Nevin Manimala

Bioinformatics. 2022 Jan 5:btac004. doi: 10.1093/bioinformatics/btac004. Online ahead of print.

ABSTRACT

SUMMARY: Bayesian inference in biological modeling commonly relies on Markov chain Monte Carlo (MCMC) sampling of a multidimensional and non-Gaussian posterior distribution that is not analytically tractable. Here, we present the implementation of a practical MCMC method in the open-source software package PyBioNetFit (PyBNF), which is designed to support parameterization of mathematical models for biological systems. The new MCMC method, am, incorporates an adaptive move proposal distribution. For warm starts, sampling can be initiated at a specified location in parameter space and with a multivariate Gaussian proposal distribution defined initially by a specified covariance matrix. Multiple chains can be generated in parallel using a computer cluster. We demonstrate that am can be used to successfully solve real-world Bayesian inference problems, including forecasting of new Coronavirus Disease 2019 case detection with Bayesian quantification of forecast uncertainty.

AVAILABILITY AND IMPLEMENTATION: PyBNF version 1.1.9, the first stable release with am, is available at PyPI and can be installed using the pip package-management system on platforms that have a working installation of Python 3. PyBNF relies on libRoadRunner and BioNetGen for simulations (e.g., numerical integration of ordinary differential equations defined in SBML or BNGL files) and Dask.Distributed for task scheduling on Linux computer clusters. The Python source code can be freely downloaded/cloned from GitHub and used and modified under terms of the BSD-3 license (https://github.com/lanl/pybnf). Online documentation covering installation/usage is available (https://pybnf.readthedocs.io/en/latest/). A tutorial video is available on YouTube (https://www.youtube.com/watch?v=2aRqpqFOiS4&t=63s).

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:34986226 | DOI:10.1093/bioinformatics/btac004

J Pediatr Psychol. 2022 Jan 5:jsab132. doi: 10.1093/jpepsy/jsab132. Online ahead of print.

ABSTRACT

OBJECTIVE: To provide national norms and percentiles for both research and clinical scoring modalities of the Vanderbilt Attention Deficit/Hyperactivity Disorder (ADHD) Diagnostic Parent Rating Scale (VADPRS) for a representative sample of children ages 5-12 in the United States.

METHOD: The five clinical subscales of the VADPRS were completed by 1,570 caregivers of children ages 5-12 in the United States, with children representative of the national population on key demographic variables including race, sex, ethnicity, family income, and family educational level. Descriptive statistics and measures of internal consistency of both dimensional and symptom count scoring were provided for each of the five clinical subscales of the inventory, as well as percentiles and group comparisons for select dimensional scoring subscales based on age and child sex.

RESULTS: Measures of internal consistency for each subscale using both scoring modalities of the VADPRS ranged from high to acceptable. There were statistically significant differences among the different subscales for both age (ADHD hyperactivity, anxiety/depression) and sex [both presentations of ADHD, oppositional defiant disorder (ODD)] for the total sample. These differences, however, were modest in magnitude and unlikely to be clinically meaningful.

CONCLUSIONS: This study enhances the research and clinical utility of the VADPRS by providing national norms and percentiles for each of its subscales. Differences between age and sex across the sample were statistically significant for two of the subscales (Hyperactivity and Anxiety/Depression) with additional subscales significant for sex alone (Inattentive and ODD), but these differences were not substantial enough to indicate a need for separate cut-offs for screening purposes.

PMID:34986222 | DOI:10.1093/jpepsy/jsab132

Hum Reprod. 2021 Dec 27;37(1):119-128. doi: 10.1093/humrep/deab242.

ABSTRACT

STUDY QUESTION: Are transfer day, developmental stage and morphology of the competent blastocyst in pregnancies leading to live birth associated with preterm birth, birthweight, length at birth and sex of the child?

SUMMARY ANSWER: A high score in blastocyst developmental stage and in trophectoderm (TE) showed a significant association with the sex of the child, while no other associations with obstetric outcomes were observed.

WHAT IS KNOWN ALREADY: The association between blastocyst assessment scores and obstetric outcomes have been reported in small single-center studies and the results are conflicting.

STUDY DESIGN, SIZE, DURATION: Multicenter historical cohort study based on exposure data (transfer day (blastocyst developmental stage reached by Day 5 or Day 6)) blastocyst developmental stage (1-6) and morphology (TE and inner cell mass (ICM): A, B, C)) and outcome data (preterm birth, birthweight, length at birth, and sex of the child) from women undergoing single blastocyst transfer resulting in a singleton pregnancy and live birth.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 16 private and university-based facilities for clinical services and research were used. A total of 7246 women, who in 2014-2018 underwent fresh-embryo transfer with a single blastocyst or frozen-thawed embryo transfer (FET) with a single blastocyst resulting in a singleton pregnancy were identified. Linking to the Danish Medical Birth Registry resulted in a total of 4842 women with a live birth being included. Cycles with pre-implantation genetic testing and donated gametes were excluded. The analyses were adjusted for female age (n = 4842), female BMI (n = 4302), female smoking (n = 4290), parity (n = 4365), infertility diagnosis (n = 4765), type of treatment (n = 4842) and center (n = 4842); some analyses additionally included gestational age (n = 4368) and sex of the child (n = 4833).

MAIN RESULTS AND THE ROLE OF CHANCE: No statistically significant associations between blastocyst assessment scores (transfer day, developmental stage, TE, ICM) and preterm birth (8.3%) or birthweight (mean 3461.7 g) were found. The adjusted association between blastocysts with a TE score of C and a TE score of A and length at birth (mean 51.6 cm) were statistically significant (adjusted mean difference 0.4 cm (95% CI: 0.02; 0.77)). Blastocysts transferred with developmental stage score 5 compared to blastocysts transferred with score 3 had a 34% increased probability of being a boy (odds ratio (OR) 1.34 (95% CI: 1.09; 1.64). Further, TE score B blastocysts compared to TE score A blastocysts had a 31% reduced probability of being a boy (OR 0.69 (95% CI: 0.60; 0.80)).

LIMITATIONS, REASONS FOR CAUTION: It is possible that some residual confounding remains.

WIDER IMPLICATIONS OF THE FINDINGS: Blastocyst selection during ART does not appear to introduce any negative effects on obstetric outcome. Therefore, clinicians and patients can be reassured that the assessment scores of the selected blastocyst will not in themselves pose a risk of preterm birth or affect birthweight and the length at birth.

STUDY FUNDING/COMPETING INTEREST(S): Unrestricted grant from Gedeon Richter Nordics AB, Sweden. None of the authors have any competing interest to declare.

TRIAL REGISTRATION NUMBER: N/A.

PMID:34986219 | DOI:10.1093/humrep/deab242

Phys Chem Chem Phys. 2022 Jan 5. doi: 10.1039/d1cp05072a. Online ahead of print.

ABSTRACT

Nucleophilicity provides important information about the chemical reactivity of organic molecules. Experimental determination of the nucleophilicity parameter is a tedious and resource-intensive approach. Herein, we present a novel machine learning protocol that uses key structural descriptors to predict the nucleophilicities of organic molecules, which agree well with the experimental values. A data driven approach was used where quantum mechanical molecular and thermodynamic descriptors from a wide range of structurally diverse nucleophiles and relevant solvents were extracted and modelled using advanced algorithms against the experimentally available nucleophilicity values. Despite the structural diversity of nucleophiles, we are able to achieve statistically robust models with a high predictive power using tree-based and neural network algorithms trained on an in-house developed unique dataset consisting of 752 nucleophilicity values and 27 molecular descriptors.

PMID:34986215 | DOI:10.1039/d1cp05072a

PLoS One. 2022 Jan 5;17(1):e0262239. doi: 10.1371/journal.pone.0262239. eCollection 2022.

ABSTRACT

INTRODUCTION: In cholera endemic areas, the periodicity of cholera outbreaks remains unpredictable, making it difficult to organize preventive efforts. Lack of data on duration of protection conferred by oral cholera vaccines further makes it difficult to determine when to deploy preemptive vaccination. We report on the immunogenicity and waning of immunity to Shanchol™ in Lukanga Swamps.

METHODS: We enrolled a cohort of 223 participants aged between 18 and 65 years old from whom serum samples were collected at baseline, day 28 before administration of the second dose, and consecutively at 6, 12, 24, 30, 36, and 48 months. Vibriocidal antibody titres were measured and expressed as geometric mean titres. Box plots and 95% CI were computed at each visit for both Inaba and Ogawa. Seroconversion was defined as a four fold or greater increase in antibody titres compared to baseline titres.

RESULTS: Overall, seroconversion against V. cholerae Inaba and Ogawa after 1st dose was 35/134 (26%) and 34/134 (25%) respectively. We observed a statistical difference in seroconversion between the two subgroups of baseline titres (low <80 and high ≥80) for both Inaba (p = 0.02) and Ogawa (p<0.0001). From a baseline of 13.58, anti-Ogawa GMT increased to 21.95 after the first dose, but rapidly waned to 14.52, 13.13, and 12.78 at months 6, 12 and 24 respectively, and then increased to 13.21, 18.67 and 23.65 at months 30, 36 and 48 respectively. A similar trend was observed for anti-Inaba GMT across the same time points.

CONCLUSION: We found that Shanchol™ was immunogenic in our study population and that vibriocidal antibodies may not be a good marker for long-term immunity. The observed rise in titres after 36 months suggests natural exposure, and this may be a critical time window opening for natural transmission in an endemic areas. We recommend re-vaccination at this time point in high risk areas.

PMID:34986195 | DOI:10.1371/journal.pone.0262239

PLoS One. 2022 Jan 5;17(1):e0262168. doi: 10.1371/journal.pone.0262168. eCollection 2022.

ABSTRACT

Tungiasis is caused by the flea tunga penetrans and results in painful skin lesions, skin infections, and permanent disability. However, limited information is available that shows the magnitude of the problem and its risk factors that help for intervention in Ethiopia. The goal of this study was to determine the prevalence and risk factors of tungiasis in children aged 5 to 14 in Mettu woreda in 2020. A community based cross sectional study was conducted among randomly selected kebeles of Mettu woreda, in Southwest Ethiopia. To select study participants, multistage sampling was used. The data were collected through physical examination of the children, interview of parents/guardians of the children, and observation of the home environment using checklists and questionnaires. The descriptive analysis was done for socio-demographic characteristics, prevalence of tungiasis, and housing conditions. A logistic regression analysis was performed, and variables in multivariable regression reported odds ratios and their 95% confidence intervals once the variables were identified using a p-value of 0.05 as a risk factor of statistical significance. The prevalence of tungiasis among children 5-14 years of age in Mettu rural woreda was 52 percent (n = 821). As a risk factor, large family size (AOR: 2.9, 95% CI: 2.13, 4.40); school attendance (AOR: 1.5, 95% CI: 1.02, 2.18), floor inside the house (AOR: 3.8, 95% CI: 1.76, 8.43); having sleeping bed (AOR: 0.16, 95% CI: 0.03, 0.82); access to protected water sources (AOR: 0.24, 95% CI: 0.15, 0.39); access to improved toilet facilities(AOR: 0.63: 95% CI: 0.44, 0.89); access to electric services (AOR: 0.30, 95% CI: 0.15, 0.62); and lack of own farmland (AOR: 0.36, 95% CI: 0.26, 0.50) were found. Therefore, planning and implementation of interventions focus on those risk factors that are particularly important. Water, sanitation and hygiene interventions, and livelihood improvement interventions are required to solve the problem in the setting.

PMID:34986188 | DOI:10.1371/journal.pone.0262168

PLoS One. 2022 Jan 5;17(1):e0262137. doi: 10.1371/journal.pone.0262137. eCollection 2022.

ABSTRACT

The main aim of the study was to investigate the role and importance of perceived risk in medical tourism (MT). The research demonstrates that the country of origin and an assessment of the respondents’ own health condition significantly moderates the impact of their attitudes on behavioral intention. The research shows a strong correlation between the risk perceived by the respondents and their attitudes towards MT services. This relationship is significantly moderated by risk awareness, aversion to risk and gender. Additionally, an important factor in the model is the level of satisfaction with medical services in their own country. The survey using a fully structured questionnaire was conducted among young consumers from Jordan, Poland and Turkey. To verify the hypotheses, a multiple regression model with interactions was used.

PMID:34986182 | DOI:10.1371/journal.pone.0262137

PLoS One. 2022 Jan 5;17(1):e0262300. doi: 10.1371/journal.pone.0262300. eCollection 2022.

ABSTRACT

INTRODUCTION: By measuring patients’ satisfaction, providers can gain insight into several elements of health care services, including the effectiveness of their care and the level of empathy they exhibit. The aim of this study was to assess patient satisfaction with pharmaceutical services and associated factors in public hospitals located in Northwestern Ethiopia.

METHODS: An institution-based quantitative cross-sectional study was used. The study was carried out in an outpatient pharmacy from January 1-June 30, 2021. Participants were selected by a systematic sampling technique. The IBM SPSS statistical package (version 23) was used to enter and analyze the collected data. The findings were presented using descriptive statistical methods. To find factors linked to satisfaction, binary logistic regression was used.

RESULTS: The final analysis included a total of 401 samples. More than half of the participants (229, or 55.1%) were female. The overall mean score of satisfaction was 30.6 out of a maximum of 100 scores. By taking this mean score as a cut-off point, 204 (50.9%) of the study participants had satisfaction with the outpatient pharmacists’ service. Participants’ responses scored on the uncomfortable and inconvenient waiting areas [AOR = 0.31; 95%CI, (0.13, 0.49)] were found to be negatively associated with the level of patients’ satisfaction. Also, the unavailability of medications [AOR = 0.12; 95%CI, (0.02, 0.37)] was negatively associated with the respondent satisfaction. Uncomfortable and inconvenient private counseling areas [AOR = 1.37; 95%CI, (0.79, 4.42)] showed a negative association with their satisfaction.

CONCLUSION: Patients’ satisfaction levels with pharmacy service were found to be greater than 50%. The socio-demographic characteristics of patients have no association with their level of satisfaction, but their perception of uncomfortable private counseling areas and waiting areas was negatively associated with their satisfaction.

PMID:34986179 | DOI:10.1371/journal.pone.0262300

PLoS Med. 2022 Jan 5;19(1):e1003887. doi: 10.1371/journal.pmed.1003887. eCollection 2022 Jan.

ABSTRACT

BACKGROUND: Adolescents living with HIV have poor virological suppression and high prevalence of common mental disorders (CMDs). In Zimbabwe, the Zvandiri adolescent peer support programme is effective at improving virological suppression. We assessed the effect of training Zvandiri peer counsellors known as Community Adolescent Treatment Supporters (CATS) in problem-solving therapy (PST) on virological suppression and mental health outcomes.

METHODS AND FINDINGS: Sixty clinics were randomised 1:1 to either normal Zvandiri peer counselling or a peer counsellor trained in PST. In January to March 2019, 842 adolescents aged 10 to 19 years and living with HIV who screened positive for CMDs were enrolled (375 (44.5%) male and 418 (49.6%) orphaned of at least one parent). The primary outcome was virological nonsuppression (viral load ≥1,000 copies/mL). Secondary outcomes were symptoms of CMDs measured with the Shona Symptom Questionnaire (SSQ ≥8) and depression measured with the Patient Health Questionnaire (PHQ-9 ≥10) and health utility score using the EQ-5D. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were estimated using logistic regression adjusting for clinic-level clustering. Case reviews and focus group discussions were used to determine feasibility of intervention delivery. At baseline, 35.1% of participants had virological nonsuppression and 70.3% had SSQ≥8. After 48 weeks, follow-up was 89.5% for viral load data and 90.9% for other outcomes. Virological nonsuppression decreased in both arms, but there was no evidence of an intervention effect (prevalence of nonsuppression 14.7% in the Zvandiri-PST arm versus 11.9% in the Zvandiri arm; AOR = 1.29; 95% CI 0.68, 2.48; p = 0.44). There was strong evidence of an apparent effect on common mental health outcomes (SSQ ≥8: 2.4% versus 10.3% [AOR = 0.19; 95% CI 0.08, 0.46; p < 0.001]; PHQ-9 ≥10: 2.9% versus 8.8% [AOR = 0.32; 95% CI 0.14, 0.78; p = 0.01]). Prevalence of EQ-5D index score <1 was 27.6% versus 38.9% (AOR = 0.56; 95% CI 0.31, 1.03; p = 0.06). Qualitative analyses found that CATS-observed participants had limited autonomy or ability to solve problems. In response, the CATS adapted the intervention to focus on empathic problem discussion to fit adolescents’ age, capacity, and circumstances, which was beneficial. Limitations include that cost data were not available and that the mental health tools were validated in adult populations, not adolescents.

CONCLUSIONS: PST training for CATS did not add to the benefit of peer support in reducing virological nonsuppression but led to improved symptoms of CMD and depression compared to standard Zvandiri care among adolescents living with HIV in Zimbabwe. Active involvement of caregivers and strengthened referral structures could increase feasibility and effectiveness.

TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201810756862405.

PMID:34986170 | DOI:10.1371/journal.pmed.1003887

PLoS Comput Biol. 2022 Jan 5;18(1):e1009770. doi: 10.1371/journal.pcbi.1009770. eCollection 2022 Jan.

ABSTRACT

[This corrects the article DOI: 10.1371/journal.pcbi.1009118.].

PMID:34986151 | DOI:10.1371/journal.pcbi.1009770