Citations

ABSTRACT Management of prostate cancer has improved over the past two decades, driven by innovations in detection of metastatic disease, biomarker characterization, and treatment. This review summarizes the latest progress in managing advanced states of this disease, spanning high risk biochemical recurrence, metastatic hormone sensitive prostate cancer (mHSPC), and metastatic castration resistant prostate cancer (mCRPC). Improved outcomes for patients have been seen with earlier use of androgen receptor pathway inhibitors in the setting of high risk biochemical recurrence and mHSPC. Meanwhile, individuals with mCRPC now represent a more diverse population, differentiated by both their previous treatments and other biological features. Advanced imaging and genomic biomarkers improve patient selection and permit more personalized therapy. Landmark clinical trials and meta-analyses have established and/or refined the role of chemotherapy, poly-ADP ribose polymerase (PARP) inhibitors, and 177 Lu-PSMA-617 in this disease space. Finally, as patients with prostate cancer are living longer, the review focuses on understanding and managing potential adverse events, including cardiac and hematologic toxicity and bone health.

TAF7, a core subunit of the general transcription factor TFIID, regulates transcription and additionally functions as an RNA chaperone that directs nascent nuclear RNAs to cytoplasmic polysomes, thereby influencing protein synthesis. Here, we identify a set of novel cytoplasmic interactors and a previously unappreciated cytoplasmic role for TAF7 in oncogenesis. BioID-mediated proximity labeling identified STAT3 and the CCT and WASH complexes as prominent cytoplasmic interactors of TAF7. These interactions were validated by co-immunoprecipitation and proximity ligation assays. We further showed that cytoplasmic TAF7 levels increased during oncogenesis in proportion to cancer cell pathogenicity. Notably, TAF7 engagement with STAT3, CCT and WASH complexes is markedly enhanced during cellular transformation, consistent with their functions in cancer progression. Together, these findings reveal a cytoplasmic TAF7 interactome and implicate elevated cytoplasmic TAF7 as associated with oncogenesis.

Background: The origin of arthrofibrosis of the knee is multifactorial; however, it is more commonly seen in patients with arthritis, prolonged immobility, or a history of trauma or surgery to the knee. Arthrofibrosis that results in a flexion contracture of the knee is commonly attributable to scarring and shortening of the posterior joint capsule as seen in the setting of operative intervention, such as anterior cruciate ligament reconstruction (ACLR). Indications: Arthroscopic posterior capsular releases of the knee are indicated in patients with recalcitrant arthrofibrosis who have (1) failed nonoperative management and (2) a flexion contracture of ≥10°. Technique Description: This arthroscopic technique utilizes posteromedial and posterolateral portals in addition to the standard anteromedial and anterolateral portals. A transpatellar tendon portal may also be used to create the posterolateral portal. Both a 30° and a 70° arthroscope are used to better visualize the posteromedial and posterolateral inferior and superior releases. In addition to releases of the capsule both inferiorly and posteriorly, the medial and lateral gastrocnemius tendons can be partially released from the femur to allow for a more adequate release. The 70° arthroscope is necessary to access the capsule posterior to the posterior cruciate ligament to ensure complete release. Results: This procedure is typically reserved for patients who have failed conservative management with extension splinting, physical therapy, and the use of corticosteroids. Persistent arthrofibrosis with flexion contracture can occur after ACLR, with an incidence as high as 38% in some series. The specific technique described in this video has documented patient-reported outcomes of achieving full extension in >90% of patients after an arthroscopic posterior capsular release at final follow-up. Discussion/Conclusion: Recalcitrant arthrofibrosis leading to a persisting extension deficit can be devastating for a patient, as it results in increased pain and stiffness, as well as a significant decrease in functionality. Performing a posterior capsular release in addition to the standard manipulation under anesthesia and lysis of adhesions/synovectomy will allow for greater knee range of motion, particularly greater knee extension. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Abstract Unvetted scientific claims about vaccines can spread rapidly and undermine decades of progress in immunization and public trust. A recent non-peer-reviewed analysis, promoted at political hearings, in the documentary “An Inconvenient Study,” and on social media, has been used to suggest that vaccinated children experience higher rates of chronic illness than unvaccinated peers. Despite standard regression models, critical flaws - uncontrolled confounding, exposure misclassification, unequal follow-up, and outcome multiplicity, invalidate causal inference. An independent group of international experts critically appraises this analysis and contrast its claims with the consistent evidence confirming vaccine safety and effectiveness. We also show how poorly designed studies can distort public discourse, amplify misinformation, and fuel vaccine hesitancy. We outline actions to strengthen research integrity, such as transparent data sharing, labeling of non-peer-reviewed content, and evidence-based communication. Safeguarding public health demands that vaccine evidence be methodologically sound, reviewed, and interpreted by qualified experts.

ABSTRACT Context effects are ubiquitous across sensory systems and reflect a general encoding principle for both simple and complex stimuli. One simple context effect, contraction bias, manifests in two-interval perception tasks as a bias of the perceived magnitude of the first stimulus toward the center of the overall magnitude range. The underlying cause of contraction bias is unclear. One explanation is that a listener’s magnitude estimate of the first stimulus is combined with a perceptual anchor, usually the mean stimulus magnitude, biasing it toward the anchor (sensory model). An alternative explanation is that a listener’s response criterion shifts, based on the magnitude of the stimulus pair, relative to the mean magnitude of the stimuli range (decision model). Two pitch-discrimination experiments were performed to test these hypotheses in the auditory domain. The first was a forced-choice discrimination task, where listeners were asked to identify the higher or lower tone in a pair. The second was a same-different task where listeners indicated whether or not the two tones in a pair differed in frequency. Contraction bias was observed in the higher-lower discrimination task, even after extensive perceptual training with feedback. In contrast, no contraction bias was observed in the same-different task. Computational models of the sensory and decision hypotheses were fit to data from both experiments. The sensory model captured the pattern of results the higher-lower experiment but erroneously predicted a contraction bias in the same-different task. The decision model produced similar predictions to the sensory model in the higher-lower task but correctly predicted no contraction bias in the same-different task, and produced lower prediction errors and more stable parameter estimates in both paradigms. Overall, the results suggest that the underlying nature of the contraction bias may reflect decision, rather than sensory, biases based on the context. AUTHOR SUMMARY Every day, people combine experiential knowledge of the world and incoming sensory information to assess their environment. Interestingly, the environment itself can substantially alter how incoming sensory information is processed and perceived. These so-called context effects occur in all sensory modalities. Here, we examine one such context effect, known as “contraction bias”, in a simple pitch-discrimination task. Prior work argued that the contraction bias occurs because observers make biased estimates of stimulus magnitudes due to the influence of recent stimulus history. By combining behavioral data and computational modeling, we offer a different explanation, more consistent with the available data, which posits that the bias can be accounted for by systematic shifts in observers’ response strategies with changes in relative stimulus magnitudes. The results shed light onto how humans compare and process sensory features within their environment.

BACKGROUND: Aortic enlargement is a powerful predictor of dissection and rupture, yet it is rarely evaluated during routine myocardial perfusion imaging, despite the widespread availability of computed tomography (CT) attenuation correction scans. The aim of this study was to determine whether fully automated, opportunistically derived, artificial intelligence-based aortic measurements from myocardial perfusion imaging CT attenuation correction scans are associated with adverse outcomes in a large multicenter cohort. METHODS: CT attenuation correction scans from patients undergoing positron emission tomography/CT and single-photon emission CT/CT myocardial perfusion imaging across 10 centers were included. A deep learning model automatically segmented the thoracic aorta, and a postprocessing algorithm extracted maximum ascending and descending diameters. The aortic size index was calculated by indexing the diameter to body surface area. RESULTS: A total of 29 339 patients (56% men; median age, 66 years [interquartile range, 58–75 years]) were included. Over a median follow-up of 3.5 years (interquartile range, 1.9–5.0 years), 5083 (17.3%) patients died. Median ascending and descending aortic size index values were 1.8 cm/m 2 (interquartile range, 1.6–2.0) and 1.5 cm/m 2 (interquartile range, 1.4–1.6), respectively, with an increase with age and higher values in females. Elevated aortic size index thresholds (ascending >2.2 cm/m 2 ; descending >1.6 cm/m 2 ) were significantly associated with increased all-cause mortality (ascending: adjusted hazard ratio, 1.16 [95% CI, 1.07–1.26], P <0.001; descending: adjusted hazard ratio, 1.23 [95% CI, 1.14–1.31]; P <0.001). Notably, the prognostic value of an abnormal aortic size index persisted independent of age, sex, and perfusion abnormalities. CONCLUSIONS: Artificial intelligence can unlock previously unused information within routine myocardial perfusion imaging CT attenuation correction scans by rapidly and automatically quantifying aortic size at scale. Opportunistic aortic measurements derived from CT attenuation correction may serve as an adjunctive risk biomarker and could add prognostic value to standard myocardial perfusion imaging without additional imaging or radiation.

BACKGROUND: Acoramidis achieves near-complete (≥90%) transthyretin stabilization and is approved to reduce cardiovascular-related mortality and hospitalization in transthyretin amyloid cardiomyopathy. Its effects on kidney function are not well characterized. METHODS: Data from randomized phase 2 (N=49) and phase 3 (N=632) studies in transthyretin amyloid cardiomyopathy were included. The estimated glomerular filtration rate (eGFR) slope was generated using a linear spline mixed-effects model. The urinary albumin-to-creatinine ratio was measured longitudinally. Relationships between changes in kidney function and clinical outcomes were explored using Cox proportional hazards models. RESULTS: Acoramidis initiation resulted in a modest acute dip in eGFR that was dose-dependent, reversible, and not associated with adverse kidney-related events. At Day 28, the mean (±SE) dip in eGFR from baseline with acoramidis was 8.5±0.48 mL/min per 1.73 m 2 ; the placebo-corrected reduction in the urinary albumin-to-creatinine ratio was 15.5% (95% CI, 0.4%–28.4%; P =0.044). The rate of decline in kidney function (chronic eGFR slope) was significantly improved with acoramidis versus placebo (−1.01 versus −3.48 mL/min per 1.73 m 2 per year; P <0.001), and the reduction in the urinary albumin-to-creatinine ratio was sustained (13.7% [95% CI, 1.7%–24.2%]; P =0.026) over time. Concomitant tafamidis use did not influence the chronic eGFR slope in either arm. Comparing acoramidis versus placebo subgroups with acute eGFR dips ≥ the median (4.89 mL/min per 1.73 m 2 ) favored acoramidis for all-cause mortality or cardiovascular-related hospitalization (hazard ratio, 0.42 [95% CI, 0.22–0.78]; P =0.006; P interaction=0.043) and cardiovascular-related hospitalization (hazard ratio, 0.34 [95% CI, 0.17–0.66]; P =0.002, P interaction=0.025). Within the placebo arm, eGFR dips portended worse outcomes. CONCLUSIONS: Acoramidis initiation resulted in an acute dip in eGFR and reductions in both the chronic eGFR slope and urinary albumin-to-creatinine ratio versus placebo without adverse kidney-related events. Acoramidis effects on kidney function may be mediated through direct kidney-protective hemodynamic effects. Importantly, the acute dip in eGFR was associated with a reduced risk of adverse clinical outcomes within the first year. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT03458130, NCT03536767, NCT03860935, NCT04988386.

Autonomous robotic-assisted surgery (RAS) has emerged as a promising objective in biomedical technology, further enhanced by miniaturization toward microrobotic-assisted surgery (μ-RAS). This reduction in scale promises minimally invasive, partially or fully automated surgical procedures, with the potential to reduce patient recovery times, lower medical costs, and enable previously unavailable procedural options. This perspective highlights the specific advances in RAS that potentially map to the microscale (μ-RAS), organized across five surgical domains: endovascular, endoluminal, laparoscopic, ophthalmic, and orthopedic. We examine both clinical demands and technological advances in surgical robotics and identify the key innovations required for progress across these surgical fields. Our contribution is distinct in combining the perspectives of both surgical experts and bioengineering innovators, outlining a roadmap for the advancement and eventual integration of autonomous RAS and μ-RAS into mainstream surgical practice.