Tag: nevin manimala

J Bioinform Comput Biol. 2023 Jun 15:2350011. doi: 10.1142/S0219720023500117. Online ahead of print.

ABSTRACT

The P53 protein levels exhibit a series of pulses in response to DNA double-stranded breaks (DSBs). However, the mechanism regarding how damage strength regulates physical parameters of p53 pulses remains to be elucidated. This paper established two mathematical models translating the mechanism of p53 dynamics in response to DSBs; the two models can reproduce many results observed in the experiments. Based on the models, numerical analysis suggested that the interval between pulses increases as the damage strength decreases, and we proposed that the p53 dynamical system in response to DSBs is modulated by frequency. Next, we found that the ATM positive self-feedback can realize the system characteristic that the pulse amplitude is independent of the damage strength. In addition, the pulse interval is negatively correlated with apoptosis; the greater the damage strength, the smaller the pulse interval, the faster the p53 accumulation rate, and the cells are more susceptible to apoptosis. These findings advance our understanding of the mechanism of p53 dynamical response and give new insights for experiments to probe the dynamics of p53 signaling.

PMID:37325863 | DOI:10.1142/S0219720023500117

Anthropol Anz. 2023 Jun 16. doi: 10.1127/anthranz/2023/1679. Online ahead of print.

ABSTRACT

Changes in the environment in which a particular population develops, including socio-economic factors, can influence craniofacial dimensions over time. The study aimed to investigate intergenerational changes in selected cranial measurements of adolescents (16-18 years of age) from Kraków, Poland. The analysis was based on the anthropometric measurements of four cohorts (years 1938, 1950, 2007 and 2020) of adolescents aged 16-18. Analysed characteristics included head breadth, length and head breadth-to-length ratio. The normality of each characteristic’s distribution was assessed using Shapiro-Wilk’s test, and the statistical significance of the differences between the cohorts was calculated using the two-way ANOVA or Kruskal-Wallis test. The pace of the secular changes of the analysed characteristics was also calculated. There was a secular increase in the head length from 1938 to 2020. The breadth of the head decreased between 1938 and 2007, but an increase was noted from 2007 to 2020. Changes analogous to head breadth were noted for the breadth-to-length ratio. The secular changes occurred the fastest between 2007 and 2020 for the length (18-year-olds), breadth (16-year old boys and 18-year-old girls) and the cephalic index (16-year old boys and 17-year-old girls). In conclusion, there was a tendency toward debrachycephalisation in the more contemporary cohorts. Observed changes may be associated with more favourable overall developmental conditions as well as possible changes in the growth tempo of the Polish population.

PMID:37325854 | DOI:10.1127/anthranz/2023/1679

Anthropol Anz. 2023 May 17. doi: 10.1127/anthranz/2023/1704. Online ahead of print.

ABSTRACT

Femoral head-neck defects are commonly reported in the anatomical and anthropological literature. The best-known types are Poirier’s facet and Allen’s fossa; however, their aetiology and definition are still debated. The aim of this study was to analyse the frequency of Poirier’s facet in the skeletal population from Radom (Poland, 14^th-19^th century). Additionally, a comparison of Poirier’s facet prevalence in two chronological periods (the populations from Radom during the 14^th-17^th century and the 18^th-19^th century) was done. The femora of 367 adult individuals (184 males, 140 females, 43 unknown sex) from the osteological collections from Radom (14^th-19^th century) (Poland) were analysed according to the frequency of Poirier’s facet. In the Late Medieval population from Radom (14^th-17^th century), Poirier’s facet was noted in 33% of individuals, while in Radom individuals from 18th-19th century, Poirier’s facet was observed in 34%. In the analysed skeletal group, Poirier’s facet was usually observed on both femoral bones. Males from 18th-19th century had more occasions of Poirier’s facet observed compared to the 14^th-17^th century males, while in females, Poirier’s facet was slightly more frequently observed in 14th-17th century Radom individuals. There were not statistically significant differences in the Poirier’s facet frequencies between males and females in Radom from the 14^th-17^th century (38% in males, 29% in females). In the Medieval and Modern skeletal series from Radom (18^th-19^th), males had significantly higher frequencies (44%) of this skeletal trait compared to females (18%). It could be hypothesised that 18^th-19^th century Radom males engaged in more demanding physical activity than females. Poor knowledge about Poirier’s facet aetiology, insufficient archaeological and historical knowledge about the Radom individuals’ lifestyle, and a small sample size from the 14^th-17^th Radom sample do not allow for drawing such unambiguous conclusions, and further analyses are needed.

PMID:37325851 | DOI:10.1127/anthranz/2023/1704

J Mark Access Health Policy. 2023 Jun 13;11(1):2218633. doi: 10.1080/20016689.2023.2218633. eCollection 2023.

ABSTRACT

BACKGROUND AND OBJECTIVES: Multiple reforms aimed at improving the Chinese population’s health have been introduced in recent years, including several designed to improve access to innovative drugs. We sought to review current factors affecting access to innovative drugs in China and to anticipate future trends.

METHODS: Targeted reviews of published literature and statistics on the Chinese healthcare system, medical insurance and reimbursement processes were conducted, as well as interviews with five Chinese experts involved in the reimbursement of innovative drugs.

RESULTS: Drug reimbursement in China is becoming increasingly centralized due to the removal of provincial pathways, the establishment of the National Healthcare Security Administration and the implementation of the National Reimbursement Drug List (NRDL), which is now the main route for drug reimbursement in China. There is also an increasing number of other channels via which patients may access innovative treatments, including various types of commercial insurance and special access. Health technology assessment (HTA) and health economic evidence are becoming pivotal elements of the NRDL decision-making process. Alongside the optimization of HTA decision making, innovative risk-sharing agreements are anticipated to be increasingly leveraged in the future to optimize access to highly specialized technologies and encourage innovation while safeguarding limited healthcare funds.

CONCLUSIONS: Drug public reimbursement in China continues to align more closely with approaches widely used in Europe in terms of HTA, health economics and pricing. Centralization of decision-making processes for public reimbursement of innovative drugs allows consistency in assessment and access, which optimizes the improvement of the Chinese population’s health.

PMID:37325810 | PMC:PMC10266112 | DOI:10.1080/20016689.2023.2218633

Front Sociol. 2023 Jun 1;8:1114095. doi: 10.3389/fsoc.2023.1114095. eCollection 2023.

ABSTRACT

In 2004 the African Union adopted an innovative gender index, the Afriacn Gender and Development Index (AGDI). It is composed of the quantitative Gender Status Index (GSI) and the qualitative African Women’s Progress Scorecard (AWPS). The tool is built on the use of national data collected by a national team of specialists. Since the beginning three cycles of implementation have occurred. After the last cycle the AGDI was revised. In this article the authors assess the implementation of the AGDI, against the background of other gender indices, and discuss the latest revisions.

PMID:37325791 | PMC:PMC10267327 | DOI:10.3389/fsoc.2023.1114095

bioRxiv. 2023 May 18:2023.05.16.540882. doi: 10.1101/2023.05.16.540882. Preprint.

ABSTRACT

MOTIVATION: The Jaccard similarity on $k$-mer sets has shown to be a convenient proxy for sequence identity. By avoiding expensive base-level alignments and comparing reduced sequence representations, tools such as MashMap can scale to massive numbers of pairwise comparisons while still providing useful similarity estimates. However, due to their reliance on minimizer winnowing, previous versions of MashMap were shown to be biased and inconsistent estimators of Jaccard similarity. This directly impacts downstream tools that rely on the accuracy of these estimates.

RESULTS: To address this, we propose the minmer winnowing scheme, which generalizes the minimizer scheme by use of a rolling minhash with multiple sampled $k$-mers per window. We show both theoretically and empirically that minmers yield an unbiased estimator of local Jaccard similarity, and we implement this scheme in an updated version of MashMap. The minmer-based implementation is over 10 times faster than the minimizer-based version under the default ANI threshold, making it well-suited for large-scale comparative genomics applications.

PMID:37325780 | PMC:PMC10268037 | DOI:10.1101/2023.05.16.540882

J R Stat Soc Ser C Appl Stat. 2023 Apr 25;72(3):718-738. doi: 10.1093/jrsssc/qlad029. eCollection 2023 Jun.

ABSTRACT

A Bayesian feature allocation model (FAM) is presented for identifying cell subpopulations based on multiple samples of cell surface or intracellular marker expression level data obtained by cytometry by time of flight (CyTOF). Cell subpopulations are characterized by differences in marker expression patterns, and cells are clustered into subpopulations based on their observed expression levels. A model-based method is used to construct cell clusters within each sample by modeling subpopulations as latent features, using a finite Indian buffet process. Non-ignorable missing data due to technical artifacts in mass cytometry instruments are accounted for by defining a static missingship mechanism. In contrast with conventional cell clustering methods, which cluster observed marker expression levels separately for each sample, the FAM-based method can be applied simultaneously to multiple samples, and also identify important cell subpopulations likely to be otherwise missed. The proposed FAM-based method is applied to jointly analyse three CyTOF datasets to study natural killer (NK) cells. Because the subpopulations identified by the FAM may define novel NK cell subsets, this statistical analysis may provide useful information about the biology of NK cells and their potential role in cancer immunotherapy which may lead, in turn, to development of improved NK cell therapies.

PMID:37325776 | PMC:PMC10264057 | DOI:10.1093/jrsssc/qlad029

J Med Genet. 2023 Jun 15:jmg-2023-109344. doi: 10.1136/jmg-2023-109344. Online ahead of print.

ABSTRACT

BACKGROUND: Polygenic risk scores (PRSs) have been used to stratify colorectal cancer (CRC) risk in the general population, whereas its role in Lynch syndrome (LS), the most common type of hereditary CRC, is still conflicting. We aimed to assess the ability of PRS to refine CRC risk prediction in European-descendant individuals with LS.

METHODS: 1465 individuals with LS (557 MLH1, 517 MSH2/EPCAM, 299 MSH6 and 92 PMS2) and 5656 CRC-free population-based controls from two independent cohorts were included. A 91-SNP PRS was applied. A Cox proportional hazard regression model with ‘family’ as a random effect and a logistic regression analysis, followed by a meta-analysis combining both cohorts were conducted.

RESULTS: Overall, we did not observe a statistically significant association between PRS and CRC risk in the entire cohort. Nevertheless, PRS was significantly associated with a slightly increased risk of CRC or advanced adenoma (AA), in those with CRC diagnosed <50 years and in individuals with multiple CRCs or AAs diagnosed <60 years.

CONCLUSION: The PRS may slightly influence CRC risk in individuals with LS in particular in more extreme phenotypes such as early-onset disease. However, the study design and recruitment strategy strongly influence the results of PRS studies. A separate analysis by genes and its combination with other genetic and non-genetic risk factors will help refine its role as a risk modifier in LS.

PMID:37321833 | DOI:10.1136/jmg-2023-109344

Ann Rheum Dis. 2023 Jun 15:ard-2023-224232. doi: 10.1136/ard-2023-224232. Online ahead of print.

ABSTRACT

OBJECTIVES: To develop a consensual definition for the term ‘early axial spondyloarthritis-axSpA’-and ‘early peripheral spondyloarthritis-pSpA’.

METHODS: The ASAS (Assessment of SpondyloArthritis international Society-Spondyloarthritis EARly definition) steering committee convened an international working group (WG). Five consecutive steps were followed: (1) systematic literature review (SLR); (2) discussion of SLR results within the WG and ASAS community; (3) a three-round Delphi survey inviting all ASAS members to select the items that should be considered for the definition; (4) presentation of Delphi results to the WG and ASAS community and (5) ASAS voting and endorsement (2023 annual meeting).

RESULTS: Following the SLR, consensus was to proceed with an expert-based definition for early axSpA (81% in favour) but not for pSpA (54% against). Importantly, early axSpA should be based on symptom duration taking solely axial symptoms into account. 151-164 ASAS members participated in the Delphi surveys. Consensus was achieved for considering the following items within early axSpA definition: duration of symptoms ≤2 years; axial symptoms defined as cervical/thoracic/back/buttock pain or morning stiffness; regardless of the presence/absence of radiographic damage. The WG agreed that in patients with a diagnosis of axSpA ‘early axSpA’ should be defined as a duration of ≤2 years of axial symptoms. Axial symptoms should include spinal/buttock pain or morning stiffness and should be considered by a rheumatologist as related to axSpA. The ASAS community endorsed this proposal (88% in favour).

CONCLUSIONS: Early axSpA has newly been defined, based on expert consensus. This ASAS definition should be adopted in research studies addressing early axSpA.

PMID:37321799 | DOI:10.1136/ard-2023-224232

Vet Parasitol Reg Stud Reports. 2023 Jul;42:100885. doi: 10.1016/j.vprsr.2023.100885. Epub 2023 May 4.

ABSTRACT

Ticks pose a substantial economic burden associated with production loss and treatment costs globally. Ethiopia has tremendous livestock resources, but its productivity is hindered by various animal health challenges in which ticks are the top priority, with a limited response to acaricidal treatments. Hence, we designed an acaricidal efficacy trial for the top commercially available Chemicals (amitraz and diazinon) to examine their efficacy against the widely distributed tick species (Amblyoma variegatum). Ticks were collected from animals admitted to veterinary clinics with no history of treatment with acaricides. Adult Immersion Technique (AIT) was employed to detect acaricidal resistance, and the mean percent control and antiparasitic efficacy were used to estimate tick susceptibility with a completely randomized laboratory-based trial (CRT). The mean weights of eggs laid by ticks subjected to amitraz and diazinon indicated that amitraz had a better egg-laying-inhibition effect than diazinon. The mean control percentages of amitraz and diazinon were 92.8 ± 5.6% and 69.7 ± 3.1%, respectively, with a highly significant difference (P-value = 0.00). The antiparasitic efficacy of the two drugs was 57.5 ± 0.96 and 37.5% ± 0.96 for amitraz and diazinon, respectively, which revealed that amitraz was statistically better than diazinon in killing adult ticks (P-value =0.026). In general, ticks treated with diazinon showed evidence of resistance development, and amitraz is relatively the most effective acaricide; we recommend its use in the study area and other locations with similar settings.

PMID:37321790 | DOI:10.1016/j.vprsr.2023.100885