Discovery of soft and hard X-ray time lags in low-mass AGNs

The scaling relations between the black hole (BH) mass and soft lag properties for both active galactic nuclei (AGNs) and BH X-ray binaries (BHXRBs) suggest the same underlying physical mechanism at work in accreting BH systems spanning a broad range of mass. However, the low-mass end of AGNs has never been explored in detail. In this work, we extend the existing scaling relations to lower-mass AGNs, which serve as anchors between the normal-mass AGNs and BHXRBs. For this purpose, we construct a sample of low-mass AGNs ($M_{\rm BH}<3\times 10^{6} M_{\rm \odot}$) from the XMM-Newton archive and measure frequency-resolved time delays between the soft (0.3-1 keV) and hard (1-4 keV) X-ray emissions. We report that the soft band lags behind the hard band emission at high frequencies $\sim[1.3-2.6]\times 10^{-3}$ Hz, which is interpreted as a sign of reverberation from the inner accretion disc in response to the direct coronal emission. At low frequencies ($\sim[3-8]\times 10^{-4}$ Hz), the hard band lags behind the soft band variations, which we explain in the context of the inward propagation of luminosity fluctuations through the corona. Assuming a lamppost geometry for the corona, we find that the X-ray source of the sample extends at an average height and radius of $\sim 10r_{\rm g}$ and $\sim 6r_{\rm g}$, respectively. Our results confirm that the scaling relations between the BH mass and soft lag amplitude/frequency derived for higher-mass AGNs can safely extrapolate to lower-mass AGNs, and the accretion process is indeed independent of the BH mass.Comment: 11 pages, 5 figures, 4 tables, Published in MNRA

Prospects for Time-Domain and Multi-Messenger Science with AXIS

The Advanced X-ray Imaging Satellite (AXIS) promises revolutionary science in the X-ray and multi-messenger time domain. AXIS will leverage excellent spatial resolution (<1.5 arcsec), sensitivity (80x that of Swift), and a large collecting area (5-10x that of Chandra) across a 24-arcmin diameter field of view to discover and characterize a wide range of X-ray transients from supernova-shock breakouts to tidal disruption events to highly variable supermassive black holes. The observatory's ability to localize and monitor faint X-ray sources opens up new opportunities to hunt for counterparts to distant binary neutron star mergers, fast radio bursts, and exotic phenomena like fast X-ray transients. AXIS will offer a response time of <2 hours to community alerts, enabling studies of gravitational wave sources, high-energy neutrino emitters, X-ray binaries, magnetars, and other targets of opportunity. This white paper highlights some of the discovery science that will be driven by AXIS in this burgeoning field of time domain and multi-messenger astrophysics.Comment: This White Paper is part of a series commissioned for the AXIS Probe Concept Mission; additional AXIS White Papers can be found at http://axis.astro.umd.ed

A review on cancer incidence in India from 25 population-based cancer registries

Background and Objective: An overview of the update of cancer incidence summary findings will be of help to researchers and clinicians for quick reference of facts in cancer control. To present an overview of cancer incidence available from the recent population-based cancer registries (PBCRs) in India from 2009 to 2011. Materials and Methods: Data on age-adjusted incidence rates and cumulative risks of cancer at various sites were collected for both sexes for six major cancer sites from the first report of the National Cancer Registry Programme (NCRP) on 25 PBCRs in India for the years 2009-2011. Site-specific risks in terms of one out of the total number of persons who develop cancer were computed. The summaries, in the form of ranges, are presented in six regions of the country in which the 20 PBCRs are located. The range of age-adjusted rates (AARs) and one out of the number of persons who develop cancer as a lifetime risk in the age of 0-64 years is presented. Results: In different regions, the highest risks for males for developing cancer in the various major sites studied were as follows: One out of 67 for cancer in the lungs in the Northeast, one out of 27 for cancer in the esophagus in the Northeast, one out of 71 for cancer in the mouth in the western region, one out of 100 cancer in the tongue in the rural western region, one out of 333 for cancer in the prostate in the northern region, and one out of 33 for cancer in the stomach in the northeastern region. The highest risks for the various sites studied were as follows: one out of 36 for cancer in the breast in the south, one out of 59 for cancer in the cervix in the western region, one out of 125 for cancer in the ovary in the northern region, one out of 63 for cancer in the esophagus in the northeastern region, one out of 250 for cancer in the mouth in three regions, and one out of 125 for cancer in the gall bladder in the western and central regions. Overall, for all cancers there is a risk of one out of 8-27 persons and one out of 10-25 persons among males and females, respectively, in the Indian population who are likely to develop cancer of any site in their lifetime during the age of 0-64 years. Conclusion: Female breast cancer in the southern region and esophagus and stomach cancers among males in the northeast region were of the highest magnitudes

Systemic immunity upon local oncolytic virotherapy armed with immunostimulatory genes may be supported by tumor-derived exosomes

Immunostimulatory gene therapy utilizing oncolytic viruses (OVs) as gene vehicles is a promising immunotherapy for cancer. Since viruses are immunogenic, systemic delivery can be troublesome due to neutralizing antibodies. Nevertheless, local delivery by intratumoral injection seems to induce systemic immune reactions. In this study, we demonstrate a novel mechanism of action of armed OV therapy suggesting that exosomes released by tumor cells infected with armed OV may participate to activate the immune system and this may also support systemic immunity. Tumor cell-derived exosomes commonly exert immunosuppressive functions. We hypothesized that exosomes derived from OV-infected tumor cells may instead be immunostimulatory. Human melanoma cells were infected by OVs armed with costimulatory molecules CD40 ligand (CD40L) and 4-1BB ligand (4-1BBL). Exosomes were purified and investigated for the presence of CD40L/4-1BBL mRNA and protein, and for their capacity to stimulate immune responses. The results show that the exosomes cargo transgenes. The exosomes from CD40L/4-1BBL-expressing tumor cells, or the viruses themselves, could stimulate robust dendritic cell (DC) activation with an enhanced level of major histocompatibility complex (MHC) and costimulatory molecules. Hence, exosomes after OV infection can locally activate immune responses at the tumor site and encounter immune cells such as DCs

The role of NK and NKT cells in the pathogenesis and improvement of multiple sclerosis following disease-modifying therapies

Background Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) that T cells become autoreactive by recognizing CNS antigens. Both innate and adaptive immune systems are involved in the pathogenesis of MS. In recent years, the impact of innate immune cells on MS pathogenesis has received more attention. CD56(bright) NK cells, as an immunoregulatory subset of NK cells, can increase the production of cytokines that modulate adaptive immune responses, whereas CD56(dim) NK cells are more active in cytolysis functions. These two main subsets of NK cells may have different effects on the onset or progression of MS. Invariant NKT (iNKT) cells are other immune cells involved in the control of autoimmune diseases; however, variant NKT (vNKT) cells, despite limited information, could play a role in MS remission via an immunoregulatory pathway. Aim We aimed to evaluate the influence of MS therapeutic agents on NK and NKT cells and NK cell subtypes. Materials and Methods The possible mechanism of each MS therapeutic agent has been presented here, focusing on the effects of different disease-modifying therapies on the number of NK and NKT subtypes. Results Expansion of CD56(bright) NK cells, reduction in the CD56(dim) cells, and enhancement in NKT cells are the more important innate immune cells alterations following the disease-modifying therapies. Conclusion Expansion of CD56(bright) NK cells or reduction in the CD56(dim) cells has been associated with a successful response to different treatments in MS. iNKT and vNKT cells could have beneficial effects on MS improving. It seems that they are enhanced due to some of MS drugs, leading to disease improvement. However, a reduction in the number of NKT cells could be due to the adverse effects of some of MS drugs on the bone marrow

Burn injury characteristics and outcomes among pediatric and adult patients admitted to Ministry of National Guard Health Affairs (MNGHA) hospitals in Saudi Arabia

Objective: This study aims to describe the characteristics and outcomes of burn injuries in pediatric and adult patients admitted to Ministry of National Guard Health Affairs (MNGHA) hospitals in Saudi Arabia. Methods: A multicenter retrospective cohort study was conducted between 2015 and 2021 in five hospitals run by the MNGHA in Saudi Arabia. The study included 555 patients who were admitted to the hospital with burns, and data were collected from an institutional trauma registry on various aspects such as sociodemographic variables, burn clinical characteristics and burn outcomes. The differences in epidemiological data, general characteristics, and outcomes of burn patients with ≤18 and >18 years of age among Saudi hospitalized patients. The associations between patient characteristics and burn outcomes were assessed using multivariable logistic regression. Results: Most of the participants representing 66.1% males and females 33.9%. Flame and contact were the most common causes of burn injuries, accounting for 43.6% and 43.2% of cases, respectively; followed by chemical (6.7%), then electrical (5.4%), and friction (1.1%). The study revealed that pediatric were the most frequently admitted age group for burn injuries with most cases occurring at home (57%). Pediatric patients had a higher percentage of hot fluid injuries, accounting for 77.5 % of cases (P = 0.00). Flame injuries were more prevalent in adults, accounting for 65.3% of cases (P < 0.05). The study reported that there were significant associations between age, gender, % TBSA, body region affected, and inhalation injury with admission to the ICU in patients with burn injuries. Relative to patients with third degree burns, first and second-degree burns were associated with a lower likelihood of mortality (OR 0.13, 95% CI: 0.03,0.51, p = 0.00). Conclusion: The study’s findings can be utilized to aid in the implementation of different prevention programs and allocate appropriate resources for treatment to reduce the incidence and morbidity of burn injuries. It is essential to continue educating the public on fire safety in the home environment. This can help raise awareness, promote household safety precautions, and encourage early medical care seeking

Boosting CAR T-cell responses in lymphoma by simultaneous targeting of CD40/4-1BB using oncolytic viral gene therapy

Pretreatment of B-cell lymphoma patients with immunostimulatory gene therapy using armed oncolytic viruses may prime tumor lesions for subsequent chimeric antigen receptor (CAR) T-cell therapy, thereby enhancing CAR T-cell functionality and possibly increasing response rates in patients. LOAd703 (delolimogene mupadenorepvec) is an oncolytic adenovirus (serotype 5/35) that encodes for the transgenes CD40L and 4-1BBL, which activate both antigen-presenting cells and T cells. Many adenoviruses failed to demonstrate efficacy in B-cell malignancies, but LOAd703 infect cells via CD46, which enables B cell infection. Herein, we investigated the therapeutic potential of LOAd703 in human B-cell lymphoma models, alone or in combination with CAR T-cell therapy. LOAd703 could infect and replicate in B-cell lymphoma cell lines (BC-3, Karpas422, Daudi, DG-75, U-698) and induced an overall enhanced immunogenic profile with upregulation of co-stimulatory molecules CD80, CD86, CD70, MHC molecules, death receptor Fas and adhesion molecule ICAM-1. Further, CAR T-cell functionality was boosted by stimulation with lymphoma cells infected with LOAd703. This was demonstrated by an augmented release of IFN-γ and granzyme B, increased expression of the degranulation marker CD107a, fewer PD-1 + TIM-3+ CAR T cells in vitro and enhanced lymphoma cell killing both in in vitro and in vivo xenograft models. In addition, LOAd703-infected lymphoma cells upregulated the secretion of several chemokines (CXCL10, CCL17, CCL22, CCL3, CCL4) essential for immune cell homing, leading to enhanced CAR T-cell migration. In conclusion, immunostimulatory LOAd703 therapy is an intriguing approach to induce anti-lymphoma immune responses and to improve CAR T-cell therapy in B-cell lymphoma