Nevin Manimala

Brief Bioinform. 2022 Mar 31:bbac088. doi: 10.1093/bib/bbac088. Online ahead of print.

ABSTRACT

Characterizing the molecular identity of a cell is an essential step in single-cell RNA sequencing (scRNA-seq) data analysis. Numerous tools exist for predicting cell identity using single-cell reference atlases. However, many challenges remain, including correcting for inherent batch effects between reference and query data andinsufficient phenotype data from the reference. One solution is to project single-cell data onto established bulk reference atlases to leverage their rich phenotype information. Sincast is a computational framework to query scRNA-seq data by projection onto bulk reference atlases. Prior to projection, single-cell data are transformed to be directly comparable to bulk data, either with pseudo-bulk aggregation or graph-based imputation to address sparse single-cell expression profiles. Sincast avoids batch effect correction, and cell identity is predicted along a continuum to highlight new cell states not found in the reference atlas. In several case study scenarios, we show that Sincast projects single cells into the correct biological niches in the expression space of the bulk reference atlas. We demonstrate the effectiveness of our imputation approach that was specifically developed for querying scRNA-seq data based on bulk reference atlases. We show that Sincast is an efficient and powerful tool for single-cell profiling that will facilitate downstream analysis of scRNA-seq data.

PMID:35362513 | DOI:10.1093/bib/bbac088

Acta Crystallogr D Struct Biol. 2022 Apr 1;78(Pt 4):410-423. doi: 10.1107/S2059798322001978. Epub 2022 Mar 16.

ABSTRACT

Cryo-electron microscopy (cryoEM) has become a well established technique to elucidate the 3D structures of biological macromolecules. Projection images from thousands of macromolecules that are assumed to be structurally identical are combined into a single 3D map representing the Coulomb potential of the macromolecule under study. This article discusses possible caveats along the image-processing path and how to avoid them to obtain a reliable 3D structure. Some of these problems are very well known in the community. These may be referred to as sample-related (such as specimen denaturation at interfaces or non-uniform projection geometry leading to underrepresented projection directions). The rest are related to the algorithms used. While some have been discussed in depth in the literature, such as the use of an incorrect initial volume, others have received much less attention. However, they are fundamental in any data-analysis approach. Chiefly among them, instabilities in estimating many of the key parameters that are required for a correct 3D reconstruction that occur all along the processing workflow are referred to, which may significantly affect the reliability of the whole process. In the field, the term overfitting has been coined to refer to some particular kinds of artifacts. It is argued that overfitting is a statistical bias in key parameter-estimation steps in the 3D reconstruction process, including intrinsic algorithmic bias. It is also shown that common tools (Fourier shell correlation) and strategies (gold standard) that are normally used to detect or prevent overfitting do not fully protect against it. Alternatively, it is proposed that detecting the bias that leads to overfitting is much easier when addressed at the level of parameter estimation, rather than detecting it once the particle images have been combined into a 3D map. Comparing the results from multiple algorithms (or at least, independent executions of the same algorithm) can detect parameter bias. These multiple executions could then be averaged to give a lower variance estimate of the underlying parameters.

PMID:35362465 | DOI:10.1107/S2059798322001978

J Neurogastroenterol Motil. 2022 Apr 30;28(2):320-326. doi: 10.5056/jnm19040.

ABSTRACT

BACKGROUND/AIMS: Sixty-eight percent of multiple sclerosis (MS) patients suffer from neurogenic bowel dysfunction (NBD). Transanal irrigation (TAI) is part of the therapeutic strategy. This retrospective study aims to assess the efficacy of TAI in MS population.

METHODS: Twenty-eight MS patients who underwent TAI after a learning period were included. We collected several demographic data: MS disease characteristics, treatments, urinary and bowel dysfunction characteristics, urodynamic parameters, results of the NBD score, the Urinary Symptom Profile (USP) score, and the Patient Global Impression of Severity score, completed by patients before the learning and during the follow-up consultation. We defined 4 specific groups depending on the NBD score severity: very minor, minor, moderate, and severe.

RESULTS: Mean follow-up was 124 days, 85.0% were initially constipated and 36% had fecal incontinence. After TAI, improvement of NBD score was higher in initial Moderate NBD score group with 75.0% of patients decreasing their NBD score into lower severity categories. Few modifications were observed for baseline Very minor and Severe NBD score groups with 60.0% and 87.5% of patients staying in the same category. Statistical improvement of USP voiding dysfunction score was observed (95% CI, -6.13–1.19; P = 0.005) without improvement of overactive bladder USP sub-score.

CONCLUSIONS: TAI is effective in NBD, especially in MS patients with initial Moderate NBD score. Improvement of voiding dysfunction following TAI confirms the pelvic organ cross-talk and the need to systematically consider and treat bowel dysfunction in MS to also improve urinary symptoms.

PMID:35362457 | DOI:10.5056/jnm19040

Diagn Cytopathol. 2022 Apr 1. doi: 10.1002/dc.24959. Online ahead of print.

ABSTRACT

BACKGROUND: Adequacy criteria of pleural fluid volume for optimal reporting are contentious, and very little literature is available to date. This problem has not been addressed in the novel International System for Reporting Serous Fluid Cytology.

MATERIALS AND METHODS: A retrospective analysis was performed on 939 pleural fluid samples. Five volume bins were created: 0-9.9 ml, 10-19.9 ml, 20-34.9 ml, 35-69.9 ml, and > 70 ml and included 203, 222, 314, 174, and 26 samples, respectively. Volume bins were compared across various categories using a Chi-square test. A malignancy fraction was used to assess diagnostic accuracy. Descriptive statistics for categorical variables were done with median and interquartile range. A ROC curve was constructed to find if pleural fluid volume can be used to detect malignancy. A cut-off volume was found which can detect malignancy with optimum sensitivity.

RESULTS: The area under the Receiver Operating Characteristic curve showed that 55% of the time, the pleural volume can detect malignancy correctly. From the coordinates of the curve it was found that for a sensitivity of 81% and specificity of 40%, a cut-off volume of 13.5 ml of pleural fluid is sufficient to detect malignancy.

CONCLUSIONS: We recommend 13.5 ml as the minimum volume cut-off for a satisfactory pleural effusion cytology report. Below this volume, the false-negative rates increase, and the specimen may be deemed as limited for a conclusive diagnosis. As the volume rises above this threshold volume, the false negativity rate decreases but does not significantly improve malignant cells’ detection.

PMID:35362266 | DOI:10.1002/dc.24959

Health Econ. 2022 Mar 31. doi: 10.1002/hec.4490. Online ahead of print.

ABSTRACT

There is a growing but mixed literature on the health effects of minimum wages. If minimum wage changes have a statistically significant impact on health, this suggests health effects should be incorporated into cost-benefit analyses to capture wider policy impacts. Whilst most existing UK based literature examines the introduction of a minimum wage, this paper exploits the 2016, 2017 and 2018 UK National Minimum Wage (NMW) increases as natural experiments using a series of difference-in-differences models. Short Form-12 (SF-12) mental and physical component summary scores are used as dependent variables. In the base case and all sensitivity analyses, the estimated impact of NMW increases on mental and physical health are insignificant. The policy implication is that health effects should not be included in cost-benefit analyses examining the NMW.

PMID:35362225 | DOI:10.1002/hec.4490

Chemistry. 2022 Mar 31. doi: 10.1002/chem.202200115. Online ahead of print.

ABSTRACT

We discuss in this CONCEPT mini-review the fundamental and polymerization chemistry of inverse vulcanization for the preparation of statistical and segmented sulfur copolymers, which have been actively developed and advanced in various applications over the past decade. We explicitly delve into a discussion of step-growth polymerization constructs to describe the inverse vulcanization process and discuss prepolymer approaches for the synthesis of segmented sulfur polyurethanes. We further discuss the advantages of inverse vulcanization in conjunction with dynamic covalent polymerization and post-polymerization modifications to prepare segmented block copolymers with enhanced thermomechanical and flame retardant properties of these materials.

PMID:35362205 | DOI:10.1002/chem.202200115

Adv Mater. 2022 Mar 31:e2202168. doi: 10.1002/adma.202202168. Online ahead of print.

ABSTRACT

Nanovaccines have emerged as promising alternatives or complements to conventional cancer treatments. Despite the progresses, specific co-delivery of antigen and adjuvant to their corresponding intracellular destinations for maximizing the activation of antitumor immune responses remains a challenge. Herein, we developed a lipid-coated iron oxide nanoparticle as nanovaccine (IONP-C/O@LP) that could co-deliver peptide antigen and adjuvant (CpG DNA) into cytosol and lysosomes of dendritic cells (DCs) through both membrane fusion and endosome-mediated endocytosis. Such two-pronged cellular uptake pattern enabled IONP-C/O@LP to synergistically activate immature DCs. Iron oxide nanoparticle also exhibited adjuvant effects by generating intracellular reactive oxygen species, which further promoted DC maturation. IONP-C/O@LP accumulated in the DCs of draining lymph nodes effectively increased the antigen-specific T cells in both tumor and spleen, inhibited tumor growth, and improved animal survival. Moreover, we have demonstrated that this nanovaccine is a general platform of delivering clinically relevant peptide antigens derived from human papilloma virus 16 to trigger antigen-specific immune responses in vivo. This article is protected by copyright. All rights reserved.

PMID:35362203 | DOI:10.1002/adma.202202168

J Adv Nurs. 2022 Apr 1. doi: 10.1111/jan.15207. Online ahead of print.

ABSTRACT

AIMS: Reproductive coercion is associated with poor health outcomes in women. This study examined exposure to and use of reproductive coercion and care seeking among college students.

DESIGN: A cross-sectional survey was administered to 2291 college students of all genders seeking care in college health and counselling centres as baseline data for a cluster-randomized controlled trial.

METHODS: Online surveys were collected (9/2015-3/2017). Descriptive statistics, chi-square, Fisher’s exact and t-tests were analysed.

RESULTS: Among female participants, 3.1% experienced reproductive coercion in the prior 4 months. Experience was associated with older age (p = .041), younger age at first intercourse (p = .004), Black/African American race (p < .001), behaviourally bisexual (p = .005), more lifetime sexual partners (p < .001) and ever pregnant (p = .010). Sexually transmitted infection (p < .001), recent drug use or smoking (p = .018; p = .001), requiring special health equipment (p = .049), poor school performance (p < .001) and all categories of violence (p = <.001-.015) were associated with women’s reproductive coercion experience. Participants who experienced reproductive coercion were more likely to seek care for both counselling and healthcare, (p = .022) and sexually transmitted infection (p = .004). Among males, 2.3% reported recent use of reproductive coercion; these participants reported sexual violence perpetration (p = .005), less condom use (p = .003) and more sexual partners than non-perpetrators (p < .001).

CONCLUSION: Although reproductive coercion was reported infrequently among college students, those students experiencing it appear to be at risk for poor health and academic outcomes. Health and counselling centres are promising settings to address RC and related health behaviours.

PMID:35362185 | DOI:10.1111/jan.15207

J Gastroenterol Hepatol. 2022 Mar 31. doi: 10.1111/jgh.15844. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) requires radiation. This study aimed to assess the clinical factors influencing radiation exposure and devise a scoring model for predicting high-dose radiation exposure.

METHODS: ERCP cases recorded between 2016 and 2019 in a single tertiary teaching hospital were retrospectively reviewed. A scoring model was created by bootstrap method in a derivation cohort (2016-2018) and was assessed in a validation cohort (2019).

RESULTS: Out of 4,223 ERCPs, 2,983 and 1,240 cases were included in the deviation and validation cohorts, respectively. In the derivation cohort, 746 cases (top 25%) comprised the high-dose exposure group, and 2,237 cases (bottom 75%) comprised the low-dose exposure group. Nine clinical parameters associated with high-dose exposure were male, pancreatic sphincterotomy, balloon dilatation, biliary or pancreatic drainage, procedures with contrast dye, endoscopist, in hospital ERCP, and spot image. Stone removal was included by bootstrap analysis. As presented in a nomogram, the weight score of each variable was as follows: male, 1; pancreatic sphincterotomy, 3; balloon dilatation, 7; stone removal, 3; biliary or pancreatic drainage, 5; procedures with contrast dye, 1; endoscopist B, 4; endoscopist C, 5; in hospital procedure, 3; and spot image, 3. A total score ≥15 suggested a high-dose radiation exposure. The sensitivity and specificity of the model for high-dose exposure were 0.562 and 0.813, respectively. In the validation cohort, the model showed reasonable predictability.

CONCLUSIONS: Various factors were associated with radiation exposure. The simple scoring system in this study could guide endoscopists in predicting the risk of high-dose radiation exposure.

PMID:35362155 | DOI:10.1111/jgh.15844

Cytopathology. 2022 Apr 1. doi: 10.1111/cyt.13123. Online ahead of print.

ABSTRACT

OBJECTIVE: The effect of rapid on-site evaluation (ROSE) combined with computed tomography-guided transthoracic core needle biopsy (CT-guided TCNB) is rarely investigated. This study aimed to evaluate the diagnostic efficiency and safety of ROSE combined with CT-guided TCNB for suspected lung cancer patients.

MATERIALS AND METHODS: Clinical data from 285 patients who received CT-guided TCNB for suspected lung cancer in Huashan Hospital from 2015 to 2018 were retrospectively analyzed. 163 of these patients underwent CT-guided TCNB combined with ROSE (ROSE group), while the remaining 122 patients underwent without ROSE (non-ROSE group). The smears obtained from TCNB were quickly processed with Diff-Quick staining and analyzed by one skilled cytologist on-site. The consistency of ROSE with the final clinicopathological diagnosis and the diagnostic efficiency and safety of ROSE combined with CT-guided TCNB in suspected lung cancer patients were evaluated.

RESULTS: ROSE was highly concordant with pathological diagnosis (κ = 0.791; p < 0.001), with the accuracy of 95.7%. The diagnostic accuracy was significantly higher in ROSE group compared with that in non-ROSE group (96.3% vs. 86.1%; p = 0.002), with overall incidences of complications of 36.8% and 23.8%, respectively. Minor pneumothorax without drainage was slightly increased in ROSE group compared with non-ROSE group (14.1% vs. 6.6%; p = 0.046). However, there was no significant difference in serious complications between the two groups.

CONCLUSION: ROSE was highly consistent with the final clinicopathological diagnosis for suspected lung cancer. ROSE further improved the diagnostic efficiency of CT-guided TCNB with no increased incidence of serious complications.

PMID:35362154 | DOI:10.1111/cyt.13123