bluuebunny/crossref_metadata_2025 huggingface dataset:
Walking speed, hip muscles strength, aerobic capacity, and self-perceived locomotion ability most explain walking confidence after stroke: a cross-sectional experimental study
Authors: Avelino Patrick R. , Menezes Kênia K.P. , Nascimento Lucas R. , Alvarenga Maria Tereza Mota , de Paula Magalhães Jordana , Teixeira-Salmela Luci Fuscaldi , Scianni Aline A.
Published: October 2022

Identifying the determinants of walking confidence can be crucial in therapeutic terms. On these bases, interventions to improve these factors could improve, in turn, walking confidence. Objective is to explore the relationship between motor impairments and activity limitation measures and walking confidence in people with chronic stroke. Walking confidence was assessed using the modified Gait Efficacy Scale. The independent variables were: strength of the hip flexors and knee flexors/extensors (measured with a dynamometer), lower limb coordination (assessed by the Lower Extremity Motor Coordination Test), dynamic balance (assessed by the Four-Square Step Test), walking speed (from the 10-m Walk Test), aerobic capacity (from the 6-Minute Walk Test), and self-perceived locomotion ability (assessed by the ABILOCO). Pearson correlation was used to explore the relationships between the variables, and multiple linear regression to identify the independent explainers of walking confidence after stroke. Ninety chronic stroke individuals (35 men), with a mean age of 68 (SD 13) years were assessed. All independent variables were significantly correlated with walking confidence. Regarding the regression analysis, these measures explained 44% (F = 9.21; P < 0.001) of the variance in walking confidence; however, only walking speed, strength of the hip flexor muscles, aerobic capacity, and perceived locomotion ability showed significance. All motor impairment and activity limitation measures correlated with walking confidence. However, the regression analysis highlighted that only walking speed, aerobic capacity, the strength of the hip flexor muscles, and perceived locomotion were independent explainers of walking confidence after stroke.
Cognitive impairment predicts engagement in inpatient stroke rehabilitation
Authors: Lowder Ryan J. , Jaywant Abhishek , Fridman Chaya B. , Toglia Joan , O’Dell Michael W.
Published: October 2022

Patient engagement during inpatient rehabilitation is an important component of rehabilitation therapy, as lower levels of engagement are associated with poorer outcomes. Cognitive deficits may impact patient engagement during inpatient stroke rehabilitation. Here, we assess whether patient performance on the cognitive tasks of the 30-min National Institute of Neurologic Disorders and Stroke – Canadian Stroke Network (NINDS-CSN) screening battery predicts engagement in inpatient stroke rehabilitation. Prospective data from 110 participants completing inpatient stroke rehabilitation at an academic medical center were utilized for the present analyses. Cognitive functioning was assessed at inpatient stroke rehabilitation admission using the NINDS-CSN cognitive battery. Patient engagement was evaluated at discharge from an inpatient rehabilitation unit using the Hopkins Rehabilitation Engagement Rating Scale. The results demonstrate that the NINDS-CSN cognitive battery, specifically subtests measuring executive functioning, attention and processing speed, predicts patient engagement in inpatient stroke rehabilitation. Cognitively impaired patients undergoing rehabilitation may benefit from modifications and interventions to increase engagement and improve functional outcomes.
Creating a Standardized Post-Fall Debrief Tool
Authors: Farley Holley , Stepanek Meghan , Aquino Carla , Whalen Madeleine
Published: October 2022

Background:

Performing post-fall debriefing improves patient outcomes through learning from defects and addresses adherence to fall prevention programs.

Local Problem:

While addressing an increase in fall rates, a quality improvement team discovered there was no standardized tool or process for completing post-fall debriefing.

Methods:

The team used the Plan-Do-Study-Act (PDSA) process to improve the post-fall debrief tool, with an analysis of pilot using the implementation science RE-AIM framework.

Interventions:

Three units with a high focus on falls and an established debriefing culture participated in pilot to generate and standardize a post-fall debrief tool.

Results:

Through 2 revisions with end user and champion feedback, the tool was refined to assess any contributing factors to the fall.

Conclusion:

Through use of the PDSA cycle, the team established content validity of the post-fall debrief tool. This tool is appropriate for inpatient adult and pediatric scale-up and complementary to current fall risk assessment tools.
Ensuring Rapid Response Team Care Aligns With Patients' Limitations of Medical Therapy
Authors: Mininni Nicolette C. , Whiteman Kimberly , Stephens Kimberly , George Elisabeth , Swanson-Biearman Brenda
Published: October 2022

Background:

Rapid response teams (RRTs) are designed to improve patient care during deterioration in clinical condition.

Local Problem:

Patients' desired limitations of medical therapy (LOMTs) were not documented or communicated to the RRT, and patients received care not aligned with their wishes.

Methods:

A multidisciplinary team developed a process for improving documentation, communication of LOMTs, and care delivery on 3 medical cardiology units. The team implemented 3 Plan-Do-Study-Act (PDSA) cycles over 6 months.

Interventions:

In cycle 1, team members taught the unit nurses, RRT members, and physicians to share LOMTs during handoff communications. Cycle 2 engaged case managers in LOMT documentation. In cycle 3, unit-based RRT simulation was conducted.

Results:

All care delivered by the RRT aligned with the documented LOMTs. Documentation of LOMTs increased from 76% to 82.5% (P = .014).

Conclusions:

Education, scripting, and simulation were successful strategies to ensure that care given during RRT events aligned with patients' wishes.
Physical Inactivity and Chronic Disease
Authors: García-Pérez-de-Sevilla Guillermo , Sánchez-Pinto Beatriz
Published: October 2022

The objective of this review is to update the state of the art regarding the influence of physical activity on the development of noncommunicable diseases (NCDs) and the physiological mechanisms that may be involved. At present, there is an urgent need to promote physical activity, as 28% of the world's population is physically inactive. Physical inactivity is responsible for 6% of the global disease burden from coronary heart disease, 7% of type 2 diabetes mellitus, 10% of breast cancers, and 10% of colon cancers. Physical inactivity is thought to promote oxidative stress, inflammation, and DNA damage and thus accelerated aging, genome instability, and predisposition to develop NCDs. In addition, physical inactivity can lead to an increase in body fat through an energy imbalance sustained over time, leading to an accumulation of visceral fat, which increases the risk of developing many NCDs, especially cardiovascular and metabolic diseases. The World Health Organization aims to reduce premature mortality from NCDs globally by one-third by 2030. Given the above, physical activity levels should be increased to reach the World Health Organization 2020 recommendations.
Comparison of Nonprofit Hospital Community Benefit Substance Abuse Identification and Practice Implementation in Appalachian and Non-Appalachian Counties
Authors: Zinn Caleb L. , Hopgood Daniel , Cronin Cory E. , Burns Ashlyn , Lenhart Margaret , Franz Berkeley
Published: October 2022

Context:

As substance use continues to be a public health crisis nationally, it disproportionately affects the Appalachian region.

Objectives:

Our research seeks to explore whether there is a greater substance use burden in Appalachia and whether that burden is being prioritized in local hospital systems' community health needs assessments (CHNAs) and implementation strategies (ISs).

Setting:

The setting for this study is the 13 states that are represented within the Appalachian region.

Participants:

This study examines CHNAs and ISs of a stratified random sample (n = 140) representing 20% of the hospital population within the identified states (those with counties within the Appalachian region). Each sampled hospital is labeled as Appalachian or non-Appalachian based on its county designation.

Main Outcome Measures:

Our main outcome measures were the percentage of hospitals listing substance abuse in their CHNAs, with comparisons between Appalachian and non-Appalachian subgroups, and percent addressing substance use in their ISs in Appalachia and non-Appalachia.

Design:

Community health needs assessments and ISs produced between the years 2018 and 2021 were gathered for each hospital within the sample; each document was then coded for the inclusion of substance use. Chi-square tests and logistic regression were employed to conduct the analysis and draw conclusions.

Results:

Although all non-Appalachian Counties that had substance use listed as a need within a CHNA correspondingly addressed that need in their ISs, only 75% of Appalachian counties that listed substance use a need went on to prioritize substance use in an IS. In addition, logistic regression indicated no significant link between overdose rates and addressing substance use.

Conclusions:

These findings further support other literature that suggests that lack of resources is limiting Appalachian health care organizations' ability to address substance use issues.
Practices Among Local Public Health Agencies to Support Evidence-Based Decision Making: A Qualitative Study
Authors: Allen Peg , Parks Renee G. , Kang Sarah J. , Dekker Debra , Jacob Rebekah R. , Mazzucca-Ragan Stephanie , Brownson Ross C.
Published: October 2022

Objectives:

Evidence-based decision making (EBDM) capacity in local public health departments is foundational to meeting both organizational and individual competencies and fulfilling expanded roles. In addition to on-the-job training, organizational supports are needed to prepare staff; yet, less is known in this area. This qualitative study explores supportive management practices instituted as part of a training and technical assistance intervention.

Design:

This qualitative study used a semistructured interview guide to elicit participants' descriptions and perceptions via key informant interviews. Verbatim transcripts were coded and thematic analyses were conducted.

Setting:

Local public health departments in a US Midwestern state participated in the project.

Participants:

Seventeen middle managers and staff from 4 local health departments participated in remote, audio-recorded interviews.

Intervention:

Following delivery of a 3½-day in-person training, the study team met with health department leadership teams for department selection of supportive agency policies and procedures to revise or newly create. Periodic remote meetings included collaborative problem-solving, sharing of informational resources, and encouragement.

Main Outcome Measures:

Included management practices instituted to support EBDM and impact on day-to-day work as described by the interview participants.

Results:

Leadership and middle management practices deemed most helpful included dedicating staff; creating specific guidelines; setting expectations; and providing trainings, resources, and guidance. Health departments with a preexisting supportive organizational culture and climate were able to move more quickly and fully to integrate supportive management practices. Workforce development included creation of locally tailored overviews for all staff members and onboarding of new staff. Staff wanted additional hands-on skill-building trainings. Several worked with partners to incorporate evidence-based processes into community health improvement plans.

Conclusions:

Ongoing on-the-job experiential learning is needed to integrate EBDM principles into day-to-day public health practice. Management practices established by leadership teams and middle managers can create supportive work environments for EBDM integration.
Systemic therapy in metastatic hormone-sensitive prostate cancer
Authors: McDonald Jodie , O’Brien Jonathan , Kostos Louise , Lawrentschuk Nathan , Azad Arun A. , Murphy Declan , Chen Kenneth
Published: October 2022

Purpose of review

The landscape of metastatic hormone sensitive prostate cancer (mHSPC) has evolved rapidly in recent years with new data from landmark trials supporting upfront treatment intensification. The developments come not only on the fronts of systemic agents but also in area of therapy to primary tumour and metastases.

Recent findings

More recently, the ARASENS and PEACE trials have taken the concept of treatment intensification further by demonstrating survival benefit from combination of chemotherapy (docetaxel) and androgen receptor pathway inhibitors (abiraterone and darolutamide) in addition to backbone therapy of androgen deprivation therapy (ADT). Intensification of treatment has also seen evidence supporting local therapy to the primary tumour with overall survival and biochemical recurrence-free survival although only evident in low volume synchronous metastases. There is emerging evidence for metastases-directed therapy as well with pooled data suggesting improved biochemical-free and ADT-free survival.

Robust clinical data has demonstrated survival benefits with treatment intensification and this should be the new standard of care. Subgroup analysis has highlighted the importance of tailoring mHSPC treatment for patients with high- and low-volume metastatic disease. However, defining the volume of disease is becoming increasingly controversial due to heterogeneity of trial patient populations and next generation molecular imaging.
Severely Reduced Kidney Function Assessed by a Single eGFR Determination at the Time of an Isolated Heart Transplant Does Not Predict Inevitable Posttransplant ESKD
Authors: Kumar Abhishek , Bonnell Levi N. , Thomas Christie P.
Published: October 2022

Background.

Consensus guidelines advise simultaneous heart kidney transplantation (SHK) in heart candidates with an estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 m2. We hypothesize that a significant fraction of such patients would not need an SHK, even though a graded increase in mortality and end-stage kidney disease (ESKD) would be seen with decrements in eGFR.

Methods.

United Network of Organ Sharing data for isolated heart transplants between 2000 and 2020 were divided into two groups based on eGFR at transplant (≤20 mL/min/1.73 m2 and 21–29 mL/min/1.73 m2 ). The primary outcome was mortality and secondary outcome was ESKD posttransplant. Cox regression and cumulative incidence competing risk methods were used to compare risk of mortality and ESKD.

Results.

There was no difference in mortality (adjusted hazard ratio [aHR] 0.82 [95% confidence interval, CI: 0.60-1.11, P = 0.21]) or ESKD (aHR 1.01 [95% CI: 0.49-2.09, P = 0.96]) between the two groups (≤20 versus 21–29). The overall incidence of ESKD for the entire cohort at 1, 5, and 10 y were 1.5%, 9.5%, and 20%.

Conclusions.

Although risk of ESKD is highest in heart candidates with an eGFR <30 mL/min/1.73 m2, <10% of patients reach ESKD within 5 y‚ and most will recover significant renal function posttransplant. More refined selection criteria are required to identify candidates for SHK.
Divergent polo boxes in KKT2 and KKT3 initiate the kinetochore assembly cascade inTrypanosoma brucei
Authors: Ishii Midori , Ludzia Patryk , Marcianò Gabriele , Allen William , Nerusheva Olga O. , Akiyoshi Bungo
Published: October 2022

Chromosome segregation requires assembly of the macromolecular kinetochore complex onto centromeric DNA. While most eukaryotes have canonical kinetochore proteins that are widely conserved among eukaryotes, evolutionarily divergent kinetoplastids have a unique set of kinetochore proteins. Little is known about the mechanism of kinetochore assembly in kinetoplastids. In this study, we have characterized two homologous kinetoplastid kinetochore proteins, KKT2 and KKT3, that constitutively localize at centromeres and promote the recruitment of other kinetochore proteins. KKT2 and KKT3 have three domains that are highly conserved among kinetoplastids: an N-terminal kinase domain of unknown function, the centromere localization domain in the middle, and the C-terminal domain that has weak similarity to polo boxes of Polo-like kinases. We show that the kinase activity of KKT2 is essential for accurate chromosome segregation, while that of KKT3 is dispensable for cell growth in the procyclic form ofTrypanosoma brucei. Crystal structures of their divergent polo boxes reveal differences between KKT2 and KKT3. We also show that the divergent polo boxes of KKT3 are sufficient to recruit KKT2 inT. brucei. Furthermore, we identify the C-terminal domain of KKT1 as a direct interaction partner for the divergent polo boxes of KKT2, but not KKT3. KKT6 is found to interact with KKT1. These results show that KKT2 and KKT3 recruit downstream kinetochore proteins by direct protein-protein interactions using their divergent polo boxes.
Risk of Myocarditis and Pericarditis Following Coronavirus Disease 2019 Messenger RNA Vaccination—A Nationwide Study
Authors: Su Wei-Ju , Liu Yu-Lun , Chang Chia-Hsuin , Lin Yen-Ching , Huang Wei-I , Wu Li-Chiu , Chen Shu-Fong , Lin Yu-Sheng , Hsieh Yee-Lin , Yang Chiao-An , Lin Chiu-Hsiang , Chan Kim-Wei Arnold , Lee Ping-Ing , Chuang Jen-Hsiang , Yang Chin-Hui
Published: October 2022

Background

An extended interval between the two primary doses may reduce the risk of myocarditis/pericarditis after COVID-19 mRNA vaccination. Taiwan has implemented a two-dose regimen with a 12-week interval for adolescents. Here we present nationwide data of mRNA COVID-19 vaccination-associated myocarditis and pericarditis in Taiwan.

Methods

Data on adverse events of myocarditis/pericarditis were from the Taiwan Vaccine Adverse Events Reporting System between March 22, 2021, and February 9, 2022. The rates according to sex, age, and vaccine type were calculated. We investigated the reporting rates among young individuals under different two-dose intervals and among those who received two doses of different vaccines.

Results

Among 204 cases who met the case definition of myocarditis/pericarditis, 75 cases occurred after the first dose and 129 after the second. The reporting rate of myocarditis/pericarditis after COVID-19 vaccination varied across sex and age groups and was highest after the second dose in males aged 12–17 years (126.79 cases per million vaccinees) for the BNT162b2 vaccine and in males aged 18–24 years (93.84 cases per million vaccinees) for the mRNA-1273 vaccine. The data did not suggest an association between longer between-dose interval and lower rate of myocarditis/pericarditis among males and females aged 18–24 or 25–29 years who received two doses of the BNT162b2 or mRNA-1273 vaccine. Rates of myocarditis/pericarditis in males and females aged 18–49 years after receiving ChAdOx1-S - mRNA-1273 vaccination was significantly higher than after ChAdOx1-S - ChAdOx1-S vaccination.

Conclusions

Myocarditis and pericarditis are rare following mRNA vaccination, with higher risk occurring in young males after the second dose.
A meta-analysis of genome-wide association studies identifies new genetic loci associated with all-cause and vascular dementia
Authors: Fongang Bernard , Sargurupremraj Muralidharan , Jian Xueqiu , Mishra Aniket , Damotte Vincent , Bis Joshua C , Kang-Hsien Fan , Li Gloria , Yang Jingyun , Hilal Saima , Knol M.J. , Concas Maria Pina , Giorgia Girotto , Riaz Moeen , Guðjónsson Alexander , Lacaze Paul , Naj Adam C , van der Lee Sven J. , Goss Monica , Ngouongo Yannick W. , Skrobot Olivia , Guðnason Vilmundur , Launer Lenore , Lopez Oscar , Haan Mary , Bosnes Ingunn , Dufouil Carole , Ganguli Mary , Cheung Ching-Lung , Bennett David A , Chen Christopher , Ilyas Kamboh M. , Satizabal Claudia , Ikram Arfan M. , Debette Stephanie , Fornage Myriam , Qiong Yang , Schellenberg Gerard D. , Winsvold Bendik , Kehoe Patrick G. , Ruiz Agustin , Lambert Jean-Charles , Weinstein Galit , Seshadri Sudha ,   the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)
Published: October 2022

Dementia is multifactorial with Alzheimer (AD) and vascular (VaD) pathologies making the largest contributions. Genome-wide association studies (GWAS) have identified over 70 genetic risk loci for AD but the genomic determinants of other dementias, including VaD remain understudied. We hypothesize that common forms of dementia will share genetic risk factors and conducted the largest GWAS to date of “all-cause dementia” (ACD) and examined the genetic overlap with VaD. Our dataset includes 809,299 individuals from European, African, Asian, and Hispanic ancestries with 46,902 and 8,702 cases of ACD and VaD, respectively. We replicated known AD loci at genome-wide significance for both ACD and VaD and conducted bioinformatic analyses to prioritize genes that are likely functionally relevant, and shared with closely related traits and risk factors. For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability (ANO3), amyloid deposition in the brain (RBFOX1), and MRI markers of small vessel disease (HBEGF). Novel VaD loci were associated with hypertension, diabetes, and neuron maintenance (SPRY2, FOXA2, AJAP1, andPSMA3). Our study identified genetic risks underlying all-cause dementia, demonstrating overlap with neurodegenerative processes, vascular risk factors (Type-II diabetes, blood pressure, lipid) and cerebral small vessel disease. These novel insights could lead to new prevention and treatment strategies for all dementias.
The influence of river discharge on gravel bar hyporheic microbial community structure and putative metabolic functions
Authors: Doloiras-Laraño Arnelyn D. , Serrana Joeselle M. , Takahashi Shinji , Takemon Yasuhiro , Watanabe Kozo
Published: October 2022

Microbial communities in the hyporheic zone (HZ) are important in self-purification as the riverbed is metabolically active and responsible for the retention, storage and mineralisation of organic matter transported to the surface water. However, studies exploring HZ microbial community responses to disturbances (e.g. floods) remain scarce.

Here, we characterised the microbial community structure among the three (downwelling, upwelling and intermediate) HZ points within and among gravel bars at high and low discharge levels in a dam-regulated river using 16S rRNA metabarcoding.

We observed significant dissimilarity in the microbial community at low discharge exhibiting local adaptation due to gravel bar spatial environmental heterogeneity. Moreover, the homogenisation effect resulted in similar microbial community structures among the three points within the gravel bars at high discharge. Microbial communities across adjacent gravel bars were dissimilar, potentially attributing to different bar morphologies.

Our study highlights the role of spatial environmental heterogeneity in the biological processes that govern microbial community structure at three hyporheic points in gravel bars at two discharge levels.

Our results are essential to understand the HZ microbial communities’ response to the river discharge levels.
Effects of the Automatic Self-Transcending Meditation on cognition and mental states in the EEG, skin conductance and behavioral performance: a pilot study
Authors: Galdino Lucas , Silva Gabriella Medeiros , Bonifácio Thiago A. S. , dos Santos Natanael Antonio , Orme-Johnson David
Published: October 2022

The main purpose of this pilot study was to investigate the immediate effects of Automatic Self-Transcending (AST) meditation on the cognitive function, EEG activity and autonomic arousal (Study 1) and characterize the frontal EEG synchrony during resting state, cognitive activity and AST mental states in traditional and wireless EEG’s (Study 2). We report the results of three healthy AST meditation volunteers in this case-report study (Case 1 - age = 26 years, meditative practice time = 2 months; Case 2 - age = 39 years, meditative practice time = 6 years; Case 3 - age = 59 years, meditative practice time = 40 years). In study 1, the volunteers performed a protocol with simultaneous recording of EEG and skin conductance while performing the Stroop test (T0), followed by 20 minutes of AST meditation and immediately the same protocol performed at T0 (T1). We analyzed P300 amplitude and latency, as well as test behavioral response and skin conductance activity before and immediately after a single session of AST. In study 2, the same volunteers performed three tasks with eyes closed on two EEG equipment (traditional and wireless): resting state, cognitive activity and one session of AST, each for 20 minutes. We measured the frontal interhemispheric coherence of alpha1 (8-10 Hz) and beta (13-30 Hz) for each condition and EEG type. Our main findings show that there is an immediate beneficial effect after AST meditation at the level of the same individual with different patterns of P300 and skin conductance activity and that AST meditation is marked by an overall increase in the frontal coherence of alpha1 and beta bands, when compared to other mental states. We conclude that 1) there is an immediate effect on cognition and executive control after AST meditation, 2) the frontal interhemispheric coherence of alpha1 and beta bands are increased during AST, and 3) wireless EEG exhibits the same characteristics observed in traditional EEG and therefore can be used to describe cortical dynamics during AST.
Multiple-trait subsampling for optimized ancestral trait reconstruction
Authors: Li Xingguang , Trovão Nídia S. , Wertheim Joel O. , Baele Guy , de Bernardi Schneider Adriano
Published: October 2022

Large datasets along with sampling bias represent a challenge for phylodynamic reconstructions, particularly when the study data are obtained from various heterogeneous sources and/or through convenience sampling. In this study, we evaluate the presence of unbalanced sampled distribution by collection date, location, and risk group of HIV-1 subtype C using a compre-hensive subsampling strategy, and assess their impact on the reconstruction of the viral spatial and risk group dynamics using phylogenetic comparative methods. Our study shows that the most suitable dataset for ancestral trait reconstruction can be obtained through subsampling by collection date, location, and risk group, particularly using multigene datasets. We also demonstrate that sampling bias is inflated when considerable information for a given trait is unavailable or of poor quality, as we observed for the risk group in the analysis of HIV-1 subtype C. In conclusion, we suggest that, even if traits are not well recorded, including them deliberately optimizes the representativeness of the original dataset rather than completely excluding them. Therefore, we advise the inclusion of as many traits as possible with the aid of subsampling approaches in order to optimize the dataset for phylodynamic analysis while reducing the computational burden. This will benefit research communities investigating the evolutionary and spatiotemporal patterns of infectious diseases.
Allee effects mediate the impact of land-use change on the thermal niche of social species
Authors: Chan Shih-Fan , Rubenstein Dustin R. , Wang Tsung-Wei , Chen Ying-Yu , Chen I-Ching , Ni Dong-Zheng , Shih Wei-Kai , Shen Sheng-Feng
Published: October 2022

Land-use change not only affects habitat availability, it can also reduce population density and limit opportunities for interactions with conspecifics, further influencing species resilience to environmental challenges. For social species whose conspecific interactions are typically cooperative in nature, little is known about how land-use change influences demography and social behavior, and how this interaction impacts a species’ climatic niche. Here, we develop a spatially explicit, individual-based model to explore how land-use changes influence population size and niche width in social organisms through the Allee effect, the positive impact of higher population density on individual fitness. We then empirically test key model predictions by studying the distribution and cooperative behavior of burying beetles (Nicrophorus nepalensis) along elevational gradients in Taiwan. In support of our model predictions, we find that beetle densities are lower in areas of greater land-use change, making it harder for individuals in these hotter environments to form cooperative groups to compete against blowflies, their primary interspecific competitor. Consequently, the beetles’ lower distributional boundary is higher in areas with greater land-use change, indicating that the beetles’ thermal niche is reduced via Allee effects in human-altered landscapes. Ultimately, land-use change not only reduces habitat availability, it also shrinks the thermal niche of social species, making them more vulnerable to climate change.
Enriching Biomedical Knowledge for Low-resource Language Through Translation
Authors: Phan Long , Dang Tai , Tran Hieu , Phan Vy , Chau Lam D. , Trinh Trieu H.
Published: October 2022

Biomedical data and benchmarks are highly valuable yet very limited in low-resource languages other than English such as Vietnamese. In this paper, we make use of a state-of-theart translation model in English-Vietnamese to translate and produce both pretrained as well as supervised data in the biomedical domains. Thanks to such large-scale translation, we introduce ViPubmedT5, a pretrained Encoder-Decoder Transformer model trained on 20 million translated abstracts from the high-quality public PubMed corpus. ViPubMedT5 demonstrates state-of-the-art results on two different biomedical benchmarks in summarization and acronym disambiguation. Further, we release ViMedNLI a new NLP task in Vietnamese translated from MedNLI using the recently public En-vi translation model and carefully refined by human experts, with evaluations of existing methods against ViPubmedT5.
Body size as a magic trait in two plant-feeding insect species
Authors: Glover Ashleigh N. , Bendall Emily E. , Terbot John W. , Payne Nicole , Webb Avery , Filbeck Ashley , Norman Gavin , Linnen Catherine R.
Published: October 2022

When gene flow accompanies speciation, recombination can decouple divergently selected loci and loci conferring reproductive isolation. This barrier to sympatric divergence disappears when assortative mating and disruptive selection involve the same “magic” trait. Although magic traits could be widespread, the relative importance of different types of magic traits to speciation remains unclear. Because body size frequently contributes to host adaptation and assortative mating in plant-feeding insects, we evaluated several magic trait predictions for this trait in a pair of sympatricNeodiprionsawfly species adapted to different pine hosts. A large morphological dataset revealed that sawfly adults from populations and species that use thicker-needled pines are consistently larger than those that use thinner needled-pines. Fitness data from recombinant backcross females revealed that egg size is under divergent selection between the preferred pines. Lastly, mating assays revealed strong size-assortative mating within and between species in three different crosses, with the strongest prezygotic isolation between populations that have the greatest interspecific size differences. Together, our data support body size as a magic trait in pine sawflies and possibly many other plant-feeding insects. Our work also demonstrates how intraspecific variation in morphology and ecology can cause geographic variation in the strength of prezygotic isolation.
Predictive nonlinear modeling of malignant myelopoiesis and tyrosine kinase inhibitor therapy
Authors: Rodriguez Jonathan , Iniguez Abdon , Jena Nilamani , Tata Prasanthi , Liu Joan , Lander Arthur D. , Lowengrub John S. , Van Etten Richard A.
Published: October 2022

Chronic myeloid leukemia (CML) is a blood cancer characterized by dysregulated production of maturing myeloid cells driven by the product of the Philadelphia chromosome, the BCR-ABL1 tyrosine kinase. Tyrosine kinase inhibitors (TKI) have proved effective in treating CML but there is still a cohort of patients who do not respond to TKI therapy even in the absence of mutations in the BCR-ABL1 kinase domain that mediate drug resistance. To discover novel strategies to improve TKI therapy in CML, we developed a nonlinear mathematical model of CML hematopoiesis that incorporates feedback control and lineage branching. Cell-cell interactions were constrained using an automated model selection method together with previous observations and newin vivodata from a chimericBCR-ABL1transgenic mouse model of CML. The resulting quantitative model captures the dynamics of normal and CML cells at various stages of the disease and exhibits variable responses to TKI treatment, consistent with those of CML patients. The model predicts that an increase in the proportion of CML stem cells in the bone marrow would decrease the tendency of the disease to respond to TKI therapy, in concordance with clinical data and confirmed experimentally in mice. The model further suggests that a key predictor of refractory response to TKI treatment is an increased probability of self-renewal of normal hematopoietic stem cells. We use these insights to develop a clinical prognostic criterion to predict the efficacy of TKI treatment and to design strategies to improve treatment response. The model predicts that stimulating the differentiation of leukemic stem cells while applying TKI therapy can significantly improve treatment outcomes.
Development of a polymicrobial checkerboard assay as a tool for determining combinatorial antibiotic effectiveness in polymicrobial communities
Authors: Black Caroline , Al Mahmud Hafij , Wilson Sabrina , Smith Allie C. , Wakeman Catherine A.
Published: October 2022

AIMS

To establish a methodology for identifying the effects of combinatorial antibiotic treatment on individual members of a polymicrobial community.

METHODS AND RESULTS

Both gentamicin and ceftazidime were diluted to concentrations ranging from 0.06 μg ml-1to 128 μg ml-1. An equal ratio polymicrobial community ofStaphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis, andAcinetobacter baumanniiwas inoculated into the combined antibiotics in the checkerboard and incubated for 18 hours in static conditions. After incubation, visible turbidity of the overall community was recorded, and bacteria from the wells were diluted to 10-3and then spot plated on selective and differential media. After 24 hours, colony-forming unit (CFU) counts were obtained for each species.

CONCLUSIONS

Visible turbidity is not truly indicative of cell viability, and the polymicrobial community can decrease the antibiotic susceptibility ofP. aeruginosa, rendering the clinically-established beneficial combination of gentamicin and ceftazidime ineffective.

SIGNIFICANCE

Previous checkerboard methodology which focuses on using visible turbidity to determine monomicrobial antibiotic susceptibility fails to account for polymicrobial cooperation that has been shown to reduce antibiotic efficacy. Our new methodology could be implemented in clinical microbiology laboratories with minimal impact on the overall time for diagnosis.
Upper Limit Efficiency Estimates for Electromicrobial Production of Drop-In Jet Fuels
Authors: Sheppard Timothy J. , Specht David , Barstow Buz
Published: October 2022

Microbes which participate in extracellular electron uptake or H2oxidation have an extraordinary ability to manufacture organic compounds using electricity as the primary source of metabolic energy. So-called electromicrobial production could be of particular value in the efficient production of hydrocarbon blends for use in aviation. Because of exacting standards for fuel energy density and the costs of new aviation infrastructure, liquid hydrocarbon fuels will be necessary for the foreseeable future, precluding direct electrification. Production of hydrocarbons using electrically-powered microbes employing fatty acid synthesis-based production of alkanes could be an efficient means to produce drop-in replacement jet fuels using renewable energy. Here, we calculate the upper limit electrical-to-energy conversion efficiency for a model jet fuel blend containing 85% straight-chain alkanes and 15% terpenoids. When using the Calvin cycle for carbon-fixation, the energy conversion efficiency iswhen using extracellular electron uptake for electron delivery andwhen using H2-oxidation. The efficiency of production of the jet fuel blend can be raised towhen using the Formolase formate-assimilation pathway and H2-oxidation, and towith the Wood-Ljungdahl pathway. The production efficiency can be further raised by swapping the well-known ADO pathway for alkane termination with for the recently discovered MCH pathway. If these systems were were supplied with electricity with a maximally-efficient silicon solar photovoltaic, even the least efficient would exceed the maximum efficiency of all known forms of photosynthesis.
Laboratory evaluation of a quaternary ammonium compound (QAC)-based antimicrobial coating used in public transport during the COVID-19 pandemic
Authors: Aranega-Bou Paz , Brown Natalie , Stigling Abigail , D’Costa Wilhemina , Verlander Neville Q , Pottage Thomas , Bennett Allan , Moore Ginny
Published: October 2022

The virucidal activity of a quaternary ammonium compound (QAC)-based antimicrobial coating used by the UK rail industry during the COVID-19 pandemic was evaluated using the bacteriophage ϕ6 as a surrogate for SARS-CoV-2. Immediately after application and in the absence of interfering substance, the product showed efficacy (>3 log10reduction) on some materials typically used in rail carriages (stainless steel, high pressure laminate and plastic), variable efficacy on glass and no efficacy (<3 log10reduction) on a train armrest made of Terluran 22. If, after application of the product, the surfaces remained undisturbed, the antimicrobial coating retained its efficacy for at least 28 days on all materials where it was effective immediately after application. However, regardless of the material coated or time since application, the presence of organic debris (fetal bovine serum) significantly reduced the viricidal activity of the coating. Wiping the surface with a wetted cloth after organic debris deposition was not sufficient to restore efficacy. We conclude that the product is likely to be of limited effectiveness in a busy multi-user environment such as public transport.

Importance

This study evaluated the performance of a commercially available antimicrobial coating used by the transport industry in the UK during the COVID-19 pandemic. While the product initially showed efficacy against ϕ6 when applied to some materials, when organic debris was subsequently deposited, the efficacy was severely diminished and could not be recovered through wiping (cleaning) the surface. This highlights the importance of including relevant materials and conditions when evaluating antimicrobial coatings in the laboratory. Further efforts are required to identify suitable infection prevention and control practices for the transport industry.
Biometric linkage of longitudinally collected electronic case report forms and confirmation of subject identity: An open framework for ODK and related tools
Authors: Roberts Chrissy h , Stott Callum , Shawe-Taylor Marianne , Chaudhry Zain , Lal Sham , Marks Michael
Published: October 2022

The availability of low-cost biometric hardware sensors and software makes it possible to rapidly, affordably and securely sample and store a unique and invariant biological signature (or biometric “template”) of participants in research and trials. This has applications in consent, linkage of case reporting forms collected at different times, and in confirmation of participant identity for purposes of safety monitoring and adherence to international data laws.

The use of mobile electronic data collection software has recently become commonplace in clinical trials and research. A raft of tools based on the open-source ODK project now provide diverse options for data management that work consistently in resource-restricted settings, but none have built-in functionality for capturing biometric templates.

In this study, we report the development and testing of a novel open-source app and associated method for capturing and matching biometric fingerprint templates during data collection with the popular data platforms ODK, KoBoToolbox, SurveyCTO, Ona and CommCare.

Using data from more than 1000 fingers, we show that fingerprint templates can be used to link data forms with high accuracy and that this accuracy increases with the addition of multiple fingerprints on each data form. By focussing on publishing open-source code and documentation, and by using an affordable (<£50) and mass-produced model of fingerprint sensor, we are able to make this platform freely available to the large global user community that utilises ODK and related data collection systems.
Identifying Contextual and Spatial Risk Factors for Post-Acute Sequelae of SARS-CoV-2 Infection: An EHR-based Cohort Study from the RECOVER Program
Authors: Zhang Yongkang , Hu Hui , Fokaidis Vasilios , Lewis V Colby , Xu Jie , Zang Chengxi , Xu Zhenxing , Wang Fei , Koropsak Michael , Bian Jiang , Hall Jaclyn , Rothman Russell L. , Shenkman Elizabeth A. , Wei Wei-Qi , Weiner Mark G. , Carton Thomas W. , Kaushal Rainu
Published: October 2022

Post-acute sequelae of SARS-CoV-2 infection (PASC) affects a wide range of organ systems among a large proportion of patients with SARS-CoV-2 infection. Although studies have identified a broad set of patient-level risk factors for PASC, little is known about the contextual and spatial risk factors for PASC. Using electronic health data of patients with COVID-19 from two large clinical research networks in New York City and Florida, we identified contextual and spatial risk factors from nearly 200 environmental characteristics for 23 PASC symptoms and conditions of eight organ systems. We conducted a two-phase environment-wide association study. In Phase 1, we ran a mixed effects logistic regression with 5-digit ZIP Code tabulation area (ZCTA5) random intercepts for each PASC outcome and each contextual and spatial factor, adjusting for a comprehensive set of patient-level confounders. In Phase 2, we ran a mixed effects logistic regression for each PASC outcome including all significant (false positive discovery adjusted p-value < 0.05) contextual and spatial characteristics identified from Phase I and adjusting for confounders. We identified air toxicants (e.g., methyl methacrylate), criteria air pollutants (e.g., sulfur dioxide), particulate matter (PM2.5) compositions (e.g., ammonium), neighborhood deprivation, and built environment (e.g., food access) that were associated with increased risk of PASC conditions related to nervous, respiratory, blood, circulatory, endocrine, and other organ systems. Specific contextual and spatial risk factors for each PASC condition and symptom were different across New York City area and Florida. Future research is warranted to extend the analyses to other regions and examine more granular contextual and spatial characteristics to inform public health efforts to help patients recover from SARS-CoV-2 infection.
Estimation of crossbridge-state during cardiomyocyte beating using second harmonic generation
Authors: Fujita Hideaki , Kaneshiro Junichi , Takeda Maki , Sasaki Kensuke , Yamamoto Rikako , Umetsu Daiki , Kuranaga Erina , Higo Shuichiro , Kondo Takumi , Asano Yasuhiro , Sakata Yasushi , Miyagawa Shigeru , Watanabe Tomonobu M
Published: October 2022

Estimation of dynamic change of crossbridge formation in living cardiomyocytes is expected to provide crucial information for elucidating cardiomyopathy mechanisms, efficacy of an intervention, and other parameters. Here, we developed an assay system to dynamically measure second harmonic generation (SHG) polarization in pulsating cardiomyocyte and proved that the SHG anisotropy derived from myosin filaments in disease-model cardiomyocytes depended on their crossbridge status, providing an evaluation method for myosin force generation. Experiments utilizing an inheritable mutation that induces excessive myosin-actin interactions revealed that the correlation between sarcomere length and SHG anisotropy represents crossbridge formation ratio during pulsation. Furthermore, the present method found that ultraviolet irradiation induced an increased population of attached crossbridges that lost force-generating ability upon myocardial differentiation, causing acquired dysfunction. Taking an advantage of infrared two-photon excitation in SHG microscopy, myocardial dysfunction could be intravitally evaluated in aDrosophiladisease model. Thus, along with the establishment of the methodology, we successfully demonstrated the applicability and effectiveness of the present method to evaluate the actomyosin activity of a drug or genetic defect on living cardiomyocytes.
Obscurin Rho GEF domains are phosphorylated by MST-family kinases but do not exhibit nucleotide exchange factor activity towards Rho GTPasesin vitro
Authors: Koch Daniel , Kho Ay Lin , Fukuzawa Atsushi , Alexandrovich Alexander , Beavil Andrew , Pfuhl Mark , Rees Martin , Gautel Mathias
Published: October 2022

Obscurin is a giant muscle protein (>800 kDa) featuring multiple signalling domains, including an SH3-DH-PH domain triplet from the Trio-subfamily of guanosine nucleotide exchange factors (GEFs). While previous research suggests that these domains can activate the small GTPases RhoA and RhoQ in cells,in vitrocharacterization of these interactions using biophysical techniques has been hampered by the intrinsic instability of obscurin GEF domains. To study substrate specificity, mechanism and regulation of obscurin GEF function by individual domains, we successfully optimized recombinant production of obscurin GEF domains and found that MST-family kinases phosphorylate the obscurin DH domain at Thr5798. Despite extensive testing of multiple GEF domain fragments, we did not detect any nucleotide exchange activityin vitroagainst 9 representative small GTPases. Bioinformatic analyses show that obscurin differs from other Trio-subfamily GEFs in several important aspects. While further research is necessary to evaluate obscurin GEF activityin vivo, our results indicate that obscurin has atypical GEF domains that, if catalytically active at all, are subject to complex regulation.