Miracle-dz/UniFAR-FTUs huggingface dataset:
Long noncoding RNA PART1 promotes progression of non‐small cell lung cancer cells via JAK‐STAT signaling pathway

Non‐small cell lung cancer (NSCLC), the major type of lung cancer, becomes the greatest threat to the life of people. Growing evidence shows prostate androgen‐regulated transcript 1 (PART1) is considered as effective markers for prostate cancer, and has been shown to be associated with poor prognosis of NSCLC. However, the tumorigenic mechanism of PART1 in NSCLC remains to be investigated. In this study, we found that the expression of PART1 was robustly induced in NSCLC tissues and cell lines. Functional studies established that overexpression of PART1 could promote NSCLC cell proliferation, migration, and invasion, while interference of PART1 inhibited NSCLC progression. Our results also identified miR‐635 as a novel target of PART1, whose expression was inhibited by PART1 in NSCLC cell lines. Moreover, gain‐ and loss‐of‐function studies revealed that PART1 could sponge miR‐635 and increase the expression of Janus kinase (JAK) and signal transducer and activator of transcription proteins (STATs). Finally, we deciphered the molecular mechanism by which PART1 contributed to promotion of NSCLC cell progression via phosphorylation and activation of JAK‐STAT signaling pathway. The animal experiment further confirmed that interference of NSCLC could suppress in vivo tumorigenic ability of NSCLC with favorable pharmacological activity via inactivation of JAK‐STAT signaling pathway. In conclusion, our findings clarified the biologic significance of PART1/miR‐635/JAK‐STAT axis in NSCLC progression and provided novel evidence that PART1 may be a new potential therapeutic target for the treatment of NSCLC.
Peptide Antagonists for P-selectin Discriminate between Sulfatide-Dependent Platelet Aggregation and PSGL-1-Mediated Cell Adhesion

Background: Membrane-exposed sulfatides are proposed to contribute to P-selectin-dependent platelet aggregation. Here, we demonstrated that P-selectin-mediated platelet aggregation on a collagen-coated surface under flow indeed depended on sulfatides and that this interaction differed considerably from the interaction of P-selectin with P-selectin Glycoprotein Ligand-1 (PSGL-1), which underlies leukocyte-endothelium adhesion. Methods and Results: Upon platelet activation, sulfatides were translocated to the platelet surface to form focal hot-spots. Interestingly, P-selectin was observed to exclusively interact with liposomes with a sulfatide density higher than 21% (w/w), indicating that the binding profile of P-selectin for sulfatide-rich liposomes was dependent on sulfatide density. Sulfatide-liposome binding to P-selectin and sulfatide/P-selectin-dependent platelet aggregation was blunted by peptide antagonists, carrying the EWVDV motif within N-terminal extensions, such as CDVEWVDVSC (half maximal inhibitory concentration IC50 = 0.2 μM), but not by the EWVDV core motif itself (IC50 > 1000 μM), albeit both being equally potent inhibitors of PSGL-1/P-selectin interaction (IC50= 7–12 μM). Conclusions: Our data suggest that the sulfatide/P-selectin interaction implicates multiple binding pockets, which only partly overlap with that of PSGL-1. These observations open ways to selectively interfere with sulfatide/P-selectin-dependent platelet aggregation without affecting PSGL-1-dependent cell adhesion.
Negative regulators of plant immunity derived from cinnamyl alcohol dehydrogenases are targeted by multiple Phytophthora Avr3a-like effectors.

Oomycete pathogens secrete numerous effectors to manipulate host immunity. While some effectors share a conserved structural fold, it remains unclear if any have conserved host targets. Avr3a-like family effectors, which are related to Phytophthora infestans effector PiAvr3a and widely distributed across diverse clades of Phytophthora species, were employed to study this question. By using yeast-two-hybrid, bimolecular fluorescence complementation, and co-immunoprecipitation assays, we identified members of the plant cinnamyl alcohol dehydrogenase 7 (CAD7) subfamily as targets of multiple Avr3a-like effectors from Phytophthora pathogens. The CAD7 subfamily has expanded in plant genomes but lost the lignin biosynthetic activity of canonical CAD subfamilies. In turn, we identified CAD7s as negative regulators of plant immunity that are induced by Phytophthora infection. Moreover, AtCAD7 was stabilized by Avr3a-like effectors and involved in suppression of pathogen-associated molecular pattern -triggered immunity, including callose deposition, ROS burst, and WRKY33 expression. Our results reveal CAD7 subfamily proteins as negative regulators of plant immunity that are exploited by multiple Avr3a-like effectors to promote infection in different host plants. This article is protected by copyright. All rights reserved.
Application and Optimization of Wavelet Transform Filter for North-Seeking Gyroscope Sensor Exposed to Vibration

Conventional wavelet transform (WT) filters have less effect on de-noising and correction of a north-seeking gyroscope sensor exposed to vibration, since the optimal wavelet decomposed level for de-noising is difficult to determine. To solve this problem, this paper proposes an optimized WT filter which is suited to the magnetic levitation gyroscope (GAT). The proposed method was tested on an equivalent mock-up network of the tunnels associated with the Hong Kong‒Zhuhai‒Macau Bridge. The gyro-observed signals exposed to vibration were collected in our experiment, and the empirical values of the optimal wavelet decomposed levels (from 6 to 10) for observed signals were constrained and validated by the high-precision Global Navigation Satellite System (GNSS) network. The result shows that the lateral breakthrough error of the tunnel was reduced from 12.1 to 3.8 mm with a ratio of 68.7%, which suggests that the method is able to correct the abnormal signal of a north-seeking gyroscope sensor exposed to vibration.
Occipital and Cerebellar Theta Burst Stimulation for Mal De Debarquement Syndrome.

BACKGROUND Individuals with Mal de Debarquement syndrome (MdDS) experience persistent oscillating vertigo lasting for months or years. Transcranial magnetic stimulation (TMS) can modulate the motion perception of MdDS. MATERIALS AND METHODS Twenty-six TMS naive individuals received single administrations of continuous theta burst stimulation (cTBS) over the occipital cortex, cerebellar vermis, and lateral cerebellar hemisphere, in randomized order. A 0-100 point Visual Analogue Scale was used to assess acute changes in oscillating vertigo severity after each session. Repeated treatments were given over the target that led to the most acute reduction in symptoms. All treatments were performed with neuronavigation using the participant's own brain MRI. The Dizziness Handicap Inventory (DHI), MdDS Balance Rating Scale (MBRS), and Hospital Anxiety and Depression Scale (HADS) were assessed weekly at four pretreatment and six posttreatment time points. RESULTS Twenty participants chose either the occipital cortex (11) or cerebellar vermis (9) targets as most effective in reducing the oscillating vertigo; one chose lateral cerebellar hemisphere; five chose none. After 10 to 12 sessions of 1,200 pulses over the target of choice, 19 of 25 treatment completers noted ≥ 25% reduction, 12 of 25 ≥50% reduction, and 8 of 25 ≥75% reduction in oscillating vertigo intensity. A one-way repeated measures ANOVA of DHI, MBRS, and HADS scores before and after treatment showed significant reductions in DHI, MBRS, and the HADS Anxiety subscore immediately after treatment with most improvement lasting through posttreatment week 6. There were no significant Depression subscore changes. Participants who had chosen vermis stimulation had comparatively worse balance at baseline than those who had chosen occipital cortex stimulation. CONCLUSION cTBS over either the occipital cortex or cerebellar vermis is effective in reducing the oscillating vertigo of MdDS acutely and may confer long-term benefits. Sustained improvement requires more frequent treatments.
Protocol of a prospective, monocentric phase I/II feasibility study investigating the safety of multimodality treatment with a combination of intraoperative chemotherapy and surgical resection in locally confined or borderline resectable pancreatic cancer: the combiCaRe study

Introduction Pancreatic cancer is a devastating disease with an exceptionally poor prognosis. Complete resection of the primary tumour followed by adjuvant chemotherapy is the current standard treatment for patients with resectable disease and the only curative treatment option. However, long-term survival remains rare. Tumour cell dissemination due to manipulation during surgery may increase the rate of future metastases and local recurrence, and perioperative chemotherapy might diminish local, distant and circulating minimal residual disease. Yet, safety and feasibility of systemic chemotherapeutic treatments during pancreatic cancer resection have to be evaluated in a first instance. Methods and analysis This is a prospective, single-centre phase I/II feasibility study to investigate the safety and tolerability of a combination of intraoperative chemotherapy and surgical resection in pancreatic cancer. Forty patients with locally confined or borderline resectable pancreatic cancer, meeting all proposed criteria will be included. Participants will receive 400 mg/m2 calcium folinate over 2 hours and 2000 mg/m2 5-fluorouracil over 48 hours, started on the day before pancreatic surgery and thus continuing during surgery. Participants will be followed until 60 days after surgery. The primary endpoint is the 30-day overall complication rate according to the Clavien-Dindo classification. Secondary endpoints comprise toxicity and treatment associated complications. Patients receiving perioperative chemotherapy will be compared with a propensity score matched contemporary control group of 70 patients with pancreatic cancer receiving the standard treatment. This trial also contains an ancillary translational study to analyse disseminated tumour cells and effects of pharmacological interventions in pancreatic cancer. Ethics and dissemination CombiCaRe has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4042787) and the Medical Ethics Committee of Heidelberg University (reference number AFmo-269/2018). The results of this trial will be presented at national and international conferences and published in peer-reviewed journals. Trial registration number German Clinical Trials Register (DRKS00015766).
Membrane attack complex (C5b‐9 complex or Mac), is strongly present in lesional skin from patients with endemic pemphigus foliaceus in El Bagre, Colombia

El Bagre endemic pemphigus foliaceus (El Bagre‐EPF) is a new variant of endemic pemphigus foliaceus present in the El Bagre area of Colombia, South America. Here, we investigate the presence of complement/C5‐b9 in lesional skin of patients and matched controls from the endemic area. We also aim to compare the patient's autoantibody levels using indirect immunofluorescent titers (IIF) and correlate with the lesional presence of complement/C5b‐9.
Long-Lasting Input-Specific Experience-Dependent Changes of Hippocampus Synaptic Function Measured in the Anesthetized Rat

Abstract How experience causes long-lasting changes in the brain is a central question in neuroscience. The common view is that synaptic function is altered by experience to change brain circuit functions that underlie conditioned behavior. We examined hippocampus synaptic circuit function in vivo, in three groups of animals, to assess the impact of experience on hippocampus function in rats. The “conditioned” group acquired a shock-conditioned place response during a cognitively-challenging, hippocampus synaptic plasticity-dependent task. The no-shock group had similar exposure to the environmental conditions but no conditioning. The home-cage group was experimentally naive. After the one-week retention test, under anesthesia, we stimulated the perforant path inputs to CA1, which terminate in stratum lacunosum moleculare (slm), and to the dentate gyrus (DG), which terminate in the molecular layer. We find synaptic compartment specific changes that differ amongst the groups. The evoked field EPSP (fEPSP) and pre-spike field response are enhanced only at the DG input layer and only in conditioned animals. The DG responses, measured by the population spiking activity and post-spike responses, are enhanced in both the conditioned and no-shock groups compared to home-cage animals. These changes are pathway specific because no differences are observed in slm of CA1. These findings demonstrate long-term, experience-dependent, pathway-specific alterations to synaptic circuit function of the hippocampus.
Meeting Farmers Where They Are – Rural Clinicians’ Views on Farmers’ Mental Health

ABSTRACT Objective: To explore rural clinicians’ understanding of farmers’ mental health and well-being, current health services, and potential responses. Methods: Qualitative design, with semi-structured, taped interviews of five family physicians and four mental health nurses-counselors practicing in rural Grey–Bruce counties, Ontario. Transcripts analyzed with N-Vivo through iterative coding of emergent themes and mapping of relationships among themes. Results: Participating rural clinicians all expressed admiration for farmers. They shared insights around three main themes: 1) farming as a unique subculture; 2) farming involved both benefits and challenges for health; and 3) farmers rarely seek care. Clinicians need to take advantage of contact opportunities to ask about mental health. Several suggested ways to meet farmers where they are, e.g., through better funding for house-farm calls and community events. Conclusion: Clinician responses to farmers’ mental health challenges include recognizing farmers’ distinct context. Complementary health promotion in conjunction with farm organizations is needed to reach farmers.
Effectiveness and Safety of Ankle Arthrodesis Versus Arthroplasty: A Prospective Multicenter Study.

BACKGROUND Newer designs and techniques of total ankle arthroplasty (TAA) have challenged the assumption of ankle arthrodesis (AA) as the primary treatment for end-stage ankle arthritis. The objective of this study was to compare physical and mental function, ankle-specific function, pain intensity, and rates of revision surgery and minor complications between these 2 procedures and to explore heterogeneous treatment effects due to age, body mass index (BMI), patient sex, comorbidities, and employment on patients treated by 1 of these 2 methods. METHODS This was a multisite prospective cohort study comparing outcomes of surgical treatment of ankle arthritis. Subjects who presented after nonoperative management had failed received either TAA or AA using standard-of-treatment care and rehabilitation. Outcomes included the Foot and Ankle Ability Measure (FAAM), Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS) scores, pain, ankle-related adverse events, and treatment success. RESULTS Five hundred and seventeen participants underwent surgery and completed a baseline assessment. At 24 months, the mean improvement in FAAM activities of daily living (ADL) and SF-36 PCS scores was significantly greater in the TAA group than in the AA group, with a difference between groups of 9 points (95% confidence interval [CI] = 3, 15) and 4 points (95% CI = 1, 7), respectively. The crude incidence risks of revision surgery and complications were greater in the AA group; however, these differences were no longer significant after adjusting for age, sex, BMI, and Functional Comorbidity Index (FCI). The treatment success rate was greater after TAA than after AA for those with an FCI of 4 (80% versus 62%) and not fully employed (81% versus 58%) but similar for those with an FCI score of 2 (81% versus 77%) and full-time employment (79% versus 78%). CONCLUSIONS At 2-year follow-up, both AA and TAA were effective. Improvement in several patient-reported outcomes was greater after TAA than after AA, without a significant difference in the rates of revision surgery and complications. LEVEL OF EVIDENCE Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Incorporating Prescription Drug Utilization Information Into the Marketplace Risk Adjustment Model Improves Payment Accuracy and Reduces Adverse Selection Incentives

Beginning with the 2018 benefit year, the Centers for Medicare and Medicaid Services started incorporating select prescription drug utilization information into the Marketplace risk adjustment model. There has been little evidence about the impact of this change on payment accuracy and the mechanisms through which it may occur. Using commercial claims in 2017 from a large national health insurer, we find that the policy change improves payment accuracy in our sample and would help mitigate insurers’ selection incentives for some enrollees through two channels: imputing missing diagnoses and varying risk scores to better capture the heterogeneity in expenditures among patients with certain health conditions. However, while improving payment accuracy overall, there are potential perverse incentives that could distort treatment choice for marginal patients. Additionally, overcompensation and undercompensation persists for certain patient subgroups, suggesting an opportunity to further refine and improve the model.
Cost‐benefit analysis of implementing a pediatric early warning system at a pediatric oncology hospital in a low‐middle income country

Hospitalized pediatric oncology patients are at high risk of clinical decline and mortality, particularly in low‐income and middle‐income countries (LMICs). Pediatric early warning systems (PEWS) assist with the early identification of deterioration. To the authors' knowledge, no studies to date have evaluated the cost‐benefit of PEWS in LMICs.
Crystal structure of 1,1,5,5-tetramethyl-1,2,5,6-tetrahydro-3a,4,7a,8-tetraaza- s-indacene-3,7-dione, C12H16N4O2

Abstract C12H16N4O2, monoclinic, P121/c1 (No. 14), a = 9.306(2) Å, b = 5.755(1) Å, c = 11.499(2) Å, β = 98.15(3)°, V = 609.6 Å3, Z = 2, Rgt(F) = 0.045, wRref(F2) = 0.075, T = 294 K.
The RNA demethylase FTO is required for maintenance of bone mass and functions to protect osteoblasts from genotoxic damage

Significance Like other complex disorders, such as diabetes and obesity, osteoporosis is strongly influenced by genetic factors. In this study, we explored the function of the fat mass and obesity-associated gene (FTO), an RNA demethyase that has been strongly linked by genome-wide association studies to obesity and bone density. We show that loss of Fto in mouse osteoblasts leads to age-related bone loss with increased susceptibility of osteoblasts to cell death. RNA profiling of osteoblasts lacking Fto prioritized FTO targets that are members of the DNA repair pathway, which are activated in response to genotoxic stimuli. Our results identify an epigenetic pathway in which FTO normally functions in bone to enhance the stability of mRNA-encoding proteins that protect osteoblasts from genotoxic damage. The fat mass and obesity-associated gene (FTO) encodes an m6A RNA demethylase that controls mRNA processing and has been linked to both obesity and bone mineral density in humans by genome-wide association studies. To examine the role of FTO in bone, we characterized the phenotype of mice lacking Fto globally (FtoKO) or selectively in osteoblasts (FtoOc KO). Both mouse models developed age-related reductions in bone volume in both the trabecular and cortical compartments. RNA profiling in osteoblasts following acute disruption of Fto revealed changes in transcripts of Hspa1a and other genes in the DNA repair pathway containing consensus m6A motifs required for demethylation by Fto. Fto KO osteoblasts were more susceptible to genotoxic agents (UV and H2O2) and exhibited increased rates of apoptosis. Importantly, forced expression of Hspa1a or inhibition of NF-κB signaling normalized the DNA damage and apoptotic rates in Fto KO osteoblasts. Furthermore, increased metabolic stress induced in mice by feeding a high-fat diet induced greater DNA damage in osteoblast of FtoOc KO mice compared to controls. These data suggest that FTO functions intrinsically in osteoblasts through Hspa1a–NF-κB signaling to enhance the stability of mRNA of proteins that function to protect cells from genotoxic damage.
Temperature-Dependent Gas Transport Behavior in Cross-Linked Liquid Crystalline Polyacrylate Membranes

Stable, cross-linked, liquid crystalline polymer (LCP) films for membrane separation applications have been fabricated from the mesogenic monomer 11-(4-cyanobiphenyl-4′-yloxy) undecyl methacrylate (CNBPh), non-mesogenic monomer 2-ethylhexyl acrylate (2-EHA), and cross-linker ethylene glycol dimethacrylate (EGDMA) using an in-situ free radical polymerization technique with UV initiation. The phase behavior of the LCP membranes was characterized using differential scanning calorimetry (DSC) and X-ray scattering, and indicated the formation of a nematic liquid crystalline (LC) phase above the glass transition temperature. The single gas transport behavior of CO2, CH4, propane, and propylene in the cross-linked LCP membranes was investigated for a range of temperatures in the LC mesophase and the isotropic phase. Solubility of the gases was dependent not only on the condensability in the LC mesophase, but also on favorable molecular interactions of penetrant gas molecules exhibiting a charge separation, such as CO2 and propylene, with the ordered polar mesogenic side chains of the LCP. Selectivities for various gas pairs generally decreased with increasing temperature and were discontinuous across the nematic–sotropic transition. Sorption behavior of CO2 and propylene exhibited a significant change due to a decrease in favorable intermolecular interactions in the disordered isotropic phase. Higher cross-link densities in the membrane generally led to decreased selectivity at low temperatures when the main chain motion was limited by the lack of mesogen mobility in the ordered nematic phase. However, at higher temperatures, increasing the cross-link density increased selectivity as the cross-links acted to limit chain mobility. Mixed gas permeation measurements for propylene and propane showed close agreement with the results of the single gas permeation experiments.
Inhibition of Influenza A Virus by Human Infant Saliva

Innate antiviral factors in saliva play a role in protection against respiratory infections. We tested the anti-influenza virus activities of saliva samples taken from human infants, 1–12 months old, with no history of prior exposure to influenza. In contrast to the inhibitory activity we observed in mouse and ferret saliva, the activity of human infant saliva was complex, with both sialic acid-dependent and independent components, the proportion of which differed between individuals. Taken as a whole, we showed that the major anti-influenza activity of infant saliva is acquired over the first year of life and is associated with sialic acid-containing molecules. The activity of sialic acid-independent inhibitors was lower overall, more variable between individuals, and less dependent on age. The results show that the saliva of very young infants can provide a degree of protection against influenza, which may be critical in the absence of adaptive immunity.