Miracle-dz/UniFAR-FTUs huggingface dataset:
Preimplantation development in ungulates: a "ménage à quatre" scenario.

In ungulates, early embryonic development differs dramatically from that of mice and humans and is characterized by an extended period of pre- and peri-implantation development in utero. After hatching from the zona pellucida, the ungulate blastocyst will stay free in the uterus for many days before implanting within the uterine wall. During this protracted peri-implantation period, an intimate dialogue between the embryo and the uterus is established through a complex series of paracrine signals. The blastocyst elongates, leading to extreme growth of extra-embryonic tissues, and at the same time, the inner cell mass moves up into the trophoblast and evolves into the embryonic disc, which is directly exposed to molecules present in the uterine fluids. In the peri-implantation period, uterine glands secrete a wide range of molecules, including enzymes, growth factors, adhesion proteins, cytokines, hormones, and nutrients like amino and fatty acids, which are collectively referred to as histotroph. The identification, role, and effects of these secretions on the biology of the conceptus are still being described; however, the studies that have been conducted to date have demonstrated that histotroph is essential for embryonic development and serves a critical function during the pre- and peri implantation periods. Here, we present an overview of current knowledge on the molecular dialogue among embryonic, extraembryonic, and maternal tissues prior to implantation. Taken together, the body of work described here demonstrates the extent to which this dialogue enables the coordination of the development of the conceptus with respect to the establishment of embryonic and extra-embryonic tissues as well as in preparation for implantation.
Return home after dysvascular major amputation of the lower limb: A multicentre observational study in the Netherlands.

OBJECTIVE To report the rates of persons returning home within one year following dysvascular major amputation of the lower limb in the Netherlands, and to identify factors associated with returning home directly after hospital admission and after discharge to care facilities. DESIGN Retrospective cohort study. PATIENTS Dysvascular major amputation of the lower limb, n = 382, mean age 71.9 years (standard deviation (SD) 12.5 years), 65% male. METHODS Medical records of all persons undergoing major amputation of the lower limb in 2012-2013 in 12 hospitals in Northern Netherlands were reviewed. Odds ratios (OR) were calculated using multivariate logistic regression. RESULTS Among persons admitted from home and surviving the hospital admission, 21% returned home, with higher odds of returning home being associated with living with a partner (OR = 2.8, p = 0.006) and younger age (< 65 years). Among those discharged to care and surviving the first year, 77% returned home within one year after amputation, with higher odds being associated with younger age (<75 years) and admission to inpatient rehabilitation (OR = 10.6, p = 0.004) or geriatric rehabilitation in skilled nursing facilities (OR = 3.5, p = 0.030). CONCLUSION Four out of 5 persons surviving dysvascular major amputation of the lower limb return home within one year, although a majority requires care in either inpatient rehabilitation or a skilled nursing facilities setting.
Help or Hindrance? The Alcohol Industry and Alcohol Control in Portugal

The influence of the alcohol industry, also known as “corporate political activity” (CPA), is documented as one of the main barriers in implementing effective alcohol control policies. In Portugal, despite an alcohol consumption above the European average, alcohol control does not feature in the current National Health Plan. The present research aimed to identify and describe the CPA of the alcohol industry in Portugal. Publicly-available data published between January 2018 and April 2019 was extracted from the main websites and social media accounts of alcohol industry trade associations, charities funded by the industry, government, and media. A “Policy Dystopia” framework, used to describe the CPA strategies of the tobacco industry, was adapted and used to perform a qualitative thematic analysis. Both instrumental and discursive strategies were found. The industry works in partnership with health authorities, belonging to the national task force responsible for planning alcohol control policies. Additionally, it emphasizes the role alcohol plays in Portuguese culture as a way to disregard evidence on control policies from other countries. This paper presents the first description of CPA by the alcohol industry in Portugal and provides evidence for the adoption of stricter control policies in the country.
Thermal impact of balloon occlusion of the coronary sinus during mitral isthmus radiofrequency ablation: an in-silico study

Abstract Purpose: Although experimental data have suggested that temporary occlusion of the coronary sinus (CS) can facilitate the creation of transmural lesions across the atrial wall (AW) during mitral isthmus radiofrequency (RF) ablation, no computer modeling study has yet been made on the effect of the blood flow inside the epicardial vessels and its stoppage by an occlusion balloon. Methods: Computer simulations using constant power were conducted to study these phenomena by two methods: (1) by setting blood velocity in the CS to zero, which mimics a distal occlusion; and (2) by including a balloon filled with air in the model just below the ablation site, which mimics a proximal occlusion. Results: For short ablations (15 s) and perpendicular electrode/tissue orientation, lesion size was smaller with proximal occlusion compared to distal or no occlusion, regardless of the AW-CS distance (from 0.5 mm to 3.4 mm). For other angulations (0 and 45°) lesion size was almost the same in all cases. For longer ablations (60 s), the internal CS blood flow (no occlusion) considerably reduced lesion size, while stoppage combined with the proximal presence of a balloon produced the largest lesions. This performance was similar for different catheter angulations (0, 45 and 90°). Balloon length (from 10 to 40 mm) was found to be an irrelevant parameter when proximal occlusion was modeled. Conclusions: Using an air-filled balloon to occlude CS facilitates mitral isthmus ablation in long ablations, while proximal occlusion could impede transmural lesions in the case of short ablations (15 s).
A Quadrupolar Bis-Triarylborane Chromophore as a Fluorimetric and Chirooptic Probe for Simultaneous and Selective Sensing of DNA, RNA and Proteins.

Invited for the cover of this issue are the groups of Todd B. Marder at the Julius-Maximilians-Universität Würzburg and Ivo Piantanida at the Ruder Boškovic Institute. The image depicts the molecular structure of a bis-triarylborane-based chromophore that is simultaneously detecting ds-DNA and proteins. Read the full text of the article at 10.1002/chem.201903936.
Allergic and Mixed Rhinitis: Diagnosis and Natural Evolution

Chronic rhinitis (CR) is divided into two main categories: allergic rhinitis (AR) and nonallergic rhinitis (NAR). These conditions are more recognizable to an experienced clinician, as they can be more clearly demarcated diagnostically. However, an additional 30% to 50% of patients with CR might have an overlap of NAR and AR, referred to as mixed rhinitis (MR). Progress in elucidating the pathophysiologic mechanisms behind MR and NAR has been made in the past several years, and there are now several guidelines published to assist the clinician in accurately diagnosing AR, NAR, and MR. Clinical history and subjective symptoms can provide clues for differentiating AR from MR and NAR, but allergy testing is recommended to confirm these conditions. Progress in accurately diagnosing patients with CR will be made as studies incorporate subjective (i.e., validated questionnaires such as the irritant index questionnaire (IIQ), medication responsiveness, and quality-of-life tools) and objective (i.e., nasal cytologic testing, nasal provocation, and biomarkers) methods characterizing rhinitis subtypes.
Repeated Fractions of X-Radiation to the Breast Fat Pads of Mice Augment Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle

Breast cancer patients are usually treated with multiple fractions of radiotherapy (RT) to the whole breast after lumpectomy. We hypothesized that repeated fractions of RT would progressively activate the autotaxin–lysophosphatidate-inflammatory cycle. To test this, a normal breast fat pad and a fat pad containing a mouse 4T1 tumor were irradiated with X-rays using a small-animal “image-guided” RT platform. A single RT dose of 7.5 Gy and three daily doses of 7.5 Gy increased ATX activity and decreased plasma adiponectin concentrations. The concentrations of IL-6 and TNFα in plasma and of VEGF, G-CSF, CCL11 and CXCL10 in the irradiated fat pad were increased, but only after three fractions of RT. In 4T1 breast tumor-bearing mice, three fractions of 7.5 Gy augmented tumor-induced increases in plasma ATX activity and decreased adiponectin levels in the tumor-associated mammary fat pad. There were also increased expressions of multiple inflammatory mediators in the tumor-associated mammary fat pad and in tumors, which was accompanied by increased infiltration of CD45+ leukocytes into tumor-associated adipose tissue. This work provides novel evidence that increased ATX production is an early response to RT and that repeated fractions of RT activate the autotaxin–lysophosphatidate-inflammatory cycle. This wound healing response to RT-induced damage could decrease the efficacy of further fractions of RT.
Croton hirtus L'Hér Extract Prevents Inflammation in RAW264.7 Macrophages Via Inhibition of NF-κB Signaling Pathway

Consumption of anti-inflammatory nutraceuticals may help treat or prevent inflammation-related illnesses such as diabetes, cardiovascular disease, and cancer. This study evaluated the effect of Croton hirtus L'Hér extract (CHE) on lipopolysaccharide (LPS)-induced nitric oxide (NO) production and nuclear factor kappa-B (NF-κB) signaling cascades. CHE significantly suppressed LPS-induced NO production and inducible nitric oxide synthase (iNOS) expression in RAW264.7 macrophages, although cyclooxygenase (COX)-2 expression was not affected. CHE also suppressed LPS-induced IκB kinase (IKK), IκB, and p65 phosphorylation in RAW264.7 cells. Western blot and immunofluorescence assays of cytosol and nuclear p65 and the catalytic subunit of NF-κB showed that CHE suppressed LPS-induced p65 translocation from the cytosol to the nucleus. CHE also suppressed LPS-induced Interleukin (IL)-6 and tumor necrosis factor (TNF)-α production in RAW264.7 cells. These results suggest that CHE prevents NO-mediated inflammation by suppressing NF-κB and inflammatory cytokines.
Serum metabolomics reveals personalized metabolic patterns for macular neovascular patient stratification.

Macular neovascular disease is a group disorder with complex pathogenesis of neovascularization for vision impairment and irreversible blindness, posing great challenges to precise diagnosis and management. We prospectively recruited participants with age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV) and pathological myopia (PM), compared with cataract patients without fundus diseases as control group. The serum metabolome was profiled by gas chromatography coupled with time-of-flight mass spectrometry (GC-TOFMS) analysis. Multivariate statistical methods as well as data mining were performed for interpretation of macular neovascularization. A total of 446 participants with macular neovascularization and 138 cataract subjects as control group were enrolled in this study. By employing GC-TOFMS, 131 metabolites were identified and 33 differentiating metabolites were highlighted in patients with macular neovascularization. For differential diagnosis, 3 panels of specific metabolomics-based biomarkers provided areas under the curve of 0.967, 0.938 and 0.877 in the discovery phase (n= 328), predictive values of 87.3%, 79% and 85.7% in the test phase (n= 256). Personalized pathway dysregulation scores measurement using lilikoi package in R language revealed pentose phosphate pathway and mitochondrial electron transport chain as the most important pathways in AMD; purine metabolism and glycolysis were identified as the major disturbed pathways in PCV while the altered thiamine metabolism and purine metabolism may contribute to PM phenotypes. Serum metabolomics are powerful for characterizing metabolic disturbances of macular neovascular. Differences in metabolic pathways may reflect underlying macular neovascularand serve as therapeutic targets for macular neovascular treatment.
Health Literacy and Medication Adherence in COPD Patients: When Caregiver Presence Is Not Sufficient

Abstract Limited health literacy (HL) is associated with a lower medication adherence in patients with chronic obstructive pulmonary disease (COPD). In this study, we examined the potential mitigating role of caregiver support on the relationship between HL and adherence to COPD medications. We conducted a prospective observational study of adults with COPD and their caregivers. HL was assessed using the Short Test of Functional Health Literacy in Adults (S-TOFHLA) and COPD medication adherence was evaluated with the Medication Adherence Rating Scale (MARS). We also collected caregiver HL data for a subset of participants. We tested whether having a caregiver impacted the relationship between HL and medication adherence using cross-sectional data collected between 2011 and 2015. Our sample included 388 COPD patients and 97 caregivers. COPD patients with low HL had a lower medication adherence (odds ratio [OR]: 0.44, 95% confidence interval [CI]: 0.24–0.81) after adjusting for sociodemographic factors. Caregiver presence was not associated with increased patient medication adherence (OR: 1.28, 95% CI: 0.79–2.08). Among the subset of patients with caregivers, low patient HL remained associated with a lower medication adherence (OR: 0.28, 95% CI: 0.09–0.82) when adjusted for caregiver HL and sociodemographic factors. Low HL is associated with lower COPD medication adherence, and this effect is not mitigated by the presence of a caregiver. These findings suggest a need for effective strategies to manage high-risk COPD patients with low HL, even among those with adequate support from caregivers, and to design interventions for both patients and caregivers with low HL.
Co-occurrence of Plasmid-Mediated Colistin Resistance (mcr-1) and Extended-Spectrum β-Lactamase Encoding Genes in Escherichia coli from Bovine Mastitic Milk in China.

Both mcr-1 phosphoethanolamine transferase enzymes and extended-spectrum β-lactamases (ESBLs) are the main plasmid-mediated mechanisms of resistance to colistin and third-generation cephalosporins, respectively, and currently considered a major concern to humans and food animals. Prevalence of mcr-1 gene in Escherichia coli from dairy cattle has rarely been reported. Our objective was to determine prevalence and characteristics of mcr-1 carrying E. coli isolated from clinical mastitis cases in large dairy farms (>500 cows) in 16 provinces of China. A total of 249 E. coli was isolated from 2,038 mastitic milk samples. Among these isolates, 2.0% (n = 5) and 19.7% (n = 49) were colistin resistant mcr-1-positive and ESBL-producing isolates, respectively. All mcr-1-positive isolates that produced ESBLs also carried the blaCTX-M-15 gene and belonged to phylogroup-A. Most mcr-1 and blaCTX-M-15 genes were located on conjugative plasmids (IncP and IncF, respectively) that were successfully transferred to transconjugants in conjugation experiments. All mcr-1-positive E. coli isolates were multidrug resistant, exhibiting resistance to common antimicrobials. Multilocus sequence typing of these mcr-1-carrying E. coli isolates revealed four sequence types, reflecting substantial diversity. Multilocus sequence analysis detected evolutionary connection of mcr-1 carrying isolates with our recently reported ESBL-producing E. coli isolates, raising concerns regarding fast dissemination between bacteria. To our knowledge, this was the first nation-wide report describing isolates of E. coli from mastitic milk samples collected on large dairy farms in China, carrying mcr-1 and blaCTX-M-15 genes on conjugative plasmids. We concluded that dairy cattle are a potential source of mcr-1-carrying and ESBL-producing E. coli.
A mixed-methods study of psychological distress following an environmental catastrophe: the case of the Hazelwood open-cut coalmine fire in Australia

ABSTRACT Background and Objectives: This study assessed the psychological impacts of six weeks of smoke exposure from the 2014 Hazelwood open-cut coalmine fire in the Latrobe Valley, Victoria, Australia, between two and three years after the incident. Design and Methods: A cross-sectional survey of adults investigated outcomes for the most exposed community, Morwell (n = 3091), compared with a similar, but minimally exposed community, Sale (n = 960). Adopting a mixed-methods research approach, 26 interviews with Morwell residents further examined qualities of the experience. Results: Morwell residents scored significantly higher on the Impact of Event Scale – Revised (difference = 6.53; 95%CI: 5.37, 7.35, p < 0.001) and Kessler 10-item general distress scale (difference = 1.69; 95%CI: 1.05, 2.33, p < 0.001). More than two years after the mine fire, Morwell residents reported moderate levels of distress related to the incident. This impact was also evident in interviews, where intrusive thoughts were the most frequently reported symptom of posttraumatic stress. Furthermore, interviews highlighted the vulnerability of people with pre-existing mental health concerns. Conclusions: The elevated psychological distress apparent within the Morwell community over two years after an extended pollution event highlights the need to improve post-incident recovery responses to such events, particularly for supporting residents that are more vulnerable.
Com1 as a Promising Protein for the Differential Diagnosis of the Two Forms of Q Fever

Coxiella burnetii is the causative agent of acute and chronic Q fever in humans. Although the isolates studied so far showed a difference in virulence potential between those causing the two forms of the disease, implying a difference in their proteomic profile, the methods used so far to diagnose the two forms of the disease do not provide sufficient discriminatory capability, and human infections may be often misdiagnosed. The aim of the current study was to identify the outer membrane Com1 (CBU_1910) as a candidate protein for serodiagnostics of Q fever. The protein was cloned, expressed, purified, and used as an antigen in ELISA. The protein was then used for the screening of sera from patients suffering from chronic Q fever endocarditis, patients whose samples were negative for phase I immunoglobulin G (IgG), patients for whom at least one sample was positive for phase I IgG, and patients suffering from any kind of rheumatoid disease. Blood donors were used as the control group. Following statistical analysis, 92.4% (122/132) of the samples tested agreed with the negative clinical diagnosis, and 72.2% (26/36) agreed with the positive clinical diagnosis. Moreover, a significant correlation to the presence of the disease (p = 0.00) was calculated. The results support the idea that a Com1 antigen-based serodiagnostic test may be useful for differential diagnosis of chronic Q fever. Further studies are required to compare more immunogenic proteins of the bacterium against samples originating from patients suffering from different forms of the disease.
Calcium Polyphosphate Nanoparticles Act as an Effective Inorganic Phosphate Source during Osteogenic Differentiation of Human Mesenchymal Stem Cells

The ability of bone-marrow-derived mesenchymal stem/stromal cells (BM-MSCs) to differentiate into osteoblasts makes them the ideal candidate for cell-based therapies targeting bone-diseases. Polyphosphate (polyP) is increasingly being studied as a potential inorganic source of phosphate for extracellular matrix mineralisation. The aim of this study is to investigate whether polyP can effectively be used as a phosphate source during the in vitro osteogenic differentiation of human BM-MSCs. Human BM-MSCs are cultivated under osteogenic conditions for 28 days with phosphate provided in the form of organic β-glycerolphosphate (BGP) or calcium-polyP nanoparticles (polyP-NP). Mineralisation is demonstrated using Alizarin red staining, cellular ATP content, and free phosphate levels are measured in both the cells and the medium. The effects of BGP or polyP-NP on alkaline phosphatase (ALP) activity and gene expression of a range of osteogenic-related markers are also assessed. PolyP-NP supplementation displays comparable effects to the classical BGP-containing osteogenic media in terms of mineralisation, ALP activity and expression of osteogenesis-associated genes. This study shows that polyP-NP act as an effective source of phosphate during mineralisation of BM-MSC. These results open new possibilities with BM-MSC-based approaches for bone repair to be achieved through doping of conventional biomaterials with polyP-NP.
KCNQ1OT1 promotes migration and inhibits apoptosis by modulating miR‐185‐5p/Rab14 axis in oral squamous cell carcinoma

Long non‐coding RNAs (lncRNAs) play essential roles in the regulation of gene transcription in carcinogenesis and metastasis via interacting with microRNA. In this study, we explored the expressions and functions of lncRNA KCNQ1OT1 and miR‐185‐5p in oral squamous cell carcinoma (OSCC) cells. KCNQ1OT1 expression in OSCC tissues and cells was examined by qRT‐PCR. Small interfering RNAs against KCNQ1OT1 (si‐ KCNQ1OT1) were used to knockdown KCNQ1OT1 in OSCC cells. Cell function was assessed by wound healing assay, transwell assay, and apoptosis detection. The binding region between KCNQ1OT1 and miR‐185‐5p was confirmed by luciferase assays. MiR‐185‐5p expression was measured by qRT‐PCR. Rab14 was confirmed as a downstream target gene of miR‐185‐5p by measuring luciferase activities. The protein level of Rab14 in OSCC cells transfected with miR‐185‐5p or si‐KCNQ1OT1 was determined by Western blot. The OSCC cell function and Rab14 expression after co‐transfection of si‐KCNQ1OT1 and miR‐185‐5p inhibitor were also examined. KCNQ1OT1 was upregulated in OSCC tissues and cells. KCNQ1OT1 silencing suppressed OSCC cell malignancy and downregulated miR‐185‐5p level, which showed upregulated expression in OSCC samples. Rab14 as a target gene of miR‐185‐5p was highly expressed in OSCC. KCNQ1OT1 knockdown impaired the invasion capability of OSCC cells, promoted apoptosis, and suppressed Rab14 expression. The inhibition of miR‐185‐5p in KCNQ1OT1 silencing cells reversed the suppression of Rab14 and restored the cancerous growth of OSCC cells. These results indicated that KCNQ1OT1 promoted OSCC tumorigenesis via the modulation of miR‐185‐5p/Rab14 axis, which may serve as a therapeutic target for the treatment of OSCC.