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The body naturally and continuously secretes sweat for thermoregulation during sedentary and routine activities at rates that can reflect underlying health conditions, including nerve damage, autonomic and metabolic disorders, and chronic stress. However, low secretion rates and evaporation pose challenges for collecting resting thermoregulatory sweat for non-invasive analysis of body physiology. Here we present wearable patches for continuous sweat monitoring at rest, using microfluidics to combat evaporation and enable selective monitoring of secretion rate. We integrate hydrophilic fillers for rapid sweat uptake into the sensing channel, reducing required sweat accumulation time towards real-time measurement. Along with sweat rate sensors, we integrate electrochemical sensors for pH, Cl − , and levodopa monitoring. We demonstrate patch functionality for dynamic sweat analysis related to routine activities, stress events, hypoglycemia-induced sweating, and Parkinson’s disease. By enabling sweat analysis compatible with sedentary, routine, and daily activities, these patches enable continuous, autonomous monitoring of body physiology at rest. Low secretion rates and evaporation pose challenges for collecting resting thermoregulatory sweat for non-invasive analysis of body physiology. Here the authors present wearable microfluidics-based patches for continuous sweat monitoring at rest that enable detection of pH, Cl − , and levodopa for dynamic sweat analysis related to routine activities, stress events, hypoglycemia-induced sweating, and Parkinson’s disease.

While there is data assessing the test performance of artificial intelligence (AI) chatbots, including the Generative Pre-trained Transformer 4.0 (GPT 4) chatbot (ChatGPT 4.0), there is scarce data on its diagnostic accuracy of clinical cases. We assessed the large language model (LLM), ChatGPT 4.0, on its ability to answer questions from the United States Medical Licensing Exam (USMLE) Step 2, as well as its ability to generate a differential diagnosis based on corresponding clinical vignettes from published case reports. A total of 109 Step 2 Clinical Knowledge (CK) practice questions were inputted into both ChatGPT 3.5 and ChatGPT 4.0, asking ChatGPT to pick the correct answer. Compared to its previous version, ChatGPT 3.5, we found improved accuracy of ChatGPT 4.0 when answering these questions, from 47.7 to 87.2% ( p  = 0.035) respectively. Utilizing the topics tested on Step 2 CK questions, we additionally found 63 corresponding published case report vignettes and asked ChatGPT 4.0 to come up with its top three differential diagnosis. ChatGPT 4.0 accurately created a shortlist of differential diagnoses in 74.6% of the 63 case reports (74.6%). We analyzed ChatGPT 4.0’s confidence in its diagnosis by asking it to rank its top three differentials from most to least likely. Out of the 47 correct diagnoses, 33 were the first (70.2%) on the differential diagnosis list, 11 were second (23.4%), and three were third (6.4%). Our study shows the continued iterative improvement in ChatGPT’s ability to answer standardized USMLE questions accurately and provides insights into ChatGPT’s clinical diagnostic accuracy.

Human and murine studies reveal that innate immune cells are able to mount enhanced responses to pathogens after primary inflammatory exposure. Innate immune memory has been shown to last for months to years, longer than the lifespan of most innate immune cells. Indeed, long-lived hematopoietic stem and progenitor cells (HSPCs) serve as a cellular reservoir for innate immune memory. In this review, we summarize the evidence that innate immune memory is epigenetically encoded in HSPCs, and we consider whether HSPC subpopulations with differentiation bias, cell autonomous epigenetic reprogramming, or both features underlie the phenomenon of central trained immunity. We further profile the significant implications of central trained immunity in stem cell transplant, aging, inflammatory diseases, and vaccination strategies for the future.

AbstractIntroductionHuman sex trafficking is a global public health crisis. Emergency departments (EDs) are important access points for trafficked persons who seek medical care. However, because of victims’ hesitancy to disclose their situation and health care practitioners' lack of training and institutional protocols, many trafficked persons go unrecognized. MethodsWe performed a scoping review of current literature. PubMed, SCOPUS, and reference lists were searched to identify articles for inclusion. We aimed to identify gaps in knowledge and shortcomings to assist this vulnerable population. Two reviewers independently screened literature search results and abstracted data from included studies. Descriptive analysis was conducted. ResultsWe selected and analyzed 23 studies that focused on adult human sex trafficking identification, screening, interventions, or education in the ED. Eight (35%) of the publications used a survey model to quantitatively assess outcomes. Many of the other publications were descriptive or qualitative in nature, with some using a structured interview approach. We have observed that no validated or consistent screening tool exists for the identification of possible adult trafficked patients in the ED. However, we found that educational interventions and screening tools can improve health care practitioners’ confidence, victim identification, and knowledge of “next steps” for victims. ConclusionsWe found that most ED clinicians and staff have little or no formal training in sex trafficking victim identification, support, institutional protocols, or available local resources. Our review demonstrates a paucity of formal training programs, validated adult screening tools, and standardized institutional protocols to aid in the care of trafficked patients in the ED.

Movement at the ankle joint serves several purposes during unimpaired locomotion, including stabilization and propulsion. While the healthy ankle can achieve 71°range of plantar/dorsiflexion, only about 30°is used in level-ground walking. Little is known about how gait is affected by isolated limitation of ankle range of motion (RoM) using end-range hard stops. To study this, we developed a simple exoskeleton that restricts ankle range of motion and evaluated the impact of this exoskeleton during level-ground treadmill walking at two speeds, in ten young adults with no ankle pathology. We found that even with 30°range of motion (±15°), significant hard-stop contact occurred compared to when there was no restricted motion, and that individuals did not adjust their gait to avoid contact in this condition. Hard-stop contact time was greater for conditions with less permitted motion, but we did not find significant differences in global kinematic asymmetry at any joint except the ankle, and only in comparisons of other conditions against simulated fusion (p<0.02 for all comparisons); providing even ±10°at the ankle did not lead us to observe significant differences in kinematic asymmetry. We also observed significant changes to ankle positive work at RoMs lower than ±15°(p<0.03 for all comparisons), but we did not observe significant changes in net work over the gait cycle at any other joint of the lower limb in any conditions except simulated fusion. These results suggest that hard-stop contact does not disturb gait enough for users to adapt to gait strategies that avoided contact, and that ankle range of motion can be restricted in level-ground walking without causing significant differences in gait kinematics and joint work.

MicroRNA-mediated post-transcriptional regulation of lung alveolar type 2 (AT2) and AT1 cell differentiation remains understudied. Here, we demonstrate that the let-7 miRNA family plays a homeostatic role in AT2 quiescence by preventing the uncontrolled accumulation of AT2 transitional cells and promoting AT1 differentiation. Using mouse and organoid models, we show that genetic ablation of let-7a1/let-7f1/let-7d cluster ( let-7afd ) in AT2 cells prevents AT1 differentiation and leads to KRT8 transitional cell accumulation in progressive pulmonary fibrosis. Integration of AGO2-eCLIP with RNA-sequencing identified direct let-7 targets within an oncogene feed-forward regulatory network, including BACH1/EZH2/MYC, which drives an aberrant fibrotic cascade. Additional CUT&RUN-sequencing analyses revealed that let-7afd loss disrupts histone acetylation and methylation, driving epigenetic reprogramming and altered gene transcription in profibrotic AT2 cells. This study identifies let-7 as a central hub linking unchecked oncogenic signaling to impaired AT2 cell plasticity and fibrogenesis. Loss of let-7, a key microRNA, causes lung alveolar stem cells to grow abnormally and dieprematurely, leading to scarring and lung damage. Here the study links let-7 loss to cancer-like signals and epigenomic gene changes, revealing new treatment paths for lung fibrosis.

Arachnoid granulations (AGs) are generally benign structures within the subarachnoid space that extend into the dural sinuses and calvarial bone. They can present in a variety of sizes but are termed ‘giant’ arachnoid granulations (GAGs) when they are larger than 1 cm in diameter or take up a significant portion of the dural sinus’ lumen. Vermiform giant arachnoid granulations are a specific type of GAG that are known for their worm-like appearance. Specifically, these vermiform GAGs can be challenging to diagnose as they can mimic other pathologies like dural sinus thrombosis, sinus cavernomas, or brain tumors. In this case series, we present two cases of vermiform giant arachnoid granulations, discuss their imaging characteristics and highlight the diagnostic challenges to improve identification and prevent misdiagnoses.

We report a case of successfully lateralized adrenal cortisol hypersecretion by adrenal venous sampling (AVS) and improved by surgery. AVS is a commonly used tool to guide surgical management of primary hyperaldosteronism. It can determine lateralization, leading to unilateral adrenalectomies of the correct side, or nonlateralization, which precludes surgery. The use of AVS in determining lateralization in hypercortisolism is a growing field of discussion. Currently, there is no defined or unanimous protocol behind procedural details and interpretation of results. In this report, we describe the AVS protocol at our institution for hypercortisolism, interpretation of the results, and corresponding surgical outcomes for a case of mild autonomous cortisol secretion.

Some individuals do not return to baseline health following SARS-CoV-2 infection, leading to a condition known as long COVID. The underlying pathophysiology of long COVID remains unknown. Given that autoantibodies have been found to play a role in severity of SARS-CoV-2 infection and certain other post-COVID sequelae, their potential role in long COVID is important to investigate. Here, we apply a well-established, unbiased, proteome-wide autoantibody detection technology (T7 phage-display assay with immunoprecipitation and next-generation sequencing, PhIP-Seq) to a robustly phenotyped cohort of 121 individuals with long COVID, 64 individuals with prior COVID-19 who reported full recovery, and 57 pre-COVID controls. While a distinct autoreactive signature was detected that separated individuals with prior SARS-CoV-2 infection from those never exposed to SARS-CoV-2, we did not detect patterns of autoreactivity that separated individuals with long COVID from individuals fully recovered from COVID-19. These data suggest that there are robust alterations in autoreactive antibody profiles due to infection; however, no association of autoreactive antibodies and long COVID was apparent by this assay.

Conventional plain-film radiography may be used as a screening method for various pathological conditions of the sinonasal cavities. However, CT scanning remains the study of choice for the imaging evaluation of acute and chronic inflammatory diseases of sinonasal cavities. MRI is superior to CT in differentiating inflammatory conditions from neoplastic processes. The most common complications of rhinosinusitis in children occur in the orbit. The information obtained from the CT scan and MRI, together with clinical findings, may be the best guidelines for clinical management and the mode of treatment. Although intracranial complications of sinusitis are relatively rare, prompt recognition of these disease states is important to prevent permanent neurological deficit or fatality. It is prudent to obtain MRI of the sinuses, orbits, and brain whenever extensive or multiple complications of sinusitis are suspected, in addition to CT scanning. Chronic rhinosinusitis is a clinical diagnosis, confirmed and staged with the CT scan of sinonasal cavities. Chronic inflammatory disease is often associated with mucosal thickening and sclerosis of the bone, particularly within the sinuses. Chronic extramucosal fungal sinusitis develops as a saprophytic growth in retained secretions in a sinus cavity. The imaging manifestations of chronic mycotic rhinosinusitis may be nonspecific or highly suggestive of the presence of fungal infection. The presence of diffuse increased attenuation within the paranasal sinuses and nasal cavity should be considered as chronic allergic hypersensitivity aspergillosis (chronic noninvasive aspergillosis) or chronic hyperplastic sinusitis and polyposis associated with desiccated, retained mucosal secretions. The MRI characteristics of fungal sinusitis depend on the stage of the disease.