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Mechanism underlying the immune checkpoint inhibitor-induced hyper-progressive state of cancer

Cancer Drug Resist. 2022 Feb 8;5(1):147-164. doi: 10.20517/cdr.2021.104. eCollection 2022.

ABSTRACT

Immune checkpoint inhibitors (ICIs) are gradually replacing chemotherapy as the cornerstone of the treatment of advanced malignant tumors because of their long-lasting and significant effect in different tumor types and greatly prolonging the survival time of patients. However, not all patients can respond to ICIs, and even rapid tumor growth after treatment with ICI has been observed in a number of clinical studies. This rapid progression phenomenon is called hyper-progressive disease (HPD). The occurrence of HPD is not uncommon. Past statistics show that the incidence of HPD is 4%-29% in different tumor types, and the progression-free survival and overall survival of patients with HPD are significantly shorter than those of the non-HPD progressor group. With the deepening of the study of HPD, we have established a preliminary understanding of HPD, but the diagnostic criteria of HPD are still not unified, and the addition of biomarkers may break this dilemma. In addition, quite a few immune cells have been found to be involved in the occurrence and development of HPD in the tumor microenvironment, indicating that the molecular mechanism of HPD may be triggered by a variety of ongoing events at the same time. In this review, we summarize past findings, including case reports, clinical trials, and fundamental research; compare the diagnostic criteria, incidence, and clinical prognostic indicators of HPD in different studies; and explore the molecular mechanism and future research direction of HPD.

PMID:35582541 | PMC:PMC8992596 | DOI:10.20517/cdr.2021.104

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Prevalence of Aggressive Behavior Toward Fellows, Residents, and Nurses at a Tertiary Care Hospital in Riyadh, Saudi Arabia

Cureus. 2022 Apr 14;14(4):e24142. doi: 10.7759/cureus.24142. eCollection 2022 Apr.

ABSTRACT

Background Workplace bullying (WPB) is a form of mistreatment toward an individual manifested by physical, verbal, or indirect aggression. Affected victims display a wide range of signs and symptoms that impact their health. This study aimed to investigate the prevalence of aggressive behavior toward healthcare workers and its effects on job satisfaction, general health, and mental health. Methodology An online survey comprising a revised version of the Negative Acts Questionnaire-Revised (NAQ-R) was distributed to the fellows, residents, and nurses working in a tertiary care hospital. The survey collected information regarding the group’s demographics and their exposure to WPB encountered in the work environment while maintaining confidentiality. Survey results were analyzed using SPSS Statistics version 25 (IBM Corp., Armonk, NY, USA). Results Among the 339 participants who filled the survey, 53% of healthcare practitioners in different services had experienced some form of WPB. Among the targeted group, it was noted that female gender (50%), age between 31 and 41 years (57.03%), nurses (51.98%), non-Saudi practitioners (41.94%), and those working in inpatient settings (49.74%) were the most commonly affected individuals in the medical facility. Furthermore, higher bullying prevalence was correlated with lower job satisfaction and mental health levels. Conclusions Age, gender, job, and nationality were factors associated with increased susceptibility to WPB. WPB in any facility is an unfortunate event, especially in a healthcare setting. It affects health practitioners by decreasing job satisfaction, jeopardizing health, and increasing the risk of harm to patients. WPB will eventually have a negative impact on the medical facility and the healthcare sector. Hence, hospital administrations should be alarmed about the rise in WPB, and adequate measures must be taken to deal with the root cause of the problem.

PMID:35582558 | PMC:PMC9107312 | DOI:10.7759/cureus.24142

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Effects of early physical therapy on motor development in children with Down syndrome

North Clin Istanb. 2022 Apr 18;9(2):156-161. doi: 10.14744/nci.2020.90001. eCollection 2022.

ABSTRACT

OBJECTIVE: The objective of the study was to compare the motor development of children with Down syndrome (DS) who received physical therapy (PT) and did not receive PT, and to show the effect of PT programs started before the age of one on movement development.

METHODS: The study included aged between 6 and 42 months, 58 children with DS. Children with DS were divided into two groups as receiving PT and non-receiving PT. Children with DS who received PT were further divided into two groups according to the age of starting PT as before and after 1 year of age. Gross motor and fine motor development of the cases were evaluated with Bayley Scales of Infant and Toddler Development III.

RESULTS: Gross motor scaled scores (GM-SS: 3.88±3.46-1.67±1.23), fine motor scaled scores (FM-SS: 4.29±3.24-1.79±0.93), and composite scores (64.4±19.5-50.38±5.38) of PT group were statistically higher than the non-PT group (p<0.05). In addition, GM-SS (5.22±4.23-2.38±1.20), FM-SS; (5.61±3.85-2.81±1.37), and composite scores (72.33±23.85-55.56±5.7) of the cases who started PT before the age of one were statistically higher than those who started after the age of one (p<0.05).

CONCLUSION: Our results revealed that PT especially when started early childhood under had a positive effect on the development of gross and fine motor in children with DS and provided a scientific basis for referring children with DS to PT programs before the age of one. Clinicians should recommend PT for children with DS in the early period.

PMID:35582517 | PMC:PMC9039636 | DOI:10.14744/nci.2020.90001

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Anidulafungin biliary passage in liver transplant patients

Transpl Infect Dis. 2022 May 17. doi: 10.1111/tid.13848. Online ahead of print.

NO ABSTRACT

PMID:35579962 | DOI:10.1111/tid.13848

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Impact of Nodal Metastases in HPV-negative Oropharyngeal Cancer

Cancer Epidemiol Biomarkers Prev. 2022 May 17:cebp.0776.2021. doi: 10.1158/1055-9965.EPI-21-0776. Online ahead of print.

ABSTRACT

BACKGROUND: The updated American Joint Committee on Cancer (AJCC) 8th Edition staging manual restructured nodal classification and staging by placing less prognostic emphasis on nodal metastases for HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). However, there was no change for HPV-negative OPSCC. The purpose of our study is to examine the impact of nodal metastases on survival in HPV-negative OPSCC.

METHODS: HPV-negative OPSCC were queried from the NCDB and SEER databases. Univariable and multivariable models were utilized to determine the impact of nodal status on overall survival. These patients were reclassified according to AJCC 8 HPV-positive criteria (TNM8+) and risk stratification was quantified with C-statistics.

RESULTS: There were 11,147 cases of HPV-negative OPSCC in the NCDB and 3,613 cases in SEER that were included in the nodal classification analysis. Unlike non-oropharyngeal malignancies, increased nodal stage is not clearly associated with survival for patients with OPSCC independent of HPV status. When the TNM8+ was applied to HPV-negative patients, there was improved concordance in the NCDB cohort, 0.561 {plus minus} 0.004 to 0.624 {plus minus} 0.004 (difference +0.063) and the SEER cohort, 0.561 {plus minus} 0.008 to 0.625 {plus minus} 0.008 (difference +0.065).

CONCLUSIONS: We demonstrated a reduced impact of nodal metastasis on OPSCC survival, independent of HPV-status and specific to OPSCC.

IMPACT: We demonstrate, that when nodal staging is de-emphasized as a part of overall staging, we see improved concordance and risk stratification for HPV-negative OPSCC. The exact mechanism of this differential impact remains unknown but offers a novel area of study.

PMID:35579907 | DOI:10.1158/1055-9965.EPI-21-0776

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Community, Time, and (Con)text: A Dynamical Systems Analysis of Online Communication and Community Health among Open-Source Software Communities

Cogn Sci. 2022 May;46(5):e13134. doi: 10.1111/cogs.13134.

ABSTRACT

Free and open-source software projects have become essential digital infrastructure over the past decade. These projects are largely created and maintained by unpaid volunteers, presenting a potential vulnerability if the projects cannot recruit and retain new volunteers. At the same time, their development on open collaborative development platforms provides a nearly complete record of the community’s interactions; this affords the opportunity to study naturally occurring language dynamics at scale and in a context with massive real-world impact. The present work takes a dynamical systems view of language to understand the ways in which communicative context and community membership shape the emergence and impact of language use-specifically, sentiment and expressions of gratitude. We then present evidence that these language dynamics shape newcomers’ likelihood of returning, although the specific impacts of different community responses are crucially modulated by the context of the newcomer’s first contact with the community.

PMID:35579857 | DOI:10.1111/cogs.13134

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Early Diagnosis and Quantitative Analysis of Stages in Retinopathy of Prematurity Based on Deep Convolutional Neural Networks

Transl Vis Sci Technol. 2022 May 2;11(5):17. doi: 10.1167/tvst.11.5.17.

ABSTRACT

PURPOSE: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. An accurate and timely diagnosis of the early stages of ROP allows ophthalmologists to recommend appropriate treatment while blindness is still preventable. The purpose of this study was to develop an automatic deep convolutional neural network-based system that provided a diagnosis of stage I to III ROP with feature parameters.

METHODS: We developed three data sets containing 18,827 retinal images of preterm infants. These retinal images were obtained from the ophthalmology department of Jiaxing Maternal and Child Health Hospital in China. After segmenting images, we calculated the region of interest (ROI). We trained our system based on segmented ROI images from the training data set, tested the performance of the classifier on the test data set, and evaluated the widths of the demarcation lines or ridges extracted by the system, as well as the ratios of vascular proliferation within the ROI on a comparison data set.

RESULTS: The trained network achieved a sensitivity of 90.21% with 97.67% specificity for the diagnosis of stage I ROP, 92.75% sensitivity with 98.74% specificity for stage II ROP, and 91.84% sensitivity with 99.29% sensitivity for stage III ROP. When the system diagnosed normal images, the sensitivity and specificity reached 95.93% and 96.41%, respectively. The widths (in pixels) of the demarcation lines or ridges for normal, stage I, stage II, and stage III were 15.22 ± 1.06, 26.35 ± 1.36, and 30.75 ± 1.55. The ratios of the vascular proliferation within the ROI were 1.40 ± 0.29, 1.54 ± 0.26, and 1.81 ± 0.33. All parameters were statistically different among the groups. When physicians integrated quantitative parameters of the extracted features with their clinic diagnosis, the κ score was significantly improved.

CONCLUSIONS: Our system achieved a high accuracy of diagnosis for stage I to III ROP. It used the quantitative analysis of the extracted features to assist physicians in providing classification decisions.

TRANSLATIONAL RELEVANCE: The high performance of the system suggests potential applications in ancillary diagnosis of the early stages of ROP.

PMID:35579887 | DOI:10.1167/tvst.11.5.17

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Analysis of a monocentric computed tomography dosimetric database using a radiation dose index monitoring software: dose levels and alerts before and after the implementation of the adaptive statistical iterative reconstruction on CT images

Radiol Med. 2022 May 17. doi: 10.1007/s11547-022-01481-w. Online ahead of print.

ABSTRACT

OBJECTIVE: To analyze dosimetric data of a single center by a radiation dose index monitoring software evaluating quantitatively the dose reduction obtained with the implementation of the adaptive statistical iterative reconstruction (ASIR) on Computed Tomography in terms of both the value of the dose length product (DLP) and the alerts provided by the dose tool.

METHODS: Dosimetric quantities were acquired using Qaelum DOSE tool (QAELUM NV, Leuven-Heverlee, Belgium). Dose data pertaining to CT examinations were performed using a General Electric Healthcare CT tomography with 64 detectors. CT dose data were collected over 4 years (January 1, 2017 to December 31, 2020) and included CT dose length product (DLP). Moreover, all CT examinations that triggered a high radiation dose (twice the median for that study description), termed alerts on Dose tool, were retrieved for the analysis. Two radiologists retrospectively assessed CT examinations in consensus for the images quality and for the causes of the alerts issued. A Chi-square test was used to assess whether there were any statistically significant differences among categorical variable while a Kruskal Wallis test was considered to assess differences statistically significant for continuous variables.

RESULTS: Differences statistically significant were found for the DLP median values between the dosimetric data recorded on 2017-2018 versus 2019-2020. The differences were linked to the implementation of ASIR technique at the end of 2018 on the CT scanner. The highest percentage of alerts was reported in the CT study group “COMPLETE ABDOMEN + CHEST + HEAD” (range from 1.26% to 2.14%). A reduction year for year was relieved linked to the CT protocol optimization with a difference statistically significant. The highest percentage of alerts was linked to wrong study label/wrong study protocol selection with a range from 29 to 40%.

CONCLUSIONS: Automated methods of radiation dose data collection allowed for detailed radiation dose analysis according to protocol and equipment over time. The use of CT ASIR technique could determine considerable reduction in radiation dose.

PMID:35579854 | DOI:10.1007/s11547-022-01481-w

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Exploring the Potential for Smoke-Free Laws to Reduce Smoking Disparities by Sexual Orientation in the USA

Int J Behav Med. 2022 May 17. doi: 10.1007/s12529-022-10099-1. Online ahead of print.

ABSTRACT

BACKGROUND: We examined associations between smoke-free laws and smoking outcomes in a nationally representative sample of US adults, including exploring whether these associations differed for heterosexual and sexual minority (SM) adults.

METHODS: We constructed county-level variables representing the percent of the population covered by state-, county-, or city-level smoke-free laws in workplaces and hospitality venues. We combined this information with restricted individual-level adult data with masked county identifiers from the National Health Interview Survey (NHIS), 2013-2018. We used modified Poisson regression to explore associations between each type of smoke-free law and the prevalence ratio (PR) of current smoking, and we used linear regression to explore associations with smoking intensity (mean cigarettes per day). We assessed interactions between smoke-free laws and SM status on the additive scale to determine whether associations were different for SM and heterosexual adults.

RESULTS: In adjusted models without interaction terms, smoke-free laws in hospitality venues were associated with lower prevalence of current smoking (PR = 0.93, 95% confidence interval (CI) = 0.89, 0.98). Both types of smoke-free laws were associated with lower mean cigarettes per day (workplace law change in mean = – 0.50, 95% CI = – 0.89, – 0.12; hospitality law change in mean = – 0.72, 95% CI = – 1.14,-0.30). We did not observe any statistically significant interactions by SM status, though statistical power was limited.

CONCLUSIONS: We did not find evidence that smoke-free laws were differentially associated with smoking outcomes for heterosexual and SM adults. Additional studies are needed to further explore the potential for tobacco control policies to address the elevated risk of smoking in SM communities.

PMID:35579845 | DOI:10.1007/s12529-022-10099-1

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Proteomic Analysis of Human Neural Stem Cell Differentiation by SWATH-MS

Methods Mol Biol. 2022 May 18. doi: 10.1007/7651_2022_462. Online ahead of print.

ABSTRACT

The unique properties of stem cells to self-renew and differentiate hold great promise in disease modelling and regenerative medicine. However, more information about basic stem cell biology and thorough characterization of available stem cell lines is needed. This is especially essential to ensure safety before any possible clinical use of stem cells or partially committed cell lines. As proteins are the key effector molecules in the cell, the proteomic characterization of cell lines, cell compartments or cell secretome and microenvironment is highly beneficial to answer above mentioned questions. Nowadays, method of choice for large-scale discovery-based proteomic analysis is mass spectrometry (MS) with data-independent acquisition (DIA). DIA is a robust, highly reproducible, high-throughput quantitative MS approach that enables relative quantification of thousands of proteins in one sample. In the current protocol, we describe a specific variant of DIA known as SWATH-MS for characterization of neural stem cell differentiation. The protocol covers the whole process from cell culture, sample preparation for MS analysis, the SWATH-MS data acquisition on TTOF 5600, the complete SWATH-MS data processing and quality control using Skyline software and the basic statistical analysis in R and MSstats package. The protocol for SWATH-MS data acquisition and analysis can be easily adapted to other samples amenable to MS-based proteomics.

PMID:35579839 | DOI:10.1007/7651_2022_462