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Hobbit hominins from Indonesia may have had even smaller ancestors

An arm bone from an ancient human that lived 700,000 years ago on the island of Flores is the smallest ever found from an adult hominin, adding a new piece to the puzzle of Homo floresiensis




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Scientists Dismayed by Stem Cell Research Ruling

Title: Scientists Dismayed by Stem Cell Research Ruling
Category: Health News
Created: 8/24/2010 2:10:00 PM
Last Editorial Review: 8/25/2010 12:00:00 AM




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Cosmetic Eye Procedure May Ease Migraines, Small Study Says

Title: Cosmetic Eye Procedure May Ease Migraines, Small Study Says
Category: Health News
Created: 8/22/2014 12:36:00 PM
Last Editorial Review: 8/25/2014 12:00:00 AM




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Antiviral Drug May Prevent Ebola, Small Study Suggests

Title: Antiviral Drug May Prevent Ebola, Small Study Suggests
Category: Health News
Created: 8/25/2015 12:00:00 AM
Last Editorial Review: 8/26/2015 12:00:00 AM




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Play It Smart: Stay in School for a Healthier Heart

Title: Play It Smart: Stay in School for a Healthier Heart
Category: Health News
Created: 8/31/2017 12:00:00 AM
Last Editorial Review: 8/31/2017 12:00:00 AM




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U.S. Opioid Deaths Take a Small Dip, as Fentanyl Leaves Deadly Mark

Title: U.S. Opioid Deaths Take a Small Dip, as Fentanyl Leaves Deadly Mark
Category: Health News
Created: 8/29/2019 12:00:00 AM
Last Editorial Review: 8/30/2019 12:00:00 AM




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Scientists Challenge Key Survival Stat Cited by U.S. Officials in Plasma Approval

Title: Scientists Challenge Key Survival Stat Cited by U.S. Officials in Plasma Approval
Category: Health News
Created: 8/25/2020 12:00:00 AM
Last Editorial Review: 8/25/2020 12:00:00 AM




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FDA Approves Wider Use of Plasma as Coronavirus Treatment

Title: FDA Approves Wider Use of Plasma as Coronavirus Treatment
Category: Health News
Created: 8/24/2020 12:00:00 AM
Last Editorial Review: 8/25/2020 12:00:00 AM




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Survivors' Plasma Still a Solid Option for Treating COVID-19, Experts Say

Title: Survivors' Plasma Still a Solid Option for Treating COVID-19, Experts Say
Category: Health News
Created: 8/26/2020 12:00:00 AM
Last Editorial Review: 8/26/2020 12:00:00 AM




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Smart Phones, Watches Can Mess With Implanted Pacemakers

Title: Smart Phones, Watches Can Mess With Implanted Pacemakers
Category: Health News
Created: 8/26/2021 12:00:00 AM
Last Editorial Review: 8/26/2021 12:00:00 AM




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Wife of California Congressman Died After Using Herbal Remedy for Diabetes, Weight Loss

Title: Wife of California Congressman Died After Using Herbal Remedy for Diabetes, Weight Loss
Category: Health News
Created: 8/25/2022 12:00:00 AM
Last Editorial Review: 8/25/2022 12:00:00 AM




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Can Your Smartphone Spot a Narrowed Neck Artery?

Title: Can Your Smartphone Spot a Narrowed Neck Artery?
Category: Health News
Created: 8/17/2022 12:00:00 AM
Last Editorial Review: 8/17/2022 12:00:00 AM




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Nerve Block Plus Lidocaine Clears Psoriasis in Small Study

Title: Nerve Block Plus Lidocaine Clears Psoriasis in Small Study
Category: Health News
Created: 8/15/2022 12:00:00 AM
Last Editorial Review: 8/16/2022 12:00:00 AM




sma

SIBO (Small Intestinal Bacterial Overgrowth)

Title: SIBO (Small Intestinal Bacterial Overgrowth)
Category: Diseases and Conditions
Created: 10/28/2005 12:00:00 AM
Last Editorial Review: 8/8/2022 12:00:00 AM




sma

Be SMART About Asthma Management: Single Maintenance and Reliever Therapy

Single maintenance and reliever therapy (SMART) is an asthma treatment approach that utilizes combined inhaled corticosteroids and long-acting β-agonists for maintenance and quick relief therapy. Despite the evidence for its benefits in asthma treatment and its adoption into American and international asthma guidelines and recommendations, SMART remains a practice of some debate. This article reviews the available evidence for SMART and offers guidance for its integration into comprehensive asthma management. Overall, short-acting β-agonist-only asthma therapy regimens should be avoided, regardless of condition severity (SOR A Recommendation). Family medicine clinicians should start SMART for patients requiring either GINA Step 3 or 4 therapy, especially if they have signs of poor adherence (SOR B Recommendation). Finally, use budesonide-formoterol over other inhaled corticosteroid/long-acting β-agonist combinations when implementing SMART (SOR B Recommendation).




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The small noncoding RNA Vaultrc5 is dispensable to mouse development [ARTICLE]

Vault RNAs (vtRNAs) are evolutionarily conserved small noncoding RNAs transcribed by RNA polymerase III. Vault RNAs were initially described as components of the vault particle, but have since been assigned multiple vault-independent functions, including regulation of PKR activity, apoptosis, autophagy, lysosome biogenesis, and viral particle trafficking. The full-length transcript has also been described as a noncanonical source of miRNAs, which are processed in a DICER-dependent manner. As central molecules in vault-dependent and independent processes, vtRNAs have been attributed numerous biological roles, including regulation of cell proliferation and survival, response to viral infections, drug resistance, and animal development. Yet, their impact to mammalian physiology remains largely unexplored. To study vault RNAs in vivo, we generated a mouse line with a conditional Vaultrc5 loss-of-function allele. Because Vaultrc5 is the sole murine vtRNA, this allele enables the characterization of the physiological requirements of this conserved class of small regulatory RNAs in mammals. Using this strain, we show that mice constitutively null for Vaultrc5 are viable and histologically normal but have a slight reduction in platelet counts, pointing to a potential role for vtRNAs in hematopoiesis. This work paves the way for further in vivo characterizations of this abundant but mysterious RNA molecule. Specifically, it enables the study of the biological consequences of constitutive or lineage-specific Vaultrc5 deletion and of the physiological requirements for an intact Vaultrc5 during normal hematopoiesis or in response to cellular stresses such as oncogene expression, viral infection, or drug treatment.




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Functional Characterization of Reduced Folate Carrier and Protein-Coupled Folate Transporter for Antifolates Accumulation in Non-Small Cell Lung Cancer Cells [Articles]

Antifolates are important for chemotherapy in non–small cell lung cancer (NSCLC). They mainly rely on reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) to enter cells. PCFT is supposed to be the dominant transporter of the two in tumors, as it operates optimally at acidic pH and has limited transport activity at physiological pH, whereas RFC operates optimally at neutral pH. In this study, we found RFC showed a slightly pH-dependent uptake of antifolates, with similar affinity values at pH 7.4 and 6.5. PCFT showed a highly pH-dependent uptake of antifolates, with an optimum pH of 6.0 for pemetrexed and 5.5 for methotrexate. The Michaelis-Menten constant (Km) value of PCFT for pemetrexed at pH 7.4 was more than 10 times higher than that at pH 6.5. Interestingly, we found that antifolate accumulations mediated by PCFT at acidic pH were significantly affected by the efflux transporter, breast cancer resistance protein (BCRP). The highest pemetrexed concentration was observed at pH 7.0–7.4 after a 60-minute accumulation in PCFT-expressing cells, which was further evidenced by the cytotoxicity of pemetrexed, with the IC50 value of pemetrexed at pH 7.4 being one-third of that at pH 6.5. In addition, the in vivo study indicated that increasing PCFT and RFC expression significantly enhanced the antitumor efficacy of pemetrexed despite the high expression of BCRP. These results suggest that both RFC and PCFT are important for antifolates accumulation in NSCLC, although there is an acidic microenvironment and high BCRP expression in tumors.

SIGNIFICANCE STATEMENT

Evaluating the role of reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) on antifolates accumulation in non–small cell lung cancer (NSCLC) is necessary for new drug designs. By using cell models, we found both RFC and PCFT were important for antifolates accumulation in NSCLC. Breast cancer resistance protein (BCRP) significantly affected PCFT-mediated antifolates accumulation at acidic pH but not RFC-mediated pemetrexed accumulation at physiological pH. High expression of PCFT or RFC enhanced the cytotoxicity and antitumor effect of pemetrexed.




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The Simultaneous Inhibition of Solute Carrier Family 6 Member 19 and Breast Cancer Resistance Protein Transporters Leads to an Increase of Indoxyl Sulfate (a Uremic Toxin) in Plasma and Kidney [Articles]

Solute carrier family 6 member 19 (SLC6A19) inhibitors are being studied as therapeutic agents for phenylketonuria. In this work, a potent SLC6A19 inhibitor (RA836) elevated rat kidney uremic toxin indoxyl sulfate (IDS) levels by intensity (arbitrary unit) of 13.7 ± 7.7 compared with vehicle 0.3 ± 0.1 (P = 0.01) as determined by tissue mass spectrometry imaging analysis. We hypothesized that increased plasma and kidney levels of IDS could be caused by the simultaneous inhibition of both Slc6a19 and a kidney IDS transporter responsible for excretion of IDS into urine. To test this, we first confirmed the formation of IDS through tryptophan metabolism by feeding rats a Trp-free diet. Inhibiting Slc6a19 with RA836 led to increased IDS in these rats. Next, RA836 and its key metabolites were evaluated in vitro for inhibiting kidney transporters such as organic anion transporter (OAT)1, OAT3, and breast cancer resistance protein (BCRP). RA836 inhibits BCRP with an IC50 of 0.045 μM but shows no significant inhibition of OAT1 or OAT3. Finally, RA836 analogs with either potent or no inhibition of SLC6A19 and/or BCRP were synthesized and administered to rats fed a normal diet. Plasma and kidney samples were collected to quantify IDS using liquid chromatography–mass spectrometry. Neither a SLC6A19 inactive but potent BCRP inhibitor nor a SLC6A19 active but weak BCRP inhibitor raised IDS levels, whereas compounds inhibiting both transporters caused IDS accumulation in rat plasma and kidney, supporting the hypothesis that rat Bcrp contributes to the excretion of IDS. In summary, we identified that inhibiting Slc6a19 increases IDS formation, while simultaneously inhibiting Bcrp results in IDS accumulation in the kidney and plasma.

SIGNIFICANCE STATEMENT

This is the first publication to decipher the mechanism for accumulation of indoxyl sulfate (IDS) (a uremic toxin) in rats via inhibition of both Slc6a19 and Bcrp. Specifically, inhibition of Slc6a19 in the gastrointestinal track increases IDS formation, and inhibition of Bcrp in the kidney blocks IDS excretion. Therefore, we should avoid inhibiting both solute carrier family 6 member 19 and breast cancer resistance protein simultaneously in humans to prevent accumulation of IDS, a known risk factor for cardiovascular disease, psychic anxiety, and mortality in chronic kidney disease patients.




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Nonclinical Pharmacokinetics Study of OLX702A-075-16, N-Acetylgalactosamine Conjugated Asymmetric Small Interfering RNA (GalNAc-asiRNA) [Articles]

In this study, the nonclinical pharmacokinetics of OLX702A-075-16, an RNA interference therapeutic currently in development, were investigated. OLX702A-075-16 is a novel N-acetylgalactosamine conjugated asymmetric small-interfering RNA (GalNAc-asiRNA) used for the treatment of an undisclosed liver disease. Its unique 16/21-mer asymmetric structure reduces nonspecific off-target effects without compromising efficacy. We investigated the plasma concentration, tissue distribution, metabolism, and renal excretion of OLX702A-075-16 following a subcutaneous administration in mice and rats. For bioanalysis, high-performance liquid chromatography with fluorescence detection was used. The results showed rapid clearance from plasma (0.5 to 1.5 hours of half-life) and predominant distribution to the liver and/or kidney. Less than 1% of the liver concentration of OLX702A-075-16 was detected in the other tissues. Metabolite profiling using liquid chromatography coupled with high-resolution mass spectrometry revealed that the intact duplex OLX702A-075-16 was the major compound in plasma. The GalNAc moiety was predominantly metabolized from the sense strand in the liver, with the unconjugated sense strand of OLX702A-075-16 accounting for more than 95% of the total exposure in the rat liver. Meanwhile, the antisense strand was metabolized by the sequential loss of nucleotides from the 3'-terminus by exonuclease, with the rat liver samples yielding the most diverse truncated forms of metabolites. Urinary excretion over 96 hours was less than 1% of the administered dose in rats. High plasma protein binding of OLX702A-075-16 likely inhibited its clearance through renal filtration.

SIGNIFICANCE STATEMENT

This study presents the first comprehensive characterization of the in vivo pharmacokinetics of GalNAc-asiRNA. The pharmacokinetic insights gained from this research will aid in understanding toxicology and efficacy, optimizing delivery platforms, and improving the predictive power of preclinical species data for human applications.




sma

Early Prediction and Impact Assessment of CYP3A4-Related Drug-Drug Interactions for Small-Molecule Anticancer Drugs Using Human-CYP3A4-Transgenic Mouse Models [Articles]

Early detection of drug-drug interactions (DDIs) can facilitate timely drug development decisions, prevent unnecessary restrictions on patient enrollment, resulting in clinical study populations that are not representative of the indicated study population, and allow for appropriate dose adjustments to ensure safety in clinical trials. All of these factors contribute to a streamlined drug approval process and enhanced patient safety. Here we describe a new approach for early prediction of the magnitude of change in exposure for cytochrome P450 (P450) CYP3A4-related DDIs of small-molecule anticancer drugs based on the model-based extrapolation of human-CYP3A4-transgenic mice pharmacokinetics to humans. Victim drugs brigatinib and lorlatinib were evaluated with the new approach in combination with the perpetrator drugs itraconazole and rifampicin. Predictions of the magnitude of change in exposure deviated at most 0.99- to 1.31-fold from clinical trial results for inhibition with itraconazole, whereas exposure predictions for the induction with rifampicin were less accurate, with deviations of 0.22- to 0.48-fold. Results for the early prediction of DDIs and their clinical impact appear promising for CYP3A4 inhibition, but validation with more victim and perpetrator drugs is essential to evaluate the performance of the new method.

SIGNIFICANCE STATEMENT

The described method offers an alternative for the early detection and assessment of potential clinical impact of CYP3A4-related drug-drug interactions. The model was able to adequately describe the inhibition of CYP3A4 metabolism and the subsequent magnitude of change in exposure. However, it was unable to accurately predict the magnitude of change in exposure of victim drugs in combination with an inducer.




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Efficacy and Toxicity of [177Lu]Lu-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: Results from the U.S. Expanded-Access Program and Comparisons with Phase 3 VISION Data

The phase 3 VISION trial demonstrated that [177Lu]Lu-PSMA-617 prolonged progression-free survival and overall survival (OS) in prostate-specific membrane antigen [PSMA]–positive metastatic castration-resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor–signaling inhibitors (ARSIs). The U.S. expanded-access program (EAP; NCT04825652) was opened to provide access to [177Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. This study aimed to evaluate the efficacy and safety profile of [177Lu]Lu-PSMA-617 within the EAP and compare the results with those from the VISION trial. Methods: Patients enrolled in the EAP at 4 institutions in the United States with available toxicity and outcome data were included. Outcome measures included OS, a prostate-specific antigen (PSA) response rate (RR) of at least 50%, and incidences of toxicity according to Common Terminology Criteria for Adverse Events version 5.0. Differences in baseline characteristics, outcome data, and toxicity between the EAP and VISION were evaluated using t testing of proportions and survival analyses. Results: In total, 117 patients with mCRPC who received [177Lu]Lu-PSMA-617 within the EAP between May 2021 and March 2022 were eligible and included in this analysis. Patients enrolled in the EAP were more heavily pretreated with ARSI (≥2 ARSI regimens: 70% vs. 46%; P < 0.001) and had worse performance status at baseline (Eastern Cooperative Oncology Group score ≥ 2: 19% vs. 7%; P < 0.001) than VISION patients. EAP and VISION patients had similar levels of grade 3 or higher anemia (18% vs. 13%; P = 0.15), thrombocytopenia (13% vs. 8%; P = 0.13), and neutropenia (3% vs. 3%; P = 0.85) and similar PSA RRs (42% vs. 46%; P = 0.50) and OS (median: 15.1 vs. 15.3 mo; P > 0.05). Conclusion: Patients with PSMA-positive mCRPC who received [177Lu]Lu-PSMA-617 within the EAP were later in their disease trajectory than VISION patients. Patients enrolled in the EAP achieved similar PSA RRs and OS and had a safety profile similar to that of the VISION trial patients.




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Initial Experience with [177Lu]Lu-PSMA-617 After Regulatory Approval for Metastatic Castration-Resistant Prostate Cancer: Efficacy, Safety, and Outcome Prediction

[177Lu]Lu-PSMA-617 was approved by the U.S. Food and Drug Administration for patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC). Since the time of regulatory approval, however, real-world data have been lacking. This study investigated the efficacy, safety, and outcome predictors of [177Lu]Lu-PSMA-617 at a major U.S. academic center. Methods: Patients with mCRPC who received [177Lu]Lu-PSMA-617 at the Johns Hopkins Hospital outside clinical trials were screened for inclusion. Patients who underwent [177Lu]Lu-PSMA-617 and had available outcome data were included in this study. Outcome data included prostate-specific antigen (PSA) response (≥50% decline), PSA progression-free survival (PFS), and overall survival (OS). Toxicity data were evaluated according to the Common Terminology Criteria for Adverse Events version 5.03. The study tested the association of baseline circulating tumor DNA mutational status in homologous recombination repair, PI3K alteration pathway, and aggressive-variant prostate cancer–associated genes with treatment outcome. Baseline PSMA PET/CT images were analyzed using SelectPSMA, an artificial intelligence algorithm, to predict treatment outcome. Associations with the observed treatment outcome were evaluated. Results: All 76 patients with PSMA-positive mCRPC who received [177Lu]Lu-PSMA-617 met the inclusion criteria. A PSA response was achieved in 30 of 74 (41%) patients. The median PSA PFS was 4.1 mo (95% CI, 2.0–6.2 mo), and the median OS was 13.7 mo (95% CI, 11.3–16.1 mo). Anemia of grade 3 or greater, thrombocytopenia, and neutropenia were observed in 9 (12%), 3 (4%), and 1 (1%), respectively, of 76 patients. Transient xerostomia was observed in 23 (28%) patients. The presence of aggressive-variant prostate cancer–associated genes was associated with a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P = 0.040). No other associations were observed between circulating tumor DNA mutational status and treatment outcomes. Eighteen of 71 (25%) patients classified by SelectPSMA as nonresponders had significantly lower rates of PSA response than patients classified as likely responders (6% vs. 51%; P < 0.001), a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P < 0.001), and a shorter OS (median, 6.3 vs. 14.5 mo; P = 0.046). Conclusion: [177Lu]Lu-PSMA-617 offered in a real-world setting after regulatory approval in the United States demonstrated antitumor activity and a favorable toxicity profile. Artificial-intelligence–based analysis of baseline PSMA PET/CT images may improve patient selection. Validation of these findings on larger cohorts is warranted.




sma

Best Patient Care Practices for Administering PSMA-Targeted Radiopharmaceutical Therapy

Optimal patient management protocols for metastatic castration-resistant prostate cancer (mCRPC) are poorly defined and even further complexified with new therapy approvals, such as radiopharmaceuticals. The prostate-specific membrane antigen (PSMA)–targeted agent 177Lu vipivotide tetraxetan ([177Lu]Lu-PSMA-617), approved after the phase III VISION study, presents physicians with additional aspects of patient management, including specific adverse event (AE) monitoring and management, as well as radiation safety. Drawing on our experience as VISION study investigators, here we provide guidance on best practices for delivering PSMA-targeted radiopharmaceutical therapy (RPT) to patients with mCRPC. After a comprehensive review of published evidence and guidelines on RPT management in prostate cancer, we identified educational gaps in managing the radiation safety and AEs associated with [177Lu]Lu-PSMA-617. Our results showed that providing sufficient education on AEs (e.g., fatigue and dry mouth) and radiation safety principles is key to effective delivery and management of patient expectations. Patient counseling by health care professionals, across disciplines, is a cornerstone of optimal patient management during PSMA-targeted RPT. Multidisciplinary collaboration is crucial, and physicians must adhere to radiation safety protocols and counsel patients on radiation safety considerations. Treatment with [177Lu]Lu-PSMA-617 is generally well tolerated; however, additional interventions may be required, such as dosing modification, medications, or transfusions. Urinary incontinence can be challenging in the context of radiation safety. Multidisciplinary collaboration between medical oncologists and nuclear medicine teams ensures that patients are monitored and managed safely and efficiently. In clinical practice, the benefit-to-risk ratio should always be evaluated on a case-by-case basis.




sma

Intra-Aneurysmal High-Resolution 4D MR Flow Imaging for Hemodynamic Imaging Markers in Intracranial Aneurysm Instability [RESEARCH]

BACKGROUND AND PURPOSE:

Prediction of aneurysm instability is crucial to guide treatment decisions and to select appropriate patients with unruptured intracranial aneurysms (IAs) for preventive treatment. High-resolution 4D MR flow imaging and 3D quantification of aneurysm morphology could offer insights and new imaging markers for aneurysm instability. In this cross-sectional study, we aim to identify 4D MR flow imaging markers for aneurysm instability by relating hemodynamics in the aneurysm sac to 3D morphologic proxy parameters for aneurysm instability.

MATERIALS AND METHODS:

In 35 patients with 37 unruptured IAs, a 3T MRA and a 7T 4D MRI flow scan were performed. Five hemodynamic parameters—peak-systolic wall shear stress (WSSMAX) and time-averaged wall shear stress (WSSMEAN), oscillatory shear index (OSI), mean velocity, and velocity pulsatility index—were correlated to 6 3D morphology proxy parameters of aneurysm instability—major axis length, volume, surface area (all 3 size parameters), flatness, shape index, and curvedness—by Pearson correlation with 95% CI. Scatterplots of hemodynamic parameters that correlated with IA size (major axis length) were created.

RESULTS:

WSSMAX and WSSMEAN correlated negatively with all 3 size parameters (strongest for WSSMEAN with volume (r = –0.70, 95% CI –0.83 to –0.49) and OSI positively (strongest with major axis length [r = 0.87, 95% CI 0.76–0.93]). WSSMAX and WSSMEAN correlated positively with shape index (r = 0.61, 95% CI 0.36–0.78 and r = 0.49, 95% CI 0.20–0.70, respectively) and OSI negatively (r = –0.82, 95% CI –0.9 to –0.68). WSSMEAN and mean velocity correlated negatively with flatness (r = –0.35, 95% CI –0.61 to –0.029 and r = –0.33, 95% CI –0.59 to 0.007, respectively) and OSI positively (r = 0.54, 95% CI 0.26–0.74). Velocity pulsatility index did not show any statistically relevant correlation.

CONCLUSIONS:

Out of the 5 included hemodynamic parameters, WSSMAX, WSSMEAN, and OSI showed the strongest correlation with morphologic 3D proxy parameters of aneurysm instability. Future studies should assess these promising new imaging marker parameters for predicting aneurysm instability in longitudinal cohorts of patients with IA.




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Synchronous T-lymphoblastic lymphoma and neuroblastoma in a 3-yr-old with novel germline SMARCA4 and EZH2 variants [RAPID CANCER COMMUNICATION]

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




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The CheckMate 816 trial: a milestone in neoadjuvant chemoimmunotherapy of nonsmall cell lung cancer

Advancements in immunotherapy in the perioperative setting have revolutionised the treatment of resectable nonsmall cell lung cancer (NSCLC). Here we present the methodology and results of the clinical trial CheckMate 816 demonstrating the benefit of neoadjuvant therapy with nivolumab plus chemotherapy compared with chemotherapy alone. Furthermore, this article discusses the implications for future practice in resectable NSCLC and the need for future research.




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Small cell lung cancer and neuroendocrine tumours

Lung cancer is one of the leading causes of death worldwide. It can broadly be divided into small cell lung cancer (SCLC) and nonsmall cell lung cancer. There have been many advances over the recent years in both fields. The purpose of this review is to provide a concise summary of SCLC for the general respiratory readership.





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A small asteroid hit Earth and burned up over the Philippines

A newly spotted asteroid named 2024 RW1 burned up in the atmosphere over the South Pacific, creating a spectacular bright flash in the sky over the Philippines just hours after first being detected




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Smartphone flaw allows hackers and governments to map your home

A newly identified smartphone vulnerability can reveal the floor plans of where you are and what you are doing - and it is possible that companies or intelligence agencies are already making use of it




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Smart speakers at crime scenes could provide valuable clues to police

Information on faces recognised, voice commands and internet searches can be extracted from an Amazon Echo smart assistant without help from the user or manufacturer




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Smart TVs take snapshots of what you watch multiple times per second

Smart TVs from Samsung and LG monitor what you are watching even when you are using the screens to display a feed from a connected laptop or video game console




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It's parents who are anxious about smartphones, not their children

Smartphones have indeed created an "anxious generation", but it isn't young people, it is their parents, argues neuroscientist Dean Burnett




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Hackers can turn your smartphone into an eavesdropping device

Motion sensors in smartphones can be turned into makeshift microphones to eavesdrop on conversations, outsmarting security features designed to stop such attacks




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Dismantle the 'Environmental Justice' Juggernaut

Eliminating this pernicious policy should be on the Trump administration's first week to-do list.




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After dismal start, UN hosts 'halftime summit' in bid to save development plan

After a dismal start, the UN is hosting a "halftime summit" about its 15-year plan to meet a series of human-development targets by 2030. Delegates will try to focus on problems like extreme poverty and gender equality while watching for sparks between the representatives of Ukraine and Russia.




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Inside Apple Mac week: New power, smarter AI, bold innovations

Apple recently announced its new lineup of Macs and rolled out Apple Intelligence, its latest artificial intelligence-powered feature for its products.



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In just 2 hours, this tiny smart home can be set up nearly anyplace

The Massimo Modular E9 is a sleek, smart and comfy tiny home in 409 square feet. Tech expert Kurt “CyberGuy" Knutsson takes a closer look at what the future of housing might look like.



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sma

Three hospitalised as car 'mounts pavement' and smashes into Piccadilly Circus restaurant



Three people have been taken to hospital after a car mounted the pavement and smashed into a restaurant in Piccadilly Circus, the Metropolitan Police have said.




sma

One dose of a smallpox vaccine still gives good protection for mpox

A single dose of a smallpox vaccine seems to lower the risk of catching mpox by around 60 per cent, and two doses would probably be even better




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Donald Trump and Elon Musk: Could U.S. election's odd couple unleash a small-government revolution?

The appointment of a political outsider like Musk could help Trump cut regulations and rein in government bureaucracy, even if the moves are unpopular




sma

Comment on The Shocking Truth About SMA: Why Every Family Should Be Informed by 먹튀검증소

<a href="https://mtverify.com/" rel="nofollow ugc">먹튀검증</a> 전문가들이 꼼꼼하게 검증한 사이트만을 소개합니다. 안심하고 베팅하세요. 먹튀검증소: https://mtverify.com/





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President-Elect Donald Trump Picks Businessman Steven Witkoff to Be Special Envoy to Middle East


President-elect Donald Trump announced that he has picked businessman and real estate investor Steven Witkoff to serve as Special Envoy to the Middle East.

The post President-Elect Donald Trump Picks Businessman Steven Witkoff to Be Special Envoy to Middle East appeared first on Breitbart.




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Best smartphones under ₹20,000 with good cameras: Redmi Note 13 Pro, Vivo T3 5G and others - Hindustan Times

  1. Best smartphones under ₹20,000 with good cameras: Redmi Note 13 Pro, Vivo T3 5G and others  Hindustan Times
  2. Best smartphones under ₹30,000 with good battery life and cameras  Mint
  3. 5 Affordable Camera Phones To Make Instagram Reels  Times Now
  4. Best Smartphones Under Rs 20,000 With Excellent Cameras, Redmi Note 13 Pro, Vivo T3 5G & More  NewsX




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Dysmantle’s Final Major Update Is Now Live on iOS Bringing In Ark Level 4, Night Terrors, Link Towers, and Much More

Back in May, Dysmantle ($9.99) from 10tons Ltd. got its final major content update on Steam. Dysmantle version 1.4.0 titled …





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Your Guide To Enjoying Transmasculine Sex

I could be biased, but sex with transmasculine people is fantastic. A warning up front: this article is not safe for work, unless it’s your very first day at the ...

The post Your Guide To Enjoying Transmasculine Sex appeared first on Star Observer.




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Baidu announces its own pair of AI smart glasses

Baidu, which is often called China's answer to Google, has launched its own pair of AI-powered smart glasses at its annual World Conference event in Shanghai. The device will run on the company's ERNIE generative AI technology and was designed to "become a private assistant," according to the Financial Times. Users will reportedly be able to interact with the device using their voice and ask it questions about what it sees in their current environment. They can also tell it to play music and even track their calories consumption. And since the glasses are equipped with cameras, they can ask it to snap photos or take videos. 

When the glasses start shipping sometime next year, they could become the Chinese consumers' alternative to Meta's and Snap's devices. Meta teamed up with Ray Ban a few years ago to release a pair of smart sunglasses that can livestream and send photos hands-free. Its latest model comes built-in with Meta's generative AI assistant that users can talk to. However, the company's device isn't officially sold in China, because its servers are blocked in the country. Baidu has yet to announce how much its glasses would cost, but Meta is selling its device for $299. 

The Baidu World Conference had a huge focus on the company's AI efforts, as it takes steps to make sure ERNIE can keep up with its competitors' technologies. It also launched a new AI image generator called iRAG that apparently experiences fewer hallucinations than its predecessor, along with a tool that enables people to create software programs even if they don't have coding expertise. According to The Times, ByteDance's Doubao is now the leading AI chatbot in China based on monthly active users as observed by Sensor Tower. ByteDance is also growing its hardware offerings and recently launched a pair of earbuds with access to its AI assistant Doubao. 

This article originally appeared on Engadget at https://www.engadget.com/ai/baidu-announces-its-own-pair-of-ai-smart-glasses-143044805.html?src=rss




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Rode's tiny $149 Wireless Micro kit is designed for smartphone users

Rode has announced the Wireless Micro, a two-mic kit with a smartphone receiver and charging case that costs just $149. The idea is to help TikTok and other creators capture much better-quality audio than their smartphone's microphone can offer. 

The receiver unit connects to the bottom of your smartphone via a USB-C or lightning port. Meanwhile, the microphones (aka transmitters) attach to the subject via integrated clips or magnetic attachments, then capture what Rode calls "pristine" quality sound. Specifically, they offer a 20-20 kHz frequency range and 73 dB signal-to-noise ratio, with a transmission range around 330 feet.

Rode

To use it, simply connect the receiver to your iOS or Android device and it will take over as the system microphone. From there, everything is automatic, as the transmitter mics are automatically paired to the receiver and sound will be captured to your camera app of choice. Levels are automatically controlled with the company's GainAssist technology. 

The omnidirectional transmitters weigh just 12 grams (0.42 ounces) and are tiny enough to be discreet when clipped onto your subject. The built-in microphones use what Rode calls "acoustic chambers" with a patent-pending design. That supposedly lets you capture clear and intelligible audio while reducing wind noise, though a pair of windmuffs is also included in the kit. 

Rode

The Wireless Micro also includes a charging case that delivers two full recharges for up to 18 hours of battery life, while giving you a secure place to store everything. 

There are a few things missing, though. You can't connect an external mic to the transmitters, unlike with other Rode wireless mics or the DJI Mic 2. There's no smartphone Bluetooth capability, and it doesn't offer a 3.5mm connection for cameras — a feature that will supposedly exist on the rumored DJI Mic Mini. Still, this looks like a great option for creators who primarily use smartphones. It's now available in a two mic kit with a receiver and charging case for $150. 

This article originally appeared on Engadget at https://www.engadget.com/audio/rodes-tiny-149-wireless-micro-kit-is-designed-for-smartphone-users-150040695.html?src=rss