Precise Fabrication and Manipulation of Individual Polymer Nanofibers.

Polymer nanofibers hold promise in a wide range of applications owing to their diverse properties, flexibility, and cost effectiveness. In this study, we introduce a polymer nanofiber drawing process in a scanning electron microscope and focused ion beam (SEM/FIB) instrument with in situ observation. We employed a nanometer-sharp tungsten needle and prepolymer microcapsules to enable nanofiber drawing in a vacuum environment. This method produces individual polymer nanofibers with diameters as small as ∼500 nm and lengths extending to millimeters, yielding nanofibers with an aspect ratio of 2000:1. The attachment to the tungsten manipulator ensures accurate transfer of the polymer nanofiber to diverse substrate types as well as fabrication of assembled structures. Our findings provide valuable insights into ultrafine polymer fiber drawing, paving the way for high-precision manipulation and assembly of polymer nanofibers.

Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Polyomavirus-positive Merkel cell carcinoma: the beginning of the beginning.

Merkel cell carcinoma (MCC) is an aggressive, fast-growing, highly metastatic neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is an oncogenic driver in the majority of MCC tumors. In this issue of the JCI, Hansen and authors report on their tracking of CD8+ T cells reactive to MCPyV T antigen (T-Ag) in the peripheral blood of 26 patients with MCC who were undergoing frontline anti-programmed cell death protein-1 (anti-PD-1) immunotherapy. They discovered unique T cell epitopes and used the power of bar-coded tetramers to portray immune checkpoint inhibitor-induced immunogenicity as a predictor of clinical response. These findings provide the foundation for therapeutic possibilities for MCC, including vaccines and adoptive T cell- and T cell receptor-driven (TCR-driven) treatments.

Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit. CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.

Pharmacodynamic effects following co-administration of cannabinoids and opioids: A scoping review of human experimental studies.

BACKGROUND: Cannabinoids are increasingly used in the management of chronic pain. Although analgesic potential has been demonstrated, cannabinoids interact with a range of bodily functions that are also influenced by chronic pain medications, including opioids. OBJECTIVE: We performed a scoping review of literature on the pharmacodynamic effects following co-administration of cannabinoids and opioids. METHODS: We systematically searched EMBASE, PubMed, and PsycINFO for studies that experimentally investigated the co-effects of cannabinoids and opioids in human-subjects. Available evidence was summarized by clinical population and organ system. A risk of bias assessment was performed. RESULTS: A total of sixteen studies met inclusion criteria. Study populations included patients with chronic non-cancer and cancer pain on long-term opioid regimens and healthy young adults without prior exposure to opioids who were subject to experimental nociceptive stimuli. Commonly administered cannabinoid agents included Δ9-tetrahydrocannabinol and/or cannabidiol. Co-administration of cannabinoids and opioids did not consistently improve pain outcomes; however, sleep and mood benefits were observed in chronic pain patients. Increased somnolence, memory and attention impairment, dizziness, gait disturbance, and nauseousness and vomiting were noted with co-administration of cannabinoids and opioids. Cardiorespiratory effects following co-administration appeared to vary according to duration of exposure, population type, and prior exposure to cannabinoids and opioids. CONCLUSIONS: The available evidence directly investigating the pharmacodynamic effects following co-administration of cannabinoids and opioids for non-analgesic outcomes is scarce and suffers from a lack of methodological reporting. As such, further research in this area with comprehensive methodologic reporting is warranted.

Relationship between maternal arterial and foetal cord carbon dioxide tension and neonatal outcome in critically ill pregnant women at delivery.

Background and Aims: No studies have evaluated the relationship between maternal arterial partial pressure of carbon dioxide (mPaCO2) and umbilical cord venous partial pressure of carbon dioxide (PCO2) in critically ill pregnant women at delivery. Based on the studies in healthy pregnant women, an mPaCO2 target of ≤50 mmHg is a suggested threshold during mechanical ventilation in critically ill parturients. We evaluated the relationship between mPaCO2 and neonatal cord gases in critically ill parturients at delivery as the primary objective. The relationship between mPaCO2 and APGAR scores at delivery was also analysed as a secondary objective. Methods: Maternal and neonatal cord gas data at delivery and APGAR scores were obtained by a retrospective chart review of 25 consecutive parturients with severe respiratory compromise who were delivered during mechanical ventilation. Linear regression was used to assess the relationship between mPaCO2 and umbilical artery and vein PCO2 and between mPaCO2 and APGAR scores at 1 and 5 min. Results: There was a positive correlation between mPaCO2 and neonatal cord venous PCO2 (P = 0.013). Foetal venous PCO2 exceeded predelivery mPaCO2 by 17.5 (7.5) mmHg. There was an inverse relationship between mPaCO2 and neonatal APGAR scores at 1 and 5 min (P = 0.006 and P = 0.007, respectively). Conclusion: Foetal cord venous PCO2 can be predicted if mPaCO2 values are known. Unlike in healthy pregnant women, there was an inverse relationship between rising mPaCO2 levels and neonatal APGAR scores in critically ill pregnant women who had several associated compounding factors.

GABAergic interneurons contribute to the fatal seizure phenotype of CLN2 disease mice.

GABAergic interneuron deficits have been implicated in the epileptogenesis of multiple neurological diseases. While epileptic seizures are a key clinical hallmark of CLN2 disease, a childhood-onset neurodegenerative lysosomal storage disorder caused by a deficiency of tripeptidyl peptidase 1 (TPP1), the etiology of these seizures remains elusive. Given that Cln2 R207X/R207X mice display fatal spontaneous seizures and an early loss of several cortical interneuron populations, we hypothesized that those two events might be causally related. To address this hypothesis, we first generated an inducible transgenic mouse expressing lysosomal membrane-tethered TPP1 (TPP1LAMP1) on the Cln2 R207X/R207X genetic background to study the cell-autonomous effects of cell-type-specific TPP1 deficiency. We crossed the TPP1LAMP1 mice with Vgat-Cre mice to introduce interneuron-specific TPP1 deficiency. Vgat-Cre ; TPP1LAMP1 mice displayed storage material accumulation in several interneuron populations both in cortex and striatum, and increased susceptibility to die after PTZ-induced seizures. Secondly, to test the role of GABAergic interneuron activity in seizure progression, we selectively activated these cells in Cln2 R207X/R207X mice using Designer Receptor Exclusively Activated by Designer Drugs (DREADDs) in in Vgat-Cre : Cln2 R207X/R207X mice. EEG monitoring revealed that DREADD-mediated activation of interneurons via chronic deschloroclozapine administration accelerated the onset of spontaneous seizures and seizure-associated death in Vgat-Cre : Cln2 R207X/R207X mice, suggesting that modulating interneuron activity can exert influence over epileptiform abnormalities in CLN2 disease. Taken together, these results provide new mechanistic insights into the underlying etiology of seizures and premature death that characterize CLN2 disease.

A role for δ subunit-containing GABA A receptors on parvalbumin positive neurons in maintaining electrocortical signatures of sleep states.

GABA A receptors containing δ subunits have been shown to mediate tonic/slow inhibition in the CNS. These receptors are typically found extrasynaptically and are activated by relatively low levels of ambient GABA in the extracellular space. In the mouse neocortex, δ subunits are expressed on the surface of some pyramidal cells as well as on parvalbumin positive (PV+) interneurons. An important function of PV+ interneurons is the organization of coordinated network activity that can be measured by EEG; however, it remains unclear what role tonic/slow inhibitory control of PV+ neurons may play in shaping oscillatory activity. After confirming a loss of functional δ mediated tonic currents in PV cells in cortical slices from mice lacking Gabrd in PV+ neurons (PV δcKO), we performed EEG recordings to survey network activity across wake and sleep states. PV δcKO mice showed altered spectral content of EEG during NREM and REM sleep that was a result of increased oscillatory activity in NREM and the emergence of transient high amplitude bursts of theta frequency activity during REM. Viral reintroduction of Gabrd to PV+ interneurons in PV δcKO mice rescued REM EEG phenotypes, supporting an important role for δ subunit mediated inhibition of PV+ interneurons for maintaining normal REM cortical oscillations. Significance statement: The impact on cortical EEG of inhibition on PV+ neurons was studied by deleting a GABA A receptor subunit selectively from these neurons. We discovered unexpected changes at low frequencies during sleep that were rescued by viral reintroduction.

Alpha-1 Antitrypsin Phenotyping: An Unmet Educational Need of Healthcare Providers.

Background: Diagnosing alpha-1 antitrypsin deficiency (A1ATD) involves two-step laboratory testing, determination of serum alpha-1 antitrypsin (A1AT) level and phenotyping if A1AT < 100 mg/dL. Whether these guidelines are effectuated in clinical practice is uncertain. To begin to address this issue, we determined whether A1AT phenotyping is performed in patients with serum A1AT 57 - 99 mg/dL at our institution. Methods: We reviewed the medical records of patients seen at Jesse Brown Veterans Affairs Medical Center from January 2019 to October 2022 with serum A1AT between 57 and 99 mg/dL. In each case, pertinent demographic, clinical, and pulmonary function tests data were extracted. Data were presented as means and standard deviation (SD) where appropriate. The Student's t-test was used for statistical analysis. P < 0.05 was considered statistically significant. Results: Thirty patients (90% males; 60 ± 18 years) with serum A1ATD < 100 mg/mL were identified. Fourteen were African Americans, four Hispanics, and 12 non-Hispanic Whites. The majority were current or ex-smokers. Fourteen (47%) patients had lung disease, 14 (47%) liver disease and one had concomitant lung and liver diseases. Mean ± SD forced expiratory volume in 1 s (FEV1) and lung diffusing capacity were 2.57 ± 1.41 L (67±19% predicated) and 18.7 ± 10 mL/min/mm Hg (64±28% predicted), respectively. Only 13 patients (43%) underwent phenotype testing (seven African Americans, five Whites, and one Hispanic). Six patients had MZ phenotype, four MS, and three SZ. One patient died from acute respiratory failure during the study period. Conclusions: Phenotyping of patients with serum A1AT 57 - 99 mg/dL at our institution is inadequate. Accordingly, regular continuous medical educational programs on A1AT phenotyping targeting healthcare providers are warranted.

Ligation of the Intersphincteric Fistula Tract as an Emergency Treatment for Cryptoglandular Anal Fistula.

Introduction: Ligation of the intersphincteric fistula tract (LIFT) is a sphincter-preserving procedure for treating anal fistula of cryptoglandular origin. Our prospective study aimed to determine the postoperative outcomes of patients undergoing LIFT in emergency and elective settings. Methods: This was a single-centre prospective observational study of the LIFT procedure for the treatment of anal fistulas. The differences in the 6-month postoperative outcomes between the emergency and elective procedures were analysed, including the healing rate, healing time, recurrence rate, recurrence time, postoperative complications and length of hospital stay. Results: Twenty-two patients were recruited for this study: 11 patients underwent LIFT as an emergency procedure (EM-LIFT), while the others underwent LIFT as an elective procedure (EL-LIFT). The healing rate for the EM-LIFT group was 90.9% (n = 10), with a median healing time of 2 months (range 0.5-4). For the EL-LIFT group, the healing rate was 100% (n = 11), with the same median healing time of 2 months (range 0.5-4). Two of the patients in the EM-LIFT group developed recurrence, with a median recurrence time of 5 months (range 4-6) and three developed recurrence in the EL-LIFT group, with the same median recurrence time of 5 months (range 4-6). There were minor postoperative complications of pain and subcutaneous infection, with no faecal incontinence. There was no statistically significant difference in postoperative outcomes between the groups. Conclusion: EM-LIFT is a feasible and safe primary procedure for active cryptoglandular-type anal fistulas.

Periodic and aperiodic changes to cortical EEG in response to pharmacological manipulation.

Cortical electroencephalograms (EEGs) may help understanding of neuropsychiatric illness and new treatment mechanisms. The aperiodic component (1/f) of EEG power spectra is often treated as noise, but recent studies suggest that changes to the aperiodic exponent of power spectra may reflect changes in excitation/inhibition balance, a concept linked to antidepressant effects, epilepsy, autism, and other clinical conditions. One confound of previous studies is behavioral state, because factors associated with behavioral state other than excitation/inhibition ratio may alter EEG parameters. Thus, to test the robustness of the aperiodic exponent as a predictor of excitation/inhibition ratio, we analyzed video-EEG during active exploration in mice of both sexes during various pharmacological manipulations with the fitting oscillations and one over f (FOOOF) algorithm. We found that GABAA receptor (GABAAR)-positive allosteric modulators increased the aperiodic exponent, consistent with the hypothesis that an increased exponent signals enhanced cortical inhibition, but other drugs (ketamine and GABAAR antagonists at subconvulsive doses) did not follow the prediction. To tilt excitation/inhibition ratio more selectively toward excitation, we suppressed the activity of parvalbumin-positive interneurons with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). Contrary to our expectations, circuit disinhibition with the DREADD increased the aperiodic exponent. We conclude that the aperiodic exponent of EEG power spectra does not yield a universally reliable marker of cortical excitation/inhibition ratio.NEW & NOTEWORTHY Neuropsychiatric illness may be associated with altered excitation/inhibition balance. A single electroencephalogram (EEG) parameter, the aperiodic exponent of power spectra, may predict the ratio between excitation and inhibition. Here, we use cortical EEGs in mice to evaluate this hypothesis, using pharmacological manipulations of known mechanism. We show that the aperiodic exponent of EEG power spectra is not a reliable marker of excitation/inhibition ratio. Thus, alternative markers of this ratio must be sought.

3D Convolutional Deep Learning for Nonlinear Estimation of Body Composition from Whole-Body Morphology.

Total and regional body composition are strongly correlated with metabolic syndrome and have been estimated non-invasively from 3D optical scans using linear parameterizations of body shape and linear regression models. Prior works produced accurate and precise predictions on many, but not all, body composition targets relative to the reference dual X-Ray absorptiometry (DXA) measurement. Here, we report the effects of replacing linear models with nonlinear parameterization and regression models on the precision and accuracy of body composition estimation in a novel application of deep 3D convolutional graph networks to human body composition modeling. We assembled an ensemble dataset of 4286 topologically standardized 3D optical scans from four different human body shape databases, DFAUST, CAESAR, Shape Up! Adults, and Shape Up! Kids and trained a parameterized shape model using a graph convolutional 3D autoencoder (3DAE) in lieu of linear PCA. We trained a nonlinear Gaussian process regression (GPR) on the 3DAE parameter space to predict body composition via correlations to paired DXA reference measurements from the Shape Up! scan subset. We tested our model on a set of 424 randomly withheld test meshes and compared the effects of nonlinear computation against prior linear models. Nonlinear GPR produced up to 20% reduction in prediction error and up to 30% increase in precision over linear regression for both sexes in 10 tested body composition variables. Deep shape features produced 6-8% reduction in prediction error over linear PCA features for males only and a 4-14% reduction in precision error for both sexes. Our best performing nonlinear model predicting body composition from deep features outperformed prior work using linear methods on all tested body composition prediction metrics in both precision and accuracy. All coefficients of determination (R2) for all predicted variables were above 0.86. We show that GPR is a more precise and accurate method for modeling body composition mappings from body shape features than linear regression. Deep 3D features learned by a graph convolutional autoencoder only improved male body composition accuracy but improved precision in both sexes. Our work achieved lower estimation RMSEs than all previous work on 10 metrics of body composition.

Molecular assembly indices of mineral heteropolyanions: some abiotic molecules are as complex as large biomolecules.

Molecular assembly indices, which measure the number of unique sequential steps theoretically required to construct a three-dimensional molecule from its constituent atomic bonds, have been proposed as potential biosignatures. A central hypothesis of assembly theory is that any molecule with an assembly index ≥15 found in significant local concentrations represents an unambiguous sign of life. We show that abiotic molecule-like heteropolyanions, which assemble in aqueous solution as precursors to some mineral crystals, range in molecular assembly indices from 2 for H2CO3 or Si(OH)4 groups to as large as 21 for the most complex known molecule-like subunits in the rare minerals ewingite and ilmajokite. Therefore, values of molecular assembly indices ≥15 do not represent unambiguous biosignatures.

Multiple Probe Measurements at Uranus Motivated by Spatial Variability.

A major motivation for multiple atmospheric probe measurements at Uranus is the understanding of dynamic processes that create and maintain spatial variation in thermal structure, composition, and horizontal winds. But origin questions-regarding the planet's formation and evolution, and conditions in the protoplanetary disk-are also major science drivers for multiprobe exploration. Spatial variation in thermal structure reveals how the atmosphere transports heat from the interior, and measuring compositional variability in the atmosphere is key to ultimately gaining an understanding of the bulk abundances of several heavy elements. We review the current knowledge of spatial variability in Uranus' atmosphere, and we outline how multiple probe exploration would advance our understanding of this variability. The other giant planets are discussed, both to connect multiprobe exploration of those atmospheres to open questions at Uranus, and to demonstrate how multiprobe exploration of Uranus itself is motivated by lessons learned about the spatial variation at Jupiter, Saturn, and Neptune. We outline the measurements of highest value from miniature secondary probes (which would complement more detailed investigation by a larger flagship probe), and present the path toward overcoming current challenges and uncertainties in areas including mission design, cost, trajectory, instrument maturity, power, and timeline.

Predictors of visceral and subcutaneous adipose tissue and muscle density: The ShapeUp! Kids study.

BACKGROUND AND AIMS: Body fat distribution, i.e., visceral (VAT), subcutaneous adipose tissue (SAT) and intramuscular fat, is important for disease prevention, but sex and ethnic differences are not well understood. Our aim was to identify anthropometric, demographic, and lifestyle predictors for these outcomes. METHODS AND RESULTS: The cross-sectional ShapeUp!Kids study was conducted among five ethnic groups aged 5-18 years. All participants completed questionnaires, anthropometric measurements, and abdominal MRI scans. VAT and SAT areas at four lumbar levels and muscle density were assessed manually. General linear models were applied to estimate coefficients of determination (R2) and to compare the fit of VAT and SAT prediction models. After exclusions, the study population had 133 male and 170 female participants. Girls had higher BMI-z scores, waist circumference (WC), and SAT than boys but lower VAT/SAT and muscle density. SAT, VAT, and VAT/SAT but not muscle density differed significantly by ethnicity. R2 values were higher for SAT than VAT across groups and improved slightly after adding WC. For SAT, R2 increased from 0.85 to 0.88 (girls) and 0.62 to 0.71 (boys) when WC was added while VAT models improved from 0.62 to 0.65 (girls) and 0.57 to 0.62 (boys). VAT values were significantly lower among Blacks than Whites with little difference for the other groups. CONCLUSION: This analysis in a multiethnic population identified BMI-z scores and WC as the major predictors of MRI-derived SAT and VAT and highlights the important ethnic differences that need to be considered in diverse populations.

Method of H2 Transfer Is Vital for Catalytic Hydrodefluorination of Perfluorooctanoic Acid (PFOA).

The efficient transfer of H2 plays a critical role in catalytic hydrogenation, particularly for the removal of recalcitrant contaminants from water. One of the most persistent contaminants, perfluorooctanoic acid (PFOA), was used to investigate how the method of H2 transfer affected the catalytic hydrodefluorination ability of elemental palladium nanoparticles (Pd0NPs). Pd0NPs were synthesized through an in situ autocatalytic reduction of Pd2+ driven by H2 from the membrane. The Pd0 nanoparticles were directly deposited onto the membrane fibers to form the catalyst film. Direct delivery of H2 to Pd0NPs through the walls of nonporous gas transfer membranes enhanced the hydrodefluorination of PFOA, compared to delivering H2 through the headspace. A higher H2 lumen pressure (20 vs 5 psig) also significantly increased the defluorination rate, although 5 psig H2 flux was sufficient for full reductive defluorination of PFOA. Calculations made using density functional theory (DFT) suggest that subsurface hydrogen delivered directly from the membrane increases and accelerates hydrodefluorination by creating a higher coverage of reactive hydrogen species on the Pd0NP catalyst compared to H2 delivery through the headspace. This study documents the crucial role of the H2 transfer method in the catalytic hydrogenation of PFOA and provides mechanistic insights into how membrane delivery accelerates hydrodefluorination.

Acute Effects of Albuterol on Ventilatory Capacity in Children with Asthma.

BACKGROUND: Children with asthma may have a reduced ventilatory capacity, which could lead to symptoms and early termination of a cardiopulmonary exercise test (CPET). The purpose of this study was to examine the effects of short-acting beta agonist (albuterol) administration on estimated ventilatory capacity in children with asthma. METHODS: Fifteen children (eleven boys, 10.6 ± 0.9 years) completed spirometry at baseline, after 180 µg of albuterol, and after the CPET in this cross-sectional study. Ventilatory capacity was calculated from forced vital capacity (FVC) and isovolume forced expiratory time from 25 to 75% of FVC (isoFET25-75) as follows: FVC/2 × [60/(2 × isoFET25-75)]. Differences in outcome variables between baseline, after albuterol administration, and after the CPET were detected with repeated measures mixed models with Bonferroni post hoc corrections. RESULTS: Estimated ventilatory capacity was higher after albuterol (68.7 ± 21.2 L/min) and after the CPET (75.8 ± 25.6 L/min) when compared with baseline (60.9 ± 22.0 L/min; P = 0.003). Because forced vital capacity did not change, the increased ventilatory capacity was primarily due to a decrease in isoFET25-75 (i.e., an increase in mid-flows or isoFEF25-75). CONCLUSION: Albuterol administration could be considered prior to CPET for children with asthma with relatively well-preserved FEV1 values to increase ventilatory capacity pre-exercise and potentially avoid symptom-limited early termination of testing.

Generative deep learning furthers the understanding of local distributions of fat and muscle on body shape and health using 3D surface scans.

BACKGROUND: Body shape, an intuitive health indicator, is deterministically driven by body composition. We developed and validated a deep learning model that generates accurate dual-energy X-ray absorptiometry (DXA) scans from three-dimensional optical body scans (3DO), enabling compositional analysis of the whole body and specified subregions. Previous works on generative medical imaging models lack quantitative validation and only report quality metrics. METHODS: Our model was self-supervised pretrained on two large clinical DXA datasets and fine-tuned using the Shape Up! Adults study dataset. Model-predicted scans from a holdout test set were evaluated using clinical commercial DXA software for compositional accuracy. RESULTS: Predicted DXA scans achieve R2 of 0.73, 0.89, and 0.99 and RMSEs of 5.32, 6.56, and 4.15 kg for total fat mass (FM), fat-free mass (FFM), and total mass, respectively. Custom subregion analysis results in R2s of 0.70-0.89 for left and right thigh composition. We demonstrate the ability of models to produce quantitatively accurate visualizations of soft tissue and bone, confirming a strong relationship between body shape and composition. CONCLUSIONS: This work highlights the potential of generative models in medical imaging and reinforces the importance of quantitative validation for assessing their clinical utility.

Body composition, measured quantities of muscle, fat, and bone, is typically assessed through dual energy X-ray absorptiometry (DXA) scans, which requires specialized equipment, trained technicians and involves exposure to radiation. Exterior body shape is dependent on body composition and recent technological advances have made three-dimensional (3D) scanning for body shape accessible and virtually ubiquitous. We developed a model which uses 3D body surface scan inputs to generate DXA scans. When analyzed with commercial software that is used clinically, our model generated images yielded accurate quantities of fat, lean, and bone. Our work highlights the strong relationship between exterior body shape and interior composition. Moreover, it suggests that with enhanced accuracy, such medical imaging models could be more widely adopted in clinical care, making the analysis of body composition more accessible and easier to obtain.