Miracle-dz/UniFAR-FTUs huggingface dataset:
Pneumococcal Polysaccharide Abrogates Conjugate-Induced Germinal Center Reaction and Depletes Antibody Secreting Cell Pool, Causing Hyporesponsiveness

Background Plain pneumococcal polysaccharide (PPS) booster administered during second year of life has been shown to cause hyporesponsiveness. We assessed the effects of PPS booster on splenic memory B cell responses and persistence of PPS-specific long-lived plasma cells in the bone marrow (BM). Methods Neonatal mice were primed subcutanously (s.c.) or intranasally (i.n.) with pneumococcal conjugate (Pnc1-TT) and the adjuvant LT-K63, and boosted with PPS+LT-K63 or saline 1, 2 or 3 times with 16 day intervals. Seven days after each booster, spleens were removed, germinal centers (GC), IgM+, IgG+ follicles and PPS-specific antibody secreting cells (AbSC) in spleen and BM enumerated. Results PPS booster s.c. , but not i.n. , compromised the Pnc1-TT-induced PPS-specific Abs by abrogating the Pnc1-TT-induced GC reaction and depleting PPS-specific AbSCs in spleen and limiting their homing to the BM. There was no difference in the frequency of PPS-specific AbSCs in spleen and BM between mice that received 1, 2 or 3 PPS boosters s.c. Repeated PPS+LT-K63 booster i.n. reduced the frequency of PPS-specific IgG+ AbSCs in BM. Conclusions PPS booster-induced hyporesponsiveness is caused by abrogation of conjugate-induced GC reaction and depletion of PPS-specific IgG+ AbSCs resulting in no homing of new PPS-specific long-lived plasma cells to the BM or survival. These results should be taken into account in design of vaccination schedules where polysaccharides are being considered.
Learning about learning: Mining human brain sub-network biomarkers from fMRI data

Modeling the brain as a functional network can reveal the relationship between distributed neurophysiological processes and functional interactions between brain structures. Existing literature on functional brain networks focuses mainly on a battery of network properties in “resting state” employing, for example, modularity, clustering, or path length among regions. In contrast, we seek to uncover functionally connected subnetworks that predict or correlate with cohort differences and are conserved within the subjects within a cohort. We focus on differences in both the rate of learning as well as overall performance in a sensorimotor task across subjects and develop a principled approach for the discovery of discriminative subgraphs of functional connectivity based on imaging acquired during practice. We discover two statistically significant subgraph regions: one involving multiple regions in the visual cortex and another involving the parietal operculum and planum temporale. High functional coherence in the former characterizes sessions in which subjects take longer to perform the task, while high coherence in the latter is associated with high learning rate (performance improvement across trials). Our proposed methodology is general, in that it can be applied to other cognitive tasks, to study learning or to differentiate between healthy patients and patients with neurological disorders, by revealing the salient interactions among brain regions associated with the observed global state. The discovery of such significant discriminative subgraphs promises a better data-driven understanding of the dynamic brain processes associated with high-level cognitive functions.
Pharmacokinetics and Disposition of Circulating Iridoids and Organic Acids in Rats Intravenously Receiving ReDuNing Injection

ReDuNing injection, prepared from a combination of Gardenia Jasminoides fruits, Lonicera japonica flower buds, and the Artemisia annua aerial part, is extensively used for treatment of viral upper respiratory tract infections in China. Iridoids, organic acids, and flavonoids are likely important compounds of the herbal injection because of their reported pharmacological properties. This study was designed to characterize pharmacokinetics and disposition of the major circulating herbal compounds in rats that received the injection intravenously. ReDuNing injection was found to contain 19 iridoids (content levels 0.01–27.93 mM), 16 organic acids (0.04–19.06 mM), and 11 flavonoids (<0.08 mM). After dosing the injection, the iridoids geniposide, secologanic acid, secoxyloganin, genipin-1-β-gentiobioside, geniposidic acid, sweroside, and shanzhiside and the organic acids chlorogenic acid, quinic acid, cryptochlorogenic acid, and neochlorogenic acid were found to be the major circulating compounds, with mean elimination half-lives of 0.2–0.9 hour; the other plasma compounds were at low exposure levels. These major circulating compounds exhibited small apparent volumes of distribution (0.03–0.34 l/kg). Most of the iridoids were eliminated predominantly via renal excretion of the unchanged compounds, whereas the organic acids were eliminated via methylation and sulfation and were excreted into urine as the unchanged and metabolized compounds. The methylated metabolites also underwent subsequent conjugations before hepatobiliary and renal excretion. In vitro data suggested that the metabolism of the organic acids in rats also occurred in humans. The current pharmacokinetic research could serve as a crucial step in identifying the chemical basis responsible for the therapeutic action of ReDuNing injection.
Flavokawain A Induces Apoptosis in MCF-7 and MDA-MB231 and Inhibits the Metastatic Process In Vitro

Introduction The kava-kava plant (Piper methsyticum) is traditionally known as the pacific elixir by the pacific islanders for its role in a wide range of biological activities. The extract of the roots of this plant contains a variety of interesting molecules including Flavokawain A and this molecule is known to have anti-cancer properties. Breast cancer is still one of the leading diagnosed cancers in women today. The metastatic process is also very pertinent in the progression of tumorigenesis. Methods MCF-7 and MDA-MB231 cells were treated with several concentrations of FKA. The apoptotic analysis was done through the MTT assay, BrdU assay, Annexin V analysis, cell cycle analysis, JC-1 mitochondrial dye, AO/PI dual staining, caspase 8/9 fluorometric assay, quantitative real time PCR and western blot. For the metastatic assays, the in vitro scratch assay, trans-well migration/invasion assay, HUVEC tube formation assay, ex vivo rat aortic ring assay, quantitative real time PCR and western blot were employed. Results We have investigated the effects of FKA on the apoptotic and metastatic process in two breast cancer cell lines. FKA induces apoptosis in both MCF-7 and MDA-MB231 in a dose dependent manner through the intrinsic mitochondrial pathway. Additionally, FKA selectively induces a G2/M arrest in the cell cycle machinery of MDA-MB231 and G1 arrest in MCF-7. This suggests that FKA's anti-cancer activity is dependent on the p53 status. Moreover, FKA also halted the migration and invasion process in MDA-MB231. The similar effects can be seen in the inhibition of the angiogenesis process as well. Conclusions FKA managed to induce apoptosis and inhibit the metastatic process in two breast cancer cell lines, in vitro. Overall, FKA may serve as a promising candidate in the search of a new anti-cancer drug especially in halting the metastatic process but further in vivo evidence is needed.
Ectoparasite community structure on three closely related seabird hosts: a multiscale approach combining ecological and genetic data

Parasite communities can be structured at different spatial scales depending on the level of organization of the hosts; hence, examining this structure should be a multiscale process. We investigated ectoparasite community structure in three closely related seabird hosts, the Mediterranean Cory's shearwater Calonectris diomedea diomedea, the Atlantic Cory's shearwater C. d. borealis and the Cape Verde shearwater C. edwardsii. This community was composed of three lice (Halipeurus abnormis, Austromenopon echinatum and Saemundssonia peusi) and one flea species (Xenopsylla gratiosa), and was considered at the infra-, component and regional community levels. We examined temporal and spatial structuring of the infracommunities, the influence of host aggregation and body condition on the component community, and the effect of genetic and geographic connectivity among host populations on the regional community. Ectoparasite infracommunities showed substantial species overlaps in temporal patterns of abundance, but species were spatially segregated within the host body. Within component communities, all ectoparasite species showed an aggregated distribution in abundance. However, aggregation patterns and their relationships with the spatial distribution of hosts within the breeding colony differed among ectoparasite species, mainly reflecting ecological differences between fleas and lice. At the regional scale, similarity in ectoparasite communities correlated with geographic distances among host colonies, but not with genetic distances. This result suggests differences in climate and habitat characteristics among host localities as a major determinant of regional communities, rather than host connectivity. Taken together, our results highlight the importance of the geographic distribution of host breeding colonies and the spatial segregation within the host body as key factors in determining ectoparasite community structure in Calonectris shearwaters.
RESTRICTION ANALYSIS OF THE RIBOSOMAL DNA INTERNAL TRANSCRIBED SPACER REGION OF CULEX RESTUANS AND MOSQUITOES IN THE CULEX PIPIENS COMPLEX

Members of the Culex pipiens Linn. complex in the eastern, southern, and central United States are the primary vectors of St. Louis encephalitis virus. Although species and subspecies in the complex can be identified as 4th-instar larvae and by characters on the male genitalia, adult females cannot be identified accurately. In this study a ribosomal DNA (rDNA) segment that includes the internal transcribed spacer region (ITS) was amplified from Culex pipiens pipiens Linn. , Culex quinquefasciatus Say, and Culex restuans Theobald. The DNA was amplified from single abdomens or single legs. The amplified rDNA segment from C.r. restuans is 90 base pairs smaller than those from members of the Cx. pipiens complex. Ribosomal DNA was amplified separately from 3 individuals for each population of Cx. pipiens and analyzed by restriction digestion. Intrapopulation variation is seen, because for each population, bands are present that are common to all 3 individuals within the population, but are also unique to that population. These results indicate that this method may provide a means for distinguishing among the mosquitoes in the Cx. pipiens complex.
Effectiveness of an Educational Intervention to Increase Human Papillomavirus Knowledge in High-Risk Minority Women

Objectives The aims of the study were to evaluate human papillomavirus (HPV) and cervical cancer knowledge in a population at high risk for cervical cancer and to determine whether knowledge and attitudes toward HPV vaccination improve after educational intervention. Materials and Methods This pre-post survey design study was conducted at the John H. Stroger Hospital of Cook County colposcopy clinic. An HPV knowledge and awareness survey was given to participants before their clinical encounter. Afterward, participants watched an educational video and repeated the survey, which was administered again at the follow-up visit. Knowledge scores and acceptability of HPV vaccination were compared across all surveys. Results Among the 104 participants who completed baseline and immediate postintervention surveys, the average baseline score was 9.6 of 20. Knowledge scores improved after the educational intervention (mean = 14.1, p < .0001) and remained elevated in the 44 participants that completed long-term follow-up (mean = 13.5, p < .0001). Acceptability of HPV vaccination for participants themselves increased from 47.1% to 76% (p < .0001) and for children/grandchildren increased from 30.8% to 71.2% (p < .0001) after the intervention. Overall, women were worried about HPV and cervical cancer for themselves and their children/grandchildren at baseline. However, the intervention improved perceptions about HPV vaccination cost, safety, adverse effects, and efficacy. Conclusions Knowledge of HPV, cervical cancer, and HPV vaccination is low in this high-risk population and may improve with a simple educational intervention. Increased knowledge was associated with an increase in vaccine acceptability and improved perceptions about HPV vaccination. Educational interventions targeted toward high-risk women are necessary to decrease cervical cancer incidence and mortality.
Toward precision medicine for preserving fertility in cancer patients: existing and emerging fertility preservation options for women

As the number of young cancer survivors increases, quality of life after cancer treatment is becoming an ever more important consideration. According to a report from the American Cancer Society, approximately 810,170 women were diagnosed with cancer in 2015 in the United States. Among female cancer survivors, 1 in 250 are of reproductive age. Anticancer therapies can result in infertility or sterility and can have long-term negative effects on bone health, cardiovascular health as a result of reproductive endocrine function. Fertility preservation has been identified by many young patients diagnosed with cancer as second only to survival in terms of importance. The development of fertility preservation technologies aims to help patients diagnosed with cancer to preserve or protect their fertility prior to exposure to chemo- or radiation therapy, thus improving their chances of having a family and enhancing their quality of life as a cancer survivor. Currently, sperm, egg, and embryo banking are standard of care for preserving fertility for reproductive-age cancer patients; ovarian tissue cryopreservation is still considered experimental. Adoption and surrogate may also need to be considered. All patients should receive information about the fertility risks associated with their cancer treatment and the fertility preservation options available in a timely manner, whether or not they decide to ultimately pursue fertility preservation. Because of the ever expanding number of options for treating cancer and preserving fertility, there is now an opportunity to take a precision medicine approach to informing patients about the fertility risks associated with their cancer treatment and the fertility preservation options that are available to them.
Activation of wild-type p53 by MDM2 inhibitors: a new strategy for lymphoma treatment

The tumor suppressor TP53 is frequently mutated or inactivated in human cancers. Mutations of TP53 are less common in lymphomas than in other tumors, but the protein is often inhibited by the overexpression of its main regulator - MDM2. In the past 10 years, major efforts have been made to develop drugs that can reactivate p53 and restore its functions. This review focuses on recent advances in the development of small inhibitors of MDM2, which are potentially relevant for the treatment of B- and T-cell lymphomas. We will describe the current state of development of these drugs and discuss their mechanism of action in these hematological malignancies.
Heterochromatin Domains: Uncoupling Epigenetic Modifications and Chromatin Structural Parameters

The mammalian genome is organized into silenced and active domains, which are constituted by chromatin fibres. The fibres are comprised of nucleosome subunits in which nearly two turns of DNA wrap around a histone protein core. This first order of DNA structure is known as the 10 nm chromatin fibre. Almost since the discovery of the nucleosome our widely accepted paradigm of genome regulation has included higher orders of chromatin organization based on the coiling or folding of the 10 nm chromatin fibre into the 30 nm chromatin fibre. These 30 nm chromatin fibres could occlude activating factors, thereby preventing transcription of genomic domains. Thus, the transition between the euchromatin “open” 10 nm and the heterochromatin “closed” 30 nm chromatin fibre would ultimately dictate genome activation and silencing. Additionally, these 30 nm fibres were thought to be further condensed into large structural heterochromatin domains defined biochemically by specific post-translational modifications of their nucleosomes’ core histones.
Work Hardening and Microstructural Effect during Dynamic Deformation of Polycrystalline Copper

Dynamic deformation of metals in the elevated strain rate interval of elastic-plastic wave propagation is relevant to technological conditions, such as structural response to impact, ballistic effects, and metal forming processes. In the present work, the work hardening of quasi-static and dynamically deformed copper using a split pressure bar was evaluated for two different grain sizes. From slip lines observations in conditions of both dynamic and quasi-static strain rates, as well as an insensitivity to grain size of the yield stress, it is suggested that copper behave like a single crystal under dynamic deformation. It is shown, for the first time, that the work hardening rate during dynamic deformation of polycrystalline copper remains higher up to the fracture.
Early childhood caries--a review.

UNLABELLED Early childhood caries (ECC) is rampant caries of the primary dentition of infants and toddlers. It represents a serious problem in dentistry as it progresses rapidly and affects young children. There is a need to identify risk factors for ECC so that targeted, cost-effective interventions can be designed. The literature indicates that immediate intervention is necessary to prevent further dental destruction, as well as more widespread health problems. CLINICAL RELEVANCE Currently, some 4 out of 10 children starting school have decay in their primary dentition. It is prudent for dentists who diagnose ECC to provide therapy or, if treatment is not possible as a result of the young age of the child and limited co-operation, then it is important to refer the patient to an appropriately trained individual for therapy.
Elevated ACKR2 expression is a common feature of inflammatory arthropathies

Abstract Objectives Chemokines are essential contributors to leucocyte accumulation at sites of inflammatory pathology. Interfering with chemokine or chemokine receptor function therefore represents a plausible therapeutic option. However, our currently limited understanding of chemokine orchestration of inflammatory responses means that such therapies have not yet been fully developed. We have a particular interest in the family of atypical chemokine receptors that fine-tune, or resolve, chemokine-driven responses. In particular we are interested in atypical chemokine receptor 2 (ACKR2), which is a scavenging receptor for inflammatory CC-chemokines and that therefore helps to resolve in vivo inflammatory responses. The objective of the current study was to examine ACKR2 expression in common arthropathies. Methods ACKR2 expression was measured by a combination of qPCR and immuno-histochemistry. In addition, circulating cytokine and chemokine levels in patient plasma were assessed using multiplexing approaches. Results Expression of ACKR2 was elevated on peripheral blood cells as well as on leucocytes and stromal cells in synovial tissue. Expression on peripheral blood leucocytes correlated with, and could be regulated by, circulating cytokines with particularly strong associations being seen with IL-6 and hepatocyte growth factor. In addition, expression within the synovium was coincident with aggregates of lymphocytes, potentially atopic follicles and sites of high inflammatory chemokine expression. Similarly increased levels of ACKR2 have been reported in psoriasis and SSc. Conclusion Our data clearly show increased ACKR2 in a variety of arthropathies and taking into account our, and others’, previous data we now propose that elevated ACKR2 expression is a common feature of inflammatory pathologies.
Role of PIN1 on in vivo periodontal tissue and in vitro cells

BACKGROUND Although expression of peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) was reported in bone tissue, the precise role of PIN1 in periodontal tissue and cells remain unclear. MATERIAL & METHODS To elucidate the roles of PIN1 in periodontal tissue, its expression in periodontal tissue and cells, and effects on in vitro 4 osteoblast differentiation and the underlying signaling mechanisms were evaluated. RESULTS PIN1 was expressed in mouse periodontal tissues including periodontal ligament cells (PDLCs), cementoblasts and osteoblasts at the developing root formation stage (postnatal, PN14) and functional stage of tooth (PN28). Treatment of PIN1 inhibitor juglone, and gene silencing by RNA interference promoted osteoblast differentiation in PDLCs and cementoblasts, whereas the overexpression of PIN1 inhibited. Moreover, osteogenic medium-induced activation of AMPK, mTOR, Akt, ERK, p38 and NF-jB pathways were enhanced by PIN1 siRNA, but attenuated by PIN1 overexpression. Runx2 expressions were induced by PIN1 siRNA, but downregulated by PIN1 overexpression. CONCLUSION In summary, this study is the first to demonstrate that PIN1 is expressed in developing periodontal tissue, and in vitro PDLCs and cementoblasts. PIN1 inhibition stimulates osteoblast differentiation, and thus may play an important role in periodontal regeneration.
Single-Image Distance Measurement by a Smart Mobile Device

Existing distance measurement methods either require multiple images and special photographing poses or only measure the height with a special view configuration. We propose a novel image-based method that can measure various types of distance from single image captured by a smart mobile device. The embedded accelerometer is used to determine the view orientation of the device. Consequently, pixels can be back-projected to the ground, thanks to the efficient calibration method using two known distances. Then the distance in pixel is transformed to a real distance in centimeter with a linear model parameterized by the magnification ratio. Various types of distance specified in the image can be computed accordingly. Experimental results demonstrate the effectiveness of the proposed method.
Surface Orchestration of Gold Nanoparticles Using Cysteamine as Linker and Folate as Navigating Molecule for Synaphic Delivery of Doxorubicin

We report synthesis, characteristics and in vitro tests of folate-conjugated gold nanoparticles (AuNPs) and doxorubicin, having Cysteamine as linker. AuNPs were chemically synthesized using sodium citrate. Characterization was done using UV-visible absorption spectroscopy, Field Emission Gun Scanning Electron Microscopy (FEG-SEM), Fourier Transform Infra Red (FTIR) spectroscopy, Particle size Analyzer. Charge distribution was studied by recording Zeta potential. AuNPs were used for attaching folic acid through a linker cysteamine-HCl and finally preparing AuNP/Cysteamine-HCl/Folic acid/Doxorubicin complex. The cell cytotoxicity was studied in MDCK cells (normal cells) and HeLa cells (cancerous cells) having high level of folate receptor expression. In-vitro drug release kinetics was calculated using standard statistical models and was found to follow Hixson-Crowell drug release kinetics model.