on 21 ratings and reports regarding health care for three populations (adults in commercial plans, adults in Medicaid plans, and children in Medicaid plans). The magnitude of case-mix adjustments, the effects of adjustments on plan rankings, and the homogeneity of these effects across plans were examined. DATA EXTRACTION All ratings and reports were linearly transformed to a possible range of 0 to 100 for comparability. PRINCIPAL FINDINGS Case-mix adjusters, especially self-rated health, have substantial effects, but these effects vary substantially from plan to plan, a violation of standard case-mix assumptions. CONCLUSION Case-mix adjustment of CAHPS data needs to be re-examined, perhaps by using demographically stratified reporting or by developing better measures of response bias.
Discontinuing Antidepressant Treatment in Major Depression

&NA; Maintenance treatments in bipolar disorders and schizophrenia are securely established, and their discontinuation is associated with high but modifiable risk of early relapse. The benefits of long‐term antidepressant treatment in major depression and the risks of discontinuing medication at various times after clinical recovery from acute depression are not as well defined. Computerized searching found 27 studies with data on depression risk over time including a total of 3037 depressive patients treated for 5.78 (0‐48) months and then followed for 16.6 (5‐66) months with antidepressants continued or discontinued. Compared with patients whose antidepressants were discontinued, those with continued treatment showed much lower relapse rates (1.85 vs. 6.24%/month), longer time to 50% relapse (48.0 vs. 14.2 months), and lower 12‐month relapse risk (19.5 vs. 44.8%) (all p < 0.001). However, longer prior treatment did not yield lower postdiscontinuation relapse risk, and differences in relapses off versus on antidepressants fell markedly with longer follow‐up. Contrary to prediction, gradual discontinuation (dose‐tapering or use of long‐acting agents) did not yield lower relapse rates. Relapse risk was not associated with diagnostic criteria. More previous illness (particularly three or more prior episodes or a chronic course) was strongly associated with higher relapse risk after discontinuation of antidepressants but had no effect on response to continued treatment; patients with infrequent prior illness showed only minor relapse differences between drug and placebo treatment.
Comparative study of adaptive and inherently sensorless observers for variable-speed induction-motor drives

State observers are key components of modern ac drives. The paper presents a comparative analysis of two state observers for induction-motor (IM) drives: the speed-adaptive observer and the inherently sensorless observer. The adaptive observer employs the time-variable full-order motor model with the rotor speed as the adaptive quantity. Thus, the speed estimation accuracy significantly impacts on the flux observer. It is shown that the popular model reference adaptive system (MRAS) speed estimator displays reduced bandwidth, and does not deliver adequate performance for the flux estimation. The inherently sensorless observer employs a full-order dual reference-frame model in order to eliminate the speed adaptation. In this way, it becomes decoupled from the speed estimator and its performance is superior to that of its adaptive counterpart. Theoretical aspects and comparative simulation results are discussed for both observers. Comparative experimental results for both observers are presented. Very low-speed-operation (3 r/min) capability of the drive with the sensorless observer is demonstrated.
Interaction of silver nitrate with readily identifiable groups: relationship to the antibacterialaction of silver ions

Microbiologically it was demonstrated that amino acids, e.g. cysteine (CySH), and othercompounds, e.g. sodium thioglycollate, containing thiol groups neutralized the activity of silvernitrate against Pseudomonas aeruginosa PAOl. Amino acids with disulphide bonds wereinactive, with the exception of l‐cystine dimethyl ester, as were all amino acids with nosulphur groups. Iodoacetamide reacted with CySH to produce a CyS–acetamide complex thatwas unable to quench the activity of Ag+. Chemical analyses using cyclic voltammetrydemonstrated that high coordination numbers (3·1) were obtained with thiol‐containingamino acids and low numbers (0·28–0·4) with other amino acids. Bothmicrobiologically and chemically, the results imply that interaction of Ag+ with thiolgroups plays an essential role in bacterial inactivation.
Bacillus anthracis Capsular Conjugates Elicit Chimpanzee Polyclonal Antibodies That Protect Mice from Pulmonary Anthrax

ABSTRACT The immunogenicity of Bacillus anthracis capsule (poly-γ-d-glutamic acid [PGA]) conjugated to recombinant B. anthracis protective antigen (rPA) or to tetanus toxoid (TT) was evaluated in two anthrax-naive juvenile chimpanzees. In a previous study of these conjugates, highly protective monoclonal antibodies (MAbs) against PGA were generated. This study examines the polyclonal antibody response of the same animals. Preimmune antibodies to PGA with titers of >103 were detected in the chimpanzees. The maximal titer of anti-PGA was induced within 1 to 2 weeks following the 1st immunization, with no booster effects following the 2nd and 3rd immunizations. Thus, the anti-PGA response in the chimpanzees resembled a secondary immune response. Screening of sera from nine unimmunized chimpanzees and six humans revealed antibodies to PGA in all samples, with an average titer of 103. An anti-PA response was also observed following immunization with PGA-rPA conjugate, similar to that seen following immunization with rPA alone. However, in contrast to anti-PGA, preimmune anti-PA antibody titers and those following the 1st immunization were ≤300, with the antibodies peaking above 104 following the 2nd immunization. The polyclonal anti-PGA shared the MAb 11D epitope and, similar to the MAbs, exerted opsonophagocytic killing of B. anthracis. Most important, the PGA-TT–induced antibodies protected mice from a lethal challenge with virulent B. anthracis spores. Our data support the use of PGA conjugates, especially PGA-rPA targeting both toxin and capsule, as expanded-spectrum anthrax vaccines.
Cytomegalovirus infection in children undergoing hematopoietic stem cell transplantation in Chile

Cytomegalovirus (CMV) infection remains as an important cause of morbidity and mortality in children undergoing hematopoietic stem cell transplantation (HSCT). Our aim was to assess the incidence, risk factors, and outcome related to CMV infection in children after HSCT in a developing country.
Theoretical Foundations for the Study of Media Multitasking among Lagos Mall Users

This paper seeks to provide a theoretical approach to the study of media multitasking. The aim of the study is achieved by examining the Information Processing Theory (IPT) and the Niche Media Theory (NMT) to show how their propositions guide the study of media multitasking among Lagos mall users. Therefore, using unobtrusive observations, in-depth interviews, and survey, smartphone use during face-to-face interactions among Lagos mall users was examined based on the proposition of the IPT that humans have limited cognitive resources, and if more resources are directed towards one information processing task, another task will be performed badly. Some researchers believe that this may not always be the case as skills are capable of aiding multitasking. However, guided by the proposition of the NMT, this paper argues that even though skills aid multitasking, there are certain implications for not just the people involved but also the forms of communication used during media multitasking. Findings, to an extent, support IPT’s proposition as there was a decline in interaction quality. However, there was an interesting twist to the NMT’s proposition on overlap. Mall users who perceived face-to-face interactions to be more superior were more likely to replace face-to-face interactions with smartphone communication.
Partial trisomy of the long arm of chromosome 1 in myelofibrosis and polycythemia vera

We have identified partial trisomy 1q in 2 patients with different hematologic disorders. The first patient was a 55‐year‐old female with myelosclerosis and myeloid metaplasia diagnosed at age 38 years presenting with anemia, fatigue, bruising, fever, and splenomegaly. At age 56, she had 50–95% myeloblast cells and 95–100 nucleated RBC precursors per 100 WBC. Chromosome analysis of unstimulated leukocytes with Q, G, and C banding showed 46,XX,‐6,+t(1;6) (q25;p22) in all metaphase cells. In vitro incorporation of Fe55 was demonstrated in 90% of metaphases by autoradiography. The second patient, a 49‐year‐old male, was diagnosed as having polycythemia vera at age 30 during a regular checkup. He since developed hepatosplenomegaly. Chromosome analysis from a direct bone marrow preparation at age 44 and 45 showed grossly normal karyotypes. At age 49, his marrow by Q and G banding showed almost 100% of cells with 46,XY,–13,+t(1;13) (q12;p12). Eleven cases of trisomy of 1q have been reported in various hematologic disorders. It is apparent that partial trisomy 1q represents another nonrandom chromosomal abnormality, in addition to the most common nonrandom chromosomal aberrations, such as the Philadelphia chromosome, trisomy 8, trisomy 9, and monosomy 7 in hematologic disorders.
Protein Content of the Diabetic Diet

The protein content of the diabetic diet remains a controversial issue because of the potential for both restricted and liberal protein intakes to exert beneficial and adverse effects in diabetes (1-5). In addition to adequate provision of energy, a certain level of protein intake is required to ensure normal growth, development, and maintenance of tissue protein stores. Variation in dietary protein may influence metabolic control of diabetes by altering gluconeogenic substrate availability as well as insulin and counterregulatory hormone secretion. Protein has also been implicated in the pathogenesis of diabetic renal disease. Diabetic nephropathy is now the single most common disorder leading to end-stage renal failure. A high protein intake is well documented to increase renal workload and glomerular filtration rate and may contribute to the progression of diabetic nephropathy (6,7). Conversely, numerous studies now indicate that lowprotein diets may impede or delay the rate of development of diabetic renal disease (8). Consideration of any potential advantages or disadvantages to changes in protein intake cannot be viewed in isolation, however, because the intake of other macronutrients is also altered and may result in independent metabolic effects and consequences in diabetes. To date, there is limited scientific data on which to establish firm nutritional recommendations for protein intake in diabetes mellitus (9). In many cases, no information is available. Often, results are derived from short-term studies that do not necessarily reflect the longterm effects. Other data is inferential in nature, arising from studies in nondiabetic subjects, and so must be cautiously interpreted before extrapolation to those with diabetes. Another issue that warrants consideration is the accumulating evidence that the protein source, whether animal or vegetable in origin, may be as important as the quantity of proteins consumed in affecting the progression of renal disease. Finally, the diabetic state can develop at any age and spans the range from infancy to the elderly. Its presence is often associated with a variety of special circumstances that may influence protein requirements and needs to be considered before making recommendations about protein intake. This review will examine the relevant scientific information that addresses these issues to provide rationale for the dietary protein recommendations for individuals with diabetes mellitus. Information presented will be restricted to that obtained in humans with an emphasis on studies performed in diabetic subjects.
Use of the heart rate-energy expenditure relationship in the individualized prescription of exercise.

evidence of an indirect nature that supports the contention that routine exercise is a necessary part of any program of preventive medicine. This is particularly true for coronary heart disease. Fox and Haskeli (1) have concluded that it is “highly prudent” to incorporate programs of increased habitual activity in the multifaceted approach to the prevention of coronary heart disease. Unfortunately, although the need for routine exercise has been clearly demonstrated, the manner in which the exercise is to be prescribed has created many questions. When prescribing an individual’s exercise program, each of the following factors needs to be specified : a) type of activity, e.g., jogging, swimming, bicycling, et cetera; b) frequency of participation, i.e., days per week; c) duration of each day’s activity; and d) the inten
Unveiling the security concerns of low carbon development: climate security analysis of the undesirable and unintended effects of mitigation and adaptation

ABSTRACT In debates of climate action, low carbon development has been widely advocated as an opportunity arising from climate change. This paper problematizes low carbon development, arguing that there are undesirable, unintended or perverse effects that give rise to distinct and serious security concerns. The literature on climate security has addressed the effects of climate threats on conflict but there is a notable paucity of research analysing the security implications of responses to climate change in the form of low carbon development. The paper presents critical analysis of the ways low carbon development yields new security concerns as well as entrenching existing ones. Five dimensions of security are examined: spatially uneven effects of low carbon development; violent imaginaries of the global south and the production of ‘ungoverned spaces’; non-violent yet harmful instances of conflict; marginalization and dispossession; depoliticized, techno-managerial effects of resilience. The paper shows that climate (in)security manifests in variegated ways between different populations and spatial scales. Consequently, how, when for whom low carbon development becomes a threat or opportunity is socially constructed and deeply political.
Tibiotalocalcaneal Arthrodesis Using a Supracondylar Femoral Nail for Advanced Tuberculous Arthritis of the Ankle

Purpose. To review 7 patients with advanced osteoarticular tuberculous arthritis of the ankle who underwent arthrodesis using a supracondylar femoral nail. Methods. All patients showed gross destruction of the articular cartilage of the tibiotalar joint with severe periarticular rarefaction on radiographs. Their pre- and one-year post-operative Foot and Ankle Outcome Scores (FAOS) were compared. All patients underwent joint debridement, complete synovial excision, and arthrodesis using a supracondylar femoral nail, followed by multidrug chemotherapy for 12 months (isoniazid, rifampicin, pyrazinamide, and ethambutol for 3 months, and isoniazid and rifampicin for 9 months). Results. All patients achieved fusion in a mean of 13 weeks and regained their preoperative level of independence. No patient had a relapse, major complications, or hardware failure. At postoperative year one, the mean FAOS for pain improved to 85 from 26, whereas the mean FAOS for quality of life improved to 60 from 5. Conclusion. Tibiotalocalcaneal arthrodesis using a supracondylar femoral nail, combined with debridement and multidrug therapy, enabled a reliable one-stage solution for advanced osteoarticular tuberculosis and early return to function.
The design of fiscal consolidation measures in the European Union: distributional effects and implications for macroeconomic recovery

The financial and economic crisis which started in the late 2000s and the fiscal consolidation measures to counter the subsequent government budget deficits have an impact on household income distribution and macroeconomic recovery. We consider the austerity measures in relation to their distributional impact and the potential channels through which fiscal consolidation can affect economic growth. We find notable variation in the size, composition and effects of fiscal consolidation. Richer households tend to bear a greater burden in most countries but spending cuts are more likely to affect liquidity constrained households casting doubts over previous findings in the macro-economic literature about the effectiveness of such measures. This suggests the need to consider more disaggregated evidence to reach robust policy conclusions.
Gender comparison of RPE at absolute and relative physiological criteria.

PURPOSE The effect of gender on ratings of perceived exertion for the overall body (RPE-O), chest (RPE-C), legs (RPE-L), and arms (RPE-A (ski)) was determined. METHODS Comparisons were made at, a) absolute oxygen uptake (VO2, L x min(-1); mL x kg(-1) x min(-1)) and heart rate (HR, b x min(-1)) and b) relative VO2 (%VO2max/peak) and HR (% HRmax/peak) reference criteria. Nine male and 10 female subjects were compared using a perceptual estimation paradigm for treadmill (weight bearing), simulated ski (partial weight bearing), and cycle (nonweight bearing) exercise. RPE was determined by the Borg 15-category scale. RESULTS For each exercise mode, RPE-O, RPE-L, RPE-A (ski), and RPE-C were higher (P < 0.05) in the female than male cohort when compared at submaximal absolute VO2 criteria. RPE did not differ between female and male cohorts when compared at mode specific relative VO2 criteria. Differences in RPE-O, RPE-L, RPE-A (ski), and RPE-C were not found between female and male subjects when comparisons were made at both absolute and relative HR. Responses were consistent for the three exercise modes. CONCLUSION RPE did not differ between gender when comparisons were made at relativized VO2 and HR reference criteria at exercise intensities between 70 and 90% of mode specific maximal/peak values.
The p.R168Q mutation is associated with the Bw phenotype and a predicted decrease in the stability of the resulting ABO glycosyltransferase

Mutation of ABO glycosyltransferase (GT) can cause protein stability changes that can result in a weak ABO phenotype. To explain the Bw phenotype of a novel ABO*Bw allele, a protein stability of the mutant GT, which enhances the information of the three‐dimensional (3D) structural analysis, was calculated.
Application of Preclinical Data to Initiate the Modified Continual Reassessment Method for Maximum Tolerated Dose—Finding Trials

This study was conducted to evaluate whether the allometric approach can be used to predict maximum tolerated dose (MTD) in humans from animal data. Twenty‐five anticancer drugs were taken from the literature and used in this analysis. The results of the study indicate that MTD can be predicted with reasonable accuracy using interspecies scaling. The predicted MTD can then be applied to the modified continual reassessment method retrospectively for the selection of initial and subsequent doses of anticancer drugs in the patient population. This approach can save time and avoid many unnecessary steps to attain MTD in humans if it could be applied prospectively.