Search

Background: Prior work documented circadian rhythm impacts on efficacy and toxicity of cancer therapies. Methods: Secondary analysis of prospective, phase II trial of metastatic HNSCC randomized to nivolumab+/−SBRT. Used cutoffs of 1100 and 1630. Timing classified by first infusion or majority of SBRT (e.g., PM SBRT defined by two or three fractions after 1630). Results: Of 62 patients, there was no significant difference in median PFS between AM nivolumab (n = 7, 175 days), PM nivolumab (n = 21, 58 days), or Mid‐Day nivolumab (n = 34, 67 days; p = 0.8). There was no significant difference in median PFS with AM SBRT (n = 4, 78 days), PM SBRT (n = 13, 111 days), or Mid‐Day SBRT (n = 15, 63 days; p = 0.8). There was no significant difference in Grade 3–4 toxicity or ORR. Sensitivity analyses with other timepoints were negative. Conclusions: Further work may elucidate circadian impacts on select patients, tumors, and therapies; however, we found no significant effect in this study. [ABSTRACT FROM AUTHOR]

Premaxillary protrusion and the performance advantages it confers are implicated in the success of diverse lineages of teleost fishes, such as Cypriniformes and Acanthomorpha. Although premaxillary protrusion has evolved independently at least five times within bony fishes, much of the functional work investigating this kinesis relates to mechanisms found only in these two clades. Few studies have characterized feeding mechanisms in less‐diverse premaxilla‐protruding lineages and fewer yet have investigated the distinctive anatomy underlying jaw kinesis in these lineages. Here, we integrated dissection, clearing and staining, histology, micro‐CT, and high‐speed videography to investigate an isolated and independent origin of jaw protrusion in the hingemouth, Phractolaemus ansorgii, which employs a complex arrangement of bones, musculature, and connective tissues to feed on benthic detritus via a deployable proboscis. Our goals were to provide an integrative account of the underlying architecture of P. ansorgii's feeding apparatus and to assess the functional consequences of this drastic deviation from the more typical teleost condition. Phractolaemus ansorgii's cranial anatomy is distinct from all other fishes in that its adducted lower jaw is caudally oriented, and it possesses a mouth at the terminal end of an elongated, tube‐like proboscis that is unique in its lack of skeletal support from the oral jaws. Instead, its mouth is supported primarily by hyaline‐cell cartilage and other rigid connective tissues, and features highly flexible lips that are covered in rows of keratinous unculi. Concomitant changes to the adductor musculature likely allow for the flexibility to protrude the mouth dorsally and ventrally as observed during different feeding behaviors, while the intrinsic compliance of the lips allows for more effective scraping of irregular surfaces. From our feeding videos, we find that P. ansorgii is capable of modulating the distance of protrusion, with maximum anterior protrusion exceeding 30% of head length. This represents a previously undescribed example of extreme jaw protrusion on par with many acanthomorph species. Protrusion is much slower in P. ansorgii—reaching an average speed of 2.74 cm/s—compared to acanthomorphs feeding on elusive prey or even benthivorous cypriniforms. However, this reorganization of cranial anatomy may reflect a greater need for dexterity to forage more precisely in multiple directions and on a wide variety of surface textures. Although this highly modified mechanism may have limited versatility over evolutionary timescales, it has persisted in solitude within Gonorynchiformes, representing a novel functional solution for benthic feeding in tropical West African rivers. [ABSTRACT FROM AUTHOR]

Introduction: In special populations, such as Reserve Officers' Training Corps (ROTC) cadets, body composition is used not only as a predictor of fitness but for additional purposes such as qualification for enlistment, load carriage, and duty fulfillment. Body mass index (BMI) is the initial measurement recorded and is considered a representation of health and physical performance capabilities. Personnel exceeding threshold values of body weight based upon their height measurement are typically further evaluated using a circumference-based method that predicts the cadets' percent body fat. Military personnel who fail to meet these body composition standards may be penalized by being denied specific positions or promotions or risk being relieved from all military duties. In order to differentiate and accurately assess the components that constitute body composition, other methods of measuring body composition that provide greater accuracy should be explored. The purpose of this study was to compare multiple body composition methods, including the military's method of circumference-based measurement, in order to identify a suitable method for Air Force ROTC programs. Materials and Methods: Participants were recruited from an Air Force ROTC Detachment at a large university in the Midwest United States. Anthropometric (height and weight) and body composition measurements (air displacement plethysmography [ADP], bioelectrical impedance analysis, skinfolds, and circumferences) were collected for each participant. A repeated-measure analysis of variance was used to compare body composition measurement methods. A Bonferroni adjustment was utilized for multiple comparisons. BMI and circumference results were displayed as a percentage of compliance according to Air Force Instruction guidelines. The university institutional review board approval was established to ensure that the design of this study protected the rights of the participants. Results: Twenty-four (21 males and 3 females) participants completed the study. A significant difference between skinfolds and bioelectrical impedance analysis occurred (P = .025). There were no other significant differences identified between other methods of body composition. Using the BMI and circumference compliant/non-compliant scale listed in the Air Force Instruction guidelines, a greater number of cadets fell into the non-compliant category according to BMI (n = 7) versus circumferences (n = 1). The circumference-based method underestimated body fat compared to the "gold standard" ADP. Conclusions: The findings from this investigation suggest that the circumference-based method can appropriately provide accurate body composition results among Air Force ROTC cadets. Results also determined that the military's circumference-based method underestimated body fat compared to the "gold standard" ADP. Although circumference-based measurements might be efficient for use in larger populations, Air Force ROTC programs should evaluate other methods of measuring body composition to best fit the needs of individual cadets. Further research should be conducted to identify body composition methods that are easy to implement and provide accurate results at the individual level. [ABSTRACT FROM AUTHOR]

Background: The PACIFIC trial established consolidative durvalumab after concurrent chemoradiation as standard‐of‐care in patients with stage III or unresectable non–small cell lung cancer (NSCLC). Black patients, however, comprised just 2% (n = 14) of randomized patients in this trial, warranting real‐world evaluation of the PACIFIC regimen in these patients. Methods: This single‐institution, multi‐site study included 105 patients with unresectable stage II/III NSCLC treated with concurrent chemoradiation followed by durvalumab between 2017 and 2021. Overall survival (OS), progression‐free survival (PFS), and grade ≥3 pneumonitis‐free survival (PNFS) were compared between Black and non‐Black patients using Kaplan–Meier and Cox regression analyses. Results: A total of 105 patients with a median follow‐up of 22.8 months (interquartile range, 11.3–37.3 months) were identified for analysis, including 57 Black (54.3%) and 48 (45.7%) non‐Black patients. The mean radiation prescription dose was higher among Black patients (61.5 ± 2.9 Gy vs. 60.5 ± 1.9 Gy; p =.031), but other treatment characteristics were balanced between groups. The median OS (not‐reached vs. 39.7 months; p =.379) and PFS (31.6 months vs. 19.3 months; p =.332) were not statistically different between groups. Eight (14.0%) Black patients discontinued durvalumab due to toxicity compared to 13 (27.1%) non‐Black patients (p =.096). The grade ≥3 pneumonitis rate was similar between Black and non‐Black patients (12.3% vs. 12.5%; p =.973), and there was no significant difference in time to grade ≥3 PNFS (p =.904). Three (5.3%) Black patients and one (2.1%) non‐Black patient developed grade 5 pneumonitis. Conclusions: The efficacy and tolerability of consolidative durvalumab after chemoradiation appears to be comparable between Black and non‐Black patients. Consolidative durvalumab after concurrent chemoradiation has similar efficacy and tolerability between Black and non‐Black patients with unresectable stage II/III non–small cell lung cancer. [ABSTRACT FROM AUTHOR]

Imagining alternatives to actual experiences is an important part of everyday life that can take many forms. One manifestation in middle childhood is the creation of elaborate imaginary worlds, called "paracosms." Retrospective reports of adults indicate that having a childhood paracosm is more commonly reported in individuals acknowledged for being highly creative. In this study, we interviewed four children aged 10 to 12 years with interconnected paracosms about the details of their imagined worlds. Our findings indicated that paracosms served as a platform for social activity with friends, a way to explore real world interests (e.g., geography, language), and a vehicle for engaging in creative pursuits (e.g., drawing, storytelling).

Background: Delayed access to care may contribute to disparities in prostate cancer (PCa). The Affordable Care Act (ACA) aimed at increasing access and reducing healthcare disparities, but its impact on timely treatment initiation for PCa men is unknown. Methods: Men with intermediate‐ and high‐risk PCa diagnosed 2010–2016 and treated with curative surgery or radiotherapy were identified in the National Cancer Database. Multivariable logistic regression modeled the effect of race and insurance type on treatment delay >180 days after diagnosis. Cochran–Armitage test measured annual trends in delays, and joinpoint regression assessed if 2014, the year the ACA became fully operationalized, was significant for inflection in crude rates of major delays. Results: Of 422,506 eligible men, 18,720 (4.4%) experienced >180‐day delay in treatment initiation. Compared to White patients, Black (OR 1.79, 95% CI 1.72–1.87, p < 0.001) and Hispanic (OR 1.37, 95% CI 1.28–1.48, p < 0.001) patients had higher odds of delay. Compared to uninsured, those with Medicaid had no difference in odds of delay (OR 0.94, 95% CI 0.84–1.06, p = 0.31), while those with private insurance (OR 0.57, 95% CI 0.52–0.63, p < 0.001) or Medicare (OR 0.64, 95% CI 0.58–0.70, p < 0.001) had lower odds of delay. Mean time to treatment significantly increased from 2010 to 2016 across all racial/ethnic groups (trend p < 0.001); 2014 was associated with a significant inflection for increase in rates of major delays. Conclusions: Non‐White and Medicaid‐insured men with localized PCa are at risk of treatment delays in the United States. Treatment delays have been consistently rising, particularly after implementation of the ACA. [ABSTRACT FROM AUTHOR]

Background: Postoperative mortality for oropharynx squamous cell carcinoma (OPSCC) with transoral robotic surgery (TORS) varies from 0.2% to 6.5% on trials; the real‐world rate is unknown. Methods: NCDB study from 2010 to 2017 for patients with cT1‐2N0‐2M0 OPSCC with Charleson–Deyo score 0–1. Ninety‐day mortality assessed from start and end of treatment at Commission on Cancer‐accredited facilities. Results: 3639 patients were treated with TORS and 1937 with radiotherapy. TORS cohort had more women and higher income, was younger, more often treated at academic centers, and more likely to have private insurance (all p < 0.05). Ninety‐day mortality was 1.3% with TORS and 0.7% or 1.4% from start or end of radiotherapy, respectively. From end of therapy, there was no significant difference on MVA between treatment modality. Conclusions: There is minimal difference between 90‐day mortality in patients treated with TORS or radiotherapy for early‐stage OPSCC. While overall rates are low, for patients with expectation of cure, work is needed to identify optimal treatment. [ABSTRACT FROM AUTHOR]

Introduction: As immunotherapy has improved distant metastasis-free survival (DMFS) in Non-Small Cell Lung Cancer (NSCLC), isolated locoregional recurrences have increased. However, management of locoregional recurrences can be challenging. We report our institutional experience with definitive intent reirradiation using Intensity Modulated Proton Therapy (IMPT). Method: Retrospective cohort study of recurrent or second primary NSCLC or LSSCLC treated with IMPT. Kaplan-Meier method and log-rank test were used for time-to-event analyses. Results: 22 patients were treated from 2019 to 2021. After first course of radiation (median 60 Gy, range 45-70 Gy), 45% received adjuvant immunotherapy. IMPT reirradiation began a median of 28.2 months (8.8-172.9 months) after initial radiotherapy. The median IMPT dose was 60 GyE (44-60 GyE). 36% received concurrent chemotherapy with IMPT and 18% received immunotherapy after IMPT. The median patient’s IMPT lung mean dose was 5.3 GyE (0.9-13.9 GyE) and 5 patients had cumulative esophagus max dose >100 GyE with 1-year overall survival (OS) 68%, 1-year local control 80%, 1-year progression free survival 45%, and 1-year DMFS 60%. Higher IMPT (HR 1.4; 95% CI 1.1-1.7, p=0.01) and initial radiotherapy mean lung doses (HR 1.3; 95% CI 1.0-1.6, p=0.04) were associated with worse OS. Two patients developed Grade 3 pneumonitis or dermatitis, one patient developed Grade 2 pneumonitis, and seven patients developed Grade 1 toxicity. There were no Grade 4 or 5 toxicities. Discussion: Definitive IMPT re-irradiation for lung cancer can prolong disease control with limited toxicity, particularly in the immunotherapy era. [ABSTRACT FROM AUTHOR]

Many ecological factors influence animal movement, including properties of the media that they move on or through. Animals moving in terrestrial environments encounter conditions that can be challenging for generating propulsion and maintaining stability, such as inclines and deformable substrates that can cause slipping and sinking. In response, tetrapods tend to adopt a more crouched posture and lower their center of mass on inclines and increase the surface area of contact on deformable substrates, such as sand. Many amphibious fishes encounter the same challenges when moving on land, but how these finned animals modulate their locomotion with respect to different environmental conditions and how these modifications compare with those seen within tetrapods is relatively understudied. Mudskippers (Gobiidae: Oxudercinae) are a particularly noteworthy group of amphibious fishes in this context given that they navigate a wide range of environmental conditions, from flat mud to inclined mangrove trees. They use a unique form of terrestrial locomotion called "crutching," where their pectoral fins synchronously lift and vault the front half of the body forward before landing on their pelvic fins, while the lower half of the body and tail are kept straight. However, recent work has shown that mudskippers modify some aspects of their locomotion when crutching on deformable surfaces, particularly those at an incline. For example, on inclined dry sand, mudskippers bent their bodies laterally and curled and extended their tails to potentially act as a secondary propulsor and/or anti-slip device. In order to gain a more comprehensive understanding of the functional diversity and context-dependency of mudskipper crutching, we compared their kinematics on different combinations of substrate types (solid, mud, and dry sand) and inclines (0°, 10°, and 20°). In addition to increasing lateral bending on deformable and inclined substrates, we found that mudskippers increased the relative contact time and contact area of their paired fins, while becoming more crouched, which are responses comparable to those seen in tetrapods and other amphibious fish. Mudskippers on these substrates also exhibited previously undocumented behaviors, such as extending and adpressing the distal portions of their pectoral fins more anteriorly, dorsoventrally bending their trunk, "belly-flopping" on sand, and "gripping" the mud substrate with their pectoral fin rays. Our study highlights potential compensatory mechanisms shared among vertebrates in terrestrial environments while also illustrating that locomotor flexibility and even novelty can emerge when animals are challenged with environmental variation. [ABSTRACT FROM AUTHOR]