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The strong gravitational field near massive blackhole is an interesting regime to test General Relativity (GR) and modified gravity theories. The knowledge of spacetime metric around a blackhole is a primary step for such tests. Solving field equations for rotating blackhole is extremely challenging task for the most modified gravity theories. Though the derivation of Kerr metric of GR is also demanding job, the magical Newmann–Janis algorithm does it without actually solving Einstein equation for rotating blackhole. Due to this notable success of Newmann–Janis algorithm in the case of Kerr metric, it has been being used to obtain rotating blackhole solution in modified gravity theories. In this work, we derive the spacetime metric for the external region of a rotating blackhole in a nonlocal gravity theory using Newmann–Janis algorithm. We also derive metric for a slowly rotating blackhole by perturbatively solving field equations of the theory. We discuss the applicability of Newmann–Janis algorithm to nonlocal gravity by comparing slow rotation limit of the metric obtained through Newmann–Janis algorithm with slowly rotating solution of the field equation.

A bstract Light bending by the strong gravity around the black hole will form the so-called black hole shadow, the shape of which can shed light on the structure of the near-horizon geometry to possibly reveal novel physics of strong gravity and black hole. In this work, we adopt both analytical and ray-tracing methods to study the black hole shadow in the presence of the infrared structure of gravity theory, which manifests the asymptotic symmetries of spacetime as the supertranslation soft hairs of the black hole. Though the black hole metrics with and without the soft hair are related by large gauge transformations, the near horizon geometries relevant for the shape of the shadow are quite different. Moreover, the Hamiltonian for the geodesic seems intrinsically different, i.e., the loss of separability due to the breaking of spherical symmetry by soft hair. By applying ray-tracing computations, we find that the soft hair, although not affecting the shape of the shadow, may change the average size and position of the shadow. Images resulting from soft hair black holes with surrounding accretion flows are also discussed.

Chronic obstructive pulmonary disease or COPD is one of the conditions that physicians frequently see in both the hospital and outpatient setting. In order to improve diagnostic and treatment outcomes, the Global Strategy for the Diagnosis, Management and Prevention of COPD, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) was created in 2001. Every year, a new report is generated based on an analysis of published studies which attempts to improve the way physicians handle COPD. GOLD reports are considered to be essential evidence-based reference tools for the implementation of effective management plans, and represent the current best practices for the care of patients with COPD. The 2017 report greatly revised the guidelines and added a few components that changed the system of COPD diagnosis and treatment. This review article addresses those changes, explains the current guidelines, and draws attention to areas that still require improvement.

Targeted protein degradation (TPD) by PROTAC (proteolysis-targeting chimera) and molecular glue small molecules is an emerging therapeutic strategy. To expand the roster of E3 ligases that can be utilized for TPD, we describe the discovery and biochemical characterization of small-molecule ligands targeting the E3 ligase KLHDC2. Furthermore, we functionalize these KLHDC2-targeting ligands into KLHDC2-based BET-family and AR PROTAC degraders and demonstrate KLHDC2-dependent target-protein degradation. Additionally, we offer insight into the assembly of the KLHDC2 E3 ligase complex. Using biochemical binding studies, X-ray crystallography and cryo-EM, we show that the KLHDC2 E3 ligase assembles into a dynamic tetramer held together via its own C terminus, and that this assembly can be modulated by substrate and ligand engagement. Using structural, biochemical, and functional assays, the authors demonstrate that the E3 ligase KLHDC2, via newly developed small-molecule ligands, can be co-opted to target critical targets for degradation.

The use of a central line or central venous catheterization was brought to attention in 1929 when Dr. Werner Forssmann self-inserted a ureteric catheter through his cubital vein and into the right side of his heart. Since that time the central line technique has developed further and has become essential for the treatment of decompensating patients. Central lines are widely used for anything from rapid fluid resuscitation, to drug administration, to parenteral nutrition, and even for administering hemodialysis. Central lines come in different sizes, types, and sites of administration. Sometimes their use can be associated with complications as well. The following review article addresses these parameters of central lines and goes into detail regarding their complications.

Background: Migraine inflicts substantial personal, social, and economic tolls on many adults in the United States (US). Acute and preventive medicines can offer some relief, but most patients are untreated or experience treatment failures. How preventive-treatment failures affect outcomes for patients no longer on preventive treatments or for patients with migraine is insufficiently understood. Objective: To measure the patient-reported health and economic burdens associated with increasing preventive-treatment failures among US adults with diagnosed migraine. Design: Retrospective, cross-sectional study. Methods: Data analyzed were from the 2023 US National Health and Wellness Survey. Participants were adults diagnosed with migraine, having ≥4 monthly migraine or headache days, having taken acute or preventive prescription migraine medications or currently taking acute prescription migraine medications, and taking no preventive migraine medications. Participants were categorized as never treated with preventive medicines, having failed 1 preventive medicine, or having failed ≥2 preventive medicines. Health-related quality of life (HRQoL) was assessed with the Migraine Disability Assessment, RAND’s 36-Item Short Form Survey Instrument, 5-Level EuroQoL instrument (EQ-5D), Work Productivity and Activity Impairment General Health version, 9-Item Patient Health Questionnaire, and 7-Item Generalized Anxiety Disorder scale. Details about medication use and health care resource use (HCRU) were collected. Data were adjusted by inverse probability of treatment weighting and compared using two-sided two-sample t-tests or Chi-square tests. Results: Patients who had failed preventive treatments had poorer HRQoL, greater work productivity loss, greater nonwork activity impairment, and greater HCRU than patients who had never taken preventive treatments. The number of preventive-treatment failures scaled with disease burden. Patients with ≥2 treatment failures had significantly lower EQ-5D scores (0.69 vs 0.73) than those for prevention-naïve patients; patients with ≥2 treatment failures had significantly higher overall work productivity loss (45.9% vs 34.9%), activity impairment (46.8% vs 36.7%), and higher rates of emergency room visits (37.0% vs 25.2%), hospitalization (23.5% vs 12.3%), and neurologist visits (17.6 vs 10.9%) than those of prevention-naïve patients. Medication overuse rates were similar among patients with any treatment failures and prevention-naïve patients (migraine-specific: 34.4%-39.3%; overall: 59.2%-62.3%). Conclusion: US adults with frequent migraines who failed preventive treatments have significantly greater unmet needs and different acute medication use patterns than adults who never took treatments.

Honey bees (Apis mellifera) provide a principal example of diphenic development. Excess feeding of female larvae results in queens (large reproductives). Moderate diet yields workers (small helpers). The signaling pathway that links provisioning to female developmental fate is not understood, yet we reasoned that it could include TOR (target of rapamycin), a nutrient- and energy-sensing kinase that controls organismal growth. Here, the role of Apis mellifera TOR (amTOR) in caste determination is examined by rapamycin/FK506 pharmacology and RNA interference (RNAi) gene knockdown. We show that in queen-destined larvae, the TOR inhibitor rapamycin induces the development of worker characters that are blocked by the antagonist FK506. Further, queen fate is associated with elevated activity of the Apis mellifera TOR encoding gene, amTOR, and amTOR gene knockdown blocks queen fate and results in individuals with worker morphology. A much-studied insect dimorphism, thereby, can be governed by the TOR pathway. Our results present the first evidence for a role of TOR in diphenic development, and suggest that adoption of this ancestral nutrient-sensing cascade is one evolutionary pathway for morphological caste differentiation in social insects.