In-silico study of the impact of system design parameters on microcalcification detection in wide-angle digital breast tomosynthesis.

Purpose: Accurate detection of microcalcifications ( µ Calcs ) is crucial for the early detection of breast cancer. Some clinical studies have indicated that digital breast tomosynthesis (DBT) systems with a wide angular range have inferior µ Calc detectability compared with those with a narrow angular range. This study aims to (1) provide guidance for optimizing wide-angle (WA) DBT for improving µ Calcs detectability and (2) prioritize key optimization factors. Approach: An in-silico DBT pipeline was constructed to evaluate µ Calc detectability of a WA DBT system under various imaging conditions: focal spot motion (FSM), angular dose distribution (ADS), detector pixel pitch, and detector electronic noise (EN). Images were simulated using a digital anthropomorphic breast phantom inserted with 120 µ m µ Calc clusters. Evaluation metrics included the signal-to-noise ratio (SNR) of the filtered channel observer and the area under the receiver operator curve (AUC) of multiple-reader multiple-case analysis. Results: Results showed that FSM degraded µ Calcs sharpness and decreased the SNR and AUC by 5.2% and 1.8%, respectively. Non-uniform ADS increased the SNR by 62.8% and the AUC by 10.2% for filtered backprojection reconstruction with a typical clinical filter setting. When EN decreased from 2000 to 200 electrons, the SNR and AUC increased by 21.6% and 5.0%, respectively. Decreasing the detector pixel pitch from 85 to 50 µ m improved the SNR and AUC by 55.6% and 7.5%, respectively. The combined improvement of a 50 µ m pixel pitch and EN200 was 89.2% in the SNR and 12.8% in the AUC. Conclusions: Based on the magnitude of impact, the priority for enhancing µ Calc detectability in WA DBT is as follows: (1) utilizing detectors with a small pixel pitch and low EN level, (2) allocating a higher dose to central projections, and (3) reducing FSM. The results from this study can potentially provide guidance for DBT system optimization in the future.

Estimation of the absorbed dose in simultaneous digital breast tomosynthesis and mechanical imaging.

Purpose: Use of mechanical imaging (MI) as complementary to digital mammography (DM), or in simultaneous digital breast tomosynthesis (DBT) and MI - DBTMI, has demonstrated the potential to increase the specificity of breast cancer screening and reduce unnecessary biopsies compared with DM. The aim of this study is to investigate the increase in the radiation dose due to the presence of an MI sensor during simultaneous image acquisition when automatic exposure control is used. Approach: A radiation dose study was conducted on clinically available breast imaging systems with and without an MI sensor present. Our estimations were based on three approaches. In the first approach, exposure values were compared in paired clinical DBT and DBTMI acquisitions in 97 women. In the second approach polymethyl methacrylate (PMMA) phantoms of various thicknesses were used, and the average glandular dose (AGD) values were compared. Finally, a rectangular PMMA phantom with a 45 mm thickness was used, and the AGD values were estimated based on air kerma measurements with an electronic dosemeter. Results: The relative increase in exposure estimated from digital imaging and communications in medicine headers when using an MI sensor in clinical DBTMI was 11.9 % ± 10.4 . For the phantom measurements of various thicknesses of PMMA, the relative increases in the AGD for DM and DBT measurements were, on average, 10.7 % ± 3.1 and 11.4 % ± 3.0 , respectively. The relative increase in the AGD using the electronic dosemeter was 11.2 % ± < 0.001 in DM and 12.2 % ± < 0.001 in DBT. The average difference in dose between the methods was 11.5 % ± 3.3 . Conclusions: Our measurements suggest that the use of simultaneous breast radiography and MI increases the AGD by an average of 11.5 % ± 3.3 . The increase in dose is within the acceptable values for mammography screening recommended by European guidelines.

Feasibility of the analytical dose calculation method for Au-198 brachytherapy.

PURPOSE: A dose calculation algorithm Computed Tomography (CT)-based analytical dose calculation method (CTanly), which can correct for subject inhomogeneity and size-dependent scatter doses, was applied to the 198Au seed. In this study, we evaluated the effectiveness of the CTanly method by comparing the gold standard Monte Carlo (MC) method and the conventional TG43 method on two virtual phantoms and patient CT images simulating oral cancer. METHODS: As virtual phantoms, a water phantom and a heterogeneous phantom with soft tissue inserted cubic fat, lung, and bone were used. A 2-mm-thick lead plate was also inserted into the heterogeneous phantom as a dose attenuator. Virtual 198Au seeds and a 2-mm-thick lead plate were placed on the patient CT images. Dose distributions obtained via the TG43 and CTanly methods were compared with those of the MC by gamma analysis with 2%/2-mm thresholds. The computation durations were also compared. RESULTS: In the water phantom, dose distributions comparable to those obtained via the MC method were obtained regardless of the algorithm. For the inhomogeneity phantom and patient case, the CTanly method showed an improvement in the gamma passing rate and dose distributions similar to those of the MC method were obtained. The computation time, which was days with the MC method, was reduced to minutes with the CTanly method. CONCLUSIONS: The CTanly method is effective for 198Au seed dose calculations and takes a shorter time to obtain the dose distributions than the MC method.

Efficacy of initial and repeat DCB angioplasty of restenotic arteriovenous fistulas compared with plain angioplasty.

PURPOSE: To evaluate the effect of drug-coated balloon (DCB) with high-dose paclitaxel for the treatment of restenotic dysfunctional arteriovenous fistulas (AVFs). MATERIALS AND METHODS: In this single-arm, multicenter, prospective, observational study, 334 patients using IN.PACT AV DCB (Medtronic Inc., Plymouth, MN) for the first time in the restenotic lesion of dysfunctional AVF between April 2021 and March 2022 were registered. RESULTS: Procedural success, defined as <30% residual stenosis, was achieved in 96.7% of cases. During a median follow-up of 7.4 months, 179 target lesion reinterventions (TLRs) were observed, and the 6-month freedom from TLR was 73.2% (68.2%-78.2%). When compared with the previous plain percutaneous transluminal angioplasty, the median time to reintervention was significantly longer with DCB (9.1 [8.0-10.6] versus 3.2 [3.0-3.4] months; P<.001). Baseline characteristics that were independently associated with TLR were: months from the last intervention (adjusted hazard ratio, 0.50 [95% confidence interval, 0.40-0.62] per doubling; P<.001), partial lesion coverage by DCB (2.13 [1.10-4.12]; P=.024), and residual stenosis after DCB (2.19 [1.53-3.12] per 15% increase; P<.001) with its time interaction (0.91 [0.86-0.97] per month; P=.003). Of the 179 TLRs, 84 used DCB once again. The median time to reintervention was significantly longer for TLR using DCB (7.1 [6.2-9.7] versus 3.3 [3.1-4.0] months; P<.001). CONCLUSIONS: DCB with high-dose paclitaxel is effective at both the initial treatment in the restenotic lesion of dysfunctional AVF and during TLR after DCB use. However, partial lesion coverage by DCB and residual stenosis should be avoided.

Ultraslow low-dose thrombolytic therapy in patients with acute mechanical prosthetic heart valve thrombosis - A prospective cohort study.

BACKGROUND: While surgery still remains the gold standard treatment for mechanical prosthetic valve thrombosis (MPVT) by many guidelines, the ultraslow low-dose thrombolytic regimen has been reported as a promising alternative. METHODS: In this prospective single-center cohort, patients with acute MPVT were treated with an ultraslow low-dose thrombolytic regimen consisting of 25 mg infusion of recombinant tissue-type plasminogen activator (rtPA) over 25 h. The regimen could be repeated in case of failure until resolution/occurrence of adverse events or a maximum cumulative dose of 150 mg. The primary outcome was the complete MPVT resolution rate; other outcomes included first-dose success rate, major bleeding, thromboembolic events, mortality, and total thrombolytic dose/duration. RESULTS: Between April 2018 to January 2024, 135 episodes of acute MPVT were treated with an ultraslow low-dose thrombolytic regimen in 118 patients. In 118/135 (87.4 %) episodes, right-sided prosthetic valve was involved. Complete success was achieved in 88.1 % of cases, with 39.5 % responding after the first dose. The median total dose was 50 mg over a median of 30 h. Only one fatal intracranial hemorrhage occurred (0.7 %), with no other bleeding or thromboembolic complications. CONCLUSION: The ultraslow low-dose thrombolytic regimen appears to exhibit high efficacy and acceptable safety in treating acute MPVT. Further large clinical trials are essential for validating these preliminary findings.

Clinical Outcome Comparison between CT-Guided Versus all MRI-Guided Scenarios in Brachytherapy for Cervical Cancer: A Single-Institute Experience.

OBJECTIVES: Image-guided adaptive brachytherapy (IGABT) is the standard of care for patients with cervical cancer. The objective of this study was to compare the treatment outcomes and adverse effects of computed tomography (CT)-guided and magnetic resonance imaging (MRI)-guided scenarios. MATERIALS AND METHODS: Data of patients with cervical cancer treated using external beam radiotherapy followed by IGABT from 2012 to 2016 were retrospectively reviewed. CT-guided IGABT was compared with the three modes of MRI-guided IGABT: pre-brachytherapy (MRI Pre-BT) without applicator insertion for fusion, planning MRI with applicator in-place in at least 1 fraction (MRI ≥1Fx), and MRI in every fraction (MRI EveryFx). Patient characteristics, oncologic outcomes, and late radiation toxicity were analyzed using descriptive, survival, and correlation statistics. RESULTS: Overall, 354 patients were evaluated with a median follow-up of 60 months. The 5-year overall survival (OS) rates were 61.5%, 65.2%, 54.4%, and 63.7% with CT-guided, MRI PreBT, MRI ≥1Fx, and MRI EveryFx IGABT, respectively with no significant differences (p = 0.522). The 5-year local control (LC) rates were 92.1%, 87.8%, 80.7%, and 76.5% (p = 0.133), respectively, with a significant difference observed between the CT-guided and MRI ≥1Fx (p = 0.018). The grade 3-4 late gastrointestinal toxicity rates were 6% in the CT-guided, MRI ≥1Fx, and MRI EveryFx, and 8% in MRI PreBT. The grade 3-4 late genitourinary toxicity rates were 4% in the CT-guided, 2% in MRI PreBT, 1% in MRI ≥1Fx, and none in MRI EveryFx. No significant differences were observed in the oncologic and toxicity outcomes among MRI PreBT, MRI ≥1Fx, and MRI EveryFx. CONCLUSIONS: CT-guided IGABT yielded an acceptable 5-year OS, LC, and toxicity profile compared with all MRI scenarios and is a potentially feasible option in resource-limited settings.

The quest for optimal ketamine dosing formula in treatment-resistant major depressive disorder.

BACKGROUND: Emerging evidence indicates that intravenous ketamine is effective in managing treatment-resistant unipolar and bipolar depression. Clinical studies highlight its favorable efficacy, safety, and tolerability profile within a dosage range of 0.5-1.0 mg/kg based on actual body weight. However, data on alternative dosage calculation methods, particularly in relation to body mass index (BMI) and therapeutic outcomes, remain limited. METHODS: This retrospective analysis of an open-label study aims to evaluate dose calculation strategies and their impact on treatment response among inpatients with treatment-resistant major depressive disorder (MDD) (n = 28). The study employed the Boer and Devine formulas to determine lean body mass (LBM) and ideal body weight (IBW), and the Mosteller formula to estimate body surface area (BSA). The calculated doses were then compared with the actual doses administered or converted to a dosage per square meter for both responders and non-responders. RESULTS: Regardless of treatment response, defined as a reduction of 50% in the Montgomery-Åsberg Depression Rating Scale, the use of alternative ketamine dosing formulas resulted in underdosing compared to the standardized dose of 0.5 mg/kg. Only two participants received higher doses (102.7% and 113.0%) when the Devine formula was applied. CONCLUSIONS: This study suggests that ketamine dosing formulas, alternative to the standardized 0.5 mg/kg based on body weight, may lead to underdosing and potentially impact outcome interpretation. To enhance dosing accuracy, future studies should consider incorporating body impedance analysis and waist-to-hip ratio measurements, as this study did not account for body composition.

The scientific nature of the linear no-threshold (LNT) model used in the system of radiological protection.

During the first half of the 20th century, it was commonly assumed that radiation-induced health effects occur only when the dose exceeds a certain threshold. This idea was discarded for stochastic effects when more knowledge was gained about the mechanisms of radiation-induced cancer. Currently, a key tenet of the international system of radiological protection is the linear no-threshold (LNT) model where the risk of radiation-induced cancer is believed to be directly proportional to the dose received, even at dose levels where the effects cannot be proven directly. The validity of the LNT approach has been questioned on the basis of a claim that only conclusions that can be verified experimentally or epidemiologically are scientific and LNT should, thus, be discarded because the system of radiological protection must be based on solid science. The aim of this publication is to demonstrate that the LNT concept can be tested in principle and fulfils the criteria of a scientific hypothesis. The fact that the system of radiological protection is also based on ethics does not render it unscientific either. One of the fundamental ethical concepts underlying the LNT model is the precautionary principle. We explain why it is the best approach, based on science and ethics (as well as practical experience), in situations of prevailing uncertainty.

Reduced-dose chemotherapy and blinatumomab as induction treatment for newly diagnosed Ph-negative B-cell precursor acute lymphoblastic leukemia: a phase 2 trial.

Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.

Dose tracking assessment for magnetic resonance guided adaptive radiotherapy of rectal cancers.

BACKGROUND: Magnetic resonance-guided adaptive radiotherapy (MRgART) at MR-Linac allows for plan optimisation on the MR-based synthetic CT (sCT) images, adjusting the target and organs at risk according to the patient's daily anatomy. Conversely, conventional linac image-guided radiotherapy (IGRT) involves rigid realignment of regions of interest to the daily anatomy, followed by the delivery of the reference computed tomography (CT) plan. This study aims to evaluate the effectiveness of MRgART versus IGRT for rectal cancer patients undergoing short-course radiotherapy, while also assessing the dose accumulation process to support the findings and determine its usefulness in enhancing treatment accuracy. METHODS: Nineteen rectal cancer patients treated with a 1.5 Tesla MR-Linac with a prescription dose of 25 Gy (5 Gy x 5) and undergoing daily adapted radiotherapy by plan optimization based on online MR-based sCT images, were included in this retrospective study. For each adapted plan ([Formula: see text]), a second plan ([Formula: see text]) was generated by recalculating the reference CT plan on the daily MR-based sCT images after rigid registration with the reference CT images to simulate the IGRT workflow. Dosimetry of [Formula: see text] and[Formula: see text]was compared for each fraction. Cumulative doses on the first and last fractions were evaluated for both workflows. The dosimetry per single fraction and the cumulative doses were compared using dose-volume histogram parameters. RESULTS: Ninety-five fractions delivered with MRgART were compared to corresponding simulated IGRT fractions. All MRgART fractions fulfilled the target clinical requirements. IGRT treatments did not meet the expected target coverage for 63 out of 94 fractions (67.0%), with 13 fractions showing a V95 median point percentage decrease of 2.78% (range, 1.65-4.16%), and 55 fractions exceeding the V107% threshold with a median value of 15.4 cc (range, 6.0-43.8 cc). For the bladder, the median [Formula: see text] values were 18.18 Gy for the adaptive fractions and 19.60 Gy for the IGRT fractions. Similarly the median [Formula: see text] values for the small bowel were 23.40 Gy and 25.69 Gy, respectively. No statistically significant differences were observed in the doses accumulated on the first or last fraction for the adaptive workflow, with results consistent with the single adaptive fractions. In contrast, accumulated doses in the IGRT workflow showed significant variations mitigating the high dose constraint, nevertheless, more than half of the patients still did not meet clinical requirements. CONCLUSIONS: MRgART for short-course rectal cancer treatments ensures that the dose delivered matches each fraction of the planned dose and the results are confirmed by the dose accumulation process, which therefore seems redundant. In contrast, IGRT may lead to target dose discrepancies and non-compliance with organs at risk constraints and dose accumulation can still highlight notable dosimetric differences.

Off-Label Use of Naltrexone in Pica and Other Compulsive Behaviors: A Report of Two Cases.

Pica is known to the medical community as an eating disorder in which individuals may ingest non-food items due to a nutritional deficiency and cause unintentional physical harm to themselves. This article discusses the cases of children with pica in addition to other comorbidities such as trichotillomania, depression, autism, and anxiety. Both patients were trialed on typical first-line treatments to address pica symptoms, including antidepressants, psychotherapy, and neurology consults, which were ineffective in treating pica symptoms. The introduction of naltrexone resulted in significant improvements, including decreased pica symptoms and improvements in depression, anxiety, and overall behaviors. These effects of naltrexone were further bolstered by the effects that occurred when both patients discontinued naltrexone for some time.

MC-Keyboard: A Practical Phase I Trial Design for Targeted Therapies and Immunotherapies Integrating Multiple-Grade Toxicities.

In targeted therapies and immunotherapies, the occurrence of low-grade (e.g., grade 1-2) toxicities (LGT) is common, while dose-limiting toxicities (DLT) are relatively rare. As a result, conventional phase I trial designs, solely based on DLTs and disregarding milder toxicities, are problematic when evaluating these novel therapies. Methods: To address this issue, we propose a novel phase I design called a multiple-constraint keyboard (MC-Keyboard) that integrates multiple toxicity constraints, accounting for both DLT and LGT, for precise dose escalation and de-escalation, and identification of the maximum tolerated dose (MTD). As a model-assisted design, an important feature of MC-Keyboard is that its dose-escalation or de-escalation rule can be pretabulated and incorporated into the trial protocol before the initiation of the trial, greatly simplifying its implementation. Results: The simulation study showed that the MC-Keyboard had high accuracy in identifying the MTD and is safer than some existing designs. Conclusion: The MC-Keyboard provides a novel, simple, and safe approach to assessing safety and identifying the MTD for targeted therapies and immunotherapies.

Unilateral Spinal Anesthesia in Hip Fracture Surgery for Geriatric Patients With High Cardiovascular Risk due to Aortic Stenosis is Safe and Effective.

Introduction: Aortic stenosis is a cause of mortality or morbidity. It complicates the selection and management of anesthetic procedures. The aim of this study was to evaluate the efficacy, hemodynamic effects and postoperative outcome of unilateral spinal anesthesia in geriatric patients with hip fractures with moderate or severe aortic stenosis. Material and Method: A retrospective observational study was conducted on geriatric high-risk patients with cardiac conditions who underwent surgery for hip fractures under unilateral spinal anesthesia with low-dose hyperbaric bupivacaine. The study period spanned from January 2018 to December 2021. The inclusion criteria were individuals with moderate to severe aortic stenosis, as defined by the American Heart Association Criteria. Data on demographic information, cardiac pathologies, hemodynamic data, data on motor and sensory block, perioperative complications, and mortality rates at 30th and 180th days were collected. Results: Mortality rates at the 30th day and 180th day were 8.9% (n:4) and 24.4% (n:11), respectively. T6 level was predominantly obtained level of anesthesia (44.4%). Motor and sensory block formation times averaged 7.6 and 4.8 minutes, respectively. Surgical procedures were performed mostly within 1 hour (66.7%), and complications were rare (11.1% hypotension). Initial analgesic effect showed a rapid resolution, with 64.4% of patients requiring analgesic within the first hour postoperatively. Conclusion: In elderly patients with moderate to severe aortic stenosis scheduled for hip fracture surgery, we posit that unilateral spinal anesthesia with ultra-low dose is safe and effective option.

Three-dimensional dose prediction based on deep convolutional neural networks for brain cancer in CyberKnife: accurate beam modelling of homogeneous tissue.

Objectives: Accurate beam modelling is essential for dose calculation in stereotactic radiation therapy (SRT), such as CyberKnife treatment. However, the present deep learning methods only involve patient anatomical images and delineated masks for training. These studies generally focus on traditional intensity-modulated radiation therapy (RT) plans. Nevertheless, this paper aims to develop a deep CNN-based method for CyberKnife plan dose prediction about brain cancer patients. It utilized modelled beam information, target delineation, and patient anatomical information. Methods: This study proposes a method that adds beam information to predict the dose distribution of CyberKnife in brain cases. A retrospective dataset of 88 brain and abdominal cancer patients treated with the Ray-tracing algorithm was performed. The datasets include patients' anatomical information (planning CT), binary masks for organs at risk (OARs) and targets, and clinical plans (containing beam information). The datasets were randomly split into 68, 6, and 14 brain cases for training, validation, and testing, respectively. Results: Our proposed method performs well in SRT dose prediction. First, for the gamma passing rates in brain cancer cases, with the 2 mm/2% criteria, we got 96.7% ± 2.9% for the body, 98.3% ± 3.0% for the planning target volume, and 100.0% ± 0.0% for the OARs with small volumes referring to the clinical plan dose. Secondly, the model predictions matched the clinical plan's dose-volume histograms reasonably well for those cases. The differences in key metrics at the target area were generally below 1.0 Gy (approximately a 3% difference relative to the prescription dose). Conclusions: The preliminary results for selected 14 brain cancer cases suggest that accurate 3-dimensional dose prediction for brain cancer in CyberKnife can be accomplished based on accurate beam modelling for homogeneous tumour tissue. More patients and other cancer sites are needed in a further study to validate the proposed method fully. Advances in knowledge: With accurate beam modelling, the deep learning model can quickly generate the dose distribution for CyberKnife cases. This method accelerates the RT planning process, significantly improves its operational efficiency, and optimizes it.

A simple HPLC-MS/MS method for the determination of polymyxin B in human plasma and its application in the pharmacokinetic study in elderly patients infected with multidrug-resistant Gram-negative bacteria.

Introduction: Polymyxin B is widely used to treat infections caused by multidrug-resistant Gram-negative bacteria. However, the pharmacokinetic study data of PB in the elderly are scarce. Herein, a simple method to measure the concentration of PB in human plasma was developed and validated by high performance liquid chromatography-tandem mass spectrometry, and it was applied to a PK study in the elderly. Methods: PB was extracted from human plasma by a rapid protein-precipitation method using 0.1% formic acid in methanol and then separated on an ultimate AQ-C18 column using linear gradient elution with a 0.5-mL/min flow rate. Subsequently, PB was detected using a mass spectrometer operated in positive-ion and multiple-reaction-monitoring modes. Results: The lower limits of quantification of the method for Polymyxin B1 and Polymyxin B2 were 1.00 and 0.10 µg/mL, respectively. The linear ranges for PB1 and PB2 were 1.00-20.02 and 0.10-2.04 µg/mL, respectively. Patients receiving a 75-mg maintenance dose every 12h had AUCss, 24 h, and Css, av values of 117.70 ± 37.03 µg h/mL and 4.14 ± 1.74 µg/mL, respectively. For patients receiving a 100 mg maintenance dose, these values were 152.73 ± 70.09 µg h/mL and 5.43 ± 2.85 µg/mL, respectively. Conclusion: The validated HPLC-MS/MS method was successfully applied to a study on the pharmacokinetics of PB in elderly patients infected with multidrug-resistant Gram-negative bacteria. Both two dose strategies in this study would have a excessive PB exposure in the elderly patients then the therapeutic window recommended by guidelines.

Unveiling Influences of metal-based nanomaterials on wheat growth and physiology: From benefits to detriments.

Metal-based nanomaterials (MNs) are widely used in agricultural production. However, our current understanding of the overall effects of MNs on crop health is insufficient. A global meta-analysis of 144 studies involving approximately 2,000 paired observations was conducted to explore the impacts of MNs on wheat growth and physiology. Our analysis revealed that the MN type plays a key role in influencing wheat growth. Ag MNs had significant negative effects on wheat growth and physiology, whereas Fe, Ti, and Zn MNs significantly increased wheat biomass and photosynthesis. Our study also observed a clear dose-specific effect, with a decrease in wheat shoot biomass with increasing MN concentrations. Meanwhile, MNs with small sizes (< 25 nm) have no significant impacts on wheat growth. Furthermore, both the root and foliar applications significantly improved wheat growth, with no considerable differences. Using a machine learning approach, we found that the MN type was the main driving factor affecting wheat shoot biomass, followed by MN dose and size. Overall, wheat growth and physiology can be negatively influenced by specific MNs, for which a high dose and small size should be avoided in practical applications. Therefore, our study can provide insights into the future design and safe use of MNs in agriculture and increase the public acceptance of nano-agriculture.

Factors influencing the third COVID-19 vaccine booster dose acceptance among older adults in northern Thailand.

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes more deaths in older adults than in younger adults. Older adults are a vulnerable group with a high need for coronavirus vaccines to decrease the severity of the disease. The aim of this analytical cross-sectional study was to determine the factors influencing third COVID-19 vaccine booster dose acceptance among older adults in northern Thailand. METHODS: The study samples were composed of 2,155 older adults living in Kamphaeng Phet Province, northern Thailand. They were randomly selected by multistage random sampling. Data were collected in a self-administered questionnaire consisting of 7 parts: (1) personal factors, (2) knowledge about COVID-19, (3) perceived susceptibility to COVID-19 infection, (4) perceived severity of COVID-19, (5) perceived benefits of the third COVID-19 vaccine booster dose, (6) perceived barriers to the third COVID-19 vaccine booster dose vaccination, and (7) the third COVID-19 vaccine booster dose acceptance. Data were analyzed via frequency, percentage, mean, standard deviation, and binary logistic regression. All the significance levels were set to 0.05. RESULTS: The results indicated that only 28.5% of older adults accepted the third COVID-19 vaccine booster dose. The factors influencing third COVID-19 vaccine booster dose acceptance among older adults included 5 variables. The participants aged ≥ 70 years was 1.37 times (95%CI = 1.12-1.69) greater than those aged < 70 years who accepted the vaccine. Participants who were married were more likely to accept the vaccine by 1.39 times (95%CI = 1.09-1.79) compared with single individuals. Those with underlying diseases tended to accept the vaccine by 1.56 times (95%CI = 1.26-1.92) more than those without underlying diseases. Those who had high perceived benefit from the COVID-19 vaccine possibly accepted the vaccine by 1.50 times (95%CI = 1.10-2.04) more than those with low perceived benefit, and those who had a low perceived barrier to the third COVID-19 booster dose vaccination seemed to accept the vaccine by 1.29 times (95%CI = 1.01-1.52) more than those with a high perceived benefit. CONCLUSION: Older adults should receive health education regarding the perceived benefit of the COVID-19 vaccine and the perceived barrier to COVID-19 vaccination, especially older adults aged < 70 years, those who are single, and those who are free of underlying diseases.

High dose opioid agonist therapy for patients with opioid use disorder: a case series exploring this patient-centered approach.

OBJECTIVES: Management of opioid withdrawal in the inpatient setting can vary widely depending on the patient, the physician, and the institution. Although buprenorphine and methadone are first-line therapy for withdrawal management, some patients experience barriers to those medications. In this case series, we explore high dose opioid agonist therapy (HDOAT) as a novel and effective option to bridge to recovery in this particular setting. METHODS: This retrospective case series includes- five patients with opioid use disorder (OUD) who were treated with HDOAT while hospitalized and reports on their outcomes. RESULTS: All five patients completed lifesaving medical therapy, engaged with community health workers for resources, and successfully transitioned to medications for opioid use disorder (MOUD). More importantly, none of the patients had patient directed discharges (PDDs). Furthermore, there were no inpatient drug uses or overdoses requiring naloxone administration, even with very high doses of oxycodone. None of the five patients were readmitted within thirty days. CONCLUSIONS: Although more rigorous research is needed, HDOAT may be a viable strategy for OUD when patients continued to decline buprenorphine or methadone on admission. This case series demonstrated the successful use of this strategy toward preventing PDDs, promoting treatment completion, and allowing substance recovery and rehabilitation, in patients who elected to defer MOUD on arrival.

The Use of Survival Dose-Rate Dependencies as Theoretical Discrimination Criteria for In-Silico Dynamic Radiobiological Models.

Introduction: Cell repair dynamics are crucial in optimizing anti-cancer therapies. Various assays (eg, comet assay and γ-H2AX) assess post-radiation repair kinetics, but interpreting such data is challenging and model-based data analyses are required. However, ambiguities in parameter calibration remain an unsolved challenge. To address this, we propose combining survival dose-rate effects with computer simulations to gain knowledge about repair kinetics. Methods: After a literature review, theoretical discriminators based on common fractionation/dose-rate-related effects were defined to discard unrealistic model dynamics. The Multi-Hit Repair (MHR) model was calibrated with canine osteosarcoma Abrams cell line data to study the discriminators' efficacy in scenarios with limited survival data. Additionally, survival dose-rate-dependent data from the human SiHa cervical cancer cell line were used to illustrate the survival behavior at diverse dose-rates and the capability of the MHR to model these data. Results: SiHa data confirmed the validity of the proposed discriminators. The discriminators filtered 99% of parameter sets, improving the calibration of Abrams cells data. Furthermore, results from both cell lines may hint universal aspects of cellular repair. Conclusions: Dose-rate theoretical discrimination criteria are an effective method to understand repair kinetics and improve radiobiological model calibration. Moreover, this methodology may be used to analyze diverse biological data using dynamic models in-silico.

An Analysis of the Radiosensitiser Applications in the Biomedical Field.

BACKGROUND: Various types of radiosensitisers have been introduced from the past until the present day for applications in the biomedical field. However, there is a lack of understanding and comparison between the various parameters introduced in addition to a lack of consensus among researchers on the optimal radiosensitiser for applications in the biomedical field. OBJECTIVE: This review aimed to investigate the usage of radiosensitisers in the biomedical field, determine their important parameters, and suggest radiosensitisers with potential among the analysed radiosensitisers. RESULTS AND CONCLUSION: This review has discussed several parameters for radiosensitisers, including median lethal dose, cell survival, tumour size, cell viability, Dose Enhancement Factor (DEF), Reactive Oxygen Species (ROS) concentration, radiosensitiser production complexity, radiosensitiser administration technique, and radiosensitiser toxicity. General trends regarding the development of radiosensitisers, including the types, effectiveness, and their production complexity, have also been discussed within this review article.