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Dynamic, responsive materials can be built using photosurfactants (PS) that self-assemble into ordered nanostructures, such as micelles or liquid crystals. These PS contain photoswitchable groups, such as azobenzene (Azo) or, more recently, arylazopyrazoles (AAPs), which change shape and polarity on photoisomerisation between the E and Z states, thus changing the self-assembled structure. Small-angle X-ray scattering (SAXS) is a powerful technique to probe the morphology of PS and can be used to measure the mechanisms of structural changes using in-situ light irradiation with rapid, time-resolved data collection. However, X-ray irradiation has been shown previously to induce Z-to-E isomerisation of Azo-PS, which can lead to inaccuracies in the measured photostationary state. Here, we investigate the effect of light and X-ray irradiation on micelles formed from two different PS, containing either an Azo or AAP photoswitch using SAXS with in-situ light irradiation. The effect of X-ray irradiation on the Z isomer is shown to depend on the photoswitch, solvent, concentration and morphology. We use this to create guidelines for future X-ray experiments using photoswitchable molecules, which can aid more accurate understanding of these materials for application in solar energy storage, catalysis or controlled drug delivery.

Beamline B21 at the Diamond Light Source synchrotron in the UK is a small-angle X-ray scattering (SAXS) beamline that specializes in high-throughput measurements via automated sample delivery systems. A system has been developed whereby a sample can be illuminated by a focused beam of light coincident with the X-ray beam. The system is compatible with the highly automated sample delivery system at the beamline and allows a beamline user to select a light source from a broad range of wavelengths across the UV and visible spectrum and to control the timing and duration of the light pulse with respect to the X-ray exposure of the SAXS measurement. The intensity of the light source has been characterized across the wavelength range enabling experiments where a quantitative measure of dose is important. Finally, the utility of the system is demonstrated via measurement of several light-responsive samples.

AIM: To report a one-year clinical outcomes of low-dose laser cycloplasty (LCP) among malignant glaucoma patients. METHODS: In this prospective, multicenter, non-comparative clinical study, participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China. Patients were followed up at 1wk, 1, 3, 6, and 12mo. Intraocular pressure (IOP), number of glaucoma medications, anterior chamber depth (ACD), and complications were recorded. Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy. Recurrence was defined by the presence of a shallow or ?at anterior chamber after initial recovery from treatment. RESULTS: A total of 34 eyes received LCP. Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg (P

This commentary reflects on the first Global Stocktake (GST) under the Paris Agreement on climate change to offer insights for advancing climate actions and informing future GST cycles. The first GST, which concluded at COP28 in 2023, demonstrates the vital importance of a comprehensive, balanced, and inclusive approach to multilateral climate action. The GST's call to transition away from fossil fuels is an important political achievement. Yet, the GST outcome also reveals gaps, shortcomings, and potential dangers ahead. Future climate negotiations, we argue, would benefit from a more integrated, holistic perspective, and more nuanced balancing of ambition and implementation. More needs to be done to protect human rights, increase loss and damage funding, go beyond technological solutions, and address gender-differentiated consequences of climate change. Moreover, a great deal of work, including by nonstate actors, will be required to ensure the first GST translates into real action on the ground.

Leon Wansleben’s new book, The Rise of Central Banks, explains how central banks have emerged as powerful monetary governors over the past half-century. Yet the book’s recognition that central banks cannot extricate themselves from quantitative easing and market bailouts begs the question: what does it mean for central banks to be dominant but captive? In this commentary, I identify the book’s ambiguities with the concept of infrastructural power the book draws from Michael Mann. Unless the dynamics of state-market interdependence are well specified, giving due attention to the sources of both public and private power, it is unclear what kind of agency central bankers are exercising if they lack sufficient autonomy to act in the public interest.

Background: Long-term vedolizumab (VDZ) outcomes in real-world cohorts have been largely limited to 1-year follow-up, with few bio-naïve patients or objective markers of inflammation assessed. Objectives: We aimed to assess factors affecting VDZ persistence including clinical, biochemical and faecal biomarker remission at 1, 3 and 5 years. Design: We performed a retrospective, observational, cohort study. Methods: All adult inflammatory bowel disease (IBD) patients who had received VDZ induction for ulcerative colitis (UC)/IBD-unclassified (IBDU) were included. Baseline phenotype and follow-up data were collected via a review of electronic medical records. Results: We included 290 patients [UC n = 271 (93.4%), IBDU n = 19 (6.6%)] with a median time on VDZ of 27.6 months (interquartile range: 14.4–43.2). At the end of follow-up, a total of 157/290 (54.1%) patients remained on VDZ. The median time to discontinuation was 14.1 months (7.0–23.3). Previous exposure to ⩾1 advanced therapy, steroid use at baseline and disease extension (E3 and E2 versus E1) were independent predictors for worse VDZ persistence. Clinical remission (partial Mayo

BackgroundThe rapid growth of web-based symptom checkers (SCs) is not matched by advances in quality assurance. Currently, there are no widely accepted criteria assessing SCs’ performance. Vignette studies are widely used to evaluate SCs, measuring the accuracy of outcome. Accuracy behaves as a composite metric as it is affected by a number of individual SC- and tester-dependent factors. In contrast to clinical studies, vignette studies have a small number of testers. Hence, measuring accuracy alone in vignette studies may not provide a reliable assessment of performance due to tester variability. ObjectiveThis study aims to investigate the impact of tester variability on the accuracy of outcome of SCs, using clinical vignettes. It further aims to investigate the feasibility of measuring isolated aspects of performance. MethodsHealthily’s SC was assessed using 114 vignettes by 3 groups of 3 testers who processed vignettes with different instructions: free interpretation of vignettes (free testers), specified chief complaints (partially free testers), and specified chief complaints with strict instruction for answering additional symptoms (restricted testers). κ statistics were calculated to assess agreement of top outcome condition and recommended triage. Crude and adjusted accuracy was measured against a gold standard. Adjusted accuracy was calculated using only results of consultations identical to the vignette, following a review and selection process. A feasibility study for assessing symptom comprehension of SCs was performed using different variations of 51 chief complaints across 3 SCs. ResultsIntertester agreement of most likely condition and triage was, respectively, 0.49 and 0.51 for the free tester group, 0.66 and 0.66 for the partially free group, and 0.72 and 0.71 for the restricted group. For the restricted group, accuracy ranged from 43.9% to 57% for individual testers, averaging 50.6% (SD 5.35%). Adjusted accuracy was 56.1%. Assessing symptom comprehension was feasible for all 3 SCs. Comprehension scores ranged from 52.9% and 68%. ConclusionsWe demonstrated that by improving standardization of the vignette testing process, there is a significant improvement in the agreement of outcome between testers. However, significant variability remained due to uncontrollable tester-dependent factors, reflected by varying outcome accuracy. Tester-dependent factors, combined with a small number of testers, limit the reliability and generalizability of outcome accuracy when used as a composite measure in vignette studies. Measuring and reporting different aspects of SC performance in isolation provides a more reliable assessment of SC performance. We developed an adjusted accuracy measure using a review and selection process to assess data algorithm quality. In addition, we demonstrated that symptom comprehension with different input methods can be feasibly compared. Future studies reporting accuracy need to apply vignette testing standardization and isolated metrics.

Abstract Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10−6), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10−8), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10−6). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control.

Rainfall frequency and intensity are expected to increase in the Arctic, with potential detrimental impacts on permafrost, leading to enhanced thawing and carbon release to the atmosphere. However, there have been very few studies on the effect of discrete rain events on permafrost in the Arctic and sub-Arctic. Conducting controlled rainfall experiments within permafrost landscapes can provide an improved understanding of the effect of changing intensity, duration, and timing of rain events on permafrost tundra ecosystems. Here, we describe the design and implementation of the Next-Generation Ecosystem Experiment Arctic Rainfall Simulator (NARS), a variable intensity (4–82 mm/h) rainfall simulator that can be used to study the effects of rainfall on permafrost stability. The NARS design includes a 3D-printed 4 cm H-flume and uses an eTape resistivity sensor that was calibrated (R2 = 0.9–0.96) to measure discharge from the system. NARS is designed to be lightweight, simple to construct, and can be easily deployed in remote locations. As a field validation of updated rainfall simulator design and modernized controls, NARS was tested on the Seward Peninsula, AK. Because of its portability, versatility in deployment, dimensions, and rainfall intensity, NARS represents a methodological innovation for researching the impacts of rainfall on permafrost environments. HIGHLIGHTS Rainfall is expected to increase in the Arctic over the next century.; The effects of rainfall on permafrost stability are poorly understood.; We developed a variable intensity rainfall simulator for use in remote areas.; The new rainfall simulator is lightweight and modernizes simulator controls.; The simulator can be used to study rain effects on permafrost.;

Sexual reproduction is a crucial process for reef building coral populations to maximize genetic diversity and recover from large scale disturbances. Mass spawning events by Acropora species represent critical opportunities for populations to persist, and a process that is increasingly exploited to actively restore degraded reefs. However, the timing and predictive capacity of coral spawning throughout the broad thermal and environmental regime of the Red Sea – a region also undergoing significant development and active reef restoration – remains patchy. We, therefore, conducted three parallel reef surveys in the central Red Sea (Al-Fahal Reef, Thuwal - Saudi Arabia) and the eastern (Shushah Island - Saudi Arabia) and western (Hurghada – Egypt) coast of the northern Red Sea. Surveys assessed the gravidity of gonads, spawning timing, alignment with the lunar cycle of 21 Acropora spp. (total n= 572 colonies) around the full moons of April and May 2023. Consistent with past observations, synchronous spawning was observed for Acropora spp. in both the central and northern Red Sea during April and May, respectively. Interestingly, corals spawned on the full moon in both Shushah and Thuwal sites. In contrast, corals in Hurghada were independent of the lunar cycle and spawned 7-9 nights before the full moon in May. By integrating our 2023 observations with the historical spawning events in Hurghada and Thuwal (2002-2022), we found that the deviation of spawning timing from the full moon day was correlated with absolute Sea Surface Temperature (SST) (earlier spawning before the full moon day, lower SST) and warming rate (earlier spawning, more rapid warming) in 6-weeks prior to spawning. As such, temperature pattern is likely one of the primary factors governing gamete release, among other factors, that likely influence spawning day within the lunar month. These correlations between SST metrics and spawning timing suggest a potential framework to predict future Acropora spp. spawning dates. Our observations demonstrate the importance of parallel efforts across borders to collect critical data needed to inform management strategies aimed at conserving and restoring coral reefs in this ecologically diverse region.

Purpose: To perform a descriptive epidemiologic analysis of National Basketball Association (NBA) injuries from 2016 to 2021, to evaluate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019, or COVID-19) on injury patterns and performance statistics, and to determine the effect of infection with SARS-CoV-2 on individual performance statistics. Methods: Injury epidemiology in the NBA from the 2016 to 2021 seasons was collected using a comprehensive online search. Injuries and time missed were categorized by injury location and type. Player positions and timing of injury were recorded. Performance statistics were collected including traditional game statistics and Second Spectrum (speed, distance) statistics. Comparisons were made over seasons and comparing the pre-COVID-19 pandemic seasons to the pandemic era seasons. Players diagnosed with COVID-19 were analyzed for changes in performance in the short or long term. Results: Of the 3,040 injuries captured, 1,880 (61.84%) were in the lower extremity. Guards (77.44%) and forwards (75.88%) had a greater proportion of soft-tissue injuries (P < .001) than centers. Guards had the highest proportion of groin (3.27%, P = .001) and hamstring (6.21%, P < .001) injuries. Despite minor differences on a per-season basis, there were no differences in injury patterns identified between pre-COVID-19 and COVID-19 eras. Of players diagnosed with COVID-19 during the NBA Bubble, there were no detriments in short- or long-term performance identified, including traditional game statistics and speed and distance traveled. Conclusions: In the NBA seasons from 2016 to 2021, most injuries were to the lower extremity. The SARS-CoV-2 pandemic did not substantially impact injury patterns in the NBA, including locations of injury and type of injury (bony or soft tissue). Furthermore, infection with SARS-CoV-2 does not appear to have a significant impact on performance in basketball-specific or speed and distance measures. Level of Evidence: Level IV, prognostic case series.

The carbon footprint of a concrete structure is directly affected by the selected concrete mixture proportions. To better understand the influence of different concrete mixtures, data was collected from Environmental Product Declarations (EPDs). Data from 39,213 U.S.A. ready-mix concrete EPDs was obtained from public repositories provided by the American Society for Testing and Materials and the National Ready Mixed Concrete Association. The EPDs in .pdf format were analyzed using a custom Python script to extract useful information for building designers, sustainability practitioners, and researchers including: life cycle assessment (LCA) midpoints (Global Warming Potential, Ozone Depletion Potential, Acidification Potential, Photochemical Ozone Creation Potential, Abiotic Depletion, Total Waste Disposed, and Consumption of Freshwater), concrete strength classes, declared unit, concrete curing time, production components, concrete manufacturers’ company and plant locations, and additional LCA information. Both the dataset and an example of the Python script used to extract the information from the EPDs are provided. This dataset enables users to quickly assess the environmental impacts (including the Global Warming Potential) of different concrete mixtures without the need for extensive data collection and analysis. In summary, this dataset provides environmental information about concrete mixtures to aid civil engineering and architectural researchers, sustainability consultants, building engineering practitioners, and environmental policymakers to make sustainability-informed decisions when specifying concrete in the U.S.A.

IntroductionPresbyopia, the leading cause of vision impairment globally, is common during working years. However, no trials have assessed presbyopia's impact on income.MethodsIn April 2017, we conducted a census among 59 Bangladesh villages to identify persons aged 35 to 65 years with presbyopia (presenting distance vision > = 6/12 bilaterally and correctable inability to see 6/13 at 40 cm with both eyes), who never had owned glasses. Participants were randomized (1:1) to receive immediate free reading glasses (intervention) or glasses delivered 8 months later (control). Visual demand of different jobs was stratified into three levels. Outcomes were between-group differences in the 8 month change in: self-reported monthly income (primary) and Near Vision Related Quality of Life (NVRQOL, secondary).ResultsAmong 10,884 census participants, 3,655 (33.6%) met vision criteria and 863 (23.6%) comprised a sample enriched for near vision-intensive jobs, but 39 (4.52%) could not be reached. All participants allocated to intervention (n = 423, 51.3%) and control (n = 401, 48.7%) received the appropriate intervention, and follow-up was available for 93.4% and 96.8% respectively. Groups were similar at baseline in all characteristics: mean age was 47 years, 50% were male, 35% literate, and about half engaged in "most near vision-intensive" occupations. Glasses wear at 8-month follow-up was 88.3% and 7.81% in intervention and control respectively. At baseline, both the intervention and control groups had a self-reported median monthly income of US$35.3. At endline, the median income for the intervention group was US$47.1 compared with US$35.3 for control, a difference of 33.4%. Predictors of greater income increase in multivariate models included intervention group allocation (OR 1.45, 95% CI 1.12, 1.88, P = 0.005), male sex (OR 2.41, 95% CI 1.84, 3.16, P ConclusionProvision of reading glasses increases income in near vision-intensive occupations, and may facilitate return to work for those currently unemployed.

Abstract Background Melanoma, the most lethal skin cancer type, occurs more frequently in Parkinson's disease (PD), and PD is more frequent in melanoma patients, suggesting disease mechanisms overlap. α‐synuclein, a protein that accumulates in PD brain, and the oncogene DJ‐1, which is associated with PD autosomal recessive forms, are both elevated in melanoma cells. Whether this indicates melanoma progression or constitutes a protective response remains unclear. We hereby investigated the molecular mechanisms through which α‐synuclein and DJ‐1 interact, suggesting novel biomarkers and targets in melanoma. Methods The Cancer Genome Atlas (TCGA) expression profiles derived from UCSC Xena were used to obtain α‐synuclein and DJ‐1 expression and correlated with survival in skin cutaneous melanoma (SKCM). Immunohistochemistry determined the expression in metastatic melanoma lymph nodes. Protein–protein interactions (PPIs) and molecular docking assessed protein binding and affinity with chemotherapeutic drugs. Further validation was performed using in vitro cellular models and ELISA immunoassays. Results α‐synuclein and DJ‐1 were upregulated in primary and metastatic SKCM. Aggregated α‐synuclein was selectively detected in metastatic melanoma lymph nodes. α‐synuclein overexpression in SK‐MEL‐28 cells induced the expression of DJ‐1, supporting PPI and a positive correlation in melanoma patients. Molecular docking revealed a stable protein complex, with differential binding to chemotherapy drugs such as temozolomide, dacarbazine, and doxorubicin. Parallel reduction of both proteins in temozolomide‐treated SK‐MEL‐28 spheroids suggests drug binding may affect protein interaction and/or stability. Conclusion α‐synuclein, together with DJ‐1, may play a role in melanoma progression and chemosensitivity, constituting novel targets for therapeutic intervention, and possible biomarkers for melanoma.

Objective To investigate factors that differentiate elderly adults in rural China who accept free vision screening and cataract surgery from those who could benefit from vision care but refuse it when offered.Design We conducted a population-based, cross-sectional study between October and December 2016. Logistic regression models were used to examine the predictors of accepting free vision screening and cataract surgery.Setting Rural communities in Handan, China.Participants Adults aged 50 years or older, with presenting visual acuity ≤6/18 in the better seeing eye, suspected by examining ophthalmologist to be due to cataract.Results Among 613 persons with cataract identified on a population basis, 596 (97.2%) completed the household survey (mean (SD) age, 71.5 (10.0) years; 79.8% female). A total of 214 persons (35.9%) refused participation, while 382 (64.1%) took part in the vision screening. A total of 193 (50.5%) participants were found eligible for surgery, while 189 (49.5%) were not. Among 99 randomly selected participants who were offered immediate free surgery, surgery was accepted by 77 participants (77.8%) and refused by 22 (22.2%). In the multivariate model, being engaged in income-generating activities (p

ObjectiveThe measures implemented to control the spread of Coronavirus disease 2019 (COVID-19) could affect children’s mental and vision health. Youth particularly from minority and socioeconomically disadvantaged backgrounds were more likely to be impacted by these measures. This study aimed to examine the mental health of children with vision impairment and associated factors in North-western China during the COVID-19 pandemic.MethodsA cross-sectional study was conducted among 2,036 secondary school children living in Ningxia Hui Autonomous Region. Participants completed a survey on sociodemographic and lifestyle information and answered the Chinese version of the 21-item Depression Anxiety Stress Scales (DASS-21) questionnaire. Presenting visual acuity was measured by a trained enumerator. Multivariate logistic regression analysis was used to identify potential risk factors for mental health problems.ResultsResponses from 1,992 (97.8%) children were included in the analysis after excluding those with incomplete mental health outcome data. The prevalence of depression, anxiety and stress symptoms within the dataset were 28.9, 46.4, and 22.3%, respectively. The distribution of children with different stress levels differed significantly between those with and without vision impairment (p = 0.03). Multivariable logistic regression analyses revealed that depression symptoms decreased with higher parental education (OR, 0.76, 95% confidence intervals (CI):0.63–0.96), longer sleep duration (OR, 0.90, 95% CI: 0.81–0.97) and longer study time (OR, 0.82, 95% CI: 0.74–0.91), whereas they increased with higher recreational screen time (OR, 1.19, 95% CI: 1.08–1.32). Anxiety symptoms decreased with higher parental education (OR, 0.80, 95% CI: 0.66–0.96) and increased with higher recreational screen time (OR, 1.15, 95% CI: 1.04–1.27) and being a left-behind child (OR, 1.26, 95% CI: 1.04–1.54). In addition, stress symptoms decreased with longer sleep duration (OR, 0.92, 95%CI: 0.85–0.99) and increased with higher number of siblings (OR, 1.10, 95% CI: 1.01–1.19), higher recreational screen time (OR, 1.15, 95% CI: 1.04–1.28) and older age (OR,1.12, 95% CI: 1.004–1.24).ConclusionA considerable proportion of our sample experienced mental health problems during the pandemic. Healthcare planners in China should consider interventions such as reducing recreational screen time, ensuring sufficient sleep, and timely detection of mental health symptoms among socioeconomically disadvantaged groups.

The recently demonstrated concept of the plasma photocathode, whereby a high-brightness bunch is initialized by laser ionization within a plasma wakefield acceleration bubble, is informally referred to as Trojan Horse wakefield acceleration. In a similar vein, the dielectric Trojan Horse concept incorporates a dielectric-lined waveguide to support a charged particle beam-driven accelerating mode and uses laser initiated ionization of neutral gas within the waveguide to generate a witness beam. One of the advantages of the dielectric Trojan Horse concept is the reduced requirements in terms of timing precision due to operation at a lower frequency. In this paper, we present experimental results on the generation and characterization of a four-bunch drive train for resonant excitation of wakefields in a cylindrical dielectric waveguide conducted at the Argonne Wakefield Accelerator facility. The results lay the foundation for the demonstration of a plasma photocathode scheme within a dielectric wakefield accelerating structure. Modifications to improve capture efficiency with improved beam transmission are suggested as well.

Importance: There are significant gaps in the literature pertaining to the locoregional control and survival rates of extramedullary plasmacytoma (EMP) with respect to various treatment approaches., Objective: To systematically evaluate the differences in radiotherapy and surgical outcomes in EMP., Data Sources: Databases including PubMed, Scopus, Web of Science, Embase, and ScienceDirect were systematically searched from their inception up to November 2023., Study Selection: Articles reporting radiotherapy and surgical outcomes of head and neck EMP were included., Data Extraction and Synthesis: A random-effects model for meta-analysis was used to obtain pooled estimates and calculate hazard ratios for survival and odds ratios for recurrence and progression of EMP., Main Outcomes and Measures: Survival, tumor control, and progression rates to multiple myeloma (MM) between radiation therapy and surgery for EMP of the head and neck., Results: Of 742 included patients from 12 studies, 527 (71.0%) were male, and the median (IQR) age was 59.1 (53-62) years. A total of 505 patients (68.1%) received radiotherapy only, while 237 (31.9%) underwent surgery-only treatment for EMP. All included patients had an initial diagnosis of EMP without MM. Comparable trends were observed in overall survival and disease-free survival (DFS) rates at 2, 3, 5, and 10 years between patients with EMP treated with radiotherapy only and surgery only. Notably, there were no significant differences in recurrence rate (odds ratio, 0.65; 95% CI, 0.20-2.06) between radiotherapy-only and surgery-only treatment. However, radiotherapy-only treatment of EMP was associated with decreased odds of progression to MM compared with surgery (odds ratio, 0.4; 95% CI, 0.1-0.9). Sensitivity analysis revealed that the radiotherapy-only population had significantly better 5-year DFS (hazard ratio, 0.55; 95% CI, 0.31-0.96) compared with surgery-only treatment., Conclusions and Relevance: This systematic review and meta-analysis provides evidence that patients with EMP receiving radiotherapy had significantly lower chances of progression to MM compared with surgery-only therapy. Additionally, radiotherapy had better 5-year DFS outcomes compared with surgery. Comparable outcomes in terms of overall survival rates, recurrence, and mortality rates were noted between radiotherapy-only and surgery-only EMP treatment groups.

Recent data have shown a continued rise in the worldwide annual incidence and mortality rates of head and neck cancers. The present standard for diagnosis and monitoring for disease recurrence or progression involves clinical examination, imaging, and invasive biopsy techniques of lesions suspected of being malignant. In addition to limitations relating to cost, time, and patient discomfort, these methodologies have inherent inaccuracies for detecting recurrence. In view of these limitations, the analysis of patient bodily fluid samples via liquid biopsy proposes a cost-effective and convenient alternative, which provides insight on the biogenetic and biomolecular underpinnings of oncologic disease processes. The monitoring of biomarkers for head and neck cancer via liquid biopsy, including circulating tumor DNA, circulating tumor cells, and circulating cell-free RNA, has shown clinical utility in the screening, diagnosis, prognostication, and monitoring of patients with various forms of head and neck cancer. The present review will provide an update on the current literature examining the use of liquid biopsy in head and neck cancer care and the clinical applicability of potential biomarkers, with a focus on viral and non-viral circulating tumor DNA. Possible future avenues for research to address specific shortcomings of liquid biopsy will be discussed.

Objective: To critically evaluate oncological and functional outcomes following transoral laser microsurgery (TLM) in patients with T3/T4a glottic and supraglottic squamous cell carcinoma (SCC)., Data Sources: A comprehensive search of five major databases-PubMed, Embase, Scopus, ScienceDirect, and Web of Science-was conducted using a combination of relevant keywords and MeSH terms., Review Methods: Systematic review and meta-analysis of odds ratio (OR), hazards ratio (HR), and proportion, focusing on oncological and functional outcomes of TLM in advanced T3/T4a glottic and supraglottic tumors. A random-effects meta-analysis model was employed., Results: The review incorporated 29 cohort studies, representing a total of 1,897 patients undergoing TLM for T3/T4a glottic and supraglottic SCC. The cumulative 5-year disease-free survival (DFS) rate for T3 glottic and supraglottic tumors was 44.4% (95% CI: 47-66%) and 62.8% (95% CI: 63-81%), while the 5-year DFS for T4 glottic and supraglottic tumors was 41.1% (95% CI: 33.4-49.2%) and 32.9% (95% CI: 19.3-50.1%), respectively. T3 glottic tumors exhibited a 2.5-fold significantly higher odds of local recurrence post-TLM compared to their T3 supraglottic tumors (95% CI: 1.6-3.9, p < 0.0001). Laryngeal preservation rates for T3glottic and supraglottic tumors were 68.9% (95% CI: 48.7-83.8%) and 88.4% (95% CI: 79.4-93.8%), respectively. Both groups showed comparable rates of tracheostomy (p = 0.48) and gastrostomy performed (p = 0.17)., Conclusions: This meta-analysis suggests that TLM is a viable larynx preservation approach in select patients with T3/T4a glottic and supraglottic tumors. However, glottic tumors may have less favorable outcomes after TLM compared to those with advanced supraglottic tumors., Level of Evidence: N/A Laryngoscope, 2024 Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Circulating tumor DNA (ctDNA) detection is an emerging technique that identifies minimal residual disease in patients with solid tumors. ctDNA can act as an adjunct method to help overcome the limitations of positron emission tomography (PET) and select patients who are at high risk for recurrence., Study Design: Retrospective Single Institutional Study., Setting: University Hospital Setting., Methods: Twenty-nine patients who underwent definitive treatment for squamous cell carcinoma of the head and neck (HNSCC) from 8/2021 to 01/2023 had ctDNA levels analyzed at 1 to 3, 6, 9, and 12 months after definitive treatment. A personalized, tumor-informed, multiplex polymerase chain reaction (PCR) next-generation sequencing (NGS) assay was used to detect the ctDNA levels. The primary outcome was recurrence-free probability (RFP), and the secondary outcomes were overall survival (OS), sensitivity, specificity, and the test's negative (NPV) and positive predictive values (PPV)., Results: The median age of patients was 65 years (interquartile range: 56-69), with majority being males (n = 22, 76%). The primary sites were larynx (n = 12), oropharynx (n = 10), and oral cavity (n = 6). Posttreatment ctDNA was detected in 7 patients, all of whom had disease recurrence. ctDNA detection after definitive treatment was associated with a higher risk of disease recurrence (hazard ratio: 9.94, 95% confidence interval: 1.56-63.3, P = .015). ctDNA identified recurrence with 100% specificity and 78% sensitivity. The NPV and PPV were 91% and 100%. PET had 78% sensitivity but only 68% specificity with 86% NPV, and 54% PPV., Conclusion: Based on our data, ctDNA can be an excellent adjunct test for posttreatment PET and can help guide physicians in cases where PET results are inconclusive and difficult to interpret., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

This study aims to evaluate the functional and prognostic outcomes associated with the internal mammary artery perforator (IMAP) flap in various head and neck defect repairs, given the current lack of clarity on its effectiveness. We performed a systematic review of various databases: PubMed, Embase, Scopus, Web of Science, and ScienceDirect using keywords such as "Internal mammary artery perforator flap" and "IMAP." Screening and data extractions were performed by two individual reviewers. Articles were considered eligible if they included sufficient information on IMAP flap features, their applications in the head and neck, and outcomes. From 264 articles analyzed, 24 studies were included for qualitative analysis. Out of which, 125 patients who received internal mammary artery perforator flaps were included. Most of the patients, 103 (88%), received pedicled IMAP flaps, and 22 (12%) received IMAP free flaps. The second internal mammary artery (IMA) was favored as the single perforator (81.5%), with the combination of the first and second IMA being the primary choice for dual perforators (92.5%). IMAP flaps were predominantly single perforator flaps (65%), with 35% being dual perforator flaps. Among various applications, IMAP flaps are commonly employed in the reconstruction of neck defects (25.5%), pharyngocutaneous fistula repair (20.8%), and burn scar contracture restoration (8%). Only seven (5.6%) patients had flap complications, including venous congestion (1.6%), partial necrosis (1.6%), complete necrosis (1.6%), and incision dehiscence (0.8%). Donor sites were predominantly closed by the primary closure (92%). 3.2% of donor sites had minor complications. The average follow-up was 12.6 (IQR: 6-18) months. This systematic review highlights the effectiveness and safety of IMAP flaps in head and neck reconstruction, with positive outcomes and minimal complications., (© 2024 Wiley Periodicals LLC.)

To comprehensively evaluate the therapeutic efficacy and safety when utilizing proton therapy (PT) versus intensity-modulated radiation therapy (IMRT) in head and neck cancer patients. Pubmed, ScienceDirect, Embase, Scopus, and Web of Science were systematically searched for studies on comparative PT and IMRT outcomes. We performed a random effect model meta-analysis to estimate the hazard ratio (HR) and odds ratio (OR) for efficacy and safety outcome variables between PT and IMRT. From 641 identified articles, 11 studies met the inclusion criteria, comprising 3087 patients (606 treated with PT and 2481 with IMRT). On toxicity analysis, PT is associated with decreased acute grade 1 nausea (OR = 0.34, 95% CI: 0.13-0.84, p = 0.02) compared to IMRT. In grade 2 toxicity, PT showed significant advantages over IMRT in mucositis (OR = 0.44, p < 0.0001), dysgeusia (OR = 0.35, p = 0.02), dysphagia (OR = 0.36, p < 0.0001), fatigue (OR = 0.29, p = 0.001), pain (OR = 0.34, p = 0.01), and weight loss (OR = 0.54, p = 0.02). Proton therapy also exhibited increased safety in grade 3 dysphagia incidence (OR = 0.44, p < 0.0001) compared to IMRT. PT demonstrated improved overall survival (OS) compared to IMRT across multiple time points: 1-year OS (HR = 0.43, p = 0.02), 2-year OS (HR = 0.44, p < 0.0001), and 5-year OS (HR = 0.78, p = 0.004). In terms of disease-free survival (DFS), PT also showed improved outcomes at 2-year DFS (HR = 0.65, p = 0.03) and 5-year DFS (HR = 0.81, p = 0.03). Proton therapy demonstrated superior overall survival (OS), disease-free survival (DFS), and better local control rate (LCR) compared to IMRT. The data also showed better safety outcomes in PT patients, particularly when involving grade 2 acute toxicity events., (© 2024 Wiley Periodicals LLC.)

Background: Temporal bone resection (TBR) with or without neck dissection (ND) is performed for otologic malignancies with occult or clinical cervical lymph node metastases. To date, characterization of post-operative complications in single institution case series may be non-representative of real-world outcomes. Here, we used data from the National Inpatient Sample (NIS) to comprehensively assess the complications encountered, their frequencies, and to identify underlying risk factors to improve future outcomes., Methods: The population was patients undergoing TBR and ND derived from the NIS between the years of 2017 and 2019. We utilized ICD-10 diagnosis codes to identify patients with post-operative complications, those discharged to non-home facilities (DNHF), and those with increased length of stay (LOS). Multivariable regression was performed to identify significant variables related to the above outcomes., Results: Ninety of 277 patients that underwent LTBR with ND had postoperative complications. Wound complications were the most frequent complication, occurring in 11 (4%) of patients, followed by CSF leak (n = 6; 2.2%), with acute respiratory failure being the most common medical complication (n = 4; 1.4%). Sixteen percent (45/277) were discharged to a facility besides home. Dementia (OR = 7.96; CI 95 3.62-17.48), anemia (OR = 2.39; CI 95 1.15-4.99), congestive heart failure (OR = 5.31; CI 95 1.82-15.45), COPD (OR = 3.70; CI 95 1.35-10.16), and history of prior stroke (OR = 8.50; CI 95 1.55-46.68) increased the odds of DNHF. When evaluating LOS (median = 5 days, IQR = 1, 9), anemia (OR = 5.49; CI 95 2.86-10.52), and Medicaid insurance (OR = 3.07; CI 95 1.06-10.52) were found to increase the LOS., Conclusions: The vast majority of patients undergoing LTBR with ND have no complications and are discharged within a week. Liver disease is a risk factor for medical complications and increased charges. Patients with dementia or a prior stroke are at risk for DNHF, and those with prior anemia are at risk for a wound complication., Lay Summary: This study identified factors related to worse post-operative outcomes in patients undergoing temporal bone resection and neck dissection. Although safe for most patients, an existing diagnosis of liver disease, stroke, dementia, and anemia specifically are at risk for developing negative outcomes., Level of Evidence: 3., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit). Methods: The clinical in vivo oncology (CIVO ® ) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4-96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure. Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment. Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development., Competing Interests: WJ, AT, and BM are employees of Presage Biosciences, Inc. CB, AM, KS, KCG, JB, MG, JF, JD, and RK are employees of and hold ownership interest (including patents (MG, JF, and RK)) in Presage Biosciences. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study (NCT04065555 and NCT06062602) received funding from Takeda Pharmaceuticals. The funder had the following involvement: study design, supply of drug, and the review of this article. The authors declare that this study (NCT04272333) received funding from Celgene Corporation. The funder had the following involvement: study design and supply of study drug. The authors declare that this study (NCT04541108) received funding from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. The funder had the following involvement: study design, supply of study drug, and the review of this article., (Copyright © 2024 Gundle, Rajasekaran, Houlton, Deutsch, Ow, Maki, Pang, Nathan, Clayburgh, Newman, Brinkmann, Wagner, Pollack, Thompson, Li, Mehta, Schiff, Wenig, Swiecicki, Tang, Davis, van Zante, Bertout, Jenkins, Turner, Grenley, Burns, Frazier, Merrell, Sottero, Derry, Gillespie, Mills and Klinghoffer.)

Background: Increased sexual activity is associated with higher human papillomavirus (HPV) rates; however, there is a lack of analysis comparing the sexual history of patients with HPV positive and HPV negative oropharyngeal cancer (OPC)., Methods: In this meta-analysis, PubMed, Scopus, and CINAHL were searched for articles that included patients with OPC and reported information regarding HPV status and either history of oral sex, number of sexual partners, or sexually transmitted infections (STI)., Results: A total of 11 studies were included with 3296 patients with OPC. Patients with HPV positive OPC were more likely than patients with HPV negative OPC to report a history of oral sex (92%, 95% CI: 87.0-97.0 vs. 74.5%, 95% CI: 50.6-98.4, p < 0.0001), higher mean number of sexual partners (18.4 partners, 95% CI: 1.5-35.4 vs. 7.2 partners, 95% CI: 1.0-13.4, p < 0.0001), and more frequent history of STI (23.7%, 95% CI: 18.4-29.0 vs. 8.8%, 95% CI: 4.7-12.8, p = 0.0001)., Conclusions: Compared to patients with HPV negative OPC, our analysis shows a larger proportion of patients with HPV positive OPC had participated in oral sex, had a higher number of sexual partners, and had a higher proportion of STI history., (© 2024 Wiley Periodicals LLC.)

Background: Dementia, a growing concern among the elderly, has an increased poor postoperative outcome that goes unrecognized by many. Our study aims to establish if dementia plays a role in the outcomes of head and neck cancer patients that undergo resections., Methods: We queried the National Inpatient Sample (NIS) database from 2016 to 2019 with a primary diagnosis of head and neck cancer who underwent surgical resection. Outcomes analyzed include postoperative delirium, ICU stay, complications, length of stay, and non-routine discharge., Results: A total of 77095 patients were included, of which 1140 patients had dementia. The mean age of the patients with dementia was 77.5 years (±9.1) versus 63.2 years (±12.1) with no dementia. Dementia patients had a higher non-home discharge rate (77.2% vs 46.8%, p = <0.001), extended length of stay (10.9 days ±14.7 vs 7.9 days ±8.8), postoperative delirium (15.4% vs 1.5%, p = <0.001), and longer ICU stay (8.3% vs 5.8%) as compared with patients with no dementia. A higher number of patients with Dementia were placed in long-term facilities (53.5% vs 14.6%) postoperatively. More dementia patients (7.9% vs 0.9%) were transferred in from another health care facility for surgery. Dementia was associated with higher odds of delirium (OR, 6.36; 95% CI, 5.2-7.77), non-routine discharge (OR, 2.05; 95% CI, 1.76-2.3), ventilation (OR, 0.8; 95% CI, 0.6-1.05), and length of stay (estimate 3.01, 95% CI, 1.84-4.184)., Conclusion: Preoperative dementia significantly impacts postoperative delirium, non-home discharge, and extended length of stay in head and neck cancer patients undergoing surgery., Level of Evidence: 3 Laryngoscope, 134:1258-1264, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

A potential role for fibroblast growth factor receptor 2 (FGFR2) in cutaneous squamous cell carcinoma (cSCC) has been reported. To demonstrate the specific role of FGFR2 in UVB-induced skin carcinogenesis and development of cSCC, we generated a keratinocyte specific, tamoxifen inducible mouse model of FGFR2 deficiency. In this mouse model, topical application of 4-hydroxy tamoxifen led to the induction of Cre recombinase to delete FGFR2 in epidermal keratinocytes of both male and female transgenic mice. Analysis of epidermal protein lysates isolated from FGFR2 deficient mice exposed to UVB showed significant reductions of phospho-FGFR (pFGFR; Y653/654) and phospho-fibroblast growth factor receptor substrate 2α as well as downstream effectors of mTORC1 signaling. Phosphorylation of signal transducer and activators of transcription 1/3 was significantly reduced as well as levels of IRF-1, DUSP6, early growth response 1, and PD-L1 compared to the control groups. Keratinocyte-specific ablation of FGFR2 also significantly inhibited epidermal hyperproliferation, hyperplasia, and inflammation after exposure to UVB. Finally, keratinocyte-specific deletion of FGFR2 significantly inhibited UVB-induced cSCC formation. Collectively, the current data demonstrate an important role of FGFR2 in UVB-induced oncogenic signaling as well as development of cSCC. In addition, the current preclinical findings suggest that inhibition of FGFR2 signaling may provide a previously unreported strategy to prevent and/or treat UVB-induced cSCC., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)