Functional Outcomes After the Sacrifice of Mandibular Condyle Using Fibula Free Flap for Immediate Surgical Reconstruction.

Introduction Head and neck cancer with mandibular invasion often necessitates composite resection, leading to defects requiring reconstruction. Microvascular fibula free flap (FFF) surgery is a common approach for this purpose. In this study, we focus on our experience with condyle sacrifice, emphasizing treatment outcomes and functional results. Additionally, we highlight a contemporary perspective by discussing surgical techniques and radiographic outcomes based on a 3D analysis of neo-condyle placement on CT imaging. Methods We studied 23 patients who had undergone segmental mandibulectomy requiring FFF reconstruction between 2009 and 2020. These were all performed by the same surgeon (M.M.) at an academic tertiary care center. Twenty-three reconstructions included condyle sacrifice. Retrospective chart review was performed with a focus on treatment, functional outcomes, and surgical technique. Results A total of 23 patients were included in the study group (13 females and 10 males) with a mean age of 58.1 years. The most common surgical indication was for oncologic purposes (n=9; 39.1%). Twenty (87%) patients required tracheostomy, and all were decannulated. In terms of surgical complications, two (8.7%) patients had a degree of arterial insufficiency and two (8.7%) developed delayed infections. The average inpatient stay was 5.61 days, with a subsequent average clinic follow-up after 16.9 days. CT or MRI imaging was available for 21 (91.3%) patients, showing 14 (66.7%) neo-condyles within the glenoid fossa. Fifteen (71.4%) patients had some element of anterior displacement (average=6.27 mm), and seven (33.3%) patients had a component of lateral displacement (average=2.23 mm). Three (13%) patients died during the follow-up period. Eighteen (90%) of the surviving patients returned to an oral diet within an average of 24.9 days. All patients returned to normal interincisal distance by 12 months. All FFFs, with and without complications, remained viable. Conclusion We achieved favorable oral function outcomes in the majority of our patients. Intriguingly, although radiographic evidence revealed anterior and/or lateral displacement of the neo-condyle, there was no observed correlation with the resumption of oral diet, trismus, or crossbite among these patients.

Temperature-dependent excited states for detecting reversible phase transitions in 2D lead(II) iodide perovskites.

Significant interest exists in water-tolerant 2D lead iodide perovskites owing to their stability and proven potential in photovoltaic and photonic applications. These materials have solid-state phase transitions that are accessible below 100 °C. Here, the study witnesses the multiple phase transitions of the last members of a series of organic-inorganic hybrid materials, [(CnH2n+1NH3)2PbI4], with even n as n = 14, 16, and 18, once again. By employing temperature-dependent steady-state photoluminescence (PL) and temperature-dependent time-resolved photoluminescence (TRPL) spectroscopy in the temperature range of -18 to +90 °C and at -196 °C, we explore the thermal responses of these materials. The investigation reveals reversible phase transitions occurring between room temperature (RT) and elevated temperatures, impacting the optical properties and emitting colors of the perovskite compounds. The longer the alkyl chain, the higher the phase transition temperature, attributed to increased conformational disorder and enhanced perovskite symmetry. The decay constants for all compounds are very close in value, which confirms the underlying excited-state dynamics, pointing to contributions primarily from inorganic components across different phases. We anticipate that our results on the detection of phase transitions in 2D perovskites will not only motivate the use of these techniques for detecting phase transitions but also would help to understand their excited states in more details to selectively use them for solar cell and next-generation display technologies.

Dual α-globin and truncated EPO receptor knockin restores hemoglobin production in α-thalassemia-derived red blood cells.

Alpha-thalassemia is an autosomal recessive disease with increasing worldwide prevalence. The molecular basis is due to mutation or deletion of one or more duplicated α-globin genes, and disease severity is directly related to the number of allelic copies compromised. The most severe form, α-thalassemia major (αTM), results from loss of all four copies of α-globin and has historically resulted in fatality in utero. However, in utero transfusions now enable survival to birth. Postnatally, patients face challenges similar to ß-thalassemia, including severe anemia and erythrotoxicity due to imbalance of ß-globin and α-globin chains. While curative, hematopoietic stem cell transplantation (HSCT) is limited by donor availability and potential transplant-related complications. Despite progress in genome editing treatments for ß-thalassemia, there is no analogous curative option for patients suffering from α-thalassemia. To address this, we designed a novel Cas9/AAV6-mediated genome editing strategy that integrates a functional α-globin gene into the ß-globin locus in αTM patient-derived hematopoietic stem and progenitor cells (HSPCs). Incorporation of a truncated erythropoietin receptor transgene into the α-globin integration cassette dramatically increased erythropoietic output from edited HSPCs and led to the most robust production of α-globin, and consequently normal hemoglobin. By directing edited HSPCs toward increased production of clinically relevant RBCs instead of other divergent cell types, this approach has the potential to mitigate the limitations of traditional HSCT for the hemoglobinopathies, including low genome editing and low engraftment rates. These findings support development of a definitive ex vivo autologous genome editing strategy that may be curative for α-thalassemia.

Achieving the Fundamental Quantum Limit of Linear Waveform Estimation.

Sensing a classical signal using a linear quantum device is a pervasive application of quantum-enhanced measurement. The fundamental precision limits of linear waveform estimation, however, are not fully understood. In certain cases, there is an unexplained gap between the known waveform-estimation quantum Cramér-Rao bound and the optimal sensitivity from quadrature measurement of the outgoing mode from the device. We resolve this gap by establishing the fundamental precision limit, the waveform-estimation Holevo Cramér-Rao bound, and how to achieve it using a nonstationary measurement. We apply our results to detuned gravitational-wave interferometry to accelerate the search for postmerger remnants from binary neutron-star mergers. If we have an unequal weighting between estimating the signal's power and phase, then we propose how to further improve the signal-to-noise ratio by a factor of sqrt[2] using this nonstationary measurement.

Reconstruction for Salvage Laryngectomy With Limited Pharyngectomy.

Importance: Closure technique for optimization of postoperative and functional outcomes following salvage laryngectomy remains an area of debate among head and neck surgeons. Objective: To investigate the association of salvage laryngectomy closure technique with early postoperative and functional outcomes. Design, Setting, and Participants: This retrospective cohort study included patients from 17 academic, tertiary care centers who underwent total laryngectomy with no or limited pharyngectomy after completing a course of definitive radiotherapy or chemoradiotherapy with curative intent between January 2011 and December 2016. Patients with defects not amenable to primary closure were excluded. Data were analyzed from February 14, 2021, to January 29, 2024. Exposures: Total laryngectomy with and without limited pharyngectomy, reconstructed by primary mucosal closure (PC), regional closure (RC), or free tissue transfer (FTT). Main Outcomes and Measures: Patients were stratified on the basis of the pharyngeal closure technique. Perioperative and long-term functional outcomes were evaluated with bivariate analyses. A multivariable regression model adjusted for historical risk factors for pharyngocutaneous fistula (PCF) was used to assess risk associated with closure technique. Relative risks (RRs) with 95% CIs were determined. Results: The study included 309 patients (256 [82.8%] male; mean age, 64.7 [range, 58.0-72.0] years). Defects were reconstructed as follows: FTT (161 patients [52.1%]), RC (64 [20.7%]), and PC (84 [27.2%]). A PCF was noted in 36 of 161 patients in the FTT group (22.4%), 25 of 64 in the RC group (39.1%), and 29 of 84 in the PC group (34.5%). On multivariable analysis, patients undergoing PC or RC had a higher risk of PCF compared with those undergoing FTT (PC: RR, 2.2 [95% CI, 1.1-4.4]; RC: RR, 2.5 [95% CI, 1.3-4.8]). Undergoing FTT was associated with a clinically meaningful reduction in risk of PCF (RR, 0.6; 95% CI, 0.4-0.9; number needed to treat, 7). Subgroup analysis comparing inset techniques for the RC group showed a higher risk of PCF associated with PC (RR, 1.8; 95% CI, 1.1-3.0) and predominately pectoralis myofascial flap with onlay technique (RR, 1.9; 95% CI, 1.2-3.2), but there was no association of pectoralis myocutaneous flap with cutaneous paddle interposition with PCF (RR, 1.2; 95% CI, 0.5-2.8) compared with FTT with cutaneous inset. There were no clinically significant differences in functional outcomes between the groups. Conclusion and Relevance: In this study of patients with limited pharyngeal defects, interpositional fasciocutaneous closure technique was associated with reduced risk of PCF in the salvage setting, which is most commonly achieved by FTT in academic practices. Closure technique was not associated with functional outcomes at 1 and 2 years postoperatively.

Copper(I) Iodide Thin Films: Deposition Methods and Hole-Transporting Performance.

The pursuit of p-type semiconductors has garnered considerable attention in academia and industry. Among the potential candidates, copper iodide (CuI) stands out as a highly promising p-type material due to its conductivity, cost-effectiveness, and low environmental impact. CuI can be employed to create thin films with >80% transparency within the visible range (400-750 nm) and utilizing various low-temperature, scalable deposition techniques. This review summarizes the deposition techniques for CuI as a hole-transport material and their performance in perovskite solar cells, thin-film transistors, and light-emitting diodes using diverse processing methods. The preparation methods of making thin films are divided into two categories: wet and neat methods. The advancements in CuI as a hole-transporting material and interface engineering techniques hold promising implications for the continued development of such devices.

Epithelial zonation along the mouse and human small intestine defines five discrete metabolic domains.

A key aspect of nutrient absorption is the exquisite division of labour across the length of the small intestine, with individual nutrients taken up at different proximal:distal positions. For millennia, the small intestine was thought to comprise three segments with indefinite borders: the duodenum, jejunum and ileum. By examining the fine-scale longitudinal transcriptional patterns that span the mouse and human small intestine, we instead identified five domains of nutrient absorption that mount distinct responses to dietary changes, and three regional stem cell populations. Molecular domain identity can be detected with machine learning, which provides a systematic method to computationally identify intestinal domains in mice. We generated a predictive model of transcriptional control of domain identity and validated the roles of Ppar-δ and Cdx1 in patterning lipid metabolism-associated genes. These findings represent a foundational framework for the zonation of absorption across the mammalian small intestine.

Aire in Autoimmunity.

The role of the autoimmune regulator (Aire) in central immune tolerance and thymic self-representation was first described more than 20 years ago, but fascinating new insights into its biology continue to emerge, particularly in the era of advanced single-cell genomics. We briefly describe the role of human genetics in the discovery of Aire, as well as insights into its function gained from genotype-phenotype correlations and the spectrum of Aire-associated autoimmunity-including insights from patients with Aire mutations with broad and diverse implications for human health. We then highlight emerging trends in Aire biology, focusing on three topic areas. First, we discuss medullary thymic epithelial diversity and the role of Aire in thymic epithelial development. Second, we highlight recent developments regarding the molecular mechanisms of Aire and its binding partners. Finally, we describe the rapidly evolving biology of the identity and function of extrathymic Aire-expressing cells (eTACs), and a novel eTAC subset called Janus cells, as well as their potential roles in immune homeostasis. Expected final online publication date for the Annual Review of Immunology, Volume 42 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Stimulant Patterns, Alone or with Other Psychotropic Classes, in Medicaid-Insured Youth Continuously Enrolled for 3-8 Years.

Objective: Little U.S. pharmacoepidemiologic study is based on treatment during continuous enrollment for periods more than a year. This study aims to show pediatric patterns of stimulant use (alone or with other psychotropic classes) from Medicaid administrative claims data for stimulant patterns of 3- to 8-year continuous enrollees. Methods: A retrospective cohort study was derived from Medicaid enrollment, pharmacy, and diagnosis claims data (2007-2014) in a mid-Atlantic state. Youth aged 2-17 years with 3-8 years of continuous enrollment treated with stimulants were compared with a date-matched comparison group treated without stimulants. Major outcomes include prevalence and duration of stimulant use and patterns of stimulant polypharmacy across relatively long enrollments (3-8 years). Results: Among 264,518 unique 2- to 17-year olds with 3-8 years of continuous enrollment, 16.5% had stimulant prescription dispensings, doubling the annual national prevalence of 8.1%. Subgroup analysis showed that the highest prevalence of stimulant use was for 6- to 11-year olds (20.4%), foster care eligible youth (42.3%), and those with 7-8 years of continuous enrollment (20.1%). Externalizing psychiatric disorders were far more common in those treated with stimulants than in those treated without stimulants. The duration of stimulant exposure overall was a median of 487 days, half that of foster care stimulant users. Stimulant polypharmacy with two or more psychotropic classes concomitantly characterized 29.8% of stimulant users. Among those with three or four or more class polypharmacy, 85% and 88%, respectively, had concomitant stimulant and antipsychotic use. The adjusted odds ratio (AOR) of three or more class polypharmacy significantly increased in 12- to 17-year-old age group (AOR = 1.8), foster care eligibility (AOR = 4.5), and among those with the longest enrollment (AOR = 1.7). Conclusions and Relevance: Stimulant prevalence in Medicaid-insured youth with continuous enrollment of 3-8 years was twice as common as in annual data sets. Future research should investigate three to five interclass stimulant polypharmacy effectiveness in reliably diagnosed community populations.

Association of Age and Sex at Onset With Glenohumeral Osteoarthritis: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of the present systematic review is to synthesize existing evidence (qualitative and quantitative) regarding age- and sex-specific differences with glenohumeral osteoarthritis. DESIGN: The electronic databases PubMed, MEDLINE, and Web of Science were searched up to March 15, 2023. Articles reporting on the association of risk factors (age and sex) with glenohumeral osteoarthritis were considered. We used Newcastle-Ottawa Scale to assess study quality. Meta-analysis was conducted to quantitatively summarize the association of age and sex with glenohumeral osteoarthritis. RESULTS: A total of 24 articles were retrieved for full-text review. Of 24 articles, 8 reporting age-specific and 5 articles reporting sex-specific associations with glenohumeral osteoarthritis were included. The odds ratio for the age (odds ratio = 3.18; 95% confidence interval = 1.10-15.92) and female sex (odds ratio = 1.78; 95% confidence interval = 0.95-3.42) were increased and observed statistically significant. CONCLUSIONS: The present systematic review and meta-analysis suggests the role of increasing age as one of the significant contributors to glenohumeral osteoarthritis. However, association of female sex with glenohumeral osteoarthritis is least convincing. Future studies are required to understand the molecular mechanisms behind the contributory role of increasing age and female sex in the establishment of glenohumeral osteoarthritis.

Routine Contrasted Chest CT Accurately Identifies Anatomic Variations of the Proximal Subscapular System.

OBJECTIVE: The vascular anatomy of the proximal subscapular artery has been previously classified into 2 major types depending on the presence of a common subscapular trunk. The purpose of this study was to determine the utility, reliability, and cost of routine chest imaging to identify these anatomical variations. METHODS: Data were collected retrospectively at a tertiary medical center for patients who were undergoing CT chest for various indications between October 2019 and October 2020. Two independent and blinded readers interpreted CT chest with contrast of 52 patients for a total 104 sides. RESULTS: The proximal branching pattern of the subscapular system was identified to have a common trunk in 99 (95%) sides. The remaining five sides (5%) demonstrated two arterial pedicles; with one patient exhibiting the variant anatomy bilaterally. CONCLUSION: Preoperative CT chest with contrast can accurately identify anatomic variation of the subscapular vascular system. For complex reconstruction requiring a single anastomosis in the vessel depleted neck, preoperative imaging can assure selection of a type I vascular anatomy of the proximal subscapular system. Preoperative imaging with contrasted CT has value in assessing this anatomy when planning for chimeric flaps involving circumflex scapular and thoracodorsal arteries. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:684-687, 2024.

Dynamic encounters with red blood cells trigger splenic marginal zone B cell retention and function.

Spleen marginal zone (MZ) B cells are important for antibody responses against blood-borne antigens. The signals they use to detect exposure to blood are not well defined. Here, using intravital two-photon microscopy in mice, we observe transient contacts between MZ B cells and red blood cells that are in flow. We show that MZ B cells use adhesion G-protein-coupled receptor ADGRE5 (CD97) for retention in the spleen. CD97 function in MZ B cells depends on its ability to undergo autoproteolytic cleavage and signaling via Gα13 and ARHGEF1. Red blood cell expression of the CD97 ligand CD55 is required for MZ B cell homeostasis. Applying a pulling force on CD97-transfected cells using an optical C-trap and CD55+ beads leads to accumulation of active RhoA and membrane retraction. Finally, we show that CD97 deficiency leads to a reduced T cell-independent IgM response. Thus, our studies provide evidence that MZ B cells use mechanosensing to position in a manner that enhances antibody responses against blood-borne antigens.

Correlating area deprivation index with initial stage at presentation and with follow up and recurrence within an advanced practice provider-led survivorship clinic.

INTRODUCTION: Living in disadvantaged neighborhoods has been shown to result in worse healthcare outcomes. The Area Deprivation Index (ADI) is a metric that ranks neighborhoods by socioeconomic disadvantage utilizing numerous factors including income, education, employment, and housing quality. METHODS: A retrospective review of all patients who underwent surveillance in an APP-led head and neck cancer survivorship clinic from Dec 2016 to Oct 2020 at an academic tertiary care center were included. Tumor characteristics, visit frequency, recurrence, number of missed appointments, loss of follow up, and ADI scores were collected. RESULTS: 543 patients were included in the study. A majority were male (69.9 %) and white race (84.9 %) with an average age of 64.6 years old. Average ADI national percentile score was 71.6(range: 17 to 100). ADI national percentile score was not predictive of tumor characteristics at initial presentation: lymphovascular invasion (p = 0.940; OR 1.0 [95 % CI: 0.9 to 1.1]), extranodal extension (p = 0.576; OR 1.0 [95 % CI: 0.9 to 1.2]), positive margins (p = 0.069; OR 0.9 [95 % CI: 0.9 to 1.0]). ADI national percentile score was not significantly correlated with loss to follow up (p = 0.153; OR 1.2 [95 % CI: 0.9 to 1.7] or cancer recurrence (p = 0.594; OR 1.0 [95 % CI: 0.9 to 1.1]). Missing one or more clinic visits was correlated with loss to follow up (p = 0.029; OR 13.1 [95 % CI: 1.3 to 131.7]. CONCLUSION: Living in a disadvantaged neighborhood did not correlate with negative tumor characteristics, loss to follow up, or recurrence within an APP-led survivorship head and neck cancer clinic.

Machine Learning Interatomic Potentials for Reactive Hydrogen Dynamics at Metal Surfaces Based on Iterative Refinement of Reaction Probabilities.

The reactive chemistry of molecular hydrogen at surfaces, notably dissociative sticking and hydrogen evolution, plays a crucial role in energy storage and fuel cells. Theoretical studies can help to decipher underlying mechanisms and reaction design, but studying dynamics at surfaces is computationally challenging due to the complex electronic structure at interfaces and the high sensitivity of dynamics to reaction barriers. In addition, ab initio molecular dynamics, based on density functional theory, is too computationally demanding to accurately predict reactive sticking or desorption probabilities, as it requires averaging over tens of thousands of initial conditions. High-dimensional machine learning-based interatomic potentials are starting to be more commonly used in gas-surface dynamics, yet robust approaches to generate reliable training data and assess how model uncertainty affects the prediction of dynamic observables are not well established. Here, we employ ensemble learning to adaptively generate training data while assessing model performance with full uncertainty quantification (UQ) for reaction probabilities of hydrogen scattering on different copper facets. We use this approach to investigate the performance of two message-passing neural networks, SchNet and PaiNN. Ensemble-based UQ and iterative refinement allow us to expose the shortcomings of the invariant pairwise-distance-based feature representation in the SchNet model for gas-surface dynamics.

Photoluminescent copper(I) iodide alkylpyridine thin films as sensors for volatile halogenated compounds.

The paper presents the fabrication and characterization of [CuI(L)]n thin films, where L represents various alkylpyridine ligands including 4-methylpyridine, 3-methylpyridine, 2-methylpyridine, 4-tbutylpyridine, 3,4-dimethylpyridine, and 3,5-dimethylpyridine. The thin films were synthesized by exposing the corresponding ligands to CuI thin films through vapor deposition. The coordination reactions occurring on the films were investigated using PXRD and time-dependent photoluminescence spectroscopy, and a comparison was made between the structures of the thin films and the corresponding powder phases. The films showed primarly blue emission (λem = 457-515 nm) and polymeric structures with excited state lifetimes ranging from 0.6 to 5.5 µs. Significantly, the studied compounds exhibited fast reversible luminescence quenching when exposed to vapors of dichloromethane and dibromomethane (15 and 30 min respectively), and the luminescence was restored upon re-exposure to the alkylpyridine ligand (after 20 min). These findings indicate that these thin films hold promise for applications as sensors (with sensitive and reversible detection capability) for volatile halogen-based compounds (VHC).