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The real reason VAR infuriates football fans and how to fix it

The controversies surrounding football’s video assistant referee (VAR) system highlight our troubled relationship with uncertainty – and point to potential solutions




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Early humans spread as far north as Siberia 400,000 years ago

A site in Siberia has evidence of human presence 417,000 years ago, raising the possibility that hominins could have reached North America much earlier than we thought




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valerian

Title: valerian
Category: Medications
Created: 7/19/2022 12:00:00 AM
Last Editorial Review: 7/19/2022 12:00:00 AM




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After Fits and Starts, New Hope for Psoriasis Patients

Title: After Fits and Starts, New Hope for Psoriasis Patients
Category: Health News
Created: 8/26/2008 2:00:00 AM
Last Editorial Review: 8/26/2008 12:00:00 AM




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Inner Workings of Gene Tied to Breast, Ovarian Cancer Revealed

Title: Inner Workings of Gene Tied to Breast, Ovarian Cancer Revealed
Category: Health News
Created: 8/22/2010 2:10:00 PM
Last Editorial Review: 8/23/2010 12:00:00 AM




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In Early Trial, Targeted Therapy Fights Advanced Melanoma

Title: In Early Trial, Targeted Therapy Fights Advanced Melanoma
Category: Health News
Created: 8/25/2010 6:10:00 PM
Last Editorial Review: 8/26/2010 12:00:00 AM




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Antibiotic Overuse May Be Bad for Body's Good Bacteria

Title: Antibiotic Overuse May Be Bad for Body's Good Bacteria
Category: Health News
Created: 8/25/2011 11:01:00 AM
Last Editorial Review: 8/25/2011 12:00:00 AM




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Alzheimer's Drug Shows Some Promise in Trials

Title: Alzheimer's Drug Shows Some Promise in Trials
Category: Health News
Created: 8/24/2012 2:05:00 PM
Last Editorial Review: 8/27/2012 12:00:00 AM




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Psoriasis Linked to Diabetes

Title: Psoriasis Linked to Diabetes
Category: Health News
Created: 8/30/2012 11:00:00 AM
Last Editorial Review: 8/30/2012 12:00:00 AM




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Could Bacteria in Skin Mites Help Cause Rosacea?

Title: Could Bacteria in Skin Mites Help Cause Rosacea?
Category: Health News
Created: 8/30/2012 10:05:00 AM
Last Editorial Review: 8/30/2012 12:00:00 AM




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New Hope for Early Detection of Ovarian Cancer

Title: New Hope for Early Detection of Ovarian Cancer
Category: Health News
Created: 8/26/2013 9:35:00 AM
Last Editorial Review: 8/26/2013 12:00:00 AM




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Skin Care Tips for Psoriasis Patients

Title: Skin Care Tips for Psoriasis Patients
Category: Health News
Created: 8/23/2013 5:35:00 PM
Last Editorial Review: 8/26/2013 12:00:00 AM




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Your Gut Bacteria May Predict Your Obesity Risk

Title: Your Gut Bacteria May Predict Your Obesity Risk
Category: Health News
Created: 8/28/2013 2:35:00 PM
Last Editorial Review: 8/29/2013 12:00:00 AM




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Blood Pressure Drugs Linked to Longer Ovarian Cancer Survival

Title: Blood Pressure Drugs Linked to Longer Ovarian Cancer Survival
Category: Health News
Created: 8/24/2015 12:00:00 AM
Last Editorial Review: 8/25/2015 12:00:00 AM




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Marriage a Blessing for Heart Attack Patients

Title: Marriage a Blessing for Heart Attack Patients
Category: Health News
Created: 8/29/2017 12:00:00 AM
Last Editorial Review: 8/30/2017 12:00:00 AM




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FDA OKs New Antibacterial Drug

Title: FDA OKs New Antibacterial Drug
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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Monkey Trials Raise Hope for Non-Addictive Opioid Alternative

Title: Monkey Trials Raise Hope for Non-Addictive Opioid Alternative
Category: Health News
Created: 8/30/2018 12:00:00 AM
Last Editorial Review: 8/31/2018 12:00:00 AM




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Climate Change Hiking Danger of Flesh-Eating Bacteria Infections

Title: Climate Change Hiking Danger of Flesh-Eating Bacteria Infections
Category: Health News
Created: 8/23/2019 12:00:00 AM
Last Editorial Review: 8/26/2019 12:00:00 AM




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Malaria Eradication Not Currently Possible: WHO

Title: Malaria Eradication Not Currently Possible: WHO
Category: Health News
Created: 8/23/2019 12:00:00 AM
Last Editorial Review: 8/26/2019 12:00:00 AM




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Men Should be Included in Breast Cancer Clinical Trials: FDA

Title: Men Should be Included in Breast Cancer Clinical Trials: FDA
Category: Health News
Created: 8/26/2019 12:00:00 AM
Last Editorial Review: 8/27/2019 12:00:00 AM




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Even a Little Drinking While Pregnant Ups Miscarriage Odds: Study

Title: Even a Little Drinking While Pregnant Ups Miscarriage Odds: Study
Category: Health News
Created: 8/27/2019 12:00:00 AM
Last Editorial Review: 8/28/2019 12:00:00 AM




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Health Tip: Living With Psoriasis

Title: Health Tip: Living With Psoriasis
Category: Health News
Created: 8/29/2019 12:00:00 AM
Last Editorial Review: 8/29/2019 12:00:00 AM




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Nourianz Approved to Treat 'Off' Episodes in Parkinson Disease

Title: Nourianz Approved to Treat 'Off' Episodes in Parkinson Disease
Category: Health News
Created: 8/28/2019 12:00:00 AM
Last Editorial Review: 8/29/2019 12:00:00 AM




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Some Vegetarian Diets Are Much Healthier Than Others

Title: Some Vegetarian Diets Are Much Healthier Than Others
Category: Health News
Created: 8/27/2020 12:00:00 AM
Last Editorial Review: 8/27/2020 12:00:00 AM




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Delta Variant Has Americans' Stress Levels Rising Again: Poll

Title: Delta Variant Has Americans' Stress Levels Rising Again: Poll
Category: Health News
Created: 8/20/2021 12:00:00 AM
Last Editorial Review: 8/23/2021 12:00:00 AM




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'Dream Vaccine' for All COVID Variants

Title: 'Dream Vaccine' for All COVID Variants
Category: Health News
Created: 8/23/2021 12:00:00 AM
Last Editorial Review: 8/24/2021 12:00:00 AM




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COVID Incubation Shorter With Each New Variant

Title: COVID Incubation Shorter With Each New Variant
Category: Health News
Created: 8/23/2022 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM




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COVID Boosters Targeted to Latest Variants Could Be Ready After Labor Day

Title: COVID Boosters Targeted to Latest Variants Could Be Ready After Labor Day
Category: Health News
Created: 8/24/2022 12:00:00 AM
Last Editorial Review: 8/24/2022 12:00:00 AM




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Cheap, Same-Day Test Could Help Spot Miscarriage Risk

Title: Cheap, Same-Day Test Could Help Spot Miscarriage Risk
Category: Health News
Created: 8/18/2022 12:00:00 AM
Last Editorial Review: 8/19/2022 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




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How Do I Know if I Have an Ovarian Cyst or Tumor?

Title: How Do I Know if I Have an Ovarian Cyst or Tumor?
Category: Diseases and Conditions
Created: 7/7/2022 12:00:00 AM
Last Editorial Review: 7/7/2022 12:00:00 AM




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Vegetarian Women at Higher Odds for Hip Fracture

Title: Vegetarian Women at Higher Odds for Hip Fracture
Category: Health News
Created: 8/11/2022 12:00:00 AM
Last Editorial Review: 8/12/2022 12:00:00 AM




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New Multiple Sclerosis Treatment Shows Promise in Trial

Title: New Multiple Sclerosis Treatment Shows Promise in Trial
Category: Health News
Created: 8/25/2022 12:00:00 AM
Last Editorial Review: 8/26/2022 12:00:00 AM




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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




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Mutational scanning of CRX classifies clinical variants and reveals biochemical properties of the transcriptional effector domain [RESEARCH]

The transcription factor (TF) cone-rod homeobox (CRX) is essential for the differentiation and maintenance of photoreceptor cell identity. Several human CRX variants cause degenerative retinopathies, but most are variants of uncertain significance. We performed a deep mutational scan (DMS) of nearly all possible single amino acid substitutions in CRX using a cell-based transcriptional reporter assay, curating a high-confidence list of nearly 2000 variants with altered transcriptional activity. In the structured homeodomain, activity scores closely aligned to a predicted structure and demonstrated position-specific constraints on amino acid substitution. In contrast, the intrinsically disordered transcriptional effector domain displayed a qualitatively different pattern of substitution effects, following compositional constraints without specific residue position requirements in the peptide chain. These compositional constraints were consistent with the acidic exposure model of transcriptional activation. We evaluated the performance of the DMS assay as a clinical variant classification tool using gold-standard classified human variants from ClinVar, identifying pathogenic variants with high specificity and moderate sensitivity. That this performance could be achieved using a synthetic reporter assay in a foreign cell type, even for a highly cell type-specific TF like CRX, suggests that this approach shows promise for DMS of other TFs that function in cell types that are not easily accessible. Together, the results of the CRX DMS identify molecular features of the CRX effector domain and demonstrate utility for integration into the clinical variant classification pipeline.




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Exploring the Impact of Varied Design Approaches and Materials in Respiratory Therapy Education




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Impact of Dimensional Variability of Primary Packaging Materials on the Break-Loose and Gliding Forces of Prefilled Syringes

A prefilled syringe (PFS) should be able to be adequately and consistently extruded during injection for optimal safe drug delivery and accurate dosing. To facilitate appropriate break-loose and gliding forces (BLGFs) required during injection, certain primary packaging materials (PPMs) such as the syringe barrel and plunger are usually coated with silicone oil, which acts as a lubricant. Due to its direct contact with drug, silicone oil can increase the number of particles in the syringe, which could lead to adverse interactions. Compliance with regulatory-defined silicone oil quantities in certain drug products, such as ophthalmics, presents a trade-off with the necessity for desirable low and consistent BLGF. In addition to its siliconization, the dimensional accuracy of the PPM has an important role in controlling the BLGF. The dimensions of the PPM are individualized depending on the product and its design and have certain tolerances that must be met during manufacturing. Most studies on ophthalmics focused on the adverse interactions between silicone oil and the drug. To the authors' knowledge, there have been no public studies so far that have investigated the impact of the dimensional variability of the PPM on the BLGF in ophthalmic PFSs. In this study, we applied advanced optical shaft and tactile measuring technologies to investigate this impact. The syringes investigated were first sampled during aseptic production and tested for the BLGF. Subsequently, defined dimensions of the PPM were measured individually. The results showed that the dimensional variability of the PPM can have a negative impact on the BLGF, despite their conformity to specifications, which indicates that the currently available market quality of PPMs is improvable for critical drug products such as ophthalmics. This study could serve as an approach to define product-specific requirements for primary packaging combinations and thus appropriate specifications based on data during the development stage of drug products.




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2024 September/October Editorial




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Reassessing Halm's clinical stability criteria in community-acquired pneumonia management

Background

Halm's clinical stability criteria have long guided antibiotic treatment and hospital discharge decisions for patients hospitalised with community-acquired pneumonia (CAP). Originally introduced in 1998, these criteria were established based on a relatively small and select patient population. Consequently, our study aims to reassess their applicability in the management of CAP in a contemporary real-world setting.

Methods

This cohort study included 2918 immunocompetent patients hospitalised with CAP from three hospitals in Denmark between 2017 and 2020. The primary outcome was time to achieve clinical stability as defined by Halm's criteria. Additionally, we examined recurrence of clinical instability and severe complications. Cumulative incidence function or Kaplan–Meier survival curves were used to analyse these outcomes, considering competing risks.

Results

The study population primarily comprised elderly individuals (median age 75 years) with significant comorbidities. The median time to clinical stability according to Halm's criteria was 4 days, with one-fifth experiencing recurrence of instability after early clinical response (stability within 3 days). Severe complications within 30 days mainly comprised mortality, with rates of 5.1% (64/1257) overall in those with early clinical response, 1.7% (18/1045) in the subgroup without do-not-resuscitate orders and 17.3% (276/1595) among the rest.

Conclusion

Halm's clinical stability criteria effectively classify CAP patients with different disease courses, yet achieving stability required more time in this ageing population with substantial comorbidities and more severe disease. Early clinical response indicates reduced risk of complications, especially in those without do-not-resuscitate orders.




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50th Anniversary Celebration Collection Special Section on New and Emerging Areas and Technologies in Drug Metabolism and Disposition, Part II--Editorial [Special Section on New and Emerging Areas and Technologies in Drug Metabolism and Disposition, Part




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Innovations in Providing HIV Index Testing Services: A Retrospective Evaluation of Partner Elicitation Models in Southern Nigeria

ABSTRACTBackground: This analysis aimed to evaluate the effectiveness of eliciting sexual partners from HIV-positive clients using the elicitation box model (where an HIV-positive index can report sexual contacts on paper and insert in a box for a health care provider to contact at a later time) compared to the conventional model (in which a health care provider elicits sexual contacts directly from clients) in Akwa Ibom, Southern Nigeria.Methods: Between March 2021 and April 2022, data were collected from index testing registers at 4 health facilities with a high volume of HIV clients currently on treatment in 4 local government areas in Akwa Ibom State. Primary outcome analyzed was the elicitation ratio (number of partners elicited per HIV-index offered index testing services). Secondary outcomes were the index testing acceptance (index HIV-positive clients accepted index testing service), testing coverage (partners tested for HIV from a list of partners elicited from HIV-index accepted index testing services), testing yield (index partners identified HIV positive from index partners HIV-tested), and linkage rate (index partners identified HIV positive and linked to antiretroviral therapy).Results: Of the total 2,705 index clients offered index testing services, 91.9% accepted, with 2,043 and 439 indexes opting for conventional elicitation and elicitation box models, respectively. A total of 3,796 sexual contacts were elicited: 2,546 using the conventional model (elicitation ratio=1:1) and 1,250 using the elicitation box model (elicitation ratio=1:3). Testing coverage was significantly higher in the conventional compared to the elicitation box model (P<.001). However, there was no significant difference in the testing yield (P=.81) and linkage rate using the conventional compared to elicitation box models (P=.13).Conclusion: The implementation of the elicitation box model resulted in an increase in partner elicitation compared to the conventional model. Increasing the testing coverage by implementing the elicitation box model should be considered.




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Strengthening Capacity for Tailored Immunization Programs Using Adult Learning Principles: A Case Study from Nigeria

ABSTRACTIntroduction: Nigeria has the highest number of children who have not received any vaccines in Africa. The training-of-trainers (TOT) model used to train program managers (PMs) and health care workers (HCWs) is ineffective for adult learning and limits immunization programs’ success. We incorporated adult learning principles (ALPs) in designing and delivering TOT for immunization PMs and HCWs to use data to engage communities for tailored immunization strategies.Methods: Our study was implemented in 3 local government areas (LGAs) of the Federal Capital Territory, Nigeria. A training curriculum was developed, integrating ALPs and technical and operational content based on best practices in delivering immunization training and the training needs assessment findings. State PMs (n=10), LGA PMs (n=30), and HCWs (n=42) were trained on the human-centered design for tailoring immunization programs (HCD-TIP) approaches using ALPs. We used interviews and surveys with purposively and conveniently sampled PMs and HCWs, respectively, and observations to assess participants’ satisfaction, knowledge and competence, behavior changes, and results. The interviews were analyzed thematically, and surveys were statistically.Results: There was a high level of satisfaction with the training among LGA PMs (100%), state PMs (91%), and HCWs (85%), with significant knowledge and competence improvements post-training (P<.001). The trained participants conducted 2 HCD sessions with 24 undervaccinated communities and co-designed 24 prototype solutions for testing. Results showed increased coverage of the pentavalent vaccine first dose (54%) and third dose (188%) across 12 participating communities. Improved community colaboration, communication skills, and data-driven approaches were the most cited behavior changes in practice.Conclusion: The application of ALPs in training, use of HCD-TIP approaches and tools, and supportive supervision enhanced PMs’ and HCWs’ capacity for tailored interventions. Countries should consider adopting a holistic approach that focuses on using these approaches in immunization programs to strengthen the health system for equitable vaccine coverage.




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Special Section on Cannabinoid Signaling in Human Health and Disease--Editorial [Special Section on Cannabinoid Signaling in Human Health and Disease-Editorial]




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Summary: Appropriate Use Criteria for the Use of Nuclear Medicine in Fever of Unknown Origin

The diagnostic work-up of patients with fever of unknown origin (FUO) begins with a thorough history and physical examination, complete blood count with differential, chest x-ray, urinalysis and culture, electrolyte panel, liver enzymes, erythrocyte sedimentation rate, and C-reactive protein level. Additional imaging procedures, including nuclear medicine tests, are generally used as second-line procedures, with 18F-FDG PET and PET/CT assuming increasingly important roles in the diagnostic work-up. The Society of Nuclear Medicine and Molecular Imaging, the Infectious Diseases Society of America, and the American College of Nuclear Medicine convened an autonomous expert work group to comprehensively review the published literature for nuclear imaging in adults and children with FUO and establish appropriate use criteria (AUC). This process was performed in accordance with the Protecting Access to Medicare Act of 2014, which requires that all referring physicians consult AUC by using a clinical decision support mechanism before ordering advanced diagnostic imaging services. The complete findings and discussions of the work group were published on January 8, 2023, and are available at https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=15666. The AUC in the final document are intended to assist referring health care providers in appropriate use of nuclear medicine imaging procedures in patients with FUO. The work group noted limitations in the current literature on nuclear medicine imaging for FUO, with the need for well-designed prospective multicenter investigations. Consensus findings from published data and expert opinions were used to create recommendations in common clinical scenarios for adults and children. Included in the complete document is a discussion of inflammation of unknown origin (IUO), a recently described entity. In view of the fact that the criteria for FUO and IUO are similar (except for fever > 38.3°C [100.9°F]) and that the most common etiologies of these 2 entities are similar, it is the expert opinion of the work group that the recommendations for nuclear medicine imaging of FUO are also applicable to IUO. These recommendations are included in the full guidance document. This summary reviews rationale, methodology, and main findings and refers the reader to the complete AUC document.




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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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Reimagining Biologically Adapted Somatostatin Receptor-Targeted Radionuclide Therapy: Perspectives Based on Personal Experience and Observations on Recent Trials




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Cytochrome P450 Enzymes: The Old Pandoras Box with an Ever-Growing Hope for Therapy Optimization and Drug Development--Editorial [Editorial]




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Seventy-Five Years of Interactions: The Department of Physiology and Pharmacology at Karolinska Institutet and Pharmacological Reviews [75th Anniversary Celebration Collection Special Section-Editorial]




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Summing Up Pharmacological Reviews 75th Anniversary Year and a Look to the Future [75th Anniversary Celebration Collection Special Section-Editorial]




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Arterial Spin-Labeling Perfusion Lightbulb Sign: An Imaging Biomarker of Pediatric Posterior Fossa Hemangioblastoma [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Hemangioblastoma is a rare vascular tumor that occurs within the central nervous system in children. Differentiating hemangioblastoma from other posterior fossa tumors can be challenging on imaging, and preoperative diagnosis can change the neurosurgical approach. We hypothesize that a "lightbulb sign" on the arterial spin-labeling (ASL) sequence (diffuse homogeneous intense hyperperfusion within the solid component of the tumor) will provide additional imaging finding to differentiate hemangioblastoma from other posterior fossa tumors.

MATERIALS AND METHODS:

In this retrospective comparative observational study, we only included pathology-proved cases of hemangioblastoma, while the control group consisted of other randomly selected pathology-proved posterior fossa tumors from January 2022 to January 2024. Two blinded neuroradiologists analyzed all applicable MRI sequences, including ASL sequence if available. ASL was analyzed for the lightbulb sign. Disagreements between the radiologists were resolved by a third pediatric neuroradiologist. 2 and Fisher exact test were used to analyze the data.

RESULTS:

Ninety-five patients were enrolled in the study; 57 (60%) were boys. The median age at diagnosis was 8 years old (interquartile range: 3–14). Of the enrolled patients, 8 had hemangioblastoma, and 87 had other posterior fossa tumors, including medulloblastoma (n = 31), pilocytic astrocytoma (n = 23), posterior fossa ependymoma type A (n = 16), and other tumors (n = 17). The comparison of hemangioblastoma versus nonhemangioblastoma showed that peripheral edema (P = .02) and T2-flow void (P = .02) favor hemangioblastoma, whereas reduced diffusion (low ADC) (P = .002) and ventricular system extension (P = .001) favor nonhemangioblastoma tumors. Forty-two cases also had ASL perfusion sequences. While high perfusion favors hemangioblastoma (P = .03), the lightbulb sign shows a complete distinction because all the ASL series of hemangioblastoma cases (n = 4) showed the lightbulb sign, whereas none of the nonhemangioblastoma cases (n = 38) showed the sign (P < .001).

CONCLUSIONS:

Lightbulb-like intense and homogeneous hyperperfusion patterns on ASL are helpful in diagnosing posterior fossa hemangioblastoma in children.