Rapid progression of orbital abscess requiring lateral canthotomy in a pediatric patient.

Subperiosteal abscess (SPA) is a rare complication of acute sinusitis in children that may develop rapidly. In this case report, we describe an 11 year-old boy who presented with a large SPA 2 days after being diagnosed with conjunctivitis. The patient required emergent lateral canthotomy and cantholysis (LCC), IV antibiotics, and emergent surgery. It is crucial that emergency physicians be able to identify and treat this vision-threatening complication.

A direct analysis method using sheath flow probe electrospray ionisation-mass spectrometry (sfPESI-MS) to detect drug residues from fingerprint forensic gel lifts.

Latent fingerprints at crime scenes are frequently recovered using forensic gel-lifters, which can help to preserve the crime scene and to enhance visualisation of traces such as blood or paint. In addition to providing fingerprint ridge detail, additional chemical information can also be recovered from gel lifts that may prove pertinent to an investigation. However, while DNA and metal ions have been shown to be able to be detected in gel-lifted fingerprints, the determination of other types of chemical information such as the presence of drugs in gel-lifted prints has not been previously shown. This study demonstrates the application of an ambient ionisation method, sheath flow probe electrospray ionisation-mass spectrometry (sfPESI-MS), to the direct analysis of gel-lifted fingerprints. A model drug compound (zolpidem) is successfully detected from gel-lifted prints from three different surface types: glass, metal, and paper. The surface activity-based separation associated with probe electrospray approaches is shown to resolve zolpidem ions from background phthalate species, significantly enhancing the response obtained from the gel-lifter. A depletion series experiment shows that the drug residue can be detected with up to 100% efficiency after eight consecutive contacts; however, detection efficiency drops to 20% after 30 contacts. The developed approach has potential application to analysis of historical gel-lifters to obtain additional chemical information.

Age-dependent changes in collagen crosslinks reduce the mechanical toughness of human meniscus.

The mechanical resilience of the knee meniscus is provided by a group of structural proteins in the extracellular matrix. Aging can alter the quantity and molecular structure of these proteins making the meniscus more susceptible to debilitating tears. In this study, we determined the effect of aging on the quantity of structural proteins and collagen crosslinks in human lateral meniscus, and examined whether the quantity of these molecules was predictive of tensile toughness (area under the stress-strain curve). Two age groups were tested: a young group under 40 and an older group over 65 years old. Using mass spectrometry, we quantified the abundance of proteins and collagen crosslinks in meniscal tissue that was adjacent to the dumbbell-shaped specimens used to measure uniaxial tensile toughness parallel or perpendicular to the circumferential fiber orientation. We found that the enzymatic collagen crosslink deoxypyridinoline had a significant positive correlation with toughness, and reductions in the quantity of this crosslink with aging were associated with a loss of toughness in the ground substance and fibers. The non-enzymatic collagen crosslink carboxymethyl-lysine increased in quantity with aging, and these increases corresponded to reductions in ground substance toughness. For the collagenous (Types I, II, IV, VI, VIII) and non-collagenous structural proteins (elastin, decorin, biglycan, prolargin) analyzed in this study, only the quantity of collagen VIII was predictive of toughness. This study provides valuable insights on the structure-function relationships of the human meniscus, and how aging causes structural adaptations that weaken the tissue's mechanical integrity.

"Mesmerizing and Terrifying": Senusret III's Unique Macrotia.

The ancient Egyptian pharaoh Senusret III was a legend to both his contemporaries and his descendants: an ideal of kingly power whose legacy of control and intimidation was remembered for centuries. Of particular note is the unique macrotia that the king's statues display. In this paper, we discuss possible etiologies of Senusret's unique presentation and ultimately conclude that Senusret's immortalized features were likely rooted in propaganda rather than a medical cause.

Civilian Moral Injury and Amygdala Functional Connectivity During Attention to Threat.

BACKGROUND: Moral injury references emotional and spiritual/existential suffering that may emerge following psychological trauma. Despite being linked to adverse mental health outcomes, little is known about the neurophysiological mechanisms of this phenomenon. In this study, we examined neural correlates of moral injury exposure and distress using the Moral Injury Exposure and Symptom Scale for Civilians. We also examined potential moderation of these effects by race (Black vs. White individuals) given the likely intersection of race-related stress with moral injury. METHODS: Forty-eight adults ages 18 to 65 years (mean age = 30.56, SD = 11.93) completed the Moral Injury Exposure and Symptom Scale for Civilians and an affective attentional control measure, the affective Stroop task (AS), during functional magnetic resonance imaging; the AS includes presentation of threat-relevant and neutral distractor stimuli. Voxelwise functional connectivity of the bilateral amygdala was examined in response to threat-relevant versus neutral AS distractor trials. RESULTS: Functional connectivity between the right amygdala and left postcentral gyrus/primary somatosensory cortex was positively correlated with the Moral Injury Exposure and Symptom Scale for Civilians exposure score (voxelwise p < .001, cluster false discovery rate-corrected p < .05) in response to threat versus neutral AS distractor trials. Follow-up analyses revealed significant effects of race; Black but not White participants demonstrated this significant pattern of amygdala-left somatosensory cortex connectivity. CONCLUSIONS: Increased exposure to potentially morally injurious events may lead to emotion-somatosensory pathway disruptions during attention to threat-relevant stimuli. These effects may be most potent for individuals who have experienced multilayered exposure to morally injurious events, including racial trauma. Moral injury appears to have a distinct neurobiological signature that involves abnormalities in connectivity of emotion-somatosensory paths, which may be amplified by race-related stress.

9S1R nullomer peptide induces mitochondrial pathology, metabolic suppression, and enhanced immune cell infiltration, in triple-negative breast cancer mouse model.

Nullomers are the shortest strings of absent amino acid (aa) sequences in a species or group of species. Primes are those nullomers that have not been detected in the genome of any species. 9S1R is a 5-aa peptide prime sequence attached to 5-arginine aa, used to treat triple negative breast cancer (TNBC) in an in vivo mouse model. This unique peptide, administered with a trehalose carrier (9S1R-NulloPT), offers enhanced solubility and exhibits distinct anti-cancer effects against TNBC. In our study, we investigated the effect of 9S1R-NulloPT on tumor growth, metabolism, metastatic burden, tumor immune-microenvironment (TME), and transcriptome of aggressive mouse TNBC tumors. Notably, treated mice had smaller tumors in the initial phase of the treatment, as compared to untreated control, and diminished in vivo and ex vivo bioluminescence at later-stages - indicative of metabolically quiescent, dying tumors. The treatment also caused changes in TME with increased infiltration of immune cells and altered tumor transcriptome, with 365 upregulated genes and 710 downregulated genes. Consistent with in vitro data, downregulated genes were enriched in cellular metabolic processes (179), specifically mitochondrial TCA cycle/oxidative phosphorylation (44), and translation machinery/ribosome biogenesis (45). The upregulated genes were associated with the developmental (13), ECM organization (12) and focal adhesion pathways (7). In conclusion, our study demonstrates that 9S1R-NulloPT effectively reduced tumor growth during its initial phase, altering the TME and tumor transcriptome. The treatment induced mitochondrial pathology which led to a metabolic deceleration in tumors, aligning with in vitro observations.

A Lesion on the "King of Kings": Neurofibromas in the Parthian Empire's Arsacid Dynasty.

Multiple kings of the Arsacid Dynasty of the ancient Parthian Empire are depicted on their coinage with a recurrent facial lesion, one that is found across multiple generations. Multiple theories have attempted to explain this phenomenon, from basal cell carcinoma to hereditary trichoepithelioma. In this paper, we suggest that these lesions are possibly a representation of the neurofibromas found in Neurofibromatosis 1, an autosomal dominant disease process.

Virologic Response to Dolutegravir Plus Lamivudine in People With Suppressed Human Immunodeficiency Virus Type 1 and Historical M184V/I: A Systematic Literature Review and Meta-analysis.

Background: To investigate the impact of the M184V/I mutation on virologic response to dolutegravir plus lamivudine (DTG + 3TC) in suppressed-switch populations, a meta-analysis was performed using virologic outcomes from people with human immunodeficiency virus type 1 (PWH) with and without M184V/I before DTG + 3TC switch in real-world studies identified via systematic literature review. Sensitivity analyses were performed using data from PWH with M184V/I in interventional studies identified via targeted literature review. Methods: Single-arm meta-analyses using common- and random-effects models were used to estimate proportions of PWH with virologic failure (VF) among real-world populations with and without M184V/I and interventional study participants with M184V/I at 24, 48, and 96 weeks. Results: Literature reviews identified 5 real-world studies from 3907 publications and 51 abstracts meeting inclusion criteria and 5 interventional studies from 1789 publications and 3 abstracts. All time points had low VF incidence in PWH with M184V/I (real-world: 1.43%-3.81%; interventional: 0.00%) and without (real-world: 0.73%-2.37%). Meta-analysis-estimated proportions (95% confidence interval) with VF were low at weeks 24, 48, and 96, respectively, for PWH with M184V/I (real-world: 0.01 [.00-.04], 0.03 [.01-.06], and 0.04 [.01-.07]; interventional: 0.00 [.00-.02], 0.00 [.00-.01], and 0.00 [.00-.03]) and without (real-world: 0.00 [.00-.02], 0.02 [.01-.04], and 0.02 [.00-.05]). One real-world study (n = 712) reported treatment-emergent M184V at VF in 1 of 652 (0.15%) PWH without prior M184V/I. Conclusions: Results suggest that prior M184V/I has minimal impact on virologic suppression after switching to DTG + 3TC and provide reassurance when considering switching regimens in virologically suppressed PWH with incomplete treatment history or limited treatment options.

Nord-Ost: Russia's Medical Failure in the 2002 Crisis.

The 2002 hostage crisis at a Moscow theater transfixed the attention of the world. While the initial assault, led by Spetsnaz commandos, successfully secured the building, the Russian security force's utter failure at coordinating with medical services led to the preventable deaths of over 100 hostages.

Climate change and seismic resilience: Key considerations for Alaska's infrastructure and built environment.

Alaska is one of the most seismically active regions of the world. Coincidentally, the state has also experienced dramatic impacts of climate change as it is warming at twice the rate of the rest of the United States. Through mechanisms such as permafrost thaw, water table fluctuation, and melting of sea ice and glaciers, climatic-driven changes to the natural and built-environment influence the seismic response of infrastructure systems. This paper discusses the challenges and needs posed by earthquake hazards and climate change to Alaska's infrastructure and built environment, drawing on the contributions of researchers and decision-makers in interviews and a workshop. It outlines policy, mitigation, and adaptation areas meriting further attention to improve the seismic resilience of Alaska's built environment from the perspectives of engineering and complementary coupled human-environmental systems.

Rational social distancing policy during epidemics with limited healthcare capacity.

Epidemics of infectious diseases posing a serious risk to human health have occurred throughout history. During recent epidemics there has been much debate about policy, including how and when to impose restrictions on behaviour. Policymakers must balance a complex spectrum of objectives, suggesting a need for quantitative tools. Whether health services might be 'overwhelmed' has emerged as a key consideration. Here we show how costly interventions, such as taxes or subsidies on behaviour, can be used to exactly align individuals' decision making with government preferences even when these are not aligned. In order to achieve this, we develop a nested optimisation algorithm of both the government intervention strategy and the resulting equilibrium behaviour of individuals. We focus on a situation in which the capacity of the healthcare system to treat patients is limited and identify conditions under which the disease dynamics respect the capacity limit. We find an extremely sharp drop in peak infections at a critical maximum infection cost in the government's objective function. This is in marked contrast to the gradual reduction of infections if individuals make decisions without government intervention. We find optimal interventions vary less strongly in time when interventions are costly to the government and that the critical cost of the policy switch depends on how costly interventions are.

Schistosomiasis: The Disease That Saved Taiwan.

From 1949 to 1950, an acute epidemic of schistosomiasis struck several elite units of the People's Liberation Army during the Chinese Civil War that were preparing for an amphibious invasion of Taiwan. The crucial delay brought by the sudden outbreak of the disease may have cost communist forces control of the strategic island, changing the geopolitical calculus of the Pacific in the decades since.

Minority-group incubators and majority-group reservoirs support the diffusion of climate change adaptations.

Successful climate change adaptation depends on the spread and maintenance of adaptive behaviours. Current theory suggests that the heterogeneity of metapopulation structure can help adaptations diffuse throughout a population. In this paper, we develop an agent-based model of the spread of adaptations in populations with minority-majority metapopulation structure, where subpopulations learn more or less frequently from their own group compared to the other group. In our simulations, minority-majority-structured populations with moderate degrees of in-group preference better spread and maintained an adaptation compared to populations with more equal-sized groups and weak homophily. Minority groups act as incubators for an adaptation, while majority groups act as reservoirs for an adaptation once it has spread widely. This means that adaptations diffuse throughout populations better when minority groups start out knowing an adaptation, as Indigenous populations often do, while cohesion among majority groups further promotes adaptation diffusion. Our work advances the goal of this theme issue by developing new theoretical insights and demonstrating the utility of cultural evolutionary theory and methods as important tools in the nascent science of culture that climate change adaptation needs. This article is part of the theme issue 'Climate change adaptation needs a science of culture'.

Transcending Borders and Bias: The Multifaceted Life and Legacy of Dr. Hector Pérez García.

Héctor Pérez García's transformative leadership in Hispanic civil rights within the U.S. remains an integral topic of academic discussion. As a dedicated physician, a resilient World War II veteran, and a fervent civil rights advocate, García seamlessly merged these roles, paving a distinct path that defined his multifaceted advocacy. His unique approach and steadfast commitment to justice and equality not only solidified his position as a transformative leader but also emphasized the importance of his endeavors in shaping the nation's historical narrative. It is this intricate interplay of his personal experiences and professional pursuits that places García at the epicenter of academic discussions around Hispanic rights and activism. This paper is committed to unpacking the nuances of García's significant contributions, while also providing a comprehensive perspective on the socio-political landscape of his time - a setting that both shaped and was profoundly affected by his groundbreaking efforts.

NeuroBridge: a prototype platform for discovery of the long-tail neuroimaging data.

Introduction: Open science initiatives have enabled sharing of large amounts of already collected data. However, significant gaps remain regarding how to find appropriate data, including underutilized data that exist in the long tail of science. We demonstrate the NeuroBridge prototype and its ability to search PubMed Central full-text papers for information relevant to neuroimaging data collected from schizophrenia and addiction studies. Methods: The NeuroBridge architecture contained the following components: (1) Extensible ontology for modeling study metadata: subject population, imaging techniques, and relevant behavioral, cognitive, or clinical data. Details are described in the companion paper in this special issue; (2) A natural-language based document processor that leveraged pre-trained deep-learning models on a small-sample document corpus to establish efficient representations for each article as a collection of machine-recognized ontological terms; (3) Integrated search using ontology-driven similarity to query PubMed Central and NeuroQuery, which provides fMRI activation maps along with PubMed source articles. Results: The NeuroBridge prototype contains a corpus of 356 papers from 2018 to 2021 describing schizophrenia and addiction neuroimaging studies, of which 186 were annotated with the NeuroBridge ontology. The search portal on the NeuroBridge website https://neurobridges.org/ provides an interactive Query Builder, where the user builds queries by selecting NeuroBridge ontology terms to preserve the ontology tree structure. For each return entry, links to the PubMed abstract as well as to the PMC full-text article, if available, are presented. For each of the returned articles, we provide a list of clinical assessments described in the Section "Methods" of the article. Articles returned from NeuroQuery based on the same search are also presented. Conclusion: The NeuroBridge prototype combines ontology-based search with natural-language text-mining approaches to demonstrate that papers relevant to a user's research question can be identified. The NeuroBridge prototype takes a first step toward identifying potential neuroimaging data described in full-text papers. Toward the overall goal of discovering "enough data of the right kind," ongoing work includes validating the document processor with a larger corpus, extending the ontology to include detailed imaging data, and extracting information regarding data availability from the returned publications and incorporating XNAT-based neuroimaging databases to enhance data accessibility.

The gut microbiota induces melanin deposits that act as substrates for fimA-mediated aggregation of Salmonella Typhimurium and enhance infection of the German cockroach vector.

When Salmonella Typhimurium is ingested by German cockroaches, the bacteria replicate in the gut and persist for at least 7 d, enabling transmission in the feces. However, the mechanisms that facilitate survival and persistence in the cockroach gut remain poorly detailed. We previously reported the formation of biofilm-like aggregate populations of S. Typhimurium in the gut of cockroaches upon ingestion. We also reported that deletion of the type-1 fimbrial subunit of S. Typhimurium, fimA, leads to a reduced bacterial load in the cockroach gut. Here, we link these observations and provide further insight into the mechanism and function of S. Typhimurium aggregation in the gut of the cockroach. We show that S. Typhimurium but not Escherichia coli forms aggregated populations in the cockroach gut, and that aggregate formation requires fimA but not the biofilm formation-related genes csgA and csgD. Furthermore, we show that S. Typhimurium aggregates are formed using small granular deposits present in the cockroach gut, which exhibit properties consistent with melanin, as substrates. These melanin deposits are prevalent in the guts of both immature and adult cockroaches from laboratory colonies and are correlated with increased gut bacterial density while being entirely absent in gnotobiotic cockroaches reared without exposure to environmental bacteria, indicating they are induced as a response to the gut microbiota. When cockroaches lacking melanin deposits in the gut are fed S. Typhimurium, they exhibit lower rates of infection than those harboring melanin deposits, demonstrating that microbiota-induced melanin deposits enhance infection of the gut of the vector. IMPORTANCE Cockroaches, including the German cockroach (Blattella germanica), can be both mechanical and biological vectors of pathogenic bacteria. Together, our data reveal a novel mechanism by which S. Typhimurium interacts with the cockroach gut and its microbiota that promotes infection of the vector. These findings exemplify the emerging but underappreciated complexity of the relationship between cockroaches and S. Typhimurium.

The histologic outcomes of indeterminate thyroid nodules with rat sarcoma mutations: A case series.

Molecular testing is an adjunct test for thyroid fine needle aspirations with indeterminate diagnoses, with certain mutations showing a greater risk of malignancy (ROM). Rat sarcoma (RAS) point mutations are the most common alterations in indeterminate thyroid nodules. While they can have a high ROM, they are also found in benign disease. This study describes the histologic outcomes of indeterminate nodules with RAS mutations. Bethesda III and IV thyroid nodules with ThyroSeq results showing RAS mutations (NRAS, KRAS, and HRAS) were identified between November 1, 2018 and February 28, 2023. Baseline patient characteristics, ThyroSeq results, and surgical diagnoses were collected. We identified 18 nodules with RAS mutations from 17 patients. Fourteen were NRAS (isolated NRAS in 6; NRAS with other abnormalities [NRAS+] in 8); one was isolated KRAS; and three were HRAS with other abnormalities (HRAS+). NRAS Q16R was the most common amino acid change. Twelve cases had follow-up. Two were malignant, a minimally invasive follicular carcinoma (NRAS+) and a papillary thyroid carcinoma, follicular variant (HRAS+). Three were noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), 2 HRAS+ and 1 NRAS+. Four were follicular adenomas, one being atypical (3 NRAS+ and one isolated NRAS). One was an oncocytic adenoma (isolated NRAS). Two were nodular hyperplasias (isolated NRAS and NRAS+, respectively). Twenty-eight percent of our RAS-mutated nodules were malignant or NIFTP. All three HRAS-mutated nodules were malignant or NIFTP. The three isolated RAS mutations with follow up were benign (adenomas or nodular hyperplasia). These findings were in line with the literature.

The form of uncertainty affects selection for social learning.

Social learning is a critical adaptation for dealing with different forms of variability. Uncertainty is a severe form of variability where the space of possible decisions or probabilities of associated outcomes are unknown. We identified four theoretically important sources of uncertainty: temporal environmental variability; payoff ambiguity; selection-set size; and effective lifespan. When these combine, it is nearly impossible to fully learn about the environment. We develop an evolutionary agent-based model to test how each form of uncertainty affects the evolution of social learning. Agents perform one of several behaviours, modelled as a multi-armed bandit, to acquire payoffs. All agents learn about behavioural payoffs individually through an adaptive behaviour-choice model that uses a softmax decision rule. Use of vertical and oblique payoff-biased social learning evolved to serve as a scaffold for adaptive individual learning - they are not opposite strategies. Different types of uncertainty had varying effects. Temporal environmental variability suppressed social learning, whereas larger selection-set size promoted social learning, even when the environment changed frequently. Payoff ambiguity and lifespan interacted with other uncertainty parameters. This study begins to explain how social learning can predominate despite highly variable real-world environments when effective individual learning helps individuals recover from learning outdated social information.

NeuroBridge ontology: computable provenance metadata to give the long tail of neuroimaging data a FAIR chance for secondary use.

Background: Despite the efforts of the neuroscience community, there are many published neuroimaging studies with data that are still not findable or accessible. Users face significant challenges in reusing neuroimaging data due to the lack of provenance metadata, such as experimental protocols, study instruments, and details about the study participants, which is also required for interoperability. To implement the FAIR guidelines for neuroimaging data, we have developed an iterative ontology engineering process and used it to create the NeuroBridge ontology. The NeuroBridge ontology is a computable model of provenance terms to implement FAIR principles and together with an international effort to annotate full text articles with ontology terms, the ontology enables users to locate relevant neuroimaging datasets. Methods: Building on our previous work in metadata modeling, and in concert with an initial annotation of a representative corpus, we modeled diagnosis terms (e.g., schizophrenia, alcohol usage disorder), magnetic resonance imaging (MRI) scan types (T1-weighted, task-based, etc.), clinical symptom assessments (PANSS, AUDIT), and a variety of other assessments. We used the feedback of the annotation team to identify missing metadata terms, which were added to the NeuroBridge ontology, and we restructured the ontology to support both the final annotation of the corpus of neuroimaging articles by a second, independent set of annotators, as well as the functionalities of the NeuroBridge search portal for neuroimaging datasets. Results: The NeuroBridge ontology consists of 660 classes with 49 properties with 3,200 axioms. The ontology includes mappings to existing ontologies, enabling the NeuroBridge ontology to be interoperable with other domain specific terminological systems. Using the ontology, we annotated 186 neuroimaging full-text articles describing the participant types, scanning, clinical and cognitive assessments. Conclusion: The NeuroBridge ontology is the first computable metadata model that represents the types of data available in recent neuroimaging studies in schizophrenia and substance use disorders research; it can be extended to include more granular terms as needed. This metadata ontology is expected to form the computational foundation to help both investigators to make their data FAIR compliant and support users to conduct reproducible neuroimaging research.

Future Evolution of Biosimilar Development by Application of Current Science and Available Evidence: The Developer's Perspective.

Biosimilars have been available in the USA for over a decade, and in Europe for almost two decades. In that time, biosimilars have become established in the treatment landscape for a wide range of diseases, facilitating patient access and affordability of healthcare. However, patients can still struggle to access biological therapies in some markets. There is a need to streamline the process of developing biosimilars without compromising their quality, safety, or efficacy. This opinion piece considers the efficiencies that could be achieved within the biosimilar approval process. In clinical trials for biosimilars, clinical efficacy endpoints have been shown to be less sensitive measures of biosimilarity than biochemical, biophysical, and biological functional assays. Additional clinical efficacy studies comparing potential biosimilars and reference products do not add information that is useful for regulatory purposes. Large clinical studies of biosimilars with immunogenicity endpoints are of limited value, given the quality control processes in place for all biologics, including biosimilars. The expectation for multiple-switch studies for US interchangeability designation should be reconsidered immediately, and the category should be eliminated in the future. As biosimilars are typically approved globally based on a single set of clinical trials, and all subsequent manufacturing changes are already carefully monitored by regulatory authorities, comparative pharmacokinetic testing of EU and US reference products is unnecessary. Manufacturers and regulators could take greater advantage of existing real-world evidence. Streamlining biosimilar development would enable biosimilar development of more and a wider variety of biological drugs, accelerating biosimilar development without impacting patient safety or effectiveness.