Rank Order Correlation Analysis Research Articles

Abstract 7195: Repurposing non-oncology drugs with MET inhibitory effect to overcome osimertinib resistance in lung cancer

Abstract Background and Aim: Osimertinib is the only 3rd generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for the 1st line therapy of advanced NSCLC patients with EGFR mutations. However, drug resistance is severely limiting its clinical efficacy. Aberrant MET activation is an important mechanism causing osimertinib resistance. There is no effective therapeutic option after osimertinib failure. This study investigated the repurposing of non-oncology MET inhibiting drug to overcome osimertinib resistance. Method: A few clinically-approved drugs with putative MET inhibitory effects were identified by a computational drug repurposing tool called “DRAR-CPI” via analysis of the chemical-protein interactome of known MET inhibitors (crizotinib, cabozantinib, foretinib, and tivantinib). Fexofenadine (FEX), originally indicated for allergic rhinitis and chronic urticaria, was chosen for detailed investigation in osimertinib-resistant NSCLC cell lines that exhibit aberrant MET activation with/without other EGFR-dependent osimertinib resistance mechanisms. The selectivity of kinase inhibition by FEX was evaluated by a KINOME profiling assay against a panel of human protein kinases. Western blot analysis was conducted to examine the activation status of Met and EGFR downstream signaling. RNA sequencing was performed to identify differentially expressed genes (DEGs) triggered by the most promising repurposed drug, presumably contributing to osimertinib resistance circumvention. Sulforhodamine B assay was used to evaluate cell proliferation. The circumvention of osimertinib resistance by FEX was further verified in a patient-derived tumor xenograft (PDX) from an advanced-stage osimertinib-refractory NSCLC patient. Result: FEX was found to inhibit recombinant MET kinase in cell-free assays in a dose- and time-dependent manner. It also inhibited MET phosphorylation and other downstream signaling molecules in osimertinib-resistant NSCLC cell lines harboring EGFR T790M+MET amplification or EGFR T790M loss+MET amplification. KINOME profiling revealed a similar kinase inhibition profile between FEX and cabozantinib using Spearman rank order correlation analysis. Among the tested osimertinib-resistant NSCLC cell lines, FEX showed the highest effectiveness in potentiating the anticancer effect of osimertinib in H820 cells (having MET amplification & EGFR T790M mutation). Transcriptome profiling analysis in H820 cells before and after FEX treatment revealed that the majority of DEGs were enriched in EMT-related biological processes and pathways. FEX was further shown to significantly potentiate the antitumor effect of osimertinib in a drug refractory PDX model, without inducing notable weight loss in the animals. Conclusion: These findings advocate the clinical evaluation of repurposing FEX to overcome osimertinib resistance. Citation Format: Kenneth K.W. To, Kwong Sak Leung, William C.S. Cho. Repurposing non-oncology drugs with MET inhibitory effect to overcome osimertinib resistance in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7195.

P006 The Impact of Growth Hormone Treatment on Cardiovascular Control in Children with Prader-Willi syndrome

Abstract Background Many children with Prader-Willi syndrome (PWS) are treated with growth hormone (GH), which may increase the risk of obstructive sleep apnoea. Children with PWS also have impaired cardiac autonomic control due to reduced parasympathetic activity, which may increase cardiovascular risk, however the impact of GH on autonomic control is yet to be elucidated. Methods Pre- and post-GH polysomnographic data in 38 children (aged 0-18 years) were retrospectively collected. Spectral analysis of heart rate variability (HRV) was used to determine total, low frequency (LF, sympathetic and parasympathetic activity), high frequency (HF, parasympathetic activity) power and LF/HF (sympathovagal balance). Data were compared with Wilcoxon Signed Rank Test and Spearman Rank Order Correlation analysis and are presented as median [interquartile range]. Results HRV data were significantly correlated with age so children were grouped into those <2 years (n=22) and >2 years (n=16). There were no significant differences in the obstructive or central apnoea-hypopnoea indexes between pre- and post-GH studies in either group. In children <2 years, there were no significant differences in total power, LF, HF and LF/HF between studies. In children >2 years, total power (1912.2 ms2, [920.2, 4916.1] vs 1010.2 ms2 [416.0, 2828.7), LF (434.0 ms2 [247.0, 1340.7] vs 278.9 ms2 [83.4, 676.0]) and HF (986.0 ms2 [321.8, 2400.6] vs 414.4 ms2 [146.2, 1152.7]) were lower (p< 0.01 for all) post-GH. Conclusions Our results demonstrate that GH decreases both sympathetic and parasympathetic activity during sleep in children >2 years, which could further increase cardiovascular risk.

Assessment of life quality and influencing factors in adults with atopic dermatitis in the Northeast of China

Atopic dermatitis (AD) affects patients’ quality of life (QOL) as well as their physical and mental health. Influencing factors of AD should be considered and minimized to the controllable range. In addition, exploring the intervention of psychiatric factors may provide new ideas for the treatment of AD. To investigate the QOL and its influencing factors in adult patients with AD, the physical and mental health of 133 AD patients in Changchun City, Jilin province, Northeast of China, was investigated by conducting online questionnaires from August 2020 to April 2022. The information about patients’ demographics, atopic comorbidities, and whether they were accompanied by anxiety and depression was collected. The Dermatology Life Quality Index and Hospital Anxiety and Depression Scale were used to assess their QOL, anxiety, depression, and psychological characteristics. Logistic regression was used to analyze their influencing factors. A total of 106 patients with valid response questionnaires were included. The survey results showed that the QOL was affected in 59.43% (63/106) of patients, while abnormal anxiety patients accounted for 8.49% (9/106) and abnormal depression patients accounted for 29.25% (31/106). Logistic regression showed that the QOL and anxiety of AD patients were not related to demographic characteristics such as age, sex, and atopic comorbidities. The risk factors of depression were middle school education or below (Wald = 4.679, P = 0.031) and outdoor working environment (Wald = 4.583, P = 0.032). Spearman’s rank-order correlation analysis of QOL, anxiety, and depression levels in dermatology showed two positive correlations (P < 0.01). AD affects patients’ QOL and has a serious negative psychological impact on patients. Dermatologists should be alert to mental symptoms when treating patients with AD.

Immunohistochemical Evaluation of Notch1 in Ovarian Tumours and Its Prognostic Implications.

Ovarian cancer is the fifth most common malignancy among women and the second most common gynaecological malignancy. Surface epithelial ovarian tumours constitute two-thirds of all ovarian tumours. Most high-grade serous carcinoma patients gain an initial complete response but eventually succumb to relapse and death leaving the overall survival grim. Therefore, new regimens targeting the pathways involved in metastasis and chemoresistance are essential for the development of more effective therapies. Notch signalling is one of the pleiotropic signalling pathways that plays a key role in differentiation and tissue morphogenesis. It has been observed that this Notch signalling pathway is seen to be deregulated in various cancers. It is thought to have an oncogenic role in ovarian cancer. Our objective in this study is to evaluate theimmunohistochemical expression pattern of Notch1 in surface epithelial ovarian tumours and its correlation with the clinicopathological profile. This study includes a total of 100 cases of borderline and malignant surface epithelial ovarian tumours. Clinical data of the patients were obtained from the medical records section. HPE slides were examined and one representative paraffin block was selected for each patient. IHC of Notch1 was performed and analyzed. The staining pattern for Notch1 was calculated using the Q score. Immunohistochemistry (IHC) evaluation of Notch1 in surface epithelial ovarian tumours in this study showed an increased intensity of Notch1 staining in high-grade serous malignant tumours.The grading and staging of tumours were compared with Notch1 expression. Statistical analysis was performed using Spearman Rank order correlation analysis. There was a significant correlation (0.01 level, two-tailed)between the grading and staging of ovarian tumours and Notch1 expression. Assessing Notch1 expression in ovarian cancer by IHC is a useful tool in view of its clinical applications, development oftargeted therapies andas a marker of prognosis. The intensity of the Notch1 stain appears to be directly proportional to the grade of tumour. This may offer a potential targeted therapy against the Notch signalling pathway in tumours that strongly express Notch1.

Levels of Procollagen Type I C-Terminal Pro-Peptide and Galectin-3, Arterial Stiffness Measured By Pulse Wave Velocity, and Cardiovascular Morbidity and Mortality in 44 Patients 2 Years After Kidney Transplantation.

BACKGROUND Cardiovascular (CV) mortality remains high despite the improvement of kidney function after kidney transplantation. In heart failure (HF), high concentrations of biomarkers of fibrosis, related to cardiac and/or vascular impairment, are associated with CV outcomes, but their significance in kidney transplantation is still unclear. Our aim was to investigate the association of procollagen type I C-terminal pro-peptide (PICP) and galectin-3 (Gal-3), markers of fibrosis, with arterial stiffness measured by pulse wave velocity (PWV) and CV morbi-mortality in kidney transplantation recipients from the prospective monocenter TRANSARTE study (Transplantation and Arteries), which compared the evolution of arterial stiffness in transplanted patients and patients remained on dialysis. MATERIAL AND METHODS PICP and Gal-3 were measured at 2 years after transplantation in 44 kidney transplantation patients. Spearman's rank-order correlation analysis was conducted to assess the relationship between biomarkers and PWV. Association of biomarkers with CV morbi-mortality was evaluated using Cox regression analysis adjusted for age, renal function, and PWV. RESULTS There was no significant correlation between PWV and PICP (r=-0.16, P=0.3) or Gal-3 (r=0.03, P=0.85). Gal-3, after adjusting for key prognostic factors, including PWV, was significantly associated with CV morbi-mortality [HR (95% CI)=4.30 (1.01-18.22), P=0.048], whereas PICP was not significantly associated with outcome. CONCLUSIONS In multivariable adjusted analysis, elevated Gal-3 concentrations were associated with CV morbi-mortality in kidney transplantation patients, whereas PICP was not. As Gal-3 was not related to PWV, other sources of fibrosis (eg, cardiac fibrosis) may be underlying the prognostic value of Gal-3 in kidney transplantation.

Knowledge, Attitudes, and Behaviors toward HIV/AIDS among Health Care Workers’ in Urban Cities in Leyte Philippines

Backgroud: The difficulty of curbing the incidence of HIV has long been associated with stigma, which has been linked to the lack of knowledge, poor attitudes, and discriminatory behaviours of healthcare workers. The study aimed to assess the knowledge, attitudes, behavior, and care barriers of healthcare workers from highly urbanised cities towards HIV/AIDS. Methods: A total of 171 healthcare workers in Leyte province were included in the study. The study utilized a self-report questionnaire and was conducted in the early quarter of 2021. Spearman rank-order correlation analysis was employed to answer the study's hypotheses. Results: Results revealed that the participants have moderate knowledge of HIV/AIDS and good work attitudes but have prejudicial attitudes and discriminatory behaviors toward their HIV/AIDS-related care. Furthermore, it was found that there is a positive correlation between knowledge and attitude, as well as attitude toward behaviors. Notably, results revealed no correlation between knowledge of HIV/AIDS and perceived behaviors. Conclusion: It can be concluded that health workers in highly urbanized cities like Leyte province have essential knowledge, attitude, and behaviors in providing care to clients suspected or confirmed of HIV/AIDS. A good attitude towards HIV suggests a likelihood of a health care provider having sufficient knowledge of HIV and practising caring behaviors.

Factors Impacting Invader-Mediated Recognition of Double-Stranded DNA.

The development of chemically modified oligonucleotides enabling robust, sequence-unrestricted recognition of complementary chromosomal DNA regions has been an aspirational goal for scientists for many decades. While several groove-binding or strand-invading probes have been developed towards this end, most enable recognition of DNA only under limited conditions (e.g., homopurine or short mixed-sequence targets, low ionic strength, fully modified probe strands). Invader probes, i.e., DNA duplexes modified with +1 interstrand zippers of intercalator-functionalized nucleotides, are predisposed to recognize DNA targets due to their labile nature and high affinity towards complementary DNA. Here, we set out to gain further insight into the design parameters that impact the thermal denaturation properties and binding affinities of Invader probes. Towards this end, ten Invader probes were designed, and their biophysical properties and binding to model DNA hairpins and chromosomal DNA targets were studied. A Spearman's rank-order correlation analysis of various parameters was then performed. Densely modified Invader probes were found to result in efficient recognition of chromosomal DNA targets with excellent binding specificity in the context of denaturing or non-denaturing fluorescence in situ hybridization (FISH) experiments. The insight gained from the initial phase of this study informed subsequent probe optimization, which yielded constructs displaying improved recognition of chromosomal DNA targets. The findings from this study will facilitate the design of efficient Invader probes for applications in the life sciences.

What was the Epidemiology and Global Burden of Disease of Hip Fractures From 1990 to 2019? Results From and Additional Analysis of the Global Burden of Disease Study 2019.

Hip fractures are associated with a high risk of death; among those who survive a hip fracture, many experience substantial decreases in quality of life. A comprehensive understanding of the epidemiology and burden of hip fractures by country, age, gender, and sociodemographic factors would provide valuable information for healthcare policymaking and clinical practice. The Global Burden of Disease (GBD) study 2019 was a global-level study estimating the burden of 369 diseases and injuries in 204 countries and territories. An exploration and additional analysis of the GBD 2019 would provide a clearer picture of the incidence and burden of hip fractures. Using data from the GBD 2019, we asked, (1) What are the global, regional, and national incidences of hip fractures, and how did they change over a recent 30-year span? (2) What is the global, regional, and national burden of hip fractures in terms of years lived with disability, and how did it change over that same period? (3) What is the leading cause of hip fractures? (4) How did the incidence and years lived with disability of patients with hip fractures change with age, gender, and sociodemographic factors? This was a cross-sectional study. Participant data were obtained from the GBD 2019 ( http://ghdx.healthdata.org/gbd-results-tool ). The GBD study is managed by the WHO, coordinated by the Institute of Health Metrics and Evaluation, and funded by the Bill and Melinda Gates Foundation. It estimates the burden of disease and injury for 204 countries by age, gender, and sociodemographic factors, and can serve as a valuable reference for health policymaking. All estimates and their 95% uncertainty interval (UI) were produced using DisMod-MR 2.1, a Bayesian meta-regression tool in the GBD 2019. In this study, we directly pulled the age-standardized incidence rate and years lived with disability rate of hip fractures by location, age, gender, and cause from the GBD 2019. Based on these data, we analyzed the association between the incidence rate and latitude of each country. Then, we calculated the estimated annual percentage change to represent trends from 1990 to 2019. We also used the Spearman rank-order correlation analysis to determine the correlation between the incidence or burden of hip fractures and the sociodemographic index, a composite index of the income per capita, average years of educational attainment, and fertility rates in a country. Globally, hip fracture incidences were estimated to be 14.2 million (95% UI 11.1 to 18.1), and the associated years lived with disability were 2.9 million (95% UI 2.0 to 4.0) in 2019, with an incidence of 182 (95% UI 142 to 231) and 37 (95% UI 25 to 50) per 100,000, respectively. A strong, positive correlation was observed between the incidence rate and the latitude of each country (rho = 0.65; p < 0.001). From 1990 to 2019, the global incidence rate for both genders remained unchanged (estimated annual percentage change 0.01 [95% confidence interval -0.08 to 0.11]), but was slightly increased in men (estimated annual percentage change 0.11 [95% CI 0.01 to 0.2]). The years lived with disability rate decreased slightly (estimated annual percentage change 0.66 [95% CI -0.73 to -0.6]). These rates were standardized by age. Falls were the leading cause of hip fractures, accounting for 66% of all patients and 55% of the total years lived with disability. The incidence of hip fractures was tightly and positively correlated with the sociodemographic index (rho 0.624; p < 0.001), while the years lived with disability rate was slightly negatively correlated (rho -0.247; p < 0.001). Most hip fractures occurred in people older than 70 years, and women had higher incidence rate (189.7 [95% UI 144.2 to 247.2] versus 166.2 [95% UI 133.2 to 205.8] per 100,000) and years lived with disability (38.4 [95% UI 26.9 to 51.6] versus 33.7 [95% UI 23.1 to 45.5] per 100,000) than men. Hip fractures are common, devastating to patients, and economically burdensome to healthcare systems globally, with falls being the leading cause. The age-standardized incidence rate has slightly increased in men. Many low-latitude countries have lower incidences, possibly because of prolonged sunlight exposure. Policies should be directed to promoting public health education about maintaining bone-protective lifestyles, enhancing the knowledge of osteoporosis management in young resident physicians and those in practice, increasing the awareness of osteoporosis screening and treatment in men, and developing more effective antiosteoporosis drugs for clinical use. Level III, prognostic study.

Do the newly proposed realignment targets for C2 and T1 slope bridge the gap between radiographic and clinical success in corrective surgery for adult cervical deformity?

Surgical correction of cervical deformity (CD) has been associated with superior alignment and functional outcomes. It has not yet been determined whether baseline or postoperative T1 slope (T1S) and C2 slope (C2S) correlate with health-related quality-of-life (HRQoL) metrics and radiographic complications, such as distal junctional kyphosis (DJK) and distal junctional failure (DJF). The objective of this study was to determine the impact of T1S and C2S deformity severity on HRQoL metrics and DJF development in patients with CD who underwent a cervical fusion procedure. All operative CD patients with upper instrumented vertebra above C7 and preoperative (baseline) and up to 2-year postoperative radiographic and HRQoL data were included. CD was defined as meeting at least one of the following radiographic parameters: C2-7 lordosis < -15°, TS1-cervical lordosis mismatch > 35°, segmental cervical kyphosis > 15° across any 3 vertebrae between C2 and T1, C2-7 sagittal vertical axis > 4 cm, McGregor's slope > 20°, or chin-brow vertical angle > 25°. Spearman's rank-order correlation and linear regression analysis assessed the impact of T1S and C2S on HRQoL metrics (Neck Disability Index [NDI], modified Japanese Orthopaedic Association [mJOA] scale, EuroQOL 5-Dimension Questionnaire [EQ-5D] visual analog scale [VAS] score, and numeric rating scale [NRS]-neck) and complications (DJK, DJF, reoperation). Logistic regression and a conditional inference tree (CIT) were used to determine radiographic thresholds for achieving optimal clinical outcome, defined as meeting good clinical outcome criteria (≥ 2 of the following: NDI < 20 or meeting minimal clinically important difference, mild myelopathy [mJOA score ≥ 14], and NRS-neck ≤ 5 or improved by ≥ 2 points), not undergoing reoperation, or developing DJF or mechanical complication by 2 years. One hundred five patients with CD met inclusion criteria. By surgical approach, 14.7% underwent an anterior-only approach, 46.1% a posterior-only approach, and 39.2% combined anterior and posterior approaches. The mean baseline radiographic parameters were T1S 28.3° ± 14.5° and C2S 25.9° ± 17.5°. Significant associations were found between 3-month C2S and mJOA score (r = -0.248, p = 0.034), NDI (r = 0.399, p = 0.001), EQ-5D VAS (r = -0.532, p < 0.001), NRS-neck (r = 0.239, p = 0.040), and NRS-back (r = 0.264, p = 0.021), while significant correlation was also found between 3-month T1S and mJOA score (r = -0.314, p = 0.026), NDI (r = 0.445, p = 0.001), EQ-5D VAS (r = -0.347, p = 0.018), and NRS-neck (r = 0.269, p = 0.049). A significant correlation was also found between development of DJF and 3-month C2S (odds ratio [OR] 1.1, 95% confidence interval [CI] 1.01-1.1, p = 0.015) as well as for T1S (OR 1.1, 95% CI 1.01-1.1, p = 0.023). Logistic regression with CIT identified thresholds for optimal outcome by 2 years: optimal 3-month T1S < 26° (OR 5.6) and C2S < 10° (OR 10.4), severe 3-month T1S < 45.5° (OR 0.2) and C2S < 38.0° (no patient above this threshold achieved optimal outcome; all p < 0.05). Patients below both optimal thresholds achieved rates of 0% for DJK and DJF, and 100% met optimal outcome. The severity of CD, defined by T1S and C2S at baseline and especially at 3 months, can be predictive of postoperative functional improvement and occurrence of worrisome complications in patients with CD, necessitating the use of thresholds in surgical planning to achieve optimal outcomes.

Hubungan antara Fear of Missing Out dengan Kecanduan Media Sosial

This study aims to determine the relationship between Fear of Missing Out and social media addiction in stdents at the Islamic University of Riau. The hypothesis in this study is positive and significant relationship between fear of missing out and social media addiction in student at the Islamic University of Riau. Subjects in this study amounted to 100 people who are student with age range of 19-25 years. Data collection uses a fear of missing out scale of 21 items and a social media addiction items. The analytical method used in this research is Spearman Rank Order correlation analysis. The results of statistical analysis obtained a correlation value of 0.264 (&gt;0.05) with a significan 0.008 (p&lt;0.05). The result of this tudy obtained a value of R = 0.304 with p &lt; 0.005 which is 0.092, this indicates that there is a significant positive relationship between fear of missing out and sosial media addiction in students at the Islamic University of Riau. That is, the higher the addiction to social media, the higher the fear of missing out and vice versa. The effeictive contribution of the social media addiction provides and active contribution of 9.2% to the fear of missing out variable while the rest is influenced by other factors.

Correlative results from NCI protocol 10250: A phase II study of temozolomide and olaparib for the treatment of advanced uterine leiomyosarcoma.

11509 Background: uLMS is an aggressive sarcoma subtype of smooth muscle origin. Chemotherapy provides limited benefit for advanced disease. 18-25% of uLMS harbor deleterious alterations in homologous recombination (HR) DNA repair genes. uLMS exhibits high levels of replicative stress. These findings prompted a phase 2 study of O+T in pretreated uLMS where O+T demonstrated activity: ORR 27%, mPFS 6.9 mos (Ingham M. et. al. ASCO 2021: #11506) Methods: NCI protocol #10250 is a single-arm, multicenter, phase 2 trial evaluating O+T in advanced uLMS pts with progression on ≥1 prior line. Pre-treatment (Pre) and on-treatment (On) biopsies were collected from 22 pts. In prespecified analysis, we evaluated for a relationship between clinical outcomes and HR gene alterations by whole exome sequencing (WES), SLFN11/MGMT expression by RNAseq, and RAD51 foci formation (functional assay). HRD scores were calculated from WES using scarHRD. Gene expression was evaluated using a Spearman rank-order correlation analysis to identify genes associated with PFS (p &lt; 0.01) and overexpressed in sensitive (S: PFS &gt; 240d) or resistant (R: PFS &lt; 240d) pts. Gene set enrichment analysis (GSEA) was performed (q = FDR-adjusted p value). Pts with available results: WES/RNAseq (16), Pre HRD score (13), Pre RAD51 foci (12). Results: 31% (5/16) pts had a mutation (Mut) or homozygous deletion (Hd) in the HR panel: ATRX Mut (2), ATR Mut, PALB2 Hd, RAD51B Hd. Pts with PALB2 and RAD51B Hd had longest PFS on study. Recurrent alterations also occurred in TP53 (56%) and RB1 (19%). Median HRD score in Pre samples was 51 (range 36-66) and 10/13 had HRD scores ≥ 42. Pre and On SLFN11 and MGMT RNA expression were not correlated with ORR/PFS. 6/13 Pre samples were HR-deficient by the RAD51 foci assay. Of pts with PFS ≥ 200d, 4/6 were HR-deficient. In Pre samples, 81 genes were overexpressed in S pts and 73 in R pts. In On samples, 146 genes were overexpressed in S pts and 127 in R pts. In On samples, GSEA identified the epithelial-mesenchymal transition enriched in S pts (q = 3.38e-7) and cell cycle pathways (E2F targets, G2M checkpoint) in R pts (q = 7.43e-4). Only 2 genes, CXCL10 and PCDH15, were differentially expressed between paired Pre and On samples (both increased in On). Gene expression signatures for replicative stress showed borderline association with worse PFS. Conclusions: Most uLMS tumors exhibit HR defects as measured by HRD scores. A subset of pts with greater benefit from O+T were identified by WES for HR genes and the RAD51 assay. There was no correlation between SLFN11 and MGMT expression and outcomes. GSEA identified pathways differentially expressed in S and R pts in On samples. O+T induced CXCL10 which has been associated with T-cell trafficking to tumors. A randomized phase 3 trial of O+T versus investigator’s choice is planned. These results provide insight into which pts may benefit most from this novel drug combination. Clinical trial information: NCT03880019.

Association between individual wheelchair skills and fitness in community-dwelling manual wheelchair users with spinal cord injuries

Purpose Wheelchair skills are a key component to promotion of community participation among persons with spinal cord injury (SCI). The objective of this secondary analysis was to examine the association between individual wheelchair skills from the Wheelchair Skills Test Questionnaire (WST-Q) and fitness among community-dwelling adults with SCI. Materials and methods Twenty-six adults were recruited to complete the WST-Q and a standard graded aerobic wheelchair exercise test on a motorized treadmill for assessing peak power output (POpeak). Results Spearman Rho rank-order correlation (ρ) analyses indicated statistically significant correlations between POpeak and six basic (ρ = 0.41–0.57), eight intermediate (ρ = 0.44–0.59), and nine advanced (ρ = 0.42–0.80) WST-Q skill scores. After controlling for sex and injury level (Partial Spearman Rho rank order) significant correlations persisted for four advanced skills (i.e., descends high curb, turns in place in wheelie position, descends steep incline in wheelie position, descends high curb in wheelie position; ρ = 0.46–0.59) and one additional skill (i.e., ascends high curb ρ = 0.51). Conclusions More advanced wheelchair skills are significantly associated with fitness in persons with SCI. The directionality of the skills-fitness relationship, specifically whether wheelchair skills facilitate greater fitness or fitness is a prerequisite for certain wheelchair skills needs to be determined in future, larger studies. However, results from this study provide a comprehensive list of wheelchair skills that are associated with fitness that can be directly applied to guide further research and practice promoting community participation among persons with SCI. Implications for Rehabilitation Significant positive associations exist between advanced wheelchair skills (i.e., descends high curb, turns in place in wheelie position, descends steep incline in wheelie position, descends high curb in wheelie position and ascends high curb) and fitness in manual wheelchair users with spinal cord injury (SCI). This study provides a list of skills associated with fitness to guide clinical practice and areas for further rehabilitation research assessing the directionality of the relationship between fitness and wheelchair skills.

Quantitative Patient-Reported Experience Measures Derived From Natural Language Processing Have a Normal Distribution and No Ceiling Effect.

Patient-reported experience measures have the potential to guide improvement in health care delivery. Many patient-reported experience measures are limited by the presence of strong ceiling effects that limit their analytical utility. We used natural language processing to develop 2 new methods of evaluating patient experience using text comments and associated ordinal and categorical ratings of willingness to recommend from 1390 patients receiving specialty or nonspecialty care at our offices. One method used multivariable analysis based on linguistic factors to derive a formula to estimate the ordinal likelihood to recommend. The other method used the meaning extraction method of thematic analysis to identify words associated with categorical ratings of likelihood to recommend with which we created an equation to compute an experience score. We measured normality of the 2 score distributions and ceiling effects. Spearman rank-order correlation analysis identified 36 emotional and linguistic constructs associated with ordinal rating of likelihood to recommend, 9 of which were independently associated in multivariable analysis. The calculation derived from this model corresponded with the original ordinal rating with an accuracy within 0.06 units on a 0 to 10 scale. This score and the score developed from thematic analysis both had a relatively normal distribution and limited or no ceiling effect. Quantitative ratings of patient experience developed using natural language processing of text comments can have relatively normal distributions and no ceiling effect.

Immune Activity and Response Differences of Oncolytic Viral Therapy in Recurrent Glioblastoma: Gene Expression Analyses of a Phase IB Study.

Previously, clinical trials of experimental virotherapy for recurrent glioblastoma multiforme (GBM) demonstrated that inoculation with a conditionally replication-competent Δγ134.5 oncolytic herpes simplex virus (oHSV), G207, was safe. Following the initial safety study, a phase Ib trial enrolled 6 adult patients diagnosed with GBM recurrence from which tumor tissue was banked for future studies. Here, we analyzed tumor RNA sequencing (RNA-seq) data obtained from pre- and posttreatment (collected 2 or 5 days after G207 injection) biopsies from the phase Ib study patients. Using a Spearman rank-order correlation analysis, we identified approximately 500 genes whose expression pattern correlated with survival duration. Many of these genes were enriched for the intrinsic IFN-mediated antiviral and adaptive immune functional responses, including immune cell chemotaxis and antigen presentation to T-cells. Furthermore, we show that the expression of several T-cell-related genes was highest in the patient with the longest survival after G207 inoculation. Our data support that the oHSV-induced type I IFN production and the subsequent recruitment of an adaptive immune response differed between enrolled patients and showed association with survival duration in patients with recurrent malignant glioma after treatment with an early generation oHSV.

Combining diffusion kurtosis imaging and clinical data for predicting the extramural venous invasion of rectal adenocarcinoma

ObjectiveThe aim of this study is to investigate the diagnostic ability of diffusion kurtosis imaging (DKI) -derived parameters combining with clinical data as risk factors for EMVI’s involvement status in rectal adenocarcinoma. Materials and MethodsPreoperative MR examination including DKI and conventional diffusion-weighted imaging (DWI) was performed on 154 rectal adenocarcinoma patients enrolled in this respective study. Kmean, Dmean, and apparent diffusion coefficient (ADC) values were calculated. Clinical information, serum tumor markers, MR and pathological assessment of EMVI were recorded. The Shapiro-Wilk test, two-sample t-test, Mann-Whitney U test, Spearman’s rank-order correlation, univariate and multivariate logistic regression analyses were used for statistical analysis. Receiver operating characteristic (ROC) curve analyses were performed to identify risk factors in EMVI involvement. ResultsOf the 154 patients, pEMVI-positive rectal tumors had significantly higher Kmean values, lower ADCmean values compared to pEMVI-negative rectal tumors. Kmean values positively correlated with mrEMVI scores, whereas ADCmean values showed a negative correlation with mrEMVI scores. However, there was no significant correlation between the Dmean values and the mrEMVI scores. Univariate analysis demonstrated increased Kmean values, decreased ADCmean values, nodal involvement, an advanced tumor stage, and a G2 tumor grade were significantly related to the pEMVI of rectal adenocarcinoma. The multivariate analysis demonstrated that the Kmean values, lymph node involvement and an advanced tumor stage (T3) were independent risk factors for EMVI. ConclusionThe potential for diffusion kurtosis imaging as a biomarker for evaluating the EMVI of rectal cancer is feasible, especially given DKI’s capability of detecting tumor heterogeneity noninvasively.

Is Ambient Weather a Risk Factor for Acute Encephalopathy Outbreaks in Children in Muzaffarpur, Bihar, India? Insight from a 9-Year Analysis.

Despite periodic outbreaks, the causes and risk factors of acute encephalitis syndrome (AES) in children of Muzaffarpur, Bihar, India, remain unknown. We explored the correlation between AES caseload and the climate parameters. Data for 1318 hospitalized children with AES during 2012-20 were used. The correlation between AES cases and daily climate parameters (temperature, sunshine, rainfall, humidity and wind speed) for the previous 24, 48 and 72 h were examined using Pearson's and Spearman's rank-order correlation and Poisson regression or negative binomial regression analyses. Most (91.8%) of the AES cases occurred during the summer season (May-July months), especially June month. Pearson's and Spearman's rank-order correlation analyses revealed that AES caseload had positive correlations with maximum (r = 0.275, ρ = 0.293) and minimum (r = 0.306, ρ = 0.306) temperatures during past 24 h and heat index (r = 0.325, ρ = 0.325) and negative correlation with humidity (r = -0.222, ρ = -0.222) and rainfall (r = -0.183, ρ = -0.183) (all p < 0.05). The correlation was consistent for the climate parameters for the past 24, 48 and 72 h. Regression analysis also documented a significant association of AES cases with daily maximum (β: 0.32-0.36) and minimum (β: 0.53-0.62) temperatures and heat index (β: 0.92-1.03) over past 24, 48 and 72 h (all p < 0.01). The number of AES cases exponentially increased when the daily maximum and minimum temperatures crossed 40°C and 31°C, respectively. The climate parameters, especially temperature appears to be a risk factor for AES in children. The definite aetiological role of heat for AES in children needs further exploration.

Automated delineation of enlarged perivascular spaces (EPVS)

AbstractBackgroundEnlarged Perivascular Spaces (EPVS) are associated with small vessel disease. The objective of this study was to develop semi‐automated techniques for the quantification of EPVS burden.MethodAn intensity‐based threshold was used to identify EPVS. A threshold of maximum plus two standard deviations of intensities of normal‐appearing white matter in the supratentorial region was used to identify EPVS. To compare the performance of the semi‐automatic approach for EPVS segmentation to visually rated EPVS scores, two regions of interest were outlined in the basal ganglia (BG) region and the centrum semiovale (CS). For both these regions, a score was generated by an experienced neurologist by visually counting the number of EPVS with a score of zero representing the absence of any EPVS, a score of 1 representing 1‐10 EPVS, a score of 2 representing 11‐20 EPVS, a score of 3 representing 21‐40 EPVS, and a score of 4 representing &gt;40 EPVS. The semi‐automatic approach provided a count of the number of EPVS that were converted to grade using the same scaling as the visual approach. Spearman Rank Order Correlation Coefficient was calculated to estimate the correlation between the two methods. Mann‐Whitney U tests of ranks are employed to determine if any group differences are present. Finally, Cohen’s kappa was used to compare the concordance between measures between the two different methods.ResultFigure 2 shows the results of the segmentation in subjects with differing EPVS burden. Spearman Rank Order Correlation analysis showed a significant correlation between the EPVS scores determined visually and those obtained semi‐automatically in 60 subjects (Table 1). Results of the Mann‐Whitney U tests showed that there was no statistically significant (p &gt; 0.05) difference between the EPVS scores obtained visually and using the semi‐automatic approach (Table 2). Cohen's κ test showed that there was moderate agreement between the two estimation methods in the BG (κ = .522, p &lt; .0001) and CS regions (κ = .571, p &lt; .0001).ConclusionThe developed method showed good concordance with expert visual read and can provide quantitative measures of EPVS burden (counts and volume) for evaluation of vascular risk.

Correlation and Correspondence between Skeletal Maturation Indicators in Hand-Wrist and Cervical Vertebra Analyses and Skeletal Maturity Score in Korean Adolescents.

This retrospective observational study aimed to examine the correlation and correspondence between skeletal maturation indicators (SMI), cervical vertebral maturation indicators (CVMI), and radius-ulna-short bones (RUS) skeletal maturity scores in Korean adolescents, and to determine whether easily obtainable SMI or CVMI can replace the RUS skeletal maturity score. A total of 1017 participants were included with both hand-wrist radiograph and lateral cephalogram acquired concurrently. From the lateral cephalogram, CVMI was determined; through the hand-wrist radiograph, SMI was categorized, and the RUS skeletal maturity score was evaluated as well. Associations were examined using the Mann–Whitney U test, Spearman’s rank-order correlation analysis, and multiple correspondence analysis. There was no statistically significant difference in chronological age between males and females; however, the SMI, CVMI, and RUS skeletal maturity scores were significantly higher in females. The SMI, CVMI, and RUS skeletal maturity scores showed a statistically significant strong degree of both positive correlation and correspondence. However, a precisely corresponding RUS skeletal maturity score was difficult to obtain for a specific CVMI and SMI stage, implying the absence of a quantitative correlation. In conclusion, detailed evaluation should be conducted using the RUS skeletal maturity score, preferably in cases that require bone age determination or residual growth estimation.

The Value of Having an Expert Sports Performance and Medicine Staff in the National Football League

An expert strength and conditioning coach can be an important component of a sports performance and medicine staff that will train their athletes to help them become more resilient to injury. Previous research in a variety of sports has shown that teams with players that have fewer games missed due to injury have achieved greater success. The purpose of this study was to determine if a relationship exists between games missed due to injury by offensive and defensive starters on National Football League (NFL) rosters and a NFL team’s ability to win during the 2010-19 NFL seasons. A Spearman rank-order correlation analysis set at (p ≤ 0.01) level of significance indicated that fewer games missed by starters in the NFL is correlated with multiple variables associated with winning such as games won per season and playoff appearances. These results were obtained after analyzing all 32 NFL teams from the 2010-19 seasons. Descriptive statistics were also used to further analyze the data set and found that teams ranked in the top-five in terms of fewest injuries outperformed the remainder of the teams in the NFL according to multiple variables associated with winning. The data in this study supports that NFL organizations should look to reduce the games missed due to injury of their athletes, which may be accomplished through hiring expert sports performance and medicine staff members, such as a strength and conditioning. hire an expert strength and conditioning coach capable of reducing the risk of athletes getting injured in order to increase their team’s chances of winning.

Retrospective Analysis of Work From Home for Civil Servants During The Covid- 19 Pandemic

The COVID-19 pandemic hitting Indonesia has created new habitual adaptations, including working from home for civil servants. This policy presents a new challenge, namely maintaining performance through achieving the effectiveness of working from home. The present study investigates the implementation of the work from home policy through Spearman's rank-order correlation analysis to examine the correlation between research variables. Furthermore, after the Kruskal-Wallis significant test, the Dunn-Bonferroni post hoc method was used to look for the differences between the factors affecting the effectiveness of working from home of the civil servants based on gender and age and education, and years of service. Data were collected through questionnaires to 437 civil servants from various government agencies, both central and regional. The study's findings indicate differences in the factors influencing the effectiveness of working from home and the skills required depending on gender, age, education, and years of service. The results also show that information technology support is not evenly distributed in implementing the work from home policy. The implication of this study suggests that the evaluation of the implementation of the work from home policy for the civil servants is beneficial for the government in considering sustainability and quality development in the future.