Miracle-dz/UniFAR-FTUs huggingface dataset:
The prognostic value of serum levels of a proliferation-inducing ligand (APRIL) in treatment-naïve patients with chronic lymphocytic leukemia

Background/aim A proliferation-inducing ligand (APRIL) has been investigated as a prognostic marker in chronic lymphocytic leukemia (CLL) patients. However, there is no cut-off level for serum APRIL (sAPRIL) levels that predict time to treatment in CLL patients. Materials and methods Between May and December 2012, 94 consecutive CLL patients and 25 healthy controls were assessed. sAPRIL levels were measured by ELISA. Demographic data and prognostic markers were obtained from the patients’ files. Treatment-naïve patients were followed up for 6.5 years for any treatment need. Results Patients were divided into 3 groups: Treatment-naïve (n = 47), chemotherapy receiving (n = 25), and those who had received chemotherapy previously (n = 22). There was no difference in median sAPRIL levels of patients who were receiving chemotherapy at the sampling time and the healthy controls, which indicates that sAPRIL levels might be influenced by treatment. For treatment-naïve patients, the best cut-off in predicting time to treatment was found at the sAPRIL level of 2.04 ng/mL, with 78% sensitivity and 63% specificity. Time to treatment was significantly earlier in the APRIL high group (n = 27) than in the APRIL low group (n = 20) (P = 0.010, log-rank test). Conclusion sAPRIL, a simple, promising blood test which can be measured by ELISA, will likely obtain a place in the wide range of prognostic markers in CLL. Prospective large-scale studies are required to validate and confirm the feasibility of the proposed cut-off level of 2.04 ng/mL as a predictor of time to treatment in treatment-naïve CLL patients.
Medicinal Uses of Natural Dye-Yielding Plants in Turkey

PPlants have been grown for natural dyes to produce a wide range of colors. N Natural dyes become increasingly important these days as synthetic dyes cause serious damage to the environment and have to be replaced. The published records show that Turkey has about 10,000 taxa of higher plants, 145 of which come from 92 genera and 51 families and can be used as dyeing sources of 17 colors. The most common families used for dyeing are Asteraceae, Rosaceae, Lamiaceae, Polygonaceae and Euphorbiaceae, and the dominating genera are Rumex, Anthemis, Euphorbia, and Salvia. Dye plants are of great medicinal value as well and can be used for producing antihelmintic, antiseptic, appetizer, carminative, diuretic, exudative, laxative, sedative and stomachic preparations.
Vascularised bone graft is an effective technique for extracortical bone bridging to combat cemented megaprosthesis loosening at the bone–implant junction

Introduction: The bone–implant junction is a potential site for aseptic loosening. Extracortical bone bridging at the bone–implant junction is advocated to improve implant fixation by forming a biological seal. We propose a novel technique with vascularised bone graft (VBG) to form an extracortical bone bridge at the bone–implant junction to enhance implant stability. We compared the clinical and radiological outcomes for tumour megaprostheses performed (1) with and without bone graft and (2) with non-vascularised versus VBG technique. Methods: Forty-six tumour megaprosthesis procedures from 1 June 2007 to 31 October 2017 were identified from hospital records. Twenty-eight operations incorporated bone graft at the bone–implant junction, and 18 did not. Of these 28 bone graft procedures, 13 involved VBG, and 15 did not (non-VBG). The VBG technique involves resecting a short segment of healthy bone beyond the oncological margin with its preserved blood supply, splitting it, then securing it over the junction. Clinical outcomes assessed included loosening, fracture and recurrence. Extracortical bone growth at the bone–implant junction was quantified radiologically at intervals 0–24 months post-operatively. The mean follow-up was 4.27 years. Results: There were five incidences (27.8%) of loosening in the non-bone graft group compared to zero in the bone graft group (p = 0.03). There was a higher radiological score of extracortical bone growth in the bone graft group compared to no bone graft at 3–24 months post-operatively (p < 0.05). Within the bone graft group, the VBG group fared superior at 6 and 12 months post-operatively compared to non-VBG (p < 0.05), as well as a lower rate of radiological junctional resorption (p = 0.04). Conclusions: We recommend bone grafting for its merits of less implant loosening. We propose the VBG technique to combat early aseptic loosening in megaprosthesis replacement as there was a higher radiological score compared to non-VBG.
Children's Road-Crossing Behavior: Emotional Decision Making and Emotion-Based Temperamental Fear and Anger.

OBJECTIVE Child pedestrian injuries represent a global public health burden. To date, most research on psychosocial factors affecting children's risk of pedestrian injury focused on cognitive aspects of children's functioning in traffic. Recent evidence suggests, however, that emotional aspects such as temperament-based fear and anger/frustration, as well as executive function-based emotional decision making, may also affect children's safety in traffic. This study examined the role of emotions on children's pedestrian behavior. Three hypotheses were considered: (a) emotion-based temperament factors of fear and anger/frustration will predict children's risky decisions and behaviors; (b) emotional decision making will predict risky pedestrian decisions and behaviors; and (c) children's pedestrian decision making will mediate relations between emotion and risky pedestrian behavior. The role of gender was also considered. METHODS In total, 140 6- to 7-year-old children (M = 6.7 years, SD = 0.39; 51% girls) participated. Parent-report subscales of Child Behavior Questionnaire measured temperamental fear and anger/frustration. The Hungry Donkey Task, a modified version of Iowa Gambling Task for children, measured children's emotional decision making, and a mobile virtual reality pedestrian environment measured child pedestrian behavior. RESULTS Greater anger/frustration, lesser fear, and more emotional decision making all predicted poorer pedestrian decision making. The mediational model demonstrated that pedestrian decision making, as assessed by delays entering safe traffic gaps, mediated the relation between emotion and risky pedestrian behavior. Analyses stratified by gender showed stronger mediation results for girls than for boys. CONCLUSIONS These results support the influence of emotions on child pedestrian behavior and reinforce the need to incorporate emotion regulation training into child pedestrian education programs.
DNA methylation changes in the hippocampus of learning and memory disorder offspring rats of lead exposure during pregnant and lactation period.

BACKGROUND Pregnant female rats exposed to lead may give birth to offspring with learning and memory disorders. Many studies have shown that there are many mechanisms that cause learning and memory impairment. Epigenetic mechanisms may play an important function in the learning and memory impairment. METHODS We examined DNA methylation changes in the hippocampus of rats with learning and memory disorder that were the offsprings of rats exposed to lead during pregnant and lactation period. The Morris Water Maze was applied as a learning and memory test, and a Roche NimbleGen's rat DNA methylation 385K Promoter Plus CpG Island Array was used for array hybridization. RESULTS The results of the integrated navigation and spacial exploration test showed that until 21 days after birth and the lactation period, the learning and memory abilities of offsprings with lead exposure during pregnant and lactation period were significantly lower than those of the control group. The hippocampus DNA methylation levels of the three types of promoters increased compared with those of the control group. According to the Gene Ontology (GO) terms, metal ion transport, cell connections, the lamellar body, the axon bulge, and methylation of various metal transporters were found to be significantly enriched. Pathway analysis showed that the hedgehog signaling pathway, neuroactive receptor-ligand interaction with the ligase pathway, and interaction between cytokines had high methylation. CONCLUSIONS DNA methylation of the whole genome in the hippocampus of the rats with learning and memory impairment induced by perinatal lead contact showed a lot of changes compared with that in the group of control.
Study of complexes of Hoechst 33258 with poly(rA)-poly(rU) depending on various ionic strengths in the water-saline solution

Abstract Comparative study of the complexes of groove-binding ligand Hoechst 33258 (H33258) with synthetic homopolynucleotides poly(rA)-poly(rU) and poly(dA)-poly(dT) has been carried out at various concentration ratios of r = ligand/nucleic acids (NA) and different ionic strengths of the water-saline solution 0.02, 0.04 and 0.1 M, using the method of UV-melting. It was revealed that the melting curves of the complexes of poly(dA)-poly(dT) with H33258 at the low concentrations of ligand are biphasic, which actually does not depend on the solution ionic strength. In the case of the complexes of poly(rA)-poly(rU)-H33258, the melting curves become quasi-biphasic only at the ionic strength 0.02 M and relatively high concentrations of the ligand. Differential melting curves (DMC) of the mentioned polynucleotides and their complexes with H33258 were obtained as well. DMC of poly(rA)-poly(rU) were found to be significantly wide at the ionic strengths of the solution 0.02 and 0.04 M and to show an intrinsic heterogeneity of double-stranded structure of this polynucleotide. Communicated by Ramaswamy H. Sarma
Habitat utilisation in a stratified upland landscape by two lagomorphs with different feeding strategies

Mountain hares (Lepus timidus L.) are summer grazers that switch to browse in winter, while rabbits (Oryctolagus cuniculus L.) eat mostly grasses throughout the year. These different feeding strategies may underlie seasonal patterns of habitat selection by the two species. In this study the habitat utilization by adult female mountain hares and adult female rabbits was studied by radio-tracking in a habitat composed of open moorland, upland pasture and young forestry plantation with an abundant ground flora. The selection of feeding habitats by populations of both species was assessed by faecal counts within the same landscape. Despite the common perception that mountain hares in Britain are associated with moorland, open moorland was avoided by the radio-tracked adult female mountain hares relative to its availability. Throughout the year, the radio-tracked hares preferred the forest and pasture habitats relative to availability. Only seven of the 20 hares radio-tracked were ever located on the moorland, which would suggest that the presence of moorland is not a prerequisite for the presence of mountain hares. Radio-tracked adult female rabbits utilized the habitats in proportion to their availability. Counts of faecal pellets indicated that utilization of forestry plantations by both species declined as a spruce forest matures although hare populations persist in mature pine plantations with an abundant ground flora. Mountain hares appear to be more adaptable than rabbits in their use of the habitats in this study, a behavioural tactic underpinned by their flexible feeding strategy. Rabbit populations would persist in areas following afforestation, especially where upland pastures are in close proximity to woodland and mountain hares would be capable of exploiting many of the new habitats that are created, at least in the early years of forest development.
Frailty is associated with poor sleep quality in the oldest old

Background/aim Sleep disorders and frailty increase with advancing age, along with physical disabilities, cognitive dysfunction, mood disorders, and social vulnerability. Thus, the study objective was to evaluate the relationship between frailty and sleep quality in the oldest old patients. Materials and methods In this study, 100 patients aged ≥80 years were assessed using comprehensive geriatric assessment (CGA) including basic activities of daily living (ADL), instrumental ADL, handgrip strength, the Geriatric Depression Scale-15, the Mini-Mental State Examination, and the Mini-Nutritional Assessment-Short Form. The sleep quality and frailty status of the patients were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and the Fried Frailty Index, respectively. Results The median age of the participants was 84 years (80–92), 55% of them were women, and 41% of them were frail. There was no statistically significant difference between the frail and nonfrail groups in terms of age, sex, and comorbidities (P > 0.050). The frail patients scored poorly according to the CGA tests when compared to the nonfrail ones (P < 0.050). The median score for the PSQI was significantly higher in the frail group, 12 points (3–19) versus 6 points (1–19) in the nonfrail patients (P < 0.001). The PSQI score (odds ratio [OR] of 1.308, 95% confidence interval [CI]: 1.092–1.566, P = 0.004), female sex (OR of 5.489, 95% CI: 1.063–28.337; P = 0.042), and the basic ADL score (OR of 0.383; 95% CI: 0.207–0.706; P = 0.002) were found to be independently associated with frailty using multivariate analysis. Conclusion Sleep quality was significantly decreased in the oldest old frail patients compared to the nonfrail ones, and poor sleep quality was independently associated with frailty. Evaluating the sleep patterns of the oldest old patients with CGA in daily geriatric practice might help to improve the quality of life of frail patients.
Not all aspirin products have equivalent antiplatelet efficacy—Aspirin formulated with magnesium stearate is less effective in preventing ischemic stroke

Magnesium stearate (MgSt) is a widely used excipient in pharmaceutical formulations but should be avoided in aspirin preparations as it hydrolyzes aspirin. We hypothesized that preparations of aspirin‐containing MgSt (MgSt‐ASA) are less effective in preventing thrombosis in clinical settings. The risk of composite cardiovascular events in patients treated with MgSt‐ASA preparations for preventing secondary stroke was evaluated.
Effect of combined chronic predictable and unpredictable stress on depression-like symptoms in mice

Background Mental stress mainly induces depression, and predictable stress, as well as a constant bombardment of chronic unpredictable micro-stressors, always coexist in daily life. However, the combined effect of predictable and unpredictable stress on depression is still not fully understood. Methods The chronic restraint stress (CRS) is to restrain the mice for 6 h per day for 3 weeks, and the chronic unpredictable mild stress (CUMS) is to stimulate the mice with 7 different stressors for 3 weeks. We evaluated the combined effect of CRS and CUMS on depression-like symptoms using behavioral tests and investigated the action mechanism through analysis of neurotransmitters, brain-derived factors, inflammatory factors, antioxidants, and intestinal microorganisms. Results Our data suggested the combined stress of CRS and CUMS caused significant weight loss, food intake reduction, depression-like behaviors—including anhedonia, learned helplessness, and reduction in spontaneous activity—and even atrophy and severe structural damage to the hippocampus in mice. Our pathogenesis study showed that combined stress-induced the reduction of glucocorticoid receptor (GR) levels, loss of oligodendrocytes (NG2 and Olig2 cells), and inhibition of neuron proliferation in the CA1, CA3, and DG regions of the hippocampus, decreased the contents of monoamine neurotransmitters (5-HT and NE) and BDNF in the cerebral cortex, caused hyperactivity of the HPA system, led to immune dysfunction, aggravated oxidative stress, and weakened the capacity of antioxidants in mice. Compared with single stress, combined stress gave rise to a more significant diversity change of the gut microbiota. Conclusions Combined stress caused significant depression-like behaviors, atrophy, and severe structural damage to the hippocampus in mice via monoamine neurotransmitter, BDNF, HPA axis, neurogenesis, and neurodegenerative, immune, oxidative stress and gut-brain axis action pathways.
Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2−, Node-Positive, High-Risk, Early Breast Cancer (monarchE)

PURPOSE Many patients with HR+, HER2− early breast cancer (EBC) will not experience recurrence or have distant recurrence with currently available standard therapies. However, up to 30% of patients with high-risk clinical and/or pathologic features may experience distant recurrence, many in the first few years. Superior treatment options are needed to prevent early recurrence and development of metastases for this group of patients. Abemaciclib is an oral, continuously dosed, CDK4/6 inhibitor approved for HR+, HER2− advanced breast cancer (ABC). Efficacy and safety of abemaciclib in ABC supported evaluation in the adjuvant setting. METHODS This open-label, phase III study included patients with HR+, HER2−, high-risk EBC, who had surgery and, as indicated, radiotherapy and/or adjuvant/neoadjuvant chemotherapy. Patients with four or more positive nodes, or one to three nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%, were eligible and randomly assigned (1:1) to standard-of-care adjuvant endocrine therapy (ET) with or without abemaciclib (150 mg twice daily for 2 years). The primary end point was invasive disease-free survival (IDFS), and secondary end points included distant relapse–free survival, overall survival, and safety. RESULTS At a preplanned efficacy interim analysis, among 5,637 randomly assigned patients, 323 IDFS events were observed in the intent-to-treat population. Abemaciclib plus ET demonstrated superior IDFS versus ET alone (P = .01; hazard ratio, 0.75; 95% CI, 0.60 to 0.93), with 2-year IDFS rates of 92.2% versus 88.7%, respectively. Safety data were consistent with the known safety profile of abemaciclib. CONCLUSION Abemaciclib when combined with ET is the first CDK4/6 inhibitor to demonstrate a significant improvement in IDFS in patients with HR+, HER2− node-positive EBC at high risk of early recurrence.
No effect of endoperoxide 4 or thromboxane A2 receptor blockade on static mechanoreflex activation in rats with heart failure

What is the central question of this study? Do endoperoxide 4 and thromboxane A2 receptors, which are receptors for cyclooxygenase products of arachidonic metabolism, on thin fibre muscle afferents play a role in the chronic mechanoreflex sensitization present in rats with heart failure with reduced ejection fraction (HF‐rEF)? What is the main finding and its importance? The data do not support a role for endoperoxide 4 receptors or thromboxane A2 receptors in the chronic mechanoreflex sensitization in HF‐rEF rats.
Impact of the number of examined lymph nodes on stage migration in node-negative gastric cancer patients: a Chinese multi-institutional analysis with propensity score matching

Background This propensity score matching (PSM) analysis assessed the influence of examined lymph nodes (ELNs) count on stage migration and survival in node-negative (pN0) gastric cancer (GC) patients. Methods We performed a retrospective analysis of 7,620 GC patients who underwent curative gastric resection in three Chinese medical centers. PSM was used to reduce the confounding effects between the pN0 GC patients with ELNs <16 or ≥16. Survival differences among various subgroups of GC patients were analyzed to assess the impact of the ELNs count on the stage migration in accordance with the overall survival (OS) of pN0 GC patients. Results After matching, the backgrounds of pN0 GC patients in the ELNs <16 (n=825) and ELNs ≥16 (n=826) groups were well-balanced. Survival analyses revealed that the ELNs count was positively correlated with the OS (P=0.001). Multiple Cox analysis indicated that the ELNs count was an independent predictor of the OS in pN0 GC patients. Stage migrations were mainly detected in subgroups of pN0 GC patients with specific pTNM stages, as follows: (I) pT2N0M0 with ELNs <16 vs. pT3N0M0 with ELNs ≥16; (II) pT3N0M0 with ELNs <16 vs. pT3N1M0 with ELNs ≥16; and (III) pT4aN0M0 with ELNs <16 vs. pT4aN1M0 with ELNs ≥16. Conclusions We show that stage migration can be detected in pN0 GC patients, and that it could be gradually reduced or prevented by increasing the ELNs count.
Management of Abemaciclib‐Associated Adverse Events in Patients with Hormone Receptor‐Positive, Human Epidermal Growth Factor Receptor 2‐Negative Advanced Breast Cancer: Safety Analysis of MONARCH 2 and MONARCH 3

Abstract Background Abemaciclib demonstrated efficacy in hormone receptor‐positive, human epidermal growth factor receptor 2‐negative advanced breast cancer. Here we provide a comprehensive summary of the most common adverse events (AEs), their management, and whether AEs or dose reductions influenced progression‐free survival (PFS), in the MONARCH 2 and 3 trials. Materials and Methods Incidence of the most clinically relevant AEs, management, and outcomes were summarized. Time‐dependent covariate analyses examined the impact of dose reductions on PFS. PFS was estimated for patients with and without early onset of diarrhea or neutropenia. Results The most frequently reported AE was diarrhea, with clinically significant diarrhea (grade ≥2) reported for 42.8% of patients taking abemaciclib. Median time to onset was 1 week, and duration ranged from 6 to 12 days, depending on grade and study. Diarrhea was adequately managed by antidiarrheal medication (72.8%), dose omissions (17.3%), and reductions (16.7%). The highest rates of grade ≥2 diarrhea were observed in the first cycles and decreased in subsequent cycles. Neutropenia (grade ≥3) occurred in 25.4% of abemaciclib‐treated patients. Neutropenia resolved with dose omissions (16.8%) and/or dose reductions (11.2%). Incidence of febrile neutropenia (0.7%) or other relevant grade ≥3 hematological events (<9%) was low. Venous thromboembolic events (5.3%) were primarily treated with anticoagulants. Interstitial lung disease/pneumonitis (3.4%) was treated with corticosteroids and/or antibiotics. PFS benefit of abemaciclib was not impacted by dose reductions or early onset of toxicities. Conclusion Abemaciclib was generally well tolerated. The most common AEs were effectively managed by supportive medications, and/or dose adjustments, with no detriment to PFS. Implications for Practice Treatment with abemaciclib plus fulvestrant or nonsteroidal aromatase inhibitors is generally well tolerated in patients with hormone receptor‐positive, human epidermal growth factor receptor 2‐negative advanced breast cancer. In MONARCH 2 and MONARCH 3, any‐grade diarrhea and grade ≥3 neutropenia were effectively managed with supportive medication and/or dose adjustment. Venous thromboembolic events were treated with anticoagulants and did not often require treatment discontinuation. Interstitial lung disease/pneumonitis was infrequent and treated with corticosteroids and/or antibiotics. Clinicians should be aware of and implement management strategies, including dose adjustments according to local labels, for commonly occurring and serious adverse events to ensure continued treatment and optimize clinical benefit/risk ratio.