bluuebunny/crossref_metadata_2025 huggingface dataset:
Are midwives ready to provide quality evidence-based care after pre-service training? Curricula assessment in four countries - Benin, Malawi, Tanzania, and Uganda
Authors: Moller Ann-Beth , Welsh Joanne , Ayebare Elizabeth , Chipeta Effie , Gross Mechthild M , Houngbo Gisele , Hounkpatin Hashim , Kandeya Bianca , Mwilike Beatrice , Nalwadda Gorrette , Petzold Max , Sognonvi Antoinette , Hanson Claudia
Published: May 2022

This research sought to map midwifery pre-service training curricula as part of the Action Leveraging Evidence to Reduce perinatal morTality and morbidity in sub-Saharan Africa (ALERT) project conducted in Benin, Malawi, Tanzania, and Uganda.

We conducted the review in two phases. In the first phase, online interviews were performed with the lead project midwives in all four study countries to get an overview of midwifery care providers’ pre-service training courses, registration, and licensing requirements. We performed a mapping review of midwifery care providers’ pre-service training curricula from different training institutions in the four study countries during the second phase.

Curricula were reviewed and mapped against the International Confederation of Midwives (ICM) Essential Competencies framework to assess whether these curricula included the minimum essential training components described in the ICM framework.

We identified 10 different professional titles for midwifery care providers. The number of years spent in pre-service training varied from one and a half to four years.

Ten pre-service curricula were obtained and the assessment revealed that none of the curricula included all ICM competencies. Main gaps identified in all curricula related to women-centred care, inclusion of women in decision making, provision of care to women with unintended or mistimed pregnancy, fundamental human rights of individuals and evidence-based learning.

This review suggests that there are skills, knowledge and behaviour gaps in pre-service training curricula for midwifery care providers when mapped to the ICM Essential Competencies framework. These gaps are similar among the different training courses in participating countries. The review also draws attention to the plethora of professional titles and different pre-service training curricula within countries.
Prevalence and demographic distribution associated with pre-eclampsia among pregnant women at a local Teaching Hospital in Ghana
Authors: Adwoa Nyarko , Kunfah Joshua A. , Akayuure Collins Adombine , Kappiah Jamilatu , Kampo Sylvanus
Published: May 2022

Background

In sub-Saharan Africa, pre-eclampsia remains a major health problem contributing to high rates of maternal mortality. Despite this condition having adverse effects on maternal and child health, its prevalence and associated risk factors are still significant, especially in developing countries including Ghana. This study aimed to assess the prevalence and demographic distributions associated with pre-eclampsia among pregnant women at the Ho Teaching Hospital.

Methods

A facility-based retrospective study was conducted by reviewing available data or hospital records of pregnant mothers who were admitted to the labour and maternity wards from January 2018 to December 2020. The data were collected using a structured checklist.

Results

A total of 5,609 deliveries were recorded from 2018 to 2020. Out of the 5,609 deliveries, 314 pre-eclampsia cases were recorded giving an overall prevalence of 5.6 %. The yearly prevalence for 2018, 2019, and 2020 were 4.6 %, 5.6 %, and 6.6 %, respectively. The most recorded pre-eclampsia cases were seen among women within the age group of 18-24 years. The data showed that 112 (35.7 %) of the mothers who had pre-eclampsia were nulliparous. Pre-eclampsia associated maternal and fetal complications were; preterm delivery 221 (70.4 %), intrauterine fetal death 62 (19.7 %), eclampsia 9 (2.9 %), HELLP syndrome 5 (1.6 %) and maternal death 17 (5.4 %). Associated factors of pre-eclampsia were parity, level of education, and occupation (p=<0.05).

Conclusion

The findings of this study showed a rising trend in the incidence of pre-eclampsia over the years at the Ho Teaching Hospital. Parity, level of education, and occupation were found to be associated with developing pre-eclampsia.
The expression of cancer stem cells and its effects on the propensity for recurrence and metastasis in bladder cancer: a systematic review
Authors: Hamid Agus Rizal Ardy Hariandy , Syadza Yasmina Zahra , Yausep Oliver Emmanuel , Indy Christanto Roberto Bagaskara , Muharia Bayu Hernawan Rahmat , Mochtar Chaidir Arif
Published: May 2022

Bladder cancer is one of the most frequent cancers of the urinary tract, associated with high recurrence rates and metastasis. Cancer stem cells (CSCs) are a subpopulation of cancer cells characterized by high self-renewal and differentiation capacities, resulting in increased cancer recurrence, larger tumor size, higher rates of metastasis, higher resistance to treatment, and overall poorer prognosis. This study aimed to evaluate the role of CSCs as a prognostic tool to predict the risks of metastasis and recurrence in bladder cancer. A literature search was conducted across seven databases from January 2000 to February 2022 for clinical studies investigating the use of CSCs to determine the prognosis of bladder cancer. The following keywords were used: (“Bladder Cancer” OR “Transitional Cell Carcinoma” OR “Urothelial Carcinoma”) AND (“Stem Cell” OR “Stem Gene”) AND (“Metastasis” OR “Recurrence”). A total of 12 studies were deemed eligible for inclusion. SOX2, IGF1R, SOX4, ALDH1, CD44, Cripto-1, OCT4, ARRB1, ARRB2, p-TFCP2L1, CDK1, DCLK1, and NANOG, which were all identified as CSC markers, have been implicated in the recurrence and metastasis of tumor in bladder cancer, which played a role as prognostic factor of bladder cancer. Given the pluripotent and highly proliferative properties of CSCs. CSCs may play a role in the complex biological behavior of bladder cancer, including, but not limited to, its high rates of recurrence, metastasis, and resistance to treatment. The detection of cancer stem cell markers offers a promising approach in determining the prognosis of bladder cancer. Further studies in this area are thus warranted and may contribute significantly to the overall management of bladder cancer.
SARS-CoV-2 infection in vaccinated individuals induces virus-specific nasal resident CD8 and CD4 T cells of broad specificity
Authors: Er Lim Joey Ming , Tan Anthony T. , Le Bert Nina , Hang Shou Kit , Hong Low Jenny Guek , Bertoletti Antonio
Published: May 2022

Rapid recognition of SARS-CoV-2-infected cells by T cells resident in the upper airway might provide an important layer of protection against COVID-19. Whether parenchymal SARS-CoV-2 vaccination or infection induce nasal resident T cells specific for distinct SARS-CoV-2 proteins is unknown. We collected T cells from the nasal secretion of COVID-19 vaccinees, who either experienced SARS-CoV-2 infection after vaccination (n=20) or not (n=15) and analyzed their phenotype, SARS-CoV-2 specificity and function. Nasal-resident IFN-γ producing SARS-CoV-2-specific CD8 and CD4 T cells were detected exclusively in vaccinees who experienced SARS-CoV-2 breakthrough infection. Importantly, the vaccine priming of Spike-specific T cells does not suppress the induction of CD8 and CD4 T cells specific for different SARS-CoV-2 proteins (i.e. NP and NSP-12) that persisted in the nasal cavity up to 3 months after infection. These data highlight the importance of viral nasal challenge in the formation of SARS-CoV-2 specific antiviral immunity at the site of primary infection and further define the immunological features of SARS-CoV-2 hybrid immunity.
Rapid estimation of cortical neuron activation thresholds by transcranial magnetic stimulation using convolutional neural networks
Authors: Aberra Aman S. , Lopez Adrian , Grill Warren M. , Peterchev Angel V.
Published: May 2022

Background

Transcranial magnetic stimulation (TMS) can modulate neural activity by evoking action potentials in subpopulations of cortical neurons. The TMS-induced electric field (E-field) can be simulated in subject-specific head models derived from MR images, but the spatial distribution of the E-field alone does not predict the physiological response. Coupling E-field models to populations of biophysically realistic neuron models yields insights into the activation mechanisms of TMS, but the significant computational cost associated with these models limits their use and eventual translation to clinically relevant applications.

Objective

The objective was to develop computationally efficient estimators of the activation thresholds of multi-compartmental cortical neuron models in response to TMS-induced E-field distributions.

Methods

Multi-scale models combining anatomically accurate finite element method (FEM) simulations of the TMS E-field with layer-specific representations of cortical neurons were used to generate a large dataset of activation thresholds. 3D convolutional neural networks (CNNs) were trained on these data to predict the activation threshold of specific model neurons given the local E-field distribution. Using training and test data from different head models, the CNN estimator was compared to an approach using the uniform E-field approximation to estimate thresholds in the non-uniform TMS-induced E-field.

Results

The 3D CNNs were more accurate than the uniform E-field approach, with mean absolute percent error (MAPE) on the test dataset below 2.5% compared to 5.9 – 9.8% with the uniform E-field approach. Further, there was a strong correlation between the CNN predicted and actual thresholds for all cell types (R2 > 0.96) compared to the uniform E-field approach (R2 = 0.62 – 0.91). The CNNs estimate thresholds with a 2 – 4 orders of magnitude reduction in the computational cost of the multi-compartmental neuron models.

Conclusion

3D CNNs can estimate rapidly and accurately the TMS activation thresholds of biophysically realistic neuron models using sparse samples of the local E-field, enabling simulating responses of large neuron populations or parameter space exploration on a personal computer.
Extended practice improves the accuracy and efficiency of goal-directed reaching guided by supplemental kinesthetic vibrotactile feedback
Authors: Shah Valay A , Thomas Ashiya , Mrotek Leigh A , Casadio Maura , Scheidt Robert A
Published: May 2022

Prior studies have shown that providing task-specific vibrotactile feedback (VTF) during reaching and stabilizing with the arm can immediately improve the accuracy and efficiency. However, such studies typically evaluate performance after less than 1 hour of practice using VTF. Here we tested the effects of extended practice using supplemental kinesthetic VTF on goal-directed reaching with the arm. Healthy young adults performed a primary reaching task and a secondary choice reaction task individually and as a dual-task. The reaching task was performed under three feedback conditions: visual feedback, proprioceptive feedback, and with supplemental kinesthetic VTF applied to the non-moving arm. We compared performances before, during, and after approximately 10 hours of practice on the VTF-guided reaching task, distributed across 20 practice sessions. Upon initial exposure to VTF-guided reaching, participants were immediately able to use the VTF to improve reaching accuracy. Performance improvements were retained from one practice session to the next. After 10 hours of practice, the accuracy and temporal efficiency of VTF-guided reaching were equivalent to or better than reaching performed without vision or VTF. However, hand paths during VTF-guided reaching exhibited a persistent strategy whereby movements were decomposed into discrete sub-movements along the cardinal axes of the VTF interface. Dual-tasking capability also improved, such that the primary and secondary tasks we performed more concurrently after extended practice. Our results demonstrate that extended practice on VTF-guided reaching can yield performance improvements that accrue in a manner increasingly resistant to dual-task interference.
Developmental Coordination Disorder: What Can We Learn From Recombinant Inbred Mice Using Motor Learning Tasks and Quantitative Trait Locus Analysis
Authors: Gill Kamaldeep , Rajan Soundara Rajan Jeffy , Chow Eric , Ashbrook David G. , Williams Robert W. , Zwicker Jill G. , Goldowitz Daniel
Published: May 2022

Developmental Coordination Disorder (DCD) is a motor skills disorder that affects 5-6% of all school-aged children. There is an indication that DCD has an underlying genetic component due to its high heritability. Therefore, we we have explored the use of a recombinant inbred family of mice known as the BXD panel to understand the genetic basis of complex traits (i.e., motor learning) through identification of Quantitative Trait Loci (QTLs). The overall aim of this study was to utilize the QTL approach to evaluate the genome-to-phenome correlation in BXD strains of mice in order to to better understanding the human presentation of DCD. Results in this current study indicate there is a spectrum of motor learning in the pre-selected BXD strains of mice with a spectrum between high and low learning capabilities. Five lines – BXD15, BXD27, BXD28, BXD75, and BXD86 – exhibited the most DCD-like phenotype, when compared to other BXD lines of interest. The results indicate that BXD15 and BXD75 struggled primarily with gross motor skills, BXD28 primarily had difficulties with fine motor skills, and BXD27 and BXD28 lines struggled with both fine and gross motor skills. The functional roles of significant QTL genes were assessed in relation to DCD-like behavior. Only Rab3a (Ras-related protein Rab-3A) emerged as a best candidate gene for the horizontal ladder rung task. This gene is found to be associated with brain and skeletal muscle development. This is the first study to specifically examine the genetic linkage of DCD using BXD lines of mice.
Serial infection with SARS-CoV-2 Omicron BA.1 and BA.2 following three-dose COVID-19 vaccination
Authors: Lapointe Hope R. , Mwimanzi Francis , Cheung Peter K. , Sang Yurou , Yaseen Fatima , Kalikawe Rebecca , Datwani Sneha , Waterworth Rachel , Umviligihozo Gisele , Ennis Siobhan , Young Landon , Dong Winnie , Kirkby Don , Burns Laura , Leung Victor , Holmes Daniel T. , DeMarco Mari L. , Simons Janet , Matic Nancy , Montaner Julio S.G. , Brumme Chanson J. , Prystajecky Natalie , Niikura Masahiro , Lowe Christopher F. , Romney Marc G. , Brockman Mark A. , Brumme Zabrina L.
Published: May 2022

SARS-CoV-2 Omicron infections are common among individuals who are vaccinated or have recovered from prior variant infection, but few reports have documented serial Omicron infections. We characterized SARS-CoV-2 humoral responses in a healthy young person who acquired laboratory-confirmed Omicron BA.1.15 ten weeks after a third dose of BNT162b2, and BA.2 thirteen weeks later. Responses were compared to those of 124 COVID-19 naive vaccinees. One month after the second and third vaccine doses, the participant’s wild-type and BA.1-specific IgG, ACE2 competition and virus neutralization activities were average for a COVID-19 naive triple-vaccinated individual. BA.1 infection boosted the participant’s responses to the cohort ≥95th percentile, but even this strong “hybrid” immunity failed to protect against BA.2. Moreover, reinfection increased BA.1 and BA.2-specific responses only modestly. Results illustrate the risk of Omicron infection in fully vaccinated individuals and highlight the importance of personal and public health measures as vaccine-induced immune responses wane.
The role of healthcare cost accounting in pricing and reimbursement in low- and middle-income countries
Authors: Guinness Lorna , Ghosh Srobana , Mehndiratta Abha , Shah Hiral Anil
Published: May 2022

Background

Progress towards universal health coverage requires evidence based policy and good quality cost data systems. Establishing these systems, can be complex, resource intensive and take time. Synthesising information on the experiences of low-and-middle income countries (LMICs) in trying to institutionalize cost data systems provides lessons for other settings.

Methods

We performed a scoping literature review, screening for publicly available peer-reviewed English-language publications alongside a grey literature search, focussing on national level health system costing in LMICs, and used a narrative synthesis approach to document experience of costing and how costing evidence is used to inform tariffs.

Results

A total of 484 papers were initially identified of which 30 papers were considered eligible. Fourteen papers reported on primary cost data collection for price-setting purposes; 18 papers provided an explanation of how cost evidence informs tariff-setting. Documented experience is largely focussed in the Asia region (n = 22) with countries at different stages of developing cost systems to inform tariff setting. Country experiences on healthcare cost accounting tend to showcase country costing experiences, methods and implementation. There is little documentation of how cost data has been incorporated into decision making and price setting. Where cost data, cost systems and costing has been used, improved transparency in decision making alongside increased service provision efficiency has followed.

Conclusions

While there are accepted and widely used methods for generating cost information, countries need to build sustainable cost systems appropriate to their settings and budgets and adopt transparent processes and methodologies for translating costs into prices.
Depiction of cell atlas and analysis of microenvironment alterations in human meniscus degeneration using single-cell transcriptomic
Authors: Fu Weili , Chen Sijie , Yang Runze , Gao Haoxiang , Li Jian , Zhang Xuegong
Published: May 2022

Background

Musculoskeletal tissue degeneration impairs the life quality and function of many people. Meniscus degeneration is a major origin of knee osteoarthritis and a common threat to athletic ability, but its cellular mechanism remains elusive.

Methods

We built a cell atlas of healthy/degenerated human meniscus using scRNA-seq to investigate meniscal microenvironment homeostasis and its changes in the degeneration process and verified findings with immunofluorescent imaging.

Results

We identified and localized cell types in inner and outer meniscus, found new chondrocyte subtypes contributing to degeneration, and revealed how cellular compositions, functions, and interactions participated in degeneration.

We found that ECM disassembly, angiogenesis, and inflammation form a positive feedback loop driving the degeneration. Comparison of cellular interactions between different degenerative states identified each cell type’s functions in the loop.

Conclusions

The study revealed changes in the meniscal microenvironment during degeneration and discovered new cell subtypes as potential therapeutic targets. The observed mechanism could also be a general model for other joint degenerations.

Funding

The National Natural Science Foundation of China (81972123, 82172508, 62050178, 61721003) and the National Key Research and Development Program of China (2021YFF1200901).
How should job crafting interventions be implemented to make their effects last? Study protocol of group concept mapping
Authors: Roczniewska Marta , Rundgren Emma Hedberg , Hasson Henna , Bakker Arnold B. , von Thiele Schwarz Ulrica
Published: May 2022

By means of job crafting (JC) employees shape and customize their job design to align it with their preferences. Research has so far shown that such bottom-up proactivity can be stimulated via JC interventions. While the overall effectiveness behind these interventions has been supported, it is unclear how to implement these interventions to make their effects lasting. The overall aim of this project will be to investigate how to implement JC interventions with lasting effects. We will apply a group concept mapping (GCM) methodology, which is a mixed methods approach for engaging stakeholder groups in a structured conceptualization process. As part of concept mapping procedures, brainstorming sessions will be conducted with experts in job crafting to identify factors expected to make job crafting intervention effects lasting. These factors will be sorted by similarity and rated by each participant in regard to their perceived importance and feasibility to ensure lasting, sustainable effects. The data will be analyzed using multidimensional scaling (MDS), hierarchical cluster analysis, descriptive and inferential statistics, resulting in a visual representation of conceptually distinguished clusters representing the factors influencing sustainability of JC interventions. In the final step of the GCM methodology, a workshop will be conducted with the participants to facilitate interpretation of the results. This study will provide knowledge relevant to organizational practitioners and scholars who want to implement JC interventions with lasting effects.
Spectrum of Adverse Event Following COVID-19 Immunization in High Altitude, Nepal
Authors: Gurung Minani , Lama Tashi , Rajbhandari Bibek , Shilpakar Olita , Maharjan Ashmita , Nepal Sujita , Gajmer Dev , Lama Kailash , Poudel Lisasha
Published: May 2022

Introduction

Nepal started vaccinating frontline workers against COVID-19, in January 2021.Side effects of the vaccine are still unknown in high altitude regions. Poor surveillance and the lack of health workers in remote places to take care of people in case of vaccination side-effects could prove to be a challenge in the drive, especially in high altitudes like Humla district, Nepal. High altitude regions are harder to access and also mobilization of vaccines and manpower is strenuous due to harsh weather conditions and complex geography. We aimed to study the spectrum of Adverse Event Following COVID-19 Immunization among the front liners of Humla district.

Methods

This is a cross-sectional study conducted in Humla district, Nepal. COVID-19 Immunization vaccine recipients were contacted through a phone call within 5 days of vaccination to record the adverse effects. Patterns and distribution of adverse effects were analyzed in high altitude settings. Ethical approval was taken from Nepal Health Research Council.

Results

Of total respondents, 84.1% (95% C.I: 80.9 to 86.9) had shown symptoms after vaccination. The average time for the appearance of symptoms was 1.27 +_ 0.60 days. For systemic effects, tenderness was the side effect seen after vaccination (63.8%) followed by other side effects like pain (58.5%), Pyrexia (37.4%), Chills (29.8%), Myalgia (28.9%) and Malaise (15.2%) while for localized effects, the symptoms such as Arthralgia (16.6%) and Bruising (16.1%) were the most common effects.

Conclusions

Serious and life threatening adverse effects following immunization were not seen in our study site which was of altitude 2500 meter and above. Our study shows a similar type of side effect pattern as that of the lower altitude regions.
Covid-19 Vaccine Acceptance Among People Incarcerated in Connecticut State Jails
Authors: Lind Margaret L. , Kennedy Byron S. , Nieto Murilo Dorion , Houde Amy J. , Sosensky Peri , Borg Ryan , Cummings Derek A.T. , Ko Albert I. , Richeson Robert P.
Published: May 2022

Objective

To assess the Connecticut Department of Correction’s (DOC) COVID-19 vaccine program within jails.

Methods

We conducted a retrospective cohort analysis among people who were incarcerated in a DOC-operated jail between February 2 and November 8, 2021, and were eligible for vaccination at the time of incarceration (intake). We compared the vaccination rates before and after incarceration using an age-adjusted survival analysis with a time-varying exposure of incarceration and an outcome of vaccination.

Results

During the study period, 3,716 people spent ≥1 night in jail and were eligible for vaccination at intake. Of these residents, 136 were vaccinated prior to incarceration, 2,265 had a recorded vaccine offer, and 476 were vaccinated while incarcerated. The age-adjusted hazard of vaccination following incarceration was significantly higher than prior to incarceration (12.5; 95% CI: 10.2-15.3).

Conclusions

We found that residents were more likely to become vaccinated in jail than the community. Though these findings highlight the utility of vaccination programs within jails, the low level of vaccination in this population speaks to the need for additional program development within jails and the community.
A comparative study of structural variant calling strategies using the Alzheimer’s Disease Sequencing Project’s whole genome family data
Authors: Malamon John S. , Farrell John J. , Xia Li Charlie , Dombroski Beth A. , Lee Wan-Ping , Das Rueben G. , Vardarajan Badri N. , Way Jessica , Kuzma Amanda B. , Valladares Otto , Leung Yuk Yee , Scanlon Allison J. , Barrera Lopez Irving Antonio , Brehony Jack , Worley Kim C. , Zhang Nancy R. , Wang Li-San , Farrer Lindsay A. , Schellenberg Gerard D.
Published: May 2022

Background

Reliable detection and accurate genotyping of structural variants (SVs) and insertion/deletions (indels) from whole-genome sequence (WGS) data is a significant challenge. We present a protocol for variant calling, quality control, call merging, sensitivity analysis, in silico genotyping, and laboratory validation protocols for generating a high-quality deletion call set from whole genome sequences as part of the Alzheimer’s Disease Sequencing Project (ADSP). This dataset contains 578 individuals from 111 families.

Methods

We applied two complementary pipelines (Scalpel and Parliament) for SV/indel calling, break-point refinement, genotyping, and local reassembly to produce a high-quality annotated call set. Sensitivity was measured in sample replicates (N=9) for all callers using in silico variant spike-in for a wide range of event sizes. We focused on deletions because these events were more reliably called. To evaluate caller specificity, we developed a novel metric called the D-score that leverages deletion sharing frequencies within and outside of families to rank recurring deletions. Assessment of overall quality across size bins was measured with the kinship coefficient. Individual callers were evaluated for computational cost, performance, sensitivity, and specificity. Quality of calls were evaluated by Sanger sequencing of predicted loss-of-function (LOF) variants, variants near AD candidate genes, and randomly selected genome-wide deletions ranging from 2 to 17,000 bp.

Results

We generated a high-quality deletion call set across a wide range of event sizes consisting of 152,301 deletions with an average of 263 per genome. A total of 114 of 146 predicted deletions (78.1%) were validated by Sanger sequencing. Scalpel was more accurate in calling deletions ≤100 bp, whereas for Parliament, sensitivity was improved for deletions > 900 bp. We validated 83.0% (88/106) and 72.5% (37/51) of calls made by Scalpel and Parliament, respectively. Eleven deletions called by both Parliament and Scalpel in the 101-900 bin were tested and all were confirmed by Sanger sequencing.

Conclusions

We developed a flexible protocol to assess the quality of deletion detection across a wide range of sizes. We also generated a truth set of Sanger sequencing validated deletions with precise breakpoints covering a wide spectrum of sizes between 1 and 17,000 bp.
Processing of task-irrelevant sounds during typical everyday activities in children
Authors: Debnath Ranjan , Wetzel Nicole
Published: May 2022

Our ability to focus on a task and ignore task-irrelevant stimuli is critical for efficient cognitive functioning. Attention control is especially required in the auditory modality as sound has privileged access to perception and consciousness. Despite this important function, little is known about auditory attention during typical everyday activities in childhood. We investigated the impact of task-irrelevant sounds on attention during three everyday activities – playing a game, reading a book, watching a movie. During these activities, environmental novel sounds were presented within a sequence of standard sounds to 7–8-year-old children and adults. We measured ERPs reflecting early sound processing and attentional orienting and theta power evoked by standard and novel sounds during these activities. Playing a game vs. reading or watching reduced early encoding of sounds in children and affected ongoing information processing and attention allocation in both groups. In adults, theta power was reduced during playing at mid-central brain areas. Results show a pattern of immature neuronal mechanisms underlying perception and attention of task-irrelevant sounds in 7–8-year-old children. While the type of activity affected the processing of irrelevant sounds in both groups, early stimulus encoding processes were more sensitive to the type of activities in children.
Model-based intensification of CHO cell cultures: one-step strategy from fed-batch to perfusion
Authors: Richelle Anne , Corbett Brandon , Agarwal Piyush , Vernersson Anton , Trygg Johan , McCready Chris
Published: May 2022

There is a growing interest in continuous processing of the biopharmaceutical industry. However, the technology transfer from traditional batch-based processes is considered a challenge as protocol and tools still remain to be established for their usage at the manufacturing scale. Here, we present a model-based approach to design optimized perfusion cultures of CHO cells using only the knowledge captured during small-scale fed-batch experiments. The novelty of the proposed model lies in the simplicity of its structure. Thanks to the introduction of a new catch-all variable representing a bulk of by-products secreted by the cells during their cultivation, the model was able to successfully predict cellular behavior under different operating modes without changes in its formalism. To our knowledge, this is the first experimentally validated model capable, with a single set of parameters, to capture culture dynamic under different operating modes and at different scales.
Population estimate, natural history and conservation of the melanisticIguana Iguanapopulation on Saba, Caribbean Netherlands
Authors: van den Burg Matthijs P. , Madden Hannah , Debrot Adolphe O.
Published: May 2022

Intraspecific diversity is among the most important biological variables, although still poorly understood for most species.Iguana iguanais a Neotropical lizard known from Central and South America, including from numerous Caribbean islands. Despite the presence of native melanisticI. iguanapopulations in the Lesser Antilles, these have received surprisingly little research attention. Here we assessed population size, distribution, degree of melanism, and additional morphological and natural history characteristics for the melanistic iguanas of Saba, Caribbean Netherlands based on a one-month fieldwork visit. Using Distance sampling from a 38-transect dataset we estimate the population size at 8233 ±2205 iguanas. Iguanas mainly occurred on the southern and eastern sides of the island, between 180-390 m (max altitude 530 m), with highest densities both in residential and certain natural areas. Historically, iguanas were relatively more common at higher altitudes, probably due to more extensive forest clearing for agricultural reasons. No relationship was found between the degree of melanism and elevation, and few animals were completely melanistic. Furthermore, we found that body-ratio data collection through photographs is biased and requires physical measuring instead. Although the population size appears larger than previously surmised, the limited nesting sites and extremely low presence of juvenile and hatchling iguanas (2.4%), is similarly worrying as the situation forI. delicatissimaon neighboring St. Eustatius. The island’s feral cat and large goat population are suspected to impact nest site quality, nest success, and hatchling survival. These aspects require urgent future research to guide necessary conservation management.
Scalable power analysis and effect size exploration of microbiome community differences with Evident
Authors: Rahman Gibraan , McDonald Daniel , Gonzalez Antonio , Vázquez-Baeza Yoshiki , Jiang Lingjing , Casals-Pascual Climent , Peddada Shyamal , Hakim Daniel , Dilmore Amanda Hazel , Nowinski Brent , Knight Rob
Published: May 2022

Differentiating microbial communities among samples is a major objective in biomedicine. Quantifying the effect size of these differences allows researchers to understand the factors most associated with communities and to optimize the design and clinical resources required to address particular research questions. Here, we present Evident, a package for effect size calculations and power analysis on microbiome data and show that Evident scales to large datasets with numerous metadata covariates.
Detection of outlier methylation from bisulfite sequencing data with novel Bioconductor package BOREALIS
Authors: Oliver Gavin R. , Jenkinson Garrett , Olson Rory J. , Schultz-Rogers Laura E. , Klee Eric W.
Published: May 2022

DNA sequencing results in genetic diagnosis of 18-40% of previously unsolved cases, while the incorporation of RNA-Seq analysis has more recently been shown to generate significant numbers of previously unattainable diagnoses. Multiple inborn diseases resulting from disorders of genomic imprinting are well characterized and a growing body of literature suggest the causative or correlative role of aberrant DNA methylation in diverse rare inherited conditions. Therefore, the systematic application of genomic-wide methylation-based sequencing for undiagnosed cases of rare disease is a logical progression from current testing paradigms. Following the rationale previously exploited in RNA-based studies of rare disease, we can assume that disease-associated methylation aberrations in an individual will demonstrate significant differences from individuals with unrelated phenotypes. Thus, aberrantly methylated sites will be outliers from a heterogeneous cohort of individuals.

Based on this rationale, we present BOREALIS: Bisulfite-seq OutlieR MEthylation At SingLe-SIte ReSolution. BOREALIS uses a beta binomial model to identify outlier methylation at single CpG site resolution from bisulfite sequencing data. This method addresses a need unmet by standard differential methylation analyses based on case-control groups. Utilizing a heterogeneous cohort of 94 rare disease patients undiagnosed following DNA-based testing we show that BOREALIS can successfully identify outlier methylation linked to phenotypically relevant genes, providing a new avenue of exploration in the quest for increased diagnostic rates in rare disease patients. We highlight the case of a patient with previously undetected hypermethylation patterns that are informing clinical decision-making. BOREALIS is implemented in R and is freely available as a Bioconductor package.
Convolutions are competitive with transformers for protein sequence pretraining
Authors: Yang Kevin K. , Fusi Nicolo , Lu Alex X.
Published: May 2022

Pretrained protein sequence language models have been shown to improve the performance of many prediction tasks, and are now routinely integrated into bioinformatics tools. However, these models largely rely on the Transformer architecture, which scales quadratically with sequence length in both run-time and memory. Therefore, state-of-the-art models have limitations on sequence length. To address this limitation, we investigated if convolutional neural network (CNN) architectures, which scale linearly with sequence length, could be as effective as transformers in protein language models. With masked language model pretraining, CNNs are competitive to and occasionally superior to Transformers across downstream applications while maintaining strong performance on sequences longer than those allowed in the current state-of-the-art Transformer models. Our work suggests that computational efficiency can be improved without sacrificing performance simply by using a CNN architecture instead of a Transformer, and emphasizes the importance of disentangling pretraining task and model architecture.
High dose dietary vitamin D allocates surplus calories to muscle and growth instead of fat via modulation of myostatin and leptin signaling
Authors: Long Caela , Tara Zahra , Casella Alex , Mark Julian , Roizen Jeffrey D.
Published: May 2022

Obesity is the leading proportional cause for diabetes, heart disease and cancer. Obesity occurs because the body stores surplus calories as fat. Fat cells secrete a hormone, leptin, that modulates energy balance at the brain. Changes in fat mass are mirrored by changes in serum leptin. Increases in leptin cause the brain to decrease appetite and increase energy expenditure. However in obesity, leptin sensitivity is decreased which mutes leptin mediated changes in appetite and energy expenditure. We have limited understanding of what controls leptin production by fat or how sensitive the brain is to leptin. Muscle produces a hormone, myostatin, that plays an analogous role to the role that leptin plays in fat. Absent myostatin leads to increased muscle mass and strength. We also do not know what controls myostatin production or sensitivity. Although fat mass and muscle mass are closely linked, the interplay between leptin and myostatin remains unexplored. Vitamin D improves lean mass via what are thought to be primarily trophic effects at the muscle. Here we show that high dose dietary vitamin D preferentially allocates excess calories to muscle and growth instead of storage as fat by decreasing myostatin production and increasing leptin production and sensitivity. That is, high dose vitamin D improves organismal energy sensing. Obesity, aging and other chronic inflammatory diseases are associated with decreased muscle function and mass. Our work provides a physiologic framework for how high-dose vitamin D would be effective in these pathologies to increase allocation of calories to muscle instead of fat and reveals novel interplay between the myostatin and leptin signaling whereby myostatin conveys energy needs to modulate leptin effects on calorie allocation. Furthermore, our work reveals how physiologic seasonal variation in vitamin D may be important in controlling season-specific metabolism and calorie allocation to fat in winter and muscle in summer.
Spatially selective stimulation of the pig vagus nerve to modulate target effect versus side effect
Authors: Blanz Stephan L. , Musselman Eric D. , Settell Megan L. , Knudsen Bruce E. , Nicolai Evan N. , Trevathan James K. , Verner Ryan S. , Begnaud Jason , Suminski Aaron J. , Williams Justin C. , Shoffstall Andrew J. , Grill Warren M. , Pelot Nicole A. , Ludwig Kip A.
Published: May 2022

Electrical stimulation of the cervical vagus nerve using implanted electrodes (VNS) is FDA-approved for the treatment of drug-resistant epilepsy, treatment-resistant depression, and most recently, chronic ischemic stroke rehabilitation. However, VNS is critically limited by the unwanted stimulation of nearby neck muscles – a result of non-specific stimulation activating motor nerve fibers within the vagus. Prior studies suggested that precise placement of small epineural electrodes can modify VNS therapeutic effects, such as cardiac responses. However, it remains unclear if placement can alter the balance between intended effect and limiting side effect.

We used an FDA investigational device exemption approved six-contact epineural cuff to deliver VNS in pigs and quantified how epineural electrode location impacts on- and off-target VNS activation. Detailed post-mortem histology was conducted to understand how the underlying neuroanatomy impacts observed functional responses. Here we report the discovery and characterization of clear neuroanatomy-dependent differences in threshold and saturation for responses related to both effect (change in heart rate) and side effect (neck muscle contractions). The histological and electrophysiological data were used to develop and validate subject-specific computation models of VNS, creating a well-grounded quantitative framework to optimize electrode location-specific activation of nerve fibers governing intended effect versus unwanted side effect.
The Queensland Twin Adolescent Brain Project, a longitudinal study of adolescent brain development
Authors: Strike Lachlan T. , Hansell Narelle K. , Chuang Kai-Hsiang , Miller Jessica L. , de Zubicaray Greig I. , Thompson Paul M. , McMahon Katie L. , Wright Margaret J.
Published: May 2022

We describe the Queensland Twin Adolescent Brain (QTAB) dataset and provide a detailed methodology and technical validation to facilitate data usage. The QTAB dataset comprises multimodal neuroimaging, as well as cognitive and mental health data collected in adolescent twins over two sessions (session 1: N = 422, age 9-14 years; session 2: N = 304, 10-16 years). The MRI protocol consisted of T1-weighted (MP2RAGE), T2-weighted, FLAIR, high-resolution TSE, SWI, resting-state fMRI, DWI, and ASL scans. Two fMRI tasks were added in session 2: an emotional conflict task and a passive movie-watching task. Outside of the scanner, we assessed cognitive function using standardised tests. We also obtained self-reports of symptoms for anxiety and depression, perceived stress, sleepiness, pubertal development measures, and risk and protective factors. We additionally collected several biological samples for genomic and metagenomic analysis. The QTAB project was established to promote health-related research in adolescence.
Sex-Related Differences in Eicosanoid Levels in Chronic Thromboembolic Pulmonary Hypertension
Authors: Alotaibi Mona , Fernandes Timothy , Tang Amber B. , Magalang Gino Alberto , Watrous Jeramie D. , Long Tao , Pretorius Victor , Madani Michael , Kim Nick H. , Jain Mohit , Cheng Susan
Published: May 2022

A sex paradox is seen in pulmonary arterial hypertension (PAH) whereby female sex is a risk factor for development of the disease but male sex is often associated with poorer outcomes. Although data are limited regarding the potential molecular mechanisms underlying sex-specific variations in PAH including its various subtypes, there is emerging evidence regarding the potential role of sex differences in pathways governing the balance between underlying inflammatory and vasoactive mechanisms. Chronic thromboembolic pulmonary hypertension (CTEPH) is a subtype of pulmonary hypertension that is classically characterized as a procoagulant state and yet also involving some degree of proinflammatory activity. Therefore, we sought to determine whether eicosanoid mediators, endogenous lipid signaling molecules that have been implicated in a range of inflammatory and vasoactive responses, vary by sex in patients with CTEPH. We studied 287 patients (43.5% female) with confirmed CTEPH from a single center and assayed plasma samples using liquid chromatography – mass spectrometry to profile 500 eicosanoid analytes. We found significant sex-specific variations in eicosanoid profiles after adjusting for age and BMI, with males demonstrating a predominance of inflammatory-pathway related eicosanoids. Sex-specific variation in eicosanoid pathway related mechanisms may underlie sexual dimorphism in CTEPH outcomes.
Device-measured physical activity, sedentary time, and sleep in patients with arrhythmogenic cardiomyopathy: descriptive values and stability over 30 measurement days
Authors: Ruiz-González David , Ramos-Maqueda Javier , Migueles Jairo H. , Antonio Vargas-Hitos José , Ruiz-Salas Amalio , Jiménez-Jáimez Juan , Soriano-Maldonado Alberto
Published: May 2022

Introduction

Regular exercise and sports are contraindicated in arrhythmogenic cardiomyopathy (AC) patients, which might lead them to an unhealthy sedentary lifestyle. This study aimed to objectively describe the patterns of physical activity (PA), sedentary time (SED), and sleep in patients with AC, and to examine the reproducibility of accelerometer-derived measures over four consecutive weeks.

Methods

A total of 71 (49.6 [SD=17.5] years) patients with AC wore a wrist-worn Axivity AX3 accelerometer for 30 consecutive days to monitor their physical activity, sedentary time, and sleep habits. The reproducibility of each metric across the 4 assessment weeks was assessed with the intraclass correlation coefficients (ICCs) derived from linear-mixed models adjusted for age, body mass index (BMI), and season.

Results

The participants spent a median of 12.2 [IQR 2.1] h/d in SED, 6.4 [IQR 1.0] h/d sleeping, and 17.9 [IQR 24.5] min/d in moderate-to-vigorous physical activity (MVPA), and 59% of the participants did not reach the 150 min/d of MVPA recommended by the WHO for people living with chronic disease. No significant differences in PA were found by sex and age groups. Otherwise, patients aged ≥50 years (n= 33) spent 38.9 min/d (95% CI 5.8 to 72.2, p≤0.05) more in periods of ≥30 minutes of SED than those <50 years. Participants with obesity (n=10) accumulated 66.6 min/d (95% CI 5.2 to 128.1, p = <0.05) more SED in periods of ≥30 minutes and 22.8 min/d (95% CI 0.7 to 44.9, p≤0.05) less MVPA than those without obesity. The ICCs ranged from 0.67 for time in bed to 0.92 for light-intensity physical activity using a 7-day assessment period. However, the ICCs increased from 0.03 for LPA to 0.18 for time in bed when an assessment period of 14 days was chosen.

Conclusion

Patients with AC engage in large periods of SED, insufficient PA and sleep. Importantly, nearly 60% of the participants did not meet the minimum amount of PA recommended by the WHO for people living with chronic diseases and only 20% met the sleep recommendations. Device-measured PA and SED are stable across weeks, indicating that a 7-day assessment period might provide a reproducible measure of PA and SED and, to a lower extent, sleep.
SARS-CoV-2 diagnostic testing rates determine the sensitivity of genomic surveillance programs
Authors: Han Alvin X. , Toporowski Amy , Sacks Jilian A. , Perkins Mark D. , Briand Sylvie , van Kerkhove Maria , Hannay Emma , Carmona Sergio , Rodriguez Bill , Parker Edyth , Nichols Brooke E. , Russell Colin A.
Published: May 2022

The first step in SARS-CoV-2 genomic surveillance is testing to identify infected people. However, global testing rates are falling as we emerge from the acute health emergency and remain low in many low- and middle-income countries (LMICs) (mean = 27 tests/100,000 people/day). We simulated COVID-19 epidemics in a prototypical LMIC to investigate how testing rates, sampling strategies, and sequencing proportions jointly impact surveillance outcomes and showed that low testing rates and spatiotemporal biases delay time-to-detection of new variants by weeks-to-months and can lead to unreliable estimates of variant prevalence even when the proportion of samples sequenced is increased. Accordingly, investments in wider access to diagnostics to support testing rates of ∼100 tests/100,000 people/day could enable more timely detection of new variants and reliable estimates of variant prevalence. The performance of global SARS-CoV-2 genomic surveillance programs is fundamentally limited by access to diagnostic testing.