Cancer-Associated Splicing Variant of Tumor Suppressor AIMP2/p38: Pathological Implication in Tumorigenesis

Although ARS-interacting multifunctional protein 2 (AIMP2, also named as MSC p38) was first found as a component for a macromolecular tRNA synthetase complex, it was recently discovered to dissociate from the complex and work as a potent tumor suppressor. Upon DNA damage, AIMP2 promotes apoptosis through the protective interaction with p53. However, it was not demonstrated whether AIMP2 was indeed pathologically linked to human cancer. In this work, we found that a splicing variant of AIMP2 lacking exon 2 (AIMP2-DX2) is highly expressed by alternative splicing in human lung cancer cells and patient's tissues. AIMP2-DX2 compromised pro-apoptotic activity of normal AIMP2 through the competitive binding to p53. The cells with higher level of AIMP2-DX2 showed higher propensity to form anchorage-independent colonies and increased resistance to cell death. Mice constitutively expressing this variant showed increased susceptibility to carcinogen-induced lung tumorigenesis. The expression ratio of AIMP2-DX2 to normal AIMP2 was increased according to lung cancer stage and showed a positive correlation with the survival of patients. Thus, this work identified an oncogenic splicing variant of a tumor suppressor, AIMP2/p38, and suggests its potential for anti-cancer target

Associations between malaria and local and global climate variability in five regions in Papua New Guinea

Background: Malaria is a significant public health issue in Papua New Guinea (PNG) as the burden is among the highest in Asia and the Pacific region. Though PNG’s vulnerability to climate change and sensitivity of malaria mosquitoes to weather are well-documented, there are few in-depth epidemiological studies conducted on the potential impacts of climate on malaria incidence in the country. Methods: This study explored what and how local weather and global climate variability impact on malaria incidence in five regions of PNG. Time series methods were applied to evaluate the associations of malaria incidence with weather and climate factors, respectively. Local weather factors including precipitation and temperature and global climate phenomena such as El Nino-Southern Oscillation (ENSO), the ENSO Modoki, the Southern Annular Mode, and the Indian Ocean Dipole were considered in analyses. Results: The results showed that malaria incidence was associated with local weather factors in most regions but at the different lag times and in directions. Meanwhile, there were trends in associations with global climate factors by geographical locations of study sites. Conclusions: Overall heterogeneous associations suggest the importance of location-specific approaches in PNG not only for further investigations but also public health interventions in repose to the potential impacts arising from climate change

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Pseudorapidity and transverse-momentum distributions of charged particles in proton-proton collisions at root s=13 TeV

The pseudorapidity (eta) and transverse-momentum (p(T)) distributions of charged particles produced in proton-proton collisions are measured at the centre-of-mass energy root s = 13 TeV. The pseudorapidity distribution in vertical bar eta vertical bar <1.8 is reported for inelastic events and for events with at least one charged particle in vertical bar eta vertical bar <1. The pseudorapidity density of charged particles produced in the pseudorapidity region vertical bar eta vertical bar <0.5 is 5.31 +/- 0.18 and 6.46 +/- 0.19 for the two event classes, respectively. The transverse-momentum distribution of charged particles is measured in the range 0.15 <p(T) <20 GeV/c and vertical bar eta vertical bar <0.8 for events with at least one charged particle in vertical bar eta vertical bar <1. The evolution of the transverse momentum spectra of charged particles is also investigated as a function of event multiplicity. The results are compared with calculations from PYTHIA and EPOS Monte Carlo generators. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Clinical Usability of Embryo Development Using a Combined Qualitative and Quantitative Approach in a Single Vitrified-Warmed Blastocyst Transfer: Assessment of Pre-Vitrified Blastocyst Diameter and Post-Warmed Blastocyst Re-Expansion Speed

Improving the safety and efficacy of assisted reproductive technology programs has been a continuous challenge. Traditionally, morphological grading has been used for embryo selection. However, only a few studies have assessed the morphokinetic variables and morphological dynamics of blastocysts. In the present study, we aimed to perform a quantitative analysis of blastocyst diameter and re-expansion speed. This in-depth morphokinetic evaluation can correlate with currently observed pregnancy outcomes. In total, 658 single vitrified-warmed blastocyst transfer cycles were performed between October 2017 and December 2021, which were divided into four groups according to the pre-vitrified blastocyst diameter. After warming, the groups were subdivided according to the blastocyst re-expansion speed. These quantitative measurements were performed using a time-lapse system. Both diameter and speed are essential in determining the blastocyst quality, while age, day of freezing, and blastocyst quality are crucial from a clinical perspective. The application of both quantitative (diameter and speed) and qualitative (blastocyst quality scores) parameters can help evaluate the clinical usability of blastocysts. This method can prove useful for embryologists in counseling their patients and determining pregnancy patient-oriented strategies

Intravenous Oxycodone versus Intravenous Morphine in Cancer Pain: A Randomized, Open-Label, Parallel-Group, Active-Control Study

Objective. To compare efficacy and safety of intravenous continuous infusion of oxycodone with morphine in patients with cancer pain. Methods. A 5-day, randomized, open-label, exploratory study at 6 sites in the Republic of Korea. Sixty-six adults aged ≥19 years with moderate-to-severe cancer pain (Numeric Rating Scale [NRS] ≥ 4) were enrolled. The study group received intravenous (IV) oxycodone, and the comparator group received IV morphine which were titrated depending on pain intensity. The efficacy endpoint is change in average NRS score from baseline to Day 5. Other assessments included worst, current, and average pain intensity; patient satisfaction; medication dose; and adverse events. Results. Both groups achieved >50% reduction in average pain intensity: from “moderate” at baseline (oxycodone versus morphine: 6.0 ± 1.8 versus 5.9 ± 1.4) to “mild” at Day 5 (2.5 ± 1.8 versus 2.8 ± 1.6). While this reduction was similar between groups (3.5 ± 2.2 versus 3.1 ± 1.8, P value = 0.562), oxycodone achieved faster pain relief (average pain: 3.0 ± 1.6 versus 3.9 ± 1.6, P value = 0.020) on Day 2 and significant NRS reductions for worst pain on Day 2 (P value = 0.045) and current pain on Day 2 (P value = 0.035) and Day 5 (P value = 0.020) compared to morphine. Patient satisfaction, adverse events, and adverse drug reactions were similar for both groups. Conclusions. For Asian patients with cancer pain, IV oxycodone is faster acting and showed similar analgesic efficacy and safety profiles as IV morphine. This trial is registered with Clinicaltrials.gov NCT02660229

Association of Antigen-Stimulated Release of Tumor Necrosis Factor-Alpha in Whole Blood with Response to Chemotherapy in Patients with Pulmonary Multidrug-Resistant Tuberculosis

BACKGROUND: We have previously reported that TNF-α levels correlate to total mycobacterial burden in tuberculosis (TB) patients. OBJECTIVE: To characterize the dynamics of cytokine responses in TB patients during chemotherapy to identify potential surrogate markers for effective treatment. METHODS: Following induction by culture filtrate proteins in whole blood, production patterns of TNF-α, IL-10, IFN-γ and IL-12 were measured in 23 non-multidrug-resistant (MDR)-TB and 16 MDR-TB patients and in 31 healthy controls. Rates of mycobacterial clearance from the sputum were then measured and compared. RESULTS: Prior to the initiation of chemotherapy, TNF-α and IL-10 levels were significantly higher in TB patients than in healthy controls while IFN-γ and IL-12 levels were similar. During chemotherapy, the levels of all 4 cytokines increased. We evaluated these responses separately in patients that did and did not clear their sputum culture at 2 and 6 months. At 2 months, decreases in both IFN-γ and IL-12 correlated strongly with a successful early response, while after 6 months of therapy, when half (7/14) of MDR-TB patients were still sputum culture positive, downregulation of TNF-α was uniquely correlated with sputum conversion between the groups. CONCLUSION: Our findings suggest the possibility that the regulation of TNF-α production in whole blood may be a more specific indicator of sputum conversion at 6 months than IFN-γ, IL-12 or IL-10 in MDR-TB patients. Copyright © 2010 S. Karger AG, Base