Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment patterns and health care resource utilization in a 1-year observational cohort study of outpatients with schizophrenia at risk of nonadherence treated with long-acting injectable antipsychotics

Purpose To describe (1) the clinical profiles and the patterns of use of long-acting injectable (LAI) antipsychotics in patients with schizophrenia at risk of nonadherence with oral antipsychotics, and in those who started treatment with LAI antipsychotics, (2) health care resource utilization and associated costs. Patients and methods A total of 597 outpatients with schizophrenia at risk of nonadherence, according to the psychiatrist’s clinical judgment, were recruited at 59 centers in a noninterventional prospective observational study of 1-year follow-up when their treatment was modified. In a post hoc analysis, the profiles of patients starting LAI or continuing with oral antipsychotics were described, and descriptive analyses of treatments, health resource utilization, and direct costs were performed in those who started an LAI antipsychotic. Results Therapy modifications involved the antipsychotic medications in 84.8% of patients, mostly because of insufficient efficacy of prior regimen. Ninety-two (15.4%) patients started an LAI antipsychotic at recruitment. Of these, only 13 (14.1%) were prescribed with first-generation antipsychotics. During 1 year, 16.3% of patients who started and 14.9% of patients who did not start an LAI antipsychotic at recruitment relapsed, contrasting with the 20.9% who had been hospitalized only within the prior 6 months. After 1 year, 74.3% of patients who started an LAI antipsychotic continued concomitant treatment with oral antipsychotics. The mean (median) total direct health care cost per patient per month during the study year among the patients starting any LAI antipsychotic at baseline was €1,407 (€897.7). Medication costs (including oral and LAI antipsychotics and concomitant medication) represented almost 44%, whereas nonmedication costs accounted for more than 55% of the mean total direct health care costs. Conclusion LAI antipsychotics were infrequently prescribed in spite of a psychiatrist-perceived risk of nonadherence to oral antipsychotics. Mean medication costs were lower than nonmedication costs.
Quantitative sensory testing

The problem. Quantitative Sensory Testing (QST) is used to characterize human cutaneous sensation in health and disease.1,2 Further development and use of QST is impeded by the current lack of agreement on which stimuli, testing procedures, and criteria for response levels should be recommended for epidemiologic surveys, controlled clinical trials, and study of patients with sensory loss and cutaneous hypersensitivity states. In this consensus statement, we define QST and make recommendations about which measurements, calibration, and validation procedures are needed to ensure that stimuli and algorithms of testing and estimating threshold are accurate and valid for use in QST. The emphasis in this report is on assessment of the sensory thresholds increasingly used in controlled clinical trials, epidemiologic studies, and clinical evaluation of patients. We suggest that only standardized, calibrated, and validated stimuli and testing approaches be used so as to get comparable results in different medical centers. The report does not address the clinical neurologist’s assessment of sensation because its usefulness is well established. This report also does not address the problems and approaches used to test sensation in experimental animals. How to assess sensation from deep structures is also not addressed. We recognize that future approaches will be found to quantitatively assess sensation in health and disease more adequately than outlined here. Better control of stimulus characteristics is needed to assess hyperalgesia (or allodynia) elicited by lightly stroking the surface of the skin. Mechanical stimulation of cutaneous hairs has not been exploited in QST. Finally, we have dealt only briefly with the subject of how to evaluate the intensity of sensation with stimulus magnitudes exceeding a patient’s threshold.
Histone lysine crotonylation during acute kidney injury in mice

ABSTRACT Acute kidney injury (AKI) is a potentially lethal condition for which no therapy is available beyond replacement of renal function. Post-translational histone modifications modulate gene expression and kidney injury. Histone crotonylation is a recently described post-translational modification. We hypothesized that histone crotonylation might modulate kidney injury. Histone crotonylation was studied in cultured murine proximal tubular cells and in kidneys from mice with AKI induced by folic acid or cisplatin. Histone lysine crotonylation was observed in tubular cells from healthy murine and human kidney tissue. Kidney tissue histone crotonylation increased during AKI. This was reproduced by exposure to the protein TWEAK in cultured tubular cells. Specifically, ChIP-seq revealed enrichment of histone crotonylation at the genes encoding the mitochondrial biogenesis regulator PGC-1α and the sirtuin-3 decrotonylase in both TWEAK-stimulated tubular cells and in AKI kidney tissue. To assess the role of crotonylation in kidney injury, crotonate was used to increase histone crotonylation in cultured tubular cells or in the kidneys in vivo. Crotonate increased the expression of PGC-1α and sirtuin-3, and decreased CCL2 expression in cultured tubular cells and healthy kidneys. Systemic crotonate administration protected from experimental AKI, preventing the decrease in renal function and in kidney PGC-1α and sirtuin-3 levels as well as the increase in CCL2 expression. For the first time, we have identified factors such as cell stress and crotonate availability that increase histone crotonylation in vivo. Overall, increasing histone crotonylation might have a beneficial effect on AKI. This is the first observation of the in vivo potential of the therapeutic manipulation of histone crotonylation in a disease state. Summary: We have assessed the effect of the epigenetic post-translational modification histone crotonylation during kidney injury in vivo and in cell culture, and the involvement of PGC-1α and SIRT3 in the process.
The Space of Binary Theta Series

The purpose of this paper is to study the space ΘD generated by the binary theta series θf attached to the primitive, positive-definite binary quadratic forms f(x, y) = ax + bxy + cy of discriminant D = b − 4ac < 0. It is curious that while much has been written about the space generated by theta series attached to quadratic forms in 2k ≥ 4 variables (cf. [10] and the references therein), the binary case does not seem to have been treated in detail in the literature. By the work of Weber[25], Hecke[8] and Schoeneberg[18], it is known that ΘD is a subspace of the space M1(|D|, ψD) of modular forms of weight 1, level |D| and Nebentypus ψD, where ψD = ( D · ) is the Kronecker-Legendre character. Contrary to the case of higher weight, the space of binary theta series is often a proper subspace of M1(|D|, ψD) (cf. Remark 16) and so it is of interest to be able to identify it inside the space of modular forms. As a first step towards this, we explain in this paper how each theta series θf can be expressed as a linear combination of the canonical (extended) Atkin-Lehner basis of M1(|D|, ψD); cf. Remark 30(b). This will be used in the next paper[12] to give an intrinsic description of the space of theta series. To this end we first observe that ΘD has a natural basis {θχ} indexed by the characters χ ∈ Cl(D)∗ of the class group Cl(D) of forms of discriminant D. It turns out that each θχ is a normalized eigenform with respect to Hecke algebra T(D); the latter is the algebra generated by all Hecke operators Tn with (n,D) = 1. Theorem 1 The space ΘD is a T(D)-submodule of M1(|D|, ψD) of multiplicity one, and has a canonical basis {θχ} consisting of normalized T(D)-eigenforms. Furthermore, θχ is a cusp form if and only if χ is not a quadratic character.
Under-surface hardness of light-cured nanofilled resin composites of different shades

The objective of the this study was to analyze the under-surface hardness of light-cured nanofilled composite resins of different shades. The specimens were resin composites of each light (B1), medium (A3), and dark (C3) shades packed in a cylinder mold and subsequently polymerized. The hardness was tested using a Knoop system. The hardness test results for the bright (B1), medium (A3), and dark (C3) shades were 82.4+1.1, 75.9+1.2 and 65.9+1.9, respectively, and indicated significant differences between the under-surface hardness of each shade. It was concluded that resin composites of darker to brigher shades demonstrated lower to higher under-surface hardness.
Second Primary Cancer in Patients with Colorectal Cancer after a Curative Resection

Background: Colorectal cancer (CRC) patients have an increased risk of developing other malignancies. Understanding the characteristics of the second primary cancer is important to establish an effective surveillance program. Methods: This study investigated 301 CRC patients to assess the risk factors for postoperative primary cancers arising from organs distinct from the colorectal area (extracolorectal cancers). The observed/expected ratio (O/E ratio) was calculated using the Osaka Cancer Registry, to determine the rate of increase in extracolorectal cancers. Results: The frequency of postoperative extracolorectal cancers was 12.6%. A logistic regression analysis showed only age to be an independent risk factor for postoperative extracolorectal cancer development. The O/E ratio of overall postoperative extracolorectal cancer was significantly higher than one (O/E ratio 2.6, p < 0.01). In each organ, the frequency of lung and gastric cancers were significantly higher than one, with O/E ratios of 3.2 and 2.7 (p < 0.01 and p < 0.05, respectively). Conclusion: The frequency of postoperative extracolorectal cancers in CRC patients was significantly higher than that in the normal population, especially for lung and gastric cancers. Clinicians should carefully follow patients for a possible recurrence of CRC and educate CRC patients with regard to the high risk of a second primary cancer.
The Social Nestwork: Tree Structure Determines Nest Placement in Kenyan Weaverbird Colonies

Group living is a life history strategy employed by many organisms. This strategy is often difficult to study because the exact boundaries of a group can be unclear. Weaverbirds present an ideal model for the study of group living, because their colonies occupy a space with discrete boundaries: a single tree. We examined one aspect of group living. nest placement, in three Kenyan weaverbird species: the Black-capped Weaver (Pseudonigrita cabanisi), Grey-capped Weaver (P. arnaudi) and White-browed Sparrow Weaver (Ploceropasser mahali). We asked which environmental, biological, and/or abiotic factors influenced their nest arrangement and location in a given tree. We used machine learning to analyze measurements taken from 16 trees and 516 nests outside the breeding season at the Mpala Research Station in Laikipia Kenya, along with climate data for the area. We found that tree architecture, number of nests per tree, and nest-specific characteristics were the main variables driving nest placement. Our results suggest that different Kenyan weaverbird species have similar priorities driving the selection of where a nest is placed within a given tree. Our work illustrates the advantage of using machine learning techniques to investigate biological questions.
Torsional Vibration Effects on Induction Machine Current and Torque Signatures in Gearbox-Based Electromechanical System

The monitoring of heavy-duty electromechanical systems is crucial for their preventive maintenance planning. In these systems, the mechanical anomalies such as load troubles, great torque dynamic variations, and torsional oscillations lead to shaft fatigue and aging of other mechanical parts such as bearings and gearboxes. In this paper, a gearbox-based electromechanical system is investigated. Initially, a simple gearbox dynamic model is used to show the effects of rotating input, output, and mesh frequency components on the electromagnetic torque and consequently on the stator current signature. By this model, the influence of transmission error, eccentricities of pinion/wheel, and teeth contact stiffness variation is demonstrated for a healthy gearbox. Then, it is shown that the electrical machine can be considered as a torque sensor through electromagnetic torque estimation for torsional vibration monitoring without any extra mechanical sensor. A test-rig based on a 5.5-kW three-phase squirrel-cage induction motor connected to a wound-rotor 4-kW induction generator via a one-stage gearbox has been used to validate the proposed method.
HIV gp120 H375 Is Unique to HIV-1 Subtype CRF01_AE and Confers Strong Resistance to the Entry Inhibitor BMS-599793, a Candidate Microbicide Drug

ABSTRACT BMS-599793 is a small molecule entry inhibitor that binds to human immunodeficiency virus type 1 (HIV-1) gp120, resulting in the inhibition of CD4-dependent entry into cells. Since BMS-599793 is currently considered a candidate microbicide drug, we evaluated its efficacy against a number of primary patient HIV isolates from different subtypes and circulating recombinant forms (CRFs) and showed that activity varied between ∼3 ρM and 7 μM at 50% effective concentrations (EC50s). Interestingly, CRF01_AE HIV-1 isolates consistently demonstrated natural resistance against this compound. Genotypic analysis of >1,600 sequences (Los Alamos HIV sequence database) indicated that a single amino acid polymorphism in Env, H375, may account for the observed BMS-599793 resistance in CRF01_AE HIV-1. Results of site-directed mutagenesis experiments confirmed this hypothesis, and in silico drug docking simulations identified a drug resistance mechanism at the molecular level. In addition, CRF01_AE viruses were shown to be resistant to multiple broadly neutralizing monoclonal antibodies. Thus, our results not only provide insight into how Env polymorphisms may contribute to entry inhibitor resistance but also may help to elucidate how HIV can evade some broadly neutralizing antibodies. Furthermore, the high frequency of H375 in CRF01_AE HIV-1, and its apparent nonoccurrence in other subtypes, could serve as a means for rapid identification of CRF01_AE infections.
Living with Asthma: An Analysis of Patients' Perspectives

Objectives. To investigate asthmatic patients’ perceptions of their disease. Methods. The study was done with the participation of 23 patients among the asthmatics whose progress is monitored regularly in a university hospital. Phenomenological methodology was used, and the first step was to determine the socio-demographic characteristics of the participants. Then, in order to determine their feelings and opinions on the subject of their asthma, each participant was asked to write a letter to answer the following question: “If asthma were a friend of yours, what would you like to say to it in a letter? ” Data were analyzed using the continuous comparative method of Colaizzi (1978; “Psychological research as a phenomenologist views it”, in Valle, R. And King, M. (Eds), Existential Phenomenological Alternatives for Psychology, Oxford University Press, New York, NY. ). For this purpose, each researcher read the letters separately and identified the important thoughts, and similar statements were classified under the same theme groups. Results. The mean age of the patients was 41.43 ± 6.23 years, and 69.6% of them were female, 73.9% were married, 34.8% were primary school graduates, and 34.7% were civil servants (with no social security problems). The statements of the asthmatics in the study were grouped according to the following themes: “The Most Important Factor in Accepting Asthma Is Time,” “It’s So Hard to Be Asthmatic,” “Being Asthmatic Means Understanding the Value of Life,” “I Don’t Like Asthma, so I Can’t Make Friends with It,” “Learning to Live with Asthma,” “One Day I May Recover from Asthma,” “Feeling Anger,” and “Suffering from Continuous Worry and Fear. ” Conclusion. Asthmatic patients need psychosocial support since they believe that there is no certain treatment for asthma, and attacks are inevitable.
Midodrine for orthostatic hypotension and recurrent reflex syncope

Objective: Symptomatic orthostatic hypotension (SOH) and recurrent reflex syncope (RRS) can be disabling. Midodrine has been proposed in the management of patients with these conditions but its impact on patient important outcomes remains uncertain. We performed a systematic review to evaluate the efficacy and safety of midodrine in patients with SOH and RRS. Methods: We searched multiple electronic databases without language restriction from their inception to June 2013. We included randomized controlled trials of patients with SOH or RRS that compared treatment with midodrine against a control and reported data on patient important outcomes. We graded the quality of evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Results: Eleven trials involving 593 patients were included in this review. Three studies addressed health-related quality of life in patients with RRS, showing improvement with midodrine: risk difference 14% (95% confidence interval [CI] −3.5 to 31.6), very low confidence. Seven studies addressed symptom improvement and provided poolable data showing improvement with midodrine in patients with SOH: risk difference 32.8% (95% CI 13.5–48), low confidence; and RRS: risk difference 63.3% (95% CI 47.6–68.2), very low confidence. Five studies reported syncope recurrence in patients with RRS showing improvement with midodrine: risk difference 37% (95% CI 20.8%–47.4%), moderate confidence. The most frequent side effects in the midodrine arm were pilomotor reactions (33.6%, risk ratio 4.58 [95% CI 2.03–10.37]). Conclusions: Evidence warranting low/moderate confidence suggests that midodrine improves clinical important outcomes in patients with SOH and RRS.
Expanding the keratin mutation database: novel and recurrent mutations and genotype–phenotype correlations in 28 patients with epidermolytic ichthyosis

Background Epidermolytic ichthyosis (EI) is a hereditary keratinization disorder caused by mutations in the keratin 1 (KRT1) or keratin 10 (KRT10) genes. In most cases of severe EI, heterozygous single point mutations are found at the highly conserved helix boundary motifs of KRT1 and KRT10 that play a critical role in filament formation. The presence of palmoplantar keratoderma suggests KRT1 mutations, whereas KRT10 mutations in most instances give rise to the nonpalmoplantar variants.
Cryohydrocytosis: increased activity of cation carriers in red cells from a patient with a band 3 mutation

Background Cryohydrocytosis is an inherited dominant hemolytic anemia characterized by mutations in a transmembrane segment of the anion exchanger (band 3 protein). Transfection experiments performed in Xenopus oocytes suggested that these mutations may convert the anion exchanger into a non-selective cation channel. The present study was performed to characterize so far unexplored ion transport pathways that may render erythrocytes of a single cryohydrocytosis patient cation-leaky. Design and Methods Cold-induced changes in cell volume were monitored using ektacytometry and density gradient centrifugation. Kinetics, temperature and inhibitor-dependence of the cation and water movements in the cryohydrocytosis patient’s erythrocytes were studied using radioactive tracers and flame photometry. Response of the membrane potential of the patient’s erythrocyte membrane to the presence of ionophores and blockers of anion and cation channels was assessed. Results In the cold, the cryohydrocytosis patient’s erythrocytes swelled in KCl-containing, but not in NaCl-containing or KNO3-containing media indicating that volume changes were mediated by an anion-coupled cation transporter. In NaCl-containing medium the net HOE-642-sensitive Na+/K+ exchange prevailed, whereas in KCl-containing medium swelling was mediated by a chloride-dependent K+ uptake. Unidirectional K+ influx measurements showed that the patient’s cells have abnormally high activities of the cation-proton exchanger and the K+,Cl− co-transporter, which can account for the observed net movements of cations. Finally, neither chloride nor cation conductance in the patient’s erythrocytes differed from that of healthy donors. Conclusions These results suggest that cross-talk between the mutated band 3 and other transporters might increase the cation permeability in cryohydrocytosis.
Can depression in psychogeriatric inpatients at one year follow-up be explained by locus of control and coping strategies?

ABSTRACT Objectives: Treatment of depression (in late life) is good. The short-term, but not long-term prognosis after treatment of depression in late life is good. To identify modifiable factors, we wanted to examine whether coping in terms of locus of control and coping strategies in depressed patients were associated with the prognosis of depression at follow-up, adjusted for sociodemographic information and health variables. Method: In total, 122 patients (mean age 75.4 years; SD = 6.6) were followed up (median 13.7 months, Q1-Q3 386-441) with a diagnostic evaluation(ICD-10) for depression and assessment of depressive symptoms (MADRS). Coping was assessed using Locus of Control of behavior (LoC-scale) and Ways of Coping questionnaire (WoC-scale). Results: At follow-up, 37.7% were diagnosed with a depressive episode. A stronger external LoC and lower MMSE-NR score at baseline were in adjusted linear regression analysis significantly more associated to higher depressive symptom scores (MADRS). More use of problem-focused coping, a lower I-ADL functioning, but not emotion-focused coping at baseline were significantly associated with being depressed (ICD-10), at follow-up in adjusted logistic regression analysis. Conclusion: LoC and coping strategies at baseline were associated with the prognosis of depression at follow-up, and may further be studied as indicators for choice of baseline intervention strategies.
Modeling the cost–effectiveness of HIV treatment: how to buy the most ‘health’ when resources are limited

Purpose of reviewTo summarize recent cost–effectiveness analyses (CEAs) that evaluate optimal treatment strategies for persons living with HIV/AIDS (PLWHA). Recent findingsEfforts to attain universal coverage of current treatment guidelines (e.g., initiation at CD4+ cell count <350 cells/&mgr;l) are generally very costeffective. Expansion of access beyond current guidelines will additionally improve clinical outcomes and aversion of new HIV infections; however, cost–effectiveness is more uncertain. Increasing access to antiretroviral therapy (ART) offers greater health benefit than investing the same funds in intensive laboratory monitoring for those on ART, particularly in those settings in which universal coverage has not yet been attained. Recommended ART regimens (e.g., tenofovir) have favorable cost–effectiveness when compared with substitution of newer, more expensive agents (e.g., rilpivirine, darunavir) or substitution of older, cheaper alternatives that are more toxic (e.g., stavudine). SummaryThere is increasing use of CEA to evaluate decisions regarding HIV treatment in order to buy the most ‘health’ with limited resources. Expansion of ART access provides substantial clinical and preventive benefit and offers favorable cost–effectiveness. Intensive laboratory monitoring may not be the highest priority in settings in which resources are constrained. Further work on the economic impact, clinical effectiveness, and feasibility of ART treatment for all (e.g., no CD4+ cell initiation criteria) is needed.