Miracle-dz/UniFAR-FTUs huggingface dataset:
The predominant roles of the sequence periodicity in the self‐assembly of collagen‐mimetic mini‐fibrils

Collagen fibrils represent a unique case of protein folding and self‐association. We have recently successfully developed triple‐helical peptides that can further self‐assemble into collagen‐mimetic mini‐fibrils. The 35 nm axially repeating structure of the mini‐fibrils, which is designated the d‐period, is highly reminiscent of the well‐known 67 nm D‐period of native collagens when examined using TEM and atomic force spectroscopy. We postulate that it is the pseudo‐identical repeating sequence units in the primary structure of the designed peptides that give rise to the d‐period of the quaternary structure of the mini‐fibrils. In this work, we characterize the self‐assembly of two additional designed peptides: peptide Col877 and peptide Col108rr. The triple‐helix domain of Col877 consists of three pseudo‐identical amino acid sequence units arranged in tandem, whereas that of Col108rr consists of three sequence units identical in amino acid composition but different in sequence. Both peptides form stable collagen triple helices, but only triple helices Col877 self‐associate laterally under fibril forming conditions to form mini‐fibrils having the predicted d‐period. The Co108rr triple helices, however, only form nonspecific aggregates having no identifiable structural features. These results further accentuate the critical involvement of the repeating sequence units in the self‐assembly of collagen mini‐fibrils; the actual amino acid sequence of each unit has only secondary effects. Collagen is essential for tissue development and function. This novel approach to creating collagen‐mimetic fibrils can potentially impact fundamental research and have a wide range of biomedical and industrial applications.
Spectrin-based membrane skeleton supports ciliogenesis

Cilia are remarkable cellular devices that power cell motility and transduce extracellular signals. To assemble a cilium, a cylindrical array of 9 doublet microtubules push out an extension of the plasma membrane. Membrane tension regulates cilium formation; however, molecular pathways that link mechanical stimuli to ciliogenesis are unclear. Using genome editing, we introduced hereditary elliptocytosis (HE)- and spinocerebellar ataxia (SCA)-associated mutations into the Caenorhabditis elegans membrane skeletal protein spectrin. We show that these mutations impair mechanical support for the plasma membrane and change cell shape. RNA sequencing (RNA-seq) analyses of spectrin-mutant animals uncovered a global down-regulation of ciliary gene expression, prompting us to investigate whether spectrin participates in ciliogenesis. Spectrin mutations affect intraflagellar transport (IFT), disrupt axonemal microtubules, and inhibit cilium formation, and the endogenous spectrin periodically distributes along cilia. Mammalian spectrin also localizes in cilia and regulates ciliogenesis. These results define a previously unrecognized yet conserved role of spectrin-based mechanical support for cilium biogenesis.
LncRNA GClnc1 promotes proliferation and invasion of bladder cancer through activation of MYC

Various studies demonstrate that long noncoding RNAs (IncRNAs) act as oncogenes or tumor suppressors in cancer. However, the function of IncRNAs in bladder cancer still remains largely unknown. In this study, we identified an IncRNA, gastric cancer–associated IncRNA1 (GClnc1), which was in high abundance in bladder cancer tissues and its expression was related to poor survival rates in patients with bladder cancer. In vitro and in vivo assays showed that GClnc1 significantly promoted cell proliferation, metastasis, and invasiveness in bladder cancer. Mechanistically, we first found that GClnc1 bound to LIN28B and promoted the expression of myelocytomatosis proto‐oncogene (MYC) through the LIN28B/let‐7a/MYC pathway. In short, GClnc1 is clinically, functionally, and mechanistically oncogenic in bladder cancer. GClnc1 may be a potential target for treating patients with bladder cancer. —Zhuang, C. , Ma, Q. , Zhuang, C. , Ye, J., Zhang, F. , Gui, Y. LncRNA GClnc1 promotes proliferation and invasion of bladder cancer through activation of MYC. FASEB J. 33, 11045–11059 (2019). www.fasebj. org
Primary Care Providers Believe That Comprehensive Medication Management Improves Their Work-Life

Purpose: In primary care, clinical pharmacists often deliver a service called comprehensive medication management (CMM). While research has identified that CMM positively influences most aspects of the Quadruple Aim, it is unclear how CMM—both the service and the role of the pharmacist—may influence the primary care provider's (PCP) clinical work, professional satisfaction, and burnout (described here as PCP's work-life). We aimed to identify how PCPs perceive CMM impacts their work-life. Methods: Sixteen PCPs were interviewed. Interview questions centered on how CMM affects their work-life. After interviews were transcribed, a codebook was developed by 2 researchers and from the codes, themes were identified. Results: PCPs spoke of the pharmacist being an added skillset and resource and a collaborative partner in caring for patients. They also described 7 outcomes of having CMM available that contribute to their work-life. These outcomes were: decreased workload, satisfaction patients are receiving better care, reassurance, decreased mental exhaustion, enhanced professional learning, increased provider access, and achievement of quality measures. Lastly, the PCPs described barriers and areas of opportunity related to CMM. Conclusion: Our findings suggest PCPs believe CMM, in general, positively affects their work-life. CMM's impact on PCPs aligns with many previously identified drivers of burnout and engagement among providers. These results shed light on how CMM may foster achievement of the Quadruple Aim.
Engineering the interactions between a plant‐produced HIV antibody and human Fc receptors

Summary Plants can provide a cost‐effective and scalable technology for production of therapeutic monoclonal antibodies, with the potential for precise engineering of glycosylation. Glycan structures in the antibody Fc region influence binding properties to Fc receptors, which opens opportunities for modulation of antibody effector functions. To test the impact of glycosylation in detail, on binding to human Fc receptors, different glycovariants of VRC01, a broadly neutralizing HIV monoclonal antibody, were generated in Nicotiana benthamiana and characterized. These include glycovariants lacking plant characteristic α1,3‐fucose and β1,2‐xylose residues and glycans extended with terminal β1,4‐galactose. Surface plasmon resonance‐based assays were established for kinetic/affinity evaluation of antibody–FcγR interactions, and revealed that antibodies with typical plant glycosylation have a limited capacity to engage FcγRI, FcγRIIa, FcγRIIb and FcγRIIIa; however, the binding characteristics can be restored and even improved with targeted glycoengineering. All plant‐made glycovariants had a slightly reduced affinity to the neonatal Fc receptor (FcRn) compared with HEK cell‐derived antibody. However, this was independent of plant glycosylation, but related to the oxidation status of two methionine residues in the Fc region. This points towards a need for process optimization to control oxidation levels and improve the quality of plant‐produced antibodies.
Feature relevance assessment for the semantic interpretation of 3D point cloud data

Abstract. The automatic analysis of large 3D point clouds represents a crucial task in photogrammetry, remote sensing and computer vision. In this paper, we propose a new methodology for the semantic interpretation of such point clouds which involves feature relevance assessment in order to reduce both processing time and memory consumption. Given a standard benchmark dataset with 1.3 million 3D points, we first extract a set of 21 geometric 3D and 2D features. Subsequently, we apply a classifier-independent ranking procedure which involves a general relevance metric in order to derive compact and robust subsets of versatile features which are generally applicable for a large variety of subsequent tasks. This metric is based on 7 different feature selection strategies and thus addresses different intrinsic properties of the given data. For the example of semantically interpreting 3D point cloud data, we demonstrate the great potential of smaller subsets consisting of only the most relevant features with 4 different state-of-the-art classifiers. The results reveal that, instead of including as many features as possible in order to compensate for lack of knowledge, a crucial task such as scene interpretation can be carried out with only few versatile features and even improved accuracy.
Detection of selected viral pathogens in dogs with canine infectious respiratory disease in Austria

Objectives To assess the prevalence of canine parainfluenza virus, canine adenovirus type 2, canine distemper virus, canine respiratory coronavirus and influenza virus A infections in: (1) privately‐owned or, (2) kennelled dogs showing signs consistent with canine infectious respiratory disease and, (3) clinically healthy dogs in Vienna, Austria. Materials and Methods Prospectively, nasal and tonsillar swabs from 214 dogs affected with infectious respiratory disease, and 50 healthy control dogs were tested for nucleic acids specific to the various viral infections. Concurrent bronchoalveolar lavage fluid from 31 dogs with chronic respiratory disease was investigated for the same viral pathogens. Additionally, anti‐canine respiratory coronavirus antibody concentrations were measured in paired blood samples from 30 acutely diseased dogs. Results Canine respiratory coronavirus (7.5%) and canine parainfluenza virus (6.5%) were the most commonly detected viruses in samples from the upper airways of dogs with respiratory infections. Serological results showed a significant seroconversion in response to coronavirus in 50% of the examined cases. None of the samples was positive for influenza virus A‐specific nucleic acid. Canine coronavirus‐specific nucleic acid was detected in 4.0% of healthy dogs. Clinical Significance Canine coronavirus should be considered as a clinically relevant cause of infectious respiratory disease in crowded dog populations. For sample collection, the nasal mucosa can be recommended as the favoured site. Analysis of paired serum samples aids verification of canine coronavirus infection in respiratory disease.
A Parent Treatment Program for Preschoolers With Obesity: A Randomized Controlled Trial

In this RCT, we evaluate a novel approach for preschool obesity, focusing on evidence-based parenting practices and the influence of intensity on treatment effects. BrightcoveDefaultPlayer10.1542/6138652457001PEDS-VA_2018-3457 Video Abstract BACKGROUND AND OBJECTIVES: Early obesity treatment seems to be the most effective, but few treatments exist. In this study, we examine the effectiveness of a parent-only treatment program with and without booster sessions (Booster or No Booster) focusing on parenting practices and standard treatment (ST). METHODS: Families of children 4 to 6 years of age with obesity were recruited from 68 child care centers in Stockholm County and randomly assigned to a parent-only program (10 weeks) with or without boosters (9 months) or to ST. Treatment effects on primary outcomes (BMI z score) and secondary outcomes (BMI and waist circumference) during a 12-month period were examined with linear mixed models. The influence of sociodemographic factors was examined by 3-way interactions. The clinically significant change in BMI z score (−0.5) was assessed with risk ratios. RESULTS: A total of 174 children (mean age: 5.3 years [SD = 0.8]; BMI z score: 3.0 [SD = 0.6], 56% girls) and their parents (60% foreign background; 39% university degree) were included in the analysis (Booster, n = 44; No Booster, n = 43; ST, n = 87). After 12 months, children in the parent-only treatment had a greater reduction in their BMI z score (0.30; 95% confidence interval [CI]: −0.45 to −0.15) compared with ST (0.07; 95% CI: −0.19 to 0.05). Comparing all 3 groups, improvements in weight status were only seen for the Booster group (−0.54; 95% CI: −0.77 to −0.30). The Booster group was 4.8 times (95% CI: 2.4 to 9.6) more likely to reach a clinically significant reduction of ≥0.5 of the BMI z score compared with ST. CONCLUSION A parent-only treatment with boosters outperformed standard care for obesity in preschoolers.
Customer Value Creation by Customer Knowledge Management

Customer knowledge management (CKM), which integrates customer relationship management (CRM) with knowledge management (KM), can be used to create a valuable leverage and direct interaction with the customers. This article proposes a conceptual framework to assess the customer value created by implementing customer knowledge conversion between vending firms and customers. A case study is used to illustrate the proposed CKM model, and the results show that customer value is manifested and magnified through four types of customer knowledge that continuously disseminated within the vendor, between the vendor and customers, and among customers. Keyword: Customer Knowledge Management, Customer Value Creation, Customer Relationship Management, Knowledge Management
Tetrodotoxin-Sensitive Sodium Channels Mediate Action Potential Firing and Excitability in Menthol-Sensitive Vglut3-Lineage Sensory Neurons

Small-diameter vesicular glutamate transporter 3-lineage (Vglut3lineage) dorsal root ganglion (DRG) neurons play an important role in mechanosensation and thermal hypersensitivity; however, little is known about their intrinsic electrical properties. We therefore set out to investigate mechanisms of excitability within this population. Calcium microfluorimetry analysis of male and female mouse DRG neurons demonstrated that the cooling compound menthol selectively activates a subset of Vglut3lineage neurons. Whole-cell recordings showed that small-diameter Vglut3lineage DRG neurons fire menthol-evoked action potentials and exhibited robust, transient receptor potential melastatin 8 (TRPM8)-dependent discharges at room temperature. This heightened excitability was confirmed by current-clamp and action potential phase-plot analyses, which showed menthol-sensitive Vglut3lineage neurons to have more depolarized membrane potentials, lower firing thresholds, and higher evoked firing frequencies compared with menthol-insensitive Vglut3lineage neurons. A biophysical analysis revealed voltage-gated sodium channel (NaV) currents in menthol-sensitive Vglut3lineage neurons were resistant to entry into slow inactivation compared with menthol-insensitive neurons. Multiplex in situ hybridization showed similar distributions of tetrodotoxin (TTX)-sensitive NaV transcripts between TRPM8-positive and -negative Vglut3lineage neurons; however, NaV1.8 transcripts, which encode TTX-resistant channels, were more prevalent in TRPM8-negative neurons. Conversely, pharmacological analyses identified distinct functional contributions of NaV subunits, with NaV1.1 driving firing in menthol-sensitive neurons, whereas other small-diameter Vglut3lineage neurons rely primarily on TTX-resistant NaV channels. Additionally, when NaV1.1 channels were blocked, the remaining NaV current readily entered into slow inactivation in menthol-sensitive Vglut3lineage neurons. Thus, these data demonstrate that TTX-sensitive NaVs drive action potential firing in menthol-sensitive sensory neurons and contribute to their heightened excitability. SIGNIFICANCE STATEMENT Somatosensory neurons encode various sensory modalities including thermoreception, mechanoreception, nociception, and itch. This report identifies a previously unknown requirement for tetrodotoxin-sensitive sodium channels in action potential firing in a discrete subpopulation of small-diameter sensory neurons that are activated by the cooling agent menthol. Together, our results provide a mechanistic understanding of factors that control intrinsic excitability in functionally distinct subsets of peripheral neurons. Furthermore, as menthol has been used for centuries as an analgesic and anti-pruritic, these findings support the viability of NaV1.1 as a therapeutic target for sensory disorders.
Minimizing the expected processing time on a flexible machine with random tool lives

We present a stochastic version of economic tool life models for machines with finite capacity tool magazines and a variable processing speed capability, where the tool life is a random variable. Using renewal theory to express the expected number of tool setups as a function of cutting speed and magazine capacity, we extend previously published deterministic mathematical programming models to the case of minimizing the expected total processing time. A numerical illustration with typical cutting tool data shows the deterministic model underestimates the optimal expected processing time by more than 8% when the coefficient of variation equals 0.3 (typical for carbide tools), and the difference exceeds 15% for single-injury tools having an exponentially distributed economic life (worst case).
Evaluation of upper tropospheric humidity from NCEP analysis and WRF Model Forecast with Kalpana observation during Indian summer monsoon 2010

This paper presents an evaluation of upper tropospheric humidity (UTH) fields from National Center for Environmental Prediction (NCEP) Global Data Assimilation System (GDAS) analysis and Weather Research and Forecasting (WRF) mesoscale model forecast with satellite derived UTH. For this purpose, UTH (weighted average of relative humidity in 200–500 hPa layer) obtained from Indian geostationary satellite Kalpana is compared with the UTH computed from NCEP analysis and WRF model forecast during the summer monsoon, 2010. Kaplana‐derived products are not included in the NCEP analysis: therefore, a comparison of the two independent datasets is promising. This study indicates that UTH derived from different sources (Kalpana UTH, NCEP Analysed and subsequent model forecasted UTH) matches very well over the Indian region. However, there are region‐specific small departures in UTH which increases the model predicted UTH. Copyright © 2012 Royal Meteorological Society
Patient-Defined Visit Priorities in Primary Care: Psychosocial Versus Medically-Related Concerns

Background: Primary care providers (PCPs) are often challenged to address multiple patient concerns during time-limited visits. The need for PCPs to limit the number of issues addressed may have a negative impact on discussion of patient-defined visit priorities. Methods: Using data from a recent clinical trial (Aligning Patients and Providers, ClinicalTrials.gov: NCT02707146), we examined the association between patient-defined visit priorities and subsequent provider actions taken during and after the visit. We tested the hypothesis that psychosocial concerns (eg, stress, anxiety, caregiving demands) are less likely to be addressed than traditional medical concerns. Results: We analyzed 147 patient-defined visit priorities submitted just before the visit by 109 patients (mean age, 59.0 ± 12.7 years; including 73.4% women, 47.7% non-White race/ethnicity). Nearly one quarter of patient-defined visit priorities were related to psychosocial concerns (35/147; 23.8%). In models adjusting for age, gender, race/ethnicity, and familiarity with PCP, patients' psychosocial priorities were significantly less likely than medical priorities to be addressed during the visit (63% vs. 88%; adjusted odds ratio [aOR], 0.16; 95% CI, 0.06 to 0.41; P < .001), to receive clinical action (51% vs. 82%; aOR, 0.15; 95% CI, 0.06 to 0.38; P < .001), or to receive post visit information from the primary care doctor (17% vs. 32%; aOR, 0.39; 95% CI, 0.14 to 1.08; P = .07). Conclusions: Patient-defined psychosocial priorities are less likely to be addressed during (or immediately after) primary care visits compared with patient-defined medical priorities.
Spleen iron, molybdenum, and manganese concentrations are coregulated in hepcidin‐deficient and secondary iron overload models in mice

Iron excess increases the hepatic expression of hepcidin, the systemic iron metabolism regulator that favors iron sequestration in the spleen. Genetic iron overload related to hepcidin insufficiency decreases the spleen iron concentration and increases hepatic iron concentration, whereas during secondary iron overload, the hepcidin expression increases together with spleen iron concentration in addition to hepatic iron concentrations increase. Links between iron metabolism and other metals being suggested, our aim was to investigate, during iron overload, the relationships between the hepatic hepcidin expression level and the hepatic and splenic concentrations of iron, manganese, copper, zinc, and molybdenum, determined using inductively coupled plasma mass spectrometry. Hepcidin‐deficient mice, secondary iron overload mice models, and their respective controls were studied. Spleen molybdenum and manganese concentrations paralleled the modulation of both spleen iron concentrations, increasing in secondary iron overload and decreasing in hepcidin deficiency related iron overload, as well as hepatic hepcidin mRNA expression. Our data suggest that iron, manganese, and molybdenum metabolisms could share mechanisms controlling their distribution that are associated to hepcidin modulation. In diseases with abnormal hepcidin levels, including chronic inflammation, special attention should be paid to those metals that can participate with the phenotype. —Cavey, T. , Latour, C. , Island, M. ‐L. , Leroyer, P., Guggenbuhl, P., Coppin, H. , Roth, M. ‐P., Bendavid, C. , Brissot, P., Ropert, M. , Loréal, O. Spleen iron, molybdenum, and manganese concentrations are coregulated in hepcidin‐deficient and secondary iron overload models in mice. FASEB J. 33, 11072–11081 (2019). www.fasebj. org
A Life Threating Subglottic and Mediastinal Hemangioma in an Infant.

Subglottic and mediastinal hemangioma are rare benign vascular tumors of childhood. They cause potentially life threatening condition which requires intervention. Several therapeutic options have been described in the literature with varying degrees of success and complications. We report a case of a stridulous 2-month old female infant with mediastinal and subglottic hemangioma. The child was treated with propranolol without the need for tracheostomy or any other surgical intervention, and with no reported side effects. Propranolol is an effective, non-invasive treatment for life threatening infantile hemangiomas compressing the airway, should be used as a firstline treatment for subglottic hemangiomas when intervention is required.
Risk Factors For Childhood And Adult Primary Brain Tumors.

Primary brain tumors account for ~1% of new cancer cases and ~2% of cancer deaths in the United States; however, they are the most commonly occurring solid tumor in children. These tumors are very heterogeneous, and can be broadly classified into malignant and benign (or non-malignant), and these histologies vary in frequency by age, sex, and race/ethnicity. Epidemiological studies have explored numerous potential risk factors, and thus far, the only validated associations for brain tumors are ionizing radiation (which increases risk in both adults and children) and history of allergies (which decreases risk in adults). Studies of genetic risk factors have identified 32 germline variants associated with increased risk for these tumors in adults (25 in glioma, 2 in meningioma, 3 in pituitary adenoma, and 2 in primary CNS lymphoma), and further studies are currently underway for other histological subtypes, as well as for various childhood brain tumors. While identifying risk factors for these tumors is difficult due to their rarity, many existing datasets can be leveraged for future discoveries in multi-institutional collaborations. Many institutions are continuing to develop large clinical databases including pre-diagnostic risk factor data, and developments in molecular characterization of tumor subtypes continue to allow for investigation of more refined phenotypes.