Category: Nevin Manimala

PLoS Comput Biol. 2022 Jun 23;18(6):e1010209. doi: 10.1371/journal.pcbi.1010209. eCollection 2022 Jun.

ABSTRACT

Measuring mechanical parameters in tissues, such as the elastic modulus of cell-cell junctions, is essential to decipher the mechanical control of morphogenesis. However, their in vivo measurement is technically challenging. Here, we formulated an image-based statistical approach to estimate the mechanical parameters of epithelial cells. Candidate mechanical models are constructed based on force-cell shape correlations obtained from image data. Substitution of the model functions into force-balance equations at the cell vertex leads to an equation with respect to the parameters of the model, by which one can estimate the parameter values using a least-squares method. A test using synthetic data confirmed the accuracy of parameter estimation and model selection. By applying this method to Drosophila epithelial tissues, we found that the magnitude and orientation of feedback between the junction tension and shrinkage, which are determined by the spring constant of the junction, were correlated with the elevation of tension and myosin-II on shrinking junctions during cell rearrangement. Further, this method clarified how alterations in tissue polarity and stretching affect the anisotropy in tension parameters. Thus, our method provides a novel approach to uncovering the mechanisms governing epithelial morphogenesis.

PMID:35737656 | DOI:10.1371/journal.pcbi.1010209

J Med Internet Res. 2022 Jun 23;24(6):e33446. doi: 10.2196/33446.

ABSTRACT

BACKGROUND: The Dutch Institute for Clinical Auditing (DICA) Medicines Program was set up in September 2018 to evaluate expensive medicine use in daily practice in terms of real-world effectiveness using only existing data sources.

OBJECTIVE: The aim of this study is to describe the potential of the addition of declaration data to quality registries to provide participating centers with benchmark information about the use of medicines and outcomes among patients.

METHODS: A total of 3 national population-based registries were linked to clinical and financial data from the hospital pharmacy, the Dutch diagnosis treatment combinations information system including in-hospital activities, and survival data from health care insurers. The first results of the real-world data (RWD) linkage are presented using descriptive statistics to assess patient, tumor, and treatment characteristics. Time-to-next-treatment (TTNT) and overall survival (OS) were estimated using the Kaplan-Meier method.

RESULTS: A total of 21 Dutch hospitals participated in the DICA Medicines Program, which included 7412 patients with colorectal cancer, 1981 patients with metastasized colon cancer, 3860 patients with lung cancer, 1253 patients with metastasized breast cancer, and 7564 patients with rheumatic disease. The data were used for hospital benchmarking to gain insights into medication use in specific patient populations, treatment information, clinical outcomes, and costs. Detailed treatment information (duration and treatment steps) led to insights into differences between hospitals in daily clinical practices. Furthermore, exploratory analyses on clinical outcomes (TTNT and OS) were possible.

CONCLUSIONS: The DICA Medicines Program shows that it is possible to gather and link RWD about medicines to 4 disease-specific population-based registries. Since these RWD became available with minimal registration burden and effort for hospitals, this method can be explored in other population-based registries to evaluate real-world efficacy.

PMID:35737449 | DOI:10.2196/33446

JMIR Form Res. 2022 Jun 23;6(6):e35797. doi: 10.2196/35797.

ABSTRACT

BACKGROUND: The use of web-based methods to collect population-based health behavior data has burgeoned over the past two decades. Researchers have used web-based platforms and research panels to study a myriad of topics. Data cleaning prior to statistical analysis of web-based survey data is an important step for data integrity. However, the data cleaning processes used by research teams are often not reported.

OBJECTIVE: The objectives of this manuscript are to describe the use of a systematic approach to clean the data collected via a web-based platform from panelists and to share lessons learned with other research teams to promote high-quality data cleaning process improvements.

METHODS: Data for this web-based survey study were collected from a research panel that is available for scientific and marketing research. Participants (N=4000) were panelists recruited either directly or through verified partners of the research panel, were aged 18 to 45 years, were living in the United States, had proficiency in the English language, and had access to the internet. Eligible participants completed a health behavior survey via Qualtrics. Informed by recommendations from the literature, our interdisciplinary research team developed and implemented a systematic and sequential plan to inform data cleaning processes. This included the following: (1) reviewing survey completion speed, (2) identifying consecutive responses, (3) identifying cases with contradictory responses, and (4) assessing the quality of open-ended responses. Implementation of these strategies is described in detail, and the Checklist for E-Survey Data Integrity is offered as a tool for other investigators.

RESULTS: Data cleaning procedures resulted in the removal of 1278 out of 4000 (31.95%) response records, which failed one or more data quality checks. First, approximately one-sixth of records (n=648, 16.20%) were removed because respondents completed the survey unrealistically quickly (ie, <10 minutes). Next, 7.30% (n=292) of records were removed because they contained evidence of consecutive responses. A total of 4.68% (n=187) of records were subsequently removed due to instances of conflicting responses. Finally, a total of 3.78% (n=151) of records were removed due to poor-quality open-ended responses. Thus, after these data cleaning steps, the final sample contained 2722 responses, representing 68.05% of the original sample.

CONCLUSIONS: Examining data integrity and promoting transparency of data cleaning reporting is imperative for web-based survey research. Ensuring a high quality of data both prior to and following data collection is important. Our systematic approach helped eliminate records flagged as being of questionable quality. Data cleaning and management procedures should be reported more frequently, and systematic approaches should be adopted as standards of good practice in this type of research.

PMID:35737436 | DOI:10.2196/35797

J AOAC Int. 2022 Jun 23:qsac068. doi: 10.1093/jaoacint/qsac068. Online ahead of print.

ABSTRACT

BACKGROUND: The 3M™ Molecular Detection Assay 2-Salmonella method is based on real time loop-mediated isothermal amplification when used with the 3M Molecular Detection System for the rapid and specific detection of Salmonella in enriched products. The 3M Molecular Detection Assay 2 – Salmonella was approved as AOAC® Performance TestedSM Certificate No. 091501 and as AOAC Official Method of AnalysisSM 2016.01.

OBJECTIVE: This matrix extension study evaluated the 3M Molecular Detection Assay 2 – Salmonella for detection of Salmonella in dried cannabis flower [>0.3% delta 9-tetrahydrocannabinol (THC)] and dried hemp flower (≤0.3% THC) at a 10 g test portion size.

METHODS: Matrix studies in dried cannabis and hemp flowers followed procedures outlined in 3M Molecular Detection Assay 2 – Salmonella Product Instructions and Standard Method Performance Requirements (SMPRs®) for Detection of Salmonella species in Cannabis and Cannabis Products (AOAC SMPR 2020.002). The method was evaluated at low, high, and non-contaminated levels.

RESULTS: Results showed no statistically significant difference between the presumptive positive 3M Molecular Detection Assay 2 – Salmonella results and the SMPR 2020.002 recommended cultural confirmations.

CONCLUSION: This study demonstrates that the 3M Molecular Detection Assay 2 – Salmonella is a reliable method for the rapid and specific detection of Salmonella in dried cannabis flower and dried hemp flower.

HIGHLIGHT: The 3M Molecular Detection Assay 2 – Salmonella method is suitable for the rapid and specific detection of Salmonella in dried cannabis flower and dried hemp flower.

PMID:35737412 | DOI:10.1093/jaoacint/qsac068

J AOAC Int. 2022 Jun 23:qsac067. doi: 10.1093/jaoacint/qsac067. Online ahead of print.

ABSTRACT

BACKGROUND: The 3M™ Molecular Detection Assay 2 – STEC Gene Screen (stx and eae) method is based on gene amplification by the use of real time loop-mediated isothermal amplification when used with the 3M Molecular Detection System for the rapid and specific detection of Shiga toxin gene (stx1 and/or stx2) and intimin gene (eae) from Shiga toxin-producing Escherichia coli (STEC) in enriched products. The 3M Molecular Detection Assay 2 – STEC Gene Screen (stx and eae) was approved as AOAC® Performance Tested MethodSM Certificate No. 071902.

OBJECTIVE: This matrix extension study evaluated the 3M Molecular Detection Assay 2 – STEC Gene Screen (stx and eae) method for detection of STECs in dried cannabis flower [>0.3% delta 9-tetrahydrocannabinol (THC)] and dried hemp flower (≤0.3% THC) at a 10 g test portion size.

METHODS: Testing followed procedures outlined in 3M Molecular Detection Assay 2 – STEC Gene Screen (stx and eae) Product Instructions and Standard Method Performance Requirements (SMPRs®) for Detection of Shiga toxin-producing Escherichia coli in Cannabis and Cannabis Products (AOAC SMPR 2020.012). The method was evaluated at low, high, and non-inoculated levels.

RESULTS: Results showed no statistically significant difference between the presumptive positive 3M Molecular Detection Assay 2 – STEC Gene Screen (stx and eae) results and the SMPR 2020.012 recommended cultural confirmations.

CONCLUSION: This study provides data that demonstrate the 3M Molecular Detection Assay 2 – STEC Gene Screen (stx and eae) is a reliable method for the rapid and specific detection of STEC organisms in dried cannabis flower and dried hemp flower.

HIGHLIGHT: The 3M Molecular Detection Assay 2 – STEC Gene Screen (stx and eae) method is suitable for the rapid and specific detection of STEC organisms in dried cannabis flower and dried hemp flower.

PMID:35737411 | DOI:10.1093/jaoacint/qsac067

J AOAC Int. 2022 Jun 23:qsac069. doi: 10.1093/jaoacint/qsac069. Online ahead of print.

ABSTRACT

BACKGROUND: The 3M™ Molecular Detection Assay 2 – STEC Gene Screen (stx) method is based on gene amplification by the use of real time loop-mediated isothermal amplification when used with the 3M Molecular Detection System for the rapid and specific detection of Shiga toxin gene (stx1 and/or stx2) from Shiga toxin-producing Escherichia coli (STEC) in enriched products. The 3M Molecular Detection Assay 2 – STEC Gene Screen (stx) was approved as AOAC® Performance Tested MethodSM Certificate No. 071903.

OBJECTIVE: This matrix extension study evaluated the 3M Molecular Detection Assay 2 – STEC Gene Screen (stx) method for detection of STECs in dried cannabis flower [>0.3% delta 9-tetrahydrocannabinol (THC)] and dried hemp flower (≤0.3% THC) at a 10 g test portion size.

METHODS: Testing followed procedures outlined in 3M Molecular Detection Assay 2 – STEC Gene Screen (stx) Product Instructions and Standard Method Performance Requirements (SMPRs®) for Detection of Shiga toxin-producing Escherichia coli in Cannabis and Cannabis Products (AOAC SMPR 2020.012). The method was evaluated at low, high, and non-inoculated levels.

RESULTS: Results showed no statistically significant difference between the presumptive positive 3M Molecular Detection Assay 2 – STEC Gene Screen (stx) results and the SMPR 2020.012 recommended cultural confirmations.

CONCLUSION: This study provides data that demonstrate the 3M Molecular Detection Assay 2 – STEC Gene Screen (stx) is a reliable method for the rapid and specific detection of STECs in dried cannabis flower and dried hemp flower.

HIGHLIGHT: The 3M Molecular Detection Assay 2 – STEC Gene Screen (stx) method is suitable for the rapid and specific detection of STECs in dried cannabis flower and dried hemp flower.

PMID:35737394 | DOI:10.1093/jaoacint/qsac069

JAMA Netw Open. 2022 Jun 1;5(6):e2218337. doi: 10.1001/jamanetworkopen.2022.18337.

ABSTRACT

IMPORTANCE: Since the 1990s, reporting guidelines have developed that uniformly require authors to report a measure of precision (confidence intervals [CIs]) in addition to effect size.

OBJECTIVE: To investigate the time trend of statistical inference and statistical reporting style in abstracts of major cancer journals.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study reviewed all abstracts published between January 1, 1990, and December 31, 2020, in 10 high-ranking cancer journals (Lancet Oncology, Journal of Clinical Oncology, Cancer Discovery, Cancer Cell, JAMA Oncology, Annals of Oncology, Molecular Cancer, Journal of Thoracic Oncology, Journal of the National Cancer Institute, and Trends in Cancer) using a previously validated computerized algorithm to search the PubMed database. For the time trend analyses, 2 journals with only a few years of existence (JAMA Oncology and Trends in Cancer) were excluded.

EXPOSURES: Calendar year, journal, and type of abstract (randomized clinical trial or other).

MAIN OUTCOMES AND MEASURES: Proportions of abstracts containing CIs, P values without CIs, and qualitative expressions of statistical significance only were compared over time among journals.

RESULTS: Overall, 24 034 of 42 509 abstracts (56.5%) contained statistical inference. Reporting of CIs increased over time in 5 of 8 journals. From 2016 to 2020, the most prevailing statistical reporting style was the presentation of CIs (3070 of 4895 [62.7%]). However, the proportion of abstracts reporting statistical inference based solely on the terms significant or nonsignificant was still 1195 of 4895 (24.4%) during this period and was most prevalent among basic science-oriented cancer journals (eg, 63 of 66 [95.5%] in Cancer Cell). A higher prevalence of CI reporting was associated with reporting of results from randomized clinical trials and the requirement to report according to guidelines (eg, 522 of 574 [90.9%] in Lancet Oncology).

CONCLUSIONS AND RELEVANCE: These findings suggest that the reporting style of statistical inference in abstracts of major cancer journals has improved over time. A requirement in journals’ instructions for authors to present statistical inference in accordance with reporting guidelines and the implementation of these guidelines in submitted manuscripts on the part of journal editors may improve reporting.

PMID:35737386 | DOI:10.1001/jamanetworkopen.2022.18337

JAMA Oncol. 2022 Jun 23. doi: 10.1001/jamaoncol.2022.1990. Online ahead of print.

ABSTRACT

IMPORTANCE: Diagnostic delays in breast cancer detection may be associated with later-stage disease and higher anxiety, but data on multilevel factors associated with diagnostic delay are limited.

OBJECTIVE: To evaluate individual-, neighborhood-, and health care-level factors associated with differences in time from abnormal screening to biopsy among racial and ethnic groups.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used data from women aged 40 to 79 years who had abnormal results in screening mammograms conducted in 109 imaging facilities across 6 US states between 2009 and 2019. Data were analyzed from February 21 to November 4, 2021.

EXPOSURES: Individual-level factors included self-reported race and ethnicity, age, family history of breast cancer, breast density, previous breast biopsy, and time since last mammogram; neighborhood-level factors included geocoded education and income based on residential zip codes and rurality; and health care-level factors included mammogram modality, screening facility academic affiliation, and facility onsite biopsy service availability. Data were also assessed by examination year.

MAIN OUTCOME AND MEASURES: The main outcome was unadjusted and adjusted relative risk (RR) of no biopsy within 30, 60, and 90 days using sequential log-binomial regression models. A secondary outcome was unadjusted and adjusted median time to biopsy using accelerated failure time models.

RESULTS: A total of 45 186 women (median [IQR] age at screening, 56 [48-65] years) with 46 185 screening mammograms with abnormal results were included. Of screening mammograms with abnormal results recommended for biopsy, 15 969 (34.6%) were not resolved within 30 days, 7493 (16.2%) were not resolved within 60 days, and 5634 (12.2%) were not resolved within 90 days. Compared with White women, there was increased risk of no biopsy within 30 and 60 days for Asian (30 days: RR, 1.66; 95% CI, 1.31-2.10; 60 days: RR, 1.58; 95% CI, 1.15-2.18), Black (30 days: RR, 1.52; 95% CI, 1.30-1.78; 60 days: 1.39; 95% CI, 1.22-1.60), and Hispanic (30 days: RR, 1.50; 95% CI, 1.24-1.81; 60 days: 1.38; 95% CI, 1.11-1.71) women; however, the unadjusted risk of no biopsy within 90 days only persisted significantly for Black women (RR, 1.28; 95% CI, 1.11-1.47). Sequential adjustment for selected individual-, neighborhood-, and health care-level factors, exclusive of screening facility, did not substantially change the risk of no biopsy within 90 days for Black women (RR, 1.27; 95% CI, 1.12-1.44). After additionally adjusting for screening facility, the increased risk for Black women persisted but showed a modest decrease (RR, 1.20; 95% CI, 1.08-1.34).

CONCLUSIONS AND RELEVANCE: In this cohort study involving a diverse cohort of US women recommended for biopsy after abnormal results on screening mammography, Black women were the most likely to experience delays to diagnostic resolution after adjusting for multilevel factors. These results suggest that adjustment for multilevel factors did not entirely account for differences in time to breast biopsy, but unmeasured factors, such as systemic racism and other health care system factors, may impact timely diagnosis.

PMID:35737381 | DOI:10.1001/jamaoncol.2022.1990

JAMA Oncol. 2022 Jun 23. doi: 10.1001/jamaoncol.2022.2286. Online ahead of print.

ABSTRACT

IMPORTANCE: It is unclear whether ERBB2-low breast cancer should be considered an individual biologic subtype distinct from ERBB2-0 breast cancer.

OBJECTIVE: To investigate whether low ERBB2 expression is associated with distinct clinicopathologic characteristics and prognosis among patients with hormone receptor (HR)-positive and triple-negative breast cancer (TNBC).

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted using data from a prospectively maintained institutional database on all consecutive patients with breast cancer undergoing surgery between January 2016 and March 2021 at Dana-Farber Brigham Cancer Center. The study included 5235 patients with stage I through III, ERBB2-negative invasive breast cancer. Tumors were classified as ERBB2-low if they had an ERBB2 immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization assay and ERBB2-0 if they had an ERBB2 IHC score of 0. Data were analyzed from September 2021 through January 2022.

EXPOSURES: Standard treatment according to institutional guidelines.

MAIN OUTCOMES AND MEASURES: Comparison of clinicopathologic characteristics and disease outcomes (pathologic complete response rate [pCR], disease-free survival, distant disease-free survival, and overall survival) between patients with ERBB2-low and ERBB2-0 breast cancer.

RESULTS: Among 5235 patients with ERBB2-negative invasive breast cancer (5191 [99.2%] women; median [range] age at primary surgery, 59.0 [21.0-95.0] years), 2917 patients (55.7%) and 2318 patients (44.3%) had ERBB2-low and ERBB2-0 tumors, respectively. Expression of HR was significantly more common among ERBB2-low compared with ERBB2-0 tumors (2643 patients [90.6%] vs 1895 patients [81.8%]; P < .001). The rate of ERBB2-low tumors increased progressively, from 296 of 739 estrogen receptor (ER)-negative tumors (40.1%) to 31 of 67 ER-low (ie, ER 1%-9%) tumors (46.3%), 37 of 67 ER-moderate (ie, ER, 10%-49%) tumors (55.2%), 2047 of 3542 ER-high (ie, ER, 50%-95%) tumors (57.8%), and 499 of 803 ER-very high (ie, ER > 95%) tumors (62.1%) (P < .001). Among 675 patients receiving neoadjuvant chemotherapy, those with ERBB2-0 tumors experienced higher pCR rates (95 patients [26.8%] vs 53 patients [16.6%]; P = .002). However, there were no statistically significant differences in pCR rate between ERBB2-low and ERBB2-0 tumors when separately analyzing HR-positive, ER-low, HR-positive without ER-low, or TNBC tumors. In exploratory survival analysis, no differences by ERBB2-low expression in disease-free survival, distant disease-free survival, or overall survival were observed among patients with HR-positive tumors or TNBC.

CONCLUSIONS AND RELEVANCE: The results of this cohort study did not support the interpretation of ERBB2-low breast cancer as a distinct biologic subtype. ERBB2-low expression was positively associated with level of ER expression, and ER-low tumors were enriched among ERBB2-0 tumors, suggesting that, given the worse prognosis of ER-low tumors, they may be associated with confounding of prognostic analyses of ERBB2-low expression.

PMID:35737367 | DOI:10.1001/jamaoncol.2022.2286

Vet Sci. 2022 Jun 14;9(6):295. doi: 10.3390/vetsci9060295.

ABSTRACT

Chronic enteropathy (CE) is a severe multifactorial gastrointestinal disease that affects dogs and is driven by poorly characterized inflammatory pathways. Imbalance of pro-inflammatory response regulators, including IL-1R8, may be due to different factors, among which the infection with Helicobacteraceae is known to lead to a vicious circle in which excessive pro-inflammatory signaling and gastrointestinal injury reinforce each other and boost the disease. We investigated the expression of IL-1R8 in large intestine biopsies of dogs with or without clinical signs of CE and with previously assessed enterohepatic Helicobacter spp. colonization status by mean of quantitative real-time PCR. Our study revealed that IL-1R8 is downregulated in both acutely (p = 0.0074) and chronically (p = 0.0159) CE affected dogs compared to healthy controls. The data also showed that IL-1R8 expression tends to decrease with colonization by Helicobacter spp. Interestingly, a negative correlation was detected between the level of expression of IL-1R8 and the severity of macroscopic lesions identified by endoscopy and the crypt hyperplasia score. We further compared the expression levels between males and females and found no statistically significant difference between the two groups. No significant difference was observed in IL-1R8 expression profiles with the age of the animals either. Interestingly, an association was uncovered between IL-1R8 expression level and dog breed. Together, our data advance knowledge on gastrointestinal pathoimmunology in dogs and highlight the potential utilization of IL-1R8 as a diagnostic, prognostic and therapeutic biomarker for canine chronic enteropathy.

PMID:35737347 | DOI:10.3390/vetsci9060295