Miracle-dz/UniFAR-FTUs huggingface dataset:
Perceived work ability at return to work in women treated for breast cancer: a questionnaire-based study

Background: Breast cancer survivors often perceive reduced work ability upon returning to work. Objectives: To identify predictors of perceived reduced work ability following return to work among women treated for breast cancer and to describe workplace interventions and support after returning to work. Methods: A questionnaire was sent to 18-65 years-old women (no. 1578) treated for breast cancer and residing in the catchment area of the Bologna Local Health Authority between 2010 and 2012. The study population was identified through a Hospital Discharge Database. The questionnaires included items about personal characteristics, cancer and work-related factors, perceived work ability and the return to work process. A multivariable logistic regression analysis was performed to identify predictors of reduced work ability upon returning to work. Results: Among the 841 respondents, 503 questionnaires were evaluable. In the study, 43.5% of the respondents reported reduced work ability with respect to the pre-diagnosis period. Reduced work ability was more common in non-cohabiting (OR=1.81, 95%CI 1.10-2.98) than in cohabiting/married women, and after mastectomy (OR=2.77, 95%CI 1.26-6.11) than after breast-conserving surgery. Office staff/sales assistants and managers were less likely to report reduced work ability (OR=0.51, 95%CI 0.30-0.88 and OR=0.21, 95%CI 0.06-0.76, respectively) than labourers. Women who perceived reduced work ability reported more frequently adjustment of work assignments, consultation of an occupational physician, insufficient support from employers and colleagues and discrimination. Conclusions: Reduced work ability is commonly perceived among women who return to work after treatment for breast cancer. Occupational physicians and general practitioners should be aware of a wide range of factors influencing this perception in order to facilitate a successful return to work.
Counterflow gradient electrophoresis for focusing and elution

Counterflow gradient electrofocusing uses the bulk flow of a liquid solution to counterbalance the electrophoretic migration of an analyte. When either the bulk velocity or the electrophoretic velocity of the analyte is made to vary across the length of the channel, there exists a unique zero‐velocity point for the analyte. This focusing method enables simultaneous separation and concentration of different analytes. The high resolution and sensitivity achieved are similar to that of isoelectric focusing, which separates analytes based on their isoelectric points, but the key difference is that analytes will instead focus based on their electrophoretic mobility. Dynamically changing the applied voltage or the counterflow rate over time will shift the zero‐velocity point, and therefore allows the focused analytes to pass through a fixed detection point, or elute from the separation channel. Throughout the review, a number of different counterflow gradient techniques will be discussed, along with their recent advancements and potential applications.
Proteomic analysis and antivenomics study of Western India Naja naja venom: correlation between venom composition and clinical manifestations of cobra bite in this region

ABSTRACT Background: Snakebite is a severe problem in the tropical countries including Indian subcontinent. Premier cases of cobra bites are being reported from western India (WI). Research design and methods: The proteome of WI N. naja venom (NnV) was deciphered by high resolution mass spectrometry analysis of venom, further fractionated by gel filtration (GF) or RP-HPLC followed by SDS-PAGE and then tandem mass spectrometric analysis of protein bands. The efficacy of commercial polyantivenom (PAV) towards WINnV was assessed by ELISA, immuno-blot, neutralization, and venom-PAV immunoaffinity chromatography studies. Results: Proteomic analysis of WINnV, GF fractions, and SDS-PAGE protein bands of RP-HPLC and GF peaks identified 14, 34, 40, and 54, distinct proteins, respectively, when searched against Elapidae database. The biochemical properties of WINnV correlated well with its proteome composition and pathophysiology of cobra envenomation, including neuroparalysis. This study also highlighted the differences in proteome composition between WINnV and previously reported Eastern India NnV. The tested antivenoms exhibited poor immuno-recognition and neutralization of low molecular mass proteins (<20 kDa), such as three-finger toxins, the major class of protein in WINnV. Conclusion: Improvements in production protocols of antivenoms is the necessity of the hour, supplemented with antibodies raised against the poorly recognized toxins.
Vitamin E: Regulatory Role on Signal Transduction

Vitamin E modulates signal transduction pathways by several molecular mechanisms. As a hydrophobic molecule located mainly in membranes it contributes together with other lipids to the physical and structural characteristics such as membrane stability, curvature, fluidity, and the organization into microdomains (lipid rafts). By acting as the main lipid‐soluble antioxidant, it protects other lipids such as mono‐ and poly‐unsaturated fatty acids (MUFA and PUFA, respectively) against chemical reactions with reactive oxygen and nitrogen species (ROS and RNS, respectively) and prevents membrane destabilization and cellular dysfunction. In cells, vitamin E affects signaling in redox‐dependent and redox‐independent molecular mechanisms by influencing the activity of enzymes and receptors involved in modulating specific signal transduction and gene expression pathways. By protecting and preventing depletion of MUFA and PUFA it indirectly enables regulatory effects that are mediated by the numerous lipid mediators derived from these lipids. In recent years, some vitamin E metabolites have been observed to affect signal transduction and gene expression and their relevance for the regulatory function of vitamin E is beginning to be elucidated. In particular, the modulation of the CD36/FAT scavenger receptor/fatty acids transporter by vitamin E may influence many cellular signaling pathways relevant for lipid homeostasis, inflammation, survival/apoptosis, angiogenesis, tumorigenesis, neurodegeneration, and senescence. Thus, vitamin E has an important role in modulating signal transduction and gene expression pathways relevant for its uptake, distribution, metabolism, and molecular action that when impaired affect physiological and patho‐physiological cellular functions relevant for the prevention of a number of diseases. © 2018 IUBMB Life, 71(4):456–478, 2019
Waterlogging-induced adventitious root formation in cucumber is regulated by ethylene and auxin through reactive oxygen species signalling.

Development of adventitious roots (ARs) at the base of the shoot is an important adaptation of plants to waterlogging stress; however, its physiological mechanisms remain unclear. Here, we investigated the regulation of AR formation under waterlogged conditions by hormones and reactive oxygen species (ROS) in Cucumis sativus L. , an agriculturally and economically important crop in China. We found that ethylene, auxin, and ROS accumulated in the waterlogged cucumber plants. On the other hand, application of the ethylene receptor inhibitor 1-methylcyclopropene (1-MCP), the auxin transport inhibitor 1-naphthylphthalamic acid (NPA), or the NADPH oxidase inhibitor diphenyleneiodonium (DPI) decreased the number of ARs induced by waterlogging. Auxin enhanced the expression of ethylene biosynthesis genes, which led to ethylene entrapment in waterlogged plants. Both ethylene and auxin induced the generation of ROS. Auxin-induced AR formation was inhibited by 1-MCP, although ethylene-induced AR formation was not inhibited by NPA. Both ethylene- and auxin-induced AR formation were counteracted by DPI. These results indicate that auxin-induced AR formation is dependent on ethylene, whereas ethylene-induced AR formation is independent of auxin. They also show that ROS signals mediate both ethylene- and auxin-induced AR formation in cucumber plants.
Effects of the potassium‐sparing diuretic amiloride on chemotherapy response in canine osteosarcoma cells

Background Osteosarcoma (OSA) is a common bone tumor of mesenchymal origin in dogs. Chemotherapy delays metastasis, yet most dogs die of this disease within 1 year of diagnosis. The high metabolic demand of cancer cells promotes proton pump upregulation, leading to acidification of the tumor microenvironment and chemoresistance. The potassium‐sparing diuretic amiloride is among a class of proton pump inhibitors prescribed for refractory heart failure treatment in dogs. Objective We hypothesized that amiloride treatment improves chemotherapy response by reducing acidification in canine OSA cells. Our objective was to assess the in vitro effects of amiloride on cell viability, apoptosis, and metabolism. Methods In vitro study. Assessments of cell viability and apoptosis were performed after single agent or combination treatment, along with calculations of pharmacological synergism using the combination index. Protein signaling during apoptosis was evaluated by Western blotting. Metabolic profiling was performed using a Seahorse bioanalyzer. Results Amiloride strongly synergized with doxorubicin in combination treatment and exhibited additive or antagonistic effects with carboplatin in canine OSA cells. Combination treatment with doxorubicin significantly upregulated p53‐mitochondrial signaling to activate apoptosis and downregulate Akt phosphorylation. Amiloride‐treated cells further exhibited metabolic switching with reductions in glycolytic capacity and maximal respiration. Conclusion and Clinical Importance Amiloride synergized with doxorubicin to potentiate apoptosis in canine OSA cells. These results justify further investigation into repurposing of amiloride as an oncology drug for the treatment of OSA in dogs.
Rôle de la mise à jour égocentrée dans la mémoire épisodique

La memoire episodique lie differents elements dans un contexte spatial et temporel particulier. Il a ete propose que lors de la recuperation d‟un episode, la re-instanciation d‟une coherence entre les elements neocorticaux soit operee grâce a une representation spatiale allocentree stockee au niveau de la structure hippocampique (i.e., codage de la position des objets entre eux, independamment de la position de l‟individu, Burgess, Becker, King, & O'Keefe, 2001; Nadel & Moscovitch, 1998). Ce travail de these propose de traiter la memoire episodique et le sentiment de projection dans son passe (i.e., conscience autonoetique) comme une qualite attribuee a une dexterite relative dans le traitement spatial egocentre mis a jour (i.e., la position, orientation et le deplacement de son corps dans l‟environnement). Le role des traitements spatiaux allocentres et egocentres mis a jour dans la memoire episodique a ete evalue experimentalement. Les resultats suggerent l‟existence d‟un lien causal entre le traitement de la mise a jour egocentre et les performances de memoire episodique. De plus, les etudes ont mis en evidence l‟existence de specificites cerebrales et comportementales de la mise a jour egocentree confirmant l‟adequation de ce traitement au modele theorique propose. Par ailleurs, en reference a cette dissociation entre l‟information egocentree mis a jour et allocentree, des etudes neuropsychologiques ont revele la presence de deficits de la mise a jour egocentree, et d‟une preservation allocentree dans l‟amnesie bihippocampique qu‟elle soit acquise ou developpementale. Enfin, l‟evaluation des consequences cerebrales lors de la recuperation episodique d‟un encodage maximisant le traitement egocentre mis a jour a permis de reveler une implication specifique des structures temporo-parietales. Ce travail de these a ete organise autour d‟un modele theorique original du fonctionnement de la memoire episodique proposant de nouvelles predictions experimentales. Les approches comportementale, neuropsychologique et en imagerie fonctionnelle soulevent a leur tour de nouvelles pistes de recherche sur le lien entre conscience de son corps et memoire episodique.
In Fimo: A Term Proposed for Excrement Examined Experimentally.

exact and elegant expressions that have standard in the scientific community. of vitro” and vivo. ” we fimo” to samples derived from human and animal excrement and scientifically. The importance of material extracted from excrement for study has recently become clear We have proposed the “in fimo” terminology in a and have been using it in international presentations, and it has been met with much favor. Here we explain the interdisciplinary rationale for our choice.
Subconjunctival draining minimally-invasive glaucoma devices for medically uncontrolled glaucoma.

BACKGROUND Glaucoma is a leading cause of irreversible blindness. Subconjunctival draining minimally-invasive glaucoma devices such as the Xen gelatin implant and InnFocus stent have been introduced as a treatment to prevent glaucoma progressing.These implants provide a channel to allow aqueous humour from the anterior chamber of the eye to drain into the subconjunctival space on the surface of the eye thus reducing intraocular pressure (IOP) and mimicking the mechanism of the most commonly undertaken glaucoma surgery, trabeculectomy. OBJECTIVES To evaluate the efficacy and safety of subconjunctival draining minimally-invasive glaucoma devices in treating people with open angle glaucoma and ocular hypertension whose condition is inadequately controlled with drops. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2018, Issue 6); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 10 July 2018. SELECTION CRITERIA We searched for randomised controlled trials (RCTs) of Xen gelatin implant or InnFocus MicroShunt to other surgical treatments (other minimally-invasive glaucoma device techniques, trabeculectomy), laser treatment or medical treatment. We also planned to include trials where these devices were combined with phacoemulsification compared to phacoemulsification alone. DATA COLLECTION AND ANALYSIS We planned to have two review authors independently extract data from reports of included studies using a data collection form and analyse data based on methods expected by Cochrane. Our primary outcome was mean change in IOP. Secondary outcomes included proportion of participants who were drop-free; proportion of participants who achieved an IOP of 21 mmHg or less, 17 mmHg or less or 14 mmHg or less; and proportion of participants experiencing intra- and postoperative complications. We planned to measure all outcomes in the short-term (six to 18 months), medium-term (18 to 36 months), and long-term (36 months onwards). MAIN RESULTS We found no completed RCTs that met our inclusion criteria. We found one ongoing study (NCT01881425). The study compares InnFocus MicroShunt to trabeculectomy in people with primary open angle glaucoma. The primary outcome is greater than 20% IOP reduction from baseline to 12 months' follow-up. A total of 889 people aged between 40 and 85 years have been enrolled. The estimated study completion date is November 2019. AUTHORS' CONCLUSIONS There is currently no high-quality evidence for the effects of subconjunctival draining minimally-invasive glaucoma devices for medically uncontrolled open angle glaucoma. Properly designed RCTs are needed to assess the medium- and long-term efficacy and safety of this technique.
Long noncoding RNA MEG3 inhibits breast cancer growth via upregulating endoplasmic reticulum stress and activating NF‐κB and p53

Long noncoding RNA (lncRNA) maternally expressed 3 (MEG3) has been implicated as a tumor suppressor gene in several human cancer types. However, little is known regarding its involvement and potential mechanism in human breast cancer. In this study, we explored the effect of MEG3 on the growth of human breast cancer cell line MDA‐MB‐231 in vitro and in vivo, and sought to elucidate the potential signaling mechanisms. Ectopic overexpression of MEG3 using a lentiviral vector Lv‐MEG3 significantly inhibited breast cancer cell growth in vitro and a cancer xenograft growth in vivo. MEG3 overexpression led to marked increase of apoptosis in breast cancer cells as determined using flow cytometry and fragmented DNA labeling. Moreover, ectopic expression of MEG3 increased the expression of endoplasmic reticulum (ER) stress–related proteins required for unfolded protein response, including glucose‐regulated protein 78 (GRP78), inositol‐requiring enzyme 1 (IRE1), protein kinase RNA (PKR)‐like ER kinase (PERK), and activated transcription factor 6 (ATF6), as well as proapoptotic proteins CCAAT/enhancer binding protein homologous protein (CHOP) and caspase‐3. Finally, MEG3 overexpression markedly increased nuclear factor κB (NF‐κB) expression, NF‐κB translocation to the nucleus, and p53 expression, whereas pharmacological inhibition of NF‐κB completely abolished MEG3‐induced activation of p53. Together, these results suggest that MEG3 inhibits breast cancer growth and induces breast cancer apoptosis, partially via the activation of the ER stress, NF‐κB and p53 pathways, and that NF‐κB signaling is required for MEG3‐induced p53 activation in breast cancer cells. Our results indicate targeting lncRNA MEG3 may represent a novel strategy for breast cancer therapy.
Prevalence of recent fentanyl use among treated users of illicit opioids in England: based on piloted urine drug screens

Abstract Objective: To use a pilot of national fentanyl screening to establish the current prevalence of recent fentanyl use among treated users of illicit opioids in the English treatment system and inform the design of a full study. Design: Cross-sectional fentanyl metabolite urine screening in randomly-selected study sites, stratified to cover all nine geographical regions of England, supplemented with self-report subsequent to a positive fentanyl test. Patients: 468 adult (18 years of age and above) patients receiving treatment for opioid use disorder, screened December 2017 to May 2018. Results: The fentanyl-positive rate in patients receiving treatment for opioid use disorder in the English treatment system was 3% (15/468, 95% CI 1.8% to 5.2%) with a per-site range (for the 10 sites in 9 regions where fentanyl was detected) of between 2% (1/57) and 15% (4/27). Self-report data indicated that the majority of fentanyl-positives (12/15, 80%) was unaware of having purchased fentanyl. Conclusions: Despite alerts already in place, patients receiving treatment for opioid use disorder, who were fentanyl-positive, were unwittingly purchasing and consuming fentanyl.
Multicomponent structures in camouflage and mimicry in butterfly wing patterns

Understanding how morphological structures are built is essential for appreciating the morphological complexity and divergence of organisms. One representative case of morphological structures is the camouflage and mimicry of butterfly wing patterns. Some previous studies have questioned whether camouflage and mimicry are truly structures, considering that they rely on coloration. Nevertheless, our recent study revealed that the leaf pattern of Kallima inachus butterfly wings evolved through the combination of changes in several pigment components in a block‐wise manner; it remains unclear whether such block‐wise structures are common in other cases of camouflage and mimicry in butterflies and how they come about. Previous studies focused solely on a set of homologous components, termed the nymphalid ground plan. In the present study, we extended the scope of the description of components by including not only the nymphalid ground plan but also other common components (i.e., ripple patterns, dependent patterns, and color fields). This extension allowed us to analyze the combinatorial building logic of structures and examine multicomponent structures of camouflage and mimicry in butterfly wing patterns. We investigated various patterns of camouflage and mimicry (e.g., masquerade, crypsis, Müllerian mimicry, Batesian mimicry) in nine species and decomposed them into an assembly of multiple components. These structural component analyses suggested that camouflage and mimicry in butterfly wing patterns are built up by combining multiple types of components. We also investigated associations between components and the kinds of camouflage and mimicry. Several components are statistically more often used to produce specific types of camouflage or mimicry. Thus, our work provides empirical evidence that camouflage and mimicry patterns of butterfly wings are mosaic structures, opening up a new avenue of studying camouflage, and mimicry from a structural perspective.
Nucleosome Positioning by an Evolutionarily Conserved Chromatin Remodeler Prevents Aberrant DNA Methylation in Neurospora

In the filamentous fungus Neurospora crassa, constitutive heterochromatin is marked by tri-methylation of histone H3 lysine 9 (H3K9me3) and DNA methylation. We identified mutations in the Neurospora defective in methylation-1 (dim-1) gene that cause defects in cytosine methylation and implicate a putative AAA-ATPase chromatin remodeler. Although it was well-established that chromatin remodelers can affect transcription by influencing DNA accessibility with nucleosomes, little was known about the role of remodelers on chromatin that is normally not transcribed, including regions of constitutive heterochromatin. We found that dim-1 mutants display both reduced DNA methylation in heterochromatic regions as well as increased DNA methylation and H3K9me3 in some intergenic regions associated with highly expressed genes. Deletion of dim-1 leads to atypically spaced nucleosomes throughout the genome and numerous changes in gene expression. DIM-1 localizes to both heterochromatin and intergenic regions that become hyper-methylated in dim-1 strains. Our findings indicate that DIM-1 normally positions nucleosomes in both heterochromatin and euchromatin and that the standard arrangement and density of nucleosomes is required for the proper function of heterochromatin machinery.
Morphological variation and covariation in mandibular molars of platyrrhine primates

Molars are highly integrated biological structures that have been used for inferring evolutionary relationships among taxa. However, parallel and convergent morphological traits can be affected by developmental and functional constraints. Here, we analyze molar shapes of platyrrhines in order to explore if platyrrhine molar diversity reflects homogeneous patterns of molar variation and covariation. We digitized 30 landmarks on mandibular first and second molars of 418 extant and 11 fossil platyrrhine specimens to determine the degree of integration of both molars when treated as a single module. We combined morphological and phylogenetic data to investigate the phylogenetic signal and to visualize the history of molar shape changes. All platyrrhine taxa show a common shape pattern suggesting that a relatively low degree of phenotypic variation is caused by convergent evolution, although molar shape carries significant phylogenetic signal. Atelidae and Pitheciidae show high levels of integration with low variation between the two molars, whereas the Cebinae/Saimiriinae, and especially Callitrichinae, show greater variation between molars and trend toward a modular organization. We hypothesize that biomechanical constraints of the masticatory apparatus, and the dietary profile of each taxon are the main factors that determine high covariation in molars. In contrast, low molar shape covariation may result from the fact that each molar exhibits a distinct ecological signal, as molars can be exposed to distinct occlusal loadings during food processing, suggesting that different selective pressures on molars can reduce overall molar integration.