Title: Recent COVID-19 Raises Odds for Clots After Surgery by 90%
Category: Health News
Created: 8/25/2021 12:00:00 AM
Last Editorial Review: 8/25/2021 12:00:00 AM

Title: Michigan Officials Puzzled by Mysterious Deaths of 30 Dogs
Category: Health News
Created: 8/24/2022 12:00:00 AM
Last Editorial Review: 8/24/2022 12:00:00 AM

Title: When Should I Be Concerned About My Sick Baby?
Category: Diseases and Conditions
Created: 8/24/2021 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM

Title: How Do I Get My Baby to Sleep Longer at Night?
Category: Diseases and Conditions
Created: 8/18/2021 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM

Title: What Is the Best Homemade Baby Food?
Category: Health and Living
Created: 7/13/2021 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM

Title: How Can You Tell if Your Baby Has an Earache?
Category: Diseases and Conditions
Created: 6/16/2021 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM

Title: What Baby Food Should I Introduce First?
Category: Health and Living
Created: 6/16/2021 12:00:00 AM
Last Editorial Review: 8/24/2022 12:00:00 AM

Title: How Can I Keep My Baby Cool in the Car Seat?
Category: Health and Living
Created: 3/17/2022 12:00:00 AM
Last Editorial Review: 8/24/2022 12:00:00 AM

Title: U.S. Government Extends Baby Formula Waivers, Rebates for WIC Families
Category: Health News
Created: 8/25/2022 12:00:00 AM
Last Editorial Review: 8/26/2022 12:00:00 AM

Title: Heat Waves That Threaten Lives Will Be Common by 2100
Category: Health News
Created: 8/26/2022 12:00:00 AM
Last Editorial Review: 8/26/2022 12:00:00 AM

Title: Cheaper Over-the-Counter Hearing Aids Should Be in Stores by October, FDA Says
Category: Health News
Created: 8/16/2022 12:00:00 AM
Last Editorial Review: 8/17/2022 12:00:00 AM

Title: When Should I Start Cleaning My Baby’s Mouth?
Category: Diseases and Conditions
Created: 11/9/2020 12:00:00 AM
Last Editorial Review: 8/11/2022 12:00:00 AM

Mapping transcriptomic variations using either short- or long-read RNA sequencing is a staple of genomic research. Long reads are able to capture entire isoforms and overcome repetitive regions, whereas short reads still provide improved coverage and error rates. Yet, open questions remain, such as how to quantitatively compare the technologies, can we combine them, and what is the benefit of such a combined view? We tackle these questions by first creating a pipeline to assess matched long- and short-read data using a variety of transcriptome statistics. We find that across data sets, algorithms, and technologies, matched short-read data detects ~30% more splice junctions, such that ~10%–30% of the splice junctions included at ≥20% by short reads are missed by long reads. In contrast, long reads detect many more intron-retention events and can detect full isoforms, pointing to the benefit of combining the technologies. We introduce MAJIQ-L, an extension of the MAJIQ software, to enable a unified view of transcriptome variations from both technologies and demonstrate its benefits. Our software can be used to assess any future long-read technology or algorithm and can be combined with short-read data for improved transcriptome analysis.

Purpose:

Sexual misconduct by physicians is a consequential violation of patient trust. The purpose of this study was to determine the frequency and patterns of sexual misconduct by physicians certified by the American Board of Family Medicine (ABFM).

The spliceosome is a eukaryotic multimegadalton RNA–protein complex that removes introns from transcripts. The spliceosome ensures the selection of each exon-intron boundary through multiple recognition events. Initially, the 5' splice site (5' SS) and branch site (BS) are bound by the U1 small nuclear ribonucleoprotein (snRNP) and the U2 snRNP, respectively, while the 3' SS is mostly determined by proximity to the branch site. A large number of splicing factors recognize the splice sites and recruit the snRNPs before the stable binding of the snRNPs occurs by base-pairing the snRNA to the transcript. Fidelity of this process is crucial, as mutations in splicing factors and U2 snRNP components are associated with many diseases. In recent years, major advances have been made in understanding how splice sites are selected in Saccharomyces cerevisiae and humans. Here, I review and discuss the current understanding of the recognition of splice sites by the spliceosome with a focus on recognition and binding of the branch site by the U2 snRNP in humans.

Human organic anion transporting polypeptide (OATP) 1B1 and 1B3 are two highly homologous liver-specific uptake transporters. However, 2’,7’-dichlorofluorescein (DCF) is preferably transported by OATP1B1. In the present study, the molecular mechanisms for the selective transport of DCF by OATP1B1 were investigated by constructing and characterizing an array of OATP1B1/1B3 chimeras and site-directed mutagenesis. Our results show that transmembrane domain (TM) 10 is crucial for the surface expression and function of OATP1B1, in which Q541 and L545 play the most important roles in DCF transport. Replacement of TM10 in OATP1B1 with its OATP1B3 counterpart led to OATP1B1’s complete intracellular retention. Q541 and L545 may interact with DCF directly via hydrogen bonding and hydrophobic interactions. The decrease of DCF uptake by Q541A and L545S was due to their reduced binding affinity for DCF as compared with OATP1B1. In addition, Q541 and L545 are also crucial for the transport of estradiol-17β-glucuronide (E17βG) but not for the transport of estrone-3-sulfate (E3S), indicating different interaction modes between DCF/E17βG and E3S in OATP1B1. Taken together, Q541 and L545 in TM10 are critical for OATP1B1-mediated DCF uptake, but their effect is substrate-dependent.

Organic anion transporting polypeptides (OATP, gene symbol SLCO) are well-recognized key determinants for the absorption, distribution, and excretion of a wide spectrum of endogenous and exogenous compounds including many antineoplastic agents. It was therefore proposed as a potential drug target for cancer therapy. In our previous study, it was found that low-dose X-ray and carbon ion irradiation both upregulated the expression of OATP family member OATP1A2 and in turn, led to a more dramatic killing effect when cancer cells were cotreated with antitumor drugs such as methotrexate. In the present study, the underlying mechanism of the phenomenon was explored in breast cancer cell line MCF-7. It was found that the nonreceptor tyrosine kinase v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES-1) was temporally coordinated with the change of OATP1A2 after irradiation. The overexpression of YES-1 significantly increased OATP1A2 both at the mRNA and protein level. The signal transducer and activator of transcription 3 (STAT3) pathway is likely the downstream target of YES-1 because phosphorylation and nuclear accumulation of STAT3 were both enhanced after overexpressing YES-1 in MCF-7 cells. Further investigation revealed that there are two possible binding sites of STAT3 localized at the upstream sequence of SLCO1A2, the encoding gene of OATP1A2. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis suggested that these two sites bound to STAT3 specifically and the overexpression of YES-1 significantly increased the association of the transcription factor with the putative binding sites. Finally, inhibition or knockdown of YES-1 attenuated the induction effect of radiation on the expression of OATP1A2.

A STING (stimulator of interferon genes) agonist GSK3996915 under investigation in early discovery for hepatitis B was orally dosed to a mouse model for understanding the parent drug distribution in liver, the target organ. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) was used to quantify the distribution of GSK3996915 in liver collected from mice administered a single oral dose at 90 mg/kg. GSK3996915 was detected with a zonal distribution localized in the portal triad and highly concentrated in the main bile ducts, indicating clearance through biliary excretion. High spatial resolution imaging showed the distribution of the parent drug localized to the cellular populations in the sinusoids, including the Kupffer cells. Additionally, a series of drug-related metabolites were observed to be localized in the central zones of the liver. These results exemplify the potential of utilizing MALDI IMS for measuring not only quantitative drug distribution and target exposure but also drug metabolism and elimination in a single suite of experiments.

Protein abundance data of drug-metabolizing enzymes and transporters (DMETs) are useful for scaling in vitro and animal data to humans for accurate prediction and interpretation of drug clearance and toxicity. Targeted DMET proteomics that relies on synthetic stable isotope-labeled surrogate peptides as calibrators is routinely used for the quantification of selected proteins; however, the technique is limited to the quantification of a small number of proteins. Although the global proteomics-based total protein approach (TPA) is emerging as a better alternative for large-scale protein quantification, the conventional TPA does not consider differential sequence coverage by identifying unique peptides across proteins. Here, we optimized the TPA approach by correcting protein abundance data by the sequence coverage, which was applied to quantify 54 DMETs for characterization of 1) differential tissue DMET abundance in the human liver, kidney, and intestine, and 2) interindividual variability of DMET proteins in individual intestinal samples (n = 13). Uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7), microsomal glutathione S-transferases (MGST1, MGST2, and MGST3) carboxylesterase 2 (CES2), and multidrug resistance-associated protein 2 (MRP2) were expressed in all three tissues, whereas, as expected, four cytochrome P450s (CYP3A4, CYP3A5, CYP2C9, and CYP4F2), UGT1A1, UGT2B17, CES1, flavin-containing monooxygenase 5, MRP3, and P-glycoprotein were present in the liver and intestine. The top three DMET proteins in individual tissues were: CES1>CYP2E1>UGT2B7 (liver), CES2>UGT2B17>CYP3A4 (intestine), and MGST1>UGT1A6>MGST2 (kidney). CYP3A4, CYP3A5, UGT2B17, CES2, and MGST2 showed high interindividual variability in the intestine. These data are relevant for enhancing in vitro to in vivo extrapolation of drug absorption and disposition and can be used to enhance the accuracy of physiologically based pharmacokinetic prediction of systemic and tissue concentration of drugs.

Mitochondrial dysfunction is a hallmark of many genetic neurodegenerative diseases, but therapeutic options to reverse mitochondrial dysfunction are limited. While recent studies support the possibility of improving mitochondrial fusion/fission dynamics and motility to correct mitochondrial dysfunction and resulting neurodegeneration in Charcot-Marie-Tooth disease (CMT) and other neuropathies, the clinical utility of reported compounds and relevance of preclinical models are uncertain. Here, we describe motor and sensory neuron dysfunction characteristic of clinical CMT type 2 A in a CRISPR/Casp-engineered Mfn2 Thr105Met (T105M) mutant knock-in mouse. We further demonstrate that daily oral treatment with a novel mitofusin activator derived from the natural product piperine can reverse these neurologic phenotypes. Piperine derivative 8015 promoted mitochondrial fusion and motility in Mfn2-deficient cells in a mitofusin-dependent manner and reversed mitochondrial dysfunction in cultured fibroblasts and reprogrammed motor neurons from a human CMT2A patient carrying the MFN2 T105M mutation. Like previous mitofusin activators, 8015 exhibited stereospecific functionality, but the more active stereoisomer, 8015-P2, is unique in that it has subnanomolar potency and undergoes entero-hepatic recirculation which extends its in vivo half-life. Daily administration of 8015-P2 to Mfn2 T105M knock-in mice for 6 weeks normalized neuromuscular and sensory dysfunction and corrected histological/ultrastructural neurodegeneration and neurogenic myoatrophy. These studies describe a more clinically relevant mouse model of CMT2A and an improved mitofusin activator derived from piperine. We posit that 8015-P2 and other piperine derivatives may benefit CMT2A or other neurodegenerative conditions wherein mitochondrial dysdynamism plays a contributory role.

Although acute inflammation serves essential functions in maintaining tissue homeostasis, chronic inflammation is causally linked to many diseases. Macrophages are a major cell type that orchestrates inflammatory processes. During inflammation, macrophages undergo polarization and activation, thereby mobilizing pro-inflammatory and anti-inflammatory transcriptional programs that regulate ensuing macrophage functions. Fatty acid binding protein 5 (FABP5) is a lipid chaperone highly expressed in macrophages. FABP5 deletion is implicated in driving macrophages toward an anti-inflammatory phenotype, yet signaling pathways regulated by macrophage-FABP5 have not been systematically profiled. We leveraged proteomic and phosphoproteomic approaches to characterize pathways modulated by FABP5 in M1 and M2 polarized bone marrow-derived macrophages (BMDMs). Stable isotope labeling by amino acids-based analysis of M1 and M2 polarized wild-type and FABP5 knockout BMDMs revealed numerous differentially regulated proteins and phosphoproteins. FABP5 deletion impacted downstream pathways associated with inflammation, cytokine production, oxidative stress, and kinase activity. Toll-like receptor 2 (TLR2) emerged as a novel target of FABP5 and pharmacological FABP5 inhibition blunted TLR2-mediated activation of downstream pathways, ascribing a novel role for FABP5 in TLR2 signaling. This study represents a comprehensive characterization of the impact of FABP5 deletion on the proteomic and phosphoproteomic landscape of M1 and M2 polarized BMDMs. Loss of FABP5 altered pathways implicated in inflammatory responses, macrophage function, and TLR2 signaling. This work provides a foundation for future studies seeking to investigate the therapeutic potential of FABP5 inhibition in pathophysiological states resulting from dysregulated inflammatory signaling.

Cannabinoid and opioid receptor activities can be modulated by a variety of post-translational mechanisms including the formation of interacting complexes. This study examines the involvement of endogenous and exogenous chaperones in modulating the abundance and activity of cannabinoid CB₁ receptor (CB₁R), opioid receptor (DOR), and CB₁R-DOR interacting complexes. Focusing on endogenous protein chaperones, namely receptor transporter proteins (RTPs), we examined relative mRNA expression in the mouse spinal cord and found RTP4 to be expressed at higher levels compared with other RTPs. Next, we assessed the effect of RTP4 on receptor abundance by manipulating RTP4 expression in cell lines. Overexpression of RTP4 causes an increase and knock-down causes a decrease in the levels of CB₁R, DOR, and CB₁R-DOR interacting complexes; this is accompanied by parallel changes in signaling. The ability of small molecule lipophilic ligands to function as exogenous chaperones was examined using receptor-selective antagonists. Long-term treatment leads to increases in receptor abundance and activity with no changes in mRNA supporting a role as pharmacological chaperones. Finally, the effect of cannabidiol (CBD), a small molecule ligand and a major active component of cannabis, on receptor abundance and activity in mice was examined. We find that CBD administration leads to increases in receptor abundance and activity in mouse spinal cord. Together, these results highlight a role for chaperones (proteins and small molecules) in modulating levels and activity of CB₁R, DOR, and their interacting complexes potentially through mechanisms including receptor maturation and trafficking.

Intrapatient intermetastatic heterogeneity (IIH) has been demonstrated in metastatic castration-resistant prostate cancer (mCRPC) patients and is of the utmost importance for radiopharmaceutical therapy (RPT) eligibility. This study was designed to determine the prevalence of IIH and RPT eligibility in mCRPC patients through a triple-tracer PET imaging strategy. Methods: This was a multisite prospective observational study in which mCRPC patients underwent both ¹⁸F-FDG and ⁶⁸Ga-prostate-specific membrane antigen (PSMA)–617 PET/CT scans. A third scan with ⁶⁸Ga-DOTATATE, a potential biomarker of neuroendocrine differentiation, was performed if an ¹⁸F-FDG–positive/⁶⁸Ga-PSMA–negative lesion was found. Per-tracer lesion positivity was defined as having an uptake at least 50% above that of the liver. IIH prevalence was defined as the percentage of participants having at least 2 lesions with discordant features on multitracer PET. Results: IIH was observed in 81 patients (82.7%), and at least 1 ¹⁸F-FDG–positive/⁶⁸Ga-PSMA–negative lesion was found in 45 patients (45.9%). Of the 37 participants who also underwent ⁶⁸Ga-DOTATATE PET/CT, 6 (16.2%) had at least 1 ⁶⁸Ga-DOTATATE–positive lesion. In total, 12 different combinations of lesion imaging phenotypes were observed. On the basis of our prespecified criteria, 52 (53.1%) participants were determined to be eligible for PSMA RPT, but none for DOTATATE RPT. Patients with IIH had a significantly shorter median overall survival than patients without IIH (9.5 mo vs. not reached; log-rank P = 0.03; hazard ratio, 2.7; 95% CI, 1.1–6.8). Conclusion: Most mCRPC patients showed IIH, which was associated with shorter overall survival. On the basis of a triple-tracer PET approach, multiple phenotypic combinations were found. Correlation of these imaging phenotypes with genomics and treatment response will be relevant for precision medicine.

Veterans are at an increased risk for prostate cancer, a disease with extraordinary clinical and molecular heterogeneity, compared with the general population. However, little is known about the underlying molecular heterogeneity within the veteran population and its impact on patient management and treatment. Using clinical and targeted tumor sequencing data from the National Veterans Affairs health system, we conducted a retrospective cohort study on 45 patients with advanced prostate cancer in the Veterans Precision Oncology Data Commons (VPODC), most of whom were metastatic castration-resistant. We characterized the mutational burden in this cohort and conducted unsupervised clustering analysis to stratify patients by molecular alterations. Veterans with prostate cancer exhibited a mutational landscape broadly similar to prior studies, including KMT2A and NOTCH1 mutations associated with neuroendocrine prostate cancer phenotype, previously reported to be enriched in veterans. We also identified several potential novel mutations in PTEN, MSH6, VHL, SMO, and ABL1. Hierarchical clustering analysis revealed two subgroups containing therapeutically targetable molecular features with novel mutational signatures distinct from those reported in the Catalogue of Somatic Mutations in Cancer database. The clustering approach presented in this study can potentially be used to clinically stratify patients based on their distinct mutational profiles and identify actionable somatic mutations for precision oncology.

Comprehensive maps of neuronal connectivity provide a foundation for understanding the structure of neural circuits. In a circuit, neurons are diverse in morphology, electrophysiology, gene expression, activity, and other neuronal properties. Thus, constructing a comprehensive connectivity map requires associating various properties of neurons, including their connectivity, at cellular resolution. A commonly used approach is to use the gene expression profiles as an anchor to which all other neuronal properties are associated. Recent advances in genomics and anatomical techniques dramatically improved the ability to determine and associate the long-range projections of neurons with their gene expression profiles. These studies revealed unprecedented details of the gene–projection relationship, but also highlighted conceptual challenges in understanding this relationship. In this article, I delve into the findings and the challenges revealed by recent studies using state-of-the-art neuroanatomical and transcriptomic techniques. Building upon these insights, I propose an approach that focuses on understanding the gene–projection relationship through basic features in gene expression profiles and projections, respectively, that associate with underlying cellular processes. I then discuss how the developmental trajectories of projections and gene expression profiles create additional challenges and necessitate interrogating the gene–projection relationship across time. Finally, I explore complementary strategies that, together, can provide a comprehensive view of the gene–projection relationship.

New research shows that bystander CPR can substantially improve a person's odds of surviving a cardiac arrest while avoiding major brain damage, especially if given immediately.

Stephen Flynn has been criticised by SNP colleagues after saying he would stay on at Westminster, even if elected to Holyrood.

Two runners saved by the same public defibrillator appeal for all the life-saving devices to be publicly available. Tens of thousands of defibs are unregistered so ‘invisible’ in an emergency.

A "renowned" restructuring advisory business has been acquired by a major player.

A baroque fiddle believed to have been played by Robert Burns will be performed live on stage in the United States for the first time.

A new digital-first Gaelic language production will be launched in Scotland after a joint agreement between BBC Alba and BBC Scotland.

Alex, Anna Marie, Chris, and Kelley come together to discuss the news of the week. #JRPGJuly is well underway for everyone on the cast. Anna Marie makes every evil choice she can. Alex dives into Anime: The Game. Chris shouldn't be playing Elder Scrolls Online because his arm hurts, and yet he still is? Meanwhile, we lost Kelley somewhere in the wastelands when she wandered off to hug all the monsties.

The post RPG Cast – Episode 591: “Save the Baby? Eat the Baby?” appeared first on RPGamer.

This week on RPG Cast, Chris asks Anna to go fix her truckers. Josh wants to date the robots. And Kelley has a hot Raymond.

The post RPG Cast – Episode 618: “Kirby’s Oral Fixation” appeared first on RPGamer.

Chris wants an OP fox with mods. Matt wears a turnip and marries a twelve year old. And Josh goes off to read the new J.R.R. Martin time loop book.

The post RPG Cast – Episode 624: “Kirby Is the New Elden Ring” appeared first on RPGamer.

Alex gets nine discs of Xenoblade soundtracks. Jason rewinds to heal. Phil tells us that Donatello is best turtle. And Chris shouts to make his problems go away.

The post RPG Cast – Episode 675: “Labyrinth of That Thing” appeared first on RPGamer.

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/

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/

Microsoft and several retailers are currently running a promotion for the standard Xbox Series X in the US.

The Xbox Series X is available for $449, a $50 discount, at the Microsoft Store, GameStop, and Best Buy. It isn't known when this deal will end.

The recently released 1 TB All-Digital Robot White Xbox Series X, 2TB Disc Drive Galaxy Black Xbox Series, and the two Xbox Series S SKUs have not been discounted at this time.

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/463036/xbox-series-x-discounted-by-50-to-449/

Online interactions are based on trust, since there are few definitive ways to certify the identity of the person with whom one is communicating. Naturally, this situation can lead to deception and manipulation, as it has—to tormenting effect—for Tegan and Sara, the popular indie rock duo whose lives have been turned upside down by a mysterious bad faith actor who, for more than a decade, has impersonated Tegan with fans, friends, and business partners.

Fanatical: The Catfishing of Tegan and Sara is an investigation into the myriad means by which the internet can be wielded to nefarious ends. More than that, though, it’s an anatomy of a crime and the complicated wreckage wrought by it, not just for the famous artists but also for the innocent admirers who were tricked into believing that fiction was reality.

Premiering on Hulu on Oct. 18, following its premiere at the Toronto International Film Festival, Erin Lee Carr’s documentary is a chilling snapshot of the unholy marriage of corrosive fandom and online duplicity. At its center are Tegan and Sara, the identical twin songstresses who began making a name for themselves in the early 2000s both for their talent and for being openly gay. This earned them a loyal fanbase of queer women and men who saw themselves reflected in Tegan and Sara, and that bond was strengthened by the siblings’ active interest in interacting with fans in person—Tegan would chat with show attendees in line and at the merch table—and on LiveJournal and other budding message-board platforms that afforded a previously unavailable degree of contact.

Read more at The Daily Beast.

From developers Cannibal Interactive, the creators of Purgatory Dungeoneer, springs forth a new labyrinth game. This one is called Labyrinth of Wild Abyss: LayeRedux and it has labyrinths. Except the labyrinths don't just have single paths to their centres, but tube monsters covered in eyes who'll stalk you slowly and methodically as you meander. Personally, it's not the vibe I'm after when I sit down in the evening and I think, "I would like to play a video game that makes me feel somewhat pleasant". But hey, it might be for you.

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Some extremely fresh vintage workwear that I bought for entirely practical reasons aside, I’m not exactly a fashion person. I have nobody to impress most days but my cat, and the only item of clothing she appears to have an opinion on is my Oodie, which is very comfortable for both of us and also smells like a chicken shop, which I imagine is more pleasant for her than me.

This aside, I found myself taking a whole bunch of Dragon Age: The Veilguard screenshots as I played just to capture the RPG’s various outfits. They are ridiculous. Incredibly intricate and detailed, as well as being obscenely impractical for the most part. I do not like any of them in the sense I would wear them, but I like all of them in the sense that they display artists allowed to run free like caffeinated weasels and indulge their every whim.

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When nightmarish sci-fi extraction shooter The Forever Winter launched into early access in September it was somewhat messy. Bugs and maddening enemy spawns diminished the tension of being a fleshy human scavenger in a mech battlefield. But one feature annoyed some players much more - fresh water. See, you need to keep your headquarters stocked with water, as it gets steadily used by your settlement's inhabitants. The catch being that this water diminishes even while you're not playing the game. If it runs out completely, then everything you've collected gets wiped. The developers have listened to complaints about this most Farmville of mechanics, and they've answered in an interesting way. Water thieves! Now, on top of the usual downward trickle, burglars will come to steal your H2O as well.

It's not as bad as it sounds.

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It was the 20-year anniversary of Halo 2 at the weekend, which saw the shooter's modern counterparts celebrating with classic multiplayer maps and long-lost levels. But also emerging from the dust of time are insights to the sequel's development back in 2004. Rolling Stone interviewed two key designers of the game and made a fun discovery. The Flood (the sickly pale alien infestation that briefly turns Halo into sci-fi horror) was partly inspired by a colourful and innocent children's book about a nice elephant.

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JUDY WOODRUFF: Now: new questions surrounding the deaths of four Green Berets in the Western African nation of Niger and the role of the president as consoler in chief.

John Yang has the story.

JOHN YANG: Sending young Americans into harm’s way can be the most serious decision a president makes. Consoling the families of the fallen has become the latest controversy to engulf President Trump.

To bolster his claim that he does more than his predecessors, Mr. Trump today invoked the dead son of his chief of staff, retired Marine general John Kelly.

PRESIDENT DONALD TRUMP: To the best of my knowledge, I think I have called every family of somebody that’s died. Now, as far as other representatives, I don’t know. I mean, you could ask General Kelly, did he get a call from Obama?

JOHN YANG: Kelly’s 29-year-old son, Robert, a Marine lieutenant, was killed in 2010 when he stepped on a land mine in Afghanistan, an episode Kelly rarely talks about publicly. Kelly and his wife did attend a 2011 Memorial Day breakfast President Obama hosted for Gold Star families.

President Trump ignited the furor when he was asked about his public silence on four Green Berets killed two weeks ago in Niger.

PRESIDENT DONALD TRUMP: If you look at President Obama and other presidents, most of them didn’t make calls. A lot of them didn’t make calls. I like to call when it’s appropriate, when I think I’m able to do it.

JOHN YANG: Reporters pressed him to back up the claim.

PRESIDENT DONALD TRUMP: I don’t know. That’s what I was told. All I can do — all I can do is ask my generals.

JOHN YANG: The response from former Obama officials was swift and forceful.

Former Attorney General Eric Holder tweeted this photo and insisted: “Stop the damn lying. I went to Dover Air Force base with 44 and saw him comfort families,” a reference to one of Mr. Obama’s late-night trips to pay his respects to troops killed in Afghanistan.

Mr. Obama and President George W. Bush often visited wounded warriors at Walter Reed and Bethesda hospitals, a practice Mr. Trump has continued. In February, the president and his daughter Ivanka went to Dover for the return of the remains of a Navy SEAL killed in Yemen, the first casualty of his administration.

So far this year, the Pentagon says 16 Americans have been killed in action. Another 17 sailors died in accidents. In the first year of the Obama presidency, 344 were killed in action.

During last year’s campaign, Mr. Trump publicly feuded with the Khans, the parents of a Muslim American soldier killed in Iraq, after they criticized him at the Democratic Convention.

Today, the Khans said: “President Trump’s selfish and divisive actions have undermined the dignity of the high office of the presidency.”

The current controversy comes as questions are being raised about how and why the four soldiers died in Niger.

Senator Jack Reed is the top Democrat on the Armed Services Committee.

SEN. JACK REED, D-R.I.: I think the administration has to be much more clear about our role in Niger and our role in other areas in Africa and other parts of the globe.

JOHN YANG: The Pentagon is investigating the deaths. Reportedly among the questions, did commanders adequately assess the risk, and was there ready access to medical support?

Today, President Trump called the families of the four dead Green Berets.

For the PBS NewsHour, I’m John Yang.

The post Trump ignites furor with claim past presidents didn’t console military families by phone appeared first on PBS NewsHour.

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JUDY WOODRUFF: And in the day’s other news: A federal judge in Hawaii struck down the Trump administration’s latest travel ban.

That temporarily blocks enforcement of the order nationwide, but the Justice Department says it will appeal. The ban extended to six mostly Muslim nations, plus North Korea and Venezuela.

Pennsylvania Congressman Tom Marino withdrew today from consideration to be President Trump’s drug czar. That followed an investigation by The Washington Post and CBS News. They found Marino was key in passing a 2016 law that limits the Drug Enforcement Administration’s ability to rein in opioid distribution.

A new verbal battle has broken out between the president and Republican Senator John McCain. It began last night in Philadelphia, when the Arizona senator and former Vietnam POW appeared to criticize Mr. Trump and his followers. He cited a list of failings.

SEN. JOHN MCCAIN, R-Ariz.: To fear the world we have organized and led for three-quarters-of-a-century, to abandon the ideals we have advanced around the globe for the sake of some half-baked, spurious nationalism cooked up by people who would rather find scapegoats than solve problems.

(CHEERING AND APPLAUSE)

JUDY WOODRUFF: The president answered by saying, “At some point, I fight back, and it won’t be pretty.”

In turn, McCain said, “I have faced tougher adversaries.”

In Afghanistan, Taliban bombings and shootings left at least 74 people dead today. The worst was Paktika province in the east, where two car bombs killed dozens, including the provincial police chief, and wounded more than 100 others. Taliban militants also staged attacks in the south and west of the country.

In Syria, militia forces backed by the U.S. say they have retaken the Islamic State group’s de facto capital. The city of Raqqa had been under ISIS control since 2014. The battle to recapture it began in June. Today, Kurdish-led fighters celebrated as they moved into the city center. The U.S. military said 90 percent of Raqqa has been taken, with pockets of militants remaining.

There’s word that U.S. airstrikes in Yemen killed dozens of Islamic State fighters on Monday. The strikes were apparently carried out by drones. The Pentagon says the targets were training camps for recruits.

In Northern Iraq, Kurdish forces withdrew from more territory today, as Iraqi government troops advanced. It came on the heels of the Kurds’ vote for independence. Federal forces and allied militia had already forced the Kurds to leave the area in and around Kirkuk and its oil fields.

Iraq’s prime minister said that paves the way for talks.

HAIDER AL-ABADI, Prime Minister, Iraq (through interpreter): I call for dialogue on the basis of partnership in one country and under the Constitution. The referendum is finished and has become a thing from the past. We hoped that they would cancel it, but we have finished it on the ground.

JUDY WOODRUFF: Meanwhile, the president of Iraqi Kurdistan, Massoud Barzani, insisted that the referendum will not be in vain.

Another 10,000 to 15,000 Rohingya Muslims fled Buddhist Myanmar for Bangladesh over the weekend. Drone video showed snaking lines of refugees making the trek to already crowded camps. Many told of villages torched by mobs and soldiers. Others said they were starved out of their homes.

Back in this country, a new fire broke out in the San Francisco Bay Area, just as crews had made major progress against other fires in Northern California. Thick smoke billowed from the new site early today, as it burned through forests in the Santa Cruz Mountains. Weary fire crews said they’re calling in more help.

ROB SHERMAN, Division Chief, Cal Fire: So, the idea is to hit it pretty hard with aircraft and then go ahead and hit it with the ground resources at the same time. We have had north winds, a lot of drying, and everything’s really, really dry. So it’s challenging.

JUDY WOODRUFF: In Southern California, yet another fire spread on Mount Wilson, about 25 miles north of downtown Los Angeles. It threatened a historic observatory and communications towers.

President Trump’s overall wealth has taken a hit, as his New York real estate loses some of its luster. Forbes ranks him 248 this year on its list of the 400 wealthiest Americans. That’s down nearly 100 points from last year. His estimated worth is $3.1 billion.

Microsoft co-founder Bill Gates again tops the list. He’s worth nearly $90 billion.

And on Wall Street, the Dow Jones industrial average traded above 23,000 for the first time. In the end, it gained 40 points to close at 22997. The Nasdaq fell a fraction, and the S&P 500 added one point.

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Secretary of State was questioned on Good Morning Britain over the pledge - with host asking 'how much will it have gone up by then?'

On 19 and 20 August, the JUICE mission will make the first ever attempt to get a gravitational boost from both Earth and the moon on its way to Jupiter

After a star explodes, the resulting supernova remnant collapses in on itself and could begin the cycle again, creating generations of stars enriched with heavy elements