Biomechanical and histological comparison of two suture configurations for soft tissue grafts: speedtrap™ versus krackow stitch.

To compare 2 different graft preparation techniques to determine biomechanical strength and resultant tissue trauma evaluated by histology. Twelve common flexors of the finger's tendons were prepared with either tubulization (SpeedTrap™) or transtendon stiches (Orthocord™). The stiffness, resistance and energy at maximum load were tested for biomechanical assessment in both groups. After load testing, Samples were stained with hematoxylin and eosin (HE) to evaluate histological damage. We observe that the time to prepare tendons with SpeedTrap™ was 8.3 times faster (1:25 min) than traditional ones (15:02 min). In all cases, the mean values for SpeedTrap™ were higher in terms of strength, stiffness and energy at maximum load than for traditional suture but without significant difference (p > 0.05). The Krackow stitch produces greater structural damage to the collagen fibers while SpeedTrap™ maintains better organized arrangement of the fibers after tubulization preparation. With the results obtained, we can conclude that the tubulization technique allows faster graft preparation with less structural damage to the manipulated tissue without altering the biomechanical resistance provided by the transtendon suture technique.

Mango Fruit Detachment of Trees after Applying a Blend Composed of HNO3 and Charcoal Activated.

As young workers prefer urban labors and migrate to USA and Canada, mango harvesting is becoming scarce on Mexican coasts. This seasonal labor is becoming expensive and when many orchards produce fruit simultaneously, grower losses increase. In this research, an innovative fruit detachment method was tested after applying a viscous paste to the pedicel of mango fruits hanging in the tree. Activated carbon or charcoal (AC), was mixed with different amounts of nitric acid to provide three AC composite blends named: light, medium, and dense. The nanomaterial was applied with a brush to the fruit pedicel/peduncle taking up to 4 h before the mango fruits felt to a net below the tree canopy. Mango detachment experiments indicated that the medium blend was the most efficient in releasing the fruit, taking an average of 2 h. The dense nano-material decreased latex exudation to 7% of the fruits. Fruit maturity emerged as a crucial factor for detachment time, followed by mango weight.

Circumvention of Topoisomerase IIα Intron 19 Intronic Polyadenylation (IPA) in Acquired Etoposide Resistant Human Leukemia K562 Cells.

DNA topoisomerase IIα (TOP2α, 170kDa, TOP2α/170) is an essential enzyme for proper chromosome dysjunction by producing transient DNA double-stranded breaks and is a significant target for DNA damage stabilizing anti-cancer agents such as etoposide. Therapeutic effects of TOP2α poisons can be limited due to acquired drug resistance. We previously demonstrated decreased TOP2α/170 levels in an etoposide-resistant human leukemia K562 subline, designated K/VP.5, accompanied by increased expression of a C-terminal truncated TOP2α isoform (90 kDa, TOP2α/90) which heterodimerized with TOP2α/170 and was a determinant of resistance by exhibiting dominant-negative effects against etoposide activity. Based on 3'-Rapid Amplification of cDNA Ends (3'-RACE), we confirmed TOP2α/90 as the translation product of a TOP2α mRNA in which a cryptic polyadenylation site (PAS) harbored in intron 19 (I19) was utilized. We hypothesized that resultant intronic polyadenylation (IPA) can would be attenuated by blocking or mutating the I19 PAS thereby circumventing acquired drug resistance. An antisense morpholino oligonucleotide (AMO) was used to hybridize/block the PAS in TOP2α pre-mRNA in K/VP.5 cells, resulting in decreased TOP2α/90 mRNA/protein levels in K/VP.5 cells and partially circumventing drug resistance. Subsequently, CRISPR/Cas9 homology-directed repair (HDR) was used to mutate the cryptic I19 PAS (AATAAA-->ACCCAA) to prevent IPA. Gene-edited clones exhibited increased TOP2α/170 and decreased TOP2α/90 mRNA/protein and demonstrated restored sensitivity to etoposide and other TOP2α-targeted drugs. Together, results indicated that blocking/mutating a cryptic I19 PAS in K/VP.5 cells reduced IPA and restored sensitivity to TOP2α-targeting drugs. Significance Statement Results presented here indicate that CRISPR/Cas9 gene editing of a cryptic polyadenylation site (PAS) within I19 of the TOP2α gene results in reversal of acquired resistance to etoposide and other TOP2-targeted drugs. An antisense morpholino oligonucleotide (AMO) targeting the PAS also partially circumvented resistance. Results demonstrate the importance of intronic polyadenylation (IPA) in acquired drug resistance and points to tractable strategies to overcome this form of resistance to TOP2-targeted agents.

A randomised clinical trial of awake prone positioning in COVID-19 suspects with acute hypoxemic respiratory failure.

Background: Awake prone position (APP) has been reported to improve oxygenation in patients with COVID-19 disease and to reduce the requirement for invasive mechanical ventilation for patients requiring support with high flow nasal cannula. There is conflicting data for patients requiring lower-level oxygen support. Research question: Does APP reduce escalation of oxygen support in COVID-19 patients requiring supplementary oxygen?The primary outcome was defined as an escalation of oxygen support from simple supplementary oxygen (NP, HM, NRB) to NIV (CPAP or BiPAP), HFNC or IMV; OR from NIV (CPAP or BiPAP) or HFNC to IMV by day30. Study design: Two center, prospective, non-blind, randomised controlled trial. Patients with confirmed or suspected COVID-19 pneumonia requiring ≥ 5 liters/min oxygen to maintain saturations ≥ 94 % were randomised to either APP or control group. The APP group received a 3-h APP session three times per day for three days. Results: Between 9 May and July 13, 2021, 89 adults were screened and 61 enrolled, 31 to awake prone position and 30 controls. There was no difference in the primary outcome, 7 (22.6 %) patients randomised to APP and 9 (30.0 %) controls required escalation of oxygen support (OR 0.68 (0.22-2.14), P = 0.51). There were no differences in any secondary outcomes, in APP did not improve oxygenation. Interpretation: In COVID-19 patients, the use of APP did not prevent escalation of oxygen support from supplementary to invasive or non-invasive ventilation or improve patient respiratory physiology. Trial registration: NCT04853979 (clinicaltrials.gov).

HPLC-Based Metabolomic Analysis and Characterization of Amaranthus cruentus Leaf and Inflorescence Extracts for Their Antidiabetic and Antihypertensive Potential.

The aim of this study was to investigate the potential of Amaranthus cruentus flavonoids (quercetin, kaempferol, catechin, hesperetin, naringenin, hesperidin, and naringin), cinnamic acid derivatives (p-coumaric acid, ferulic acid, and caffeic acid), and benzoic acids (vanillic acid and 4-hydroxybenzoic acid) as antioxidants, antidiabetic, and antihypertensive agents. An analytical method for simultaneous quantification of flavonoids, cinnamic acid derivatives, and benzoic acids for metabolomic analysis of leaves and inflorescences from A. cruentus was developed with HPLC-UV-DAD. Evaluation of linearity, limit of detection, limit of quantitation, precision, and recovery was used to validate the analytical method developed. Maximum total flavonoids contents (5.2 mg/g of lyophilized material) and cinnamic acid derivatives contents (0.6 mg/g of lyophilized material) were found in leaves. Using UV-Vis spectrophotometry, the maximum total betacyanin contents (74.4 mg/g of lyophilized material) and betaxanthin contents (31 mg/g of lyophilized material) were found in inflorescences. The leaf extract showed the highest activity in removing DPPH radicals. In vitro antidiabetic activity of extracts was performed with pancreatic α-glucosidase and intestinal α-amylase, and compared to acarbose. Both extracts exhibited a reduction in enzyme activity from 57 to 74%. Furthermore, the in vivo tests on normoglycemic murine models showed improved glucose homeostasis after sucrose load, which was significantly different from the control. In vitro antihypertensive activity of extracts was performed with angiotensin-converting enzyme and contrasted to captopril; both extracts exhibited a reduction of enzyme activity from 53 to 58%. The leaf extract induced a 45% relaxation in an ex vivo aorta model. In the molecular docking analysis, isoamaranthin and isogomphrenin-I showed predictive binding affinity for α-glucosidases (human maltase-glucoamylase and human sucrase-isomaltase), while catechin displayed binding affinity for human angiotensin-converting enzyme. The data from this study highlights the potential of A. cruentus as a functional food.

Vacuolar Degradation of Plant Organelles.

Plants continuously remodel and degrade their organelles due to damage from their metabolic activities and environmental stressors, as well as an integral part of their cell differentiation programs. Whereas certain organelles use local hydrolytic enzymes for limited remodeling, most of pathways that control the partial or complete dismantling of organelles rely on vacuolar degradation. Specifically, selective autophagic pathways play a crucial role in recognizing and sorting plant organelle cargo for vacuolar clearance, especially under cellular stress conditions induced by factors like heat, drought, and damaging light. In these short reviews, we discuss the mechanisms that control the vacuolar degradation of chloroplasts, mitochondria, endoplasmic reticulum, Golgi, and peroxisomes, with an emphasis on autophagy, recently discovered selective autophagy receptors for plant organelles, and crosstalk with other catabolic pathways.

Characterization of the Relative Change in Objective and Subjective Metrics by Baselining Patients Who Have Wearable Technology Before Total Knee Arthroplasty.

BACKGROUND: Wearable sensors and associated supporting technologies (ie, patient applications) can provide both objective (joint position, step counts, etc.) and subjective data (ie, pain scores and patient-reported outcome measures) to track a patient's episode of care. Establishing a subjective and objective baseline of a patient's experience may arguably be beneficial for multiple reasons, including setting recovery expectations for the patient and demonstrating the effectiveness or success of the intervention. METHODS: In this pilot study, we characterized a subset of patients (n = 82 from 7 surgeons) using a wearable sensor system at least 6 days before total knee arthroplasty and provided postsurgical data up to 50 days postintervention. The 5-day average before surgery for total step counts (activity), achieved flexion and extension on a progress test (functional limit) and visual analog scale daily pain score were calculated. The difference from baseline was then calculated for each patient for each day postsurgery and reported as averages. RESULTS: On average, a patient will experience a relative deficit of 4,000 steps immediately following surgery that will return to near-baseline levels 50 days postintervention. A 30° deficit in flexion and a 10° deficit in extension will return at a similar rate as steps. Relative pain scores will worsen with an increase of approximately 3 points immediately following surgery. However, pain will decrease by 2 points relative to baseline between 40 and 50 days. CONCLUSIONS: The results of this pilot study demonstrate a method to baseline a patient's presurgical subjective and objective data and to provide a reference for postsurgical recovery expectations. Applications for these data include benchmarking for evaluating intervention success as well as setting patient expectations.

Incorporating plan complexity into the statistical process control of volumetric modulated arc therapy pre-treatment verifications.

BACKGROUND: Statistical process control (SPC) is a powerful statistical tool for process monitoring that has been highly recommended in healthcare applications, including radiation therapy quality assurance (QA). The AAPM TG-218 report described the clinical implementation of SPC for Volumetric Modulated Arc Therapy (VMAT) pre-treatment verifications, pointing out the need to adjust tolerance limits based on plan complexity. However, the quantification of plan complexity and its integration into SPC remains an unresolved challenge. PURPOSE: The primary aim of this study is to investigate the incorporation of plan complexity into the SPC framework for VMAT pre-treatment verifications. The study explores and evaluates various strategies for this incorporation, discussing their merits and limitations, and provides recommendations for clinical application. METHODS: A retrospective analysis was conducted on 309 VMAT plans from diverse anatomical sites using the PTW OCTAVIUS 4D device for QA measurements. Gamma Passing Rates (GPR) were obtained, and lower control limits were computed using both the conventional Shewhart method and three heuristic methods (scaled weighted variance, weighted standard deviations, and skewness correction) to accommodate non-normal data distributions. The 'Identify-Eliminate-Recalculate' method was employed for robust analysis. Eight complexity metrics were analyzed and two distinct strategies for incorporating plan complexity into SPC were assessed. The first strategy focused on establishing control limits for different treatment sites, while the second was based on the determination of control limits as a function of individual plan complexity. The study extensively examines the correlation between control limits and plan complexity and assesses the impact of complexity metrics on the control process. RESULTS: The control limits established using SPC were strongly influenced by the complexity of treatment plans. In the first strategy, a clear correlation was found between control limits and average plan complexity for each site. The second approach derived control limits based on individual plan complexity metrics, enabling tailored tolerance limits. In both strategies, tolerance limits inversely correlated with plan complexity, resulting in all highly complex plans being classified as in control. In contrast, when plans were collectively analyzed without considering complexity, all the out-of-control plans were highly complex. CONCLUSIONS: Incorporating plan complexity into SPC for VMAT verifications requires meticulous and comprehensive analysis. To ensure overall process control, we advocate for stringent control and minimization of plan complexity during treatment planning, especially when control limits are adjusted based on plan complexity.

A radiotherapy community data-driven approach to determine which complexity metrics best predict the impact of atypical TPS beam modeling on clinical dose calculation accuracy.

PURPOSE: To quantify the impact of treatment planning system beam model parameters, based on the actual spread in radiotherapy community data, on clinical treatment plans and determine which complexity metrics best describe the impact beam modeling errors have on dose accuracy. METHODS: Ten beam modeling parameters for a Varian accelerator were modified in RayStation to match radiotherapy community data at the 2.5, 25, 50, 75, and 97.5 percentile levels. These modifications were evaluated on 25 patient cases, including prostate, non-small cell lung, H&N, brain, and mesothelioma, generating 1,000 plan perturbations. Differences in the mean planned dose to clinical target volumes (CTV) and organs at risk (OAR) were evaluated with respect to the planned dose using the reference (50th-percentile) parameter values. Correlation between CTV dose differences, and 18 different complexity metrics were evaluated using linear regression; R-squared values were used to determine the best metric. RESULTS: Perturbations to MLC offset and transmission parameters demonstrated the greatest changes in dose: up to 5.7% in CTVs and 16.7% for OARs. More complex clinical plans showed greater dose perturbation with atypical beam model parameters. The mean MLC Gap and Tongue & Groove index (TGi) complexity metrics best described the impact of TPS beam modeling variations on clinical dose delivery across all anatomical sites; similar, though not identical, trends between complexity and dose perturbation were observed among all sites. CONCLUSION: Extreme values for MLC offset and MLC transmission beam modeling parameters were found to most substantially impact the dose distribution of clinical plans and careful attention should be given to these beam modeling parameters. The mean MLC Gap and TGi complexity metrics were best suited to identifying clinical plans most sensitive to beam modeling errors; this could help provide focus for clinical QA in identifying unacceptable plans.

Thyroid hormone action in adult neurogliogenic niches: the known and unknown.

Over the last decades, thyroid hormones (THs) signaling has been established as a key signaling cue for the proper maintenance of brain functions in adult mammals, including humans. One of the most fascinating roles of THs in the mature mammalian brain is their ability to regulate adult neurogliogenic processes. In this respect, THs control the generation of new neuronal and glial progenitors from neural stem cells (NSCs) as well as their final differentiation and maturation programs. In this review, we summarize current knowledge on the cellular organization of adult rodent neurogliogenic niches encompassing well-established niches in the subventricular zone (SVZ) lining the lateral ventricles, the hippocampal subgranular zone (SGZ), and the hypothalamus, but also less characterized niches in the striatum and the cerebral cortex. We then discuss critical questions regarding how THs availability is regulated in the respective niches in rodents and larger mammals as well as how modulating THs availability in those niches interferes with lineage decision and progression at the molecular, cellular, and functional levels. Based on those alterations, we explore the novel therapeutic avenues aiming at harnessing THs regulatory influences on neurogliogenic output to stimulate repair processes by influencing the generation of either new neurons (i.e. Alzheimer's, Parkinson's diseases), oligodendrocytes (multiple sclerosis) or both (stroke). Finally, we point out future challenges, which will shape research in this exciting field in the upcoming years.

Phylogenomics of Tetraopes longhorn beetles unravels their evolutionary history and biogeographic origins.

Tetraopes longhorn beetles are known for their resistance to milkweed plant toxins and their coevolutionary dynamics with milkweed plants (Asclepias). This association is considered a textbook example of coevolution, in which each species of Tetraopes is specialized to feed on one or a few species of Asclepias. A major challenge to investigating coevolutionary hypotheses and conducting molecular ecology studies lies in the limited understanding of the evolutionary history and biogeographical patterns of Tetraopes. By integrating genomic, morphological, paleontological, and geographical data, we present a robust phylogeny of Tetraopes and their relatives, using three inference methods with varying subsets of data, encompassing 2-12 thousand UCE loci. We elucidate the diversification patterns of Tetraopes species across major biogeographical regions and their colonization of the American continent. Our findings suggest that the genus originated in Central America approximately 21 million years ago during the Miocene and diversified from the Mid-Miocene to the Pleistocene. These events coincided with intense geological activity in Central America. Additionally, independent colonization events in North America occurred from the Late Miocene to the early Pleistocene, potentially contributing to the early diversification of the group. Our data suggest that a common ancestor of Tetraopini migrated into North America, likely facilitated by North Atlantic land bridges, while closely related tribes diverged in Asia and Europe during the Paleocene. Establishing a robust and densely sampled phylogeny of Tetraopes beetles provides a foundation for investigating micro- and macroevolutionary phenomena, including clinal variation, coevolution, and detoxification mechanisms in this ecologically important group.

4-aminopyridine improves evoked potentials and ambulation in the taiep rat: A model of hypomyelination with atrophy of basal ganglia and cerebellum.

The taiep rat is a tubulin mutant with an early hypomyelination followed by progressive demyelination of the central nervous system due to a point mutation in the Tubb4a gene. It shows clinical, radiological, and pathological signs like those of the human leukodystrophy hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). Taiep rats had tremor, ataxia, immobility episodes, epilepsy, and paralysis; the acronym of these signs given the name to this autosomal recessive trait. The aim of this study was to analyze the characteristics of somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) in adult taiep rats and in a patient suffering from H-ABC. Additionally, we evaluated the effects of 4-aminopyridine (4-AP) on sensory responses and locomotion and finally, we compared myelin loss in the spinal cord of adult taiep and wild type (WT) rats using immunostaining. Our results showed delayed SSEPs in the upper and the absence of them in the lower extremities in a human patient. In taiep rats SSEPs had a delayed second negative evoked responses and were more susceptible to delayed responses with iterative stimulation with respect to WT. MEPs were produced by bipolar stimulation of the primary motor cortex generating a direct wave in WT rats followed by several indirect waves, but taiep rats had fused MEPs. Importantly, taiep SSEPs improved after systemic administration of 4-AP, a potassium channel blocker, and this drug induced an increase in the horizontal displacement measured in a novelty-induced locomotor test. In taiep subjects have a significant decrease in the immunostaining of myelin in the anterior and ventral funiculi of the lumbar spinal cord with respect to WT rats. In conclusion, evoked potentials are useful to evaluate myelin alterations in a leukodystrophy, which improved after systemic administration of 4-AP. Our results have a translational value because our findings have implications in future medical trials for H-ABC patients or with other leukodystrophies.

Use of CRISPR/Cas9 with Homology-Directed Repair to Gene-Edit Topoisomerase IIß in Human Leukemia K562 Cells: Generation of a Resistance Phenotype.

DNA topoisomerase IIß (TOP2ß/180; 180 kDa) is a nuclear enzyme that regulates DNA topology by generation of short-lived DNA double-strand breaks, primarily during transcription. TOP2ß/180 can be a target for DNA damage-stabilizing anticancer drugs, whose efficacy is often limited by chemoresistance. Our laboratory previously demonstrated reduced levels of TOP2ß/180 (and the paralog TOP2α/170) in an acquired etoposide-resistant human leukemia (K562) clonal cell line, K/VP.5, in part due to overexpression of microRNA-9-3p/5p impacting post-transcriptional events. To evaluate the effect on drug sensitivity upon reduction/elimination of TOP2ß/180, a premature stop codon was generated at the TOP2ß/180 gene exon 19/intron 19 boundary (AGAA//GTAA→ATAG//GTAA) in parental K562 cells (which contain four TOP2ß/180 alleles) by CRISPR/Cas9 editing with homology-directed repair to disrupt production of full-length TOP2ß/180. Gene-edited clones were identified and verified by quantitative polymerase chain reaction and Sanger sequencing, respectively. Characterization of TOP2ß/180 gene-edited clones, with one or all four TOP2ß/180 alleles mutated, revealed partial or complete loss of TOP2ß mRNA/protein, respectively. The loss of TOP2ß/180 protein correlated with decreased (2-{4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy}propionic acid)-induced DNA damage and partial resistance in growth inhibition assays. Partial resistance to mitoxantrone was also noted in the gene-edited clone with all four TOP2ß/180 alleles modified. No cross-resistance to etoposide or mAMSA was noted in the gene-edited clones. Results demonstrated the role of TOP2ß/180 in drug sensitivity/resistance in K562 cells and revealed differential paralog activity of TOP2-targeted agents. SIGNIFICANCE STATEMENT: Data indicated that CRISPR/Cas9 editing of the exon 19/intron 19 boundary in the TOP2ß/180 gene to introduce a premature stop codon resulted in partial to complete disruption of TOP2ß/180 expression in human leukemia (K562) cells depending on the number of edited alleles. Edited clones were partially resistant to mitoxantrone and XK469, while lacking resistance to etoposide and mAMSA. Results demonstrated the import of TOP2ß/180 in drug sensitivity/resistance in K562 cells and revealed differential paralog activity of TOP2-targeted agents.

International Delphi Study on Wound Closure and Incision Management in Joint Arthroplasty Part 2: Total Hip Arthroplasty.

BACKGROUND: This modified Delphi study aimed to develop a consensus on optimal wound closure and incision management strategies for total hip arthroplasty (THA). Given the critical nature of wound care and incision management in influencing patient outcomes, this study sought to synthesize evidence-based best practices for wound care in THA procedures. METHODS: An international panel of 20 orthopedic surgeons from Europe, Canada, and the United States evaluated a targeted literature review of 18 statements (14 specific to THA and 4 related to both THA and total knee arthroplasty). There were 3 rounds of anonymous voting per topic using a modified 5-point Likert scale with a predetermined consensus threshold of ≥ 75% agreement necessary for a statement to be accepted. RESULTS: After 3 rounds of voting, consensus was achieved for all 18 statements. Notable recommendations for THA wound management included (1) the use of barbed sutures over non-barbed sutures (shorter closing times and overall cost savings); (2) the use of subcuticular sutures over skin staples (lower risk of superficial infections and higher patient preferences, but longer closing times); (3) the use of mesh-adhesives over silver-impregnated dressings (lower rate of wound complications); (4) for at-risk patients, the use of negative pressure wound therapy over other dressings (lower wound complications and reoperations, as well as fewer dressing changes); and (5) the use of triclosan-coated sutures (lower risk of surgical site infection) over standard sutures. CONCLUSIONS: Through a structured modified Delphi approach, a panel of 20 orthopedic surgeons reached consensus on all 18 statements pertaining to wound closure and incision management in THA. This study provides a foundational framework for establishing evidence-based best practices, aiming to reduce variability in patient outcomes and to enhance the overall quality of care in THA procedures.

Insights on the role of thyroid hormone transport in neurosensory organs and implication for the Allan-Herndon-Dudley syndrome.

Thyroid hormones play an important role during the development and functioning of the different sensory systems. In order to exert their actions, thyroid hormones need to access their target cells through transmembrane transporter proteins, among which the monocarboxylate transporter 8 (MCT8) stands out for its pathophysiological relevance. Mutations in the gene encoding for MCT8 lead to the Allan-Herndon-Dudley syndrome (AHDS), a rare disease characterised by severe neuromotor and cognitive impairments. The impact of MCT8 deficiency in the neurosensory capacity of AHDS patients is less clear, with only a few patients displaying visual and auditory impairments. In this review we aim to gather data from different animal models regarding thyroid hormone transport and action in the different neurosensory systems that could aid to identify potential neurosensorial alterations in MCT8-deficient patients.

Improving the modelling of a multi-leaf collimator with tilted leaf sides used in radiotherapy.

Background and purpose: Multi-leaf collimators (MLCs) with tilted leaf sides have a complex transmission behaviour that is not easily matched by radiotherapy treatment planning systems (TPSs). We sought to develop an MLC model that can accurately match test fields and clinically relevant plans at different centres. Materials and methods: Two new MLC models were developed and evaluated within a research version of a commercial TPS. Prototype I used adjusted-constant transmissions and Prototype II used variable transmissions at the tongue-and-groove and leaf-tip regions. Three different centres evaluated these prototypes for a tilted MLC and compared them with their initial MLC model using test fields and patient-specific quality-assurance measurements of clinically relevant plans. For the latter, gamma passing rates (GPR) at 2 %/2mm were recorded. Results: For the prototypes the same set of MLC parameters could be used at all centres, with only a slight adjustment of the offset parameter. For centres A and C, average GPR were >95 % and within 0.5 % GPR difference between the standard, and prototype models. In center B, prototypes I and II improved the agreement in clinically relevant plans, with an increase in GPR of 2.3 % ± 0.8 % and 3.0 ± 0.8 %, respectively. Conclusions: The prototype MLC models were either similar or superior to the initial MLC model, and simpler to configure because fewer trade-offs were required. Prototype I performed comparably to the more sophisticated Prototype II and its configuration can be easily standardized, which can be useful to reduce variability and improve safety in clinical practice.

Multileaf collimator characterization and modeling for a 1.5 T MR-linac using static synchronous and asynchronous sweeping gaps.

Objective.The Elekta unity MR-linac delivers step-and-shoot intensity modulated radiotherapy plans using a multileaf collimator (MLC) based on the Agility MLC used on conventional Elekta linacs. Currently, details of the physical Unity MLC and the computational model within its treatment planning system (TPS)Monacoare lacking in published literature. Recently, a novel approach to characterize the physical properties of MLCs was introduced using dynamic synchronous and asynchronous sweeping gap (aSG) tests. Our objective was to develop a step-and-shoot version of the dynamic aSG test to characterize the Unity MLC and the computational MLC models in theMonacoandRayStationTPSs.Approach.Dynamic aSG were discretized into a step-and-shoot aSG by investigating the number of segments/sweep and the minimal number of monitor units (MU) per segment. The step-and-shoot aSG tests were compared to the dynamic aSG tests on a conventional linac at a source-to-detector distance of 143.5 cm, mimicking the Unity configuration. the step-and-shoot aSG tests were used to characterize the Unity MLC through measurements and dose calculations in both TPSs.Main results.The step-and-shoot aSGs tests with 100 segments and 5 MU/segment gave results very similar to the dynamic aSG experiments. The effective tongue-and-groove width of the Unity gradually increased up to 1.4 cm from the leaf tip end. The MLC models inRayStationandMonacoagreed with experimental data within 2.0% and 10%, respectively. The largest discrepancies inMonacowere found for aSG tests with >10 mm leaf interdigitation, which are non-typical for clinical plans.Significance.The step-and-shoot aSG tests accurately characterize the MLC in step-and-shoot delivery mode. The MLC model inRayStation2023B accurately describes the tongue-and-groove and leaf tip effects whereasMonacooverestimates the tongue-and-groove shadowing further away from the leaf tip end.

Survivin/BIRC5 as a novel molecular effector at the crossroads of glucose metabolism and radioresistance in head and neck squamous cell carcinoma.

BACKGROUND: Metabolic reprogramming and abnormal glucose metabolism are hallmarks of head and neck squamous cell carcinoma (HNSCC). Certain oncogenes can promote cancer-related metabolic changes, but understanding their crosstalk in HNSCC biology and treatment is essential for identifying predictive biomarkers and developing target therapies. METHODS: We assessed the value of survivin/BIRC5 as a radioresistance factor potentially modulated by glucose for predicting therapeutic sensitivity and prognosis of HNSCC in a cohort of 32 patients. Additionally, we conducted in vitro experiments to explore the role of survivin/BIRC5 in glucose metabolism concerning radiation response. RESULTS: Tumoral BIRC5 expression is associated with serum glucose and predicts locoregional disease-free survival and lower BIRC5 mRNA levels are associated with better outcomes. Upregulation of BIRC5 by radiation depends on glucose levels and provokes a pro-tumoral and radioresistant phenotype in surviving cells. CONCLUSIONS: Survivin/BIRC5 might be independently associated with the risk of recurrence in patients with HNSCC.

International Delphi Study on Wound Closure and Dressing Management in Joint Arthroplasty: Part 1: Total Knee Arthroplasty.

BACKGROUND: The purpose of this modified Delphi study was to obtain consensus on wound closure and dressing management in total knee arthroplasty (TKA). METHODS: The Delphi panel included 20 orthopaedic surgeons from Europe and North America. There were 26 statements identified using a targeted literature review. Consensus was developed for the statements with up to three rounds of anonymous voting per topic. Panelists ranked their agreement with each statement on a five-point Likert scale. An a priori threshold of ≥ 75% was required for consensus. RESULTS: All 26 statements achieved consensus after three rounds of anonymous voting. Wound closure-related interventions that were recommended for use in TKA included: 1) closing in semi-flexion versus extension (superior range of motion); 2) using aspirin for venous thromboembolism prophylaxis over other agents (reduces wound complications); 3) barbed sutures over non-barbed sutures (lower wound complications, better cosmetic appearances, shorter closing times, and overall cost savings); 4) mesh-adhesives over other skin closure methods (lower wound complications, higher patient satisfaction scores, lower rates of readmission); 5) silver-impregnated dressings over standard dressings (lower wound complications, decreased infections, fewer dressing changes); 6) in high-risk patients, negative pressure wound therapy over other dressings (lower wound complications, decreased reoperations, fewer dressing changes); and 7) using triclosan-coated over non-antimicrobial-coated sutures (lower risks of surgical site infection). CONCLUSIONS: Using a modified Delphi approach, the panel achieved consensus on 26 statements pertaining to wound closure and dressing management in TKA. This study forms the basis for identifying critical evidence supported by clinical practice for wound management to help reduce variability, advance standardization, and ultimately improve outcomes during TKA. The results presented here can serve as the foundation for knowledge, education, and improved clinical outcomes for surgeons performing TKAs.

Multi-institutional generalizability of a plan complexity machine learning model for predicting pre-treatment quality assurance results in radiotherapy.

Background and purpose: Treatment plans in radiotherapy are subject to measurement-based pre-treatment verifications. In this study, plan complexity metrics (PCMs) were calculated per beam and used as input features to develop a predictive model. The aim of this study was to determine the robustness against differences in machine type and institutional-specific quality assurance (QA). Material and methods: A number of 567 beams were collected, where 477 passed and 90 failed the pre-treatment QA. Treatment plans of different anatomical regions were included. One type of linear accelerator was represented. For all beams, 16 PCMs were calculated. A random forest classifier was trained to distinct between acceptable and non-acceptable beams. The model was validated on other datasets to investigate its robustness. Firstly, plans for another machine type from the same institution were evaluated. Secondly, an inter-institutional validation was conducted on three datasets from different centres with their associated QA. Results: Intra-institutionally, the PCMs beam modulation, mean MLC gap, Q1 gap, and Modulation Complexity Score were the most informative to detect failing beams. Eighty-tree percent of the failed beams (15/18) were detected correctly. The model could not detect over-modulated beams of another machine type. Inter-institutionally, the model performance reached higher accuracy for centres with comparable equipment both for treatment and QA as the local institute. Conclusions: The study demonstrates that the robustness decreases when major differences appear in the QA platform or in planning strategies, but that it is feasible to extrapolate institutional-specific trained models between centres with similar clinical practice. Predictive models should be developed for each machine type.