Search

Force Field X (FFX) is an open-source software package for atomic resolution modeling of genetic variants and organic crystals that leverages advanced potential energy functions and experimental data. FFX currently consists of nine modular packages with novel algorithms that include global optimization via a many-body expansion, acid–base chemistry using polarizable constant-pH molecular dynamics, estimation of free energy differences, generalized Kirkwood implicit solvent models, and many more. Applications of FFX focus on the use and development of a crystal structure prediction pipeline, biomolecular structure refinement against experimental datasets, and estimation of the thermodynamic effects of genetic variants on both proteins and nucleic acids. The use of Parallel Java and OpenMM combines to offer shared memory, message passing, and graphics processing unit parallelization for high performance simulations. Overall, the FFX platform serves as a computational microscope to study systems ranging from organic crystals to solvated biomolecular systems. [ABSTRACT FROM AUTHOR]

In recent years, museums have been acknowledged as powerful geopolitical sites. In this article, we explore the military museums of southern Arizona, primarily the Pima Air and Space Museum in Tucson, as a unique kind of infrastructure where the museum and the military meet. Drawing on participant observation, we explore how the museum experience provides crucial affective and emotional dimensions to the ideological production the military is involved in. This article also uses geographic information systems to begin charting connections between these museums and their immediate surroundings in the city and region, as well as the wider territories that the military museums help to maintain. As military infrastructure morphs into museum experiences, we consider the epistemic violence that results and consider how it might also be a form of slow infrastructural violence, insofar as it helps maintain unequal relations of power and ongoing violence around the world and in the city itself. [ABSTRACT FROM AUTHOR]

Objective: To analyze the local field potentials (LFPs) in patients with focal drugresistant epilepsy (DRE) from the anterior nucleus of the thalamus (ANT) during inter-ictal state and seizure state. Method: ANT stereotactic EEG (SEEG) recordings were studied in four patients with focal temporal lobe epilepsy. SEEG data was classified as inter-ictal and ictal state and sub-categorized into electrographic (ESz), focal aware seizure (FAS), focal with impaired awareness (FIA), or focal to bilateral tonic-clonic seizure (FBTC). LFP was analyzed at 4 Hz, 8 Hz, 16 Hz, 32 Hz, high gamma (100 Hz), and ripples (200 Hz) using spectrogram analysis and a statistical comparison of normalized power spectral density (PSD) averaged during seizures versus preictal baseline segments. Result: The LFP recordings were analyzed for 162 seizures (127 ESz, 23 FAS, 6 FIA, and 6 FBTC). Based on time-frequency data (spectrogram), a broad band of activity, occurring between 2 and 6 Hz and centered at 4 Hz, and thin-band activity occurring specifically at 8 Hz on the frequency spectrogram were observed during the inter-ictal state. Statistically significant changes in LFP-PSD were seen for FAS, FIA, and FBTC. We observed a significant gain in LFP at the lower frequency band during FAS at 4 Hz, FIA, and FBTC at 4, 8, and 16 Hz while also observing increases at higher frequencies during FBTC at 100 and 200 Hz and a decrease during FAS seizures at 32 Hz. In contrast, no significant change in LFP power was seen for electrographic seizures. Interpretation: Our observations from a limited dataset indicate that all clinical seizure types, but not electrographic seizures, caused a change in ANT-LFP based on the magnitude of the associated power spectral density (PSD). Future work will be needed to validate the use of ANT-LFP at these frequencies as accurate measurements of seizure occurrence and severity. This work represents a first step toward understanding ANT thalamic LFP patterns during focal seizures and developing adaptive DBS strategies. [ABSTRACT FROM AUTHOR]

Introduction: Innovative, culturally safe strategies are required to address the disproportionate level of poorer health outcomes for Indigenous people in Australia compared to non-Indigenous populations. An emerging body of evidence supports the efficacy of Indigenous-specific health assessments, or health checks, despite poor uptake since their introduction in Australia. This poor uptake is attributed to a range of system, patient and provider barriers. Services have begun to deliver preventative health assessments as a community event to address barriers faced by Aboriginal and Torres Strait Islander people in accessing quality preventative care. However, there is a lack of literature exploring how community events have increased the uptake of Indigenous specific health assessments to date. We expect this review will underpin a larger study to better understand how community engagement supports increased uptake of health checks. The objective of this scoping review was to investigate what is currently known about how community events have been used to increase uptake of Indigenous-specific health assessments. Methods: A scoping review guided by the Joanna Briggs Institute methodology for scoping reviews was conducted. A search was completed in eight electronic databases using keywords relating to Aboriginal and Torres Strait Islander health, community engagement and preventative health assessments. Published and unpublished sources of evidence were included in the review. As this study aims to explore the entire published literature on the topic, and given there was an expectation that the subject itself is specific, no date ranges were included in the search criteria. Extracted data were reviewed by numerical analysis and conventional content analysis to conduct a narrative synthesis, allowing a summary of the main findings, and addressing the research question. Results: Eighteen sources met the eligibility criteria and were included in the scoping review. Programs varied widely in the characteristics of program design and delivery across geographical location, setting of delivery, program format and target population. Programs employed a range of methods to engage with community, including incentivising participation, identifying and addressing specific community healthcare needs, and utilising cultural or sporting ambassadors to promote the program. The conventional content analysis identified three key themes regarding how community events have been used to increase uptake of health checks: adapting the program to the community; providing a culturally safe participant experience; and prioritising community engagement. Discussion: The findings indicate that an individualised approach to community events is important to their success. Aboriginal Controlled Community Health Services may be best placed to have responsibility for program design and implementation to ensure community control of programs. Aboriginal health workers play a critical role in ensuring the programs deliver culturally safe healthcare, and a clear role for Aboriginal health workers in program delivery is important in their success. An authentic commitment to community engagement is important for program uptake, including the use of passionate cultural ambassadors and individualised cultural programs. Conclusion: Community events are a promising and wellregarded strategy to increase uptake of Indigenous-specific health assessments. Future research that explores how specific community supports increase engagement with Health Check Day programs and evaluates the delivery of 715 health check programs will strengthen the capacity of Aboriginal Community Controlled Health Services to delivery this intervention effectively. [ABSTRACT FROM AUTHOR]

Background: Screening with anti-Epstein-Barr virus (EBV) serology and endoscopy decreased nasopharyngeal carcinoma (NPC) mortality in Guangdong in a randomized trial. We conducted a secondary analysis of this trial using local incidence and cost data to optimize screening programs, hypothesizing that screening could be cost-effective in southern China. Methods: Screening costs and life-years after NPC diagnosis were obtained from the Guangdong trial's intent-to-screen population (men and women aged 30-69). Seropositive subjects were rescreened annually for 5 years. Thereafter, we evaluated 12 screening strategies in Guangdong and Guangxi using a validated model. Strategies used combinations of serology, nasopharyngeal swab PCR (NP PCR), endoscopy, and MRI from trial subcohorts. Incidence data and costs were obtained from local cancer registries and the provincial healthcare system. Results: In the intent-to-screen population, screening with serology and endoscopy was cost-effective (¥42,366/life-year, 0.52 GDP per capita). Screening for 5 to 15 years between ages 35 and 59 years met a willingness-to-pay threshold of 1.5 GDP/quality-adjusted life-years in all modeled populations. Despite doubling costs, adding MRI could be cost-effective via improved sensitivity. NP PCR triage reduced endoscopy/MRI referrals by 37%. One-lifetime screen could reduce NPC mortality by approximately 20%. Conclusions: EBV-based serologic screening for NPC is likely to be cost-effective in southern China. Among seropositive subjects, the preferred strategies use endoscopy alone or selective endoscopy triaged by MRI with or without NP PCR. These data may aid the design of screening programs in this region. Impact: These findings support population-based screening in southern China by defining the target population, cost-effectiveness, and optimized screening approach. [ABSTRACT FROM AUTHOR]

Background: ARDS is a heterogeneous syndrome with distinct clinical phenotypes. Here we investigate whether the presence or absence of large pulmonary ultrasonographic consolidations can categorize COVID-19 ARDS patients requiring mechanical ventilation into distinct clinical phenotypes. Methods: This is a retrospective study performed in a tertiary-level intensive care unit in Israel between April and September 2020. Data collected included lung ultrasound (LUS) findings, respiratory parameters, and treatment interventions. The primary outcome was a composite of three ARDS interventions: prone positioning, high PEEP, or a high dose of inhaled nitric oxide. Results: A total of 128 LUS scans were conducted among 23 patients. The mean age was 65 and about two-thirds were males. 81 scans identified large consolidation and were classified as "C-type", and 47 scans showed multiple B-lines with no or small consolidation and were classified as "B-type". The presence of a "C-type" study had 2.5 times increased chance of receiving the composite primary outcome of advanced ARDS interventions despite similar SOFA scores, Pao2/FiO2 ratio, and markers of disease severity (OR = 2.49, %95CI 1.40–4.44). Conclusion: The presence of a "C-type" profile with LUS consolidation potentially represents a distinct COVID-19 ARDS subphenotype that is more likely to require aggressive ARDS interventions. Further studies are required to validate this phenotype in a larger cohort and determine causality, diagnostic, and treatment responses. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

DASHH-1A is a quality metric used across HEMS and CCT programs to evaluate the safety and effectiveness of their airway management performance. The ability to achieve DASHH-1A success is multifactorial. This quality improvement project aimed to improve our program's DASHH-1A success rate. With excellent airway practitioners on our staff, we were perplexed as to why we did not meet the GAMUT achievable benchmark of care in DASHH-1A airway management. Our objective was to determine what may be impacting our success rates, both negatively and positively, to ultimately improve our DASHH-1A success rates. Four investigators each reviewed a different patient population (interfacility trauma, interfacility medical, scene trauma, scene medical) to evaluate trends in their respective cohorts which may impact our DASHH-1A success. A brief literature review of current RSI practices was also conducted. Following these studies, we implemented a performance improvement plan and compared our adult DASHH-1A success rates for the 16 month periods pre- and post-intervention. All pediatric and crash airways were excluded. We revised our RSI protocol to include a bundle of care for all RSI airway attempts, which was then reviewed monthly at department CQI meetings. In addition to prior RSI mandates, we specified parameters to initiate additional airway, ventilation, and/or hemodynamic resuscitative efforts; mandated bag-mask ventilation during the period between paralytic administration and initiation of laryngoscopy; mandated use of a real-time, call-and-response RSI checklist; and implemented a standardized documentation template to capture those interventions performed. Pre-intervention DASHH-1A success rate was 63% (38/60 advanced airways). This improved to 72% (39/54 advanced airways) in the post-intervention period. This resulted in an improvement of our DASHH-1A success, with an absolute difference of 8.9% and a relative increase of 14%. A notable finding revealed that we had a 92% compliance rate with the utilization of our full DASHH-1A bundle. The implementation of a DASHH-1A bundle of care had a high degree of compliance and was shown to improve our program's overall adult DASHH-1A success rate. A limitation of our study was our small sample size, n = 114 total patients. Recommendations for further studies would include a multi-center pre/post study to review similar programs' DASHH-1A airway success. [ABSTRACT FROM AUTHOR]

Nearly 1% of babies are born with congenital heart disease (CHD) - many of whom will require heart surgery within the first few years of life. A detailed understanding of cardiac maturation can help to expand our knowledge on cardiac diseases that develop during gestation, identify age-appropriate drug therapies, and inform clinical care decisions related to surgical repair and postoperative management. Yet, to date, our knowledge of the temporal changes that cardiomyocytes undergo during postnatal development is limited. In this study, we collected right atrial tissue samples from pediatric patients (n=117) undergoing heart surgery. Patients were stratified into five age groups. We measured age-dependent adaptations in cardiac gene expression, and used computational modeling to simulate action potential and calcium transients. Enrichment of differentially expressed genes (DEGs) revealed age-dependent changes in several key biological processes (e.g., cell cycle, structural organization), cardiac ion channels, and calcium handling genes. Gene-associated changes in ionic currents exhibited age-dependent trends, with changes in calcium handling ( I NCX ) and repolarization ( I K1 ) most strongly associated with an age-dependent decrease in the action potential plateau potential and increase in triangulation, respectively. We observed a shift in repolarization reserve, with lower I Kr expression in younger patients, a finding potentially tied to an increased amplitude of I Ks that could be triggered by elevated sympathetic activation in pediatric patients. Collectively, this study provides valuable insights into age-dependent changes in human cardiac gene expression and electrophysiology, shedding light on molecular mechanisms underlying cardiac maturation and function throughout development.

Background: In the United States (US), Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) disproportionately impacts Asian Americans (AA) and Native Hawaiians and other Pacific Islanders (NHPI) who have no access to screening. EBV-based screening trials in Asia have detected most cases at early stages. We sought to identify a US target population for NPC screening and hypothesized that once-lifetime screening could be cost-effective., Methods: We obtained NPC incidence data from the SEER Asian and Pacific Islander datasets. We estimated the number needed to screen, mortality reduction, and resource utilization using a validated model and performance data from trials. Six evaluated strategies incorporated serology, nasopharyngeal swab PCR, and endoscopy or MRI., Results: Intermediate-incidence and high-incidence populations accounted for 10.7% of US person-years yet 42.7% of cases. Anti-BNLF2b screening with selective endoscopy was the preferred strategy. In high-incidence populations, the median NNS to detect one case was 1,992, with a median of 7.12 NPC deaths averted per 100,000 screened. Screening met the willingness-to-pay threshold in all five high-incidence populations (median ICER/GDP 0.82) and among men in intermediate-incidence populations., Conclusions: Nearly half of NPC in the US arises among the 10% with AA or NHPI ethnicity. A suitable target population for US screening trials would be men and women age 35-65 of Chinese, Sāmoan, or Southeast Asian ethnicity, or men age 35-60 of Guamanian/Chamorro, Filipino, or Native Hawaiian ethnicity. Once-lifetime anti-BNLF2b screening could be cost-effective., Impact: These data may aid the design of US screening trials. Targeted NPC screening might mitigate health disparities.

The novel Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, created a need for evidence-based guidelines for the evaluation, management, and follow-up after infection. Data have become rapidly available, creating a challenge for medical providers to stay abreast of the ever-evolving recommendations. This document, written collaboratively by pediatric cardiovascular experts, pediatricians, and sports medicine specialists, is focused on SARS-- CoV-2-related pediatric cardiac manifestations. It aims to provide a systemic review of high-yield literature related to all cardiovascular entities as a tool for primary pediatric clinicians to utilize as they consider the cardiac consequences of acute SARS-CoV-2 infection, MIS-C, vaccine-related myocarditis, return-to-play, and long COVID-19 syndrome., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Humans must often keep multiple task goals in mind, at different levels of priority and immediacy, while also interacting with the environment. We might need to remember information for an upcoming task while engaged in more immediate actions. Consequently, actively maintained working memory (WM) content may bleed into ongoing but unrelated motor behavior. Here, we experimentally test the impact of WM maintenance on action execution, and we transcranially stimulate lateral prefrontal cortex (PFC) to parse its functional contributions to WM-motor interactions. We first created a task scenario wherein human participants (both sexes) executed cued hand movements during WM maintenance. We manipulated the compatibility between WM and movement goals at the trial level and the statistical likelihood that the two would be compatible at the block level. We found that remembering directional words (e.g., 'left', 'down') biased the trajectory and speed of hand movements that occurred during the WM delay, but the bias was dampened in blocks when WM content predictably conflicted with movement goals. Then we targeted left lateral PFC with two different transcranial magnetic stimulation (TMS) protocols before participants completed the task. We found that an intermittent theta-burst protocol, which is thought to be excitatory, dampened sensitivity to block-level control demands (i.e., proactive control), while a continuous theta-burst protocol, which is thought to be inhibitory, dampened adaptation to trial-by-trial conflict (i.e., reactive control). Therefore, lateral PFC is involved in controlling the interplay between WM content and manual action, but different PFC mechanisms may support different time-scales of adaptive control., Competing Interests: Conflict of interest: The authors declare no competing financial interests.

We recently discovered that disrupting phospholipid biosynthesis by eliminating the Ino2/4 transcriptional regulator impairs endoplasmic reticulum (ER)-associated degradation (ERAD) in Saccharomyces cerevisiae , but the mechanism is unclear. Phosphatidylcholine deficiency has been reported to accelerate degradation of Sec61 translocon beta subunit Sbh1 and ERAD cofactor Cue1. Here, we found that, unlike targeted phosphatidylcholine depletion, INO4 deletion does not destabilize Sbh1 or Cue1. However, we observed altered electrophoretic mobility of Sbh1 in ino4 Δ yeast, consistent with phospholipid-responsive post-translational modification. A better understanding of the molecular consequences of disrupted lipid homeostasis could lead to enhanced treatments for conditions associated with perturbed lipid biosynthesis., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Background: Nasopharyngeal carcinoma (NPC) has an extremely high incidence rate in Southern China, resulting in a severe disease burden for the local population. Current EBV serologic screening is limited by false positives, and there is opportunity to integrate polygenic risk scores for personalized screening which may enhance cost-effectiveness and resource utilization., Methods: A Markov model was developed based on epidemiological and genetic data specific to endemic areas of China, and further compared polygenic risk-stratified screening [subjects with a 10-year absolute risk (AR) greater than a threshold risk underwent EBV serological screening] to age-based screening (EBV serological screening for all subjects). For each initial screening age (30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, and 65-69 years), a modeled cohort of 100,000 participants was screened until age 69, and then followed until age 79., Results: Among subjects aged 30 to 54 years, polygenic risk-stratified screening strategies were more cost-effective than age-based screening strategies, and almost comprised the cost-effectiveness efficiency frontier. For men, screening strategies with a 1-year frequency and a 10-year absolute risk (AR) threshold of 0.7% or higher were cost-effective, with an incremental cost-effectiveness ratio (ICER) below the willingness to pay (¥203,810, twice the local per capita GDP). Specifically, the strategies with a 10-year AR threshold of 0.7% or 0.8% are the most cost-effective strategies, with an ICER ranging from ¥159,752 to ¥201,738 compared to lower-cost non-dominated strategies on the cost-effectiveness frontiers. The optimal strategies have a higher probability (29.4-35.8%) of being cost-effective compared to other strategies on the frontier. Additionally, they reduce the need for nasopharyngoscopies by 5.1-27.7% compared to optimal age-based strategies. Likewise, for women aged 30-54 years, the optimal strategy with a 0.3% threshold showed similar results. Among subjects aged 55 to 69 years, age-based screening strategies were more cost-effective for men, while no screening may be preferred for women., Conclusion: Our economic evaluation found that the polygenic risk-stratified screening could improve the cost-effectiveness among individuals aged 30-54, providing valuable guidance for NPC prevention and control policies in endemic areas of China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Miller, Xue, Tang, Lei, Zheng, Diao, Wang, Liao, Wu, Zheng, Zhou, Li, Zhang, Chen, Yu, Li, Ji, Sun, He and Jia.)