bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of the psychomotor vigilance test to aid in the selection of risk controls in an air medical transport operation
Authors: Mollicone Daniel J , Kan Kevin , Coats Sara , Mott Christopher , van Wollen Matthew , Hatch Arvida , Gallagher Joseph , Williams Sheryl , Motzkin David
Published: January 2023

Study Objectives

This study evaluated the utility and ecological validity of the 3-minute psychomotor vigilance test (PVT) completed by safety-critical personnel in an air medical transport operation as part of a fatigue risk management program.

Methods

Crewmembers in an air medical transport operation self-administered an alertness assessment incorporating a 3-minute PVT at different time points during their duty schedule. The prevalence of alertness deficits was evaluated based on a failure threshold of 12 errors considering both lapses and false starts. To evaluate the ecological validity of the PVT, the relative frequency of failed assessments was evaluated relative to crewmember position, timing of the assessment within the duty schedule, time of day, and sleep quantity in the last 24 h.

Results

2.1% of assessments were associated with a failing PVT score. Crewmember position, timing of assessment within the duty shift, time of day, and sleep quantity in the last 24 h were found to affect the relative frequency of failed assessments. Obtaining less than 7–9 h of sleep was associated with systematic increases in the failure rate (F[1, 54 612] = 168.1, p < .001). Obtaining less than 4 h of sleep was associated with a frequency of a failed assessment 2.99 times higher than the frequency of a failed assessment when obtaining 7–9 h of sleep.

Conclusions

Results provide evidence for the utility and ecological validity of the PVT as well as the suitability of the PVT failure threshold to support fatigue risk management in safety-critical operations.
Mancozeb-induced hepatotoxicity: protective role of curcumin in rat animal model
Authors: Aprioku Jonah Sydney , Amamina Ayanabia Monica , Nnabuenyi Perpetua Amarachi
Published: January 2023

Background

Mancozeb—a widely used fungicide in the agricultural sector—is believed to cause toxicity by increasing oxidative stress. This work investigated the efficacy of curcumin in protecting mancozeb-induced hepatotoxicity.

Materials and Methods

Mature Wistar rats were assigned into 4 equal groups: control, mancozeb (30 mg/kg/day, ip), curcumin (100 mg/kg/day, po), and mancozeb+curcumin. The experiment lasted for 10 days.

Results

Our results reported that mancozeb elevated aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, gamma glutamyltranspeptidase enzyme activities, and total bilirubin level in plasma; and decreased total protein and albumin levels, compared with the control group (P < 0.05–0.001). Hepatic tissue levels of malondialdehyde, and advanced oxidation protein products were significantly increased; whereas activities of superoxide dismutase, catalase, glutathione peroxidase, as well as levels of reduced glutathione, vitamin C, and total protein were reduced (P < 0.05–0.001). Histopathological examination showed marked histological changes. Co-treatment with curcumin improved the antioxidant activity; reversed oxidative stress and biochemical changes; and restored most of the liver histo-morphological alterations; thus, attenuating the hepatic toxicities induced by mancozeb.

Conclusion

These results indicated that curcumin could protect against detrimental hepatic effects induced by mancozeb.
Emergence and pandemic spread of small ruminant lentiviruses
Authors: Carrozza Maria-Luisa , Niewiadomska Anna-Maria , Mazzei Maurizio , Abi-Said Mounir R , Hué Stéphane , Hughes Joseph , Gatseva Anna , Gifford Robert J
Published: January 2023

Small ruminant lentiviruses (SRLVs) cause chronic, persistent infections in populations of domestic sheep (Ovis aries) and goats (Capra hircus) worldwide. The vast majority of SRLV infections involve two genotypes (A and B) that spread in association with the emergence of global livestock trade. However, SRLVs have likely been present in Eurasian ruminant populations since at least the early Neolithic period. Here, we use phylogenetic and phylogeographic approaches to reconstruct the origin of pandemic SRLV strains and infer their historical pattern of global spread. We constructed an open computational resource (‘Lentivirus-GLUE’) via which an up-to-date database of published SRLV sequences, multiple sequence alignments (MSAs), and sequence-associated metadata can be maintained. We used data collated in Lentivirus-GLUE to perform a comprehensive phylogenetic investigation of global SRLV diversity. Phylogenies reconstructed from genome-length alignments reveal that the deep divisions in the SRLV phylogeny are consistent with an ancient split into Eastern (A-like) and Western (B-like) lineages as agricultural systems disseminated out of domestication centres during the Neolithic period. These findings are also consistent with historical and phylogeographic evidence linking the early 20th century emergence of SRLV-A to the international export of Central Asian Karakul sheep. Investigating the global diversity of SRLVs can help reveal how anthropogenic factors have impacted the ecology and evolution of livestock diseases. The open resources generated in our study can expedite these studies and can also serve more broadly to facilitate the use of genomic data in SRLV diagnostics and research.
“Nursing (Her) Storytelling”
Authors: Alameda-Cuesta Almudena , Blanco-Fuente Irene , Bonilla-Campos Amparo , Casado-Aparicio Elena , Domínguez-Castillo M. Pilar , García-Dauder Dau , Lara-Rodríguez Ángel Luis , López-Sáez Miguel Ángel , Velázquez-Berrio Nerea , Romero-Bachiller Carmen
Published: January 2023

The aim of this article is to share theoretical and methodological reflections on a project on feminist epistemologies and health activism. Based on the analysis of 12 life stories and 1 group interview, an approach based on ethnographic fiction is proposed through the creation of a serial story in podcast format. This approach helps in generating emotions to facilitate understanding and awareness of the issues raised and in showing everyday practices as ways of constructing knowledge. It also avoids turning life stories into academic artifacts with little transformational capacity.
Locating Culturally Safe Care in Narratives of Historical Trauma and Health in Guam
Authors: Joo-Castro Lucy , Emerson Amanda M.
Published: January 2023

We sought to understand contemporary health beliefs and practices of the CHamorus of Guam in the context of their perceptions of historical trauma. Narrative analysis of 20 story-eliciting interviews with 10 CHamoru adults identified stories of health and illness and living in-betweenness, wherein participants described navigation between health practices of Traditional and Western cultures in the centuries-long involvement with the colonizing culture. Those connections pointed to a conceptual third-space, informed by Homi Bhabha, in which historical trauma and the in-betweenness of Traditional and Western health open new possibilities of what culturally safe health care might look like for CHamorus.
Alliance for Innovation on Maternal Health
Authors: Hameed Afshan B. , Haddock Alison , Wolfe Diana S. , Florio Karen , Drummond Nora , Allen Christie , Taylor Isabel , Kendig Susan , Presumey-Leblanc Garssandra , Greenwood Emily
Published: January 2023

Cardiac conditions are the leading cause of pregnancy-related deaths and disproportionately affect non-Hispanic Black people. Multidisciplinary maternal mortality review committees have found that most people who died from cardiac conditions during pregnancy or postpartum were not diagnosed with a cardiovascular disease before death and that more than 80% of all pregnancy-related deaths, regardless of cause, were preventable. In addition, other obstetric complications, such as preeclampsia and gestational diabetes, are associated with future cardiovascular disease risk. Those with cardiac risk factors and those with congenital and acquired heart disease require specialized care during pregnancy and postpartum to minimize risk of preventable morbidity and mortality. This bundle provides guidance for health care teams to develop coordinated, multidisciplinary care for pregnant and postpartum people with cardiac conditions and to respond to cardio–obstetric emergencies. This bundle is one of several core patient safety bundles developed by the Alliance for Innovation on Maternal Health that provide condition- or event-specific clinical practices for implementation in appropriate care settings. The Cardiac Conditions in Obstetric Care bundle is organized into five domains: 1) Readiness, 2) Recognition and Prevention, 3) Response, 4) Reporting and Systems Learning, and 5) Respectful Care. This bundle is the first by the Alliance to be developed with the fifth domain of Respectful Care. The Respectful Care domain provides essential best practices to support respectful, equitable, and supportive care to all patients. Further health equity considerations are integrated into elements in each domain.
Anti-Müllerian Hormone Level Decline in Patients Undergoing Hysterectomy With and Without Oophorectomy Compared With Natural Menopause
Authors: Santoro Nanette , Flyckt Rebecca , Davis Anne , Finkelstein Joel , Crawford Sybil , Sun Fangbai , Derby Carol , Morrison Anthony , Sluss Patrick , Zhang Heping
Published: January 2023

OBJECTIVE:

To evaluate the relationship between hysterectomy with and without ovarian conservation and the onset of ovarian failure using anti-müllerian hormone (AMH) levels and imputed final menstrual period (FMP).

METHODS:

A total of 1,428 women with an observed FMP and 232 women who underwent hysterectomy (159 with bilateral salpingo-oophorectomy [BSO], 13 with one ovary conserved, and 60 with both ovaries conserved) and who had serial AMH measurements were included from SWAN (The Study of Women’s Health Across the Nation), a multi-ethnic, multi-site, community-based study. Anti-müllerian hormone levels were sampled annually with at least one presurgery or pre-FMP measurement at least one postsurgery or post-FMP measurement. Surgery-related differences in patterns of AMH levels with respect to surgery date or FMP were estimated using piecewise linear mixed modeling; differences in age at first undetectable AMH level were estimated using survival analyses.

RESULTS:

Patients with conservation of one or both ovaries or natural menopause demonstrated similar patterns of decline in AMH levels when anchored to surgery or FMP. Patients with hysterectomy (all types) had a later counterfactual FMP (52.9±0.2 SEM) compared with the observed FMP in those with natural menopause (52.1±0.1 years, P=.002). Those undergoing BSO had an immediate reduction in AMH level to undetectable after surgery.

CONCLUSION:

Hysterectomy does not lead to a more rapid decline in AMH levels postoperatively compared with natural menopause. Patients undergoing BSO have a rapid loss of AMH, consistent with complete removal of the ovaries. These data suggest that hysterectomy as currently performed does not compromise ovarian reserve.
Pharmacologic Interventions to Minimize Fluid Absorption at the Time of Hysteroscopy
Authors: Désilets Jade , Zakhari Andrew , Chagnon Miguel , Ekmekjian Taline , Nguyen Dong Bach , Smith Jessica Papillon , Mansour Fady W. , Krishnamurthy Srinivasan
Published: January 2023

OBJECTIVE:

To assess which interventions are effective in reducing fluid absorption at the time of hysteroscopy.

DATA SOURCE:

Ovid MEDLINE, Ovid EMBASE, PubMed (non-MEDLINE records only), EBM Reviews—Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Web of Science were searched from inception to February 2022 without restriction on language or geographic origin.

METHODS OF STUDY SELECTION:

Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, all English-language, full-text articles reporting fluid balance, with an intervention and comparator arm, were included. Title and abstract screening and full-text review were completed independently by two authors. Conflicts were resolved through discussion and consensus. Studies' risk of bias was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale for observational studies.

TABULATION, INTEGRATION, AND RESULTS:

The search identified 906 studies, 28 of which were eligible for inclusion, examining the following interventions: gonadotropin-releasing hormone (GnRH) agonist; ulipristal acetate; vasopressin; danazol; oxytocin; and local, general, and regional anesthesia. A significant reduction in mean fluid absorption was seen in patients preoperatively treated with danazol (−175.7 mL, 95% CI −325.4 to −26.0) and a GnRH agonist (−139.68 mL, 95% CI −203.2, −76.2) compared with patients in a control group. Ulipristal acetate and type of anesthesia showed no difference. Data on type of anesthesia and vasopressin use were not amenable to meta-analysis; however, four studies favored vasopressin over control regarding fluid absorption. Mean operative time was reduced after preoperative treatment with ulipristal acetate (−7.1 min, 95% CI −11.31 to −2.9), danazol (−7.5 min, 95% CI −8.7 to −6.3), and a GnRH agonist (−3.3 min, 95% CI −5.6 to −0.98).

CONCLUSION:

Preoperative treatment with a GnRH agonist and danazol were both found to be effective in reducing fluid absorption and operative time across a range of hysteroscopic procedures. High-quality research aimed at evaluating other interventions, such as combined hormonal contraception, progestin therapy, and vasopressin, are still lacking in the literature.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42021233804.
An Update on Human Papillomavirus Vaccination in the United States
Authors: Boitano Teresa K.L. , Ketch Peter W. , Scarinci Isabel C. , Huh Warner K.
Published: January 2023

Cervical cancer remains a significant disease in the United States. Although the human papillomavirus (HPV) vaccine has been approved for those aged 9–26 years and for some individuals up to age 45 years, there are many circumstances in which health care professionals may not know whether the vaccine should be recommended, such as for patients with previous infection, health care workers, and those older than age 26 years. This article highlights the evidence that the HPV vaccine is a safe and highly effective way to prevent cervical cancer, with the strongest predictor of vaccine uptake being practitioner recommendation.
Association Between Publicly Funded Contraceptive Services and the Abortion Rate in Texas, 2010–2015
Authors: Madison Anita M. , Powers Daniel , Maslowsky Julie , Goyal Vinita
Published: January 2023

OBJECTIVE:

To evaluate how the availability of contraceptive services was associated with a change in the abortion rate before and after Texas' legislative changes to the family planning budget in 2011 and abortion access in 2013.

METHODS:

In this cross-sectional study, we obtained 2010 and 2015 data on contraceptive provision (number of publicly funded clinics and number of contraceptive clients served per 1,000 reproductive-aged women) from the Guttmacher Institute and county-level abortion data from the Texas Department of State Health Services. We categorized counties as having an abortion rate that increased or declined less than the national rate between 2010 and 2015 (low-decline counties) compared with those having an abortion rate that declined equal to or greater than the national rate between 2010 and 2015 (high-decline counties). We evaluated differences in contraceptive provision between high-decline and low-decline counties and evaluated county characteristics (racial and ethnic composition, unemployment, poverty, uninsured, education, distance to an abortion clinic, deliveries covered by Medicaid, and Catholic hospital marketplace dominance) as potential confounders.

RESULTS:

Of 157 counties that had at least one contraceptive clinic in either 2010 or 2015, 49 were low-decline counties and 108 were high-decline counties. Although the total number of publicly funded family planning clinics increased by 10.8%, there was a 4.7% decrease in the total number of contraceptive clients served statewide. Compared with low-decline counties, high-decline counties had a higher median number of contraceptive clients served per 1,000 women aged 18–44 years (31.9 vs 60.7, P<.05) in 2015. Between 2010 and 2015, the abortion rate decreased 19.7% for each 1.0% increase in contraceptive clients served.

CONCLUSION:

Texas counties with higher abortion-rate declines had more publicly funded contraceptive clinics and served more contraceptive clients than counties with lower declines, which may indicate the importance of greater access to publicly funded contraceptive services.
Predictors of Self-Management Behaviors After Discharge Among Unplanned Dialysis Patients
Authors: KAO Yu-Yin , LEE Chien-Te , WANG Ruey-Hsia
Published: January 2023

Background

Patients with unplanned dialysis must perform self-management behaviors to maintain their health in the community after discharge. Understanding the factors that predict the postdischarge self-management behaviors of patients with unplanned dialysis can assist nurses to implement appropriate discharge plans for this population.

Purpose

This study was designed to predict the effects of uncertainty in illness, self-care knowledge, and social-support-related needs during hospitalization on the self-management behaviors of patients with unplanned dialysis during their first 3 months after discharge from the hospital.

Methods

One hundred sixty-nine patients with unplanned dialysis from the nephrology department of a medical center in Taiwan were enrolled in this prospective study using convenience sampling. At hospital admission, demographic, uncertainty in illness, self-care knowledge, and social support information was collected using a structured questionnaire. Information on self-management behavior was collected at 3 months postdischarge when the patients visited outpatient clinics.

Results

Hierarchical multiple regression analyses showed that self-care knowledge, uncertainty in illness, and social support were important predictors of self-management behaviors at 3 months postdischarge, explaining 65.6% of the total variance in self-management behaviors. Social support increased the variance in self-management behaviors by 27.9%.

Conclusions/Implications for Practice

Comprehensive discharge planning to improve the postdischarge self-management behaviors of patients with unplanned dialysis should involve interventions to improve self-care knowledge, reduce uncertainty in illness, and increase social support. Building social support should be given priority attention.
Perioperative Impella 5.5 Support for Surgical Aortic Valve Replacement: Pull Back/Push Through Technique, Safeguards, and Pitfalls
Authors: Al Rameni Dina , Akay Mehmet , Salas de Armas Ismael , Patel Manish K. , Patel Jayeshkumar , Marcano Juan , Sarateanu Cristian Sorin , Kar Biswajit , Gregoric Igor D.
Published: January 2023

In patients undergoing aortic valve surgery, preoperative reduced left ventricular ejection fraction is not uncommon and is associated with poor outcomes. Mechanical circulatory support (MCS) may be preemptively used in patients presenting with high periprocedural risk. The Impella 5.5 is a percutaneous left ventricular assist device that has been increasingly used in various cardiac surgeries. In this article, we present a step-by-step guide, safeguards, and pitfalls on how to replace the aortic valve and preserve this transaortic MCS device for postoperative support in patients with concomitant aortic valve pathology and left ventricular dysfunction.
Who decides? Consent for healthcare decisions of minors in the United States
Authors: Stettner Nichole M. , Lavelle Ella N. , Cafferty Patrick
Published: January 2023

Purpose of review

The purpose of this review is to examine when parents and legal guardians have the authority to make medical decisions on behalf of the minors in their care, when the decisions of healthcare professionals may supersede those of parents and guardians, and under what conditions minors can make healthcare decisions for themselves.

Recent findings

The coronavirus disease 2019 (COVID-19) pandemic has reignited discussion of who should make healthcare decisions for minors. Though serious adverse reactions to COVID-19 vaccines are rare, hesitancy toward pediatric COVID-19 vaccination is prevalent among parents in the United States. This has contributed to large numbers of minors who are not up-to-date or not fully vaccinated against severe acute respiratory syndrome coronavirus 2 infection. Surveys reveal a majority of minors in the United States are willing to receive a COVID-19 vaccine. A number of scholars have recommended allowing adolescents the ability to consent to COVID-19 vaccination without parental approval.

Allowing adolescents with a minimum age of 15 to consent to vaccination without parental or guardian approval will more quickly enable adolescents to receive new vaccines as they become available, such as the COVID-19 bivalent vaccine.
Association Between Fear of Cancer Recurrence, Fatigue, and Healthy Lifestyle Behaviors Among Breast Cancer Survivors in South Korea
Authors: Jun Hye Suk , Lee Kyungmi
Published: January 2023

Background

Improving healthy lifestyle behaviors in breast cancer survivors can promote their physical and mental health, thereby reducing the risk of cancer recurrence. Therefore, it is crucial to identify and control the factors affecting healthy lifestyle behaviors among breast cancer survivors.

Objective

This study aimed to examine the effects of physiological, psychological, and situational factors and symptoms on healthy lifestyle behaviors in breast cancer survivors.

Methods

Data were collected from August to September 2021, and a questionnaire was administered through an online breast cancer patient community’s bulletin board. Finally, 162 questionnaires were included in the analysis.

Results

The model was statistically significant, explaining 33.2% of the variance. A decrease in healthy lifestyle behaviors in breast cancer survivors was influenced by an age of 40 years or younger, 5 years or more since a breast cancer diagnosis, low income, fear of cancer recurrence, and fatigue.

Conclusions

Intervention strategies, such as easily accessible online content that accounts for age and survival period after cancer diagnosis, should be used to promote healthy lifestyle behaviors among breast cancer survivors. Healthcare providers should be given appropriate guidelines on managing patients’ fear of cancer recurrence and reducing fatigue to ensure timely access to clinical interventions. Adequate financial support from local communities and governments is needed to promote healthy lifestyle behaviors.

Implications for Practice

To improve breast cancer survivors’ healthy lifestyle behaviors, an understanding of the influencing factors and a multidimensional approach are required. Nurses play a role in developing and implementing interventions to improve healthy lifestyle behaviors.
Predictive Value of Ablative Margin Assessment After Microwave Ablation for Local Tumor Progression in Medium and Large Hepatocellular Carcinoma: Computed Tomography–Computed Tomography Image Fusion Method Versus Side-by-Side Method
Authors: Zhou Hongyu , Yang Guanghao , Jing Xiang , Zhou Yan , Ding Jianmin , Wang Yandong , Wang Fengmei , Zhao Lei
Published: January 2023

Objective

This study aimed to explore the feasibility and predictive value for local tumor progression (LTP) of the computed tomography (CT)–CT image fusion method versus side-by-side method to assess ablative margin (AM) in hepatocellular carcinoma ≥3 cm in diameter.

Materials and Methods

We selected patients with hepatocellular carcinoma ≥3 cm in diameter who underwent microwave ablation and had complete tumor ablation. We used the CT-CT image fusion method and side-by-side method to assess AM separately and divided the lesions into 3 groups: group I, minimum ablative margin (min-AM) <0 mm (the ablation zone did not fully cover the tumor); group II, 0 mm ≤ min-AM <5 mm; and group III, min-AM ≥5 mm.

Results

A total of 71 patients involving 71 lesions were included. The κ coefficient for the agreement between the CT-CT image fusion method and the side-by-side method in assessing min-AM was 0.14 (P = 0.028). Cumulative LTP rate was significantly different between groups by min-AM from the CT-CT image fusion method (P < 0.05) but not by min-AM from the side-by-side method (P = 0.807). Seventeen of the 20 LTP lesions were located at min-AM on fused CT images, with consistency rate of 85%.

Conclusions

Compared with the side-by-side method, the CT-CT image fusion method is more accurate in assessing the AM of eccentrically ablated lesions and shows better predictive value for LTP. The min-AM based on CT-CT image fusion assessment is an important influencing factor for LTP.
ouR Space Commentary: Wellness Perspective From SABI’s Early Career Committee
Authors: Chaurasia Aditi , Yu Lei , Kim Nancy , Wentland Andrew , Pirasteh Ali
Published: January 2023

Radiologists and members-in-training are experiencing higher (and escalating) rates of burnout, resulting in a profound impact on the health of physicians, patients, and the community. Lately, the radiology community has demonstrated a growing awareness of this phenomenon, which has led to emphasis on practicing and promoting wellness. With a myriad of factors contributing to burnout in radiology, a multifaceted approach is pivotal for counteracting burnout and fostering overall well-being, including efforts driven at both organizational and individual levels. This article discusses perspectives from the members of the Early Career Committee at the Society for Advanced Body Imaging (SABI); it explores their beliefs and practical strategies for maintaining personal well-being.
Divergent ecological responses to typhoon disturbance revealed via landscape-scale acoustic monitoring
Authors: Ross Samuel R.P-J. , Friedman Nicholas R. , Dudley Kenneth L. , Yoshida Takuma , Yoshimura Masashi , Economo Evan P. , Armitage David W. , Donohue Ian
Published: January 2023

Climate change is increasing the frequency, intensity, and duration of extreme weather events across the globe. Understanding the capacity for ecological communities to withstand and recover from such events is critical. Typhoons are extreme weather events that are expected to broadly homogenise ecological dynamics through structural damage to vegetation and longer-term effects of salinization. Given their unpredictable nature, monitoring ecological responses to typhoons is challenging, particularly for mobile animals such as birds. Here, we report spatially variable ecological responses to typhoons across terrestrial landscapes. Using a high temporal resolution passive acoustic monitoring network across 24 sites on the subtropical island of Okinawa, Japan, we found that typhoons elicit divergent ecological responses among Okinawa’s diverse terrestrial habitats, as indicated by increased spatial variability of biological sound production (biophony) and individual species detections. This suggests that soniferous communities are capable of a diversity of different responses to typhoons. That is, spatial insurance effects among local ecological communities provide resilience to typhoons at the landscape scale. Even though site-level typhoon impacts on soundscapes and bird detections were not particularly strong, monitoring at scale with high temporal resolution across a broad spatial extent nevertheless enabled detection of spatial heterogeneity in typhoon responses. Further, species-level responses mirrored those of acoustic indices, underscoring the utility of such indices for revealing insight into fundamental questions concerning disturbance and stability. Our findings demonstrate the significant potential of landscape-scale acoustic sensor networks to capture the understudied ecological impacts of unpredictable extreme weather events.
MaGplotR: a software for the analysis and visualization of multiple MaGeCK screen datasets through aggregation
Authors: Matía Alejandro , Lorenzo Maria M. , Peng Duo
Published: January 2023

Motivation

MaGplotR analyzes multiple CRISPR screen datasets, identifies common hits, couples the hits to enrichment analysis and cluster plots, and produces publication-level plots. Output plots give information on the quality control of the screen data (e.g., sgRNA distribution) and show the best hits by aggregation from multiple screen experiments. To maximize comparability, rank is used to identify common hits. MaGplotR can also be used to analyze experiments where a control condition is used for multiple treatment conditions. MaGplotR is easy to use, with even just one argument.

Availability and implementation

MaGplotR is open-source code under MIT license. It is available athttps://github.com/alematia/MaGplotR.

Contact

alejandro.matia@inia.csic.es
Inferring neuron-neuron communications from single-cell transcriptomics through NeuronChat
Authors: Zhao Wei , Johnston Kevin G. , Ren Honglei , Xu Xiangmin , Nie Qing
Published: January 2023

Neural communication networks form the fundamental basis for brain function. These communication networks are enabled by emitted ligands such as neurotransmitters, which activate receptor complexes to facilitate communication. Thus, neural communication is fundamentally dependent on the transcriptome. Here we develop NeuronChat, a method and package for the inference, visualization and analysis of neural-specific communication networks among pre-defined cell groups using single-cell expression data. We incorporate a manually curated molecular interaction database of neural signaling for both human and mouse, and benchmark NeuronChat on several published datasets to validate its ability in predicting neural connectivity. Then, we apply NeuronChat to three different neural tissue datasets to illustrate its functionalities in identifying interneural communication networks, revealing conserved or context-specific interactions across different biological contexts, and predicting communication pattern changes in diseased brains with autism spectrum disorder. Finally, we demonstrate NeuronChat can utilize spatial transcriptomics data to infer and visualize neural-specific cell-cell communication.
KOMPUTE: Imputing summary statistics of missing phenotypes in high-throughput model organism data
Authors: Warkentin Coby , O’Connell Michael J. , Lee Donghyung
Published: January 2023

Motivation

The International Mouse Phenotyping Consortium (IMPC) is striving to build a comprehensive functional catalog of mammalian protein-coding genes by systematically producing and phenotyping gene-knockout mice for almost every protein-coding gene in the mouse genome and by testing associations between gene loss-of-function and phenotype. To date, the IMPC has identified over 90,000 gene-phenotype associations, but many phenotypes have not yet been measured for each gene, resulting in largely incomplete data; about 75.6% of association summary statistics are still missing in the latest IMPC summary statistics dataset (IMPC release version 16).

Results

To overcome these challenges, we propose KOMPUTE, a novel method for imputing missing summary statistics in the IMPC dataset. Using conditional distribution properties of multivariate normal, KOMPUTE estimates association Z-scores of unmeasured phenotypes for a particular gene as a conditional expectation given the Z-scores of measured phenotypes. We evaluate the efficacy of the proposed method for recovering missing Z-scores using simulated and real-world data sets and compare it to a singular value decomposition (SVD) matrix completion method. Our results show that KOMPUTE outperforms the comparison method across different scenarios.

Availability and implementation

An R package for KOMPUTE is publicly available athttps://github.com/statsleelab/kompute, along with usage examples and results for different phenotype domains athttps://statsleelab.github.io/komputeExamples.

Contact

leed13@miamioh.edu

Supplementary information

Supplementary data are available atBioinformaticsonline.
Non-Invasive Prenatal Diagnosis of Single Gene Disorders with enhanced Relative Haplotype Dosage Analysis for diagnostic implementation
Authors: Pacault Mathilde , Verebi Camille , Champion Magali , Orhant Lucie , Perrier Alexandre , Girodon Emmanuelle , Leturcq France , Vidaud Dominique , Férec Claude , Bienvenu Thierry , Daveau Romain , Nectoux Juliette
Published: January 2023

Non-invasive prenatal diagnosis for single-gene disorders (SGD-NIPD) has been widely adopted by patients, but is mostly limited to the exclusion of paternal or de novo mutations. Indeed, it is still difficult to infer the inheritance of maternal allele from cell free DNA (cfDNA) analysis. Based on the study of maternal haplotypes imbalance in cfDNA, relative haplotype dosage (RHDO) was developed to address this challenge. Although RHDO has proven to be reliable, robust control of statistical error and explicit delineation of critical parameters for assessing the quality of analysis have not been fully considered yet.

Here we propose a universal and adaptable enhanced-RHDO procedure (eRHDO) through an automated bioinformatics pipeline with a didactical visualization of results that aims to be applied for any SGD-NIPD in routine care. A training cohort of 43 families carriers forCFTR, NF1, DMD, or F8mutations allowed the characterization and optimal setting of several adjustable data variables, such as minimal sequencing depth and type 1 and type 2 statistical errors, as well as the quality assessment for intermediate steps and final result through block score and concordance score. Validation was successfully carried out on 56 pregnancies of the test cohort. Finally, computer simulations were used to estimate the effect of fetal-fraction, sequencing depth and number of informative SNPs on the quality of results. Our workflow proved to be robust, as we obtained 94.9% conclusive and correctly inferred fetal genotypes, without any false negative or false positive result.

By standardizing data generation and analysis, we fully describe a turnkey protocol for laboratories wishing to offer eRHDO-based non-invasive prenatal diagnosis for single-gene disorders as an alternative to conventional prenatal diagnosis.
Germination timing under climate change: warmer springs favor early germination of range-wide cork oak populations
Authors: Benito Garzón Marta , Baillou Fany , e Silva Filipe Costa , Faria Carla , Marchi Maurizio , Stiti Bouthenia , Vendramin Giovanni Giuseppe , Vizcaíno-Palomar Natalia
Published: January 2023

Climate change is favoring the northward shift of Mediterranean species which are expanding their ranges at their leading edges, becoming natural candidates for increasing forest biodiversity in these regions. However, current knowledge on tree populations’ responses to climate change is mostly based on adult trees, even if tree early developmental stages are far more sensitive to climate and tightly linked to fitness. To fill this knowledge gap, we investigated the potential adaptation of cork oak range-wide populations to increasing spring temperature in germination and post-germination traits. We sowed 701 acorns from 11 populations at 15, 20 and 25°C, monitored germination daily and measured post-germination traits. We model germination timing through Cox’s proportional-hazards models, assess populations’ adaptation to spring temperature transfer distances and quantify the effect of acorn mass and storage duration on all considered traits with fixed-effects models. We predict germination and post-germination climate niches under current and RCP 8.5 2080 scenarios. Large differences in germination timing are due to both the population origin and temperature treatment; germination and survival rates showed a sub-optimality towards warmer-than-origin temperatures and heavier acorns produced faster growing seedlings. The timing of germination is the early stage trait most affected by increasing spring temperatures, with germination in 2080 predicted to be 12 days earlier than to date in the northern part of the species’ range. Warmer spring temperatures will significantly accelerate the germination of other recalcitrant Mediterranean species, which could alter seedlings developmental environment and ultimately populations’ regeneration and species composition. As such, germination timing should receive more attention by scientists and stakeholders, and should be included in forest vulnerability assessments and assisted migration programs aiming at long-term forest regeneration to adapt forests to climate change.
RNA-to-image multi-cancer synthesis using cascaded diffusion models
Authors: Carrillo-Perez Francisco , Pizurica Marija , Zheng Yuanning , Nandi Tarak Nath , Madduri Ravi , Shen Jeanne , Gevaert Olivier
Published: January 2023

Data scarcity presents a significant obstacle in the field of biomedicine, where acquiring diverse and sufficient datasets can be costly and challenging. Synthetic data generation offers a potential solution to this problem by expanding dataset sizes, thereby enabling the training of more robust and generalizable machine learning models. Although previous studies have explored synthetic data generation for cancer diagnosis, they have predominantly focused on single modality settings, such as whole-slide image tiles or RNA-Seq data. To bridge this gap, we propose a novel approach, RNA-Cascaded-Diffusion-Model or RNA-CDM, for performing RNA-to-image synthesis in a multi-cancer context, drawing inspiration from successful text-to-image synthesis models used in natural images. In our approach, we employ a variational auto-encoder to reduce the dimensionality of a patient’s gene expression profile, effectively distinguishing between different types of cancer. Subsequently, we employ a cascaded diffusion model to synthesize realistic whole-slide image tiles using the latent representation derived from the patient’s RNA-Seq data. Our results demonstrate that the generated tiles accurately preserve the distribution of cell types observed in real-world data, with state-of-the-art cell identification models successfully detecting important cell types in the synthetic samples. Furthermore, we illustrate that the synthetic tiles maintain the cell fraction observed in bulk RNA-Seq data and that modifications in gene expression affect the composition of cell types in the synthetic tiles. Next, we utilize the synthetic data generated by RNA-CDM to pretrain machine learning models and observe improved performance compared to training from scratch. Our study emphasizes the potential usefulness of synthetic data in developing machine learning models in sarce-data settings, while also highlighting the possibility of imputing missing data modalities by leveraging the available information. In conclusion, our proposed RNA-CDM approach for synthetic data generation in biomedicine, particularly in the context of cancer diagnosis, offers a novel and promising solution to address data scarcity. By generating synthetic data that aligns with real-world distributions and leveraging it to pretrain machine learning models, we contribute to the development of robust clinical decision support systems and potential advancements in precision medicine.
Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function
Authors: Santi Alice , Kay Emily J , Neilson Lisa J , McGarry Lynn , Lilla Sergio , Mullin Margaret , Paul Nikki R , Fercoq Frédéric , Koulouras Grigorios , Blanco Giovanny Rodriguez , Athineos Dimitris , Mason Susan , Hughes Mark , Kieffer Yann , Nixon Colin , Blyth Karen , Mechta-Grigoriou Fatima , Carlin Leo M , Zanivan Sara
Published: January 2023

Intercellular communication between different cell types in solid tumors contributes to tumor growth and metastatic dissemination. The secretome of cancer-associated fibroblasts (CAFs) plays major roles in these processes. Using human mammary CAFs, we unveil a mechanism of cell-cell communication between CAFs with myofibroblast phenotype and endothelial cells (ECs) based on intercellular protein transfer through extracellular vesicles (EVs). CAFs transfer proteins to ECs, including plasma membrane receptors, which we have identified by using mass spectrometry- based proteomics. Using THY1 as an example of transferred plasma membrane-bound protein, we show that CAF-derived proteins can influence how ECs interact with other cell types. Here, we show that CAFs produce high amounts of matrix-bound EVs that have a key role in protein transfer. Hence, our work paves the way for further studies to understand how CAF-derived matrix-bound EVs influence tumor pathology by regulating functions of neighboring cancer, stromal and immune cells.

One sentence summary

CAFs with a myofibroblastic-like phenotype transfer proteins to ECs, including plasma membrane receptors, through matrix-bound EVs
Manifold Learning for fMRI time-varying FC
Authors: Gonzalez-Castillo Javier , Fernandez Isabel , Lam Ka Chun , Handwerker Daniel A , Pereira Francisco , Bandettini Peter A
Published: January 2023

Whole-brain functional connectivity (FC) measured with functional MRI (fMRI) evolve over time in meaningful ways at temporal scales going from years (e.g., development) to seconds (e.g., within-scan time-varyingFC(tvFC)). Yet, our ability to exploretvFCis severely constrained by its large dimensionality (several thousands). To overcome this difficulty, researchers seek to generate low dimensional representations (e.g.,2Dand3Dscatter plots) expected to retain its most informative aspects (e.g., relationships to behavior, disease progression). Limited prior empirical work suggests that manifold learning techniques (MLTs)—namely those seeking to infer a low dimensional non-linear surface (i.e., the manifold) where most of the data lies—are good candidates for accomplishing this task. Here we explore this possibility in detail. First, we discuss why one should expect tvFCdata to lie on a low dimensional manifold. Second, we estimate what is the intrinsic dimension (i.e., minimum number of latent dimensions;ID) oftvFCdata manifolds. Third, we describe the inner workings of three state-of-the-artMLTs: Laplacian Eigenmaps (LE), T-distributed Stochastic Neighbor Embedding (T-SNE), and Uniform Manifold Approximation and Projection (UMAP). For each method, we empirically evaluate its ability to generate neuro-biologically meaningful representations oftvFCdata, as well as their robustness against hyper-parameter selection. Our results show thattvFCdata has anIDthat ranges between 4 and 26, and thatIDvaries significantly between rest and task states. We also show how all three methods can effectively capture subject identity and task being performed:UMAPandT-SNEcan capture these two levels of detail concurrently, but LEcould only capture one at a time. We observed substantial variability in embedding quality acrossMLTs, and within-MLTas a function of hyper-parameter selection. To help alleviate this issue, we provide heuristics that can inform future studies. Finally, we also demonstrate the importance of feature normalization when combining data across subjects and the role that temporal autocorrelation plays in the application ofMLTstotvFCdata. Overall, we conclude that whileMLTscan be useful to generate summary views of labeledtvFCdata, their application to unlabeled data such as resting-state remains challenging.
SYNGAP1 deficiency disrupts neoteny in human cortical neurons in vivo
Authors: Vermaercke Ben , Iwata Ryohei , Weirda Keimpe , Boubakar Leïla , Rodriguez Paula , Ditkowska Martyna , Bonin Vincent , Vanderhaeghen Pierre
Published: January 2023

Intellectual deficiency (ID) and autism spectrum disorder (ASD) originate from disrupted development of human-specific cognitive functions. Human brain ontogeny is characterized by a considerably prolonged, neotenic, cortical neuron development. Neuronal neoteny could be disrupted in ID/ASD, but this was never tested because of the difficulties to study developing human cortical circuits. Here we use xenotransplantation of human cortical neurons into the mouse cortex to study the in vivo neuronal consequences of SYNGAP1 haploinsufficiency, a frequent cause of ID/ASD. We find that SYNGAP1 deficient neurons display strong acceleration of morphological and functional synaptic development. At the circuit level, SYNGAP1 haploinsufficient neurons display disrupted neoteny, with faster integration into cortical circuits and acquisition of sensory responsiveness months ahead of time. These data link neuronal neoteny to ID/ASD, with important implications for diagnosis and treatments.
Dally is not essential for Dpp spreading or internalization but for Dpp stability by antagonizing Tkv-mediated Dpp internalization
Authors: Simon Niklas , Safyan Abu , Pyrowolakis George , Matsuda Shinya
Published: January 2023

Dpp/BMP acts as a morphogen to provide positional information in the Drosophila wing disc. Key cell-surface molecules to control Dpp morphogen gradient formation and signaling are heparan sulfate proteoglycans (HSPGs). In the wing disc, two HSPGs, the glypicans Division abnormally delayed (Dally) and Dally-like (Dlp) have been suggested to act redundantly to control these processes through direct interaction of their heparan sulfate (HS) chains with Dpp. Based on this assumption, a number of models on how glypicans control Dpp gradient formation and signaling have been proposed, including facilitating or hindering Dpp spreading, stabilizing Dpp on the cell surface, or recycling Dpp. However, how distinct HSPGs act remains largely unknown. Here we generate genome-engineering platforms for the two glypicans and find that only Dally is critical for Dpp gradient formation and signaling through interaction of its core protein with Dpp. We also find that this interaction is not sufficient and that the HS chains of Dally are essential for these functions largely without interacting with Dpp. We provide evidence that the HS chains of Dally are not essential for spreading or recycling of Dpp but for stabilizing Dpp on the cell surface by antagonizing receptor-mediated Dpp internalization. These results provide new insights into how distinct HSPGs control morphogen gradient formation and signaling during development.
PML mutants resistant to arsenic induced degradation fail to generate the appropriate SUMO and ubiquitin signals required for RNF4 and p97 recruitment
Authors: Jaffray Ellis G. , Tatham Michael H. , Rojas-Fernandez Alejandro , Ibrahim Adel , Ball Graeme , Hay Ronald T.
Published: January 2023

Arsenic is an effective treatment for Acute Promyelocytic Leukaemia as it induces degradation of the Promyelocytic Leukaemia (PML) – retinoic acid receptor alpha (RARA) oncogenic fusion protein. Some patients relapse with arsenic resistant disease because of missense mutations in PML. To determine the mechanistic basis for arsenic resistance we reconstituted PML-/- cells with YFP fusions of wild type (WT) and two mutant forms of PMLV found in patients refractory to arsenic, A216T and L217F. Both mutants formed PML bodies that were larger, but less numerous than WT and neither responded to arsenic by degradation. Analysis of immunoprecipitated PML bodies indicated that while WT PML experiences increased SUMO1, SUMO2/3 and ubiquitin conjugation, A216T PML is almost completely unresponsive and therefore does not recruit the SUMO targeted ubiquitin E3 ligase RNF4. Compared to WT PML, L217F PML was modified to a similar extent by SUMO2 but not SUMO1 and although it recruited RNF4, it failed to develop the appropriate poly-ubiquitin conjugates required to recruit the segregase p97, which is essential for PML degradation.