Tag: statistics

Science. 2023 Sep 22;381(6664):eadd1250. doi: 10.1126/science.add1250. Epub 2023 Sep 22.

ABSTRACT

Short tandem repeats (STRs) are enriched in eukaryotic cis-regulatory elements and alter gene expression, yet how they regulate transcription remains unknown. We found that STRs modulate transcription factor (TF)-DNA affinities and apparent on-rates by about 70-fold by directly binding TF DNA-binding domains, with energetic impacts exceeding many consensus motif mutations. STRs maximize the number of weakly preferred microstates near target sites, thereby increasing TF density, with impacts well predicted by statistical mechanics. Confirming that STRs also affect TF binding in cells, neural networks trained only on in vivo occupancies predicted effects identical to those observed in vitro. Approximately 90% of TFs preferentially bound STRs that need not resemble known motifs, providing a cis-regulatory mechanism to target TFs to genomic sites.

PMID:37733848 | DOI:10.1126/science.add1250

PLoS Comput Biol. 2023 Sep 21;19(9):e1011396. doi: 10.1371/journal.pcbi.1011396. Online ahead of print.

ABSTRACT

Personalized prediction of chronic diseases is crucial for reducing the disease burden. However, previous studies on chronic diseases have not adequately considered the relationship between chronic diseases. To explore the patient-wise risk of multiple chronic diseases, we developed a multitask learning Cox (MTL-Cox) model for personalized prediction of nine typical chronic diseases on the UK Biobank dataset. MTL-Cox employs a multitask learning framework to train semiparametric multivariable Cox models. To comprehensively estimate the performance of the MTL-Cox model, we measured it via five commonly used survival analysis metrics: concordance index, area under the curve (AUC), specificity, sensitivity, and Youden index. In addition, we verified the validity of the MTL-Cox model framework in the Weihai physical examination dataset, from Shandong province, China. The MTL-Cox model achieved a statistically significant (p<0.05) improvement in results compared with competing methods in the evaluation metrics of the concordance index, AUC, sensitivity, and Youden index using the paired-sample Wilcoxon signed-rank test. In particular, the MTL-Cox model improved prediction accuracy by up to 12% compared to other models. We also applied the MTL-Cox model to rank the absolute risk of nine chronic diseases in patients on the UK Biobank dataset. This was the first known study to use the multitask learning-based Cox model to predict the personalized risk of the nine chronic diseases. The study can contribute to early screening, personalized risk ranking, and diagnosing of chronic diseases.

PMID:37733837 | DOI:10.1371/journal.pcbi.1011396

Stapp Car Crash J. 2022 Nov;66:31-68. doi: 10.4271/2022-22-0002.

ABSTRACT

The American population is getting heavier and automated vehicles will accommodate unconventional postures. While studies replicating mid-size and upright fore-aft seated occupants are numerous, experiments with post-mortem human subjects (PMHS) with obese and reclined occupants are sparse. The objective of this study was to compare the kinematics of the head-neck, torso and pelvis, and document injuries and injury patterns in frontal impacts. Six PMHS with a mean body mass index of 38.2 ± 5.3 kg/m2 were equally divided between upright and reclined groups (seatback: 23°, 45°), restrained by a three-point integrated belt, positioned on a semi-rigid seat, and exposed to low and moderate velocities (15, 32 km/h). Data included belt loads, spinal accelerations, kinematics, and injuries from x-rays, computed tomography, and necropsy. At 15 km/h speed, no significant difference in the occupant kinematics and evidence of orthopedic failure was observed. At 32 km/h speed, the primary difference between the cohorts was significantly larger Z displacements in the reclined occupant at the head (190 ± 32 mm, vs. 105 ± 33 mm p < 0.05) and femur (52 ± 18 mm vs. 30 ± 10 mm, p < 0.05). All the moderate-speed tests produced at least one thorax injury. Rib fractures were scattered around the circumference of the rib-cage in the upright, while they were primarily concentrated on the anterior aspect of the rib-cage in two reclined specimens. Although MAIS was the same in both groups, the reclined specimens had more bi-cortical rib fractures, suggesting the potential for pneumothorax. While not statistical, these results suggest enhanced injuries with reclined obese occupants. These results could serve as a data set for validating the response of restrained obese anthropometric test device (ATDs) and computational human body models.

PMID:37733821 | DOI:10.4271/2022-22-0002

PLoS Comput Biol. 2023 Sep 21;19(9):e1010704. doi: 10.1371/journal.pcbi.1010704. Online ahead of print.

ABSTRACT

In many organisms, interactions among genes lead to multiple functional states, and changes to interactions can lead to transitions into new states. These transitions can be related to bifurcations (or critical points) in dynamical systems theory. Characterizing these collective transitions is a major challenge for systems biology. Here, we develop a statistical method for identifying bistability near a continuous transition directly from high-dimensional gene expression data. We apply the method to data from honey bees, where a known developmental transition occurs between bees performing tasks in the nest and leaving the nest to forage. Our method, which makes use of the expected shape of the distribution of gene expression levels near a transition, successfully identifies the emergence of bistability and links it to genes that are known to be involved in the behavioral transition. This proof of concept demonstrates that going beyond correlative analysis to infer the shape of gene expression distributions might be used more generally to identify collective transitions from gene expression data.

PMID:37733808 | DOI:10.1371/journal.pcbi.1010704

PLoS One. 2023 Sep 21;18(9):e0278428. doi: 10.1371/journal.pone.0278428. eCollection 2023.

ABSTRACT

Football (soccer) is a very popular team sport among African women and girls, with player numbers continuing to rise at all levels of the sport. Whereas the participation in football and associated injuries are on the rise, there are not enough sports and exercise medicine (SEM) personnel to attend to these women football players. While Africa may not currently have enough SEM trained medical doctors and/or physiotherapists, it has relatively higher numbers of other healthcare workers; for example, nurses, who lead healthcare services provision from community to tertiary levels. The primary objective of this study will be to compare sports medicine practices; injury prevention behaviours; injury risk parameters; incidence and prevalence of injuries and illnesses in teams with and without a Football Nurse during one competitive season in Malawi’s Women’s football league. This study will be a cluster randomised control trial will recruit 24 teams from the Women’s Football League in Malawi, which will be randomised to either the intervention group or the control group. A cohort of 12 nurses will receive training in basic football medicine; after which they will be attached to a total of 12 women’s football teams (intervention group) during one competitive season. The Football Nurses will be directly report to a physiotherapist or doctor in their district to whom they will refer serious injuries for investigations, or further management. The teams with Football Nurses will be compared to other teams that will not have Football Nurses. We expect to develop a low cost, sustainable and context relevant solution to manage the treatment gap of football injuries/illnesses in underserved communities such as women’s football. Trial registration number: Pan African Clinical Trial Registry (PACTR202205481965514).

PMID:37733774 | DOI:10.1371/journal.pone.0278428

Acta Med Litu. 2022;29(2):225-235. doi: 10.15388/Amed.2022.29.2.9. Epub 2022 Jun 29.

ABSTRACT

BACKGROUND AND OBJECTIVES: The most effective treatment of infertility is in vitro fertilization (IVF). IVF with Preimplantation Genetic Testing (PGT) allows to identify embryos with a genetic abnormality associated with a specific medical disorder and to select the most optimal embryos for the transfer. PGT is divided into structural rearrangement testing (PGT-SR), monogenetic disorder testing (PGT-M), and aneuploidy testing (PGT-A). This study mostly analyzes PGT-SR, also describes a few cases of PGT-M. The aim of this study was to implement PGT procedure at Vilnius University Hospital Santaros Klinikos (VUHSK) Santaros Fertility Centre (SFC) and to perform retrospective analysis of PGT procedures after the implementation.

MATERIALS AND METHODS: A single-center retrospective analysis was carried out. The study population included infertile couples who underwent PGT at SFC, VUHSK from January 01st, 2017 to December 31st, 2020. Ion PGM platform (Life Technologies, USA) and Ion ReproSeq PGS View Kit (Life Technologies, USA) were used for the whole genome amplification. Results were assessed using descriptive statistics.

RESULTS: PGT was successfully implemented in VUHSK in 2017. During the analyzed time period, thirty-four PGT procedures were performed for 26 couples. Two procedures were performed in 2017, 7 procedures – in 2018, 13 – in 2019, and 12 – in 2020. In comparison with all IVF procedures, 2.5% procedures were IVF with PGT, a highest percentage was in 2020 (3.8% of all procedures). The main indication for PGT was balanced chromosomal rearrangements (in 85.3% cases). In all 34 cases 515 oocytes were aspirated in total, 309 oocytes were fertilized, oocytes fertilization rate exceeded 60%. A normal diploid karyotype was found in 46 (16.8%) biopsied embryos. Out of all PGT procedures, 9 (26.5%) resulted in a clinical pregnancy. Six (66.7%) pregnancies were confirmed in 2019, and 3 (33.3%) – in 2020. Three (33.3%) pregnancies resulted in spontaneous abortion, 6 (66.7%) – in delivery.

CONCLUSIONS: The implementation of PGT in VUHSK was successful. The most common indication for PGT was a reciprocal translocation. Oocytes fertilization rate exceeded 60%, a normal karyotype was found less than in one-fifth of biopsied embryos. A highest clinical pregnancy rate was achieved in 2019 when almost half of women conceived, which is probably related to the experience gained by the multidisciplinary team. This is the first study analyzing IVF with PGT in Lithuania, however, the results should be interpreted with caution due to a low number of total procedures performed.

PMID:37733426 | PMC:PMC9799000 | DOI:10.15388/Amed.2022.29.2.9

Neurol Res. 2023 Sep 21:1-9. doi: 10.1080/01616412.2023.2257439. Online ahead of print.

ABSTRACT

AIM: The Dubousset Functional Test (DFT) ia a practical four-component assessment test to assess the physical function and balance capacities. The study aimed to examine the reliability, validity, responsiveness of the DFT in stroke survivors.

METHODS: This study included a total of 57 post-stroke patients (age 60.16 ± 15.08 years). The participants were divided into two groups according to the duration of stroke (6-12 months, 12 months and more). Reliability of DFT test was evaluated with Intraclass Correlation Coefficient (ICC). The correlation between the DFT and The Timed Up and Go test (TUG), dual-task TUG, Functional Reach Test (FRT), 3-meter backward walk test (3MBWT), Tinetti Performance Oriented Mobility Assessment (POMA) was used for the validity.

RESULTS: For total post-stroke patients, ICC values were between 0.899 and 0.984 (excellent agreement). For stroke patients have 6-12 months stroke duration ICC values were between 0.831 and 0.988 (excellent agreement). For post-stroke patients have 6-12 months stroke duration ICC values were between 0.858 and 0.992 (excellent agreement). For total stroke post-patients the correlation with four component of DFT and TUG, dual-task TUG, FRT, 3MBWT and POMA was found to be statistically significant (p < 0.001).

CONCLUSION: The DFT has excellent reliability and validity in post-stroke patients. Therefore, it may be a clinically suitable test for detecting balance and physical function.

PMID:37733422 | DOI:10.1080/01616412.2023.2257439

Acta Med Litu. 2022;29(2):271-294. doi: 10.15388/Amed.2022.29.2.13. Epub 2022 Jun 29.

ABSTRACT

BACKGROUND: Nonsyndromic craniofacial clefts are relatively common congenital malformations which could create a significant negative effect on the health status and life quality of affected individuals within the pediatric population. Multiple cleft candidate genes and their coded proteins have been described with their possible involvement during cleft formation. Some of these proteins like Homeobox Protein BarH-like 1 (BARX1), Distal-Less Homeobox 4 (DLX4), Forkhead Box E1 (FOXE1), Homeobox Protein Hox-B3 (HOXB3), and Muscle Segment Homeobox 2 (MSX2) have been associated with the formation of craniofacial clefts. Understanding the pathogenetic mechanisms of nonsyndromic craniofacial cleft formation could provide a better knowledge in cleft management and could be a possible basis for development and improvement of cleft treatment options. This study investigates the presence of BARX1, DLX4, FOXE1, HOXB3, and MSX2 positive cells by using immunohistochemistry in different types of cleft-affected tissue while determining their possible connection with cleft pathogenesis process.

MATERIALS AND METHODS: Craniofacial cleft tissue material was obtained during cleft-correcting surgery from patients with nonsyndromic craniofacial cleft diagnosis. Tissue material was gathered from patients who had unilateral cleft lip (n=36), bilateral cleft lip (n=13), and cleft palate (n=26). Control group (n=7) tissue material was received from individuals without any craniofacial clefts. The number of factor positive cells in the control group and patient group tissue was evaluated by using the semiquantitative counting method. Data was evaluated with the use of nonparametric statistical methods.

RESULTS: Statistically significant differences were identified between the number of BARX1, FOXE1, HOXB3, and MSX2-containing cells in controls and cleft patient groups but no statistically significant difference was found for DLX4. Statistically significant correlations between the evaluated factors were also notified in cleft patient groups.

CONCLUSIONS: HOXB3 could be more associated with morphopathogenesis of unilateral cleft lip during postnatal course of the disorder. FOXE1 and BARX1 could be involved with both unilateral and bilateral cleft lip morphopathogenesis. The persistence of MSX2 in all evaluated cleft types could indicate its possible interaction within multiple cleft types. DLX4 most likely is not involved with postnatal cleft morphopathogenesis process.

PMID:37733420 | PMC:PMC9799009 | DOI:10.15388/Amed.2022.29.2.13

JMIR Res Protoc. 2023 Sep 21;12:e48400. doi: 10.2196/48400.

ABSTRACT

BACKGROUND: Since they are key witnesses to the systemic difficulties and social inequities experienced by vulnerable patients, health and social service (HSS) professionals and clinical managers must act as change agents. Using their expertise to achieve greater social justice, change agents employ a wide range of actions that span a continuum from the clinical (microsystem) to the societal (macrosystem) sphere and involve actors inside and outside the HSS system. Typically, however, clinical professionals and managers act in a circumscribed manner, that is, within the clinical sphere and with patients and colleagues. Among the hypotheses explaining this reduced scope of action is the fear of reprisal. Little is known about the prevalence of this fear and its complex dynamics.

OBJECTIVE: The overall aim is to gain a better understanding of the complex dynamic process leading to clinical professionals’ and managers’ fear of reprisal in their change agent actions and senior administrators’ and managers’ determination of wrongdoing. The objectives are (1) to estimate the prevalence of fear of reprisal among clinical professionals and managers; (2) to identify the factors involved in (a) the emergence of this fear among clinical professionals and managers, and (b) the determination of wrongdoing by senior administrators and managers; (3) to describe the process of emergence of (a) the fear of reprisal among clinical professionals and managers, and (b) the determination of wrongdoing by senior administrators and managers; and (4) to document the legal and ethical issues associated with the factors identified (objective 2) and the processes described (objective 3).

METHODS: Based on the Exit, Voice, Loyalty, Neglect model, a 3-part sequential mixed methods design will include (1) a web-based survey (objective 1), (2) a qualitative grounded theory design (objectives 2 and 3), and (3) legal and ethical analysis (objective 4). Survey: 77,794 clinical professionals or clinical managers working in the Québec public HSS system will be contacted via email. Data will be analyzed using descriptive statistics. Grounded theory design: for each of the 3 types of participants (clinical professionals, clinical managers, and senior administrators and managers), a theoretical sample of 15 to 30 people will be selected via various strategies. Data will be independently analyzed using constant comparison process. Legal and ethical analysis: situations described by participants will be analyzed using, respectively, applicable legislation and jurisprudence and 2 ethical models.

RESULTS: This ongoing study began in June 2022 and is scheduled for completion by March 2027.

CONCLUSIONS: Instead of acting, fear of reprisal could induce clinical professionals to tolerate situations that run counter to their social justice values. To ensure they use their capacities for serving a population that is or could become vulnerable, it is important to know the prevalence of the fear of reprisal and gain a better understanding of its complex dynamics.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48400.

PMID:37733408 | DOI:10.2196/48400

JMIR Aging. 2023 Sep 21;6:e41185. doi: 10.2196/41185.

ABSTRACT

BACKGROUND: Informal carers play a major role in supporting relatives and friends who are sick, disabled, or frail. Access to information, guidance, and support that are relevant to the lives and circumstances of carers is critical to carers feeling supported in their role. When unmet, this need is known to adversely affect carer resilience and well-being. To address this problem, Care Companion was co-designed with current and former carers and stakeholders as a free-to-use, web-based resource to provide access to a broad range of tailored information, including links to local and national resources.

OBJECTIVE: This study aimed to investigate the real-world uptake and use of Care Companion in 1 region of England (with known carer population of approximately 100,000), with local health, community, and social care teams being asked to actively promote its use.

METHODS: The study had a convergent parallel, mixed methods design and drew on the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework. Data included metrics from carers’ use of Care Companion, surveys completed by users recruited through general practice, and interviews with carers and health and social care providers regarding their views about Care Companion and their response to it. Quantitative data were analyzed using descriptive statistics. Interview data were analyzed thematically and synthesized to create overarching themes. The qualitative findings were used for in-depth exploration and interpretation of quantitative results.

RESULTS: Despite awareness-raising activities by relevant health, social care, and community organizations, there was limited uptake with only 556 carers (0.87% of the known carer population of 100,000) registering to use Care Companion in total, with median of 2 (mean 7.2; mode 2) visits per registered user. Interviews with carers (n=29) and stakeholders (n=12) identified 7 key themes that influenced registration, use, and perceived value: stakeholders’ signposting of carers to Care Companion, expectations about Care Companion, activity levels and conflicting priorities, experience of using Care Companion, relevance to personal circumstances, social isolation and networks, and experience with digital technology. Although many interviewed carers felt that it was potentially useful, few considered it as being of direct relevance to their own circumstances. For some, concerns about social isolation and lack of hands-on support were more pressing issues than the need for information.

CONCLUSIONS: The gap between the enthusiastic views expressed by carers during Care Companion’s co-design and the subsequent low level of uptake and user experience observed in this evaluation suggests that the co-design process may have lacked a sufficiently diverse set of viewpoints. Numerous factors were identified as contributing to Care Companion’s level of use, some of which might have been anticipated during its co-design. More emphasis on the development and implementation, including continuing co-design support after deployment, may have supported increased use.

PMID:37733406 | DOI:10.2196/41185