Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and validation of a prediction index for hand-foot skin reaction in cancer patients receiving sorafenib

Background This study describes a repeated measures prediction index to identify patients at high risk of ≥ grade 2 hand-foot skin reaction (HFSR) before each week of sorafenib therapy. Methods Data from 451 patients who received a sorafenib (400 mg bid) as part of a clinical trial were reviewed (Escudier B, Eisen T, Stadler WM et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007; 356: 125–134). Generalized estimating equations were used to develop the final risk model. A risk-scoring algorithm (range 0–58) was then derived from the final model coefficients. External validation was then carried out on a new sample of 1145 patients who received sorafenib under an expanded access program. Results Pretreatment white blood cell count, female gender, good performance status, presence of lung and liver metastases and number of affected organs were predictors for ≥ grade 2 HFSR. A nonlinear association between HFSR risk and treatment duration was also identified where risk was maximized at week 5 followed by a gradual decline. Before each week of therapy, patients with risk scores >40 would be considered at high risk for developing ≥ grade 2 HFSR. Conclusions The application and planned continued refinement of this prediction tool will be an important source of patient-specific risk information for the development of moderate to severe HFSR.
Phosphate treatment of firing range soils: lead fixation or phosphorus release?

Phosphate treatment of lead (Pb)-contaminated soils relies on the premise that Pb converts to the thermodynamically stable, insoluble mineral class of pyromorphites. Recent research showed that treatment performance is kinetically controlled and strongly dependent on soil pH; this study employed an acidic phosphate (P) form, monobasic calcium phosphate (MCP), to investigate treatment performance of Pb occurring in an alkaline-buffered and an acidic firing range soil. The results of leaching, X-ray powder diffraction (XRPD), and modeling analyses showed that P and Pb dissolution in the alkaline soil and transformation reactions were kinetically controlled, so that: (i) TCLP (toxicity characteristic leaching procedure) and SPLP (synthetic precipitation leaching procedure) results were poor to marginal even at high MCP dosages; (ii) brushite (Ca(HPO(4)). 2H(2)O) and cerussite (PbCO(3)) persisted in XRPD patterns; and, (iii) geochemical modeling failed to predict leaching and phase assemblages. In the acidic soil, Pb-P reactions promoted further soil acidification, improved TCLP performance, and generated better agreement with the equilibrium-based model; however, SPLP and modeling results showed that Pb concentrations could not be reduced below 15 microg/L mainly due to the low soil pH. The marginal or inadequate Pb immobilization was observed in both soils despite the elevated MCP dosages, which were well in excess of the pyromorphite stoichiometric ratio (P/Pb = 0.6). Additionally, P leaching concentrations and rates were extremely high (>300 mg/L), under both SPLP and deionized (DI) water extraction conditions, and as predicted by thermodynamic equilibrium. The performance and sustainability of phosphate-based treatment therefore seem questionable.
Evidence of Central and Peripheral Vestibular Pathology in Blast-Related Traumatic Brain Injury

Objective: To prospectively assay the vestibular and oculomotor systems of blast-exposed service members with traumatic brain injury (TBI). Study Design: Prospective, nonblinded, nonrandomized descriptive study. Setting: Tertiary care facility (Department of Defense Medical Center). Patients: Twenty-four service members recovering from blast-related TBI sustained in Iraq or Afghanistan. Interventions: Focused history and physical, videonystagmography (VNG), rotational chair, cervical vestibular-evoked myogenic potentials, computerized dynamic posturography, and self-report measures. Results: Vestibular testing confirms a greater incidence of vestibular and oculomotor dysfunction in symptomatic (vestibular-like dizziness) personnel with blast-related TBI relative to asymptomatic group members. VNG in the symptomatic group revealed abnormal nystagmus or oculomotor findings in 6 of 12 subjects tested. Similarly, rotational chair testing in this group revealed evidence of both peripheral (4/12) and central (2/12) vestibular pathology. By contrast, the asymptomatic group revealed less vestibular impairment with 1 of 10 rotational chair abnormalities. The asymptomatic group was further characterized by fewer aberrant nystagmus findings (4/12 abnormal VNGs). Computerized dynamic posturography testing revealed no significant differences between groups. Self-report measures demonstrated differences between groups. Conclusion: Vestibular function testing confirms a greater incidence of peripheral vestibular hypofunction in dizzy service members with blast-related TBI relative to those who are asymptomatic. Additionally, oculomotor abnormalities and/or nystagmus consistent with central involvement were present in 10 of the 24 study participants tested. The precise cause of these findings remains unknown.
Loneliness in Married, Widowed, Divorced, and Never-Married Older Adults

Predictors of loneliness were investigated in married, widowed, divorced, and never-married older adults. Contacts with adult children, siblings, friends, and neighbors showed a stronger negative relationship with loneliness in unmarried than in married adults. However, divorced and widowed adults were more likely to profit from contact with adult children, whereas never-married and childless unmarried respondents profited most from contacts with siblings, friends, and neighbors. A better functional status was associated with less loneliness in divorced, widowed, and nevermarried adults, but not in married adults. Furthermore, unmarried men showed higher levels of loneliness than unmarried women, whereas only small sex differences in loneliness were found in married respondents. Sex differences in the loneliness of divorced and never-married adults were eliminated by controlling for sex differences in contact with children, siblings, and friends. However, widowers were lonelier than widows even after controlling for sex differences in these contacts.
Proximate and developmental analysis

of the original article: Voluntary acts are preceded by electrophysiological "readiness potentials" (RPs). With spontaneous acts involving no preplanning, the main negative RP shift begins at about —550 ms. Such RPs were used to indicate the minimum onset times for the cerebral activity that precedes a fully endogenous voluntary act. The time of conscious intention to act was obtained from the subject's recall of the spatial clock position of a revolving spot at the time of his initial awareness of intending or wanting to move (W). W occurred at about -200 ms. Control experiments, in which a skin stimulus was timed (S), helped evaluate each subject's error in reporting the clock times for awareness of any perceived event. For spontaneous voluntary acts, RP onset preceded the uncorrected Ws by about 350 ms and the Ws corrected for S by about 400 ms. The direction of this difference was consistent and significant throughout, regardless of which of several measures of RP onset or W were used. It was concluded that cerebral initiation of a spontaneous voluntary act begins unconsciously. However, it was found that the final decision to act could still be consciously controlled during the 150 ms or so remaining after the specific conscious intention appears. Subjects can in fact "veto " motor performance during a 100-200-ms period before a prearranged time to act. The role of conscious will would be not to initiate a specific voluntary act but rather to select and control volitional outcome. It is proposed that conscious will can function in a permissive fashion, either to permit or to prevent the motor implementation of the intention to act that arises unconsciously. Alternatively, there may be the need for a conscious activation or triggering, without which the final motor output would not follow the unconscious cerebral initiating and preparatory processes. Voluntary process and the readiness potential: Asking the right questions
Immunosuppressive therapy: a potential alternative to bone marrow transplantation as initial therapy for acquired severe aplastic anemia in childhood?

PURPOSE Currently bone marrow transplantation (BMT) with an HLA-identical sibling donor is recommended as optimal therapy for children with acquired severe aplastic anemia (SAA). Immunosuppressive therapy (IST) has become a very successful initial therapy for SAA in children lacking a related bone marrow donor. We wished to evaluate whether current IST regimens may be as efficacious as BMT. PATIENTS AND METHODS A retrospective review identified children treated for SAA over a 12-year period. Children with a related donor received a BMT. Children lacking a donor were treated with IST followed by a "rescue" BMT if IST was ineffective. IST consisted of anti-thymocyte globulin and steroid +/- cyclosporine A. Transfusion independence and survival rates were compared between the two groups. RESULTS Twenty-seven children were identified. Nine received a related BMT; seven of these survive and are transfusion independent (median follow-up 54 months). Sixteen of 18 patients who received IST are transfusion-independent survivors, including three of four patients who received a rescue BMT (median follow-up 33.5 months). Actuarial survival is 75% (95% CI = 45%, 105%) and 92% (95% CI = 78%, 107%) for the BMT and IST groups, respectively (p = 0.15). Severe toxicity was not experienced by any patient as a result of IST. CONCLUSIONS Equivalent rates of transfusion independence and survival were experienced by patients receiving BMT and IST. We propose that a prospective trial be undertaken to evaluate IST as initial therapy in all children with SAA, to be followed by BMT if there is inadequate response.
Resistance to compression of weakened roots subjected to different root reconstruction protocols

Objective This study evaluated, in vitro, the fracture resistance of human non-vital teeth restored with different reconstruction protocols. Material and methods Forty human anterior roots of similar shape and dimensions were assigned to four groups (n=10), according to the root reconstruction protocol: Group I (control): non-weakened roots with glass fiber post; Group II: roots with composite resin by incremental technique and glass fiber post; Group III: roots with accessory glass fiber posts and glass fiber post; and Group IV: roots with anatomic glass fiber post technique. Following post cementation and core reconstruction, the roots were embedded in chemically activated acrylic resin and submitted to fracture resistance testing, with a compressive load at an angle of 45º in relation to the long axis of the root at a speed of 0.5 mm/min until fracture. All data were statistically analyzed with bilateral Dunnett's test (α=0.05). Results Group I presented higher mean values of fracture resistance when compared with the three experimental groups, which, in turn, presented similar resistance to fracture among each other. None of the techniques of root reconstruction with intraradicular posts improved root strength, and the incremental technique was suggested as being the most recommendable, since the type of fracture that occurred allowed the remaining dental structure to be repaired. Conclusion The results of this in vitro study suggest that the healthy remaining radicular dentin is more important to increase fracture resistance than the root reconstruction protocol.
Alcohol consumption and unsafe sexual behavior in discrete events

Recent studies with samples of homosexual men have demonstrated that drinking in conjunction with sexual activity is strongly related to unsafe sexual activities known to increase the risk of AIDS transmission. Most existing studies have assessed the relationship of general measures of drinking and general frequency of risky sexual activities. Such a design, however, does not establish that drinking and risky behaviors occurred on the same occasion. In this study, adult respondents were asked about the circumstances of two sexual encounters: their most recent sexual experience and their most recent encounter involving a new sexual partner. The characteristics of encounters that involved and did not involve drinking are described. The results showed that encounters with new partners were more likely to involve alcohol, but that the presence of alcohol was not significantly associated with risky sexual activity. These findings suggest that analyses of event‐specific data illuminate a different aspect of the.
Faster Evaluation of Multidimensional Integrals

In a recent paper Keister proposed two quadrature rules as alternatives to Monte Carlo for certain multidimensional integrals and reported his test results. In earlier work we had shown that the quasi-Monte Carlo method with generalized Faure points is very effective for a variety of high dimensional integrals occurng in mathematical finance. In this paper we report test results of this method on Keister's examples of dimension 9 and 25, and also for examples of dimension 60, 80 and 100. For the 25 dimensional integral we achieved accuracy of 0.01 with less than 500 points while the two methods tested by Keister used more than 220,000 points. In all of our tests, for n sample points we obtained an empirical convergence rate proportional to n^{-1} rather than the n^{-1/2} of Monte Carlo.
Attachment Theory, Family System Theory, and the Child Presenting with Significant Behavioral Concerns

Allied health and medical professionals—specifically child and family therapists—will be familiar with referrals involving children who have been identified as exhibiting behavioral concerns of some description. This paper will propose that clarity regarding conceptualization of childhood behavioral concerns is aided by a knowledge of both attachment theory and family systems theory and that when applied simultaneously, these theories increase the relevance of the other. In particular, there will be a description of attachment classifications in systemic terms, thus highlighting the relevance of attachment classifications outside of the Strange Situation experiment. Second, the relevance of first- and second-order cybernetics will be discussed with the intention of describing differences between caregivers' approaches to the concerns at hand. Finally, it will be suggested that multiple levels of theory should be considered when responding to childhood behavioral concerns from an attachment/systemic perspe.
Computerised Cognitive Behavioural Therapy for Insomnia: A Systematic Review and Meta-Analysis

Background: Computerised cognitive behavioural therapy (CCBT) is an innovative mode of delivering services to patients with psychological disorders. The present paper uses a meta-analysis to systematically review and evaluate the effectiveness of CCBT for insomnia (CCBT-I). Method: A comprehensive search was conducted on 7 databases including MEDLINE, PsycINFO, EMBASE, CINAHL, Cochrane Library, Social Sciences Citation Index and PubMed (up to March 2011). Search terms covered 3 concepts: (1) [internet, web, online, computer-aided, computer-assisted, computer-guided, computerized OR computerised] AND (2) [CBT, cognitive therapy, behavio(u)ral therapy OR behavio(u)r therapy] AND (3) [insomnia, sleep disorders OR sleeping problem]. Results: 533 potentially relevant papers were identified, and 6 randomised controlled trials (RCTs) that met the selection criteria were included in the review and analysis. Two RCTs were done by the same group of investigators (Ritterband and colleagues) using the same internet programmes. Post-treatment mean differences between groups showed that the effects of CCBT-I on sleep quality, sleep efficiency, the number of awakenings, sleep onset latency and the Insomnia Severity Index were significant, ranging from small to large effect sizes. However, effects on wake time after sleep onset, total sleep time and time in bed were non-significant. On average, the number needed to treat was 3.59. The treatment adherence rate for CCBT-I was high (78%). Conclusion: The results lend support to CCBT as a mildly to moderately effective self-help therapy in the short run for insomnia. CCBT-I can be an acceptable form of low-intensity treatment in the stepped care model for insomnia.
Lack of association between Chlamydia trachomatis infection and cervical cancer--Taq Man realtime PCR assay findings.

BACKGROUND Cervical cancer is one of the most common cancers in developing countries and the second most common type of cancer in women globally. Several recent studies suggested a co factor role for Chlamydia trachomatis in pathogenesis of cervical cancer. This study aimed to evaluate existence of C. trachomatis DNA in pathologic blocks of patients with cervical cancer. MATERIALS AND METHODS Seventy-six formaldehyde fixed paraffin embedded tissue specimens from patients with histologically proven history of cervical cancer as well as 150 blocks from healthy peoples were included in the present study. Thin slices were prepared from selected blocks followed by deparaffinization and DNA extraction; the presence of C. trachomatis DNA was examined by Taq Man real-time PCR. RESULTS Our TaqMan real time PCR assay with cervical specimens of patients with cervical cancer showed that there was no C. trachomatis DNA. Also, we found three positive specimens among our control group. CONCLUSION It seems that based on results obtained from the specimens examined in the present study, there is no association between the presence of C. trachomatis DNA in cervical specimens and cervical cancer.
Biotin Protein Ligase from Saccharomyces cerevisiae

Catalytically active biotin protein ligase fromSaccharomyces cerevisiae (EC 6.3.4.15) was overexpressed inEscherichia coli and purified to near homogeneity in three steps. Kinetic analysis demonstrated that the substrates ATP, biotin, and the biotin-accepting protein bind in an ordered manner in the reaction mechanism. Treatment with any of three proteases of differing specificity in vitro revealed that the sequence between residues 240 and 260 was extremely sensitive to proteolysis, suggesting that it forms an exposed linker between an N-terminal 27-kDa domain and the C-terminal 50-kDa domain containing the active site. The protease susceptibility of this linker region was considerably reduced in the presence of ATP and biotin. A second protease-sensitive sequence, located in the presumptive catalytic site, was protected against digestion by the substrates. Expression of N-terminally truncated variants of the yeast enzyme failed to complement E. colistrains defective in biotin protein ligase activity. In vitro assays performed with purified N-terminally truncated enzyme revealed that removal of the N-terminal domain reduced BPL activity by greater than 3500-fold. Our data indicate that both the N-terminal domain and the C-terminal domain containing the active site are necessary for complete catalytic function.
Impairments in Mice Lacking Shank 1 : Reduced Levels of Ultrasonic Vocalizations and Scent Marking Behavior

Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1 null mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1 mice as compared to wildtype Shank1 littermate controls. Shank1 pups emitted fewer vocalizations than Shank1 pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1 males deposited fewer scent marks in proximity to female urine than Shank1 males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1 mice changed their calling pattern dependent on previous female interactions, while Shank1 mice were unaffected, indicating a failure of Shank1 males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1 mice are consistent with a phenotype relevant to social communication deficits in autism. Citation: Wöhr M, Roullet FI, Hung AY, Sheng M, Crawley JN (2011) Communication Impairments in Mice Lacking Shank1: Reduced Levels of Ultrasonic Vocalizations and Scent Marking Behavior. PLoS ONE 6(6): e20631. doi:10.1371/journal.pone. 0020631 Editor: Wim E. Crusio, Université de Bordeaux and Centre National de la Recherche Scientifique, France Received January 26, 2011; Accepted May 6, 2011; Published June 9, 2011 This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Funding: This work was supported by the National Institute of Mental Health Intramural Research Program and Simons Foundation (M.S. & A.H.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: markus.woehr@staff.uni-marburg.de (MW); crawleyj@mail.nih. gov (JNC) ¤ Current address: Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg, Germany
Activity of abundant and rare bacteria in a coastal ocean

The surface layer of the oceans and other aquatic environments contains many bacteria that range in activity, from dormant cells to those with high rates of metabolism. However, little experimental evidence exists about the activity of specific bacterial taxa, especially rare ones. Here we explore the relationship between abundance and activity by documenting changes in abundance over time and by examining the ratio of 16S rRNA to rRNA genes (rDNA) of individual bacterial taxa. The V1–V2 region of 16S rRNA and rDNA was analyzed by tag pyrosequencing in a 3-y study of surface waters off the Delaware coast. Over half of the bacterial taxa actively cycled between abundant and rare, whereas about 12% always remained rare and potentially inactive. There was a significant correlation between the relative abundance of 16S rRNA and the relative abundance of 16S rDNA for most individual taxa. However, 16S rRNA:rDNA ratios were significantly higher in about 20% of the taxa when they were rare than when abundant. Relationships between 16S rRNA and rDNA frequencies were confirmed for five taxa by quantitative PCR. Our findings suggest that though abundance follows activity in the majority of the taxa, a significant portion of the rare community is active, with growth rates that decrease as abundance increases.