Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of spatial and temporal variations in trace element concentrations using honeybees (Apis mellifera) as bioindicators

With the increase in anthropogenic activities metal pollution is also increased and needs to be closely monitored. In this study honeybees were used as bioindicators to monitor metal pollution. Metal pollution in honeybees represents pollution present in air, water and soil. Concentrations of As, Cs, Hg, Mo, Sb, Se, U and V were measured. The aim of this study was to assess spatial and temporal variations of metal concentrations in honeybees. Samples of honeybees were taken at five different regions in Serbia (Belgrade - BG, Pančevo - PA, Pavliš - PV, Mesić - MS, and Kostolac - TPP) during 2014. Spatial variations were observed for Sb, which had higher concentrations in BG compared to all other regions, and for U, with higher concentrations in the TPP region. High concentrations of Sb in BG were attributed to intense traffic, while higher U concentrations in the TPP region are due to the vicinity of coal fired power plants. In order to assess temporal variations at two locations (PA and PV) samples were taken during July and September of 2014 and June, July, August and September of 2015. During 2014 observing months of sampling higher concentrations in July were detected for Sb and U in BG, which is attributed to lifecycle of plants and honeybees. During the same year higher concentrations in September were observed for As, Sb in PA and Hg in PV. This is due to high precipitation during the peak of bee activity in spring/summer of 2014. No differences between months of sampling were detected during 2015. Between 2014 and 2015 statistically significant differences were observed for Hg, Mo and V; all elements had higher concentrations in 2014. This is in accordance with the trend of reduction of metal concentrations in the bodies of honeybees throughout the years in this region.
A Novel Treatment With Obinutuzumab-Chlorambucil in a Patient With B-Cell Prolymphocytic Leukemia: A Case Report and Review of the Literature

We report the case of a patient with B-cell prolymphocytic leukemia who was successfully treated with the novel humanized monoclonal antibody obinutuzumab. This patient was previously treated with the combination of rituximab and bendamustine and had recurrent infusion reactions. Her treatment with rituximab and bendamustine was discontinued when she developed disease progression after 3 cycles of therapy. She was then treated with obinutuzumab 1000 mg on day 1 of every cycle and chlorambucil 0.5 mg/kg on days 1 and 15 every 28 days to which she had greater tolerability. After 4 cycles of treatment, she had resolution of her clinical symptoms, massive splenomegaly, and normalization of her white blood cell count.
Knee Surgery Is Associated With Greater Odds of Knee Osteoarthritis Diagnosis.

CONTEXT Knee osteoarthritis (OA) frequently develops following knee injury/surgery. It is accepted that knee injury/surgery precipitates OA with previous studies examining this link in terms of years after injury/surgery. However, postinjury OA prevalence has not been examined by decade of life; thereby, limiting our understanding of the age at which patients are diagnosed with posttraumatic knee OA. OBJECTIVE Evaluate the association between the knee injury and/or surgical history, present age, and history of receiving a diagnosis of knee OA. DESIGN Cross-sectional survey. SETTING Online survey. PARTICIPANTS A total of 3660 adults were recruited through ResearchMatch©. Of these, 1723 (47.1%) were included for analysis due to history of (1) knee surgery (SURG: n = 276; age = 53.8 [15.3] y; and body mass index [BMI] = 29.9 [8.0] kg/m2), (2) nonsurgical knee injury (INJ: n = 449; age = 46.0 [15.6] y; and BMI = 27.5 [6.9] kg/m2), or (3) no knee injury (CTRL: n = 998; age = 44.0 [25.2] y; and BMI = 26.9 [6.6] kg/m2). Respondents were subdivided by decade of life (20-29 through 70+). INTERVENTION An electronic survey regarding knee injury history, treatment, and diagnosis of knee OA. MAIN OUTCOME MEASURES Binary logistic regression determined the association between knee surgical status and OA by decade of life. Participants with no histories of OA or lower-extremity injury were the referent categories. BMI was a covariate in all analyses. RESULTS SURG respondents were more likely to report having knee OA than CTRL for all age groups (odds ratios: 11.43-53.03; P < .001). INJ respondents aged 30 years and older were more likely to have OA than CTRL (odds ratios: 2.99-14.22; P < .04). BMI influenced associations for respondents in their 50s (P = .001) and 60s (P < .001) only. CONCLUSIONS INJ increased the odds of reporting a physician diagnosis of knee OA in adults as young as 30 to 39 years. Importantly, SURG yielded 3 to 4 times greater odds of being diagnosed with knee OA compared with INJ in adults as young as 20 to 29 years. Delaying disease onset in these young adults is imperative to optimize the quality of life long term after surgery.
Sleep-Related Issues in Children and Adolescents Presenting at Community Mental Health Clinics.

Objective To examine sleep-related issues in children and adolescents presenting at community clinics with diverse mental health concerns using a brief sleep questionnaire and to examine whether sleep issues would improve with mental health interventions. Method Study 1: A questionnaire-based study that used a modified version of the Pittsburgh Sleep Quality Index to measure sleep-related issues in youth aged 4-18 years presenting at community mental health clinics. Study 2: A pre/post-treatment study that used the same questionnaire to measure changes in sleep-related issues in youth aged 4-19 years participating in a group mental health intervention. The main outcome measure for both studies was global sleep score. Results Using the recommended cut-off score of 5, 31% of children aged 4-11 years and 71% of adolescents aged 12-18 years had problematic sleep. Sleep-related issues did not differ by presenting mental health concern. The group intervention was associated with improved sleep for parent-reported child sleep and self-reported adolescent sleep, but not for parent-reported adolescent sleep. Conclusions Problematic sleep is very common in youth with mental health concerns. More research is needed to understand best practices for assessment and treatment of sleep issues that are comorbid with mental health issues in children and adolescents.
Left DLPFC rTMS Reduces the Development of Long-Term Muscle Pain

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Zinc depletion induces ribosome hibernation in mycobacteria

Significance Mycobacteria as well as other bacteria remodel their ribosomes in response to zinc depletion by replacing zinc-binding ribosomal proteins with zinc-free paralogues, releasing zinc for other metabolic processes. In this study, we show that the remodeled ribosome acquires a structurally stable but functionally inactive and aminoglycoside-resistant state in zinc-starved Mycobacterium smegmatis. Conversely, M. smegmatis cells that are growth arrested in zinc-rich conditions have unstable ribosomes and reduced survival. We further provide evidence for ribosome remodeling in Mycobacterium tuberculosis in host tissues, suggesting that ribosome hibernation occurs during TB infections. Our findings could offer insights into mechanisms of persistence and antibiotic tolerance of mycobacterial infections. Bacteria respond to zinc starvation by replacing ribosomal proteins that have the zinc-binding CXXC motif (C+) with their zinc-free (C−) paralogues. Consequences of this process beyond zinc homeostasis are unknown. Here, we show that the C− ribosome in Mycobacterium smegmatis is the exclusive target of a bacterial protein Y homolog, referred to as mycobacterial-specific protein Y (MPY), which binds to the decoding region of the 30S subunit, thereby inactivating the ribosome. MPY binding is dependent on another mycobacterial protein, MPY recruitment factor (MRF), which is induced on zinc depletion, and interacts with C− ribosomes. MPY binding confers structural stability to C− ribosomes, promoting survival of growth-arrested cells under zinc-limiting conditions. Binding of MPY also has direct influence on the dynamics of aminoglycoside-binding pockets of the C− ribosome to inhibit binding of these antibiotics. Together, our data suggest that zinc limitation leads to ribosome hibernation and aminoglycoside resistance in mycobacteria. Furthermore, our observation of the expression of the proteins of C− ribosomes in Mycobacterium tuberculosis in a mouse model of infection suggests that ribosome hibernation could be relevant in our understanding of persistence and drug tolerance of the pathogen encountered during chemotherapy of TB.
Single Step Process for Crystalline Ni-B Compounds

Crystalline Ni2B, Ni3B, and Ni4B3 are synthesized by a single-step method using autogenous pressure from the reaction of NaBH4 and Ni precursors. The effect of reaction temperature, pressure, time, and starting materials on the composition of synthesized products, particle morphologies, and magnetic properties is demonstrated. High yields of Ni2B (>98%) are achieved at 2.3–3.4 MPa and ~670 °C over five hours. Crystalline Ni3B or Ni4B3 form in conjunction with Ni2B at higher temperature or higher autogenous pressure in proportions influenced by the ratios of initial reactants. For the same starting ratios of reactants, a longer reaction time or higher pressure shifts equilibria to lower yields of Ni2B. Using this approach, yields of ~88% Ni4B3 (single phase orthorhombic) and ~72% Ni3B are obtained for conditions 1.9 MPa < Pmax < 4.9 MPa and 670 °C < Tmax < 725 °C. Gas-solid reaction is the dominant transformation mechanism that results in formation of Ni2B at lower temperatures than conventional solid-state methods.
Predicting real-world behaviour: Cognition-emotion links across adulthood and everyday functioning at work

ABSTRACT Inspired by the discovery of positive age trends in emotional well-being across adulthood, lifespan researchers have uncovered fascinating age differences in cognition–emotion interactions in healthy adult samples, for example in emotion processing, memory, reactivity, perception, and regulation. Taking stock of this body of research, I identify four trends and five remaining gaps in our understanding of emotional functioning in adulthood. In particular, I suggest that the field should pay stronger attention to the prediction of real-world behaviour. Using the sample case of work functioning, I outline gaps in current knowledge, including the lack of data on middle-aged adults, the neglect of relevant cognitive-emotional mechanisms, and the unclear role of life experience. Filling these gaps will enable progress in research on emotional aging in and beyond the work setting and enhance its practical utility for individuals, organisations, and society.
Impact of a Clinical Decision Support Tool on Cancer Pain Management in Opioid-Tolerant Inpatients

Background: Pain is both common and undertreated in the hematology/oncology population despite national guidelines and a focus from The Joint Commission. Objective: Herein, we describe the features of a pain clinical decision support tool (PCDST) embedded into the electronic medical record (EMR) and report its impact on oncology inpatients at risk for uncontrolled pain. Methods: The PCDST was developed to identify patients with potentially uncontrolled pain, defined as a pain score ≥4. Clinical pharmacists were encouraged to use the tool to determine whether interventions were needed to better control pain. Pain and safety outcomes between 2 cohorts of opioid-tolerant adult inpatients presenting with severe pain were compared prior to and following the implementation of the PCDST. Results: The primary endpoint, attainment of analgesia at 24 hours from admission, was met in 10 of 30 (33.3%) patients in the preimplementation group and in 14 of 32 (43.8%) of patients in the postimplementation group (P = .78). Secondary endpoints including time to analgesia, mean pain score, frequency of pharmacy intervention, and National Comprehensive Cancer Network (NCCN) guideline–adherent pain regimens were not found to be statistically significantly different between the 2 groups. The number of mean nursing pain assessments in the first 24 hours from admission was found to be significantly higher in the postimplementation group compared with the preimplementation group (12 vs 7.4, P < .001). Safety events were rare and not statistically different between groups. Conclusion: Overall, a modest, but statistically nonsignificant, improvement in pain outcomes was associated with patients admitted after the implementation of a pharmacist-managed electronic pain scoring tool.
Genetic structure in Red Junglefowl (Gallus gallus) populations: Strong spatial patterns in the wild ancestors of domestic chickens in a core distribution range

Abstract Red Junglefowl (Gallus gallus) are among the few remaining ancestors of an extant domesticated livestock species, the domestic chicken, that still occur in the wild. Little is known about genetic diversity, population structure, and demography of wild Red Junglefowl in their natural habitats. Extinction threats from habitat loss or genetic alteration from domestic introgression exacerbate further the conservation status of this progenitor species. In a previous study, we reported extraordinary adaptive genetic variation in the MHC B‐locus in wild Red Junglefowl and no evidence of allelic introgression between wild and domestic chickens was observed. In this study, we characterized spatial genetic variation and population structure in naturally occurring populations of Red Junglefowl in their core distribution range in South Central Vietnam. A sample of 212 Red Junglefowl was obtained from geographically and ecologically diverse habitats across an area of 250 × 350 km. We used amplified fragment‐length polymorphism markers obtained from 431 loci to determine whether genetic diversity and population structure varies. We found that Red Junglefowl are widely distributed but form small and isolated populations. Strong spatial genetic patterns occur at both local and regional scales. At local scale, population stratification can be identified to approximately 5 km. At regional scale, we identified distinct populations of Red Junglefowl in the southern lowlands, northern highlands, and eastern coastal portions of the study area. Both local and long‐distance genetic patterns observed in wild Red Junglefowl may reflect the species’ ground‐dwelling and territorial characteristics, including dispersal barriers imposed by the Annamite Mountain Range. Spatially explicit analyses with neutral genetic markers can be highly informative and here elevates the conservation profile of the wild ancestors of domesticated chickens.
Biomarkers for immune therapy in melanoma

Immune checkpoint inhibitors have dramatically transformed melanoma treatment options. However, intrinsic and acquired resistance remain fundamental limitations to extending the benefits to all patients. Understanding molecular and clinical features that correlate with response to treatment (biomarkers) may unravel therapeutic resistance, assist in treatment decision-making, and facilitate drug development. An intensive effort to characterize these biomarkers is underway. Herein, we highlight promising molecular biomarkers involving the tumor microenvironment, host immune response, and microbiome. We particularly focus on anti-programmed death-1 therapy but will also briefly cover anti-cytotoxic T lymphocyte antigen-4 and novel combination therapies.
Comparative Transcriptome Analysis for Understanding Predator-Induced Polyphenism in the Water Flea Daphnia pulex

The crustacean Daphnia pulex is one of the best model organisms for studying inducible defense mechanisms due to their inducible morphology in response to the predator Chaoborus larvae. In this study, multiple developmental stages of D. pulex were exposed to C. flavicans larvae and transcriptome profiles of samples from late embryo to fifth instar were sequenced by the RNA-seq technique to investigate the genetic background underlying inducible defenses. In comparison, differentially expressed genes between defensive and normal morphs were identified, including 908 genes in late embryo, 1383 genes in the first-third (1–3) instar, and 1042 genes in fourth-fifth (4–5) instar. Gene ontology enrichment analysis showed that structural constituents of the cuticle and structural molecule activity genes were prominent up-regulated genes in late embryos. Down-regulated genes in late embryos and 1–3 instar comprised metabolic process, hydrolase activity, and peptidase activity gene classes. Pathway analysis indicated that small molecule neurotransmitter pathways were potentially involved in the development of inducible defenses. The characterization of genes and pathways in multiple developmental stages can improve our understanding of inducible defense responses of D. pulex to predation at the molecular level.
Retrospective study of changes in ocular coherence tomography characteristics after failed macular hole surgery and outcomes of fluid-gas exchange for persistent macular hole

Purpose: The aim is to study the changes in ocular coherence tomography (OCT) parameters of large (≥400 μ) full-thickness macular holes (FTMHs) after a failed surgery and evaluate the outcome of fluid-gas exchange (FGE) in the treatment of persistent macular hole and role of OCT in predicting outcome after the secondary intervention. Methods: Changes occurring in the OCT parameters of FTMH after a failed vitrectomy were evaluated. FGE was done in an operating room with three pars plana sclerostomy ports. The anatomical and functional outcomes of FGE for these persistent macular holes were also assessed. Anatomical closure was defined as the flattening of the hole with resolution of subretinal cuff of fluid. Anatomical success after FGE was defined as flattening of macular hole with the resolution of subretinal cuff of fluid and neurosensory retina completely covering the fovea. Functional success was defined as an improvement of at least one line of best-corrected visual acuity (BCVA). Results: Twenty-eight eyes (28 patients) were included in the study. After the failed vitrectomy, OCT showed an increase in the base diameter, opening diameter, and height of the hole. After the secondary procedure, anatomical closure was achieved in 89.3% eyes. Mean BCVA improved from logMAR 0.88 ± 0.24 (20/152) to logMAR 0.66 ± 0.24 (20/91) (P < 0.001). Eight (28.6%) patients achieved final BCVA ≥20/60. Functional success was obtained in 19 patients (67.9%). There was no association between anatomical success after FGE and any of the pre-FGE OCT parameters or indices. Conclusion: Unsuccessful surgery causes swelling of the outer and middle retinal layers with retraction of inner layers of the retina. Performing FGE while visualizing the retina is a good option for the treatment of large persistent macular holes as it causes complete drying of the macula, better success rates, and a reduced complication rate. Pre-FGE OCT does not help in predicting the outcome of FGE for persistent macular hole.
Nilotinib as Coadjuvant Treatment with Doxorubicin in Patients with Sarcomas: A Phase I Trial of the Spanish Group for Research on Sarcoma

Purpose: Nilotinib plus doxorubicin showed to be synergistic regarding apoptosis in several sarcoma cell lines. A phase I/II trial was thus designed to explore the feasibility of nilotinib as coadjuvant of doxorubicin by inhibiting MRP-1/P-gp efflux activity. The phase I part of the study is presented here. Patients and Methods: Nilotinib 400 mg/12 hours was administered in fixed dose from day 1 to 6, and doxorubicin on day 5 of each cycle. Three dose escalation levels for doxorubicin at 60, 65, and 75 mg/m2 were planned. Cycles were repeated every 3 weeks for a total of 4 cycles. Eligible subtypes were retroperitoneal liposarcoma, leiomyosarcoma, and unresectable/metastatic high-grade chondrosarcoma. Results: Thirteen patients were enrolled: 7 chondrosarcoma, 4 liposarcoma, and 2 leiomyosarcoma. In 46 cycles administered, the most relevant grade 3/4 adverse effects per patient were neutropenia 54%, febrile neutropenia 15%, and asthenia 8%. No cardiac toxicity was observed. Only one dose-limiting toxicity (febrile neutropenia) was reported in the third dose level. With regard to efficacy, 1 partial response (1 liposarcoma), 9 stable diseases (5 chondrosarcoma, 2 liposarcoma, 1 leiomyosarcoma), and 3 progressive diseases (2 chondrosarcoma and 1 leiomyosarcoma) were present. ABCB1 and ABCC1 RNA expression levels decreased by 58.47-fold and 1.47-fold, respectively, on day 5 of the cycle. Conclusions: Combination of MRP-1/P-gp inhibitor, nilotinib, as coadjuvant with doxorubicin is feasible; it appears not to add substantial toxicity compared with doxorubicin alone. Pharmacodynamic study supports this concept. The recommended dose for the phase II part for doxorubicin was 75 mg/m2. Clin Cancer Res; 24(21); 5239–49. ©2018 AACR.
Prenatal Exposure to Ambient Pesticides and Preterm Birth and Term Low Birthweight in Agricultural Regions of California

Findings from studies of prenatal exposure to pesticides and adverse birth outcomes have been equivocal so far. We examined prenatal exposure to agricultural pesticides in relation to preterm birth and term low birthweight, respectively, in children born between 1998 and 2010, randomly selected from California birth records. We estimated residential exposure to agriculturally applied pesticides within 2 km of residential addresses at birth by pregnancy trimester for 17 individual pesticides and three chemical classes (organophosphates, pyrethroids, and carbamates). Among maternal addresses located within 2 km of any agricultural pesticide application, we identified 24,693 preterm and 220,297 term births, and 4412 term low birthweight and 194,732 term normal birthweight infants. First or second trimester exposure to individual pesticides (e.g., glyphosates, paraquat, imidacloprid) or exposure to 2 or more pesticides in the three chemical classes were associated with a small increase (3–7%) in risk for preterm birth; associations were stronger for female offspring. We did not find associations between term low birthweight and exposure to pesticides other than myclobutanil (OR: 1.11; 95% CI: 1.04–1.20) and possibly the pyrethroids class. Our improved exposure assessment revealed that first and second trimester exposure to pesticides is associated with preterm delivery but is rarely linked with term low birthweight.