Miracle-dz/UniFAR-FTUs huggingface dataset:
Gammaherpesvirus Colonization of the Spleen Requires Lytic Replication in B Cells

ABSTRACT Gammaherpesviruses infect lymphocytes and cause lymphocytic cancers. Murid herpesvirus-4 (MuHV-4), Epstein-Barr virus, and Kaposi's sarcoma-associated herpesvirus all infect B cells. Latent infection can spread by B cell recirculation and proliferation, but whether this alone achieves systemic infection is unclear. To test the need of MuHV-4 for lytic infection in B cells, we flanked its essential ORF50 lytic transactivator with loxP sites and then infected mice expressing B cell-specific Cre (CD19-Cre). The floxed virus replicated normally in Cre− mice. In CD19-Cre mice, nasal and lymph node infections were maintained; but there was little splenomegaly, and splenic virus loads remained low. Cre-mediated removal of other essential lytic genes gave a similar phenotype. CD19-Cre spleen infection by intraperitoneal virus was also impaired. Therefore, MuHV-4 had to emerge lytically from B cells to colonize the spleen. An important role for B cell lytic infection in host colonization is consistent with the large CD8+ T cell responses made to gammaherpesvirus lytic antigens during infectious mononucleosis and suggests that vaccine-induced immunity capable of suppressing B cell lytic infection might reduce long-term virus loads. IMPORTANCE Gammaherpesviruses cause B cell cancers. Most models of host colonization derive from cell cultures with continuous, virus-driven B cell proliferation. However, vaccines based on these models have worked poorly. To test whether proliferating B cells suffice for host colonization, we inactivated the capacity of MuHV-4, a gammaherpesvirus of mice, to reemerge from B cells. The modified virus was able to colonize a first wave of B cells in lymph nodes but spread poorly to B cells in secondary sites such as the spleen. Consequently, viral loads remained low. These results were consistent with virus-driven B cell proliferation exploiting normal host pathways and thus having to transfer lytically to new B cells for new proliferation. We conclude that viral lytic infection is a potential target to reduce B cell proliferation.
Functional organization of cytoplasmic portals controlling access to the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel pore

The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl− channel that apparently has evolved from an ancestral active transporter. Key to the CFTR's switch from pump to channel function may have been the appearance of one or more “lateral portals. ” Such portals connect the cytoplasm to the transmembrane channel pore, allowing a continuous pathway for the electrodiffusional movement of Cl− ions. However, these portals remain the least well-characterized part of the Cl− transport pathway; even the number of functional portals is uncertain, and if multiple portals do exist, their relative functional contributions are unknown. Here, we used patch-clamp recording to identify the contributions of positively charged amino acid side chains located in CFTR's cytoplasmic transmembrane extensions to portal function. Mutagenesis-mediated neutralization of several charged side chains reduced single-channel Cl− conductance. However, these same mutations differentially affected channel blockade by cytoplasmic suramin and Pt(NO2)42− anions. We considered and tested several models by which the contribution of these positively charged side chains to one or more independent or non-independent portals to the pore could affect Cl− conductance and interactions with blockers. Overall, our results suggest the existence of a single portal that is lined by several positively charged side chains that interact electrostatically with both Cl− and blocking anions. We further propose that mutations at other sites indirectly alter the function of this single portal. Comparison of our functional results with recent structural information on CFTR completes our picture of the overall molecular architecture of the Cl− permeation pathway.
Molecular Epidemiology of Colistin-Resistant, Carbapenemase-Producing Klebsiella pneumoniae in Serbia from 2013 to 2016

ABSTRACT Twenty-seven colistin-resistant, carbapenemase-producing Klebsiella pneumoniae isolates were identified from hospitals in Serbia. All isolates were blaCTX-M-15 positive; ST101, ST888, ST437, ST336, and ST307 were blaOXA-48 positive; and ST340 was blaNDM-1 positive. ST307 had an insertion, and ST336 had a premature stop codon in the mgrB gene. Amino acid substitutions were detected in PmrAB of isolates ST101, ST888, ST336, and ST307. The mcr-1 and mcr-2 were not detected. An increase in phoP, phoQ, and pmrK gene transcription was detected for all sequence types.
Modulation of the intestinal bile acid/farnesoid X receptor/fibroblast growth factor 15 axis improves alcoholic liver disease in mice

Alcoholic liver disease (ALD) is associated with changes in the intestinal microbiota. Functional consequences of alcohol‐associated dysbiosis are largely unknown. The aim of this study was to identify a mechanism of how changes in the intestinal microbiota contribute to ALD. Metagenomic sequencing of intestinal contents demonstrated that chronic ethanol feeding in mice is associated with an over‐representation of bacterial genomic DNA encoding choloylglycine hydrolase, which deconjugates bile acids in the intestine. Bile acid analysis confirmed an increased amount of unconjugated bile acids in the small intestine after ethanol administration. Mediated by a lower farnesoid X receptor (FXR) activity in enterocytes, lower fibroblast growth factor (FGF)‐15 protein secretion was associated with increased hepatic cytochrome P450 enzyme (Cyp)‐7a1 protein expression and circulating bile acid levels. Depletion of the commensal microbiota with nonabsorbable antibiotics attenuated hepatic Cyp7a1 expression and reduced ALD in mice, suggesting that increased bile acid synthesis is dependent on gut bacteria. To restore intestinal FXR activity, we used a pharmacological intervention with the intestine‐restricted FXR agonist fexaramine, which protected mice from ethanol‐induced liver injury. Whereas bile acid metabolism was only minimally altered, fexaramine treatment stabilized the gut barrier and significantly modulated hepatic genes involved in lipid metabolism. To link the beneficial metabolic effect to FGF15, a nontumorigenic FGF19 variant—a human FGF15 ortholog—was overexpressed in mice using adeno‐associated viruses. FGF19 treatment showed similarly beneficial metabolic effects and ameliorated alcoholic steatohepatitis. Conclusion: Taken together, alcohol‐associated metagenomic changes result in alterations of bile acid profiles. Targeted interventions improve bile acid–FXR–FGF15 signaling by modulation of hepatic Cyp7a1 and lipid metabolism, and reduce ethanol‐induced liver disease in mice. (Hepatology 2018;67:2150‐2166).
Three‐year randomized study of manual and power toothbrush effects on pre‐existing gingival recession

Abstract Aim To compare long‐term effects of brushing with an oscillating–rotating power toothbrush or an ADA reference manual toothbrush on pre‐existing gingival recession. Materials and Methods In this controlled, prospective, single‐blind, parallel‐group study, healthy subjects with pre‐existing recession were randomized and brushed with a power toothbrush (n = 55) or an ADA reference manual toothbrush (n = 54) for a 3‐year study period. Subjects were required to brush their teeth twice daily for 2 min. using a standard fluoride toothpaste. During the study, subjects were assessed for clinical attachment loss and probing pocket depths to the nearest mm at six sites per tooth by the same calibrated examiner. Gingival recession was calculated at pre‐existing sites as the difference between clinical attachment loss and probing pocket depths. Hard and soft oral tissues were examined to assess safety. Results After 35 ± 2 months, mean gingival recession did not differ significantly between groups, but was significantly reduced from baseline (p < 0.001), from 2.35 ± 0.35 mm to 1.90 ± 0.58 mm in the power and from 2.26 ± 0.31 mm to 1.81 ± 0.66 mm in the manual group. Conclusions Gingival recession in subjects with pre‐existing recession was significantly reduced after 3 years of brushing with either a power or manual toothbrush.
[Disability after stroke: a longitudinal study in moderate and severe stroke patients included in a multidisciplinary rehabilitation program].

INTRODUCTION Stroke is a recognized cause of disability among adults. However the impact that the deficits that occur after a moderate/severe stroke have on long-term disability, as well as the response of the resultant deficits to rehabilitation, are not completely understood. PATIENTS AND METHODS A total of 396 patients with a modified Rankin score >= 3 after an ischemic (n = 221) or hemorrhagic (n = 175) stroke were included in this study. All patients were assessed with cognitive, behavior, emotional, motor and functional domains. All patients were assessed at baseline and six months after inclusion in a multidisciplinary rehabilitation program. RESULTS Risk of falling (Berg Balance Scale < 45 in 83.1% of the sample at baseline and 49.5% at follow-up) and functional problems (82.8% with a Barthel Index < 75 at baseline and 53% at follow-up) were the most prevalent deficits. Emotional disturbances were those that most improved while behavioral problems were those that did less. Although global disability improved during treatment among most patients, only 11% of our patients, especially those with preserved cognitive function at baseline, could be classified as patients with mild disability at follow-up. CONCLUSIONS Stroke consequences are multidimensional. The symptoms that the stroke can cause in multiple domains, as well as the pattern of recovery are widely diverse, with prevalence of behavioral long-term disturbances.
Maintenance of Microbial Cooperation Mediated by Public Goods in Single- and Multiple-Trait Scenarios

ABSTRACT Microbes often form densely populated communities, which favor competitive and cooperative interactions. Cooperation among bacteria often occurs through the production of metabolically costly molecules produced by certain individuals that become available to other neighboring individuals; such molecules are called public goods. This type of cooperation is susceptible to exploitation, since nonproducers of a public good can benefit from it while saving the cost of its production (cheating), gaining a fitness advantage over producers (cooperators). Thus, in mixed cultures, cheaters can increase in frequency in the population, relative to cooperators. Sometimes, and as predicted by simple game-theoretic arguments, such increases in the frequency of cheaters cause loss of the cooperative traits by exhaustion of the public goods, eventually leading to a collapse of the entire population. In other cases, however, both cooperators and cheaters remain in coexistence. This raises the question of how cooperation is maintained in microbial populations. Several strategies to prevent cheating have been studied in the context of a single trait and a unique environmental constraint. In this review, we describe current knowledge on the evolutionary stability of microbial cooperation and discuss recent discoveries describing the mechanisms operating in multiple-trait and multiple-constraint settings. We conclude with a consideration of the consequences of these complex interactions, and we briefly discuss the potential role of social interactions involving multiple traits and multiple environmental constraints in the evolution of specialization and division of labor in microbes.
Architecture Design of a Memory Subsystem for Massive MIMO Baseband Processing

This brief presents an on-chip memory subsystem for massive multiple-input-multiple-output (MIMO) baseband processing at the base station. In massive MIMO systems, the required memory bandwidth and capacity are orders of magnitude higher than those used in conventional wireless systems, due to the large number of serving antennas. These are further combined with design targets on low access latency and flexibility in data organization and access modes. This brief applies and improves the concept of parallel memories to achieve the challenging design target with low hardware overhead. As a case study, a memory subsystem for 128-antenna and 16-user massive MIMO systems is evaluated using ST 28-nm technology. According to postlayout simulation results, the proposed memory subsystem provides 512-Gb/s throughput and offers 1-Mb capacity with a cost of 0.30 mm2.
Preeclampsia and scleroderma: a prospective nationwide analysis

Introduction. In a preliminary case‐control study, women with scleroderma more frequently reported having had hypertensive complications during pregnancy compared with healthy women. Material and methods. To prospectively investigate this possible association, we conducted a nation‐wide cohort analysis of a major hypertensive complication during pregnancy, namely preeclampsia, and later scleroderma. Analyses were based on Danish register‐based birth and hospital contact data on preeclampsia and scleroderma. We followed 778,758 women from time of giving birth between 1978 and 2010 to end of follow‐up, emigration, death, or scleroderma diagnosis, whichever occurred first. The association was evaluated by incidence rate ratios, obtained in Poisson regression models. Results. We report that preeclampsia is associated with a 69% significantly increased risk of later developing scleroderma. Conclusions. Though these findings do not impact clinical care directly, the association of preeclampsia with scleroderma underscores the significant relation of preeclampsia and other adverse pregnancy outcomes with later disease in women and should be included in patient counseling and education.
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.

n engl j med 373;1 nejm.org july 2, 2015 23 The authors’ full names, academic de‐ grees, and affiliations are listed in the Ap‐ pendix. Address reprint requests to Dr. Hodi at Dana–Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, or at stephen_hodi@ dfci . harvard . edu; or to Dr. Wolchok at the Department of Medi‐ cine and Ludwig Center, Memorial Sloan Kettering Cancer Center, 1275 York Ave., Box 340, New York, NY 10065, or at wolchokj@ mskcc . org.
Posıtıve effect of platelet rich fibrin on osseointegration

Background Leukocyte-platelet rich fibrin (L-PRF) is a second generation platelet concentrate clinically used to accelerate tissue healing and bone regeneration. Achieving reduced implant osseointegration time could provide immediate or early loading of implants. The aim of this study was to evaluate the L-PRF-induced osseointegration and bone-implant contact (BIC) in an experimental animal model. Material and Methods Twelve 4-month-old New Zealand white rabbits were used. Following general anesthesia, 3-5 mL of blood was obtained from the central artery in rabbit ear and L-PRF was prepared. Two implant cavities (5 mm long and 3 mm in diameter) were created in each tibia with a total of four cavities in each animal. Two of these cavities were selected and covered with PRF (test group). The remaining L-PRF was used to soak the implants placed into the L-PRF covered sockets. Other cavities were left as controls. In total, 48 implants were placed. Animals were sacrificed after two, three, or four weeks. Histological samples were obtained and peri-implant tissues were histomorphometrically evaluated for bone-to-implant contact and new bone formation. Results Histomorphometric analyses of the defects revealed that the L-PRF was detectable up to the second week. Application of L-PRF increased the rate and amount of new bone formation in the experimental group compared to the control group. Bone-to-implant contact was enhanced when the surface was pre-wetted with L-PRF (p<0.01). Conclusions The results of this study demonstrated that L-PRF application may increases amount and rate of new bone formation during the early healing period and provides a faster osseointegration around implants. Key words:Dental implants, platelet rich fibrin, osseointegration, bone regeneration, matrix for growth factors.
[Human granulocytic ehrlichiosis in Europe].

Human granulocytic ehrlichiosis is an emerging infectious disease, which is transmitted by the tick Ixodes ricinus in Europe, like other diseases: Lyme disease, tick-borne encephalitis, babesiosis. This tick lives in the forest and its hematophagic activity ranges from April to October. Flu and febrile symptoms ten days after tick bite should suggest diagnosing the disease. Disease evolution is generally favorable, even if serious complications may occur. Leukopenia, thrombocytopenia, and elevated serum transaminases are common laboratory findings. Complementary assays useful for the diagnosis are: blood smear, indirect immunofluorescence, and polymerase chain reaction. Biological diagnostic criteria are more and more accurate, with the evolution of knowledge and technique. Tetracycline treatment generally leads to clinical and biological recovery. Informing physicians and occupationally exposed people should reinforce current prevention measures against tick bites.
Heat Transfer and Thermal Radiation at a General Three-Dimensional in a Nanofluid through a Porous Medium

In this chapter, the magnetohydrodynamic effects on heat transfer and thermal radiation at a stagnation point flowing in a nanofluid containing different types of nanoparticles namely, copper (Cu), alumina (Al 2 O 3 ) and titania (TiO 2 ) through a porous medium have been investigated numerically. By using appropriate transformation for velocity and temperature into a set of non-linear coupled ordinary differential equations which are solved numerically. Numerical results are presented for velocity and temperature profiles for different parameters of the problem. Also, the effects of the pertinent parameters on the skin friction and the heat fluxes are obtained and discussed numerically and illustrated graphically.
Increased fear learning, spatial learning as well as neophobia in Rgs2−/− mice

Anxiety disorders result from a complex interplay of genetic and environmental factors such as stress. On the level of cellular signaling, regulator of G protein signaling 2 (Rgs2) has been implicated in human and rodent anxiety. However, there is limited knowledge about the role of Rgs2 in fear learning and reactivity to stress. In this study, Rgs2−/− mice showed increased fear learning, male mice displayed increased contextual and cued fear learning, while females showed selectively enhanced cued fear learning. Male Rgs2−/− mice displayed increased long‐term‐contextual fear memory, but increased cued fear extinction. Learning in spatial non‐aversive paradigms was also increased in Rgs2−/− mice. Female, but not male mice show increased spatial learning in the Barnes maze, while male mice showed enhanced place preference in the IntelliCage, rendering enhanced cognitive function non‐specific for aversive stimuli. Consistent with the previous results, Rgs2 deletion resulted in increased innate anxiety, including neophobic behavior expressed as hypolocomotion, in three different tests based on the approach‐avoidance conflict. Acute electric foot shock stress provoked hypolocomotion in several exploration‐based tests, suggesting fear generalization in both genotypes. Rgs2 deletion was associated with reduced monoaminergic neurotransmitter levels in the hippocampus and prefrontal cortex and disturbed corresponding GPCR expression of the adrenergic, serotonergic, dopaminergic and neuropeptide Y system. Taken together, Rgs2 deletion promotes improved cognitive function as well as increased anxiety‐like behavior, but has no effect on acute stress reactivity. These effects may be related to the observed disruption of the monoaminergic systems.
Concept design of robotic modules for needlescopic surgery

Abstract Background: Many minimally invasive surgical procedures and assisting robotic systems have been developed to further minimize the number and size of incisions in the body surface. This paper presents a new idea combining the advantages of modular robotic surgery, single incision laparoscopic surgery and needlescopic surgery. Material and methods: In the proposed concept, modules carrying therapeutic or diagnostic tools are inserted in the abdominal cavity from the navel as in single incision laparoscopic surgery and assembled to 3-mm needle shafts penetrating the abdominal wall. Results: A three degree-of-freedom robotic module measuring 16 mm in diameter and 51 mm in length was designed and prototyped. The performance of the three connected robotic modules was evaluated. Conclusion: A new idea of modular robotic surgery was proposed, and demonstrated by prototyping a 3-DOF robotic module. The performance of the connected robotic modules was evaluated, and the challenges and future work were summarized.
On the hydrogen bond increasing in polyethylene oxide aqueous solution induced by exposure to electromagnetic fields

The objective of the present article is to study the behaviour of Polyethylene oxide in aqueous solution exposed separately to a 50 Hz electromagnetic field (EMF) at the intensity of 1mT and to 900MHzmicrowaves at the average magnetic flux density of 16 mA/m. Fourier transform infrared spectroscopy was used to investigate the alterations of the vibration bands in PEO induced by exposures to EMFs. The 3000ÂÂ1000 cm-1 region was investigated, involving the stretching vibrations of ether band, CÂÂH symmetric-antisymmetric and wagging vibrations of methylene groups, and in particular the CÂÂOÂÂC stretching band. A decrease in intensity of symmetric and asymmetric stretching CH2 vibration bands was observed after exposures to 50 Hz EMF and MWs. The CÂÂOÂÂC stretching band around 1080 cm-1 resulted to increase in intensity after exposures. This result can be attributed to the increase of formation of the intermolecular hydrogen bonding occurred in PEO aqueous solution after exposure. In addition, an increase of the methylene wagging vibration at 1349 cm-1 band was observed in exposed sample spectra, that can be related to a decrease of the PEO crystallization process induced by exposure to EMFs, which is in well accordance with the conclusion that hydrogen bond increases in PEO aqueous solution under exposure to EMFs.
Influence of Process Parameters on Surface Roughness and Wettability of Aluminum-Matrix Materials

Super hydrophobic surface has a good application prospect in industry, agriculture and daily life. By controlling the concentration and etching time of hydrochloric acid, different rough structures were prepared on the aluminum-matrix surface, and the relationship of roughness & CA were established to explore the influence of process parameters on the surface roughness and surface wettability. It is found that the concentration and time of hydrochloric acid significantly affect the surface roughness and contact angle (CA). When the concentration of hydrochloric acid is 1.5mol/L and the etching time is 90s, the surface roughness is the best and the maximum CA is obtained. After sodium hydroxide treatment, the hierarchical structure with micro and macro scale was formed, which significantly reduced the contact area between the water droplet and the surface, and the maximum roughness and CA was achieved. The relationship between surface roughness and CA shows that the roughness can amplify the hydrophile/hydrophobicity. Therefore, a better surface of superhydrophobic surface can be obtained by increasing the surface roughness.