Miracle-dz/UniFAR-FTUs huggingface dataset:
The Rationale for Photobiomodulation Therapy of Vaginal Tissue for Treatment of Genitourinary Syndrome of Menopause: An Analysis of Its Mechanism of Action, and Current Clinical Outcomes

Abstract Objective: Light, particularly in the visible to far-infrared spectrum, has been applied to the female genital tract with lasers and other devices for nearly 50 years. These have included procedures on both normal and neoplastic tissues, management of condylomata, endometriosis, and menometrorrhagia, and, more recently, a number of fractional laser devices have been applied for the management of genitourinary syndrome of menopause (GSM) and stress urinary incontinence (SUI), and to achieve so-called vaginal rejuvenation. Photobiomodulation therapy (PBMT) has been proposed as an alternative for use in managing GSM and SUI. Methods: This article reviews the biological basis, symptoms, and management of GSM, and investigates the current status and rationale for the use of PBMT. Results and conclusions: Based on the preliminary evidence available, PBMT is safe and appears to be efficacious in treating GSM.
Ovarian Cancer Immunotherapy: Turning up the Heat

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies. Despite surgery and chemotherapy, 5-years survival rates have improved only modestly over the past few decades remaining at 45% for advanced stages. Therefore, novel therapies are urgently needed. The presence of tumor-infiltrating lymphocytes (TILs) in OC tumor microenvironment (TME) has already proved to be correlated with overall survival (OS), while immune evasion mechanisms are associated with poor prognosis. Although these data indicate that immunotherapy has a strong rationale in OC, single agent immune-checkpoints inhibitors (ICIs) have shown only modest results in this malignancy. In this review, we will discuss immune-targeting combination therapies and adoptive cell therapy (ACT), highlighting the challenges represented by these strategies, which aim at disrupting the stroma-tumor barrier to boost immune system against ovarian cancer.
Role of Nociceptor Toll-like Receptor 4 (TLR4) in Opioid-Induced Hyperalgesia and Hyperalgesic Priming

In addition to analgesia, opioids produce opioid-induced hyperalgesia (OIH) and neuroplasticity characterized by prolongation of inflammatory-mediator-induced hyperalgesia (hyperalgesic priming). We evaluated the hypothesis that hyperalgesia and priming induced by opioids are mediated by similar nociceptor mechanisms. In male rats, we first evaluated the role of nociceptor Toll-like receptor 4 (TLR4) in OIH and priming induced by systemic low-dose morphine (LDM, 0.03 mg/kg). Intrathecal oligodeoxynucleotide antisense to TLR4 mRNA (TLR4 AS-ODN) prevented OIH and prolongation of prostaglandin E2 hyperalgesia (priming) induced by LDM. In contrast, high-dose morphine (HDM, 3 mg/kg) increased nociceptive threshold (analgesia) and induced priming, neither of which was attenuated by TLR4 AS-ODN. Protein kinase C ε (PKCε) AS-ODN also prevented LDM-induced hyperalgesia and priming, whereas analgesia and priming induced by HDM were unaffected. Treatment with isolectin B4 (IB4)-saporin or SSP-saporin (which deplete IB4+ and peptidergic nociceptors, respectively), or their combination, prevented systemic LDM-induced hyperalgesia, but not priming. HDM-induced priming, but not analgesia, was markedly attenuated in both saporin-treated groups. In conclusion, whereas OIH and priming induced by LDM share receptor and second messenger mechanisms in common, action at TLR4 and signaling via PKCε, HDM-induced analgesia, and priming are neither TLR4 nor PKCε dependent. OIH produced by LDM is mediated by both IB4+ and peptidergic nociceptors, whereas priming is not dependent on the same population. In contrast, priming induced by HDM is mediated by both IB4+ and peptidergic nociceptors. Implications for the use of low-dose opioids combined with nonopioid analgesics and in the treatment of opioid use disorder are discussed. SIGNIFICANCE STATEMENT Opioid-induced hyperalgesia (OIH) and priming are common side effects of opioid agonists such as morphine, which acts at μ-opioid receptors. We demonstrate that OIH and priming induced by systemic low-dose morphine (LDM) share action at Toll-like receptor 4 (TLR4) and signaling via protein kinase C ε (PKCε) in common, whereas systemic high-dose morphine (HDM)-induced analgesia and priming are neither TLR4 nor PKCε dependent. OIH produced by systemic LDM is mediated by isolectin B4-positive (IB4+) and peptidergic nociceptors, whereas priming is dependent on a different class of nociceptors. Priming induced by systemic HDM is, however, mediated by both IB4+ and peptidergic nociceptors. Our findings may provide useful information for the use of low-dose opioids combined with nonopioid analgesics to treat pain and opioid use disorders.
Architecture of the nuclear pore complex symmetric core

Introduction—The nuclear pore complex (NPC) is the primary gateway for transport of macromolecules between the nucleus and cytoplasm, serving as both a critical mediator and regulator of gene expression. NPCs are enormous ~120 MDa macromolecular machines embedded in the nuclear envelope, each containing ~1000 protein subunits, termed nucleoporins. Despite substantial progress in visualizing the overall shape of the NPC by cryoelectron tomography and in determining atomic resolution crystal structures of nucleoporins, the molecular architecture of the assembled NPC remains poorly understood, hindering the design of mechanistic studies that could investigate its many roles in cell biology. Rationale—Existing cryoelectron tomographic reconstructions of the NPC remain too low in resolution to allow for de novo structure determination of the NPC or unbiased docking of nucleoporin fragment crystal structures. We sought to bridge this resolution gap by first defining the interaction network of the NPC, focusing on the evolutionarily conserved symmetric core. We developed protocols to reconstitute NPC protomers from purified, recombinant proteins, which enabled the generation of a high-resolution biochemical interaction map of the NPC symmetric core. We next determined high-resolution crystal structures of key nucleoporin interactions, providing spatial restraints for their relative orientation. Lastly, by superposing crystal structures that overlapped in sequence, we generated accurate full-length structures of the large scaffold nucleoporins. Supported by this biochemical data, we used sequential, unbiased searches to place the nucleoporin crystal structures into a previously determined cryoelectron tomographic reconstruction of the intact human NPC, thus generating a composite structure of the entire NPC symmetric core. Results—Our analysis revealed that the inner and outer rings of the NPC utilize disparate mechanisms of interaction. While the structured coat nucleoporins of the outer ring form extensive surface contacts, the scaffold proteins of the inner ring are bridged by flexible sequences in linker Correspondence: hoelz@caltech.edu (A.H.). #these authors contributed equally to this work Supplementary Materials: Materials and Methods Figs. S1–S59 Tables S1–S10 References (50–67) The authors declare no financial conflicts of interest. HHS Public Access Author manuscript Science. Author manuscript; available in PMC 2017 January 03. Published in final edited form as: Science. 2016 April 15; 352(6283): aaf1015. doi:10.1126/science.aaf1015. A uhor M anscript
Intranasal Administration of Mesenchymal Stem Cells Ameliorates the Abnormal Dopamine Transmission System and Inflammatory Reaction in the R6/2 Mouse Model of Huntington Disease

Intrastriatal administration of mesenchymal stem cells (MSCs) has shown beneficial effects in rodent models of Huntington disease (HD). However, the invasive nature of surgical procedure and its potential to trigger the host immune response may limit its clinical use. Hence, we sought to evaluate the non-invasive intranasal administration (INA) of MSC delivery as an effective alternative route in HD. GFP-expressing MSCs derived from bone marrow were intranasally administered to 4-week-old R6/2 HD transgenic mice. MSCs were detected in the olfactory bulb, midbrain and striatum five days post-delivery. Compared to phosphate-buffered saline (PBS)-treated littermates, MSC-treated R6/2 mice showed an increased survival rate and attenuated circadian activity disruption assessed by locomotor activity. MSCs increased the protein expression of DARPP-32 and tyrosine hydroxylase (TH) and downregulated gene expression of inflammatory modulators in the brain 7.5 weeks after INA. While vehicle treated R6/2 mice displayed decreased Iba1 expression and altered microglial morphology in comparison to the wild type littermates, MSCs restored both, Iba1 level and the thickness of microglial processes in the striatum of R6/2 mice. Our results demonstrate significantly ameliorated phenotypes of R6/2 mice after MSCs administration via INA, suggesting this method as an effective delivering route of cells to the brain for HD therapy.
Acute physical exercise increases APPL1/PI3K signaling in the hypothalamus of lean mice

Adiponectin is an adipokine that acts in the control of energy homeostasis. The adaptor protein containing the pleckstrin homology domain, phosphotyrosine‐binding domain, and leucine zipper motif 1 (APPL1) is a key protein in the adiponectin signaling. The APPL1 mediates a positive effect on the insulin signaling through the interaction with the phosphoinositide 3‐kinase (PI3K). Thus, the present study aimed to explore the effects of an acute physical exercise session on the hypothalamic adiponectin signaling. Firstly, using bioinformatics analysis, we found a negative correlation between hypothalamic APPL1 mRNA levels and food consumption in several strains of genetically diverse BXD mice. Also, the mice and the human database revealed a positive correlation between the levels of APPL1 mRNA and PI3K mRNA. At the molecular level, the exercised mice showed increased APPL1 and PI3K (p110) protein contents in the hypothalamus of Swiss mice. Furthermore, the exercise increases co‐localization between APPL1 and PI3K p110 predominantly in neurons of the arcuate nucleus of hypothalamus (ARC). Finally, we found an acute exercise session reduced the food intake 5 hr after the end of fasting. In conclusion, our results indicate that physical exercise reduces the food intake and increases some proteins related to adiponectin pathway in the hypothalamus of lean mice.
Impact of AM fungi and Rock-phosphate on mycorrhizal colonization, growth and nutrition of Tylophora indica (Burm. f.) Merril. under glass house conditions

An investigation was carried out on the mycorrhizal colonization, growth and nutrition of Tylophora indica ( T. indica) inoculated with Glomus fasciculatum (GF) and rock phosphate (RP) in nutrient deficient sterilized soil using earthen pots under glasshouse conditions. Significantly higher percentage of mycorrhizal colonization was recorded in the treatment where both GF and RP were present. After 45, 90, 135 and 180 days of plant growth 33.6, 52.5, 76.4 and 92.3 percent root colonization was recorded in GF+RP inoculated plants as compared to 29.2, 44.8, 63.7 and 81.9% respectively in GF alone-inoculated plants. GF and RP combination has improved plant growth, shoot and root dry weights and nutrient uptake more than in single inoculation and in uninoculated control plants.
Institutional Investors and Long-Term Investment: Evidence from Chile

Developing countries are trying to develop long-term financial markets and institutional investors are expected to play a key role. This paper uses unique evidence on the universe of institutional investors from the leading case of Chile to study to what extent mutual funds, pension funds, and insurance companies hold and bid for long-term instruments, and which factors affect their choices. The paper uses monthly asset-level portfolios to show that, despite the expectations, mutual and pension funds invest mostly in short-term assets relative to insurance companies. The significant difference across maturity structures is not driven by the supply side of debt or tactical behavior. Instead, it seems to be explained by manager incentives (related to short-run monitoring and the liability structure) that, combined with risk factors, tilt portfolios toward short-term instruments, even when long-term investing yields higher returns. Thus, the expansion of large institutional investors does not necessarily imply longer-term markets.
Numerical Study of Turbulent Flow and Convective Heat Transfer Characteristics in Helical Rectangular Ducts

Three-dimensional turbulent forced convective heat transfer and its flow characteristics in helical rectangular ducts are simulated using SST k-omega turbulence model. The velocity field and temperature field at different axial locations along the axial direction are analyzed for different inlet Reynolds numbers, different curvatures, and torsions. The causes of heat transfer differences between the inner and outer wall of the helical rectangular ducts are discussed as well as the differences between helical and straight duct. A secondary flow is generated due to the centrifugal effect between the inner and outer walls. For the present study, the flow and thermal field become periodic after the first turn. It is found that Reynolds number can enhance the overall heat transfer. Instead, torsion and curvature change the overall heat transfer slightly. But the aspect ratio of the rectangular cross section can significantly affect heat transfer coefficient.
Spatial and temporal distributions of surface mass balance between Concordia and Vostok stations, Antarctica, from combined radar and ice core data: first results and detailed error analysis

Abstract. Results from ground-penetrating radar (GPR) measurements and shallow ice cores carried out during a scientific traverse between Dome Concordia (DC) and Vostok stations are presented in order to infer both spatial and temporal characteristics of snow accumulation over the East Antarctic Plateau. Spatially continuous accumulation rates along the traverse are computed from the identification of three equally spaced radar reflections spanning about the last 600 years. Accurate dating of these internal reflection horizons (IRHs) is obtained from a depth–age relationship derived from volcanic horizons and bomb testing fallouts on a DC ice core and shows a very good consistency when tested against extra ice cores drilled along the radar profile. Accumulation rates are then inferred by accounting for density profiles down to each IRH. For the latter purpose, a careful error analysis showed that using a single and more accurate density profile along a DC core provided more reliable results than trying to include the potential spatial variability in density from extra (but less accurate) ice cores distributed along the profile. The most striking feature is an accumulation pattern that remains constant through time with persistent gradients such as a marked decrease from 26 mm w.e. yr−1 at DC to 20 mm w.e. yr−1 at the south-west end of the profile over the last 234 years on average (with a similar decrease from 25 to 19 mm w.e. yr−1 over the last 592 years). As for the time dependency, despite an overall consistency with similar measurements carried out along the main East Antarctic divides, interpreting possible trends remains difficult. Indeed, error bars in our measurements are still too large to unambiguously infer an apparent time increase in accumulation rate. For the proposed absolute values, maximum margins of error are in the range 4 mm w.e. yr−1 (last 234 years) to 2 mm w.e. yr−1 (last 592 years), a decrease with depth mainly resulting from the time-averaging when computing accumulation rates.
Angiofibroma of the Eyelid: A Rare Clinical and Histologic Variant.

A flesh-colored, supraciliary lesion of the left upper eyelid in a 47-year-old man was excised for cosmetic reasons. Histopathology and immunohistochemistry demonstrated CD34-positive benign spindle cells, factor XIIIa-positive dendritic cells, and CD163-positive histiocytes, all dispersed within a diffuse collagenous background. Prominent loose perivascular cuffs of fibroblastic cells and collagen surrounded small blood vessels. Interpreted as an angiofibroma, the histopathology bore resemblance to that of a single previously-reported forearm lesion termed a "dermal fibroma with a distinctive perivascular cell arrangement. " The lesion represents the first eyelid example of an unusual variant of angiofibroma.
Socio-economic Aspects of Goat Production in a Rural Agro-pastoral System of Uganda

A study was conducted to document the socio-economic aspects of goat production in Teso region, Uganda. Data was collected by using a questionnaire administered to 114 purposively selected goat owners. Majority (87%) of de fecto household heads were male. About 41.2% of the farmers were aged ≥51 years. The average number of goats per household was 9.2 (range 3-31). Most farmers (63.2%) owned ≤5 acres of land. Indigenous goats were mainly acquired by buying (85%) while exotic goats and their crosses were acquired from government programs (34%). Goats have a number of roles, though mainly kept as a source of cash income (98.2%), followed by socio-cultural values (69.3%). A large percentage of farmers (67%) earned ≤US $40 p.a from goat production. The biggest problem in marketing of goats was high taxation. Majority of goat owners were men (84.86%) but a few cases (average 15.14%) of women that owned goats independently were also reported. Women and children participated less in decision making, although they were responsible for many goat production related activities. In conclusion, goat production can play an important role in improving rural livelihoods. Commercialisation, especially targeting women and youths would be desirable for improved profitability of smallholder production systems.
Obinutuzumab as bridging therapy for successful manufacturing of axicabtagene ciloleucel for transformed follicular lymphoma with circulating cells

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Evaluation of GeneXpert Mycobacterium tuberculosis/Rifampin for the detection of Mycobacterium tuberculosis complex and rifampicin resistance in nonrespiratory clinical specimens

Background: The objective of this study is to assess the performance of Xpert Mycobacterium tuberculosis (MTB)/rifampin (RIF), an automated molecular test for MTB and resistance to RIF, against smear microscopy and culture method for the diagnosis of MTB infection. Methods: This is a retrospective analysis of 168 nonrespiratory patient specimens suspected of tuberculosis (TB) at TB Laboratory of Dubai Health Authority in the United Arab Emirates between September 2016 and November 2018. Each sample underwent smear microscopy, mycobacterial culture, and GeneXpert MTB/RIF test. Results: Of 168 nonrespiratory samples, 52 samples were positive by both culture and Xpert MTB/RIF, 9 samples were detected positive only by culture. Sensitivity, specificity, positive predictive value, and negative value of the Xpert MTB/RIF test were 82.69%, 100%, 100%, and 92.80%, respectively. No false positive was yielded by the Xpert MTB/RIF, and all 116 samples were true negative by Xpert MTB/RIF. The sensitivity of the Xpert MTB/RIF was 76.92% in lymph node tissue and aspirates, 66.67% in cerebrospinal fluid, 100% in gastric lavage and aspirate, 81.25% in other body fluids, 100% in pus, 85.71% in urine, and 66.67% in other tissue samples. Of 168 strains, five strains were rifampicin resistant by phenotypic and Xpert MTB/RIF and 163 were susceptible to rifampicin with culture and Xpert MTB/RIF. Conclusion: The performance of Xpert MTB/RIF assay was comparable to the gold standard culture method for identification of MTB in nonrespiratory clinical specimens. It does not replace the gold standard culture method, but it helps to achieve better sensitivity and obtain rapid results within 2 h.
Uterine Dendritic Cells Modulation by Mesenchymal Stem Cells Provides A Protective Microenvironment at The Feto-Maternal Interface: Improved Pregnancy Outcome in Abortion-Prone Mice

Objective Dendritic cells (DCs) as major regulators of the immune response in the decidua play a pivotal role in establishment and maintenance of pregnancy. Immunological disorders are considered to be the main causes of unexplained recurrent spontaneous abortions (RSAs). Recently, we reported that mesenchymal stem cells (MSCs) therapy could improve fetal survival and reduce the abortion rate in abortion-prone mice, although the precise mechanisms of this action are poorly understood. Since MSCs have been shown to exert immunomodulatory effects on the immune cells, especially DCs, this study was performed to investigate the capability of MSCs to modulate the frequency, maturation state, and phenotype of uterine DCs (uDCs) as a potential mechanism for the improvement of pregnancy outcome. Materials and Methods In this experimental study, adipose-derived MSCs were intraperitoneally administered to abortion-prone pregnant mice on the fourth day of gestation. On the day 13.5 of pregnancy, after the determination of abortion rates, the frequency, phenotype, and maturation state of uDCs were analyzed using flow cytometry. Results Our results indicated that the administration of MSCs, at the implantation window, could significantly decrease the abortion rate and besides, increase the frequency of uDCs. MSCs administration also remarkably decreased the expression of DCs maturation markers (MHC-II, CD86, and CD40) on uDCs. However, we did not find any difference in the expression of CD11b on uDCs in MSCs-treated compared to control mice. Conclusion Regarding the mutual role of uDCs in establishment of a particular immunological state required for appropriate implantation, proper maternal immune responses and development of successful pregnancy, it seems that the modulation of uDCs by MSCs could be considered as one of the main mechanisms responsible for the positive effect of MSCs on treatment of RSA.
The Solvent Boundary Potential: A New Approach for Computer Simulation of Large Systems #

The paper presents the theoretical framework for the development of a new solvent boundary method for computer simulations and its possible application to the simulation of nitric oxide synthase. Different approaches for the construction of a solvent boundary potential are reviewed and their strengths and weaknesses are discussed. A new solvent boundary potential is proposed which combines the mean field force approximation with the Green’s function approach for treating long–range electrostatic interactions, and introduces a novel strategy to treat electrostriction effects due to ions crossing the solvent boundary. Finally, a series of computational tests are devised in order to assess the validity and efficiency of the new solvent boundary potential.