Miracle-dz/UniFAR-FTUs huggingface dataset:
Cryo-EM Structures of the Klebsiella pneumoniae AcrB Multidrug Efflux Pump

Klebsiella pneumoniae has emerged as one of the most problematic and highly antibiotic-resistant pathogens worldwide. It is the second most common causative agent involved in secondary bacterial infection in COVID-19 patients. K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae is a major concern in global public health because of the high mortality rate of this infection. ABSTRACT The continued challenges of the COVID-19 pandemic combined with the growing problem of antimicrobial-resistant bacterial infections has severely impacted global health. Specifically, the Gram-negative pathogen Klebsiella pneumoniae is one of the most prevalent causes of secondary bacterial infection in COVID-19 patients, with approximately an 83% mortality rate observed among COVID-19 patients with these bacterial coinfections. K. pneumoniae belongs to the ESKAPE group of pathogens, a group that commonly gives rise to severe infections that are often life-threatening. Recently, K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae has drawn wide public attention, as the mortality rate for this infection can be as high as 71%. The most predominant and clinically important multidrug efflux system in K. pneumoniae is the acriflavine resistance B (AcrB) multidrug efflux pump. This pump mediates resistance to different classes of structurally diverse antimicrobial agents, including quinolones, β-lactams, tetracyclines, macrolides, aminoglycosides, and chloramphenicol. We here report single-particle cryo-electron microscopy (cryo-EM) structures of K. pneumoniae AcrB, in both the absence and the presence of the antibiotic erythromycin. These structures allow us to elucidate specific pump-drug interactions and pinpoint exactly how this pump recognizes antibiotics. IMPORTANCE Klebsiella pneumoniae has emerged as one of the most problematic and highly antibiotic-resistant pathogens worldwide. It is the second most common causative agent involved in secondary bacterial infection in COVID-19 patients. K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae is a major concern in global public health because of the high mortality rate of this infection. Its drug resistance is due, in a significant part, to active efflux of these bactericides, a major mechanism that K. pneumoniae uses to resist to the action of multiple classes of antibiotics. Here, we report cryo-electron microscopy (cryo-EM) structures of the prevalent and clinically important K. pneumoniae AcrB multidrug efflux pump, in both the absence and the presence of the erythromycin antibiotic. These structures allow us to understand the action mechanism for drug recognition in this pump. Our studies will ultimately inform an era in structure-guided drug design to combat multidrug resistance in these Gram-negative pathogens.
Effects of aerobic exercise performed during pregnancy on hypertension and gestational diabetes: a systematic review and meta-analysis.

INTRODUCTION Gestational diabetes mellitus (GDM) and gestational hypertension (GH) are the most common pregnancy complications, predisposing to adverse pregnancy outcomes and being a major cause of maternal morbidity and mortality, often associated with significantly higher health risks for the mother and her offspring. The aim of this study was to systematically evaluate the effects of aerobic exercise performed during pregnancy on GDM, GH, and pregnancy outcomes. EVIDENCE ACQUISITION The databases PubMed, EMbase, Web of Science, China Knowledge Network, Wan fang, and Wipu were searched for clinical randomized controlled trials of exercise interventions on GDM, GH, and pregnancy outcomes, and data were analyzed and systematically evaluated using RevMan 5.3 according to the inclusion and exclusion criteria. EVIDENCE SYNTHESIS Meta-analysis showed that, in terms of pregnancy complications, aerobic exercise intervention reduced the incidence of maternal GDM better than the control group, with a statistically significant difference (OR=0.39, 95% CI: 0.30, 0.50, P<0.00001); aerobic exercise intervention reduced the incidence of maternal GH better than the control group, with a statistically significant difference (OR=0.38, 95% CI: 0.27, 0.54, P<0.00001). CONCLUSIONS The results in pregnancy suggest that aerobic exercise is advantageous for pregnant women, as it reduces the incidence of GDM and GH and improves the incidence of adverse pregnancy outcomes to a certain extent.
A map of D/H on Mars in the thermal infrared using EXES aboard SOFIA

On a planetary scale, the D/H ratio on Mars is a key diagnostic for understanding the past history of water on the planet; locally, it can help to constrain the sources and sinks of water vapor through the monitoring of condensation and sublimation processes. To obtain simultaneous measurements of H2O and HDO lines, we have used the Echelle Cross Echelle Spectrograph (EXES) instrument aboard the Stratospheric Observatory for Infrared Astronomy (SOFIA) facility to map the abundances of these two species over the Martian disk. High-resolution spectra (R = 6 × 104) were recorded in the 1383−1390 cm-1 range (7.2 μm) on April 08, 2014. Mars was very close to opposition and near northern summer solstice (Ls = 113°). Maps of the H2O and HDO mixing ratios were retrieved from the line depth ratios of weak H2O and HDO transitions divided by a weak CO2 line. As expected for this season, the H2O and HDO maps show a distinct enhancement toward polar regions, and their mixing ratios are consistent with previous measurements and with predictions by the global climate models, except at the north pole where the EXES values are weaker. We derive a disk-integrated D/H ratio of 6.8 (+1.6, −1.0) × 10-4. It is higher than the value in Earth’s oceans by a factor 4.4 (+1.0, −0.6). The D/H map also shows an enhancement from southern to northern latitudes, with values ranging from about 3.5 times to 6.0 times the VSMOW (Vienna standard mean ocean water) value. The D/H distribution shows a depletion over the Tharsis mountains and is consistent with observed latitudinal variations. The variations in D/H with latitude and altitude agree with the models and with the isotope fractionation expected from condensation and sublimation processes.
Comparative Study of MPPT and Parameter Estimation of PV cells

The presented work focuses on utilising machine learning techniques to accurately estimate accurate values for known and unknown parameters of the PVLIB model for solar cells and photovoltaic modules.Finding accurate model parameters of circuits for photovoltaic (PV) cells is important for a variety of tasks. An Artificial Neural Network (ANN) algorithm was employed, which outperformed other metaheuristic and machine learning algorithms in terms of computational efficiency. To validate the consistency of the data and output, the results were compared against other machine learning algorithms based on irradiance and temperature. A Bland Altman test was conducted that resulted in more than 95 percent accuracy rate. Upon validation, the ANN algorithm was utilised to estimate the parameters and their respective values.
Trac Grooming on the Path

In a WDM network, routing a request consists in assigning it a route in the physical network and a wavelength. If each request uses at most 1/C of the bandwidth of the wavelength, we will say that the grooming factor is C. That means that on a given edge of the network we can groom (group) at most C requests on the same wavelength. With this constraint the objective can be either to minimize the number of wavelengths (related to the transmission cost) or minimize the number of Add Drop Multiplexer (shortly ADM) used in the network (related to the cost of the nodes). Here we consider the case where the network is a path on N nodes, PN. Thus the routing is unique. For a given grooming factor C minimizing the number of wavelengths is an easy problem, well known and related to the load problem. But minimizing the number of ADM’s is NP-complete for a general set of requests and no results are known. Here we show how to model the problem as a graph partition problem and using tools of design theory we completely solve the case where C = 2 and where we have a static uniform all-to-all trac (requests being all pairs of vertices).
Generalized Hebbian learning for ellipse fitting

In this paper, we investigate the use of a neural network employing Genralised Hebbian Learning for the approximation of an image of a hypothetically ellipsoidal object as an ellipse. Further, we discuss how the same algorithm is used with higher dimensional data to model hyperellipsoids, with the basic aim at a specific application, namely the modelling of an object as an ellipsoid given a set of 3-dimensional points.
Demography in epidemics modelling

Classical models of epidemics by Ross and McKendrick have to be revisited in order to take into account the demography (fecundity, mortality and migration) both of host and vector populations and also the diffusion and mutation of infectious agents. The classical models are supposing the populations involved in the infectious disease to be constant during the epidemic wave, but the presently observed pandemics show that the duration of their spread during months or years imposes to take into account the host and vector population changes, and also the transient or permanent migration and diffusion of hosts (susceptible or infected), as well as those of vectors and infectious agents. One example is presented concerning the malaria in Mali.
Long-Term Health Consequences After Ovarian Removal at Benign Hysterectomy

BACKGROUND More evidence is needed to substantiate current recommendations about removing ovaries during hysterectomy for benign conditions. OBJECTIVE To compare long-term outcomes in women with and without bilateral salpingo-oophorectomy (BSO) during hysterectomy for benign conditions. DESIGN Emulated target trial using data from a population-based cohort. SETTING Women in Denmark aged 20 years or older during 1977 to 2017. PARTICIPANTS 142 985 women with hysterectomy for a benign condition, 22 974 with BSO and 120 011 without. INTERVENTION Benign hysterectomy with or without BSO. MEASUREMENTS The primary outcomes were overall hospitalization for cardiovascular disease (CVD), overall cancer incidence, and all-cause mortality through December 2018. RESULTS Compared with women without BSO, women with BSO who were younger than 45 years at surgery had a higher 10-year cumulative risk for hospitalization for CVD (risk difference [RD], 1.19 percentage points [95% CI, 0.09 to 2.43 percentage points]). Women with BSO had a higher 10-year cumulative risk for cancer for ages 45 to 54 years (RD, 0.73 percentage point [CI, 0.05 to 1.38 percentage points]), 55 to 64 years (RD, 1.92 percentage points [CI, 0.69 to 3.25 percentage points]), and 65 years or older (RD, 2.54 percentage points [CI, 0.91 to 4.25 percentage points]). Women with BSO had higher 10-year mortality in all age groups, although the differences were statistically significant only for ages 45 to 54 years (RD, 0.79 percentage point [CI, 0.27 to 1.30 percentage points]). The mortality at 20 years was inconsistent with that at 10 years in women aged 65 years or older. LIMITATION Age was a proxy for menopausal status. CONCLUSION The authors find that these results support current recommendations for conserving ovaries in premenopausal women without a high risk for ovarian cancer and suggest a cautious approach in postmenopausal women. PRIMARY FUNDING SOURCE The Danish Cancer Society's Scientific Committee and the Mermaid Project.
Approximation of the Rosenblatt process by semimartingales

ABSTRACT In this paper, we consider the optimal approximation of a Rosenblatt process based on semimartingales of the form where (y1, y2)↦a(y1, y2) is a square integrable process and B is a standard Brownian motion. We show that there exists a unique semimartingale closest to Rosenblatt process if a is deterministic.
Balloon-assisted technique for endoscopic en bloc retrieval of a large gastric gastrointestinal stromal tumor specimen

A 64-year-old woman underwent gastroscopy and abdominal computed tomography, which revealed a 4.0×3.5 cm gastric gastrointestinal stromal tumor (GIST) in the anterior wall of the stomach (▶Fig. 1 a). After full evaluation, an endoscopic full-thickness resection technique was used to achieve complete resection (▶Fig. 1b). It is very important to retrieve the complete specimen to allow for subsequent pathological evaluation; however, retrieval is difficult for specimen larger than 3.5 cm. Wu et al. successfully applied a balloon-assisted technique for removal of large esophageal foreign bodies [1]. Therefore, we applied this technique for endoscopic en bloc retrieval of a large gastric GISTspecimen (▶Video 1). After the wound had been completely sutured by clips and endoloop, attempts were made to retrieve the specimen with a snare, but passage through the cardia was impossible owing to the angle between the fundus of the stomach and the cardia. A transparent cap with a balloon, which could be expanded to a maximum outer diameter of 4.0 cm (Vedkang, Changzhou, China) was connected to the front end of the endoscope (▶Fig. 1 c). With the balloon expanded to 4.0 cm, the snare could easily drag the specimen into the esophagus. At the entrance of the esophagus, the resistance was greater, so the balloon size was reduced and the dragging force of the snare was increased to hold the transparent cap in place and prevent the balloon from slipping. Finally, the specimen was successfully removed in its entirety, and no bleeding or perforation was observed in the gastric cardia or esophageal mucosa. The specimen volume was 4.0 ×3.5 × 3.5 cm (▶Fig. 1d). Histological examination showed a GIST with low risk for disease progression and negative vertical and horizontal margins. The patient had no complications and was discharged successfully 1 week after surgery.
Imaging Approach to Portal Hypertension

Abstract Increase in portal venous pressure (termed portal hypertension) is seen in a variety of liver diseases. Imaging tests are useful to detect portal hypertension and identify its cause. Noninvasive tests like abdominal ultrasound and Doppler studies are routinely done in clinical practice for this indication. Cross-sectional studies like computed tomography and magnetic resonance imaging are especially useful to delineate morphological abnormalities in the liver. Invasive tests like assessment of hepatic venous pressure gradient are done less frequently for specific indications. Distinctive imaging findings help differentiate the different causes of portal hypertension like cirrhosis and vascular liver disorders like noncirrhotic portal hypertension, extrahepatic portal venous obstruction, and Budd–Chiari syndrome. Radiological interventions are increasingly used to treat complications of portal hypertension like refractory ascites or refractory bleeding from gastroesophageal varices.
An Assessment of the Three Popular Prognostic Scoring Systems for Chronic Myelomonocytic Leukemia (CMML) in an Indian Context

Abstract Introduction: Chronic myelomonocytic leukemia (CMML) is a rare clonal hematopoietic neoplasm with a prevalence of 1.05 to 1.94 cases per 1,00,000 population. There are multiple prognostic scoring system used in practice for CMML, which include both cytogenetic and next-generation sequencing based. Objective This study assesses the clinicohematological profile of CMML patients, along with comparison of three widely used prognostic scoring systems for CMML (CMML-specific prognostic scoring system, MD Anderson prognostic score, Mayo prognostic model). Materials and Methods : This study is an 8-year retrospective study. All relevant data had been retrieved and reviewed by the authors. Inclusion and exclusion criteria: All the cases that were diagnosed before 2016 as per 2008 criteria were reclassified, (2) all the cases that were positive for the mutations associated with myeloproliferative neoplasms were excluded, and (3) cases with more than or equal to 20% blast/blast equivalents were excluded. A univariate analysis was done followed by a multivariate analysis for all the parameters constituting each scoring system. Lastly, a receiver operating characteristic curve was plotted for all the three scoring systems. Result : There were total 23 patients, with a median age of 63 years and a male to female ratio of 2.3:1. Cytogenetic aberration and genetic mutation were observed in 6 and 3 cases, respectively. The median overall survival (OS) was 48 months and the median leukemia-free survival was 12 months. Post-multivariate analysis, the parameters with significant impact on OS were absolute monocyte count more than 10 × 10^9/L, myeloid precursors in peripheral blood, hemoglobin less than 10g/dL, platelet less than 100 × 10^9/L, hemoglobin less than 12g/dL, and absolute lymphocyte count more than 2.5 × 10^9/L. Conclusion : To summarize, we discovered CPSS to be a better prognostic tool for a setup like ours, since molecular investigations are not always readily available for each case. More such researches are needed in the near future so that we can design better prognostic tools and see for their usefulness in real life.
Combined Brillouin and Raman scattering spectroscopy in 2PP printed structures

The arising 3D printing technologies open new possibilities for the production of optical devices, e.g. of optical waveguides. Using two-photon polymerization (2PP), arbitrary three-dimensional structures with resolution below the diffraction limit can be manufactured, thus allowing for new and versatile applications in photonics. Recent demonstration of phononic metamaterials using 2PP fabrication rely on homogeneous mechanical properties of the photopolymer. Thus, the state of polymerization can be used as process parameter to develop adaptable phononic crystals. Here we demonstrate an optical setup that combines Brillouin- and Raman-scattering experiments to measure the mechanical and chemical characteristics with respect to the polymerization state.
The ASC inflammasome adapter controls the extent of peripheral protein aggregate deposition in inflammation-associated amyloidosis

ASC-containing inflammasomes form specks, extracellular aggregates which enhance the aggregation of Aβ amyloid in Alzheimer’s disease. This raises the question whether ASC participates to additional aggregation proteinopathies. Here we show that ASC controls the extent of inflammation-associated AA amyloidosis, a systemic disease caused by the aggregation of the acute-phase reactant serum amyloid A (SAA). Using superresolution microscopy, we found that ASC colocalized tightly with SAA in human AA amyloidosis. Purified recombinant ASC specks accelerated SAA fibril formation in vitro. Mass spectrometry after limited proteolysis showed that ASC interacts with SAA via its pyrin domain. In a murine model of inflammation-associated AA amyloidosis, splenic AA amyloid load was conspicuously decreased in Pycardtm1Vmd/tm1Vmd mice which lack ASC. This reduction was not a consequence of enhanced amyloid phagocytosis, as SAA stimulation increased phagocytic activity in Pycard+/+, but not in Pycard-/- macrophages. Treatment with anti-ASC antibodies decreased the amyloid loads in wild-type mice suffering from AA amyloidosis. The prevalence of natural anti-ASC IgG (-logEC50 ≥ 2) in 19,334 hospital patients was <0.01%, suggesting that anti-ASC antibody treatment modalities would not be confounded by natural autoimmunity. Higher anti-ASC titers did not correlate with any specific disease, suggesting that anti-ASC immunotherapy may be well-tolerated. These findings expand the role played by ASC to extraneural proteinopathies of humans and experimental animals and suggest that anti-ASC immunotherapy may contribute to resolving such diseases.
Arabidopsis NF-YCs interact with CRY2 and PIF4/5 to repress blue light-mediated hypocotyl growth

Plants can not move automatically, thus they have to perceive the changing environment (light, temperate and so on) by developing the adapted phenotypes. Light-induced hypocotyl length is an ideal phenotype for studying how plants response to light. So far, many signaling components in light-induced hypocotyl growth have been reported. Here, we focused on identifying transcription factors (TFs) involved in blue light-induced hypocotyl growth by constructing Arabidopsis TFs overexpressing lines and screening blue light-induced hypocotyl length. Finally, we found that three NF-YC proteins, NF-YC7, NF-YC5 and NF-YC8 (NF-YCs as short name), develop longer hypocotyls than the wild type under blue light. While deficient mutants, nf-yc5nf-yc7 and nf-yc7nf-yc8, fail to promote the hypocotyl elongation under blue light. NF-YCs physically interacted with CRY2 and PIF4/5, while the NF-YCs-PIF4/5 interactions were repressed by CRY2. Moreover, overexpression of CRY2 or deficiency of PIF4/5 repressed the hypocotyl elongation induced by NF-YC7 under blue light. Further investigation revealed that NF-YC7 increased the blue light-induced CRY2 degradation and regulated the activities of PIF4/5. Taking together, this study provided a new insight into that NF-YCs function as CRY2-and PIF4/5-interacting proteins and modulate their stabilization to repress the blue light-mediated hypocotyl growth. Author Summary Light is an essential environmental factor for plants growth and development. Plants response to light signaling by displaying short hypocotyls, green leaves, and so on. The mechanisms of light responding to light have aroused extensive attention. In this study, we clarified that NF-YC family members NF-YC5/7/8 interact with CRY2, PIF4/5 and modulate their stabilization to repress the blue light-mediated hypocotyl growth. It was the first time for reporting NF-Y family members function as CRY2-and PIF4/5-interacting proteins. Therefore, this study provides a novel understanding how plants adapt to light.