Nevin Manimala

Cytometry A. 2022 Jan 9. doi: 10.1002/cyto.a.24533. Online ahead of print.

ABSTRACT

Automated cell segmentation is key for rapid and accurate investigation of cell responses. As instrumentation resolving power increases, clear delineation of newly revealed cellular features at the sub-micron through nanoscale becomes important. Reliance on manual investigation of myriad small features retards investigation; however, use of deep learning methods has great potential to reveal cell features both at high accuracy and high speed, which may lead to new discoveries in the near term. In this study, semantic cell segmentation systems were investigated by implementing fully convolutional neural networks called U-nets for segmentation of astrocytes cultured on Poly-L-lysine-functionalized planar glass. The network hyperparameters were determined by changing the number of network layers, loss functions, and input image modalities. Atomic force microscopy (AFM) images were selected for investigation as these are inherently nanoscale and are also dimensional. AFM height, deflection, and friction images were used as inputs separately and together, and the segmentation performances were investigated on five-fold cross-validation data. Transfer learning methods, including VGG16, VGG19, and Xception, were used to improve cell segmentation performance. We find that AFM height images inherit more discriminative features than AFM deflection and AFM friction images for cell segmentation. When transfer learning methods are applied, statistically significant segmentation performance improvements are observed. Segmentation performance was compared to classical image processing algorithms and other algorithms in use by considering both AFM and electron microscopy segmentation. An accuracy of 0.9849, Matthews correlation coefficient of 0.9218, and Dice’s similarity coefficient of 0.9306 were obtained on the AFM test images. Performance evaluations show that the proposed system can be successfully used for AFM cell segmentation with high precision. This article is protected by copyright. All rights reserved.

PMID:35000269 | DOI:10.1002/cyto.a.24533

Mol Oncol. 2022 Jan 9. doi: 10.1002/1878-0261.13179. Online ahead of print.

ABSTRACT

Breast cancer is a heterogeneous disease that comprises multiple histological and molecular subtypes. To gain insight into mutations that drive breast tumorigenesis, we describe a pipeline for the identification and validation of tumor suppressor genes. Based on an in vivo genome-wide CRISPR/Cas9-screen in Trp53^+/- heterozygous mice, we identified tumor suppressor genes that include the scaffold protein Axin1, the protein kinase A regulatory subunit gene Prkar1a, as well as the proof-of-concept genes Pten, Nf1 and Trp53 itself. Ex vivo editing of primary mammary epithelial organoids was performed to further interrogate the roles of Axin1 and Prkar1a. Increased proliferation and profound changes in mammary organoid morphology were observed for Axin1/Trp53 and Prkar1a/Trp53 double mutants compared to Pten/Trp53 double mutants. Furthermore, direct in vivo genome editing via intraductal injection of lentiviruses engineered to express dual short-guide RNAs revealed that mutagenesis of Trp53 and either Prkar1a, Axin1 or Pten markedly accelerated tumor development compared to Trp53-only mutants. This proof-of-principle study highlights the application of in vivo CRISPR/Cas9-editing for uncovering cooperativity between defects in tumor suppressor genes that elicit mammary tumorigenesis.

PMID:35000262 | DOI:10.1002/1878-0261.13179

J Psychiatr Ment Health Nurs. 2022 Jan 9. doi: 10.1111/jpm.12818. Online ahead of print.

ABSTRACT

INTRODUCTION: HT has been widely used to promote mental health. However, heterogeneity and sample size issues of randomised-controlled trials made it challenging to illustrate effect sizes across the evidence.

AIM: The purpose of this meta-analysis was to explore the effect of HT on mental health.

METHODS: We used the PRISMA framework. A keyword search of Web of Science, PubMed, ProQuest, and Cochrane was performed. The inclusion criteria were HT with RCTs and mental health assessments. A random-effects model was used to perform the meta-analysis.

RESULTS: A total of 1,056 records were searched, and 18 eligible studies extracted. The included RCTs had no statistical heterogeneity and publication bias. The meta-analysis showed that the HT experimental groups had a significant and positive impact on mental health compared to the control groups (effect size = 0.55).

DISCUSSION: HT should be considered for enhancing mental health. The included studies had no negative outcomes and the most common HT intervention was at least eight sessions. Therefore, HT should be considered to enhance mental health. However, the concealed allocation and blinding processes should be improved in future studies.

IMPLICATIONS FOR PRACTICE: This study recommends that HT should be integrated into healthcare settings to improve mental health.

PMID:35000249 | DOI:10.1111/jpm.12818

Mol Ecol. 2022 Jan 9. doi: 10.1111/mec.16343. Online ahead of print.

ABSTRACT

The shifts in adaptive strategies revealed by ecological succession and the mechanisms that facilitate these shifts are fundamental to ecology. These adaptive strategies could be particularly important in communities of arbuscular mycorrhizal fungi (AMF) mutualistic with sorghum where strong AMF succession replaces initially ruderal species with competitive ones and where the strongest plant response to drought is to manage these AMF. Although most studies of agriculturally important fungi focus on parasites, the mutualistic symbionts, AMF, constitute a research system of human-associated fungi whose relative simplicity and synchrony are conducive to experimental ecology. First, we hypothesize that, when irrigation is stopped to mimic drought, competitive AMF species should be replaced by AMF species tolerant to drought stress. We then, for the first time, correlate AMF abundance and host plant transcription to test two novel hypotheses about the mechanisms behind the shift from ruderal to competitive AMF. Surprisingly, despite imposing drought stress, we found no stress tolerant AMF, likely due to our agricultural system having been irrigated for nearly six decades. Remarkably, we found strong and differential correlation between the successional shift from ruderal to competitive AMF and sorghum genes whose products (i) produce and release strigolactone signals, (ii) perceive mycorrhizal-lipochitinoligosaccharide (Myc-LCO) signals, (iii) provide plant lipid and sugar to AMF and, (iv) import minerals and water provided by AMF. These novel insights frame new hypotheses about AMF adaptive evolution and suggest a rationale for selecting AMF to reduce inputs and maximize yields in commercial agriculture.

PMID:35000239 | DOI:10.1111/mec.16343

J Oral Rehabil. 2022 Jan 9. doi: 10.1111/joor.13304. Online ahead of print.

ABSTRACT

BACKGROUND: Parkinson’s disease (PD) is a neurodegenerative condition affecting quality of life. Due to a worsening of oral health in PD patients with the progression of the disease, oral health-related quality of life (OHRQoL) could be impaired as well.

OBJECTIVES: To assess whether PD patients in The Netherlands experience worse OHRQoL than historical controls, and to investigate which factors are associated with OHRQoL in PD patients.

MATERIAL & METHODS: In total, 341 PD patients (65.5 ± 8.4 years) and 411 historical controls (62.6 ± 5.3 years) participated. Both groups completed a questionnaire. The PD patients were asked questions regarding demographics, PD, oral health, and OHRQoL. The historical controls filled in demographic information and questions regarding OHRQoL. The latter construct was assessed using the Dutch 14-item version of the Oral Health Impact Profile (OHIP-14). Data were analysed using independent samples t-tests and univariate and multivariate linear regression analysis.

RESULTS: The mean OHIP-14 score was higher in PD patients (19.1 ± 6.7) than in historical controls (16.5 ± 4.4) (t(239)=6.5; p<0.001). OHRQoL in PD patients was statistically significant associated with motor aspects of experiences of daily living (B=0.31; t(315)=7.03p<0.001), worsening of the oral environment during disease course (B=3.39; t(315)=4.21p<0.001), being dentate (B= -5.60; t(315)=-4.5; p<0.001), tooth wear (B=2.25; t(315)=3.29; p=0.001), and possible burning mouth syndrome (B=5.87; t(315)=2.87; p=0.004).

CONCLUSION: PD patients had a lower OHRQoL than historical controls. Besides, PD-related variables and oral health-related variables were associated with OHRQoL.

PMID:35000220 | DOI:10.1111/joor.13304

Equine Vet J. 2022 Jan 9. doi: 10.1111/evj.13553. Online ahead of print.

ABSTRACT

BACKGROUND: Superficial digital flexor tendon (SDFT) injury is common in racehorses and a significant cause of lost training days and wastage in the industry.

OBJECTIVES: To compare the post-injury performance of Thoroughbred and Standardbred racehorses diagnosed with SDFT tendonitis treated with intralesional bone marrow and superior check desmotomy or managed conservatively and further, to compare this performance with that of uninjured racehorses.

STUDY DESIGN: Retrospective and case controlled.

METHODS: Medical and race records of racehorses treated surgically or managed conservatively for SDFT tendonitis were collated. Signalment, lesion severity and treatment were identified and performance post-injury compared. Performance of the treatment groups was further assessed by comparison with uninjured racehorses matched for age, sex, number of starts pre-injury and randomly selected from the cases’ last races.

RESULTS: The study population comprised 114 racehorses divided into surgical (39/114), conservative (38/114) and control groups (37/114). Horses that had surgery were more likely to return to racing than those managed conservatively [OR 4.7 95%CI (1.6-14.3), p= 0.006]. Standardbreds were more likely to return to race compared to Thoroughbreds [OR 4.0 95%CI 1.2-13.3), p=0.03)]. There was no statistical significant difference in average number of placings, average number of wins and post-injury earnings between the surgically treated and conservatively managed groups (p=0.9, p=0.9 and p=0.7 respectively). The average number of lifetime starts post-injury/post-selection between surgery, conservative and control groups were not statistically significantly different (p=0.2). Surgically treated horses had a statistically significantly shorter time to start post-injury compared to the conservative group (p=0.04).

MAIN LIMITATIONS: The retrospective nature of the study precludes an actual fit as a non-randomised clinical trial and the non-randomised nature of the allocation of the treatment groups is biased.

CONCLUSIONS: Surgical intervention of superficial digital flexor tendonitis in racehorses suffering flexor tendon injury showed a higher likelihood of return to racing than conservative treatment.

PMID:35000213 | DOI:10.1111/evj.13553

Biomed Chromatogr. 2022 Jan 9:e5331. doi: 10.1002/bmc.5331. Online ahead of print.

ABSTRACT

Gleditsiae spina, the thorn of Gleditsia sinensis Lam., has a long history of being used as a traditional medicine in East Asian countries. However, only a few biologically active substances have been identified from Gleditsiae spina. In this study, the epidermis, xylem and pith of Gleditsiae spina, respectively, namely Gs-E, Gs-X and Gs-P, were studied. We used a widely targeted metabolomics method to investigate the chemical composition in Gs-E, Gs-X and Gs-P. A total of 728 putative metabolites were identified from Gleditsiae spina, including 211 primary metabolites and 517 secondary metabolites. These primary and secondary metabolites could be categorized into more than 10 different classes. Flavonoids, phenolic acids, lipids, and amino acids and derivatives, and organic acids constituted the main metabolite groups. Multivariate statistical analysis showed that the Gs-E, Gs-X and Gs-P samples could be clearly separated. Differential accumulated metabolite (DAM) analysis revealed that more than half of the DAMs exhibited the highest relative concentrations in Gs-E, and most of the DAMs showed the lowest relative concentrations in Gs-X. Moreover, 11 common differential primary metabolites and 79 common differential secondary metabolites were detected in all comparison groups. These results further our understanding of chemical composition and metabolite accumulation of Gleditsiae spina.

PMID:35000209 | DOI:10.1002/bmc.5331

Pacing Clin Electrophysiol. 2022 Jan 9. doi: 10.1111/pace.14441. Online ahead of print.

ABSTRACT

BACKGROUND: QRS area, a three-dimensional QRS complex, is a novel vectorcardiography method of measuring the magnitude of electrical forces in the heart. Hypothetically, a greater QRS area denotes higher dyssynchrony and indicates potential benefits from cardiac resynchronization therapy (CRT). Previous studies suggest a positive correlation between QRS area and the degree of response to CRT, but its clinical use remains unclear. We performed a meta-analysis of the relationship between QRS area and survival benefit following CRT.

METHODS: We comprehensively searched the MEDLINE, EMBASE, and Cochrane databases from inception to August 2021. We included studies with prospective and retrospective cohort designs that reported QRS area before CRT and total mortality. Data from each study were analyzed using a random-effects model. The results were reported as a hazard ratio (HR) and 95% confidence intervals.

RESULTS: Five observational studies including 4,931 patients were identified. The cut-off values between large and small QRS areas ranged from 102-116 μVs. Our analysis showed a larger QRS area was statistically associated with increased 5-year survival in patients implanted with CRT (HR pooled 0.48, 95% CI 0.46-0.51, I² = 54%, P < 0.0001). Greater QRS area reduction (pre- and post-implantation) were associated with a lower total mortality rate (HR pooled 0.45, 95% CI 0.38-0.52, I² = 0%, P < 0.0001).

CONCLUSION: Larger pre-implantation QRS area was associated with increased survival after CRT. QRS area reduction following CRT implantation was also associated with lower mortality. QRS area may potentially become an additional selection criterion for CRT implantations. This article is protected by copyright. All rights reserved.

PMID:35000207 | DOI:10.1111/pace.14441

J Zoo Wildl Med. 2021 Dec;52(4):1247-1256. doi: 10.1638/2020-0184.

ABSTRACT

Diagnostic hematology can prove challenging to the exotic animal practitioner presented with a nonhuman primate patient. Few point-of-care automated cell counters are calibrated for primate samples. Twenty-one samples from 17 nonhuman primates presented to an exotic animal practice were analyzed. Samples were run on both canine and feline settings on each of two veterinary point-of-care analyzers: one that assays by impedance technology, and one that assays by laser flow cytometry. Samples were also sent to a reference laboratory to be assayed on an analyzer that performs simultaneous impedance and laser measurements of blood cells and has been calibrated for use in nonhuman primates. Fourteen analytes were assessed for each sample on each machine. Manual hematocrits and total white blood cell counts were also performed on 16 of the samples. Statistical analysis indicated some variance between individual parameters, but overall correlation was acceptable.

PMID:34998296 | DOI:10.1638/2020-0184

J Zoo Wildl Med. 2021 Dec;52(4):1241-1246. doi: 10.1638/2021-0039.

ABSTRACT

Plasma separator tubes (PSTs) are a variant of lithium heparin blood tube containing a polymer gel, which, when centrifuged, creates a physical barrier between plasma and blood cells. Their use is common in laboratory procedures of reptilian species. This study aimed to determine whether the use of plasma separator tubes impacts plasma biochemistry data in green sea turtles (Chelonia mydas) at time of collection and after 24 hr of contact time with the separator gel after centrifugation at refrigerator temperature. A single blood sample was collected from 42 rehabilitating green sea turtles at the Sea Turtle Healing Center, Brevard Zoo, Melbourne, Florida, USA and divided into one lithium heparin tube [LHT (0 hr)] and two PSTs. After immediate centrifugation of all three tubes, plasma was transferred from the LHT (0 hr) and one PST (0 hr) into tubes without additive. The plasma was left in contact with the separator gel in the second PST (24 hr). After 24 hr of refrigeration, all three plasma aliquots were analyzed for the following 23 analytes: sodium, potassium, chloride, carbon dioxide, calcium, phosphorus, magnesium, iron, total protein, albumin, globulin (calculated), aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltransferase, creatine kinase, glucose, urea nitrogen, creatinine, uric acid, triglyceride, and cholesterol. No statistically significant differences were found for any biochemical analytes between LHT (0 hr), PST (0 hr), and PST (24 hr). The use of PST does not appear to impact routine plasma biochemical analytes in green sea turtles and analytes appear stable in refrigerated plasma for up to 24 hr after centrifugation when using PSTs.

PMID:34998295 | DOI:10.1638/2021-0039