Miracle-dz/UniFAR-FTUs huggingface dataset:
Shared reference materials harmonize lipidomics across MS-based detection platforms and laboratories

Quantitative MS of human plasma lipids is a promising technology for translation into clinical applications. Current MS-based lipidomic methods rely on either direct infusion (DI) or chromatographic lipid separation methods (including reversed phase and hydrophilic interaction LC). However, the use of lipid markers in laboratory medicine is limited by the lack of reference values, largely because of considerable differences in the concentrations measured by different laboratories worldwide. These inconsistencies can be explained by the use of different sample preparation protocols, method-specific calibration procedures, and other experimental and data-reporting parameters, even when using identical starting materials. Here, we systematically investigated the roles of some of these variables in multiple approaches to lipid analysis of plasma samples from healthy adults by considering: 1) different sample introduction methods (separation vs. DI methods); 2) different MS instruments; and 3) between-laboratory differences in comparable analytical platforms. Each of these experimental variables resulted in different quantitative results, even with the inclusion of isotope-labeled internal standards for individual lipid classes. We demonstrated that appropriate normalization to commonly available reference samples (i.e., “shared references”) can largely correct for these systematic method-specific quantitative biases. Thus, to harmonize data in the field of lipidomics, in-house long-term references should be complemented by a commonly available shared reference sample, such as NIST SRM 1950, in the case of human plasma.
RNAi‐mediated stable silencing of TaCSN5 confers broad‐spectrum resistance to Puccinia striiformis f. sp. tritici

Abstract The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is a versatile regulator of plant growth, development, and response to diverse pathogens. However, little research has been done to understand the function of those CSN genes in broad‐spectrum resistance to pathogens. In this study, we found that the transcript levels of wheat TaCSN5 were induced in response to inoculation with Puccinia striiformis f. sp. tritici (Pst) and treatment with salicylic acid (SA). Overexpression of TaCSN5 in Arabidopsis resulted in increased susceptibility to Pseudomonas syringae pv. tomato DC3000 infection accompanied by down‐regulation of AtPR1 expression. Overexpression of TaCSN5 in wheat lines significantly increased susceptibility to Pst accompanied by decreased SA accumulation, whereas TaCSN5‐RNAi wheat lines exhibited opposite trends. Moreover, we found that TaCSN5 negatively regulated TaG3NPR1 genes involved in the SA signalling pathway. In addition, TaCSN5‐RNAi lines showed increased resistance to multiple races of Pst. Taken together, we demonstrate that TaCSN5 contributes to negative regulation of wheat resistance to Pst in an SA‐dependent manner.
The Estimated Lifetime Medical Cost of Chlamydia, Gonorrhea, and Trichomoniasis in the United States, 2018.

BACKGROUND The purpose of this study was to provide updated estimates of the average lifetime medical cost per infection for chlamydia, gonorrhea, and trichomoniasis. METHODS We adapted a published decision tree model that allowed for 7 possible outcomes of infection: (1) symptomatic infection, treated, no sequelae; (2) symptomatic infection, not treated, sequelae; (3) symptomatic infection, not treated, no sequelae; (4) asymptomatic infection, treated, sequelae; (5) asymptomatic infection, treated, no sequelae; (6) asymptomatic infection, not treated, sequelae; and (7) asymptomatic infection, not treated, no sequelae. The base case values and ranges we applied for the model inputs (i.e., the probability and cost assumptions) were based on published studies. RESULTS The estimated lifetime medical cost per infection for men and women, respectively, was $46 (95% credibility interval: $32-62) and $262 ($127-483) for chlamydia, $78 ($36-145) and $254 ($96-518) for gonorrhea, and $5 ($1-14) and $36 ($17-58) for trichomoniasis. Cost estimates for men were most sensitive to assumptions regarding the probability that the infection is symptomatic, the probability of treatment if asymptomatic, and the cost of treatment of infection. Cost estimates for chlamydia and gonorrhea in women were most sensitive to assumptions regarding the probability and cost of subsequent pelvic inflammatory disease (PID). CONCLUSIONS These estimates of the lifetime medical cost per infection can inform updated estimates of the total annual cost of sexually transmitted infections (STIs) in the United States, as well as analyses of the value and cost-effectiveness of STI prevention interventions.
Antiproliferative potential of moluccella laevis L. aerial parts family lamiaceae (labiatae), supported by phytochemical investigation and molecular docking study

Abstract The current biologically guided study aimed the in vitro investigation of cytotoxic activity, identification of the phytochemical content of Moluccella laevis L. aerial parts and supporting this activity by a molecular docking study. Aqueous fraction demonstrated the most potent cytotoxic effect against CACO-2 with IC50 = 0.067 ± 0.01 μg/mL. Furthermore, EtOAc fraction showed a remarkable cytotoxic activity against MCF-7 cell line with IC50 = 0.35 ± 0.02 μg/mL. Consequently, total ethanolic extract (TEE) and its fractions were subjected to LC-HR-ESI-MS metabolic profiling to discover the constituents that possibly underlie their cytotoxicity. Twenty compounds were tentatively identified from metabolic analysis. Furthermore, eight compounds were isolated. In silico docking study revealed that stachydrine is more likely to account for the antiproliferative activity of both EtOAc and aqueous fractions, probably via its moderate inhibition of receptor tyrosine kinases.
A Proposal for Guiding and Trapping of Cold Atoms in the AC Field of Current-Carrying Wires

We pro pose a novel ac elec tro-magnetic guid ing and trap ping of cold neu tral at oms, which is b ased on the in ter ac tion of a mag netic di pole mo ment of guided and trapped atom with both an ac quadrupole mag netic field in the trans verse di rec tion and a dc-bias mag netic field along the guid ing axis. The time-averaged mag netic po ten tial and force for the at oms are cal cu lated. And the re sults show that the po ten tial is high enough to col lect and guide nearly all of the cold at oms from a stan dard mag neto-optical trap with a tem per a ture of ~ 120 µK. The ma nip u la tion of cold at oms is a fun da men tal phys i cal prob lem in atom op tics. Atom can be guided over a long distance with out losses with high spa tial ac cu racy, which open a new way of atom de po si tion in atom li thog ra phy. The spa tial res o lu tion of tra di tional li thog ra phy is lim ited by the dif frac tion of light waves. The guid ing of at oms by means of near field con fig u ra tions per mits to over come this lim i ta tion. The state and spe cies se lec tively of atom guid ing per mits to ex tract and de liver the cho sen at oms from one vac uum cham ber to an other, which is of ten used in atom op tics ex per i ments. 1 Trapping of at oms in a re stricted space vol ume has con sid er able in ter est of phys i cal in ves ti ga tions with small amount of at oms and de vel op ment of new tech nol o gies on the lo cal iza tion of spa tial mo tion of at oms. Im por tant phys i cal ap pli ca tion of trap ping at oms in clude im prove ment of ac cu racy and sen si tiv ity of spec tral mea sure ments, stud ies of quan tum sta tis ti cal ef fect in atomic in sam ple at low tem per a ture, such as the Bose-Einstein con den sa tion (BEC), stops and stor age light in cold atomic me dium. 2
The search for RNA-binding proteins: a technical and interdisciplinary challenge

RNA-binding proteins are customarily regarded as important facilitators of gene expression. In recent years, RNA–protein interactions have also emerged as a pervasive force in the regulation of homeostasis. The compendium of proteins with provable RNA-binding function has swelled from the hundreds to the thousands astride the partnership of mass spectrometry-based proteomics and RNA sequencing. At the foundation of these advances is the adaptation of RNA-centric capture methods that can extract bound protein that has been cross-linked in its native environment. These methods reveal snapshots in time displaying an extensive network of regulation and a wealth of data that can be used for both the discovery of RNA-binding function and the molecular interfaces at which these interactions occur. This review will focus on the impact of these developments on our broader perception of post-transcriptional regulation, and how the technical features of current capture methods, as applied in mammalian systems, create a challenging medium for interpretation by systems biologists and target validation by experimental researchers.
Functional roles of GRP78 in hepatitis B virus infectivity and antigen secretion

Viruses utilize cellular proteins to mediate their life cycle. However, the hepatitis B virus (HBV) life cycle is still mysterious and remains to be elucidated. Here, GRP78/BiP/HSPA5, a 78 kDa glucose‐regulated protein, was identified as a preS2 interacting protein. Pulldown assay showed the interaction of glucose‐regulated protein 78 (GRP78) with both the preS2 domain‐containing large S and middle S proteins expressed in a human hepatocellular cell line. The immunofluorescence studies revealed that the preS2 colocalized with GRP78. Interestingly, it was found that preS2 specifically bound to the ATPase domain of GRP78. To understand how GRP78 plays a role in HBV infection, stably GRP78‐expressing cells were established, which promoted HBV infectivity and replication. In contrast, knockdown of GRP78 changed the HBV antigen secretion but not the viral DNA amplification. Taken together, these results suggest that GRP78 should interact with preS2 via the ATPase domain and modulate both the HBV infectivity and HBV antigen secretion.
Endometriosis-associated ovarian carcinomas: insights into pathogenesis, diagnostics, and therapeutic targets—a narrative review

Endometriosis is a benign gynecologic condition affecting up to one woman out of ten of reproductive age. It is defined by the presence of endometrial-like tissue in localizations outside of the uterine cavity. It often causes symptoms such as chronic pain, most frequently associated with the menstrual cycle, and infertility, but may also be oligo- or asymptomatic. There is evidence that some ovarian carcinoma (OC) histotypes, mainly the ovarian clear cell (OCCC) and endometrioid (EnOC) carcinoma, may arise from endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interacting domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which frequently co-occur. In ARID1A deficient cancers preclinical experimental data suggest different targetable mechanisms including epigenetic regulation, cell cycle, genomic instability, the PI3K/AKT/mTOR pathway, inflammatory pathways, immune modulation, or metabolic alterations as potential precision oncology approaches. Most of these strategies are relying on the concept of synthetic lethality in which tumors deficient in ARID1A are more sensitive to the different compounds. Some of these approaches are currently being or have recently been investigated in early clinical trials. The remarkably frequent occurrence of these mutations in endometriosis-associated ovarian cancer, the occurrence in a relatively young population, and the high proportion of platinum-resistant disease certainly warrants further investigation of precision oncology opportunities in this population. Furthermore, advanced knowledge about oncogenic mutations involved in endometriosis-associated ovarian carcinomas may be potentially useful for early cancer detection. However, this approach may be complicated by the frequent occurrence of somatic mutations in benign endometriotic tissue as recent studies suggest. In this narrative review of the current literature, we will discuss the data available on endometriosis-associated ovarian carcinoma, with special emphasis on epidemiology, diagnosis and molecular changes that could have therapeutic implications and clinical applicability in the future.
Overall survival in stage IV EGFR mutation‑positive NSCLC: Comparing first‑, second‑ and third‑generation EGFR‑TKIs (Review).

A substantial (40‑60%) proportion of patients with non‑small cell lung carcinoma (NSCLC) have epidermal growth factor receptor (EGFR) mutations, a crucial therapeutic target in NSCLC. Treatment strategies for patients with advanced‑stage NSCLC have markedly changed, from the empirical use of cytotoxic agents to targeted regimens. EGFR tyrosine kinase inhibitors (TKIs), the first‑line therapy for advanced NSCLC, are reported to be the most effective. Although progression‑free survival (PFS) and objective response rates have long been used as endpoints, meeting these endpoints may not necessarily coincide with an increase in overall survival (OS) among patients with advanced lung cancer. Recently, the FLAURA study with the third‑generation, irreversible, oral EGFR‑TKI, osimertinib, demonstrated an extended median OS by 6.8 months compared with standard EGFR‑TKIs, with a 20% reduction in the risk of mortality [osimertinib, 38.6; EGFR‑TKIs, 31.8; hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.641‑0.997; P=0.046]; this was in addition to meeting the primary endpoint of clinically and statistically significant PFS. Osimertinib was also shown to lead to a statistically significant reduction in the risk of central nervous system disease progression (HR, 0.48; 95% CI, 0.26‑0.86; P=0.014). Notably, 28% of patients remained on osimertinib treatment for 3 years, considerably longer than those in the comparator group (9%). The duration of first subsequent treatment with osimertinib was 25.5 months compared with 13.7 months with standard EGFR‑TKIs (HR, 0.478; 95% CI, 0.393‑0.581; P<0.0001). Thus, the long‑term OS benefit with first‑line osimertinib highlights a promising option in the management of stage IV NSCLC. The present narrative review compares the OS benefit of first‑, second‑ and third‑generation EGFR‑TKIs for patients with stage IV EGFR mutation‑positive NSCLC and discusses their role in disease management.
Direct EXAFS evidence for incorporation of As5+ in the tetrahedral site of natural andraditic garnet

Abstract Exceptionally high-quality X-ray absorption spectroscopy (XAS) spectra of the As K-edge measured on a garnet from the Central Oslo Rift (Jamtveit et al. 1993) are presented and interpreted. The best fit to the extended X-ray absorption fine structure (EXAFS) spectrum indicates that arsenic occurs predominantly as As5+ in the tetrahedral Si4+ site. The first shell As-O bond lengths of 1.69 Å are identical to those observed for As5+-O in sodium arsenate and the edge position of 11872 eV is also characteristic of As5+. Determination of oxidized As within the structure places an important constraint on fluid chemistry, but perhaps even more importantly, EXAFS fitting of outer shells (As- Ca 3.07, 3.75, 5.71, 6.11 Å; As-Fe/Al 3.47, 5.35 Å; As-Si 3.88, 5.60, 5.91 Å) in this high-quality data set gives unequivocal evidence that AsO4-3 substitutes for SiO4-4 in the garnet tetrahedral site. This is, to the best of our knowledge, the first such XAS study yielding direct evidence, through outer shell fitting, for both the coordination environment and oxidation state of arsenic within (as opposed to sorbed onto) a silicate mineral.
Characterization of the interaction between two Anti-viral drugs and Egg albumin

The binding of two anti-viral drugs (1. Quercetin [Q] and 2. Amantadine [A]) to Egg albumin [EA] was investigated by fluorescence spectroscopy under simulation of physiological conditions. The quenching mechanism was suggested according to the fluorescence measurement. The Stern-Volmer quenching constants were determined. In addition, binding constants were also calculated at room temperature.
DNA methylation profile of genes involved in inflammation and autoimmunity correlates with vascular function in morbidly obese adults

ABSTRACT Obesity is a major risk factor for cardiovascular disease. Blood-detected epigenetic profiles may serve as non-invasive clinically relevant biomarkers. Therefore, we investigated DNA methylation of genes involved in inflammation in peripheral blood of obese subjects and lean controls and their correlation with cardiometabolic measurements. We obtained blood and adipose tissue (AT) samples from bariatric patients (n = 24) and control adults (n = 24). AT-isolated arterioles were tested for flow-induced dilation (FID) and production of nitric oxide (NO) and reactive oxygen species (ROS). Brachial artery flow-mediated dilation (FMD) was measured via doppler ultrasound. Promoter methylation of 94 genes involved in inflammation and autoimmunity were analysed in whole-blood DNA in relation to vascular function and cardiometabolic risk factors. 77 genes had ahigher methylated fraction in the controls compare obese subjects and 28 proinflammatory genes were significantly hypomethylated in the obese individuals; on top of these genes are CXCL1, CXCL12, CXCL6, IGF2BP2, HDAC4, IL12A, and IL17RA. Fifteen of these genes had significantly higher mRNA in obese subjects compared to controls; on top of these genes are CXCL6, TLR5, IL6ST, EGR1, IL15RA, and HDAC4. Methylation % inversely correlated with BMI, total fat %, visceral fat%, blood pressure, fasting plasma insulin, serum IL6 and C-reactive protein, arteriolar ROS, and alcohol consumption and positive correlations with lean %, HDL, plasma folate and vitamin B12, arteriolar FID and NO production, and brachial FMD. Our results suggest that vascular dysfunction in obese adults may be attributed to asystemic hypomethylation and over expression of the immune-related genes.
Does previous open or percutaneous renal stone surgery affect retrograde intrarenal surgery outcomes?

Background/aim Open or percutaneous renal stone surgery can have an adverse effect on the collecting system of the kidney. We evaluated retrograde intrarenal surgery outcomes in patients with ≤30 mm renal stones who had open or percutaneous renal stone surgery history. Materials and methods A total of 707 patients who underwent retrograde intrarenal surgery treatment were included in this study. Fifty-six patients had open or percutaneous renal stone surgery history (Group 1) and the remaining did not (Group 2, n = 651). The groups were compared in terms of age, stone size, stone-free rates, and complications. Results The mean age of the patients was 51.16 ± 14.8 and 45.95 ± 14.6 years in Groups 1 and 2, respectively (p = 0.008). The mean stone size was 14.97 ± 6.1 mm and 16.47 ± 6.9 mm in Groups 1 and 2, respectively (p = 0.107). The stone-free rates were 71.4% and 84.1% in Group 1 and 2 respectively and it was significantly higher in Group 2 (p = 0.013). The overall rate of postoperative complications was higher in Group 1 (p = 0.019), but there was no difference between the two groups in terms of Clavien 1–2 and 3–4a complication rates. Conclusion Our results showed that having a history of open or percutaneous renal stone surgery has a negative effect on the success and complication rates in retrograde intrarenal surgery. Therefore, patients should be well informed before this operation.
Improved Operational Stability of Polymer Light‐Emitting Diodes Based on Silver Nanowire Electrode Through Pre‐Bias Conditioning Treatment

For the first time, highly efficient and flexible polymer light emitting diodes (PLEDs) based on silver nanowire (AgNW) electrode, with improved operational stability by simply applying pre‐bias conditioning treatment, are demonstrated. Reverse bias conditioning performed before J–V–L measurement of the PLEDs enables the rough AgNW networks to function properly as a bottom electrode by stabilizing current characteristics, and the devices continue to show consistent operational performances. Conditions of applied bias and thicknesses of active layer are controlled for optimization and it is found that high reverse voltage is required to obtain current stabilization. Adequate thickness of polymer is also necessary to avoid breakdown induced by reverse bias. The essential effect of pre‐bias conditioning on the improved performances of PLEDs is investigated, and it is found that morphological change of AgNW networks contribute to the improvement in device performance. Some of the AgNWs that appear to be pathway of leakage current are deformed, and surface roughness (RMS) of the AgNW film is decreased while the sheet resistance of the film is maintained when the reverse bias conditioning is applied. It is also revealed that pre‐bias conditioning is independent from directionality of the applied bias when utilizing insulating polymer sandwiched between two electrodes.
Structure of the gonoduct of the viviparous teleost Cnesterodon decemmaculatus (Jenyns, 1842) (Poeciliidae)

During embryogenesis, teleost females do not develop Müllerian ducts, which form the oviducts in all other vertebrates. Thus, when they reach sexual maturity they do not have oviducts. In viviparous teleosts, the lack of oviducts means that the development of the embryos occurs as an intraovarian gestation, unique among vertebrates. The ovary is an unpaired hollow organ whose cavity is continuous with the caudal portion, the gonoduct, characterized by the absence of germinal cells, which opens to the exterior at the gonopore. The gonoduct attains essential function as a barrier between the germinal region of the ovary and the exterior during all reproductive stages. This study describes the functional morphology of the gonoduct in the viviparous teleost Cnesterodon decemmaculatus during non‐gestation (previtellogenesis and vitellogenesis) and gestation. The ovaries were processed using histological techniques and stained with hematoxylin–eosin, and periodic acid Schiff. The gonoduct has two regions: cephalic and caudal, and is formed by three histological layers, which are, from inside to the periphery: (a) tunica mucosa; (b) tunica muscularis; and (c) tunica serosa. In the cephalic region there are mucosal folds extending into the lumen and forming a structure similar to a cervix. The histology of the gonoduct indicates essential functions, that is, (a) the control of the luminal diameter in the limit to the germinal region of the ovary by the presence of a cervix; (b) during insemination the gonoduct receives the spermatozoa, may store and transport them to the germinal region; (c) the presence of melano‐macrophage centers indicates support of immunological processes, especially during gestation when these centers increase in size; (d) production of exocrine secretions; and (e) it is the birth canal, internally lined by an ciliated epithelium and surrounded by smooth musclesboth tissues supposedly supporting the birth process.