Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT): A Phase Ib Dose-Escalation Study of Venetoclax Combined With Modified Intensive Chemotherapy.

PURPOSE The B-cell lymphoma 2 (BCL-2) inhibitor venetoclax has an emerging role in acute myeloid leukemia (AML), with promising response rates in combination with hypomethylating agents or low-dose cytarabine in older patients. The tolerability and efficacy of venetoclax in combination with intensive chemotherapy in AML is unknown. PATIENTS AND METHODS Patients with AML who were ≥ 65 years (≥ 60 years if monosomal karyotype) and fit for intensive chemotherapy were allocated to venetoclax dose-escalation cohorts (range, 50-600 mg). Venetoclax was administered orally for 14 days each cycle. During induction, a 7-day prephase/dose ramp-up (days -6 to 0) was followed by an additional 7 days of venetoclax combined with infusional cytarabine 100 mg/m2 on days 1-5 and idarubicin 12 mg/m2 intravenously on days 2-3 (ie, 5 + 2). Consolidation (4 cycles) included 14 days of venetoclax (days -6 to 7) combined with cytarabine (days 1-2) and idarubicin (day 1). Maintenance venetoclax was permitted (7 cycles). The primary objective was to assess the optimal dose schedule of venetoclax with 5 + 2. RESULTS Fifty-one patients with a median age of 72 years (range, 63-80 years) were included. The maximum tolerated dose was not reached with venetoclax 600 mg/day. The main grade ≥ 3 nonhematologic toxicities during induction were febrile neutropenia (55%) and sepsis (35%). In contrast to induction, platelet recovery was notably delayed during consolidation cycles. The overall response rate (complete remission [CR]/CR with incomplete count recovery) was 72%; it was 97% in de novo AML and was 43% in secondary AML. During the venetoclax prephase, marrow blast reductions (≥ 50%) were noted in NPM1-, IDH2-, and SRSF2-mutant AML. CONCLUSION Venetoclax combined with 5 + 2 induction chemotherapy was safe and tolerable in fit older patients with AML. Although the optimal postremission therapy remains to be determined, the high remission rate in de novo AML warrants additional investigation (ANZ Clinical Trial Registry No. ACTRN12616000445471).
Early life adversity decreases pre-adolescent fear expression by accelerating amygdala PV cell development

Early life adversity (ELA) is associated with increased risk for stress-related disorders later in life. The link between ELA and risk for psychopathology is well established but the developmental mechanisms remain unclear. Using a mouse model of resource insecurity, limited bedding (LB), we tested the effects of LB on the development of fear learning and neuronal structures involved in emotional regulation, the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA). LB delayed the ability of peri-weanling (21 days old) mice to express, but not form, an auditory conditioned fear memory. LB accelerated the developmental emergence of parvalbumin (PV)-positive cells in the BLA and increased anatomical connections between PL and BLA. Fear expression in LB mice was rescued through optogenetic inactivation of PV-positive cells in the BLA. The current results provide a model of transiently blunted emotional reactivity in early development, with latent fear-associated memories emerging later in adolescence.
Children with type 1 diabetes have elevated high-sensitivity C-reactive protein compared with a control group

Introduction Our objective was to compare high-sensitivity C-reactive protein (hsCRP) levels in children with type 1 diabetes, healthy controls, and children with obesity. Additionally, we aimed to analyze the association between hsCRP levels and glycemic control measured by glycohemoglobin A (HbA1c) and anthropometric and biochemical variables. Research design and methods We conducted a non-randomized descriptive study of children with type 1 diabetes matched for sex and age with a control group and group with obesity. We recorded anthropometric parameters and studied variables related to diabetes, blood pressure, lipid profile, and HbA1c. hsCRP was measured by ELISA. Results We included 49 children with type 1 diabetes, 46 controls, and 40 children with obesity. hsCRP levels were significantly higher in the group with type 1 diabetes compared with controls and nearly significantly lower than in the group comprising children with obesity. We found no correlation between hsCRP and HbA1c and characteristics of type 1 diabetes with the exception of albumin to creatinine ratio. Statistically significant association was found between hsCRP and body mass index (BMI) and waist circumference Z-score. Conclusions The higher hsCRP levels observed in children with type 1 diabetes compared with a control group with a similar BMI suggest a basal inflammatory state that could increase cardiovascular risk. The main factors related to hsCRP are BMI and waist circumference, so obesity prevention should be a priority when performing follow-up in children with type 1 diabetes.
Optimization of scotta as growth medium to preserve biodiversity and maximise bacterial cells concentration of natural starter cultures for Pecorino Romano PDO cheese.

Preservation of cheese microbiota biodiversity is central to the sensory quality of traditional and PDO cheeses. Lyophilized commercial selected starters, being advantageous in terms of cells concentration, are supplanting natural cultures causing important loss of microbial biodiversity in the dairy environment. Biodiversity could be recovered using natural starter cultures, however their cells concentration after propagation is lower than the commercial ones. Two autochthonous and biodiverse starter cultures (MixA and MixB) coming from scotta (residual whey from Ricotta cheese manufacture), collected in the 1960 s from Pecorino Romano PDO cheese manufactures, were revitalized in reconstituted commercial powder scotta. The aim of this study was the propagation of the microbial starter mixes increasing their bacterial concentration in the pellet, reducing nonessential scotta components by a fast and not-expensive method, without changing the microbial community balance. The behaviour of each mix inoculated in scotta was compared to that in half-concentrated, clarified, and half-concentrated-clarified scotta. Higher cells concentration in the pellets from the modified scotta was obtained, without changing technological performances and microbial fingerprint. The pellets obtained were reinoculated in commercial scotta for the preparation of the scotta-innesto (the typical starter for Pecorino Romano), and no differences were observed among the treatments after incubation. The reduction of nonessential scotta's components could help the reproduction of natural starter cultures preserving their properties.
Nutrition and immune system: from the Mediterranean diet to dietary supplementary through the microbiota

Abstract The interaction between nutrition and the immune system is very complex. In particular, at every stage of the immune response, specific micronutrients, including vitamins and minerals play a key role and often synergistic, and the deficiency of only one essential nutrient may impair immunity. An individual’s overall nutrition status and pattern of dietary intake (comprised of nutrients and non-nutritive bioactive compounds and food) and any supplementation with nutraceuticals including vitamins and minerals, can influence positively or negatively the function of the immune system. This influence can occur at various levels from the innate immune system and adaptive immune system to the microbiome. Although there are conflicting evidence, the current results point out that dietary supplementation with some nutrients such as vitamin D and zinc may modulate immune function. An update on the complex relationship between nutrition, diet, and the immune system through gut microbiota is the aim of this current review. Indeed, we will provide the overview of the link among immune function, nutrition and gut microbiota, paying particular attention at the effect of the Mediterranean diet on the immune system, and finally we will speculate the possible role of the main one functional supplements on immune function.
Depressive symptoms rather than executive functioning predict group cognitive behavioural therapy outcome in binge eating disorder

Abstract Executive functions play an important role in mediating self‐control and self‐regulation. It has been suggested that the inability to control eating in Binge Eating Disorder (BED) may indicate inefficiencies in executive functioning. This study investigated whether executive functioning predicted cognitive behavioural therapy outcome in BED while accounting for other possible predictors: depressive symptoms, interpersonal factors, eating disorder psychopathology, and self‐esteem. Executive functioning and other predictors were assessed in 91 patients with BED by means of neuropsychological tests and questionnaires at baseline. Eating disorder (ED) symptoms were assessed during treatment at variable time points. Potential predictor variables were investigated using multivariate Cox regression models. Recovery was defined by means of two different indicators based on the Eating Disorder Examination‐Questionnaire: (a) showing a 50% reduction in baseline symptom ED severity and/or reaching the clinical significance cut‐off; and (b) achieving abstinence of objective binge eating. Severity of depressive symptoms was a significant predictor for outcome on both indicators. Patients with no or mild depressive symptoms recovered faster (i.e., 50% reduction in ED symptoms and abstinence of objective binge eating) than those with severe depressive symptoms, which is in line with previous studies. Executive functioning was not related to treatment outcome in this study.
Yin Yang 1 is a potent activator of human T lymphotropic virus type 1 LTR-driven gene expression via RNA binding

Significance Human T lymphotropic virus type 1 (HTLV-1) is a retrovirus that mainly transforms CD4+ T cells, ultimately leading to the development of adult T cell leukemia/lymphoma or HTLV-1-associated myelopathy/tropical spastic paraparesis, both of which have limited treatment options. A deeper understanding of how the virus hijacks host factors for replication is critical for the development of new therapies. In this study, we discovered that a host transcription factor, Yin Yang 1 (YY1) is a potent activator of HTLV-1 gene expression. Surprisingly, it does so by binding to viral RNA, instead of the classical DNA–transcription factor interaction. Our results provide insights into host–viral interactions, as well as the biology of cellular transcription factors. Yin Yang 1 (YY1) is a DNA-binding transcription factor that either activates or represses gene expression. YY1 has previously been implicated in the transcriptional silencing of many retroviruses by binding to DNA sequences in the U3 region of the viral long terminal repeat (LTR). We here show that YY1 overexpression leads to profound activation, rather than repression, of human T lymphotropic virus type 1 (HTLV-1) expression, while YY1 down-regulation reduces HTLV-1 expression. The YY1 responsive element mapped not to YY1 DNA-binding sites in the HTLV-1 LTR but to the R region. The HTLV-1 R sequence alone is sufficient to provide YY1 responsiveness to a nonresponsive promoter, but only in the sense orientation and only when included as part of the mRNA. YY1 binds to the R region of HTLV-1 RNA in vitro and in vivo, leading to increased transcription initiation and elongation. The findings indicate that YY1 is a potent transactivator of HTLV-1 gene expression acting via binding viral RNA, rather than DNA.
Detecting a decline in whale shark Rhincodon typus sightings in the Andaman Sea, Thailand, using ecotourist operator-collected data

In this paper, we analyse long-term whale shark Rhincodon typus sightings collected by ecotourist operators and evaluate the validity of conclusions drawn from the data for scientific and conservation purposes. To date information about the basic ecology and movements of whale sharks is sparse, and only recently has the species received global conservation attention. A dive company in Phuket, Thailand, documented whale shark sightings in the Andaman Sea for 10 years along 300 km of coastline. Whale shark sightings, corrected for effort, dropped by 96% between 1998 and 2001. Combining the seasons from 1992 to 1998, the number of whale shark sightings increased significantly from October to May. The sizes of sharks observed suggest that the majority were juveniles. We discuss the limitations of using ecotourist operators as non-specialist volunteers for data collection but conclude that their use can be beneficial for long-term, broad geographic studies such as this.
PPM1D Knockdown Suppresses Cell Proliferation, Promotes Cell Apoptosis, and Activates p38 MAPK/p53 Signaling Pathway in Acute Myeloid Leukemia

Objectives: This study was to explore the effect of protein phosphatase, Mg2+/Mn2+ dependent 1D knockdown on proliferation and apoptosis as well as p38 MAPK/p53 signaling pathway in acute myeloid leukemia. Methods: The expression of protein phosphatase, Mg2+/Mn2+ dependent 1D was detected in acute myeloid leukemia cell lines including SKM-1, KG-1, AML-193, and THP-1 cells, and normal bone marrow mononuclear cells isolated from healthy donors. The knockdown of protein phosphatase, Mg2+/Mn2+ dependent 1D was conducted by transfecting small interfering RNA into AML-193 cells and KG-1 cells. Results: The relative messenger RNA/protein expressions of protein phosphatase, Mg2+/Mn2+ dependent 1D were higher in SKM-1, KG-1, AML-193, and THP-1 cells compared with control cells (normal bone marrow mononuclear cells). After transfecting protein phosphatase, Mg2+/Mn2+ dependent 1D small interfering RNA into AML-193 cells and KG-1 cells, both messenger RNA and protein expressions of protein phosphatase, Mg2+/Mn2+ dependent 1D were significantly reduced, indicating the successful transfection. Most importantly, knockdown of protein phosphatase, Mg2+/Mn2+ dependent 1D suppressed cell proliferation and promoted cell apoptosis in AML-193 cells and KG-1 cells. In addition, knockdown of protein phosphatase, Mg2+/Mn2+ dependent 1D enhanced the expressions of p-p38 and p53 in AML-193 cells and KG-1 cells. The above observation suggested that protein phosphatase, Mg2+/Mn2+ dependent 1D knockdown suppressed cell proliferation, promoted cell apoptosis, and activated p38 MAPK/p53 signaling pathway in acute myeloid leukemia cells. Conclusion: Protein phosphatase, Mg2+/Mn2+ dependent 1D is implicated in acute myeloid leukemia carcinogenesis, which illuminates its potential role as a treatment target for acute myeloid leukemia.
Letter to the Editor: Use of Pregenomic Hepatitis B Virus RNA and Hepatitis B Core–Related Antigen to Predict Cure of Hepatitis B Virus Infection

I read with great interest the article by Carey and colleagues on the dynamics of pregenomic hepatitis B virus (HBV) RNA and hepatitis B core related antigen (HBcrAg) among patients on nucleos(t)ide analogue (NA) therapy(1). Both HBcrAg and HBV RNA are products of transcriptional activities of covalently closed circular DNA (cccDNA). Although HBcrAg is a test for 3 HBV proteins, it measures primarily hepatitis B core antigen in hepatitis B e antigen (HBeAg)-negative patients. Carey and colleagues reported that patients who developed severe flare after stopping NA tend to have detectable and higher HBV RNA and HBcrAg levels than those who have milder flares.
Efficacy of Impact® to manage blackleg (Leptosphaeria maculans) in canola

The efficacy of the fungicide Impact® (a.i. flutriafol at 250 g/L) was tested for control of blackleg (Leptosphaeria maculans), and for improved yield and oil content in canola (Brassica napus) cultivars with varying levels of blackleg resistance. Field trials were conducted in 1996 in Western Australia at 3 locations (Merredin, Wongan Hills, Mt Barker) in paddocks containing 1–4-year-old blackleg-infested residues. The fungicide (400 mL product/ha) was coated on a double superphosphate fertiliser and applied at seeding. Blackleg was substantially reduced and the seed yield improved following the application of Impact® in most treatments at all locations except Mt Barker, where the fungicide had no effect on reducing the blackleg severity. The percentage reduction in blackleg severity with Impact® ranged between 18 and 59% and 1 and 43% at Merredin and Wongan Hills, respectively, in cultivars with different levels of resistance and exposed to infected residues of various ages. Likewise, the application of Impact® increased the seed yield by 40–322, 186–357, and 71–426 kg/ha at Merredin, Wongan Hills, and Mt Barker, respectively, on residue of various ages. Seed oil content was also improved following the application of Impact® in most treatments at all locations. The improvement in seed yield when using Impact® was variable for different ages of the residue, and was greater under severe to moderate disease conditions caused by exposure to more recent residues than under the milder disease conditions resulting from older residues. In general, susceptible to moderately resistant cultivars showed greater improvement in yield than resistant cultivars. The rates of Impact® were further evaluated in paddocks containing 3-year-old residue in field trials at the same 3 locations during 1997. The fungicide was applied at 200, 400, and 800 mL product/ha. Although blackleg severity was substantially reduced following application of Impact® at 400 and 800 mL/ha compared with 0 and 200 mL/ha, yield was improved only in some cultivars and at some locations.
Captação e aproveitamento da radiação solar pelas culturas da soja e do feijão e por plantas daninhas

Com o objetivo de desenvolver tecnicas para a criacao de um programa de manejo integrado de plantas daninhas (MIPD), avaliou-se neste trabalho, em condicoes de campo, o desempenho das culturas do feijao (Phaseolus vulgaris L.) e da soja [Glycine max (L.) Merrill] e das plantas daninhas picao-preto (Bidens pilosa L.), dois biotipos de leiteiro (Euphorbia heterophylla L.) (sensivel e resistente a herbicidas inibidores da enzima ALS), e carrapicho-beico-de-boi [Desmodium tortuosum (SW.) DC. ], quanto a eficiencia na captacao e ao aproveitamento da radiacao solar, por meio do calculo dos indices taxa de producao de biomassa seca total (Ct), taxa de producao de biomassa seca foliar (Cf), uso eficiente da radiacao (i), taxa de assimilacao liquida (EA), area foliar especifica (SA), indice de area foliar (L), razao de massa foliar (FW) e razao de area foliar (FA). O experimento foi desenvolvido em Argissolo Vermelho-Amarelo em Vicosa, MG. Nao se observou diferenca para todas as caracteristicas avaliadas entre os biotipos de E. heterophylla. A soja apresentou a maior taxa de producao de biomassa seca total ao longo do seu ciclo e tambem o maior indice de area foliar evidenciando sua maior capacidade em captar luz e em sombrear plantas competidoras. O feijao, sobretudo apos o florescimento, foi a planta mais eficaz em drenar seus fotoassimilados para a formacao de folhas. A soja apresentou maior eficiencia em converter a radiacao interceptada em biomassa.
Seed dispersal of fleshy‐fruited invasive plants by birds: contributing factors and management options

The ecology of seed dispersal by vertebrates has been investigated extensively over recent decades, yet only limited research has been conducted on how suites of invasive plants and frugivorous birds interact. In this review, we examine how plant fruit traits (morphology, colour and display, nutritional quality, accessibility and phenology), avian traits (fruit handling techniques, gut passage time and effect, bird movements and social behaviour and dietary composition) and landscape structure (fruit neighbourhood, habitat loss and fragmentation and perch tree effects) affect frugivory and seed dispersal in invasive plants. This functional approach could be used to develop generic models of seed dispersal distributions for suites of invasive plant species and improve management efficiencies. Four broad research approaches are described that could direct management of bird‐dispersed invasive plants at the landscape scale, by manipulating dispersal. First, research is needed to quantify the effect of biological control agents on dispersal, particularly how changes in fruit production and/or quality affect fruit choice by frugivores, dispersal distributions of seed and post‐dispersal processes. Second, we explore how seed dispersal could be directed, such as by manipulating perch structures and/or vegetation density to attract frugivorous birds after they have been foraging on invasive plant fruits. Third, the major sources of seed spread could be identified and removed (i.e. targeting core or satellite infestations, particular habitats and creating barrier zones). Fourth, alternative food resources could be provided for frugivores, to replace fruits of invasive plants, and their use quantified.
Differential contributions of endogenous and exogenous nutrients to egg components in wild Baltic Common Eiders (Somateria mollissima): A test of alternative stable isotope approaches

ABSTRACT The relative importance of nutrients derived from feeding on breeding vs. nonbreeding grounds to the formation of eggs is crucial for predicting how the breeding success of migrating birds responds to changes in food availability during any part of their annual cycle. Eiders have been considered a classical capital breeder, but this assumption has rarely been tested. The measurement of naturally occurring stable isotopes in egg components, together with those in endogenous and exogenous nutrient endpoints, allow the estimation of the relative sources of nutrients to eggs, but these mixing models rely critically on appropriate isotopic discrimination factors that link egg isotope values with their source. A recent captive study using Spectacled Eiders (Somateria fischeri) provided estimates of these isotopic discrimination factors for income breeding. We applied these discrimination factors for investigating nutrient allocation strategies in Common Eiders (Somateria mollisima) breeding in the northern Baltic (Tvärminne, Finland) and wintering in Danish waters, sourced during 2009–2012. Our overall estimates of protein sources using isotopic mixing models were mixed for egg yolk (median: 44.5–56.5% endogenous) and overwhelmingly exogenous for egg albumen (0.4–0.7%). We tested our conclusions also with a single (δ15N) model and with a more parsimonious δ13C discrimination factor between diet and egg albumen, and both supported little to no endogenous reserves being used for egg albumen. A strong positive correlation between egg lipid δ13C and lipid-free yolk δ13C suggests similar metabolic pathways between diet sources and these egg macromolecules. The applicability of isotope discrimination factors used in nutrient allocation studies derived from captive populations needs to be tested in wild populations. Our results support the idea that potential food limitation not only at the wintering areas, but also at the breeding grounds, can limit breeding success of Baltic Common Eiders, which are currently declining.