Nevin Manimala

Heredity (Edinb). 2023 Feb 4. doi: 10.1038/s41437-023-00595-9. Online ahead of print.

ABSTRACT

A long-standing goal in the field of polyploid biology has been the derivation of mathematical models of gamete mode formation. These models form the basis of statistical inference and evolutionary theory. Here, we present 3-locus models of gamete mode formation in autotetraploids without and with preferential cross-over formation. The three loci are assumed to occur on one arm of the same chromosome. For preferential cross-over formation, one of the three loci affects the tendency for sets of sister chromatids to pair and therefore affects rates of recombination. The models are derived such that the process of double reduction is a function of rates of synaptic partner switches and recombination, as opposed to being independent of these processes. We assume potentially one synaptic partner switch per meiosis. We also assume the coefficient of coincidence is one, such that cross-over events are independent, given a set of cross-over rates. Illustrative cases are examined demonstrating differences in the gamete mode probabilities without and with preferential cross-over formation. Lastly, we explore the accuracy of maximum likelihood estimates of the probability of synaptic partner switches and preferential cross-over formation when the locus controlling preference is at a proximal, middle, or distal location on the chromosome arm. All Supplementary Information is available at https://github.com/ckgriswold/3-locus-autotetraploid-meiosis .

PMID:36739333 | DOI:10.1038/s41437-023-00595-9

Acta Med Port. 2023 Feb 1;36(2):105-112. doi: 10.20344/amp.17290. Epub 2023 Feb 1.

ABSTRACT

INTRODUCTION: A growing number of countries have legalized the process of hastening death. At a time when laws decriminalizing hastened death have been passed in the Portuguese Parliament, the development of research related with decision making regarding this issue is of crucial importance. This study seeks to evaluate, in a sample of Portuguese doctors, whether the presentation of clinical vignettes changes the agreement with the practice of hastened death compared with general scenarios.

MATERIAL AND METHODS: A questionnaire was distributed among academic physicians from medical schools across Portugal to assess their level of agreement or disagreement with the practice of hastened death. The questionnaire included eight standard cases and eight clinical vignettes framed under conditions defined by law for the practice of hastened death. Differences were analyzed using the t-Student test for paired samples.

RESULTS: There were statistically significant differences in five scenarios (t = 3.46; p < 0.05; t = 2.47; p < 0.05; t = 4.28; p < 0.05; t = 3.38; p < 0.05; t = 3.66; p < 0.05) with greater agreement concerning the clinical vignettes. The highest acceptance was found in the requests made by adults with terminal and incurable illnesses.

CONCLUSION: Agreement increased when the clinical vignette was presented in comparison with the respective standard for most of the cases of hastened death presented.

PMID:36738190 | DOI:10.20344/amp.17290

J Appl Gerontol. 2023 Feb 4:7334648231155444. doi: 10.1177/07334648231155444. Online ahead of print.

ABSTRACT

Background: Persons living with dementia (PLWD) are more likely to be hospitalized than individuals without dementia. Little is known about key features (i.e., structural capabilities) in primary care practices where PLWD receive care. This study assessed the relationship between structural capabilities (i.e., care coordination, community integration, and reminder systems) and hospitalizations among PLWD. Methods: We conducted a secondary analysis of cross-sectional data from 5001 PLWD in 192 practices and used three datasets: nurse practitioner surveys, Medicare claims, and Minimum Data Set. Using generalized estimating equations, we evaluated the association between structural capabilities and hospitalizations. Results: PLWD who received care from practices with care coordination were less likely to have hospitalizations (OR = 0.62, p < .05). No statistically significant associations were observed between community integration and reminder systems and hospitalizations. Conclusion: Primary care practices need to tailor structural capabilities to address the needs of PLWD to reduce hospitalizations.

PMID:36738162 | DOI:10.1177/07334648231155444

Mol Ecol. 2023 Feb 4. doi: 10.1111/mec.16873. Online ahead of print.

ABSTRACT

The dynamical structure of ecological communities results from interactions among taxa that change with shifts in species composition in space and time. However, our ability to study the interplay of ecological and evolutionary processes on community assembly remains relatively unexplored due to the difficulty of measuring community structure over long temporal scales. Here, we made use of a geological chronosequence across the Hawaiian Islands, representing 50 years to 4.15 million years of ecosystem development, to sample 11 communities of arthropods and their associated plant taxa using semi-quantitative DNA metabarcoding. We then examined how ecological communities changed with community age by calculating quantitative network statistics for bipartite networks of arthropod-plant associations. The average number of interactions per species (linkage density), ratio of plant to arthropod species (vulnerability), and uniformity of energy flow (interaction evenness) increased significantly in concert with community age. The index of specialization H₂ ‘ has a curvilinear relationship with community age. Our analyses suggest that younger communities are characterized by fewer but stronger interactions, while biotic associations become more even and diverse as communities mature. These shifts in structure became especially prominent on East Maui (~0.5 my) and older volcanos, after enough time had elapsed for adaptation and specialization to act on populations in situ. Such natural progression of specialization during community assembly is likely impeded by the rapid infiltration of non-native species, with special risk to younger or more recently disturbed communities that are composed of fewer specialized relationships.

PMID:36738159 | DOI:10.1111/mec.16873

Res Synth Methods. 2023 Feb 4. doi: 10.1002/jrsm.1624. Online ahead of print.

ABSTRACT

Reference intervals, or reference ranges, aid medical decision-making by containing a pre-specified proportion (e.g. 95%) of the measurements in a representative healthy population. We recently proposed three approaches for estimating a reference interval from a meta-analysis based on a random effects model: a frequentist approach, a Bayesian posterior predictive interval, and an empirical approach. Because the Bayesian posterior predictive interval becomes wider to incorporate estimation uncertainty, it may systematically contain greater than 95% of measurements when the number of studies is small or the between study heterogeneity is large. The frequentist and empirical approaches also captured a median of less than 95% of measurements in this setting, and 95% confidence or credible intervals for the reference interval limits were not developed. In this update, we describe how one can instead use Bayesian methods to summarize the appropriate quantiles (e.g. 2.5^th and 97.5^th ) of the marginal distribution of individuals across studies and construct a credible interval describing the estimation uncertainty in the lower and upper limits of the reference interval. We demonstrate through simulations that this method performs well in capturing 95% of values from the marginal distribution and maintains a median coverage of near 95% of the marginal distribution even when the number of studies is small, or the between-study heterogeneity is large. We also compare the results of this method to those obtained from the three previously proposed methods in the original case study of the meta-analysis of frontal subjective postural vertical measurements. This article is protected by copyright. All rights reserved.

PMID:36738156 | DOI:10.1002/jrsm.1624

Int J Med Robot. 2023 Feb 3:e2504. doi: 10.1002/rcs.2504. Online ahead of print.

ABSTRACT

BACKGROUND: Our objective was to compare the coronal mechanical axis after total knee replacement (TKR) obtained in three groups of patients subjected to conventional, navigated, and robotic surgery.

METHODS: Retrospective analysis.

RESULTS: 124 knees were included (36 conventional, 41 navigated, 47 robotic). No statistically significant differences were found between the postOp tibiofemoral angle of the conventional, navigated and robotic groups (p=0.396). A repeated-measure analysis of preOp-to-postOp also found no significant differences (p=0.387). There were no differences in the proportion of outliers(+3-degree) found (p=0.211). Nevertheless, a higher proportion of patients in the robotic group improved their mechanical alignment, as compared with conventional surgery (p=0.023), although no differences were found when comparing with navigation (p=0.121).

CONCLUSIONS: No statistically significant differences were found with respect to the postOp alignment achieved. However, statistically significant differences were detected between robotic and conventional surgery when considering the percentage of patients with improved limb alignment. This article is protected by copyright. All rights reserved.

PMID:36738122 | DOI:10.1002/rcs.2504

J Magn Reson Imaging. 2023 Feb 3. doi: 10.1002/jmri.28600. Online ahead of print.

ABSTRACT

BACKGROUND: Nonmass enhancement (NME) breast lesions are considered to be the leading cause of unnecessary biopsies. Diffusion-weighted imaging (DWI) or dynamic contrast-enhanced (DCE) sequences are typically used to differentiate between benign and malignant NMEs. It is important to know which one is more effective and reliable.

PURPOSE: To compare the diagnostic performance of DCE curves and DWI in discriminating benign and malignant NME lesions on the basis of morphologic characteristics assessment on contrast-enhanced (CE)-MRI images.

STUDY TYPE: Retrospective.

SUBJECTS: A total of 180 patients with 184 lesions in the training cohort and 75 patients with 77 lesions in the validation cohort with pathological results.

FIELD STRENGTH/SEQUENCE: A 3.0 T/multi-b-value DWI (b values = 0, 50, 1000, and 2000 sec/mm² ) and time-resolved angiography with stochastic trajectories and volume-interpolated breath-hold examination (TWIST-VIBE) sequence.

ASSESSMENT: In the training cohort, a diagnostic model for morphology based on the distribution and internal enhancement characteristics was first constructed. The apparent diffusion coefficient (ADC) model (ADC + morphology) and the time-intensity curves (TIC) model (TIC + morphology) were then established using binary logistic regression with pathological results as the reference standard. Both models were compared for sensitivity, specificity, and area under the curve (AUC) in the training and the validation cohort.

STATISTICAL TESTS: Receiver operating characteristic (ROC) curve analysis and two-sample t-tests/Mann-Whitney U-test/Chi-square test were performed. P < 0.05 was considered statistically significant.

RESULTS: For the TIC/ADC model in the training cohort, sensitivities were 0.924/0.814, specificities were 0.615/0.615, and AUCs were 0.811 (95%, 0.727, 0.894)/0.769 (95%, 0.681, 0.856). The AUC of the TIC-ADC combined model was significantly higher than ADC model alone, while comparable with the TIC model (P = 0.494). In the validation cohort, the AUCs of TIC/ADC model were 0.799/0.635.

DATA CONCLUSION: Based on the morphologic analyses, the performance of the TIC model was found to be superior than the ADC model for differentiating between benign and malignant NME lesions.

EVIDENCE LEVEL: 4.

TECHNICAL EFFICACY: Stage 2.

PMID:36738118 | DOI:10.1002/jmri.28600

Cancer. 2023 Feb 3. doi: 10.1002/cncr.34665. Online ahead of print.

ABSTRACT

BACKGROUND: The gold standard for the identification of Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) patients is gene expression profiling. Because of its diverse nature, its identification is extremely difficult and expensive. On the genomic and proteomic landscape of Ph-like ALL patients, there is a paucity of published literature from developing countries.

METHODS: The authors used digital barcoded nCounter NanoString gene expression profiling for its detection, followed by molecular and proteomic characterization using fluorescence in situ hybridization and liquid chromatography-tandem mass spectrometry (LC-MS/MS).

RESULTS: The authors found 32.05% Ph-like ALL patients and their median age at presentation was considerably higher than Ph-negative ALL cases (p = .0306). Furthermore, we identified 20% CRLF2 overexpressed cases having 8.33% CRLF2-IGH translocation with concomitant R683S mutation and 8.33% CRLF2-P2RY8 translocation. In 80% of CRLF2 downregulated cases, we identified 10% as having JAK2 rearrangement. Minimal residual disease-positivity was more common in Ph-like ALL cases (55.55% vs. 25% in Ph-negative ALL cases). Immunoglobulin J chain (Jchain), small nuclear ribonucleoprotein SmD1 (SNRPD1), immunoglobulin κ constant (IGKC), NADH dehydrogenase (ubiquinone) 1 α subcomplex subunit 2 (NDUFA2), histone H2AX (H2AFX), charged multivesicular body protein 4b (CHMP4B), and carbonyl reductase (NADPH) (CBR1) proteins were identified to be substantially expressed in Ph-like ALL patients, using LC-MS/MS. Gene enrichment analysis indicated that involvement of spliceosomal mediated messenger RNA splicing pathway and four microRNAs was statistically significant in Ph-like ALL patients.

CONCLUSIONS: For the first time, we have described incidence, molecular, and proteomic characterization of Ph-like ALL, in developing nations.

PLAIN LANGUAGE SUMMARY: In developing countries, detecting Philadelphia (Ph)-like B-lineage acute lymphoblastic leukemia is complicated and challenging due to its diverse genetic landscape. There is no well-defined and cost-effective methodology for its detection. The incidence of this high-risk subtype is very high in adult cases, and there is an urgent need for its accurate detection. We have developed an online PHi-RACE classifier for its rapid detection, followed by delineating the genomic and proteomic landscape of Ph-like acute lymphoblastic leukemias for the first time in Indian patients.

PMID:36738086 | DOI:10.1002/cncr.34665

Addiction. 2023 Feb 3. doi: 10.1111/add.16156. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The COVID-19 pandemic disrupted healthcare provision in the United States and prompted increases in telehealth-delivery of care. This study measured alcohol use disorder (AUD) treatment trends across visit modalities before and during COVID-19.

DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: We conducted a national, retrospective cohort study with interrupted time series models to estimate the impact of COVID-19 on AUD treatment in the Veterans Health Administration (VHA) in the United States, during pre-COVID-19 (March 2019 to February 2020) and COVID-19 (March 2020 to February 2021) periods. We analyzed monthly trends in telephone, video and in-person visits for AUD treatment and compared patient and treatment characteristics of patients receiving AUD treatment between the pre-COVID-19 and COVID-19 periods. AUD was defined using International Classification of Diseases, 10th Revision (ICD-10) codes for alcohol abuse (F10.1) and alcohol dependence (F10.2) which have previously been used to study AUD in VHA.

FINDINGS: The predicted percentage of VHA patients with an AUD diagnosis receiving any AUD treatment at the beginning of the pre-COVID period was 13.8% (n=49,494). The predicted percentage decreased by 4.3% (P=0.001) immediately at the start of the COVID-19 period due to a decline in AUD psychotherapy. Despite an increase of 0.3% per month (P=0.026) following the start of COVID-19, the predicted percentage of VHA patients with an AUD diagnosis receiving any AUD treatment at the end of the study period remained below the pre-COVID-19 period. In February 2021, AUD psychotherapy visits were primarily delivered by video (50%, 58,748), followed by in-person (36.6%, 43,251) and telephone (13.8%, 16,299), while AUD pharmacotherapy visits were delivered by telephone (38.9%, 3,623) followed by in-person (34.3%, 3,193) and video (26.8%, 2,498) modalities. Characteristics of VHA patients receiving AUD treatment were largely similar between pre-COVID-19 and COVID-19 periods.

CONCLUSIONS: Despite increased telehealth use, the percentage of US Veterans Health Administration patients with an alcohol use disorder (AUD) diagnosis receiving AUD treatment declined during COVID-19 (March 2020 to February 2021) mainly due to a decrease in psychotherapy.

PMID:36738085 | DOI:10.1111/add.16156

Food Res Int. 2023 Feb;164:112386. doi: 10.1016/j.foodres.2022.112386. Epub 2022 Dec 28.

ABSTRACT

The tocopherol (T) and tocotrienol (T3) profile were investigated in the present study for four hundred and eighteen plant oil samples, including thirty-one families, eighty-two species, and five cross-species. Fifteen species were dominated by tocotrienols, while sixty-seven – by tocopherols. The mean proportion of γ-T was almost half of the total tocochromanol content (49.3%) in the investigated samples, while α-T constituted to one quarter (25.0%), and the remaining other tocochromanols were present as minor constituents. A strong relationship between the taxonomic plant origin and the presence of the characteristic tocochromanol profile in oils obtained from those plants was noted. This is the first study to demonstrate that not only monocotyledonous, but also dicotyledons families can be rich in tocotrienols. The usefulness of statistical tools – principal component analysis (PCA) and hierarchical cluster analysis (HCA) for plant sample discrimination based on their tocochromanol profile was also shown.

PMID:36737971 | DOI:10.1016/j.foodres.2022.112386