Search

This dissertation, “Technological Futures,” examines animated media from mainland China, as it transitioned from the political regime of the Republic of China to that of the People’s Republic of China. This study emphasizes the role of animation and animated media in promulgating new modes of education, in representing national and natural histories, and in disseminating popular science. The dissertation argues that animation served as a new visual vernacular and pedagogical mode for socialist Chinese media, while also conceptualizing animation as pushing past the boundaries of genre studies and questions of medium specificity.A broader, mass media context for a visual mode of animation emerged beginning in the 1950s and 1960s, encompassing not only animated films but also science education films, photographic slides, and popular science films and texts. This dissertation contends that such media in socialist China enabled the formation of new socialist subjectivities, national historical narratives, and spatio-temporal reality. To support these claims, this dissertation examines animated media from this period in conjunction with internal studio documents, film bureau censorship reports, educational publications, and critical essays published by animators and filmmakers. The research here finds that the use of animated media was fraught with questions of how to teach perception, and how to reconcile scientific representations of reality together with futuristic visions of the future. “Technological Futures” finds that during its earliest developmental stages, the socialist Chinese state utilized the affordances of animation—in its imaginative form, motion, and space—to envision its past, present, and future as nation.

Background Remdesivir (RDV) has been a mainstay of COVID-19 therapy for hospitalized patients. Impact of RDV timing in relationship to symptom-onset in hospitalized patients remains unclear, though early treatment is theorized to improve antiviral activity and clinical outcomes. Methods This was a single-center retrospective study of adult patients hospitalized for severe COVID-19 treated with RDV. Patient charts were reviewed by 2 independent investigators to determine disease course and outcomes. Patients were stratified based on time from symptom-onset to RDV (short: ≤7 vs. long: >7 days). The primary outcome was time to clinical recovery within 28 days. Secondary outcomes were proportion of patients recovered and proportion discharged from the hospital within 10, 14, and 28 days; and mortality within 28 days. Time to recovery was analyzed using the Kaplan-Meier method and the significance was tested by log rank tests. Cox’s proportional hazards models were used to estimate hazard ratios (HR). Fisher’s exact test was used to compare recovery rates between groups. Results Overall, 405 patient charts were reviewed, and 337 met the inclusion criteria. On the first day of RDV, 178 (53%) of patients had symptoms for 7 days. Patients in the short symptom duration group were slightly older (66.5 vs. 59 years, p=0.004) and had more co-morbidities. Median time to recovery was 7 (95% CI 5-9) in the short- vs. 5 (95% CI 4-6) days in the long-symptom duration groups, respectively, p=0.066. By day 10, 111 (62%) vs. 116 (73%) patients met the clinical recovery definition (p=0.048), and 113 (63%) vs. 119 (75%) patients were discharged from the hospital (p=0.026) in the short- vs. long-symptom duration groups, respectively. In the Cox’s proportional hazards model, age, disease severity, and co-morbidities (kidney, liver, chronic respiratory diseases, and type II diabetes mellitus) were associated with longer recovery times. Conclusion In this cohort, long duration of symptoms ( >7 days) prior to initiation of RDV therapy was not associated with longer recovery time or longer hospitalization. Additional studies are needed to elucidate benefits of RDV therapy in relationship to the time course of severe COVID-19 in hospitalized patients. Disclosures Ramy H. Elshaboury, PharmD, Eli Lilly: Honoraria|Gilead Sciences: Grant/Research Support Fiona Cheung, PharmD, Pfizer Inc.: Employee Bryan Polsonetti, PharmD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds Essy Mozaffari, PharmD, MPH, MBA, Gilead: Employee|Gilead: Stocks/Bonds Linda Chen, MPH, Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds|UCB pharmaceuticals: Stocks/Bonds Elizabeth Hohmann, MD, Gilead: Advisor/Consultant|Kowa Pharmaceuticals: Advisor/Consultant|Tend, Inc: Grant/Research Support.

Human papillomavirus (HPV)-mediated oncogenesis confers increased sensitivity to radiotherapy and HPV head and neck cancer is associated with improved patient outcomes. As such, management of HPV-related head and neck cancer requires a multidisciplinary approach that balances maximizing locoregional control with minimizing treatment-related toxicity. We highlight considerations in radiation dose and target delineation, as well as considerations for chemoradiation, postoperative radiotherapy, and single modality, definitive radiotherapy.

To evaluate treatment satisfaction, level of anxiety, confidence about traveling with midazolam nasal spray (MDZ-NS), and health-related quality of life in patients with seizure clusters and their caregivers after repeated, intermittent use of MDZ-NS in the outpatient setting.We analyzed the psychosocial outcome data from a phase 3, open-label extension trial (ARTEMIS-2; P261-402; NCT01529034) in patients 12 years of age and older with seizure clusters on a stable regimen of antiseizure medications. Caregivers administered MDZ-NS 5 mg when patients experienced a seizure cluster. A second dose could be given if seizures did not terminate within 10 min or recurred from 10 min to 6 h. Treatment Satisfaction Questionnaire for Medication (TSQM), the Intranasal Therapy Impact Questionnaire (ITIQ), and the Short Form-12 Health Survey version 2 (SF-12v2) were self-administered by patients and/or caregivers at prespecified visits.Of the one hundred and seventy-five patients enrolled in ARTEMIS-2, 161 (92.0%) received ≥ 1 dose of MDZ-NS and had a post-treatment seizure-related assessment and were included in the Efficacy Evaluable Set in this analysis, with a total of 1,998 treated seizure clusters over a median duration of 16.8 months. All TSQM scales showed improvement from the baseline of the double-blind ARTEMIS-1 trial (NCT01390220) to the last visit in ARTEMIS-2, indicating greater satisfaction with MDZ-NS across all domains, with a mean change from baseline of 8.8, 6.1, 4.3, and 6.2 for effectiveness (n = 135), side effects (n = 139), convenience (n = 139), and global satisfaction (n = 138), respectively. Change from baseline in TSQM scores generally increased with repeated MDZ-NS use. In both patients and caregivers, anxiety generally lessened with repeated MDZ-NS use, with a mean improvement in ITIQ scores in patients' anxiety since receiving MDZ-NS from 2.5 (n = 138) to 3.5 (n = 145) from visit 1 to the last visit (and from 2.6 [n = 156] to 3.6 [n = 160] for caregivers), respectively. From visit 1 (screening and enrollment in ARTEMIS-2) to visit 10 (after 16 seizure cluster episodes treated with MDZ-NS), the proportions of patients and caregivers who answered "strongly agree" or "agree" for confidence about traveling with an intranasal spray remained ≥ 79% and generally increased over repeated MDZ-NS use. Small positive mean changes in SF-12v2 scores from baseline to the last visit were observed in both patients and caregivers, respectively, for the domains of physical functioning (0.9, 1.1), role-physical (2.4, 0.3), bodily pain (1.7, 0.3), general health (0.6, 1.2), and role-emotional (2.1, 0.3), and in the physical health component (1.6, 1.0).Patients and caregivers perceived MDZ-NS favorably, with improvement from baseline on perceived effectiveness, side effects, convenience, and global satisfaction in the TSQM. This is supported by progressively lower anxiety and higher confidence levels about traveling with MDZ-NS over repeated intermittent use in the ITIQ. The positive mean changes observed in SF-12v2 scores from baseline to the last visit were small in magnitude. Limitations of this exploratory analysis include the open-label trial design and that these questionnaires have not been directly validated in epilepsy to identify clinically important changes; however, this does not mean these findings are not clinically meaningful. Overall, MDZ-NS is a socially acceptable drug device for outpatient treatment of seizure clusters that has the potential to improve quality of life and overall independence.

The Peterson comparison formula proved by Woodward relates the three-pointed Gromov-Witten invariants for the quantum cohomology of partial flag varieties to those for the complete flag. Another such comparison can be obtained by composing a combinatorial version of the Peterson isomorphism with a result of Lapointe and Morse relating quantum Littlewood-Richardson coefficients for the Grassmannian to k-Schur analogs in the homology of the affine Grassmannian obtained by adding rim hooks. We show that these comparisons on quantum cohomology are equivalent, up to Postnikov's strange duality isomorphism., 28 pages; added several references, final version to appear in Algebr. Represent. Theory

We compute the Euler characteristic of the structure sheaf of the Brill–Noether locus of linear series with special vanishing at up to two marked points. When the Brill–Noether number $\rho $ is zero, we recover the Castelnuovo formula for the number of special linear series on a general curve; when $\rho =1$, we recover the formulas of Eisenbud-Harris, Pirola, and Chan–Martín–Pflueger–Teixidor for the arithmetic genus of a Brill–Noether curve of special divisors. These computations are obtained as applications of a new determinantal formula for the $K$-theory class of certain degeneracy loci. Our degeneracy locus formula also specializes to new determinantal expressions for the double Grothendieck polynomials corresponding to 321-avoiding permutations and gives double versions of the flagged skew Grothendieck polynomials recently introduced by Matsumura. Our result extends the formula of Billey–Jockusch–Stanley expressing Schubert polynomials for 321-avoiding permutations as generating functions for flagged skew tableaux.

The most common cancer caused by human papillomavirus (HPV) infection in the United States is oropharyngeal cancer (OPC), and its incidence has been rising since the turn of the century. Because of substantial long-term morbidities with chemoradiation and the favorable prognosis of HPV-positive OPC, identifying the optimal deintensification strategy for this group has been a keystone of academic head-and-neck surgery, radiation oncology, and medical oncology for over the past decade. However, the first generation of randomized chemotherapy deintensification trials failed to change the standard of care, triggering concern over the feasibility of de-escalation. National database studies estimate that up to one third of patients receive nonstandard de-escalated treatments, which have subspecialty-specific nuances. A synthesis of the multidisciplinary deintensification data and current treatment standards is important for the oncology community to reinforce best practices and ensure optimal patient outcomes. In this review, the authors present a summary and comparison of prospective HPV-positive OPC de-escalation trials. Chemotherapy attenuation compromises outcomes without reducing toxicity. Limited data comparing transoral robotic surgery (TORS) with radiation raise concern over toxicity and outcomes with TORS. There are promising data to support de-escalating adjuvant therapy after TORS, but consensus on treatment indications is needed. Encouraging radiation deintensification strategies have been reported (upfront dose reduction and induction chemotherapy-based patient selection), but level I evidence is years away. Ultimately, stage and HPV status may be insufficient to guide de-escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real-time surveillance.

We demonstrate that a neural network pre-trained on text and fine-tuned on code solves mathematics course problems, explains solutions, and generates new questions at a human level. We automatically synthesize programs using few-shot learning and OpenAI's Codex transformer and execute them to solve course problems at 81% automatic accuracy. We curate a new dataset of questions from MIT's largest mathematics courses (Single Variable and Multivariable Calculus, Differential Equations, Introduction to Probability and Statistics, Linear Algebra, and Mathematics for Computer Science) and Columbia University's Computational Linear Algebra. We solve questions from a MATH dataset (on Prealgebra, Algebra, Counting and Probability, Intermediate Algebra, Number Theory, and Precalculus), the latest benchmark of advanced mathematics problems designed to assess mathematical reasoning. We randomly sample questions and generate solutions with multiple modalities, including numbers, equations, and plots. The latest GPT-3 language model pre-trained on text automatically solves only 18.8% of these university questions using zero-shot learning and 30.8% using few-shot learning and the most recent chain of thought prompting. In contrast, program synthesis with few-shot learning using Codex fine-tuned on code generates programs that automatically solve 81% of these questions. Our approach improves the previous state-of-the-art automatic solution accuracy on the benchmark topics from 8.8% to 81.1%. We perform a survey to evaluate the quality and difficulty of generated questions. This work is the first to automatically solve university-level mathematics course questions at a human level and the first work to explain and generate university-level mathematics course questions at scale, a milestone for higher education., Comment: 181 pages, 8 figures, 280 tables

High-dose (HD) cisplatin remains the standard of care with chemoradiation for locally advanced oropharyngeal cancer (OPC). Cooperative group trials mandate bolus-HD (100 mg/m2 × 1 day, every 3 weeks) cisplatin administration at the beginning of the week to optimize radiosensitization-a requirement which may be unnecessary. This analysis evaluates the impact of chemotherapy administration day of week (DOW) on outcomes. We also report our institutional experience with an alternate dosing schedule, split-HD (50 mg/m2 × 2 days, every 3 weeks). We retrospectively reviewed 435 definitive chemoradiation OPC patients from 10 December 2001 to 23 December 2014. Those receiving non-HD cisplatin regimens or induction chemotherapy were excluded. Data collected included DOW, dosing schedule (bolus-HD vs split-HD), smoking, total cumulative dose (TCD), stage, Karnofsky Performance Status, human papillomavirus status and creatinine (baseline, peak and posttreatment baseline). Local failure (LF), regional failure (RF), locoregional failure (LRF), distant metastasis (DM), any failure (AF, either LRF or DM) and overall survival (OS) were calculated from radiation therapy start. Median follow-up was 8.0 years (1.8 months-17.0 years). DOW, dosing schedule and TCD were not associated with any outcomes in univariable or multivariable regression models. There was no statistically significant difference in creatinine or association with TCD in split-HD vs bolus-HD. There was no statistically significant association between DOW and outcomes, suggesting that cisplatin could be administered any day. Split-HD had no observed differences in outcomes, renal toxicity or TCD compared to bolus-HD cisplatin. Our data suggest that there is some flexibility of when and how to give HD cisplatin compared to clinical trial mandates.

Background Proton beam radiation therapy (PBRT) has dosimetric advantages compared to photon radiation therapy for the treatment of major salivary gland tumors (MSGTs). Methods Patients with non-metastatic MSGTs treated at a single proton therapy center from October 2013 to October 2018 were retrospectively reviewed. Results Sixty-eight patients with MSGTs were included and the most common site and histology were the parotid gland (75.0%) and adenoid cystic carcinoma (22.1%), respectively. The 3-year rates of locoregional control, progression-free survival, and overall survival were 95.1% (95% CI: 89.9%-100.0%), 80.7% (70.2%-92.7%), and 96.1% (95% CI: 90.9%-100.0%), respectively. Conclusion In a large cohort of MSGTs treated with PBRT, the rates of locoregional control were high in short-term follow-up and treatment was well tolerated.

PurposeDue to the high demand of concrete, significant volume of natural resources is required, including virgin aggregates. Many studies have shown that the production of concrete has one of the highest CO2 levels. Although efforts are in place to recycle, enormous effects on landfill and the wider environment remain. Research has suggested the importance of reusing construction and demolition waste such as aggregate for use in recycled concrete. However, robust construction and demolition waste reduction strategies are required. There have been numerous researches on the use of recycled concrete and its management in the construction industry. This paper further consolidates this position.Design/methodology/approachThis paper exhibits the barriers and benefits of using recycled aggregates for construction industry. This is achieved via reviewing the current construction and demolition waste reduction strategies used mainly in three countries: the UK, Australia and Japan. These countries were selected since they seemingly have similar construction industry and environment. Subsequently, evolving barriers and benefits of using recycled aggregates for construction industry are also reviewed and discussed. And to support such focus, robust construction and demolition waste reduction strategies will be advocated.FindingsThe findings are summarized as follows. The recycling construction and demolition waste could have a positive net benefit compared to the procurement and production of virgin aggregate materials with the same properties. This is not only financially beneficial but also environmentally viable, as fewer resources would be required to produce the same aggregate material. There are effective ways to achieve a high recycle rate target, as demonstrated by Japan. The implementation of a similar recycling process could be implemented globally to achieve a more effective recycle rate through the help of governments at all levels. By creating awareness about the financial and environmental benefits of using recycled aggregate products, large recycling companies can be also enticed to follow suit.Practical implicationsThe findings from this paper can ultimately support the construction industry to further consolidate and advocate the use of recycled aggregates.Originality/valueTo achieve the research aim, this paper reviews some of the main sustainability factors of recycled aggregates (including coarse and fine aggregates) and provides comparison to virgin aggregates.

Because of the national emergency triggered by the coronavirus disease 2019 (COVID‐19) pandemic, government‐mandated public health directives have drastically changed not only social norms but also the practice of oncologic medicine. Timely head and neck cancer (HNC) treatment must be prioritized, even during emergencies. Because severe acute respiratory syndrome coronavirus 2 predominantly resides in the sinonasal/oral/oropharyngeal tracts, nonessential mucosal procedures are restricted, and HNCs are being triaged toward nonsurgical treatments when cures are comparable. Consequently, radiation utilization will likely increase during this pandemic. Even in radiation oncology, standard in‐person and endoscopic evaluations are being restrained to limit exposure risks and preserve personal protective equipment for other frontline workers. The authors have implemented telemedicine and multidisciplinary conferences to continue to offer standard‐of‐care HNC treatments during this uniquely challenging time. Because of the lack of feasibility data on telemedicine for HNC, they report their early experience at a high‐volume cancer center at the domestic epicenter of the COVID‐19 crisis., Cancer care is undeniably affected by the coronavirus disease 2019 (COVID‐19) public health emergency, but quality cancer care must persist. A high‐volume cancer center from the domestic epicenter of the COVID‐19 crisis shares its multidisciplinary approach to integrating current public health restrictions and adopting telemedicine to optimize the care of patients with head and neck cancer; it is hoped that this center's experience will provide helpful insights to oncology colleagues.

We show that the product in the quantum K-ring of a generalized flag manifold $G/P$ involves only finitely many powers of the Novikov variables. In contrast to previous approaches to this finiteness question, we exploit the finite difference module structure of quantum K-theory. At the core of the proof is a bound on the asymptotic growth of the $J$-function, which in turn comes from an analysis of the singularities of the zastava spaces studied in geometric representation theory. An appendix by H. Iritani establishes the equivalence between finiteness and a quadratic growth condition on certain shift operators.

Purpose To demonstrate temporal lobe necrosis (TLN) rate and clinical/dose-volume factors associated with TLN in radiation-naïve patients with head and neck cancer treated with proton therapy where the field of radiation involved the skull base. Materials and Methods Medical records and dosimetric data for radiation-naïve patients with head and neck cancer receiving proton therapy to the skull base were retrospectively reviewed. Patients with Results Between 2013 and 2019, 234 patients were included. The median follow-up time was 22.5 months (range = 3.2–69.3). Overall TLN rates of any grade, ≥ grade 2, and ≥ grade 3 were 5.6% (N = 13), 2.1%, and 0.9%, respectively. The estimated 2-year TLN rate was 4.6%, and the 2-year rate of any brain necrosis was 6.8%. The median time to TLN was 20.9 months from proton completion. Absolute volume receiving 40, 50, 60, and 70 GyRBE (absolute volume [aV]); mean and maximum dose received by the temporal lobe; and dose to the 0.5, 1, and 2 cm3 volume receiving the maximum dose (D0.5cm3, D1cm3, and D2cm3, respectively) of the temporal lobe were associated with greater TLN risk while clinical parameters showed no correlation. Among volume parameters, aV50 gave maximum AUC (0.921), and D2cm3 gave the highest AUC (0.935) among dose parameters. The 11-cm3 cutoff value for aV50 and 62 GyRBE for D2cm3 showed maximum specificity and sensitivity. Conclusion The estimated 2-year TLN rate was 4.6% with a low rate of toxicities ≥grade 3; aV50 ≤11 cm3, D2cm3 ≤62 GyRBE and other cutoff values are suggested as constraints in proton therapy planning to minimize the risk of any grade TLN. Patients whose temporal lobe(s) unavoidably receive higher doses than these thresholds should be carefully followed with MRI after proton therapy.

Background: Recent advances in computational psychiatry have identified latent cognitive and perceptual states that predispose to psychotic symptoms. Behavioral data fit to Bayesian models have demonstrated an overreliance on priors (i.e., prior overweighting) during perception in select samples of individuals with hallucinations, corresponding to increased precision of prior expectations over incoming sensory evidence. However, the clinical utility of this observation depends on the extent to which it reflects static symptom risk or current symptom state. Methods: To determine whether task performance and estimated prior weighting relate to specific elements of symptom expression, a large, heterogeneous, and deeply phenotyped sample of hallucinators (n = 249) and nonhallucinators (n = 209) performed the conditioned hallucination (CH) task. Results: We found that CH rates predicted stable measures of hallucination status (i.e., peak frequency). However, CH rates were more sensitive to hallucination state (i.e., recent frequency), significantly correlating with recent hallucination severity and driven by heightened reliance on past experiences (priors). To further test the sensitivity of CH rate and prior weighting to symptom severity, a subset of participants with hallucinations (n = 40) performed a repeated-measures version of the CH task. Changes in both CH frequency and prior weighting varied with changes in auditory hallucination frequency on follow-up. Conclusions: These results indicate that CH rate and prior overweighting are state markers of hallucination status, potentially useful in tracking disease development and treatment response.

Background: Multiple renal arteries (MRA) are often encountered during living-donor kidney transplantation (LDKT), requiring surgeons to pursue complex renovascular reconstructions prior to graft implantation. With improvements in reconstruction and anastomosis techniques, allografts with MRA can be successfully transplanted with similar outcomes to allografts with a single renal artery. Here, we describe in detail various surgical techniques for reconstruction of MRA grafts with the intent of creating a single arterial inflow.Methods: We retrospectively reviewed the medical records of all LDKT recipients with laparoscopically procured MRA kidneys between March 2008 and July 2021. Recipient and donor characteristics, operative data, type of reconstruction, and recipient outcomes were analyzed. The primary outcomes were the incidence of developing delayed graft function (DGF) and/or a vascular or urological complication within 12 months post-transplant.Results: Seventy-three LDKT recipients of MRA donor allografts were evaluated. Two renal arteries (RA) were encountered in 62 allografts (84.9%) and three RA in 11 allografts (15.1%). Renal artery reconstruction was performed in 95.8% (70/73) of patients. Eighteen different reconstruction techniques of MRA were utilized, the most common being side-to-side anastomosis in allografts with two RA (N = 44) and side-to-side-to-side anastomosis in allografts with three RA (N = 4). Interposition grafting was performed in seven cases (9.6%). A single ostium was created in 69 cases (94.5%), and the median warm ischemia time was 27 (range 20–42) minutes. None of the patients developed DGF or post-operative vascular or urological complications. Median creatinine at 3, 6, and 12 months post-transplant remained stable at 1.1 mg/dl. With a median follow-up of 30.4 months post-transplant, only one graft failure has been observed–death-censored graft survival was 98.6%.Conclusion: Complex reconstruction techniques to create a single renal artery ostium for graft implantation anastomosis in allografts with MRA show acceptable warm ischemic times, with no increased risk of post-operative vascular or urological complications.

Background: We previously reported that graft failure due to nonadherence (GFNA) was a major cause of graft loss in kidney transplantation. Here, among 150 prospectively-followed kidney transplant recipients at 18 years post-transplant, we provide: updated (longer-term) estimates of cause-specific graft loss probabilities, risk factors for developing GFNA, and detailed characterizations of patients’ overt nonadherent (NA) behavior, including timing, extent, and clinical consequences. Methods: Determination of the patient becoming NA in taking his/her immunosuppressive medications, and the underlying cause of graft loss, were determined prospectively by the attending physicians. For never-functioning-graft, GFNA, GF due to causes other than NA (Other GF), and death with a functioning graft (DWFG), cumulative incidence functions were used to estimate the cumulative probabilities of cause-specific graft loss. Cox stepwise regression was used to determine significant multivariable predictors for the hazard rate of developing GFNA. Results: GFNA was a major cause of graft loss (22/150 patients), particularly among African-American and Hispanic recipients

In mitosis, sequences on sister chromatids are preferred as DNA repair templates, whereas in meiosis interhomolog-based repair is promoted. The switch of template preference during homologous recombinational (HR) repair of DNA breaks is a defining event in sexual reproduction. This preference is needed to establish linkages between homologous chromosomes that support meiotic chromosome segregation. In budding yeast, a central activity that enforces meiotic interhomolog bias is encoded in a meiosis-specific protein kinase complex, consisting of Red1, Hop1 and Mek1 (i.e., the RHM complex). Activation of Mek1 kinase in meiosis – dictated by complex formation and upstream DNA break-dependent signaling – leads to modification of HR factors and the establishment of interhomolog HR repair bias. How meiotic repair bias is established is a central question with implications for sexual reproduction, genetic diversity and genome stability. Studying the role of the RHM complex in DNA repair is complicated by the fact that Red1 and Hop1 are required for efficient meiotic DNA break formation. Here, we conditionally express RHM components in mitotically-dividing cells to show that these factors can autonomously establish the RHM complex outside of its physiological environment. In vivo analysis is complemented with in vitro biochemical reconstitution to analyze the composition of a Red1-Hop1 subcomplex. The RHM complex can be activated under DNA damaging conditions in mitotically-dividing cells, and activation depends on upstream Mec1 kinase function. We use this system to perform a structure-function analysis of RHM complex formation and Mek1 activation. Finally, we demonstrate that expressing active Mek1 in mitosis leads to rad51Δ-like DNA break sensitivity, suggesting that activation of the RHM complex is sufficient to reconstitute (parts of) its physiological function in mediating HR-based repair. This system should enable querying downstream effects of RHM complex action on DNA repair dynamics and template bias. Human homologs of Red1 and Hop1 are often aberrantly re-expressed in cancer cells. Our system has the potential to inform on (dys)functional effects of these genes on genome stability during human tumorigenesis.

Background Numerous studies and guidelines suggest an outcome detriment from radiation treatment breaks (rTBs) and the need for compensatory dosing in patients with head and neck cancer. Methods In a consecutive cohort of 521 patients with oropharyngeal squamous cell carcinoma (OPSCC), we investigated the impact of rTBs and prolongation of overall treatment time (OTT) on OS, DFS, LRC, and cancer recurrence using competing risk and multivariate analyses. Results Neither OTT prolongation by ≤2 days nor rTBs of ≤3 days were associated with detriments to clinical outcomes. Consecutive breaks of ≥3 days were also not significantly associated with detriment to clinical outcomes. There was significantly increased competing mortality in those with longer breaks. Conclusions In OPSCC patients treated with definitive concurrent chemoradiotherapy, there is no significant association between disease failure and total rTBs of ≤3 consecutive or scattered days. Further investigation is needed for longer breaks.

Endobronchial sarcoid lesions have previously been described and visualized upon bronchoscopy in adult patients with pulmonary sarcoid involvement. Endobronchial ultrasound-guided transbronchial fine-needle aspiration (EBUS-TBNA) has come into favor as the preferred method of diagnosis, but it remains a novel technique in pediatric pulmonology. We describe the first two known cases of visualized endobronchial sarcoid lesions in the pediatric population with pathological confirmation of sarcoidosis with endobronchial and EBUS-TBNA biopsies.

ImportancePatients with oropharyngeal carcinoma (OPC) treated with radiotherapy often experience substantial toxic effects, even with modern techniques such as intensity-modulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) has a potential advantage over IMRT due to reduced dose to the surrounding organs at risk; however, data are scarce given the limited availability and use of IMPT.ObjectiveTo compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic OPC treated with IMPT vs IMRT with or without chemotherapy.Design, Setting, and ParticipantsThis retrospective cohort study included patients aged 18 years or older with newly diagnosed nonmetastatic OPC who received curative-intent radiotherapy with IMPT or IMRT at a single-institution tertiary academic cancer center from January 1, 2018, to December 31, 2021, with follow-up through December 31, 2021.ExposuresIMPT or IMRT with or without chemotherapy.Main Outcomes and MeasuresThe main outcomes were the incidence of acute and chronic (present after ≥6 months) treatment-related adverse events (AEs) and oncologic outcomes, including locoregional recurrence (LRR), progression-free survival (PFS), and overall survival (OS). Fisher exact tests and χ2 tests were used to evaluate associations between toxic effects and treatment modality (IMPT vs IMRT), and the Kaplan-Meier method was used to compare LRR, PFS, and OS between the 2 groups.ResultsThe study included 292 patients with OPC (272 [93%] with human papillomavirus [HPV]-p16–positive tumors); 254 (87%) were men, 38 (13%) were women, and the median age was 64 years (IQR, 58-71 years). Fifty-eight patients (20%) were treated with IMPT, and 234 (80%) were treated with IMRT. Median follow-up was 26 months (IQR, 17-36 months). Most patients (283 [97%]) received a dose to the primary tumor of 70 Gy. Fifty-seven of the patients treated with IMPT (98%) and 215 of those treated with IMRT (92%) had HPV-p16–positive disease. There were no significant differences in 3-year OS (97% IMPT vs 91% IMRT; P = .18), PFS (82% IMPT vs 85% IMRT; P = .62), or LRR (5% IMPT vs 4% IMRT; P = .59). The incidence of acute toxic effects was significantly higher for IMRT compared with IMPT for oral pain of grade 2 or greater (42 [72%] IMPT vs 217 [93%] IMRT; P P P P P = .003), nausea of grade 2 or greater (0 [0%] IMPT vs 18 [8%] IMRT; P = .04), and weight loss of grade 2 or greater (22 [37%] IMPT vs 138 [59%] IMRT; P Conclusions and RelevanceIn this study, curative-intent radiotherapy with IMPT for nonmetastatic OPC was associated with a significantly reduced acute toxicity burden compared with IMRT, with few chronic toxic effects and favorable oncologic outcomes, including locoregional recurrence of only 5% at 2 years. Prospective randomized clinical trials comparing these 2 technologies and of patient-reported outcomes are warranted.

PURPOSE Telomerase reverse transcriptase ( TERT) promoter mutations are prognostic in many cancers and have been observed in human papillomavirus (HPV)–negative head and neck squamous cell carcinomas (HNSCCs). However, the role of TERT promoter mutations in HPV-negative HNSCCs remains poorly understood in these cancers, which have increased risk for locoregional failure (LRF). PATIENTS AND METHODS We retrospectively identified patients who were diagnosed with HNSCC between July 1, 2004, and October 12, 2017, at Memorial Sloan Kettering Cancer Center and whose tumors underwent next-generation sequencing using the MSK-IMPACT panel. Patients with HPV-positive oropharyngeal squamous cell carcinoma (SCC) were excluded. Cumulative incidence of LRF, patterns of failure, and overall survival were measured. RESULTS We identified 117 patients with SCC of the oral cavity (OSCC), larynx, hypopharynx, or HPV-negative oropharynx whose tumors underwent next-generation sequencing. Sequencing was performed on 95 tumors that were obtained after recurrence and 22 that were obtained before recurrence. TERT promoter mutations were enriched in OSCC compared with laryngopharyngeal cancers (81.1% v 7.0%; P < .001), which was the largest genetic difference between these anatomic disease subsites. TERT promoter mutations were associated with LRF in OSCCs (Gray's test, P < .001) and in the overall cohort (Gray's test, P < .001). On multivariate analysis, TERT promoter mutations were associated with an increased risk for LRF (subdistribution hazard ratio, 2.82; 95% CI, 1.47 to 5.42; P = .0019), independent of oral cavity primary site and TP53 mutation status. CONCLUSION TERT promoter status is associated with the cumulative incidence of LRF and patterns of failure. TERT promoter mutations may define a subset of OSCCs with unique pathogenesis that is associated with an increased risk of LRF. Validation in prospective cohorts is warranted.

Background/Objectives: Laparoscopic living donor nephrectomy (LLDN) of the right kidney is currently considered as part of standard of care; however, dealing with the renal hilum when performing ligation/division of its renal vessels is still a main concern. Here, we describe a simple-to-perform technique, i.e., flipping the fully mobilized right kidney to the midline so that the renal artery becomes anteriorly, which offers better visualization and easier dissection of the renal vessels (achieving maximized lengths) when performing hand-assisted LLDN of the right kidney. Methods: Living donors who underwent hand-assisted LLDN of the right kidney, along with their respective renal transplant recipients, were included in this report. Donor characteristics included renal artery and vein lengths; recipient characteristics included creatinine at months 12 – 36. Graft vein and arterial anastomosis data were also reported. Results: Nineteen living donors and 19 recipients, with median donor and recipient ages being 39 (24 – 60) and 53 (3 – 81) years, respectively, were included. None of the 38 patients had intra- or postoperative complications. Donor renal vein was anastomosed to the right external iliac vein (n = 16), right common iliac vein (n = 2), and inferior vena cava (n = 1). Gonadal vein (n = 1) and deceased donor iliac vein (n = 2) were used to increase the right renal vein length in 3 cases. Four donor kidneys had 2 arteries reconstructed side by side. None of the recipients developed any vascular or urological complications. Conclusions: The laparoscopic technique described is safe and allows better visualization of the right hilum, mainly the renal artery, and helps in stapling the renal vein and renal artery.

The aim of the present study was to identify whether the quantitative metrics from pre-treatment (TX) non-Gaussian intravoxel incoherent motion (NGIVIM) diffusion weighted (DW-) and fast exchange regime (FXR) dynamic contrast enhanced (DCE)-MRI can predict patients with locoregional failure (LRF) in nasopharyngeal carcinoma (NPC). Twenty-nine NPC patients underwent pre-TX DW- and DCE-MRI on a 3T MR scanner. DW imaging data from primary tumors were fitted to monoexponential (ADC) and NGIVIM (D, D*, f, and K) models. The metrics Ktrans, ve, and τi were estimated using the FXR model. Cumulative incidence (CI) analysis and Fine-Gray (FG) modeling were performed considering death as a competing risk. Mean ve values were significantly different between patients with and without LRF (p = 0.03). Mean f values showed a trend towards the difference between the groups (p = 0.08). Histograms exhibited inter primary tumor heterogeneity. The CI curves showed significant differences for the dichotomized cutoff value of ADC ≤ 0.68 × 10−3 (mm2/s), D ≤ 0.74 × 10−3 (mm2/s), and f ≤ 0.18 (p &lt, 0.05). τi ≤ 0.89 (s) cutoff value showed borderline significance (p = 0.098). FG’s modeling showed a significant difference for the K cutoff value of ≤0.86 (p = 0.034). Results suggest that the role of pre-TX NGIVIM DW- and FXR DCE-MRI-derived metrics for predicting LRF in NPC than alone.