Tag: pubmed

Mol Syst Biol. 2021 Nov;17(11):e10323. doi: 10.15252/msb.202110323.

ABSTRACT

Recent advances in genome-wide technologies have enabled analyses using small cell numbers of even single cells. However, obtaining tissue epigenomes with cell-type resolution from large organs and tissues still remains challenging, especially when the available material is limited. Here, we present a ChIL-based approach for analyzing the diverse cellular dynamics at the tissue level using high-depth epigenomic data. “ChIL for tissues” allows the analysis of a single tissue section and can reproducibly generate epigenomic profiles from several tissue types, based on the distribution of target epigenomic states, tissue morphology, and number of cells. The proposed method enabled the independent evaluation of changes in cell populations and gene activation in cells from regenerating skeletal muscle tissues, using a statistical model of RNA polymerase II distribution on gene loci. Thus, the integrative analyses performed using ChIL can elucidate in vivo cell-type dynamics of tissues.

PMID:34730297 | DOI:10.15252/msb.202110323

Compr Rev Food Sci Food Saf. 2021 Nov 3. doi: 10.1111/1541-4337.12860. Online ahead of print.

ABSTRACT

Systematic review and meta-analysis were conducted to quantify the effects of processing stages and interventions on the prevalence and concentration of Campylobacter on broiler carcasses. To comprehensively capture relevant evidence, six databases were searched using the keywords “Campylobacter” and “broiler chicken.” The literature search yielded 10,450 unique citations, and after applying predetermined inclusion and exclusion criteria, 72 and 53 relevant citations were included in meta-analyses for processing stages and interventions, respectively. As the two primary outcomes, log reduction and prevalence changes were estimated for each stage or intervention using a random-effects meta-analysis approach whenever possible. The outcome-level quality assessment was conducted following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The analysis revealed that scalding and chilling majorly reduces the prevalence and concentration of Campylobacter. Immersion chilling reduces the concentration regardless of chemical additives, but its effect on prevalence is not conclusive. The effects of carcass washing applications remain uncertain due to the inconsistency and imprecision of both outcomes. Defeathering and evisceration were identified as stages that can increase both prevalence and concentration. Both chemical and physical processing interventions provide limited efficacy in concentration and prevalence reduction. Major limitations of the review were inconsistency and imprecision at the outcome level and reporting issues and data gaps at the study level. The results are expected to inform quantitative microbial risk assessment model development and support evidence-based decision-making.

PMID:34730272 | DOI:10.1111/1541-4337.12860

Stat Med. 2021 Nov 3. doi: 10.1002/sim.9242. Online ahead of print.

ABSTRACT

There is a growing trend to combine a new targeted or immunotherapy agent with the cancer-specific standard of care to treat different types of cancers. We propose a master-protocol-based, Bayesian phase I/II platform design to co-develop combination (BPCC) therapies in multiple indications. Under the BPCC design, only a single master protocol is needed, and the combined drug is evaluated in different indications in a concurrent or staggered fashion. For each indication, we jointly model dose-toxicity and -efficacy relationships and employ Bayesian hierarchical models to borrow information across them for more efficient indication-specific decision-making. To account for the characteristic of targeted or immunotherapy agents that their efficacy may not monotonically increase with the dose, and often plateau at high doses, we use the utility to quantify the risk-benefit tradeoff of the treatment. At each interim, we update the toxicity and efficacy model, as well as the estimate of the utility, based on the observed data across indications to inform the indication-specific decision of dose escalation and de-escalation and identify the optimal biological dose for each indication. Simulation study shows that the BPCC design has desirable operating characteristics, and that it provides an efficient approach to accelerate the development of combination therapies.

PMID:34730248 | DOI:10.1002/sim.9242

Eur J Heart Fail. 2021 Nov 3. doi: 10.1002/ejhf.2375. Online ahead of print.

ABSTRACT

AIMS: To evaluate the performance of the WATCH-DM risk score, a clinical risk score for heart failure (HF), in patients with dysglycemia and in combination with natriuretic peptides (NP).

METHODS AND RESULTS: Adults with diabetes/pre-diabetes free of HF at baseline from 4 cohort studies (ARIC, CHS, FHS, and MESA) were included. The machine learning- [WATCH-DM(ml)] and integer-based [WATCH-DM(i)] scores were used to estimate the 5-year risk of incident HF. Discrimination was assessed by Harrell’s concordance index (C-index) and calibration by the Greenwood-Nam-D’Agostino (GND) statistic. Improvement in model performance with the addition of NP-levels was assessed by C-index and continuous net reclassification improvement (NRI). Of the 8938 participants included, 3554 (39.8%) had diabetes and 432 (4.8%) developed HF within 5-years. The WATCH-DM(ml) and WATCH-DM (i) scores demonstrated high discrimination for predicting HF risk among individuals with dysglycemia (C-indices = 0.80 and 0.71) respectively, with no evidence of miscalibration (GND P-value ≥0.10). The C-index of elevated NP-levels alone for predicting incident HF among individuals with dysglycemia was significantly higher among participants with low/intermediate (<13) vs. high (≥13) WATCH-DM(i) scores [0.71(95%CI = 0.68-0.74) vs. 0.64(95%CI = 0.61-0.66)]. When NP-levels were combined with the WATCH-DM(i) score, HF risk discrimination improvement and NRI varied across the spectrum of risk with greater improvement observed at low/intermediate risk (WATCH-DM(i) < 13) vs. high risk (WATCH-DM(i) ≥13) (C-index = 0.73 vs. 0.71; NRI = 0.45 vs. 0.17, respectively).

CONCLUSION: The WATCH-DM risk score can accurately predict incident HF risk in community-based individuals with dysglycemia. The addition of NP-levels is associated with greater improvement in the HF risk prediction performance among individuals with low/intermediate risk than those with high risk. This article is protected by copyright. All rights reserved.

PMID:34730265 | DOI:10.1002/ejhf.2375

Acta Obstet Gynecol Scand. 2021 Nov 3. doi: 10.1111/aogs.14277. Online ahead of print.

ABSTRACT

INTRODUCTION: Conflicting reports of increases and decreases in rates of preterm birth (PTB) and stillbirth in the general population during the coronavirus disease 2019 (COVID-19) pandemic have surfaced. The objective of our study was to conduct a living systematic review and meta-analyses of studies reporting pregnancy and neonatal outcomes by comparing the pandemic and pre-pandemic periods.

MATERIAL AND METHODS: We searched PubMed and Embase databases, reference lists of articles published up until August 14, 2021 and included English language studies that compared outcomes between the COVID-19 pandemic time period and the pre-pandemic time periods. Risk of bias was assessed using the Newcastle-Ottawa scale. We conducted random-effects meta-analysis using the inverse variance method.

RESULTS: Forty-five studies with low-to-moderate risk of bias, reporting on 1 843 665 pregnancies during the pandemic period and 23 564 552 pregnancies during the pre-pandemic period, were included. There was significant reduction in unadjusted estimates of PTB (35 studies, unadjusted odds ratio [uaOR] 0.95, 95% CI 0.92-0.98), but not in adjusted estimates (six studies, adjusted OR [aOR] 0.95, 95% CI 0.80-1.13). This reduction was noted in studies from single centers/health areas (25 studies, uaOR 0.90, 95% CI 0.86-0.96) but not in regional/national studies (10 studies, uaOR 0.99, 95% CI 0.95-1.02). There was reduction in spontaneous PTB (six studies, uaOR 0.89, 95% CI 0.81-0.96) and induced PTB (five studies, uaOR 0.89, 95% CI 0.81-0.97). There was no difference in the odds of stillbirth between the pandemic and pre-pandemic time periods (24 studies, uaOR 1.11, 95% CI 0.97-1.26 and four studies, aOR 1.06, 95% CI 0.81-1.38). There was an increase in mean birthweight during the pandemic period compared with the pre-pandemic period (six studies, mean difference 17 g, 95% CI 7-28 g). The odds of maternal mortality were increased (four studies, uaOR 1.15, 95% CI 1.05-1.26); however, only unadjusted estimates were available and the result was mostly influenced by one study from Mexico. There was significant publication bias for the outcome of PTB.

CONCLUSIONS: The COVID-19 pandemic may be associated with a reduction in PTB; however, referral bias cannot be excluded. There was no statistically significant difference in stillbirth between pandemic and pre-pandemic periods.

PMID:34730232 | DOI:10.1111/aogs.14277

Epilepsia. 2021 Nov 3. doi: 10.1111/epi.17109. Online ahead of print.

ABSTRACT

OBJECTIVE: Psychogenic nonepileptic seizures (PNES) are characterized by multifocal and global abnormalities in brain function and connectivity. Only a few studies have examined neuroanatomic correlates of PNES. Traumatic brain injury (TBI) is reported in 83% of patients with PNES and may be a key component of PNES pathophysiology. In this study, we included patients with TBI preceding the onset of PNES (TBI-PNES) and TBI without PNES (TBI-only) to identify neuromorphometric abnormalities associated with PNES.

METHODS: Adults diagnosed with TBI-PNES (n = 62) or TBI-only (n = 59) completed psychological questionnaires and underwent 3-T magnetic resonance imaging. Imaging data were analyzed by voxel- and surface-based morphometry. Voxelwise general linear models computed group differences in gray matter volume, cortical thickness, sulcal depth, fractal dimension (FDf), and gyrification. Statistical models were assessed with permutation-based testing at 5000 iterations with the Threshold-Free Cluster Enhancement toolbox. Logarithmically scaled p-values corrected for multiple comparisons using familywise error were considered significant at p < .05. Post hoc analyses determined the association between structural and psychological measures (p < .05).

RESULTS: TBI-PNES participants demonstrated atrophy of the left inferior frontal gyrus and the right cerebellum VIII. Relative to TBI-only, TBI-PNES participants had decreased FDf in the right superior parietal gyrus and decreased sulcal depth in the left insular cortex. Significant clusters were positively correlated with global assessment of functioning scores, and demonstrated varying negative associations with measures of anxiety, depression, somatization, and global severity of symptoms.

SIGNIFICANCE: The diagnosis of PNES was associated with brain atrophy and reduced cortical folding in regions implicated in emotion processing, regulation, and response inhibition. Cortical folds primarily develop during the third trimester of pregnancy and remain relatively constant throughout the remainder of one’s life. Thus, the observed aberrations in FDf and sulcal depth could originate early in development. The convergence of environmental, developmental, and neurobiological factors may coalesce to reflect the neuropathophysiological substrate of PNES.

PMID:34730239 | DOI:10.1111/epi.17109

Eur Rev Med Pharmacol Sci. 2021 Oct;25(20):6349-6355. doi: 10.26355/eurrev_202110_27008.

ABSTRACT

OBJECTIVE: Pupillometry has been used to assess pain intensity and response to analgesic drugs in adults. The aim of this study was to verify the usefulness and effectiveness of the pupillometer to assess pain and depth of sedation in pediatric patients undergoing painful procedures and to optimize pain management by observing pupillary variations induced by opioids.

PATIENTS AND METHODS: This is a prospective, monocentric study conducted in the sedation room of the Pediatric Intensive Care Unit of Fondazione Policlinico A. Gemelli in Rome. A population of 22 pediatric patients who underwent painful procedures was enrolled. Eleven children were sedated by opioid drugs. Heart rate, systolic blood pressure, diastolic blood pressure, bispectral index, maximum pupil size (Size), pupil change (CH), Neurological Pupil Index (NPi) were collected over four times: before starting the procedure; before the painful stimulus (when the patient was sedated); when the painful stimulus was applied; at the end of the procedure. A NeurOptics NPi-200 pupillometer was used for the study.

RESULTS: Statistical significance in the variation of haemodynamic parameters was less significant than the variation obtained by analyzing the pupillary parameters: a significant change in NPi and CH in the transition from wakefulness to sedation and from the application of the painful stimulus to awakening was found in both study populations, patients who have received opioids and patients who have not received opioids. Changes in the mean CH of the pupil diameter correlate with the depth of sedation, and the size values vary in relation to the administration of opioids.

CONCLUSIONS: Our findings highlight the potential role of pupillometry as a non-invasive method to objectively quantitate pain response in children to reach an efficient analgesic approach.

PMID:34730216 | DOI:10.26355/eurrev_202110_27008

Med Phys. 2021 Nov 3. doi: 10.1002/mp.15332. Online ahead of print.

ABSTRACT

BACKGROUND: The prevalence of thyroid diseases has been increasing year by year. In this study, we established and validated a deep learning method (Cascade region-based convolutional neural network, R-CNN) based on ultrasound videos for automatic detection and segmentation of the thyroid gland and its surrounding tissues in order to reduce the workload of radiologists and improve the detection and diagnosis rate of thyroid disease.

METHODS: 71 patients with normal thyroid ultrasound were included. The ultrasound videos of 59 patients were used as the training dataset, the data of 12 patients were used as the validation dataset, and in addition, the data of 9 patents were used as the testing dataset. Ultrasound videos of thyroid examination, including five standard sections (left and right lobe transverse scan, central isthmus transverse scan, left and right lobe longitudinal scan), were collected from all patients. The radiologists labeled the neck tissues, including anterior cervical muscle, cricoid cartilage, trachea, thyroid gland, endothyroid vessels, carotid artery, internal jugular vein, and esophagus. A large dataset was constructed to train and test the deep learning method. The performance was evaluated using the COCO metrics AP, AP50, and AP75. We compared the Cascade R-CNN with a state-of-the-art method CenterMask in the test dataset.

RESULTS: We annotated 166817, 34364 and 29227 regions in training, validation and testing samples. The model could achieve a good detection performance for the thyroid left lobe, right lobe, isthmus, muscles, trachea, carotid artery, and jugular vein; the AP₅₀ of these tissues were 86.5%, 87.5%, 89.1%, 96.1%, 96.6%, 97.7%, and 91.8%, respectively. In addition, the model showed good segmentation performance for the muscles, trachea, and carotid artery; the AP₅₀ of these tissues were 96%, 96.6%, and 97.8%, respectively. For the left lobe, right lobe, isthmus, esophagus, and jugular vein, AP₅₀ was ≥86%. However, the segmentation results for the cricoid cartilage and endothyroid vessels were not high (AP₅₀ of 53.9% and 48.5%, respectively). For fair comparison, the performance of Cascade R-CNN is better than that of CenterMask for detection and segmentation tasks. The difference was statistically significant (P < 0.05).

CONCLUSIONS: The new method could successfully detect and segment the thyroid gland and its surrounding tissues. This article is protected by copyright. All rights reserved.

PMID:34730231 | DOI:10.1002/mp.15332

Eur Rev Med Pharmacol Sci. 2021 Oct;25(20):6339-6348. doi: 10.26355/eurrev_202110_27006.

ABSTRACT

OBJECTIVE: Acute Cholecystitis (AC) accounts for a significant proportion of patients presenting to the Emergency Department with abdominal pain. We suggest grading the severity of AC with a simple system: TNM, an acronym borrowed by cancer staging where T indicated Temperature, N neutrophils and M Multiple organ failure. This retrospective-prospective observational study evaluates the predictive value of TNM score on mortality of patients with AC.

PATIENTS AND METHODS: TNM was developed in a training cohort of 178 patients with AC who underwent cholecystectomy from February 2005 to December 2012 (retrospectives data). To verify the prognostic value of TNM score, we prospectively recruited 172 patients who were consecutively included and treated from January 2013 to July 2020 as the validation cohort. After defining the categories T, N and M, patients were grouped in stages. The variables analyzed were age, sex, American Society of Anesthesiologists (ASA) score, blood transfusion, temperature, neutrophils count, preoperative organ failure, immune-compromised status, stage.

RESULTS: In the training cohort TNM staging was: none patient at stage 0; 6 patients at stage I; 71 patients at stage II; 71 patients at stage III; 30 patients at stage IV. Death occurred in 51 patients. ASA score, neutrophils count, preoperative organ failure, stage III-IV emerged as statistically significant different prognostic factors. ASA score (III-IV) and stage (III-IV) were significant independent predictors of post-operative mortality in multivariate analysis. Comparable results were observed in the validation cohort.

CONCLUSIONS: TNM classification is very easy to use; it helps to define the mortality risk and it is useful to objectively compare patients with AC.

PMID:34730215 | DOI:10.26355/eurrev_202110_27006

Eur Rev Med Pharmacol Sci. 2021 Oct;25(20):6311-6318. doi: 10.26355/eurrev_202110_27001.

ABSTRACT

OBJECTIVE: This study was done to determine UI prevalence among women in Saudi Arabia and identify the associated risk factors.

PATIENTS AND METHODS: This cross-sectional study was conducted from January 2020 to September 2020 in Saudi women who came to the Urology Department at King Khalid Hospital, Majmaah, Saudi Arabia. In the age group of 20 to 50 years, Saudi women who are not seriously ill or pregnant or in the postnatal period or diagnosed with pelvic organ prolapse were included as participants. A semi-structured questionnaire modified from the International Consultation Incontinence Questionnaire-Short Form was used to collect data on frequency, the severity, consequences, and impact of UI on quality of life. Data were analyzed by SPSS 23 (IBM, Armonk, NY, USA) with the calculation of mean and standard deviation for quantitative variables. Logistic regression analyses were applied to determine the predictors of UI.

RESULTS: A total of 451 participants were included in the final analysis. The mean age of the study population was 42.52 years (SD 11.75). Among risk factors, 45 (10%) had diabetes, 56 (12.4%) had hypertension, 36 (8%) had asthma, 80 (17.7%) had UTI/STDs. Out of 451 participants, 188 (41.7%) had urinary incontinence (UI). Sociodemographic characteristics and risk factors like family income, urinary and genital infections (UTI/STDs), pelvic/uterine prolapse, any other disease, and cough were found to have a statistically significant association with urinary incontinence (p-value <0.05).

CONCLUSIONS: The prevalence of UI was 41.7% among the study population. The various risk factors associated with UI are older age, parity, multiple vaginal deliveries, hypertension, history of asthma, and chronic cough. Poor health-seeking behavior was observed. Creating awareness and the need for early diagnosis with timely intervention is recommended.

PMID:34730211 | DOI:10.26355/eurrev_202110_27001