bluuebunny/crossref_metadata_2025 huggingface dataset:
Acceptability and Usability of Self-Sampling for the Detection of Sexually Transmitted Infections Among Transgender Women: The TransOdara Multicentric Study in Brazil
Authors: McCartney Daniel Jason , Bassichetto Katia Cristina , Leal Andrea Fachel , Knauth Daniela , Dourado Inês , Magno Laio , Carvalho da Silva Roberto José , Mayaud Philippe , Veras Maria Amélia ,   for the TransOdara Research Group
Published: March 2024

Background

The effective testing of sexually transmitted infections (STIs) requires sampling from potential infection sites. This study aimed to assess the choice, satisfaction, and performance of self-collected samples (SCS) from potential infection sites for STI testing among transgender women in Brazil.

Methods

TransOdara was a multicentric, cross-sectional STI prevalence study conducted in 5 Brazilian cities. Using respondent-driven sampling, 1317 transgender women 18 years or older were recruited. Participants completed interviewer-led questionnaires and provided swab samples from multiple sites (anorectal, oropharyngeal, genital) for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and human papillomavirus (HPV) testing. Participants were given a choice of SCS or provider-collected samples (PCS) at each site.

Results

Most participants selected SCS for anorectal (74.9%; 95% confidence interval [CI], 72.4–77.3) and genital (72.7%; 95% CI, 70.2–75.1) sites, whereas fewer chose for oropharyngeal samples (49.8%; 95% CI, 47.0–52.6). For future testing, most participants expressed a preference for SCS for genital (72.2%; 95% CI, 69.5–74.7) and anorectal (70.2%; 95% CI, 67.6–72.7) sites. There was no significant difference in the positive test results for CT and NG between SCS and PCS at anorectal and oropharyngeal sites, or for HPV at anorectal and genital (penile or neovaginal) sites.

Conclusions

This study demonstrated a high level of acceptability and usability of self-sampling for STI testing among transgender women. A preference for SCS was evident at the anorectal and genital sites, and the results of SCS were comparable to those of PCS. The findings suggest that multisite STI testing utilizing self-collection methods as a provided option can be effectively integrated into sexual health services for transgender women.
Extragenital Sexually Transmitted Infections Among High-Risk Men Who Have Sex With Men in Johannesburg, South Africa
Authors: Dias Bianca Da Costa , Sekgele Windy , Nhlapo Duduzile , Mahlangu Mahlape P. , Venter Johanna M.E. , Maseko Dumisile V. , Müller Etienne E. , Greeves Maurice , Botha Paul , Radebe Frans , Kufa Tendesayi , Kularatne Ranmini S.
Published: March 2024

Background

In South Africa, extragenital etiological sexually transmitted infection (STI) screening among men who have sex with men (MSM) is not routinely available. We aimed to determine the prevalence of STI pathogens at rectal and pharyngeal sites, syphilis seroprevalence, and associated risk factors among a selection of high-risk MSM without symptomatic urethritis attending a men's health clinic in Johannesburg, South Africa.

Methods

A cross-sectional study was conducted in 2022. Enrolled clients self-reported demographic, sexual behavioral risks, and clinical information. Client or clinician-collected rectal and pharyngeal swabs were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis. C. trachomatis–positive rectal samples were reflex tested for lymphogranuloma venereum. Blood specimens were screened for syphilis. Univariate and multivariate regression models were used to determine factors independently associated with the presence of an extragenital STI or syphilis.

Results

Among the 97 participants (median age, 29 years), 24.7% had an extragenital STI and 9.4% had high nontreponemal antibody titers (rapid plasma reagin ≥1:16). Rectal STIs were detected in 26.4% participants: N. gonorrhoeae (14.3%), C. trachomatis (9.9%), and M. genitalium (5.5%). Pharyngeal STIs were less prevalent (4.1%). Overall, the prevalence of any STI was 41%. Sex under the influence of drugs (adjusted odds ratio, 4.94; 95% confidence interval, 1.56–15.69) and engaging in condomless receptive anal intercourse with a casual partner (adjusted odds ratio, 8.36; 95% confidence interval, 1.73–40.28) were independent risk factors for having an extragenital STI.

Conclusions

The high burden of extragenital STIs and active syphilis in asymptomatic MSM underscores the importance of routine etiological screening in this key population, as the syndromic approach would not enable detection or treatment of these infections.
Low-Acuity Pediatric Emergency Department Utilization
Authors: Ziemnik Lisa , Parker Noah , Bufi Kyra , Waters Kristen , Almeda Jacob , Stolfi Adrienne
Published: March 2024

Objectives

Proper emergency department (ED) utilization is a hallmark of population health. Emergency department overcrowding due to nonurgent visits causes increased stress to healthcare staff, higher costs, and longer wait times for more urgent cases. This study sought to better understand post pandemic reasons caregivers have when bringing in their children for nonurgent visits and devise effective interventions to improve caregiver choice for non-ED care for nonurgent conditions.

Methods

Surveys were conducted at an urban pediatric hospital for Emergency Severity Index (ESI) level 3 to 5 visits. A total of 602 surveys were completed with 8 being excluded from analysis. Survey responses and anonymized demographic information were collected. Responses were compared between surveys grouped by respondent age category, relation to child, child's race, insurance type, and ESI levels.

Results

Primary reasons given for nonurgent ED visits were perceived urgency (74.2%, n = 441), ED superiority to other locations (23.9%, n = 142), and referral to the ED by a third party (17.7%, n = 105). Of those who cited perceived urgency as a reason, 80.5% (n = 355) wanted to lessen their child's pain/discomfort as soon as possible, but only 13.6% said that their child was too ill to be seen anywhere else (n = 60). Demographic differences occurred in the proportions of respondents citing some of the primary and secondary reasons for bringing their child to the ED.

Conclusions

This study highlights 3 key findings. An immediate desire for care plays a key role in caregiver decision making for low-acuity visits. There is potential socioeconomic and racial bias in where care is recommended that needs to be further explored in this region. Cross community interventions that target key reasons for seeking low-acuity care have the highest likelihood of impacting the use of the ED for low-acuity conditions.
Evolution of Intravenous Medication Errors and Preventive Systemic Defenses in Hospital Settings—A Narrative Review of Recent Evidence
Authors: Kuitunen Sini , Airaksinen Marja , Holmström Anna-Riia
Published: March 2024

Objectives

Intravenous drug administration has been associated with severe medication errors in hospitals. The present narrative review is based on a systematic literature search, and aimed to describe the recent evolution in research on systemic causes and defenses in intravenous medication errors in hospitals.

Methods

This narrative review was based on Reason’s theory of systems-based risk management. A systematic literature search covering the period from June 2016 to October 2021 was conducted on Medline (Ovid). We used the search strategy and selection criteria developed for our previous systematic reviews. The included articles were analyzed and compared to our previous reviews.

Results

The updated search found 435 articles. Of the 63 included articles, 16 focused on systemic causes of intravenous medication errors, and 47 on systemic defenses. A high proportion (n = 24, 38%) of the studies were conducted in the United States or Canada. Most of the studies focused on drug administration (n = 21/63, 33%) and preparation (n = 19/63, 30%). Compared to our previous review of error causes, more studies (n = 5/16, 31%) utilized research designs with a prospective risk management approach. Within articles related to systemic defenses, smart infusion pumps remained most widely studied (n = 10/47, 21%), while those related to preparation technologies (n = 7/47, 15%) had increased.

Conclusions

This narrative review demonstrates a growing interest in systems-based risk management for intravenous drug therapy and in introducing new technology, particularly smart infusion pumps and preparation systems, as systemic defenses. When introducing new technologies, prospective assessment and continuous monitoring of emerging safety risks should be conducted.
Khmer translation and cultural adaptation of the Locomotor Capabilities Index-5
Authors: Ramstrand Nerrolyn , Maddock Alan , Heang Thearith , Ean Nil , Kheng Sisary
Published: March 2024

Background:

Mobility is a major goal of prosthetic and orthotic rehabilitation, and use of outcome measures to evaluate mobility is necessary for good clinical practice. To support the use of outcome measures worldwide, work is needed to translate relevant instruments and adapt them for use in multiple cultures.

Objectives:

The objective of this research was to use a standardized method to translate the Locomotor Capabilities Index-5 (LCI-5) into Khmer, the national language in Cambodia, and to evaluate its cultural integrity by assessing it with a group of prosthesis and orthosis users.

Study design:

Instrument translation and cultural validation.

Methods:

Two forward translations of the LCI-5 were produced and then reconciled into a single document. The Khmer version was back translated into English, and a group of experts reviewed the back translation. Two rounds of cognitive interviews were conducted with lower-limb prosthetic and orthotic users who provided feedback.

Results:

During the reconciliation process, minor changes were made to 6 of the 14 items. Changes were most often made to better reflect the conceptual meaning of the original English version. Cognitive interviews resulted in the addition of a new response alternative.

Conclusions:

Use of a standardized method to translate the LCI-5 resulted in a linguistically and culturally valid Khmer version of the instrument. Following appropriate psychometric testing, this instrument will facilitate measurement of mobility in prosthetic and orthotic clinical practice in Cambodia as well as support national and multinational research.
Identifying Implementation Determinants and Strategies for Long-Acting Injectable Cabotegravir-Rilpivirine in People with HIV Who Are Virally Unsuppressed
Authors: Hickey Matthew D. , Grochowski Janet , Mayorga-Munoz Francis , Oskarsson Jon , Imbert Elizabeth , Spinelli Matthew , Szumowski John D. , Appa Ayesha , Koester Kimberly , Dauria Emily F. , McNulty Moira , Colasanti Jonathan , Havlir Diane V , Gandhi Monica , Christopoulos Katerina A.
Published: March 2024

Background:

Early evidence suggests long-acting injectable cabotegravir and rilpivirine (LA-CAB/RPV) may be beneficial for people with HIV (PWH) who are unable to attain viral suppression (VS) on oral therapy. Limited guidance exists on implementation strategies for this population.

Setting:

Ward 86, a clinic serving publicly insured PWH in San Francisco

Methods:

We describe multi-level determinants of and strategies for LA-CAB/RPV implementation for PWH without VS, using the Consolidated Framework for Implementation Research. To assess patient and provider-level determinants, we drew on pre-implementation qualitative data. To assess inner and outer context determinants, we undertook a structured mapping process.

Results:

Key patient-level determinants included perceived ability to adhere to injections despite oral adherence difficulties and care engagement challenges posed by unmet subsistence needs; strategies to address these determinants included a direct-to-inject approach, small financial incentives, and designated drop-in days. Provider-level determinants included lack of time to obtain LA-CAB/RPV, assess injection response, and follow-up late injections; strategies included centralizing eligibility review with the clinic pharmacist, a pharmacy technician to handle procurement and monitoring, regular multidisciplinary review of patients, and development of a clinic protocol. Ward 86 did not experience many outer context barriers due to rapid and unconstrained inclusion of LA-CAB/RPV on local formularies and ability of its affiliated hospital pharmacy to stock the medication.

Conclusion:

Multi-level strategies to support LA-CAB/RPV implementation for PWH without VS are required, which may necessitate additional resources in some settings to implement safely and effectively. Advocacy to eliminate outer-context barriers, including prior authorizations and specialty pharmacy restrictions, is needed.
Treatment of Bone Metastases of Breast Cancer With 177Lu-DOTA-IBA
Authors: Deng Jia , Yang Jian , Cheng Zixuan , Chen Yue
Published: March 2024

Bone metastasis of breast cancer often presents as osteolytic. 177Lu-DOTA-ibandronic acid (177Lu-DOTA-IBA) is a new radioactive drug for bone metastasis lesion. We report a case of recurrent intermittent pain due to bone metastasis, who demonstrated a satisfactory therapy response after 2 cycles of 177Lu-DOTA-IBA. In addition, the patient did not have any observable adverse effects.
Enchondroma on Bone Scan and PSMA PET/CT in a Patient With Prostate cancer
Authors: DeSai Charisma , Flynt Lesley , Tewari Sanjit Om , Lu Yang
Published: March 2024

A 54-year-old man with Gleason 9 prostate cancer with reported nodal and skeletal metastases was referred to us. Outside hospital reports described abnormal left proximal humerus activity on bone scan concerning for metastasis; however, concurrent PSMA PET/CT did not show activity in this lesion. Further review of the PET/CT images revealed characteristic features of enchondroma in the left humeral lesion.
Mandibular Body Osteotomy Combined with Sagittal Split Ramus Osteotomy for the Treatment of Severe Skeletal Class Ⅲ Malocclusion with Ankylosed Teeth
Authors: Zhong Yuhao , Qin Zhenyao , Wu Guomin
Published: March 2024

This study presents a combination of 2 different surgery procedures performed on the mandible as part of the treatment aiming to improve the facial profile and occlusal function of patients with severe skeletal class Ⅲ malocclusion and bilateral edentulous gaps. The teeth next to the edentulous gaps were found to be ankylosed. Mandibular setback by bilateral sagittal split ramus osteotomies and mandibular body osteotomies, combined with Le Fort Ⅰ level maxillary advancement were performed, since the chief complaint of the patient was a concave profile. As a result, the skeletal class Ⅲ malocclusion had been corrected, a satisfying facial profile had been achieved, and no apparent adverse effect was found. Thus, it has been proved that the combination of sagittal split ramus osteotomy and mandibular body osteotomy is available for correcting skeletal class Ⅲ malocclusion.
An initiative to assess and improve the resources and patient care processes used among Chest Wall Injury Society collaborative centers study (CWIS-CC2)
Authors: Eriksson Evert A. , Waite Amanda , Whitbeck SarahAnn S. , Bach John A. , Bauman Zachary M. , Cavlovic Lindsey , Dale Kate , DeVoe William B. , Doben Andrew R. , Edwards John G. , Forrester Joseph D. , Kaye Adam J. , Green John M. , Hsu Jeremy , Hufford Andrea , Janowak Christopher F. , Kartiko Susan , Moore Ernest E. , Patel Bhavik , Pieracci Fredric , Sarani Babak , Schubl Sebastian D. , Semon Gregory , Thomas Bradley W. , Tung Jamie , Van Lieshout Esther M.M. , White Thomas W. , Wijffels Mathieu M.E. , Wullschleger Martin E.
Published: March 2024

BACKGROUND

Over the last two decades, the acute management of rib fractures has changed significantly. In 2021, the Chest Wall injury Society (CWIS) began recognizing centers that epitomize their mission as CWIS Collaborative Centers. The primary aim of this study was to determine the resources, surgical expertise, access to care, and institutional support that are present among centers.

METHODS

A survey was performed including all CWIS Collaborative Centers evaluating the resources available at their hospital for the treatment of patients with chest wall injury. Data about each chest wall injury center care process, availability of resources, institutional support, research support, and educational offerings were recorded.

RESULTS

Data were collected from 20 trauma centers resulting in an 80% response rate. These trauma centers were made up of 5 international and 15 US-based trauma centers. Eighty percent (16 of 20) have dedicated care team members for the evaluation and management of rib fractures. Twenty-five percent (5 of 20) have a dedicated rib fracture service with a separate call schedule. Staffing for chest wall injury clinics consists of a multidisciplinary team: with attending surgeons in all clinics, 80% (8 of 10) with advanced practice providers and 70% (7 of 10) with care coordinators. Forty percent (8 of 20) of centers have dedicated rib fracture research support, and 35% (7 of 20) have surgical stabilization of rib fracture (SSRF)–related grants. Forty percent (8 of 20) of centers have marketing support, and 30% (8 of 20) have a web page support to bring awareness to their center. At these trauma centers, a median of 4 (1–9) surgeons perform SSRFs. In the majority of trauma centers, the trauma surgeons perform SSRF.

CONCLUSION

Considerable similarities and differences exist within these CWIS collaborative centers. These differences in resources are hypothesis generating in determining the optimal chest wall injury center. These findings may generate several patient care and team process questions to optimize patient care, patient experience, provider satisfaction, research productivity, education, and outreach.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level V.
Multipad agarose plate: a rapid and high-throughput approach for antibiotic susceptibility testing
Authors: Kals Morten , Mancini Leonardo , Kotar Jurij , Donald Allen , Cicuta Pietro
Published: March 2024

We describe a phenotypic antibiotic susceptibility testing (AST) method that can provide an eightfold speed-up in turnaround time compared with the current clinical standard by leveraging advances in microscopy and single-cell imaging. A newly developed growth plate containing 96 agarose pads, termed the multipad agarose plate (MAP), can be assembled at low cost. Pads can be prepared with dilution series of antibiotics. Bacteria are seeded on the pads and automatically imaged using brightfield microscopy, with a fully automated segmentation pipeline quantifying microcolony formation and growth rate. Using a test set of nine antibiotics with very different targets, we demonstrate that accurate minimum inhibitory concentration (MIC) measurements can be performed based on the growth rate of microcolonies within 3 h of incubation with the antibiotic when started from exponential phase. Faster, reliable and high-throughput methods for AST, such as MAP, could improve patient care by expediting treatment initiation and alleviating the burden of antimicrobial resistance.
A model free method of predicting transient dynamics in anaerobic digestion
Authors: Heggerud Christopher M. , Hastings Alan
Published: March 2024

Transient dynamics pose unique challenges when dealing with predictions and management of ecological systems yet little headway has been made on understanding when an ecological system might be in a transient state. As a start we consider a specific model, here focusing on a canonical model for anaerobic digestion. Through a series of simplifications, we analyse the potential of the model for transient dynamics, and the driving mechanisms. Using a stochastic analogue of this model, we create synthetic ecological data. Thus, combining our understanding of the deterministic transient dynamics with the use of empirical dynamical modelling, we propose several new metrics to indicate when the synthetic time series is leaving a transient state.
Transfemoral prosthetic simulators versus amputees: ground reaction forces and spatio-temporal parameters in gait
Authors: Kobayashi Toshiki , Jor Abu , He Yufan , Hu Mingyu , Koh Mark W. P. , Hisano Genki , Hara Takeshi , Hobara Hiroaki
Published: March 2024

This study aimed to compare the ground reaction forces (GRFs) and spatio-temporal parameters as well as their asymmetry ratios in gait between individuals wearing a transfemoral prosthetic simulator (TFSim) and individuals with unilateral transfemoral amputation (TFAmp) across a range of walking speeds (2.0–5.5 km h
−1
). The study recruited 10 non-disabled individuals using TFSim and 10 individuals with unilateral TFAmp using a transfemoral prosthesis. Data were collected using an instrumented treadmill with built-in force plates, and subsequently, the GRFs and spatio-temporal parameters, as well as their asymmetry ratios, were analysed. When comparing the TFSim and TFAmp groups, no significant differences were found among the gait parameters and asymmetry ratios of all tested metrics except the vertical GRFs. The TFSim may not realistically reproduce the vertical GRFs during the weight acceptance and push-off phases. The structural and functional variations in prosthetic limbs and components between the TFSim and TFAmp groups may be primary contributors to the difference in the vertical GRFs. These results suggest that TFSim might be able to emulate the gait of individuals with TFAmp regarding the majority of spatio-temporal and GRF parameters. However, the vertical GRFs of TFSim should be interpreted with caution.
Periodic finite-band solutions to the focusing nonlinear Schrödinger equation by the Fokas method: inverse and direct problems
Authors: Shepelsky Dmitry , Karpenko Iryna , Bogdanov Stepan , Prilepsky Jaroslaw E.
Published: March 2024

We consider the Riemann–Hilbert (RH) approach to the construction of periodic finite-band solutions to the focusing nonlinear Schrödinger (NLS) equation. An RH problem for the solution of the finite-band problem has been recently derived via the Fokas method (Deconincket al.2021Lett. Math. Phys.111, 1–18. (doi:10.1007/s11005-021-01356-7); Fokas & Lenells. 2021Proc. R. Soc. A477, 20200605. (doi:10.1007/s11005-021-01356-7)) Building on this method, a finite-band solution to the NLS equation can be given in terms of the solution of an associated RH problem, the jump conditions for which are characterized by specifying the endpoints of the arcs defining the contour of the RH problem and the constants (so-called phases) involved in the jump matrices. In our work, we solve the problem of retrieving the phases given the solution of the NLS equation evaluated at a fixed time. Our findings are corroborated by numerical examples of phases computation, demonstrating the viability of the method proposed.
Different currencies for calculating resource phenology result in opposite inferences about trophic mismatches
Authors: Versluijs Tom S. L. , Zhemchuzhnikov Mikhail K. , Kutcherov Dmitry , Roslin Tomas , Schmidt Niels Martin , van Gils Jan A. , Reneerkens Jeroen
Published: March 2024

Shifts in phenology are among the key responses of organisms to climate change. When rates of phenological change differ between interacting species they may result in phenological asynchrony. Studies have found conflicting patterns concerning the direction and magnitude of changes in synchrony, which have been attributed to biological factors. A hitherto overlooked additional explanation are differences in the currency used to quantify resource phenology, such as abundance and biomass. Studying an insectivorous bird (the sanderling) and its prey, we show that the median date of cumulative arthropod biomass occurred, on average, 6.9 days after the median date of cumulative arthropod abundance. In some years this difference could be as large as 21 days. For 23 years, hatch dates of sanderlings became less synchronized with the median date of arthropod abundance, but more synchronized with the median date of arthropod biomass. The currency-specific trends can be explained by our finding that mean biomass per arthropod specimen increased with date. Using a conceptual simulation, we show that estimated rates of phenological change for abundance and biomass can differ depending on temporal shifts in the size distribution of resources. We conclude that studies of trophic mismatch based on different currencies for resource phenology can be incompatible with each other.
Multi-trait diversification in marine diatoms in constant and warmed environments
Authors: Hinners Jana , Argyle Phoebe A. , Walworth Nathan G. , Doblin Martina A. , Levine Naomi M. , Collins Sinéad
Published: March 2024

Phytoplankton are photosynthetic marine microbes that affect food webs, nutrient cycles and climate regulation. Their roles are determined by correlated phytoplankton functional traits including cell size, chlorophyll content and cellular composition. Here, we explore patterns of evolution in interrelated trait values and correlations. Because both chance events and natural selection contribute to phytoplankton trait evolution, we used population bottlenecks to diversify six genotypes of Thalassiosirid diatoms. We then evolved them as large populations in two environments. Interspecific variation and within-species evolution were visualized for nine traits and their correlations using reduced axes (a trait-scape). Our main findings are that shifts in trait values resulted in movement of evolving populations within the trait-scape in both environments, but were more frequent when large populations evolved in a novel environment. Which trait relationships evolved was population-specific, but greater departures from ancestral trait correlations were associated with lower population growth rates. There was no single master trait that could be used to understand multi-trait evolution. Instead, repeatable multi-trait evolution occurred along a major axis of variation defined by several diatom traits and trait relationships. Because trait-scapes capture changes in trait relationships and values together, they offer an insightful way to study multi-trait variation.
Cancer invasion and anaerobic bacteria: new insights into mechanisms
Authors: Hurst Rachel , Brewer Daniel S. , Gihawi Abraham , Wain John , Cooper Colin S.
Published: March 2024

There is growing evidence that altered microbiota abundance of a range of specific anaerobic bacteria are associated with cancer, including Peptoniphilus spp., Porphyromonas spp., Fusobacterium spp., Fenollaria spp., Prevotella spp., Sneathia spp., Veillonella spp. and Anaerococcus spp. linked to multiple cancer types. In this review we explore these pathogenic associations. The mechanisms by which bacteria are known or predicted to interact with human cells are reviewed and we present an overview of the interlinked mechanisms and hypotheses of how multiple intracellular anaerobic bacterial pathogens may act together to cause host cell and tissue microenvironment changes associated with carcinogenesis and cancer cell invasion. These include combined effects on changes in cell signalling, DNA damage, cellular metabolism and immune evasion. Strategies for early detection and eradication of anaerobic cancer-associated bacterial pathogens that may prevent cancer progression are proposed.
A multi-colour fluorogenic tag and its application in Candida albicans
Authors: Devos Jonas , Van Dijck Patrick , Van Genechten Wouter
Published: March 2024

Fluorescent proteins (FPs) have always been a crucial part of molecular research in life sciences, including the research into the human fungal pathogen Candida albicans, but have obvious shortcomings such as their relatively large size and long maturation time. However, the next generation of FPs overcome these issues and rely on the binding of a fluorogen for the protein to become fluorescently active. This generation of FPs includes the improved version of Fluorescence activating and Absorption Shifting Tag (iFAST). The binding between the fluorogen and the iFAST protein is reversible, thus resulting in reversible fluorescence. The fluorogens of iFAST are analogues of 4-hydroxylbenzylidene-rhodanine (HBR). These HBR analogues differ in spectral properties depending on functional group substitutions, which gives the iFAST system flexibility in terms of absorbance and emission maxima. In this work we describe and illustrate the application of iFAST as a protein tag and its reversible multi-colour characteristics in C. albicans.
Surface-based Tractography uncovers ‘What’ and ‘Where’ Pathways in Prefrontal Cortex
Authors: Bedini Marco , Olivetti Emanuele , Avesani Paolo , Baldauf Daniel
Published: March 2024

The frontal eye field (FEF) and the inferior frontal junction (IFJ) are prefrontal regions that mediate top-down functions, with mounting neuroimaging evidence suggesting that they specialize in controlling spatial versus non-spatial processing, respectively. We hypothesized that their unique patterns of structural connectivity underlie these specialized roles. To accurately infer the localization of FEF and IFJ in standard space, we performed an activation likelihood estimation meta-analysis of fMRI paradigms that reliably targeted these regions. Using surface-based probabilistic tractography methods at the individual subject level, we tracked streamlines ipsilaterally from the inferred FEF and IFJ activation peaks to the dorsal and ventral visual streams mapped on the native white matter surface parcellated using the multimodal Glasser atlas. By contrasting FEF and IFJ connectivity likelihoods, we found predominant structural connectivity from the FEF to regions of the dorsal visual stream compared to the IFJ (particularly in the left hemisphere), and conversely, predominant structural connectivity from the IFJ to regions of the ventral visual stream compared to the FEF bilaterally. Additionally, we analyzed the cortical terminations of the superior longitudinal fasciculus to the FEF and IFJ, implicating its first and third branches as segregated pathways mediating their communication to the posterior parietal cortex. The structural connectivity fingerprints of the FEF and IFJ support the view that the two visual stream architectures extend to the posterior lateral prefrontal cortex and provide converging anatomical evidence of their specialization in spatial versus non-spatial control.
Mapping the distribution of seagrass meadows from space with deep convolutional neural networks
Authors: Giménez-Romero Àlex , Ferchichi Dhafer , Moreno-Spiegelberg Pablo , Sintes Tomàs , Matías Manuel A.
Published: March 2024

Seagrass meadows play a vital role in supporting coastal communities by promoting biodiversity, mitigating coastal erosion and contributing to local economies. These ecosystems face significant threats, including habitat loss and degradation or climate change. United Nations has recognized the urgency of conserving marine ecosystems, highlighting the need for evidence-based conservation strategies and high-quality monitoring. However, traditional monitoring approaches are often time-consuming, labor-intensive, and costly, limiting their scalability and effectiveness. The growing availability of remote sensing data coupled to the rise of machine learning technologies offer an unprecedented opportunity to develop autonomous, efficient and scalable monitoring systems. Despite many efforts, the development of such systems for seagrass meadows remains a challenge, with recent attempts presenting several limitations such as limited satellite imagery, inadequate metrics for evaluating model performance or insufficient ground truth data, leading to simple proof of concepts rather than useful solutions. Here, we overcome these limitations by developing a comprehensive framework to mapPosidonia oceanicameadows in the Mediterranean Sea using an extensive georeferenced habitat dataset and diverse satellite imagery for model training. We successfully evaluate the model generalization capability across different regions and provide the trained model for broader application in biodiversity monitoring and management.
An experimental study of free flight kinematics in a miniature parasitoid waspTrichogramma telengai
Authors: Lapina Nadezhda A. , Farisenkov Sergey E. , Shcherbakov Evgeny O. , Kolomenskiy Dmitry , Polilov Alexey A.
Published: March 2024

Body size is the major factor to the flight mechanics in animals. To fly at low Reynolds numbers, miniature insects have adaptations in kinematics and wing structure. Many microinsects have bristled wings, which reduce inertia and power requirements when providing good aerodynamic efficiency. But both bristled and membranous-winged microinsects fly at Reynolds numbers of about 10. Yet, the kinematics of the smallest known membranous-winged species have not been studied sufficiently. The available data are limited to the forewings of a relatively large parasitoid waspEncarsia formosa. We studied kinematics of wings and body and flight performance in one of the smallest membranous-winged wasps, Trichogramma telengai (0.5 mm body length,Re= 12).T. telengaireaches 29 cm s-1speed and 7 m s-2acceleration in horizontal flight which are comparable with the flight performance of other microinsects. The wingbeat cycle is characterized by high frequency (283 Hz) and stroke amplitude (149°) and includes U-shaped strokes at high angles of attack and prolonged clap-and-fling. The hindwings move with a slight phase shift and smaller amplitude than the forewings.T. telengaidiffers from large membranous-winged insects and miniature featherwing beetles in kinematics, but it is fundamentally similar toE. formosa(Re= 18, membranous wings) and thripsFrankliniella occidentalis(Re= 15, bristled wings). We showed that, atRe≈ 101, both membranous and bristled-winged insects have sufficient flight performance. Further study of the bristled-winged insects will make it possible to define the size limits of effectiveness of different wing structures.
Museomics ofCarabusgiant ground beetles shows an Oligocene origin andin situAlpine diversification
Authors: PAULI Marie T , GAUTHIER Jeremy , LABEDAN Marjorie , BLANC Mickael , BILAT Julia , TOUSSAINT Emmanuel F.A.
Published: March 2024

The development of museomics represents a major paradigm shift in the use of natural history collection specimens for systematics and evolutionary biology. New approaches in this field allow the sequencing of hundreds to thousands of loci from across the genome using historical DNA. HyRAD-X, a recently introduced capture method using bench-top designed probes, has proved very efficient for recovering genomic-scale datasets using natural history collection specimens. Using this technique at both the intra- and interspecific levels, we infer the most robust phylogeny to date for Arcifera, an ecologically and morphologically diverse clade ofCarabusgiant ground beetles. We successfully generated a genomic dataset of up to 1965 HyRAD-X loci for all described species, permitting inference of a robust dated phylogenomic tree for this clade. Our species delimitation and population genomic analyses suggest that the current classification for Arcifera is in line with its evolutionary history. Our results suggest an origin of Arcifera in the late Oligocene followed by speciation events during the warm mid-Miocene unlinked to Pleistocene glaciations. The dynamic paleogeographic history of the Palearctic region likely contributed to the diversification of this lineage with a relatively ancient colonization of the proto-Alps followed byin situspeciation where most species of Arcifera are currently found sometimes syntopically likely as a result of post-glaciations secondary contacts.
Discrete Time Modeling of Stock-Recruit Relationships with Life-History Stanzas
Authors: Frank Anna-Simone , Schaarschmidt Ute , Nash Richard D. M. , Subbey Sam
Published: March 2024

The stock-recruit relationship is a foundational concept in fisheries science, bridging the connection between parental populations (stock) and progeny (recruits). Traditional approaches describe this relationship using closedform analytical functions, which represent only a restricted subset of the broader class of possibilities. This paper advocates for a novel approach that integrates discrete time modeling with a life-history cycle framework, incorporating distinct stanzas and developmental processes. By breaking down the life cycle into identifiable stages, we capture the step-wise progression of life history traits and the factors influencing recruitment outcomes. Through numerical simulations, we explore the advantages of this approach, including complexity handling, dynamic behavior modeling, and scenario exploration. Our simulation results show that we are able to generate a broad spectrum of stock-recruit relationships (including the traditional ones), which best reflect variability observed in nature. We demonstrate how this framework allows for the identification of critical stages, and integration of various factors that influence recruitment. This holistic approach enhances our comprehension of the intricate interactions shaping stock-recruit relationships and advances our understanding of sustainable population dynamics.

Highlights

A novel multi-stage life-cycle model is presented.

Model simulations reveal three different Stock-Recruitment (SR) patterns.

Our approach contributes to enhanced understanding of SR relationships.
A Systematic Assessment of Robustness in CNS Safety Pharmacology
Authors: Reiber Maria , Stirling Helen , Ahuis Tim P. , Arias Washington , Aulehner Katharina , Dreßler Ute , Kas Martien J.H. , Kela Johanna , Kerker Kimberly , Kuosmanen Tarja , Lorenz Helga , Pennington Alexander T. , von Rüden Eva-Lotta , Schauerte Heike , Seiffert Isabel , Talbot Steven R. , Torturo Christina , Virtanen Sami , Waldron Ann-Marie , Ramboz Sylvie , Potschka Heidrun
Published: March 2024

Irwin tests are key preclinical study elements for characterizing drug-induced neurological side effects. This multicenter study aimed to assess the robustness of Irwin tests across multinational sites during three stages of protocol harmonization. The projects were part of the EQIPD framework (EnhancedQuality inPreclinicalData,https://quality-preclinical-data.eu/), aiming to increase success rates in transition from preclinical testing to clinical application. Female and male NMRI mice were assigned to one of three groups (vehicle, 0.1 mg/kg MK-801, 0.3 mg/kg MK-801). Irwin scores were assessed at baseline and multiple times following injection of MK-801, a non-competitive NMDA antagonist, using local protocols (stage 1), a shared protocol with harmonized environmental design (stage 2), and fully harmonized Irwin scoring protocols (stage 3). The analysis based on the four functional domains (motor, autonomic, sedation, and excitation) revealed substantial data variability in stages 1 and 2. Although there was still marked overall heterogeneity between sites in stage 3 after complete harmonization of the Irwin scoring scheme, heterogeneity was only moderate within functional domains. When comparing treatment groups vs. vehicle, we found large effect sizes in the motor domain and subtle to moderate effects in the excitation-related and autonomic domain. The pronounced interlaboratory variability in Irwin datasets for the CNS-active compound MK-801 needs to be carefully considered by companies and experimenters when making decisions during drug development. While environmental and general study design had a minor impact, the study suggests that harmonization of parameters and their scoring can limit variability and increase robustness.
Role of Posterior Medial Thalamus in the Modulation of Striatal Circuitry and Choice Behavior
Authors: Yonk Alex J. , Linares-García Ivan , Pasternak Logan , Juliani Sofia E. , Gradwell Mark A. , George Arlene J. , Margolis David J.
Published: March 2024

The posterior medial (POm) thalamus is heavily interconnected with sensory and motor circuitry and is likely involved in behavioral modulation and sensorimotor integration. POm provides axonal projections to the dorsal striatum, a hotspot of sensorimotor processing, yet the role of POm-striatal projections has remained undetermined. Using optogenetics with slice electrophysiology, we found that POm provides robust synaptic input to direct and indirect pathway striatal spiny projection neurons (D1- and D2-SPNs, respectively) and parvalbumin-expressing fast spiking interneurons (PVs). During the performance of a whisker-based tactile discrimination task, POm-striatal projections displayed learning-related activation correlating with anticipatory, but not reward-related, pupil dilation. Inhibition of POm-striatal axons across learning caused slower reaction times and an increase in the number of training sessions for expert performance. Our data indicate that POm-striatal inputs provide a behaviorally relevant arousal-related signal, which may prime striatal circuitry for efficient integration of subsequent choice-related inputs.
A basic framework governing splice-site choice in eukaryotes
Authors: Dent Craig I , Prodic Stefan , Balakrishnan Aiswarya , Georges James , Chhabra Aaryan , Mukherjee Sourav , Coutts Jordyn , Gitonobel Michael , Sarwade Rucha D , Rosenbluh Joseph , D’Amato Mauro , Das Partha P , Guo Ya-Long , Fournier-Level Alexandre , Burke Richard , Sureshkumar Sridevi , Powell David , Balasubramanian Sureshkumar
Published: March 2024

Changes in splicing are observed between cells, tissues, organs, individuals, and species. These changes can mediate phenotypic variation ranging from flowering time differences in plants to genetic diseases in humans. However, the genomic determinants of splicing variation are largely unknown. Here, we quantified the usage of individual splice-sites and uncover extensive variation between individuals (genotypes) in Arabidopsis, Drosophila and Humans. We used this robust quantitative measure as a phenotype and mapped variation in splice-site usage using Genome-Wide Association Studies (GWAS). By carrying out more than 130,000 GWAS with splice-site usage phenotypes, we reveal genetic variants associated with differential usage of specific splice-sites. Our analysis conclusively shows that most of the common, genetically controlled variation in splicing iscisand there are no majortranshotspots in any of the three analyzed species. High-resolution mapping allowed us to determine genome-wide patterns that govern splice-site choice. We reveal that the variability in the intronic hexamer sequence (GT[N]4or [N]4AG) differentiates intrinsic splice-site strength and is among the primary determinants of splice-site choice. Experimental analysis validates the primary role for intronic hexamer sequences in conferring splice-site decisions. Transcriptome analyses in diverse species across the tree of life reveals that hexamer rankings explains splice-site choices from yeast to plants to humans, forming the basic framework of the splicing code in eukaryotes.
Broad therapeutic benefit of myosin inhibition in hypertrophic cardiomyopathy
Authors: Sen-Martín Laura , Fernández-Trasancos Ángel , López-Unzu Miguel Á. , Pathak Divya , Ferrarini Alessia , Labrador-Cantarero Verónica , Sánchez-Ortiz David , Pricolo María Rosaria , Vicente Natalia , Velázquez-Carreras Diana , Sánchez-García Lucía , Nicolás-Ávila Jose Ángel , Sánchez-Díaz María , Schlossarek Saskia , Cussó Lorena , Desco Manuel , Villalba-Orero María , Guzmán-Martínez Gabriela , Calvo Enrique , Barriales-Villa Roberto , Vázquez Jesús , Sánchez-Cabo Fátima , Hidalgo Andrés , Carrier Lucie , Spudich James A. , Ruppel Kathleen M. , Alegre-Cebollada Jorge
Published: March 2024

Myosin inhibitor mavacamten is the only targeted treatment available for hypertrophic cardiomyopathy (HCM), a disease caused by hundreds of genetic variants that affect mainly sarcomeric myosin and its negative regulator cardiac myosin-binding protein C (cMyBP-C, encoded byMYBPC3). Here, we have examined whether the reported limited efficacy of mavacamten in a fraction of HCM patients can result from dissimilar HCM pathomechanisms triggered by different genetic variants, a scenario particularly relevant forMYBPC3-associated HCM. To this aim, we have generated knock-in mice including missense pathogenic variant cMyBP-C p.R502W, which, different from patients who carry truncations in the protein, develop progressive pathogenic myocardial remodeling in the absence of alterations of cMyBP-C levels and localization. Mechanistically, we find that mutation R502W reduces the binding affinity of cMyBP-C for myosin without inducing a shift towards more active myosin conformations as observed when cMyBP-C levels are reduced. Despite these diverging molecular alterations, we show that mavacamten blunts myocardial remodeling both in R502W and cMyBP-C-deficient, knock-out hearts. These beneficial effects are accompanied by improved tolerance to exercise only in R502W animals. Hence, our results indicate that myosin inhibition is effective to treat HCM caused by both truncating and missense variants inMYBPC3regardless of the primary pathomechanisms they elicit.
Primate V2 Receptive Fields Derived from Anatomically Identified Large-Scale V1 Inputs
Authors: Hassanpour Mahlega S , Merlin Sam , Federer Frederick , Zaidi Qasim , Angelucci Alessandra
Published: March 2024

In the primate visual system, visual object recognition involves a series of cortical areas arranged hierarchically along the ventral visual pathway. As information flows through this hierarchy, neurons become progressively tuned to more complex image features. The circuit mechanisms and computations underlying the increasing complexity of these receptive fields (RFs) remain unidentified. To understand how this complexity emerges in the secondary visual area (V2), we investigated the functional organization of inputs from the primary visual cortex (V1) to V2 by combining retrograde anatomical tracing of these inputs with functional imaging of feature maps in macaque monkey V1 and V2. We found that V1 neurons sending inputs to single V2 orientation columns have a broad range of preferred orientations, but are strongly biased towards the orientation represented at the injected V2 site. For each V2 site, we then constructed a feedforward model based on the linear combination of its anatomically-identified large-scale V1 inputs, and studied the response proprieties of the generated V2 RFs. We found that V2 RFs derived from the linear feedforward model were either elongated versions of V1 filters or had spatially complex structures. These modeled RFs predicted V2 neuron responses to oriented grating stimuli with high accuracy. Remarkably, this simple model also explained the greater selectivity to naturalistic textures of V2 cells compared to their V1 input cells. Our results demonstrate that simple linear combinations of feedforward inputs can account for the orientation selectivity and texture sensitivity of V2 RFs.
QuartPlotR: A quarternary phase diagram tool
Authors: Veluchamy Alaguraj , Bowler Chris
Published: March 2024

Motivation

Large scale studies involving exploratory data analysis and important key discoveries require platform that provides comprehensive visualization. Density distribution analysis across multiple datasets is intuitive and summarization, visualization could reveal several biological information. Integration and visualization of sequence and annotation features in the context of composition of genomic mutation, microbiota, population are significantly challenging.

Results

We propose a simple, novel strategy of visualization of multidimensional datasets involving multiple layers of data distribution which are interconnected. Also, we have implemented this phase diagram in an easy-to-use tool QuartPlotR, a resource for plotting charts from different genomic datasets. A generic data access and plotting framework has been designed and this is implemented as an R package.

Availability

https://github.com/AlagurajVeluchamy/QuartPlotR.

Contact

alaguraj.veluchamy@stjude.org

Supplementary information

Supplementary data are available atBioinformaticsonline.