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Chemical Senses

Oxford University Press (OUP)

Preprints posted in the last 30 days, ranked by how well they match Chemical Senses's content profile, based on 30 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

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Global practices in paediatric olfactory dysfunction: a cross-sectional survey of paediatric ENT surgeons

Spencer, G. M.; Karim, K.; Dzioba, A.; Graham, M. E.; You, P.; Hummel, T.; Gellrich, J.; Coyle, P.; Burns, H.; Peer, S.; Zawawi, F.; Lechien, J. R.; Schriever, V. A.; Bhargava, E. K.; Whitcroft, K. L.

2026-06-06 otolaryngology 10.64898/2026.06.04.26354942 medRxiv
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Background: Olfactory dysfunction (OD) in children remains underdiagnosed and poorly characterised. Despite its known impacts on nutrition, quality of life, safety awareness, and psychosocial development, no standardised diagnostic or management pathway currently exists for paediatric OD. This study aimed to characterise global practice patterns and identify diagnostic and therapeutic challenges unique to paediatric care. Methodology/Principal: A 44-item cross-sectional online survey was distributed to a verified international network of paediatric otolaryngologists across 36 countries via a closed professional platform. The survey assessed five domains: diagnostic practices, management protocols, technology and innovation, education and training, and barriers to effective care. Regional grouping was used to facilitate meaningful statistical comparisons. Categorical variables were evaluated using chi-square tests, with odds ratios and 95% confidence intervals reported for significant findings. Results: Of 351 potential participants, 167 responded (47.6% response rate). Most respondents (83%) reported seeing children with OD, yet 95% saw fewer than ten such patients annually. Psychophysical testing was never performed by 54.8% of respondents, while 88.4% routinely ordered cross-sectional imaging. Testing frequency increased significantly with patient age (Cochran's Q p<0.001). The most common barriers to objective testing were insufficient training (44.3%), time constraints (29.9%), and funding limitations (28.1%). Multidisciplinary collaboration was negligible. Significant regional variation was observed across most practice domains. Conclusions: Paediatric OD care is characterised by functional underinvestigation, fragmented multidisciplinary collaboration, and systemic educational gaps. These findings support urgent development of standardised clinical guidelines, age-appropriate validated assessment tools, and formal interdisciplinary care pathways.

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Cation Enrichment and Hypersialylation in Chronic Rhinosinusitis Mucus

Wood, A. M.; Detwiler, R. E.; Coughlin, M.; Pollard, C. E.; Alt, J. A.; Pulsipher, A.; Kramer Stratton, J.

2026-05-27 otolaryngology 10.64898/2026.05.23.26353957 medRxiv
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Background: Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory airway disease associated with impaired mucociliary clearance and persistent inflammation. While prior work has focused on inflammatory and molecular pathways, the physicochemical properties of mucus itself remain poorly characterized. This study aimed to define compositional and biophysical features of CRS mucus that may contribute to dysfunction. Methods: A prospective cross-sectional study was conducted in 15 adults undergoing endoscopic sinus surgery (11 CRS, 4 controls). Mucus was collected from the middle meatus. Hydration was measured by lyophilization. Ionic composition was quantified using mass spectrometry. Viscoelasticity was assessed via oscillatory shear rheology. Total protein, total carbohydrate, sialic acid (Sia) and fucose (Fuc) content were quantified using enzymatic and chemical assays. Statistical comparisons were performed using nonparametric tests. Results: CRS mucus exhibited significantly higher Ca2+; and Mg2+; concentrations (approximately two-fold; p<0.05) and increased variability in hydration and ion content compared to controls. Rheology showed greater heterogeneity and a non-significant trend toward increased viscoelasticity in CRS. Total protein and carbohydrate content were not significantly different; however, the carbohydrate-to-protein ratio was significantly reduced in CRS (p=0.04). Sia content and Sia-to-carbohydrate ratio were significantly elevated in CRS (p=0.04 and p=0.002), particularly in CRS with nasal polyps. Fuc content did not differ between groups. Conclusions: CRS mucus demonstrates coordinated alterations in ionic composition and glycosylation, characterized by increased cation content, hypersialylation, and reduced carbohydrate-to-protein ratios. These changes may contribute to altered mucus properties and impaired mucociliary clearance, highlighting mucus composition as a potential therapeutic target in CRS.

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Automated analysis of feeding dynamics from electromyographic recordings in a blood-sucking insect

Salas Morales, H.; Ortega-Insaurralde, I.; Armentano, M.; Monteserin, A.; Schilman, P. E.; Barrozo, R. B.

2026-05-31 zoology 10.64898/2026.05.29.728826 medRxiv
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Feeding behavior in blood-sucking insects relies on gustatory evaluation to decide on sustained ingestion, yet quantifying this process from electromyogram (EMG) recordings is labor-intensive. Here we developed MyoRec, an automated computational framework employing machine learning to analyse EMG signals from the triatomine bug Rhodnius prolixus. Using recordings under appetitive and aversive conditions, a convolutional neural network detected ingestion events with 97.7% accuracy. Automated analysis revealed distinct feeding dynamics, with prolonged ingestion and higher pumping frequency under appetitive stimuli, compared to rapid feeding cessation under aversive stimuli. MyoRec substantially reduces analysis time while maintaining accuracy, providing a scalable tool to investigate how gustatory cues modulate feeding decisions in hematophagous insects.

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Targeted mRNA restoration of ciliary function in DNAI1-related primary ciliary dyskinesia: ex vivo rescue in patient-derived nasal spheroids, A pilot study

Nygaard, C. M. T.; Herrera-Cid, C. R.; Nedergaard, L.; Johansen, S. G.; Matthews, J. G.; Couch, J. A.; Qvist, T.; Nielsen, K. G.; Christensen, S. T.; Marthin, J. K.

2026-05-28 physiology 10.64898/2026.05.26.727937 medRxiv
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RationalePrimary Ciliary Dyskinesia (PCD) is a genetic disorder characterized by impaired ciliary function, defective mucociliary clearance, and progressive lung disease. Pathogenic variants in the DNAI1 gene are a well-known cause of PCD. Currently, no approved therapies address the underlying genetic defect. RCT1100 is an inhaled mRNA therapy encoding DNAI1 currently under clinical development. This study evaluates the functional effects of RCT1100 using a fast three-dimensional explant spheroid (3DE-S) model consisting of apical-out undifferentiated nasal epithelial cells derived from patients with DNAI1 PCD. Methods3DE-S were generated from nasal brushings of five patients with confirmed biallelic DNAI1 variants. RCT1100 was administered from day 5 directly to culture wells three times weekly for two weeks. Spheroid motility was assessed throughout treatment by quantifying the proportion of moving spheroid rolling and their movement velocity. Following six doses, spheroids were harvested for high-speed video microscopy for assessment of ciliary beat frequency. ResultsEvaluable data were obtained from three of five patient samples; two samples were excluded due to contamination. After six doses of RCT1100, ciliary beat frequency increased from a baseline range of 2.8-3.5 Hz to 6.7-6.8 Hz post-harvesting. Mean spheroid movement velocity increased from 0.11 {micro}m/sec to 3.87 {micro}m/sec following dosing with 10 {micro}g/mL RCT1100, with more than 80% of spheroids exhibiting coordinated rolling motion pattern. ConclusionThe 3DE-S is a robust platform for evaluating targeted therapies. RCT1100 significantly restored ciliary function, supporting its therapeutic potential and highlighting the utility of spheroid-based systems for precision medicine approaches in DNAI1 PCD.

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Personalized multi-assay profiling of respiratory motile ciliopathies and mRNA therapy

Ithakisiou, G. N.; Cleijpool, P.; Dreyer, H. H. M.; Bosch, B. M.; Hornman, W.; Hoenselaar, D.; Tziouvelis, M.; Gerritsen, A.; Smith, M. B.; den Hertog-Oosterhoff, L. A.; Bhattacharjee, R. B.; Wang, Z.; Lombana, T. N.; Wustman, B. A.; van der Ent, C. K.; de Winter-Groot, K. M.; van Beuningen, S. F. B.; Haarman, E. G.; Paff, T.; Beekman, J. M.; Amatngalim, G. D.; Yetkin-Arik, B.

2026-05-23 cell biology 10.64898/2026.05.21.726963 medRxiv
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IntroductionImpaired motile cilia function contributes to many respiratory disorders, but therapies targeting this cellular defect are currently lacking. Personalized airway epithelial models combined with quantitative, complementary ciliary assays can pave the way for the development of such therapies. However, existing airway epithelial cultures often show variable ciliogenesis, and ciliary function is frequently assessed using a single assay that does not capture the phenotypic heterogeneity of ciliary dysfunction. Here, we established a personalized, multi-assay in vitro platform using human nasal epithelial cells (HNECs) to assess ciliary function and therapeutic response, using primary ciliary dyskinesia (PCD) as a model disease. MethodsHNECs from 8 healthy individuals and 13 individuals with PCD carrying distinct disease-associated variants were obtained by nasal brushing. Cells were differentiated under optimized conditions, including {gamma}-secretase/Notch and BMP pathway inhibitors and a low liquid-liquid interface, to generate highly ciliated 2D epithelial cultures. Ciliary function was assessed using ciliary beat frequency, bead transport, and apical-out nasal organoid rotation assays. Therapeutic rescue was assessed in HNECs harboring DNAI1 alterations using DNAI1 mRNA-loaded lipid nanoparticles. ResultsOptimized differentiation yielded reproducibly multiciliated HNEC cultures. The multi-assay platform distinguished healthy from PCD-derived HNECs and revealed individual- and genotype-specific patterns of ciliary dysfunction not captured by a single assay. Basolateral administration of DNAI1 mRNA-loaded lipid nanoparticles resulted in partial, dose-dependent recovery of ciliary function in DNAI1-deficient HNECs. ConclusionThis study establishes a standardized, individual-specific multi-assay nasal epithelial platform for functional phenotyping of motile cilia and preclinical evaluation of emerging therapies, with demonstrated utility in PCD.

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Determinants of total and inhaled allergen-specific immunoglobulin E in the middle-aged and elderly population

Al Fatly, M.; Leonard, S.; van Daele, P.; Helleman, G.; Tobari-azandeh, E.; Lahousse, L.; Veenbergen, S.; Chaker, L.

2026-05-15 allergy and immunology 10.64898/2026.05.12.26352742 medRxiv
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Background: The determinants of immunoglobulin E (IgE) remain poorly understood in older adults, a population with an increasing burden of chronic diseases. Identifying IgE's determinants may improve its clinical interpretation in the evaluation of allergic and IgE-related conditions. Objective: To investigate age, sex, smoking, alcohol, body mass index (BMI), corticosteroid use, and season as potential determinants of total IgE (tIgE) and inhaled allergen-specific IgE (sIgE). Methods: Using Rotterdam Study data, we investigated the determinants of tIgE and sIgE using multivariable linear regression. Longitudinal changes and the effects of corticosteroids were assessed with linear mixed models. Results: We included 8769 participants, of which 478 had repeated IgE measurements. Age showed a U-shaped relationship with tIgE and L-shaped relationship with sIgE (both p<0.001). Women had lower tIgE (OR [95%CI]: 0.69 [0.65-0.74]), whereas current smokers (1.34 [1.23-1.46]), higher BMI (1.01 [1.01-1.02]), topical corticosteroid users (1.27 [1.07-1.50]) and inhaled corticosteroid users (1.93 [1.64-2.26]) showed higher tIgE. Women (0.96 [0.92-1.00]), former smokers (0.87 [0.83-0.91]) and current smokers (0.72 [0.68-0.76]) had lower sIgE, whereas topical corticosteroid users (1.20 [1.07-1.35]) and inhaled corticosteroid users (1.20 [1.07-1.35]) showed higher sIgE. Over time, tIgE and sIgE decreased (p<0.001) but did not significantly change after corticosteroid use. Conclusion: We identified age, sex, smoking, BMI, season and topical and inhaled corticosteroids as determinants of tIgE and sIgE. Incorporating these determinants may improve IgE's clinical interpretation for the diagnosis and management of allergic and IgE-related conditions. Future research should investigate how these determinants shape IgE's relationship with chronic diseases in aging populations.

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Application of modern mathematical methods for species discrimination in the water fleas (Cladocera: Branchiopoda) that appear similar to the human eye: case of Bosmina (Bosmina) longirostris (O.F. Muller, 1776) from European Eurasia and Sakhalin Island

Garibian, P.; Rubleva, V.; Burlakov, A.; Valeyev, V.; Kasatkina, A.; Kirova, V.

2026-05-22 zoology 10.64898/2026.05.20.726562 medRxiv
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Intraspecific morphological variability presents a complex challenge for biological systematics and biomonitoring, particularly for organisms with high phenotypic plasticity, such as zooplankton. Morphological differences between individuals of the water flea species Bosmina longirostris (Crustacea: Cladocera) are difficult to distinguish visually, parthenogenetic females look morphologically uniform within the species; nevertheless, they demonstrate differences attributable to their geographic origin and developmental stage. A reference dataset of microscopic images was created for the study, including populations from two geographically separated regions (seven ones from European Russia and seven ones from Sakhalin Island in the Pacific Ocean (Far East of Russia) and two age groups, demonstrating the ability of a neural network classify to successfully the intraspecific morphological variation. This study demonstrates that deep learning methods are prospective for the detection and understanding of fine morphological intraspecific differences in the cladocerans.

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Mu-opioid receptor expression across cell-type specific afferents to the ventral tegmental area in male mice.

Hohmeister, M.; Culver, O. P.; Jhou, T.

2026-05-23 neuroscience 10.64898/2026.05.21.726769 medRxiv
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The addictive properties of opioids are due in part to these drugs ability to alter ventral tegmental area (VTA) activity via activation of mu opioid receptors (MORs) on local and distal inputs. Prior studies have identified numerous opioid-modulated afferents to the VTA, some of which show differing levels of functional modulation by opioids, but the degree to which this parallels differences in receptor expression is not known. Hence, we used retrograde labeling combined with RNAscope to examine oprm1 mRNA expression in VTA-projecting afferents arising from a variety of distal brain regions. Because opioids are thought to be particularly influential on GABAergic afferents to the VTA, we also examined colocalization of oprm1 with GABAergic markers in VTA-projecting neurons. Interestingly, we found that oprm1 mRNA is present in both GABAergic and non-GABAergic VTA-projecting neurons. However, many (though not all) GABAergic afferents expressed higher levels of oprm1 compared to most non-GABAergic afferents (especially those arising from the cortex). These results complement previous anatomical studies that had examined oprm1 expression in these regions but in a non-quantitative way and without regard to their efferent targets. Our findings encourage future work to examine the functional implications of MOR sensitivity within these afferent pathways.

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Aqp1aa and Aqp4a mediate collecting duct water permeability in a marine teleost

Watanabe, E.; Ota, C.; Imaizumi, G.; Sakamoto, Y.; Suzuki, Y.; Kato, A.

2026-05-19 physiology 10.64898/2026.05.16.725598 medRxiv
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Regulation of water permeability in the collecting duct is important for osmoregulatory acclimation in teleost fish. In hyperosmotic environments such as seawater (SW), the teleost kidney functions as a site of divalent ion excretion. The collecting ducts reabsorb Na+, Cl-, and water, thereby reducing urine volume and producing small amounts of isotonic urine with high concentrations of divalent ions. In hypoosmotic environments such as freshwater (FW) or low-salinity brackish water (BW), the kidney produces large volumes of hypotonic urine and serves as a site of water excretion; under these conditions, the collecting ducts reabsorb Na+ and Cl- but not water. To identify aquaporins (Aqps) involved in regulating water permeability in the collecting ducts of teleosts, we analyzed renal Aqp expression in a euryhaline marine fish, the Japanese pufferfish (Takifugu rubripes), which possesses 16 Aqp genes in its genome, seven of which (Aqp1aa, 1ab, 3a, 4a, 7, 8bb, and 11a) are expressed in the kidney. Quantitative RT-PCR analysis showed that Aqp1aa and Aqp4a were highly expressed in collecting duct tissues, and that Aqp1aa expression was markedly reduced in fish acclimated to BW. Immunohistochemistry revealed apical localization of Aqp1aa and basolateral localization of Aqp4 in collecting duct cells, with apical Aqp1aa downregulated in BW. These results suggest that Aqp1aa and Aqp4 mediate water reabsorption in SW and that downregulation of Aqp1aa contributes to hypotonic urine production in BW. NEW & NOTEWORTHYRegulation of water permeability in the collecting duct is important for osmoregulation in teleost fish. Expression analyses of aquaporins (Aqps) in the marine pufferfish Takifugu rubripes showed that Aqp1aa and Aqp4a are highly expressed in the collecting duct and localized to the apical and basolateral membranes, respectively. Renal Aqp1aa expression was markedly reduced in fish acclimated to hypoosmotic brackish water. These results indicate that collecting duct water permeability is regulated by Aqp1aa expression.

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Mast cell score associates with wide-spread mast cell symptoms and comorbidities in patients with hEDS and HSD

Wilson, F. C.; Zangerle, D. J.; Rozen, L. E.; Fliess, J. J.; Darakjian, A. A.; Sacco, K. A.; Hamilton, C.; Strandes, M. W.; Puls, A. M.; Hartmoyer, C. J.; Witola Reyes, S. N.; Menton, S. M.; Dudenkov, D. V.; Gonzalez-Estrada, A.; Solomon, S. C.; Stephens, I.; Wang, B. W. E.; Atwal, P. S.; Shufelt, C. L.; Botella, R. M.; Zeman, A. M.; Knight, D. R. T.; Gajarawala, S. N.; Bruno, K. A.; Fairweather, D.

2026-06-02 allergy and immunology 10.64898/2026.05.31.26354552 medRxiv
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Background: Wide-spread mast cell (MC)-associated symptoms and MC activation syndrome (MCAS) are often reported in patients with hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). The goal of this study was to develop a novel MC score based on 11 self-reported MC-related conditions with clinical and research utility to better understand MC symptoms in hEDS and HSD patients. Methods: From November 1, 2019, to June 13, 2025, patients (n=2,141) filled out an Intake Questionnaire at the Mayo Clinic Florida EDS Clinic that included 11 self-reported questions related to categories of MC-related conditions for a MC score ranging from 0/11 to 11/11. Based on the MC score distribution in hEDS and HSD patients, a MC score of 0-1 was considered a low MC score and [&ge;]5 was considered a high MC score. Symptoms/comorbidities were compared between patients with high vs. low MC scores. Results: From the 2,141 hEDS/HSD patients, 535 (25.0%) had a MC score [&ge;]5 (Hi MC). MCAS-specific symptoms such as nausea and vomiting were reported more often in hEDS/HSD patients with a high vs. low MC score (p<0.0001). Random clinical blood tryptase and urinary MC markers were not elevated in patients with high MC scores (n=50/group), although high MC scores were found to significantly reduce urinary creatinine levels indicating that the protein used to normalize data was affected by MC activity. In contrast, random blood IgE, tryptase and major basic protein (MBP) by ELISA were increased in patients with high MC scores (e.g., IgE hEDS p=0.0004, HSD p=0.003). Of note, the percentage of patients reporting abuse or post-traumatic stress disorder was nearly doubled in patients with high vs. low MC scores (Abuse and PTSD: hEDS p < 0.0001; HSD p < 0.0001). Overall, 109/135 (80.7%) in hEDS and 129/135 (95.6%) in HSD reported more symptoms/comorbidities if they had a high MC score. Conclusions: We found that hEDS/HSD patients with high MC scores self-reported more widespread symptoms/comorbidities and higher MC-related blood markers than patients with low MC scores indicating the utility of this tool to evaluate the level of widespread MC activity in hEDS, HSD and other patients.

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Compatibility of National Food Composition Databases with USDA FoodData Central: A Seven-Country LLM-Based Analysis

Nakagawa, S.; Yamamoto, A.

2026-06-01 nutrition 10.64898/2026.05.23.26353942 medRxiv
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To evaluate the international interoperability of food composition databases, we assessed the compatibility of seven national food composition tables with USDA FoodData Central (FDC) using the LLM-based matching method reported previously (Nakagawa and Yamamoto, 2026). Databases from four English-speaking countries (Canada, United Kingdom, Australia, and New Zealand), South Korea, and Japan were compared with 8,158 USDA FDC entries (SR Legacy and Foundation Foods, excluding Survey/FNDDS). Match rates varied by country (62.0-89.7%) and food category. After excluding six USDA categories unsuitable for cross-national comparison, 45.2% of the remaining 6,290 entries were not matched by any country. Canada showed the highest concordance, reflecting shared North American food supply. Japan and South Korea showed similar low coverage for vegetables and spices. These findings suggest that while USDA FDC represents a practical foundation for a globally comprehensive food composition database given its breadth, systematic incorporation of country-specific foods and classification schemes will be necessary to achieve true international interoperability.

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Stereotaxic targeting of the Dorsal Vagal Complex

Robar, B.; Smith, H. E.; Heisler, L. K.; Filippi, B. M.; Martinez de Morentin, P. B.

2026-06-04 neuroscience 10.64898/2026.06.01.729222 medRxiv
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The Dorsal Vagal Complex (DVC) is a critical brainstem relay for visceral sensory information, sympathetic regulation, and gut-brain communication. Current weight-reducing pharmacotherapies are reported to target this brainstem region to elicit their main satiety actions. Despite its importance, no published step-by-step protocol exists for stereotaxic targeting of this region in rodents. Here, we present a detailed protocol for bilateral administration of substances into the DVC of mice using the atlanto-occipital membrane approach. We describe the surgical access, obex-referenced coordinate system, injection parameters, and we provide a histological validation. This protocol is useful for the study of DVC cells and efferent and afferent neuronal DVC circuits using common neuroscience tools such as tracings, optogenetics or chemogenetics. For complete details on the use and execution of this protocol, please refer to Martinez de Morentin et al.(Martinez De Morentin et al., 2024)

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Rental housing may contribute to racial and ethnic disparities in upper respiratory infections

Bhavnani, D.; Dunphy, P.; Wilkinson, M.; Haber, A. L.; Matsui, E. C.

2026-05-17 epidemiology 10.64898/2026.05.13.26351511 medRxiv
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Objective: Upper respiratory infections (URI) are the major trigger of asthma exacerbations in children with asthma and are more likely to be reported by Black and Mexican American children compared to White children in the US. We aimed to evaluate the extent to which obesity, nicotine exposure, household size, and socioeconomic status (SES) explained this excess URI risk among all children and among children with asthma. Study Design: Data collected on children aged 6-17 years from the National Health and Nutritional Examination Survey (2007-2012) were analyzed using survey weights and a mediation approach. Household SES was analyzed as a cumulative score reflecting income poverty ratio, education, and rental housing. URI was defined as cough, cold, phlegm, runny nose, or other respiratory illness (excluding hay fever and allergies) in the past 7 days. Results: Obesity and serum cotinine, a marker of nicotine exposure, explained little to none of the excess risk of URI while SES explained 36.4% (95% CI=34.1, 38.6) in Black and 28.5% (95% CI=26.7, 30.5) in Mexican American children. Living in rental housing and income poverty ratio<2, explained half (49.6%, 95% CI=46.9-52.3) and 20% (19.7%, 95% CI=18.9-20.5) of the excess URI risk among Black children, respectively. In Mexican American children, rental housing and low educational attainment each explained approximately 15-17% of the excess URI risk. Results were comparable among children with asthma. Conclusions: Markers of poverty, such as rental housing, contributed substantially to the excess risk of URI among Black and Mexican American children, including among those with asthma.

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Functional characterization and classification of mechanosensitive bladder afferents

Manrique-Maldonado, G.; Sun, X.; Daugherty, S. L.; Beckel, J. M.; Carattino, M. D.

2026-06-01 physiology 10.64898/2026.05.27.728257 medRxiv
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Normal urinary bladder function relies on afferent fibers that detect and integrate mechanical and chemical cues related to bladder distension. Though, the molecular identity and function of the various sensory neuron types involved in bladder function have yet to be fully elucidated. Here, we introduce a novel framework for the functional classification of mechanosensitive bladder afferents based on their differential responses to physiological (15 l/min) and noxious filling (30 s at intravesical pressures of 10, 20, 30, 40, 50, and 60 cmH2O). Our data reveal the presence of three distinct types of mechanosensitive bladder afferents, two that respond to physiological distension (type I and II) and one that is activated by noxious stimulation (type III). Of the two populations that respond to physiological filling, one displays a linear increase in firing with bladder filling (type I), while the firing of the other plateaus as intravesical pressure increases (type II). Fast filling (130 l/min) increases the discharge of all three afferent types, with the effect being most pronounced in those responding to noxious stimulation (type III). Corroborating the existence of three functionally distinct bladder afferent populations, Yoda1, a selective PIEZO1 channel activator, significantly increased the firing rate of types I and III during slow filling and of type III during noxious stimulation. In summary, we present a reliable and reproducible method for studying and classifying bladder afferents, while providing compelling evidence for the existence of functionally distinct populations of mechanosensitive afferents, each activated and regulated by distinct mechanisms. New & NoteworthyUsing a novel approach, we identify three types of mechanosensitive afferents innervating the urinary bladder, two that respond to slow filling and one that is activated only by noxious distension. The three afferent types display distinct firing patterns during rapid filling and in response to the PIEZO1 channel agonist Yoda1.

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A Comprehensive, Low-Cost Multistation ENT Simulation Curriculum for Medical Students: Five Reproducible Task Trainers for Foundational Otolaryngology Skills

Jefferies, T. J.; LaVigne, M. K.

2026-05-21 medical education 10.64898/2026.05.18.26353510 medRxiv
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Introduction: Early exposure to otolaryngology (ENT) procedural skills in undergraduate medical education is limited by patient safety concerns, restricted clinical opportunities, and the cost of commercial simulators. As a result, essential ENT skills are often underrepresented in structured, hands-on curricula for medical students. Methods: We developed a low-cost, multistation ENT simulation curriculum consisting of five reproducible task trainers: ear examination and otologic procedures, mirror laryngoscopy, rigid and flexible endoscopic navigation, introductory mastoid drilling, and emergency cricothyrotomy. The curriculum was delivered as a 2-hour, faculty-led workshop during a third-year medical student otolaryngology rotation. Learners rotated through stations in small groups. Pre- and post-workshop surveys assessed self-reported anatomical familiarity, procedural confidence, and educational value using a 5-point Likert scale, with additional qualitative feedback collected. Results: All participants completed pre- and post-workshop evaluations. Learners demonstrated increased confidence across all assessed anatomical and procedural domains, including otoscopy, endoscopy, mirror laryngoscopy, mastoid drilling orientation, and cricothyroid membrane identification. Educational value ratings were high across all stations, with mean scores ranging from 4.33 to 5.00. Qualitative feedback emphasized the realism, accessibility, and benefit of hands-on practice in a low-stakes learning environment. Conclusion: This low-cost, multistation ENT simulation curriculum provides a feasible and reproducible approach for introducing foundational otolaryngology skills to medical students. The structured format and affordable models support early procedural exposure and may enhance learner preparedness prior to supervised clinical encounters, particularly in settings with limited simulation resources.

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Fecal untargeted metabolomic and short-chain fatty acid analyses in cats with chronic kidney disease

Schmidt, T.; Quimby, J.; Whitehouse, W. H.; Aronson, L.; Suchodolski, J. S.; Li, Q.

2026-05-14 molecular biology 10.64898/2026.05.12.724333 medRxiv
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BackgroundThe gut-kidney axis plays a direct role in gastrointestinal and kidney health. Gut-derived metabolites like uremic toxins are associated with the pathophysiology of feline chronic kidney disease (CKD). The aim of the study was to identify novel fecal biomarkers and investigate the roles of gastrointestinal metabolites in feline CKD. ResultsFecal samples from 41 healthy non-CKD (control) and 67 CKD cats, including 5 IRIS stage 1 (CKD1), 37 stage 2a (CKD2a), 18 stage 2b (CKD2b), and 7 stage 3 (CKD3), were subject to fecal untargeted metabolomics and targeted short-chain fatty acid (SCFA) analyses. Multiple linear regression, adjusted for sex, age, body weight and study site, identified 64 differential metabolites between control and across CKD groups (P<0.0001 and FDR<0.10). Approximately 65% of the metabolites were lipids, including polyunsaturated long-chain fatty acids, acylcarnitines, and ceramides. Random Forest algorithm selected N1-methyl-2-pyridone-5-carboxamide (2PY), a uremic toxin from nicotinamide catabolism, as the top fecal marker for classifying feline CKD. Fecal 2PY was increased in CKD1 (P = 0.03), CKD2a, CKD2b, and CKD3 (all P<0.0001) compared to the controls. Data mining revealed serum concentration of 2PY was significantly increased with severity of CKD in cats, possibly due to impaired renal excretion. Cholesterol and arachidonic acid, markers for enterocyte shedding and inflammation, were increased in CKD3 versus control (both P<0.05). In healthy non-CKD cats, evident suggested fecal lipids increased with age (P<0.0001), and were higher in females versus males (P<0.0001). While fecal indole and p-cresol were increased in CKD3 versus control (both P<0.05), no change was observed in indoxyl sulfate (IS) or p-cresol sulfate (PCS). Fecal indole-3-acetic acid (IAA) was decreased in several CKD groups compared to the controls (all P<0.05). Finally, two branched SCFAs, isobutyrate and isovalerate, were increased in CKD3 versus control (both P<0.05). ConclusionsThe study revealed 2PY as a novel marker and unveiled profound alterations in intestinal lipid compositions with a potential link to gut barrier integrity and inflammation in CKD.

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Inhibition of TYK2 attenuates hyper IL-6- and Oncostatin M-mediated Calcium Signalling in Sensory Neurons

Pritchard, T. A.; Gupta, R.; Higham, J.; Aziz, Q.; Bulmer, D.

2026-05-19 neuroscience 10.64898/2026.05.15.725418 medRxiv
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Inflammatory bowel disease (IBD) is characterised by chronic pain, a debilitating symptom for which effective treatments are few and far between. IBD pathogenesis includes the prevalence of a variety of pro-inflammatory cytokines, including the Interleukin-6 (IL-6) family members Il-6 and Oncostatin M (OSM). Previous research has shown disruption of OSM signaling can modulate nociceptor sensitization and activation, however the downstream signalling pathway is unknown. When an in silico analysis of murine colonic sensory neuronal populations was undertaken for receptor expression for OSM and other factors necessary for intracellular signaling, we can find diverse expression indicative of functional signaling. We were able to observe that hyper Il-6 (Il-6 bound to the soluble Il-6 receptor) and OSM can elicit activation of a subset of murine sensory neurons by finding an increase in calcium mobilization following superfusion. This could then be attenuated by the pharmacologic inhibition of all janus kinases or interestingly, TYK2 alone. Furthermore, inhibition of transient receptor potential vanilloid 1 or transient receptor potential ankyrin 1 ion channels, which are known to be sensitized by OSM in other sensory neurons also reduced the proportion of OSM-responsive neurons. This further understanding of OSM signaling in sensory neurons creates avenues for more extensive research into the molecular mechanisms occurring as well as the potential to exploit these therapeutically to induce analgesia in a subset of neurons.

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Case-level artificial intelligence for multi-photo teledermatology submissions: development and internal validation using patient-submitted dermatology images

Patel, V. P.; Sheth, N.; Patel, A.; Patel, Y.

2026-06-01 dermatology 10.64898/2026.05.21.26353816 medRxiv
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Background: Store-and-forward teledermatology commonly relies on several patient-submitted photographs of the same concern, but most dermatology artificial intelligence models classify single images independently. Objective: To develop and internally validate a case-level diagnostic-support model that aggregates multiple patient-submitted photographs for common dermatologic conditions. Methods: We conducted a retrospective diagnostic-modeling study using the Skin Condition Image Network, a public dataset of deidentified self-taken dermatology images from US adults. We curated 2,336 cases comprising 5,041 images across 10 common inflammatory, allergic, and infectious conditions. Cases were split at the submission level into training, validation, and held-out test sets. Frozen general-purpose and dermatology-specific encoders were compared with image-level classifiers and a gated-attention multiple instance learning model that generated one case-level output from 1-3 images. Results: The strongest image-level baseline, dermatology-specific embeddings with random forest classification, achieved macro/micro ROC-AUCs of 0.797/0.854. Case-level aggregation improved discrimination, with dermatology-specific embeddings plus multiple instance learning achieving mean macro/micro ROC-AUCs of 0.819/0.863 across repeated stratified experiments. The locked final model achieved macro/micro ROC-AUCs of 0.800/0.849 on the held-out test set. Balanced-threshold sensitivity/specificity examples were 0.702/0.688 for eczema and 0.818/0.826 for urticaria. Limitations: Internal validation used a 10-condition subset from a US volunteer dataset; external validation, calibration, subgroup performance analysis, and prospective workflow studies are required. Conclusion: Modeling the teledermatology submission as a multi-image case better reflects asynchronous dermatology workflow than single-image classification. The model is preliminary clinician-facing support for structured review and triage, not autonomous diagnosis.

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Association Between Purchase of Organic Food and Hypertension Among US Adults: NHANES 2007-2010

Choi, C.; Nianogo, R. A.; Chen, L.; Arah, O. A.

2026-05-17 epidemiology 10.64898/2026.05.13.26353146 medRxiv
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Background: An increasing demand for organic food has risen due to perceived health benefits. Current evidence for the health effects of organic food is limited. Objective: To evaluate the association between organic food purchase as a proxy for organic food consumption and hypertension in a nationally representative population of the US. Methods: This was a cross-sectional study that included 9173 participants aged >= 18 and had available data of both organic food purchase and hypertension from the National Health and Nutrition Examination Survey 2007-2010. Organic food purchase and frequency were obtained from survey questionnaires. Hypertension was defined as having either a systolic BP >= 130 mm Hg/ diastolic BP >= 80 mm Hg, currently taking antihypertensive medication, or self-reported diagnosis of hypertension. We used multivariable logistic regression with sample weights and adjustment of potential confounders to assess associations (adjusted odds ratio [aOR] and 95% confidence intervals [CI]) between organic food purchase and hypertension status. Results: Findings suggest an 11% decrease in odds of hypertension (aOR = 0.89, 95% CI: 0.75-1.06) among organic food purchasers compared to non-purchasers. Lower odds of hypertension were observed across all categories of organic food purchasing frequency, with 13% lower among rarely purchasing organic food (aOR = 0.87, 95% CI: 0.67-1.14), 9% lower (aOR = 0.91, 95% CI: 0.71-1.16) among sometimes purchasing organic food, and 17% lower (aOR = 0.83, 95% CI: 0.55-1.27) among always or mostly purchasing organic food, as compared to those who never purchased organic food. Conclusion: Our findings suggest that organic food purchase, a proxy for organic food consumption, may be associated with lower odds of hypertension. These findings may reflect either the true benefits of organic food consumption, including lower pesticide amounts and higher nutrient content, or the health-seeking behaviors among health-conscious, healthy, and highly educated individuals.

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Assessing the reliability of immunofluorescence image analysis with artificial intelligence

Bertin, D.; Bongrand, P.; Bardin, N.

2026-05-18 allergy and immunology 10.64898/2026.05.10.26352837 medRxiv
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In view of the outstanding progress of machine learning (ML) and growing cost of health systems, it is a current challenge to incorporate artificial intelligence tools into actual medical practice. Here we explored the feasibility and reliability of using machine learning to perform an important immunological investigation that currently requires experienced biologists : Anti-nuclear cytoplasmic antibodies (ANCAs) are important markers for vasculitis and they may be evidenced by microscopic examination of cells labeled with patients' sera. The use of a reliable ML classifier to discriminate between positive and negative samples would increase the rapidity and decrease the cost of immunofluorescence-based ANCA detection. Here, we tested seven well-documented ML algorithms, ranging from simple models such as k nearest neighbors to more complex convolutional neural networks involving millions of adjustable parameter. We studied the feasibility and reliability of classifying 1114 serum samples that had been collected for about 3 years and assayed with conventional procedure. We compared four strategies consisting of assaying either whole microscope fields or individual cell images, and natural images or histograms. The following conclusions were obtained : (i) Several different strategies allowed us to build models stable enough to discriminate between positive and negative samples collected during about 27 months, with a comparison to human classification yielding a kappa index of about 0.7, that may be considered as fairly good and intermediate between the performance of junior and senior biologists. (ii) Simpler ML models combined with theoretical thinking might provide the most rapid and efficient way of developing a reliable test within the framework of a single institution. (iii) In addition, the interpretability of the simplest model provided some theoretical insight into important classification parameters. (iv) An important point and caveat is that the multiplicity and versatility of currently available tools make it an essential requirement to test repeatedly a given model, that must be chosen as simple as possible, to achieve a reliability compatible with medical use. It is concluded that our study provides a strong incentive to incorporate ML tools in well defined medical tests, which might reduce the risk of human errors and pave the way to fully automatic procedures.