The Influence of Impedance on the Efficacy of Radiofrequency Ablation for Benign Thyroid Nodules.

OBJECTIVE: Radiofrequency ablation (RFA) uses the heat generated by a high-frequency alternating electric current, and according to Ohm's and Joule's law, the delivered current is inversely proportional to the circuit impedance. The primary objective of this study was to investigate whether tissue impedance during radiofrequency ablation (RFA) for benign thyroid nodules is related to the degree of volume reduction. METHODS: This observational study included consecutive patients treated with RFA for benign thyroid nodules from February 2020 to August 2023. Technical effectiveness was defined as a volume reduction percentage (VRP) >75% at 6 months after the treatment. Multivariate logistic regression analyses were performed to identify the potential role of clinical factors and changes in tissue impedance on technique effectiveness. RESULTS: Totally 72 patients were included with 73 benign thyroid nodules. Maximal impedance peaks reached <18 times, and mean procedural impedance ≤300 Ω were significantly associated with a volume decrease of >75% at bivariate analysis. These cutoff points were exploratory, as no existing literature suggests these variables are related to the degree of volume reduction. After adjusting for age, volume, and composition, significant associations were found for mean electrical impedance in the multivariate analysis (OR = 4.86 [confidence interval [CI] 1.29-18.26], p = 0.019). The energy adjusted by volume (delivered energy) was not associated with a VRP >75% (p = 0.7746). CONCLUSIONS: This study suggests that a mean procedural impedance

Switch-2 determines Mg2+ADP-release kinetics and fine-tunes the duty ratio of Dictyostelium class-1 myosins.

Though myosins share a structurally conserved motor domain, single amino acid variations of active site elements, including the P-loop, switch-1 and switch-2, which act as nucleotide sensors, can substantially determine the kinetic signature of a myosin, i.e., to either perform fast movement or enable long-range transport and tension generation. Switch-2 essentially contributes to the ATP hydrolysis reaction and determines product release. With few exceptions, class-1 myosin harbor a tyrosine in the switch-2 consensus sequence DIYGFE, at a position where class-2 myosins and a selection of myosins from other classes have a substitution. Here, we addressed the role of the tyrosine in switch-2 of class-1 myosins as potential determinant of the duty ratio. We generated constitutively active motor domain constructs of two class-1 myosins from the social amoeba Dictyostelium discoideum, namely, Myo1E, a high duty ratio myosin and Myo1B, a low duty ratio myosin. In Myo1E we introduced mutation Y388F and in Myo1B mutation F387Y. The detailed functional characterization by steady-state and transient kinetic experiments, combined with in vitro motility and landing assays revealed an almost reciprocal relationship of a number of critical kinetic parameters and equilibrium constants between wild-type and mutants that dictate the lifetime of the strongly actin-attached states of myosin. The Y-to-F mutation increased the duty ratio of Moy1B by almost one order of magnitude, while the introduction of the phenylalanine in switch-2 of Myo1E transformed the myosin into a low duty ratio motor. These data together with structural considerations propose a role of switch-2 in fine-tuning ADP release through a mechanism, where the class-specific tyrosine together with surrounding residues contributes to the coordination of Mg2+ and ADP. Our results highlight the importance of conserved switch-2 residues in class-1 myosins for efficient chemo-mechanical coupling, revealing that switch-2 is important to adjust the duty ratio of the amoeboid class-1 myosins for performing movement, transport or gating functions.

Long-wave infrared pulsed external-cavity QCL spectrometer using a hollow waveguide gas cell.

A spectrometer built using an external cavity pulsed quantum cascade laser is described. The spectrometer has a tuning range from 10 - 13 µm (1,000 - 769 cm-1) and is designed to target volatile organic compounds (VOCs) which often exhibit water-free molecular absorption within the region. The spectrometer utilizes a hollow silica waveguide gas cell which has an internal volume of a few millilitres, a fast response time (∼1 s), and is advantageous when only low sample volumes, similar to the cell volume, are available. Propane is used as a test gas because it is easy to handle, and its spectral profile is comparable to VOCs of interest. Its absorption in the region is primarily within the ν21 band which spans from 10.55 - 11.16 µm (948 - 896 cm-1). Spectral measurements at a range of concentrations show good linearity and an Allan deviation of absorbance values recorded over a 100-minute period indicates a minimum detectable absorbance of 3.5×10-5 at an integration time of 75 s.

GI.1 Norovirus Neutralizing Antibody Levels Are Correlated with GI.1 Histo-blood Group Antigen-Blocking Antibody Levels.

BACKGROUND: The in vitro cultivation of human noroviruses allows a comparison of antibody levels measured in neutralization and histoblood group antigen (HBGA)-blocking assays. METHODS: Serum samples collected during the evaluation of an investigational norovirus vaccine (HIL-214 [formerly TAK-214]) were assayed for neutralizing antibody levels against the vaccine's prototype Norwalk virus/GI.1 (P1) virus strain. Results were compared to those previously determined using HBGA-blocking assays. RESULTS: Neutralizing antibody seroresponses were observed in 83% of 24 vaccinated adults, and antibody levels were highly correlated (r=0.81, P<0.001) with those measured by HBGA-blocking. CONCLUSIONS: GI.1-specific HBGA-blocking antibodies are a surrogate for neutralization of GI.1 norovirus.

Automatized self-supervised learning for skin lesion screening.

Melanoma, the deadliest form of skin cancer, has seen a steady increase in incidence rates worldwide, posing a significant challenge to dermatologists. Early detection is crucial for improving patient survival rates. However, performing total body screening (TBS), i.e., identifying suspicious lesions or ugly ducklings (UDs) by visual inspection, can be challenging and often requires sound expertise in pigmented lesions. To assist users of varying expertise levels, an artificial intelligence (AI) decision support tool was developed. Our solution identifies and characterizes UDs from real-world wide-field patient images. It employs a state-of-the-art object detection algorithm to locate and isolate all skin lesions present in a patient's total body images. These lesions are then sorted based on their level of suspiciousness using a self-supervised AI approach, tailored to the specific context of the patient under examination. A clinical validation study was conducted to evaluate the tool's performance. The results demonstrated an average sensitivity of 95% for the top-10 AI-identified UDs on skin lesions selected by the majority of experts in pigmented skin lesions. The study also found that the tool increased dermatologists' confidence when formulating a diagnosis, and the average majority agreement with the top-10 AI-identified UDs reached 100% when assisted by our tool. With the development of this AI-based decision support tool, we aim to address the shortage of specialists, enable faster consultation times for patients, and demonstrate the impact and usability of AI-assisted screening. Future developments will include expanding the dataset to include histologically confirmed melanoma and validating the tool for additional body regions.

Micrometeorite collections: a review and their current status.

Micrometeorites are estimated to represent the main part of the present flux of extraterrestrial matter found on the Earth's surface and provide valuable samples to probe the interplanetary medium. Here, we describe large and representative collections of micrometeorites currently available to the scientific community. These include Antarctic collections from surface ice and snow, as well as glacial sediments from the eroded top of nunataks-summits outcropping from the icesheet-and moraines. Collections extracted from deep-sea sediments (DSS) produced a large number of micrometeorites, in particular, iron-rich cosmic spherules that are rarer in other collections. Collections from the old and stable surface of the Atacama Desert show that finding large numbers of micrometeorites is not restricted to polar regions or DSS. The advent of rooftop collections marks an important step into involving citizen science in the study of micrometeorites, as well as providing potential sampling locations over all latitudes to explore the modern flux. We explore their strengths of the collections to address specific scientific questions and their potential weaknesses. The future of micrometeorite research will involve the finding of large fossil micrometeorite collections and benefit from recent advances in sampling cosmic dust directly from the air. This article is part of the theme issue 'Dust in the Solar System and beyond'.

Records of fleas (Siphonaptera) from Delaware.

We present an annotated checklist of fleas (Siphonaptera) known to occur in the state of Delaware based on an examination of Siphonaptera collections at the University of Delaware and the Carnegie Museum of Natural History, as well as new specimens of fleas we collected from wildlife, other hosts, and tick flags. We review published records and compile them herein with our new records, which include 3 species previously unreported from Delaware. With these additions, there are now 18 flea species from 19 avian and mammalian hosts documented from Delaware.

Consolidative Proton Radiotherapy for Pediatric Extramedullary Ocular Acute Myeloid Leukemia.

Purpose: Pediatric acute myeloid leukemia (AML) often involves extramedullary sites, which can be resistant to standard induction chemotherapy. Consolidative radiation therapy can be used in select cases to improve local control rates and help bridge patients to curative stem cell transplants. However, there is no previously published data to support the use of proton radiotherapy (PT) in this setting. We present radiographic findings and pathologic outcomes of the first reported patient with extramedullary ocular AML to be treated with PT. Patients and Methods: Details regarding diagnostic evaluation and treatment were obtained from the electronic medical records at the University of Florida Proton Therapy Institute, Nemours Children's Health, and St. Joseph's Children's Hospital. Results: This 7-month-old patient presented with biopsy-proven relapsed AML in the bilateral anterior chambers of the eyes, which did not resolve with induction chemotherapy. The patient then received PT to a dose of 24 cobalt gray equivalent to both eyes and was found to have no evidence of disease following treatment. Conclusion: This case provides further evidence that consolidative radiotherapy may be considered for select patients with extramedullary AML who have limited response to induction chemotherapy. Given the increased prevalence of extramedullary AML in pediatric patients, it is worth considering the utilization of PT to mitigate damage to nearby organs and the risk of secondary malignancies.

International Skin Imaging Collaboration-Designated Diagnoses (ISIC-DX): Consensus terminology for lesion diagnostic labeling.

BACKGROUND: A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms. OBJECTIVES: To achieve expert consensus on diagnostic terms for skin neoplasms and their hierarchical mapping. METHODS: Diagnostic terms were extracted from textbooks, publications and extant diagnostic codes. Terms were hierarchically mapped to super-categories (e.g. 'benign') and cellular/tissue-differentiation categories (e.g. 'melanocytic'), and appended with pertinent-modifiers and synonyms. These terms were evaluated using a modified-Delphi consensus approach. Experts from the International-Skin-Imaging-Collaboration (ISIC) were surveyed on agreement with terms and their hierarchical mapping; they could suggest modifying, deleting or adding terms. Consensus threshold was >75% for the initial rounds and >50% for the final round. RESULTS: Eighteen experts completed all Delphi rounds. Of 379 terms, 356 (94%) reached consensus in round one. Eleven of 226 (5%) benign-category terms, 6/140 (4%) malignant-category terms and 6/13 (46%) indeterminate-category terms did not reach initial agreement. Following three rounds, final consensus consisted of 362 terms mapped to 3 super-categories and 41 cellular/tissue-differentiation categories. CONCLUSIONS: We have created, agreed upon, and made public a taxonomy for skin neoplasms and their hierarchical mapping. Further study will be needed to evaluate the utility and completeness of the lexicon.

Bacterial Colonization on Endoscopic Materials and Surgical Field Without Infections After Transoral Endoscopic Thyroidectomy.

INTRODUCTION: Our aim was to determine whether bacteria contamination occurred within the surgical field or on endoscopic equipment during surgery using the transoral endoscopic thyroidectomy vestibular approach (TOETVA). MATERIALS AND METHODS: Participants were recruited from patients planned for TOETVA between May 2017 and December 2019. Bacterial samples were taken before and at the conclusion of the TOETVA procedure. The preoperative and postoperative samples were taken from the endoscopic materials and inferior oral vestibulum using a sterile flocked swab. RESULTS: The study resulted in 480 samples (80 TOETVAs). No vestibular, port site, or neck infections occurred in any of the patients. Three (3.7%) out of 80 patients developed postoperative fever. Our results show different microbial communities during TOETVA. The most prevalent species detected were S treptococcus species. Multivariate logistic regression analyses revealed that the degree of contamination depended on the sampling site (inferior vestibulum > equipment) ( P =0.03). In addition, the abundance of bacteria was affected by operative time ( P =0.013). There were no significant differences observed in isolation frequencies of bacteria in malignancy ( P =0.34). CONCLUSIONS: TOETVA surgery is categorized as a "clean-contaminated" operation. A swab identified the common colonizers of oral microbiota on the endoscopic equipment and within the surgical field.

A RANGE-WIDE ECTOPARASITE SURVEY FOR ALLEGHENY WOODRATS (NEOTOMA MAGISTER).

Allegheny woodrats (Neotoma magister) are karst-specializing rodents that are rare or in conservation need in many states within their current range. Parasitism and habitat fragmentation have been suggested as primary reasons for declining populations. The presence, prevalence, and impact of ectoparasites, including fleas, ticks, and bots, is not fully understood rangewide. We collected Allegheny woodrat ectoparasites across 8 states in their range, identifying parasites via morphological and genetic means. Across contributions from 8 states, we discovered 2 woodrat-specific fleas parasitizing Allegheny woodrats: Orchopeas pennsylvanicus (all contributing states, n = 228) and Epitedia cavernicola (Indiana only, n = 9). The former was a new state record in New Jersey and Ohio. Woodrat specialists Ixodes woodi were morphologically identified as the dominant tick species (n = 38), and our contributions to genetic databases may ease confusion in future efforts. Three generalist species of ticks representing 8 individuals were identified as Dermacentor variabilis, Amblyomma americanum, and Ixodes scapularis. Only 2 bot fly species were recognized in Allegheny woodrats: 1 squirrel bot (Cuterebra emasculator) and 10 individuals of Cuterebra sp. not genetically conspecific to any known eastern U.S. rodent bot. The host specificity for fleas is not surprising, given that previous small-scale surveys and ticks primarily appear to be a mix of genus-specific (Ixodes woodi) and generalist species. There remains uncertainty with bots via morphological and genetic analyses. Our survey presents a wide-ranging baseline survey for Allegheny woodrats across their range, emphasizing the diversity (or specificity) of parasite groups for this species. An understanding of Allegheny woodrats and the health impact of ectoparasites is imperative because they face myriad challenges rangewide, especially considering the bot-driven demise of 1 woodrat in our study. Ectoparasites can have a marked impact on already-declining woodrat populations across their range and should not be overlooked in future surveys.

The association of health-care contact days with physical function and survival in CCTG/AGITG CO.17.

INTRODUCTION: Although contact days-days with health-care contact outside home-are increasingly adopted as a measure of time toxicity and treatment burden, they could also serve as a surrogate of treatment-related harm. We sought to assess the association between contact days and patient-reported outcomes and the prognostic ability of contact days. METHODS: We conducted a secondary analysis of CO.17 that evaluated cetuximab vs supportive care in patients with advanced colorectal cancer. CO.17 collected European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 instrument data. We assessed the association between number of contact days in a window and changes in physical function and global health status and the association between number of contact days in the first 4 weeks with overall survival. RESULTS: There was a negative association between the number of contact days and change in physical function (per each additional contact day: at 4 weeks, 1.50-point decrease; 8 weeks, 1.06-point decrease; P < .0001 for both) but not with global health status. This negative association was seen in patients receiving cetuximab but not supportive care. More contact days in the first 4 weeks was associated with worse overall survival for all participants and patients receiving cetuximab (per each additional contact day: all participants, adjusted hazard ratio [HR] = 1.07, 95% confidence interval [CI] = 1.05 to 1.10; and cetuximab, adjusted HR = 1.08, 95% CI = 1.05 to 1.11; P < .0001 for both). CONCLUSIONS: In this secondary analysis of a clinical trial, more contact days early in the course were associated with declines in physical function and worse survival in all participants and in participants receiving cancer-directed treatment. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00079066.

Access to Oncology Medicines in Canada: Consensus Forum for Recommendations for Improvement.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients' access to best care. A modified Delphi methodology was used to identify consensus on 30 questions involving five themes: accountability, disparities, endpoints, timeliness, and cost-effectiveness. It was agreed that greater transparency is required across regulatory and HTA processes. Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding. Canadian health care providers request improvements in timely access to life-saving therapeutics in line with other comparator countries. Clinicians expect urgent improvements in Canadian health systems to give our patients their best chance of survival.

Systematic investigation of inadequate food access at a large southeastern land grant university.

Over the past decade, the impact of low food security on student well-being and academic performance has become a growing concern at institutions of higher education across the U.S. This mixed methods study adds to the growing body of evidence on the association between student socio-demographic and economic characteristics and food security. An online survey covering food access, student well-being, and housing security was sent to 35,337 undergraduate and graduate students at a large southeastern land grant university. A total of 2,116 complete responses were received; a 6% response rate. The survey responses also included 176 written statements by students. The survey found that 16% of both undergraduate and graduate students had low or very low food security, as defined by a modified USDA food security measure. The socio-demographic and economic characteristics that were linked to a higher likelihood of low food security included: having a GPA of less than 3.0, having a disability, being an international student, being a first-generation student, being a transfer student, going into debt to pay for food, being a Black or African American student, having poor mental health, having uncertain living arrangements, and having no medical insurance. Recommendations for enhancing student access to food, housing, and mental health services are discussed.

Long-term Quality of Life After Thyroidectomy: Transoral Endoscopic Thyroidectomy Vestibular Approach Versus Transcervical Approach.

OBJECTIVE: To compare long-term health-related quality of life (HRQOL) after Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA) and transcervical approach (TCA) thyroidectomy. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. METHODS: A web-based survey was distributed to patients at our institution who met the criteria for TOETVA and underwent thyroidectomy by TOETVA or TCA between August 2017 and October 2021. All survey participants were at least 6 months postsurgery. Minors, non-English speakers, and patients who received concomitant neck dissection or reoperative thyroidectomy were excluded from the study. The survey assessed quality of life through 4 standardized instruments: the Dermatology Life Quality Index (DLQI), the Eating Assessment Tool (EAT-10), the Voice Handicap Index (VHI-10), and the Short Form Health Survey (SF-36). RESULTS: A total of 108 TOETVA and 129 TCA patients were included in the study. The median age of respondents was 44 (36, 54; 25th, 75th percentile) years and median time from surgery to survey was 35 (22, 45; 25th, 75th percentile) months. TOETVA group DLQI (0.63 vs 0.99; P = .17), VHI-10 (1.94 vs 1.67; P = .35), EAT-10 (2.14 vs 2.32; P = .29), SF-36 physical component (52.25 vs 51.00; P = .25), and SF-36 mental component (47.74 vs 47.29; P = .87) scores were all similar to those of the TCA group. Scrutinizing specific DLQI questions, individuals in the TOETVA group were less self-conscious of their skin as compared to the TCA group (Q2; 0.08 vs 0.26, P = .03). CONCLUSION: Long-term HRQOL after TOETVA is similar to TCA, with significantly lower skin-related self-consciousness.

A clinical practice review of percutaneous ethanol injection for thyroid nodules: state of the art for benign, cystic lesions.

Percutaneous ethanol injection (PEI) is a widely used treatment option for cystic and predominantly cystic thyroid nodules. It has several advantages over other treatment modalities. Compared to surgery, PEI is less painful, can be performed in the outpatient setting, and carries less risk of transient or permanent side effects. Compared to other minimally invasive techniques such as radiofrequency ablation (RFA), PEI is less expensive and does not require specialized equipment. PEI performs well in the context of cystic nodules. PEI does not perform as well as other techniques in solid nodules, so its use as a primary treatment is limited to cystic and predominantly cystic thyroid nodules. However, PEI is also being explored as an adjunct treatment to improve ablation of solid nodules with other techniques. Here, we provide a clinical review discussing the genesis, mechanism of action, and patient selection with respect to ethanol ablation, as well as the procedure itself. Predictors of operative success, failure, and common adverse events are also summarized. Altogether, PEI allows impressive volume reduction rates with minimal complications. Several recent studies have also evaluated the long-term impact of PEI up to 10 years after treatment and revealed maintenance of robust treatment efficacy with no undesirable long-term sequelae. Thus, PEI remains the treatment of choice for benign but symptomatic cystic and predominantly cystic thyroid nodules.

Current status of optoacoustic breast imaging and future trends in clinical application: is it ready for prime time?

Optoacoustic imaging (OAI) is an emerging field with increasing applications in patients and exploratory clinical trials for breast cancer. Optoacoustic imaging (or photoacoustic imaging) employs non-ionizing, laser light to create thermoelastic expansion in tissues and detect the resulting ultrasonic emission. By combining high optical contrast capabilities with the high spatial resolution and anatomic detail of grayscale ultrasound, OAI offers unique opportunities for visualizing biological function of tissues in vivo. Over the past decade, human breast applications of OAI, including benign/malignant mass differentiation, distinguishing cancer molecular subtype, and predicting metastatic potential, have significantly increased. We discuss the current state of optoacoustic breast imaging, as well as future opportunities and clinical application trends. CLINICAL RELEVANCE STATEMENT: Optoacoustic imaging is a novel breast imaging technique that enables the assessment of breast cancer lesions and tumor biology without the risk of ionizing radiation exposure, intravenous contrast, or radionuclide injection. KEY POINTS: • Optoacoustic imaging (OAI) is a safe, non-invasive imaging technique with thriving research and high potential clinical impact. • OAI has been considered a complementary tool to current standard breast imaging techniques. • OAI combines parametric maps of molecules that absorb light and scatter acoustic waves (like hemoglobin, melanin, lipids, and water) with anatomical images, facilitating scalable and real-time molecular evaluation of tissues.

Somatic Versus Germline: A Case Series of Three Children With ATM-Mutated Medulloblastoma.

Somatic versus Germline-A Case Series of Three Children with ATM- mutated Medulloblastoma.

Little patients, big impacts: a narrative review of palliative and emergent radiotherapy for pediatric cancers.

BACKGROUND AND OBJECTIVE: The use of radiotherapy (RT) in the palliative and emergent settings for pediatric cancers is an under-utilized resource. Our objective was to provide an evidence-based review of the data to increase awareness of the benefit for this population along with providing guidance on pediatric specific treatment considerations for palliative care physicians, pediatric oncologists, and radiation oncologists. METHODS: A narrative review was performed querying PubMed, MEDLINE, ClinicalTrials.gov databases, and supplemented with review articles, survey studies, current and recent clinical trials. When limited data existed, well-designed retrospective and prospective studies in the adult setting were evaluated and expert opinion was provided from pediatric oncologists. KEY CONTENT AND FINDINGS: Pediatric specific treatment considerations include the use of anesthesia, impact of treatment on the developing child, and logistical challenges of RT. Treatment modality and dose selection are driven by histology and symptomatic site of pain, where we discuss detailed recommendations for hematologic, central nervous system, and solid tumors. For palliative RT, an underlying principle of searching for the lowest effective dose to balance response rate with minimal acute and late treatment related morbidity and logistical hardships is of paramount importance when caring for a pediatric patient. Lastly, we outline how to effectively communicate this option to patients and their caregivers. CONCLUSIONS: Palliative RT can be of valuable benefit in most settings for patients with pediatric cancer. There is an unmet need for prospective data to inform on dose-fractionation along with patient and caregiver reported outcomes.