Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Aspirin on Cancer Incidence and Mortality in Older Adults

Abstract Background ASPirin in Reducing Events in the Elderly, a randomized, double-blind, placebo-controlled trial of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast, prior randomized controlled trials, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality. Methods 19 114 Australian and US community-dwelling participants aged 70 years and older (US minorities 65 years and older) without cardiovascular disease, dementia, or physical disability were randomly assigned and followed for a median of 4.7 years. Fatal and nonfatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records. Results 981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64). Conclusions In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and, thus, suggest caution with its use in this age group.
Chemotherapy‐induced peripheral neuropathy: Identifying the research gaps and associated changes to clinical trial design

To the authors' knowledge, the empiric identification of agents and interventions to mitigate chemotherapy‐induced peripheral neuropathy (CIPN) has resulted in only 1 agent that modestly mitigates it and no agents or interventions that prevent its development. This speaks to the need for a mechanistic understanding of CIPN to develop effective interventions.
A guide for an anatomically sensitive dentine microsampling and age-alignment approach for human teeth isotopic sequences.

OBJECTIVES Stable isotope analysis of sequential dentine samples is a potentially powerful method to reveal insights into early life-histories of individuals in the past. Dentine incremental growth structures are complex, however, and current approaches that apply horizontal sectioning of demineralized tooth halves or quarters risk combining multiple growth layers and may include unwanted cementum or secondary dentine. They also require destruction of large parts of a tooth. Here, we present a less destructive and relatively straightforward protocol that reduces damage, increases temporal resolution, and improves the accuracy of age-alignment between individuals. MATERIAL AND METHODS We outline a protocol that includes the sampling of small (1 mm diameter) cylindrical plug transects from a thin section, along with an age-alignment scheme predicated on average growth rates for dentine areas. RESULTS AND DISCUSSION The proposed protocol is readily applicable and more anatomically sensitive than horizontal slicing. Micro-samples are smaller (in both length and depth), hence minimizing temporal overlap and avoid directions that may contravene growth pattern. They completely avoid areas where secondary and tertiary dentine or cementum can be deposited. Age-alignment is improved by using growth ratios of anatomical tooth zones. CONCLUSION This method minimizes destruction, enables finer temporal resolution and facilitates data comparison. It can be readily combined with fluorescence imaging-based or other pre-screening methods of dentine collagen preservation.
Mitotic regulation by Polo-like kinase 1 and the Chromosomal Passenger Complex

During mitosis, the duplicated genome must be accurately divided between two daughter cells. Polo-like kinase 1 (Plk1) and Aurora B kinase, together with its binding partners Incenp, Survivin and Borealin (chromosomal passenger complex, CPC), have key roles in coordinating mitotic events. The accuracy of cell division is safeguarded by a signaling cascade termed the mitotic spindle checkpoint (SC), which ensures that chromosomes are not physically separated before correct bipolar attachments have been formed between kinetochores and spindle microtubules (MT). An inhibitory “wait anaphase” signal, which delays chromosome separation (anaphase onset), is created at individual kinetochores and broadcasted throughout the cell in response to lack of kinetochore-microtubule (kMT) attachment or proper interkinetochore tension. It is believed that the fast turnover of SC molecules at kinetochores contributes to the cell’s ability to produce this signal and enables rapid responses to changing cellular conditions. Kinetochores that lack MT attachment and tension express a certain phosphoepitope called the 3F3/2 phosphoepitope, which has been linked to SC signaling. In the experimental part, we investigated the regulation of the 3F3/2 phosphoepitope, analyzed whether CPC molecules turn over at centromeres, and dissected the mitotic roles of the CPC using a microinjection technique that allowed precise temporal control over its function. We found that the kinetochore 3F3/2 phosphoepitope is created by Plk1, and that CPC proteins exhibit constant exchange at centromeres. Moreover, we found that CPC function is necessary in the regulation of chromatid movements and spindle morphology in anaphase. In summary, we identified new functions of key mitotic regulators Plk1 and CPC, and provided insighs into the coordination of mitotic events.
The role of NOX4 in pulmonary diseases

Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is a subtype of the NOX family, which is mainly expressed in the pulmonary vasculature and pulmonary endothelial cells in the respiratory system. NOX4 has unique characteristics, and is a constitutively active enzyme that primarily produces hydrogen peroxide. The signaling pathways associated with NOX4 are complicated. Negative and positive feedback play significant roles in regulating NOX4 expression. The role of NOX4 is controversial because NOX4 plays a protective or damaging role in different respiratory diseases. This review summarizes the structure, enzymatic properties, regulation, and signaling pathways of NOX4. This review then introduces the roles of NOX4 in different diseases in the respiratory system, such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis.
Do spontaneously decreasing estradiol levels prior to triggering of ovulation adversely impact in vitro fertilization outcomes?

Objective The aim of this study was to explore the potential adverse effect of spontaneously decreasing serum estradiol (SE) levels on in vitro fertilization (IVF) outcomes. Methods This retrospective single-subject study analyzed IVF cycles conducted at a hospital IVF unit between 2010 and 2017. Overall, 2,417 cycles were analyzed. Only cycles with spontaneously decreasing SE before human chorionic gonadotropin (hCG) triggering were included. Each patient served as her own control, and subsequent cycles were analyzed for recurrent SE decreases. The main outcome was the number of oocytes retrieved. Results Cycle characteristics were similar between the study (SE decrease) and control groups, with the exception of the median SE on the day of hCG triggering (899.7 pg/mL; interquartile range [IQR], 193–2,116 pg/mL vs. 1,566.8 pg/mL; IQR, 249–2,970 pg/mL; p < 0.001). The study group, relative to the control group, had significantly fewer total oocytes (5 [IQR, 2–9] vs. 7 [IQR, 3–11]; p = 0.002) and significantly fewer metaphase II (MII) oocytes (3 [IQR, 1–6] vs. 4 [IQR, 2–8]; p = 0.001) retrieved. The study group had fewer cleavage-stage embryos than the control cycles (3 [IQR, 1–6] vs. 4 [IQR, 2–7]; p = 0.012). Compared to cycles with a ≤ 20% SE decrease, cycles with a > 20% decrease had significantly fewer total and MII oocytes retrieved. SE decrease recurred in 12% of patients. Conclusion A spontaneous decrease in SE levels adversely affected IVF outcomes, with a linear correlation between the percentage decrease and the number of oocytes retrieved. SE decrease can repeat in later cycles.
Repetitive mild traumatic brain injuries in mice during adolescence cause sexually dimorphic behavioural deficits and neuroinflammatory dynamics.

Adolescent brain injuries have devastating impacts on life-long health as adolescence is a critical period for brain development. Adolescents are susceptible to mild traumatic brain injuries (mTBI) acquired from collisions in contact sports, which are often sustained in a repetitive nature (RmTBI), and cause compounding, sexually-dimorphic neurological deficits. Neuroinflammation accompanies RmTBIs and may be a central driving force for chronic neurological decline. To date, the impact of neuroinflammation and sex-specific dynamics during adolescent RmTBIs has been understudied. A lateral impact model (LIM) was developed that mimics the biomechanical forces commonly experienced in human mTBIs. Here, we report novel sexually dimorphic neurobehavioral and neuroinflammatory responses using LIM to model adolescent RmTBIs. We first subjected adolescent male C57Bl/6 mice to 1, 3, or 5 RmTBIs at 24-hour intervals and quantified neurobehavioral deficits, and brain volumetric and structural changes by MRI. Five RmTBIs caused significant motor deficits, increased brain volume in cortex, hippocampus, and corpus callosum, and reduced white matter integrity in the corpus callosum. We then compared neurobehavioral deficits in adolescent male and female mice and observed sex-specific deficits in motor function, while both sexes had dysfunction in learning and memory. Flow cytometric quantification of neuroinflammatory responses revealed time- and sex-dependent infiltration of peripheral macrophages and T-cells, and male-specific decreases in microglia number. Using immunohistochemistry, we report specific microglia density decreases in male mice in the motor cortex and thalamus. We show novel neuroinflammatory responses following adolescent brain injuries that expands the current understanding of RmTBI pathophysiology in this critical neurodevelopmental period.
Zinc Content and Storage Period in Formulated African Indigenous Food Products

Preservation of agricultural produce is one of the central problems facing developing countries, where foods consumed are basically staple food crops and cereals. Owing to the lack or inadequacy of preservation methods, large quantities of urgently needed food spoil there. These problems will be aggravated by the growing dietary needs of these burgeoning populations. Six food products were formulated (cookies, pre-cooked flour, fermented four, noodles, crackers and sim-balls) based on indigenous grains, nuts, seeds, roots and vegetables as follows: finger millet (Eleusine coracana), groundnuts (Arachis hypogaea), simsim (Sesamum orientale L.), cassava (Manihot esculenta) and slenderleaf (Crotalaria ochroleuca and Crotalaria brevidens). Raw materials were dried, spatially roasted, grinded and fermented ready for product formulation. The formulations were analyzed for zinc content monthly for three months. Zinc analysis was done according to the standard procedure described in AOAC (2000). There were high zinc levels in the formulated indigenous food products which could be attributed to increased diversity of the crops used to formulate the products as not a single crop was used but a combination of at least two crops. As storage time increased, the content also increased, it is therefore evident that storage period increased zinc content of the products.
Stomatal immunity against fungal invasion comprises not only chitin-induced stomatal closure but also chitosan-induced guard cell death

Significance Fungal disease is a major threat to agriculture and consequently human nutrition. Many pathogenic fungi penetrate through stomata. This study reveals that chitin oligosaccharide (CTOS) from fungal cell wall induces stomatal closure through its receptor CERK1, Ca2+, and S-type anion channel SLAC1, which would prevent fungal penetration. It is also shown that conversion of CTOS to chitosan oligosaccharide (CSOS) is a possible fungal strategy to circumvent stomatal immunity. At higher concentration, guard cells perceive CSOS, resulting in guard cell death, which potentially contributes to plant defense halting fungal infection through stomata. The finding of active guard cell death represents a conceptual advance in understanding of stomatal immunity and would guide future research on guard cell–microbe interaction and crop protection. Many pathogenic fungi exploit stomata as invasion routes, causing destructive diseases of major cereal crops. Intensive interaction is expected to occur between guard cells and fungi. In the present study, we took advantage of well-conserved molecules derived from the fungal cell wall, chitin oligosaccharide (CTOS), and chitosan oligosaccharide (CSOS) to study how guard cells respond to fungal invasion. In Arabidopsis, CTOS induced stomatal closure through a signaling mediated by its receptor CERK1, Ca2+, and a major S-type anion channel, SLAC1. CSOS, which is converted from CTOS by chitin deacetylases from invading fungi, did not induce stomatal closure, suggesting that this conversion is a fungal strategy to evade stomatal closure. At higher concentrations, CSOS but not CTOS induced guard cell death in a manner dependent on Ca2+ but not CERK1. These results suggest that stomatal immunity against fungal invasion comprises not only CTOS-induced stomatal closure but also CSOS-induced guard cell death.
Molecular Approaches to the Study of Trichothecene Production in Fusarium Species

Fusarium is a wide spread group of toxigenic and plant pathogenic filamentous fungi, with a record of devastating infections on many kinds of economically important plants. Fusarium is the causative agent of Fusarium Head Blight (FHB) or scab, ear, stem or stalk rot in economically important cereals, especially wheat and barley, dry rot in potatoes and crown rot in banana. FHB infection adversely affect the quality and marketability of grain by reducing yield, discoloring and shriveling of seeds and contamination of the grain with mycotoxins that eventually result in heavy losses of several billion dollars to wheat and barley farmers worldwide. The importance of these fungi and their toxins in human health cannot be underestimated. Fusarium has been established as the causative of alimentary toxic aleukia (ATA). Fusarium secretes a vast array of toxins that include trichothecenes, fumonisins, zearalenone, beuvericin etc. Trichothecenes are sequiterpenoids in nature and are classified into 4 groups. Type A trichothecenes such as T-2, Hydroxy T-2 (HT-2) and Diacetoxyscirpenol (DAS) are produced by F. sporotrichioides, F. poae, F. equiseti and the type B trichothecenes such as deoxynivalenol (DON) synthesized by F. culmorum, F. graminearum and Nivalenol (NIV) by F. graminearum, F. poae, F. equiseti. Trichothecenes are significantly phytotoxic and paves the way for Fusarial colonization of the plant and is probably important in controlling the spread of other fungal strains. Trichothecenes are commonly reported as contaminants in breakfast cereals or cereal products and vegetables, as they are stable under normal cooking conditions. DON is the most prevalent among the trichothecenes in wheat and wheat based products, followed by the toxins such as NIV, DAS and T-2.
Inhibition of matrix degrading enzymes and invasion in rat glioblastoma (C6) Cells

Pamela Gabelloni 1 , Eleonora Da Pozzo 1 , Barbara Costa 2 , Elisa Nuti 3 , Francesca Casalini 3 , Sara Bendinelli 1 , Armando Rossello 3 , Claudia Martini 1 . 1:Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy 2:Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy 3:Department oh Pharmaceutical Science, University of Pisa, Pisa, Italy gabelloni@farm.unipi. it; dapozzo@farm.unipi. it
Association between monocyte to high-density lipoprotein cholesterol ratio and bicuspid aortic valve degeneration

Background/aim From a pathophysiological point of view, inflammation is thought to be more dominant in bicuspid aortic valve (BAV) stenosis than tricuspid aortic valve (TAV) stenosis. Our study aimed to determine the association between monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR), a new inflammatory marker, and the speed of progression of stenosis and pathophysiology of BAV stenosis. Materials and methods A total of 210 severe aortic stenosis patients (70 consecutive BAV patients, 140 matched TAV patients) were retrospectively enrolled in the study. Clinical and echocardiographic data and laboratory results related to our research were collected retrospectively from the patients’ records. MHR was measured as the ratio of the absolute monocyte count to the HDL-C value. Results Seventy BAV (mean age: 72.0 ± 9.1 years, 42.9% female) and 140 TAV patients (mean age: 77.9 ± 8.3 years, 51.4% female) with severe aortic stenosis were enrolled in this study. There was no difference between the two groups in terms of another baseline demographic or clinic findings except age (P < 0.001). Monocyte count, hemoglobin level, mean platelet volume was significantly higher, and HDL-C level was significantly lower in the BAV group, while other lipid and CBC parameters were found to be similar. In the multivariate analysis, MHR (P = 0.005, 95% CI: 0.90–0.98) and, as expected, age (P = 0.001, 95% CI: 1.02–1.11) were found to be significant as the independent predictor of BAV, after adjusting for other risk factors. Conclusion Our study showed a significant correlation between increased MHR and BAV. MHR was determined as a significant independent predictor for the speed of progression and diagnosis of severe BAV stenosis in multivariate analysis.
Efficacy of psychotherapy for anxiety reduction in hospital management of women successfully treated for preterm labor: a randomized controlled trial

ABSTRACT Preterm labor (PTL) is associated with high anxiety and stress in pregnant women. The study investigated the effect of adding psychotherapy to hospital management of pregnant women with successfully treated for PTLon improving anxiety, pregnancy stress, and perceived control. In a randomized controlled trial study, sixty pregnant women with gestational ages of 24 to 37 weeks and successfully treated forPTL were randomly divided into the experimental (n = 30) and control group (n = 30). The experimental group received psychotherapy along with medical care in individual face-to-facesessions, 1 h per day for 6 consecutive days.The control group received medical care for PTL. Objective outcomes were assessed via the State-Anxiety Inventory, Prenatal Distress Questionnaire (NuPDQ), and Perceived Pregnancy Control at pre-trial and post-trial. The results revealed that psychotherapy significantly improved mean pregnancy distress (45.80 ± 2.29 vs. 43.80 ± 1.93), state anxiety (47.46 ± 5.92 vs. 41.60 ± 5.46), and perceived control (2.86 ± 1.59 vs. 5.26 ± 1.38) in women with PTL from beginning to end of the intervention. The findings suggest that adding psychotherapy to hospital management of women successfully treated for PTLcan be considered a potential method to reduce anxiety and pregnancy-specific stress.
Alginate as Promising Natural Biodegradable Polymer for Pharmaceutical, Food, and Biomedical Applications.

Alginates are biopolymers usually obtained from brown seaweed, brown algae (Ochrophyta, Phaeophyceae), and bacteria (Azatobacter vineland and Pseudomonas species) belonging to the family of polycationic copolymers. They are biocompatible, biodegradable, non-antigenic, and non-toxic biopolymer with molecular mass ranges from 32,000-40,000 g/mol in commercial grades. These can be used as edible films or coatings in food industries and also some natural or chemical additives could be incorporated into them to modify their functional, mechanical, nutritional as well as organoleptic properties. Due to their high viscosity and extraordinary shear-thinning effect, they can be used as dietary fibers, thickening, gelling and stabilizing agents. Commercial alginates have vast applications in the fields of biomedical engineering, biotechnology, environmental contaminants treatments, food processing, and pharmaceuticals. Alginates can be used in wound dressings, bone regeneration, neovascularization, protein delivery, cell delivery, theranostic agents, oral drug delivery, controlled release systems, raft formulations, immobilization of biological agents and treatment of environmental contaminants. Various carrier systems can be formulated by the use of alginates like hydrogel, tablets, microcapsules, films, matrices, microspheres, liposomes, nanoparticles, beads, cochleate, floating and supersaturated drug delivery systems. This review presents a broad range of promising applications of alginates and it can be a great interest to scientists and industries engaged in exploring its hidden potential.
Preventing acute kidney injury: assessing awareness to temporarily discontinue 'at-risk' medicines during acute illness in a New Zealand cohort.

AIM The objective of this research is to determine community dwelling patients' awareness of temporarily discontinuing medicines during acute illness, and the actions they would undertake when acutely unwell. METHOD Adults taking long-term oral medicines for chronic health conditions completed a four-question self-completion paper-based questionnaire collecting data requiring quantitative analysis. Recruitment occurred in six participating Hawke's Bay community pharmacies during 2017 and 2018. RESULTS One hundred and thirty people completed the survey. Seventeen (13%) recalled receiving guidance from a health professional on which medicines to stop during excessive vomiting or diarrhoea. Only three people, however, would stop their medicines. Eighteen percent (17/95) of participants aged 65 years and older were prescribed both a NSAID and either an angiotensin-converting-enzyme inhibitor (ACEi) or angiotensin-II receptor blocker (ARB); five reported receiving advice to withhold medicines. Three participants were prescribed a Triple Whammy combination; none reported being advised to withhold medicines. CONCLUSION A small proportion of the participants recalled receiving guidance to temporarily withhold medicines during acute illness; many indicated the advice would not be followed. The results indicate a degree of acute kidney injury prior (AKI) at-risk prescribing. There are opportunities to empower people to self-manage at-risk medicines during periods of acute illness.