Wound vacuum-assisted closure temporization after tumor resection of soft tissue sarcomas-A cost analysis in a propensity-score matched population.

BACKGROUND: Vacuum-assisted closure (VAC) temporization is a technique associated with high local control rates used in myxofibrosarcoma. We sought to compare the costs and postoperative outcomes of VAC temporization and single-stage (SS) excision/reconstruction. METHODS: We conducted a retrospective analysis of patients with myxofibrosarcoma surgically treated at our institution between 2000 and 2022. Variables of interest included total, direct, and indirect costs for initial episode of care, 90 days and 1 year after initial admission, and postoperative outcomes. Costs were compared between the VAC temporization and SS groups. RESULTS: After matching, 13 patients in the SS group and 23 in the VAC group were analyzed. We found no difference in median and mean total inpatient costs, between the VAC temporization and SS group. While total 90-day and 1-year costs were higher in the VAC group compared to the SS group, mean costs were similar. There were no differences in postoperative complications between groups. A subanalysis of the entire cohort (n = 139) revealed lower local recurrence and overall death rates in the VAC temporization group. CONCLUSION: VAC temporization had similar inpatient costs and postoperative outcomes to SS excision/reconstruction. While median 90-day and 1-year costs were higher in the VAC group, mean costs did not differ.

Cemented and Press-fit Femoral Stems for the Management of Oncologic Femoral Tumors.

BACKGROUND: Stem fixation in reconstruction after resection of femoral tumors is debated. Cemented stems offer immediate stability but risk aseptic loosening, while press-fit stems allow bone ingrowth but risk stress shielding and subsidence. Our retrospective review aimed to determine implant failure rates and their associated factors, as well as the rates of infection, debridement, and mortality for both fixation groups (cemented or press-fit stems) used in patients undergoing resection of femoral tumor disease and subsequent arthroplasty. METHODS: We retrospectively studied 252 patients who underwent resection of femoral tumors and subsequent arthroplasty using cemented (n = 173; 69%) or press-fit (noncemented) (n = 79; 31%) stems between 1999 and 2020. Implant failure was the primary outcome, with secondary outcomes including rates of implant infection, debridement, and mortality. Multivariable regression was done to assess risk factors for implant failures. RESULTS: The study found implant failure rates of 11% and 18% for cemented stems and press-fit stems, respectively. Lower stem to diaphyseal ratios (P = 0.024) and younger patients (P = 0.008) were associated with a higher risk of implant failure in cemented stems. The infection rates were 14% and 10% for cemented and press-fit stems, respectively. Debridement rates were 16% and 13% for cemented and press-fit stems, respectively, while the 1-year mortality rate was 16% for cemented stems and 1.5% for press-fit stems. CONCLUSIONS: This study is the largest of its kind, providing patient characteristics and outcomes in both cemented and press-fit stems in the setting of reconstruction for femoral tumors. Both methods can be effective, with outcomes dependent on patient-specific factors, such as life expectancy, activity level, and body habitus, as well as proper implant fit. Additional studies of both implants and longer follow-up are required to elucidate the optimal fixation method for each individual patient. LEVEL OF EVIDENCE: Level III, retrospective noncomparative study.

Mapping the Single-cell Differentiation Landscape of Osteosarcoma.

PURPOSE: The genetic intratumoral heterogeneity observed in human osteosarcomas (OS) poses challenges for drug development and the study of cell fate, plasticity, and differentiation, processes linked to tumor grade, cell metastasis, and survival. EXPERIMENTAL DESIGN: To pinpoint errors in OS differentiation, we transcriptionally profiled 31,527 cells from a tissue-engineered model that directsMSCs toward adipogenic and osteoblastic fates. Incorporating pre-existing chondrocyte data, we applied trajectory analysis and non-negative matrix factorization (NMF) to generate the first human mesenchymal differentiation atlas. RESULTS: This 'roadmap' served as a reference to delineate the cellular composition of morphologically complex OS tumors and quantify each cell's lineage commitment. Projecting a bulk RNA-seq OS dataset onto this roadmap unveiled a correlation between a stem-like transcriptomic phenotype and poorer survival outcomes. CONCLUSIONS: Our study quantifies OS differentiation and lineage, a prerequisite to better understanding lineage-specific differentiation bottlenecks that might someday be targeted therapeutically.

Association between dopamine receptor D2 Taq IA gene polymorphism (rs1800497) and personality traits.

Objective: This study aimed to find a potential association between the DRD2 Taq1A gene polymorphism (rs1800497 C32806T) and personality traits. Methods: In all, 249 youths were recruited for this study. The Short-form Revised Eysenck Personality Questionnaire was administered to assess personality traits. The participants were genotyped for the DRD2 Taq1A polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. Statistical analysis was carried out to find a possible association between the genotypes and aspects of personality traits assessed. Results: The frequencies of the A1 and A2 alleles in our sampled population were 215 (43.2%) and 283 (56.8%), while the frequencies of A1A1, A1A2, and A2A2 were 67 (26.9%), 81 (32.5%), and 101 (40.6%), respectively. The study population was not in Hardy-Weinberg equilibrium (χ2 = 17.64, p < 0.001). The A2 allele was significantly associated with extraversion. Although this allele was also associated with neuroticism, psychoticism, and lie, the association was not significant. Conclusion: The A2 allele of the DRD2 Taq1A polymorphism was found to be more associated with extraversion, as measured by the Short-form Revised Eysenck Personality Questionnaire.

Myositis ossificans mimicking bone surface osteosarcoma: case report with literature review.

Myositis ossificans, a benign tumor composed of spindle cells and osteoblasts, can clinically and radiologically mimic osteosarcoma. While recognition and accurate diagnosis of myositis ossificans can be a challenge, this is critical as it may allow a conservative surgical approach to maximize functional outcomes. Herein, we present a patient with surface myositis ossificans confirmed genetically by the presence of COL1A1::USP6 gene fusion, along with a literature review. Due to the enhanced visualization of the bone matrix, computed tomography (CT) imaging may be a superior imaging modality to magnetic resonance (MR) imaging. Staged biopsies with samples obtained from the periphery and center of the lesions may allow pathologists to discern the zonal distribution histologically. Furthermore, immunohistochemistry fluorescence in situ hybridization and molecular testing can aid in the distinction of myositis ossificans from mimics. Because of their resemblance to other bone tumors, these cases of myositis ossificans highlight the importance of a multidisciplinary approach integrating clinical, radiologic, and pathologic analysis and involving serial imaging, sampling, and judicious use of ancillary immunohistochemical and molecular testing.

Trauma exposure across the lifespan among individuals engaged in treatment with medication for opioid use disorder: differences by gender, PTSD status, and chronic pain.

BACKGROUND: There is little study of lifetime trauma exposure among individuals engaged in medication treatment for opioid use disorder (MOUD). A multisite study provided the opportunity to examine the prevalence of lifetime trauma and differences by gender, PTSD status, and chronic pain. METHODS: A cross-sectional study examined baseline data from participants (N = 303) enrolled in a randomized controlled trial of a mind-body intervention as an adjunct to MOUD. All participants were stabilized on MOUD. Measures included the Trauma Life Events Questionnaire (TLEQ), the Brief Pain Inventory (BPI), and the Posttraumatic Stress Disorder Checklist (PCL-5). Analyses involved descriptive statistics, independent sample t-tests, and linear and logistic regression. RESULTS: Participants were self-identified as women (n = 157), men (n = 144), and non-binary (n = 2). Fifty-seven percent (n = 172) self-reported chronic pain, and 41% (n = 124) scored above the screening cut-off for PTSD. Women reported significantly more intimate partner violence (85%) vs 73%) and adult sexual assault (57% vs 13%), while men reported more physical assault (81% vs 61%) and witnessing trauma (66% vs 48%). Men and women experienced substantial childhood physical abuse, witnessed intimate partner violence as children, and reported an equivalent exposure to accidents as adults. The number of traumatic events predicted PTSD symptom severity and PTSD diagnostic status. Participants with chronic pain, compared to those without chronic pain, had significantly more traumatic events in childhood (85% vs 75%). CONCLUSION: The study found a high prevalence of lifetime trauma among people in MOUD. Results highlight the need for comprehensive assessment and mental health services to address trauma among those in MOUD treatment. TRIAL REGISTRATION: NCT04082637.

Piperine Enhances Antimalarial Activity of Methyl Gallate and Palmatine Combination.

PURPOSE: Artemisinin combination therapies, the first-line antimalarials in Nigeria, have reportedly suffered multiple failures in malaria treatment, hence the search for novel combination of other compounds. Methyl gallate and palmatine have been reported to exhibit antiplasmodial activities but the antimalarial activity of their combination has not been evaluated. Therefore, the evaluation of the combination of methyl gallate and palmatine for antimalarial activity in vitro and in vivo in the presence of piperine was carried out. MATERIALS AND METHODS: The inhibitory potential of methyl gallate and palmatine combination on ß-hematin (hemozoin) formation was studied in vitro. Also, the antimalarial activity of methyl gallate and palmatine combination with/without a bioenhancer (piperine) was evaluated in Plasmodium berghei NK65-infected mice. RESULTS: Methyl gallate and palmatine in the ratio 3:2 acted synergistically in vitro and had the highest inhibitory effect (IC50 = 0.73 µg/mL) on ß-hematin (hemozoin) formation. The 3:2 combination of methyl gallate and palmatine exhibited no antimalarial activity in vivo in the absence of piperine but caused reduction in parasitemia that exceeded 40% in the presence of piperine at the dose of 25 mg/kg body weight on days 6 and 8 post-inoculation in mice. CONCLUSION: The 3:2 combination of methyl gallate and palmatine in the presence of piperine exhibited antimalarial activity in vivo, possibly by synergistic inhibition of hemozoin formation which may cause accumulation of haem within the food vacuole of Plasmodium spp. and its death.

Exploring the use of metabarcoding to reveal eukaryotic associations with mononchids nematodes.

Nematodes play a vital ecological role in soil and marine ecosystems, but there is limited information about their dietary diversity and feeding habits. Due to methodological challenges, the available information is based on inference rather than confirmed observations. The lack of correct dietary requirements also hampers rearing experiments. To achieve insight into the prey of mononchid nematodes, this study employed high-throughput Illumina paired-end sequencing using universal eukaryotic species 18S primers on 10 pooled mononchid nematode species, namely Mylonchulus brachyuris, M. brevicaudatus, Mylonchulus sp., Clarkus parvus, Prionchulus sp. M. hawaiiensis, M. sigmaturellus, M. vulvapapillatus, Anatonchus sp. and Miconchus sp. The results indicate that mononchids are associated with a remarkable diversity of eukaryotes, including fungi, algae, and protists. While the metabarcoding approach, first introduced here for mononchids, proved to be a simple and rapid method, it has several limitations and crucial methodological challenges that should be addressed in future studies. Ultimately, such methods should be able to evaluate the dietary complexity of nematodes and provide a valuable avenue for unraveling the dietary requirements of previously unculturable nematodes. This can contribute to the methodology of understanding their feeding habits and contributions to ecosystem dynamics.

Biomarkers associated with pulmonary exacerbations in a randomized trial of nintedanib for radiation pneumonitis.

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) is a common side effect of thoracic radiotherapy and often has a long course characterized by acute exacerbations and progression to permanent lung fibrosis. There are no validated biomarkers of prognosis in patients diagnosed with RP. MATERIALS AND METHODS: We analyzed a time course of serum chemokines, cytokines, and other proteins from patients with grade 2+ RP in a randomized clinical trial of a steroid taper plus nintedanib, a multiple tyrosine kinase inhibitor, versus placebo plus a steroid taper for the treatment of RP. Weighted gene correlation network analysis (WGCNA) and univariable zero inflated Poisson models were used to identify groups of correlated analytes and their associations with clinical outcomes. RESULTS: Thirty enrolled patients had biomarker data available, and 17 patients had enough analytes tested for network analysis. WGNCA identified ten analytes, including transforming growth factor beta-1 (TGF-ß1), monocyte chemoattractant protein-1 (MCP-1), and platelet-derived growth factor (PDGF), that in aggregate were correlated with the occurrence of pulmonary exacerbations (p = 0.008), the total number of acute pulmonary exacerbations (p = 0.002), and treatment arm (p = 0.036). By univariable analysis, an increase in rate of change of two components of the RP module were associated with an increased incidence rate of pulmonary exacerbations: interleukin 5 (IL-5, incidence rate ratio (IRR) 1.02, 95% CI 1.01-1.04, p = 0.002), and tumor necrosis factor superfamily 12 (TNFSF12, IRR 1.06, CI 1-1.11, p = 0.036). An increased slope of epidermal growth factor (EGF) was associated with a decreased incidence rate of exacerbations (IRR 0.94, CI 0.89-1, p = 0.036). CONCLUSION: We identified a panel of serum biomarkers that showed association with nintedanib treatment and acute pulmonary exacerbations in patients with RP. A confirmatory study will be needed to validate this panel for use as a prognostic tool in patients with RP.

Diagnostic accuracy of transvaginal ultrasonography and hysterosalpingography in the detection of uterine cavity pathologies among infertile women.

Background: Uterine cavity pathology may affect the endometrium or myometrium, resulting in distortion of the uterine cavity, and is responsible for 2%-5% of infertility. The methods for its assessment usually involve imaging modalities like pelvic ultrasonography, often transvaginal-(TVS), and hysterosalpingography-(HSG), with hysteroscopy-(HSC) as the gold standard. However, HSC is not readily available in resource-poor-settings. Purpose: To determine and compare the diagnostic accuracy of TVS and HSG in detecting uterine cavity pathology using HSC as a gold standard. Materials and Methods: A cross-sectional analytical study of consenting infertile women for evaluation of the uterine cavity using transvaginal-ultrasonography, hysterosalpingogram, and hysteroscopy. The primary-outcome-measures were the sensitivity, specificity, and accuracy of TVS and HSG in detecting uterine cavity abnormalities using HSG as the gold standard. Results: Eighty-eight participants were analysed for this study. The lesions confirmed on HSC were intrauterine-adhesions (43.1%), endometrial polyps (14.8%), submucous fibroids (18.2%), intrauterine-septum (13.6%), and cavity distortion (14.8%). The overall sensitivity with TVS was 57.7%, with a specificity of 97.6%, a positive-predictive-value (PPV) of 88.2%, and a negative-predictive-value (NPV) of 88.2%, giving a percentage-accuracy of 88.2%. In comparison, HSG had a sensitivity of 72.1%, a specificity of 99.4%, a PPV of 97.4%, and an NPV of 92.0%, giving an overall accuracy of 92.9%. The detection rates of TVS and HSG in this category were: fibroids (97.7% vs 89.8%; p = .0004) and adhesions (73.9% vs 87.5%; p = .0002), respectively. Conclusion: HSG appears to be the superior modality for detection of obliterative uterine cavity pathologies, while TVS is better suited for myometrium and endometrial lesions.

Assessing wild turkey productivity before and after a 14-day delay in the start date of the spring hunting season in Tennessee.

Ten state wildlife management agencies in the United States, including six within the Southeast, have delayed their spring wild turkey (Meleagris gallopavo) hunting seasons since 2017 by five or more days to address concerns related to the potential effects of hunting on wild turkey seasonal productivity. One hypothesis posits that if the spring hunting season is too early, there may be insufficient time for males to breed hens before being harvested, thus leading to reduced seasonal productivity. We conducted an experiment to determine whether delaying the wild turkey hunting season by 2 weeks in south-middle Tennessee would affect various reproductive rates. In 2021 and 2022, the Tennessee Fish and Wildlife Commission experimentally delayed the spring hunting season to open 14 days later than the traditional date (the Saturday closest to 1 April) in Giles, Lawrence, and Wayne counties. We monitored reproductive rates from 2017 to 2022 in these three counties as well as two adjacent counties, Bedford and Maury, that were not delayed. We used a Before-After-Control-Impact design to analyze the proportion of hens nesting, clutch size, hatchability, nest success, poult survival and hen survival with linear mixed-effect models and AIC model selection to detect relationships between the 14-day delay and reproductive parameters. We detected no relationship (p > .05) between the 14-day delay and any individual reproductive parameter. In addition, recruitment (hen poults per hen that survived until the next breeding season) was very low (<0.5) and did not increase because of the 14-day delay. The traditional Tennessee start date had been in place since 1986 while the turkey harvest increased markedly until about 2006 and more recently stabilized. Our data indicate that moving the start of the hunting season from a period just prior to peak nest initiation to 2 weeks later, to coincide with a period just prior to peak nest incubation initiation, resulted in no change to productivity or populations in wild turkey flocks in south-middle Tennessee.

Postoperative Outcomes of Total Humerus Replacement for Oncologic Reconstruction of the Upper Limb: A Systematic Review of the Literature.

BACKGROUND: Total humerus replacement (THR) is a reconstruction procedure performed after resection of massive humeral tumors. However, there is limited literature on the rates of failure and functional outcomes of this implant. Our study aimed to determine the main failure modes, implant survival, and postoperative functional outcomes of THR. METHODS: A comprehensive search of the PubMed and Embase databases was conducted. We registered our study on PROSPERO (448684) and used the Strengthening the Reporting of Observational Studies in Epidemiology checklist for quality assessment. The Henderson classification was used to assess endoprosthesis failure and the Musculoskeletal Tumor Society (MSTS) score for functional outcomes. Weighted means and standard deviations were calculated. RESULTS: Ten studies comprising 171 patients undergoing THR were finally included. The overall failure rate was 32.2%. Tumor progression (12.6%) and prosthetic infections (9.4%) were the most common failure modes, followed by soft-tissue failures (5.9%), aseptic loosening (3.5%), and structural failure (1.8%). Two-year, 5-year, and 10-year implant survival rates for the entire cohort were 86%, 81%, and 69.3%. Ten-year implant survival for primary THRs was 78.3%, compared with 38.6% for revision THRs (p = 0.049). The mean MSTS score at the last follow-up was 77%. Patients whose implants did not fail had a higher MSTS score (79.3%) than those with failed implants (71.4%) (p = 0.02). CONCLUSION: One-third of THR will fail, mostly due to tumor progression and prosthetic infection. Overall functional scores were acceptable, with MSTS scores displaying great hand and elbow function but limited shoulder function. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

The roles of yeast formins and their regulators Bud6 and Bil2 in the pheromone response.

In response to pheromone Saccharomyces cerevisiae extend a mating projection. This process depends on the formation of polarized actin cables which direct secretion to the mating tip and translocate the nucleus for karyogamy. Here, we demonstrate that proper mating projection formation requires the formin Bni1, as well as the actin nucleation promoting activities of Bud6, but not the formin Bnr1. Further, Bni1 is required for pheromone gradient tracking. Our work also reveals unexpected new functions for Bil2 in the pheromone response. Previously we identified Bil2 as a direct inhibitor of Bnr1 during vegetative cell growth. Here, we show that Bil2 has Bnr1-independent functions in spatially focusing Bni1-GFP at mating projection tips, and in vitro Bil2 and its binding partner Bud6 organize Bni1 into clusters that nucleate actin assembly. bil2∆ cells also display entangled Bni1-generated actin cable arrays and defects in secretory vesicle transport and nuclear positioning. At low pheromone concentrations, bil2∆ cells are delayed in establishing a polarity axis, and at high concentrations they prematurely form a second and a third mating projection. Together, these results suggest that Bil2 promotes the proper formation and timing of mating projections by organizing Bni1 and maintaining a persistent axis of polarized growth.

Occupational biopsychosocial factors associated with neck pain intensity, neck-disability, and sick leave: A cross-sectional study of construction labourers in an African population.

INTRODUCTION: The burden and impact of neck pain is high in African countries including Nigeria. This study investigated the occupational biomechanical and occupational psychosocial factors associated with neck pain intensity, neck disability and sick leave amongst construction labourers in an urban Nigerian population. METHODS: This cross-sectional study measured clinical neck pain outcomes, occupational biomechanical factors, and occupational psychosocial factors. Descriptive, and univariate/multivariate inferential statistical analyses were conducted. RESULTS: Significant independent factors associated with neck pain intensity were order and pace of tasks being dependent on others (ß = 0.35; p<0.0001); inability to take breaks in addition to scheduled breaks (ß = 0.25; p<0.0001); inability to work because of unexpected events (ß = 0.21; p<0.0001); inability to control the order and pace of tasks (ß = 0.20; p<0.0001); and weight of load (ß = 0.17; p<0.0001); accounting for 53% of the variance in neck pain intensity. Significant independent factors associated with neck disability were weight of load (ß = 0.30; p<0.0001); duration of load carriage (ß = 0.16; p = 0.01); working under time pressure/deadlines (ß = 0.16; p = 0.02); and accounting for 20% of the variance in neck disability. Significant independent factor associated with sick leave was duration of load carriage (ß = 0.15; p = 0.04), in a non-significant regression model explaining -4% of the variance in sick leave. Addition of pain intensity significantly explained more variance in neck disability (31.0%) but less variance in sick leave (-5%), which was not statistically significant (F (10, 190) = 0.902, p = 0.533). CONCLUSIONS: Occupational biomechanical factors may be more important than occupational psychosocial factors in explaining neck disability and sick leave. In contrast, occupational psychosocial factors may be more important than occupational biomechanical factors in explaining neck pain intensity in this population in Nigeria.

Design and Implementation of an Opt-Out, End-to-End, Preemptive DPYD Testing Program for Patients Planned for a Systemic Fluoropyrimidine.

PURPOSE: Several allelic variants of the gene DPYD encoding dihydropyrimidine dehydrogenase (DPD) are associated with impaired metabolism of the systemic fluoropyrimidine fluorouracil (5FU) and its oral prodrug, capecitabine, which elevates the risk for severe toxicity. Following a patient death related to capecitabine toxicity in which DPD deficiency was suspected, a multidisciplinary advisory panel was convened to develop an institution-wide approach to future patients planned for a systemic fluoropyrimidine. METHODS: The panel selected an opt-out testing strategy which focused on developing reliable processes to collect and report test results and targeted education. An electronic health record-based automated reminder was designed to activate when a 5FU- or capecitabine-containing chemotherapy regimen was ordered for a patient without prior exposure to either agent and without a prior DPYD sequencing test result. DPYD testing was standardized across all sites of care, and a closed loop reporting system for abnormal test results was created. Before implementation, targeted education was provided to providers, pharmacists, and nurses, and a failure mode and effects analysis was performed. Program rollout was staged over a 6-month period. RESULTS: At 10 months, the rate of preemptive testing increased from a baseline of 26% to a sustained rate of >90%. In the six network sites, the testing rate increased from 9% to 96%. A total of 1,043 patients have been tested preemptively; allelic variants have been identified in 43 (4.1%). Among 25 evaluable patients, dose reduction or change to a non-fluoropyrimidine-based regimen was accomplished in 96%. CONCLUSION: Preemptive DPYD testing is feasible, and high rates of testing can be achieved using an opt-out, reminder-based program. We provide the details of the implementation and encourage others to emulate it.

Introgression and disruption of migration routes have shaped the genetic integrity of wildebeest populations.

The blue wildebeest (Connochaetes taurinus) is a keystone species in savanna ecosystems from southern to eastern Africa, and is well known for its spectacular migrations and locally extreme abundance. In contrast, the black wildebeest (C. gnou) is endemic to southern Africa, barely escaped extinction in the 1900s and is feared to be in danger of genetic swamping from the blue wildebeest. Despite the ecological importance of the wildebeest, there is a lack of understanding of how its unique migratory ecology has affected its gene flow, genetic structure and phylogeography. Here, we analyze whole genomes from 121 blue and 22 black wildebeest across the genus' range. We find discrete genetic structure consistent with the morphologically defined subspecies. Unexpectedly, our analyses reveal no signs of recent interspecific admixture, but rather a late Pleistocene introgression of black wildebeest into the southern blue wildebeest populations. Finally, we find that migratory blue wildebeest populations exhibit a combination of long-range panmixia, higher genetic diversity and lower inbreeding levels compared to neighboring populations whose migration has recently been disrupted. These findings provide crucial insights into the evolutionary history of the wildebeest, and tangible genetic evidence for the negative effects of anthropogenic activities on highly migratory ungulates.

An 18F-FDG PET/CT and Mean Lung Dose Model to Predict Early Radiation Pneumonitis in Stage III Non-Small Cell Lung Cancer Patients Treated with Chemoradiation and Immunotherapy.

Radiation pneumonitis (RP) that develops early (i.e., within 3 mo) (RPEarly) after completion of concurrent chemoradiation (cCRT) leads to treatment discontinuation and poorer survival for patients with stage III non-small cell lung cancer. Since no RPEarly risk model exists, we explored whether published RP models and pretreatment 18F-FDG PET/CT-derived features predict RPEarly Methods: One hundred sixty patients with stage III non-small cell lung cancer treated with cCRT and consolidative immunotherapy were analyzed for RPEarly Three published RP models that included the mean lung dose (MLD) and patient characteristics were examined. Pretreatment 18F-FDG PET/CT normal-lung SUV featured included the following: 10th percentile of SUV (SUVP10), 90th percentile of SUV (SUVP90), SUVmax, SUVmean, minimum SUV, and SD. Associations between models/features and RPEarly were assessed using area under the receiver-operating characteristic curve (AUC), P values, and the Hosmer-Lemeshow test (pHL). The cohort was randomly split, with similar RPEarly rates, into a 70%/30% derivation/internal validation subset. Results: Twenty (13%) patients developed RPEarly Predictors for RPEarly were MLD alone (AUC, 0.72; P = 0.02; pHL, 0.87), SUVP10, SUVP90, and SUVmean (AUC, 0.70-0.74; P = 0.003-0.006; pHL, 0.67-0.70). The combined MLD and SUVP90 model generalized in the validation subset and was deemed the final RPEarly model (RPEarly risk = 1/[1+e(- x )]; x = -6.08 + [0.17 × MLD] + [1.63 × SUVP90]). The final model refitted in the 160 patients indicated improvement over the published MLD-alone model (AUC, 0.77 vs. 0.72; P = 0.0001 vs. 0.02; pHL, 0.65 vs. 0.87). Conclusion: Patients at risk for RPEarly can be detected with high certainty by combining the normal lung's MLD and pretreatment 18F-FDG PET/CT SUVP90 This refined model can be used to identify patients at an elevated risk for premature immunotherapy discontinuation due to RPEarly and could allow for interventions to improve treatment outcomes.

Auto-segmentation of neck nodal metastases using self-distilled masked image transformer on longitudinal MR images.

Objectives: Auto-segmentation promises greater speed and lower inter-reader variability than manual segmentations in radiation oncology clinical practice. This study aims to implement and evaluate the accuracy of the auto-segmentation algorithm, "Masked Image modeling using the vision Transformers (SMIT)," for neck nodal metastases on longitudinal T2-weighted (T2w) MR images in oropharyngeal squamous cell carcinoma (OPSCC) patients. Methods: This prospective clinical trial study included 123 human papillomaviruses (HPV-positive [+]) related OSPCC patients who received concurrent chemoradiotherapy. T2w MR images were acquired on 3 T at pre-treatment (Tx), week 0, and intra-Tx weeks (1-3). Manual delineations of metastatic neck nodes from 123 OPSCC patients were used for the SMIT auto-segmentation, and total tumor volumes were calculated. Standard statistical analyses compared contour volumes from SMIT vs manual segmentation (Wilcoxon signed-rank test [WSRT]), and Spearman's rank correlation coefficients (ρ) were computed. Segmentation accuracy was evaluated on the test data set using the dice similarity coefficient (DSC) metric value. P-values <0.05 were considered significant. Results: No significant difference in manual and SMIT delineated tumor volume at pre-Tx (8.68 ± 7.15 vs 8.38 ± 7.01 cm3, P = 0.26 [WSRT]), and the Bland-Altman method established the limits of agreement as -1.71 to 2.31 cm3, with a mean difference of 0.30 cm3. SMIT model and manually delineated tumor volume estimates were highly correlated (ρ = 0.84-0.96, P < 0.001). The mean DSC metric values were 0.86, 0.85, 0.77, and 0.79 at the pre-Tx and intra-Tx weeks (1-3), respectively. Conclusions: The SMIT algorithm provides sufficient segmentation accuracy for oncological applications in HPV+ OPSCC. Advances in knowledge: First evaluation of auto-segmentation with SMIT using longitudinal T2w MRI in HPV+ OPSCC.

Molecular characterization of non-aureus staphylococci and Mammaliicoccus from Hipposideros bats in Southwest Nigeria.

Bats are not only ecologically valuable mammals but also reservoirs of zoonotic pathogens. Their vast population, ability to fly, and inhabit diverse ecological niches could play some role in the spread of antibiotic resistance. This study investigated non-aureus staphylococci and Mammaliicoccus colonization in the Hipposideros bats at Obafemi Awolowo University, Ile-Ife, Nigeria. Pharyngeal samples (n = 23) of the insectivorous bats were analyzed, and the presumptive non-aureus staphylococcal and Mammaliicoccus isolates were confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The isolates were characterized based on antibiotic susceptibility testing and whole-genome sequencing (WGS). Six bacterial genomes were assembled, and three species were identified, including Mammaliicoccus sciuri (n = 4), Staphylococcus gallinarum (n = 1), and Staphylococcus nepalensis (n = 1). All the isolates were resistant to clindamycin, while the M. sciuri and S. gallinarum isolates were also resistant to fusidic acid. WGS analysis revealed that the M. sciuri and S. gallinarum isolates were mecA-positive. In addition, the M. sciuri isolates possessed some virulence (icaA, icaB, icaC, and sspA) genes. Multi-locus sequence typing identified two new M. sciuri sequence types (STs) 233 and ST234. The identification of these new STs in a migratory mammal deserves close monitoring because previously known ST57, ST60, and ST65 sharing ack (8), ftsZ (13), glpK (14), gmk (6), and tpiA (10) alleles with ST233 and ST234 have been linked to mastitis in animals. Moreover, the broad host range of M. sciuri could facilitate the dispersal of antibiotic resistance genes. This study provides evidence of the importance of including migratory animals in monitoring the development and spread of antibiotic resistance.

Histology-guided mathematical model of tumor oxygenation: sensitivity analysis of physical and computational parameters.

A hybrid off-lattice agent-based model has been developed to reconstruct the tumor tissue oxygenation landscape based on histology images and simulated interactions between vasculature and cells with microenvironment metabolites. Here, we performed a robustness sensitivity analysis of that model's physical and computational parameters. We found that changes in the domain boundary conditions, the initial conditions, and the Michaelis constant are negligible and, thus, do not affect the model outputs. The model is also not sensitive to small perturbations of the vascular influx or the maximum consumption rate of oxygen. However, the model is sensitive to large perturbations of these parameters and changes in the tissue boundary condition, emphasizing an imperative aim to measure these parameters experimentally.