ps {alpha}2-Macroglobulin-like protein 1 can conȷugate and inhibit proteases through their hydroxyl groups, because of an enhanced reactivity of its thiol ester [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-04T00:06:05-08:00 Proteins in the α-macroglobulin (αM) superfamily use thiol esters to form covalent conjugation products upon their proteolytic activation. αM protease inhibitors use theirs to conjugate proteases and preferentially react with primary amines (e.g. on lysine side chains), whereas those of αM complement components C3 and C4B have an increased hydroxyl reactivity that is conveyed by a conserved histidine residue and allows conjugation to cell surface glycans. Human α2-macroglobulin–like protein 1 (A2ML1) is a monomeric protease inhibitor but has the hydroxyl reactivity–conveying histidine residue. Here, we have investigated the role of hydroxyl reactivity in a protease inhibitor by comparing recombinant WT A2ML1 and the A2ML1 H1084N mutant in which this histidine is removed. Both of A2ML1s' thiol esters were reactive toward the amine substrate glycine, but only WT A2ML1 reacted with the hydroxyl substrate glycerol, demonstrating that His-1084 increases the hydroxyl reactivity of A2ML1's thiol ester. Although both A2ML1s conjugated and inhibited thermolysin, His-1084 was required for the conjugation and inhibition of acetylated thermolysin, which lacks primary amines. Using MS, we identified an ester bond formed between a thermolysin serine residue and the A2ML1 thiol ester. These results demonstrate that a histidine-enhanced hydroxyl reactivity can contribute to protease inhibition by an αM protein. His-1084 did not improve A2ML1's protease inhibition at pH 5, indicating that A2ML1's hydroxyl reactivity is not an adaption to its acidic epidermal environment. Full Article
ps Snapshots during the catalytic cycle of a histidine acid phytase reveal an induced-fit structural mechanism [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Highly engineered phytases, which sequentially hydrolyze the hexakisphosphate ester of inositol known as phytic acid, are routinely added to the feeds of monogastric animals to improve phosphate bioavailability. New phytases are sought as starting points to further optimize the rate and extent of dephosphorylation of phytate in the animal digestive tract. Multiple inositol polyphosphate phosphatases (MINPPs) are clade 2 histidine phosphatases (HP2P) able to carry out the stepwise hydrolysis of phytate. MINPPs are not restricted by a strong positional specificity making them attractive targets for development as feed enzymes. Here, we describe the characterization of a MINPP from the Gram-positive bacterium Bifidobacterium longum (BlMINPP). BlMINPP has a typical HP2P-fold but, unusually, possesses a large α-domain polypeptide insertion relative to other MINPPs. This insertion, termed the U-loop, spans the active site and contributes to substrate specificity pockets underpopulated in other HP2Ps. Mutagenesis of U-loop residues reveals its contribution to enzyme kinetics and thermostability. Moreover, four crystal structures of the protein along the catalytic cycle capture, for the first time in an HP2P, a large ligand-driven α-domain motion essential to allow substrate access to the active site. This motion recruits residues both downstream of a molecular hinge and on the U-loop to participate in specificity subsites, and mutagenesis identified a mobile lysine residue as a key determinant of positional specificity of the enzyme. Taken together, these data provide important new insights to the factors determining stability, substrate recognition, and the structural mechanism of hydrolysis in this industrially important group of enzymes. Full Article
ps What will authorizing the return of US troops mean for Somalia? By www.chathamhouse.org Published On :: Fri, 17 Jun 2022 12:47:32 +0000 What will authorizing the return of US troops mean for Somalia? Explainer Video aboudiaf.drupal 17 June 2022 Ahmed Soliman examines what the reintroduction of US military means for Somalia. He says the strategy remains to try and reduce al-Shabaab’s threat, suppress its ability to carry out operations, and target its senior leadership. There is more of a recognition now that the focus needs to be on restoring an effective security sector within Somalia and ensuring their forces are ready, but this also requires better coordination between the federal government and federal member states which it is hoped will happen in this new administration. Full Article
ps The added value of 18F-FDG PET/CT compared to 68Ga-PSMA PET/CT in patients with castration-resistant prostate cancer By jnm.snmjournals.org Published On :: 2021-04-23T13:46:28-07:00 Purpose: The 68Ga-PSMA PET/CT is a commonly used imaging modality in prostate cancers. However, few studies have compared the diagnostic efficiency between 68Ga-PSMA and 18F-FDG PET/CT and evaluated whether a heterogeneous metabolic phenotype (especially PSMA-FDG+ lesions) exists in patients with castration-resistant prostate cancer (CRPC). We determined the added value of 18F-FDG PET/CT compared to 68Ga-PSMA PET/CT in CRPC patients and identified CRPC patients who may benefit from additional 18F-FDG PET/CT. Methods: Data of 56 patients with CRPC who underwent both 68Ga-PSMA and 18F-FDG PET/CT from May 2018 to February 2021 were retrospectively analysed. Patients were classified into two groups with or without PSMA-FDG+ lesions. The differences in patient characteristics between the two groups and predictors of patients who having at least one PSMA-FDG+ lesion were analysed. Results: Although both the detection rate (75.0% vs. 51.8%, P = 0.004) and positive lesion number (135 vs. 95) of 68Ga-PSMA PET/CT were higher than 18F-FDG PET/CT, there were still 13/56 (23.2%) patients with at least one PSMA-FDG+ lesion. The prostate-specific antigen (PSA) and Gleason score were both higher in the patients with PSMA-FDG+ lesions than in those without PSMA-FDG+ lesions (P = 0.04 and P<0.001, respectively). Multivariate regression analysis showed that the Gleason score (≥8) and PSA (≥7.9 ng/mL) were associated with the detection rate of patients who had PSMA-FDG+ lesions (P = 0.01 and P = 0.04, respectively). The incidences of having PSMA-FDG+ lesions in low-probability (Gleason score<8 and PSA<7.9 ng/mL), medium-probability (Gleason score≥8 and PSA<7.9 ng/mL or Gleason score<8 and PSA≥7.9 ng/mL), and high-probability (Gleason score≥8 and PSA≥7.9 ng/mL) groups were 0%, 21.7%, and 61.5%, respectively (P<0.001). Conclusion: Gleason score and PSA are significant predictors for PSMA-FDG+ lesions, and CRPC patients with high Gleason score and PSA may benefit from additional 18F-FDG PET/CT. Full Article
ps Challenges with 177Lu-PSMA-617 Radiopharmaceutical Therapy in Clinical Practice By jnm.snmjournals.org Published On :: 2024-09-19T06:38:07-07:00 Full Article
ps Pattern of Failure in Patients with Biochemical Recurrence After PSMA Radioguided Surgery By jnm.snmjournals.org Published On :: 2024-09-26T12:46:37-07:00 Visual Abstract Full Article
ps Comparison of Posttherapy 4- and 24-Hour [177Lu]Lu-PSMA SPECT/CT and Pretherapy PSMA PET/CT in Assessment of Disease in Men with Metastatic Castration-Resistant Prostate Cancer By jnm.snmjournals.org Published On :: 2024-10-30T08:04:16-07:00 Visual Abstract Full Article
ps Outcomes for Patients with Metastatic Castration-Resistant Prostate Cancer and Liver Metastasis Receiving [177Lu]Lu-PSMA-617 By jnm.snmjournals.org Published On :: 2024-10-30T08:04:14-07:00 Visual Abstract Full Article
ps Clinical, Pathologic, and Imaging Variables Associated with Prostate Cancer Detection by PSMA PET/CT and Multiparametric MRI By jnm.snmjournals.org Published On :: 2024-10-30T08:04:14-07:00 Visual Abstract Full Article
ps FAP and PSMA Expression by Immunohistochemistry and PET Imaging in Castration-Resistant Prostate Cancer: A Translational Pilot Study By jnm.snmjournals.org Published On :: 2024-10-30T08:04:15-07:00 Visual Abstract Full Article
ps SPECT/CT in Early Response Assessment of Patients with Metastatic Castration-Resistant Prostate Cancer Receiving 177Lu-PSMA-617 By jnm.snmjournals.org Published On :: 2024-11-07T04:28:32-08:00 Visual Abstract Full Article
ps Feasibility of 177Lu-PSMA Administration as Outpatient Procedure for Prostate Cancer By jnm.snmjournals.org Published On :: 2024-11-07T04:28:31-08:00 Full Article
ps Pacific Rim: Inside the Counter-Offensive—The TTPs Used to Neutralize China-Based Threats By news.sophos.com Published On :: Thu, 31 Oct 2024 12:56:23 +0000 Sophos X-Ops unveils five-year investigation tracking China-based groups targeting perimeter devices Full Article Security Operations Chinese APT Chinese spying featured Pacific Rim Story Sophos Firewall state-sponsored attackers
ps Bengal cat lovers in Australia get psspsspss’d in Google-driven Gootloader campaign By news.sophos.com Published On :: Wed, 06 Nov 2024 11:30:41 +0000 The Internet is full of cats—and in this case, malware-delivering fake cat websites used for very targeted search engine optimization. Full Article Security Operations Threat Research Gootloader Javascript loader search engine poisoning SEO Poisoning
ps Global Proteome and Phosphoproteome Characterization of Sepsis-induced Kidney Injury By www.mcponline.org Published On :: 2020-12-01 Yi-Han LinDec 1, 2020; 19:2030-2046Research Full Article
ps Unraveling the MAX2 Protein Network in Arabidopsis thaliana: Identification of the Protein Phosphatase PAPP5 as a Novel MAX2 Interactor By www.mcponline.org Published On :: 2020-12-28 Sylwia StrukDec 28, 2020; 0:RA119.001766v1-mcp.RA119.001766Research Full Article
ps ProAlanase is an Effective Alternative to Trypsin for Proteomics Applications and Disulfide Bond Mapping By www.mcponline.org Published On :: 2020-12-01 Diana SamodovaDec 1, 2020; 19:2139-2156Technological Innovation and Resources Full Article
ps LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients By www.jlr.org Published On :: 2020-12-01 Auguste DargentDec 1, 2020; 61:1776-1783Research Articles Full Article
ps Human CETP lacks lipopolysaccharide transfer activity, but worsens inflammation and sepsis outcomes in mice By www.jlr.org Published On :: 2020-12-09 Aloïs DusuelDec 9, 2020; 0:jlr.RA120000704v1-jlr.RA120000704Research Articles Full Article
ps Update on LIPID MAPS classification, nomenclature, and shorthand notation for MS-derived lipid structures By www.jlr.org Published On :: 2020-12-01 Gerhard LiebischDec 1, 2020; 61:1539-1555Special Report Full Article
ps Human CETP lacks lipopolysaccharide transfer activity, but worsens inflammation and sepsis outcomes in mice [Research Articles] By www.jlr.org Published On :: 2020-12-09T11:36:34-08:00 Bacterial lipopolysaccharides (LPSs or endotoxins) can bind most proteins of the lipid transfer/LPS-binding protein (LT/LBP) family in host organisms. The LPS-bound LT/LBP proteins then trigger either an LPS-induced proinflammatory cascade or LPS binding to lipoproteins that are involved in endotoxin inactivation and detoxification. Cholesteryl ester transfer protein (CETP) is an LT/LBP member, but its impact on LPS metabolism and sepsis outcome is unclear. Here, we performed fluorescent LPS transfer assays to assess the ability of CETP to bind and transfer LPS. The effects of intravenous (iv) infusion of purified LPS or polymicrobial infection (cecal ligation and puncture [CLP]) were compared in transgenic mice expressing human CETP and wild-type mice naturally having no CETP activity. CETP displayed no LPS transfer activity in vitro, but it tended to reduce biliary excretion of LPS in vivo. The CETP expression in mice was associated with significantly lower basal plasma lipid levels and with higher mortality rates in both models of endotoxemia and sepsis. Furthermore, CETPTg plasma modified cytokine production of macrophages in vitro. In conclusion, despite having no direct LPS binding and transfer property, human CETP worsens sepsis outcomes in mice by altering the protective effects of plasma lipoproteins against endotoxemia, inflammation, and infection. Full Article
ps Lipid sensing tips the balance for a key cholesterol synthesis enzyme [Images in Lipid Research] By www.jlr.org Published On :: 2020-11-01T00:05:43-07:00 Full Article
ps LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients [Research Articles] By www.jlr.org Published On :: 2020-12-01T00:05:39-08:00 Lipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. An extracorporeal removal method by polymyxin (PMX) B direct hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by lipoproteins, including LDLs. Lipoproteins are critical for physiological LPS clearance, as LPSs are carried by LDLs to the liver for elimination. We hypothesized that LDL apheresis could be an alternate method for LPS removal. First, we demonstrated in vitro that LDL apheresis microbeads are almost as efficient as PMX beads to reduce LPS concentration in LPS-spiked human plasma, whereas it is not active in PBS. We found that PMX was also adsorbing lipoproteins, although less specifically. Then, we found that endogenous LPS of patients treated by LDL apheresis for familial hypercholesterolemia is also removed during their LDL apheresis sessions, with both electrostatic-based devices and filtration devices. Finally, LPS circulating in the plasma of septic shock and severe sepsis patients with gram-negative bacteremia was also removed in vitro by LDL adsorption. Overall, these results underline the importance of lipoproteins for LPS clearance, making them a prime target to study and treat endotoxemia-related conditions. Full Article
ps Update on LIPID MAPS classification, nomenclature, and shorthand notation for MS-derived lipid structures [Special Reports] By www.jlr.org Published On :: 2020-12-01T00:05:39-08:00 A comprehensive and standardized system to report lipid structures analyzed by MS is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e., annotation of ring double bond equivalents and number of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolution powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stable isotope-labeled compounds in metabolic labeling experiments or as internal standards. This update on lipid classification, nomenclature, and shorthand annotation for lipid mass spectra is considered a standard for lipid data presentation. Full Article
ps Benefits of Collisional Cross Section Assisted Precursor Selection (caps-PASEF) for Cross-linking Mass Spectrometry [Research] By www.mcponline.org Published On :: 2020-10-01T00:05:25-07:00 Ion mobility separates molecules in the gas-phase based on their physico-chemical properties, providing information about their size as collisional cross-sections. The timsTOF Pro combines trapped ion mobility with a quadrupole, collision cell and a TOF mass analyzer, to probe ions at high speeds with on-the-fly fragmentation. Here, we show that on this platform ion mobility is beneficial for cross-linking MS (XL-MS). Cross-linking reagents covalently link amino acids in proximity, resulting in peptide pairs after proteolytic digestion. These cross-linked peptides are typically present at low abundance in the background of normal peptides, which can partially be resolved by using enrichable cross-linking reagents. Even with a very efficient enrichable cross-linking reagent, like PhoX, the analysis of cross-linked peptides is still hampered by the co-enrichment of peptides connected to a partially hydrolyzed reagent – termed mono-linked peptides. For experiments aiming to uncover protein-protein interactions these are unwanted byproducts. Here, we demonstrate that gas-phase separation by ion mobility enables the separation of mono-linked peptides from cross-linked peptide pairs. A clear partition between these two classes is observed at a CCS of 500 Å2 and a monoisotopic mass of 2 kDa, which can be used for targeted precursor selection. A total of 50-70% of the mono-linked peptides are prevented from sequencing, allowing the analysis to focus on sequencing the relevant cross-linked peptide pairs. In applications to both simple proteins and protein mixtures and a complete highly complex lysate this approach provides a substantial increase in detected cross-linked peptides. Full Article
ps ProAlanase is an Effective Alternative to Trypsin for Proteomics Applications and Disulfide Bond Mapping [Technological Innovation and Resources] By www.mcponline.org Published On :: 2020-12-01T00:05:33-08:00 Trypsin is the protease of choice in bottom-up proteomics. However, its application can be limited by the amino acid composition of target proteins and the pH of the digestion solution. In this study we characterize ProAlanase, a protease from the fungus Aspergillus niger that cleaves primarily on the C-terminal side of proline and alanine residues. ProAlanase achieves high proteolytic activity and specificity when digestion is carried out at acidic pH (1.5) for relatively short (2 h) time periods. To elucidate the potential of ProAlanase in proteomics applications, we conducted a series of investigations comprising comparative multi-enzymatic profiling of a human cell line proteome, histone PTM analysis, ancient bone protein identification, phosphosite mapping and de novo sequencing of a proline-rich protein and disulfide bond mapping in mAb. The results demonstrate that ProAlanase is highly suitable for proteomics analysis of the arginine- and lysine-rich histones, enabling high sequence coverage of multiple histone family members. It also facilitates an efficient digestion of bone collagen thanks to the cleavage at the C terminus of hydroxyproline which is highly prevalent in collagen. This allows to identify complementary proteins in ProAlanase- and trypsin-digested ancient bone samples, as well as to increase sequence coverage of noncollagenous proteins. Moreover, digestion with ProAlanase improves protein sequence coverage and phosphosite localization for the proline-rich protein Notch3 intracellular domain (N3ICD). Furthermore, we achieve a nearly complete coverage of N3ICD protein by de novo sequencing using the combination of ProAlanase and tryptic peptides. Finally, we demonstrate that ProAlanase is efficient in disulfide bond mapping, showing high coverage of disulfide-containing regions in a nonreduced mAb. Full Article
ps Global Proteome and Phosphoproteome Characterization of Sepsis-induced Kidney Injury [Research] By www.mcponline.org Published On :: 2020-12-01T00:05:33-08:00 Sepsis-induced acute kidney injury (S-AKI) is the most common complication in hospitalized and critically ill patients, highlighted by a rapid decline of kidney function occurring a few hours or days after sepsis onset. Systemic inflammation elicited by microbial infections is believed to lead to kidney damage under immunocompromised conditions. However, although AKI has been recognized as a disease with long-term sequelae, partly because of the associated higher risk of chronic kidney disease (CKD), the understanding of kidney pathophysiology at the molecular level and the global view of dynamic regulations in situ after S-AKI, including the transition to CKD, remains limited. Existing studies of S-AKI mainly focus on deriving sepsis biomarkers from body fluids. In the present study, we constructed a mid-severity septic murine model using cecal ligation and puncture (CLP), and examined the temporal changes to the kidney proteome and phosphoproteome at day 2 and day 7 after CLP surgery, corresponding to S-AKI and the transition to CKD, respectively, by employing an ultrafast and economical filter-based sample processing method combined with the label-free quantitation approach. Collectively, we identified 2,119 proteins and 2950 phosphosites through multi-proteomics analyses. Among them, we identified an array of highly promising candidate marker proteins indicative of disease onset and progression accompanied by immunoblot validations, and further denoted the pathways that are specifically responsive to S-AKI and its transition to CKD, which include regulation of cell metabolism regulation, oxidative stress, and energy consumption in the diseased kidneys. Our data can serve as an enriched resource for the identification of mechanisms and biomarkers for sepsis-induced kidney diseases. Full Article
ps Unraveling the MAX2 Protein Network in Arabidopsis thaliana: Identification of the Protein Phosphatase PAPP5 as a Novel MAX2 Interactor [Research] By www.mcponline.org Published On :: 2020-12-28T07:35:13-08:00 The F-box protein MORE AXILLARY GROWTH 2 (MAX2) is a central component in the signaling cascade of strigolactones (SLs) as well as of the smoke derived karrikins (KARs) and the so far unknown endogenous KAI2 ligand (KL). The two groups of molecules are involved in overlapping and unique developmental processes, and signal-specific outcomes are attributed to perception by the paralogous α/β-hydrolases DWARF14 (D14) for SL and KARRIKIN INSENSITIVE 2/ HYPOSENSITIVE TO LIGHT (KAI2/HTL) for KAR/KL. Additionally, depending on which receptor is activated, specific members of the SUPPRESSOR OF MAX2 1 (SMAX1) – LIKE (SMXL) family control KAR/KL and SL responses. As proteins that function in the same signal transduction pathway often occur in large protein complexes, we aimed at discovering new players of the MAX2, D14 and KAI2 protein network by tandem affinity purification using Arabidopsis cell cultures. When using MAX2 as a bait, various proteins were co-purified among which general components of the Skp1-Cullin-F-box complex and members of the CONSTITUTIVE PHOTOMORPHOGENIC 9 signalosome. Here, we report the identification of a novel interactor of MAX2, a type 5 serine/threonine protein phosphatase, designated PHYTOCHROME-ASSOCIATED PROTEIN PHOSPHATASE 5 (PAPP5). Quantitative affinity purification pointed at PAPP5 as being more present in KAI2 rather than D14 protein complexes. In agreement, mutant analysis suggests that PAPP5 modulates KAR/KL-dependent seed germination in suboptimal conditions and seedling development. Additionally, a phosphopeptide enrichment experiment revealed that PAPP5 might dephosphorylate MAX2 in vivo independently of the synthetic strigolactone analog, rac-GR24. Together, by analyzing the protein complexes to which MAX2, D14 and KAI2 belong, we revealed a new MAX2 interactor, PAPP5, that might act through dephosphorylation of MAX2 to control mainly KAR/KL- related phenotypes and, hence, provide another link with the light pathway. Full Article
ps Kinetic investigation of the polymerase and exonuclease activities of human DNA polymerase ϵ holoenzyme [DNA and Chromosomes] By www.jbc.org Published On :: 2020-12-11T00:06:21-08:00 In eukaryotic DNA replication, DNA polymerase ε (Polε) is responsible for leading strand synthesis, whereas DNA polymerases α and δ synthesize the lagging strand. The human Polε (hPolε) holoenzyme is comprised of the catalytic p261 subunit and the noncatalytic p59, p17, and p12 small subunits. So far, the contribution of the noncatalytic subunits to hPolε function is not well understood. Using pre-steady-state kinetic methods, we established a minimal kinetic mechanism for DNA polymerization and editing catalyzed by the hPolε holoenzyme. Compared with the 140-kDa N-terminal catalytic fragment of p261 (p261N), which we kinetically characterized in our earlier studies, the presence of the p261 C-terminal domain (p261C) and the three small subunits increased the DNA binding affinity and the base substitution fidelity. Although the small subunits enhanced correct nucleotide incorporation efficiency, there was a wide range of rate constants when incorporating a correct nucleotide over a single-base mismatch. Surprisingly, the 3'→5' exonuclease activity of the hPolε holoenzyme was significantly slower than that of p261N when editing both matched and mismatched DNA substrates. This suggests that the presence of p261C and the three small subunits regulates the 3'→5' exonuclease activity of the hPolε holoenzyme. Together, the 3'→5' exonuclease activity and the variable mismatch extension activity modulate the overall fidelity of the hPolε holoenzyme by up to 3 orders of magnitude. Thus, the presence of p261C and the three noncatalytic subunits optimizes the dual enzymatic activities of the catalytic p261 subunit and makes the hPolε holoenzyme an efficient and faithful replicative DNA polymerase. Full Article
ps Diabetes: One in 10 patients on NHS’s “soups and shakes” diet plan went into remission By www.bmj.com Published On :: Tuesday, August 6, 2024 - 07:56 Full Article
ps Rammya Mathew: GPs have to be able to request MRI scans for patients in primary care By www.bmj.com Published On :: 2024-11-12T09:11:25-08:00 At a recent clinical meeting, I heard that GPs local to me are about to lose the ability to request magnetic resonance imaging (MRI) scans for patients presenting with musculoskeletal symptoms. We’re instead advised to refer our patients to a musculoskeletal clinical assessment and triage service (CATS)—staffed largely by musculoskeletal advanced practitioners, who will assess our patients and determine whether imaging is warranted.The hope is that fewer patients will have unnecessary imaging and that this will reduce the potential harms of overdiagnosis. Radiologists rarely report musculoskeletal MRI scans as entirely normal, and it can be hard to know what to do with abnormal findings on an MRI. More often than not, patients with abnormal scans are referred to orthopaedic teams, even though there may not necessarily be a surgical target.At a population level, this is problematic on two fronts. Firstly, MRI scans are expensive and need to be used judiciously.... Full Article
ps [68Ga]Ga-PSMA-11 PET/CT-Positive Hepatic Inflammatory Pseudotumor: Possible PSMA-Avid Pitfall in Nuclear Imaging By jnm.snmjournals.org Published On :: 2024-10-01T04:08:08-07:00 Full Article
ps Composite Prediction Score to Interpret Bone Focal Uptake in Hormone-Sensitive Prostate Cancer Patients Imaged with [18F]PSMA-1007 PET/CT By jnm.snmjournals.org Published On :: 2024-10-01T04:08:08-07:00 Unspecific bone uptake (UBU) related to [18F]PSMA-1007 PET/CT imaging represents a clinical challenge. We aimed to assess whether a combination of clinical, biochemical, and imaging parameters could predict skeletal metastases in patients with [18F]PSMA-1007 bone focal uptake, aiding in result interpretation. Methods: We retrospectively analyzed [18F]PSMA-1007 PET/CT performed in hormone-sensitive prostate cancer (PCa) patients at 3 tertiary-level cancer centers. A fourth center was involved in performing an external validation. For each, a volume of interest was drawn using a threshold method to extract SUVmax, SUVmean, PSMA tumor volume, and total lesion PSMA. The same volume of interest was applied to CT images to calculate the mean Hounsfield units (HUmean) and maximum Hounsfield units. Clinical and laboratory data were collected from electronic medical records. A composite reference standard, including follow-up histopathology, biochemistry, and imaging data, was used to distinguish between PCa bone metastases and UBU. PET readers with less (n = 2) or more (n = 2) experience, masked to the reference standard, were asked to visually rate a subset of focal bone uptake (n = 178) as PCa metastases or not. Results: In total, 448 bone [18F]PSMA-1007 focal uptake specimens were identified in 267 PCa patients. Of the 448 uptake samples, 188 (41.9%) corresponded to PCa metastases. Ongoing androgen deprivation therapy at PET/CT (P < 0.001) with determination of SUVmax (P < 0.001) and HUmean (P < 0.001) independently predicted bone metastases. A composite prediction score, the bone uptake metastatic probability (BUMP) score, achieving an area under the receiver-operating-characteristic curve (AUC) of 0.87, was validated through a 10-fold internal and external validation (n = 89 bone uptake, 51% metastatic; AUC, 0.92). The BUMP score’s AUC was significantly higher than that of HUmean (AUC, 0.62) and remained high among lesions with HUmean in the first tertile (AUC, 0.80). A decision-curve analysis showed a higher net benefit with the score. Compared with the visual assessment, the BUMP score provided added value in terms of specificity in less-experienced PET readers (88% vs. 54%, P < 0.001). Conclusion: The BUMP score accurately distinguished UBU from bone metastases in PCa patients with [18F]PSMA-1007 focal bone uptake at PET imaging, offering additional value compared with the simple assessment of the osteoblastic CT correlate. Its use could help clinicians interpret imaging results, particularly those with less experience, potentially reducing the risk of patient overstaging. Full Article
ps Clinical Factors That Influence Repeat 68Ga-PSMA-11 PET/CT Scan Positivity in Patients with Recurrent Prostate Cancer Under Observation After a Negative 68Ga-PSMA-11 PET/CT Scan: A Single-Center Retrospective Study By jnm.snmjournals.org Published On :: 2024-10-01T04:08:08-07:00 This analysis aimed to identify clinical factors associated with positivity on repeat 68Ga-PSMA-11 PET/CT after a negative scan in patients with recurrent prostate cancer (PCa) under observation. Methods: This single-center, retrospective analysis included patients who underwent at least 2 68Ga-PSMA-11 PET/CT scans (PET1 and PET2) at UCLA between October 2016 and June 2021 for recurrent PCa with negative PET1 and no PCa-related treatments between the 2 scans. Using Prostate Cancer Molecular Imaging Standardized Evaluation criteria to define negative and positive scans, the final cohort was divided into PET2-negative (PET2-Neg) and PET2-positive (PET2-Pos). The same PET1 was used twice in the more than 2 PET cases with inclusion criteria fulfilled. Patient characteristics and clinical parameters were compared between the 2 cohorts using Mann–Whitney U test and Fisher exact test. Areas under the curve (AUCs) of the receiver operating characteristic and the Youden index were computed to determine the discrimination ability of statistically significant factors and specific cut points that maximized sensitivity and specificity, respectively. Results: The final analysis included 83 sets of 2 PET/CT scans from 70 patients. Thirty-nine of 83 (47%) sets were PET2-Neg, and 44 of 83 (53%) sets were PET2-Pos. Prostate-specific antigen (PSA) increased from PET1 to PET2 for all 83 (100%) sets of scans. Median PSA at PET1 was 0.4 ng/mL (interquartile range, 0.2–1.0) and at PET2 was 1.6 ng/mL (interquartile range, 0.9–3.8). We found higher serum PSA at PET2 (median, 1.8 vs. 1.1 ng/mL; P = 0.015), absolute PSA difference (median, 1.4 vs. 0.7 ng/mL; P = 0.006), percentage of PSA change (median, +270.4% vs. +150.0%: P = 0.031), and median PSA velocity (0.044 vs. 0.017 ng/mL/wk, P = 0.002) and shorter PSA doubling time (DT; median, 5.1 vs. 8.3 mo; P = 0.006) in the PET2-Pos cohort than in the PET2-Neg cohort. Receiver operating characteristic curves showed cutoffs for PSA at PET2 of 4.80 ng/mL (sensitivity, 34%; specificity, 92%; AUC, 0.66), absolute PSA difference of 0.95 ng/mL (sensitivity, 62%; specificity, 71%; AUC, 0.68), percentage of PSA change of a positive 289.50% (sensitivity, 48%; specificity, 82%; AUC, 0.64), PSA velocity of 0.033 ng/mL/wk (sensitivity, 57%; specificity, 80%; AUC, 0.70), and PSA DT of 7.91 mo (sensitivity, 71%; specificity, 62%; AUC, 0.67). Conclusion: Patients with recurrent PCa under observation after a negative 68Ga-PSMA-11 PET/CT scan with markedly elevated serum PSA levels and shorter PSA DT are more likely to have positive findings on repeat 68Ga-PSMA-11 PET/CT. Full Article
ps Defense helps Miami Dolphins beat Los Angeles Rams, snap three-game skid By www.upi.com Published On :: Tue, 12 Nov 2024 07:52:55 -0500 Linebacker Quinton Bell and Miami Dolphins defenders deleted drives and put the Los Angeles Rams offense in quicksand, holding them without a touchdown to propel a primetime victory and snap a three-game losing streak. Full Article
ps Fantasy football: Justin Herbert among top add/drops for Week 11 By www.upi.com Published On :: Tue, 12 Nov 2024 14:26:44 -0500 Justin Herbert, Russell Wilson and Quentin Johnston lead UPI senior sports writer Alex Butler's fantasy football waiver wire priority list for Week 11 of the 2024 NFL season. Full Article
ps PSC: Anton Simulations Reveal How Alzheimer’s Fibril Growth May Accelerate By www.hpcwire.com Published On :: Fri, 25 Oct 2024 12:29:54 +0000 Oct. 25, 2024 — Aggregation of proteins underlies many human disorders, including Alzheimer’s. Teams from the New Jersey Institute of Technology and Princeton University joined forces to study how the amyloid […] The post PSC: Anton Simulations Reveal How Alzheimer’s Fibril Growth May Accelerate appeared first on HPCwire. Full Article
ps OSI Open AI Definition Stops Short of Requiring Open Data for LLMs By www.hpcwire.com Published On :: Wed, 06 Nov 2024 21:00:10 +0000 The movement toward open source AI made progress today when the Open Source Initiative released the first Open Source AI Definition (OSAID). While the OSAID provides one step forward, the […] The post OSI Open AI Definition Stops Short of Requiring Open Data for LLMs appeared first on HPCwire. Full Article Features Apache 2 ChatGPT Llama3 LLMs open data open models Open Source AI Definition OSAID OSI
ps IBM Develops New Quantum Benchmarking Tool — Benchpress By www.hpcwire.com Published On :: Thu, 26 Sep 2024 18:14:56 +0000 Benchmarking is an important topic in quantum computing. There’s consensus it’s needed but opinions vary widely on how to go about it. Last week, IBM introduced a new tool — […] The post IBM Develops New Quantum Benchmarking Tool — Benchpress appeared first on HPCwire. Full Article Short Takes
ps MinIO Optimizes Arm-Based Chipsets for High-Performance AI By www.hpcwire.com Published On :: Mon, 04 Nov 2024 21:01:04 +0000 REDWOOD CITY, Calif., Nov. 4, 2024 — MinIO has announced compelling new optimizations and benchmarks for Arm-based chipsets powering on its object store. These optimizations underscore the relevance of low-power, […] The post MinIO Optimizes Arm-Based Chipsets for High-Performance AI appeared first on HPCwire. Full Article
ps Slipping on Your New Year's Resolutions? Science Tips to Get on Track By www.scientificamerican.com Published On :: Mon, 22 Jan 2024 16:30:00 GMT Studies of goal setting reveal why it’s so hard to keep resolutions—and how to make ones that actually stick Full Article Health Fitness Mind & Brain Behavior
ps Valentine's Day Got You Blue? There's an Upside By www.scientificamerican.com Published On :: Wed, 14 Feb 2024 12:15:00 GMT Unpleasant emotions like sadness and anger can feel overwhelming, but recent research suggests they can trigger behaviors that lead to something better Full Article Mind & Brain Cognition Neuroscience
ps ORNL Develops Solution to Residual Stress Challenges in 3D-Printed Metal Structures By www.hpcwire.com Published On :: Tue, 26 Mar 2024 21:42:30 +0000 March 26, 2024 — Scientists at the Department of Energy’s Oak Ridge National Laboratory have determined how to avoid costly and potentially irreparable damage to large metallic parts fabricated through […] The post ORNL Develops Solution to Residual Stress Challenges in 3D-Printed Metal Structures appeared first on HPCwire. Full Article
ps BSC Develops AI Model to Predict Stroke Risk Using Mobile Devices By www.hpcwire.com Published On :: Fri, 08 Nov 2024 14:26:21 +0000 Nov. 8, 2024 — Barcelona Supercomputing Center‘s Innostroke project aims to transform the prevention and monitoring of stroke, one of the leading causes of death and disability worldwide, through artificial […] The post BSC Develops AI Model to Predict Stroke Risk Using Mobile Devices appeared first on HPCwire. Full Article
ps Trump taps John Ratcliffe, ex-national intelligence chief, for CIA director By www.upi.com Published On :: Tue, 12 Nov 2024 19:27:29 -0500 President-elect Donald Trump announced his choice Tuesday for CIA Director, tapping his former intelligence chief John Ratcliffe, who he called a "warrior of truth." Full Article
ps President-elect Trump taps S.D. Gov. Kristi Noem to lead Department of Homeland Security By www.upi.com Published On :: Tue, 12 Nov 2024 22:14:57 -0500 President-elect Donald Trump on Monday announced plans to nominate South Dakota Gov. Kristi Noem to head the Department of Homeland Security of his incoming administration. Full Article
ps 3 Powerful Steps To Finally Accept Yourself (P) By www.spring.org.uk Published On :: Sun, 27 Oct 2024 18:00:00 +0000 Struggling to be kind to yourself? Learn how to direct compassion inwards with these simple techniques. Full Article Acceptance premium-only
ps Persuasion: 10 Techniques Psychologists Recommend To Influence Anyone (P) By www.spring.org.uk Published On :: Sun, 10 Nov 2024 18:00:00 +0000 Many people overthink persuasion, when it is the most natural approaches that work best. Full Article Persuasion premium-only
ps 6 Tips to Make Your Mark in the Field of Psychology By www.whatispsychology.biz Published On :: Mon, 06 May 2024 11:50:03 +0000 Psychology is a vast and dynamic field that offers numerous opportunities for individuals to make a significant impact. Whether through clinical practice, research, or teaching, the possibilities are endless for those eager to contribute to the understanding of human behavior and mental processes. To truly make your mark in psychology, it’s essential to focus on […] The post 6 Tips to Make Your Mark in the Field of Psychology first appeared on What is Psychology?. Full Article Educational Psychology Psychology News Universities And Online Psychology Lectures newsnow online psychology degree psychology classes online psychology course online psychology online programs
ps Efficiency Hacks for Graduate Students in Psychology By www.whatispsychology.biz Published On :: Thu, 30 May 2024 11:55:10 +0000 Graduate school in psychology can be a demanding journey. The constant stream of research, coursework, and clinical practice requires effective strategies to stay organized and productive. Here are some practical tips to help you navigate your graduate studies more efficiently. Organize Your Study Space Creating a dedicated, clutter-free study space is crucial. Your environment can […] The post Efficiency Hacks for Graduate Students in Psychology first appeared on What is Psychology?. Full Article Cognitive Psychology Definitions Educational Psychology Psychology News Universities And Online Psychology Lectures best study tips do better in school get better grades improve academic grades newsnow