Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancers regulate progression of development in mammalian cells

During development and differentiation of an organism, accurate gene regulation is central for cells to maintain and balance their differentiation processes. Transcriptional interactions between cis-acting DNA elements such as promoters and enhancers are the basis for precise and balanced transcriptional regulation. We identified modules of combinations of binding sites in proximal and distal regulatory regions upstream of all transcription start sites (TSSs) in silico and applied these modules to gene expression time-series of mouse embryonic development and differentiation of human stem cells. In addition to tissue-specific regulation controlled by combinations of transcription factors (TFs) binding at promoters, we observed that in particular the combination of TFs binding at promoters together with TFs binding at the respective enhancers regulate highly specifically temporal progression during development: whereas 40% of TFs were specific for time intervals, 79% of TF pairs and even 97% of promoter–enhancer modules showed specificity for single time intervals of the human stem cells. Predominantly SP1 and E2F contributed to temporal specificity at promoters and the forkhead (FOX) family of TFs at enhancer regions. Altogether, we characterized three classes of TFs: with binding sites being enriched at the TSS (like SP1), depleted at the TSS (like FOX), and rather uniformly distributed.
The effect of moisture on the dielectric relaxations in wood

The dielectric constant ϵ′ and the loss factor ϵ″ of moistened wood were measured over a wide range of moisture content (MC), 0–40 wt% in the temperature range −196 to 0°C, and in the frequency range 30 Hz to 1 M Hz. Three relaxations were observed depending on the MC and frequency. The first ϵ″ peak at −103°C (30 Hz) in oven-dried wood is known to be due to the methylol rotation in the amorphous regions. A new ϵ″ peak (second peak), which appeared for MC >0.6 wt% at −110 to −40°C (30Hz) depending on the MC, is assigned to the local mode motions of the complexes between moisture and polar groups in the wood system; it is enhanced as the overall loosening of the initial hydrogen bond network is promoted by the extended hydration due to further sorption of moisture. The peak temperatures and the activation energies for these relaxations changed complexly depending on the MC. At MC > 10 wt%, a novel ϵ″ peak (third peak) was disclosed around −40°C (30 Hz) as a shoulder of the ionic conduction. This novel peak may be attributed to the water frozen in wood on the basis of the peak temperature, relaxation strength vs. MC, the activation energy, and the fact that the peak is not observed for the sorption of various polar organic solvents. This suggests that some of the moisture sorbed by wood may probably exist in a frozen state at low temperatures, even at a MC well below the commonly accepted fiber saturation point.
ADVERTISEMENT‐CALL PREFERENCES IN DIPLOID‐TETRAPLOID TREEFROGS (HYLA CHRYSOSCELIS AND HYLA VERSICOLOR): IMPLICATIONS FOR MATE CHOICE AND THE EVOLUTION OF COMMUNICATION SYSTEMS

Abstract Signals used for mate choice and receiver preferences are often assumed to coevolve in a lock‐step fashion. However, sender‐receiver coevolution can also be nonparallel: even if species differences in signals are mainly quantitative, females of some closely related species have qualitatively different preferences and underlying mechanisms. T o‐alternative playback experiments using synthetic calls that differed in fine‐scale temporal properties identified the receiver criteria in females of the treefrog Hyla chrysoscelis for comparison with female criteria in a cryptic tetraploid species (H. versicolor); detailed preference functions were also generated for both species based on natural patterns of variation in temporal properties. The species were similar in three respects: (1) pulses of constant frequency were as attractive as the frequency‐modulated pulses typical of conspecific calls; (2) changes in preferences with temperature paralleled temperature‐dependent changes in male calls; and (3) preference functions were unimodal, with weakly defined peaks estimated at values slightly higher than the estimated means in conspecific calls. There were also species differences: (1) preference function slopes were steeper in H. chrysoscelis than in H. versicolor; (2) preferences were more intensity independent in H. chrysoscelis than in H. versicolor; (3) a synergistic effect of differences in pulse rate and shape on preference strength occurred in H. versicolor but not in H. chrysoscelis; and (4) a preference for the pulse shape typical of conspecific calls was expressed at the species‐typical pulse duration in H. versicolor but not in H. chrysoscelis. However, females of H. chrysoscelis did express a preference based on pulse shape when tested with longer‐than‐average pulses, suggesting a hypothesis that could account for some examples of nonparallel coevolution. Namely, preferences can be hidden or revealed depending on the direction of quantitative change in a signal property relative to the threshold for resolving differences in that property. The results of the experiments reported here also predict patterns of mate choice within and between contemporary populations. First, intraspecific mate choice in both species is expected to be strongly influenced by variation in temperature among calling males. Second, simultaneous differences in pulse rate and pulse shape are required for effective species discrimination by females of H. versicolor but not by females of H. chrysoscelis. Third, there is greater potential for sexual selection within populations and for discrimination against calls produced by males in other geographically remote populations in H. chrysoscelis than in H. versicolor.
Development of the QoL.BD: a disorder-specific scale to assess quality of life in bipolar disorder.

BACKGROUND There is wide recognition that symptom ratings alone are inadequate to measure outcomes in bipolar disorder (BD), and quality of life (QoL) has been proposed as an important separable construct. Although a literature on QoL in BD exists, there is no disorder-specific measure of QoL in BD. In 2004, we embarked upon a four-year mixed-method program of research to develop such a measure that could function as an outcome tool in clinical trials of pharmacological or psychosocial treatment interventions, longitudinal monitoring, or routine clinical care. METHODS The project was informed by standard protocols for the development of disorder-specific QoL measures. Two phases of scale development were pursued across four empirical studies. Item generation involved a qualitative investigation of individuals with BD, family members, and field experts (Study 1), as well as a literature review. Item reduction analyses were conducted using an intensive small-N design with affected individuals (Study 2), a large field sample (Study 3), and a final small-N item reduction study, again involving individuals with the disorder and field experts (Study 4). RESULTS Initial field testing of the Quality of Life in Bipolar Disorder (QoL.BD) scale supports use of the instrument as a feasible, reliable and valid disorder-specific QoL measure for BD. Internal reliability of the QoL.BD is impressive, test-retest reliability is appropriate, and the direction and magnitude of correlations with external measures are as expected. As a new instrument, the QoL.BD must be compared against existing options for measuring QoL in this population. Significantly, data suggest that the greater specificity of the QoL.BD relative to the Quality of Life Enjoyment and Satisfaction Questionnaire renders the new instrument more sensitive to clinical change in BD. CONCLUSIONS Quality of life scales can provide important information additional to that provided by traditional assessments of outcome in BD. Our intensive, mixed-method development of the QoL.BD has produced a useful additional measure of well-being for this complex and often disabling condition.
Older patients with early-stage diffuse large B-cell lymphoma: the role of consolidation radiotherapy after chemoimmunotherapy

Abstract The purpose of this study was to examine the association between RT and overall survival for older patients (>60 years) with early-stage diffuse large B-cell lymphoma (DLBCL) using standard and propensity score (PS)-adjusted Cox proportional hazards models. From 1998 to 2012, 2207 patients were over the age of 60 years, received chemoimmunotherapy with or without RT and were included in this study. Use of consolidation RT was associated with lower clinical stage, head/neck involved site, lack of ‘B’ symptoms, lower co-morbidity score, and higher socioeconomic status (all p < .05). Examining 1721 patients for survival outcomes (1998–2008), the 5-year overall survival for patients receiving RT was 80.1% versus 69.8% for those not receiving RT (p < .01). After PS-matching for co-variates, RT use remained associated with improved overall survival (HR = 0.63, 95% CI, 0.51–0.79, p < .01). Over the study period, RT utilization decreased from 38.5% to 28.8%. Consolidation RT was associated with improved OS for older patients with early-stage DLBCL receiving chemoimmunotherapy.
Serum levels of sCD137 (4‐1BB) ligand are prognostic factors for progression in acute myeloid leukemia but not in non‐Hodgkin's lymphoma

Abstract: CD178 (Fas/APO‐1 ligand) and CD137 ligand (CD137L) have previously been described in sera of patients with various malignancies and play an important role in the pathogenesis of various diseases. Recently, we demonstrated that low levels of soluble (s) CD137L and high levels of sCD178 correlate significantly with a long progression free survival in patients with myelodysplastic syndrome (MDS). In this study, we correlated sCD137L and sCD178 levels in sera of 42 samples of patients with acute myeloid leukemia (AML) and 46 samples of patients with non‐Hodgkin's lymphoma (NHL) with stages, subtypes, and the clinical course of the diseases and determined cut‐off values with maximum probability for significant differentiation between cases with higher/lower probability for progress free survival. In contrast to patients with MDS, surprisingly no correlation between sCD178 levels and different subtypes and stages or with prognosis in AML or NHL were observed. Regarding sCD137L, NHL‐patients displayed lower levels compared with AML. Statistically significant higher median levels of sCD137L are present in patients with undifferentiated AML (M1/M2, 1470 pg/mL), poor cytogenetic risk (288 pg/mL) and higher levels of BM‐blasts (186 pg/mL) compared with patients with monocytoid AML (M4/M5, 89 pg/mL), intermediate cytogenetic risk (59 pg/mL) and lower levels of BM‐blasts (14 pg/mL) respectively. Furthermore, in AML patients sCD137L levels correlate significantly with the probabilities to achieve complete remission (CR), stay in CR or with progress of the disease. Taken together, our data demonstrate that sCD137L can be used as a prognostic factor not only in MDS but also in AML.
The impact of bilateral or unilateral cataract surgery on visual functioning: when does second eye cataract surgery benefit patients?

Aim To examine the impact of bilateral or unilateral cataract surgery on visual functioning. Methods The Singapore Malay Eye Study is a population-based study of 3280 Singapore Malay patients aged 40–80 years, of which 3225 had data available for inclusion. Cataracts were graded from digital lens photographs according to the Wisconsin scale. Study subjects were categorised as having: bilateral cataract surgery performed; unilateral cataract surgery performed with minimal cataract in the fellow eye; unilateral cataract surgery performed with significant cataract in the fellow eye; and bilateral cataract. Visual functioning was assessed using the modified VF-9 scale culturally adapted for Singaporean individuals, validated by Rasch analysis. The overall Rasch-modified vision-specific functioning score was compared across the four groups after adjusting for confounders such as age, gender, ocular and systemic comorbidities. Results Persons with bilateral cataract had poorer visual functioning than those who had bilateral cataract surgery (mean visual functioning scores 3.38 vs 3.11, respectively, p=0.029). When compared with bilateral surgery, visual functioning improvements among patients with unilateral cataract surgery depended on the status of the fellow eye, with improvements only seen if the fellow eye had significant cataract (mean visual functioning scores 2.81 vs 3.25, p=0.019) or poor visual acuity (mean visual functioning scores 2.78 vs 3.25, p=0.018) after adjusting for confounders. Conclusions Bilateral cataract surgery was associated with greater visual functioning over unilateral cataract surgery when the fellow eye had a significant cataract or poor presenting visual acuity, supporting the current practice of second eye surgery depending on the fellow eye's cataract status and visual acuity.
Wives giving care to husbands with Alzheimer's disease: a process of interpretive caring.

Wives giving care to spouses with dementia are a particularly vulnerable segment of the caregiving population. In this article a grounded theory study of 20 such wives is described, with their experiences explained as a process of interpretive caring. Wives began the process by either seeing changes in their husbands or recognizing changes in their work. Following this, the wives moved on to a phase of drawing inferences about what they observed and then took over their husbands' roles and responsibilities. These changes prompted the wives to rewrite identities for their husbands that incorporated the dementia and to rewrite identities for themselves to reflect their new roles, abilities, and strengths. Finally, the wives set about constructing a new daily life to sustain both partners. This process is neutral and allows for positive aspects of caring to be considered along with grief and frustration.
Control of idiotope expression by monoclonal anti‐idiotope and idiotope‐bearing antibody

Preinjection of C57BL/6 mice with nano‐to microgram amounts of a monoclonal IgG1 antibody directed against a binding site‐related idiotope of the anti‐NP [(4‐hydroxy‐3‐nitro‐phenyl)acetyl] antibody B1‐8 results in enhancement or suppression of the corresponding and of another B1‐8 idiotope in a subsequent anti‐NP response, depending on the dose of the injected anti‐idiotope antibody. The enhancing and suppressive effects appear two weeks after anti‐idiotope administration and are maximal after 6–8 weeks. They are predominantly expressed at the level of IgG, not IgM, antibodies. Enhancement of idiotype expression, i.e. idiotypic memory, can also be induced by the injection of idiotypic antibody of the IgM class, namely antibody B1‐8. This effect might represent one of the general mechanisms by which immunological memory is established.
Preparation and characterization of soluble eggshell membrane protein/PLGA electrospun nanofibers for guided tissue regeneration membrane

Guided tissue regeneration (GTR) is a widely used method in periodontal therapy, which involves the placement of a barrier membrane to exclude migration of epithelium and ensure repopulation of periodontal ligament cells. The objective of this study is to prepare and evaluate a new type of soluble eggshell membrane protein (SEP)/poly (lactic-co-glycolic acid) (PLGA) nanofibers using electrospinning method for GTR membrane application. SEP/PLGA nanofibers were successfully prepared with various blending ratios. The morphology, chemical composition, surface wettability, and mechanical properties of the nanofibers were characterized using scanning electron microscopy (SEM), contact angle measurement, Fourier transform-infrared spectroscopy (FTIR), and a universal testing machine. L-929 fibroblast cells were used to evaluate the biocompatibility of SEP/PLGA nanofibers and investigate the interaction between cells and nanofibers. Results showed that the SEP/PLGA electrospun membrane was composed of uniform, bead-free nanofibers, which formed an interconnected porous network structure. Mechanical property of SEP has been greatly improved by the addition of PLGA. The biological study results showed that SEP/PLGA nanofibers could enhance cell attachment, spreading, and proliferation. The study indicated the potential of SEP/PLGA nanofibers for GTR application and provided a basis for future optimization.
Precessing warped accretion discs in X‐ray binaries

We study the radiation-driven warping of accretion discs in the context of X-ray binaries. The latest evolutionary equations are adopted, which extend the classical alpha theory to time-dependent thin discs with non-linear warps. We also develop accurate, analytical expressions for the tidal torque and the radiation torque, including self-shadowing. We investigate the possible non-linear dynamics of the system within the framework of bifurcation theory. First, we re-examine the stability of an initially flat disc to the Pringle instability. Then we compute directly the branches of non-linear solutions representing steadily precessing discs. Finally, we determine the stability of the non-linear solutions. Each problem involves only ordinary differential equations, allowing a rapid, accurate and well-resolved solution. We find that radiation-driven warping is probably not a common occurrence in low-mass X-ray binaries. We also find that stable, steadily precessing discs exist for a narrow range of parameters close to the stability limit. This could explain why so few systems show clear, repeatable ‘superorbital’ variations. The best examples of such systems, Her X-1, SS 433 and LMC X-4, all lie close to the stability limit for a reasonable choice of parameters. Systems far from the stability limit, including Cyg X-2, Cen X-3 and SMC X-1, probably experience quasi-periodic or chaotic variability as first noticed recently by Wijers and Pringle. We show that radiation-driven warping provides a coherent and persuasive framework but that it does not provide a generic explanation for the long-term variabilities in all X-ray binaries.
Genetic Modulation of Rpd3 Expression Impairs Long-Term Courtship Memory in Drosophila

There is increasing evidence that regulation of local chromatin structure is a critical mechanism underlying the consolidation of long-term memory (LTM), however considerably less is understood about the specific mechanisms by which these epigenetic effects are mediated. Furthermore, the importance of histone acetylation in Drosophila memory has not been reported. The histone deacetylase (HDAC) Rpd3 is abundant in the adult fly brain, suggesting a post-mitotic function. Here, we investigated the role of Rpd3 in long-term courtship memory in Drosophila. We found that while modulation of Rpd3 levels predominantly in the adult mushroom body had no observed impact on immediate recall or one-hour memory, 24-hour LTM was severely impaired. Surprisingly, both overexpression as well as RNAi-mediated knockdown of Rpd3 resulted in impairment of long-term courtship memory, suggesting that the dose of Rpd3 is critical for normal LTM.
Clinicopathologic features predicting involvement of non- sentinel axillary lymph nodes in Iranian women with breast cancer.

BACKGROUND Almost half of the breast cancer patients with positive sentinel lymph nodes have no additional disease in the remaining axillary lymph nodes. This group of patients do not benefit from complete axillary lymph node dissection. This study was designed to assess the clinicopathologic factors that predict non-sentinel lymph node metastasis in Iranian breast cancer patients with positive sentinel lymph nodes. MATERIALS AND METHODS The records of patients who underwent sentinel lymph node biopsy, between 2003 and 2012, were reviewed. Patients with at least one positive sentinel lymph node who underwent completion axillary lymph node dissection were enrolled in the present study. Demographic and clinicopathologic characteristics including age, primary tumor size, histological and nuclear grade, lymphovascular invasion, perineural invasion, extracapsular invasion, and number of harvested lymph nodes, were evaluated. RESULTS The data of 167 patients were analyzed. A total of 92 (55.1%) had non-sentinel lymph node metastasis. Univariate analysis of data revealed that age, primary tumor size, histological grade, lymphovascular invasion, perineural invasion, extracapsular invasion, and the number of positive sentinel lymph nodes to the total number of harvested sentinel lymph nodes ratio, were associated with non-sentinel lymph node metastasis. After logistic regression analysis, age (OR=0.13; 95% CI, 0.02-0.8), primary tumor size (OR=7.7; 95% CI, 1.4-42.2), lymphovascular invasion (OR=19.4; 95% CI, 1.4- 268.6), extracapsular invasion (OR=13.3; 95% CI, 2.3-76), and the number of positive sentinel lymph nodes to the total number of harvested sentinel lymph nodes ratio (OR=20.2; 95% CI, 3.4-121.9), were significantly associated with non-sentinel lymph node metastasis. CONCLUSIONS According to this study, age, primary tumor size, lymphovascular invasion, extracapsular invasion, and the ratio of positive sentinel lymph nodes to the total number of harvested sentinel lymph nodes, were found to be independent predictors of non-sentinel lymph node metastasis.
Sarcopenic obesity and complex interventions with nutrition and exercise in community-dwelling older persons – a narrative review

One of the many threats to independent life is the age-related loss of muscle mass and muscle function commonly referred to as sarcopenia. Another important health risk in old age leading to functional decline is obesity. Obesity prevalence in older persons is increasing, and like sarcopenia, severe obesity has been consistently associated with several negative health outcomes, disabilities, falls, and mobility limitations. Both sarcopenia and obesity pose a health risk for older persons per se, but in combination, they synergistically increase the risk for negative health outcomes and an earlier onset of disability. This combination of sarcopenia and obesity is commonly referred to as sarcopenic obesity. The present narrative review reports the current knowledge on the effects of complex interventions containing nutrition and exercise interventions in community-dwelling older persons with sarcopenic obesity. To date, several complex interventions with different outcomes have been conducted and have shown promise in counteracting either sarcopenia or obesity, but only a few studies have addressed the complex syndrome of sarcopenic obesity. Strong evidence exists on exercise interventions in sarcopenia, especially on strength training, and for obese older persons, strength exercise in combination with a dietary weight loss intervention demonstrated positive effects on muscle function and body fat. The differences in study protocols and target populations make it impossible at the moment to extract data for a meta-analysis or give state-of-the-art recommendations based on reliable evidence. A conclusion that can be drawn from this narrative review is that more exercise programs containing strength and aerobic exercise in combination with dietary interventions including a supervised weight loss program and/or protein supplements should be conducted in order to investigate possible positive effects on sarcopenic obesity.