bluuebunny/crossref_metadata_2025 huggingface dataset:
Diet-induced Resolution of Macular Oedema following Remission of Type 2 Diabetes Mellitus in a patient undergoing Therapeutic Carbohydrate Reduction
Authors: Hains Lewis R , Bacchi Stephen , Martin Rachelle , Chan Weng Onn , Muecke James S
Published: June 2024

Purpose:

There is growing evidence to support the potential role of low-carbohydrate healthy fat (LCHF) and ketogenic diets (therapeutic carbohydrate reduction - TCR) in the management of diabetes mellitus. This case explores the use of a ketogenic diet to manage type 2 diabetes mellitus (T2DM) in a middle-aged female with insulin-dependent disease.

Method:

The patient presented to an optometrist with a history of blurred vision and was diagnosed with mild macular oedema (MO) in both eyes. Following review by an ophthalmologist and subsequently her general practitioner and endocrinologist, she was referred to a nutritionist specialising in therapeutic carbohydrate reduction.

Result:

Within two weeks of the dietary change, the patient was able to cease her regular insulin and returned to normoglycaemia. Within four weeks of her initial appointment with the nutritionist, ophthalmology follow-up found a reduction in MO in both eyes. At the last review 18 months later, MO in both eyes had completely resolved.

Conclusion:

This novel case demonstrates a clinical application of therapeutic carbohydrate reduction and requires further research.
Improving Inpatient Colonoscopy Bowel Preparation: A Successful Quality Improvement Project
Authors: Damjanovska Sofi , Watanabe Shota , Karb Daniel B. , Kurin Michael , Isenberg Gerard
Published: June 2024

Inadequate inpatient bowel preparation can lead to repeat procedures, prolonged hospital stays, and increased financial burden. In this quality improvement project, the authors developed an electronic medical record (EMR)-based order set with precise instructions and anticipatory guidance for inpatient bowel preparation before colonoscopy. The current study is a nonrandomized intervention study. The authors compared 2 groups: an intervention group using a newly developed, consensus-based, standardized EMR bowel preparation order set and a control group using previously existing EMR bowel preparation orders. Bowel preparation outcomes were followed over the course of 16 months. The aim was to improve inpatient colonoscopy bowel preparation, as evaluated by the Boston Bowel Preparation Scale, procedure delays, and length of hospital stay. We additionally evaluated the groups’ demographics and patient-level factors. A total of 459 inpatient colonoscopies were evaluated over a 16-month period. The intervention group consisted of 227 inpatient colonoscopies, while the control group consisted of 232. The intervention group showed superior Boston Bowel Preparation Scale score and decreased length of hospital stay. The number of adequate bowel preparations increased in the intervention group when compared to the control group from 77% to 86%. The creation of an EMR-based order set is a low-cost and sustainable action that can be easily implemented throughout a hospital system.
A Tool to Teach and Assess Clinical Nurse Specialist Student Prescribing Competency
Authors: Saunders Mitzi M.
Published: June 2024

Purpose/Aims

The purpose of this study was to assess the usefulness of a tool designed to develop and evaluate clinical nurse specialist (CNS) student competency and confidence in prescribing therapeutic agents. Specifically, the aims were to identify students’ perceptions of the tool’s (1) helpfulness in learning to prescribe, (2) impact on confidence as a prescriber, and (3) recommended use in CNS education.

Design

An exploratory design was used.

Methods

Students used the tool in patient care with a supervising mentor during clinical rotations. Students completed surveys after using the tool at 2 points in time. Data were analyzed using descriptive statistics.

Results

Of the 18 students, 5 students completed the survey at time 1 and 6 students at time 2. The aims were met in that students perceived the tool to be helpful during CNS prescribing activities, felt confident about prescribing after using the tool, and agreed the tool should be used in CNS education.

Conclusion

Replication of the study with larger samples of CNS students and psychometric analyses of the tool is recommended by the study’s findings to support its use in CNS education beyond the study site.
Outcome Evaluation of a Health System Clinical Nurse Specialist Fellowship Program
Authors: Rader Tiffany , Keen Alyson , Wornhoff Brandee , Powers Jan
Published: June 2024

Purpose

Healthcare is a complex adaptive system, requiring agile, innovative leaders to transform care. Clinical nurse specialists (CNSs) are uniquely positioned to influence change and achieve high-quality outcomes. Nurse leaders need strategies to onboard and retain CNSs considering high demand across the nation. The purpose of this program evaluation was to describe the core components and outcomes of CNS fellowship programs.

Design

This program evaluation used the Kirkpatrick Model as a framework to assess learning and knowledge translation.

Methods

The study was conducted within 3 Indiana healthcare organizations. Clinical nurse specialist leaders from each organization identified fellowship core components and analyzed team composition (ie, percentage of CNS team that was current/past fellows). Current and past CNS fellows were invited to participate in a survey evaluating program effectiveness, impact on role transition, project leadership, and outcomes achieved.

Results

Overlap was identified among 85% (17/20) of the core components, team composition was 71% (25/35) past/current fellows, and retention was 100% (12/12). Of the 23 invited, 18 (78%) participated in the program evaluation. Program effectiveness was evaluated as very/extremely effective by 94% (17/18) of participants. Themes salient to independent practice transition were applying learning, achieving influence, and developing relationally, contributing to incremental gain of the CNS perspective (ie, CNS values and guiding principles influencing critical thinking and behavior).

Conclusion

Nurse leaders should consider fellowship implementation to recruit and retain CNS talent within organizations.
Embracing a New Evidence-Based Thought Paradigm of Sepsis
Authors: Richardson Lindsay , Graham Julie-Kathryn
Published: June 2024

In 1991, sepsis was first defined by the Society of Critical Care Medicine as the systemic inflammatory response syndrome, in the presence of infection. Systemic inflammatory response syndrome is an adaptive host response to infection, as well as to other insults like trauma and stress. Research pertaining to sepsis was guided by this adaptive definition for 25 years. After established guidelines for sepsis management were challenged in 2014, sepsis was redefined in 2016 as a dysregulated host response to infection. However, there still remains no consensus on which immunologic or metabolic mechanisms have become dysregulated. We sought to examine sepsis literature published after the 2016 consensus definition and compare it to the original systemic inflammatory response syndrome paradigm proposed in 1991. The purpose of this intensive analysis was to recommend a new sepsis archetype, with consideration to dysregulated immunologic and metabolic mechanisms that have recently been identified in sepsis. Nurses and other clinicians must shift their thought paradigm toward an evidence-based dysregulated model, in order to improve on sepsis recognition and management.
Effectively Communicating Practice Changes to Frontline Nurses
Authors: Tertinek Nicholas , Hole Ashley , Inumerables Faye
Published: June 2024

Purpose/Objectives

Communication of practice changes to frontline nurses across an organization can be difficult. Frequent daily communication to all nursing staff can be ineffective and lead to email fatigue and information overload. The purpose of this article is to further describe the communication intervention developed to disseminate practice changes and the critical modifications made over time to ensure its continued success and sustainability.

Description of the Project/Program

In 2019, this team from a multisite institution developed a monthly email correspondence, called the Evidence-Based Practice Update, sent to local leaders to disseminate important policy and practice updates and reminders to more than 3400 nurses. This strategy was initially successful in reaching the nurses yet lacked a method to ensure accountability that each nurse has read the content. A quick response code was added to track monthly readership, and clinical nurse specialists were leveraged to ensure practice changes reached, reviewed, and understood by nurses across the institution.

Outcome

Metrics were tracked for quick response code scans and demonstrated an increase in readership over time. By combining various alerts into the single correspondence, fewer daily notifications to staff were sent. The EBP Update email dissemination structure involving local leaders was well received.

Conclusion

This article describes how a standardized communication strategy coupled with thoughtful leadership engagement improved uptake of important practice information by nurses across a vast institution.
Multiple Imputation of Race and Hispanic Ethnicity in National Surveillance Data for Chlamydia, Gonorrhea, and Syphilis
Authors: Pondo Tracy , Torrone Elizabeth , Pagaoa Melissa
Published: June 2024

Background

Disease burden of sexually transmitted infections such as chlamydia, gonorrhea, and syphilis is often compared across age categories, sex categories, and race and ethnicity categories. Missing data may prevent researchers from accurately characterizing health disparities between populations. This article describes the methods used to impute race and Hispanic ethnicity in a large national surveillance data set.

Methods

All US cases of chlamydia, gonorrhea, and syphilis (excluding congenital syphilis) reported through the National Notifiable Diseases Surveillance System from the year 2019 were included in the analyses. We used fully conditional specification to impute missing race and Hispanic ethnicity data. After imputation, reported case rates were calculated, by disease, for each race and Hispanic ethnicity category using Vintage 2019 Population and Housing Unit Estimates from the US Census. We then used case counts from subsets that contained only complete race and Hispanic ethnicity information to investigate if the confidence intervals from the multiply imputed data included the observed number of cases in each race and Hispanic ethnicity category.

Results

Among the 2,553,038 cases reported in 2019, race and Hispanic ethnicity were multiply imputed for 9% of syphilis cases, 22% of gonorrhea cases, and 33% of chlamydia cases. In the subset analyses, every nonzero rate of reported cases was contained within the confidence intervals that were calculated from multiply imputed data.

Conclusions

Confidence intervals that account for the uncertainty of the predictions are an advantage of multiple imputation over complete-case analysis because a realistic variance estimate allows for valid hypothesis testing results.
Results of the Sukuma Ndoda (“Stand up, Man”) HIV Self-Screening and Assisted Linkage to Care Project in Johannesburg: A Quasi-Experimental Pre–Post Evaluation
Authors: Lippman Sheri A. , Grignon Jessica S. , Ditshwane Boitumelo , West Rebecca L. , Gilmore Hailey J. , Mazibuko Sipho , Mongwe Livhuwani G. , Neilands Torsten B. , Gutin Sarah A. , O’Connor Cara , Santana Maideline A. , Majam Mohammed
Published: June 2024

Background:

HIV testing rates among South African men lag behind rates for women and national targets. Community-based HIV self-screening (HIVSS) distribution and follow-up by community health workers (CHWs) is a scalable option to increase testing coverage, diagnosis, and treatment initiation. We provided HIVSS and assisted linkage to care to men not recently tested (within the past 12 months) residing in high-HIV-burden areas of Johannesburg.

Methods:

CHWs distributed HIVSS in 6 clinic catchment areas. Follow-up to encourage confirmatory testing and antiretroviral therapy initiation was conducted through personal support (PS) or an automated short message service (SMS) follow-up and linkage system in 3 clinic areas each. Using a quasi-experimental pre–post design, we compared differences in the proportion of men testing in the clinic catchment areas during the HIVSS campaign (June–August 2019) to the 3 months prior (March–May 2019) and compared treatment initiations by assisted linkage strategy.

Results:

Among 4793 participants accepting HIVSS, 62% had never tested. Among 3993 participants with follow-up data, 90.6% reported using their HIVSS kit. Testing coverage among men increased by 156%, from under 4% when only clinic-based HIV testing services were available to 9.5% when HIVSS and HIV testing services were available (z = −11.6; P < 0.01). Reported test use was higher for men followed through PS (99% vs. 68% in SMS); however, significantly more men reported reactive self-test results in the SMS group compared with PS (6.4% vs. 2.0%), resulting in more antiretroviral therapy initiations in the SMS group compared with PS (23 vs. 9; P < 0.01).

Conclusions:

CHW HIVSS distribution significantly increases testing among men. While PS enabled personalized follow-up, reporting differences indicate SMS is more acceptable and better aligned with expectations of privacy associated with HIVSS.
Advances in functional and structural imaging of the brainstem: implications for disease
Authors: Cai Jiayue , Wang Yuheng , McKeown Martin J.
Published: June 2024

Purpose of review

The brainstem's complex anatomy and relatively small size means that structural and functional assessment of this structure is done less frequently compared to other brain areas. However, recent years have seen substantial progress in brainstem imaging, enabling more detailed investigations into its structure and function, as well as its role in neuropathology.

Recent findings

Advancements in ultrahigh field MRI technology have allowed for unprecedented spatial resolution in brainstem imaging, facilitating the new creation of detailed brainstem-specific atlases. Methodological improvements have significantly enhanced the accuracy of physiological (cardiac and respiratory) noise correction within brainstem imaging studies. These technological and methodological advancements have allowed for in-depth analyses of the brainstem's anatomy, including quantitative assessments and examinations of structural connectivity within both gray and white matter. Furthermore, functional studies, including assessments of activation patterns and functional connectivity, have revealed the brainstem's roles in both specialized functions and broader neural integration. Notably, these investigations have identified alterations in brainstem structure and function associated with various neurological disorders.

The aforementioned developments have allowed for a greater appreciation of the importance of the brainstem in the wider context of neuroscience and clinical neurology.
Identification of Salmonella enterica biovars Gallinarum and Pullorum and their antibiotic resistance pattern in integrated crop-livestock farms and poultry meats
Authors: Julianingsih Dita , Alvarado-Martinez Zabdiel , Tabashsum Zajeba , Tung Chuan-Wei , Aditya Arpita , Kapadia Sarika , Maskey Saloni , Mohapatra Aditi , Biswas Debabrata
Published: June 2024

Due to consumer demand, many conventional poultry farms are now growing poultry without antibiotics or synthetic chemicals. In addition to this, pasture/organic poultry farms have increased significantly in the USA, and they are also antibiotic- and chemical-free. According to recent reports, both antibiotic-free conventional and pasture poultry farmers are facing the reemergence of bacterial diseases. Bacterial diseases cause higher mortality rates in birds and lead to non-profitable poultry farming. This study investigated the prevalence of Salmonella enterica subsp. enterica serovar Gallinarum biovars Gallinarum (S. Gallinarum), the causative agent of fowl typhoid, and Salmonella enterica subsp. enterica serovar Gallinarum biovars Pullorum (S. Pullorum), the causative agent of pullorum disease, within integrated crop-livestock/pasture farm environments and their processed products. A total of 1,286 samples were collected from 6 farms and adjacent 13 markets to determine the prevalence of S. Gallinarum and S. Pullorum by using both microbiological culture and molecular techniques. Antibiotic resistance pattern of the confirmed isolates was subsequently determined with an antibiogram assay following the Clinical Laboratory Standards Institute guidelines for relevant antibiotics. S. Pullorum was detected in 11 samples (2.7%), while S. Gallinarum was found in 6 samples (1.5%) out of a total of 403 samples at the pre-harvest level. At the post-harvest level, only S. Gallinarum was identified in 14 meat samples out of 883 (1.6%) recovered from samples collected from retail markets. Antibiogram showed S. Gallinarum and S. Pullorum to be highly resistant to cephradine, trimethoprim-sulfamethoxazole, amoxicillin, streptomycin, and ampicillin. This data demonstrates that both S. Pullorum and S. Gallinarum are commonly present in farm poultry environments as well as the products sold in the markets, which warrants implementation of regular surveillance and monitoring programs, as well as potentially requiring future control strategies to reduce S. Pullorum and S. Gallinarum transmission.
Whole genome sequences of marine bacteria presenting the ability to promote the growth of the diatom Phaeodactylum tricornutum
Authors: Martins Rodrigo , Bertrand Constança , Quintas-Nunes Francisco , Reynolds-Brandão Pedro , Barreto Crespo Maria , Nascimento Francisco X
Published: June 2024

2. Abstract

We describe the whole genome sequences of seven diverse marine bacteria isolated from Portuguese environments that presented the ability of promoting the growth of the model diatom, Phaeodactylum tricornutum. The bacterial genome sequences will contribute for the study of genetic and molecular mechanisms involved in diatom-bacteria interactions.
A dynamic transmission model for assessing the impact of pneumococcal vaccination in the United States
Authors: Malik Tufail M , Bakker Kevin M , Oidtman Rachel J , Sharomi Oluwaseun , Meleleo Giulio , Nachbar Robert B , Elbasha Elamin H
Published: June 2024

Streptococcus pneumoniae(SP) is a bacterial pathogen that kills more than 300,000 children every year across the globe. Multiple vaccines exist that prevent pneumococcal disease, with each vaccine covering a variable number of the more than 100 known serotypes. Due to the high effectiveness of these vaccines, each new pneumococcal conjugate vaccine (PCV) introduction has resulted in a decrease in vaccine-type disease and a shift in the serotype distribution towards non-vaccine types in a phenomenon called serotype replacement. Here, an age-structured compartmental model was created that reproduced historical carriage transmission dynamics in the United States and was used to evaluate the population-level impact of new vaccine introductions into the pediatric population. The model incorporates co-colonization and serotype competition, which drives replacement of the vaccine types by the non-vaccine types. The model was calibrated to historical age- and serotype-specific invasive pneumococcal disease (IPD) data from the United States. Vaccine-specific coverage and effectiveness were integrated in accordance with the recommended timelines for each age group. Demographic parameters were derived from US-population-specific databases, while population mixing patterns were informed by US-specific published literature on age-group based mixing matrices. The calibrated model was then used to project the epidemiological impact of PCV15, a 15-valent pneumococcal vaccine, compared with the status quo vaccination with PCV13 and demonstrated the value of added serotypes in PCV15. Projections revealed that PCV15 would reduce IPD incidence by 6.04% (range: 6.01% to 6.06%) over 10 years when compared to PCV13.
Sex differences in the associations of socioeconomic factors and cognitive performance with family history of Alzheimer’s disease
Authors: He Jun , Cabrera-Mendoza Brenda , Friligkou Eleni , Mecca Adam P. , van Dyck Christopher H. , Pathak Gita A. , Polimanti Renato
Published: June 2024

INTRODUCTION

While higher socioeconomic factors (SEF) and cognitive performance (CP) have been associated with reduced Alzheimer’s disease (AD) risk, recent evidence highlighted that these factors may have opposite effects on family history of AD (FHAD).

METHODS

Leveraging data from the UK Biobank (N=448,100) and the All of Us Research Program (N=240,319), we applied generalized linear regression models, polygenic risk scoring (PRS), and one-sample Mendelian randomization (MR) to test the sex-specific SEF and CP associations with AD and FHAD.

RESULTS

Observational and genetically informed analyses highlighted that higher SEF and CP were associated with reduced AD and sibling-FHAD, while these factors were associated with increased parent-FHAD. We also observed that population minorities may present different patterns with respect to sibling-FHAD vs. parent-FHAD. Sex differences in FHAD associations were identified in ancestry-specific and SEF PRS and MR results.

DISCUSSION

This study contributes to understanding the sex-specific relationships linking SEF and CP to FHAD, highlighting the potential role of reporting, recall, and surviving-related dynamics.
Machine learning and the labour market: A portrait of occupational and worker inequities in Canada
Authors: Jetha Arif , Liao Qing , Vahid Shahidi Faraz , Vu Viet , Biswas Aviroop , Smith Brendan , Smith Peter
Published: June 2024

Introduction

Machine learning (ML) is increasingly used by Canadian workplaces. Concerningly, the impact of ML may be inequitable and disrupt social determinants of health. The aim of this study is to estimate the number of workers in occupations highly exposed to ML and describe differences in ML exposure represents according to occupational and worker sociodemographic factors.

Methods

Canadian occupations were scored according to the extent to which they were made up of job tasks that could be performed by ML. Eight years of data from Canada’s Labour Force Survey were pooled and the number of Canadians in occupations with high or low exposed to machine learning were estimated. The relationship between gender, hourly wages, educational attainment and occupational job skills, experience and training requirements and ML exposure was examined using stratified logistic regression models.

Results

Approximately, 1.9 million Canadians are working in occupations with high ML exposure and 744,250 workers were employed in occupations with low ML exposure. Women were more likely to be employed in occupations with high ML exposure than men. Workers with greater educational attainment and in occupations with higher wages and greater job skills requirements were more likely to experience high ML exposure. Women, especially those with less educational attainment and in jobs with greater job skills, training and experience requirements, were disproportionately exposed to ML.

Conclusion

ML has the potential to widen inequities in the working population. Disadvantaged segments of the workforce may be most likely to be employed in occupations with high ML exposure. ML may have a gendered effect and disproportionately impact certain groups of women when compared to men. We provide a critical evidence base to develop strategic responses that ensure inclusion in a working world where ML is commonplace.

KEY MESSAGES

What is already known on this topic

The Canadian labour market is undergoing an artificial intelligence (AI) revolution that has the potential to have widespread impact on a range of occupations and worker groups.

It is unclear how which the adoption of machine learning (ML), an AI subfield, within the working world might contribute to inequities within the labour market.

What this study adds

Segments of the workforce which have been previously disadvantaged may be most likely to work in occupations most likely to be affected by ML.

ML may have a gendered effect and disproportionately impact some groups of women when compared to men.

How this study might affect research, practice or policy

Findings can inform targeted policies and programs that optimize the economic benefits of ML while addressing disparities that can emerge because of the adoption of the technology on workers.
Impact and Assessment of Mechanical Tension in Bowel Anastomosis: a Scoping Review
Authors: Khalid Muhammad Usman , Ali Danish , Wu Jie Ying , Khan Aimal
Published: June 2024

Background

While tension on anastomoses is primarily regarded as a critical factor in anastomotic leaks and failure, assessing this tension is based on subjective surgeon estimation. There is currently no clinically available tool to assess mechanical tension on an anastomosis objectively. Some animal and human studies have previously evaluated anastomotic tension, but no comprehensive review discusses the different methods and types of tension measured.

Objectives

To summarize the current state of the literature regarding the measurement and impact of tension on bowel anastomoses.

Design

This scoping review was conducted with a systematic search of literature in the PubMed, SCOPUS, and EMBASE databases. Key terms used were anastomoses/anastomosis, tension, bowel, surgery, intestine, tissue, small bowel, large bowel, bowel, mucosal tissue, and other corollary terms. Data were synthesized in tables, and summarized paragraphically, with studies assessed using the New-Castle Ottawa scale where possible. Emphasis was placed on method of tension assessment, outcomes, and factors relating to tension.

Results

Anastomotic leak and tension are strongly associated, with the presence of tension making leaks up to 10 times more likely. While freedom from tension has traditionally been measured via the surrogate measure of adequate bowel mobilization, this remains a subjective and imprecise method. The literature describes several techniques to allow adequate mobilization, such as splenic flexure mobilization or division of the omentum. However, basing the estimate of tension on subjective assessment has some inherent drawbacks. Animal and cadaveric studies have been the frontier for objective measurement of wall tension, with the use of scaffolds, suture types, and prostheses to bolster the natural tolerance of the bowel. However, these tend to use tensiometers to measure tension, along with automated machines or pulley and ratcheting systems to increase tension in specified intervals. These are universally destructive due to their design of measuring maximal tensile load as well as not being easily adaptable to the operating room.

Conclusions

The current literature does not study objective measurement of bowel tension in live human subjects. Bowel mobilization is a common method to reduce tension, but it relies on subjective judgment, which varies between surgeons. Given the recognized importance of tension, developing an objective, safe, intra-operative method to measure bowel wall tension would be a valuable surgical tool.
Who participates in ‘participatory design’ of WASH infrastructure: a mixed-methods process evaluation
Authors: Mink Thea L. , Salinger Allison P. , Francis Naomi , Batagol Becky , Burge Kerrie , Ilhamsyah Noor , Malumu Losalini , Marzaman Liza , Prescott Michaela , Putri Nur Intan , Sinharoy Sheela S.
Published: June 2024

Inclusive participation is critical for community-based water, sanitation and hygiene (WASH) interventions, especially in complex environments such as urban informal settlements. We conducted a mixed-methods, theory-driven process evaluation to evaluate participation, barriers to participation, and participant satisfaction within the Revitalising Informal Settlements and their Environments (RISE) trial in Makassar, Indonesia and Suva, Fiji (ACTRN12618000633280;https://www.anzctr.org.au/).

RISE conducted participatory design activities, including community-level design workshops and household visits, to co-design WASH infrastructure. Household surveys, conducted with women and men after RISE participatory design in Makassar (N=320) and Suva (N=503), captured self-reported participation in RISE activities and satisfaction with influence over RISE decision-making. We used multivariable regression models to assess socio-demographic predictors of participation and satisfaction. Qualitative data were also collected after participatory design and analyzed thematically.

Most respondents from Makassar (89%) and Suva (75%) participated in at least one RISE co-design activity. Statistically significant predictors of participation included gender, age, and marital status in Makassar and disability status and education in Suva. Most participants in Makassar (66%) and Suva (70%) were satisfied with their level of influence over RISE decision-making. In Makassar, no significant predictors of satisfaction were identified. In Suva, significant predictors of satisfaction included gender, religion, and marital status, with women wantingmoreinfluence and religious minorities and unmarried participants wantinglessinfluence over decisions. Qualitative data showed that most participants felt satisfied by RISE’s inclusive and participatory design, although some residents reported distrust with RISE and feeling excluded from activities by community representatives.

While RISE participatory design activities achieved good reach and satisfaction overall, we identified specific gender and social inequities in participation and influence over decision-making. We recommend that WASH interventions reflect on the quality of their engagement with communities and local organizations in order to identify and appropriately include groups of interest.
Increased 5-HT2Areceptor signalling efficacy differentiates serotonergic psychedelics from non-psychedelics
Authors: Ippolito Aurelija , Vasudevan Sri , Hurley Shaun , Gilmour Gary , Westhorpe Frederick , Churchill Grant , Sharp Trevor
Published: June 2024

Background and Purpose

Serotonergic psychedelic drugs are under renewed investigation for the potential treatment of several psychiatric disorders. While all serotonergic psychedelics have 5-HT2Areceptor activity, the explanation for why some 5-HT2Areceptor agonists are not psychedelic is unknown. To address this question, we investigated the 5-HT2Areceptor signalling bias and efficacy of a panel of psychedelics and non-psychedelics.

Experimental Approach

G -coupled (Ca2+and IP) and β-arrestin2 signalling effects of eight chemically diverse psychedelics (psilocin, 5-MeO-DMT, LSD, mescaline, 25B-NBOMe and DOI) and non-psychedelics (lisuride and TBG) were characterised using SH-SY5Y cells expressing recombinant human 5-HT2Areceptors. Measurements of signalling efficacy and bias were derived from dose-responses curves for each agonist, compared to 5-HT. Follow-up experiments sought to confirm the generality of findings using rat C6 cells expressing endogenous 5-HT2Areceptors.

Key Results

In SH-SY5Y cells, all psychedelics were partial agonists at both 5-HT2Areceptor signalling pathways and none showed significant signalling bias. In comparison, in SH-SY5Y cells the non-psychedelics lisuride and TBG were not distinguishable from psychedelics in terms of biased agonist properties, but both exhibited the lowest 5-HT2Areceptor signalling efficacy of all drugs tested, a result confirmed in C6 cells.

Conclusion and Implications

In summary, all psychedelics tested were unbiased, partial 5-HT2Areceptor agonists. Importantly, the non-psychedelics lisuride and TBG were discriminated from psychedelics, not through biased signalling but rather by relatively low efficacy. Thus, 5-HT2Areceptor signalling efficacy and not bias provides a possible explanation for why some 5-HT2Areceptor agonists are not psychedelic.
Central place foragers, prey depletion halos, and how behavioral niche partitioning promotes consumer coexistence
Authors: Rueffler Claus , Lehmann Laurent
Published: June 2024

Many seabirds congregate in large colonies for breeding, a time when they are central place foragers. An influential idea in seabird ecology posits that competition during breeding results in an area of reduced prey availability around colonies, a phenomenon known as Ashmole’s halo, and that this limits colony size. This idea has gained empirical support, including the finding that species coexisting within a colony might be able to do so by foraging on a single prey species but at different distances. Here, we provide a comprehensive mathematical model for central place foragers exploiting a single prey in a two-dimensional environment, where the prey distribution is the result of intrinsic birth and death, movement in space and mortality due to foraging birds (we also consider a variant tailored toward colonial social insects). Bird predation at different distances occurs according to an ideal free foraging distribution that maximizes prey delivery under flight and search costs. We fully characterize the birds’ ideal free distribution and the prey distribution it generates. Our results show that prey depletion halos around breeding colonies are a robust phenomenon and that the birds’ ideal free distribution is sensitive to prey movement. Furthermore, coexistence of several seabird species on a single prey easily emerges through behavioral niche partitioning whenever trait differences between species entail trade-offs between efficiently exploiting a scarce prey close to the colony and a more abundant prey far away. Such behavioral-based coexistence-inducing mechanism should generalize to other habitat and diet choice scenarios.

Significance statement

This study presents a mathematical model to explore the distribution of foraging trips among seabirds breeding on isolated islands, providing insight into the emergence of prey depletion halos around colonies. Our findings reveal that such halos are a robust feature of central place foraging, independent of prey dynamics. Additionally, the model shows that trait-mediated niche partitioning promotes coexistence among species through behavioral segregation into different circular zones around the island. This partitioning occurs despite a shared preference to forage close to the island, where flight costs are lowest. The study advances understanding of ecological coexistence mechanisms and suggests broader applicability to other predator-prey systems beyond seabird ecology, offering a new perspective on community assembly under shared preferences.
Confinement modulates axial patterning in regenerating Hydra
Authors: Maroudas-Sacks Yonit , Garion Liora , Suganthan S , Popović Marko , Keren Kinneret
Published: June 2024

The establishment of the body plan is a major step in animal morphogenesis. The role of mechanical forces and feedback in patterning the body plan remains unclear. Here we explore this question, by studying regenerating Hydra tissues confined in narrow cylindrical channels which constrain their morphology. We find that frustration between the orientation of the channel and the inherited axis in the regenerating tissues can lead to the formation of a multiaxial body plan. The morphological outcome is directly related to the pattern of nematic topological defects that emerges in the organization of the supracellular actomyosin fibers. When the inherited axis, which can be read out from the initial alignment of the supracellular fibers in the confined spheroid, is parallel to the channel’s axis, the tissue regenerates normally into animals with a single body axis aligned with the channel. However, regenerating spheroids that are confined in a frustrated perpendicular configuration often develop excess defects (including negatively-charged -½ defects) and regenerate into multiaxial morphologies. The influence of mechanical constraints on the regenerated body plan argues against an axial patterning mechanism that is based solely on inherited gradients of biochemical morphogens. We further show that the dependence of the regeneration outcomes on the initial tissue orientation can be recapitulated by a biophysical model which considers the coupled dynamics of the nematic organization of the actomyosin fibers and a morphogen concentration field, incorporating a mechanochemical feedback loop involving strain-dependent morphogen production at defect sites.
Lifestyle factors in the biomedical literature: An ontology and comprehensive resources for named entity recognition
Authors: Nourani Esmaeil , Koutrouli Mikaela , Xie Yijia , Vagiaki Danai , Pyysalo Sampo , Nastou Katerina , Brunak Søren , Juhl Jensen Lars
Published: June 2024

Motivation

Despite lifestyle factors (LSFs) being increasingly acknowledged in shaping individual health trajectories, particularly in chronic diseases, they have still not been systematically described in the biomedical literature. This is in part because no named entity recognition (NER) system exists, which can comprehensively detect all types of LSFs in text. The task is challenging due to their inherent diversity, lack of a comprehensive LSF classification for dictionary-based NER, and lack of a corpus for deep learning-based NER.

Results

We present a novel Lifestyle Factor Ontology (LSFO), which we used to develop a dictionarybased system for recognition and normalization of LSFs. Additionally, we introduce a manually annotated corpus for LSFs (LSF200) suitable for training and evaluation of NER systems, and use it to train a transformer-based system. Evaluating the performance of both NER systems on the corpus revealed an F-score of 64% for the dictionary-based system and 76% for the transformer-based system. Largescale application of these systems on PubMed abstracts and PMC Open Access articles identified over 300 million mentions of LSF in the biomedical literature.

Availability

LSFO, the annotated LSF200 corpus, and the detected LSFs in PubMed and PMC-OA articles using both NER systems, are available under open licenses via the following GitHub repository:https://github.com/EsmaeilNourani/LSFO-expansion. This repository contains links to two associated GitHub repositories and a Zenodo project related to the study. LSFO is also available at BioPortal:https://bioportal.bioontology.org/ontologies/LSFO.

Contact

katerina.nastou@cpr.ku.dk,soren.brunak@cpr.ku.dk,lars.juhl.jensen@cpr.ku.dk

Supplementary information

Supplementary data are available atBioinformaticsonline.
Wavenumber-dependent transmission of subthreshold waves on electrical synapses network model ofCaenorhabditis elegans
Authors: Chang Iksoo , Chung Taegon , Kim Sangyeol
Published: June 2024

Recent experimental studies showed that electrically coupled neural networks like in mammalian inferior olive nucleus generate synchronized rhythmic activity by the subthreshold sinusoidal-like oscillations of the membrane voltage. Understanding the basic mechanism and its implication of such phenomena in the nervous system bears fundamental importance and requires preemptively the connectome information of a given nervous system. Inspired by these necessities of developing a theoretical and computational model to this end and, however, in the absence of connectome information for the inferior olive nucleus, here we investigated interference phenomena of the subthreshold oscillations in the reference systemCaenorhabditis elegansfor which the structural anatomical connectome was completely known recently. We evaluated how strongly the sinusoidal wave was transmitted between arbitrary two cells in the model network. The region of cell-pairs that are good at transmitting waves changed according to the wavenumber of the wave, for which we named a wavenumber-dependent transmission map. Also, we unraveled that 1) the transmission of all cell-pairs disappeared beyond a threshold wavenumber, 2) long-distance and regular patterned transmission existed in the body-wall muscles part of the model network, and 3) major hub cell-pairs of the transmission were identified for many wavenumber conditions. A theoretical and computational model presented in this study provided fundamental insight for understanding how the multi-path constructive/destructive interference of the subthreshold oscillations propagating on electrically coupled neural networks could generate wavenumber-dependent synchronized rhythmic activity.
Chaperone-mediated heterotypic phase separation regulates liquid-to-solid phase transitions into amyloid fibrils
Authors: Rai Sandeep K. , Khanna Roopali , Sarbahi Anusha , Joshi Ashish , Mukhopadhyay Samrat
Published: June 2024

Biomolecular condensates formed via the phase separation of proteins and nucleic acids are thought to regulate a myriad of cellular processes with exquisite spatiotemporal precision. However, such highly dynamic, viscoelastic, mesoscopic, intracellular membraneless bodies can undergo aberrant liquid-to-solid transitions into a range of amyloid-like species. The formation of such pathological assemblies necessitates their clearance by the cellular protein quality control machinery comprising molecular chaperones. Nonetheless, the mechanism underlying the chaperone-mediated regulation of protein homeostasis within biomolecular condensates remains elusive. Here, we present a unique case demonstrating that a heat shock protein 40 (Hsp40), Ydj1, promotes the heterotypic phase separation of intrinsically disordered tau via intermolecular electrostatic and hydrophobic interactions. Through a diverse array of tools involving high-resolution fluorescence imaging, single-droplet steady-state and picosecond time-resolved fluorescence anisotropy, and single-molecule FRET (Förster resonance energy transfer), we elucidate the diverse structural conformations of tau present within phase-separated heterotypic condensates that are otherwise predisposed to aggregation. Our vibrational Raman spectroscopy and electron microscopy data show that the presence of Ydj1 in tau-Ydj1 condensates abolishes the formation of amyloid fibrils, unlike tau-only droplets. By sequentially deleting segments, we identify amyloidogenic hexapeptide motifs located in the hydrophobic microtubule-binding region of tau that foster contacts with the peptide-binding regions of Ydj1, promoting the formation of tau-Ydj1 binary condensates. Additionally, we show that the underlying network of interactions governing these condensates can be further tuned by RNA. Our results underscore an intriguing interplay of molecular drivers that govern chaperone-associated phase separation, with broader implications for the chaperoning of a wide range of intrinsically disordered proteins involved in physiology and disease.
Phylogenomics of the North American Desert RadiationLinanthus(Polemoniaceae) Reveals Mixed Trait Lability and No Single Geographic Mode of Speciation
Authors: Anghel Ioana G. , Smith Lydia L. , Lichter-Marck Isaac H. , Zapata Felipe
Published: June 2024

Premise

Understanding how arid-adapted plants have diversified in harsh environments is a central question in evolutionary biology.Linanthus(Polemoniaceae) occurs in biodiverse dry areas of Western North America and exhibits extensive floral trait variation, multiple color polymorphisms, differences in blooming time, and variation in life history strategies. Here, we reconstruct the evolutionary history of this group.

Methods

We generated restriction-site associated (ddRAD) sequences for 180 individuals and target capture (TC) sequences for 63 individuals, with complete species sampling. Using maximum likelihood and pseudo-coalescent approaches, we inferred phylogenies ofLinanthusand used these phylogenies to model the evolution of phenotypic traits and investigate the geographic speciation history of this genus.

Key results

Shallow relationships are consistent and well supported with both ddRAD and TC data. Most species are monophyletic despite rampant local sympatry and range overlap, suggesting strong isolating barriers. The non-monophyly of some species is possibly due to rapid speciation or issues with current species delimitation. Perenniality likely evolved from annuality, a rare shift in angiosperms. Night blooming evolved three times independently. Flower color polymorphism is an evolutionarily labile trait and is likely ancestral. No single geographic mode of speciation characterizes the radiation but most species overlap in range, suggesting they evolved in parapatry.

Conclusions

Our results illustrate the complexity of phylogenetic inference for recent radiations, even with multiple sources of genomic data and extensive sampling. This analysis provides a foundation to understand aridity adaptations, such as evolution of flower color polymorphisms, night blooming, and perenniality, as well as speciation mechanisms.
Towards measurements of absolute membrane potential in Bacillus subtilis using fluorescence lifetime
Authors: Roy Debjit , Michalet Xavier , Miller Evan W. , Bharadwaj Kiran , Weiss Shimon
Published: June 2024

Membrane potential (MP) changes can provide a simple readout of bacterial functional and metabolic state or stress levels. While several optical methods exist for measuring fast changes in MP in excitable cells, there is a dearth of such methods for absolute and precise measurements of steady-state membrane potentials (MPs) in bacterial cells. Conventional electrode-based methods for the measurement of MP are not suitable for calibrating optical methods in small bacterial cells. While optical measurement based on Nernstian indicators have been successfully used, they do not provide absolute or precise quantification of MP or its changes. We present a novel, calibrated MP recording approach to address this gap. In this study, we used a fluorescence lifetime-based approach to obtain a single-cell resolved distribution of the membrane potential and its changes upon extracellular chemical perturbation in a population of bacterial cells for the first time. Our method is based on (i) a unique VoltageFluor (VF) optical transducer, whose fluorescence lifetime varies as a function of MP via photoinduced electron transfer (PeT) and (ii) a quantitative phasor-FLIM analysis for high-throughput readout. This method allows MP changes to be easily visualized, recorded and quantified. By artificially modulating potassium concentration gradients across the membrane using an ionophore, we have obtained aBacillus subtilis-specific MP versus VF lifetime calibration and estimated the MP for unperturbedB. subtiliscells to be −65 mV (in MSgg), −127 mV (in M9) and that for chemically depolarized cells as −14 mV (in MSgg). We observed a population level MP heterogeneity of ∼6-10 mV indicating a considerable degree of diversity of physiological and metabolic states among individual cells. Our work paves the way for deeper insights into bacterial electrophysiology and bioelectricity research.