Miracle-dz/UniFAR-FTUs huggingface dataset:
The Assessment of Decisional Capacity: Gender Differences, Corresponding Medical and Psychiatric Illness, and Their Impact on Decisional Capacity

Abstract To date, gender differences and decisional capacity have not been studied. Altogether, decisional capacity assessments were required twice as often for male than for female patients. While female patients more commonly had endocrine disorders, male patients more commonly had neurological disorders, which contributed to decisional capacity impairment. Psychiatrically, mood disorders were more common in women and substance use disorders in men. Regarding decisional capacity tasks, men more frequently requested to sign out against medical advice. Overall, the ability to make appropriate health care decisions did not vary between genders. Although more decisional capacity assessments were requested for male patients, the degree to which decisional capacity existed did not vary between genders. Male patients more often displayed substance use and neurological disorders and more frequently requested to sign out against medical advice. Cognitive disorders caused more impairment for men than for women.
A chemical genomics screen highlights the essential role of mitochondria in HIF-1 regulation

Hypoxia-inducible factor-1 (HIF-1) plays an essential role in tumor development and progression by regulating genes that are vital for proliferation, glycolysis, angiogenesis, and metastasis. To identify strategies of targeting the HIF-1 pathway, we screened a siRNA library against the entire druggable genome and a small-molecule library consisting of 691,200 compounds using a HIF-1 reporter cell line. Although the siRNA library screen failed to reveal any druggable targets, the small-molecule library screen identified a class of alkyliminophenylacetate compounds that inhibit hypoxia-induced HIF-1 reporter activity at single-digit nanomolar concentrations. These compounds were found to inhibit hypoxia but not deferoxamine-induced HIF-1α protein stabilization. Further analysis indicated that the alkyliminophenylacetate compounds likely inhibit the HIF-1 pathway through blocking the hypoxia-induced mitochondrial reactive oxygen species (ROS) production. Strikingly, all of the nonalkyliminophenylacetate HIF-1 inhibitors identified from the small-molecule library screen were also found to target mitochondria like the alkyliminophenylacetate compounds. The exclusive enrichment of mitochondria inhibitors from a library of >600,000 diverse compounds by using the HIF-1 reporter assay highlights the essential role of mitochondria in HIF-1 regulation. These results also suggest that targeting mitochondrial ROS production might be a highly effective way of blocking HIF-1 activity in tumors.
Ecological rules governing helminth–microparasite coinfection

Coinfection of a host by multiple parasite species has important epidemiological and clinical implications. However, the direction and magnitude of effects vary considerably among systems, and, until now, there has been no general framework within which to explain this variation. Community ecology has great potential for application to such problems in biomedicine. Here, metaanalysis of data from 54 experiments on laboratory mice reveals that basic ecological rules govern the outcome of coinfection across a broad spectrum of parasite taxa. Specifically, resource-based (“bottom-up”) and predator-based (“top-down”) control mechanisms combined to determine microparasite population size in helminth-coinfected hosts. Coinfection imposed bottom-up control (resulting in decreased microparasite density) when a helminth that causes anemia was paired with a microparasite species that requires host red blood cells. At the same time, coinfection impaired top-down control of microparasites by the immune system: the greater the helminth-induced suppression of the inflammatory cytokine interferon (IFN)-γ, the greater the increase in microparasite density. These results suggest that microparasite population growth will be most explosive when underlying helminths do not impose resource limitations but do strongly modulate IFN-γ responses. Surprisingly simple rules and an ecological framework within which to analyze biomedical data thus emerge from analysis of this dataset. Through such an interdisciplinary lens, predicting the outcome of coinfection may become tractable.
Ligand-modulated folding of the full-length adenine riboswitch probed by NMR and single-molecule FRET spectroscopy

Abstract The full-length translation-regulating add adenine riboswitch (Asw) from Vibrio vulnificus has a more complex conformational space than its isolated aptamer domain. In addition to the predicted apo (apoA) and holo conformation that feature the conserved three-way junctional purine riboswitch aptamer, it adopts a second apo (apoB) conformation with a fundamentally different secondary structure. Here, we characterized the ligand-dependent conformational dynamics of the full-length add Asw by NMR and by single-molecule FRET (smFRET) spectroscopy. Both methods revealed an adenine-induced secondary structure switch from the apoB-form to the apoA-form that involves no tertiary structural interactions between aptamer and expression platform. This strongly suggests that the add Asw triggers translation by capturing the apoA-form secondary structure in the holo state. Intriguingly, NMR indicated a homogenous, docked aptamer kissing loop fold for apoA and holo, while smFRET showed persistent aptamer kissing loop docking dynamics between comparably stable, undocked and docked substates of the apoA and the holo conformation. Unraveling the folding of large junctional riboswitches thus requires the integration of complementary solution structural techniques such as NMR and smFRET.
New problems in old polio patients: results of a survey of 539 polio survivors.

Abstract Presented are the results of a questionnaire survey on new health problems in 539 polio survivors. The most common new problems were fatigue, weakness in previously affected and unaffected muscles, muscle pain, and joint pain. The median time from polio to the onset of these problems ranged from 30 to 40 years. Factors at onset of polio most strongly associated with developing these new health problems were: being hospitalized, being over 10 years old, being on a ventilator, and having paralytic involvement of all four limbs. The differential diagnoses of these new problems, implications for treatment and areas for future research are discussed.
Acceptability and Feasibility of Reiki for Symptom Management in Children Receiving Palliative Care

Complementary therapies are chosen by parents of children receiving palliative care to augment the use of traditional medications for symptom management without the increased side effects additional medications may bring. Pain and anxiety are common symptoms for children receiving palliative care. Reiki therapy is a light touch therapy that has been examined in adults but not with children until recently. This dissertation addresses the evidence for complementary therapies for children experiencing pain and anxiety, Reiki therapy for pain and anxiety in adults, and evidence based complementary therapies for young children considering developmental stage. The main study is a quasi-experimental mixed methods pilot study design examining the acceptability and the feasibility of a Reiki therapy intervention for children ages 7 to 16 years receiving palliative care. We measured pain, anxiety, and relaxation operationalized as heart and respiratory rates pre and post Reiki therapy interventions at each of two home visits. We completed a structured interview separately with parents and children to elicit their views on the Reiki therapy experience. Paired student t-tests or Wilcoxon signed rank tests were calculated comparing the pre and post Reiki scores separately for verbal and non-verbal children for each treatment, over the entire intervention, and independent sample t-tests or Mann-Whitney tests comparing children based on demographic variables. We approached 24 child-parent dyads, 21 (87.5%) agreed to participate and signed consents while 3 (12.5%) declined to participate. Of the 21 dyads, 16 completed the study (eight verbal and eight non-verbal children). Statistical significance was obtained for verbal children for heart rate for treatment two (t=3.550, p = 0.009) and for nonverbal children for pain for treatment two (Z = -2.023, p = 0.063); however effect sizes using Cohen’s d levels were medium to large for both verbal and non-verbal children for pain and anxiety. Children and their parents told us their experiences with Reiki therapy. Themes found in interviews augment the quantitative results. Themes included Feeling Better, Hard to Judge, and Still Going On, which helped clarify the quantitative results. Results support further study of Reiki therapy for symptom management in children.
Buprenorphine tapering schedule and illicit opioid use.

AIMS To compare the effects of a short or long taper schedule after buprenorphine stabilization on participant outcomes as measured by opioid-free urine tests at the end of each taper period. DESIGN This multi-site study sponsored by Clinical Trials Network (CTN, a branch of the US National Institute on Drug Abuse) was conducted from 2003 to 2005 to compare two taper conditions (7 days and 28 days). Data were collected at weekly clinic visits to the end of the taper periods, and at 1-month and 3-month post-taper follow-up visits. SETTING Eleven out-patient treatment programs in 10 US cities. INTERVENTION Non-blinded dosing with Suboxone during the 1-month stabilization phase included 3 weeks of flexible dosing as determined appropriate by the study physicians. A fixed dose was required for the final week before beginning the taper phase. MEASUREMENTS The percentage of participants in each taper group providing urine samples free of illicit opioids at the end of the taper and at follow-up. FINDINGS At the end of the taper, 44% of the 7-day taper group (n = 255) provided opioid-free urine specimens compared to 30% of the 28-day taper group (n = 261; P = 0.0007). There were no differences at the 1-month and 3-month follow-ups (7-day = 18% and 12%; 28-day = 18% and 13%, 1 month and 3 months, respectively). CONCLUSION For individuals terminating buprenorphine pharmacotherapy for opioid dependence, there appears to be no advantage in prolonging the duration of taper.
Thyroid Disorders in Accra, Ghana: A Retrospective Histopathological Study at the Korle-Bu Teaching Hospital

There is a scarcity of data on thyroid disorders in Ghana. This retrospective study examined the spectrum and incidence of thyroid disorders by reviewing all thyroid disorders reported in the De-partment of Pathology, Korle-Bu Teaching Hospital (KBTH) between 2004 and 2010. Data was collected on the clinical and histological characteristics of all thyroid disorders reported during the study. 1300 (3.7%) cases were reported, representing an annual incidence of 185.7 cases. The ages ranged from 1-86 years with a mean of 41.5 (SD=13.9). Most [353 (27.4%)] of the cases were be-tween 30-39 years group. Majority, 1141(87.8%) were females. The top eight common thyroid dis-eases were; non-toxic multinodular goitre 1002(77.5%), follicular adenoma 86(6.6%), diffuse toxic goitre 42 (3.2%), papillary thyroid carcinoma 40(3.1%), thyroglossal duct cyst 35(2.7%), Hashimo-to’s thyroiditis 28(2.2%), lymphocytic thyroiditis 22(1.7%) and follicular carcinoma 17(1.3%). Sixty-six (43.4%) of the neoplastic thyroid disorders were malignant with a prevalence of 0.18 among thy-roid samples and annual incidence of 9.40 cases. The commonest thyroid cancer was papillary car-cinoma 40(60.6 %), with a mean age of 38.3 SD=16.1 years, majority, 34 (82.9%), were women. A wide spectrum of thyroid disorders exists in Ghana, with an annual incidence of 185.7 cases. The commonest malignant thyroid disorder was papillary carcinoma, though iodine deficiency is en-demic in Ghana and on this basis; one would have expected follicular carcinoma to be the com-monest thyroid cancer in Ghana. Keywords: Multinodular; Goitre; Papillary; Follicular; Adenoma, Ghana Journal of Medical and Biomedical Sciences (2013) 2(1), 1-7
PWM technique for inverter with sinusoidal output current

A sinusoidal pulse width-modulation (PWM) technique suitable for single-chip microprocessor-based control is described. The scheme can be regarded as a digital alternative of the analog subharmonic method (SHM) in the sense that online real-time PWM control is possible and synchronization between carrier wave and signal wave is unnecessary. The maximum output voltage is 15% larger and the number of switchings is 30% less than those obtained by SHM. The PWM pulse creation principle is explained. As the calculation of the optimal PWM pattern needs only three multiplications, it can be executed online with a minimum ROM capacity using a conventional microprocessor. Experimental results are reported demonstrating the validity of the proposed scheme. <<ETX>>
HOCOMOCO: towards a complete collection of transcription factor binding models for human and mouse via large-scale ChIP-Seq analysis

Abstract We present a major update of the HOCOMOCO collection that consists of patterns describing DNA binding specificities for human and mouse transcription factors. In this release, we profited from a nearly doubled volume of published in vivo experiments on transcription factor (TF) binding to expand the repertoire of binding models, replace low-quality models previously based on in vitro data only and cover more than a hundred TFs with previously unknown binding specificities. This was achieved by systematic motif discovery from more than five thousand ChIP-Seq experiments uniformly processed within the BioUML framework with several ChIP-Seq peak calling tools and aggregated in the GTRD database. HOCOMOCO v11 contains binding models for 453 mouse and 680 human transcription factors and includes 1302 mononucleotide and 576 dinucleotide position weight matrices, which describe primary binding preferences of each transcription factor and reliable alternative binding specificities. An interactive interface and bulk downloads are available on the web: http://hocomoco.autosome. ru and http://www.cbrc. kaust.edu. sa/hocomoco11. In this release, we complement HOCOMOCO by MoLoTool (Motif Location Toolbox, http://molotool.autosome.ru) that applies HOCOMOCO models for visualization of binding sites in short DNA sequences.
Parents who quit smoking and their adult children's smoking cessation: a 20-year follow-up study.

AIMS Extending our earlier findings from a longitudinal cohort study, this study examines parents' early and late smoking cessation as predictors of their young adult children's smoking cessation. DESIGN Parents' early smoking cessation status was assessed when their children were aged 8 years; parents' late smoking cessation was assessed when their children were aged 17 years. Young adult children's smoking cessation, of at least 6 months duration, was assessed at age 28 years. SETTING Forty Washington State school districts. PARTICIPANTS AND MEASUREMENTS Participants were 991 at least weekly smokers at age 17 whose parents were ever regular smokers and who also reported their smoking status at age 28. Questionnaire data were gathered on parents and their children (49% female and 91% Caucasian) in a longitudinal cohort (84% retention). FINDINGS Among children who smoked daily at age 17, parents' quitting early (i.e. by the time their children were aged 8) was associated with a 1.7 times higher odds of these children quitting by age 28 compared to those whose parents did not quit [odds ratio (OR) 1.70; 95% confidence interval (CI) 1.23, 2.36]. Results were similar among children who smoked weekly at age 17 (OR 1.91; 95% CI 1.41, 2.58). There was a similar, but non-significant, pattern of results among those whose parents quit late. CONCLUSIONS Supporting our earlier findings, results suggest that parents' early smoking cessation has a long-term influence on their adult children's smoking cessation. Parents who smoke should be encouraged to quit when their children are young.
Domestication of the donkey: Timing, processes, and indicators

Domestication of the donkey from the African wild ass transformed ancient transport systems in Africa and Asia and the organization of early cities and pastoral societies. Genetic research suggests an African origin for the donkey, but pinpointing the timing and location of domestication has been challenging because donkeys are uncommon in the archaeological record and markers for early phases of animal domestication are hard to determine. We present previously undescribed evidence for the earliest transport use of the donkey and new paleopathological indicators for early phases of donkey domestication. Findings are based on skeletal data from 10 ≈5,000-year-old ass skeletons recently discovered entombed in an early pharaonic mortuary complex at Abydos, Middle Egypt, and a concurrent study of 53 modern donkey and African wild ass skeletons. Morphometric studies showed that Abydos metacarpals were similar in overall proportions to those of wild ass, but individual measurements varied. Midshaft breadths resembled wild ass, but midshaft depths and distal breadths were intermediate between wild ass and domestic donkey. Despite this, all of the Abydos skeletons exhibited a range of osteopathologies consistent with load carrying. Morphological similarities to wild ass show that, despite their use as beasts of burden, donkeys were still undergoing considerable phenotypic change during the early Dynastic period in Egypt. This pattern is consistent with recent studies of other domestic animals that suggest that the process of domestication is slower and less linear than previously thought.
Increasing the Number of Care Leavers in 'Settled, Safe Accommodation'

This review tells us what works in increasing the number of care leavers in 'settled, safe accommodation', on the basis of a systematic review of the research literature and analysis of key data. It aims to provide evidence that will help service providers to improve services and, ultimately, outcomes for children, young people and their families. For young people, being in 'settled, safe accommodation' is a top priority on leaving care and is about where they live, rent that is affordable, and being helped in budgeting and in managing their accommodation.
Genetic and non-genetic influences on the development of co-occurring alcohol problem use and internalizing symptomatology in adolescence: a review.

AIMS Alcohol problem use during adolescence has been linked to a variety of adverse consequences, including cigarette and illicit drug use, delinquency, adverse effects on pubertal brain development and increased risk of morbidity and mortality. In addition, heavy alcohol-drinking adolescents are at increased risk of comorbid psychopathology, including internalizing symptomatology (especially depression and anxiety). A range of genetic and non-genetic factors have been implicated in both alcohol problem use as well as internalizing symptomatology. However, to what extent shared risk factors contribute to their comorbidity in adolescence is poorly understood. DESIGN We conducted a systematic review on Medline, PsycINFO, Embase and Web of Science to identify epidemiological and molecular genetic studies published between November 1997 and November 2007 that examined risk factors that may be shared in common between alcohol problem use and internalizing symptomatology in adolescence. FINDINGS Externalizing disorders, family alcohol problems and stress, as well as the serotonin transporter (5-HTT) S-allele, the monoamine oxidase A (MAOA) low-activity alleles and the dopamine D2 receptor (DDR2) Taq A1 allele have been associated most frequently with both traits. An increasing number of papers are focusing upon the role of gene-gene (epistasis) and gene-environment interactions in the development of comorbid alcohol problem use and internalizing symptomatology. CONCLUSIONS Further research in adolescents is warranted; the increasing availability of large longitudinal genetically informative studies will provide the evidence base from which effective prevention and intervention strategies for comorbid alcohol problems and internalizing symptomatology can be developed.
Role of hybrid tRNA-binding states in ribosomal translocation

During translation, tRNAs must move rapidly to their adjacent sites in the ribosome while maintaining precise pairing with mRNA. This movement (translocation) occurs in a stepwise manner with hybrid-state intermediates, but it is unclear how these hybrid states relate to kinetically defined events of translocation. Here we analyze mutations at position 2394 of 23S rRNA in a pre-steady-state kinetic analysis of translocation. These mutations target the 50S E site and are predicted to inhibit P/E state formation. Each mutation decreases growth rate, the maximal rate of translocation (ktrans), and the apparent affinity of EF-G for the pretranslocation complex (i.e., increases K1/2). The magnitude of these defects follows the trend A > G > U. Because the C2394A mutation did not decrease the rate of single-turnover GTP hydrolysis, the >20-fold increase in K1/2 conferred by C2394A can be attributed to neither the initial binding of EF-G nor the subsequent GTP hydrolysis step. We propose that C2394A inhibits a later step, P/E state formation, to confer its effects on translocation. Replacement of the peptidyl group with an aminoacyl group, which is predicted to inhibit A/P state formation, decreases ktrans without increasing K1/2. These data suggest that movements of tRNA into the P/E and A/P sites are separable events. This mutational study allows tRNA movements with respect to both subunits to be integrated into a kinetic model for translocation.
Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/β-secretase expression

Although the role of APP and PSEN genes in genetic Alzheimer's disease (AD) cases is well established, fairly little is known about the molecular mechanisms affecting Aβ generation in sporadic AD. Deficiency in Aβ clearance is certainly a possibility, but increased expression of proteins like APP or BACE1/β-secretase may also be associated with the disease. We therefore investigated changes in microRNA (miRNA) expression profiles of sporadic AD patients and found that several miRNAs potentially involved in the regulation of APP and BACE1 expression appeared to be decreased in diseased brain. We show here that miR-29a, -29b-1, and -9 can regulate BACE1 expression in vitro. The miR-29a/b-1 cluster was significantly (and AD-dementia-specific) decreased in AD patients displaying abnormally high BACE1 protein. Similar correlations between expression of this cluster and BACE1 were found during brain development and in primary neuronal cultures. Finally, we provide evidence for a potential causal relationship between miR-29a/b-1 expression and Aβ generation in a cell culture model. We propose that loss of specific miRNAs can contribute to increased BACE1 and Aβ levels in sporadic AD.