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The Minor Phytocannabinoid Delta-8-Tetrahydrocannabinol Attenuates Collagen-Induced Arthritic Inflammation and Pain-Depressed Behaviors [Special Section: Cannabinoid Signaling in Human Health and Disease]

Patients with arthritis report using cannabis for pain management, and the major cannabinoid delta-9-tetrahydrocannabinol (9-THC) has anti-inflammatory properties, yet the effects of minor cannabinoids on arthritis are largely unknown. The goal of the present study was to determine the antiarthritic potential of the minor cannabinoid delta-8-tetrahydrocannabinol (8-THC) using the collagen-induced arthritis (CIA) mouse model. Adult male DBA/1J mice were immunized and boosted 21 days later with an emulsion of collagen and complete Freund’s adjuvant. Beginning on the day of the booster, mice were administered twice-daily injections of 8-THC (3 or 30 mg/kg), the steroid dexamethasone (2 mg/kg), or vehicle for two weeks. Dorsal-ventral paw thickness and qualitative measures of arthritis were recorded daily, and latency to fall from an inverted grid was measured on alternating days, to determine arthritis severity and functional impairment. On the final day of testing, spontaneous wire-climbing behavior and temperature preference in a thermal gradient ring were measured to assess CIA-depressed behavior. The 8-THC treatment (30 mg/kg) reduced paw swelling and qualitative signs of arthritis. 8-THC also blocked CIA-depressed climbing and CIA-induced preference for a heated floor without producing locomotor effects but did not affect latency to fall from a wire grid. In alignment with the morphologic and behavioral assessments in vivo, histology revealed that 8-THC reduced synovial inflammation, proteoglycan loss and cartilage and bone erosion in the foot joints in a dose-dependent manner. Together, these findings suggest that 8-THC not only blocked morphologic changes but also prevented functional loss caused by collagen-induced arthritis.

SIGNIFICANCE STATEMENT

Despite increasing use of cannabis products, the potential effects of minor cannabinoids are largely unknown. Here, the minor cannabinoid delta-8-tetrahydrocannabinol blocked the development of experimentally induced arthritis by preventing both pathophysiological as well as functional effects of the disease model. These data support the development of novel cannabinoid treatments for inflammatory arthritis.




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The Potential of Cannabichromene (CBC) as a Therapeutic Agent [Special Section: Cannabinoid Signaling in Human Health and Disease-Minireview]

There is a growing interest in the use of medicinal plants to treat a variety of diseases, and one of the most commonly used medicinal plants globally is Cannabis sativa. The two most abundant cannabinoids (9-tetrahydrocannabinol and cannabidiol) have been governmentally approved to treat selected medical conditions; however, the plant produces over 100 cannabinoids, including cannabichromene (CBC). Although the cannabinoids share a common precursor molecule, cannabigerol, they are structurally and pharmacologically unique. These differences may engender differing therapeutic potentials. In this review, we will examine what is currently known about CBC with regards to pharmacodynamics, pharmacokinetics, and receptor profile. We will also discuss the therapeutic areas that have been examined for this cannabinoid, notably antinociceptive, antibacterial, and anti-seizure activities. Finally, we will discuss areas where new research is needed and potential novel medicinal applications for CBC.

SIGNIFICANCE STATEMENT

Cannabichromene (CBC) has been suggested to have disparate therapeutic benefits such as anti-inflammatory, anticonvulsant, antibacterial, and antinociceptive effects. Most of the focus on the medical benefits of cannabinoids has been focused on 9-tetrahydrocannabinol and cannabidiol. The preliminary studies on CBC indicate that this phytocannabinoid may have unique therapeutic potential that warrants further investigation. Following easier access to hemp, CBC products are commercially available over-the-counter and are being widely utilized with little or no evidence of their safety or efficacy.




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The Dawning of a New Age of Preclinical Analgesic Drug Screening [Viewpoint]




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Preclinical Evaluation of 226Ac as a Theranostic Agent: Imaging, Dosimetry, and Therapy

226Ac (t1/2 = 29.37 h) has been proposed as a theranostic radioisotope leveraging both its diagnostic -emissions and therapeutic α-emissions. 226Ac emits 158 and 230 keV -photons ideal for quantitative SPECT imaging and acts as an in vivo generator of 4 high-energy α-particles. Because of these nuclear decay properties, 226Ac has potential to act as a standalone theranostic isotope. In this proof-of-concept study, we evaluated a preclinical 226Ac-radiopharmaceutical for its theranostic efficacy and present the first 226Ac-targeted α-therapy study. Methods: 226Ac was produced at TRIUMF and labeled with the chelator-peptide bioconjugate crown-TATE. [226Ac]Ac-crown-TATE was selected to target neuroendocrine tumors in male NRG mice bearing AR42J tumor xenografts for SPECT imaging, biodistribution, and therapy studies. A preclinical SPECT/CT scanner acquired quantitative images reconstructed from both the 158 and the 230 keV emissions. Mice in the biodistribution study were euthanized at 1, 3, 5, 24, and 48 h after injection, and internal radiation dosimetry was derived for the tumor and organs of interest to establish appropriate therapeutic activity levels. Mice in the therapy study were administered 125, 250, or 375 kBq treatments and were monitored for tumor size and body condition. Results: We present quantitative SPECT images of the in vivo biodistribution of [226Ac]Ac-crown-TATE, which showed agreement with ex vivo measurements. Biodistribution studies demonstrated high uptake (>30%IA/g at 5 h after injection) and retention in the tumor, with an estimated mean absorbed dose coefficient of 222 mGy/kBq. [226Ac]Ac-crown-TATE treatments significantly extended the median survival from 7 d in the control groups to 16, 24, and 27 d in the 125, 250, and 375 kBq treatment groups, respectively. Survival was prolonged by slowing tumor growth, and no weight loss or toxicities were observed. Conclusion: This study highlights the theranostic potential of 226Ac as a standalone therapeutic isotope in addition to its demonstrated diagnostic capabilities to assess dosimetry in matched 225Ac-radiopharmaceuticals. Future studies will investigate maximum dose and toxicity to further explore the therapeutic potential of 226Ac-radiopharmaceuticals.




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Routine Use of [64Cu]Cu-DOTATATE PET/CT in a Neuroendocrine Tumor Center: Referral Patterns and Image Results of 2,249 Consecutive Scans

The role of somatostatin receptor (SSTR) PET/CT, using 68Ga-based tracers or [64Cu]Cu-DOTATATE (64Cu-DOTATATE), in the management of patients with neuroendocrine neoplasm (NEN) is guided by appropriate use criteria (AUC). In this study, we performed systematic analyses of referral patterns and image findings of routine 64Cu-DOTATATE PET/CT scans to support AUC development. Methods: We included all clinical routine 64Cu-DOTATATE PET/CT scans performed between April 10, 2018 (start of clinical use), and May 2, 2022, at Copenhagen University Hospital–Rigshospitalet. We reviewed the referral text and image report of each scan and classified the indication according to clinical scenarios as listed in the AUC. Results: In total, 1,290 patients underwent 2,249 64Cu-DOTATATE PET/CT scans. Monitoring of patients with NEN seen both on conventional imaging and on SSTR PET without clinical evidence of progression was the most common indication (defined as "may be appropriate" in the AUC) and accounted for 703 (31.3%) scans. Initial staging after NEN diagnosis ("appropriate" in the AUC) and restaging after curative-intent surgery ("may be appropriate" in the AUC) accounted for 221 (9.8%) and 241 (10.7%) scans, respectively. Selection of patients eligible for peptide receptor radionuclide therapy ("appropriate" in the AUC) and restaging after peptide receptor radionuclide therapy completion ("appropriate" in the AUC) accounted for 95 (4.2%) and 115 (5.1%) scans, respectively. The number of scans performed for indications not defined in the AUC was 371 (16.5%). Image result analysis revealed no disease in 669 scans (29.7%), stable disease in 582 (25.9%), and progression in 461 (20.5%). In 99 of the 461 (21.5%) scans, progression was detected on PET but not on CT. Conclusion: Our study provided real-life data that may contribute to support development of 64Cu-DOTATATE/SSTR PET/CT guidelines including AUC. Some scenarios listed as "may be appropriate" in the current AUC were frequent in our data. Monitoring of patients with NEN without clinical evidence of progression was the most frequent indication for 64Cu-DOTATATE PET/CT, in which disease progression was detected in more than one third, and a large proportion was visible by PET only. We therefore conclude that this scenario could potentially be classified as appropriate.




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[18F]AlF-NOTA-FAPI-04 PET/CT for Predicting Pathologic Response of Resectable Esophageal Squamous Cell Carcinoma to Neoadjuvant Camrelizumab and Chemotherapy: A Phase II Clinical Trial

This single-center, single-arm, phase II trial (ChiCTR2100050057) investigated the ability of 18F-labeled fibroblast activation protein inhibitor ([18F]AlF-NOTA-FAPI-04, denoted as 18F-FAPI) PET/CT to predict the response to neoadjuvant camrelizumab plus chemotherapy (nCC) in locally advanced esophageal squamous cell carcinoma (LA-ESCC). Methods: This study included 32 newly diagnosed LA-ESCC participants who underwent 18F-FAPI PET/CT at baseline, of whom 23 also underwent scanning after 2 cycles of nCC. The participants underwent surgery after 2 cycles of nCC. Recorded PET parameters included maximum, peak, and mean SUVs and tumor-to-background ratios (TBRs), metabolic tumor volume, and total lesion FAP expression. PET parameters were compared between patient groups with good and poor pathologic responses, and the predictive performance for treatment response was analyzed. Results: The good and poor response groups each included 16 participants (16/32, 50.0%). On 18F-FAPI PET/CT, the posttreatment SUVs were significantly lower in good responders than in poor responders, whereas the changes in SUVs with treatment were significantly higher (all P < 0.05). SUVmax (area under the curve [AUC], 0.87; P = 0.0026), SUVpeak (AUC, 0.89; P = 0.0017), SUVmean (AUC, 0.88; P = 0.0021), TBRmax (AUC, 0.86; P = 0.0031), and TBRmean (AUC, 0.88; P = 0.0021) after nCC were significant predictors of pathologic response to nCC, with sensitivities of 63.64%–81.82% and specificities of 83.33%–100%. Changes in SUVmax (AUC, 0.81; P = 0.0116), SUVpeak (AUC, 0.82; P = 0.0097), SUVmean (AUC, 0.81; P = 0.0116), and TBRmean (AUC, 0.74; P = 0.0489) also were significant predictors of the pathologic response to nCC, with sensitivities and specificities in similar ranges. Conclusion: 18F-FAPI PET/CT parameters after treatment and their changes from baseline can predict the pathologic response to nCC in LA-ESCC participants.




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Impact of 18F-FES PET/CT on Clinical Decisions in the Management of Recurrent or Metastatic Breast Cancer

The clinical impact of 16α-18F-fluoro-17β-estradiol (18F-FES) PET/CT on patient management has not been well investigated. The aim of this study was to assess the clinical impact of 18F-FES PET/CT on the management of patients with recurrent or metastatic breast cancer. Methods: Study subjects were identified retrospectively from a database of a prospective trial for postmarketing surveillance of 18F-FES between 2021 and 2023. Patients who were suspected or known to have recurrent or metastatic estrogen receptor–positive breast cancer based on a routine standard workup were included. Planned management before and actual management after 18F-FES PET/CT were assessed by 2 experienced medical oncologists via medical chart review. A 5-point questionnaire was provided to evaluate the value of 18F-FES PET/CT for management planning. The rate of intention-to-treat and interdisciplinary changes, and the impact of 18F-FES PET/CT according to PET/CT result or clinical indication, were examined. Results: Of the 344 included patients, 120 (35%) experienced a change in management after 18F-FES PET/CT. In 139 (40%) patients,18F-FES PET/CT supported the existing management decision without a change in management. Intention-to-treat and interdisciplinary changes accounted for 64% (77/120) and 68% (82/120) of all changes, respectively. A higher rate of change was observed when lesions were 18F-FES–negative (44% [36/81]) than 18F-FES–positive (30% [51/172]) or mixed 18F-FES–positive/negative (36% [33/91]). Regarding clinical indications, the highest rate of change was shown when evaluating the origins of metastasis of double primary cancers (64% [9/14]). Conclusion: 18F-FES PET/CT modified the management of recurrent or metastatic breast cancer, serving as an impactful imaging modality in clinical practice.




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Is the Clinical Application of CXCR4 Imaging in the Diagnosis and Management of Primary Aldosteronism Really Happening?




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Prevalence of Rathke Cleft and Other Incidental Pituitary Gland Findings on Contrast-Enhanced 3D Fat-Saturated T1 MPRAGE at 7T MRI [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

A cleftlike nonenhancing hypointensity was observed repeatedly in the pituitary gland at the adenohypophysis/neurohypophysis border on contrast-enhanced 3D fat-saturated T1-MPRAGE using clinical 7T MRI. Our primary goal was to assess the prevalence of this finding. The secondary goals were to evaluate the frequency of other incidental pituitary lesions, MRI artifacts, and their effect on pituitary imaging on the contrast-enhanced 3D fat-saturated T1 MPRAGE at 7T.

MATERIALS AND METHODS:

One hundred patients who underwent 7T neuroimaging between October 27, 2021, and August 10, 2023, were included. Each case was evaluated for cleftlike pituitary hypointensity, pituitary masses, and artifacts on contrast-enhanced 3D fat-saturated T1 MPRAGE. Follow-up examinations were evaluated if present. The average prevalence for each finding was calculated, as were descriptive statistics for age and sex.

RESULTS:

A cleftlike hypointensity was present in 66% of 7T MRIs. There were no significant differences between the "cleftlike present" and "cleftlike absent" groups regarding sex (P = .39) and age (P = .32). The cleftlike hypointensity was demonstrated on follow-up MRIs in 3/3 patients with 7T, 1/12 with 3T, and 1/5 with 1.5T. A mass was found in 22%, while 75% had no mass and 3% were indeterminate. A mass was found in 18 (27%) of the cleftlike present and 4 (13%) of the cleftlike absent groups. The most common mass types were Rathke cleft cyst in 7 (31.8%) patients, "Rathke cleft cyst versus entrapped CSF" in 6 (27.3%), and microadenoma in 6 (22.2%) in the cleftlike present group. There were no significant differences in the mass types between the cleftlike present and cleftlike absent groups (P = .23). Susceptibility and/or motion artifacts were frequent using contrast-enhanced 3D fat-saturated T1 MPRAGE (54%). Artifact-free scans were significantly more frequent in the cleftlike present group (P = .03).

CONCLUSIONS:

A cleftlike nonenhancing hypointensity was frequently seen on the contrast-enhanced 3D fat-saturated T1 MPRAGE images at 7T MRI, which most likely represents a normal embryologic Rathke cleft remnant and cannot be seen in lower-field-strength MRIs. Susceptibility and motion artifacts are common in the sella. They may affect image quality, and the artifacts at 7T may lead to an underestimation of the prevalence of the Rathke cleft and other incidental findings.




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Probabilistic Presurgical Language fMRI Atlas of Patients with Brain Tumors [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and Silent Word Generation language paradigms using a large sample of patients with brain tumors.

MATERIALS AND METHODS:

The atlas was developed using retrospectively collected fMRI data from patients with brain tumors who underwent their first standard-of-care presurgical language fMRI scan at our institution between July 18, 2015, and May 13, 2022. Three hundred seventeen patients (861 fMRI scans) were used to develop the language functional atlas. An independent presurgical language fMRI data set of 39 patients with brain tumors from a previous study was used to evaluate our atlas. Family-wise error–corrected binary functional activation maps from sentence completion, letter fluency, and category fluency presurgical fMRI were used to create probability overlap maps and pooled probabilistic overlap maps in Montreal Neurological Institute standard space. The Wilcoxon signed-rank test was used to determine a significant difference in the maximum Dice coefficient for our atlas compared with a meta-analysis-based template with respect to expert-delineated primary language area activations.

RESULTS:

Probabilities of activating the left anterior primary language area and left posterior primary language area in the temporal lobe were 87.9% and 91.5%, respectively, for sentence completion, 88.5% and 74.2%, respectively, for letter fluency, and 83.6% and 67.6%, respectively, for category fluency. Maximum Dice coefficients for templates derived from our language atlas were significantly higher than the meta-analysis-based template in the left anterior primary language area (0.351 and 0.326, respectively, P < .05) and the left posterior primary language area in the temporal lobe (0.274 and 0.244, respectively, P < .005).

CONCLUSIONS:

Brain tumor patient- and paradigm-specific probabilistic language atlases were developed. These atlases had superior spatial agreement with fMRI activations in individual patients compared with the meta-analysis-based template.




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Differences in Cervical Spine Fractures in Patients Younger or Older Than 65 Years of Age: Implications for the Canadian C-Spine Rule [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

There has been a distinction made in the 2001 Canadian C-Spine Rule regarding patients 65 and older and younger than 65 years of age as far as indications for cervical spine CT scanning. We sought to determine if there are differences in the symptoms, mechanisms of injury, fracture locations, and types that are still relevant in 2024.

MATERIALS AND METHODS:

The institutional review board approved this retrospective study of cervical spine CT emergency department results from 2 hospitals in our health system after reviewing 5 years of data in patients experiencing trauma. In addition to the primary variable of age (younger than 65 years and 65 years and older), we looked at injury mechanism, fracture types, sites, symptoms, and operative or medical treatments. Because the demographics of our home site is different from most towns in the United States, we provide race/ethnicity data.

RESULTS:

Of 21,986 cervical spine CTs, 190/9455 (2.0%) participants 65 years of age and older and 199/12,531 (1.6%) participants younger than 65 years of age had fractures (total, 389/21,986, 1.8%). There were more cases of falls from standing (106, 55.8%) and falls from a height (46, 4.2%) in those 65 years and older and this mechanism was associated with a higher risk of C1 and C2 fractures (52, 27.4%; and 78, 41.1%, respectively). Among the C1 fractures, anterior and posterior arch fractures predominated (37, 19.5%). For C2 fractures, types 2 and 3 odontoid fractures (39, 20.5%; and 12, 6.3%) were more common in the older cohort. Motor vehicle collisions were more common in the younger cohort (89, 44.7%), and they were associated with more C5–C7 fractures (47, 23.6%; 60, 30.2%; and 66, 33.2%, respectively) including the facets (49, 24.6%), spinous processes (31, 15.6%), and transverse processes (52, 26.1%). Overall, the rates of instability, surgical intervention, and asymptomatic fractures were similar in the 2 age groups.

CONCLUSIONS:

Cervical spine fractures appear in about 1.8% of the CT scans performed in a busy emergency department environment. Fractures in the elderly occur more commonly due to falls, are located at C1 and C2, and may involve ligamentous injuries. Younger patients incur trauma more commonly due to motor vehicle collisions, and they are more likely to affect the posterior elements, especially C5–C7. The differences in trends for fractures in the 65 years of age and older and younger than 65 years of age groups have persisted since the Canadian C-Spine Rule 1996–1998 data were collected.




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Predictors and Outcomes of Periprocedural Intracranial Hemorrhage after Stenting for Symptomatic Intracranial Atherosclerotic Stenosis [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Periprocedural intracranial hemorrhage is one of common complications after stent placement for symptomatic intracranial atherosclerotic stenosis. This study was conducted to demonstrate predictors and long-term outcomes of periprocedural intracranial hemorrhage after stent placement for symptomatic intracranial atherosclerotic stenosis.

MATERIALS AND METHODS:

We retrospectively analyzed patients with symptomatic intracranial atherosclerotic stenosis stent placement in a prospective cohort at a high-volume stroke center. Clinical, radiologic, and periprocedural characteristics and long-term outcomes were reviewed. Periprocedural intracranial hemorrhage was classified as procedure-related hemorrhage (PRH) and non-procedure-related hemorrhage (NPRH). The long-term outcomes were compared between patients with PRH and NPRH, and the predictors of NPRH were explored.

RESULTS:

Among 1849 patients, 24 (1.3%) had periprocedural intracranial hemorrhage, including PRH (4) and NPRH (20). The postprocedural 30-day mRS was 0–2 in 9 (37.5%) cases, 3–5 in 5 (20.8%) cases, and 6 in 10 (41.7%) cases. For the 14 survivors, the long-term (median of 78 months) mRS were 0–2 in 10 (76.9%) cases and 3–5 in 3 (23.1%) cases. The proportion of poor long-term outcomes (mRS ≥3) in patients with NPRH was significantly higher than those with PRH (68.4% versus 0%, P = .024). Anterior circulation (P = .002), high preprocedural stenosis rate (P < .001), and cerebral infarction within 30 days (P = .006) were independent predictors of NPRH after stent placement.

CONCLUSIONS:

Patients with NPRH had worse outcomes than those with PRH after stent placement for symptomatic ICAS. Anterior circulation, severe preprocedural stenosis, and recent infarction are independent predictors of NPRH.




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Optimal Endovascular Therapy Technique for Isolated Intracranial Atherothrombotic Stroke-Related Large-Vessel Occlusion in the Acute-to-Subacute Stage [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Reocclusion after treatment is a concern in endovascular therapy for isolated intracranial atherothrombotic stroke-related large-vessel occlusion (AT-LVO). However, the optimal endovascular therapy technique for AT-LVO has not yet been investigated. This study evaluated the optimal endovascular therapy technique for AT-LVO in a real-world setting.

MATERIALS AND METHODS:

We conducted a historical, multicenter registry study at 51 centers that enrolled patients with AT-LVO. We divided the patients into 3 groups based on the endovascular therapy technique: mechanical thrombectomy alone, percutaneous transluminal angioplasty (PTA), and stent deployment. Mechanical thrombectomy alone was classified into the mechanical thrombectomy-only group; PTA and mechanical thrombectomy–PTA, into the PTA group; and mechanical thrombectomy–stent deployment, mechanical thrombectomy–PTA–stent deployment, PTA–stent deployment, and stent deployment–only into the stent group. The primary outcome was incidence of reocclusion of the treated vessels within 90 days of endovascular therapy completion.

RESULTS:

We enrolled 770 patients and analyzed 509 patients. The rates in the mechanical thrombectomy-only, PTA, and stent deployment groups were 40.7%, 44.4%, and 14.9%, respectively. Incidence rate of residual stenosis >70% of final angiography was significantly higher in the mechanical thrombectomy-only group than in the PTA and stent deployment groups (mechanical thrombectomy-only versus PTA versus stent deployment: 34.5% versus 26.3% versus 13.2%, P = .002). Reocclusion rate was significantly lower in the PTA group than in the mechanical thrombectomy-only group (adjusted hazard ratio, 0.48; 95% CI, 0.29–0.80). Of the patients, 83.5% experienced reocclusion within 10 days after endovascular therapy. Alarmingly, a substantial subset (approximately 62.0%) of patients experienced reocclusion within 2 days of endovascular therapy. Incidence of mRS scores of 0–2 ninety days after endovascular therapy was not significantly different among the 3 groups. Incidences of symptomatic intracranial hemorrhage, any other intracranial hemorrhage, and death were not significantly different.

CONCLUSIONS:

Incidence rate of reocclusion was significantly lower in the PTA group than in the mechanical thrombectomy-only group. We found no meaningful difference in reocclusion rates between the stent deployment and mechanical thrombectomy-only groups. In Japan, glycoprotein IIb/IIIa inhibitors are not reimbursed. Therefore, PTA might be the preferred choice for AT-LVOs due to the higher reocclusion risk with mechanical thrombectomy-only. Reocclusion was likely to occur within 10 days, particularly within 2 days post-endovascular therapy.




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Deep Learning-Based Reconstruction of 3D T1 SPACE Vessel Wall Imaging Provides Improved Image Quality with Reduced Scan Times: A Preliminary Study [ARTIFICIAL INTELLIGENCE]

BACKGROUND AND PURPOSE:

Intracranial vessel wall imaging is technically challenging to implement, given the simultaneous requirements of high spatial resolution, excellent blood and CSF signal suppression, and clinically acceptable gradient times. Herein, we present our preliminary findings on the evaluation of a deep learning–optimized sequence using T1-weighted imaging.

MATERIALS AND METHODS:

Clinical and optimized deep learning–based image reconstruction T1 3D Sampling Perfection with Application optimized Contrast using different flip angle Evolution (SPACE) were evaluated, comparing noncontrast sequences in 10 healthy controls and postcontrast sequences in 5 consecutive patients. Images were reviewed on a Likert-like scale by 4 fellowship-trained neuroradiologists. Scores (range, 1–4) were separately assigned for 11 vessel segments in terms of vessel wall and lumen delineation. Additionally, images were evaluated in terms of overall background noise, image sharpness, and homogeneous CSF signal. Segment-wise scores were compared using paired samples t tests.

RESULTS:

The scan time for the clinical and deep learning–based image reconstruction sequences were 7:26 minutes and 5:23 minutes respectively. Deep learning–based image reconstruction images showed consistently higher wall signal and lumen visualization scores, with the differences being statistically significant in most vessel segments on both pre- and postcontrast images. Deep learning–based image reconstruction had lower background noise, higher image sharpness, and uniform CSF signal. Depiction of intracranial pathologies was better or similar on the deep learning–based image reconstruction.

CONCLUSIONS:

Our preliminary findings suggest that deep learning–based image reconstruction–optimized intracranial vessel wall imaging sequences may be helpful in achieving shorter gradient times with improved vessel wall visualization and overall image quality. These improvements may help with wider adoption of intracranial vessel wall imaging in clinical practice and should be further validated on a larger cohort.




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Spinal CSF Leaks: The Neuroradiologist Transforming Care [SPINE IMAGING AND SPINE IMAGE-GUIDED INTERVENTIONS]

Spinal CSF leak care has evolved during the past several years due to pivotal advances in its diagnosis and treatment. To the reader of the American Journal of Neuroradiology (AJNR), it has been impossible to miss the exponential increase in groundbreaking research on spinal CSF leaks and spontaneous intracranial hypotension (SIH). While many clinical specialties have contributed to these successes, the neuroradiologist has been instrumental in driving this transformation due to innovations in noninvasive imaging, novel myelographic techniques, and image-guided therapies. In this editorial, we will delve into the exciting advancements in spinal CSF leak diagnosis and treatment and celebrate the vital role of the neuroradiologist at the forefront of this revolution, with particular attention paid to CSF leak–related work published in the AJNR.




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Selection of Affibody Molecules Using Phage Display

Affibody molecules are small (6-kDa) affinity proteins generated by directed evolution for specific binding to various target molecules. The first step in this workflow involves the generation of an affibody library. This is then followed by amplification of the library, which can then be used for biopanning using multiple methods. This protocol describes amplification of affibody libraries, followed by biopanning using phage display and analysis of the selection output. The general procedure is mainly for selection of first-generation affibody molecules from large naive (unbiased) libraries, typically yielding affibody hits with affinities in the low nanomolar range. For selection from affinity maturation libraries with the aim of isolating variants of even higher affinities, the procedure is similar, but parameters such as target concentration and washing are adjusted to achieve the proper stringency.




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Healthcare avoidance during the early stages of the COVID-19 pandemic and all-cause mortality: a longitudinal community-based study

BackgroundDuring the COVID-19 pandemic, global trends of reduced healthcare-seeking behaviour were observed. This raises concerns about the consequences of healthcare avoidance for population health.AimTo determine the association between healthcare avoidance during the early stages of the COVID-19 pandemic and all-cause mortality.Design and settingThis was a 32-month follow-up within the population-based Rotterdam Study, after sending a COVID-19 questionnaire at the onset of the pandemic in April 2020 to all communty dwelling participants (n = 6241/8732, response rate 71.5%).MethodCox proportional hazards models assessed the risk of all-cause mortality among respondents who avoided health care because of the COVID-19 pandemic. Mortality status was collected through municipality registries and medical records.ResultsOf 5656 respondents, one-fifth avoided health care because of the COVID-19 pandemic (n = 1143). Compared with non-avoiders, those who avoided health care more often reported symptoms of depression (n = 357, 31.2% versus n = 554, 12.3%) and anxiety (n = 340, 29.7% versus n = 549, 12.2%), and more often rated their health as poor to fair (n = 336, 29.4% versus n = 457, 10.1%) . Those who avoided health care had an increased adjusted risk of all-cause mortality (hazard ratio [HR] 1.30, 95% confidence interval [CI] = 1.01 to 1.67), which remained nearly identical after adjustment for history of any non-communicable disease (HR 1.20, 95% CI = 0.93 to 1.54). However, this association attenuated after additional adjustment for mental and physical self-perceived health factors (HR 0.93, 95% CI = 0.71 to 1.20).ConclusionThis study found an increased risk of all-cause mortality among individuals who avoided health care during COVID-19. These individuals were characterised by poor mental and physical self-perceived health. Therefore, interventions should be targeted to these vulnerable individuals to safeguard their access to primary and specialist care to limit health disparities, inside and beyond healthcare crises.




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Weight management with orlistat in type 2 diabetes: an electronic health records study

BackgroundOrlistat is recommended as an adjunct to diet and exercise for weight loss in the treatment of type 2 diabetes mellitus (T2DM).AimTo explore associations between patient characteristics and orlistat prescribing, and to determine associations of orlistat with weight loss in T2DM and prediabetes.Design and settingCohort study using anonymised health records from a UK database of general practice.MethodThe UK Clinical Practice Research Datalink (CPRD) Aurum database was searched to compile a cohort of patients aged ≥18 years, first diagnosed with T2DM or prediabetes in 2016 or 2017. Once the data had been collated, multivariable logistic regression models were used to determine associations with starting orlistat and stopping it early (<12 weeks of prescriptions) and orlistat’s associations with weight loss in those who had not been prescribed second-line antidiabetic medications.ResultsOut of 100 552 patients with incident T2DM or prediabetes, 655 (0.8%) patients with T2DM and 128 (0.7%) patients with prediabetes were prescribed orlistat. Younger people, females, those in areas of deprivation, current smokers, those coprescribed metformin, and those recorded as having hypertension were statistically significantly more likely to be prescribed orlistat; higher baseline glycated haemoglobin levels were associated with early stopping. In comparison with patients not on orlistat, those who continued using it for ≥12 weeks were more likely to lose ≥5% weight (adjusted odds ratio [AOR] 1.69, 95% confidence interval [CI] = 1.07 to 2.67) but those who stopped orlistat early were less likely to lose ≥5% weight (AOR 0.56, 95% CI = 0.29 to 1.09).ConclusionOrlistat was significantly associated with weight loss in patients with T2DM and prediabetes when taken for at least 12 weeks; however, it was infrequently prescribed and often taken for <12 weeks. Orlistat may be a useful adjunct to lifestyle modifications for patients with T2DM and prediabetes, but barriers to continued use means it may not be effective for everyone in managing weight loss.




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Can&#x2019;t prescribe, can&#x2019;t dispense: the challenge of medicine shortages




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Face-to-Face Relationships Still Matter in a Digital Age: A Call for a 5th C in the Core Tenets of Primary Care [Reflections]

We primary care clinicians, scholars, and leaders ascribe value to Barbara Starfield’s core tenets of primary care—the 4 Cs: first contact, comprehensiveness, coordination, and continuity. In today’s era of rapid technological advancements and dwindling resources, what are the implications for face-to-face interactions of patient-clinician relationships? We propose adding a 5th C: "Contiguity." Contiguity—or physical proximity and presence—is a key dimension that not only enables the necessary technical aspects of a physical exam but also authenticates the most human aspects of a relationship and occurs specifically when we are physically vulnerable and responsible for the other before us. This, in turn, may best enable us to bridge difference and nurture trust with our patients. We measure what we value and, thus, naming Contiguity as a core tenet assures that we will not lose sight of this keystone in a patient’s relationship with their personal physician.




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A Cluster-Randomized Study of Technology-Assisted Health Coaching for Weight Management in Primary Care [Original Research]

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.

METHODS

This cluster-randomized controlled trial enrolled 19 primary care teams with 63 clinicians; 9 teams were randomized to GEM and 10 to enhanced usual care (EUC). The GEM intervention included 1 in-person and up to 12 telephone-delivered coaching sessions. Coaches supported goal setting and engagement with weight management programs, facilitated by a software tool. Patients in the EUC arm received educational handouts. We enrolled patients who spoke English or Spanish, were aged 18 to 69 years, and either were overweight (body mass index 25-29 kg/m2) with a weight-related comorbidity or had obesity (body mass index ≥30 kg/m2). The primary outcome (weight change at 12 months) and exploratory outcomes (eg, program attendance, diet, physical activity) were analyzed according to intention to treat.

RESULTS

We enrolled 489 patients (220 in the GEM arm, 269 in the EUC arm). Their mean (SD) age was 49.8 (12.1) years; 44% were male, 41% Hispanic, and 44% non-Hispanic Black. At 12 months, the mean adjusted weight change (standard error) was –1.4 (0.8) kg in the GEM arm vs –0.8 (1.6) kg in the EUC arm, a nonsignificant difference (P = .48). There were no statistically significant differences in secondary outcomes. Exploratory analyses showed that the GEM arm had a greater change than the EUC arm in mean number of weekly minutes of moderate to vigorous physical activity other than walking, a finding that may warrant further exploration.

CONCLUSIONS

The GEM intervention did not achieve clinically important weight loss in primary care. Although this was a negative study possibly affected by health system resource limitations and disruptions, its findings can guide the development of similar interventions. Future studies could explore the efficacy of higher-intensity interventions and interventions that include medication and bariatric surgery options, in addition to lifestyle modification.




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[PERSPECTIVES] New Paradigms in the Clinical Management of Li-Fraumeni Syndrome

Approximately 8.5%–16.2% of childhood cancers are associated with a pathogenic/likely pathogenic germline variant—a prevalence that is likely to rise with improvements in phenotype recognition, sequencing, and variant validation. One highly informative, classical hereditary cancer predisposition syndrome is Li–Fraumeni syndrome (LFS), associated with germline variants in the TP53 tumor suppressor gene, and a >90% cumulative lifetime cancer risk. In seeking to improve outcomes for young LFS patients, we must improve the specificity and sensitivity of existing cancer surveillance programs and explore how to complement early detection strategies with pharmacology-based risk-reduction interventions. Here, we describe novel precision screening technologies and clinical strategies for cancer risk reduction. In particular, we summarize the biomarkers for early diagnosis and risk stratification of LFS patients from birth, noninvasive and machine learning–based cancer screening, and drugs that have shown the potential to be repurposed for cancer prevention.




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Management of opioid use disorder: 2024 update to the national clinical practice guideline [Guideline]

Background

In an evolving landscape of practices and policies, reviewing and incorporating the latest scientific evidence is necessary to ensure optimal clinical management for people with opioid use disorder. We provide a synopsis of the 2024 update of the 2018 National Guideline for the Clinical Management of Opioid Use Disorder, from the Canadian Research Initiative in Substance Matters.

Methods

For this update, we followed the United States Institute of Medicine’s Standards for Developing Trustworthy Clinical Practice Guidelines and used the Appraisal of Guidelines Research and Evaluation—Recommendation Excellence tool to ensure guideline quality. We carried out a comprehensive systematic literature review, capturing the relevant literature from Jan. 1, 2017, to Sept. 14, 2023. We drafted and graded recommendations according to the Grading of Recommendations, Assessments, Development and Evaluation approach. A multidisciplinary external national committee, which included people with living or lived experience of opioid use disorder, provided input that was incorporated into the guideline.

Recommendations

From the initial 11 recommendations in the 2018 guideline, 3 remained unchanged, and 8 were updated. Specifically, 4 recommendations were consolidated into a single revised recommendation; 1 recommendation was split into 2; another recommendation was moved to become a special consideration; and 2 recommendations were revised. Key changes have arisen from substantial evidence supporting that methadone and buprenorphine are similarly effective, particularly in reducing opioid use and adverse events, and both are now considered preferred first-line treatment options. Slow-release oral morphine is recommended as a second-line option. Psychosocial interventions can be offered as adjunctive treatment but should not be mandatory. The guideline reaffirms the importance of avoiding withdrawal management as a standalone intervention and of incorporating evidence-based harm reduction services along the continuum of care.

Interpretation

This guideline update presents new recommendations based on the latest literature for standardized management of opioid use disorder. The aim is to establish a robust foundation upon which provincial and territorial bodies can develop guidance for optimal care.




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Stage III NSCLC treatment options: too many choices

Stage III nonsmall cell lung cancer (NSCLC) represents a wide range of tumour (T1 to T4) and nodal (N0 to N3) components, requiring variable management and a multidisciplinary approach. Recent advancements in minimally invasive techniques, molecular biology and novel drug discoveries have accelerated the refinement of stage III NSCLC management. The latest developments in staging include the forthcoming update of the nodal component in the 9th TNM (tumour–node–metastasis) edition, which emphasises the critical role for endobronchial ultrasonography in mediastinal staging. Recent treatment developments include the use of immunotherapy and targeted molecular therapy in both the neoadjuvant and adjuvant setting, either in combination with other modalities or used alone as consolidation. Surgical and radiotherapy advancements have further enhanced patient outcomes. These developments have significantly improved the prognosis for patients with stage III NSCLC. Fast-changing recommendations have also brought about a challenge, with clinicians facing a number of options to choose from. Therefore, a multimodal approach by a multidisciplinary team has become even more crucial in managing stage III NSCLC.




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Management of central sleep apnoea: a review of non-hypercapnic causes

Central sleep apnoea (CSA) is characterised by recurrent episodes of airway cessation or reduction in the absence of respiratory effort. Although CSA is less common than obstructive sleep apnoea, it shares similar symptoms. CSA can be secondary to various medical conditions, high altitude and medication exposure. CSA can also emerge during obstructive sleep apnoea therapy. There are a range of treatment options and selecting the right therapy requires an understanding of the pathophysiology of CSA. This review explores the aetiology, pathophysiology and clinical management of non-hypercapnic CSA.




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Controversies in the clinical management of chronic pulmonary aspergillosis

Chronic pulmonary aspergillosis has a range of manifestations from indolent nodules to semi-invasive infection. Patients may be asymptomatic or have chronic symptoms such as cough and weight loss or present with life-threatening haemoptysis. The physician can choose from a range of available therapies including medical therapy with antifungals, minimally invasive therapy with intracavitary antifungal therapy and surgery involving open thoracotomy or video-assisted thoracoscopic surgery. The patients with the most severe forms of pulmonary infection may not be surgical candidates due to their underlying pulmonary condition. The management of haemoptysis can include tranexamic acid, bronchial artery embolisation, antifungals or surgery. There are few controlled studies to inform clinicians managing complex cases, so a multidisciplinary approach may be helpful.




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Palliative care in lung cancer: tumour- and treatment-related complications in lung cancer and their management

Palliative care pertains to the holistic multidimensional concept of "patient-centred" care. It is an interprofessional specialty, primarily aiming to improve quality of care for cancer patients and their families, from the time of diagnosis of malignant disease, over the continuum of cancer care, and extending after the patient's death to the period of bereavement to support the patient's family. There are various complex and frequently unmet needs of lung cancer patients and their families/caregivers, not only physical but also psychological, social, spiritual and cultural. Systematic monitoring of patients’ symptoms using validated questionnaires and patient-reported outcomes (PROs), on a regular basis, is highly encouraged and recommended in recent guidelines on the role of PRO measures in the continuum of cancer clinical care. It improves patient–physician communication, physician awareness of symptoms, symptom control, patient satisfaction, health-related quality of life and cost-effectiveness. This implies that all treating physicians should improve their skills in communication with lung cancer patients/relatives and become more familiar with this multidimensional assessment, repeatedly screening patients for palliative care needs. Therefore, they should receive education and training to develop palliative care knowledge, skills and attitudes. This review is dedicated to lung cancer palliative care essentials that should be within the competences of treating physicians, i.e. pneumologists/thoracic oncologists.




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HBO Boss on Working With George R.R. Martin: ‘Marriages Can Be Difficult’



HBO's Casey Bloys was asked about the Game of Thrones author's spicy take on House of the Dragon season two.



  • Television
  • Game of Thrones
  • George RR Martin
  • HBO
  • House of the Dragon

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Students can be agents of change: Talking about activism in universities with Jade Ho

Jade Ho explains what is possible for university students when they are given opportunities to learn about –and get involved with– social justice and labour issues in their own communities.

The post Students can be agents of change: Talking about activism in universities with Jade Ho appeared first on rabble.ca.




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Two thirds of Celtic fans want fan board put in place as 'poor' engagement called out

Two thirds of Celtic fans believe the club should have an independently elected Fan Advisory Board according to new research from the University of Glasgow.




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Andy Murray announces Glasgow and Edinburgh stage shows as part of UK tour

Sir Andy Murray will swap Centre Court for the stage next summer as he embarks on a tour discussing his illustrious tennis career.




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'Digital-first' Gaelic language production launched by BBC Alba and BBC Scotland

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





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RPG Cast – Episode 680: “Warning: Spicy Sausage”

Phil laughs at stupid Diablo IV hardcore deaths. Kelley goes for the all cannon ending. Jason is depressed and wants to play Dirge of Cerberus. Ryan doesn't have enough turn based RPGs in his life. Also, happy 100th birthday to Paw's grandfather!

The post RPG Cast – Episode 680: “Warning: Spicy Sausage” appeared first on RPGamer.




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Nintendo and The Pokemon Company Seeking Injunction and Damages from Pocketpair

Nintendo and The Pokémon Company in September filed a patent infringement lawsuit against Palworld developer Pocketpair. 

At the time Nintendo did not share which patents Palworld infringed on, however, Pocketpair has now revealed what patents Nintendo are claiming were infringed on.

"As announced on September 19, 2024, The Pokémon Company and Nintendo Co Ltd (hereinafter referred to as the Plaintiffs) have filed a patent infringement lawsuit against us," said Pocketpair. "We have received inquiries from various media outlets regarding the status of the lawsuit, and we would like to report the details and current status of this case as follows.

"The Plaintiffs claim that Palworld, released by us on January 19, 2024, infringes upon the following three patents held by the Plaintiffs, and are seeking an injunction against the game and compensation for a portion of the damages incurred between the date of registration of the patents and the date of filing of this lawsuit."

Nintendo and The Pokémon Company are each seeking an injunction and damages of five million yen plus late payment damages.

Pocketpair added, "We will continue to assert our position in this case through future legal proceedings. Please note that we will refrain from responding individually to inquiries regarding this case. If any matters arise that require public notice, we will announce them on our website, etc."

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/463022/nintendo-and-the-pokemon-company-seeking-injunction-and-damages-from-pocketpair/




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Dragon Age: The Veilguard Debuts in 2nd on the Australian Charts

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

There were three new releases in the top 10 this week with Dragon Age: The Veilguard debuting in second place, Horizon Zero Dawn Remastered in fourth place, and Life Is Strange: Double Exposure in ninth place.

Hogwarts Legacy is up one spot to third place, EA Sports FC 25 remained in fifth place, and Super Mario Party Jamboree dropped from second to sixth place.

Red Dead Redemption is in seventh place, NBA 2K25 is in eight place, and Battlefield 2042 rounds out the top 10.

Here are the top 10 best-selling titles in Australia 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. EA Sports FC 25 
  6. Super Mario Party Jamboree
  7. Red Dead Redemption
  8. NBA 2K25
  9. Life Is Strange: Double Exposure - NEW
  10. Battlefield 2042

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/463028/dragon-age-the-veilguard-debuts-in-2nd-on-the-australian-charts/




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Dragon Age: The Veilguard Debuts in 2nd on the New Zealand Charts

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/




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The trick to Dragon Age's lore is that the lore is lying, says original "uber-plot" writer David Gaider

Part of the fun of Dragon Age's fantasy is that it's inconsistent - or at least, inconsistent by the standards of fantasy RPGs, which often break down into a million neatly organised and interlocking codex entries. It all rides on who you speak to. The humans believe one thing about the origins and workings of Thedas, the elves another, the qunari something else entirely. These differences are the basis for many factional disagreements and thus, many core series plot developments. According to former lead writer David Gaider, however, there's an "uber-plot" behind it all that may one day be resolved and bring the series to a close, assuming BioWare continue to refer to his original (and closely guarded) narrative documents.

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I am deeply enamoured by Dragon Age: The Veilguard's intricate and ridiculous fashion design

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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Dragon Age: The Veilguard on PC is the surprise AAA tech success of 2024

There’s plenty that you could justifiably expect from a Bioware RPG: chats with mates, opportunities to get those mates horribly killed, surviving mates turning to the side then walking offscreen. But I don’t think anyone expected Dragon Age: The Veilguard to be, at least on a purely technical level, one of the smoothest-performing, settings-rich AAA PC releases of the year so far.

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Dragon Age: The Veilguard won't get expansions, reports say, as BioWare move to the next Mass Effect

BioWare currently has no plans for Dragon Age: The Veilguard expansions, according to reports. Instead the studio will support the fantasy RPG with smaller updates and otherwise turn their full attention towards Mass Effect 5.

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Factorio: Space Age review: a stellar expansion produces a masterful final form

To say that Factorio: Space Age throws out the rulebook is an understatement. It'd be more fitting to say it's somehow automated the whole process: an inserter plucked out the rulebook from my brain and deposited it in hot magma, while a new rulebook was churned out in a nearby machine and plopped into my brain from the other side - only for that to be immediately plucked out and incinerated as well. With each new planet and each new phase, Space Age reinvents itself. I'm battling hyperbole here, but ah hell, I admit defeat. Factorio: Space Age is a masterpiece, the final form of perhaps the most well-crafted building game I'll ever play.

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Dragon Age: The Veilguard is Veil-good on the Steam Deck

Discourse? Look mate, I’m just here to test the Steam Deck. Dragon Age: The Veilguard runs like a tap on any halfway decent desktop hardware, so was naturally going to be worth trying on the weaker Deck. And sure enough, Bioware’s RPG (which is really more of an action game with the occasional verbal spar) settles comfortably into handheld life.

In fact, Valve have festooned its Steam page with a Verified medal, a seal of approval for any game that performs and controls well on the Steam Deck without any glaring weaknesses or impractical annoyances. It’s still worth playing around with the settings – more on those later – but I’ll back up that official assessment, having played for several hours without so much as an undersized tooltip.

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The Raid homage Acts Of Blood is Sifu’s jankier, snackier cousin

Calling a game ‘no frills’ or ‘no nonsense’ is always a back-handed compliment, because it sounds like you're saying it's a bit straightforward and simple. And yes, that’s exactly what I’m saying here. Acts Of Blood feels like a spiffy PS2 action brawler; a slightly tighter old Yakuza game, or a stripped-back Sifu. It’s snacky and a bit janky, but it’s also great coffee break fodder, assuming you want to spend your break breaking a selection of heavy objects over the crumbly skulls of ne’er-do-wells. I mean, they might have done some things well, I don’t know them. But they aren’t doing any well to my character in the game, so violence it is.

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Sega are delisting over 60 'classic' games from Steam, including Crazy Taxi and Streets Of Rage

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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Roblox is limiting access to social hangouts and unrated games for children aged under 13

Roblox is making changes in an attempt to keep younger players safe in the online platform. Beginning later this month, children under the age of 13 will no longer be able to search, discover or play unrated experiences within Roblox, and will be unable to access social hangout experiences.

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Brits warned as spreading condition affecting young people earning above minimum wage



New research has revealed a growing mental phenomena sweeping the UK, which may only affect those with a certain income




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DWP hints at change to PIP disability assessments after humiliating hurdles outrage



A Labour minister confirmed that the application process for Personal Independence Payment is being 'kept under review'




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Could we take the entire solar system on a voyage through space?

To transport our planet across the universe, we would need to bring the whole solar system to sustain life on Earth – on this episode of Dead Planets Society, our hosts contemplate how to shepherd all that baggage on this scenic journey




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Astronomy Photographer of the Year showcases world's best space images

See the world's best space images from the Astronomy Photographer of the Year 2024 award