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Antimicrobial Activity of Ceftolozane-Tazobactam and Comparators against Clinical Isolates of Haemophilus influenzae from the United States and Europe [Susceptibility]

Nine hundred Haemophilus influenzae clinical isolates from 83 U.S. and European medical centers were tested for susceptibility by reference broth microdilution methods against ceftolozane-tazobactam and comparators. Results were stratified by β-lactamase production and infection type. Overall, ceftolozane-tazobactam MIC50/90 values were 0.12/0.25 mg/liter, and 99.0% of isolates were inhibited at the susceptible breakpoint of ≤0.5 mg/liter; the highest MIC value was only 2 mg/liter. Our results support using ceftolozane-tazobactam to treat H. influenzae infections.




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Unorthodox Parenteral {beta}-Lactam and {beta}-Lactamase Inhibitor Combinations: Flouting Antimicrobial Stewardship and Compromising Patient Care [Commentary]

In India and China, indigenous drug manufacturers market arbitrarily combined parenteral β-lactam and β-lactamase inhibitors (BL-BLIs). In these fixed-dose combinations, sulbactam or tazobactam is indiscriminately combined with parenteral cephalosporins, with BLI doses kept in ratios similar to those for the approved BL-BLIs. Such combinations have been introduced into clinical practice without mandatory drug development studies involving pharmacokinetic/pharmacodynamic, safety, and efficacy assessments being undertaken. Such unorthodox combinations compromise clinical outcomes and also potentially contribute to resistance development.




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Levonadifloxacin, a Novel Benzoquinolizine Fluoroquinolone, Modulates Lipopolysaccharide-Induced Inflammatory Responses in Human Whole-Blood Assay and Murine Acute Lung Injury Model [Pharmacology]

Fluoroquinolones are reported to possess immunomodulatory activity; hence, a novel benzoquinolizine fluoroquinolone, levonadifloxacin, was evaluated in lipopolysaccharide-stimulated human whole-blood (HWB) and mouse acute lung injury (ALI) models. Levonadifloxacin significantly mitigated the inflammatory responses in an HWB assay through inhibition of proinflammatory cytokines and in the ALI model by lowering lung total white blood cell count, myeloperoxidase, and cytokine levels. The immunomodulatory effect of levonadifloxacin, along with promising antibacterial activity, is expected to provide clinical benefits in the treatment of infections.




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Editorial Board [Masthead]




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Noncoding Variants Connect Enhancer Dysregulation with Nuclear Receptor Signaling in Hematopoietic Malignancies [Research Articles]

Mutations in protein-coding genes are well established as the basis for human cancer, yet how alterations within noncoding genome, a substantial fraction of which contain cis-regulatory elements (CRE), contribute to cancer pathophysiology remains elusive. Here, we developed an integrative approach to systematically identify and characterize noncoding regulatory variants with functional consequences in human hematopoietic malignancies. Combining targeted resequencing of hematopoietic lineage–associated CREs and mutation discovery, we uncovered 1,836 recurrently mutated CREs containing leukemia-associated noncoding variants. By enhanced CRISPR/dCas9–based CRE perturbation screening and functional analyses, we identified 218 variant-associated oncogenic or tumor-suppressive CREs in human leukemia. Noncoding variants at KRAS and PER2 enhancers reside in proximity to nuclear receptor (NR) binding regions and modulate transcriptional activities in response to NR signaling in leukemia cells. NR binding sites frequently colocalize with noncoding variants across cancer types. Hence, recurrent noncoding variants connect enhancer dysregulation with nuclear receptor signaling in hematopoietic malignancies.

Significance:

We describe an integrative approach to identify noncoding variants in human leukemia, and reveal cohorts of variant-associated oncogenic and tumor-suppressive cis-regulatory elements including KRAS and PER2 enhancers. Our findings support a model in which noncoding regulatory variants connect enhancer dysregulation with nuclear receptor signaling to modulate gene programs in hematopoietic malignancies.

See related commentary by van Galen, p. 646.

This article is highlighted in the In This Issue feature, p. 627




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New Drug-Discovery Assay Identifies Novel Mutant-EGFR Inhibitors [Drug Discovery]

The MaMTH-DS assay detected inhibitors of mutant EGFR in non–small cell lung cancer cells.




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[Cell Signaling] Store-Operated Calcium Channels: From Function to Structure and Back Again

Store-operated calcium (Ca2+) entry (SOCE) occurs through a widely distributed family of ion channels activated by the loss of Ca2+ from the endoplasmic reticulum (ER). The best understood of these is the Ca2+ release-activated Ca2+ (CRAC) channel, which is notable for its unique activation mechanism as well as its many essential physiological functions and the diverse pathologies that result from dysregulation. In response to ER Ca2+ depletion, CRAC channels are formed through a diffusion trap mechanism at ER–plasma membrane (PM) junctions, where the ER Ca2+-sensing stromal interaction molecule (STIM) proteins bind and activate hexamers of Orai pore-forming proteins to trigger Ca2+ entry. Cell biological studies are clarifying the architecture of ER–PM junctions, their roles in Ca2+ and lipid transport, and functional interactions with cytoskeletal proteins. Molecular structures of STIM and Orai have inspired a multitude of mutagenesis and electrophysiological studies that reveal potential mechanisms for how STIM is toggled between inactive and active states, how it binds and activates Orai, and the importance of STIM-binding stoichiometry for opening the channel and establishing its signature characteristics of extremely high Ca2+ selectivity and low Ca2+ conductance.




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[Molecular Pathology] Pharmacologic Approaches for Adapting Proteostasis in the Secretory Pathway to Ameliorate Protein Conformational Diseases

Maintenance of the proteome, ensuring the proper locations, proper conformations, appropriate concentrations, etc., is essential to preserve the health of an organism in the face of environmental insults, infectious diseases, and the challenges associated with aging. Maintaining the proteome is even more difficult in the background of inherited mutations that render a given protein and others handled by the same proteostasis machinery misfolding prone and/or aggregation prone. Maintenance of the proteome or maintaining proteostasis requires the orchestration of protein synthesis, folding, trafficking, and degradation by way of highly conserved, interacting, and competitive proteostasis pathways. Each subcellular compartment has a unique proteostasis network compromising common and specialized proteostasis maintenance pathways. Stress-responsive signaling pathways detect the misfolding and/or aggregation of proteins in specific subcellular compartments using stress sensors and respond by generating an active transcription factor. Subsequent transcriptional programs up-regulate proteostasis network capacity (i.e., ability to fold and degrade proteins in that compartment). Stress-responsive signaling pathways can also be linked by way of signaling cascades to nontranscriptional means to reestablish proteostasis (e.g., by translational attenuation). Proteostasis is also strongly influenced by the inherent kinetics and thermodynamics of the folding, misfolding, and aggregation of individual proteins, and these sequence-based attributes in combination with proteostasis network capacity together influence proteostasis. In this review, we will focus on the growing body of evidence that proteostasis deficits leading to human pathology can be reversed by pharmacologic adaptation of proteostasis network capacity through stress-responsive signaling pathway activation. The power of this approach will be exemplified by focusing on the ATF6 arm of the unfolded protein response stress responsive-signaling pathway that regulates proteostasis network capacity of the secretory pathway.




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A Case of Euglycemic Diabetic Ketoacidosis Triggered by a Ketogenic Diet in a Patient With Type 2 Diabetes Using a Sodium-Glucose Cotransporter 2 Inhibitor




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Optimizing Diabetes Care With the Standardized Continuous Glucose Monitoring Report




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Flash Continuous Home Glucose Monitoring to Improve Adherence to Self-Monitoring of Blood Glucose and Self-Efficacy in Adolescents With Type 1 Diabetes

Adolescents with type 1 diabetes face self-management challenges that make it difficult for them to achieve good glycemic control. In our population of adolescents with poorly controlled type 1 diabetes, the use of continuous glucose monitoring (CGM) improved patients’ glycemic time in range (TIR) and identified hypoglycemia more frequently than with intermittent self-monitoring of blood glucose throughout a 4-week interval. However, the adolescents were unable to synthesize this information to problem-solve or reduce the frequency of hypoglycemic events. Setting SMART (specific, measurable, achievable, relevant, and time-bound) diabetes management goals and providing intensive diabetes education and support could increase adolescents’ TIR and prevent hypoglycemia.




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Continuous Glucose Monitoring As a Behavior Modification Tool

Real-time continuous glucose monitoring (CGM) use may lead to behavioral modifications in food selection and physical activity, but there are limited data on the utility of CGM in facilitating lifestyle changes. This article describes an 18-item survey developed to explore whether patients currently using CGM believe the technology has caused them to change their behavior.




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Maternal Epigenetic Regulation Contributes to Prevention of Estrogen Receptor-negative Mammary Cancer with Broccoli Sprout Consumption

Cruciferous vegetables have been of special interest due to the rich presence of bioactive compounds such as sulforaphane which show promising potential on cancer prevention and therapy as an epigenetic dietary strategy. Abnormal epigenetic alteration as one of the primary contributors to tumor development is closely related to breast cancer initiation and progression. In the present study, we investigated the effect of dietary broccoli sprouts (BSp), a common cruciferous vegetable, on prevention of estrogen receptor (ER)-negative mammary tumors at three different temporal exposure windows using a spontaneous breast cancer mouse model. Our findings indicate that maternal BSp treatment exhibited profound inhibitory and preventive effects on mammary cancer formation in the nontreated mouse offspring. The BSp diet administered to adult mice also showed suppressive effects on mammary cancer but was not as profound as the maternal BSp preventive effects. Moreover, such protective effects were linked with differentially expressed tumor- and epigenetic-related genes, as well as altered global histone acetylation, DNA methylation, and DNA hydroxymethylation levels. We also found that the expression changes of tumor-related genes were associated with the levels of histone methylation of H3K4 and H3K9 in the gene promoter regions. In addition, BSp-enriched sulforaphane was shown to increase protein expression of tumor suppressor genes such as p16 and p53 and inhibit the protein levels of Bmi1, DNA methyltransferases, and histone deacetylases in ERα-negative breast cancer cell lines. Collectively, these results suggest that maternal exposure to key phytochemicals may contribute to ER-negative mammary tumor prevention in their offspring through epigenetic regulations.




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Retraction: Insulin-Like Growth Factor I Suppresses Bone Morphogenetic Protein Signaling in Prostate Cancer Cells by Activating mTOR Signaling




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Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Is Associated with Indigenous American Ancestry in Latin American Women

Women of Latin American origin in the United States are more likely to be diagnosed with advanced breast cancer and have a higher risk of mortality than non-Hispanic White women. Studies in U.S. Latinas and Latin American women have reported a high incidence of HER2 positive (+) tumors; however, the factors contributing to this observation are unknown. Genome-wide genotype data for 1,312 patients from the Peruvian Genetics and Genomics of Breast Cancer Study (PEGEN-BC) were used to estimate genetic ancestry. We tested the association between HER2 status and genetic ancestry using logistic and multinomial logistic regression models. Findings were replicated in 616 samples from Mexico and Colombia. Average Indigenous American (IA) ancestry differed by subtype. In multivariate models, the odds of having an HER2+ tumor increased by a factor of 1.20 with every 10% increase in IA ancestry proportion (95% CI, 1.07–1.35; P = 0.001). The association between HER2 status and IA ancestry was independently replicated in samples from Mexico and Colombia. Results suggest that the high prevalence of HER2+ tumors in Latinas could be due in part to the presence of population-specific genetic variant(s) affecting HER2 expression in breast cancer.Significance:The positive association between Indigenous American genetic ancestry and HER2+ breast cancer suggests that the high incidence of HER2+ subtypes in Latinas might be due to population and subtype-specific genetic risk variants.




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[PERSPECTIVES] RNA Regulators in Leukemia and Lymphoma

Posttranscriptional regulation of mRNA is a powerful and tightly controlled process in which cells command the integrity, diversity, and abundance of their protein products. RNA-binding proteins (RBPs) are the principal players that control many intermediary steps of posttranscriptional regulation. Recent advances in this field have discovered the importance of RBPs in hematological diseases. Herein we will review a number of RBPs that have been determined to play critical functions in leukemia and lymphoma. Furthermore, we will discuss the potential therapeutic strategies that are currently being studied to specifically target RBPs in these diseases.




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Involvement of the Olfactory Apparatus by Gliomas [HEAD & NECK]

SUMMARY:

The olfactory bulbs and tracts are central nervous system white matter tracts maintained by central neuroglia. Although rare, gliomas can originate from and progress to involve the olfactory apparatus. Through a Health Insurance Portability and Accountability Act–compliant retrospective review of the institutional teaching files and brain MR imaging reports spanning 10 years, we identified 12 cases of gliomas involving the olfactory bulbs and tracts, including 6 cases of glioblastoma, 2 cases of anaplastic oligodendroglioma, and 1 case each of pilocytic astrocytoma, diffuse (grade II) astrocytoma, anaplastic astrocytoma (grade III), and diffuse midline glioma. All except the pilocytic astrocytoma occurred in patients with known primary glial tumors elsewhere. Imaging findings of olfactory tumor involvement ranged from well-demarcated enhancing masses to ill-defined enhancing infiltrative lesions to nonenhancing masslike FLAIR signal abnormality within the olfactory tracts. Familiarity with the imaging findings of glioma involvement of the olfactory nerves is important for timely diagnosis and treatment of recurrent gliomas and to distinguish them from other disease processes.




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CT Angiography in Evaluating Large-Vessel Occlusion in Acute Anterior Circulation Ischemic Stroke: Factors Associated with Diagnostic Error in Clinical Practice [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

It is currently not completely clear how well radiologists perform in evaluating large-vessel occlusion on CTA in acute ischemic stroke. The purpose of this study was to investigate potential factors associated with diagnostic error.

MATERIALS AND METHODS:

Five hundred twenty consecutive patients with a clinical diagnosis of acute ischemic stroke (49.4% men; mean age, 72 years) who underwent CTA to evaluate large-vessel occlusion of the proximal anterior circulation were included. CTA scans were retrospectively reviewed by a consensus panel of 2 neuroradiologists. Logistic regression analysis was performed to investigate the association between several variables and missed large-vessel occlusion at the initial CTA interpretation.

RESULTS:

The prevalence of large-vessel occlusion was 16% (84/520 patients); 20% (17/84) of large-vessel occlusions were missed at the initial CTA evaluation. In multivariate analysis, non-neuroradiologists were more likely to miss large-vessel occlusion compared with neuroradiologists (OR = 5.62; 95% CI, 1.06–29.85; P = .04), and occlusions of the M2 segment were more likely to be missed compared with occlusions of the distal internal carotid artery and/or M1 segment (OR = 5.69; 95% CI, 1.44–22.57; P = .01). There were no calcified emboli in initially correctly identified large-vessel occlusions. However, calcified emboli were present in 4 of 17 (24%) initially missed or misinterpreted large-vessel occlusions.

CONCLUSIONS:

Several factors may have an association with missing a large-vessel occlusion on CTA, including the CTA interpreter (non-neuroradiologists versus neuroradiologists), large-vessel occlusion location (M2 segment versus the distal internal carotid artery and/or M1 segment), and large-vessel occlusion caused by calcified emboli. Awareness of these factors may improve the accuracy in interpreting CTA and eventually improve stroke outcome.




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Novel Coronavirus: What Neuroradiologists as Citizens of the World Need to Know [EDITORIALS]




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Beautiful, clean, mordern room for rent near Tan Son Nhat airport, 3 minutes by motorcycle

The room is beautiful, clean and convenience. On top of that, it nears to the airport. We have free wifi, amenities, modern furniture, elevator, TV. We also have a kitchen shared with everyone. In the kitchen, we have modern equipment for cooking. We have laundry, clothes drier,....




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Factory for rent in Binh Phuoc

Area: 15.000m2 (Available electrical production systems, automatic fire systems, 24/24 camera, full valid papers) Address: Minh Hung 3 industrial park, Binh Phuoc province Suitable for many industrial fields such as Mechanics, Apparel, Leather, Wood, Plastic ... Contact: 08980131...




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Vietnam’s industrial real estate draws foreign investors amid U.S.-China trade war

The trade war between the United States and China has turned real estate investors' interest to Southeast Asian countries, in which the Vietnamese industrial market emerges as a bright spot in the region.




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Which type of real estate is attracting Hanoi investors?

According to Batdongsan.com.vn’s real estate market report for the third quarter (Q3) of 2019, besides the attraction of traditional markets, resort real estate segment is witnessing the rise of emerging markets. Notably, Hanoi investors overwhelmed in term of the number of searches for resort real estate on the website.




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Digital storytelling: Selling properties with ease in a hyper-connected world

Three marketing experts share their unconventional means of capturing the attention of potential homeowners of today.




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Nice 6-storey house for rent on Nguyen Thien Thuat Street, Nha Trang city, 0366363204

- The building is located at 22 Nguyen Thien Thuat, Tan Lap, Nha Trang city. - Nice and strong house, modern design, spacious and airy living space with 2 frontages of road - Land area: 96m2 - Construction area: 576 m2. Wide frontage: 5 m wide, 19.6 m long, 1 ground floor for bus...




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Hot! 3-storey shophouse for sale in Thao Dien D2, 300m2, near metro station - Call +84 948 522 889

- Sublease investor commits to profit within 6 years , plan price 25$/m2 - Area: 191.2m2 - Price: $1,060,000 -The Developer is the company of Fraser Singapore which is very famous in other countries because this is the first project in Vietnam so the Developer sells with not much...




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9 negative impacts of land fever investors should know

The upsurge of land price leads to a real estate bubble, pushing up production costs, creating a virtual tendency and gradually increasing bad debt.




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A guide for foreign investors in HCMC real estate

One of the most notable changes introduced by Vietnam’s new 2014 property law and its regulations is the revision of the right for overseas Vietnamese, foreign individuals and organizations to own residential houses.




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Most popular mistakes made by new real estate investors

Regardless of age, all first-time real estate investors are prone to making the same mistakes. Here are some dos and don’ts for new investors.




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A simple guide for buy-to-rent investors

Many people see buy-to-rent as an attractive income investment in a time of low rates and stock market volatility. But if you are considering investing in property - or improving your returns on a buy-to-rent you already own - it's important to do things right.




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4 challenges ahead for investors joining apartment market

Tens of thousands of new apartments enter the Ho Chi Minh City market every year, putting pressure on investors who want to reap returns from rental apartments.




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भारत के लिए MG Motor ला रही है सस्ती इलेक्ट्रिक कार, कीमत 10 लाख से कम

भारतीय ऑटोमोबाइल बाजार में इलेक्ट्रिक व्हीकल्स की मांग बढ़ रही है। लोग इलेक्ट्रिक वाहनों की तरफ आकर्षित हो रहे हैं क्योंकि यह पारंपरिक ईंधन की बजाए बैटरी पर चलती है। इससे तेल और पैसे दोनों की बचत होती है।




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इंटरनेट पर छा गई कस्टमाइज्ड Royal Enfield Interceptor 650, 'Tamraj' का लुक कर देगा दीवाना

Royal Enfield (रॉयल एनफील्ड) मोटरसाइकिल बाइकर्स की पसंद होने के साथ साथ बाइक मॉडिफाई करने वालों में भी लोकप्रिय है। देशभर में ऐसी कई स्टार्ट-अप कंपनियां खुल गई हैं जिन्हें एनफील्ड को कस्टमाइज करने में महारथ हासिल हैं।




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Hyundai motor ने अपने ग्राहकों के लिए शुरू की ये 5 स्कीम, कार खरीदने का है बेहतर मौका

आपके पास Hyundai की कार खरीदने का एक बेहतरीन मौका है। दरअसल कंपनी ने अपने ग्राहकों के लिए 5 अनूठी कार फाइनेंस स्कीम का एलान किया है।




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Mortal Kombat 11: Aftermath Expansion Announced, Adds 3 New Characters and New Story

Publisher Warner Bros. Interactive Entertainment and developer NetherRealms Studios have announced a new expansion for Mortal Kombat 11 called Aftermath. It will release on May 26.

The Mortal Kombat 11: Aftermath expansion adds a new cinematic story, three characters and three new skins for $39.99. The three new characters are Fujin, Sheeva, and RoboCop).

A $59.99 Mortal Kombat: Aftermath Kollection has also been announced. It includes the base game, Kombat Pack DLC and the Aftermath expansion. 

View the announcement trailer for the expansion and RoboCop reveal trailer below:

Here is an overview of the expansion:

Mortal Kombat 11: Aftermath is a new expansion for the hit videogame, Mortal Kombat 11, the best-selling title in franchise history that was named Fighting Game of the Year at the 2019 D.I.C.E. Awards. Developed by award-winning NetherRealm Studios, Mortal Kombat 11: Aftermath expands the critically acclaimed story campaign with an all-new, cinematic narrative centered around trust and deceit, while also adding new playable characters in returning Mortal Kombat fighters, Fujin and Sheeva, and guest character, RoboCop, who is making his series debut.

Key Features:

  • Franchise-First Story Expansion – The critically acclaimed story campaign continues with an all-new cinematic narrative that picks up directly where Mortal Kombat 11 left off. Fire God Liu Kang, the new keeper of time and protector of Earthrealm, must now enlist the help of unlikely allies and familiar foes to forge a new history as the fate of two worlds hang in the balance.
  • Exciting New Characters Join the Roster – New playable characters join the fight with the triumphant return of Fujin, the God of Wind who serves as Earthrealm’s protector alongside his brother Raiden, and Sheeva, the fourarmed, half-human and half-dragon queen of the ancient Shokan race. RoboCop, the iconic, highly advanced cybernetic police officer, makes his first appearance in the franchise, continuing the pedigree of popular Mortal Kombat guest fighters. RoboCop in Mortal Kombat 11: Aftermath features the voice and likeness of actor Peter Weller, who portrayed the popular character in both the original RoboCop (1987) film and RoboCop 2 (1990) sequel. Mortal Kombat 11: Aftermath will also include three new character skin packs to be released over time.
  • Fan-Favorite Stages, Stage Fatalities & Friendships Return – In conjunction with the Mortal Kombat 11: Aftermath release, all Mortal Kombat 11 owners will have access to a free content update featuring new Stages, including the return of the Klassic Dead Pool and Soul Chamber arenas; Stage Fatalities, the fan-favorite finishing moves that use the environment to destroy opponents; and the popular Friendships feature, allowing players to take down their adversaries with a hint of kindness.
  • New Players Can Join the Fight with Mortal Kombat 11: Aftermath Kollection – Offers the perfect opportunity for new players to join the fight, featuring all characters, story content, game modes and pre-order bonuses in one ultimate package. This compilation includes Mortal Kombat 11 along with all content from Mortal Kombat 11: Aftermath and the previously released Mortal Kombat 11 Kombat Pack, containing six playable characters—Shang Tsung, Nightwolf, Sindel, Terminator T-800, The Joker and Spawn – plus 25 additional character skins. The Mortal Kombat 11: Aftermath Kollection can be pre-ordered for $59.99 (SRP) with digital pre-orders offering immediate access to Mortal Kombat 11 and the Kombat Pack upon purchase. The physical version will be available this June in the Americas only.
  • Upgrade Options for Current Mortal Kombat 11 Owners – Those who have already purchased Mortal Kombat 11 can pre-order the Mortal Kombat 11 Aftermath expansion for $39.99 (SRP) or the Mortal Kombat 11: Aftermath + Kombat Pack Bundle for $49.99 (SRP).
  • Pre-order for Exclusive Content – All preorders* receive the Eternal Klash Skin Pack at launch, featuring three new character skin variants – “Unbound Rage” Scorpion inspired by Mortal Kombat (2011), “Son of Arctika” Sub-Zero inspired by Mortal Kombat: Deception and “Kori Power” Frost, a Klassic version of the Lin Kuie warrior.
  • Best-In-Class, Brutal Kombat  Mortal Kombat 11 is the latest installment in the critically acclaimed franchise, providing a deeper and more personalized experience than ever before. The best-selling title is packed to the brim with multiple features and modes for all players, including the Story mode, Custom Character Variation System, Towers of Time, Kombat League, The Krypt and the signature roster returning and franchise-first fighters, all equipped with powerful Krushing Blows and unique Fatalities that display devastatingly brutal cinematic visuals.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443404/mortal-kombat-11-aftermath-expansion-announced-adds-3-new-characters-and-new-story/




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The Last of Us Part II Story Trailer Released

Publisher Sony Interactive Entertainment and developer Naughty Dog have released the story trailer for The Last of Us Part II ahead of the game's release next month.

View the trailer below:

Here is an overview of the game:

Five years after their dangerous journey across the post-pandemic United States, Ellie and Joel have settled down in Jackson, Wyoming. Living amongst a thriving community of survivors has allowed them peace and stability, despite the constant threat of the infected and other, more desperate survivors. When a violent event disrupts that peace, Ellie embarks on a relentless journey to carry out justice and find closure. As she hunts those responsible one by one, she is confronted with the devastating physical and emotional repercussions of her actions.

Key Features:

  • A Complex and Emotional Story – Experience the escalating moral conflicts created by Ellie’s relentless pursuit of vengeance. The cycle of violence left in her wake will challenge your notions of right versus wrong, good versus evil, and hero versus villain.

    A Beautiful Yet Dangerous World – Set out on Ellie’s journey, taking her from the peaceful mountains and forests of Jackson to the lush, overgrown ruins of greater Seattle. Encounter new survivor groups, unfamiliar and treacherous environments, and terrifying evolutions of the infected. Brought to life by the latest iteration of the Naughty Dog engine, the deadly characters and world are more realistic and meticulously detailed than ever before.

  • Tense and Desperate Action-Survival Gameplay – New and evolved gameplay systems deliver upon the life-or-death stakes of Ellie’s journey through the hostile world. Feel her desperate struggle for survival through improved features such as high-intensity melee combat, fluid movement, and dynamic stealth. A broad variety of weapons, crafting items, skills, and upgrades allows you to personalize Ellie’s capabilities to your play style.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443406/the-last-of-us-part-ii-story-trailer-released/




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Final Fantasy VII Remake Tops the US PlayStation Store Downloads in April 2020

Sony has released the US PlayStation Store downloads charts for March 2020. Final Fantasy VII Remake topped the PS4 charts, Beat Saber topped the PlayStation VR charts, and Call of Duty: Warzone topped the Free-to-Play Games chart. Fortnite – The Iris Pack topped the DLC and Expansions chart.

Here is the complete list of charts:

PS4 Games
1 Final Fantasy VII Remake
2 Call of Duty: Modern Warfare
3 NBA 2K20
4 Grand Theft Auto V
5 Call of Duty: Modern Warfare 2 Campaign Remastered
6 Resident Evil 3
7 Minecraft
8 EA Sports FIFA 20
9 Monopoly Plus
10 Marvel’s Spider-Man
11 Madden NFL 20
12 Tom Clancy’s Rainbow Six Siege
13 Uno
14 Predator: Hunting Grounds
15 MLB The Show 20
16 Red Dead Redemption 2
17 Need for Speed Heat
18 Rocket League
19 God of War
20 Kingdom Hearts III
PS VR Games
1 Beat Saber
2 Creed Rise to Glory
3 Job Simulator
4 Rick and Morty: Virtual Rick-ality
5 Arizona Sunshine
6 Superhot VR
7 Vacation Simulator
8 Drunkn Bar Fight
9 Astro Bot Rescue Mission
10 The Room VR: A Dark Matter
Free-to-Play Games
1 Call of Duty: Warzone
2 Fortnite
3 Apex Legends
4 Destiny 2
5 Brawlhalla
6 Dauntless
7 3on3 FreeStyle
8 Warframe
9 Paladins
10 Warface
DLC and Expansions
1 Fortnite – The Iris Pack
2 GTA Online: Criminal Enterprise Starter Pack
3 Fortnite – Bassassin Challenge Pack
4 Marvel’s Spider-Man: The City That Never Sleeps
5 Mortal Kombat 11 Kombat Pack
6 Call of Duty: Modern Warfare – Atlanta FaZe Pack
7 Need for Speed Heat – McLaren F1 Black Market Delivery
8 Call of Duty Black Ops III: Zombies Chronicles
9 Dragon Ball Z: Kakarot Season Pass
10 Mortal Kombat 11 – Shao Kahn

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443430/final-fantasy-vii-remake-tops-the-us-playstation-store-downloads-in-april-2020/




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GTAV Tops the EU PlayStation Store Downloads in April 2020, Final Fantasy VII Remake Debuts in 4th

Sony has released the Europe PlayStation Store downloads charts for April 2020. Grand Theft Auto V topped the PS4 charts, Blood and Truth topped the PlayStation VR charts, and Call of Duty: Warzone topped the Free-to-Play Games chart. Fortnite – The Iris Pack topped the DLC and Expansions chart.

Final Fantasy VII Remake debuted in fourth on the PS4 charts. Resident Evil 3 debuted in 10th place.

Here is the complete list of charts:

PlayStation 4

  1. Grand Theft Auto V (3)
  2. EA SPORTS FIFA 20 (2)
  3. Call of Duty: Modern Warfare (1)
  4. FINAL FANTASY VII REMAKE (New)
  5. NBA 2K20 (RE)
  6. Call of Duty: Modern Warfare 2 Campaign Remastered (20)
  7. EA SPORTS UFC 3 (RE)
  8. Minecraft (5)
  9. Marvel’s Spider-Man (RE)
  10. RESIDENT EVIL 3 (New)
  11. MONOPOLY PLUS (RE)
  12. Rocket League (11)
  13. Assassin’s Creed Odyssey (10)
  14. Days Gone (RE)
  15. TOM CLANCY’S RAINBOW SIX | SIEGE (RE)
  16. Red Dead Redemption 2 (19)
  17. The Crew 2 (13)
  18. Tom Clancy’s The Division 2 (RE)
  19. eFootball PES 2020 (RE)
  20. Need for Speed Heat (RE)

PlayStation VR

  1. Blood and Truth (5)
  2. Beat Saber (1)
  3. Creed: Rise to Glory (9)
  4. Job Simulator (2)
  5. RICK AND MORTY: VIRTUAL RICK-ALITY (RE)
  6. ASTRO BOT Rescue Mission (RE)
  7. Until Dawn: Rush of Blood (RE)
  8. BOXVR (RE)
  9. Farpoint (RE)
  10. SUPERHOT VR (4)

DLC

  1. Fortnite – The Iris Pack (1)
  2. Fortnite – Bassassin Challenge Pack (3)
  3. GTA Online: Criminal Enterprise Starter Pack (5)
  4. Marvel’s Spider-Man: The City That Never Sleeps – Season Pass (RE)
  5. Assassin’s Creed Odyssey – Season pass (RE)
  6. Fortnite: Save the World – Standard Founder’s Pack (10)
  7. The Division 2 – Warlords of New York – Expansion (2)
  8. Need for Speed Heat – McLaren F1 Black Market Delivery (6)
  9. Modern Warfare – Atlanta FaZe Pack (New)
  10. Assassin’s Creed Origins – The Hidden Ones (RE)

Free-to-Play

  1. Call of Duty: Warzone (1)
  2. Fortnite (2)
  3. Apex Legends (3)
  4. Brawlhalla (5)
  5. DON’T EVEN THINK (New)
  6. eFootball PES 2020 LITE (4)
  7. Destiny 2 (New)
  8. WORLD OF WARSHIPS: LEGENDS (7)
  9. DRAGON BALL XENOVERSE 2 Lite Version (6)
  10. Paladins (9)

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443431/gtav-tops-the-eu-playstation-store-downloads-in-april-2020-final-fantasy-vii-remake-debuts-in-4th/




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