In-office Transoral Hilar Sialolithotomy: A Cost-Effective and Patient-Centered Procedure.

Transoral sialolithotomy performed in-office under local anesthesia is routinely performed for distal submandibular stones. We demonstrate the senior author's novel practice of in-office transoral sialolithotomy for hilar and intraglandular stones. A review of cases performed by the senior author revealed similar rates of complication and stone recurrence as those reported in the literature from removal under general anesthesia. Laryngoscope, 2024.

Harmonic dependence of thermal magnetic particle imaging.

Advances in instrumentation and tracer materials are still required to enable sensitive, accurate, and localized in situ 3D temperature monitoring by magnetic particle imaging (MPI). We have developed a high-resolution magnetic particle imaging instrument and implemented a low-noise multi-harmonic lock-in detection method to observe and quantify temperature variations in iron oxide nanoparticle tracers using the harmonic ratio method for determining temperature. Using isolated harmonics for MPI and temperature imaging revealed an apparent dependence of imaging resolution on harmonic number. Thus, we present experimental and simulation studies to quantify the imaging resolution dependence on temperature and harmonic number, and directly validate the fundamental origin of MPI imaging resolution on harmonic number based on the concept of a harmonic point-spread-function.

Phylogenomic evolutionary insights in the fern family Gleicheniaceae.

The pantropical fern family Gleicheniaceae comprises approximately 157 species. Seven genera are currently recognized in the family, although their monophyly is still uncertain due to low sampling in phylogenetic studies. We examined the monophyly of the genera through extended sampling, using the first phylogenomic inference of the family including data from both nuclear and plastid genomes. Seventy-six samples were sequenced (70 Gleicheniaceae species and six outgroups) using high throughput sequencing, including all seven currently recognized genera. Plastid and nuclear data were recovered and assembled; the nuclear data was phased to reduce paralogy as well as hybrid noise in the final recovered topology. Maximum likelihood trees were built for each locus, and a concatenated dataset was built for both datasets. A species tree based on a multispecies coalescent model was generated, and divergence time analyses performed. We here present the first genomic phylogenetic inferences concerning Gleicheniaceae, confirming the monophyly of most genera except Sticherus, which we recovered as paraphyletic. Although most of the extant genera of Gleicheniaceae originated during the Mesozoic, several genera show Neogene and even Quaternary diversifications, and our results suggest that reticulation and polyploidy may have played significant roles during this diversification. However, some genera, such as Rouxopteris and Stromatopteris, appear to represent evolutionary relicts.

A first-in-human phase 1 study of cavrotolimod, a TLR9 agonist spherical nucleic acid, in healthy participants: Evidence of immune activation.

Introduction: Tumor immunotherapy is designed to control malignancies through the host immune response but requires circumventing tumor-dysregulated immunomodulation through immunostimulation, relieving immunorepression, or a combination of both approaches. Here we designed and characterized cavrotolimod (formerly AST-008), an immunostimulatory spherical nucleic acid (SNA) compound targeting Toll-like receptor 9 (TLR9). We assessed the safety and pharmacodynamic (PD) properties of cavrotolimod in healthy participants in a first-in-human Phase 1 study under protocol AST-008-101 (NCT03086278; https://clinicaltrials.gov/ct2/show/NCT03086278). Methods: Healthy participants aged 18 to 40 years were enrolled to evaluate four dose levels of cavrotolimod across four cohorts. Each cohort included four participants, and all received a single subcutaneous dose of cavrotolimod. The dose levels were 5, 10, 12.5 and 18.8 µg/kg. Results and discussion: Cavrotolimod was well tolerated and elicited no serious adverse events or dose limiting toxicities at the doses tested. The results demonstrated that cavrotolimod is a potent innate immune activator, specifically stimulating Th1-type immune responses, and exhibits PD properties that may result in anti-tumor effects in patients with cancer. This study suggests that cavrotolimod is a promising clinical immunotherapy agent.

Presentation and evaluation of an atypical, supraclavicular mass in a pediatric patient.

Although the vast majority of pediatric neck masses are benign, pediatric malignancies commonly present in the supraclavicular region. We present the case of a 4-year-old male who presented with a mass in the trapezius muscle with accompanying lymphadenopathy. An extensive work-up was performed to exclude malignancy, and the patient was ultimately diagnosed with a benign monocytic mass, which surgically excised. He has been doing well since surgery with no evidence of recurrence. A review of the literature revealed this case to be the first of its kind to be reported.

Deep vicariance and frequent transoceanic dispersal shape the evolutionary history of a globally distributed fern family.

PREMISE: The historical biogeography of ferns is typically expected to be dominated by long-distance dispersal due to their minuscule spores. However, few studies have inferred the historical biogeography of a large and widely distributed group of ferns to test this hypothesis. Our aims were to determine the extent to which long-distance dispersal vs. vicariance have shaped the history of the fern family Blechnaceae, to explore ecological correlates of dispersal and diversification, and to determine whether these patterns differ between the northern and southern hemispheres. METHODS: We used sequence data for three chloroplast loci to infer a time-calibrated phylogeny for 154 of 265 species of Blechnaceae, including representatives of all genera in the family. This tree was used to conduct ancestral range reconstruction and stochastic character mapping, estimate diversification rates, and identify ecological correlates of diversification. RESULTS: Blechnaceae originated in Eurasia and began diversifying in the late Cretaceous. A lineage comprising most extant diversity diversified principally in the austral Pacific region around the Paleocene-Eocene Thermal Maximum. Land connections that existed near the poles during periods of warm climates likely facilitated migration of several lineages, with subsequent climate-mediated vicariance shaping current distributions. Long-distance dispersal is frequent and asymmetrical, with New Zealand/Pacific Islands, Australia, and tropical America being major source areas. CONCLUSIONS: Ancient vicariance and extensive long-distance dispersal have shaped the history of Blechnaceae in both the northern and southern hemispheres. The exceptional diversity in austral regions appears to reflect rapid speciation in these areas; mechanisms underlying this evolutionary success remain uncertain.

Loop modification of the traditional three-loop pulley pattern improves the biomechanical properties and resistance to 3-mm gap formation in a canine common calcanean teno-osseous avulsion model.

OBJECTIVE: To compare the biomechanical properties and gapping characteristics following loop modification of a 3-loop-pulley (3LP) pattern in an ex vivo canine common calcaneal tendon (CCT) avulsion repair model. SAMPLE: 56 skeletally mature hindlimbs from 28 canine cadavers. PROCEDURES: The CCTs were randomized to 1 of 4 experimental groups (n = 14/group) then sharply transected at the teno-osseous junction. Groups consisted of a 3LP, 4-loop-pulley (4LP), 5-loop-pulley (5LP), or 6-loop-pulley (6LP) pattern with loops placed 60° apart using size-0 polypropylene. Yield, peak, and failure loads, construct stiffness, loads to produce a 3-mm teno-osseous gap, and failure mode were evaluated and compared between groups. RESULTS: Yield (P = 0.001), peak (P < 0.001), and failure loads (P < 0.001), construct stiffness (P < 0.001), and loads to 3-mm gap formation (P = 0.005) were all significantly greater for 6LP compared to all other groups. Mode of failure did not differ among groups (P = 0.733) with 75% (42/56) of repairs failing by mechanism of core sutures pulling through the tendinous tissue. Pattern modification by increasing the number of loops increased the repair site strength by 1.4, 1.6, and 1.8 times for 4LP, 5LP, and 6LP compared to 3LP, respectively. CLINICAL RELEVANCE: Increasing the number of suture loops compared to a traditional 3LP repair is a relatively simple technique modification that significantly increases teno-osseous repair site strength and loads required to cause 3-mm gap formation. The results of this study justify further focused investigation of increasing the number of suture loops in vivo for teno-osseous CCT repair in dogs.

Effect of calcanean bone-tunnel orientation for teno-osseous repair in a canine common calcanean tendon avulsion model.

OBJECTIVE: To determine the influence of bone-tunnel anchoring technique on teno-osseous repair of the common calcanean tendon (CCT) in dogs. STUDY DESIGN: Randomized, ex vivo, biomechanical. POPULATION: Forty-two skeletally mature canine hindlimbs. METHODS: Canine hindlimbs were dissected to produce a model simulating avulsion of the CCT and accessory tendons from the calcaneus. Hindlimbs were randomized to 1 of 3 anchoring techniques (n = 14/group): a single transverse tunnel (TT), vertical tunnels (VT), or modified bone tunnels (MT) for teno-osseous repair in a 3-loop-pulley (3LP) pattern using 0 USP polypropylene. Yield, peak and failure loads, construct stiffness, loads to produce a 3 mm teno-osseous gap, and failure modes were compared between groups. RESULTS: The only difference detected consisted of TT constructs yielding at loads 25% higher than MT constructs (P = .027). CONCLUSION: Although yield loads were lower in MT constructs than other groups, the bone-tunnel anchoring techniques tested here did not appear to influence the biomechanical properties or gapping characteristics of teno-osseous repairs in this canine CCT avulsion model. CLINICAL SIGNIFICANCE: All drilling techniques and bone-tunnel orientations tested in the study reported here offer viable options to reattach the CCT to the calcaneus. Surgeons should evaluate how bone-tunnel orientation may affect placement of adjunctive fixation methods to stabilize the talocrural joint after primary CCT repair in dogs.

A permineralized Early Cretaceous lycopsid from China and the evolution of crown clubmosses.

Lycopodiaceae are one of three surviving families of lycopsids, a lineage of vascular plants with a fossil history dating to at least the Early Devonian or perhaps the Late Silurian (c. 415 Ma). Many fossils have been linked to crown Lycopodiaceae, but the lack of well-preserved material has hindered definitive recognition of this group in the paleobotanical record. New, exceptionally well-preserved permineralized lycopsid fossils from the Early Cretaceous (125.6 ± 1.0 Ma) of Inner Mongolia, China, were examined in detail using acetate peel and micro-computed tomography techniques. The anatomy of extant Lycopodiaceae was analyzed for comparison using fluorescence microscopy. Phylogenetic relationships of the new fossil to extant Lycopodiaceae were evaluated using parsimony and maximum likelihood analyses. Lycopodicaulis oellgaardii gen. et sp. nov. provides the earliest unequivocal and best-documented evidence of crown Lycopodiaceae and Lycopodioideae, based on anatomically-preserved fossil material. Recognition of Lycopodicaulis in Asia during the Early Cretaceous indicates the presence of crown Lycopodiaceae at this time, and striking similarities of stem anatomy with extant species provide a framework for the understanding of the interaction of branching and vascular anatomy in crown-group lycopsids.

Advanced characterization of magnetization dynamics in iron oxide magnetic nanoparticle tracers.

Characterization of the magnetization dynamics of single-domain magnetic nanoparticles (MNPs) is important for magnetic particle imaging (MPI), magnetic resonance imaging (MRI), and emerging medical diagnostic/therapeutic technologies. Depending on particle size and temperature, nanoparticle magnetization relaxation time constants span from nanoseconds to seconds. In solution, relaxation occurs via coupled Brownian and Néel relaxation mechanisms. Even though their coexistence complicates analysis, the presence of two timescales presents opportunities for more direct control of magnetization behavior if the two processes can be understood, isolated, and tuned. Using high frequency coils and sample temperature tunability, we demonstrate unambiguous determination of the specific relaxation processes for iron oxide nanoparticles using both time and frequency domain techniques. Furthermore, we study the evolution of the fast dynamics at ≈ 10 nanosecond timescales, for magnetic field amplitudes relevant to MPI.

"Vaccine Passports" May Backfire: Findings from a Cross-Sectional Study in the UK and Israel on Willingness to Get Vaccinated against COVID-19.

Domestic "vaccine passports" are being implemented across the world as a way of increasing vaccinated people's freedom of movement and to encourage vaccination. However, these vaccine passports may affect people's vaccination decisions in unintended and undesirable ways. This cross-sectional study investigated whether people's willingness and motivation to get vaccinated relate to their psychological needs (autonomy, competence and relatedness), and how vaccine passports might affect these needs. Across two countries and 1358 participants, we found that need frustration-particularly autonomy frustration-was associated with lower willingness to get vaccinated and with a shift from self-determined to external motivation. In Israel (a country with vaccine passports), people reported greater autonomy frustration than in the UK (a country without vaccine passports). Our findings suggest that control measures, such as domestic vaccine passports, may have detrimental effects on people's autonomy, motivation, and willingness to get vaccinated. Policies should strive to achieve a highly vaccinated population by supporting individuals' autonomous motivation to get vaccinated and using messages of autonomy and relatedness, rather than applying pressure and external controls.

Iatrogenic orbital cerebrospinal fluid leak in a young pediatric patient: Factors to consider.

Orbital abscess and subperiosteal abscess are pathologies which may require surgical treatment in the pediatric patient. Though rare, orbital cerebrospinal fluid (CSF) leak is a serious complication of abscess drainage. This paper presents a unique 5-month-old male with transorbital abscess drainage complicated by CSF leak. An endoscope was used to repair the defect through the orbitotomy incision. There was no evidence of persistent leak at follow-up. The surgical approach likely contributed to the complication, and the otolaryngologist played a key role in the leak repair. This case should serve to raise the awareness regarding considerations to avoid orbital CSF leak.

Insights into the evolutionary history and widespread occurrence of antheridiogen systems in ferns.

Sex expression of homosporous ferns is controlled by multiple factors, one being the antheridiogen system. Antheridiogens are pheromones released by sexually mature female fern gametophytes, turning nearby asexual gametophytes precociously male. Nevertheless, not all species respond. It is still unknown how many fern species use antheridiogens, how the antheridiogen system evolved, and whether it is affected by polyploidy and/or apomixis. We tested the response of 68 fern species to antheridiogens in cultivation. These results were combined with a comprehensive review of literature to form the largest dataset of antheridiogen interactions to date. Analyzed species also were coded as apomictic or sexual and diploid or polyploid. Our final dataset contains a total of 498 interactions involving 208 species (c. 2% of all ferns). About 65% of studied species respond to antheridiogen. Multiple antheridiogen types were delimited and their evolution is discussed. Antheridiogen responsiveness was not significantly affected by apomixis or polyploidy. Antheridiogens are widely used by ferns to direct sex expression. The antheridiogen system likely evolved multiple times and provides homosporous ferns with the benefits often associated with heterospory, such as increased rates of outcrossing. Despite expectations, antheridiogens may be beneficial to polyploids and apomicts.

Tissue engineering applications in otolaryngology-The state of translation.

While tissue engineering holds significant potential to address current limitations in reconstructive surgery of the head and neck, few constructs have made their way into routine clinical use. In this review, we aim to appraise the state of head and neck tissue engineering over the past five years, with a specific focus on otologic, nasal, craniofacial bone, and laryngotracheal applications. A comprehensive scoping search of the PubMed database was performed and over 2000 article hits were returned with 290 articles included in the final review. These publications have addressed the hallmark characteristics of tissue engineering (cellular source, scaffold, and growth signaling) for head and neck anatomical sites. While there have been promising reports of effective tissue engineered interventions in small groups of human patients, the majority of research remains constrained to in vitro and in vivo studies aimed at furthering the understanding of the biological processes involved in tissue engineering. Further, differences in functional and cosmetic properties of the ear, nose, airway, and craniofacial bone affect the emphasis of investigation at each site. While otolaryngologists currently play a role in tissue engineering translational research, continued multidisciplinary efforts will likely be required to push the state of translation towards tissue-engineered constructs available for routine clinical use. LEVEL OF EVIDENCE: NA.

Respiratory viral panels and pediatric airway evaluation: The role of testing for upper respiratory infections to stratify perioperative risk.

OBJECTIVES: Children admitted with stridor and respiratory distress comprise a complex patient group that requires the otolaryngologist to decide when to assess and intervene with direct laryngoscopy and bronchoscopy (DLB). Historically, the diagnosis of viral upper respiratory tract infection (URTI) can lead to postponement of surgery due to concerns of perioperative complications related to acute illness. Respiratory viral panels (RVP) are often used to confirm the presence of recent or active viral infection and can affect the differential diagnosis of upper airway obstruction. This study examined whether positive RVP testing is associated with perioperative complications and operative findings in pediatric patients undergoing inpatient DLB. METHODS: A retrospective chart review of 132 pediatric patient encounters was performed. Viral testing results, DLB indication, DLB findings, and perioperative complications were compared. RESULTS: Sixty encounters (45.5%) involved a positive RVP, and 72 (54.5%) involved a negative RVP. Those with positive RVP were less likely to have a preoperative structural airway diagnosis (P =.0250) and more likely to have a history of recurrent upper respiratory infections (P =.0464). The most common reason for DLB was the need to assess the airway due to concern for structural pathology. Anatomic abnormalities were seen in a majority of encounters (77.3%) Laryngospasm occurred in 1 (1.7%) RVP positive and 1 (1.4%) RVP negative encounter, and 2 (2.8%) RVP negative encounters required reintubation. No other major complications were observed. No association was noted between RVP results and incidence of major or minor complication. CONCLUSIONS: Major perioperative complications after surgical intervention with DLB for the management of complex, inpatient children with stridor and respiratory distress are rare. RVP positivity, specific pathogens identified on RVP, and presence of URI symptoms were not associated with perioperative complications.

AC magnetometry with active stabilization and harmonic suppression for magnetic nanoparticle spectroscopy and thermometry.

Magnetic nanoparticle (MNP) thermometry based on magnetic particle spectroscopy (MPS) is explored as a potential approach for realizing in-situ temperature measurement of 3D objects. MNP thermometry relies on the nonlinear magnetization response to an AC drive field. This nonlinear response has functional dependence on frequency and temperature, governed by the complex magnetization dynamics of MNPs suspended in solution. In this work, we introduce our approach for accurate and precise AC magnetization measurements using actively stabilized drive fields ranging from DC to 10 kHz. To isolate the harmonic response of MNPs from the drive field, we also perform active cancellation to reach drive field suppression up to 120 dB. Active stabilization and cancellation are utilized for real-time, sensitive measurements of AC magnetization of commercial samples, with stability on the timescale of hours. Initial results for MNP thermometry are demonstrated using this technique, and we achieved a total temperature uncertainty of 410 mK and 170 mK at 100 ms and 10 s integration time, respectively.