Deep-Learning Models for Abdominal CT Organ Segmentation in Children: Development and Validation in Internal and Heterogeneous Public Datasets.

Background: Deep-learning abdominal organ segmentation algorithms have shown excellent results in adults; validation in children is sparse. Objective: To develop and validate deep-learning models for liver, spleen, and pancreas segmentation on pediatric CT examinations. Methods: This retrospective study developed and validated deep-learning models for liver, spleen, and pancreas segmentation using 1731 CT examinations (1504 training, 221 testing), derived from three internal institutional pediatric (age ≤18) datasets (n=483) and three public datasets comprising pediatric and adult examinations with various pathologies (n=1248). Three deep-learning model architectures (SegResNet, DynUNet, and SwinUNETR) from the Medical Open Network for AI (MONAI) framework underwent training using native training (NT), relying solely on institutional datasets, and transfer learning (TL), incorporating pre-training on public datasets. For comparison, TotalSegmentator (TS), a publicly available segmentation model, was applied to test data without further training. Segmentation performance was evaluated using mean Dice similarity coefficient (DSC), with manual segmentations as reference. Results: For internal pediatric data, DSC for normal liver was 0.953 (TS), 0.964-0.965 (NT models), and 0.965-0.966 (TL models); normal spleen, 0.914 (TS), 0.942-0.945 (NT models), and 0.937-0.945 (TL models); normal pancreas, 0.733 (TS), 0.774-0.785 (NT models), and 0.775-0.786 (TL models); pancreas with pancreatitis, 0.703 (TS), 0.590-0.640 (NT models), and 0.667-0.711 (TL models). For public pediatric data, DSC for liver was 0.952 (TS), 0.876-0.908 (NT models), and 0.941-0.946 (TL models); spleen, 0.905 (TS), 0.771-0.827 (NT models), and 0.897-0.926 (TL models); pancreas, 0.700 (TS), 0.577-0.648 (NT models), and 0.693-0.736 (TL models). For public primarily adult data, DSC for liver was 0.991 (TS), 0.633-0.750 (NT models), and 0.926-0.952 (TL models); spleen, 0.983 (TS), 0.569-0.604 (NT models), and 0.923-0.947 (TL models); pancreas, 0.909 (TS), 0.148-0.241 (NT models), and 0.699-0.775 (TL models). DynUNet-TL was selected as the best-performing NT or TL model and was made available as an opensource MONAI bundle (https://github.com/cchmc-dll/pediatric_abdominal_segmentation_bundle.git). Conclusion: TL models trained on heterogeneous public datasets and fine-tuned using institutional pediatric data outperformed internal NT models and TotalSegmentator across internal and external pediatric test data. Segmentation performance was better in liver and spleen than in pancreas. Clinical Impact: The selected model may be used for various volumetry applications in pediatric imaging.

High freezing sensitivity of legumes relative to other herbaceous species in northern temperate plant communities.

BACKGROUND AND AIMS: Reduced snow cover and increased air temperature variability are predicted to expose overwintering herbaceous plants to more severe freezing in some northern temperate regions. Legumes are a key functional group that may exhibit lower freezing tolerance than other species these regions, but this trend only has been observed for non-native legumes. Our aim was to confirm if this trend is restricted to non-native legumes or whether native legumes in these regions also exhibit low freezing tolerance. METHODS: First, we transplanted legumes (five non-native species and four native species) into either an old field (non-native) or a prairie (native) and used snow removal to expose the plots to increased soil freezing. Second, we grew plants in mesocosms (old field) and pots (prairie species) and exposed them in controlled environment chambers to a range of freezing treatments (control, 0, -5 or -10 °C) in winter or spring. We assessed freezing responses by comparing differences in biomass, cover and nodulation between freezing (or snow removal) treatments and controls. KEY RESULTS: Among legume species, lower freezing tolerance was positively correlated with a lower proportion of nodulated plants and active nodules, and under controlled conditions, freezing-induced reductions in aboveground biomass were lower on average in native legumes than in non-native legumes. Nevertheless, both non-native and native legume (except Desmodium canadense) exhibited greater reductions in biomass in response to increased freezing than their non-leguminous neighbors, both in controlled environments and in the field. CONCLUSIONS: These results demonstrate that both native and non-native legumes exhibit low freezing tolerance relative to other herbaceous species in northern temperate plant communities. By reducing legume biomass and nodulation, increased soil freezing could reduce N inputs into these systems.

Ultraflexible electrodes for recording neural activity in the mouse spinal cord during motor behavior.

Implantable electrode arrays are powerful tools for directly interrogating neural circuitry in the brain, but implementing this technology in the spinal cord in behaving animals has been challenging due to the spinal cord's significant motion with respect to the vertebral column during behavior. Consequently, the individual and ensemble activity of spinal neurons processing motor commands remains poorly understood. Here, we demonstrate that custom ultraflexible 1-µm-thick polyimide nanoelectronic threads can conduct laminar recordings of many neuronal units within the lumbar spinal cord of unrestrained, freely moving mice. The extracellular action potentials have high signal-to-noise ratio, exhibit well-isolated feature clusters, and reveal diverse patterns of activity during locomotion. Furthermore, chronic recordings demonstrate the stable tracking of single units and their functional tuning over multiple days. This technology provides a path for elucidating how spinal circuits compute motor actions.

Unzipping hBN with ultrashort mid-infrared pulses.

Manipulating the nanostructure of materials is critical for numerous applications in electronics, magnetics, and photonics. However, conventional methods such as lithography and laser writing require cleanroom facilities or leave residue. We describe an approach to creating atomically sharp line defects in hexagonal boron nitride (hBN) at room temperature by direct optical phonon excitation with a mid-infrared pulsed laser from free space. We term this phenomenon "unzipping" to describe the rapid formation and growth of a crack tens of nanometers wide from a point within the laser-driven region. Formation of these features is attributed to the large atomic displacement and high local bond strain produced by strongly driving the crystal at a natural resonance. This process occurs only via coherent phonon excitation and is highly sensitive to the relative orientation of the crystal axes and the laser polarization. Its cleanliness, directionality, and sharpness enable applications such as polariton cavities, phonon-wave coupling, and in situ flake cleaving.

Nonadiabatic dynamics of molecules interacting with metal surfaces: A quantum-classical approach based on Langevin dynamics and the hierarchical equations of motion.

A novel mixed quantum-classical approach to simulating nonadiabatic dynamics of molecules at metal surfaces is presented. The method combines the numerically exact hierarchical equations of motion approach for the quantum electronic degrees of freedom with Langevin dynamics for the classical degrees of freedom, namely, low-frequency vibrational modes within the molecule. The approach extends previous mixed quantum-classical methods based on Langevin equations to models containing strong electron-electron or quantum electronic-vibrational interactions, while maintaining a nonperturbative and non-Markovian treatment of the molecule-metal coupling. To demonstrate the approach, nonequilibrium transport observables are calculated for a molecular nanojunction containing strong interactions.

Association between continuous glucose monitoring metrics and clinical outcomes in adults with type 1 diabetes in a real-world setting.

AIMS: Continuous glucose monitoring (CGM) metrics can assist diabetes management. Consensus statements recommend > 70 % time in range (TIR) and ≤ 36 % glucose coefficient of variation (CV). However, how these targets perform in clinical practice is unknown. This retrospective, longitudinal cohort study analyzed relationships between TIR, CV, glycated hemoglobin (HbA1c), and hypoglycemia in a real-world setting. METHODS: Data of 542 adults with type 1 diabetes who used CGM (January 2014-July 2020) were analyzed. Associations between TIR and HbA1c at the same and subsequent visits, incidence rate ratios (IRRs) for hypoglycemia at different CVs, and number of hypoglycemic events at cross-sections of HbA1c and CV were estimated by regression. RESULTS: TIR was inversely related to HbA1c; for every 10 % increase in TIR, HbA1c was significantly reduced by 0.34 % (4 mmol/mol) and 0.20 % (2 mmol/mol) at the same and subsequent visits, respectively. Level 2 hypoglycemia was significantly reduced at CV < 30 %, 30-33 %, 33.1-36 %, and 36.1-40 %: adjusted IRRs vs CV ≥ 40.1 % of 0.14, 0.28, 0.32, and 0.50, respectively. Hypoglycemic events were reduced at lower CV across HbA1c levels and at higher HbA1c across CV levels. CONCLUSION: This study quantifies HbA1c improvements with increased TIR and hypoglycemia reductions with improved CV in clinical practice.

An Ovine Model Yields Histology and Gene Expression Changes Consistent with Laryngotracheal Stenosis.

OBJECTIVES: Animal models for laryngotracheal stenosis (LTS) are critical to understand underlying mechanisms and study new therapies. Current animal models for LTS are limited by small airway sizes compared to human. The objective of this study was to develop and validate a novel, large animal ovine model for LTS. METHODS: Sheep underwent either bleomycin-coated polypropylene brush injury to the subglottis (n = 6) or airway stent placement (n = 2) via suspension microlaryngoscopy. Laryngotracheal complexes were harvested 4 weeks following injury or stent placement. For the airway injury group, biopsies (n = 3 at each site) were collected of tracheal scar and distal normal regions, and analyzed for fibrotic gene expression. Lamina propria (LP) thickness was compared between injured and normal areas of trachea. RESULTS: No mortality occurred in sheep undergoing airway injury or stent placement. There was no migration of tracheal stents. After protocol optimization, LP thickness was significantly increased in injured trachea (Sheep #3: 529.0 vs. 850.8 um; Sheep #4: 933.0 vs. 1693.2 um; Sheep #5: 743.7 vs. 1378.4 um; Sheep #6: 305.7 vs. 2257.6 um). A significant 62-fold, 20-fold, 16-fold, 16-fold, and 9-fold change of COL1, COL3, COL5, FN1, and TGFB1 was observed in injured scar specimen relative to unaffected airway, respectively. CONCLUSION: An ovine LTS model produces histologic and transcriptional changes consistent with fibrosis seen in human LTS. Airway stent placement in this model is safe and feasible. This large airway model is a reliable and reproducible method to assess the efficacy of novel LTS therapies prior to clinical translation. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Tunable exciton valley-pseudospin orders in moiré superlattices.

Excitons in two-dimensional (2D) semiconductors have offered an attractive platform for optoelectronic and valleytronic devices. Further realizations of correlated phases of excitons promise device concepts not possible in the single particle picture. Here we report tunable exciton "spin" orders in WSe2/WS2 moiré superlattices. We find evidence of an in-plane (xy) order of exciton "spin"-here, valley pseudospin-around exciton filling vex = 1, which strongly suppresses the out-of-plane "spin" polarization. Upon increasing vex or applying a small magnetic field of ~10 mT, it transitions into an out-of-plane ferromagnetic (FM-z) spin order that spontaneously enhances the "spin" polarization, i.e., the circular helicity of emission light is higher than the excitation. The phase diagram is qualitatively captured by a spin-1/2 Bose-Hubbard model and is distinct from the fermion case. Our study paves the way for engineering exotic phases of matter from correlated spinor bosons, opening the door to a host of unconventional quantum devices.

Synthesis, Structure, and Properties of CuBiSeCl2: A Chalcohalide Material with Low Thermal Conductivity.

Mixed anion halide-chalcogenide materials have recently attracted attention for a variety of applications, owing to their desirable optoelectronic properties. We report the synthesis of a previously unreported mixed-metal chalcohalide material, CuBiSeCl2 (Pnma), accessed through a simple, low-temperature solid-state route. The physical structure is characterized through single-crystal X-ray diffraction and reveals significant Cu displacement within the CuSe2Cl4 octahedra. The electronic structure of CuBiSeCl2 is investigated computationally, which indicates highly anisotropic charge carrier effective masses, and by experimental verification using X-ray photoelectron spectroscopy, which reveals a valence band dominated by Cu orbitals. The band gap is measured to be 1.33(2) eV, a suitable value for solar absorption applications. The electronic and thermal properties, including resistivity, Seebeck coefficient, thermal conductivity, and heat capacity, are also measured, and it is found that CuBiSeCl2 exhibits a low room temperature thermal conductivity of 0.27(4) W K-1 m-1, realized through modifications to the phonon landscape through increased bonding anisotropy.

A Comprehensive Flow Cytometry Panel for Analysis of Idiopathic Subglottic Stenosis.

OBJECTIVE: To present a comprehensive flow cytometry panel for idiopathic subglottic stenosis (iSGS). STUDY DESIGN: Controlled ex vivo cohort study. SETTING: Tertiary care academic hospital in a metropolitan area. METHODS: Flow cytometry and single-cell RNA sequencing were performed on 9 paired normal and scar tissue samples from iSGS patients. Flow cytometry was used to assess the presence of myeloid (CD11b, CD14, CD15, Siglec8), lymphoid (CD3, CD4, CD8, gamma delta [γδ], FOXP3), endothelial (CD31), fibroblast (CD90, SMA), and epithelial (CD326, CK5) markers. RESULTS: On flow cytometry, iSGS scar is characterized by an increased presence of myeloid, lymphoid, endothelial, and fibroblast cell types, but a decreased presence of epithelial cells. In the myeloid lineage, iSGS scar samples demonstrated increased CD11b+ monocytes (P < .001), Siglec8+ eosinophils (P = .03), and CD14+ monocytes (P = .02). In the lymphoid lineage, iSGS scar demonstrated increased CD3+ T-cells (P < .001), CD4+ helper T-cells (P < .001), γδ+ T-cells (P < .001), and FOXP3+ regulatory T-cells (P = .002). iSGS scar exhibited specific increases in CD90+ (P = .04) and SMA+ (P < .001) fibroblasts but decreased CD326+ (E-cadherin) epithelial cells (P = .01) relative to normal samples. CONCLUSION: We present a comprehensive flow cytometry panel for iSGS. This flow panel may serve as a common platform among airway scientists to elucidate the cellular mechanisms underpinning iSGS and other upper airway pathologies. Scar iSGS samples demonstrate a distinct cellular profile relative to normal iSGS specimens, exhibiting increased fibroblast, endothelial, and inflammatory cell types but decreased epithelium.

Plasmodium falciparum genetic diversity and multiplicity of infection based on msp-1, msp-2, glurp and microsatellite genetic markers in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: In sub-Saharan Africa (SSA), Plasmodium falciparum causes most of the malaria cases. Despite its crucial roles in disease severity and drug resistance, comprehensive data on Plasmodium falciparum genetic diversity and multiplicity of infection (MOI) are sparse in SSA. This study summarizes available information on genetic diversity and MOI, focusing on key markers (msp-1, msp-2, glurp, and microsatellites). The systematic review aimed to evaluate their influence on malaria transmission dynamics and offer insights for enhancing malaria control measures in SSA. METHODS: The review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Two reviewers conducted article screening, assessed the risk of bias (RoB), and performed data abstraction. Meta-analysis was performed using the random-effects model in STATA version 17. RESULTS: The review included 52 articles: 39 cross-sectional studies and 13 Randomized Controlled Trial (RCT)/cohort studies, involving 11,640 genotyped parasite isolates from 23 SSA countries. The overall pooled mean expected heterozygosity was 0.65 (95% CI: 0.51-0.78). Regionally, values varied: East (0.58), Central (0.84), Southern (0.74), and West Africa (0.69). Overall pooled allele frequencies of msp-1 alleles K1, MAD20, and RO33 were 61%, 44%, and 40%, respectively, while msp-2 I/C 3D7 and FC27 alleles were 61% and 55%. Central Africa reported higher frequencies (K1: 74%, MAD20: 51%, RO33: 48%) than East Africa (K1: 46%, MAD20: 42%, RO33: 31%). For msp-2, East Africa had 60% and 55% for I/C 3D7 and FC27 alleles, while West Africa had 62% and 50%, respectively. The pooled allele frequency for glurp was 66%. The overall pooled mean MOI was 2.09 (95% CI: 1.88-2.30), with regional variations: East (2.05), Central (2.37), Southern (2.16), and West Africa (1.96). The overall prevalence of polyclonal Plasmodium falciparum infections was 63% (95% CI: 56-70), with regional prevalences as follows: East (62%), West (61%), Central (65%), and South Africa (71%). CONCLUSION: The study shows substantial regional variation in Plasmodium falciparum parasite genetic diversity and MOI in SSA. These findings suggest a need for malaria control strategies and surveillance efforts considering regional-specific factors underlying Plasmodium falciparum infection.

Using Risk Ratios to Quantify Potential Behavior-Environment Relations.

Behavior-environment functional relations are the units of explanation in applied behavior analysis (ABA). Whether hypothesized experimentally or descriptively, quantification of putative functional relations improves our ability to predict and influence behavior. Risk ratios are an accessible, straightforward quantitative analysis that can serve this purpose. They have been employed to great effect in other fields (e.g., medicine, public health), but are rarely used within ABA. In this tutorial, we describe risk ratios and how they are calculated, discuss why risk ratios are well suited for quantifying behavior-environment relations, and illustrate their utility and applicability across five demonstrations from real clinical cases. Recommendations for the use of risk ratios in research and practice are discussed.

Importance of methodological pluralism in deriving counterfactuals for evidence-based conservation.

Most protected area impact research that uses counterfactuals draws heavily on quantitative methods, data, and knowledge types, making it valuable in producing generalizations but limited in temporal scope, historical detail, and habitat diversity and coverage of ecosystem services. We devised a methodological pluralistic approach, which supports social science qualitative methods, narratives, mixed methods, and interdisciplinarity, to fully unlock the potential of counterfactuals in ensuring a place-based and detailed understanding of the socioecological context and impacts of protected areas. We applied this approach to derive possible counterfactual conditions for the impact of a montane protected area on 40 years of vegetation change in the Cape Floristic Region-a global biodiversity hotspot and UNESCO World Heritage Site in South Africa. We incorporated diverse methods, knowledge, and information sources, drawing on before-after protected area comparisons for inside and outside the protected area. A significant increase in shrubland vegetation (17-30%) was observed and attributed primarily to a decline in frequent burning for grazing. This also occurred outside the protected area and was driven by socioeconomic drivers and not by concerns over biodiversity conservation or land degradation. Had the protected area not been established the area would have seen intensification of cultivation and increased road networks, buildings, and water storage in dams. Our approach increased historical temporal coverage of socioecological change and contextualized assumptions around causality. Protected area impact evaluation should reengage in place-based research that fully incorporates pluralism in methodologies for constructing counterfactuals in a way that builds regional and global understanding from the local level upward. We devised 10 key principles for deriving counterfactuals grounded in methodological pluralism, covering aspects of collaboration, cocreation, inter- and transdisciplinarity, diverse values and lived experiences, multiple knowledge types, multiple possible causal mechanisms, social science qualitative methods, perceptions, perspectives, and narratives.

Importancia del pluralismo metodológico en la derivación de situaciones contrafactuales para la conservación basada en evidencias Resumen La mayoría de las investigaciones sobre el impacto de las áreas protegidas que usan situaciones contrafactuales se basan en gran medida en métodos cuantitativos, datos y tipos de conocimiento, por lo que son muy valiosas para producir generalizaciones, pero limitadas en el enfoque temporal, el detalle histórico y la diversidad de hábitats y cobertura de los servicios ambientales. Diseñamos una estrategia metodológica pluralista, la cual apoya los métodos cualitativos de las ciencias sociales, narrativas, métodos mixtos e interdisciplinarios para utilizar por completo el potencial de las situaciones contrafactuales para asegurar un conocimiento detallado y basado en el lugar del contexto socio ecológico y el impacto de las áreas protegidas. Aplicamos esta estrategia para derivar las posibles condiciones contrafactuales del impacto de un área protegida montañosa sobre 40 años de cambio de vegetación en el reino florístico del Cabo ­ un punto caliente de biodiversidad y Sitio de Patrimonio Mundial de la UNESCO en Sudáfrica. Incorporamos varios métodos, conocimientos y fuentes de información a partir de las comparaciones antes­después dentro y fuera del área protegida. Observamos un incremento significativo en la vegetación del matorral (17­30%), el cual atribuimos principalmente en la disminución de la quema frecuente para el pastoreo. Esto también ocurrió fuera del área protegida y fue causado por factores socioeconómicos y no por preocupación por la conservación de la biodiversidad o por la degradación del suelo. De no haberse establecido el área protegida, la zona habría sufrido una intensificación de cultivos y un incremento de carreteras, edificios y almacenamiento de agua en presas. Nuestra estrategia incrementó la cobertura histórica temporal del cambio socio­ecológico y contextualizó las suposiciones sobre la causalidad. La evaluación del impacto del área protegida debe volver a la investigación basada en el lugar que incorpora de lleno el pluralismo en la metodología para construir situaciones contrafactuales de una forma que genere conocimiento regional y global a partir del nivel local y hacia arriba. Diseñamos diez principios clave para derivar las situaciones contrafactuales basados en el pluralismo metodológico, la cobertura de los aspectos de colaboración, creación conjunta, inter­ y transdisciplinariedad, valores diversos y experiencias vividas, varios tipos de conocimiento, diferentes mecanismos causales posibles, métodos cualitativos de las ciencias sociales, percepciones, perspectivas, historias y narrativas.

Tenofovir-Diphosphate and Emtricitabine-Triphosphate Adherence Benchmarks in Dried Blood Spots for Persons with HIV Receiving Tenofovir Alafenamide and Emtricitabine-based Antiretroviral Therapy (QUANTI-TAF).

BACKGROUND: QUANTI-TAF aimed to establish tenofovir-diphosphate/emtricitabine-triphosphate (TFV-DP/FTC-TP) adherence benchmarks in dried blood spots (DBS) for persons with HIV (PWH) receiving tenofovir alafenamide/emtricitabine (TAF/FTC)-based antiretroviral therapy (ART). METHODS: During a 16-week pharmacokinetic study, PWH received TAF/FTC-based ART co-encapsulated with an ingestible sensor to directly measure cumulative (enrollment to final visit) and 10-day adherence. At monthly visits, intraerythrocytic concentrations of TAF/FTC anabolites (TFV-DP/FTC-TP) in DBS were quantified by LC-MS/MS and summarized at steady-state (week 12 or 16) as median (IQR). Linear mixed-effects models evaluated factors associated with TFV-DP/FTC-TP. RESULTS: 84 participants (86% male, 11% female, and 4% transgender), predominantly receiving bictegravir/TAF/FTC (73%) enrolled. 92% completed week 12 or 16 (94% receiving unboosted ART). TFV-DP for <85% (7/72), ≥85%-<95% (9/72), and ≥95% (56/72) cumulative adherence was 2696 (2039-4108), 3117 (2332-3339), and 3344 (2605-4293) fmol/punches. All participants with ≥85% cumulative adherence had TFV-DP ≥1800 fmol/punches. Adjusting for cumulative adherence, TFV-DP was higher with boosted ART, lower BMI, and in non-Blacks. FTC-TP for <85% (14/77), ≥85%-<95% (6/77), and ≥95% (57/77) 10-day adherence was 3.52 (2.64-4.48), 4.58 (4.39-5.06), and 4.96 (4.21-6.26) pmol/punches. All participants with ≥85% 10-day adherence had FTC-TP ≥2.5 pmol/punches. Low-level viremia (HIV-1 RNA ≥20-<200 copies/mL) occurred at 60/335 (18%) visits in 33/84 (39%) participants (range: 20-149 copies/mL), with similar TFV-DP (3177 [2494-4149] fmol/punches) compared with HIV-1 RNA <20 copies/mL visits (3279 [2580-4407] fmol/punches). CONCLUSIONS: We propose PK-based TFV-DP (≥1800 fmol/punches)/FTC-TP (≥2.5 pmol/punches) benchmarks in DBS for PWH receiving unboosted TAF/FTC-based ART with ≥85% adherence. In the setting of high adherence, low-level viremia was common.

The growing threat of NDM-producing E. coli with penicillin-binding protein 3 mutations in the United States - is there a potential role for durlobactam?

We report identification of 5 patients with infections caused by NDM-5-producing E. coli harboring PBP3 mutations that showed reduced susceptibility to aztreonam-avibactam and cefiderocol. Durlobactam, a novel diazabicyclooctane ß-lactamase inhibitor, demonstrated minimum inhibitory concentrations ranging from 0.5 to 2 µg/mL supporting future investigations into a potential role in clinical management.

Adoptive transfer of CD49a+ Tissue resident memory cells reverses pulmonary fibrosis in mice.

Pulmonary fibrosis is a devastating disease with no effective treatments to cure, stop or reverse the unremitting, fatal fibrosis. A critical barrier to treating this disease is the lack of understanding of the pathways leading to fibrosis as well as those regulating the resolution of fibrosis. Fibrosis is the pathologic side of normal tissue repair that results when the normal wound healing programs go awry. Successful resolution of tissue injury requires several highly coordinated pathways, and this research focuses on the interplay between these overlapping pathways: immune effectors, inflammatory mediators and fibroproliferation in the resolution of fibrosis. Previously we have successfully prevented, mitigated, and even reversed established fibrosis using vaccinia vaccination immunotherapy in two models of murine lung fibrosis. The mechanism by which vaccinia reverses fibrosis is by vaccine induced lung specific Th1 skewed tissue resident memory (TRMs) in the lung. In this study, we isolated a population of vaccine induced TRMs - CD49a+ CD4+ T cells - that are both necessary and sufficient to reverse established pulmonary fibrosis. Using adoptive cellular therapy, we demonstrate that intratracheal administration of CD49a+ CD4+ TRMs into established fibrosis, reverses the fibrosis histologically, by promoting a decrease in collagen, and functionally, by improving lung function, without the need for vaccination. Furthermore, co-culture of in vitro derived CD49+ CD4+ human TRMs with human fibroblasts from individuals with idiopathic pulmonary fibrosis (IPF) results in the down regulation of IPF fibroblast collagen production. Lastly, we demonstrate in human IPF lung histologic samples that CD49a+ CD4+ TRMs, which can down regulate human IPF fibroblast function, fail to increase in the IPF lungs, thus potentially failing to promote resolution. Thus, we define a novel unappreciated role for tissue resident memory T cells in regulating established lung fibrosis to promote resolution of fibrosis and re-establish lung homeostasis. We demonstrate that immunotherapy, in the form of adoptive transfer of CD49a+ CD4+ TRMs into the lungs of mice with established fibrosis, not only stops progression of the fibrosis but more importantly reverses the fibrosis. These studies provide the insight and preclinical rationale for a novel paradigm shifting approach of using cellular immunotherapy to treat lung fibrosis.

Revision Nasal Reconstruction After Previous Forehead Flap.

Reconstructing the nose poses considerable challenges, even for the most skilled surgeons. Significant nasal reconstructions often require later revisions to address persistent issues in both form and function, and it is crucial to discuss this possibility with the patient before embarking on the reconstructive process. Minor revisions can often be managed by making direct incisions between nasal subunits, coupled with soft tissue sculpting or the use of structural grafts for augmentation. When minor adjustments prove insufficient, the initial reconstruction may need to be entirely revised with a second forehead flap.

Analysis of variability and trends in medical school clerkship grades.

Background: Medical school clerkship grades are used to evaluate orthopedic surgery residency applicants, however, high interinstitutional variability in grade distribution calls into question the utility of clerkship grades when evaluating applicants from different medical schools. This study aims to evaluate the variability in grade distribution among medical schools and look for trends in grade distribution over recent years. Methods: Applications submitted to Rush University's orthopedic surgery residency program from 2015, 2019, and 2022 were collected from the Electronic Residency Application Service. Applications from the top 100 schools according to the 2023-2024 U.S. News and World Report Research Rankings were reviewed. The percentage of "honors" grades awarded by medical schools for the surgery and internal medicine clerkships were extracted from applicants' Medical Student Performance Evaluation letters. Results: The median percentage of honors given in 2022 was 36.0 % (range 10.0-82.0) for the surgery clerkship and 33.0 % (range 6.7-80.0) for the internal medicine clerkship. Honors were given 6.6 % more in the surgery clerkship in 2022 compared to 2015. There was a negative correlation between a higher (worse) U.S. News and World Report research ranking and the percentage of honors awarded in 2022 for the surgery and internal medicine clerkships. Conclusion: There is substantial interinstitutional variability in the rate that medical schools award an "honors" grade with evidence of grade inflation in the surgery clerkship. Residency programs using clerkship grades to compare applicants should do so cautiously provided the variability demonstrated in this study.