Over 4 decades of research support the link between Alzheimer disease (AD) and somatostatin [somatotropin-releasing inhibitory factor (SRIF)]. SRIF and SRIF-expressing neurons play an essential role in brain function, modulating hippocampal activity and memory formation. Loss of SRIF and SRIF-expressing neurons in the brain rests at the center of a series of interdependent pathological events driven by amyloid-β peptide (Aβ), culminating in cognitive decline and dementia. The connection between the SRIF and AD further extends to the neuropsychiatric symptoms, seizure activity, and inflammation, whereas preclinical AD investigations show SRIF or SRIF receptor agonist administration capable of enhancing cognition. SRIF receptor subtype-4 activation in particular presents unique attributes, with the potential to mitigate learning and memory decline, reduce comorbid symptoms, and enhance enzymatic degradation of Aβ in the brain. Here, we review the links between SRIF and AD along with the therapeutic implications.

Our knowledge of the roles of individual cytochrome P450 (P450) enzymes in drug metabolism has developed considerably in the past 30 years, and this base has been of considerable use in avoiding serious issues with drug interactions and issues due to variations. Some newer approaches are being considered for "phenotyping" metabolism reactions with new drug candidates. Endogenous biomarkers are being used for noninvasive estimation of levels of individual P450 enzymes. There is also the matter of some remaining "orphan" P450s, which have yet to be assigned reactions. Practical problems that continue in drug development include predicting drug-drug interactions, predicting the effects of polymorphic and other P450 variations, and evaluating interspecies differences in drug metabolism, particularly in the context of "metabolism in safety testing" regulatory issues ["disproportionate (human) metabolites"].

BACKGROUND AND PURPOSE:

Neuronal ceroid lipofuscinoses are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for neuronal ceroid lipofuscinosis type 2 (CLN2), a subtype of neuronal ceroid lipofuscinoses. The aim of this study was to quantify brain volume loss in CLN2 disease in patients on ERT in comparison with a natural history cohort using MRI.

BACKGROUND AND PURPOSE:

World Health Organization (WHO) grade 2 and 3 diffuse gliomas account for approximately 5% of primary brain tumors. They are invasive and infiltrative tumors and have considerable morbidity, causing progressive neurologic deterioration. The mean survival time is <10 years from diagnosis. Surgical debulking represents first-line management. The extent of resection is associated with progression-free and overall survival. Radiologic assessment of the extent of resection is challenging. This can be underestimated on early postoperative MRI, meaning that accurate assessment may be achieved only on delayed follow-up imaging. We hypothesized that DWI may help facilitate more reliable estimates of the extent of resection on early postoperative MRI. This study aimed to assess the utility of DWI in early postoperative MRI to evaluate the extent of resection.

BACKGROUND AND PURPOSE:

Recently, artificial intelligence tools have been deployed with increasing speed in educational and clinical settings. However, the use of artificial intelligence by trainees across different levels of experience has not been well-studied. This study investigates the impact of artificial intelligence assistance on the diagnostic accuracy for intracranial hemorrhage and large-vessel occlusion by medical students and resident trainees.

SUMMARY:

The 2021 World Health Organization Classification of Tumors of the Central Nervous System (CNS5), introduced significant changes, impacting tumors ranging from glial to ependymal neoplasms. Ependymal tumors were previously classified and graded based on histopathology, which had limited clinical and prognostic utility. The updated CNS5 classification now divides ependymomas into 10 subgroups based on anatomic location (supratentorial, posterior fossa, and spinal compartment) and genomic markers. Supratentorial tumors are defined by zinc finger translocation associated (ZFTA) (formerly v-rel avian reticuloendotheliosis viral oncogene [RELA]), or yes-associated protein 1 (YAP1) fusion; posterior fossa tumors are classified into groups A (PFA) and B (PFB), spinal ependymomas are defined by MYCN amplification. Subependymomas are present across all these anatomic compartments. The new classification kept an open category of "not elsewhere classified" or "not otherwise specified" if no pathogenic gene fusion is identified or if the molecular diagnosis is not feasible. Although there is significant overlap in the imaging findings of these tumors, a neuroradiologist needs to be familiar with updated CNS5 classification to understand tumor behavior, for example, the higher tendency for tumor recurrence along the dural flap for ZFTA fusion-positive ependymomas. On imaging, supratentorial ZFTA-fused ependymomas are preferentially located in the cerebral cortex, carrying predominant cystic components. YAP1-MAMLD1-fused ependymomas are intra- or periventricular with prominent multinodular solid components and have significantly better prognosis than ZFTA-fused counterparts. PFA ependymomas are aggressive paramedian masses with frequent calcification, seen in young children, originating from the lateral part of the fourth ventricular roof. PFB ependymomas are usually midline, noncalcified solid-cystic masses seen in adolescents and young adults arising from the fourth ventricular floor. PFA has a poorer prognosis, higher recurrence, and higher metastatic rate than PFB. Myxopapillary spinal ependymomas are now considered grade II due to high recurrence rates. Spinal-MYCN ependymomas are aggressive tumors with frequent leptomeningeal spread, relapse, and poor prognosis. Subependymomas are noninvasive, intraventricular, slow-growing benign tumors with an excellent prognosis. Currently, the molecular classification does not enhance the clinicopathologic understanding of subependymoma and myxopapillary categories. However, given the molecular advancements, this will likely change in the future. This review provides an updated molecular classification of ependymoma, discusses the individual imaging characteristics, and briefly outlines the latest targeted molecular therapies.

Metastatic porocarcinomas (PCs) are vanishingly rare, highly aggressive skin adnexal tumors with mortality rates exceeding 70%. Their rarity has precluded the understanding of their disease pathogenesis, let alone the conduct of clinical trials to evaluate treatment strategies. There are no effective agents for unresectable PCs. Here, we successfully demonstrate how functional precision medicine was implemented in the clinic for a metastatic PC with no known systemic treatment options. Comprehensive genomic profiling of the tumor specimen did not yield any actionable genomic aberrations. However, ex vivo drug testing predicted pazopanib efficacy, and indeed, administration of pazopanib elicited remarkable clinicoradiological response. Pazopanib and its class of drugs should be evaluated for efficacy in other cases of PC, and the rationale for efficacy should be determined when PC tumor models become available. A functional precision medicine approach could be useful to derive effective treatment options for rare cancers.

T-lymphoblastic lymphoma (T-LLy) is the most common lymphoblastic lymphoma in children and often presents with a mediastinal mass. Lymphomatous suprarenal masses are possible but rare. Here, we discuss the case of a previously healthy 3-yr-old male who presented with mediastinal T-LLy with bilateral suprarenal masses. Following initial treatment, surgical biopsy of persisting adrenal masses revealed bilateral neuroblastoma (NBL). A clinical genetics panel for germline cancer predisposition did not identify any pathogenic variants. Combination large panel (864 genes) profiling analysis in the context of a precision oncology study revealed two novel likely pathogenic heterozygous variants: SMARCA4 c.1420-1G > T p.? and EZH2 c.1943G > C p.(Ile631Phefs*44). Somatic analysis revealed potential second hits/somatic variants in EZH2 (in the T-LLy) and a segmental loss in Chromosome 19p encompassing SMARCA4 (in the NBL). Synchronous cancers, especially at a young age, warrant genetic evaluation for cancer predisposition; enrollment in a precision oncology program assessing germline and tumor DNA can fulfill that purpose, particularly when standard first-line genetic testing is negative and in the setting of tumors that are not classic for common cancer predisposition syndromes.

BackgroundIncident benzodiazepine prescriptions in primary care for anxiety decreased between 2003 and 2018. However, from 2008, incident prescribing of benzodiazepines for anxiety increased among those aged 18–34 years. There are increasing concerns around prescribing of benzodiazepines. Further, although guidelines state benzodiazepines should only be prescribed short term, in 2017, 44% of incident prescriptions were prescribed for longer than the recommended duration of 2–4 weeks.AimTo understand when and why GPs prescribe benzodiazepines for anxiety in young adults.Design and settingA qualitative study was undertaken using in-depth interviews with 17 GPs from 10 general practices in South West England.MethodInterviews were conducted by telephone or videocall. A topic guide was used to ensure consistency across interviews. Interviews were audio-recorded, transcribed verbatim, and data analysed using reflexive thematic analysis.ResultsGPs described caution in prescribing benzodiazepines for anxiety in young adults, but thought they had an important role in acute situations. GPs described caution in prescribing duration, but some thought longer-term prescriptions could be appropriate. In light of these views, some GPs questioned whether primary care needs to revisit how clinicians are using benzodiazepines. GPs perceived that some young adults requested benzodiazepines and suggested this might be because they wanted quick symptom relief. GPs noted that refusing to prescribe felt uncomfortable and that the number of young adults presenting to general practice, already dependent on benzodiazepines, had increased.ConclusionPatient-driven factors for prescribing benzodiazepines suggest there are current unmet treatment needs among young adults with anxiety. Given increases in prescribing in this age group, it may be timely to revisit the role of benzodiazepines in the management of people with anxiety in primary care.

PURPOSE

We undertook a trial to test the efficacy of a technology-assisted health coaching intervention for weight management, called Goals for Eating and Moving (GEM), within primary care.

Over the past decades the zebrafish has emerged as an excellent model organism with which to study the biology of all glial cell types in nervous system development, plasticity, and regeneration. In this review, which builds on the earlier work by Lyons and Talbot in 2015, we will summarize how the relative ease to manipulate the zebrafish genome and its suitability for intravital imaging have helped understand principles of glial cell biology with a focus on oligodendrocytes, microglia, and astrocytes. We will highlight recent findings on the diverse properties and functions of these glial cell types in the central nervous system and discuss open questions and future directions of the field.

A nudibranch from the midnight zone has fingers on its tail, collects food with a hood, and glows.

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JUDY WOODRUFF: And in the day’s other news: More than 300 people are now confirmed dead after Saturday’s massive truck bombing in Somalia, one of the world’s worst attacks in years.

Nearly 400 more were wounded. The government blamed the al-Qaida-linked Al-Shabaab group. Rescue crews today searched for survivors at the scene of the bombing, a crowded street in the capital, Mogadishu. With dozens still missing, officials say they expect the death toll to rise.

OSMAN LIBAH IBRAHIM, Deputy Minister for Natural Resources, Somalia (through interpreter): More bodies are gradually being found and removed from the rubble. There are other people who are under the rubble. We have heard them as they scream for help. My biggest worry is that even the wounded are succumbing to their injuries.

JUDY WOODRUFF: The attack happened two days after Somalia’s defense minister and army chief resigned for undisclosed reasons.

There’s been yet another shift to the right in European politics; 31-year-old conservative Sebastian Kurz, Austria’s foreign minister, is set to become that country’s next leader. But he’s short of a majority in Parliament and will likely form a coalition with the far-right Freedom Party. It was founded by ex-Nazis in the 1950s.

Kurz has called for the European Union to focus more on internal trade and securing borders. He celebrated in Vienna.

SEBASTIAN KURZ, Austrian People’s Party (through interpreter): I have a big request for you. Use today to celebrate. You all have earned it through hard work and dedication. At the same time, I need to tell you that tomorrow the work starts. We didn’t just run to win the elections. We did so to bring Austria back to the top. We ran in this election to achieve real change.

JUDY WOODRUFF: A final result in the election is likely to be decided on Thursday.

Wildfires that broke out over the weekend in Portugal have killed at least 35 people, including a one-month-old infant. Today, more than 5,300 firefighters with some 1,600 vehicles were battling the fires, some of which officials say were started by arsonists. Wildfires have also left at least four people dead in neighboring Spain.

Army Sergeant Bowe Bergdahl pleaded guilty today to desertion and misbehavior before the enemy. He was captured by the Taliban in 2009, after leaving his post in Afghanistan. It prompted an intense search and a prisoner swap. Bergdahl appeared before a military judge in Fort Bragg, North Carolina, today. The 31-year-old could be sentenced to life in prison. He said his actions were very inexcusable, adding he didn’t — quote — “think there’d be any reason to pull off a crucial mission to look for one guy.”

The truck driver in deadly immigrant smuggling run has pleaded guilty in court. San Antonio police found at least 39 immigrants, 10 of whom died, packed into a sweltering semi-trailer last year and died. The driver, James Matthew Bradley Jr., pleaded to conspiracy and transporting immigrants, resulting in death. He faces now up to life in prison.

A New Jersey man has been convicted of planting two pressure-cooker bombs on New York City streets last year. Ahmed Khan Rahimi faces a maximum sentence of life in prison for charges including using a weapon of mass destruction. One of the bombs exploded in Manhattan’s Chelsea neighborhood, wounding 30. The second didn’t detonate. Officials said Rahimi was inspired by ISIS and al-Qaida.

JOHN MILLER, Deputy Commissioner, NYPD Intelligence & Counterterrorism: Ahmed Khan Rahimi learned a lesson which we keep reminding people of. This is the wrong place to try and carry out an act of terrorism. Witnesses will come forward, evidence will be developed, arrests will be made, prosecutions will be brought forth, and they will be successful.

JUDY WOODRUFF: Prosecutors said Rahimi also planted a pipe bomb in Seaside Heights, New Jersey, but no one was injured.

Colin Kaepernick has filed a grievance against the national football league. The former San Francisco 49ers quarterback says that he remains unsigned due to collusion by team owners over his national anthem protests. Kaepernick sparked a debate when he kneeled during the anthem last year, protesting police mistreatment of African-Americans.

On Wall Street today, the Dow Jones industrial average gained 85 points to close at 22957. The Nasdaq rose 18. And the S&P 500 added four.

It was a milestone day in the world of astronomy. For the first time, researchers say they have detected gravitational waves with a flash of light from the same cosmic event. The dual observation supports Albert Einstein’s general theory of relativity. The ripples in space and the light burst were caused by the collision of two neutron stars. They were first detected in August.

The post News Wrap: Dozens missing after deadly Mogadishu truck bombing appeared first on PBS NewsHour.

TOKYO — U.S. and Japanese diplomats agreed Tuesday to maximize pressure on North Korea to resolve tensions over its nuclear program, while citing the need to be prepared for the worst if diplomacy fails.

U.S. Deputy Secretary of State John Sullivan, after meeting his Japanese counterpart, Shinsuke Sugiyama, told reporters that the focus at the State Department is still on diplomacy to solve the problem and eventually denuclearize the Korean Peninsula.

“We must, however, with our allies in Japan and South Korea and elsewhere, be prepared for the worst should diplomacy fail,” he said. The U.S. must be prepared to defend itself and its allies, he said.

Sugiyama, briefing reporters separately, reiterated Japan’s support for President Donald Trump’s policy of keeping all options open, but stressed the need for a diplomatic solution by bolstering cooperation among Japan, U.S. and South Korea, as well as via cooperation with China and Russia.

The two diplomats will join their South Korean counterpart in Seoul for further talks Wednesday on North Korea.

READ MORE: Rex Tillerson says continue diplomacy with North Korea ‘until first bomb drops’

The talks come as the U.S. and South Korea hold joint naval drills this week. They regularly conduct joint exercises, though North Korea condemns them as an invasion rehearsal.

North Korea’s deputy U.N. ambassador warned on Monday that the situation on the peninsula “has reached the touch-and-go point and a nuclear war may break out any moment.”

Kim In Ryong told the U.N. General Assembly’s disarmament committee that North Korea has been subjected to a direct nuclear threat from the United States and has the right to possess nuclear weapons in self-defense.

He pointed to military exercises and what he called a U.S. plan to stage a “secret operation aimed at the removal of our supreme leadership.”

Kim’s speech follows increasingly tough U.N. sanctions. Russian President Vladimir Putin said his country is curtailing economic, scientific and other ties with North Korea in line with U.N. sanctions, and the European Union announced new sanctions as well.

The post U.S., Japan agree to maximize diplomatic pressure on North Korea appeared first on PBS NewsHour.

Anna Marie wonders why we can't be friends. Jonathan becomes a Marbula One fan. Kelley engages "pants off, games on" mode. And Chris learns that the only person he's cheating is himself...and his dire gryphon.

The post RPG Cast – Episode 584: “A Crater Sized Hole Filled with Funko Pops!” appeared first on RPGamer.

Kelley watches the American Sailor Moon pilot acid trip fever dream. Tam is going off to get 800 glamour shots. Chris gets carded while trying to buy a Mara.

The post RPG Cast – Episode 644: “Is That a Demon Machine Making a Pizza?” appeared first on RPGamer.

Kelley hoards all the PS5s. Chris needs a build for the I'm Bad playstyle. And Josh gets treatment for his cat's demon tapeworm.

The post RPG Cast – Episode 645: “Rob Zombie’s Drag-Gula Lost” appeared first on RPGamer.

Matt makes twenty slices of toast. Josh is still fighting sewer rat six. Kelley's dog is NOT a baby. And Chris saves E3 with the power of...no...he can't do it. No GEX allowed.

The post RPG Cast – Episode 684: “Remember What I Said at the Fazoli’s Drive Thru?” appeared first on RPGamer.

Chris wonders if they serve tea at British rock concerts. Kelley gets smashed in the face with a chicken. Josh learns about alliance diaper gnomes. Do not google "diaper gnomes."

The post RPG Cast – Episode 699: “Contained Pizza Mess” appeared first on RPGamer.

Kelley becomes a Battletoads Jedi. Chris visits Atelier Risa the pleasure planet. Robert will pay the price of free-to-play. Josh patents our new adult animation series.

The post RPG Cast – Episode 729: “Zelda Goes to IKEA” appeared first on RPGamer.

Audiovisual pioneers Kristina Karpysheva and Alexandr Letsius on creating colossal, mind-bending installations.

The post Interview: 404.zero appeared first on Fact Magazine.

World-building, identity and decolonising spaces in the digital and offline realms.

The post Interview: Gabriel Massan & LYZZA appeared first on Fact Magazine.

A TV series based on the video game series Mass Effect is officially in development at Amazon, according to a report from Variety.

F9: The Fast Saga writer Daniel Casey will write and be an executive producer on the series. Karim Zreik will also be an executive producer under his Cedar Tree Productions, which is under an overall deal at Amazon.

Ari Arad and BioWare's Michael Gamble will also be executive producers. Arad previously was a producer on other video game adaptations - Borderlands and Uncharted.

Developer BioWare is developing a new entry in the Mass Effect series. 

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 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463013/mass-effect-tv-series-has-been-greenlit-by-amazon/

Call of Duty: Black Ops 6 has remained in first place on the New Zealand charts, according to IGEA for the week ending November 3, 2024.

There were two new releases in the top 10 this week with Dragon Age: The Veilguard debuting in second place and Horizon Zero Dawn Remastered in fourth place.

Hogwarts Legacy is down one spot to third place, Grand Theft Auto V is up three spots to fifth place, and NBA 2K25 climbed from ninth to sixth place.

Red Dead Redemption is in seventh place, Borderlands 3 is in eight place, Battlefield 2042 is in ninth place, and EA Sports FC 25 rounds out the top 10.

Here are the top 10 best-selling titles in New Zealand for the week:

1. Call of Duty: Black Ops 6
2. Dragon Age: The Veilguard - NEW
3. Hogwarts Legacy
4. Horizon Zero Dawn Remastered - NEW
5. Grand Theft Auto V
6. NBA 2K25
7. Red Dead Redemption
8. Borderlands 3
9. Battlefield 2042
10. EA Sports FC 25 

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 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463029/dragon-age-the-veilguard-debuts-in-2nd-on-the-new-zealand-charts/

When I was reviewing Final Fantasy VII Rebirth a few months ago, it looked set to be my Game of the Year. Metaphor: ReFantazio was still a distant concept and, I thought, communication of that concept was anything great. It turns out that I was really underestimating Atlus at the time. It's been eight years since Persona 5, and maybe I had begun to forget its magic, because as a JRPG from the creators of Persona 5, the magic is undoubtedly there in Metaphor: ReFantazio.

When I was younger, I used to watch the Columbo series, where you know the culprit's identity right away at the start. Metaphor: ReFantazio is a bit like that, because the introduction shows the King of Euchronia (Metaphor's fantasy world) being murdered in his sleep by an ambitious aristocrat named Louis, which throws the whole country into turmoil. From there, the protagonist and the comrades he meets all have different reasons for sharing the same goal: to prevent the wicked Louis from seizing the throne.

As simple as it seems, the narrative has its fair share of surprises. This has to do with the tremendous wealth of characters in the game. Due to a certain magic, the race for the throne is turned into an election, in which the protagonists gets to runs. Adding to the eight playable characters, you meet several competitors and followers who back you. All of them have personal stories and strange personalities that make Metaphor's adventure strikingly vivid.

The sub-stories are quite interesting for most part, for they convey a range of different emotions: sometime are heart-breaking, sometime heart-warming or just purely fun, and they'll keep you engaged for hours. They often leave you in suspense, since the structure of the game has you experiencing them little by little. And, just like in Persona, you can spend extensive time with your allies in a whole lot of mini sequences that play a great part in making the cast truly unforgettable.

But that doesn't mean you'll forget about the main story. Metaphor: ReFantazio offers some fascinating chapters. Take for instance the Opera house one, it's a breathtaking chapter very reminiscent of the great Final Fantasy VI, absolutely loaded with memorable sequences, grandiose fights, and striking reveals. And in the end, the whole game is like that. The thirst for more is real, as Atlus always drops a little something to make you eager to progress and feel engaged - a new character, intense combat, a shocking truth, stunning landscapes, etc. Even the most common NPCs sometimes tell a tale that blows your mind. Metaphor: ReFantazio has so much to offer in terms of characters, creativity, and storytelling that I couldn't help feeling overwhelmed at times.

The incongruity of an election in a kingdom ruled by Royals for ages is in reality an occasion for the story to develop elaborate thoughts about democracy and society. The protagonist always carries with him a strange book about an ideal world, where people have equal chances, decide their own fates, and live in harmony. It's a dream-like realm wholly different from Euchronia, which is a medieval regime plagued by injustice, greed, and poverty.

But there are whispers of a past, of a very advanced civilisation that ultimately failed, creating a scenario that raises the question of the relationship between democracy and freedom. There are also different tribes in the game, and it's worth noticing that the protagonist's party has one representative of each tribe, like a call for tolerance in a kingdom known for its inequality. The narrative therefore has powerful philosophic elements - something that only the greatest works in JRPG history possess.

Metaphor: ReFantazio boasts world design like you seldom see, starting with the giant flying rock that has symbolized it since reveal. Here again Atlus' creativity is absolutely inspired. The designers left their comfort zone and came up with an innovative take on characters, meaning that they ditched the classical human hero or heroine. You befriend an elf-like girl, a bat-like character or a maiden with a third eye, but no real typical human. The result is a party that literally breathes fantasy, a bit like Final Fantasy Tactics Advance did in its time. Humans exist, though, but on the opposite side of the divide.

These so-called Humans are twisted and awfully misshapen creatures roaming Euchronia as dangerous enemies. Atlus went beyond the boundaries of the bizarre with these designs and the result is amazing. I could also mention the funny Runner, a land vessel with legs that the party owns. Just travelling with it feels incredible. There are numerous examples like this, but in short the world is packed with wonders that I've never seen in a game before.

As for combat, Metaphor: ReFantazio is a good old turn-based JRPG, where strategy and careful planning matter. Characters wield the power of Archetypes, abstract figures that party members turn into when attacking. Archetypes are essentially jobs, hence my mention of Final Fantasy Tactics above. You can equip a character with an archetype, and they then acquire attack and passive skills specific to that archetype. For example, the Gunner can deal what is called "pierce" damage from behind, the Warrior heavy "slash" damage with its greatsword, and the Mage masters the natural elements.

There are also very complex Archetypes like the Masked Dancer, which can wear different masks to mimic other Archetypes, or the all-powerful Summoner, who masters absolutely ever type of damage once you acquire the corresponding stones (needless to say, these are incredibly difficult to come by). Unlike Persona 5, every character can equip any archetype, so you can choose the allies you like the most. Besides that, the currently-equipped Archetype can also inherit a couple of skills or spells from another, allowing for very elaborate lineups.

Combat isn't simplistic or easy; basic skills won't do much against bosses or even the relatively big enemies within dungeons. For these, the player must analyze how Archetypes can cooperate. Two Healers can, for example, cast a light spell on all opponents, while a single healer only targets one. Three magic-type archetypes lets the Mage unleash the mightiest fire spell available, which comes in handy at times. Such cooperation skills take more than one turn crystal (as turns are represented in game), but you can save turn crystals by exploiting the enemy's weakness, like you can in Shin Megami Tensei and its spin-offs.

The possibilities offered by Archetypes are fantastic and their complexity goes well beyond anything I've experienced from Atlus thus far. You have several types of Archetypes that work against a set weakness (three Archetype lineages have fire spells, for example). So you can choose the ones that fit your current goal or preferences. Boss fights are no joke and it's a renewed pleasure to overcome the various (tough) challenges after devising the right strategy. Metaphor: ReFantazio also lives up to Persona 5 in two particular aspects: main dungeons are never short of surprises, and the presentation of the battle menu is once again fantastic.

Like in Persona, Metaphor: ReFantazio is played in limited time. There's an in-game calendar with deadlines set to clear the main dungeons. So you can't have everyone master every archetype - you need to choose and use every day wisely. Unlike Persona 5, which gives you fixed Personas that you have to figure out how to use optimally, building characters and Archetypes in Metaphor: ReFantazio must be planned well ahead of time. This a fundamental difference between the two and the reason why this new IP elevates Atlus' core gameplay conceits, which were already very good. Exploration is important and quite entertaining too: you can tackle tricky secondary dungeons, discover special shops, or visit your followers. 

The latter provide perks, like increased slots for inherited skills, greater experience gain and, most importantly, the ability to unlock advanced Archetypes. The Healer can become the Cleric, for instance, with far superior healing capabilities, and you can become a General after being a Commander, gaining powerful ice skills in addition to the potent fire skills the latter had.

The whole game must be seen as a wide array of possibilities, with the player finding their own way to victory with their choices and favorite characters. As far as I'm concerned, this feels rewarding beyond anything I expected. Overflowing with content, the game is very long (around 70 hours), even with Atlus allowing you save time (any low-level enemy on the map can be beaten instantly without entering a turn-based battle, and you'll still gain experience and materials). 

The visuals are Metaphor's clear weakness. The game modeling isn't what you'd expect from a PS5 game in 2024, and I'd say it's fairly underwhelming for PS4 too. The backgrounds aren't very sharp and you see aliasing here and there. Secondary dungeons look very common; actually, they don't look like much of anything really. And there are several towers to explore across Euchronia, but the interior of each tower looks the exact same everytime. This kind of reuse of assets is fairly disappointing for a game of this magnitude. I shiver at the thought of what Metaphor: ReFantazio could have looked like with a Final Fantasy-sized budget. I expect it would have been my first perfect score, but it looks like I'll need to withhold that one once again.

One aspect that does score perfect marks is the original music score. Here again, I was pretty sure that Final Fantasy VII Rebirth would be my soundtrack of the year, but Metaphor's music blows it away completely. Atlus' sound team has crafted vibrant choruses befitting the heroic fantasy genre, but with such unorthodox compositions that it felt fresh to my ears. Other vocals and melodies are bewitching to the point they lift your spirit in battle or dungeons. And there's the strange theme of Virga island, with its weird vocals and hypnotic murmurs. It sounds like a tribal chant from afar, a bit like what Genshin Impact achieved with the Natlan soundtrack two months ago. The music is a splendid journey in itself.   

Metaphor: ReFantazio is the type of game you feel was made to achieve something greater than just sales. It's a completely new world, boasting an immense wealth of gameplay, characters, locations, and music, redefining heroic fantasy like no JRPG has done for decades. Atlus' latest title is also a fantastic challenge for turn-based combat and strategy lovers, with highly enjoyable and rewarding dungeons. Put another way, Metaphor: ReFantazio is the golden age of fantasy JRPGs, revived from the ashes in all its majesty, no less.

During the day, Thomas is a normal account manager. But at night he becomes Ryuzaki57, an extreme otaku gamer hungry for Japanese games (preferably with pretty girls in the main role). He spends a lot of time on F2P RPGs, but never misses the lastest interesting releases. Feel free to contact on twitter at @Ryuz4ki57

Full Article - https://www.vgchartz.com/article/463032/metaphor-refantazio-ps5/

Neowiz announced it has signed a global publishing rights partnership with Warsaw, Poland-based developer Zakazane to publish the first title from the studio. The game from Zakazane is a single-player noir western RPG.

Zakazane is led by Jan Bartkowicz, Piotr Chomiak, Radosław Gwarek, and Marta Sobek, and features developers who previously worked at central European game companies, including  CD Projekt RED and 11 bit studios.

"Neowiz is committed to delivering remarkable, story-driven games that resonate with gamers worldwide, and we’re actively searching for talented developers with a passion for well-crafted narratives,” said Neowiz co-CEO Seung-Cheol Kim.

"When we first met Zakazane, we felt an immediate kinship around their passion for developing projects that profoundly captivate audiences. Their upcoming neo-western RPG will be a key addition to our portfolio and reflects our ambition to build lasting franchises across PC and consoles. Together, we will create a brand that unites quality and storytelling for gamers to cherish for years to come."

Zakazane CEO and co-founder Jan Barkowicz, "We found a great understanding of our vision with Neowiz, who got excited about our debut title the minute we showed them the demo. In conversations that followed, they never tried to steer us away from our principles but rather to make sure we stick to our guns. It’s clear both sides understand that games can become important to people on a personal level, making them both valuable works of culture and good business."

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 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463035/neowiz-to-publish-western-rpg-by-poland-based-developer-zakazane/

Publisher Xbox Game Studios and developer Compulsion Games have released a 30-minute long documentary on for South of Midnight titled "Weaving Hazel's Journey."

The video share a behind-the-scenes look at the upcoming third-person action-adventure game. It explores the development and world building, as well as providing a look at new gameplay.

View the documentary below:

South of Midnight will launch for the Xbox Series X|S, PC via Steam and Microsoft Store, and Xbox Game Pass in 2025.

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 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463044/south-of-midnight-gets-30-minute-weaving-hazels-journey-documentary/

Journalists at CNN, including some of the network’s biggest personalities, are living in fear of “inevitable” layoffs and pay cuts as its new CEO looks to shore up finances amid declining ratings.

That’s according to The Ankler, which reported Wednesday that 77-year-old Chris Wallace—whose already been relegated to a weekend program—is among the network’s most well-known names whose future is in limbo.

Wallace’s $8.5 million contract, signed by the ex-CNN boss Jeff Zucker to recruit him away from Fox News three years ago, is reportedly up and he was spotted in CEO Mark Thompson’s office on Tuesday.

Read more at The Daily Beast.

The Real Housewives of Salt Lake City is TV’s best soap opera, week after week offering twists more shocking than secret twins and characters returning from the dead. That’s because it’s all real, happening in the most haunted suburb in the continental United States.

Where else do two women connect over knowing the long-lost birth father of one’s child? Is there another city where women squabble over body positivity in a parking lot off the side of a snowy mountain? Surely, there’s no other place on Earth where Lisa Barlow could come across anywhere near a voice of reason.

But that all happens here in Salt Lake City. Five episodes in, Season 5 has continued to evolve into the most captivating season in modern Real Housewives history, carried by the ever-changing bonds between our OGs and a team of wonderfully bizarre newbies.

Read more at The Daily Beast.

Relatives of Lyle and Erik Menendez spoke in an interview Wednesday about their long-running fears that the brothers had been abused for years before they killed their parents.

After a press conference in which they’d called for the imprisoned siblings’ freedom, the family members told Chris Cuomo on NewsNation about how their suspicions only deepened as time passed.

“Over the years we really did know that there was abuse at gut-level. But as time goes on and we all talked to each other more and more, it validates the fears and the gut-level reactions that we had,” the brothers’ cousin Karen VanderMolen-Copley told Cuomo. “That solidified the knowledge that the sexual abuse actually did occur, because that’s not something you want to believe, and then once you talk to each other it becomes more and more obvious.”

Read more at The Daily Beast.

Stationeers and Icarus developers RocketWerkz are making a spiritual successor to beloved space sim Kerbal Space Program, which is currently titled "Kitten Space Agency" in a flagrant display of adherence to wholesome internet trends. It's based on an actual Kerbal Space Program 2 pitch the studio threw at Take-Two subsidiary Private Division back in the day. RocketWerkz CEO and original DayZ creator Dean Hall has hired several former KSP and KSP2 developers to work on the game, and is describing it on social media as a "KSP killer".

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Some days, I wonder if every word written before a trailer is actually superfluous. It’s a visual medium, after all. What can a description achieve save to clumsily gesture at the true shape of something; a dog-eared tour brochure for a thrilling weekend spelunking in Plato’s cave? I can usually shake this feeling, but gory zombie action game Showa American Story is my breaking point. There is nothing I can impart about this thing that will not be conveyed better by allowing its new trailer to wash over you like a tide of sheer videogame. Here’s it:

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I have zero archaeology experience or knowledge, but I bet archaeologists really love their jobs (for the most part). They get to analyse and discover cool artefacts and educate us on the histories of forgotten civilisations. That's dreamy stuff, that is. But I do wonder what it's like for archaeologists to discover and study something they shouldn't have; something with a disturbing secret - a curse, maybe. Bite-sized horror game The Children Of Clay explores this idea and I'd like more of it, please.

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Hori's latest addition to its controller lineup, the "Horipad Wireless for Steam," is now available for preorder on Amazon. After already releasing in Japan at the end of October, now the gamepad is coming to the US.

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Life simulation game Inzoi will launch on PC via Steam early access on 28th March 2025, publishers Krafton have announced. Billed as a potential Sims 4 usurper, and equipped with syrupy Unreal Engine 5 visuals, it was originally slated for launch this year.

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Sega are delisting several bundles of 'classic' games from digital stores, along with "select individual" games. On Steam specifically, this adds up to over 60 games in total, including several actual classics including the original Streets Of Rage trilogy, Crazy Taxi, and Jet Set Radio.

The games will be removed on December 6th but will remain playable to those who already own them.

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Could tower defence be the ultimate "it's Friday and I am here in body only" genre? I haven't really thought about it before, but Rift Riff's effusively laidback crowd control has me pondering those optimal moments in any tower defender when the incoming horde hits the flamer-MG triangle just right, and you can settle back comfortably into the role of clockwatcher.

Rift Riff encourages this behaviour by being nice to look at. Created by a trio of developers including Hidden Folks designer Adriaan de Jongh, it's a world of spacey, sun-carved mountains, forests and monoliths. The towers resemble the sacred architecture of Monument Valley, and the colour scheme and general ambience remind me of Cocoon. There's a demo, if you fancy it.

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Warhammer 40,000: Gladius - Relics Of War developers Proxy Studios have just released Zephon, a new 4X strategy game set in a manky, post-apocalyptic world. It's got hexagonal maps, flesh trees, gangly Evangelion-grade giants, "otherworldly hymns of decay", nuclear bombs, and a player-led "blend of magic and cyberpunk" that extends from the city architecture to the research component. All of which is my cup of giblets. Here's the launch trailer.

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Great God Grove is, in a word, bonkers. I’ve stopped a small community from completing a blood ritual, played the role of matchmaker to a group of lonely hearts that involved organising a date with god, and plastered a statue with paint as part of a revolutionary movement to uplift the power of art. My time with GGG has been a pick n’ mix of colourful escapades, and together with its story of godly woes, striking art style, vacuum-based puzzle-solving, and nightmare-inducing puppet work, I’m now a die-hard LimboLane devotee.

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Here’s a Steam quote for you: ‘The Rise Of The Golden Idol is the best game I’ve ever played where I spent most of my time staring at the screen going “well what chuffing well is it, then?!” Fiendish but fair, this detective puzzler demands a heady mix of observation, deduction, and logic, but rewards you with a progressively engaging story, and steadily more infuriatingly brilliant puzzles. Despite teaching you everything you need to know in the tutorial, it still manages to introduce new wrinkles and twists on the formula with each fresh chapter. My verdict? Imagine me lying my floor, massaging my temple with one hand and giving a fat thumbs up with the other.

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It is nearly time for one of astronomy's top annual sights – the Perseid meteor shower. This year is a bit special, says Abigail Beall

‘Little red dot’ galaxies seen by JWST appear to be much more tightly packed with stars than other galaxies, raising big questions about how they came to be this way

Exoplanets in binary star systems usually orbit both stars, but astronomers have now spotted three planets orbiting one or the other star in a pair

A distant planet should have been consumed when its star expanded to become a red giant, perhaps offering insights into planetary migration

Cracks running through samples of asteroid Ryugu were probably formed by the repeated thawing and freezing of water inside it, which could have helped asteroids like this carry the building blocks of life to early Earth

Andrew McConnell's otherworldly photograph captures a Russian cosmonaut in front of the just-landed Soyuz MS spacecraft in Kazakhstan's remote grasslands