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Malaria remains a serious global health challenge, yet treatment and control programs are threatened by drug resistance. Dihydroorotate dehydrogenase (DHODH) was clinically validated as a target for treatment and prevention of malaria through human studies with DSM265, but currently no drugs against this target are in clinical use. We used structure-based computational tools including free energy perturbation (FEP+) to discover highly ligand efficient, potent, and selective pyrazole-based PlasmodiumDHODH inhibitors through a scaffold hop from a pyrrole-based series. Optimized pyrazole-based compounds were identified with low nM-to-pM Plasmodium falciparumcell potency and oral activity in a humanized SCID mouse malaria infection model. The lead compound DSM1465 is more potent and has improved absorption, distribution, metabolism and excretion/pharmacokinetic (ADME/PK) properties compared to DSM265 that support the potential for once-monthly chemoprevention at a low dose. This compound meets the objective of identifying compounds with potential to be used for monthly chemoprevention in Africa to support malaria elimination efforts.

Technology is growing expeditiously and the demand for new innovative software and devices is encouraging to design and develop new software to cater to the needs of next-generation interactions. Traditional online meeting platforms do not support immersive AR meetings. To stimulate immersive technology of interactive applications, a software application is designed and developed for conducting a remote meeting through AR glasses and laptop or desktop computers. The aim of this paper is to introduce utility-based immersive web portal 'remote assistance' (RA) results of conducting various performance tests on the immersive web portal to validate the RA application through a novel framework to evaluate user experience in using AR web portal. The RA application is a comprehensive online meeting platform that connects the meeting participants remotely and facilitates the hands-free streaming of critical operations, screenshot sharing, annotations, loading, and interaction of the 3D models.

Autoimmune or inflammatory rheumatic diseases (AIRDs) increase the risk for poor COVID‐19 outcomes. Although rurality is associated with higher post–COVID‐19 mortality in the general population, whether rurality elevates this risk among people with AIRD is unknown. We assessed associations between rurality and post–COVID‐19 all‐cause mortality, up to two years post infection, among people with AIRD using a large nationally sampled US cohort. This retrospective study used the National COVID Cohort Collaborative, a medical records repository containing COVID‐19 patient data. We included adults with two or more AIRD diagnostic codes and a COVID‐19 diagnosis documented between April 2020 and March 2023. Rural residency was categorized using patient residential zip codes. We adjusted for AIRD medications and glucocorticoid prescription, age, sex, race and ethnicity, tobacco or substance use, comorbid burden, and SARS‐CoV‐2 variant‐dominant periods. Multivariable Cox proportional hazards with inverse probability treatment weighting assessed associations between rurality and two‐year all‐cause mortality. Among the 86,467 SARS‐CoV‐2–infected persons with AIRD, we observed a higher risk for two‐year post–COVID‐19 mortality in rural versus urban dwellers. Rural‐residing persons with AIRD had higher two‐year all‐cause mortality risk (adjusted hazard ratio 1.24, 95% confidence interval 1.19–1.29). Glucocorticoid, immunosuppressive, and rituximab prescriptions were associated with a higher risk for two‐year post–COVID‐19 mortality, whereas risk with nonbiologic or biologic disease‐modifying antirheumatic drugs was lower. Rural residence in people with AIRD was independently associated with higher two‐year post–COVID‐19 mortality in a large US cohort after adjusting for background risk factors. Policymakers and health care providers should consider these findings when designing interventions to improve outcomes in people with AIRD following SARS‐CoV‐2 infection, especially among high‐risk rural residents.

Traumatic injury is associated with several pulmonary complications, including pulmonary contusion, transfusion-related acute lung injury (TRALI), and the development of acute respiratory distress syndrome (ARDS). There is a lack of literature on these patients supported with veno-venous extracorporeal oxygenation (VV ECMO). Understanding the safety of using VV ECMO to support trauma patients and the ability to hold anticoagulation is important to broaden utilization. This is a single-center retrospective cohort study of adult trauma patients cannulated for VV ECMO during their initial admission over an 8 year period (2014–2021). We hypothesize that anticoagulation can be held in trauma patients on VV ECMO without increasing mortality or prothrombotic complications. We also describe the coagulopathy of traumatically injured patients on VV ECMO. Withholding anticoagulation was not associated with mortality in our study population, and there were no significant differences in bleeding or clotting complications between patients who did and did not receive systemic anticoagulation. Patients in the nonsurvivor group had increased coagulopathy both pre- and post-cannulation. Our study suggests anticoagulation can be safely withheld in traumatically injured VV ECMO patients without increasing mortality, complication rates, or transfusion requirements. Future, multicenter prospective studies with larger sample sizes are required to confirm our results.

As the size of deep neural networks (DNNs) continues to grow, their runtime latency also scales. While model pruning and neural architecture search (NAS) can effectively reduce the computation workload, their effectiveness fails to consistently translate into runtime latency reduction. In this article, we identify the root cause behind the mismatch between workload reduction and latency reduction is general processing unit (GPU) tail effect—a classic system issue caused by resource underutilization in the last processing wave of the GPU. We conduct detailed DNN workload characterization and demonstrate the prevalence of GPU tail effect across different DNN architectures, and meanwhile reveal that the unique deep structure and the lightweight layer workload of DNNs exacerbate the tail effect for DNN inference. We then propose a tail-awareness design space enhancement and DNN optimization algorithm to optimize existing NAS and pruning designs and achieve better runtime latency and model accuracy performance. Extensive experiments show 11%–27% latency reduction over SOTA DNN pruning and NAS methods.

Surface electromyography (sEMG)-based automated grasp recognition (AGR) has emerged as a vital technology in the field of automatic control, human-machine interfaces, prosthetics, virtual reality (VR), etc. Grasp recognition comes under the category of hand gesture recognition (HGR). However, due to its unique characteristics, traits, and advanced applications, such as a robotic hand with 3-D-grasping capability, gaming, etc., it differs from other hand gestures in the case of force estimation and degree of freedom (DOF). This article provides a comprehensive review of available state-of-the-art methodologies for sEMG-based AGR. The review covers sensing modalities, datasets focusing on different grasps types (including power, precision, cylindrical, spherical, tripod, lateral, hook, and palmar grasps), sEMG acquisition systems, pre-processing techniques, multiresolution analysis (MRA), feature extraction process, and identification systems focusing on machine learning (ML), deep neural networks (DNNs), and model-based approaches. This review provides a detailed year-by-year chronological analysis and comparison of grasp recognition techniques with specific focus on number of subjects and types of grasps. Furthermore, some open research issues have been pointed out from the reviewed literature, and possible future prospects for these challenges have also been presented. Finally, several industry domains that can incorporate sEMG-based AGR systems in future are also discussed.

Study Design Review article.Objectives A review of literature on the epidemiology, natural course, pathobiology and clinical implications of vertebral endplate changes.Methods A literature search was performed using the Cochrane Database of Systematic Reviews, EMBASE, and PubMed. Studies published over the last 10 years were analysed. The searches were performed using Medical Subject Headings terms, and the subheadings used were “Vertebral endplate changes”, “Modic changes”, “Disc Endplate Bone Marrow complex”.Results The disc, endplate (EP), and bone marrow region of the spine constitute a unified morphological and functional unit, with isolated degeneration of any one structure being uncommon. Disc degeneration causes endplate defects, which result in direct communication and a constant cross-talk between the disc and the vertebral body. This may result in a persistent inflammatory state of the vertebral bone marrow, serving as a major pain generator. This review article focuses on vertebral endplate changes and how the current understanding has progressed from the Modic classification to the Disc Endplate Bone Marrow complex classification. It provides a clear portrayal of the natural course of these alterations and their clinical implications in low back pain.Conclusions In light of the heightened interest and current prominence of vertebral endplate changes within the spine community, we must progress beyond the Modic changes to achieve a comprehensive understanding. The DEBM complex classification will play a major part in disc degeneration research and clinical care, representing a considerable advancement in our understanding of the vertebral endplate changes over the classical Modic changes.

Background:Noncompressible torso hemorrhage remains a leading cause of potentially preventable deaths. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) has emerged as an adjunct temporizing hemorrhage control. The complete occlusion strategy with the ER-REBOA catheter can cause distal ischemia when used for longer than 30 min. To specifically address this limitation, the pREBOA-PRO catheter was developed. The objective of the current study is to investigate the impact of longer, partial occlusion times provided by pREBOA-PRO on acute kidney injury and mortality. Methods:This is a retrospective analysis of the Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery registry as of August 2023. Patients in the pREBOA-PRO group (n = 110) receiving partial occlusion in Zone 1 were contrasted to patients in the ER-REBOA group (n = 752) treated with complete occlusion in Zone 1. Between-group comparisons included demographics, clinical presentation, aortic occlusion strategy, clinical complications, and mortality. Results:Demographics, clinical presentation, and mortality were indistinguishable between groups, except for age which was higher in the ER-REBOA group (44 vs.38, P< 0.002). The partial aortic occlusion strategy was employed more often in the pREBOA-PRO group (87% vs.33%, P< 0.05) and for longer periods (59 min vs.50 min, P< 0.003). In contrast, AKI occurred less frequently in the pREBOA-PRO group (19% vs.33%, P< 0.05). Conclusions:The more frequently partial and longer occlusion times in Zone 1 with the use of pREBOA-PRO resulted in lower AKI incidence suggesting that this newer device is a safer extended bridge to hemorrhage control.

Most of the complications can occur after lung resection for lung cancer. Most of complications occur in the early postoperative period but delayed complications are also recognized. Respiratory and cardiovascular complications predominate after lung surgery. Nonspecific clinical manifestations can make these complications challenging to diagnose. Imaging plays a vital role in recognizing and treating these complications in a timely manner. Hence, it is important to understand the expected anatomic alterations following lung cancer resection, and the spectrum of postsurgical complications and their respective imaging manifestations to avoid misinterpretations or delay in diagnosis.

Radiation therapy (RT) using conventional or newer high precision techniques, including 3-dimensional conformal radiotherapy, intensity-modulated RT, stereotactic body RT, and proton therapy, is an important component in the treatment of patients with lung cancer. Interpreting images for these patients requires knowledge of the radiation technique used, the expected temporal evolution of radiation-induced lung injury (RILI), and patient-specific parameters such as previous radiotherapy and concurrent chemoradiotherapy or immunotherapy. This review discusses factors that affect the development and severity of RILI and its radiologic manifestations, differences between conventional and high-precision dose radiotherapy techniques, and common complications following RT.

Electrochemical aptamer-based biosensors (E-aptasensors) are emerging platforms for point-of-care (POC) detection of complex biofluids. Human saliva particularly offers a noninvasive matrix and unprecedented convenience for detecting illicit drugs, such as cocaine. However, the sensitivity of cocaine E-aptasensors is significantly compromised in saliva. Herein, we investigated the influence of salivary components on the sensing performance of a methylene blue (MB)-labeled classic cocaine aptamer by square-wave voltammetry (SWV), and in parallel, we report the development and optimization of a disposable E-aptasensor for cocaine detection fabricated by laser ablation. Cyclic voltammetry (CV), scanning electron microscopy (SEM), and atomic force microscopy (AFM) were used to study the cleanliness and surface topography of the disposable electrode surface. To enhance the sensing performance of the disposable platform, we developed a co-immobilization strategy by introducing both the target and 6-mercapto-1-hexanol (MCH) into the aptamer immobilization solution, achieving optimal sensing performance at the aptamer-to-MCH ratio of 1:100. In a buffer solution, we revealed that the aptasensor performs best at low ionic strength, the absence of multivalent ions, and neutral pH conditions, while salivary components such as viscosity and mucin have minimal impact. However, upon transition to human saliva, the presence of salivary proteins exerted a profound effect on the sensing performance. To reduce this impact, we discovered that a high NaCl concentration could significantly enhance the sensing response in saliva. This approach circumvents centrifugation and extensive dilution and facilitates cocaine detection in human saliva through a straightforward “mix-and-detect” method. This disposable aptasensor achieved a limit of detection (LOD) of 3.7 μM in 90% saliva, demonstrating immense promise for the application of electrochemical aptasensors in detecting cocaine, especially when administered via smoking.

Robot assisted radical prostatectomy (RARP) is commonly performed using either the anterior (AF) or posterior first (PF) approaches, depending upon where the dissection begins. While there is some data comparing outcomes of conventional RARP and Retzius sparing posterior RARP, there is limited data comparing outcomes between the AF and PF approaches to conventional RARP. We compared the two approaches in terms of perioperative, functional, and oncological outcomes.

•There is an increasing prevalence of amyloidosis in the general population.•The data for structural interventions in this population are limited.•We demonstrate increasing utilization of all structural interventions in patients with amyloidosis.•Thus, more focus is necessary to study the amyloidosis population to determine the optimal therapeutic approach.

To evaluate the impact of total duration of intraretinal fluid (IRF) exposure on visual acuity and vision-related quality of life in patients with neovascular age-related macular degeneration (nAMD).