Unintentional emissions of polychlorinated naphthalenes in China: Sources, composition, and historical trends.

Polychlorinated naphthalenes (PCNs) are detrimental to human health and the environment. With the commercial production of PCNs banned, unintentional releases have emerged as a significant environmental source. However, relevant information is still scarce. In this study, provincial emissions for eight PCNs homologues from 37 sources in the Chinese mainland during the period of 1960-2019 were estimated based on a source-specific and time-varying emission factor database. The results showed that the total PCNs emissions in 2019 reached 757.0 kg with Hebei ranked at the top among all the provinces and iron & steel industry as the biggest source. Low-chlorinated PCNs comprised 90% of emissions by mass, while highly chlorinated PCNs dominated in terms of toxicity, highlighting divergent priorities for mitigating emissions and safeguarding human health. The emissions showed an overall upward trend from 1960 to 2019 driven by emission increase from iron & steel industry in terms of source, and from North China and East China in terms of geographic area. Per-capita emissions followed an inverted U-shaped environmental Kuznets curve while emission intensities decreased with increasing per-capita Gross Domestic Product (GDP) following a nearly linear pattern when log-transformed.

A novel scoring system based on magnetic resonance imaging for the prediction of the difficulty of ultrasound-guided high-intensity focused ultrasound ablation for uterine fibroids.

OBJECTIVE: To develop a novel scoring system based on magnetic resonance imaging (MRI) for predicting the difficulty of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for uterine fibroids. MATERIALS AND METHODS: A total of 637 patients with uterine fibroids were enrolled. Sonication time, non-perfused volume ratio (NPVR), and ultrasound energy delivered for ablating 1 mm3 of fibroid tissue volume (E/V) were each classified as three levels and assigned scores from 0 to 2, respectively. Treatment difficulty level was then assessed by adding up the scores of sonication time, NPVR and E/V for each patient. The patients with score lower than 3 were categorized into low difficulty group, with score equal to or greater than 3 were categorized into high difficulty group. The potential predictors for treatment difficulty were compared between the two groups. Multifactorial logistic regression analysis model was created by analyzing the variables. The difficulty score system was developed using the beta coefficients of the logistic model. RESULTS: Signal intensity on T2WI, fibroid location index, largest diameter of fibroids, abdominal wall thickness, homogeneity of the signal of fibroids, and uterine position were independent influencing factors for the difficulty of USgHIFU for uterine fibroids. A prediction equation was obtained: difficulty score = 17 × uterine position (anteverted =0, retroverted =1)+71 × signal intensity (hypointense = 0, isointense/hyperintense = 1) +8 × enhancement (homogenous = 0, heterogeneous = 1)+25×(largest diameter of fibroids-20) +35 × (fibroid location index -0.2) +1×(abdominal wall thickness -5). CONCLUSIONS: This scoring system established based on MRI findings can be used to reliably predict the difficulty level of USgHIFU treatment of uterine fibroids.

Assessing methane emissions and soil carbon stocks in the Camargue coastal wetlands: Management implications for climate change regulation.

Coastal wetlands are crucial in climate change regulation due to their capacity to act as either sinks or sources of carbon, resulting from the balance between greenhouse gas (GHG) emissions, mainly methane (CH4), and soil carbon sequestration. Despite the paramount role of wetlands in climate regulation few studies investigate both aspects. The Camargue is one of the largest wetlands in Europe, yet the ways in which environmental and anthropic factors drive carbon dynamics remain poorly studied. We examined GHG emissions and soil organic carbon (SOC) stocks and accumulation rates in twelve representative wetlands, including two rice fields, to gain insights into the carbon dynamics and how it is influenced by hydrology and salinity. Mean CH4 rates ranged between - 87.0 and 131.0 mg m-2 h-1and the main drivers were water conductivity and redox, water table depth and soil temperature. High emission rates were restricted to freshwater conditions during summer flooding periods whereas they were low in wetlands subjected to summer drought and water conductivity higher than 10 mS cm-1. Nitrous oxide emissions were low, ranging from - 0.5 to 0.9 mg N2O m-2 h-1. The SOC stocks in the upper meter ranged from 17 to 90 Mg OC ha-1. Our research highlights the critical role of low-saline wetlands in carbon budgeting which potentially are large sources of CH4 but also contain the largest SOC stocks in the Camargue. Natural hydroperiods, involving summer drought, can maintain them as carbon sinks, but altered hydrology can transform them into sources. Artificial freshwater supply during summer leads to substantial CH4 emissions, offsetting their SOC accumulation rates. In conclusion, we advocate for readjusting the altered hydrology in marshes and for the search of management compromises to ensure the compatibility of economic and leisure activities with the preservation of the inherent climate-regulating capacity of coastal wetlands.

"Phosphoproteomic quantification based on phosphopeptide intensity or occupancy? An evaluation based on casein kinase 2 downstream effects".

Quantitative phosphoproteomic data has mostly been reported from experiments comparing relative phosphopeptides intensities in two or more different conditions, while the ideal parameter to compare is phosphopeptides occupancies. This term is scarcely used and therefore barely implemented in phosphoproteomics studies, and this should be of concern for the scientific journals. In order to demonstrate the relevance of this issue, here we show how the method of choice affects the interpretation of the data. The phosphoproteomic profile modulated in two AML cell lines after CK2 inhibition with CIGB-300 or CX-4945 is shown. Following the downstream action of CK2 the phosphosite intensity and occupancy results were compared to validate the best approach for quantitative phosphoproteomic studies. Even when the total number of quantified phosphopeptides was higher by using the intensity calculation, in all the cases the percent of CK2 consensus sequences which were down-regulated in response to CK2 inhibition was higher using the phosphosite occupancy quantification. To note, a high number of CK2 consensus sequences was found down-regulated with at least a 10% or 15% of phosphosite occupancy variation illustrating that low thresholds of occupancy modulation might be indicative of biological effect. Additionally, several biological processes only appear significantly over-represented in the phosphoproteome quantified by occupancy. The functional enrichment analysis per ranges of occupancy variations also illustrated clear differences among AML cell lines subjected to CK2 inhibition by CX-4945. A low overlap between the phosphoproteomes quantified by intensity and occupancy was obtained illustrating that new developments in proteomics techniques are needed to improve the performance of the occupancy approach. Even in such context, results indicate that occupancy quantification performs better than phosphorylation quantification based on intensity reinforcing the importance of such quantification approach to describe phosphoproteomic data.

Allogeneic blood or marrow transplantation using haploidentical grandchildren donors and post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis.

BACKGROUND: High-dose post-transplant cyclophosphamide allows safe and effective use of allografts from haploidentical relatives (siblings, parents and children) in patients undergoing allogeneic blood or marrow transplant (alloBMT). More recently, second- and third-degree relatives have also been shown to be safe allograft donors. An increasing number of older patients undergoing alloBMT have been receiving allografts from haploidentical donors. However, older patients are more likely to have older siblings and children, and older donor age is associated with worse outcomes. OBJECTIVE: In the current study, we report the safety and utility of grandchildren as haploidentical donors and compared with children as donors in patients undergoing alloBMT. METHODS: We compared characteristics and outcomes of alloBMT patients aged 55 years and older with children older than 30 years as donors (C group; n = 276) and those with grandchildren as donors (GC group; n = 40). Because many important baseline characteristics predict outcomes after alloBMT, we performed propensity score matched analysis based on recipient age, alloBMT year, disease, graft source and haematopoietic cell transplantation comorbidity index (HCT-CI). RESULTS: The median age of recipients was 67 years (range 55-79) in the C group and 73 years (range 57-78) in the GC group. More than 70% of recipients in the GC group were older than 70 years, compared with 27% in the C group. The median donor age was 37 years (range 31-52) in the C group and 20 years (range 14-34) in the GC group. More patients in the GC group had HCT-CI scores ≥3 than in the C group (32.5% vs. 23%, p = 0.27). Two-year overall survival did not differ between the two groups (GC 62% vs. C 60%, hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.53-1.75, p = 0.90) despite recipients of allografts from grandchildren being older. The 2-year RFS was 55% in the C group compared with 50% in the GC group (HR 1.05, 95% CI 0.62-1.77, p = 0.85). Non-relapse mortality subdistribution [SD] (SDHR 1.36, 95% 0.70-2.63, p = 0.36), relapse (SDHR 0.72, 95% CI 0.33-1.58, p = 0.42) or relapse-free survival (HR 1.05, 95% CI 0.62-1.77, p = 0.85). Propensity score matching analysis showed no significant differences in 2-year overall survival (GC 64% vs. C 53%; HR 0.77, 95% CI 0.42-1.42, p = 0.40), non-relapse mortality (SDHR 1.26, 95% 0.66-2.41, p = 0.48), relapse (SDHR 0.57, 95% CI 0.21-1.52, p = 0.26) or relapse-free survival (HR 0.94, 95% CI 0.57-1.54, p = 0.81). CONCLUSION: Our results indicate that outcomes of alloBMT patients with grandchild donors are similar to those with child donors, despite recipients' older age and higher comorbidities in the GC group. Grandchildren should be considered when selecting a donor for older alloBMT recipients.

Nonparametric second-order estimation for spatiotemporal point patterns.

Many existing methodologies for analyzing spatiotemporal point patterns are developed based on the assumption of stationarity in both space and time for the second-order intensity or pair correlation. In practice, however, such an assumption often lacks validity or proves to be unrealistic. In this paper, we propose a novel and flexible nonparametric approach for estimating the second-order characteristics of spatiotemporal point processes, accommodating non-stationary temporal correlations. Our proposed method employs kernel smoothing and effectively accounts for spatial and temporal correlations differently. Under a spatially increasing-domain asymptotic framework, we establish consistency of the proposed estimators, which can be constructed using different first-order intensity estimators to enhance practicality. Simulation results reveal that our method, in comparison with existing approaches, significantly improves statistical efficiency. An application to a COVID-19 dataset further illustrates the flexibility and interpretability of our procedure.

The efficacy of high-intensity laser therapy in wound healing: a narrative review.

High-intensity laser therapy (HILT) has recently been incorporated into wound management therapeutic protocols (Mosca RC et al. (2019) Photobiomodulation Therapy for Wound Care: A Potent, Noninvasive, Photoceutical Approach. Adv Skin Wound Care 32(4):157-167. https://doi.org/10.1097/01.ASW.0000553600.97572.d2 ). Laser therapy is increasingly used as an adjunct to therapeutic interventions in clinical practice (Dundar U et al. (2015) Effect of high-intensity laser therapy in the management of myofascial pain syndrome of the trapezius: a double-blind, placebo-controlled study. Lasers Med Sci 30(1):325-332. https://doi.org/10.1007/s10103-014-1671-8 ). This study aimed to evaluate the efficacy of HILT and the potential benefits of incorporating co- interventions alongside HILT in wound management. The following databases were searched up to April 2023: Embase, MEDLINE, PubMed, and Cinahl, as well as manual searches. The search keywords included high- intensity laser therapy, high-power laser therapy, laser therapy, wound, ulcer, and wound healing. The primary measures were decreased wound surface area (WSA) and improved wound appearance (WA) or other objective wound assessment tools containing these two values. Six human studies investigating HILT in wound healing treatment and one animal study assessing the wound-healing effects of HILT in acute wounds of mice were selected (Thabet AAE, Mahran HG, Ebid AA, Alshehri MA. Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci.;30(4):570-575. doi:, Ebid AA, Thabet A, Helal O (2018) (2011) Efficacy of pulsed high intensity Nd: Yag Laser in Treatment of Chronic Diabetic Foot Ulcer. Energy for Health pp. 25-30); (Ebid AA, El-Kafy EM, Alayat MS (2013) Effect of pulsed Nd: YAG laser in the treatment of neuropathic foot ulcers in children with spina bifida: a randomized controlled study. Photomed Laser Surg 31(12):565-570. https://doi.org/10.1089/pho.2013.3533 ); (Hong SE et al. (2016) Effects of neodymium-yttrium-aluminum garnet (Nd: YAG) pulsed high-intensity laser therapy on full thickness wound healing in an experimental animal model. J Cosmet Laser Ther 18(8):432-437. https://doi.org/10.1080/14764172.2016.1202421 ); (Lu Q et al. (2021) Clinical effects of high-intensity laser therapy on patients with chronic refractory wounds: a randomised controlled trial. BMJ Open 11(7):e045866. https://doi.org/10.1136/bmjopen-2020-045866 ); (Pereira FLC et al. (2020) Use of a High-Power Laser for Wound Healing: A Case Report. J Lasers Med Sci 11(1):112-114. https://doi.org/10.15171/jlms.2020.19 ); (Thabet AAE et al. (2018) Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci 30(4):570-575. https://doi.org/10.1589/jpts.30.570 ); (Nussbaum EL, Baxter GD, Lilge L (2003) A Review of Laser Technology and Light-Tissue Interactions as a Background to Therapeutic Applications of Low Intensity Lasers and Other Light Sources. Phys Therapy Reviews 8(1):31-44. https://doi.org/10.1002/lsm.20769 ). This limited number of studies exhibited varying treatment parameters, blinding procedures, wound etiologies, irradiation protocols, and testing areas (Thabet AAE, Mahran HG, Ebid AA, Alshehri MA. Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci. ;30(4):570-575. doi:, Ebid AA, Thabet A, Helal O (2018) (2011) Efficacy of pulsed high intensity Nd: Yag Laser in Treatment of Chronic Diabetic Foot Ulcer. Energy for Health pp. 25-30); (Ebid AA, El-Kafy EM, Alayat MS (2013) Effect of pulsed Nd: YAG laser in the treatment of neuropathic foot ulcers in children with spina bifida: a randomized controlled study. Photomed Laser Surg 31(12):565-570. https://doi.org/10.1089/pho.2013.3533 ); (Hong SE et al. (2016) Effects of neodymium-yttrium-aluminum garnet (Nd: YAG) pulsed high-intensity laser therapy on full thickness wound healing in an experimental animal model. J Cosmet Laser Ther 18(8):432-437. https://doi.org/10.1080/14764172.2016.1202421 ); (Lu Q et al. (2021) Clinical effects of high-intensity laser therapy on patients with chronic refractory wounds: a randomised controlled trial. BMJ Open 11(7):e045866. https://doi.org/10.1136/bmjopen-2020-045866 ); (Pereira FLC et al. (2020) Use of a High-Power Laser for Wound Healing: A Case Report. J Lasers Med Sci 11(1):112-114. https://doi.org/10.15171/jlms.2020.19 ); (Thabet AAE et al. (2018) Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci 30(4):570-575. https://doi.org/10.1589/jpts.30.570 ); (Nussbaum EL, Baxter GD, Lilge L (2003) A Review of Laser Technology and Light-Tissue Interactions as a Background to Therapeutic Applications of Low Intensity Lasers and Other Light Sources. Phys Therapy Reviews 8(1):31-44. https://doi.org/10.1002/lsm.20769 ). All selected studies demonstrated favorable results in improving wound conditions (Thabet AAE, Mahran HG, Ebid AA, Alshehri MA. Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci. ;30(4):570-575. doi:, Ebid AA, Thabet A, Helal O (2018) (2011) Efficacy of pulsed high intensity Nd: Yag Laser in Treatment of Chronic Diabetic Foot Ulcer. Energy for Health pp. 25-30); (Ebid AA, El-Kafy EM, Alayat MS (2013) Effect of pulsed Nd: YAG laser in the treatment of neuropathic foot ulcers in children with spina bifida: a randomized controlled study. Photomed Laser Surg 31(12):565-570. https://doi.org/10.1089/pho.2013.3533 ); (Hong SE et al. (2016) Effects of neodymium-yttrium-aluminum garnet (Nd: YAG) pulsed high-intensity laser therapy on full thickness wound healing in an experimental animal model. J Cosmet Laser Ther 18(8):432-437. https://doi.org/10.1080/14764172.2016.1202421 ); (Lu Q et al. (2021) Clinical effects of high-intensity laser therapy on patients with chronic refractory wounds: a randomised controlled trial. BMJ Open 11(7):e045866. https://doi.org/10.1136/bmjopen-2020-045866 ); (Pereira FLC et al. (2020) Use of a High-Power Laser for Wound Healing: A Case Report. J Lasers Med Sci 11(1):112-114. https://doi.org/10.15171/jlms.2020.19 ); (Thabet AAE et al. (2018) Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci 30(4):570-575. https://doi.org/10.1589/jpts.30.570 ); (Nussbaum EL, Baxter GD, Lilge L (2003) A Review of Laser Technology and Light-Tissue Interactions as a Background to Therapeutic Applications of Low Intensity Lasers and Other Light Sources. Phys Therapy Reviews 8(1):31-44. https://doi.org/10.1002/lsm.20769 ). Although insufficient data support using HILT in wound management, the promising results encourage further research. HILT appears effective in wound healing, but more high-quality studies are needed to identify optimal laser protocols.

Revealing the dual impact of VOCs on recycled rubber workers: Health risk and odor perception.

Volatile organic compounds (VOCs) pose potential hazards to human health and contribute significantly to odor pollution. This study examined VOC emissions from a representative recycled rubber industry, evaluating the occupational health risks for frontline workers in various workshops. Variables such as gender and workshop-specific concentration variations were considered using Monte Carlo simulation methods. Employees in the five production workshops and office areas face noncarcinogenic health risks with hazard indices (HIs) greater than 1, with the rubber compounding phase presenting the highest risk. Acetaldehyde is identified as the primary noncarcinogenic health risk substance, with hazard quotient (HQ) values exceeding 1 in all workshops. Carcinogenic health risks vary by area, with the highest risks found in compounding and refining workshops. Formaldehyde poses the greatest risk in rubber grinding workshops and offices, with cumulative weights exceeding unacceptable levels of M80.58 % and W77.56 % in grinding and M94.98 % and W92.24 % in the office. Male workers face 4-7 % greater noncarcinogenic VOC health risks than females and 5-14 % greater carcinogenic risks from individual VOCs, increasing their susceptibility to health risks caused by VOCs. Additionally, our analysis of odor identification and intensity classification revealed that 53 VOCs are capable of causing odor pollution, with several substances reaching odor levels of 2 or higher. The predominant perceived odors, as reflected in the odor wheel, include categories such as "solvent/aromatic" and "sweet/fruit," with aldehydes being the primary odor-causing substances. In summary, emissions of VOCs from rubber industrial processes not only pose substantial health risks to workers but also contribute significantly to odor pollution. Consequently, enterprises must prioritize optimizing workplace conditions to ensure the occupational health and well-being of their employees.

Effects of high-intensity interval training on sleep disturbances associated with posttraumatic stress disorder.

Sleep disturbances are common in individuals with posttraumatic stress disorder. Exercise interventions are a promising approach in the treatment of sleep disorders, but little is known about the efficacy of exercise interventions for sleep disturbances associated with posttraumatic stress disorder. A total of 40 individuals with posttraumatic stress disorder were randomized to six sessions of either high-intensity interval training or low-to-moderate-intensity training, administered within 12 days. Sleep quality was assessed over 24 days from baseline to post with the Pittsburgh Sleep Quality Index, a sleep log, and a waist-worn actigraphy. Analyses revealed that, regardless of group allocation, Pittsburgh Sleep Quality Index score improved significantly by 2.28 points for high-intensity interval training and 1.70 points for low-to-moderate-intensity training (d = 0.56 for high-intensity interval training; 0.49 for low-to-moderate-intensity training) over time, while there were no significant changes in any sleep log or actigraphy measure. Analysis of a subsample of those affected by clinically significant sleep disturbances (n = 24) revealed a significant time effect with no difference between exercise interventions: Pittsburgh Sleep Quality Index improved significantly by 2.65 points for high-intensity interval training and 2.89 points for low-to-moderate-intensity training (d = 0.53 for high-intensity interval training; 0.88 for low-to-moderate-intensity training), and actigraphy measure of wake after sleep onset was reduced significantly by 14.39 minutes for high-intensity interval training and 6.96 minutes for low-to-moderate-intensity training (d = 0.47 for high-intensity interval training; 0.11 for low-to-moderate-intensity training) from baseline to post. In our pilot study, we found an improvement in sleep quality from pre- to post-assessment. There were no significant differences between exercise groups. Further studies are needed to investigate whether the found time effects reflect the exercise intervention or unrelated factors.

Quantitative Assessment of Intervertebral Disc Degeneration Using the Disc Signal Intensity Index in Patients With Spine-Related Pain.

Objective This is a retrospective observational study that aims to investigate the association between disc signal intensity index (DSI2) scores and patient-reported outcome measures in patients with lumbar spine disorders. Methods We introduced DSI2 to quantitatively assess disc degeneration. MRI records of patients with lumbar spine-related pain between 2019 and 2022 were analyzed retrospectively. Patient demographics and outcomes were collected, including the Numerical Rating Scale of Pain and EuroQol Group 5 Dimension 5-Level Quality of Life (EQ-5D-5L) scores. The DSI2 was calculated by dividing the mean signal intensity of the L1-S1 discs by that of the CSF on midsagittal T2-weighted MRI images. Results Each DSI2 level corresponded to a Pfirrmann grade score at the respective lumbar level. Multivariable linear regression analysis using the EQ-5D-5L as the objective variable identified BMI (p = 0.007) and average DSI2 (p = 0.018) as independent risk factors for EQ-5D-5L deterioration. However, the mean Pfirrmann grade score was not an independent risk factor (p = 0.58). Conclusion Our study using DSI2 showed the relationship between disc degeneration and EQ-5D-5L deterioration. Distinct from the Pfirrmann grading system, the DSI2 method is a promising alternative for future disc research that excellently detects the subtle progression of degeneration.

Current challenges in conditioning regimens for MDS transplantation.

Myelodysplastic syndrome (MDS) is a very heterogeneous clonal disorder. Patients with "higher-risk" MDS, defined by specific recurrent genetic abnormalities, have a poor prognosis because of a high risk of progression to secondary acute myeloid leukemia with low chemosensitivity. Allogeneic hematopoietic stem cell transplantation remains the only treatment that offers durable disease control because the donor immune system allows graft-versus-MDS effects. In terms of preparation steps before transplantation, targeting the malignant clone by increasing the conditioning regimen intensity is still a matter of intense debate. MDS is mainly diagnosed in older patients, and high toxicity related to common myeloablative conditioning regimens has been reported. Efforts to include new drugs in the conditioning regimen to achieve the best malignant clone control without increasing toxicity have been made over the past 20 years. We summarized these retrospective and prospective studies and evaluated the limitations of the available evidence to delineate the ideal conditioning regimen.

Trends in use of intensive care during hospitalizations at the end-of-life among older adults with advanced cancer.

BACKGROUND: High-intensity end-of-life (EOL) care, marked by admission to intensive care units (ICUs) or in-hospital death, can be costly and burdensome. Recent trends in use of ICUs, life-sustaining treatments (LSTs), and noninvasive ventilation (NIV) during EOL hospitalizations among older adults with advanced cancer and patterns of in-hospital death are unknown. METHODS: We used SEER-Medicare data (2003-2017) to identify beneficiaries with advanced solid cancer (summary stage 7) who died within 3 years of diagnosis. We identified EOL hospitalizations (within 30 days of death), classifying them by increasing intensity of care into: (1) without ICU; (2) with ICU but without LST (invasive mechanical ventilation, tracheostomy, gastrostomy, acute dialysis) or NIV; (3) with ICU and NIV but without LST; and (4) with ICU and LST use. We constructed a multinomial regression model to evaluate trends in risk-adjusted hospitalization, overall and across hospitalization categories, adjusting for sociodemographics, cancer characteristics, comorbidities, and frailty. We evaluated trends in in-hospital death across categories. RESULTS: Of 226,263 Medicare beneficiaries with advanced cancer, 138,305 (61.1%) were hospitalized at EOL [Age, Mean (SD):77.9(7.1) years; 45.5% female]. Overall, EOL hospitalizations remained high throughout, from 78.1% (95% CI: 77.4, 78.7) in 2004 to 75.5% (95% CI: 74.5, 76.2) in 2017. Hospitalizations without ICU use decreased from 49.3% (95% CI: 48.5, 50.2) to 35.0% (95% CI: 34.2, 35.9) while hospitalizations with more intensive care increased, from 23.7% (95% CI: 23.0, 24.4) to 28.7% (95% CI: 27.9, 29.5) for ICU without LST or NIV, 0.8% (95% CI: 0.6, 0.9) to 3.8% (95% CI: 3.4, 4.1) for ICU with NIV but without LST, and 4.3% (95% CI: 4.0, 4.7) to 8.0% (95% CI: 7.5, 8.5) for ICU with LST use. Among those who experienced in-hospital death, the proportion receiving ICU care increased from 46.5% to 65.0%. CONCLUSIONS: Among older adults with advanced cancer, EOL hospitalization rates remained stable from 2004-2017. However, intensity of care during EOL hospitalizations increased as evidenced by increasing use of ICUs, LSTs, and NIV.

A simple predictor for donor-specific anti-HLA antibody desensitisation in haploidentical haematopoietic stem cell transplantation.

Donor-specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first-line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre-TPE serum correlated well with DSA value in post-TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non-responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non-responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre-TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT.

Weighted ultrasound entropy imaging for HIFU ablation monitoring with improved sensitivity and contrast.

BACKGROUND: Although B-mode imaging has been widely used in ultrasound-guided high-intensity focused ultrasound (HIFU) treatment, challenges remain in improving its quality and sensitivity for monitoring the thermal dose. Recently, quantitative ultrasound (QUS) imaging has been recognized with the potential to better sense the changes in the microstructure of ablated tissues. PURPOSE: This study proposed to use a QUS method called weighted ultrasound entropy (WUE) imaging to monitor the HIFU ablation. METHODS: Based on ex-vivo and in-vivo experiments, WUE images reflecting tissue changes during HIFU treatment under different acoustic power levels (174-308 W) were reconstructed with a newly established imaging framework. The performance of the proposed WUE imaging in the monitoring of HIFU treatment was compared with the corresponding B-mode images in terms of their contrast-to-noise ratios (CNRs) between the focal region and the background. RESULTS: It was found that HIFU irradiation with higher power generated larger WUE values in the focal region, and the bright spots grew in size as the acoustic sonication proceeded. Compared with the in-situ B-mode images, the WUE images had higher image quality in indicating lesion formation, with a 39.2%-53.4% improvement in the CNR at different stages. Meanwhile, a correlation (R = 0.84) between the damage area estimated in WUE images and that measured from the dissected ex-vivo tissue samples was found. CONCLUSIONS: WUE imaging is more sensitive and accurate than B-mode imaging in monitoring HIFU therapy. These findings suggest that WUE imaging could be a promising technique for assisting ultrasound-guided HIFU ablation.

Dosimetric effect of collimator rotation on intensity modulated radiotherapy and volumetric modulated arc therapy for rectal cancer radiotherapy.

INTRODUCTION: Intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) are the main radiotherapy techniques for treating and managing rectal cancer. Collimator rotation is one of the crucial parameters in radiotherapy planning, and its alteration can cause dosimetric variations. This study assessed the effect of collimator rotation on the dosimetric results of various IMRT and VMAT plans for rectal cancer. MATERIALS AND METHODS: Computed tomography (CT) images of 20 male patients with rectal cancer were utilized for IMRT and VMAT treatment planning with various collimator angles. Nine different IMRT techniques (5, 7, and 9 coplanar fields with collimator angles of 0°, 45°, and 90°) and six different VMAT techniques (1 and 2 full coplanar arcs with collimator angles of 0°, 45°, and 90°) were planned for each patient. The dosimetric results of various treatment techniques for target tissue (conformity index [CI] and homogeneity index [HI]) and organs at risk (OARs) sparing (parameters obtained from OARs dose-volume histograms [DVH]) as well as radiobiological findings were analyzed and compared. RESULTS: The 7-fields IMRT technique demonstrated lower bladder doses (V40Gy, V45Gy), unaffected by collimator rotation. The 9-fields IMRT and 2-arcs VMAT (excluding the 90-degree collimator) had the lowest V35Gy and V45Gy. A 90-degree collimator rotation in 2-arcs VMAT significantly increased small bowel and bladder V45Gy, femoral head doses, and HI values. Radiobiologically, the 90-degree rotation had adverse effects on small bowel NTCP (normal tissue complication probability). No superiority was found for a 45-degree collimator rotation over 0 or 30 degrees in VMAT techniques. CONCLUSION: Collimator rotation had minimal impact on dosimetric parameters in IMRT planning but is significant in VMAT techniques. A 90-degree rotation in VMAT, particularly in a 2-full arc technique, adversely affects PTV homogeneity index, bladder dose, and small bowel NTCP. Other evaluated collimator angles did not significantly affect VMAT dosimetrical or radiobiological outcomes.

Proton Therapy Reduces the Effective Dose to Immune Cells in Mediastinal Hodgkin Lymphoma Patients.

Purpose: Effective dose to circulating immune cells (EDIC) is associated with survival in lung and esophageal cancer patients. This study aimed to evaluate the benefit of intensity-modulated proton therapy (IMPT) for EDIC reduction compared with volumetric modulated arc therapy (VMAT) in mediastinal Hodgkin lymphoma (mHL) patients. Materials and Methods: Ten consecutive mHL patients treated with involved-site IMPT after frontline chemotherapy were included. The mean dose to the heart, lung, and liver and the integral dose to the body were obtained, and we calculated EDIC based on these variables. The effective dose to circulating immune cells was compared between IMPT and VMAT schedules. Results: The median EDIC was reduced from 1.93 Gy (range: 1.31-3.87) with VMAT to 1.08 Gy (0.53-2.09) with IMPT (P < .01). Integral dose reduction was the main driver of EDIC reduction with IMPT, followed by lung sparing. Conclusion: Intensity-modulated proton therapy significantly reduced EDIC in mHL patients undergoing consolidation involved-site radiation therapy. Integral dose reduction combined with improved lung sparing was the main driver of EDIC reduction with IMPT.

Case report: Sequential treatment strategy for advanced basal cell carcinoma in Gorlin-Goltz syndrome: integration of vismodegib, radiotherapy, surgery, and high-intensity focused ultrasound.

Managing advanced basal cell carcinoma (BCC) in patients with Gorlin-Goltz syndrome presents unique clinical challenges due to the tumor's aggressive nature and potential for widespread metastasis. This case study details a sequential treatment regimen for a 68-year-old female patient with an extensive, inoperable BCC. Employing a multimodal approach that integrates radiotherapy, the Hedgehog pathway inhibitor vismodegib, and High-Intensity Focused Ultrasound (HIFU), we demonstrate the potential for nearly complete remission in a patient with advanced BCC. Initial treatment with radiotherapy and vismodegib reduced tumor size significantly, but the largest mass displayed resistance over time, signifying the need for innovative therapies. Subsequent HIFU treatment targeted individual lesions, showcasing a non-invasive method that provided precise treatment while mitigating systemic side effects. The case emphasizes the necessity of continual adaptation in treatment plans to address the development of resistance and underscores the importance of incorporating new technologies and targeted therapies for complex BCC cases. The successful outcome of this integrated strategy suggests a promising direction for future research and highlights the importance of multidisciplinary approaches that tailor treatment to individual patient needs, tumor characteristics, and evolving therapeutic landscapes.

Transcranial Focused Ultrasound Targeting the Amygdala May Increase Psychophysiological and Subjective Negative Emotional Reactivity in Healthy Older Adults.

Background: The amygdala is highly implicated in an array of psychiatric disorders but is not accessible using currently available noninvasive neuromodulatory techniques. Low-intensity transcranial focused ultrasound (TFUS) is a neuromodulatory technique that has the capability of reaching subcortical regions noninvasively. Methods: We studied healthy older adult participants (N = 21, ages 48-79 years) who received TFUS targeting the right amygdala and left entorhinal cortex (active control region) using a 2-visit within-participant crossover design. Before and after TFUS, behavioral measures were collected via the State-Trait Anxiety Inventory and an emotional reactivity and regulation task utilizing neutral and negatively valenced images from the International Affective Picture System. Heart rate and self-reported emotional valence and arousal were measured during the emotional reactivity and regulation task to investigate subjective and physiological responses to the task. Results: Significant increases in both self-reported arousal in response to negative images and heart rate during emotional reactivity and regulation task intertrial intervals were observed when TFUS targeted the amygdala; these changes were not evident when the entorhinal cortex was targeted. No significant changes were found for state anxiety, self-reported valence to the negative images, cardiac response to the negative images, or emotion regulation. Conclusions: The results of this study provide preliminary evidence that a single session of TFUS targeting the amygdala may alter psychophysiological and subjective emotional responses, indicating some potential for future neuropsychiatric applications. However, more work on TFUS parameters and targeting optimization is necessary to determine how to elicit changes in a more clinically advantageous way.

Transcranial focused ultrasound (TFUS) is an emerging brain stimulation technique with the ability to noninvasively alter the activity of deep brain regions. Studying the potential for TFUS to alter behavioral response and processing, this study employed MRI-guided TFUS targeting the right amygdala in older adults. We found that TFUS targeting the right amygdala increased self-reported arousal in response to negative images, providing preliminary evidence that a single session of TFUS may be capable of affecting emotional reactivity.

Model-based navigation of transcranial focused ultrasound neuromodulation in humans: Application to targeting of the amygdala and thalamus.

BACKGROUND: Transcranial focused ultrasound (tFUS) neuromodulation has shown promise in animals but is challenging to translate to humans because of the thicker skull that heavily scatters ultrasound waves. OBJECTIVE: We develop and disseminate a model-based navigation (MBN) tool for acoustic dose delivery in the presence of skull aberrations that is easy to use by non-specialists. METHODS: We pre-compute acoustic beams for thousands of virtual transducer locations on the scalp of the subject under study. We use the hybrid angular spectrum solver mSOUND, which runs in ∼4 seconds per solve per CPU yielding pre-computation times under one hour for scalp meshes with up to 4,000 faces and a parallelization factor of 5. We combine this pre-computed set of beam solutions with optical tracking, thus allowing real-time display of the tFUS beam as the operator freely navigates the transducer around the subject' scalp. We assess the impact of MBN versus line-of-sight targeting (LOST) positioning in simulations of 13 subjects. RESULTS: Our navigation tool has a display refresh rate of ∼10 Hz. In our simulations, MBN increased the acoustic dose in the thalamus and amygdala by 8-67% compared to LOST and avoided complete target misses that affected 10-20% of LOST cases. MBN yields a lower variability of the deposited dose across subjects than LOST. CONCLUSIONS: MBN may yield greater and more consistent (less variable) ultrasound dose deposition than transducer placement with line-of-sight targeting, and thus may become a helpful tool to improve the efficacy of tFUS neuromodulation.

Influence of footshock number and intensity on the behavioral and endocrine response to fear conditioning and cognitive fear generalization in male rats.

Foot-shock paradigms have provided valuable insights into the neurobiology of stress and fear conditioning. An extensive body of literature indicates that shock exposure can elicit both conditioned and unconditioned effects, although delineating between the two is a challenging task. This distinction holds crucial implications not only for the theoretical interpretation of fear conditioning, but also for properly evaluating putative preclinical models of post-traumatic stress disorder (PTSD) involving shock exposure. The characteristics of shocks (intensity and number) affect the strength of learning, but how these characteristics interact to influence conditioned and unconditioned consequences of shocks are poorly known. In this study, we aimed to investigate in adult male rats the impact of varying shock number and intensity on the endocrine and behavioral response to contextual fear conditioning and fear generalization to a novel environment markedly distinct from the shock context (i.e., fear generalization). Classical biological markers of stress (i.e., ACTH, corticosterone, and prolactin) were sensitive to manipulations of shock parameters, whereas these parameters had a limited effect on contextual fear conditioning (evaluated by freezing and distance traveled). In contrast, behavior in different novel contexts (fear generalization) was specifically sensitive to shock intensity. Notably, altered behavior in novel contexts markedly improved, but not completely normalized after fear extinction, hypoactivity apparently being the result of both conditioned and unconditioned effects of foot-shock exposure. The present results will contribute to a better understanding of shock exposure as a putative animal model of PTSD.