Chronic obstructive pulmonary disease (COPD) is characterised by persistent respiratory symptoms and airflow limitation, which is caused by small airway disease (bronchiolitis) and alveolar destruction (emphysema) [1]. Patients primarily suffering from severe emphysema are often limited in exercise capacity due to the consequences of hyperinflation [2].

Purpose:

To provide a better understanding of the interplay between the immune system and brain metastases to advance therapeutic options for this life-threatening disease.

Current treatments for Acanthamoeba keratitis rely on a combination of chlorhexidine gluconate, propamidine isethionate, and polyhexamethylene biguanide. These disinfectants are nonspecific and inherently toxic, which limits their effectiveness. Furthermore, in 10% of cases, recurrent infection ensues due to the difficulty in killing both trophozoites and double-walled cysts. Therefore, development of efficient, safe, and target-specific drugs which are capable of preventing recurrent Acanthamoeba infection is a critical unmet need for averting blindness. Since both trophozoites and cysts contain specific sets of membrane sterols, we hypothesized that antifungal drugs targeting sterol 14-demethylase (CYP51), known as conazoles, would have deleterious effects on A. castellanii trophozoites and cysts. To test this hypothesis, we first performed a systematic screen of the FDA-approved conazoles against A. castellanii trophozoites using a bioluminescence-based viability assay adapted and optimized for Acanthamoeba. The most potent drugs were then evaluated against cysts. Isavuconazole and posaconazole demonstrated low nanomolar potency against trophozoites of three clinical strains of A. castellanii. Furthermore, isavuconazole killed trophozoites within 24 h and suppressed excystment of preformed Acanthamoeba cysts into trophozoites. The rapid action of isavuconazole was also evident from the morphological changes at nanomolar drug concentrations causing rounding of trophozoites within 24 h of exposure. Given that isavuconazole has an excellent safety profile, is well tolerated in humans, and blocks A. castellanii excystation, this opens an opportunity for the cost-effective repurposing of isavuconazole for the treatment of primary and recurring Acanthamoeba keratitis.

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.

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.

The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score was developed to establish a simple, standardized scoring system for researchers to quantify adherence to the 2018 WCRF/AICR Cancer Prevention Recommendations and assess its impact on cancer risk and other health-related outcomes. The aim of this commentary is to clarify potential points of ambiguity in its application, focusing on aspects related to specific subscore components (physical activity, fast foods, alcohol, and sugar-sweetened drinks), how to address different data needs due to varied data collection instruments, and future exploratory score approaches. Overall, we encourage researchers to utilize the standardized score to enhance comparability across populations and countries. Researchers who may adapt or augment the 2018 WCRF/AICR Score are strongly encouraged to provide detailed descriptions of their methods to promote transparency and reproducibility.

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.

BACKGROUND AND PURPOSE:

Conventional nonadhesive liquid embolic agents currently are the criterion standard for endovascular embolization of cerebral AVMs. However, inadequate distal penetration into the nidus and unstable proximal plug formation are the major limitations of this approach and of the currently available embolic materials. The aim of this study was to evaluate the hypothetic efficacy of combining liquid embolic agents with different properties and viscosities for use in endovascular embolization of cerebral AVMs.

BACKGROUND AND PURPOSE:

Detailed insight into the composition of thrombi retrieved from patients with ischemic stroke by mechanical thrombectomy might improve pathophysiologic understanding and therapy. Thus, this study searched for links between histologic thrombus composition and stroke subtypes and mechanical thrombectomy results.

Đồ án Quy hoạch phân khu xây dựng tỷ lệ 1/2.000 Khu Công nghiệp - Đô thị Becamex A (Phân khu 7), Khu kinh tế Nhơn Hội với tổng diện tích lập quy hoạch là 1.425,4ha vừa được UBND tỉnh Bình Định phê duyệt.

Prime Minister Nguyen Xuan Phuc has just asked the Ministry of Construction (MoC) to promulgate regulations on amendments and supplements to construction standards and rules for condominiums, condotels, resort villas, officetels and rooms for rent.

Prof. Jason Pomeroy talks about the rise of the digital economy and its impact on the workplace.

(function () { var vjs = videojs("hapyak-player-225918-6090"); vjs.one("loadedmetadata", function () { hapyak.viewer({ apiKey: "dd426e8a5f6c45db9ca6", projectId: 225918, plugins: { annotationSources: {"brightcove.cuepoints": true} }, resetVariables: true, player: […]

The post Fundamentals for Creating a Shoppable Interactive Video for eCommerce appeared first on e-Learning Feeds.

Microsoft has announced it will share new information on the Xbox Series X every month in 2020 starting with the May 7th episode of Inside Xbox, which will showcase gameplay from third-party partners. Microsoft is calling it "Xbox 20/20." The event starts at 8am PT / 11am ET. 

"These monthly moments will take place throughout the rest of the year and will be a way for us to engage, connect and celebrate with you about what’s in store for the next generation of gaming, including what’s next for Xbox Series X, Xbox Game Studios, Xbox Game Pass and Project xCloud," said Microsoft. "Every month will bring something different. Stay tuned to Xbox Wire for more details."

The company did reveal the July event will be focused on upcoming first-party games from Xbox Game Studios. 

"A number of our studio teams are looking forward to sharing first looks at new gameplay, insights from development teams being optimized for Xbox Series X, and brand-new game announcements," said Microsoft.  "We cannot wait to share this initial look at what some of those teams are working on."

A new teaser video of the May 7 Inside Xbox event has been posted online and the closed captions reveals it is the "New Xbox Sound." It is possible it is the new bootup screen for the Xbox Series X. View the video below:

The Inside Xbox event for May 7 can be watched from multiple streaming sites:

• Facebook
• Mixer
• Twitch
• Twitter
• YouTube (4K stream)

Read more information below:

This is a momentous year for Xbox, with our next-gen console paving the way for all our games and services to come together in even better ways. Here’s what 2020 looks like, just to start:

• Our goal remains to launch Xbox Series X and Halo Infinite this Holiday
• All 15 Xbox Game Studios teams are hard at work on next-generation games for Xbox Series X and Xbox Game Pass
• The best development teams around the world are working hard to have their games ready to play on Xbox Series X this holiday
• For PC players, we plan to support the community by making all our major releases at launch available with Xbox Game Pass for PC, including Halo Infinite, Wasteland 3, Minecraft Dungeons and of course, Microsoft Flight Simulator.
• We have new updates and titles lined up for Xbox Game Pass for console and PC
• We’re expanding Project xCloud into new countries and on new devices—and later this year Project xCloud and Xbox Game Pass will come together, enabling you and your friends to play together in more ways.

It’s a lot – and that’s saying something in 2020, a year which could be summed up as “a lot.” With all this in mind, we set out to create new touchpoints to celebrate gaming and share what’s next with our global community.

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/443394/xbox-series-x-news-planned-for-every-month-of-2020-starts-with-inside-xbox-gameplay-reveals-on-may-7/

Microsoft has announced many new titles coming to Xbox Game Pass for console and Windows PC in May. The list of games includes DayZ, Final Fantasy IX, and Fractured Minds, Endless Legend and the previously announced Red Dead Redemption 2 for console and Halo 2: Anniversary for Halo: The Master Chief Collection for PC.

Here is the list of games coming soon to Xbox Game Pass for Console:

DayZ (ID@Xbox) – May 7
An unforgiving, authentic, open world game where each one of 60 players on a server follows a single goal: Survive as long as they can, by any means necessary. There are no superficial tips, waypoints, or help given to you. Every decision matters with no saves and no extra lives where mistakes can be lethal. Your choices and decisions will create a gameplay experience that’s completely unique.

Red Dead Redemption 2 – May 7
America, 1899. Arthur Morgan and the Van der Linde gang are outlaws on the run. With federal agents and the best bounty hunters in the nation massing on their heels, the gang must rob, steal, and fight their way across the rugged heartland of America to survive. As deepening internal divisions threaten to tear the gang apart, Arthur must make a choice between his own ideals and loyalty to the gang who raised him. Includes access to Red Dead Online (Xbox Live Gold required).

Final Fantasy IX – May 14
Zidane and the Tantalus Theater Troupe have kidnapped Princess Garnet, the heir of Alexandria. To their surprise, however, the princess herself yearned to escape the castle. Through a series of unusual circumstances, she and her personal guard, Steiner, fall in with Zidane and set out on an incredible journey in this classic entry in the heralded Final Fantasy series.

Fractured Minds (ID@Xbox) – May 19
Fractured Minds is an immersive artistic short game, exploring anxiety and mental health issues. Embark on a journey through the human psyche to experience the everyday challenges associated with these conditions.

Here is the list of games coming soon to Xbox Game Pass for PC:

Endless Legend
Jump in to this 4X strategy game as you lead one of eight unique civilizations, each with their own unique gameplay and story. Food must be grown, industries built, science and magic advanced, and wealth collected. Your planet holds a history of unexplained apocalypse, and the winter you just survived was the worst on record. You have a city, a loyal populace, and a few troops; your power and magic should be sufficient to keep them alive. But beyond that, nothing is certain… Where will you go, what will you find, and how will you react?

Final Fantasy IX
Zidane and the Tantalus Theater Troupe have a plan to kidnap Princess Garnet, the heir of Alexandria. To their surprise, the princess herself beats them to the punch and orchestrates her own escape with their unwitting help, granting her the freedom she yearned for beyond the castle walls. Through a series of unusual circumstances, she and her personal guard, Steiner, fall in with Zidane and his crew, and set out on an incredible journey in this classic Final Fantasy adventure.

Halo Master Chief Collection: Halo 2
Halo 2: Anniversary comes to PC as the next installment in Halo: The Master Chief Collection. Following the destruction of the first Halo ring, Master Chief returns to Earth to prevent the Covenant invasion, leading to a battle with long-hidden secrets that will dramatically alter the course of the Human-Covenant Conflict forever.

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/443405/xbox-game-pass-adds-dayz-final-fantasy-ix-and-more-in-may/

Paris Games Week 2020 organizer SELL announced it has cancelled this years event due to concerns over the ongoing coronavirus (COVID-19) pandemic. The event was set to run from October 23 to 27. 

Read the message from SELL below:

Dear players,

It is with great emotion that we have made the difficult decision to cancel Paris Games Week, initially scheduled from 23rd to 27th October and which would have marked our 10th anniversary.

The current context and the necessary anticipation of both the technical and logistical complexities of an event such as Paris Games Week have led us to cancel this edition.

This year should have been special, with a line-up full of new releases, and an anniversary edition which we were thrilled to celebrate with you.

We are going to work with all the industry players to enable us all to live our passion. We are already preparing next year’s edition and are looking forward to seeing you again.

Our Very Best Regards,

The Paris Games Week Team

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/443416/paris-games-week-2020-cancelled-due-to-coronavirus-pandemic/

Bloober Team has announced psychological horror game, The Medium, for Xbox Series X and Windows PC via Steam. It will launch this holiday season and be available on Xbox Game Pass.

"Every one of our games has a central theme that drives its creative and technological design," said Bloober Team CEO Piotr Babieno.

"In The Medium, we focus on perspective and perception. When you change your point of view, you discover that things are more complicated and nuanced than you initially thought. The Medium is our most ambitious game ever and we can’t wait to show you how we’re translating this vision into a psychological horror."

View the reveal trailer below:

Here is an overview of the game:

Become a medium living in two different worlds: the real one and the spirit one. Haunted by the vision of a child’s murder, you travel to an abandoned hotel resort, which many years ago became the stage of an unthinkable tragedy. There you begin your search for difficult answers.

As a medium with access to both worlds, you have a wider perspective and can see more clearly that there’s no one simple truth to what others perceive. Nothing is what it seems, everything has another side.

The Medium features a “dual” soundtrack by Bloober Team’s Arkadiusz Reikowski and legendary composer Akira Yamaoka of Silent Hill fame.

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/443420/psychological-horror-game-the-medium-announced-for-xbox-series-x-and-pc/

ebb software has released a new trailer for the Xbox Series X version of the atmospheric first-person horror adventure, Scorn. The game is in development for the Xbox Series X and Windows PC via Steam and Windows Store.

View the Xbox Series X trailer below:

Here is an overview of the game:

Scorn is set in a nightmarish universe of odd forms and somber tapestry. It is designed around the idea of "being thrown into the world". Isolated and lost inside this dream-like world, you will explore different interconnected regions in a non-linear fashion. Every location contains its own theme, puzzles and characters that are integral in creating a cohesive world.

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/443422/horror-adventure-game-scorn-xbox-series-x-trailer-released/

Ubisoft has released the first look gameplay trailer for Assassin’s Creed Valhalla. The gameplay is "representative of Xbox Series X gameplay."

"As developers, we’re always excited to work with new hardware because it gives us a greater ability to express our creative vision," said Assassin’s Creed Valhalla creative director Ashraf Ismail. "Assassin’s Creed has always been committed to exploring new technologies and leveraging new consoles’ abilities to deliver the most immersive experience possible. We are excited to be collaborating closely with Microsoft to bring Assassin’s Creed Valhalla to the Xbox Series X."

View the Assassin’s Creed Valhalla gameplay trailer below:

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/443428/assassins-creed-valhalla-gets-xbox-series-x-first-look-gameplay-trailer/

After lots and lots of #hype in the form of a livestream digital painting reveal that was the precursor to a proper trailer which was also just a precursor to what we were assured would be a first look at actual gameplay, folks were a bit let down by the not very gameplay-looking new video for […]

This anime-style action game about fighting off the creatively-named “others” was one of the many trailers we peeped during Xbox’s big reveal real yesterday. Bandai Namco have announced that Scarlet Nexus is actually coming to PC as well, so we’ll get to do a bit of monster butt-kickin’ too. Is that an evil bouquet of […]

As any good Guardian knows, Destiny 2 isn’t just a jargon-filled sci-fi loot ’em up. It’s just as much, if not more so, a far-future fashion show. But in a game about constantly trading out new gear, keeping a fresh look has always felt a little contentious. This week, Bungie revealed that Year 4 will […]

Stuck for things to play this weekend? After offering their exhaustive JRPG lineup at a pittance last week, Square Enix have this week gutted the price of their Eidos Anthology bundle on Steam as part of their “Stay Home & Play” campaign – offering 54 PC classics, contemporary bangers and bizarre curiosities for just under […]

Ancestors is the latest attempt to gamify millions of years of evolution but doesn't have the excitement gene, says Jacob Aron

Tech firms are making record profits but paying little tax. Now global leaders are discussing ways to make them pay their fair share

The covid-19 pandemic has many of us stuck at home. The result could completely reshape how we use the internet, writes Annalee Newitz

Psychologist Pete Etchells explores what the scientific research has to say about game violence and addiction and busts some myths

Strange as it may sound, Animal Crossing: New Horizons feels like where Breath of the Wild should have ended up gameplay-wise.

This post contains spoilers for Dead to Me Season 2.

Maybe it’s the surreality of, well, everything lately—or maybe it’s just aged like the fine wines all of its characters toss back by the bottle. Whatever the reason, Dead to Me Season 2 hits even better than Season 1—fighting off a sophomore slump with a fresh batch of twists, dramatic ironies, and, most importantly, some more Christina Applegate angsting out to metal. Perhaps this season’s smartest move, however, is a trope pulled straight out of Soapy Dramas 101: Bringing James Marsden back to play his own twin.

Series creator Liz Feldman was sending the usual thank-you notes back and forth with cast and crew after Season 1 wrapped when she received a particularly amusing message from Marsden.

Read more at The Daily Beast.

A tiny meteorite found in Antarctica doesn’t match any asteroid or comet we know of. Instead, it must have come from a mystery parent body that’s full of water

The interstellar comet Borisov, which flew past Earth in December, is full of carbon monoxide ice that implies its home star is smaller and colder than our sun

After more than three long years, the Justice Department has finally lived up to its name by dropping charges against my former boss, former National Security Adviser and retired Army Lt. Gen. Michael Flynn. He should have never been prosecuted.

Will Flynn be the right wing's Nelson Mandela? Of course that's insulting - but so is this entire presidency

Megyn Kelly's exclusive sit down with Tara Reade

New labor economy data paints a fuller - and bleaker - picture of the economy.

In their search for killer apps, robotics companies should look at the amazing evolution of computers

The machine would use an “alphabet of human thoughts” and rules to combine them

OpenAI’s GPT-2 program churns out natural language that’s remarkably coherent—and that’s a problem

DJ D-Nice, Miley Cyrus, Ben Gibbard, and a lot of Diplo.

Hindsight is 20/20, even if you’re smizing.

Whether they feature office bumbling, demon slaying, or parcel delivering, these games couldn’t have come at a better time.