Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced In-source Fragmentation Annotation Enables Novel Data Independent Acquisition and Autonomous METLIN Molecular Identification.

Electrospray ionization (ESI) in-source fragmentation (ISF) has traditionally been minimized to promote precursor molecular ion formation, and therefore its value in molecular identification underappreciated. In-source annotation algorithms have been shown to increase confidence in putative identifications by using ubiquitous in-source fragments. However, these in-source annotation algorithms are limited by ESI sources that are generally designed to minimize ISF. In this study, enhanced in-source fragmentation annotation (eISA) was created by tuning the ISF conditions to generate in-source fragmentation patterns comparable with higher energy fragments generated at higher collision energies as deposited in the METLIN MS/MS library, without compromising the intensity of precursor ions (median loss ≤ 10% in both positive and negative ionization modes). The analysis of 50 molecules was used to validate the approach in comparison to MS/MS spectra produced via data dependent acquisition (DDA) and data independent acquisition (DIA) mode with quadrupole time-of-flight mass spectrometry (QTOF-MS). Enhanced ISF as compared to QTOF DDA, enables for higher peak intensities for the precursor ions (median: 18 times in negative mode and 210 times in positive mode), with the eISA fragmentation patterns consistent with METLIN for over 90% of the molecules with respect to fragment relative intensity and m/z. eISA also provides higher peak intensity as opposed to QTOF DIA for over 60% of the precursor ions in negative mode (median increase: 20%) and for 88% of the precursor ions in positive mode (median increase: 80%). Molecular identification with eISA was also successfully validated from the analysis of a metabolic extract from macrophages. An interesting side benefit of enhanced ISF is that it significantly improved molecular identification confidence with low resolution single quadrupole mass spectrometry-based untargeted LC/MS experiments. Overall, enhanced ISF allowed for eISA to be used as a more sensitive alternative to other QTOF DIA and DDA approaches, and further, it enables the acquisition of ESI TOF and ESI single quadrupole mass spectrometry instrumentation spectra with improved molecular identification confidence.
Edge and Cloud Collaborative Entity Recommendation Method towards the IoT Search

There are massive entities with strong denaturation of state in the physical world, and users have urgent needs for real-time and intelligent acquisition of entity information, thus recommendation technologies that can actively provide instant and precise entity state information come into being. Existing IoT data recommendation methods ignore the characteristics of IoT data and user search behavior; thus the recommendation performances are relatively limited. Considering the time-varying characteristics of the IoT entity state and the characteristics of user search behavior, an edge-cloud collaborative entity recommendation method is proposed via combining the advantages of edge computing and cloud computing. First, an entity recommendation system architecture based on the collaboration between edge and cloud is designed. Then, an entity identification method suitable for edge is presented, which takes into account the feature information of entities and carries out effective entity identification based on the deep clustering model, so as to improve the real-time and accuracy of entity state information search. Furthermore, an interest group division method applied in cloud is devised, which fully considers user’s potential search needs and divides user interest groups based on clustering model for enhancing the quality of recommendation system. Simulation results demonstrate that the proposed recommendation method can effectively improve the real-time and accuracy performance of entity recommendation in comparison with traditional methods.
Nephrotoxic Effects in Zebrafish after Prolonged Exposure to Aristolochic Acid

With the aim to explore the possibility to generate a zebrafish model of renal fibrosis, in this study the fibrogenic renal effect of aristolochic acid I (AAI) after immersion was assessed. This compound is highly nephrotoxic able to elicit renal fibrosis after exposure of rats and humans. Our results reveal that larval zebrafish at 15 days dpf (days post-fertilization) exposed for 8 days to 0.5 µM AAI showed clear signs of AKI (acute kidney injury). The damage resulted in the relative loss of the functional glomerular filtration barrier. Conversely, we did not observe any deposition of collagen, nor could we immunodetect α-SMA, a hallmark of myofibroblasts, in the tubules. In addition, no increase in gene expression of fibrogenesis biomarkers after whole animal RNA extraction was found. As zebrafish have a high capability for tissue regeneration possibly impeding fibrogenic processes, we also used a tert−/− zebrafish line exhibiting telomerase deficiency and impaired tissue homeostasis. AAI-treated tert−/− larvae displayed an increased sensitivity towards 0.5 µM AAI. Importantly, after AAI treatment a mild collagen deposition could be found in the tubules. The outcome implies that sustained AKI induced by nephrotoxic compounds combined with defective tert−/− stem cells can produce a fibrotic response.
Myeloid‐derived suppressor cells promote epithelial ovarian cancer cell stemness by inducing the CSF2/p‐STAT3 signalling pathway

Myeloid‐derived suppressor cells (MDSCs) are known to contribute to tumour immune evasion, and studies have verified that MDSCs can induce cancer stem cells (CSCs) and promote tumour immune evasion in breast cancers, cervical cancers and glioblastoma. However, the potential function of MDSCs in regulating CSCs in epithelial ovarian cancer (EOC) progression is unknown. Our results indicated that compared to nonmalignant ovarian patients, EOC patients showed a significantly increased proportion of MDSCs in the peripheral blood. In addition, MDSCs dramatically promoted tumour sphere formation, cell colony formation and CSC accumulation, and MDSCs enhanced the expression of the stemness biomarkers NANOG and c‐MYC in EOC cells during coculture. Moreover, the mechanisms by which MDSCs enhance EOC stemness were further explored, and 586 differentially expressed genes were found in EOC cells cocultured with or without MDSCs; during coculture, the expression level of colony‐stimulating factor 2 (CSF2) was significantly increased in EOC cells cocultured with MDSCs. Furthermore, the depletion of CSF2 in EOC cells was successfully performed, the promotive effects of MDSCs on EOC cell stemness could be markedly reversed by downregulating CSF2 expression, p‐STAT3 signalling pathway molecules were also altered, and the p‐STAT3 inhibitor could markedly reverse the promotive effects of MDSCs on EOC cell stemness. In addition, the CSF2 expression level was correlated with EOC clinical staging. Therefore, MDSCs enhance the stemness of EOC cells by inducing the CSF2/p‐STAT3 signalling pathway. Targeting MDSCs or CSF2 may be a reasonable strategy for enhancing the efficacy of conventional treatments.
Estrogen receptor alpha signaling in extrahypothalamic neurons during late puberty decreases bone size and strength in female but not in male mice

Sexually dimorphic bone structure emerges largely during puberty. Sex steroids are critical for peak bone mass acquisition in both genders. In particular, the biphasic effects of estrogens mediate the skeletal sexual dimorphism. However, so far the stimulatory vs inhibitory actions of estrogens on bone mass are not fully explained by direct effects on bone cells. Recently, it has become evident that there is possible neuroendocrine action of estrogen receptor alpha (ERα) on the skeleton. Based on these considerations, we hypothesized that neuronal ERα‐signaling may contribute to the skeletal growth during puberty. Here, we generated mice with tamoxifen‐inducible Thy1‐Cre mediated ERα inactivation during late puberty specifically in extrahypothalamic neurons (N‐ERαKO). Inactivation of neuronal ERα did not alter the body weight in males, whereas N‐ERαKO females exhibited a higher body weight and increased body and bone length compared to their control littermates at 16 weeks of age. Ex vivo microCT analysis showed increased radial bone expansion of the midshaft femur in female N‐ERαKO along with higher serum levels of insulin‐like growth factor (IGF)‐1 as well as IGF‐binding protein (IGFBP)‐3. Furthermore, the 3‐point bending test revealed increased bone strength in female N‐ERαKO. In contrast, inactivation of neuronal ERα had no major effect on bone growth in males. In conclusion, we demonstrate that central ERα‐signaling limits longitudinal bone growth and radial bone expansion specifically in females potentially by interacting with the GH/IGF‐1 axis.
Against all odds—why UK mothers’ breastfeeding beyond infancy are turning to their international peers for emotional and informative support

Abstract The health benefits of breastfeeding are well documented and current recommendations are that women should breastfeed their child for two years and beyond. Despite this the UK has the lowest initiation breastfeeding rates in the world. Additionally, a considerably small percentage of women who do successfully initiate go on to breastfeed past infancy. This could in part be explained by the lack of support women receive when breastfeeding an older child. In this study we provide insight into women’s experiences of healthcare interventions during the transition from breastfeeding an infant to a toddler. We conducted semi-structured interviews with 24 women with experience of breastfeeding at least one child past the age of twelve months. We used a theory driven thematic analysis to identify pertinent themes that ran through the interviews. As mothers progressed through their breastfeeding journey they faced increased social stigma. They also experienced a change in attitudes from healthcare professionals as support was replaced by judgement. This negatively impacted upon trust in healthcare professionals and the advice they offered. In response, the women turned to volunteering organizations and closed social media groups for emotional support and healthcare advice. These women experienced specific issues regarding breastfeeding in toddlerhood as opposed to infancy. They needed specialized interventions tailored for this. Social media was highlighted as a useful platform for supporting women who breastfeed beyond infancy. It allowed these women to feel part of a supportive international community and gain access to practical advice. Healthcare professionals should explore ways to engage in digital platforms to provide support to mothers’ breastfeeding beyond infancy.
Can a Respiratory Severity Score Accurately Assess Respiratory Distress in Children with Bronchiolitis in a Resource-Limited Setting?

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Estetrol (E4): the new estrogenic component of combined oral contraceptives

Estetrol (E4) is a natural fetal estrogenic steroid discovered in 1965 at the Karolinska Institutet in Stockholm (Sweden) [1]. It was studied for a period of 20 years originally as a biomarker of fetal wellbeing during pregnancy [2] before being abandoned as a weak estrogen: research into the potential physiological effects and applications of E4 resumed in 2001. E4 is a steroid hormone with four -OH groups, two more than estradiol (E2), the estrogen physiologically produced by the granulosa cells of human ovaries (Figure 1) [3]. The fetal liver is the exclusive site responsible for 15αand 16α-hydroxylation [4]: for this reason, E4 is only present during pregnancy from9weeks of gestation until only shortly after birth [5] but its physiological role is still unknown. The two additional -OH groups have a crucial impact on the oral pharmacokinetics: the half-life of E4 is 20–28 hours, compared with only 10–20 minutes for estriol (E3), 1–2 hours for natural E2 and 10–12hours formicronized E2. E4 isminimally, if at all,metabolized and not reconverted to E3 or E2 [6]. Receptor binding and target interaction studies showed E4 to have high selectivity for the estrogen receptors (ER), indicating a potential for low risk of side effects. No specific toxicity for E4 has been observed to date [6]. Combined oral contraceptives (COCs) traditionally contain an estrogen and a progestin component. Estrogens stabilize the endometrium, regulating vaginal bleeding, and they reduce follicle development and the secretion of follicle-stimulating hormone (FSH). Ethinyl estradiol (EE) is the most common estrogen used in COCs because of its demonstrated efficacy and safety over 60 years: it has been associated with a satisfactory bleeding pattern but its impact on liver function and vascular endothelium can produce rare cardiovascular thrombotic complications (arterial and venous) during COC use. Different strategies have been developed to reduce this effect, such as decreasing the EE dose, improving the progestinic modulation with androgenic progestins and, since 2009, substituting EE with E2 [7], but the optimal combination is yet to be discovered. The introduction of E4 may improve the safety and tolerability of COCs in the near future. To investigate the potential clinical use of E4 as a safe and well-tolerated estrogenic component of COCs, some dosefinding and comparative studies have begun to emerge in recent years. The complete experimental programme for these studies is reported in Table 1.
Wearable Hand Module and Real-Time Tracking Algorithms for Measuring Finger Joint Angles of Different Hand Sizes with High Accuracy Using FBG Strain Sensor

This paper presents a wearable hand module which was made of five fiber Bragg grating (FBG) strain sensor and algorithms to achieve high accuracy even when worn on different hand sizes of users. For real-time calculation with high accuracy, FBG strain sensors move continuously according to the size of the hand and the bending of the joint. Representatively, four algorithms were proposed; point strain (PTS), area summation (AREA), proportional summation (PS), and PS/interference (PS/I or PS/I_α). For more accurate and efficient assessments, 3D printed hand replica with different finger sizes was adopted and quantitative evaluations were performed for index~little fingers (77 to 117 mm) and thumb (68~78 mm). For index~little fingers, the optimized algorithms were PS and PS/I_α. For thumb, the optimized algorithms were PS/I_α and AREA. The average error angle of the wearable hand module was observed to be 0.47 ± 2.51° and mean absolute error (MAE) was achieved at 1.63 ± 1.97°. These results showed that more accurate hand modules than other glove modules applied to different hand sizes can be manufactured using FBG strain sensors which move continuously and algorithms for tracking this movable FBG sensors.
Annual Surveillance Summary: Vancomycin-Resistant Enterococci (VRE) Infections in the Military Health System (MHS), 2016

Abstract : The EpiData Center Department (EDC) conducts routine surveillance of vancomycin-resistant enterococci (VRE) incidence and prevalence among all beneficiaries seeking care within the Military Health System (MHS). This report describes demographics, clinical characteristics, prescription practices, and antibiotic resistance patterns observed for VRE in calendar year (CY) 2016. Multiple data sources were linked to assess descriptive and clinical factors related to VRE. Health Level 7 (HL7)-formatted Composite Health Care System (CHCS) microbiology data identified Enterococcus species infections with vancomycin resistance. These infections were matched to HL7-formatted CHCS pharmacy data to assess prescription practices, the Standard Inpatient Data Record (SIDR) to determine healthcare-associated exposures, Defense Manpower Data Center (DMDC) rosters to determine burden among Department of Defense (DOD) active duty (AD) service members, and the DMDC Contingency Tracking System (CTS) to determine Department of the Navy (DON) deployment-related infections. In 2016, VRE infection rates declined among MHS beneficiaries to 1.38 per 100,000 persons per year, following a three-year incline from 2013-2015. The United States (US) West and South regions had the highest rates, and healthcare-associated (HA) cases comprised the largest proportion of all infections identified (87 ). While the majority of all prevalent infections were classified as hospital-onset (HO) (45 ), a substantial proportion was also identified as community-onset (CO) (31 ). Treatment for VRE infections among DOD beneficiaries primarily included daptomycin and linezolid, which remained effective throughout 2016. These findings warrant continued surveillance to understand the evolving impact of VRE within the MHS.
Risk of Major Adverse Cardiovascular Events, Severe Hypoglycemia, and All-Cause Mortality for Widely Used Antihyperglycemic Dual and Triple Therapies for Type 2 Diabetes Management: A Cohort Study of All Danish Users

OBJECTIVE The vast number of antihyperglycemic medications and growing amount of evidence make clinical decision making difficult. The aim of this study was to investigate the safety of antihyperglycemic dual and triple therapies for type 2 diabetes management with respect to major adverse cardiovascular events, severe hypoglycemia, and all-cause mortality in a real-life clinical setting. RESEARCH DESIGN AND METHODS Cox regression models were constructed to analyze 20 years of data from the Danish National Patient Registry with respect to effect of the antihyperglycemic therapies on the three end points. RESULTS A total of 66,807 people with type 2 diabetes were treated with metformin (MET) plus a combination of second- and third-line therapies. People on MET plus sulfonylurea (SU) had the highest risk of all end points, except for severe hypoglycemia, for which people on MET plus basal insulin (BASAL) had a higher risk. The lowest risk of major adverse cardiovascular events was seen for people on a regimen including a glucagon-like peptide 1 (GLP-1) receptor agonist. People treated with MET, GLP-1, and BASAL had a lower risk of all three end points than people treated with MET and BASAL, especially for severe hypoglycemia. The lowest risk of all three end points was, in general, seen for people treated with MET, sodium–glucose cotransporter 2 inhibitor, and GLP-1. CONCLUSIONS Findings from this study do not support SU as the second-line treatment choice for patients with type 2 diabetes. Moreover, the results indicate that adding a GLP-1 in people treated with MET and BASAL could be considered, especially if those people suffer from severe hypoglycemia.
Elucidating the Structure-Function Relationship of Solvent and Cross-Linker on Affinity-Based Release from Cyclodextrin Hydrogels

Minocycline (MNC) is a tetracycline antibiotic capable of associating with cyclodextrin (CD), and it is a frontline drug for many instances of implant infection. Due to its broad-spectrum activity and long half-life, MNC represents an ideal drug for localized delivery; however, classic polymer formulations, particularly hydrogels, result in biphasic release less suitable for sustained anti-microbial action. A polymer delivery system capable of sustained, steady drug delivery rates poses an attractive target to maximize the antimicrobial activity of MNC. Here, we formed insoluble hydrogels of polymerized CD (pCD) with a range of crosslinking densities, and then assessed loading, release, and antimicrobial activity of MNC. MNC loads between 5–12 wt % and releases from pCD hydrogels for >14 days. pCD loaded with MNC shows extended antimicrobial activity against S. aureus for >40 days and E. coli for >70 days. We evaluated a range of water/ethanol blends to test our hypothesis that solvent polarity will impact drug-CD association as a function of hydrogel swelling and crosslinking. Increased polymer crosslinking and decreased solvent polarity both reduced MNC loading, but solvent polarity showed a dramatic reduction independent of hydrogel swelling. Due to its high solubility and excellent delivery profile, MNC represents a unique drug to probe the structure-function relationship between drug, affinity group, and polymer crosslinking ratio.
A Hadoop-Based Platform for Patient Classification and Disease Diagnosis in Healthcare Applications

Nowadays, the increasing number of patients accompanied with the emergence of new symptoms and diseases makes heath monitoring and assessment a complicated task for medical staff and hospitals. Indeed, the processing of big and heterogeneous data collected by biomedical sensors along with the need of patients’ classification and disease diagnosis become major challenges for several health-based sensing applications. Thus, the combination between remote sensing devices and the big data technologies have been proven as an efficient and low cost solution for healthcare applications. In this paper, we propose a robust big data analytics platform for real time patient monitoring and decision making to help both hospital and medical staff. The proposed platform relies on big data technologies and data analysis techniques and consists of four layers: real time patient monitoring, real time decision and data storage, patient classification and disease diagnosis, and data retrieval and visualization. To evaluate the performance of our platform, we implemented our platform based on the Hadoop ecosystem and we applied the proposed algorithms over real health data. The obtained results show the effectiveness of our platform in terms of efficiently performing patient classification and disease diagnosis in healthcare applications.
Electrical Phase Control Based on Graphene Surface Plasmon Polaritons in Mid-infrared

Phase modulation of light is the core of many optoelectronic applications, such as electro-optic switch, sensors and modulators. Graphene Surface plasmon polaritons (SPPs) exhibit unique properties in phase modulation including dynamic tunability, a small driving voltage and small device size. In this paper, the novel phase modulation capability of graphene SPPs in mid-infrared are confirmed through theory and simulation. The results show that graphene SPPs can realize continuous tuning of the phase shift at multiple wavelengths in mid-infrared, covering the phase range from 0° to 360°. Based on these results, a sandwich waveguide structure of dielectric–graphene–dielectric with a device length of 800 nm is proposed, which shows up to 381° phase modulation range at an operating wavelength of 6.55 µm, given a 1 V driving voltage. In addition, the structure size is much shorter than the wavelength in mid-infrared and can realize sub-wavelength operation. This work paves the way to develop graphene-based tunable devices for mid-infrared wave-front control.