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Nevin Manimala Statistics

Cigarette Smoke Triggers Loss of Corneal Endothelial Cells and Disruption of Descemet’s Membrane Proteins in Mice

Invest Ophthalmol Vis Sci. 2021 Mar 1;62(3):3. doi: 10.1167/iovs.62.3.3.

ABSTRACT

PURPOSE: To investigate changes at a molecular level in the mouse corneal endothelium (CE) exposed to chronic cigarette smoke (CS).

METHODS: Pregnant mice (gestation days 18-20) were placed in a whole-body exposure smoking chamber, and a few days later pups were born. After 3.5 months of CS exposure, a ConfoScan4 scanning microscope was used to examine the corneal endothelial cells (CECs) of CS-exposed and control (Ct) mice. The CE was peeled under a microscope and maintained as four biological replicates (two male and two female) for CS-exposed and Ct mice; each replicate consisted of 16 CEs. The proteome of the CE was investigated through mass spectrometry.

RESULTS: The CE images of CS-exposed and Ct mice revealed a difference in the shape of CECs accompanied by a nearly 10% decrease in CEC density (P < 0.00003) following CS exposure. Proteome profiling identified a total of 524 proteins exhibiting statistically significant changes in CE from CS-exposed mice. Importantly, proteins associated with Descemet’s membrane (DM), including COL4α1, COL4α2, COL4α3, COL4α4, COL4α5, COL4α6, COL8α1, COL8α2, and FN1, among others, exhibited diminished protein levels in the CE of CS-exposed mice.

CONCLUSIONS: Our data confirm that exposure to CS results in reduced CEC density accompanied by diminished levels of multiple collagen and extracellular matrix proteins associated with DM.

PMID:33651877 | DOI:10.1167/iovs.62.3.3

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Nevin Manimala Statistics

Magnitude and associated factors of peripheral cytopenia among HIV-infected children attending at University of Gondar Specialized Referral Hospital, Northwest Ethiopia

PLoS One. 2021 Mar 2;16(3):e0247878. doi: 10.1371/journal.pone.0247878. eCollection 2021.

ABSTRACT

BACKGROUND: Isolated or multi lineage cytopenia are the most common clinicopathological features and independently associated with increased risk of disease progression and death among human immunodeficiency virus infected children. In the study area, there is scarcity of data about the magnitude of various cytopenia.

OBJECTIVES: Aimed to determine the magnitude and associated factors of peripheral cytopenia among HIV infected children at the University of Gondar Specialized Referral Hospital ART clinic, Northwest Ethiopia.

METHODS: Institutional based cross-sectional study was conducted on 255 HIV infected children from January- April 2020. None probable convenient sampling technique was used to select the study participant. Socio demographic data were collected by pre tested structured questionnaire via face-to-face interview and their medical data were obtained from their follow-up medical records. Moreover, blood specimens were collected and examined for complete blood count, viral load and blood film, whereas stool specimens were collected and examined for intestinal parasites. Bi-variable and multi-variable logistic regression models were fitted to identify associated factors of cytopenia. P-Value <0.05 was considered as statistically significant.

RESULT: The overall magnitude of peripheral cytopenia was 38.9%. Anemia, leukopenia, lymphopenia, thrombocytopenia and bi-cytopenia were 21.2%, 12.2%, 11%, 1.6% and 3.9% respectively. Being in the age group of 2-10 years (AOR = 5.38, 95%CI 2.33-12.46), AZT based regimen (AOR = 5.44, 95%CI: 2.24-13.21), no eating green vegetables (AOR = 2.49, 95% CI: 1.26-4.92) and having plasma viral load >1000 copies /ml (AOR = 5.38, 95%CI: 2.22-13.03) showed significant association with anemia.

CONCLUSION: Anemia was the predominant peripheral cytopenia among HIV infected children in this study. It was strongly associated with AZT based drug type, age below 10 years and high viral load. Critical stress should be given for early investigation and management of cytopenia in addition to the use of alternative drug which leads to higher viral suppression and lower risk of toxicity issue.

PMID:33651817 | DOI:10.1371/journal.pone.0247878

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Nevin Manimala Statistics

When women eat last: Discrimination at home and women’s mental health

PLoS One. 2021 Mar 2;16(3):e0247065. doi: 10.1371/journal.pone.0247065. eCollection 2021.

ABSTRACT

The 2011 India Human Development Survey found that in about a quarter of Indian households, women are expected to have their meals after men have finished eating. This study investigates whether this form of gender discrimination is associated with worse mental health outcomes for women. Our primary data source is a new, state-representative mobile phone survey of women ages 18-65 in Bihar, Jharkhand, and Maharashtra in 2018. We measure mental health using questions from the World Health Organization’s Self-Reporting Questionnaire. We find that, for women in these states, eating last is correlated with worse mental health, even after accounting for differences in socioeconomic status. We discuss two possible mechanisms for this relationship: eating last may be associated with worse mental health because it is associated with worse physical health, or eating last may be associated with poor mental health because it is associated with less autonomy, or both.

PMID:33651820 | DOI:10.1371/journal.pone.0247065

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Nevin Manimala Statistics

Chronic obstructive Eustachian tube dysfunction: CT assessment with Valsalva maneuver and ETS-7 score

PLoS One. 2021 Mar 2;16(3):e0247708. doi: 10.1371/journal.pone.0247708. eCollection 2021.

ABSTRACT

Chronic obstructive Eustachian tube dysfunction (ETD) is a common disorder of the middle ear. In recent years, two main diagnostic tools have become available: Eustachian tube score (ETS-7) and computed tomography (CT) combined with Valsalva maneuver. The aim of this study is to evaluate the outcomes of ETS-7 and CT in a group of patients affected by middle ear atelectasis with a strong suspicion of ETD. Three males and nine females, affected by middle ear atelectasis with retraction of the TM were enrolled. Each patient underwent to Eustachian tube dysfunction evaluation adopting the ETS-7 score and a temporal bone CT with Valsalva maneuver. The ears analyzed at steady state were divided into 2 groups: ETS<7 group and ETS≥ 7 group. The same division was applied for the ears analyzed after the Valsalva maneuver: ETS<7 group and ETS≥ 7 group. ETs were categorized as “well defined” (WD) and “not defined” (ND). The results of the analysis of the ETS-7 score in all 24 ears showed that 42% presented ETS ≥7, while 58% had ETS <7, indicating a diagnosis of ETD. In the ETS<7 group after Valsalva, ET was visualized in 33% of patients. In the ETS≥7 group it was WD in 29% after the Valsalva manoeuver. In both groups the comparison between the visualization of the ET before and after the Valsalva manoeuver did not present a statistical difference. No correlation emerged between ET evaluation with CT scan during Valsalva maneuver and ETS-7 score. It confirms that there is not a gold standard for the study of ET dysfunction.

PMID:33651800 | DOI:10.1371/journal.pone.0247708

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Optimising passive surveillance of a neglected tropical disease in the era of elimination: A modelling study

PLoS Negl Trop Dis. 2021 Mar 2;15(3):e0008599. doi: 10.1371/journal.pntd.0008599. Online ahead of print.

ABSTRACT

BACKGROUND: Surveillance is an essential component of global programs to eliminate infectious diseases and avert epidemics of (re-)emerging diseases. As the numbers of cases decline, costs of treatment and control diminish but those for surveillance remain high even after the ‘last’ case. Reducing surveillance may risk missing persistent or (re-)emerging foci of disease. Here, we use a simulation-based approach to determine the minimal number of passive surveillance sites required to ensure maximum coverage of a population at-risk (PAR) of an infectious disease.

METHODOLOGY AND PRINCIPAL FINDINGS: For this study, we use Gambian human African trypanosomiasis (g-HAT) in north-western Uganda, a neglected tropical disease (NTD) which has been reduced to historically low levels (<1000 cases/year globally), as an example. To quantify travel time to diagnostic facilities, a proxy for surveillance coverage, we produced a high spatial-resolution resistance surface and performed cost-distance analyses. We simulated travel time for the PAR with different numbers (1-170) and locations (170,000 total placement combinations) of diagnostic facilities, quantifying the percentage of the PAR within 1h and 5h travel of the facilities, as per in-country targets. Our simulations indicate that a 70% reduction (51/170) in diagnostic centres still exceeded minimal targets of coverage even for remote populations, with >95% of a total PAR of ~3million individuals living ≤1h from a diagnostic centre, and we demonstrate an approach to best place these facilities, informing a minimal impact scale back.

CONCLUSIONS: Our results highlight that surveillance of g-HAT in north-western Uganda can be scaled back without substantially reducing coverage of the PAR. The methodology described can contribute to cost-effective and equable strategies for the surveillance of NTDs and other infectious diseases approaching elimination or (re-)emergence.

PMID:33651803 | DOI:10.1371/journal.pntd.0008599

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Short-range template switching in great ape genomes explored using pair hidden Markov models

PLoS Genet. 2021 Mar 2;17(3):e1009221. doi: 10.1371/journal.pgen.1009221. Online ahead of print.

ABSTRACT

Many complex genomic rearrangements arise through template switch errors, which occur in DNA replication when there is a transient polymerase switch to an alternate template nearby in three-dimensional space. While typically investigated at kilobase-to-megabase scales, the genomic and evolutionary consequences of this mutational process are not well characterised at smaller scales, where they are often interpreted as clusters of independent substitutions, insertions and deletions. Here we present an improved statistical approach using pair hidden Markov models, and use it to detect and describe short-range template switches underlying clusters of mutations in the multi-way alignment of hominid genomes. Using robust statistics derived from evolutionary genomic simulations, we show that template switch events have been widespread in the evolution of the great apes’ genomes and provide a parsimonious explanation for the presence of many complex mutation clusters in their phylogenetic context. Larger-scale mechanisms of genome rearrangement are typically associated with structural features around breakpoints, and accordingly we show that atypical patterns of secondary structure formation and DNA bending are present at the initial template switch loci. Our methods improve on previous non-probabilistic approaches for computational detection of template switch mutations, allowing the statistical significance of events to be assessed. By specifying realistic evolutionary parameters based on the genomes and taxa involved, our methods can be readily adapted to other intra- or inter-species comparisons.

PMID:33651813 | DOI:10.1371/journal.pgen.1009221

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Nevin Manimala Statistics

Can a Deep-learning Model for the Automated Detection of Vertebral Fractures Approach the Performance Level of Human Subspecialists?

Clin Orthop Relat Res. 2021 Feb 26. doi: 10.1097/CORR.0000000000001685. Online ahead of print.

ABSTRACT

BACKGROUND: Vertebral fractures are the most common osteoporotic fractures in older individuals. Recent studies suggest that the performance of artificial intelligence is equal to humans in detecting osteoporotic fractures, such as fractures of the hip, distal radius, and proximal humerus. However, whether artificial intelligence performs as well in the detection of vertebral fractures on plain lateral spine radiographs has not yet been reported.

QUESTIONS/PURPOSES: (1) What is the accuracy, sensitivity, specificity, and interobserver reliability (kappa value) of an artificial intelligence model in detecting vertebral fractures, based on Genant fracture grades, using plain lateral spine radiographs compared with values obtained by human observers? (2) Do patients’ clinical data, including the anatomic location of the fracture (thoracic or lumbar spine), T-score on dual-energy x-ray absorptiometry, or fracture grade severity, affect the performance of an artificial intelligence model? (3) How does the artificial intelligence model perform on external validation?

METHODS: Between 2016 and 2018, 1019 patients older than 60 years were treated for vertebral fractures in our institution. Seventy-eight patients were excluded because of missing CT or MRI scans (24% [19]), poor image quality in plain lateral radiographs of spines (54% [42]), multiple myeloma (5% [4]), and prior spine instrumentation (17% [13]). The plain lateral radiographs of 941 patients (one radiograph per person), with a mean age of 76 ± 12 years, and 1101 vertebral fractures between T7 and L5 were retrospectively evaluated for training (n = 565), validating (n = 188), and testing (n = 188) of an artificial intelligence deep-learning model. The gold standard for diagnosis (ground truth) of a vertebral fracture is the interpretation of the CT or MRI reports by a spine surgeon and a radiologist independently. If there were any disagreements between human observers, the corresponding CT or MRI images would be rechecked by them together to reach a consensus. For the Genant classification, the injured vertebral body height was measured in the anterior, middle, and posterior third. Fractures were classified as Grade 1 (< 25%), Grade 2 (26% to 40%), or Grade 3 (> 40%). The framework of the artificial intelligence deep-learning model included object detection, data preprocessing of radiographs, and classification to detect vertebral fractures. Approximately 90 seconds was needed to complete the procedure and obtain the artificial intelligence model results when applied clinically. The accuracy, sensitivity, specificity, interobserver reliability (kappa value), receiver operating characteristic curve, and area under the curve (AUC) were analyzed. The bootstrapping method was applied to our testing dataset and external validation dataset. The accuracy, sensitivity, and specificity were used to investigate whether fracture anatomic location or T-score in dual-energy x-ray absorptiometry report affected the performance of the artificial intelligence model. The receiver operating characteristic curve and AUC were used to investigate the relationship between the performance of the artificial intelligence model and fracture grade. External validation with a similar age population and plain lateral radiographs from another medical institute was also performed to investigate the performance of the artificial intelligence model.

RESULTS: The artificial intelligence model with ensemble method demonstrated excellent accuracy (93% [773 of 830] of vertebrae), sensitivity (91% [129 of 141]), and specificity (93% [644 of 689]) for detecting vertebral fractures of the lumbar spine. The interobserver reliability (kappa value) of the artificial intelligence performance and human observers for thoracic and lumbar vertebrae were 0.72 (95% CI 0.65 to 0.80; p < 0.001) and 0.77 (95% CI 0.72 to 0.83; p < 0.001), respectively. The AUCs for Grades 1, 2, and 3 vertebral fractures were 0.919, 0.989, and 0.990, respectively. The artificial intelligence model with ensemble method demonstrated poorer performance for discriminating normal osteoporotic lumbar vertebrae, with a specificity of 91% (260 of 285) compared with nonosteoporotic lumbar vertebrae, with a specificity of 95% (222 of 234). There was a higher sensitivity 97% (60 of 62) for detecting osteoporotic (dual-energy x-ray absorptiometry T-score ≤ -2.5) lumbar vertebral fractures, implying easier detection, than for nonosteoporotic vertebral fractures (83% [39 of 47]). The artificial intelligence model also demonstrated better detection of lumbar vertebral fractures compared with detection of thoracic vertebral fractures based on the external dataset using various radiographic techniques. Based on the dataset for external validation, the overall accuracy, sensitivity, and specificity on bootstrapping method were 89%, 83%, and 95%, respectively.

CONCLUSION: The artificial intelligence model detected vertebral fractures on plain lateral radiographs with high accuracy, sensitivity, and specificity, especially for osteoporotic lumbar vertebral fractures (Genant Grades 2 and 3). The rapid reporting of results using this artificial intelligence model may improve the efficiency of diagnosing vertebral fractures. The testing model is available at http://140.113.114.104/vght_demo/corr/. One or multiple plain lateral radiographs of the spine in the Digital Imaging and Communications in Medicine format can be uploaded to see the performance of the artificial intelligence model.

LEVEL OF EVIDENCE: Level II, diagnostic study.

PMID:33651768 | DOI:10.1097/CORR.0000000000001685

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Nevin Manimala Statistics

Impact of burnout on empathy

N Z Med J. 2021 Feb 19;134(1530):12-20.

ABSTRACT

AIM: Burnout has a damaging effect on both the wellbeing of medical professionals and patients alike. Empathy is an important part of the therapeutic relationship and could be damaged by burnout. We aimed to describe the prevalence of burnout, assess levels of empathy and explore the relationship between burnout and empathy among senior medical officers (SMOs). We hypothesised that there would be a negative correlation between empathy and burnout.

METHOD: This was a cross-sectional observational study involving SMOs from a variety of specialities. The focus is on SMOs with relatively prolonged contact times with patients. Email invitations were sent out requesting participation in an electronic survey on the QuestionPro platform. The survey comprised 42 questions enquiring about demographics, empathy (Jefferson Scale of Physician Empathy) and burnout (Copenhagen Burnout Inventory). Correlational analyses were performed.

RESULTS: Three hundred and fourteen invitations were sent out and 178 responses were received (56.7% response rate). Forty-five percent of SMOs surveyed were experiencing high levels of personal burnout. There was a statistically significant negative correlation between empathy and patient-related burnout (p=0.018).

CONCLUSIONS: The results show high levels of personal burnout among SMOs and suggest that empathy reduces as patient-related burnout increases. The nature of this relationship is a complex one, and other contributing variables should be considered.

PMID:33651773

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Nevin Manimala Statistics

Stochastic simulation algorithms for Interacting Particle Systems

PLoS One. 2021 Mar 2;16(3):e0247046. doi: 10.1371/journal.pone.0247046. eCollection 2021.

ABSTRACT

Interacting Particle Systems (IPSs) are used to model spatio-temporal stochastic systems in many disparate areas of science. We design an algorithmic framework that reduces IPS simulation to simulation of well-mixed Chemical Reaction Networks (CRNs). This framework minimizes the number of associated reaction channels and decouples the computational cost of the simulations from the size of the lattice. Decoupling allows our software to make use of a wide class of techniques typically reserved for well-mixed CRNs. We implement the direct stochastic simulation algorithm in the open source programming language Julia. We also apply our algorithms to several complex spatial stochastic phenomena. including a rock-paper-scissors game, cancer growth in response to immunotherapy, and lipid oxidation dynamics. Our approach aids in standardizing mathematical models and in generating hypotheses based on concrete mechanistic behavior across a wide range of observed spatial phenomena.

PMID:33651796 | DOI:10.1371/journal.pone.0247046

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Nevin Manimala Statistics

The Weekend Effect in Septic Shock Patients Using the Nationwide Emergency Department Sample Database

Shock. 2021 Feb 25. doi: 10.1097/SHK.0000000000001766. Online ahead of print.

ABSTRACT

BACKGROUND: The weekend effect is the increased mortality in hospitalized patients admitted on the weekend. The aim of this study was to examine the effect of weekend admissions on septic shock patients.

METHODS: This is a retrospective observational study of the 2014 Nationwide Emergency Department Sample Database (NEDS). Septic shock patients were included in this study using ICD-9-CM codes. Descriptive analysis was done, in addition to bivariate analysis to compare variables based on admission day. Multivariate analysis was conducted to examine the association between admission day and mortality in septic shock patients after adjusting for potential confounding factors.

RESULTS: A total of 364,604 septic shock patients were included in this study. The average age was 67.19 years, and 51.1% were males. 73.0% of patients presented on weekdays. 32.3% of septic shock patients died during their hospital stay. After adjusting for confounders, there was no significant difference in the ED or in-hospital mortality of septic shock patients admitted on the weekend compared to those admitted during weekdays, (OR = 1.00 [95%CI: 0.97 – 1.03], p-value = 0.985).

CONCLUSION: There was no statistically significant difference in overall mortality between septic shock patients admitted on the weekend or weekday. Our results are contradictory to previous studies showing an increased mortality with the weekend effect. The previous observations which have been made may not stand up with current treatment protocols.

PMID:33651724 | DOI:10.1097/SHK.0000000000001766