Miracle-dz/UniFAR-FTUs huggingface dataset:
Emerging combination treatment strategies containing novel agents in newly diagnosed multiple myeloma

Treatment strategies for multiple myeloma have changed substantially over the past 10 years following the introduction of bortezomib and the immunomodulatory drugs thalidomide and lenalidomide. In the front‐line setting, combination regimens incorporating these novel agents are demonstrating substantial activity, which is translating into improved outcomes compared with previous standards of care. Response rates and depth of response that were previously only seen with high‐dose therapy plus stem‐cell transplantation (HDT–SCT) can now be achieved with new induction regimens utilizing these novel agents. This has raised the need for trials that will determine the clinical benefit of early SCT in patients that have already achieved a high quality of response. Here, we review the improvements in response and outcome that are seen with these novel‐agent regimens, both as induction therapy prior to HDT–SCT and in non‐transplant patients, and highlight the latest data from key studies of various novel combinations, including regimens featuring bortezomib plus thalidomide or lenalidomide. We also review data on response and outcomes in patients with poor prognostic characteristics that indicate that the adverse impact typically seen with these factors may be overcome using novel‐agent therapy.
Cold Pressor-Induced Pain Does Not Impair WAIS-IV Processing Speed Index or Working Memory Index Performance

Chronic pain frequently involves cognitive complaints such as concentration and memory deficits, but studies of the effects of pain on cognition have not consistently demonstrated deficits and have not typically utilized standard neuropsychological instruments. Effects of cold pressor-induced pain on Wechsler Adult Intelligence Scale-Fourth Edition Processing Speed Index (PSI) and Working Memory Index (WMI) performance was examined in nonclinical volunteers (n = 40). All took one PSI subtest and one WMI subtest normally, and then took different PSI and WMI subtests during cold pressor-induced pain or painless warm-water immersion. Scaled scores for normal administration versus pain or painless water immersion did not differ and there was no interaction between group (control vs. pain) and manner of administration, despite moderately severe mean pain ratings (M = 6.8 on a 0–10 pain-rating scale). Results indicate that induced pain in nonclinical volunteers does not impair PSI or WMI performance, and they suggest that chronic pain per se should not be expected to substantially affect these cognitive functions. However, patients with chronic pain may differ from nonclinical volunteers in their experience of pain, potentially limiting generalizability.
Studies of penetrance and anticipation in five autosomal‐dominant restless legs syndrome pedigrees

Restless legs syndrome (RLS) can occur with an autosomal‐dominant mode of inheritance. To determine if there are distinguishing features of RLS pedigrees which might clarify molecular mechanisms of pathogenesis, five pedigrees with 81 affected members were analyzed for age of onset, sex ratio, and transmission pattern. One‐factor analysis of variance of ages of onset between generations was carried out, and segregation ratios were calculated for each generation. These kindreds showed an autosomal‐dominant mode of inheritance and a male:female ratio of 1:1.4 (p = 0.15). One of the five analyzed pedigrees shows some evidence of reduced penetrance. In two of the five analyzed pedigrees, there is statistical support for anticipation (p < 0.05). These variations in penetrance and anticipation suggest possible genetic heterogeneity.
An Equalization Approach to Feedback Stabilization Over Fading Channels

This paper proposes an equalization approach to mean-square (MS) feedback stabilization for multi-input/multi-output (MIMO) discrete-time systems over fading channels. An orthogonal encode/decode matrix pair is placed at the two ends of the fading channel, thereby equalizing the complementary sensitivity in the MS sense. By adopting the notion of the MS stability in an input-output setting, and using the signal-to-noise ratio (SNR) and encode/decode matrix as additional design parameters, we are able to convert the networked stabilization over fading channels into an equivalent constrained H2 optimal control, and derive the MS stabilizability conditions over linear time-invariant controllers. Our results recover the existing MS stabilizability condition under the state feedback. For output feedback control, we provide a characterization of the minimum network resource for the SNR required to stabilize the networked control system over the fading channel, and develop the synthesis algorithms for design of the orthogonal coding matrix and output feedback controller in different scenarios. Our results show that the MS stabilization problem as formulated in this paper admits the closed-form solution for MIMO plants with unstable block zeros, and is mathematically tractable for more general MIMO plants. Two numerical examples are worked out to illustrate our results.
Clinical and microbiological studies of children and adolescents receiving orthodontic treatment.

PURPOSE This case-controlled study examined clinical and microbiological parameters in Brazilian children and adolescents receiving orthodontic treatment using fixed orthodontic appliances or removable orthodontic appliances. METHODS The plaque index, gingival index, number of decayed, missing and filled teeth, and probing pocket depth was measured on each fully erupted tooth in 30 patients treated with fixed orthodontic appliances and an equal number of age and sex-matched control subjects. The same parameters were also measured in 18 patients treated with removable orthodontic appliances and an equal number of age and sex-matched control subjects. In the patients treated with fixed orthodontic appliances, subgingival plaque samples were collected from four teeth with orthodontic brackets and from four teeth with orthodontic bands. In the patients with removable appliances, subgingival plaque samples were collected from clasped maxillary permanent first molar teeth and from four unclasped permanent teeth. Samples of unstimulated whole saliva and samples from the dorsal surface of the tongue were also obtained from each subject. Each sample was analyzed for the presence of 19 target bacteria by dot blot. A subset of samples was examined by direct amplification of bacterial nucleic acids. RESULTS Compared to their respective age and sex-matched controls, whole mouth means for plaque index and gingival index were significantly elevated in both the fixed and removable orthodontic groups. There was no difference in the DMFT. Subjects with fixed orthodontic appliances had a higher prevalence of each of the target species except for L. fermentum, Neisseriaceae and S. mutans. The prevalence of A. naeslundii and Streptococcus sp. was significantly higher on teeth with orthodontic brackets alone compared to teeth with both orthodontic bands and brackets. Subjects with removable orthodontic appliances had a higher prevalence of A. actinomycetemcomitans, C. rectus, E. corrodens, L. fermentum, Neisseriaceae, and spirochetes. The prevalence of Neisseriaceae was significantly higher on unclasped teeth compared to clasped teeth. There was no difference between sample sites for the target bacteria except for A. actinomycetemcomitans that was detected less frequently in saliva. Orthodontic patients demonstrated higher proportions of gram negative species by direct amplification of nucleic acids including species frequently associated with periodontal disease as well as rarely cultivable or non-cultivable species such as Abiotrophia defectiva, Gemella haemolysans, Granulicatella adiacens, Lautropia sp. , Terrahaemophilus aromaticivorans, and TM7 bacterium.
Abstract coherent categories.

Many studies have demonstrated the importance of the knowledge that interrelates features in people's mental representation of categories and that makes our conception of categories coherent. This article focuses on abstract coherent categories, coherent categories that are also abstract because they are defined by relations independently of any features. Four experiments demonstrate that abstract coherent categories are learned more easily than control categories with identical features and statistical structure, and also that participants induced an abstract representation of the category by granting category membership to exemplars with completely novel features. The authors argue that the human conceptual system is heavily populated with abstract coherent concepts, including conceptions of social groups, societal institutions, legal, political, and military scenarios, and many superordinate categories, such as classes of natural kinds.
Efecto de la lisofosfatidilcolina en la reacción del acrosoma de espermatozoides caninos

Los lisofosfolipidos desestabilizan la membrana plasmatica del espermatozoide y promueven su fusion con la membrana acrosomica externa, acelerando la reaccion del acrosoma (RA). La lisofosfatidilcolina (LC) ha sido utilizada para inducir la RA en espermatozoides capacitados de diferentes mamiferos. El objetivo de este estudio fue evaluar el efecto de la LC en la induccion de la RA en espermatozoides caninos. Se utilizaron diferentes concentraciones de LC (0, 100, 200 y 300 µg/mL) por 15 minutos para inducir la RA en espermatozoides incubados por 0, 3 y 4 horas en un medio capacitante (mCCM). La vitalidad y el estado acrosomal se determino por la tecnica de doble fluorescencia Aglutinina de Pisum sativum con Isotiocianato de Fluoresceina (PSA-FITC) y Hoechst 33258. La prueba de analisis de varianza (ANOVA) fue utilizada para el analisis estadistico. Concentraciones de 200 y 300 µg/mL de LC reducen significativamente (P 0,05). Sin embargo, se observo un incremento significativo (P
Arabidopsis Genes AS 1 , AS 2 , and JAG Negatively Regulate Boundary-Specifying Genes to Promote Sepal and Petal Development 1 [ W ]

National Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China (B.X., H.W., H.H.); State Key Laboratory of Genetic Engineering, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai 200433, China (Z.L., Y.Z., A.D.); and Department of Biology and the Huck Institute for the Life Sciences, Pennsylvania State University, University Park, Pennsylvania 16802 (H.M.)
Comparative efficacy and safety of amorolfine nail lacquer 2% versus 5% once weekly

Altogether 157 patients with onychomycosis affecting not more than 80% of the surface area of nail with intact lunula and matrix were treated once weekly for up to 6 months with amorolfine nail lacquer (2 or 5%) in a double‐blind randomized design. Clinical examinations were carried out before, monthly during, and 1 and 3 months after therapy. Mycological examinations were performed before, 1 and 3 months after therapy. One hundred patients were evaluated. According to the overall assessment by the investigators, which was based on the clinical response and mycological findings, there was cure in 12% improvement in 55% and failure in 33% of the 2% group. The corresponding figures in the 5% group were: cure in 38% improvement in 32% and failure in 30%. The difference in the number of cures was statistically significant in favour of the 5% nail lacquer. The most common pathogens isolated were Trichophyton rubrum in 59% of cases and Trichophyton mentagrophytes in 22%. Three months after the end of the treatment the mycological culture was negative in 55% of the 2% group and in 60% of the 5% group. Both concentrations were well tolerated. Only three patients (2%) experienced mild local adverse events. No systemic side‐effects occurred and no patient discontinued treatment due to an adverse event. In conclusion, the 5% nail lacquer was more effective than the 2% nail lacquer when used once weekly for up to 6 months for the treatment of mild to moderate onychomycosis, and both concentrations were well tolerated.
Nursing Issues in Caring for Children with Moyamoya Vasculopathy and Their Families

&NA; Moyamoya vasculopathy is a rare, progressive neurovascular condition that may cause recurrent transient ischemic attacks, ischemic strokes, hemorrhagic strokes, or neurologic decline in children. Children with moyamoya disease have no clear contributing etiology, but children with moyamoya syndrome have contributory diagnoses such as Down syndrome or neurofibromatosis. The concerns and lived experiences of children affected by this disease and their families have not been well explored or addressed in the nursing literature. Nurses who understand this lived experience increase their own knowledge of the disease so they can manage the complex medical issues, educate families about the disease, and provide emotional support.
Immunohistochemical Findings in Embryonal Small Round Cell Tumors With Molecular Diagnostic Confirmation

The diagnosis of pediatric tumors relies heavily on immunohistochemical staining of small tissue biopsies, since many entities share a "small blue cell" phenotype. More recently, molecular genetic analysis for detection of specific gene fusion products has become available. With the increased use of such molecular techniques, the authors have noted that tumors with proven molecular diagnoses can exhibit unusual patterns of immunohistochemical staining. This study examines pediatric tumors with a "small blue cell" phenotype in which molecular diagnoses were available where applicable. A panel of immunohistochemical stains was performed (S100, CD56, NB84, CD99 [MIC2], Bcl-2, CD117, CD34, desmin, MNF116, and WT1). In the 370 sections from 37 cases, all primitive neuroectodermal tumors, with and without the presence of t(11;22), demonstrated uniform membranous membrane staining with CD99 (MIC2) and focal staining with CD56, NB84, MNF116, and WT1. All rhabdomyosarcomas, both alveolar and embryonal, demonstrated uniform desmin, CD56, and cytoplasmic WT1 immunostaining. Desmoplastic small round cell tumors showed positive cytokeratin staining, with half having "dot-like" cytoplasmic desmin and WT1 positivity; some showed focal positivity for NB84, CD99, and Bcl-2. The "undifferentiated" sarcomas showed the widest range of staining, with no marker staining all cases. Neuroblastomas exhibited uniform strong staining for CD56 and NB84 and marked cytoplasmic Bcl-2 positivity, and some cases showed cytoplasmic WT1 expression. Blastematous Wilms' tumors showed uniform strong membranous staining for CD56, uniform cytoplasmic staining for Bcl-2, and nuclear expression of WT1. Embryonal pediatric malignancies can demonstrate apparently nonspecific expression patterns for several antigens, which may reflect developmental immaturity rather than specific differentiation pathways.
Role of Input Correlations in Shaping the Variability and Noise Correlations of Evoked Activity in the Neocortex

Recent analysis of evoked activity recorded across different brain regions and tasks revealed a marked decrease in noise correlations and trial-by-trial variability. Given the importance of correlations and variability for information processing within the rate coding paradigm, several mechanisms have been proposed to explain the reduction in these quantities despite an increase in firing rates. These models suggest that anatomical clusters and/or tightly balanced excitation–inhibition can generate intrinsic network dynamics that may exhibit a reduction in noise correlations and trial-by-trial variability when perturbed by an external input. Such mechanisms based on the recurrent feedback crucially ignore the contribution of feedforward input to the statistics of the evoked activity. Therefore, we investigated how statistical properties of the feedforward input shape the statistics of the evoked activity. Specifically, we focused on the effect of input correlation structure on the noise correlations and trial-by-trial variability. We show that the ability of neurons to transfer the input firing rate, correlation, and variability to the output depends on the correlations within the presynaptic pool of a neuron, and that an input with even weak within-correlations can be sufficient to reduce noise correlations and trial-by-trial variability, without requiring any specific recurrent connectivity structure. In general, depending on the ongoing activity state, feedforward input could either increase or decrease noise correlation and trial-by-trial variability. Thus, we propose that evoked activity statistics are jointly determined by the feedforward and feedback inputs.
Bioelectric correlates of kanamycin intoxication.

Young guinea pigs were given a series of subcutaneous injections of kanamycin (400 mg/kg body weight for 8-14 days) and after at least a two-week waiting period various electrical responses from the cochlea were measured. After the experiments the cochlea was perfused with osmic acid, surface preparations were used to obtain sensory (hair) cell counts, and cochleograms were prepared. In this report the relationship between the various electrical in dices of cochlear function (cochlear microphonic: CM. summating potential: SP, and whole nerve action potential: AP) and the degree and configuration of sensory cell damage is discussed. The electrode potentials were obtained with the differential electrode technique and localized CM and SP responses were collected from the first and often the third cochlear turns. Both the differential (DIF) and the average (AVE) SP components were studied. The results reveral that the CM production of inner hair cells alone is about 30-40 dB below that of the outer hair cells.
Development in self-rated health among older people as determinant of social relations

Aim: The purpose of this study was to analyse whether development in self-rated health (SRH) over four years was associated with the structure of and satisfaction with social relations, at four and eight years follow-up, among elderly women and men. Methods: A longitudinal questionnaire-based study was undertaken of non-institutionalized Danes, aged 70 - 95 years, with baseline in 1986. The response rate at baseline was 69%, n=1,231. First follow-up was carried out in 1990, with 91% of eligible individuals participating (n=911). Second follow-up took place in 1994, where 83% of eligible individuals participated (n=542). The association was studied between development in SRH from 1986 to 1990 and social relations in 1990 and in 1994. Results: A sustained poor SRH predicted low contact frequency OR=1.7 (1.1 - 2.6), small contact diversity OR=1.6 (1.0 - 2.6) and low contact satisfaction OR=3.4 (2.3 - 5.2) in the two-point analyses. Furthermore, a deterioration in SRH predicted poor contact satisfaction OR=2.8 (1.7 - 4.5). All analyses were adjusted for age, gender, mental health, functional ability, cohabitation status, and a measure of social relations at baseline. Results for the three-point analyses were similar to those for the two-point analyses. The associations were weaker for contact satisfaction OR=2.8 (1.7 - 4.7), but stronger for contact frequency OR=2.5 (1.4 - 4.4) and diversity OR=2.1 (1.2 - 3.6). Conclusion: Sustained poor SRH and, to some degree, deterioration in SRH were predictors of poor social relations after four and eight years.
Effect of tropically adapted sire breeds on preweaning growth of F1 Angus calves and reproductive performance of their Angus dams.

The objective of this study was to determine the effect of tropically adapted sire breeds on preweaning growth performance of F1 calves and on reproductive performance of their Angus dams. Angus (A) cows were bred in two consecutive years (1992 and 1993) by AI using semen from Brahman (B; Bos indicus; n = 10), Senepol (S; Bos taurus; n = 10), and Tuli (T; Sanga; n = 9) bulls. A total of 82 B x A, 85 S x A, and 91 T x A calves were born. The statistical model included the fixed effects of year, sire breed, calf sex, sire breed x calf sex, and cow parity and the random effect of sire within sire breed. Birth weight, weaning weight, 205-d adjusted weaning weight, ADG from birth to weaning, and hip height at weaning were greater (P < .001) for B x A calves than for S x A or T x A calves. Greater differences were detected between sexes for B x A than for S x A and T x A (for all traits sire breed x calf sex, P < .05). Sire breed affected (P < .01) the percentage of unassisted calvings (B x A, 87%; S x A, 98%; and T x A, 100%) and tended (P < .10) to affect the percentage of calves that survived until weaning (B x A, 90%; S x A, 94%; and T x A, 98%). Sire breed of calf did not affect (P > .10) length of gestation, and sire breed did not affect the interval from calving to first observed estrus or pregnancy in Angus dams. These results demonstrate that preweaning growth performance of B x A calves was greater than that of either S x A or T x A calves. However, use of Brahman sires on Angus dams led to calving problems and tended to reduce the percentage of calves that survived until weaning. Thus, heavier weaning weights of B x A calves would be an advantage for cow-calf producers marketing calves, but heavier birth weights and calving difficulty attributed to Brahman sires would be a disadvantage.
Type-D personality but not implantable cardioverter-defibrillator indication is associated with impaired health-related quality of life 3 months post-implantation.

AIMS Little is known about the impact of ICD indication (primary vs. secondary) on health-related quality of life (HRQL). Indication may also interact with psychological factors, such as personality. Using a prospective design, we examined whether ICD indication and type-D personality (i.e. experiencing increased negative emotions paired with emotional non-expression) serve as modulators of HRQL at baseline and 3 months post-implantation. METHODS AND RESULTS Consecutively implanted ICD patients (n = 154) completed the Type-D Scale (DS14) at baseline and the Short-Form Health Survey 36 (SF-36) at baseline and 3 months. Of all patients, 82 (53%) received an ICD due to prophylactic reasons; the prevalence of type-D was 23%. Indication had no influence on HRQL (P = 0.75). Further stratification by personality showed a main effect for type-D personality (P < 0.001), with type-D patients generally experiencing poorer HRQL; there was no main effect for indication (P = 0.45) nor was the interaction effect indication by type-D significant (P = 0.22). There was a significant improvement in HRQL over time (P = 0.001). Type-D remained an independent predictor of impaired HRQL, adjusting for clinical factors and shocks during follow-up (P < 0.001). However, in adjusted analysis there was no longer a significant change in HRQL over time (P = 0.099). CONCLUSION Type-D personality but not ICD indication was associated with impaired HRQL at the time of implantation and at 3 months. In the quest for enhancing risk stratification in clinical practice, personality factors, such as type-D, should not be ignored, as both type-D and poor HRQL have been associated with increased risk of mortality in cardiac patients.