Category: Nevin Manimala

Ann Intern Med. 2022 Jun 14. doi: 10.7326/M22-0276. Online ahead of print.

ABSTRACT

Whereas diagnostic tests help detect the cause of signs and symptoms, prognostic tests assist in evaluating the probable course of the disease and future outcome. Studies to evaluate prognostic tests are longitudinal, which introduces sources of bias different from those for diagnostic accuracy studies. At present, systematic reviews of prognostic tests often use the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool to assess risk of bias and applicability of included studies because no equivalent instrument exists for prognostic accuracy studies.

QUAPAS (Quality Assessment of Prognostic Accuracy Studies) is an adaptation of QUADAS-2 for prognostic accuracy studies. Questions likely to identify bias were evaluated in parallel and collated from QUIPS (Quality in Prognosis Studies) and PROBAST (Prediction Model Risk of Bias Assessment Tool) and paired to the corresponding question (or domain) in QUADAS-2. A steering group conducted and reviewed 3 rounds of modifications before arriving at the final set of domains and signaling questions.

QUAPAS follows the same steps as QUADAS-2: Specify the review question, tailor the tool, draw a flow diagram, judge risk of bias, and identify applicability concerns. Risk of bias is judged across the following 5 domains: participants, index test, outcome, flow and timing, and analysis. Signaling questions assist the final judgment for each domain. Applicability concerns are assessed for the first 4 domains.

The authors used QUAPAS in parallel with QUADAS-2 and QUIPS in a systematic review of prognostic accuracy studies. QUAPAS improved the assessment of the flow and timing domain and flagged a study at risk of bias in the new analysis domain. Judgment of risk of bias in the analysis domain was challenging because of sparse reporting of statistical methods.

PMID:35696685 | DOI:10.7326/M22-0276

J Clin Oncol. 2022 Jun 13:JCO2200307. doi: 10.1200/JCO.22.00307. Online ahead of print.

ABSTRACT

PURPOSE: Representativeness in acute leukemia clinical research is essential for achieving health equity. The National Cancer Institute’s mandate for Comprehensive Cancer Centers (CCCs) to define and assume responsibility for cancer control and treatment across a geographic catchment area provides an enforceable mechanism to target and potentially remediate participatory inequities.

METHODS: We examined enrollee characteristics across 15 Cancer and Leukemia Group B/Alliance cooperative group adult acute leukemia clinical trials (N = 3,734) from 1998 to 2013, including participation in optional companion biobanks. We determined enrollment odds by race-ethnicity for all participants adjusted for national incidence, and for those enrolled at CCCs adjusted for catchment area incidence. We modeled biobank participation by sociodemographics using logistic regression.

RESULTS: Non-Hispanic (NH)-White patients were more likely to be enrolled than NH-Black, NH-Asian, or Hispanic patients (odds ratio [OR] 0.75, 0.48, and 0.44, respectively; all P < .001), but less likely than NH-Native American patients (OR 1.91; P < .001), adjusted for national incidence. Enrollment odds were lower for NH-Black, NH-Asian, and Hispanic patients at CCCs adjusted for catchment area incidence (OR 0.57, 0.26, and 0.32, respectively; P < .001); differences were driven by overenrollment of NH-White patients from outside self-defined catchment areas (18.1% v 12.3%; χ²P = .01) and by CCCs with less absolute enrollee diversity (rank sum P = .03). Among all enrollees, NH-White race-ethnicity and lower neighborhood deprivation correlated with biobank participation (OR 1.81 and 1.45, respectively; P = .01 and .03). For CCC enrollees, the correlation of race-ethnicity with biobank participation was attenuated by a measure accounting for their site’s degree of enrollment disparity but not neighborhood deprivation.

CONCLUSION: Acute leukemia clinical research disparities are substantial and driven by structural trial enrollment barriers at CCCs. Real-time CCC access and enrollment monitoring is needed to better align research participation with local populations.

PMID:35696629 | DOI:10.1200/JCO.22.00307

JCO Glob Oncol. 2022 Jun;8:e2100360. doi: 10.1200/GO.21.00360.

ABSTRACT

PURPOSE: We annually treat more than 800 new patients with cervical cancer, where the majority (approximately 60%) have locally advanced disease and approximately 40% of them are infected with HIV. To optimally care for this large number of patients in low-income settings is difficult. From July 2011, we started using 45.0 Gy/15# hypofractionated radiotherapy (HFRT) as a substitute to 50.0 Gy/25# conventional fractionated radiotherapy (CFRT), for the treatment of locally advanced cervical cancer (LACC). This study aims at comparing the 5-year treatment outcomes between patients with LACC, known HIV serostatus, and treated with either CFRT or HFRT.

METHODS: A retrospective study was conducted according to demographic/clinical data, radiotherapy fractionations, and outcomes. Factors considered were FIGO stages IIB-IIIB, known HIV serostatus, and had completed external-beam radiotherapy and intracavitary brachytherapy. The primary end point was overall survival; the secondary end points were toxicity and compliance.

RESULTS: The study included 221 patients. Squamous cell carcinomas were 95.1% and adenocarcinomas 2.3%. The median age was 45.0 (interquartile range, 38.0-52.0) years. Stages IIB, IIIA, and IIIB were 38.9%, 6.3%, and 54.8%, respectively. HIV-positive and HIV-negative were 87 (39.4%) and 134 (60.6%), respectively. Chemoradiation was administered in 100 (45.2%), and 52 (52.0%) completed chemotherapy. CFRT/HFRT were 116 (52.5%)/105 (47.5%). At 24 months, the overall response was 54.1% for HIV-negative compared with 45.0% for HIV-positive (P value .262). There was no significant differences in acute/late toxicity grades ≥ 2 for HIV-negative/positive treated with HFRT/CFRT. At 60 months, the survival probabilities were 45.7% and 27.7% for HIV-negative and HIV-positive treated with CFRT (P value = .006), whereas it was 44.2% and 30.7% for HIV-negative and HIV-positive treated with HFRT (P value = .048), respectively.

CONCLUSION: For the treatment of LACC with known HIV serology, there was no significant statistical difference in terms of response, toxicity, and compliance between CFRT and HFRT. However, the difference in overall survival between HIV-negative and HIV-positive was significant.

PMID:35696625 | DOI:10.1200/GO.21.00360

Proc Natl Acad Sci U S A. 2022 Jun 21;119(25):e2119281119. doi: 10.1073/pnas.2119281119. Epub 2022 Jun 13.

ABSTRACT

Haplotype-based analyses have recently been leveraged to interrogate the fine-scale structure in specific geographic regions, notably in Europe, although an equivalent haplotype-based understanding across the whole of Europe with these tools is lacking. Furthermore, study of identity-by-descent (IBD) sharing in a large sample of haplotypes across Europe would allow a direct comparison between different demographic histories of different regions. The UK Biobank (UKBB) is a population-scale dataset of genotype and phenotype data collected from the United Kingdom, with established sampling of worldwide ancestries. The exact content of these non-UK ancestries is largely uncharacterized, where study could highlight valuable intracontinental ancestry references with deep phenotyping within the UKBB. In this context, we sought to investigate the sample of European ancestry captured in the UKBB. We studied the haplotypes of 5,500 UKBB individuals with a European birthplace; investigated the population structure and demographic history in Europe, showing in parallel the variety of footprints of demographic history in different genetic regions around Europe; and expand knowledge of the genetic landscape of the east and southeast of Europe. Providing an updated map of European genetics, we leverage IBD-segment sharing to explore the extent of population isolation and size across the continent. In addition to building and expanding upon previous knowledge in Europe, our results show the UKBB as a source of diverse ancestries beyond Britain. These worldwide ancestries sampled in the UKBB may complement and inform researchers interested in specific communities or regions not limited to Britain.

PMID:35696575 | DOI:10.1073/pnas.2119281119

J Cell Biochem. 2022 Jun 13. doi: 10.1002/jcb.30297. Online ahead of print.

ABSTRACT

Epigenetics factors are critical for normal cell function and their regulation is sensitive to malignancy development. EHMT2/G9a and KDM2b are key epigenetics players in different cancer types. However, their expression profiles and related consequences in acute myeloid leukemia (AML) patients have not been known yet. In addition to routine lab work, expression levels of EHMT2/G9a and KDM2b were determined in 110 adult and pediatric patients with De Novo AML. Relations between their expression and patients’ clinical data were tested by statistical methods. EHMT2/G9a and KDM2b were highly expressed in AML patients against control cases and associated with the presence of adverse genomic alterations. In response to induction chemotherapy, EHMT2/G9a and KDM2b showed to be significantly high in resistant and relapsed patients in comparison to the complete remission group. KDM2b overexpression was associated with CD11c (integrin alpha X) downregulation. Kaplan-Meier analysis indicated that EHMT2/G9a and KDM2b overexpression was correlated with poor survival status in AML patients. We conclude that EHMT2/G9a and KDM2b expression levels could be used as independent prognostic factors for AML disease.

PMID:35696556 | DOI:10.1002/jcb.30297

J Cell Biochem. 2022 Jun 13. doi: 10.1002/jcb.30296. Online ahead of print.

ABSTRACT

The Hedgehog (Hh) pathway has emerged as a potential target for effectual hepatic repair based on convincing clinical and preclinical evidence that proves its significance in regulating hepatic damage. The purpose of this study is to probe the effect of quercetin on liver fibrosis through the modulation of the Hh pathway. Healthy male Wistar rats were divided into four groups (n = 10). The control group was treated with saline, rats in the remaining three groups received twice a week intoxication with intraperitoneal injections of thioacetamide (200 mg/kg) for the induction of hepatic fibrosis for 6 weeks. After 28 days of quercetin and silymarin treatment, histological changes, serum biochemical index, antioxidant enzyme activity, key mediators of Hh pathway and inflammation were analyzed. Serological analysis showed statistically improved cholesterol, H.D.L-Cholesterol, and L.D.L-Cholesterol in the treatment groups. Superoxide dismutase and glutathione levels were found to be increased after the treatment with quercetin and silymarin. mRNA expression of important mediators of the Hh signaling, and inflammation including Shh, Ihh, Ptch-1, Smo, Hhip, Gli-3, TNF-α, NFκ-β, and Socs-3 were significantly downregulated after the use of quercetin and silymarin. Quercetin also minimized the thioacetamide-induced histopathological changes, as confirmed by a lower degree of hepatic lobule degeneration, the intralobular occurrence of inflammatory cells, and a lower degree of hepatocytic necrosis. Sudan Black B staining showed remarked lipids improvements in the treatment groups. Taken together, these findings demonstrate that quercetin could ameliorate hepatic fibrosis by antagonizing the hedgehog pathway and also suggest the hedgehog pathway as a potential therapeutic target for the treatment of liver fibrosis.

PMID:35696520 | DOI:10.1002/jcb.30296

J Texture Stud. 2022 Jun 13. doi: 10.1111/jtxs.12703. Online ahead of print.

ABSTRACT

Children with Down syndrome (DS) display a disproportionate number of health challenges, including feeding and swallowing difficulties and food texture sensitivities. To start to address food texture challenges early in life, the aim of this research was to understand mealtime behaviours and identify preferred food textures of children with DS. Children (ages 11 to 58 months) with DS (n=111) and without (typically developing, TD; n=107) participated in a home use test evaluating snack products of varying textures. Parents recorded their children’s reactions to each food product; a panel of trained coders coded videos for mealtime behaviours. Children were also identified as food texture sensitive (TS) or non-texture sensitive (NTS). Results showed that age, TS, the presence of a DS diagnosis and the TS*DS interaction influenced the child’s behaviours to the food products. Children with DS were more likely to increase distance from the food, mouth/suck on the food, and less likely to chew/much on the food compared to children TD. Children with DS also ate significantly less than typically developing children. Similar mealtime behaviours were observed between the children with TD/<30 months of age and children with DS regardless of age (p<0.05). While children with DS/TS had a higher disposition for the dissolvable texture, along with products that were salty and cheesy, children with DS/NTS had a greater tolerance for more textures in general, including crunchy and grainy. Overall, this research identified mealtime behaviours in children with DS, determined overall disposition of children with DS to foods of differences sensory properties, and demonstrated the influence of TS on a child’s disposition to a food. This research will be extended to develop acceptable and innovative food products for children with DS/TS. This article is protected by copyright. All rights reserved.

PMID:35696524 | DOI:10.1111/jtxs.12703

J Agric Food Chem. 2022 Jun 13. doi: 10.1021/acs.jafc.2c01447. Online ahead of print.

ABSTRACT

The price of mammalian milk from different animal species varies greatly due to differences in their yield and nutritional value. Therefore, the authenticity of dairy products has become a hotspot issue in the market due to the replacement or partial admixture of high-cost milk with its low-cost analog. Herein, four common commercial varieties of milk, including goat milk, buffalo milk, Holstein cow milk, and Jersey cow milk, were successfully profiled and differentiated from each other by rapid evaporative ionization mass spectrometry (REIMS) combined with chemometric analysis. This method was developed as a real-time lipid fingerprinting technique. Moreover, the established chemometric algorithms based on multivariate statistical methods mainly involved principal component analysis, orthogonal partial least squares-discriminant analysis, and linear discriminant analysis as the screening and verifying tools to provide insights into the distinctive molecules constituting the four varieties of milk. The ions with m/z 229.1800, 243.1976, 257.2112, 285.2443, 299.2596, 313.2746, 341.3057, 355.2863, 383.3174, 411.3488, 439.3822, 551.5051, 577.5200, 628.5547, 656.5884, 661.5455, 682.6015, and 684.6146 were selected as potential classified markers. The results of the present work suggest that the proposed method could serve as a reference for recognizing dairy fraudulence related to animal species and expand the application field of REIMS technology.

PMID:35696488 | DOI:10.1021/acs.jafc.2c01447

IEEE J Biomed Health Inform. 2022 Jun 13;PP. doi: 10.1109/JBHI.2022.3182869. Online ahead of print.

ABSTRACT

Real-time mental stress monitoring from surgeons and surgical staff in operating rooms may reduce surgical injuries, improve performance and quality of medical care, and accelerate implementation of stress-management strategies. Motivated by the increase in usage of objective and subjective metrics for cognitive monitoring and by the gap in reviews of experimental design setups and data analytics, a systematic review of 71 studies on mental stress and workload measurement in surgical settings, published in 2001-2020, is presented. Almost 61% of selected papers used both objective and subjective measures, followed by 25% that only administered subjective tools – mostly consisting of validated instruments and customized surveys. An overall increase in the total number of publications on intraoperative stress assessment was observed from mid-2010 s along with a momentum in the use of both subjective and real-time objective measures. Cardiac activity, including heart-rate variability metrics, stress hormones, and eye-tracking metrics were the most frequently and electroencephalography (EEG) was the least frequently used objective measures. Around 40% of selected papers collected at least two objective measures, 41% used wearable devices, 23% performed synchronization and annotation, and 76% conducted baseline or multi-point data acquisition. Furthermore, 93% used a variety of statistical techniques, 14% applied regression models, and only one study released a public, anonymized dataset. This review of data modalities, experimental setups, and analysis techniques for intraoperative stress monitoring highlights the initiatives of surgical data science and motivates research on computational techniques for mental and surgical skills assessment and cognition-guided surgery.

PMID:35696473 | DOI:10.1109/JBHI.2022.3182869

IEEE Trans Pattern Anal Mach Intell. 2022 Jun 13;PP. doi: 10.1109/TPAMI.2022.3181472. Online ahead of print.

ABSTRACT

Convolutional neural networks (CNNs) have achieved superior accuracy in many visual-related tasks. However, the inference process through a CNN’s intermediate layers is opaque, making it difficult to interpret such networks or develop trust in their operation. In this paper, we introduce SIGN method for modeling the network’s hidden layer activity using probabilistic models. The activity patterns in layers of interest are modeled as Gaussian mixture models, and transition probabilities between clusters in consecutive modeled layers are estimated to identify paths of inference. For fully connected networks, the entire layer activity is clustered, and the resulting model is a hidden Markov model. For convolutional layers, spatial columns of activity are clustered, and a maximum likelihood model is developed for mining an explanatory inference graph. The graph describes the hierarchy of activity clusters most relevant for network prediction. We show that such inference graphs are useful for understanding the general inference process of a class, as well as explaining the (correct or incorrect) decisions the network makes about specific images. In addition, SIGN provide interesting observations regarding hidden layer activity in general, including the concentration of memorization in a single middle layer in fully connected networks, and a highly local nature of column activities in the top CNN layers.

PMID:35696462 | DOI:10.1109/TPAMI.2022.3181472