Imaging Modalities for Head and Neck Cancer: Present and Future.

Several imaging modalities are utilized in the diagnosis, treatment, and surveillance of head and neck cancer. First-line imaging remains computed tomography (CT); however, MRI, PET with CT (PET/CT), and ultrasound are often used. In the last decade, several new imaging modalities have been developed that have the potential to improve early detection, modify treatment, decrease treatment morbidity, and augment surveillance. Among these, molecular imaging, lymph node mapping, and adjustments to endoscopic techniques are promising. The present review focuses on existing imaging, novel techniques, and the recent changes to imaging practices within the field.

When to Start Computer-Based Auditory Training After Cochlear Implantation: Effects on Quality of Life and Speech Recognition.

OBJECTIVE: Computer-based auditory training (CBAT) has been shown to improve outcomes in adult cochlear implant (CI) users. This study evaluates in new CI users whether starting CBAT within 3 months of activation or later impacts CI outcomes. STUDY DESIGN: Prospective natural experiment. SETTING: Tertiary academic medical center. PATIENTS: Sixty-five new adult CI users. INTERVENTIONS: CBAT use over the first-year postactivation. MAIN OUTCOME MEASURES: Speech recognition scores and CIQOL-35 Profile score improvements between CI recipients who started CBAT resources early (<3 mo) and late (3-12 mo) postactivation. RESULTS: A total of 43 CI recipients started using CBAT within 3 months postactivation (early) and 22 after 3 months (late). Patients who used CBAT within 3 months postactivation showed significantly greater improvement in consonant-nucleus-consonant words (CNCw) (48.3 ± 24.2% vs 27.8 ± 24.9%; d = 0.84), AzBio Sentences in quiet (55.1 ± 28.0% vs 35.7 ± 36.5%; d = 0.62), and CIQOL-35 listening domain scores (18.2 ± 16.3 vs 6.9 ± 12.9, d = 0.73 [0.023, 1.43]), at 3 months postactivation, compared to those who had not yet initiated CBAT. However, by 12 months postactivation, after which all CI recipients had started CBAT, there were no differences observed between patients who started CBAT early or late in speech recognition scores (CNCw: d = 0.26 [-0.35, 0.88]; AzBio: d = 0.37 [-0.23, 0.97]) or in any CIQOL global or domain score (d-range = 0.014-0.47). CONCLUSIONS: Auditory training with self-directed computer software (CBAT) may yield speech recognition and quality-of-life benefits for new adult CI recipients. While early users showed greater improvement in outcomes at 3 months postactivation than users who started later, both groups achieved similar benefits by 12 months postactivation.

Propositional density: cognitive impairment and aging.

It is important to understand the relationship between cognitive abilities and language processing. Here, we explore a burgeoning area of research that harnesses semantic indices to predict cognitive impairment and track cognitive decline. One such index, propositional density, quantifies the information conveyed per language segment. Despite some variation stemming from methodological, sampling, and measurement differences, we suggest that propositional density has diagnostic and assessment value. This paper surveys existing studies that have used propositional density in the context of cognitive aging and impairment and offers some insights into the use of this index to highlight differences in cognition. We also suggest further explorations of basic research involving this concept, and some applications for assessing cognitive health.

Implementation of a pharmacist-guided pharmacogenomics dosing service at a rural NCI-designated comprehensive cancer center.

INTRODUCTION: The goal of pharmacogenetic testing is to identify genetic variants with significant implications on drug safety and efficacy. Several professional organizations and institutions have demonstrated the value of pharmacist involvement in the implementation of pharmacogenomic services. Therefore, we aimed to establish a pharmacist-guided model for interpretation of pharmacogenetic results for all oncology patients seen at the Dartmouth Cancer Center (DCC) in Lebanon, NH. METHODS: A pilot of a pharmacist-guided pharmacogenomics dosing service was implemented at the DCC. Pharmacy services included review of results from a next generation sequencing panel for DPYD, TPMT, NUDT15, and UGT1A1 variants. The pharmacist wrote a note in the electronic health record (EHR) detailing actionable drug-gene interactions and drug-dosing guidance, which was then routed to the treating oncologist. Outcomes collected included highlighting actionable mutations and defining pharmacist interventions. In addition, time spent formulating and documenting patient-specific drug-dosing recommendations was collected. RESULTS: From February 2024 through May 2024, a total of 71 patients with pharmacogenetic results, provided by the clinical molecular laboratory at Dartmouth Health, were reviewed by the pharmacist. The majority of patients tested were diagnosed with a malignancy of gastrointestinal origin. Twenty-one patients were found to have actionable variants in at least one of the four genes evaluated, and five of the 21 identified patients had active treatment plans for which dose changes were then implemented. CONCLUSIONS: Implementation of a pharmacist-guided pharmacogenomics based dosing service aided in optimizing drug therapy and has positioned Dartmouth Health for further expansion of pharmacogenomics and personalized patient care.

Human retrograde amnesia and memory consolidation.

This paper reports a reassessment of published literature on the question of whether retrograde amnesia data from patients with severe trauma supports the idea that there is ongoing consolidation of long-lasting memories. That is, memory consolidation continues for decades with older memories being increasingly consolidated, and, thus, more protected from forgetting. Our analysis was limited to patients with specific traumas rather than neurodegenerative conditions that can be complicated by the additional presence of significant anterograde amnesia. These constraints were used because trauma patients have a definitive start to their amnesia allowing comparison of their memories before this event, unlike when there is an undefined amnesia onset. Our results revealed that the standard account of retrograde amnesia only fits part of the data, with more than half not conforming to this account. Specifically, damage to different brain areas was associated with different patterns of retrograde amnesia. Those cases where the standard retrograde amnesia account was held tended to involve damage to the hippocampus and temporal lobes, as expected. Future directions to better understand the influence of retrograde amnesia and memory consolidation are suggested.

A comparative analysis of peritoneal flap and intestinal vaginoplasty for management of vaginal stenosis.

BACKGROUND: In transgender or non-binary patients (TGNB) with failed penile inversion vaginoplasty (PIV), peritoneal flap vaginoplasty (PFV) and intestinal segment vaginoplasty (ISV) facilitate restoration of neovaginal depth and sexual function. This study compared the outcomes of revision PFV and ISV in TGNB patients with failed PIV. METHODS: TGNB patients who underwent secondary PFV or ISV from December 2018 to April 2023 were reviewed. RESULTS: Twenty-one (5.8%) patients underwent secondary PFV and 24 (6.6%) underwent secondary ISV, due to vaginal stenosis (n = 45, 100.0%). Mean duration to first successful dilation and average vaginal depth were comparable between the groups. Seven (33.3%) PFV patients experienced short-term complications, including introital dehiscence (n = 2, 9.5%), vaginal stenosis (n = 2, 9.5%), vaginal bleeding (n = 2, 9.5%), and reoperation (n = 2, 9.5%). Nine (42.9%) experienced long-term complications, including urethrovaginal fistula formation (n = 2, 9.5%), hypergranulation (n = 2, 9.5%), vaginal stenosis (n = 7, 33.3%), and reoperation (n = 6, 28.6%). Ten (41.7%) ISV patients experienced short-term complications, including dehiscence (n = 4, 19.0%), ileus (n = 2, 8.3%), introital stenosis (n = 2, 9.5%), and reoperation due to vaginal bleeding (n = 2, 8.3%). Six (25.0%) experienced long-term complications, including introital stenosis (n = 3, 12.5%), mucosal prolapse (n = 2, 8.3%), and reoperation due to mucosal prolapse (n = 4, 16.7%). Secondary PFV had a higher rate of vaginal stenosis (p = 0.003). There were no cases of partial or full-thickness flap necrosis. CONCLUSION: Revision PFV and ISV represent viable techniques for addressing vaginal stenosis secondary to PIV. Although PFV and ISV had comparable rates of short-term complications, ISV demonstrated a lower incidence of recurrent vaginal stenosis, which may inform operative decision-making.

A novel study: fragmented and holistic forgetting.

According to recent theoretical work, certain event memories are more likely to be remembered or forgotten in their entirety. This prior work focused on collections of concepts, such as person-location-object triples. To explore this idea with complex materials, we created triples of people, locations, objects, or activities from events in real-world novels. People who had read one of the included novels were provided with one element from these triples (the cue) and asked to identify which of six alternatives best went with it. The results revealed that memory for the narrative events remained stable across many years. Moreover, people recalled events in a more holistic manner than would be expected by chance. This was more likely the more causally important an event was. This pattern of performance also remained stable over time. Our results are consistent with the idea that event models involve integrating separate elements into a single coherent representation, and this is likely to stay integrated over long periods of time. However, the degree to which this is so appears to be related to how well-integrated the information is within a larger set of events.

Recurrent evolution of small body size and loss of the sword ornament in Northern swordtail fish.

Across the tree of life, species have repeatedly evolved similar phenotypes. While well-studied for ecological traits, there is also evidence for recurrent evolution of sexually selected traits. Swordtail fish (Xiphophorus) are a classic model system for studying sexual selection, and female Xiphophorus exhibit strong mate preferences for large male body size and a range of sexually dimorphic ornaments. Interestingly, sexually selected traits have also been lost multiple times in the genus. However, there has been uncertainty over the number of losses of ornamentation and large body size because phylogenetic relationships between species in this group have historically been controversial, partially due to prevalent gene flow. Here, we use whole-genome sequencing approaches to re-examine phylogenetic relationships within a Xiphophorus clade that varies in the presence and absence of sexually selected traits. Using wild-caught individuals, we determine the phylogenetic placement of a small, unornamented species, X. continens, confirming an additional loss of ornamentation and large body size in the clade. With these revised phylogenetic relationships, we analyze evidence for coevolution between body size and other sexually selected traits using phylogenetic comparative methods. These results provide insights into the evolutionary pressures driving the recurrent loss of suites of sexually selected traits.

Dependence of tropical cyclone seeds and climate sensitivity on tropical cloud response.

Projections of future tropical cyclone frequency are uncertain, ranging from a slight increase to a considerable decrease according to climate models. Estimation of how much the Earth's surface temperature warms in response to greenhouse gas increase, quantified by effective climate sensitivity, is also uncertain. These two uncertainties have historically been studied independently as they concern different scales: One quantifies the extreme weather and the other the mean climate. Here, we show that these two uncertainties are not independent and are both influenced by the response of tropical clouds to warming. Across climate models, we show an anticorrelation between shortwave cloud radiative feedback and changes in the frequency of seed vortices, a prevalent type of tropical cyclone precursors. We further show an anticorrelation between effective climate sensitivity and tropical cyclone frequency changes, suggesting that global tropical cyclone frequency tends to decrease more substantially in models with larger temperature increase.

Artificial Intelligence Driven Prehospital ECG Interpretation for the Reduction of False Positive Emergent Cardiac Catheterization Lab Activations: A Retrospective Cohort Study.

OBJECTIVES: Data suggest patients suffering acute coronary occlusion myocardial infarction (OMI) benefit from prompt primary percutaneous intervention (PPCI). Many emergency medical services (EMS) activate catheterization labs to reduce time to PPCI, but suffer a high burden of inappropriate activations. Artificial intelligence (AI) algorithms show promise to improve electrocardiogram (ECG) interpretation. The primary objective was to evaluate the potential of AI to reduce false positive activations without missing OMI. METHODS: Electrocardiograms were categorized by (1) STEMI criteria, (2) ECG integrated device software and (3) a proprietary AI algorithm (Queen of Hearts (QOH), Powerful Medical). If multiple ECGs were obtained and any one tracing was positive for a given method, that diagnostic method was considered positive. The primary outcome was OMI defined as an angiographic culprit lesion with either TIMI 0-2 flow; or TIMI 3 flow with either peak high sensitivity troponin-I > 5000 ng/L or new wall motion abnormality. The primary analysis was per-patient proportion of false positives. RESULTS: A total of 140 patients were screened and 117 met criteria. Of these, 48 met the primary outcome criteria of OMI. There were 80 positives by STEMI criteria, 88 by device algorithm, and 77 by AI software. All approaches reduced false positives, 27% for STEMI, 22% for device software, and 34% for AI (p < 0.01 for all). The reduction in false positives did not significantly differ between STEMI criteria and AI software (p = 0.19) but STEMI criteria missed 6 (5%) OMIs, while AI missed none (p = 0.01). CONCLUSIONS: In this single-center retrospective study, an AI-driven algorithm reduced false positive diagnoses of OMI compared to EMS clinician gestalt. Compared to AI (which missed no OMI), STEMI criteria also reduced false positives but missed 6 true OMI. External validation of these findings in prospective cohorts is indicated.

Geographic Differences in School Success Among Children and Adolescents in the United States.

The purpose of this study was to examine the relationship between rurality and challenges to school success: lack of school engagement, school absenteeism, and repeated grade. Cross-sectional data from the 2020 to 2021 National Survey of Children's Health, children ages 6 to 17 (n = 42,089), was used. Bivariate and multivariable logistic regression models were used to examine the associations between residence rurality and each outcome of interest. In bivariate analysis, rural children were more likely to have school absenteeism and repeat a school grade. In our adjusted models, there were no differences between rurality and the three measures of school success. Rural and urban children may be vulnerable to different risk factors for school failure. Findings from this study may be used by school nurses and policymakers as they design and implement programs in rural schools.

Validation studies and multi-omics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior.

Sensitivity to the subjective reinforcing properties of opioids has a genetic component and can predict addiction liability of opioid compounds. We previously identified Zhx2 as a candidate gene underlying increased brain concentration of the oxycodone ( OXY ) metabolite oxymorphone ( OMOR ) in BALB/cJ ( J ) versus BALB/cByJ ( By ) females that could increase OXY state-dependent reward. A large structural intronic variant is associated with a robust reduction of Zhx2 expression in J mice, which we hypothesized enhances OMOR levels and OXY addiction-like behaviors. We tested this hypothesis by restoring the Zhx2 loss-of-function in Js ( MVKO ) and modeling the loss-of-function variant through knocking out the Zhx2 coding exon ( E3KO ) in Bys and assessing brain OXY metabolite levels and behavior. Consistent with our hypothesis, Zhx2 E3KO females showed an increase in brain OMOR levels and OXY-induced locomotor activity. However, contrary to our hypothesis, state-dependent expression of OXY-CPP was decreased in E3KO females and increased in E3KO males. We also overexpressed Zhx2 in the livers and brains of Js and observed Zhx2 overexpression in select brain regions that was associated with reduced OXY state-dependent learning. Integrative transcriptomic and proteomic analysis of E3KO mice identified astrocyte function, cell adhesion, extracellular matrix properties, and endothelial cell functions as pathways influencing brain OXY metabolite concentration and behavior. These results support Zhx2 as a quantitative trait gene underlying brain OMOR concentration that is associated with changes in OXY behavior and implicate potential quantitative trait mechanisms that together inform our overall understanding of Zhx2 in brain function.

Value Defects in Spine Surgery: How to Reduce Wasteful Care and Improve Value.

Technological innovation has advanced the efficacy of spine surgery for patients; however, these advances do not consistently translate into clinical effectiveness. Some patients who undergo spine surgery experience continued chronic back pain and other complications that were not present before the procedure. Defects in healthcare value, such as the lack of clinical benefit from spine surgery, are, unfortunately, common, and the US healthcare system spends $1.4 trillion annually on value defects. In this article, we examine how avoidable complications, postacute healthcare use, revision surgeries, and readmissions among spine surgery patients contribute to $67 million of wasteful spending on value defects. Furthermore, we estimate that almost $27 million of these costs could be recuperated simply by redirecting patients to facilities referred to as centers of excellence. In total, quality improvement efforts are costly to implement but may only cost about $36 million to fully correct the $67 million in finances misappropriated to value defects. The objectives of this article are to present an approach to eliminate defects in spine surgery, including a center-of-excellence framework for eliminating defects specific to this group of procedures.

Dialysis More Available Than Patient Education in Counties With High Diabetes Prevalence.

Introduction: Poorly controlled diabetes is a principal cause of end stage renal disease (ESRD), generating an estimated 44% of new cases. Diabetes self-management education and support (DSMES) has been documented to reduce adverse outcomes such as ESRD. Helping patients better manage their condition could ultimately reduce ESRD prevalence. Methods: We compared the county-level availability of DSMES and dialysis as of November 2022 sorted by the estimated prevalence of diabetes among residents aged 18 years or older. The locations of DSMES programs and ESRD dialysis facilities were obtained from 2 professional organizations and the Centers for Medicare & Medicade Services. Estimated diabetes prevalence was obtained from the Centers for Disease Control and Prevention's PLACES data set. Counties were considered to have high diabetes prevalence if they fell into the top quartile for diabetes prevalence in 2019 (≥14.4% of adults). Analyses were conducted in 2023. Results: DSMES was available in 41.0% of counties but in only 20.7% of counties with high diabetes prevalence versus 47.9% of low prevalence counties. Dialysis facilities were present in 59.2% of all counties, in 52.8% of all high diabetes prevalence counties, and in 61.4% of other counties. DSMES availability was linked to the presence of a hospital in the county, with only 6.3% of counties without a hospital offering the service. Implications: DSMES could play a role in reducing the prevalence of ESRD. Public health professionals need to be aware of the differing levels of local availability of this service and work to develop partnerships to provide DSMES in high-prevalence areas not currently served.

Plant antagonistic facilitation across environmental gradients: a soil-resource ecosystem engineering model.

Theory questions the persistence of nonreciprocal interactions in which one plant has a positive net effect on a neighbor that, in return, has a negative net impact on its benefactor - a phenomenon known as antagonistic facilitation. We develop a spatially explicit consumer-resource model for belowground plant competition between ecosystem engineers, plants able to mine resources and make them available for any other plant in the community, and exploiters. We use the model to determine in what environmental conditions antagonistic facilitation via soil-resource engineering emerges as an optimal strategy. Antagonistic facilitation emerges in stressful environments where ecosystem engineers' self-benefits from mining resources outweigh the competition with opportunistic neighbors. Among all potential causes of stress considered in the model, the key environmental parameter driving changes in the interaction between plants is the proportion of the resource that becomes readily available for plant consumption in the absence of any mining activity. Our results align with theories of primary succession and the stress gradient hypothesis. However, we find that the total root biomass and its spatial allocation through the root system, often used to measure the sign of the interaction between plants, do not predict facilitation reliably.

Asymmetric triangular body-cover model of the vocal folds with bilateral intrinsic muscle activation.

Many voice disorders are linked to imbalanced muscle activity and known to exhibit asymmetric vocal fold vibration. However, the relation between imbalanced muscle activation and asymmetric vocal fold vibration is not well understood. This study introduces an asymmetric triangular body-cover model of the vocal folds, controlled by the activation of bilateral intrinsic laryngeal muscles, to investigate the effects of muscle imbalance on vocal fold oscillation. Various scenarios were considered, encompassing imbalance in individual muscles and muscle pairs, as well as accounting for asymmetry in lumped element parameters. Measurements of amplitude and phase asymmetries were employed to match the oscillatory behavior of two pathological cases: unilateral paralysis and muscle tension dysphonia. The resulting simulations exhibit muscle imbalance consistent with expectations in the composition of these voice disorders, yielding asymmetries exceeding 30% for paralysis and below 5% for dysphonia. This underscores the relevance of muscle imbalance in representing phonatory scenarios and its potential for characterizing asymmetry in vocal fold vibration.

Functional overlap of inborn errors of immunity and metabolism genes defines T cell metabolic vulnerabilities.

Inborn errors of metabolism (IEMs) and immunity (IEIs) are Mendelian diseases in which complex phenotypes and patient rarity have limited clinical understanding. Whereas few genes have been annotated as contributing to both IEMs and IEIs, immunometabolic demands suggested greater functional overlap. Here, CRISPR screens tested IEM genes for immunologic roles and IEI genes for metabolic effects and found considerable previously unappreciated crossover. Analysis of IEMs showed that N-linked glycosylation and the hexosamine pathway enzyme Gfpt1 are critical for T cell expansion and function. Further, T helper (TH1) cells synthesized uridine diphosphate N-acetylglucosamine more rapidly and were more impaired by Gfpt1 deficiency than TH17 cells. Screening IEI genes found that Bcl11b promotes the CD4 T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress. Thus, a high degree of functional overlap exists between IEM and IEI genes, and immunometabolic mechanisms may underlie a previously underappreciated intersection of these disorders.

A standardized image processing and data quality platform for rodent fMRI.

Functional magnetic resonance imaging in rodents holds great potential for advancing our understanding of brain networks. Unlike the human community, there remains no standardized resource in rodents for image processing, analysis and quality control, posing significant reproducibility limitations. Our software platform, Rodent Automated Bold Improvement of EPI Sequences, is a pipeline designed to address these limitations for preprocessing, quality control, and confound correction, along with best practices for reproducibility and transparency. We demonstrate the robustness of the preprocessing workflow by validating performance across multiple acquisition sites and both mouse and rat data. Building upon a thorough investigation into data quality metrics across acquisition sites, we introduce guidelines for the quality control of network analysis and offer recommendations for addressing issues. Taken together, this software platform will allow the emerging community to adopt reproducible practices and foster progress in translational neuroscience.

Acoustic response of patchy-saturated porous media: Coupling Biot's poroelasticity equations for mono- and biphasic pore fluids.

Patchy saturation is a term used in the seismic prospecting literature to describe the state of a geological formation in which two immiscible pore fluids prevail in mesoscopic-scale clusters. If the pore fluids have contrasting compressibilities, wave-induced fluid pressure diffusion (FPD) processes may induce significant attenuation and velocity dispersion on seismic waves. Biot's monophasic poroelasticity theory is widely used to model the seismic response of rocks containing binary patches of two immiscible pore fluids. Even though effective fluid approximations may help to represent more realistic partially saturated patches using Biot's monophasic equations, the so inferred dissipation may not be representative of actual biphasic FPD phenomena. In this work, Biot's equations for mono- and biphasic fluids are combined to model FPD processes in porous media, comprising fully and partially saturated patches. An analytical solution for one-dimensional layered patchy-saturated media is presented which permits to explain some, as of yet enigmatic, experimentally observed characteristics such as increased seismic attenuation and stiffening effects occurring at low saturations. The results show that the existence of an additional diffusive wave mode within partially saturated patches may render conventional binary and effective fluid approaches incorrect and error prone.

Surgeon and Care Team Network Measures and Timely Breast Cancer Treatment.

Importance: Cancer treatment delay is a recognized marker of worse outcomes. Timely treatment may be associated with physician patient-sharing network characteristics, yet this remains understudied. Objective: To examine the associations of surgeon and care team patient-sharing network measures with breast cancer treatment delay. Design, Setting, and Participants: This cross-sectional study of Medicare claims in a US population-based setting was conducted from 2017 to 2020. Eligible participants included patients with breast cancer who received surgery and the subset who went on to receive adjuvant therapy. Patient-sharing networks were constructed for treating physicians. Data were analyzed from September 2023 to February 2024. Exposures: Surgeon linchpin score (a measure of local uniqueness or scarcity) and care density (a measure of physician team familiarity) were assessed. Surgeons were considered linchpins if their linchpin score was in the top 15%. The care density of a patient's physician team was calculated on preoperative teams for surgically-treated patients and postoperative teams for adjuvant therapy-receiving patients. Main Outcomes and Measures: The primary outcomes were surgical and adjuvant delay, which were defined as greater than 60 days between biopsy and surgery and greater than 60 days between surgery and adjuvant therapy, respectively. Results: The study cohort included 56 433 patients (18 004 aged 70-74 years [31.9%]) who were mostly from urban areas (44 931 patients [79.6%]). Among these patients, 8009 (14.2%) experienced surgical delay. Linchpin surgeon status (locally unique surgeon) was not statistically associated with surgical delay; however, patients with high preoperative care density (ie, high team familiarity) had lower odds of surgical delay compared with those with low preoperative care density (odds ratio [OR], 0.58; 95% CI, 0.53-0.63). Of the 29 458 patients who received adjuvant therapy after surgery, 5700 (19.3%) experienced adjuvant delay. Patients with a linchpin surgeon had greater odds of adjuvant delay compared with those with a nonlinchpin surgeon (OR, 1.30; 95% CI, 1.13-1.49). Compared with those with low postoperative care density, there were lower odds of adjuvant delay for patients with high postoperative care density (OR, 0.77; 95% CI, 0.69-0.87) and medium postoperative care density (OR, 0.85; 95% CI, 0.77-0.94). Conclusions and Relevance: In this cross-sectional study of Medicare claims, network measures capturing physician scarcity and team familiarity were associated with timely treatment. These results may help guide system-level interventions to reduce cancer treatment delays.