An exceptionally well-preserved specimen of the articulated rhodophyte Permocalculus, compared with P. tenellus sensu Elliott, 1955, is described from fine-grained Upper Permian limestones of the Khuff Formation of Saudi Arabia. Longitudinal medullary and sheaf-like cortical filaments extend through the uniserial series of elongate-globular, concave- and convex-terminating, interlocking segments for which they are interpreted to have functioned in articulation. The filaments tend to splay and branch laterally into the cortex where they terminate at the pores. At the terminal aperture, the filaments extend as bifurcating and possibly trifurcating branches and may serve as the origin of a new segment. Numerous elongate-globular chambers, up to five in each row and intimately involved with the filaments, are developed in the outer medulla and are considered to represent reproductive sporangia. The specimen is considered to have occupied predominantly low-energy, normal to slightly elevated salinity, shallow conditions within the subtidal regime of a lagoon.

OBJECTIVE

Type 2 diabetes is characterized by increased death rate. In order to tackle this dramatic event, it becomes essential to discover novel biomarkers capable of identifying high-risk patients to be exposed to more aggressive preventive and treatment strategies. hs-CRP and serum amyloid P component (SAP) are two acute-phase inflammation proteins, which interact physically and share structural and functional features. We investigated their combined role in associating with and improving prediction of mortality in type 2 diabetes.

OBJECTIVE

We aimed to evaluate trends in bone mineral density (BMD) and the prevalence of osteoporosis/osteopenia in U.S. adults with prediabetes and normal glucose regulation (NGR) and further investigate the association among prediabetes, osteopenia/osteoporosis, and fracture.

Testosterone is an important determinant of endothelial function and vascular health in men. As both factors play a role in mortality after allogeneic stem cell transplantation (alloSCT), we retrospectively evaluated the impact of pre-transplant testosterone levels on outcome in male patients undergoing alloSCT. In the discovery cohort (n=346), an impact on outcome was observed only in the subgroup of patients allografted for acute myeloid leukemia (AML) (n=176, hereafter termed ‘training cohort’). In the training cohort, lower pre-transplant testosterone levels were significantly associated with shorter overall survival (OS) [hazard ratio (HR) for a decrease of 100 ng/dL: 1.11, P=0.045]. This was based on a higher hazard of non-relapse mortality (NRM) (cause-specific HR: 1.25, P=0.013), but not relapse (cause-specific HR: 1.06, P=0.277) in the multivariable models. These findings were replicated in a confirmation cohort of 168 male patients allografted for AML in a different center (OS, HR: 1.15, P=0.012 and NRM, cause-specific HR: 1.23; P=0.008). Next, an optimized cut-off point for pre-transplant testosterone was derived from the training set and evaluated in the confirmation cohort. In multivariable models, low pre-transplant testosterone status (<250 ng/dL) was associated with worse OS (hazard ratio 1.95, P=0.021) and increased NRM (cause-specific HR 2.68, P=0.011) but not with relapse (cause-specific HR: 1.28, P=0.551). Our findings may provide a rationale for prospective studies on testosterone/androgen assessment and supplementation in male patients undergoing alloSCT for AML.

Human bone marrow stromal cells (BMSC) are key elements of the hematopoietic environment and they play a central role in bone and bone marrow physiology. However, how key stromal cell functions are regulated is largely unknown. We analyzed the role of the immediate early response transcription factor EGR1 as key stromal cell regulator and found that EGR1 was highly expressed in prospectively-isolated primary BMSC, down-regulated upon culture, and low in non-colony-forming CD45^neg stromal cells. Furthermore, EGR1 expression was lower in proliferative regenerating adult and fetal primary cells compared to adult steady-state BMSC. Overexpression of EGR1 in stromal cells induced potent hematopoietic stroma support as indicated by an increased production of transplantable CD34⁺CD90⁺ hematopoietic stem cells in expansion co-cultures. The improvement in bone marrow stroma support function was mediated by increased expression of hematopoietic supporting genes, such as VCAM1 and CCL28. Furthermore, EGR1 overexpression markedly decreased stromal cell proliferation whereas EGR1 knockdown caused the opposite effects. These findings thus show that EGR1 is a key stromal transcription factor with a dual role in regulating proliferation and hematopoietic stroma support function that is controlling a genetic program to co-ordinate the specific functions of BMSC in their different biological contexts.

The bone marrow niche is a complex and dynamic structure composed of a multitude of cell types which functionally create an interactive network facilitating hematopoietic stem cell development and maintenance. Its specific role in the pathogenesis, response to therapy, and transformation of myeloproliferative neoplasms has only recently been explored. Niche functionality is likely affected not only by the genomic background of the myeloproliferative neoplasm-associated mutated hematopoietic stem cells, but also by disease-associated ‘chronic inflammation’, and subsequent adaptive and innate immune responses. ‘Cross-talk’ between mutated hematopoietic stem cells and multiple niche components may contribute to propagating disease progression and mediating drug resistance. In this timely article, we will review current knowledge surrounding the deregulated bone marrow niche in myeloproliferative neoplasms and suggest how this may be targeted, either directly or indirectly, potentially influencing therapeutic choices both now and in the future.

PURPOSE

General practitioners (GPs) are part of the US physician workforce, but little is known about who they are, what they do, and how they differ from family physicians (FPs). We describe self-identified GPs and compare them with board-certified FPs.

Background and objectives

Bioelectrical impedance analysis (BIA) devices can help assess volume overload in patients receiving maintenance peritoneal dialysis. However, the effects of BIA on the short-term hard end points of peritoneal dialysis lack consistency. This study aimed to test whether BIA-guided fluid management could improve short-term outcomes in patients on peritoneal dialysis.

Vibralactone, a hybrid compound derived from phenols and a prenyl group, is a strong pancreatic lipase inhibitor with a rare fused bicyclic β-lactone skeleton. Recently, a researcher reported a vibralactone derivative (compound C1) that caused inhibition of pancreatic lipase with a half-maximal inhibitory concentration of 14 nM determined by structure-based optimization, suggesting a potential candidate as a new antiobesity treatment. In the present study, we sought to identify the main gene encoding prenyltransferase in Stereum vibrans, which is responsible for the prenylation of phenol leading to vibralactone synthesis. Two RNA silencing transformants of the identified gene (vib-PT) were obtained through Agrobacterium tumefaciens-mediated transformation. Compared to wild-type strains, the transformants showed a decrease in vib-PT expression ranging from 11.0 to 56.0% at 5, 10, and 15 days in reverse transcription-quantitative PCR analysis, along with a reduction in primary vibralactone production of 37 to 64% at 15 and 21 days, respectively, as determined using ultra-high-performance liquid chromatography-mass spectrometry analysis. A soluble and enzymatically active fusion Vib-PT protein was obtained by expressing vib-PT in Escherichia coli, and the enzyme’s optimal reaction conditions and catalytic efficiency (K_m/k_cat) were determined. In vitro experiments established that Vib-PT catalyzed the C-prenylation at C-3 of 4-hydroxy-benzaldehyde and the O-prenylation at the 4-hydroxy of 4-hydroxy-benzenemethanol in the presence of dimethylallyl diphosphate. Moreover, Vib-PT shows promiscuity toward aromatic compounds and prenyl donors.

IMPORTANCE Vibralactone is a lead compound with a novel skeleton structure that shows strong inhibitory activity against pancreatic lipase. Vibralactone is not encoded by the genome directly but rather is synthesized from phenol, followed by prenylation and other enzyme reactions. Here, we used an RNA silencing approach to identify and characterize a prenyltransferase in a basidiomycete species that is responsible for the synthesis of vibralactone. The identified gene, vib-PT, was expressed in Escherichia coli to obtain a soluble and enzymatically active fusion Vib-PT protein. In vitro characterization of the enzyme demonstrated the catalytic mechanism of prenylation and broad substrate range for different aromatic acceptors and prenyl donors. These characteristics highlight the possibility of Vib-PT to generate prenylated derivatives of aromatics and other compounds as improved bioactive agents or potential prodrugs.

Gastrointestinal (GI) or gut microbiotas play essential roles in host development and physiology. These roles are influenced partly by the microbial community composition. During early developmental stages, the ecological processes underlying the assembly and successional changes in host GI community composition are influenced by numerous factors, including dispersal from the surrounding environment, age-dependent changes in the gut environment, and changes in dietary regimes. However, the relative importance of these factors to the gut microbiota is not well understood. We examined the effects of environmental (diet and water sources) and host early ontogenetic development on the diversity of and the compositional changes in the gut microbiota of a primitive teleost fish, the lake sturgeon (Acipenser fulvescens), based on massively parallel sequencing of the 16S rRNA gene. Fish larvae were raised in environments that differed in water source (stream versus filtered groundwater) and diet (supplemented versus nonsupplemented Artemia fish). We quantified the gut microbial community structure at three stages (prefeeding and 1 and 2 weeks after exogenous feeding began). The diversity declined and the community composition differed significantly among stages; however, only modest differences associated with dietary or water source treatments were documented. Many taxa present in the gut were over- or underrepresented relative to neutral expectations in each sampling period. The findings indicate dynamic relationships between the gut microbiota composition and host gastrointestinal physiology, with comparatively smaller influences being associated with the rearing environments. Neutral models of community assembly could not be rejected, but selectivity associated with microbe-host GI tract interactions through early ontogenetic stages was evident. The results have implications for sturgeon conservation and aquaculture production specifically and applications of microbe-based management in teleost fish generally.

IMPORTANCE We quantified the effects of environment (diet and water sources) and host early ontogenetic development on the diversity of and compositional changes in gut microbial communities based on massively parallel sequencing of the 16S rRNA genes from the GI tracts of larval lake sturgeon (Acipenser fulvescens). The gut microbial community diversity declined and the community composition differed significantly among ontogenetic stages; however, only modest differences associated with dietary or water source treatments were documented. Selectivity associated with microbe-host GI tract interactions through early ontogenetic stages was evident. The results have implications for lake sturgeon and early larval ecology and survival in their natural habitat and for conservation and aquaculture production specifically, as well as applications of microbe-based management in teleost fish generally.

BACKGROUND:

Prescribing of levothyroxine and rates of thyroid function testing may be sensitive to minor changes in the upper limit of the reference range for thyroid-stimulating hormone (TSH) that increase the proportion of abnormal results. We evaluated the population-level change in levothyroxine prescribing and TSH testing after a minor planned decrease in the upper limit of the reference range for TSH in a large urban centre with a single medical laboratory.

Purpose:

Radium-223 is approved for metastatic castration-resistant prostate cancer (mCRPC) based on improved overall survival, and delay in skeletal related events. However, it is not associated with PSA or radiographic response, which poses a challenge in real-time assessment of its efficacy. Surrogate markers of treatment outcomes may facilitate tailoring treatment duration with radium-223, by limiting the duration of therapy with radium-223 in these patients. Here, we sought to investigate the utility of bone metabolic markers (BMMs) as surrogate markers of response to radium-223 in mCRPC.

A strain of extensively drug-resistant (XDR) Salmonella enterica serovar Typhi has caused a large ongoing outbreak in Pakistan since 2016. In Ontario, Canada, 10 cases of mainly bloodstream infections (n = 9) were identified in patients who traveled to Pakistan. Whole-genome sequencing showed that Canadian cases were genetically related to the Pakistan outbreak strain. The appearance of XDR typhoid cases in Ontario prompted a provincial wide alert to physicians to recommend treatment with carbapenems or azithromycin in suspected typhoid cases with travel history to Pakistan.

Quinolones, such as the antimalarial atovaquone, are inhibitors of the malarial mitochondrial cytochrome bc₁ complex, a target critical to the survival of both liver- and blood-stage parasites, making these drugs useful as both prophylaxis and treatment. Recently, several derivatives of endochin have been optimized to produce novel quinolones that are active in vitro and in animal models. While these quinolones exhibit potent ex vivo activity against Plasmodium falciparum and Plasmodium vivax, their activity against the zoonotic agent Plasmodium knowlesi is unknown. We screened several of these novel endochin-like quinolones (ELQs) for their activity against P. knowlesi in vitro and compared this with their activity against P. falciparum tested under identical conditions. We demonstrated that ELQs are potent against P. knowlesi (50% effective concentration, <117 nM) and equally effective against P. falciparum. We then screened selected quinolones and partner drugs using a longer exposure (2.5 life cycles) and found that proguanil is 10-fold less potent against P. knowlesi than P. falciparum, while the quinolones demonstrate similar potency. Finally, we used isobologram analysis to compare combinations of the ELQs with either proguanil or atovaquone. We show that all quinolone combinations with proguanil are synergistic against P. falciparum. However, against P. knowlesi, no evidence of synergy between proguanil and the quinolones was found. Importantly, the combination of the novel quinolone ELQ-300 with atovaquone was synergistic against both species. Our data identify potentially important species differences in proguanil susceptibility and in the interaction of proguanil with quinolones and support the ongoing development of novel quinolones as potent antimalarials that target multiple species.

Nacubactam is a novel β-lactamase inhibitor with dual mechanisms of action as an inhibitor of serine β-lactamases (classes A and C and some class D) and an inhibitor of penicillin binding protein 2 in Enterobacteriaceae. The safety, tolerability, and pharmacokinetics of intravenous nacubactam were evaluated in single- and multiple-ascending-dose, placebo-controlled studies. Healthy participants received single ascending doses of nacubactam of 50 to 8,000 mg, multiple ascending doses of nacubactam of 1,000 to 4,000 mg every 8 h (q8h) for up to 7 days, or nacubactam of 2,000 mg plus meropenem of 2,000 mg q8h for 6 days after a 3-day lead-in period. Nacubactam was generally well tolerated, with the most frequently reported adverse events (AEs) being mild to moderate complications associated with intravenous access and headache. There was no apparent relationship between drug dose and the pattern, incidence, or severity of AEs. No clinically relevant dose-related trends were observed in laboratory safety test results. No serious AEs, dose-limiting AEs, or deaths were reported. After single or multiple doses, nacubactam pharmacokinetics appeared linear, and exposure increased in an approximately dose-proportional manner across the dose range investigated. Nacubactam was excreted largely unchanged into urine. Coadministration of nacubactam with meropenem did not significantly alter the pharmacokinetics of either drug. These findings support the continued clinical development of nacubactam and demonstrate the suitability of meropenem as a potential β-lactam partner for nacubactam. (The studies described in this paper have been registered at ClinicalTrials.gov under NCT02134834 [single ascending dose study] and NCT02972255 [multiple ascending dose study].)

Dalbavancin offers a possible treatment option for infectious peritonitis associated with peritoneal dialysis (PD) due to its coverage of Gram-positive bacteria and pharmacokinetic properties. We aimed to evaluate the clinical pharmacokinetics (PK) and pharmacodynamics of dalbavancin in a prospective, randomized, open-label, crossover PK study of adult patients with end-stage renal disease ESRD who were receiving PD. Sampling occurred prior to a single 30-min infusion of dalbavancin at 1,500 mg and at 1, 2, 3, 4, and 6 h and 7 and 14 days postadministration. Concentration-time data were analyzed via noncompartmental analysis. Pharmacodynamic parameters against common infectious peritonitis-causing pathogens were evaluated. Ten patients were enrolled. Patients were a median of 55 years old and had a median weight of 78.2 kg, 50% were female, and 70% were Caucasian. The terminal plasma half-life of dalbavancin was 181.4 ± 35.5 h. The day 0 to day 14 dalbavancin mean area under the curve (AUC) was 40,573.2 ± 9,800.3 mg·h/liter. The terminal-phase half-life of dalbavancin within the peritoneal fluid was 4.309 x 10⁸ ± 1.140 x 10⁹ h. The day 0 to day 14 dalbavancin mean peritoneal fluid AUC was 2,125.0 ± 1,794.3 mg·h/liter. The target plasma AUC/MIC was attained with the intravenous dose in all 10 patients for all Staphylococcus and Streptococcus species at the recommended MIC breakpoints. The intraperitoneal arm of the study was stopped early, because the first 3 patients experienced moderate to severe pain and bloating within 1 h following the administration of dalbavancin. Dalbavancin at 1,500 mg administered intravenously can be utilized without dose adjustment in peritoneal dialysis patients and will likely achieve the necessary peritoneal fluid concentrations to treat peritonitis caused by typical Gram-positive pathogens.

Enterococcus faecium strains are commonly resistant to vancomycin and β-lactams. In addition, E. faecium often causes biofilm-associated infections and these infections are difficult to treat. In this context, we investigated the activity of dosing regimens using daptomycin (DAP) (8, 10, 12, and 14 mg/kg of body weight/day) alone and in combination with ceftaroline (CPT), ampicillin (AMP), ertapenem (ERT), and rifampin (RIF) against 2 clinical strains of biofilm-producing vancomycin-resistant Enterococcus faecium (VREfm), namely, strains S447 and HOU503, in an in vitro biofilm model. HOU503 harbors common LiaS and LiaR substitutions, whereas S447 lacks mutations associated with the LiaFSR pathway. MIC results demonstrated that both strains were susceptible to DAP and resistant to CPT, AMP, ERT, and RIF. The 168-h pharmacokinetic/pharmacodynamic (PK/PD) CDC biofilm reactor models (simulating human antibiotic exposures) were used with titanium and polyurethane coupons to evaluate the efficacy of antibiotic combinations. DAP 12 and 14 achieved bactericidal activity against S447 but lacked such effect against HOU503. Addition of ERT and RIF enhanced DAP activity, allowing DAP 8 and 10 plus ERT or RIF to produce bactericidal activity against both strains at 168 h. While DAP 8 and 10 plus CPT improved killing, they did not reach bactericidal reduction against S447. Combination of AMP, CPT, ERT, or RIF resulted in enhanced and bactericidal activity for DAP against HOU503 at 168 h. Our data provide further support for the use of combinations of DAP with AMP, ERT, CPT, and RIF in infections caused by biofilm producing VREfm. Further research involving DAP combinations against biofilm-producing enterococci is warranted.

Omadacycline is an aminomethylcycline antibiotic with in vitro activity against pathogens causing community-acquired bacterial pneumonia (CABP). This study investigated the activity of omadacycline against Legionella pneumophila strains isolated between 1995 and 2014 from nosocomial or community-acquired respiratory infections. Omadacycline exhibited extracellular activity similar to comparator antibiotics; intracellular penetrance was found by day 3 of omadacycline exposure. These results support the utility of omadacycline as an effective antibiotic for the treatment of CABP caused by L. pneumophila.

Tilorone is a 50-year-old synthetic small-molecule compound with antiviral activity that is proposed to induce interferon after oral administration. This drug is used as a broad-spectrum antiviral in several countries of the Russian Federation. We have recently described activity in vitro and in vivo against the Ebola virus. After a broad screening of additional viruses, we now describe in vitro activity against Chikungunya virus (CHIK) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV).

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.

Background:

Sex steroid hormones and sex hormone–binding globulin (SHBG) have been implicated in the etiology of invasive breast cancer, but their associations with risk of the precursor lesion, ductal carcinoma in situ (DCIS) of the breast, remain unclear.

Background:

Asian Americans are at higher risk for noncardia gastric cancers (NCGC) relative to non-Hispanic Whites (NHW). Asian Americans are genetically, linguistically, and culturally heterogeneous, yet have mostly been treated as a single population in prior studies. This aggregation may obscure important subgroup-specific cancer patterns.

Tobacco smoking is the primary risk factor for lung cancer, driven by the addictive nature of nicotine and the indisputable carcinogenicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as well as other compounds. The integration of lung cancer chemoprevention with smoking cessation is one potential approach to reduce this risk and mitigate lung cancer mortality. Experimental data from our group suggest that kava, commonly consumed in the South Pacific Islands as a beverage to promote relaxation, may reduce lung cancer risk by enhancing NNK detoxification and reducing NNK-derived DNA damage. Building upon these observations, we conducted a pilot clinical trial to evaluate the effects of a 7-day course of kava on NNK metabolism in active smokers. The primary objective was to compare urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL plus its glucuronides, major metabolites of NNK) before and after kava administration as an indicator of NNK detoxification. Secondary objectives included determining kava's safety, its effects on DNA damage, tobacco use, and cortisol (a biomarker of stress). Kava increased urinary excretion of total NNAL and reduced urinary 3-methyladenine in participants, suggestive of its ability to reduce the carcinogenicity of NNK. Kava also reduced urinary total nicotine equivalents, indicative of its potential to facilitate tobacco cessation. Plasma cortisol and urinary total cortisol equivalents were reduced upon kava use, which may contribute to reductions in tobacco use. These results demonstrate the potential of kava intake to reduce lung cancer risk among smokers.

Nguyen Tran Nam, former Deputy Minister of Construction, also President of the Vietnam Real Estate Association (VNREA) says in comparison to buying, renting a home is a better solution for young Vietnamese.

Many people have headaches considering landed house or condominium (condo) for their accommodation choice. By analyzing the pros and cons of each of these types, the infographic below will help you make the right choice.

Lots of people sell their current home at the same time as buying a new one, forming a property chain. Selling before you buy has risks, but it can also have great advantages.

Assassin’s Creed Valhalla creative director Ashraf Ismail previously stated the game will feature a "large map" in terms of England. There will be four major English kingdoms: Wessex, Northumbria, East Anglia, and Mercia. There will also be three major cities: London, Winchester and Jórvík (now called York).

Since the game takes place in southern England Ismail was asked via Twitter if the game will feature Stonehenge and he replied "oh, can you ever!" with a GIF of a man nodding yes. 

Here is an overview of the game:

In Assassin’s Creed Valhalla, you are Eivor, a fierce Viking warrior raised on tales of battle and glory. Explore a dynamic and beautiful open world set against the brutal backdrop of England’s Dark Ages. Raid your enemies, grow your settlement, and build your political power in your quest to earn your place among the gods in Valhalla.

Key Features:

• Write Your Viking Saga – Advanced RPG mechanics allow you to shape the growth of your character and influence the world around you. With every choice you make, from political alliances and combat strategy to dialogue and gear progression, you will carve your own path to glory.
• Visceral Combat System – Dual-wield powerful weapons such as axes, swords, and even shields to relive the ruthless fighting style of the Viking warriors. Brutally decapitate your foes, vanquish them from afar, or stealthily assassinate targets with your hidden blade. Challenge yourself with the most varied collection of deadly enemies ever found in an Assassin’s Creed game.
• A Dark Age Open World – Sail from the harsh and mysterious shores of Norway to the beautiful but forbidding kingdoms of England and beyond. Immerse yourself in the Viking way of life through fishing, hunting, drinking games, and more.
• Lead Epic Raids – Launch massive assaults against Saxon troops and fortresses throughout England. Lead your clan in surprise attacks from your longship and pillage enemy territories to bring riches and resources back to your people.
• Grow Your Settlement – Construct and upgrade buildings that allow for deep customization, including a barracks, blacksmith, tattoo parlor, and more. Recruit new members to your clan and personalize your Viking experience.
• Mercenary Vikings – Create and customize a unique Viking raider within your clan and share it online with friends to use during their own raids.

Assassin’s Creed Valhalla will launch for Xbox Series X, PlayStation 5, PlayStation 4, Xbox One, Windows PC, and Google Stadia in Holiday 2020. The game will support Smart Delivery on the Xbox. This means if you purchase the game on the Xbox One or Xbox Series X, you will automatically gain access to the other version of the game. 

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/443400/assassins-creed-valhalla-to-feature-stonehenge/

Publisher Private Division and developer V1 Interactive announced Disintegration will launch for the PlayStation 4, Xbox One and Windows PC via Steam on June 16 for $49.99.

View the story trailer below:

Here is an overview of the game:

Disintegration is a sci-fi, first-person shooter that blends real-time tactical elements to create an entirely new experience. Set in a world ripped apart by famine, scarce resources, and the planet on the brink of destruction, humanity has developed a process to survive its harsh reality known as Integration, in which a human brain is transferred to a robotic armature. From the ensuing chaos, an aggressive, militaristic legion, known as the Rayonne, gain control and begins to impose the once optional process of Integration onto the rest of humanity to consolidate their power.

Players command Romer Shoal, an incredibly-skilled Gravcycle pilot, who leads a small band of outlaws to fight back against an overwhelming Rayonne force. Over the course of a thrilling single-player campaign, players will control a Gravcycle loaded with weaponry, leading Romer and his team across a series of diverse missions packed with action, explosions, and plot twists, to beat back the Rayonne forces and give the last vestiges of humanity hope to prevail.

In addition to the full single-player campaign, Disintegration features frenetic player-versus-player multiplayer where pilots and their crews compete in three game modes and six distinct maps. Players can select from nine highly-stylized “Crews” which lend themselves to different playstyles.

Multiplayer provides a host of cosmetic customizations that can be purchased or earned in-game, including pilot and crew skins, cosmetic Gravcycle customizations, and a variety of banners. In addition to the multiplayer content at release, the team at V1 will be supporting the game post-launch with seasonal content drops.

Key Features:

• Tactical Gravcycle Combat – Pilot a heavily armed Gravcycle featuring a variety of firepower, maneuverability, and abilities.
• Riveting Single-player Campaign – From Marcus Lehto, the co-creator of Halo and creative director of Halo: Reach, comes an all-new sci-fi saga. Play as Romer Shoal and confront the Rayonne, a rising global army set on eliminating what remains of humanity.
• Frenetic Multiplayer Action – Battle across a variety of maps in three intense, team-based five-versus-five multiplayer modes. Choose your favorite Gravcycle and lead your crew alongside your teammates, competing against opposing pilots to win objective-based matches.

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/443412/disintegration-launches-june-16-for-ps4-xbox-one-and-steam/

Publisher Wired Productions and developer Camel 101 have delayed psychological horror game, Those Who Remain, from May 15 to May 28 for the PlayStation 4, Xbox One and Windows PC via Steam. 

View the official release date trailer below:

Here is an overview of the game:

As the lights go out, the embers of darkness are stoked in the sleepy town of Dormont.

Whispers of disappearances carry through the town as a burgeoning, uneasy and irrational fear begins to spread and darkness comes to be an unwelcome reflection to Those Who Remain.

Some mistakes should never happen, not when your life is complete – and yet they do. Edward had the good life, a beautiful wife and the perfect little girl, yet finds himself several whiskeys down and driving through the night of Dormont to end his secret affair – in a bid to fix his mistakes.

As Edward pulls into the Golden Oak Motel, he is unaware just how much this night will change his life…

Key Features:

The horrors and darkness that thrive in the corner of every eye are torn loose…

Those Who Remain places you in an up-close, psychological horror story set in the sleepy town of Dormont – a town in a spiralling split from the fabric of reality, warped by darkness and the deeds of the Citizens who reside.

Confront the uncomfortable horrors reflected by the darkness and survive the night of Dormont as Edward is confronted with a test of his sanity, morality and the shadows of evil that lurks below.

• Darkness Has Eyes -Navigate and survive the encroaching darkness and stay in the protection of the light by any means[br]
• Worlds Torn Asunder – Pave your way ahead by moving between Dormont and its dark otherworldly counterpart to further solve the mysteries held within the dark
• Conscience of Choice – Choose to help any surviving citizens of Dormont you encounter or leave them to the darkness. Innocence cannot always be assumed, and the township of Dormont hides a cursed trove of secrets
• Savor your Sanity – Keep your sanity in check as you delve deeper into the darkness of Dormont – expected rules of the real world have been torn apart
• Follow your Path – Your decisions and choices will determine the fate of Edward, through multiple different branching outcomes

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/443413/those-who-remain-delayed-to-may-28-for-ps4-xbox-one-and-steam/

Publisher Raw Fury and developer Out of the Blue have announced adventure game, Call of the Sea, for the Xbox Series X, Xbox One and Windows PC via Steam. It will launch in late 2020.

View the reveal trailer below:

Here is an overview of the game:

It is 1934, in the far reaches of the South Pacific. Norah has crossed the ocean following the trail of her missing husband’s expedition and finds herself on a lush island paradise—a nameless, forgotten place, dotted with the remnants of a lost civilization.

What strange secrets does it hold, and what might Norah unearth in her quest for the truth?

Key Features:

• Explore the Beauty – Explore a stunning tropical island (meticulously modeled in Unreal Engine 4), brimming with fantastic sights, lost ruins and occult mysteries.
• Meet Norah – Experience an emotional, charming character study of a woman on a journey of self-discovery, fully voiced by Cissy Jones (Firewatch, The Walking Dead: Season 1).’
  Dive into the Deep – Immerse yourself in a story-driven adventure full of suspense and surreal surprises.
• Search for Meaning – Investigate the clues left by a previous voyage, piece together what happened, and solve a variety of clever puzzles.

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/443418/call-of-the-sea-announced-for-xbox-series-x-xbox-one-and-pc/

Publisher Deep Silver and developer Fishlabs have announced Chorus: Rise as One for the Xbox Series X, PlayStation 4, PlayStation 4, Xbox One, and Windows PC. It will launch in 2021.

View the announcement trailer below:

Here is an overview of the game:

Take control of Nara, once the Circle’s deadliest warrior, now their most wanted fugitive, on a quest to destroy the dark cult that created her. Unlock devastating weapons and mind-bending abilities in a true evolution of the space-combat shooter. Along with Forsaken, her sentient starfighter, explore ancient temples, engage in exhilarating zero-g combat, and venture beyond our waking reality.

Key Features:

• Journey of Redemption – Lead Nara, an ace pilot facing her haunted past, and Forsaken, her sentient ship on a quest for redemption across the galaxy.
• Venture Beyond the Void – Enter a dark new universe, teeming with mystery that balances the scale and spectacle of exploration with fast-paced action.
• One Pilot, One Ship, One Living Weapon – Attain unique weapons. Unlock deadly abilities. Chain powers together to become the ultimate living weapon.

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/443419/chorus-rise-as-one-announced-for-xbox-series-x-ps5-ps4-xbox-one-and-pc/

Codemasters during the latest Inside Xbox event announced Dirt 5 for the Xbox Series X. The game will also launch for the PlayStation 5, PlayStation 4, Xbox One, and Google Stadia. It will release in October 2020.

View the announcement trailer below:

Read an overview of the game via Xbox below:

Fresh out of the box from the latest Inside Xbox, myself and the whole Codemasters team are delighted to reveal Dirt 5 to the world (but especially you), launching this year on both Xbox One and Xbox Series X.

For a while now, our dedicated development team in Cheshire, UK has been under the hood of this machine, turning a concept into reality. Well, gaming reality. You get what I mean. That concept? To make the boldest, bravest, most stylish off-road racing game ever made, where intense, competitive action is just the beginning of what blows you away in Dirt 5.

To the uninitiated who may not be clued up on the legacy of Dirt, let’s go for a drive, all the way back to 1998, when Colin McRae Rally brought the world of off-road racing into gaming and into the mainstream. With the series morphing into Dirt in 2007, it’s delivered high-impact extreme racing ever since – most recently through the brutal, ultra-realistic Dirt Rally 2.0. This time around with Dirt 5, we’re doing things a little… differently.

Take a peek at our announce trailer, first revealed exclusively during Inside Xbox, and you’ll see what we mean – from the stunning locations, to the epic racing, to the variety of vehicles and surfaces. We’re putting you behind the wheel of incredible off-road machines, in iconic real-world settings, to race through dynamic routes and extreme conditions. But don’t forget the concept. All that racing action is only part of the story.

We wanted to go bigger, in all possible ways. Take Career, which hands you a deep story-based mode with a star-studded cast, led by the legendary Troy Baker and Nolan North. These legendary voices of gaming, and some familiar names from the car culture world, lay out a story with decision-based changes and a proper narrative to get your teeth into.

There’s the franchise’s deepest livery editor and in-race Photo Mode, where you can show off your creative side. Then you’ve got the 12-player multiplayer action with playful objective-based modes, the four-player split-screen for offline frolics with your pals, and even more brand new features we’ll be revealing more on soon… I’m basically listing stuff at this point, but there’s so much going on here!

And not to forget: Everything we’re laying out here is raised up a notch through the, quite frankly, intimidating power of Xbox Series X. The team here has made use of the tools to create an unprecedented level of graphical fidelity and optimized performance. What does that mean for you in Dirt 5? Constant action, greater potential in gameplay, and seeing every spec of mud kick up and splat onto your windscreen. Ah, bliss.

Before I leave you, I wanted to give you a pro tip; a little pocket of knowledge to store away until Dirt 5 bursts onto the scene this Autumn. When you jump into this game, forget the norm. Forget expectations. Forget the ‘regular’ way of playing. Dirt 5 dares you – and rewards you – for being creative, stylish, and sometimes for being a straight-up lunatic.

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/443421/dirt-5-announced-coming-to-xbox-series-x-ps5-ps4-xbox-one/

Developer Systemic Reaction has announced three-player, online cooperative shooter, Second Extinction, for the Xbox Series X, Xbox One and Windows PC via Steam.

"I’m very proud of what our team has created," said Systemic Reaction managing director Tobias Andersson. "As a live game, we plan to support Second Extinction long-term, as we do with all our titles. We can’t wait for players to team up, start playing, and become part of our community."

Lead producer Brynley Gibson added, "Second Extinction is a real passion project for our tight-knit team, and we’re just getting started. It’s incredible how far we’ve come in this short time, and I’m super excited to reveal more details, including our live roadmap, in the coming months."

View the announcement trailer below:

Here is an overview of the game:

Second Extinction is an intense three-player cooperative shooter, where your goal is to wipe out the mutated dinosaurs that have taken over the planet. Teamwork is  vital as you adopt the role of one of the survivors, using a unique combination of  weapons, abilities and skills to take on the vast number of enemies. Fight through  a maelstrom of bullets, bombs, teeth, claws and gore, it’s up to you to reclaim  Earth!

Key Features:

• Intense Three-Player Co-Op – Earth is overrun by mutated dinosaurs! Team up with up to two other resistance fighters to take it back in short but intense combat operations.
• Battle Mutated Monstrosities – These dinos are nothing like the ones in your history books! From electric raptors  to behemoth T-Rexes that tower over the horizon, these deadly creatures have evolved into the ultimate killing machines.
• Experience Spectacular Action – Combine your fireteam’s unique weapons and abilities for explosive results  against overwhelming opposition in challenging combat set pieces.
• Take Part in a Joint Effort – Your actions, together with the rest of the community, will shape the course of  the war against the dinosaurs.

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/443423/fps-second-extinction-announced-for-xbox-series-x-xbox-one-and-pc/

Bandai Namco has announced a new RPG, Scarlet Nexus, for the Xbox Series X and Xbox One. It will feature Smart Delivery. A release date was not announced. 

"The next generation of video game home consoles lets the development team realize the full potential of Scarlet Nexus," said producer Keita Iizuka. "Players can expect visuals and psychic battles with high resolution and frame rate along with fully interactive real-time battles with dynamic animation. Utilizing Smart Delivery on Xbox Series X also means players can enjoy the best version of Scarlet Nexus regardless of whether they are playing on the next generation with Xbox Series X or Xbox One."

Bandai Namco America senior brand manager Stephen Akana added, "Scarlet Nexus aims to change the way gamers view Japanese RPGs with a powerful futuristic aesthetic as well as a streamlined combat system that balances fast-paced action with strategic planning. Lead by an extremely talented team at Bandai Namco Studios, including members from fan-favorite title Tales of Vesperia, Scarlet Nexus combines years of game development experience with the excitement and creative freedom of the power behind the next generation of home console systems."

View the announcement trailer below:

Here is an overview of the game:

Scarlet Nexus takes place in the far distant future, where a psionic hormone was discovered in the human brain, granting people extra-sensory powers and changed the world as we knew it. As humanity entered this new era, deranged mutants known as Others began to descend from the sky with a hunger for human brains. Impervious to conventional weapons, those with acute extra-sensory abilities, known as psionics, were our only chance to fight the onslaught from above and preserve humanity. Since then, psionics have been scouted for their talents and recruited to the Other Suppression Force, humanity’s last line of defense.

In Scarlet Nexus, players will take on the role of Yuito Sumeragi, armed with a talent in psycho-kinesis, and explore the futuristic city of New Himuka and uncover the mysteries of a Brain Punk future caught between technology and physic abilities. With these psycho-kinetic powers, the world becomes an important ally. Lift, break, and hurl pieces of the environment to build attack combos and lay waste to enemies.

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/443425/bandai-namco-announces-rpg-scarlet-nexus-for-xbox-series-x-and-xbox-one/