Combinations of two imaging parameters to improve bone mineral density (BMD) assessment in patients with lumbar degenerative diseases.

PURPOSE: To explore whether combining the Hounsfield unit (HU) values and vertebral bone quality (VBQ) scores can improve the BMD assessment in patients with lumbar degenerative diseases. METHODS: The HU values were measured by CT image, and VBQ scores were calculated by lumbar MRI image. The correlations of the opportunistic imaging parameters to the lowest T-scores were analyzed. Receiver-operating characteristic curve (ROC) analysis was used to evaluate the accuracy in detecting osteoporosis. Finally, the specificity and sensitivity of different combined methods of the HU values and VBQ scores in the diagnosis of osteoporosis were compared. RESULTS: Patients with osteoporosis had the lowest HU values and the highest VBQ scores. The correlation coefficients between the VBQ scores and the T-scores were smaller than HU values (L1 HU value: 0.702; average HU value:0.700; L1 VBQ score: -0.413; VBQ score: -0.386). The areas under the curve (AUCs) of the HU values were greater than those of the VBQ scores, and the AUCs of the L1 VBQ score were similar to the VBQ score (L1 HU value: 0.850; average HU value:0.857; L1 VBQ score: 0.704; VBQ score: 0.673). When combining the two imaging parameters in series, the specificity of the detection of osteoporosis was improved (L1 HU value and L1 VBQ score: 87.3%; Average HU value and VBQ score: 85.9%). When combining the two imaging parameters in parallel, the sensitivity of the detection of osteoporosis was improved (L1 HU value or L1 VBQ score: 88.1%; Average HU value or VBQ score: 91.5%). CONCLUSIONS: Combinations of the HU values and VBQ scores could improve the diagnostic performance of osteoporosis. In addition, considering the same diagnostic performance but easier measurement, parameters at the single-segment level were recommended to assist in the diagnosis of osteoporosis.

Atom-economic and stereoselective catalytic synthesis of fully substituted enol esters/carbonates of amides in acyclic systems enabled by boron Lewis acid catalysis.

Carboacyloxylation of internal alkynes is emerging as a powerful and straightforward strategy for enol ester synthesis. However, the reported examples come with limitations, including the utilization of noble metal catalysts, the control of regio- and Z/E selectivity, and an application in the synthesis of enol carbonates. Herein, a boron Lewis acid-catalyzed intermolecular carboacyloxylation of ynamides with esters to access fully substituted acyclic enol esters in high yield with generally high Z/E selectivity (up to >96 : 4) is reported. Most importantly, readily available allylic carbonates are also compatible with this difunctionalization reaction, representing an atom-economic, catalytic and stereoselective protocol for the construction of acyclic ß,ß-disubstituted enol carbonates of amides for the first time. The application of the carboacyloxylation products to decarboxylative allylations provided a ready access to enantioenriched α-quaternary amides. Moreover, experimental studies and theoretical calculations were performed to illustrate the reaction mechanism and rationalize the stereochemistry.

Dual-Input Transformer: An End-to-End Model for Preoperative Assessment of Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Ultrasonography.

Neoadjuvant chemotherapy (NAC) is the primary method to reduce the burden of tumor and metastasis; in the treatment of breast cancer, it may provide additional opportunities for breast-conserving surgery. Preoperative assessment of pathological complete response (PCR) to NAC is important for developing individualized treatment approaches and predicting patient prognosis. Compared to magnetic resonance imaging (MRI) and mammography, ultrasonography (US) has the advantages of simplicity, flexibility, and real-time imaging. Moreover, it does not require radiation and can provide multi-time acquisition of the tumor during NAC treatment. Recently, deep learning radiomics models based on multi-time-point US images for the prediction of NAC effectiveness have been proposed. To further improve the prediction performance, we carefully designed four supporting modules for our proposed dual-input transformer (DiT): isolated tokens-to-token patch embedding module, shared position embedding, time embedding, and weighted average pooling feature representation modules. The design of each module considers the characteristics of the US images at multiple time points. We validated our model on our retrospective US dataset composed of 484 cases from two centers whose consistency is not sufficiently high. Patients were allocated to training (n = 297), validation (n = 99), and external test (n = 88) sets. The results show that our model can achieve better performance than the Siamese CNN and the standard tokens-to-token vision transformer without using multi-time-point images. The ablation study also proved the effectiveness of each module designed for DiT.

Artificial intelligence-powered smartphone application, AICaries, improves at-home dental caries screening in children: Moderated and unmoderated usability test.

Early Childhood Caries (ECC) is the most common childhood disease worldwide and a health disparity among underserved children. ECC is preventable and reversible if detected early. However, many children from low-income families encounter barriers to dental care. An at-home caries detection technology could potentially improve access to dental care regardless of patients' economic status and address the overwhelming prevalence of ECC. Our team has developed a smartphone application (app), AICaries, that uses artificial intelligence (AI)-powered technology to detect caries using children's teeth photos. We used mixed methods to assess the acceptance, usability, and feasibility of the AICaries app among underserved parent-child dyads. We conducted moderated usability testing (Step 1) with ten parent-child dyads using "Think-aloud" methods to assess the flow and functionality of the app and analyze the data to refine the app and procedures. Next, we conducted unmoderated field testing (Step 2) with 32 parent-child dyads to test the app within their natural environment (home) over two weeks. We administered the System Usability Scale (SUS) and conducted semi-structured individual interviews with parents and conducted thematic analyses. AICaries app received a 78.4 SUS score from the participants, indicating an excellent acceptance. Notably, the majority (78.5%) of parent-taken photos of children's teeth were satisfactory in quality for detection of caries using the AI app. Parents suggested using community health workers to provide training to parents needing assistance in taking high quality photos of their young child's teeth. Perceived benefits from using the AICaries app include convenient at-home caries screening, informative on caries risk and education, and engaging family members. Data from this study support future clinical trial that evaluates the real-world impact of using this innovative smartphone app on early detection and prevention of ECC among low-income children.

Clustering of longitudinal physical activity trajectories among young females with selection of associated factors.

We examined multi-level factors related to the longitudinal physical activity trajectories of adolescent girls to determine the important predictors for physical activity. The Trial of Activity in Adolescent Girls (TAAG) Maryland site recruited participants at age 14 (n = 566) and followed up with these girls at age 17 (n = 553) and age 23 (n = 442). Individual, social factors and perceived environmental factors were assessed by questionnaire; body mass index was measured at age 14 and age 17, and self-reported at age 23. Neighborhood factors were assessed by geographic information systems. The outcome, moderate-to-vigorous physical activity (MVPA) minutes in a day, was assessed from accelerometers. A mixture of linear mixed-effects models with double penalization on fixed effects and random effects was used to identify the intrinsic grouping of participants with similar physical activity trajectory patterns and the most relevant predictors within the groups simultaneously. Three clusters of participants were identified. Two hundred and forty participants were clustered as "maintainers" and had consistently low MVPA over time; 289 participants were clustered as "decreasers" who had decreasing MVPA over time; 39 participants were grouped as "increasers" and had increasing MVPA over time. Each of the three clusters has its own cluster-specific factors identified using the clustering method, indicating that each cluster has unique characteristics.

Assessment of Primary Colorectal Cancer CT Radiomics to Predict Metachronous Liver Metastasis.

Objectives: To establish and validate a machine learning-based CT radiomics model to predict metachronous liver metastasis (MLM) in patients with colorectal cancer. Methods: In total, 323 patients were retrospectively recruited from two independent institutions to develop and evaluate the CT radiomics model. Then, 1288 radiomics features were extracted to decode the imaging phenotypes of colorectal cancer on CT images. The optimal radiomics features were selected using a recursive feature elimination selector configured by a support vector machine. To reduce the bias caused by an unbalanced dataset, the synthetic minority oversampling technique was applied to resample the minority samples in the datasets. Then, both radiomics and clinical features were used to train the multilayer perceptron classifier to develop two classification models. Finally, a score-level fusion model was developed to further improve the model performance. Results: The area under the curve (AUC) was 0.78 ± 0.07 for the tumour feature model and 0.79 ± 0.08 for the clinical feature model. The fusion model achieved the best performance, with AUCs of 0.79 ± 0.08 and 0.72 ± 0.07 in the internal and external validation cohorts. Conclusions: Radiomics models based on baseline colorectal contrast-enhanced CT have high potential for MLM prediction. The fusion model combining radiomics and clinical features can provide valuable biomarkers to identify patients with a high risk of colorectal liver metastases.

Assessment of an Innovative Mobile Dentistry eHygiene Model Amid the COVID-19 Pandemic in the National Dental Practice-Based Research Network: Protocol for Design, Implementation, and Usability Testing.

BACKGROUND: Amid COVID-19, and other possible future infectious disease pandemics, dentistry needs to consider modified dental examination regimens that render quality care, are cost effective, and ensure the safety of patients and dental health care personnel (DHCP). Traditional dental examinations, which number more than 300 million per year in the United States, rely on person-to-person tactile examinations, pose challenges to infection control, and consume large quantities of advanced-level personal protective equipment (PPE). Therefore, our long-term goal is to develop an innovative mobile dentistry (mDent) model that takes these issues into account. This model supplements the traditional dental practice with virtual visits, supported by mobile devices such as mobile telephones, tablets, and wireless infrastructure. The mDent model leverages the advantages of digital mobile health (mHealth) tools such as intraoral cameras to deliver virtual oral examinations, treatment planning, and interactive oral health management, on a broad population basis. Conversion of the traditional dental examinations to mDent virtual examinations builds upon (1) the reliability of teledentistry, which uses intraoral photos and live videos to make diagnostic decisions, and (2) rapid advancement in mHealth tool utilization. OBJECTIVE: In this pilot project, we designed a 2-stage implementation study to assess 2 critical components of the mDent model: virtual hygiene examination (eHygiene) and patient self-taken intraoral photos (SELFIE). Our specific aims are to (1) assess the acceptance and barriers of mDent eHygiene among patients and DHCP, (2) assess the economic impact of mDent eHygiene, and (3) assess the patient's capability to generate intraoral photos using mHealth tools (exploratory aim, SELFIE). METHODS: This study will access the rich resources of the National Dental Practice-Based Research Network to recruit 12 dentists, 12 hygienists, and 144 patients from 12 practices. For aims 1 and 2, we will use role-specific questionnaires to collect quantitative data on eHygiene acceptance and economic impact. The questionnaire components include participant characteristics, the System Usability Scale, a dentist-patient communication scale, practice operation cost, and patient opportunity cost. We will further conduct a series of iterative qualitative research activities using individual interviews to further elicit feedback and suggestion for changes to the mDent eHygiene model. For aim 3, we will use mixed methods (quantitative and qualitative) to assess the patient's capability of taking intraoral photos, by analyzing obtained photos and recorded videos. RESULTS: The study is supported by the US National Institute of Dental and Craniofacial Research. This study received "single" institutional review board approval in August 2021. Data collection and analysis are expected to conclude by December 2021 and March 2022, respectively. CONCLUSIONS: The study results will inform the logistics of conducting virtual dental examinations and empowering patients with mHealth tools, providing better safety and preserving PPE amid the COVID-19 and possible future pandemics. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/32345.

Utility of ctDNA in predicting response to neoadjuvant chemoradiotherapy and prognosis assessment in locally advanced rectal cancer: A prospective cohort study.

BACKGROUND: For locally advanced rectal cancer (LARC) patients who receive neoadjuvant chemoradiotherapy (nCRT), there are no reliable indicators to accurately predict pathological complete response (pCR) before surgery. For patients with clinical complete response (cCR), a "Watch and Wait" (W&W) approach can be adopted to improve quality of life. However, W&W approach may increase the recurrence risk in patients who are judged to be cCR but have minimal residual disease (MRD). Magnetic resonance imaging (MRI) is a major tool to evaluate response to nCRT; however, its ability to predict pCR needs to be improved. In this prospective cohort study, we explored the value of circulating tumor DNA (ctDNA) in combination with MRI in the prediction of pCR before surgery and investigated the utility of ctDNA in risk stratification and prognostic prediction for patients undergoing nCRT and total mesorectal excision (TME). METHODS AND FINDINGS: We recruited 119 Chinese LARC patients (cT3-4/N0-2/M0; median age of 57; 85 males) who were treated with nCRT plus TME at Fudan University Shanghai Cancer Center (China) from February 7, 2016 to October 31, 2017. Plasma samples at baseline, during nCRT, and after surgery were collected. A total of 531 plasma samples were collected and subjected to deep targeted panel sequencing of 422 cancer-related genes. The association among ctDNA status, treatment response, and prognosis was analyzed. The performance of ctDNA alone, MRI alone, and combining ctDNA with MRI was evaluated for their ability to predict pCR/non-pCR. Ranging from complete tumor regression (pathological tumor regression grade 0; pTRG0) to poor regression (pTRG3), the ctDNA clearance rate during nCRT showed a significant decreasing trend (95.7%, 77.8%, 71.1%, and 66.7% in pTRG 0, 1, 2, and 3 groups, respectively, P = 0.008), while the detection rate of acquired mutations in ctDNA showed an increasing trend (3.8%, 8.3%, 19.2%, and 23.1% in pTRG 0, 1, 2, and 3 groups, respectively, P = 0.02). Univariable logistic regression showed that ctDNA clearance was associated with a low probability of non-pCR (odds ratio = 0.11, 95% confidence interval [95% CI] = 0.01 to 0.6, P = 0.04). A risk score predictive model, which incorporated both ctDNA (i.e., features of baseline ctDNA, ctDNA clearance, and acquired mutation status) and MRI tumor regression grade (mrTRG), was developed and demonstrated improved performance in predicting pCR/non-pCR (area under the curve [AUC] = 0.886, 95% CI = 0.810 to 0.962) compared with models derived from only ctDNA (AUC = 0.818, 95% CI = 0.725 to 0.912) or only mrTRG (AUC = 0.729, 95% CI = 0.641 to 0.816). The detection of potential colorectal cancer (CRC) driver genes in ctDNA after nCRT indicated a significantly worse recurrence-free survival (RFS) (hazard ratio [HR] = 9.29, 95% CI = 3.74 to 23.10, P < 0.001). Patients with detectable driver mutations and positive high-risk feature (HR_feature) after surgery had the highest recurrence risk (HR = 90.29, 95% CI = 17.01 to 479.26, P < 0.001). Limitations include relatively small sample size, lack of independent external validation, no serial ctDNA testing after surgery, and a relatively short follow-up period. CONCLUSIONS: The model combining ctDNA and MRI improved the predictive performance compared with the models derived from individual information, and combining ctDNA with HR_feature can stratify patients with a high risk of recurrence. Therefore, ctDNA can supplement MRI to better predict nCRT response, and it could potentially help patient selection for nonoperative management and guide the treatment strategy for those with different recurrence risks.

Oral health and Candida carriage in socioeconomically disadvantaged US pregnant women.

BACKGROUND: Despite the well-documented associations between poor maternal oral health and increased risk for adverse birth outcomes and dental caries in children after birth, prenatal oral health care is under-utilized, especially among the underserved population. In addition, oral Candida has recently been suggested as a potential culprit for children's dental caries, with evident maternal contributions. Therefore, this study aimed to obtain epidemiological data on the oral health and oral Candida carriage in a cohort of underserved US pregnant women, and reveal factors associated with their oral Candida carriage. METHODS: Demographic-medical-oral hygiene practice data were collected. Comprehensive oral examination was conducted. Caries status and plaque index were recorded. Oral samples (saliva, plaque and swab) were processed to identify Candida species and Streptococcus mutans by culturing-dependent and -independent methods. Multiple logistic regression analyses were used to identify factors associated with oral Candida carriage and caries severity. RESULTS: Eighty-two socioeconomically disadvantaged women (48 pregnant and 34 non-pregnant) were enrolled. More pregnant women (79.1%) had > = 1 untreated decayed tooth when compared to their non-pregnant counterparts (47.1%) (p = 0.01). The average number of decayed teeth in pregnant and non-pregnant women was 3.9 and 3.1 (p > 0.05). Caries severity was positively associated with race (African American vs. white), plaque index and salivary Candida albicans level. C. albicans was the most predominant/abundant Candida strain, with cheek and tonsil as the most common colonized sites. The detection of C. albicans was 56%/56% in saliva and 40%/47% in plaque of the pregnant and non-pregnant groups, respectively. Study women's oral Candida carriage is positively associated with hypertension [p = 0.03, odds ratio = 14.47(1.28, 163.51)], decayed teeth number [p = 0.04, odds ratio = 1.31 (1.01,1.69)] and salivary S. mutans level [p = 0.03, odds ratio = 4.80 (1.18-19.43)]. CONCLUSIONS: Socioeconomically disadvantaged US women are in need of improved prenatal oral health, a large proportion of them have untreated decayed teeth and high carriage of oral Candida. Due to the observed significant association between the decayed teeth number and oral Candida carriage, providing oral health care during pregnancy (including limiting decayed teeth) will not only improve women's oral health, but also present as a promising approach to reduce oral Candida carriage in women.

Longitudinal Sedentary Time Among Females Aged 17 to 23 Years.

INTRODUCTION: Time spent in sedentary behaviors is a newer risk factor for poor cardiometabolic health. This study examined longitudinal correlates of sedentary time among a cohort of females from about age 17 to age 23 years. METHODS: The cohort included females originally participating in the Trial of Activity for Adolescent Girls Maryland site who had assessments in 2009 and 2015 (n=431). Percentage daily time in sedentary behaviors was determined from accelerometers. Sociodemographics, psychosocial factors, and health behaviors were assessed by questionnaire. Lasso variable selection identified potential variables included in linear mixed effects models. As a secondary analysis, a k-means algorithm for longitudinal data identified homogeneous clusters of individual sedentary time trajectories. RESULTS: Percentage daily sedentary time did not change over time (67% to 68%). Not of black race (p=0.04), higher father's education (p<0.001), more weekday computer hours (p<0.001), more weekend TV hours (p=0.01), more physical activity barriers (p=0.003), fewer days per week driving (p=0.01), and more vehicles in the household (p=0.02) were associated with greater sedentary time. Cluster analysis resulted in two patterns: more (70%) versus less (60%) time being sedentary. The more sedentary individuals were more likely to be college graduates (p<0.001), have a higher income (p=0.03), and work fewer hours (p=0.009). They were also less likely to be married or in a common-law relationship (p=0.05) or in a parenting role (p=0.02). CONCLUSIONS: Time spent in sedentary behaviors remained stable. Factors associated with sedentary time were significant across the socioecologic framework and included several factors indicating higher SES.

Dynamic 1H-MRS assessment of brain tumors: a novel approach for differential diagnosis of glioma.

PURPOSE: To determine whether the changes of [Cho/NAA] ratio in patients with glioma, measured by dynamic 1H-MRS can be used to differentiate between high-grade and low-grade gliomas. MATERIALS AND METHODS: This prospective study was approved by the institutional ethics committee. Written informed consent was obtained. Forty-nine patients with biopsy-proven glioma and 20 normal control subjects were recruited in this study. The maximum [Cho/NAA] ratios, acquired at 0 min, and at 6 min, were calculated and assessed from volume of interests (VOI) in the tumor areas and in the surrounding normal tissue for each patient. Absolute difference in the [Cho/NAA] ratios, from MRS acquired at 0 and 6 min, in high-grade glioma, low-grade glioma, and control subjects were compared. RESULTS: The maximum [Cho/NAA] ratio acquired from the tumor area at the 0 min is 6.08 ± 2.02, which was significantly different (p = .017) from that acquired after 6 min, 4.87 ± 2.13. The [Cho/NAA] ratio from the surrounding normal tissue area did not change significantly from spectra acquired at different times (0 min, 6 min). Absolute difference in [Cho/NAA] ratios acquired at 0 and 6 min time points were significantly higher (P < 0.001) in high-grade glioma (= 3.86 ± 3.31) than in low-grade glioma (= 0.81 ± 0.90), and control subjects (0.061 ± 0.026, P = 0.000), while there was no significantly difference in low-grade glioma and control subjects. CONCLUSIONS: Dynamic 1H-MRS can be useful for differential diagnosis between high-grade and low-grade gliomas as well as insight into the heterogeneity within the tumor.

Multilevel correlates of physical activity for early, mid, and late adolescent girls.

BACKGROUND: We examined associations among multilevel variables and girls' physical activity to determine whether they vary at different adolescent ages. METHODS: All field sites of the Trial of Activity for Adolescent Girls contributed participants from 6th (n = 1576) and 8th grades (n = 3085). The Maryland site contributed an 11th grade sample (n = 589). Questionnaires were used to obtain demographic and psychosocial information (individual- and social-level variables); height, weight, and triceps skinfold to assess body composition; interviews and surveys for school-level data; and geographical information systems and self-report for neighborhood-level variables. Moderate to vigorous physical activity minutes (MVPA) were assessed from accelerometers. Mixed models (13 individual, 5 social, 15 school, 12 neighborhood variables) were used to determine multilevel associations. RESULTS: Variables at individual, social, school, and neighborhood levels were associated with MVPA, but differed across grades. Lower percent body fat, higher social support from friends, and lower school math scores were associated with higher MVPA at 6th and 8th grade. Higher physical activity self-efficacy was associated with higher MVPA at 11th grade. Only lower physical activity barriers were associated with higher MVPA at all grades. CONCLUSION: MVPA is a complex behavior with fluid, multilevel correlates that differ among girls across middle and high school.

Combined diffusion- and perfusion-weighted imaging: a new way for the assessment of hemispheric transient ischemic attack patients.

Abnormalities in diffusion-weighted and perfusion-weighted magnetic resonance images not only occur in stroke patients but also in transient ischemic attack patients. We found magnetic resonance images were abnormal in 28 patients (68%): 15 had diffusion-weighted imaging abnormalities, 7 had both diffusion-weighted imaging and perfusion-weighted imaging defects and 6 had an isolated perfusion-weighted imaging abnormality. Patients with shorter onset to magnetic resonance imaging, large artery atherothrombosis, coronary artery disease, hyperlipidemia and hemiparesis were more likely to show perfusion-weighted imaging abnormalities. Compared with patients who had a good prognosis, in poor prognosis patients, the relative cerebral blood flow and relative cerebral blood volume was significantly higher. The data suggest that transient ischemic attack patients are more likely to have a poor prognosis when white matter of the symptomatic side shows hyperperfusion within 24 h of symptom onset; however, patients are more likely to have a good prognosis when white matter of the symptomatic side shows hypoperfusion.

[Assessment of upper jaw extraction versus upper and lower jaw extraction treatment for class II division 1 malocclusion using peer assessment rating index].

OBJECTIVE: To assess the outcome of orthodontic treatment with upper jaw or upper and lower jaw extraction for Class II division 1 malocclusion using the peer assessment rating (PAR) index. METHODS: 28 patients with Class II division 1 were extracted two first premolars or second premolars of upper jaw, and 24 patients were extracted four premolars of upper and lower jaw N. The PAR was applied on pre-and post-orthodontic treatment dental casts for the fifty-two cases. RESULTS: The upper and lower jaw extraction groups had significantly higher initial PAR scores and the weighted PAR total scores (P<0.05). Although significantly different before treatment, both groups were not statistically different after treatment (P>0.05). CONCLUSION: The upper and lower jaw extraction cases showed more severe dental displacement. Both treatment can acquire successful results.

[Primary assessment of treatment effect of thymosin alpha1 on chemotherapy-induced neurotoxicity].

BACKGROUND & OBJECTIVE: Clinical trails showed that thymosin alpha1 offers protection from toxicities (nausea, vomiting, fatigue) of chemotherapy. This study was designed to investigate the protection of thymosin alpha1 to nervous system. METHODS: Twenty-two patients with advanced lung cancer, or advanced breast cancer were treated with vinorelbine (25 mg/m(2), d(1), d(8)) combined with cisplatin (80 mg/m(2), d(1)), or gemcitabine (1.25 g/m(2), d(1), d(8)) combined with cisplatin (80 mg/m(2), d(1)),or paclitaxel (80 mg/m(2), d(1), d(8), d(15)) combined with carboplatin (AUC=6 d(1)),or paclitaxel (80 mg/m(2), d(1), d(8), d(15)) combined with epirubicin (80 mg/m(2), d(1)). They all experienced grade 2 to 4 of neurotoxicities according to common toxicity criteria of National Cancer Institute after chemotherapy. The same chemotherapy regimens were combined with thymosin alpha1 (1.6 mg/d for 4 days before chemotherapy, and 1.6 mg twice weekly for 1-3 weeks after chemotherapy began) in the next cycle. Clinical neurologic evaluation was performed at baseline every week. RESULTS: In 10 patients (45.4%), neurotoxicities reduced from grade 2-4 before chemotherapy to less than grade 2 after chemotherapy. CONCLUSION: Thymosin alpha1 may prevent patients from chemotherapy-induced neurotoxicities.