Deep learning reconstruction for zero echo time lung magnetic resonance imaging: impact on image quality and lesion detection.

AIMS: This study aimed to examine the impact of deep-learning reconstruction (DLR) on zero echo time (ZTE) lung MRI. MATERIALS AND METHODS: Fifty-nine patients who underwent both chest CT and ZTE lung magnetic resonance imaging (MRI) were enrolled. Noise reduction in ZTE lung MRI was compared using various DLR intensities (DLR-M, DLR-H) and conventional image filtering techniques (NF1 âˆ¼ NF4). The normalized noise power spectrum (NPS) was analysed through phantom experiments. Image sharpness was evaluated using a blur metric. We compared subjective image quality and the detection of sub-centimetre nodules and emphysema between the original and noise-reduced images. Statistical analyses included the Wilcoxon signed-rank and McNemar's tests, with inter-reader agreement assessed via Kappa coefficients. RESULTS: NPS peaks were lower in NF1 through NF4, DLR-M, and DLR-H compared to the original images. While the average spatial frequency of the NPS shifted towards lower frequencies with increasing NF levels, it remained unchanged with DLR. Blur metric values of NF1∼NF4 were significantly higher than those of the original images (p<0.008). However, there were no significant differences in blur metric values between DLR-M, DLR-H, and the original images. Image quality was rated highest for DLR-H, with a statistically significant improvement over the original (p<0.05). DLR-H showed higher diagnostic confidence for detecting sub-centimetre nodules than the original images. DLR-H showed higher diagnostic performance than the original for detecting emphysema. CONCLUSIONS: DLR can improve ZTE lung MRI quality while preserving image texture and sharpness, thereby enhancing the potential of ZTE for evaluating pulmonary parenchymal disease.

The nucleus acts as a ruler tailoring cell responses to spatial constraints.

The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. In this study, we found that cells measure the degree of spatial confinement by using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope. This activates signaling to the actomyosin cortex via nuclear envelope stretch-sensitive proteins, up-regulating cell contractility. We established that the tailored contractile response constitutes a nuclear ruler-based signaling pathway involved in migratory cell behaviors. Cells rely on the nuclear ruler to modulate the motive force that enables their passage through restrictive pores in complex three-dimensional environments, a process relevant to cancer cell invasion, immune responses, and embryonic development.

The human lung mucosa drives differential Mycobacterium tuberculosis infection outcome in the alveolar epithelium.

Mycobacterium tuberculosis (M.tb) is deposited into the alveolus where it first encounters the alveolar lining fluid (ALF) prior contacts host cells. We demonstrated that M.tb-exposure to human ALF alters its cell surface, driving better M.tb infection control by professional phagocytes. Contrary to these findings, our results with non-professional phagocytes alveolar epithelial cells (ATs) define two distinct subsets of human ALFs; where M.tb exposure to Low (L)-ALF or High(H)-ALF results in low or high intracellular bacterial growth rates in ATs, respectively. H-ALF exposed-M.tb growth within ATs was independent of M.tb-uptake, M.tb-trafficking, and M.tb-infection induced cytotoxicity; however, it was associated with enhanced bacterial replication within LAMP-1+/ABCA1+ compartments. H-ALF exposed-M.tb infection of ATs decreased AT immune mediator production, decreased AT surface adhesion expression, and downregulated macrophage inflammatory responses. Composition analysis of H-ALF vs. L-ALF showed H-ALF with higher protein tyrosine nitration and less functional ALF-innate proteins important in M.tb pathogenesis. Replenishment of H-ALF with functional ALF-innate proteins reversed the H-ALF-M.tb growth rate to the levels observed for L-ALF-M.tb. These results indicate that dysfunctionality of innate proteins in the H-ALF phenotype promotes M.tb replication within ATs, while limiting inflammation and phagocyte activation, thus potentiating ATs as a reservoir for M.tb replication and survival.

Network approach identifies Pacer as an autophagy protein involved in ALS pathogenesis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a multifactorial fatal motoneuron disease without a cure. Ten percent of ALS cases can be pointed to a clear genetic cause, while the remaining 90% is classified as sporadic. Our study was aimed to uncover new connections within the ALS network through a bioinformatic approach, by which we identified C13orf18, recently named Pacer, as a new component of the autophagic machinery and potentially involved in ALS pathogenesis. METHODS: Initially, we identified Pacer using a network-based bioinformatic analysis. Expression of Pacer was then investigated in vivo using spinal cord tissue from two ALS mouse models (SOD1G93A and TDP43A315T) and sporadic ALS patients. Mechanistic studies were performed in cell culture using the mouse motoneuron cell line NSC34. Loss of function of Pacer was achieved by knockdown using short-hairpin constructs. The effect of Pacer repression was investigated in the context of autophagy, SOD1 aggregation, and neuronal death. RESULTS: Using an unbiased network-based approach, we integrated all available ALS data to identify new functional interactions involved in ALS pathogenesis. We found that Pacer associates to an ALS-specific subnetwork composed of components of the autophagy pathway, one of the main cellular processes affected in the disease. Interestingly, we found that Pacer levels are significantly reduced in spinal cord tissue from sporadic ALS patients and in tissues from two ALS mouse models. In vitro, Pacer deficiency lead to impaired autophagy and accumulation of ALS-associated protein aggregates, which correlated with the induction of cell death. CONCLUSIONS: This study, therefore, identifies Pacer as a new regulator of proteostasis associated with ALS pathology.

Rafting behaviour of seabirds as a proxy to describe surface ocean currents in the Balearic Sea.

Spatio-temporal variability of surface geostrophic mesoscale currents in the Balearic Sea (western Mediterranean) is characterized from satellite altimetry in combination with in-situ velocity measurements collected, among others, by drifting buoys, gliders and high-frequency radar. Here, we explore the use of tracking data from living organisms in the Balearic Sea as an alternative way to acquire in-situ velocity measurements. Specifically, we use GPS-tracks of resting Scopoli's shearwaters Calonectris diomedea, that act as passive drifters, and compare them with satellite-derived velocity patterns. Results suggest that animal-borne GPS data can be used to identify rafting behaviour outside of the breeding colonies and, furthermore, as a proxy to describe local sea surface currents. Four rafting patterns were identified according to the prevailing driving forces responsible for the observed trajectories. We find that 76% of the bird trajectories are associated with the combined effects of slippage and Ekman drift and/or surface drag; 59% are directly driven by the sea surface currents. Shearwaters are therefore likely to be passively transported by these driving forces while resting. The tracks are generally consistent with the mesoscale features observed in satellite data and identified with eddy-tracking software.

Mycobacterium tuberculosis cell wall released fragments by the action of the human lung mucosa modulate macrophages to control infection in an IL-10-dependent manner.

Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis, is a major public health challenge facing the world. During infection, M.tb is deposited in the lung alveolar space where it comes in contact with the lung mucosa, known as alveolar lining fluid (ALF), an environment that M.tb encounters at different stages of the infection and disease. ALF is abundant in homeostatic and antimicrobial hydrolytic enzymes, also known as hydrolases. Here we demonstrate that ALF hydrolases, at their physiological concentrations and upon contact with M.tb, release M.tb cell envelope fragments into the milieu. These released fragments are bioactive, but non-cytotoxic, regulate the function of macrophages, and thus are capable of modulating the immune response contributing to the control of M.tb infection by human macrophages. Specifically, macrophages exposed to fragments derived from the exposure of M.tb to ALF were able to control the infection primarily by increasing phagosome-lysosome fusion and acidification events. This enhanced control was found to be dependent on fragment-induced interleukin-10 (IL-10) production but also involves the STAT3 signaling pathway in an IL-10-independent manner. Collectively our data indicate that M.tb fragments released upon contact with lung mucosa hydrolases participate in the host immune response to M.tb infection through innate immune modulation.

Improved Search for a Light Sterile Neutrino with the Full Configuration of the Daya Bay Experiment.

This Letter reports an improved search for light sterile neutrino mixing in the electron antineutrino disappearance channel with the full configuration of the Daya Bay Reactor Neutrino Experiment. With an additional 404 days of data collected in eight antineutrino detectors, this search benefits from 3.6 times the statistics available to the previous publication, as well as from improvements in energy calibration and background reduction. A relative comparison of the rate and energy spectrum of reactor antineutrinos in the three experimental halls yields no evidence of sterile neutrino mixing in the 2×10^{-4}≲|Δm_{41}^{2}|≲0.3 eV^{2} mass range. The resulting limits on sin^{2}2θ_{14} are improved by approx imately a factor of 2 over previous results and constitute the most stringent constraints to date in the |Δm_{41}^{2}|≲0.2 eV^{2} region.

Limits on Active to Sterile Neutrino Oscillations from Disappearance Searches in the MINOS, Daya Bay, and Bugey-3 Experiments.

Searches for a light sterile neutrino have been performed independently by the MINOS and the Daya Bay experiments using the muon (anti)neutrino and electron antineutrino disappearance channels, respectively. In this Letter, results from both experiments are combined with those from the Bugey-3 reactor neutrino experiment to constrain oscillations into light sterile neutrinos. The three experiments are sensitive to complementary regions of parameter space, enabling the combined analysis to probe regions allowed by the Liquid Scintillator Neutrino Detector (LSND) and MiniBooNE experiments in a minimally extended four-neutrino flavor framework. Stringent limits on sin^{2}2θ_{µe} are set over 6 orders of magnitude in the sterile mass-squared splitting Δm_{41}^{2}. The sterile-neutrino mixing phase space allowed by the LSND and MiniBooNE experiments is excluded for Δm_{41}^{2}<0.8 eV^{2} at 95% CL_{s}.

Measurement of the Reactor Antineutrino Flux and Spectrum at Daya Bay.

This Letter reports a measurement of the flux and energy spectrum of electron antineutrinos from six 2.9 GWth nuclear reactors with six detectors deployed in two near (effective baselines 512 and 561 m) and one far (1579 m) underground experimental halls in the Daya Bay experiment. Using 217 days of data, 296 721 and 41 589 inverse ß decay (IBD) candidates were detected in the near and far halls, respectively. The measured IBD yield is (1.55±0.04) ×10(-18) cm(2) GW(-1) day(-1) or (5.92±0.14) ×10(-43) cm(2) fission(-1). This flux measurement is consistent with previous short-baseline reactor antineutrino experiments and is 0.946±0.022 (0.991±0.023) relative to the flux predicted with the Huber-Mueller (ILL-Vogel) fissile antineutrino model. The measured IBD positron energy spectrum deviates from both spectral predictions by more than 2σ over the full energy range with a local significance of up to ∼4σ between 4-6 MeV. A reactor antineutrino spectrum of IBD reactions is extracted from the measured positron energy spectrum for model-independent predictions.

New measurement of antineutrino oscillation with the full detector configuration at Daya Bay.

We report a new measurement of electron antineutrino disappearance using the fully constructed Daya Bay Reactor Neutrino Experiment. The final two of eight antineutrino detectors were installed in the summer of 2012. Including the 404 days of data collected from October 2012 to November 2013 resulted in a total exposure of 6.9×10^{5} GW_{th} ton days, a 3.6 times increase over our previous results. Improvements in energy calibration limited variations between detectors to 0.2%. Removal of six ^{241}Am-^{13}C radioactive calibration sources reduced the background by a factor of 2 for the detectors in the experimental hall furthest from the reactors. Direct prediction of the antineutrino signal in the far detectors based on the measurements in the near detectors explicitly minimized the dependence of the measurement on models of reactor antineutrino emission. The uncertainties in our estimates of sin^{2}2θ_{13} and |Δm_{ee}^{2}| were halved as a result of these improvements. An analysis of the relative antineutrino rates and energy spectra between detectors gave sin^{2}2θ_{13}=0.084±0.005 and |Δm_{ee}^{2}|=(2.42±0.11)×10^{-3} eV^{2} in the three-neutrino framework.

Search for a light sterile neutrino at Daya Bay.

A search for light sterile neutrino mixing was performed with the first 217 days of data from the Daya Bay Reactor Antineutrino Experiment. The experiment's unique configuration of multiple baselines from six 2.9 GW(th) nuclear reactors to six antineutrino detectors deployed in two near (effective baselines 512 m and 561 m) and one far (1579 m) underground experimental halls makes it possible to test for oscillations to a fourth (sterile) neutrino in the 10(-3) eV(2)<|Δm(41)(2) |< 0.3 eV(2) range. The relative spectral distortion due to the disappearance of electron antineutrinos was found to be consistent with that of the three-flavor oscillation model. The derived limits on sin(2) 2θ(14) cover the 10(-3) eV(2) ≲ |Δm(41)(2)| ≲ 0.1 eV(2) region, which was largely unexplored.

[Possible denosumab-induced jaw osteonecrosis in the treatment of osteoporosis. A case report]. / Posible osteonecrosis mandibular inducida por denosumab en el tratamiento de la osteoporosis. A propósito de un caso.

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Spectral measurement of electron antineutrino oscillation amplitude and frequency at Daya Bay.

A measurement of the energy dependence of antineutrino disappearance at the Daya Bay reactor neutrino experiment is reported. Electron antineutrinos (ν¯(e)) from six 2.9 GW(th) reactors were detected with six detectors deployed in two near (effective baselines 512 and 561 m) and one far (1579 m) underground experimental halls. Using 217 days of data, 41 589 (203 809 and 92 912) antineutrino candidates were detected in the far hall (near halls). An improved measurement of the oscillation amplitude sin(2)2θ(13)=0.090(-0.009)(+0.008) and the first direct measurement of the ν¯(e) mass-squared difference |Δm(ee)2|=(2.59(-0.20)(+0.19))×10(-3) eV2 is obtained using the observed ν¯(e) rates and energy spectra in a three-neutrino framework. This value of |Δm(ee)2| is consistent with |Δm(µµ)2| measured by muon neutrino disappearance, supporting the three-flavor oscillation model.

[Observational retrospective study to evaluate the effectiveness and safety of treatment schemes with bortezomib for multiple myeloma in our hospital]. / Estudio observacional restrospectivo para evaluar la efectividad y seguridad de esquemas de tratamiento con bortezomib para el mieloma múltiple en nuestro hospital.

OBJECTIVES: To analyse therapeutic regimens including bortezomib used in our centre for the treatment of multiple myeloma, to evaluate its effectiveness and safety in clinical practice in our hospital, and to assess the appropriateness of the indications described in guidelines. MATERIAL AND METHODS: Retrospective analysis of patients diagnosed with multiple myeloma in the period between January 2008 and December 2009 (24 months) that received treatment with a regimen including bortezomib. We analysed demographic variables (age, sex), disease characteristics (type of multiple myeloma, stage, and clinical cytogenetic abnormalities), concomitant drugs, response, and side effects of the regimen including bortezomib. RESULTS: We included 59 patients who were diagnosed with multiple myeloma (25 males and 34 females) with an average age of 63 years (range 30-82 years). The overall response rate for patients who received first-line regimens with bortezomib ranged between 69% (vincristine, carmustine, cyclophosphamide, melphalan and prednisone/vincristine, carmustine, doxorubicin, and dexamethasone plus bortezomib) and 82% (bortezomib, melphalan and oral prednisone). When we analysed the salvage treatment regimens: Bortezomib-Dexamethasone, Bortezomib-Cyclophosphamide-Dexamethasone and bortezomib, doxorubicin, melphalan alternating with thalidomide, cyclophosphamide, and dexamethasone achieved overall response rates of 72%, 77% and 89%, respectively. Adverse reactions to bortezomib or a treatment regimen that included it occurred in 32 (54%) patients, highlighting neurotoxicity in 19 patients (32%) and gastrointestinal toxicity in 12 (20%). CONCLUSIONS: The results of our study show the important role of bortezomib in the treatment of multiple myeloma, with response rates and side effects comparable to published data, although the conditions for using it in clinical practice are not yet recognized in the guidelines for use.

[Review of the stabitlity of photosensitive medications]. / Revisión de la estabilidad de los medicamentos fotosensibles.

OBJECTIVES: Identify the photosensitive drugs included in the hospital pharmacotherapeutic guide and search for stability data on the storage, reconstitution, and dilution of these compounds. METHODS: The data were obtained by referencing technical specifications, information provided by drug laboratories, and in some cases, we performed a more extensive bibliographic search (tertiary sources and conference lectures) for each particular medication. We also performed a data search on the PubMed information database (from 2004 to 2009). The drugs were placed in alphabetical order by brand since the stability of each drug when exposed to light does not depend exclusively on the primary active ingredient. Eight columns describe the principal characteristics of the drugs: brand name, active ingredient, laboratory, storage, reconstitution and dilution conditions, observations, and references. RESULTS: The listing was comprised of 139 photosensitive medicines, of the 1,954 included in the pharmacotherapeutical guide (table 1). CONCLUSIONS: The lack of studies published on the stability of photosensitive medications provided the need for an internal review at our hospital. It is important for drug-producing laboratories to perform photo-sensitivity tests on their products, with the results presented in the technical specifications in order to provide more accessible and reliable information. We believe that this should be required by law.

[Esthesioneuroblastoma. Description of a case and review of the literature]. / Estesioneuroblastoma. Presentación de un caso clínico y revisión de la bibliografía.

The esthesioneuroblastoma is a malignant and rare type of the nasal cavity. Affected patients usually present with a progressive nasal obstruction, rhinorrea and epistaxis. Metastasis occurs in about 30% of patiens, the most common sites for metastasis are the cervical lymph nodes, less frequent in anothers organs. The optimum management is probably surgery combined with radiotherapy, the chemotherapy is usually reserved for local advanced tumor

Compensation by the CIEMAT/NIST-method of long-term effects in LSC measurements of beta emitters.

A systematic evaluation of activity concentrations of 3H, 63Ni and 14C by using the CIEMAT/NIST method has been carried out over time intervals of 4, 2.4 and 2.3 years, respectively. It proves that the CIEMAT/NIST method can compensate, with no need for additional checking sources or procedures, for count losses and quench parameter reduction in long-term measurements with LSC spectrometers and allows one to obtain very accurate activity concentration values by using a quench curve close to the nuclide measurements. If this requirement of the method is not fulfilled, significant discrepancies, up to 5.6% for 3H, 1.5% for 63Ni and 0.35% for 14C, can be obtained in only 1-year time difference.

A method for the comparison of performance of gamma-ray spectrometry calibration cocktails.

In order to make quantitative assessments about the usefulness of different gamma-ray emitting radionuclide cocktails to carry out efficiency calibrations of gamma-ray spectrometers, a method has been developed that allows the comparison of their different performances and to optimize the choice of gamma energy lines for the radionuclides within a specific cocktail. The method has been applied to compare different cocktail configurations obtained from measurements made in the laboratory with monoenergetic radionuclides, and their relative performances are presented and discussed.

Standardization of 32P/33P and 204Tl by liquid scintillation counting.

Two solutions, one of 32P with a significant contribution of 33P, and another one of 204Tl were standardized by liquid scintillation counting in the frame of two intercomparison exercises organized by the BIPM in 2002. For the 32P solution, the counting efficiencies for 32P and 33P were obtained by the CIEMAT/NIST method. The individual contributions of 32P and 33P were determined by fitting a set of measurements to a function of the half-lives and counting efficiencies of both component nuclides. 204Tl was also standardized by the CIEMAT/NIST method using two counters, three scintillators, HiSafe 3, Insta-Gel Plus and Ultima-Gold, and two different kinds of samples. A total of 480 samples were measured over 45 days with results in full agreement within the uncertainties considered. The efficiency values are also compared to those used in the previous 204Tl intercomparison (1997).